FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Sahani, DV Hayano, K Galluzzo, A Zhu, AX AF Sahani, Dushyant V. Hayano, Koichi Galluzzo, Anna Zhu, Andrew X. TI Measuring Treatment Response to Systemic Therapy and Predicting Outcome in Biliary Tract Cancer: Comparing Tumor Size, Volume, Density, and Metabolism SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE biliary tract cancer; CT; PET; RECIST; tumor density ID POSITRON-EMISSION-TOMOGRAPHY; METASTATIC COLORECTAL-CANCER; CELL LUNG-CANCER; SOLID TUMORS; EVALUATION CRITERIA; PREOPERATIVE CHEMOTHERAPY; IMAGING TECHNIQUES; BEVACIZUMAB; OXALIPLATIN; GEMCITABINE AB OBJECTIVE. The purpose of this study was to evaluate the response of biliary tract cancer treated with multidrug chemotherapy using FDG PET in comparison with morphologic and density changes. MATERIALS AND METHODS. In this phase II clinical trial, 28 patients with unresectable or metastatic biliary tract cancers treated with gemcitabine and oxaliplatin combined with bevacizumab (GEMOX-B) underwent FDG PET and contrast-enhanced CT at baseline and after the second cycle of the therapy (8 weeks). A single reviewer recorded tumor maximum standardized uptake value (SUVmax) along with size, volume (3D-sphere), and density. The percentage changes of the parameters were compared with progression-free survival at 7 months. Overall survival was compared with the percentage change of SUVmax. RESULTS. After 8 weeks, measurable reductions (+/- SD) in size (7.05 +/- 4.19 to 5.52 +/- 3.28 cm, -21.70%), volume (411.38 +/- 540.08 to 212.41 +/- 293.45 cm(3), -48.36%), and density (60.76 +/- 20.65 to 50.68 +/- 16.89 HU, -15.59%) were noted along with a substantial drop in SUVmax (5.95 +/- 1.95 to 3.36 +/- 1.28, -43.52%). The SUVmax change showed positive correlations with tumor size change (R-2 = 0.39, p = 0.0004) and volumetric change (R-2 = 0.34, p = 0.001). Patients who showed a larger drop in SUVmax at 8 weeks correlated with favorable progression-free survival (p = 0.02). ROC analysis showed that a 45% reduction in SUVmax was the best cutoff value to detect favorable progression-free survival patients. When we used this cutoff value, KaplanMeier analysis showed that patients with tumors showing greater reduction in SUVmax had favorable progression-free survival and overall survival (p = 0.0009, p = 0.03). CONCLUSION. In biliary tract cancers treated with GEMOX-B, the reduction of SUVmax after therapy is a better predictor for survival than morphologic and density changes. C1 [Sahani, Dushyant V.; Hayano, Koichi; Galluzzo, Anna] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Zhu, Andrew X.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org NR 32 TC 1 Z9 1 U1 1 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 APR PY 2015 VL 204 IS 4 BP 776 EP 781 DI 10.2214/AJR.14.13223 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CE2AN UT WOS:000351614700032 PM 25794066 ER PT J AU Asvadi, NH Arellano, RS AF Asvadi, Nazanin H. Arellano, Ronald S. TI Hydrodissection-Assisted Image-Guided Percutaneous Biopsy of Abdominal and Pelvic Lesions: Experience With Seven Patients SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE hydrodissection; percutaneous biopsy; retroperitoneum ID RADIOFREQUENCY ABLATION; DISPLACEMENT; CARCINOMA; INJECTION; ACCESS AB OBJECTIVE. The purpose of this study was to evaluate the effectiveness of retroperitoneal organ displacement for image-guided percutaneous biopsy. CONCLUSION. Organ displacement using 0.9% saline or 5% dextrose in water (D5W) can create safe access routes for targeted abdominal and pelvic biopsies. C1 [Asvadi, Nazanin H.; Arellano, Ronald S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Intervent Radiol,Dept Radiol, Boston, MA 02114 USA. RP Asvadi, NH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Intervent Radiol,Dept Radiol, White 270, Boston, MA 02114 USA. EM nasvadi@mgh.harvard.edu NR 8 TC 3 Z9 3 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2015 VL 204 IS 4 BP 865 EP 867 DI 10.2214/AJR.14.13040 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CE2AN UT WOS:000351614700045 PM 25794079 ER PT J AU Padole, A Khawaja, RDA Kalra, MK Singh, S AF Padole, Atul Khawaja, Ranish Deedar Ali Kalra, Mannudeep K. Singh, Sarabjeet TI CT Radiation Dose and Iterative Reconstruction Techniques SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT image quality; CT radiation dose optimization; iterative reconstruction techniques ID FILTERED BACK-PROJECTION; LOW TUBE VOLTAGE; COMPUTED-TOMOGRAPHY; IMAGE QUALITY; CRANIAL CT; REDUCTION; ANGIOGRAPHY; ALGORITHM; HYBRID C1 [Padole, Atul; Khawaja, Ranish Deedar Ali; Kalra, Mannudeep K.; Singh, Sarabjeet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Singh, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,Founders 202, Boston, MA 02114 USA. EM ssingh6@mgh.harvard.edu NR 24 TC 16 Z9 16 U1 1 U2 7 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2015 VL 204 IS 4 BP W384 EP W387 DI 10.2214/AJR.14.13241 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CE2AN UT WOS:000351614700002 PM 25794087 ER PT J AU Sistrom, CL Dreyer, K Weilburg, JB Perloff, JN Tompkins, CP Ferris, TG AF Sistrom, Chris L. Dreyer, Keith Weilburg, Jeffrey B. Perloff, Jennifer N. Tompkins, Christopher P. Ferris, Timothy G. TI Images of Imaging: How to Process and Display Imaging Utilization for Large Populations SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE big data; geocoding; health services research; imaging cost; imaging utilization; informatics; Medicare; regional variation; visual analytics ID UTILIZATION MANAGEMENT; GEOGRAPHIC-VARIATION; MEDICARE DATA; RADIOLOGY; CARE; TRENDS; NONRADIOLOGISTS; APPROPRIATENESS; SPECIALTY; SYSTEMS AB OBJECTIVE. We propose a method of processing and displaying imaging utilization data for large populations. CONCLUSION. The comprehensive and finely grained picture of imaging utilization yielded by our methods is a first step toward population-based imaging utilization management. We believe that our methods for the categorization and display of imaging utilization will prove to be widely useful. C1 [Sistrom, Chris L.] Univ Florida, Ctr Hlth, Dept Radiol, Gainesville, FL 32610 USA. [Sistrom, Chris L.; Dreyer, Keith] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Sistrom, Chris L.; Weilburg, Jeffrey B.; Ferris, Timothy G.] Massachusetts Gen Phys Org, Boston, MA USA. [Sistrom, Chris L.; Perloff, Jennifer N.; Tompkins, Christopher P.] Brandeis Univ, Heller Sch Social Policy & Management, Schneider Inst Healthcare Syst, Waltham, MA USA. RP Sistrom, CL (reprint author), Univ Florida, Ctr Hlth, Dept Radiol, POB 100374, Gainesville, FL 32610 USA. EM sistrc@radiology.ufl.edu NR 47 TC 1 Z9 1 U1 0 U2 3 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 APR PY 2015 VL 204 IS 4 BP W405 EP W412 DI 10.2214/AJR.14.13593 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CE2AN UT WOS:000351614700005 PM 25794090 ER PT J AU Tasaki, M Wamala, I Tena, A Villani, V Sekijima, M Pathiraja, V Wilkinson, RA Pratts, S Cormack, T Clayman, E Arn, JS Shimizu, A Fishman, JA Sachs, DH Yamada, K AF Tasaki, M. Wamala, I. Tena, A. Villani, V. Sekijima, M. Pathiraja, V. Wilkinson, R. A. Pratts, S. Cormack, T. Clayman, E. Arn, J. S. Shimizu, A. Fishman, J. A. Sachs, D. H. Yamada, K. TI High Incidence of Xenogenic Bone Marrow Engraftment in Pig-to-Baboon Intra-Bone Bone Marrow Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article ID NONLETHAL PREPARATIVE REGIMEN; MIXED CHIMERISM; MINIATURE SWINE; RENAL-TRANSPLANTATION; XENOGRAFT REJECTION; ALLOGRAFT TOLERANCE; CYNOMOLGUS MONKEYS; KNOCKOUT PIGS; CELLS; INDUCTION AB Previous attempts of -1,3-galactocyltransferase knockout (GalTKO) pig bone marrow (BM) transplantation (Tx) into baboons have demonstrated a loss of macro-chimerism within 24h in most cases. In order to achieve improved engraftment with persistence of peripheral chimerism, we have developed a new strategy of intra-bone BM (IBBM) Tx. Six baboons received GalTKO BM cells, with one-half of the cells transplanted into the bilateral tibiae directly and the remaining cells injected intravenously (IBBM/BM-Tx) with a conditioning immunosuppressive regimen. In order to assess immune responses induced by the combined IBBM/BM-Tx, three recipients received donor SLA-matched GalTKO kidneys in the peri-operative period of IBBM/BM-Tx (Group 1), and the others received kidneys 2 months after IBBM/BM-Tx (Group 2). Peripheral macro-chimerism was continuously detectable for up to 13 days (mean 7.7 days; range 3-13) post-IBBM/BM-Tx and in three animals, macro-chimerism reappeared at days 10, 14 and 21. Pig CFUs, indicating porcine progenitor cell engraftment, were detected in the host BM in four of six recipients on days 14, 15, 19 and 28. In addition, anti-pig unresponsiveness was observed by in vitro assays. GalTKO/pCMV-kidneys survived for extended periods (47 and 60 days). This strategy may provide a potent adjunct for inducing xenogeneic tolerance through BM-Tx. C1 [Yamada, K.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Yamada, K (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. EM kaz.yamada@tbrc.mgh.harvard.edu OI Villani, Vincenzo/0000-0002-6078-9766 FU NIH/NIAID [2P01AI45897]; MGH Swine Facility grant [C06 RR020135-01] FX The authors would like to thank Dr. Isabel Hanekamp for her helpful advice and review of this manuscript. We thank Dr. Keith Reimann for anti-CD154 mAb (5C8 chimeric Ab) for this research. This research was supported by the Project 1 of the NIH/NIAID 2P01AI45897 (KY), the core facility of NIH/NIAID 2P01AI45897 (JAF and RAW), and the MGH Swine Facility grant C06 RR020135-01 (DHS). NR 36 TC 5 Z9 6 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2015 VL 15 IS 4 BP 974 EP 983 DI 10.1111/ajt.13070 PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA CE2US UT WOS:000351675600017 PM 25676635 ER PT J AU Adler, JT Hyder, JA Elias, N Nguyen, LL Markmann, JF Delmonico, FL Yeh, H AF Adler, J. T. Hyder, J. A. Elias, N. Nguyen, L. L. Markmann, J. F. Delmonico, F. L. Yeh, H. TI Socioeconomic Status and Ethnicity of Deceased Donor Kidney Recipients Compared to Their Donors SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article ID DISPARITIES GEOCODING PROJECT; ORGAN DONATION; RENAL-TRANSPLANTATION; UNITED-STATES; QUALITATIVE LITERATURE; ACCESS; HEALTH; CARE; BARRIERS; DETERMINANTS AB Public perception and misperceptions of socioeconomic disparities affect the willingness to donate organs. To improve our understanding of the flow of deceased donor kidneys, we analyzed socioeconomic status (SES) and racial/ethnic gradients between donors and recipients. In a retrospective cohort study, traditional demographic and socioeconomic factors, as well as an SES index, were compared in 56,697 deceased kidney donor and recipient pairs transplanted between 2007 and 2012. Kidneys were more likely to be transplanted in recipients of the same racial/ethnic group as the donor (p<0.001). Kidneys tended to go to recipients of lower SES index (50.5% of the time, p<0.001), a relationship that remained after adjusting for other available markers of donor organ quality and SES (p<0.001). Deceased donor kidneys do not appear to be transplanted from donors of lower SES to recipients of higher SES; this information may be useful in counseling potential donors and their families regarding the distribution of their organ gifts. C1 [Adler, J. T.; Hyder, J. A.; Nguyen, L. L.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Adler, J. T.; Elias, N.; Markmann, J. F.; Delmonico, F. L.; Yeh, H.] Massachusetts Gen Hosp, Div Transplant Surg, Boston, MA 02114 USA. [Hyder, J. A.] Mayo Clin, Dept Anesthesiol, Rochester, MN USA. [Elias, N.; Nguyen, L. L.; Markmann, J. F.; Delmonico, F. L.; Yeh, H.] Harvard Univ, Sch Med, Boston, MA USA. [Nguyen, L. L.] Brigham & Womens Hosp, Div Vasc & Endovasc Surg, Boston, MA 02115 USA. RP Yeh, H (reprint author), Massachusetts Gen Hosp, Div Transplant Surg, Boston, MA 02114 USA. EM hyeh@partners.org OI Adler, Joel/0000-0001-8190-3444 FU Arthur Tracy Cabot fellowship from the Center for Surgery and Public Health at Brigham and Women's Hospital FX JTA is funded by the Arthur Tracy Cabot fellowship from the Center for Surgery and Public Health at Brigham and Women's Hospital. NR 34 TC 2 Z9 2 U1 2 U2 6 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 APR PY 2015 VL 15 IS 4 BP 1061 EP 1067 DI 10.1111/ajt.13097 PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA CE2US UT WOS:000351675600026 PM 25758952 ER PT J AU Katz, M Luciano, MS Carlson, K Luo, P Marks, WJ Larson, PS Starr, PA Follett, KA Weaver, FM Stern, MB Reda, DJ Ostrem, JL AF Katz, Maya Luciano, Marta San Carlson, Kimberly Luo, Ping Marks, William J., Jr. Larson, Paul S. Starr, Philip A. Follett, Kenneth A. Weaver, Frances M. Stern, Matthew B. Reda, Domenic J. Ostrem, Jill L. CA CSP 468 Study Grp TI Differential Effects of Deep Brain Stimulation Target on Motor Subtypes in Parkinson's Disease SO ANNALS OF NEUROLOGY LA English DT Article ID SUBTHALAMIC NUCLEUS STIMULATION; RANDOMIZED CONTROLLED-TRIAL; PALLIDAL STIMULATION; MEDICAL THERAPY; OUTCOMES; TREMOR; METAANALYSIS; MULTICENTER; DOPAMINE; PD AB ObjectiveThe Veterans Administration Cooperative Studies Program #468, a multicenter study that randomized Parkinson's disease (PD) patients to either subthalamic nucleus (STN) or globus pallidus internus (GPi) deep brain stimulation (DBS), found that stimulation at either target provided similar overall motoric benefits. We conducted an additional analysis of this data set to evaluate whether PD motor subtypes responded differently to the 2 stimulation targets. MethodsWe classified 235 subjects by motor subtype: tremor dominant (TD), intermediate (I), or postural instability gait difficulty (PIGD), based on pre-DBS baseline Unified Parkinson's Disease Rating Scale (UPDRS) scores off-medication. The primary outcome was change in UPDRS part III (UPDRS-III) off-medication scores from baseline to 24 months post-DBS, compared among subjects with particular PD motor subtypes and by DBS target (STN vs GPi). Changes in tremor, rigidity, akinesia, and gait scores were also assessed using the UPDRS. ResultsTD patients had greater mean overall motor improvement, measured by UPDRS-III, after GPi DBS, compared to STN DBS (17.513.0 vs 14.6 +/- 14.9, p=0.02), with improvement in gait accounting for this difference. Regardless of stimulation target, PIGD subjects had lower mean overall improvement in UPDRS-III scores compared with I or TD subjects (8.7 +/- 12.2 vs 21.7 +/- 11.2 vs 16.3 +/- 13.8, p=0.001). InterpretationOur results suggest that responsiveness to both GPi and STN DBS is similar among different PD motor subtypes, although the TD motor subtype may have a greater response to GPi DBS with respect to gait. PIGD patients obtained less overall benefit from stimulation. Ann Neurol 2015;77:710-719 C1 [Katz, Maya; Luciano, Marta San; Marks, William J., Jr.; Ostrem, Jill L.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94131 USA. [Katz, Maya; Luciano, Marta San; Marks, William J., Jr.; Ostrem, Jill L.] San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, San Francisco, CA USA. [Carlson, Kimberly; Reda, Domenic J.] Dept Vet Affairs, Off Res & Dev, Cooperat Studies Program, Washington, DC USA. [Luo, Ping] Domen Reda & Kimberly Carlson Hines VA Cooperat S, Hines, IL USA. [Larson, Paul S.; Starr, Philip A.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94131 USA. [Follett, Kenneth A.] Univ Nebraska Med Ctr, Dept Neurosurg, Omaha, NE USA. [Weaver, Frances M.] Edward J Hines Jr VA Hosp, Ctr Innovat Complex Chron Healthcare, Hines, IL USA. [Weaver, Frances M.] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. [Stern, Matthew B.] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. RP Katz, M (reprint author), Univ Calif San Francisco, 1635 Divisadero St,Suite 520, San Francisco, CA 94131 USA. EM maya.katz@ucsfmedctr.org FU Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development; NIH National Institute of Neurological Disorders and Stroke; Medtronic FX The CSP #468 study was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development, the NIH National Institute of Neurological Disorders and Stroke, and Medtronic. Our additional analysis of the original study received no specific funding support. NR 36 TC 5 Z9 5 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2015 VL 77 IS 4 BP 710 EP 719 DI 10.1002/ana.24374 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CE8OK UT WOS:000352102500015 PM 25627340 ER PT J AU Galley, CE Haynes, AB AF Galley, Christy E. Haynes, Alex B. TI Beyond "A Chance to Cut Is a Chance to Cure" Surgical Quality in the Cancer Care Continuum SO ANNALS OF SURGERY LA English DT Editorial Material ID 1022 PALLIATIVE PROCEDURES; COLORECTAL-CANCER; ANASTOMOTIC LEAKAGE; CURATIVE RESECTION; OUTCOMES ANALYSIS; SURGERY; IMPACT; COMPLICATIONS; SURVIVAL C1 [Haynes, Alex B.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Ariadne Labs, Boston, MA USA. RP Haynes, AB (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM abhaynes@partners.org NR 10 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 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD APR PY 2015 VL 261 IS 4 BP 637 EP 638 DI 10.1097/SLA.0000000000001134 PG 2 WC Surgery SC Surgery GA CE2VV UT WOS:000351679500028 ER PT J AU Luketich, JD Pennathur, A Franchetti, Y Catalano, PJ Swanson, S Sugarbaker, DJ De Hoyos, A Maddaus, MA Nguyen, NT Benson, AB Fernando, HC AF Luketich, James D. Pennathur, Arjun Franchetti, Yoko Catalano, Paul J. Swanson, Scott Sugarbaker, David J. De Hoyos, Alberto Maddaus, Michael A. Nguyen, Ninh T. Benson, Al B. Fernando, Hiran C. TI Minimally Invasive Esophagectomy Results of a Prospective Phase II Multicenter Trial-the Eastern Cooperative Oncology Group (E2202) Study SO ANNALS OF SURGERY LA English DT Article DE esophagectomy; esophageal resection; MIE; minimally invasive; surgical procedures ID LIMITED TRANSHIATAL RESECTION; BARRETTS-ESOPHAGUS; HOSPITAL VOLUME; CANCER; MORTALITY; OUTCOMES; MORBIDITY; SURGERY; ADENOCARCINOMA; CARCINOMA AB Objective: The primary aim of this trial was to assess the feasibility of minimally invasive esophagectomy (MIE) in a multi-institutional setting. Background: Esophagectomy is an important, potentially curative treatment for localized esophageal cancer, but is a complex operation. MIE may decrease the morbidity and mortality of resection, and single-institution studies have demonstrated successful outcomes with MIE. Methods: We conducted a multicenter, phase II, prospective, cooperative group study (coordinated by the Eastern Cooperative Oncology Group) to evaluate the feasibility of MIE. Patients with biopsy-proven high-grade dysplasia or esophageal cancer were enrolled at 17 credentialed sites. Protocol surgery consisted of either 3-stage MIE or Ivor Lewis MIE. The primary end point was 30-day mortality. Secondary end points included adverse events, duration of hospital-stay, and 3-year outcomes. Results: Protocol surgery was completed in 95 of the 104 patients eligible for the primary analysis (91.3%). The 30-day mortality in eligible patients who underwent MIE was 2.1%; perioperative mortality in all registered patients eligible for primary analysis was 2.9%. Median intensive care unit and hospital stay were 2 and 9 days, respectively. Grade 3 or higher adverse events included anastomotic leak (8.6%), acute respiratory distress syndrome (5.7%), pneumonitis (3.8%), and atrial fibrillation (2.9%). At a median follow-up of 35.8 months, the estimated 3-year overall survival was 58.4% (95% confidence interval: 47.7%-67.6%). Locoregional recurrence occurred in only 7 patients (6.7%). Conclusions: This prospective multicenter study demonstrated that MIE is feasible and safe with low perioperative morbidity and mortality and good oncological results. This approach can be adopted by other centers with appropriate expertise in open esophagectomy and minimally invasive surgery. C1 [Luketich, James D.; Pennathur, Arjun] Univ Pittsburgh, Dept Cardiothorac Surg, Pittsburgh, PA 15213 USA. [Franchetti, Yoko; Catalano, Paul J.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Swanson, Scott; Sugarbaker, David J.] Brigham & Womens Hosp, Dept Thorac Surg, Boston, MA 02115 USA. [De Hoyos, Alberto; Benson, Al B.] Northwestern Univ, Dept Med, Div Hematol Oncol, Chicago, IL 60611 USA. [Maddaus, Michael A.] Univ Minnesota, Dept Surg, Div Thorac & Foregut Surg, Minneapolis, MN 55455 USA. [Nguyen, Ninh T.] Univ Calif Irvine, Med Ctr, Dept Surg, Div Gastrointestinal Surg, Orange, CA USA. [Fernando, Hiran C.] Boston Med Ctr, Dept Cardiothorac Surg, Boston, MA USA. RP Luketich, JD (reprint author), Univ Pittsburgh, Med Ctr, Dept Cardiothorac Surg, 200 Lothrop St,Suite C-800, Pittsburgh, PA 15213 USA. EM luketichjd@upmc.edu FU National Cancer Institute, National Institutes of Health [CA23318, CA66636, CA21115, CA39229, CA32291, CA17145]; Department of Health and Human Services FX The authors have no relevant conflicts of interest related to this article. This study was coordinated by the Eastern Cooperative Oncology Group and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA39229, CA32291, CA17145 and from the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. NR 29 TC 19 Z9 25 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD APR PY 2015 VL 261 IS 4 BP 702 EP 707 DI 10.1097/SLA.0000000000000993 PG 6 WC Surgery SC Surgery GA CE2VV UT WOS:000351679500038 PM 25575253 ER PT J AU Yan, SC Tsurumi, A Que, YA Ryan, CM Bandyopadhaya, A Morgan, AA Flaherty, PJ Tompkins, RG Rahme, LG AF Yan, Shuangchun Tsurumi, Amy Que, Yok-Ai Ryan, Colleen M. Bandyopadhaya, Arunava Morgan, Alexander A. Flaherty, Patrick J. Tompkins, Ronald G. Rahme, Laurence G. TI Prediction of Multiple Infections After Severe Burn Trauma A Prospective Cohort Study SO ANNALS OF SURGERY LA English DT Article DE burn; genomics; infection; predictive models; prognosis; sepsis; trauma ID PSEUDOMONAS-AERUGINOSA; INJURED PATIENTS; SEPSIS TREATMENT; MORTALITY; SUSCEPTIBILITY; CARE; RISK; IMMUNOSUPPRESSION; COMPLICATIONS; PROBABILITY AB Objective: To develop predictive models for early triage of burn patients based on hypersusceptibility to repeated infections. Background: Infection remains a major cause of mortality and morbidity after severe trauma, demanding new strategies to combat infections. Models for infection prediction are lacking. Methods: Secondary analysis of 459 burn patients (>= 16 years old) with 20% or more total body surface area burns recruited from 6 US burn centers. We compared blood transcriptomes with a 180-hour cutoff on the injury-to-transcriptome interval of 47 patients (<= 1 infection episode) to those of 66 hypersusceptible patients [multiple (>= 2) infection episodes (MIE)]. We used LASSO regression to select biomarkers and multivariate logistic regression to built models, accuracy of which were assessed by area under receiver operating characteristic curve (AUROC) and cross-validation. Results: Three predictive models were developed using covariates of (1) clinical characteristics; (2) expression profiles of 14 genomic probes; (3) combining (1) and (2). The genomic and clinical models were highly predictive of MIE status [AUROC(Genomic) = 0.946 (95% CI: 0.906-0.986); AUROC(Clinical) = 0.864 (CI: 0.794-0.933); AUROC(Genomic)/AUROC(Clinical) P = 0.044]. Combined model has an increased AUROC(Combined) of 0.967 (CI: 0.940-0.993) compared with the individual models (AUROC(Combined)/AUROC(Clinical) P = 0.0069). Hypersusceptible patients show early alterations in immune-related signaling pathways, epigenetic modulation, and chromatin remodeling. Conclusions: Early triage of burn patients more susceptible to infections can be made using clinical characteristics and/or genomic signatures. Genomic signature suggests new insights into the pathophysiology of hypersuscepti-bility to infection may lead to novel potential therapeutic or prophylactic targets. C1 [Yan, Shuangchun; Tsurumi, Amy; Ryan, Colleen M.; Bandyopadhaya, Arunava; Tompkins, Ronald G.; Rahme, Laurence G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Yan, Shuangchun; Tsurumi, Amy; Bandyopadhaya, Arunava; Rahme, Laurence G.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02114 USA. [Yan, Shuangchun; Tsurumi, Amy; Ryan, Colleen M.; Bandyopadhaya, Arunava; Rahme, Laurence G.] Shriners Hosp Children Boston, Boston, MA USA. [Que, Yok-Ai] Univ Lausanne, Dept Fundamental Microbiol, Lausanne, Switzerland. [Morgan, Alexander A.] Stanford Univ, Sch Med, Dept Biochem, Palo Alto, CA 94304 USA. [Morgan, Alexander A.] Stanford Univ, Sch Med, Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA. [Flaherty, Patrick J.] Worcester Polytech Inst, Dept Biomed Engn, Worcester, MA USA. [Flaherty, Patrick J.] Worcester Polytech Inst, Program Bioinformat & Computat Biol, Worcester, MA USA. RP Rahme, LG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM rahme@molbio.mgh.harvard.edu OI Yan, Shuangchun/0000-0002-9924-283X FU US Army Medical Research Acquisition Act of US Department of Defense, Congressionally Directed Medical Research Programs (CDMRP), Defense Medical Research and Development Program (DMRDP) Basic Research Award [W81XWH-10-DMRDP-BRA]; National Institute of General Medical Sciences [5U54GM062119] FX This work was supported by the US Army Medical Research Acquisition Act of US Department of Defense, Congressionally Directed Medical Research Programs (CDMRP), Defense Medical Research and Development Program (DMRDP) Basic Research Award, W81XWH-10-DMRDP-BRA to LGR. The investigators acknowledge the contribution of the Inflammation and the Host Response to Injury Large-scale Collaborative Project Award 5U54GM062119 from the National Institute of General Medical Sciences. The authors thank W. Xu, W. Xiao, and A. A. Tzika for suggestions on the data analysis. NR 57 TC 5 Z9 5 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD APR PY 2015 VL 261 IS 4 BP 781 EP 792 DI 10.1097/SLA.0000000000000759 PG 12 WC Surgery SC Surgery GA CE2VV UT WOS:000351679500049 PM 24950278 ER PT J AU Tanabe, KK AF Tanabe, Kenneth K. TI Are We Thinking? A Commentary on "Is Partial-ALPPS Safer Than ALPPS? A Single-center Experience" SO ANNALS OF SURGERY LA English DT Editorial Material ID PORTAL-VEIN LIGATION; LIVER C1 [Tanabe, Kenneth K.] Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA. [Tanabe, Kenneth K.] Harvard Univ, Sch Med, Boston, MA USA. RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA. EM ktanabe@partners.org NR 10 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD APR PY 2015 VL 261 IS 4 BP E93 EP E93 DI 10.1097/SLA.0000000000001088 PG 1 WC Surgery SC Surgery GA CE2VV UT WOS:000351679500002 PM 25563881 ER PT J AU Singh, JA AF Singh, Jasvinder A. TI When gout goes to the heart: does gout equal a cardiovascular disease risk factor? SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Editorial Material ID EVIDENCE BASED RECOMMENDATIONS; PERIPHERAL ARTERIAL-DISEASE; ACUTE MYOCARDIAL-INFARCTION; URIC-ACID LEVEL; RHEUMATOID-ARTHRITIS; INDEPENDENT IMPACT; TASK-FORCE; MORTALITY; HYPERURICEMIA; METAANALYSIS C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Med, 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 NR 28 TC 4 Z9 4 U1 0 U2 0 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 APR PY 2015 VL 74 IS 4 BP 631 EP 634 DI 10.1136/annrheumdis-2014-206432 PG 4 WC Rheumatology SC Rheumatology GA CE2AV UT WOS:000351615700003 PM 25603830 ER PT J AU Cerdeira, AS Thadhani, R AF Cerdeira, Ana Sofia Thadhani, Ravi TI "Interfering" With Preeclampsia SO ARTHRITIS & RHEUMATOLOGY LA English DT Editorial Material ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; ENDOTHELIAL DYSFUNCTION; SOLUBLE ENDOGLIN; I INTERFERONS; ALPHA; PATHOGENESIS; INHIBITION; MECHANISMS; DISEASE; RISK C1 [Cerdeira, Ana Sofia] Univ Oxford, Oxford, England. [Thadhani, Ravi] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Thadhani, Ravi] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Thadhani, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol,Dept Med, 55 Fruit St,GRB 1008 G, Boston, MA 02114 USA. EM rthadhani@mgh.harvard.edu NR 22 TC 1 Z9 1 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD APR PY 2015 VL 67 IS 4 BP 862 EP 864 DI 10.1002/art.39028 PG 3 WC Rheumatology SC Rheumatology GA CE5AJ UT WOS:000351841800003 PM 25605672 ER PT J AU Holsen, LM Goldstein, JM AF Holsen, Laura M. Goldstein, Jill M. TI Valuation and Cognitive Circuitry in Anorexia Nervosa: Disentangling Appetite from the Effort to Obtain a Reward SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID STRESS; WOMEN C1 [Holsen, Laura M.; Goldstein, Jill M.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Holsen, Laura M.; Goldstein, Jill M.] Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Dept Med, Div Womens Hlth, Boston, MA 02120 USA. [Holsen, Laura M.; Goldstein, Jill M.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02120 USA. [Goldstein, Jill M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Charlestown, MA USA. [Goldstein, Jill M.] MIT, Charlestown, MA USA. RP Goldstein, JM (reprint author), Brigham & Womens Hosp, Div Womens Hlth, One Brigham Circle,1620 Tremont St, Boston, MA 02120 USA. EM jill_goldstein@hms.harvard.edu FU NIMH NIH HHS [K01 MH091222] NR 10 TC 0 Z9 0 U1 0 U2 5 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 APR 1 PY 2015 VL 77 IS 7 BP 604 EP 606 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CE8KX UT WOS:000352092300004 PM 25766686 ER PT J AU King, JA Geisler, D Ritschel, F Boehm, I Seidel, M Roschinski, B Soltwedel, L Zwipp, J Pfuhl, G Marxen, M Roessner, V Ehrlich, S AF King, Joseph A. Geisler, Daniel Ritschel, Franziska Boehm, Ilka Seidel, Maria Roschinski, Benjamin Soltwedel, Laura Zwipp, Johannes Pfuhl, Gerit Marxen, Michael Roessner, Veit Ehrlich, Stefan TI Global Cortical Thinning in Acute Anorexia Nervosa Normalizes Following Long-Term Weight Restoration SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Anorexia nervosa; Cerebral cortex; Cortical thickness; FreeSurfer; MRI; Subcortical structures ID HUMAN CEREBRAL-CORTEX; VOXEL-BASED MORPHOMETRY; WHITE-MATTER VOLUME; SURFACE-BASED ANALYSIS; BODY-MASS INDEX; BULIMIA-NERVOSA; GRAY-MATTER; EATING-DISORDERS; BRAIN STRUCTURE; COORDINATE SYSTEM AB BACKGROUND: Anorexia nervosa (AN) is a serious eating disorder characterized by self-starvation, extreme weight loss, and alterations in brain structure. Structural magnetic resonance imaging studies have documented brain volume reductions in acute AN, but it is unclear whether they are 1) regionally specific, or 2) reversible following weight restoration. Here, we measured cortical thickness (CT) for the first time in AN. METHODS: Structural magnetic resonance imaging data were acquired from adolescent and young adult female patients with acute AN (n = 40), recovered patients following long-term weight restoration (n = 34), and an equal number of age-matched healthy control subjects. Group differences in CT were tested with well-validated procedures implemented in FreeSurfer. The mediating role of clinical variables including body mass index and drive for thinness were explored. For completeness, we also used FreeSurfer's subcortical segmentation stream to test group differences in volumes of select gray matter regions of interest. RESULTS: Vertex-wise analyses revealed significant thinning of over 85% of the cortical surface in patients with acute AN and CT normalization in recovered patients following long-term weight restoration, although normal age-related trajectories were absent in the disorder. This pattern of results was largely mirrored in subcortical volumes. We also observed a strong negative correlation between CT and drive for thinness in extrastriate regions involved in body perception. CONCLUSIONS: Structural brain anomalies in AN as expressed in CT and subcortical volume are primarily the consequence of malnutrition and unlikely to reflect premorbid trait markers or permanent scars, but longitudinal data are needed. C1 [King, Joseph A.; Geisler, Daniel; Ritschel, Franziska; Boehm, Ilka; Seidel, Maria; Roschinski, Benjamin; Soltwedel, Laura; Pfuhl, Gerit; Roessner, Veit; Ehrlich, Stefan] Tech Univ Dresden, Univ Hosp CG Carus, Fac Med, Eating Disorder Serv & Res Ctr,Dept Child & Adole, D-01307 Dresden, Germany. [Pfuhl, Gerit] Univ Tromso, Dept Psychol, Tromso, Norway. [Marxen, Michael] Tech Univ Dresden, Univ Hosp CG Carus, Fac Med, Dept Psychiat, D-01307 Dresden, Germany. [Marxen, Michael] Tech Univ Dresden, Univ Hosp CG Carus, Fac Med, Neuroimaging Ctr, D-01307 Dresden, Germany. [Ehrlich, Stefan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging,MIT, Charlestown, MA USA. [Ehrlich, Stefan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA USA. RP Ehrlich, S (reprint author), Tech Univ Dresden, Univ Hosp CG Carus, Fac Med, Dept Psychiat, Fetscherstr 74,CNY Bldg 120,Suite 100, D-01307 Dresden, Germany. EM transden.lab@gmail.com OI Pfuhl, Gerit/0000-0002-3271-6447 FU Deutsche Forschungsgemeinschaft [EH 367/5-1, SFB 940]; Swiss Anorexia Nervosa Foundation; Eli Lilly; Janssen-Cilag; Medice; Novartis FX This work was supported by the Deutsche Forschungsgemeinschaft (EH 367/5-1 and SFB 940) and the Swiss Anorexia Nervosa Foundation.; In the last 2 years, Dr. Roessner has received lecture fees from Eli Lilly, Janssen-Cilag, Medice, and Novartis and was a member of advisory boards of Eli Lilly and Novartis. NR 91 TC 21 Z9 21 U1 2 U2 19 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 APR 1 PY 2015 VL 77 IS 7 BP 624 EP 632 DI 10.1016/j.biopsych.2014.09.005 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CE8KX UT WOS:000352092300007 PM 25433902 ER PT J AU Juster, RP Hatzenbuehler, ML Mendrek, A Pfaus, JG Smith, NG Johnson, PJ Lefebvre-Louis, JP Raymond, C Marin, MF Sindi, S Lupien, SJ Pruessner, JC AF Juster, Robert-Paul Hatzenbuehler, Mark L. Mendrek, Adrianna Pfaus, James G. Smith, Nathan Grant Johnson, Philip Jai Lefebvre-Louis, Jean-Philippe Raymond, Catherine Marin, Marie-France Sindi, Shireen Lupien, Sonia J. Pruessner, Jens C. TI Sexual Orientation Modulates Endocrine Stress Reactivity SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Cortisol; Gender diversity; Sex differences; Sexual orientation; Stress reactivity; Trier Social Stress Test ID SOCIAL-EVALUATIVE THREAT; PITUITARY-ADRENAL AXIS; SELF-ESTEEM; PSYCHOLOGICAL STRESS; PSYCHOSOCIAL STRESS; PERSONALITY-TRAITS; CORTISOL RESPONSES; EMOTION REGULATION; LIFE-SPAN; IMPACT AB BACKGROUND: Biological sex differences and sociocultural gender diversity influence endocrine stress reactivity. Although numerous studies have shown that men typically activate stronger stress responses than women when exposed to laboratory-based psychosocial stressors, it is unclear whether sexual orientation further modulates stress reactivity. Given that lesbian, gay, and bisexual (LGB) individuals frequently report heightened distress secondary to stigma-related stressors, we investigated whether cortisol stress reactivity differs between LGB individuals and heterosexual individuals in response to a well-validated psychosocial stressor. METHODS: The study population comprised 87 healthy adults (mean age, 25 years) who were grouped according to their biological sex and their gendered sexual orientation: lesbian/bisexual women (n = 20), heterosexual women (n = 21), gay/bisexual men (n = 26), and heterosexual men (n = 20). Investigators collected 10 salivary cortisol samples throughout a 2-hour afternoon visit involving exposure to the Trier Social Stress Test modified to maximize between-sex differences. RESULTS: Relative to heterosexual women, lesbian/bisexual women showed higher cortisol stress reactivity 40 min after exposure to the stressor. In contrast, gay/bisexual men displayed lower overall cortisol concentrations throughout testing compared with heterosexual men. Main findings were significant while adjusting for sex hormones (estradiol-to-progesterone ratio in women and testosterone in men), age, self-esteem, and disclosure status (whether LGB participants had completed their "coming out"). CONCLUSIONS: Our results provide novel evidence for gender-based modulation of cortisol stress reactivity based on sexual orientation that goes beyond well-established between-sex differences. This study raises several important avenues for future research related to the physiologic functioning of LGB populations and gender diversity more broadly. C1 [Juster, Robert-Paul; Raymond, Catherine; Marin, Marie-France; Sindi, Shireen; Lupien, Sonia J.] Fernand Seguin Res Ctr, Ctr Studies Human Stress, Montreal, PQ H1N 3M5, Canada. [Juster, Robert-Paul; Sindi, Shireen; Pruessner, Jens C.] McGill Univ, Integrated Program Neurosci, Montreal, PQ, Canada. [Pruessner, Jens C.] McGill Univ, Dept Psychiat, Douglas Inst, Montreal, PQ, Canada. [Hatzenbuehler, Mark L.] Columbia Univ, Mailman Sch Publ Hlth, Dept Sociomed Sci, New York, NY USA. [Mendrek, Adrianna; Lupien, Sonia J.] Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada. [Raymond, Catherine] Univ Montreal, Dept Neurosci, Montreal, PQ, Canada. [Mendrek, Adrianna] Bishops Univ, Dept Psychol, Sherbrooke, PQ, Canada. [Pfaus, James G.] Concordia Univ, Dept Psychol, Montreal, PQ H3G 1M8, Canada. [Smith, Nathan Grant] Univ Houston, Dept Educ Psychol, Houston, TX USA. [Johnson, Philip Jai] Univ Minnesota, Ctr Sexual Hlth, Dept Family Med & Community Hlth, Sch Med, Minneapolis, MN 55455 USA. [Lefebvre-Louis, Jean-Philippe] Univ Quebec, Dept Social Work, Montreal, PQ H3C 3P8, Canada. [Marin, Marie-France] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. RP Juster, RP (reprint author), Fernand Seguin Res Ctr, Ctr Studies Human Stress, 7401 Hochelaga,Pavil Louis Riel,Unit 226, Montreal, PQ H1N 3M5, Canada. EM robert.juster@mail.mcgill.ca OI Mendrek, Adrianna/0000-0001-8056-5228; Smith, Nathan/0000-0002-3142-686X; Sindi, Shireen/0000-0002-3786-0552 FU Canadian Institutes of Health Research Grant [222055]; Canadian Institute of Gender and Health [GSC 91039]; Institute of Aging of the Canadian Institutes of Health Research [SIA 95402]; National Institute on Drug Abuse [K01 DA032558] FX This work was supported by Canadian Institutes of Health Research Grant No. 222055 (SJL). SJL held a senior investigator chair on Gender and Mental Health from the Canadian Institute of Gender and Health (Grant No. GSC 91039). R-PJ held a doctoral scholarship from the Institute of Aging of the Canadian Institutes of Health Research (Grant No. SIA 95402). MLH holds a Mentored Research Scientist Development Award from the National Institute on Drug Abuse (Grant No. K01 DA032558). NR 54 TC 9 Z9 11 U1 2 U2 21 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 APR 1 PY 2015 VL 77 IS 7 BP 668 EP 676 DI 10.1016/j.biopsych.2014.08.013 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CE8KX UT WOS:000352092300012 PM 25444167 ER PT J AU Shulman, HM Cardona, DM Greenson, JK Hingorani, S Horn, T Huber, E Kreft, A Longerich, T Morton, T Myerson, D Prieto, VG Rosenberg, A Treister, N Washington, K Ziemer, M Pavletic, SZ Lee, SJ Flowers, MED Schultz, KR Jagasia, M Martin, PJ Vogelsang, GB Kleiner, DE AF Shulman, Howard M. Cardona, Diana M. Greenson, Joel K. Hingorani, Sangeeta Horn, Thomas Huber, Elisabeth Kreft, Andreas Longerich, Thomas Morton, Thomas Myerson, David Prieto, Victor G. Rosenberg, Avi Treister, Nathaniel Washington, Kay Ziemer, Mirjana Pavletic, Steven Z. Lee, Stephanie J. Flowers, Mary E. D. Schultz, Kirk R. Jagasia, Madan Martin, Paul J. Vogelsang, Georgia B. Kleiner, David E. TI NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: II. The 2014 Pathology Working Group Report SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Chronic graft-versus-host disease; Allogeneic hematopoietic cell transplantation; Consensus; Diagnosis; Pathology; Histology ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; DONOR LYMPHOCYTE INFUSION; BRONCHIOLITIS OBLITERANS SYNDROME; FIBROSING CHOLESTATIC HEPATITIS; MOFETIL-RELATED COLITIS; MINOR SALIVARY-GLANDS; MYCOPHENOLATE-MOFETIL; NEPHROTIC SYNDROME; HISTOLOGIC FEATURES AB The 2005 National Institute of Health (NIH) Consensus Conference outlined histopathological diagnostic criteria for the major organ systems affected by both acute and chronic graft-versus-host disease (GVHD). The 2014 Consensus Conference led to this updated document with new information from histopathological studies of GVHD in the gut, liver, skin, and oral mucosa and an expanded discussion of GVHD in the lungs and kidneys. The recommendations for final histological diagnostic categories have been simplified from 4 categories to 3: no GVHD, possible GVHD, and likely GVHD, based on better reproducibility achieved by combining the previous categories of "consistent with GVHD" and "definite GVHD" into the single category of "likely GVHD." Issues remain in the histopathological characterization of GVHD, particularly with respect to the threshold of histological changes required for diagnostic certainty. Guidance is provided for the incorporation of biopsy information into prospective clinical studies of GVHD, particularly with respect to biomarker validation. Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation. C1 [Shulman, Howard M.; Hingorani, Sangeeta; Myerson, David; Lee, Stephanie J.; Flowers, Mary E. D.; Martin, Paul J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Cardona, Diana M.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC USA. [Greenson, Joel K.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Hingorani, Sangeeta; Morton, Thomas] Univ Washington, Dept Pediat Gastroenterol & Pathol, Seattle, WA 98195 USA. [Hingorani, Sangeeta] Seattle Childrens Hosp, Seattle, WA USA. [Horn, Thomas] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Huber, Elisabeth] Univ Regensburg, Inst Pathol, D-93053 Regensburg, Germany. [Kreft, Andreas] Univ Med Ctr Mainz, Inst Pathol, Mainz, Germany. [Longerich, Thomas] Univ Hosp RWTH Aachen, Inst Pathol, Aachen, Germany. [Myerson, David] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Prieto, Victor G.; Kleiner, David E.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Rosenberg, Avi] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Treister, Nathaniel] Dana Farber Brigham & Womens Canc Ctr, Div Oral Med & Dent, Boston, MA USA. [Washington, Kay] Vanderbilt Univ, Dept Pathol Microbiol & Immunol, Nashville, TN 37235 USA. [Ziemer, Mirjana] Univ Hosp Leipzig, Dept Dermatol, Leipzig, Germany. [Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. [Schultz, Kirk R.] Univ British Columbia, BC Childrens Hosp, Dept Pediat, Vancouver, BC V5Z 1M9, Canada. [Jagasia, Madan] Vanderbilt Univ, Med Ctr, Div Hematol Oncol, Nashville, TN USA. [Vogelsang, Georgia B.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD USA. RP Kleiner, DE (reprint author), NCI, Lab Oratory Pathol, Bldg 10,Room 2B50,MSC 1500,10 Ctr Dr, Bethesda, MD 20892 USA. EM kleinerd@mail.nih.gov OI Rosenberg, Avi/0000-0003-2356-950X FU National Institutes of Health's National Cancer Institute; Center for Cancer Research; Intramural Research Program and Division of Cancer Treatment and Diagnosis; Cancer Therapy Evaluation Program; Office of Rare Disease Research, National Center for Advancing Translational Sciences; Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources; National Cancer Institute [CA18029, CA118953]; National Institutes of Health; American Society for Blood and Marrow Transplantation; Center for International Bone and Marrow Transplant Research; ORDR/NCATS; NCI; German-Austrian-Swiss chronic GVHD Consortium; National Marrow Donor Program; Health Resources and Services Administration; Division of Transplantation; US Department of Human Health and Services; Canadian Blood and Marrow Transplant Group; European Group for Blood and Marrow Transplantation; Pediatric Blood and Marrow Transplant Consortium; Brazilian Chronic GVHD consortium; Deutsche Jose Carreras Leukamie-Stiftung FX This project was supported by the National Institutes of Health's National Cancer Institute, Center for Cancer Research, Intramural Research Program and Division of Cancer Treatment and Diagnosis, Cancer Therapy Evaluation Program; Office of Rare Disease Research, National Center for Advancing Translational Sciences; Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources. This work was also supported in part by grants CA18029 and CA118953 from the National Cancer Institute and the National Institutes of Health. The authors want to acknowledge the following individuals and organizations that, by their participation, made this project possible: American Society for Blood and Marrow Transplantation, Center for International Bone and Marrow Transplant Research, US Chronic GVHD Consortium (supported by ORDR/NCATS and NCI), German-Austrian-Swiss chronic GVHD Consortium, National Marrow Donor Program, the Health Resources and Services Administration, Division of Transplantation, US Department of Human Health and Services, Canadian Blood and Marrow Transplant Group, European Group for Blood and Marrow Transplantation, Pediatric Blood and Marrow Transplant Consortium, and the representatives of the Brazilian Chronic GVHD consortium (Drs. Maria Claudia Moreira, Marcia de Matos Silva and Vaneuza Funke) and Deutsche Jose Carreras Leukamie-Stiftung. The organizers are indebted to patients and patient and research advocacy groups, who made this process much more meaningful by their engagement. Acknowledgement goes to the Meredith Cowden GVHD foundation for facilitating the initial planning meeting in Cleveland in November of 2013 in conjunction with the National GVHD Symposium. The project group also recognizes the contributions of numerous colleagues in the field of blood and marrow transplantation in the United States and internationally, medical specialists and consultants, the pharmaceutical industry, and the National Institutes of Health and US Food and Drug Administration professional staff for their intellectual input, dedication, and enthusiasm on the road to completion of these documents. The opinions expressed are those of the authors and do not represent the position of the National Cancer Institute, the National Heart, Lung and Blood Institute, the National Institute of Allergy and Infectious Diseases, the National Institutes of Health, the Food and Drug Administration, or the United States Government. NR 148 TC 19 Z9 20 U1 2 U2 6 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 APR PY 2015 VL 21 IS 4 BP 589 EP 603 DI 10.1016/j.bbmt.2014.12.031 PG 15 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CE4GY UT WOS:000351790300004 PM 25639770 ER PT J AU Arora, M Hemmer, MT Ahn, KW Klein, JP Cutler, CS Urbano-Ispizua, A Courie, DR Alousi, AM Gale, RP Inamoto, Y Weisdorf, DJ Li, P Antin, JH Bolwell, BJ Boyiadzis, M Cahn, JY Cairo, MS Isola, LM Jacobsohn, DA Jagasia, M Klumpp, TR Petersdorf, EW Santarone, S Schouten, HC Wingard, JR Spellman, SR Pavletic, SZ Lee, SJ Horowitz, MM Flowers, MED AF Arora, Mukta Hemmer, Michael T. Ahn, Kwang Woo Klein, John P. Cutler, Corey S. Urbano-Ispizua, Alvaro Courie, Daniel R. Alousi, Amin M. Gale, Robert Peter Inamoto, Yoshihiro Weisdorf, Daniel J. Li, Peigang Antin, Joseph H. Bolwell, Brian J. Boyiadzis, Michael Cahn, Jean-Yves Cairo, Mitchell S. Isola, Luis M. Jacobsohn, David A. Jagasia, Madan Klumpp, Thomas R. Petersdorf, Effie W. Santarone, Stella Schouten, Harry C. Wingard, John R. Spellman, Stephen R. Pavletic, Steven Z. Lee, Stephanie J. Horowitz, Mary M. Flowers, Mary E. D. TI Center for International Blood and Marrow Transplant Research Chronic Graft-versus-Host Disease Risk Score Predicts Mortality in an Independent Validation Cohort SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Chronic graft-versus-host disease (CGVHD); Risk score; Nonrelapse mortality ID CHRONIC GVHD; IMMUNOSUPPRESSIVE TREATMENT; CELL TRANSPLANTATION; CONSENSUS CRITERIA; SURVIVAL; OUTCOMES; CLASSIFICATION; PREDNISONE; CONSORTIUM; DURATION AB We previously reported a risk score that predicted mortality in patients with chronic graft-versus-host disease (CGVHD) after hematopoietic stem cell transplantation (HCT) between 1995 and 2004 and reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We sought to validate this risk score in an independent CIBMTR cohort of 1128 patients with CGVHD who underwent transplantation between 2005 and 2007 using the same inclusion criteria and risk score calculations. According to the sum of the overall risk score (range, 1 to 12), patients were assigned to 4 risk groups (RGs): RG1 (0 to 2), RG2 (3 to 6), RG3 (7 to 8), and RG4 (9 to 10). RG3 and RG4 were combined, as RG4 accounted for only 1% of the total cohort. Cumulative incidences of nonrelapse mortality (NRM) and probability of overall survival were significantly different between each RG (all P < .01). NRM and overall survival at 5 years after CGVHD for each RG were 17% and 72% in RG1, 26% and 53% in RG2, and 44% and 25% in RG3, respectively (all P < .01). Our study validates the prognostic value of the CIBMTR CGVHD RGs for overall survival and NRM in a contemporary transplantation population. The CIBMTR CGVHD RGs can be used to predict major outcomes, tailor treatment planning, and enroll patients in clinical trials. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Arora, Mukta; Weisdorf, Daniel J.] Univ Minnesota, Med Ctr, Div Hematol Oncol & Transplantat, Dept Med, Minneapolis, MN 55455 USA. [Hemmer, Michael T.; Ahn, Kwang Woo; Klein, John P.; Horowitz, Mary M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplantat Res, Dept Med, Milwaukee, WI 53226 USA. [Ahn, Kwang Woo; Klein, John P.] Med Coll Wisconsin, Div Biostat, Inst Hlth & Soc, Milwaukee, WI 53226 USA. [Cutler, Corey S.; Antin, Joseph H.] Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. [Urbano-Ispizua, Alvaro] Univ Barcelona, Dept Hematol, Hosp Clin, IDIBAPS, Barcelona, Spain. [Urbano-Ispizua, Alvaro] Inst Res Josep Carreras, Barcelona, Spain. [Courie, Daniel R.] Univ Michigan, Dept Internal Med, Blood & Marrow Transplant Program, Ann Arbor, MI 48109 USA. [Alousi, Amin M.] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplant & Cellular Therapy, Houston, TX 77030 USA. [Gale, Robert Peter] Univ London Imperial Coll Sci Technol & Med, Hematol Res Ctr, Div Expt Med, Dept Med, London, England. [Inamoto, Yoshihiro] Natl Canc Ctr, Div Hematopoiet Stem Cell Transplantat, Tokyo, Japan. [Bolwell, Brian J.] Cleveland Clin, Leukemia Program, Hematol Oncol & Blood Disorders, Taussig Canc Inst, Cleveland, OH 44106 USA. [Boyiadzis, Michael] Univ Pittsburgh, Dept Med, Ctr Canc, Med Ctr, Pittsburgh, PA USA. [Cahn, Jean-Yves] Univ Hosp, Dept Hematol, Grenoble, France. [Cairo, Mitchell S.] New York Med Coll, Dept Pediat Hematol Oncol, Valhalla, NY 10595 USA. [Isola, Luis M.] Mt Sinai Med Ctr, Div Blood & Marrow Transplantat, New York, NY 10029 USA. [Jacobsohn, David A.] Childrens Natl Med Ctr, Div Blood & Marrow Transplantat, Ctr Canc & Blood Disorders, Washington, DC 20010 USA. [Jagasia, Madan] Vanderbilt Univ, Div Hematol Oncol, Med Ctr, Nashville, TN 37235 USA. [Klumpp, Thomas R.] Temple Univ, Sch Med, Dept Med, Bone Marrow Transplant Program, Philadelphia, PA 19122 USA. [Petersdorf, Effie W.; Lee, Stephanie J.; Flowers, Mary E. D.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Santarone, Stella] Osped Civile, Dept Hematol, BMT Ctr, Pescara, Italy. [Schouten, Harry C.] Acad Ziekenhuis, Dept Hematol, Maastricht, Netherlands. [Wingard, John R.] Shands Canc Ctr, Div Hematol & Oncol, Dept Med, Gainesville, FL USA. [Wingard, John R.] Univ Florida, Gainesville, FL USA. [Spellman, Stephen R.] Ctr Int Blood & Marrow Transplantat Res, Natl Marrow Donor Program, Minneapolis, MN USA. [Pavletic, Steven Z.] NCI, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. RP Flowers, MED (reprint author), Fred Hutchinson Canc Res Ctr, D5-290,POB 19024, Seattle, WA 98109 USA. EM mflowers@fhcrc.org FU National Cancer Institute (NCI) [U24-CA076518]; National Heart, Lung, and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID); NHLBI [5U10HL069294]; NCI; Health Resources and Services Administration (HRSA/DHHS) [HHSH250201200016C]; Office of Naval Research [N00014-13-1-0039, N00014-14-1-0028]; Actinium Pharmaceuticals; Allos Therapeutics, Inc.; Amgen, Inc.; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; TerumoBCT; Teva Neuroscience, Inc.; THERAKOS, Inc.; University of Minnesota; University of Utah; Wellpoint, Inc. FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a grant/cooperative agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); 2 grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals; Allos Therapeutics, Inc.; *Amgen, Inc.; anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; *Blue Cross and Blue Shield Association; *Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; *Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; *Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; *Milliman USA, Inc.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; *Remedy Informatics; *Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; *Tarix Pharmaceuticals; *TerumoBCT; *Teva Neuroscience, Inc.; *THERAKOS, Inc.; University of Minnesota; University of Utah; and *Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration, or any other agency of the US Government. NR 30 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD APR PY 2015 VL 21 IS 4 BP 640 EP 645 DI 10.1016/j.bbmt.2014.10.022 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CE4GY UT WOS:000351790300010 PM 25528390 ER PT J AU Ballen, KK Logan, BR Laughlin, MJ He, WS Ambruso, DR Armitage, SE Beddard, RL Bhatla, D Hwang, WYK Kiss, JE Koegler, G Kurtzberg, J Nagler, A Oh, D Petz, LD Price, TH Quinones, RR Ratanatharathorn, V Rizzo, JD Sazama, K Scaradavou, A Schuster, MW Sender, LS Shpa, EJ Spellman, SR Sutton, M Weitekamp, LA Wingard, JR Eapen, M AF Ballen, Karen K. Logan, Brent R. Laughlin, Mary J. He, Wensheng Ambruso, Daniel R. Armitage, Susan E. Beddard, Rachel L. Bhatla, Deepika Hwang, William Y. K. Kiss, Joseph E. Koegler, Gesine Kurtzberg, Joanne Nagler, Arnon Oh, David Petz, Lawrence D. Price, Thomas H. Quinones, Ralph R. Ratanatharathorn, Voravit Rizzo, J. Douglas Sazama, Kathleen Scaradavou, Andromachi Schuster, Michael W. Sender, Leonard S. Shpa, Elizabeth J. Spellman, Stephen R. Sutton, Millicent Weitekamp, Lee Ann Wingard, John R. Eapen, Mary TI Effect of Cord Blood Processing on Transplantation Outcomes after Single Myeloablative Umbilical Cord Blood Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Cord blood bank; Processing methods; Survival ID STEM-CELL TRANSPLANTATION; UNRELATED DONOR; GRAFT SOURCE; ADULTS; RECONSTITUTION; SELECTION; LEUKEMIA; SYSTEM; IMPACT AB Variations in cord blood manufacturing and administration are common, and the optimal practice is not known. We compared processing and banking practices at 16 public cord blood banks (CBB) in the United States and assessed transplantation outcomes on 530 single umbilical cord blood (UCB) myeloablative transplantations for hematologic malignancies facilitated by these banks. UCB banking practices were separated into 3 mutually exclusive groups based on whether processing was automated or manual, units were plasma and red blood cell reduced, or buffy coat production method or plasma reduced. Compared with the automated processing system for units, the day 28 neutrophil recovery was significantly lower after transplantation of units that were manually processed and plasma reduced (red cell replete) (odds ratio, .19; P = .001) or plasma and red cell reduced (odds ratio, .54; P = .05). Day 100 survival did not differ by CBB. However, day 100 survival was better with units that were thawed with the dextran-albumin wash method compared with the "no wash" or "dilution only" techniques (odds ratio, 1.82; P = .04). In conclusion, CBB processing has no significant effect on early (day 100) survival despite differences in kinetics of neutrophil recovery. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Ballen, Karen K.] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. [Logan, Brent R.; He, Wensheng; Rizzo, J. Douglas; Eapen, Mary] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Dept Med, Milwaukee, WI 53226 USA. [Logan, Brent R.] Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA. [Laughlin, Mary J.] Cleveland Cord Blood Ctr, Cleveland, OH USA. [Ambruso, Daniel R.] Childrens Hosp Colorado, Ctr Canc & Blood Disorders, Aurora, CO USA. [Armitage, Susan E.; Shpa, Elizabeth J.] MD Anderson Cord Blood Bank, Houston, TX USA. [Beddard, Rachel L.] South Texas Blood & Tissue Ctr, San Antonio, TX USA. [Bhatla, Deepika] St Louis Cord Blood Bank, St Louis, MO USA. [Hwang, William Y. K.] Singapore Cord Blood Bank Ltd, Singapore, Singapore. [Kiss, Joseph E.] Inst Transfus Med, Pittsburgh, PA USA. [Koegler, Gesine] Dusseldorf Cord Blood Bank, Dusseldorf, Germany. [Kurtzberg, Joanne] Duke Univ, Dept Pediat, Med Ctr, Div Pediat Blood & Marrow Transplantat, Durham, NC 27706 USA. [Kurtzberg, Joanne] Carolinas Cord Blood Bank, Durham, NC USA. [Nagler, Arnon] Sheba Med Ctr, Bone Marrow Transplantat Dept, Div Internal Med, Tel Hashomer, Israel. [Nagler, Arnon] Sheba Cord Blood Bank, Ramat Gan, Israel. [Oh, David] San Diego Blood Bank, San Diego, CA USA. [Petz, Lawrence D.] StemCyte, Covina, CA USA. [Price, Thomas H.] Puget Sound Blood Ctr, Seattle, WA 98104 USA. [Quinones, Ralph R.] Univ Colorado Cord Blood Bank, Aurora, CO USA. [Ratanatharathorn, Voravit] Wayne State Univ, Karmanos Canc Inst, Dept Clin Arrangements, Detroit, MI USA. [Ratanatharathorn, Voravit] JP McCarthy Cord Stem Cell Bank, Detroit, MI USA. [Sazama, Kathleen; Wingard, John R.] LifeSouth Commun Blood Ctr, Gainesville, FL USA. [Scaradavou, Andromachi] New York Blood Ctr, Natl Cord Blood Program, Long Isl City, NY USA. [Schuster, Michael W.] SUNY Stony Brook, Med Ctr, Dept Med, Stony Brook, NY 11794 USA. [Schuster, Michael W.] Gift Life Bone Marrow Fdn, Boca Raton, FL USA. [Sender, Leonard S.] Childrens Hosp, Orange Cty Cord Blood Bank, Orange, CA USA. [Spellman, Stephen R.] Ctr Int Blood & Marrow Transplant Res, Natl Marrow Donor Program, Minneapolis, MN USA. [Sutton, Millicent] Commun Blood Serv, Camden, NJ USA. [Weitekamp, Lee Ann] Michigan Blood Cord Blood Bank, Grand Rapidt, Michoacan, Mexico. [Wingard, John R.] Shands HealthCare, Div Hematol & Oncol, Dept Med, Gainesville, FL USA. [Wingard, John R.] Univ Florida, Gainesville, FL USA. RP Eapen, M (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, 9200 West Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA. EM meapen@mcw.edu FU Public Health Service from the National Cancer Institute [U24-CA076518]; National Heart, Lung, and Blood Institute; National Institute of Allergy and Infectious Diseases; NHLBI [5U10HL069294]; I; Health Resources and Services Administration (HRSA/DHHS) [HHSH250201200016C]; Office of Naval Research [N00014-12-1-0142, N00014-13-1-0039]; Actinium Pharmaceuticals; Allos Therapeutics, Inc.; Amgen; Be The Match Foundation; Blue Cross and Blue Shield Association; Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc.; Roswell Park Cancer Institute; HistoGenetics; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; Medac GmbH; Medical College of Wisconsin; Merck Co., Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte; A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Terumo BCT; Teva Neuroscience, Inc.; Therakos; University of Minnesota; University of Utah FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute, the National Heart, Lung, and Blood Institute and the National Institute of Allergy and Infectious Diseases; a grant/cooperative agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); 2 grants N00014-12-1-0142 and N00014-13-1-0039 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals; Allos Therapeutics, Inc.; *Amgen; anonymous donation to the Medical College of Wisconsin; Ariad; Be The Match Foundation; *Blue Cross and Blue Shield Association; *Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; *Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; *Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc.; Roswell Park Cancer Institute; HistoGenetics; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; Medac GmbH; The Medical College of Wisconsin; Merck & Co., Inc.; Millennium: The Takeda Oncology Co.; *Milliman USA, Inc.; *Miltenyi Biotec; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; *Remedy Informatics; *Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; *Tarix Pharmaceuticals; *Terumo BCT; *Teva Neuroscience, Inc.; *Therakos; University of Minnesota; University of Utah; and *WellPoint The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration or any other agency of the US Government. NR 26 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 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD APR PY 2015 VL 21 IS 4 BP 688 EP 695 DI 10.1016/j.bbmt.2014.12.017 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CE4GY UT WOS:000351790300017 PM 25543094 ER PT J AU Mahindra, A Raval, G Mehta, P Brazauskas, R Zhang, MJ Zhong, XB Bird, JM Freytes, CO Hale, GA Herzig, R Holmberg, LA Kamble, RT Kumar, S Lazarus, HM Majhail, NS Marks, DI Moreb, JS Olsson, R Saber, W Savani, BN Schiller, GJ Tay, J Vogl, DT Waller, EK Wiernik, PH Wirk, B Lonial, S Krishnan, AY Dispenzieri, A Brandenburg, NA Gale, RP Hari, PN AF Mahindra, Anuj Raval, Girindra Mehta, Paulette Brazauskas, Ruta Zhang, Mei-Jie Zhong, Xiaobo Bird, Jennifer M. Freytes, Cesar O. Hale, Gregory A. Herzig, Roger Holmberg, Leona A. Kamble, Rammurti T. Kumar, Shaji Lazarus, Hillard M. Majhail, Navneet S. Marks, David I. Moreb, Jan S. Olsson, Richard Saber, Wael Savani, Bipin N. Schiller, Gary J. Tay, Jason Vogl, Dan T. Waller, Edmund K. Wiernik, Peter H. Wirk, Baldeep Lonial, Sagar Krishnan, Amrita Y. Dispenzieri, Angela Brandenburg, Nancy A. Gale, Robert Peter Hari, Parameswaran N. TI New Cancers after Autotransplantations for Multiple Myeloma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Myeloma; Second cancer; Transplantation ID STEM-CELL TRANSPLANTATION; 2ND PRIMARY MALIGNANCIES; MYELODYSPLASTIC SYNDROMES; ACUTE-LEUKEMIA; LENALIDOMIDE; THERAPY; NEOPLASMS; RISK; CHEMOTHERAPY; METAANALYSIS AB We describe baseline incidence and risk factors for new cancers in 4161 persons receiving autotransplants for multiple myeloma in the United States from 1990 to 2010. Observed incidence of invasive new cancers was compared with expected incidence relative to the US population. The cohort represented 13,387 person-years at-risk. In total, 163 new cancers were observed, for a crude incidence rate of 1.2 new cancers per 100 person-years and cumulative incidences of 2.6% (95% confidence interval [CI], 2.09 to 3.17), 4.2% (95% Cl, 3.49 to 5.00), and 6.1% (95% CI, 5.08 to 7.24) at 3, 5, and 7 years, respectively. The incidence of new cancers in the autotransplantation cohort was similar to age-, race-, and gender-adjusted comparison subjects with an observed/expected (O/E) ratio of 1.00 (99% CI, .81 to 1.22). However, acute myeloid leukemia and melanoma were observed at higher than expected rates with 0/E ratios of 5.19 (99% CI, 1.67 to 12.04; P = .0004), and 3.58 (99% CI, 1.82 to 6.29; P < .0001), respectively. Obesity, older age, and male gender were associated with increased risks of new cancers in multivariate analyses. This large data set provides a baseline for comparison and defines the histologic type specific risk for new cancers in patients with MM receiving post-autotransplantation therapies, such as maintenance. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Mahindra, Anuj] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Raval, Girindra] Jefferson Reg Med Ctr, Pine Bluff, AR USA. [Mehta, Paulette] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Mehta, Paulette] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. [Brazauskas, Ruta; Zhang, Mei-Jie; Zhong, Xiaobo; Saber, Wael] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Dept Med, Milwaukee, WI 53226 USA. [Brazauskas, Ruta; Zhang, Mei-Jie] Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA. [Bird, Jennifer M.; Marks, David I.] Univ Hosp Bristol NHS Trust, Bristol, Avon, England. [Freytes, Cesar O.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Freytes, Cesar O.] Univ Texas Hlth Sci, Ctr San Antonio, San Antonio, TX USA. [Hale, Gregory A.] All Childrens Hosp, St Petersburg, FL USA. [Herzig, Roger] Univ Louisville Hosp, James Brown Canc Ctr, Louisville, KY USA. [Holmberg, Leona A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Kamble, Rammurti T.] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Kumar, Shaji; Dispenzieri, Angela] Mayo Clin, Rochester, MN USA. [Lazarus, Hillard M.] Univ Hosp, Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA. [Majhail, Navneet S.] Cleveland Clin, Cleveland, OH 44106 USA. [Moreb, Jan S.] Shands HealthCare, Gainesville, FL USA. [Moreb, Jan S.] Univ Florida, Gainesville, FL USA. [Olsson, Richard] Karolinska Inst, Dept Lab Med, Div Therapeut Immunol, Stockholm, Sweden. [Olsson, Richard] Uppsala Univ, Ctr Clin Res Sormland, Uppsala, Sweden. [Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Nashville, TN 37235 USA. [Schiller, Gary J.] Univ Calif Los Angeles, Ctr Hlth Sci, Nashville, TN USA. [Tay, Jason] Univ Ottawa, Ottawa, ON, Canada. Univ Penn, Abramson Canc Ctr, Med Ctr, Philadelphia, PA 19104 USA. [Waller, Edmund K.; Lonial, Sagar] Emory Univ Hosp, Winship Canc Inst, Atlanta, GA 30322 USA. [Wiernik, Peter H.] Our Lady Mercy Med Ctr, Bronx, NY USA. [Wirk, Baldeep] SUNY Stony Brook, Med Ctr, Stony Brook, NY 11794 USA. [Krishnan, Amrita Y.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Brandenburg, Nancy A.] Celgene Corp, Summit, NJ USA. [Gale, Robert Peter] Univ London Imperial Coll Sci Technol & Med, London, England. RP Hari, PN (reprint author), Ctr Int Blood & Marrow Transplant Res, Med colIege Wisconsin, Div Hematol & Oncol, 9200W Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA. EM phari@mcw.edu OI Olsson, Richard/0000-0001-5970-2128; Hari, Parameswaran/0000-0002-8800-297X; Dispenzieri, Angela/0000-0001-8780-9512 FU Public Health Service Grant from the National Cancer Institute [U24-CA076518]; National Heart, Lung, and Blood Institute; National Institute of Allergy and Infectious Diseases; NHLBI [5U10HL069294]; NCI; Health Resources and Services Administration [HHSH250201200016C]; Office of Naval Research [N00014-12-1-0142, N00014-13-1-0039]; Actinium Pharmaceuticals; Allos Therapeutics, Inc.; Amgen; Be The Match Foundation; Blue Cross and Blue Shield Association; Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc.; Roswell Park Cancer Institute; HistoGenetics; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; Leukemia & Lymphoma Society; Medac GmbH; Medical College of Wisconsin; Merck Co., Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte; Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Terumo BCT; Teva Neuroscience, Inc.; Therakos; University of Minnesota; University of Utah; WellPoint FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute, the National Heart, Lung, and Blood Institute and the National Institute of Allergy and Infectious Diseases; a grant/cooperative agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration; 2 grants N00014-12-1-0142 and N00014-13-1-0039 from the Office of Naval Research; and grants from Actinium Pharmaceuticals; Allos Therapeutics, Inc.; Amgen; anonymous donation to the Medical College of Wisconsin; Ariad; Be The Match Foundation; Blue Cross and Blue Shield Association; Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc.; Roswell Park Cancer Institute; HistoGenetics; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co., Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Terumo BCT; Teva Neuroscience, Inc.; Therakos; University of Minnesota; University of Utah; and WellPoint The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration or any other agency of the US Government. Additional support for this study was provided by Celgene Corporation. NR 28 TC 4 Z9 4 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD APR PY 2015 VL 21 IS 4 BP 738 EP 745 DI 10.1016/j.bbmt.2014.12.028 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CE4GY UT WOS:000351790300024 PM 25555448 ER PT J AU MacMillan, ML Robin, M Harris, AC DeFor, TE Martin, PJ Alousi, A Ho, VT Bolanos-Meade, J Ferrara, JLM Jones, R Arora, M Blazar, BR Holtan, SG Jacobsohn, D Pasquini, M Socie, G Antin, JH Levine, JE Weisdorf, DJ AF MacMillan, Margaret L. Robin, Marie Harris, Andrew C. DeFor, Todd E. Martin, Paul J. Alousi, Amin Ho, Vincent T. Bolanos-Meade, Javier Ferrara, James L. M. Jones, Richard Arora, Mukta Blazar, Bruce R. Holtan, Shernan G. Jacobsohn, David Pasquini, Marcelo Socie, Gerard Antin, Joseph H. Levine, John E. Weisdorf, Daniel J. TI A Refined Risk Score for Acute Graft-versus-Host Disease that Predicts Response to Initial Therapy, Survival, and Transplant-Related Mortality SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Graft-versus-host disease; Grading systems; Risk score; Transplant-related mortality; Survival; Allogeneic hematopoietic cell transplantation ID CLINICAL-TRIALS NETWORK; IBMTR SEVERITY INDEX; MARROW-TRANSPLANTATION; GRADING SYSTEMS; GVHD; RECLASSIFICATION; BIOMARKERS; MARKER; BLOOD AB To develop a novel acute graft-versus-host disease (GVHD) risk score, we examined the GVHD clinical stage and grade of 1723 patients at the onset of treatment with systemic steroids. Using clinical grouping, descriptive statistics and recursive partitioning, we identified poorly responsive, high-risk (HR) acute GVHD by the number of involved organs and severity of GVHD at onset. The overall response (complete response/ partial response) rate 28 days after initiation of steroid therapy for acute GVHD was lower in the 269 patients with HR-GVHD than in the 1454 patients with standard risk (SR)-GVHD (44% [95% confidence interval (CI) 38% to 50%] versus 68% [95% Cl, 66% to 70%], P <.001). Patients with HR-GVHD were less likely to respond at day 28 (odds ratio [OR], 3; 95% CI,.2 to.4; P <.001) and had higher risks of mortality (relative risk, 2.1; 95% Cl, 1.7 to 2.6; P <.001) and transplant-related mortality (relative risk, 2.5; 95% Cl, 2.0% to 3.2%, P <.001) than patients with SR-GVHD. This refined definition of acute GVHD risk is a better predictor of response, survival, and transplant-related mortality than other published acute GVHD risk scores. Patients with HR-GVHD are candidates for studies investigating new treatment approaches. Likewise, patients with SR-GVHD are candidates for studies investigating less toxic therapy. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [MacMillan, Margaret L.; DeFor, Todd E.; Arora, Mukta; Blazar, Bruce R.; Holtan, Shernan G.; Weisdorf, Daniel J.] Univ Minnesota, Blood & Marrow Transplant Program, Minneapolis, MN 55455 USA. [MacMillan, Margaret L.; Blazar, Bruce R.] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. [Robin, Marie; Socie, Gerard] Hop St Louis, Paris, France. [Harris, Andrew C.; Ferrara, James L. M.; Levine, John E.] Univ Michigan, Blood & Marrow Transplant Program, Ann Arbor, MI 48109 USA. [DeFor, Todd E.] Univ Minnesota, Mason Canc Ctr, Dept Biostat & Informat Core, Minneapolis, MN 55455 USA. [Martin, Paul J.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Alousi, Amin] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Alousi, Amin; Ho, Vincent T.; Bolanos-Meade, Javier; Ferrara, James L. M.; Jones, Richard; Jacobsohn, David; Pasquini, Marcelo; Antin, Joseph H.; Levine, John E.; Weisdorf, Daniel J.] Blood & Marrow Transplant Clin Trials Network GVH, Milwaukee, WI USA. [Ho, Vincent T.; Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bolanos-Meade, Javier] Johns Hopkins Univ, Baltimore, MD USA. [Arora, Mukta; Holtan, Shernan G.; Weisdorf, Daniel J.] Univ Minnesota, Dept Med, Minneapolis, MN USA. [Jacobsohn, David] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Pasquini, Marcelo] Med Coll Wisconsin, Milwaukee, WI 53226 USA. RP MacMillan, ML (reprint author), Univ Minnesota, Dept Pediat, MMC 484,420 Delaware St SE, Minneapolis, MN 55455 USA. EM macmi002@umn.edu OI Harris, Andrew/0000-0002-4538-8817 FU National Institutes of Health, National Cancer Institute [2P01CA065493]; National Institutes of Health, Blood and Marrow Transplant Clinical Trials Network [U10HL069290] FX Financial disclosure: This study was supported in part by the National Institutes of Health, National Cancer Institute grant 2P01CA065493 and the National Institutes of Health, Blood and Marrow Transplant Clinical Trials Network grant U10HL069290. NR 21 TC 24 Z9 24 U1 2 U2 5 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 APR PY 2015 VL 21 IS 4 BP 761 EP 767 DI 10.1016/j.bbmt.2015.01.001 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CE4GY UT WOS:000351790300027 PM 25585275 ER PT J AU Jana, P Maiti, S Kahn, NN Sinha, AK AF Jana, Pradipta Maiti, Smarajit Kahn, Nighat N. Sinha, Asru K. TI Estriol-induced fibrinolysis due to the activation of plasminogen to plasmin by nitric oxide synthesis in platelets SO BLOOD COAGULATION & FIBRINOLYSIS LA English DT Article DE human serum albumin precursor; nongenomic expression of the estriol effect; plasmin; plasminogen activation ID HUMAN-BLOOD-PLATELETS; THROMBOLYSIS; PURIFICATION; STIMULATION; ENDOTHELIUM; THROMBOSIS; SYNTHASE; ESTROGEN; RECEPTOR; KINETICS AB Estriol, an oestrogen, at 0.6 nmol/l was reported to inhibit ADP-induced platelet aggregation through nitric oxide synthesis. As nitric oxide has been reported to cause fibrinolysis due to the activation of plasminogen to plasmin, the role of estriol as a fibrinolytic agent was investigated. Also, the mechanism of estriol-induced nitric oxide synthesis in anucleated platelets was investigated. The estriol-induced lysis of platelet-rich plasma (PRP) clot was determined by photography of the clot lysis and by the assay of fibrin degradation products in the lysate and was obtained by SDS-PAGE. Nitric oxide was determined by methemoglobin method. The platelet membrane protein was isolated from the platelets by using Triton X-100 (0.05% v/v). The binding of estriol to the protein was determined by Scatchard plot by using an ELISA for estriol. Estriol at 0.6 nmol/l was found to lyse the clotted PRP due to fibrinolysis that produced fibrin degradation products in the lysate. The amino acid analysis of the platelet membrane protein, which resembles with nitric oxide synthase (NOS) activity, was activated nearly 10-fold over the control in the presence of estriol and was identified to be a human serum albumin precursor (Mr. 69 kDa) that binds to estriol with Kd(1) of 6.0x10(-9) mol/l and 39 +/- 2 molecules of estriol bound the NOS molecule. The estriol-induced nitric oxide is capable of inducing fibrinolysis of the clotted PRP. The binding of estriol to platelet membrane NOS activated the enzyme in the absence of DNA in the platelet. Blood Coagul Fibrinolysis 26: 316-323 Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. C1 [Jana, Pradipta; Sinha, Asru K.] Sinha Inst Med Sci & Technol, Kolkata, India. [Jana, Pradipta; Maiti, Smarajit] Vidyasagar Univ, Oriental Inst Sci & Technol, Cell & Mol Therapeut Lab, Post Grad Dept Biochem & Biotechnol, Medinipur, W Bengal, India. [Kahn, Nighat N.] James J Peters VA Med Ctr, Bronx, NY USA. RP Sinha, AK (reprint author), Sinha Inst Med Sci & Technol, 288 Kendua Main Rd, Kolkata 700084, W Bengal, India. EM asruksinha@yahoo.com NR 32 TC 1 Z9 1 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0957-5235 EI 1473-5733 J9 BLOOD COAGUL FIBRIN JI Blood Coagul. Fibrinolysis PD APR PY 2015 VL 26 IS 3 BP 316 EP 323 DI 10.1097/MBC.0000000000000085 PG 8 WC Hematology SC Hematology GA CE5PQ UT WOS:000351888000015 PM 24695088 ER PT J AU Azimi, E Lerner, EA Elmariah, SB AF Azimi, E. Lerner, E. A. Elmariah, S. B. TI Altered manifestations of skin disease at sites affected by neurological deficit SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID ATOPIC-DERMATITIS; NEUROGENIC INFLAMMATION; IMMUNE FUNCTION; SENSORY NERVES; PSORIASIS; PATIENT; REMISSION; PEPTIDE; NEUROPEPTIDES; HEMIPARESIS AB Background The contribution of the nervous system to inflammation in general and inflammatory skin disease in particular has been underappreciated. It is now apparent that an intact neural component is required for the conventional clinical manifestations of many inflammatory skin diseases. Objectives To investigate the relationship between nerve damage and skin disease. Methods Previous individual reports since 1966 were collected systematically and the clinical observations described therein were placed within current concepts of neurogenic inflammation. Results We reviewed the literature and identified 23 cases of alterations in the appearance or distribution of skin disorders in patients with acquired central or peripheral neural damage or dysfunction. In 19 cases, near or complete resolution of pre-existing skin lesions occurred in areas directly or indirectly supplied by a subsequently injured nervous system. Exacerbation or new onset of skin lesions occurred in only four cases. The neural deficits described included damage within the peripheral or central nervous system resulting in pure sensory, pure motor or combined sensory and motor deficits. Conclusions These cases highlight the importance of neural innervation and neurogenic inflammation in the development of inflammatory skin disease and prompt further examination of the use of neural blockade as an adjunctive therapy in the treatment of inflammatory dermatoses. C1 [Elmariah, S. B.] Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Elmariah, SB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. EM sbelmariah@mgh.harvard.edu FU Dermatology Foundation; LEO Pharma; NIH [1R01AR057744] FX This work was supported by a career development award to S.B.E. from the Dermatology Foundation and an unrestricted research grant from LEO Pharma and NIH grant 1R01AR057744 to E.A.L. NR 44 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD APR PY 2015 VL 172 IS 4 BP 988 EP 993 DI 10.1111/bjd.13352 PG 6 WC Dermatology SC Dermatology GA CE6MV UT WOS:000351952100058 PM 25132518 ER PT J AU Purschke, M Asrani, FA Sabir, SA Farinelli, WA Anderson, RR AF Purschke, M. Asrani, F. A. Sabir, S. A. Farinelli, W. A. Anderson, R. R. TI Novel methods for generating fractional epidermal micrografts SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID KOEBNER PHENOMENON; IN-VITRO; VITILIGO; MELANOCYTES; LEUKODERMA; LESIONS AB Background Epidermal suction blister grafts are an effective treatment for chronic wounds or vitiligo, but this treatment is time consuming and limited to small areas. Objectives To compare two novel strategies to create fractional epidermal grafts. Methods Epidermal blisters were raised from fresh human skin ex vivo at 38-40 degrees C, with suction of 380-510 mmHg. In Strategy 1, a 1-cm blister was micromeshed into approximately 500 pieces, transferred to elastic adhesive dressing, then pneumatically expanded to approximately nine times the original blister area. In Strategy 2, a 25-cm(2) array of 100 small blisters was raised, simultaneously harvested and captured directly onto an adhesive dressing. Measurements were taken for the pneumatic expansion limit, the release of microblisters upon hydration of the dressing adhesive, light microscopy, epidermal cell viability and positive L-3,4 dihydroxyphenylalanine melanocyte presence in blisters. Results Both strategies yielded viable fractional epidermal microblister arrays, carried on a dressing for transfer to graft recipient sites. The microblisters were gradually released upon hydration of the dressing adhesive. Strategy 2 has major advantages as only small blisters are made at the donor site, skilful dissection and physical expansion are not required and the strategy can be scaled to create large-area grafts. Conclusions Strategy 2 is the more practical method for fractional epidermal micrografting to treat larger lesions with less donor-site trauma and has recently been commercialized. C1 [Purschke, M.; Asrani, F. A.; Farinelli, W. A.; Anderson, R. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02139 USA. [Sabir, S. A.] Massachusetts Gen Hosp, CIMIT, Boston, MA 02114 USA. RP Purschke, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02139 USA. EM mpurschke@mgh.harvard.edu FU Department of Defense [FA9550-11-1-0331] FX This work was partially supported by a Department of Defense grant 'Research to Develop and Apply Biophotonics to Military Medicine Needs' (Grant number: FA9550-11-1-0331) and by a departmental sundry fund. NR 23 TC 4 Z9 4 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD APR PY 2015 VL 172 IS 4 BP 1021 EP 1028 DI 10.1111/bjd.13468 PG 8 WC Dermatology SC Dermatology GA CE6MV UT WOS:000351952100063 PM 25307844 ER PT J AU Field, KM Jordan, JT Wen, PY Rosenthal, MA Reardon, DA AF Field, Kathryn M. Jordan, Justin T. Wen, Patrick Y. Rosenthal, Mark A. Reardon, David A. TI Bevacizumab and Glioblastoma: Scientific Review, Newly Reported Updates, and Ongoing Controversies SO CANCER LA English DT Review DE glioblastoma; bevacizumab; angiogenesis; vascular endothelial growth factor; malignant glioma ID ENDOTHELIAL GROWTH-FACTOR; HIGH-GRADE GLIOMAS; PHASE-II TRIAL; RECURRENT MALIGNANT GLIOMA; PROGRESSION-FREE SURVIVAL; NEWLY-DIAGNOSED GLIOBLASTOMA; RESPONSE ASSESSMENT CRITERIA; SINGLE-AGENT BEVACIZUMAB; PRIMARY BRAIN-TUMORS; ANTI-VEGF ANTIBODY AB Anti-angiogenic therapy for glioblastoma has been in the spotlight for several years, as researchers and clinicians strive to find agents with meaningful efficacy against glioblastoma. Bevacizumab in particular, in the second half of the last decade, became the most significant breakthrough in anti-glioblastoma therapy since temozolomide. Optimism for bevacizumab has been somewhat challenged given recent clinical trials that have raised questions regarding its clinical effectiveness, the optimal timing of its use and the validity of endpoints, among other issues. In addition, uncertainty has recently arisen regarding the effects of bevacizumab on quality of life and neurocognitive function, two key clinical endpoints of unquestionable significance among glioblastoma patients. In this review, we highlight these controversies and other recent work related to bevacizumab for glioblastoma. Cancer 2015;121:997-1007. (c) 2014 American Cancer Society. Bevacizumab provides benefit for patients with recurrent glioblastoma. The results of recent trials have indicated that its role among newly diagnosed patients remains unclear. C1 [Field, Kathryn M.; Rosenthal, Mark A.] Royal Melbourne Hosp, Dept Med Oncol, Melbourne, Vic, Australia. [Jordan, Justin T.; Wen, Patrick Y.; Reardon, David A.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RP Field, KM (reprint author), Royal Melbourne Hosp, Dept Med Oncol, Grattan St, Parkville, Vic 3050, Australia. EM Kathryn.Field@mh.org.au FU Roche; Merck Sharp and Dohme; Genentech; Genentech/Roche; EMD Serono; Merck/Schering; Novartis; Amgen FX Dr. Field received conference travel grants from Roche and Merck Sharp and Dohme and has received Speaker's honoraria from Roche and acted as Principal Investigator of a clinical trial funded by Roche (Roche was not a sponsor of the trial) for work performed outside of the current study. Dr. Wen received research support from Genentech for work performed as part of the current study and is a member of the Roche Advisory Board. Dr. Rosenthal has received honoraria from Roche as a member of the Roche Advisory Board. Dr. Reardon is a member of the Roche Advisory Board and has received personal fees from Genentech/Roche, EMD Serono, Merck/Schering, Novartis, and Amgen for work performed outside of the current study. NR 88 TC 17 Z9 17 U1 0 U2 15 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 APR 1 PY 2015 VL 121 IS 7 BP 997 EP 1007 DI 10.1002/cncr.28935 PG 11 WC Oncology SC Oncology GA CE2AW UT WOS:000351615800007 PM 25263092 ER PT J AU Dabaja, BS Vanderplas, AM Crosby-Thompson, AL Abel, GA Czuczman, MS Friedberg, JW Gordon, LI Kaminski, M Niland, J Millenson, M Nademanee, AP Zelenetz, A LaCasce, AS Rodriguez, MA AF Dabaja, Bouthaina S. Vanderplas, Ann M. Crosby-Thompson, Allison L. Abel, Gregory A. Czuczman, Myron S. Friedberg, Jonathan W. Gordon, Leo I. Kaminski, Mark Niland, Joyce Millenson, Michael Nademanee, Auayporn P. Zelenetz, Andrew LaCasce, Ann S. Rodriguez, Maria Alma TI Radiation for Diffuse Large B-Cell Lymphoma in the Rituximab Era: Analysis of the National Comprehensive Cancer Network Lymphoma Outcomes Project SO CANCER LA English DT Article DE consolidation; early stage; radiation; rituximab; cyclophosphamide; doxorubicin; vincristine; and prednisone (R-CHOP) ID LOCALIZED AGGRESSIVE LYMPHOMA; CHEMOTHERAPY PLUS RITUXIMAB; NON-HODGKINS-LYMPHOMA; ELDERLY-PATIENTS; FDG-PET; RADIOTHERAPY; CHOP; CLASSIFICATION; SURVIVAL; DISEASE AB BACKGROUNDThe role of consolidation radiotherapy was examined for patients with diffuse large B-cell lymphoma who were treated at institutions of the National Comprehensive Cancer Network during the rituximab era. METHODSFailure-free survival (FFS) and overall survival (OS) were analyzed in terms of patient and treatment characteristics. Potential associations were investigated with univariate and multivariate survival analysis and matched pair analysis. RESULTSThere were 841 patients, and most (710 or 84%) received 6 to 8 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP); 293 (35%) received consolidation radiation therapy (RT). Failure occurred for 181 patients: 126 patients (70%) who did not receive RT and 55 patients (30%) who did. At 5 years, both OS and FFS rates were better for patients who had received RT versus those who did not (OS, 91% vs 83% [P=.01]; FFS, 83% vs 76% [P=.05]). A matched pair analysis (217 pairs matched by age, stage, International Prognostic Index [IPI] score, B symptoms, disease bulk, and response to chemotherapy) showed that the receipt of RT improved OS (hazard ratio [HR], 0.53 [P=.07]) and FFS (HR, 0.77 [P=.34]) for patients with stage III/IV disease, but too few events took place among those with stage I/II disease for meaningful comparisons (HR for OS, 0.94 [P=.89]; HR for FFS, 1.81 [P=.15]). A multivariate analysis suggested that the IPI score and the response to chemotherapy had the greatest influence on outcomes. CONCLUSIONSThere was a trend of higher OS and FFS rates for patients who had received consolidation RT after R-CHOP (especially for patients with stage III/IV disease), but the difference did not reach statistical significance. Cancer 2014. (c) 2014 American Cancer Society. Cancer 2015;121:1032-1039. (c) 2014 American Cancer Society. The potential impact of consolidation on the overall survival and failure-free survival of patients with diffuse large B-cell lymphoma has been evaluated. Patients who receive consolidation radiation therapy are associated with a nonsignificant trend of higher overall survival and failure-free survival rates after adjustments for confounding factors. C1 [Dabaja, Bouthaina S.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Vanderplas, Ann M.; Niland, Joyce] City Hope Natl Med Ctr, Dept Biostat, Duarte, CA 91010 USA. [Crosby-Thompson, Allison L.; Abel, Gregory A.; LaCasce, Ann S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Czuczman, Myron S.] Roswell Pk Canc Inst, Dept Med Oncol & Immunol, Buffalo, NY 14263 USA. [Friedberg, Jonathan W.] Univ Rochester, Dept Hematol Oncol, James P Wilmot Canc Ctr, Rochester, NY USA. [Gordon, Leo I.] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Kaminski, Mark] Univ Michigan, Ctr Canc, Ann Arbor, MI 48109 USA. [Millenson, Michael] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Nademanee, Auayporn P.] City Hope Natl Med Ctr, Dept Hematol & Hematopoiet Cell Transplantat, Duarte, CA 91010 USA. [Zelenetz, Andrew] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Rodriguez, Maria Alma] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX 77030 USA. RP Dabaja, BS (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, 1515 Holcombe Blvd,Unit 97, Houston, TX 77030 USA. EM bdabaja@mdanderson.org FU Cancer Center Support (Core) Grant [CA016672] FX This study was supported in part by a Cancer Center Support (Core) Grant (CA016672) to the University of Texas MD Anderson Cancer Center. NR 22 TC 12 Z9 13 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD APR 1 PY 2015 VL 121 IS 7 BP 1032 EP 1039 DI 10.1002/cncr.29113 PG 8 WC Oncology SC Oncology GA CE2AW UT WOS:000351615800011 PM 25492236 ER PT J AU Hobbs, GS Landrum, MB Arora, NK Ganz, PA van Ryn, M Weeks, JC Mack, JW Keating, NL AF Hobbs, Gabriela S. Landrum, Mary Beth Arora, Neeraj K. Ganz, Patricia A. van Ryn, Michelle Weeks, Jane C. Mack, Jennifer W. Keating, Nancy L. TI The Role of Families in Decisions Regarding Cancer Treatments SO CANCER LA English DT Article DE cohort study; colorectal neoplasms; lung neoplasms; decision-making; shared; professional-family relations ID CARE OUTCOMES RESEARCH; BREAST-CANCER; SOCIAL SUPPORT; OF-LIFE; QUALITY; PATIENT; PARTICIPATION; COMMUNICATION; COMPANIONS; CAREGIVERS AB BACKGROUNDShared decision-making is an important component of patient-centered care and is associated with improved outcomes. To the authors' knowledge, little is known concerning the extent and predictors of the involvement of a patient's family in decisions regarding cancer treatments. METHODSThe Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium is a large, multiregional, prospective cohort study of the cancer care and outcomes of patients with lung and colorectal cancer. Participants reported the roles of their families in decision-making regarding treatment. Multinomial logistic regression was used to assess patient factors associated with family roles in decisions. RESULTSAmong 5284 patients, 80 (1.5%) reported family-controlled decisions, with the highest adjusted rates (12.8%) noted among non-English-speaking Asians. Among the 5204 remaining patients, 49.4% reported equally sharing decisions with family, 22.1% reported some family input, and 28.5% reported little family input. In adjusted analyses, patients who were married, female, older, and insured more often reported equally shared decisions with family (all P <.001). Adjusted family involvement varied by race/ethnicity and language, with Chinese-speaking Asian (59.8%) and Spanish-speaking Hispanic (54.8%) patients equally sharing decisions with family more often than white individuals (47.6%). Veterans Affairs patients were least likely to report sharing decisions with family, even after adjustment for marital status and social support (P <.001). CONCLUSIONSThe majority of patients with newly diagnosed lung or colorectal cancer involve family members in treatment decisions. Non-English-speaking Asians and Hispanics rely significantly on family. Further studies are needed to determine the impact of family involvement in treatment decisions on outcomes; until then, physicians should consider eliciting patients' preferences for family involvement. Cancer 2015;121:1079-1087. (c) 2015 American Cancer Society. In this large study of patients with newly diagnosed lung or colorectal cancer, the majority of patients reported involving family members in treatment decisions. Non-English-speaking Asian and Hispanic patients were particularly likely to rely on family for decision-making. C1 [Hobbs, Gabriela S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med Oncol, Boston, MA USA. [Landrum, Mary Beth; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Arora, Neeraj K.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90024 USA. [Ganz, Patricia A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA. [van Ryn, Michelle] Mayo Clin, Hlth Serv Res, Rochester, MN USA. [Weeks, Jane C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Populat Sci,Dept Med Oncol, Boston, MA 02115 USA. [Mack, Jennifer W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, 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 OI Hobbs, Gabriela/0000-0002-0199-9333 FU National Cancer Institute (NCI) [U01CA093344]; NCI [U01CA093332]; Harvard Medical School/Northern California Cancer Center [U01CA093324]; RAND/University of California at Los Angeles [U01CA093348]; University of Alabama at Birmingham [U01CA093329]; University of Iowa [U01 CA093339]; University of North Carolina [U01CA093326]; Department of Veterans Affairs [CRS02-164] FX This work of the Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium was supported by grants from the National Cancer Institute (NCI) to the Statistical Coordinating Center (U01CA093344) and the NCI-supported Primary Data Collection and Research Centers (Dana-Farber Cancer Institute/Cancer Research Network [U01CA093332], Harvard Medical School/Northern California Cancer Center [U01CA093324], RAND/University of California at Los Angeles [U01CA093348], University of Alabama at Birmingham [U01CA093329], University of Iowa [U01 CA093339], and University of North Carolina [U01CA093326]) and by a Department of Veterans Affairs grant to the Durham VA Medical Center (CRS02-164). NR 33 TC 11 Z9 11 U1 3 U2 16 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 APR 1 PY 2015 VL 121 IS 7 BP 1079 EP 1087 DI 10.1002/cncr.29064 PG 9 WC Oncology SC Oncology GA CE2AW UT WOS:000351615800017 PM 25708952 ER PT J AU Zhang, XH Wu, K Giovannucci, EL Ma, J Colditz, GA Fuchs, CS Willett, WC Stampfer, MJ Nimptsch, K Ogino, S Wei, EK AF Zhang, Xuehong Wu, Kana Giovannucci, Edward L. Ma, Jing Colditz, Graham A. Fuchs, Charles S. Willett, Walter C. Stampfer, Meir J. Nimptsch, Katharina Ogino, Shuji Wei, Esther K. TI Early Life Body Fatness and Risk of Colorectal Cancer in US Women and Men-Results from Two Large Cohort Studies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; MASS INDEX; COLON-CANCER; C-PEPTIDE; FOLLOW-UP; PHYSICAL-ACTIVITY; YOUNG ADULTHOOD; CHRONIC DISEASE; NURSES HEALTH; RECTAL-CANCER AB Background: The association between body fatness before adulthood and later risk of colorectal cancer remains unclear. We hypothesized that, independent of adult body fatness, early life body fatness would be associated with a higher risk of developing colorectal cancer. Methods: We assessed body fatness during childhood and adolescence using a validated 9-level somatotype and inquired body weight in young adulthood in the Nurses' Health Study and Health Professionals Follow-up Study. We used the Cox proportional hazard regression modeling to estimate relative risks [RR, 95% confidence intervals (CI)] adjusting for adult body mass index (BMI) and other known colorectal cancer risk factors. Results: We identified 2,100 incident colorectal cancer cases (1,292 in women and 808 in men) during 22 years of follow-up. Among women, the RR (95% CI) for childhood body fatness of level 5 or higher versus level 1 was 1.28 (1.04-1.58; P-trend = 0.08) and for adolescent body fatness, it was 1.27 (1.01-1.60; P-trend = 0.23). The corresponding RRs for men were 1.04 (0.82-1.31; P-trend = 0.48) and 0.98 (0.75-1.27; P-trend = 0.20), respectively. Results were generally similar across anatomic subsites within the colorectum. In addition, the RRs comparing BMI categories >= 27.5 to <19 kg/m(2) were 1.44 (1.06-1.95, at age 18; P-trend = 0.009) for women and 1.18 (0.84-1.65, at age 21; P-trend = 0.57) for men. Conclusion: Increased body fatness in early life, independent of adult obesity, might be a risk factor for colorectal cancer in women, but we observed a weaker association in men. Impact: Our findings support the growing evidence that early life body fatness affects the risk of colorectal cancer many decades later. (C) 2015 AACR. C1 [Zhang, Xuehong; Giovannucci, Edward L.; Ma, Jing; Fuchs, Charles S.; Willett, Walter C.; Stampfer, Meir J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Network Med, Boston, MA 02115 USA. [Wu, Kana; Giovannucci, Edward L.; Willett, Walter C.; Stampfer, Meir J.] Harvard Univ, Sch Med, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward L.; Willett, Walter C.; Stampfer, Meir J.; Ogino, Shuji] Harvard Univ, Sch Med, Dept Epidemiol, Boston, MA 02115 USA. [Colditz, Graham A.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Nimptsch, Katharina] Max Delbruck Ctr Mol Med, Berlin, Germany. [Ogino, Shuji] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Wei, Esther K.] California Pacific Med Ctr Res Inst, San Francisco, CA USA. RP Zhang, XH (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, 181 Longwood Ave,Room 355, Boston, MA 02115 USA. EM poxue@channing.harvard.edu RI Colditz, Graham/A-3963-2009; OI Colditz, Graham/0000-0002-7307-0291; Nimptsch, Katharina/0000-0001-7877-205X FU American Institute of Cancer Research; NIH [R03CA125837, R03CA176717, P50CA127003, UM1CA167552, P01CA87969, R01CA151993, 1U54CA155626, P01 CA55075] FX This work was supported by a grant from American Institute of Cancer Research and the NIH grants R03CA125837 (to E.K. Wei), R03CA176717 (to X. Zhang), P50CA127003 (to C.S. Fuchs), UM1CA167552 (to W.C. Willett), P01CA87969 (to E.L. Giovannucci, M.J. Stampfer, and S.E. Hankinson), R01CA151993 (to S. Ogino), 1U54CA155626 (to F. Hu), and P01 CA55075 (to W.C. Willett). NR 50 TC 16 Z9 16 U1 3 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2015 VL 24 IS 4 BP 690 EP 697 DI 10.1158/1055-9965.EPI-14-0909-T PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CE6NV UT WOS:000351955900007 PM 25777804 ER PT J AU Brown, M Chinnaiyan, A Farsetti, A Livingston, DM Loda, M Schuele, R Mihich, E AF Brown, Myles Chinnaiyan, Arul Farsetti, Antonella Livingston, David M. Loda, Massimo Schuele, Roland Mihich, Enrico TI 26th Pezcoller Symposium: Cancers Driven by Hormones SO CANCER RESEARCH LA English DT Editorial Material AB This symposium was held in Trento, Italy, on June 19-21, 2014, and was focused on advances in biology, physiology, and pathology of neoplasms affected by hormones, especially breast and prostate cancers. The stem cell function, the genetic and epigenetic interactions with hormones, the mechanisms of estrogen receptor transcription, biochemical markers and therapeutic targets in breast cancer, promotion of breast cancer carcinogenesis by progesterone, the basis for prostate cancer progression and the relevance of DNA repair processes, androgen receptor programming during prostate carcinogenesis, the metabolic stress role in tumor survival, and the diagnostic use of imaging in prostate cancer were discussed. C1 [Brown, Myles; Mihich, Enrico] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Chinnaiyan, Arul] Univ Michigan, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA. [Farsetti, Antonella] CNR, Inst Cell Biol & Neurobiol, Rome, Italy. [Livingston, David M.] Dana Farber Canc Inst, Canc Biol, Boston, MA 02115 USA. [Loda, Massimo] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Schuele, Roland] Univ Freiburg, Med Ctr, Clin Res Ctr, Freiburg, Germany. RP Mihich, E (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM enrico_mihich@dfci.harvard.edu OI Brown, Myles/0000-0002-8213-1658 NR 0 TC 0 Z9 1 U1 1 U2 3 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 APR 1 PY 2015 VL 75 IS 7 BP 1177 EP 1180 DI 10.1158/0008-5472.CAN-14-2902 PG 4 WC Oncology SC Oncology GA CE6LW UT WOS:000351948900003 PM 25788695 ER PT J AU Osman, AA Neskey, DM Katsonis, P Patel, AA Ward, AM Hsu, TK Hicks, SC McDonald, TO Ow, TJ Alves, MO Pickering, CR Skinner, HD Zhao, M Sturgis, EM Kies, MS El-Naggar, A Perrone, F Licitra, L Bossi, P Kimmel, M Frederick, MJ Lichtarge, O Myers, JN AF Osman, Abdullah A. Neskey, David M. Katsonis, Panagiotis Patel, Ameeta A. Ward, Alexandra M. Hsu, Teng-Kuei Hicks, Stephanie C. McDonald, Thomas O. Ow, Thomas J. Alves, Marcus Ortega Pickering, Curtis R. Skinner, Heath D. Zhao, Mei Sturgis, Eric M. Kies, Merrill S. El-Naggar, Adel Perrone, Federica Licitra, Lisa Bossi, Paolo Kimmel, Marek Frederick, Mitchell J. Lichtarge, Olivier Myers, Jeffrey N. TI Evolutionary Action Score of TP53 Coding Variants Is Predictive of Platinum Response in Head and Neck Cancer Patients SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; LOCALLY ADVANCED HEAD; MUTANT P53 GAIN; DNA-DAMAGE; MUTATIONS; PHOSPHORYLATION; CHEMOTHERAPY; INHIBITION; RADIATION; TRANSACTIVATION AB TP53 is the most frequently altered gene in head and neck squamous cell carcinoma (HNSCC), with mutations occurring in over two thirds of cases; however, the predictive response of these mutations to cisplatin-based therapy remains elusive. In the current study, we evaluate the ability of the Evolutionary Action score of TP53-coding variants (EAp53) to predict the impact of TP53 mutations on response to chemotherapy. The EAp53 approach clearly identifies a subset of high-risk TP53 mutations associated with decreased sensitivity to cisplatin both in vitro and in vivo in preclinical models of HNSCC. Furthermore, EAp53 can predict response to treatment and, more importantly, a survival benefit for a subset of head and neck cancer patients treated with platinum-based therapy. Prospective evaluation of this novel scoring system should enable more precise treatment selection for patients with HNSCC. C1 [Osman, Abdullah A.; Patel, Ameeta A.; Ward, Alexandra M.; Pickering, Curtis R.; Zhao, Mei; Frederick, Mitchell J.; Myers, Jeffrey N.] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA. [Neskey, David M.] Med Univ S Carolina, Hollings Canc Ctr, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Katsonis, Panagiotis; Hsu, Teng-Kuei; Lichtarge, Olivier] Baylor Coll Med, Dept Human & Mol Genet, Houston, TX 77030 USA. [Hicks, Stephanie C.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [McDonald, Thomas O.; Kimmel, Marek] Rice Univ, Dept Stat, Houston, TX 77251 USA. [Ow, Thomas J.] Albert Einstein Coll Med, Dept Otolaryngol Head & Neck Surg, Bronx, NY USA. [Alves, Marcus Ortega] Tufts Med Ctr, Dept Internal Med, Boston, MA USA. [Skinner, Heath D.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Radiat Oncol, Houston, TX 77030 USA. [Sturgis, Eric M.; Kies, Merrill S.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. [El-Naggar, Adel] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Perrone, Federica] Ist Nazl Tumori, Fdn Ist Ric & Cura Carattere Sci, Dept Pathol, I-20133 Milan, Italy. [Licitra, Lisa; Bossi, Paolo] Ist Nazl Tumori, Fdn Ist Ric & Cura Carattere Sci, Head & Neck Med Oncol Unit, I-20133 Milan, Italy. RP Myers, JN (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM jmyers@mdanderson.org RI Perrone, Federica/S-6171-2016; Licitra, Lisa/C-6271-2017; Bossi, Paolo/D-1807-2017; OI Perrone, Federica/0000-0003-4406-8245; Licitra, Lisa/0000-0003-0623-4118; Bossi, Paolo/0000-0003-0135-0224; Hicks, Stephanie/0000-0002-7858-0231 FU University of Texas MD Anderson Cancer Center PANTHEON; NIH [P50CA097007, C168485, 5 R90 DK071505]; NIH/NIDCR [R01 DE14613, R01 DE024601]; Cancer Prevention and Research Institute of Texas (CPRIT) [RP120258]; National Research Science Award Institutional Research Training [T32GA60374]; Cancer Center Support [GM066099]; NSF [CCF 0905536, DBI 0851393] FX This work was supported by the University of Texas MD Anderson Cancer Center PANTHEON program (philanthropic support to J.N. Myers), the NIH Specialized Program of Research Excellence Grant P50CA097007 (J.N. Myers), the NIH/NIDCR R01 DE14613 and R01 DE024601 (J.N. Myers), Cancer Prevention and Research Institute of Texas (CPRIT) RP120258 (J.N. Myers), National Research Science Award Institutional Research Training Grant T32GA60374 (J.N. Myers), the NIH Program Project Grant C168485 (J.N. Myers), and the Cancer Center Support Grant CA016672 (J.N. Myers). This work was also supported by NIH RO1 GM079656 (O. Lichtarge), R01 GM066099 (O. Lichtarge), and NSF CCF 0905536 (O. lichtarge) and DBI 0851393 (O. Lichtarge), and Pharmacoinformatics Training Program of the Keck Center of the Gulf Coast Consortia NIH grant no 5 R90 DK071505 (P. Katsonis). NR 36 TC 10 Z9 10 U1 1 U2 8 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 APR 1 PY 2015 VL 75 IS 7 BP 1205 EP 1215 DI 10.1158/0008-5472.CAN-14-2729 PG 11 WC Oncology SC Oncology GA CE6LW UT WOS:000351948900008 PM 25691460 ER PT J AU Rice, WL Shcherbakova, DM Verkhusha, VV Kumar, ATN AF Rice, William L. Shcherbakova, Daria M. Verkhusha, Vladislav V. Kumar, Anand T. N. TI In Vivo Tomographic Imaging of Deep-Seated Cancer Using Fluorescence Lifetime Contrast SO CANCER RESEARCH LA English DT Article ID TIME-RESOLVED FLUORESCENCE; TURBID MEDIA; WHOLE-BODY; BREAST-CANCER; SMALL ANIMALS; PROTEINS; REPORTER; PROBES; TUMORS; CELLS AB Preclinical cancer research would benefit from noninvasive imaging methods that allow tracking and visualization of early-stage metastasis in vivo. Although fluorescent proteins revolutionized intravital microscopy, two major challenges that still remain are tissue autofluorescence and hemoglobin absorption, which act to limit intravital optical techniques to large or subcutaneous tumors. Here, we use time-domain (TD) technology for the effective separation of tissue autofluorescence from extrinsic fluorophores, based on their distinct fluorescence lifetimes. In addition, we use cancer cells labeled with near infrared fluorescent proteins (iRFP) to allow deep-tissue imaging. Our results demonstrate that TD imaging allows the detection of metastasis in deep-seated organs of living mice with a more than 20-fold increase in sensitivity compared with conventional continuous wave techniques. Furthermore, the distinct fluorescence lifetimes of iRFPs enable lifetime multiplexing of three different tumors, each expressing unique iRFP labels in the same animal. Fluorescence tomographic reconstructions reveal three-dimensional distributions of iRFP720-expressing cancer cells in lungs and brain of live mice, allowing ready longitudinal monitoring of cancer cell fate with greater sensitivity than otherwise currently possible. (C)2015 AACR. C1 [Rice, William L.; Kumar, Anand T. N.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02474 USA. [Rice, William L.; Kumar, Anand T. N.] Harvard Univ, Sch Med, Boston, MA USA. [Shcherbakova, Daria M.; Verkhusha, Vladislav V.] Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10467 USA. [Verkhusha, Vladislav V.] Univ Helsinki, Fac Med, Dept Biochem & Dev Biol, Helsinki, Finland. RP Kumar, ATN (reprint author), Massachusetts Gen Hosp, Martinos Ctr, Mass Gen Hosp, Room 2301, Charlestown, MA 02474 USA. EM ankumar@nmr.mgh.harvard.edu FU U.S. National Institutes of Health [R01-EB105325, CA164468, GM073913, GM1108579] FX This work was supported by grants R01-EB105325, CA164468, GM073913, and GM1108579 from the U.S. National Institutes of Health. NR 34 TC 13 Z9 13 U1 5 U2 17 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 APR 1 PY 2015 VL 75 IS 7 BP 1236 EP 1243 DI 10.1158/0008-5472.CAN-14-3001 PG 8 WC Oncology SC Oncology GA CE6LW UT WOS:000351948900011 PM 25670171 ER PT J AU Hirata, H Hinoda, Y Shahryari, V Deng, GR Nakajima, K Tabatabai, ZL Ishii, N Dahiya, R AF Hirata, Hiroshi Hinoda, Yuji Shahryari, Varahram Deng, Guoren Nakajima, Koichi Tabatabai, Z. Laura Ishii, Nobuhisa Dahiya, Rajvir TI Long Noncoding RNA MALAT1 Promotes Aggressive Renal Cell Carcinoma through Ezh2 and Interacts with miR-205 SO CANCER RESEARCH LA English DT Article ID BLADDER-CANCER METASTASIS; KIDNEY CANCER; TUMOR-SUPPRESSOR; UP-REGULATION; TRANSCRIPTION; EXPRESSION; HOTAIR; REGION; CERNA; EPIMUTATION AB Recently, long noncoding RNAs (lncRNA) have emerged as new gene regulators and prognostic markers in several cancers, including renal cell carcinoma (RCC). In this study, we investigated the contributions of the lncRNA MALAT1 in RCC with a specific focus on its transcriptional regulation and its interactions with Ezh2 and miR-205. We found that MALAT1 expression was higher in human RCC tissues, where it was associated with reduced patient survival. MALAT1 silencing decreased RCC cell proliferation and invasion and increased apoptosis. Mechanistic investigations showed that MALAT1 was transcriptionally activated by c-Fos and that it interacted with Ezh2. After MALAT1 silencing, E-cadherin expression was increased, whereas beta-catenin expression was decreased through Ezh2. Reciprocal interaction between MALAT1 and miR-205 was also observed. Lastly, MALAT1 bound Ezh2 and oncogenesis facilitated by MALAT1 was inhibited by Ezh2 depletion, thereby blocking epithelial-mesenchymal transition via E-cadherin recovery and beta-catenin downregulation. Overall, our findings illuminate how overexpression of MALAT1 confers an oncogenic function in RCC that may offer a novel theranostic marker in this disease. (C)2015 AACR. C1 [Hirata, Hiroshi; Shahryari, Varahram; Deng, Guoren; Dahiya, Rajvir] San Francisco VA Med Ctr, Dept Urol, San Francisco, CA 94121 USA. [Hirata, Hiroshi; Shahryari, Varahram; Deng, Guoren; Tabatabai, Z. Laura; Dahiya, Rajvir] Univ Calif San Francisco, San Francisco, CA 94121 USA. [Hinoda, Yuji] Yamaguchi Univ, Grad Sch Med, Dept Oncol & Lab Med, Yamaguchi, Japan. [Nakajima, Koichi; Ishii, Nobuhisa] Toho Univ, Fac Med, Dept Urol, Tokyo, Japan. [Tabatabai, Z. Laura] San Francisco VA Med Ctr, Dept Pathol, San Francisco, CA 94121 USA. RP Dahiya, R (reprint author), San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM rdahiya@urology.ucsf.edu FU National Center for Research Resources of the National Institutes of Health [RO1CA130860, RO1CA138642, RO1CA160079, 101BX001123]; VA Merit Review; VA Program Project; Yamada Science Foundation FX This study was supported by National Center for Research Resources of the National Institutes of Health through grant numbers RO1CA130860, RO1CA138642, RO1CA160079, and 101BX001123, VA Merit Review, VA Program Project (Principal Investigator, R. Dahiya), and Yamada Science Foundation. NR 48 TC 82 Z9 88 U1 11 U2 29 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 APR 1 PY 2015 VL 75 IS 7 BP 1322 EP 1331 DI 10.1158/0008-5472.CAN-14-2931 PG 10 WC Oncology SC Oncology GA CE6LW UT WOS:000351948900019 PM 25600645 ER PT J AU Yoshida, T Kim, JH Carver, K Su, Y Weremowicz, S Mulvey, L Yamamoto, S Brennan, C Mei, SL Long, H Yao, J Polyak, K AF Yoshida, Taku Kim, Jee Hyun Carver, Kristopher Su, Ying Weremowicz, Stanislawa Mulvey, Laura Yamamoto, Shoji Brennan, Cameron Mei, Shenglin Long, Henry Yao, Jun Polyak, Kornelia TI CLK2 Is an Oncogenic Kinase and Splicing Regulator in Breast Cancer SO CANCER RESEARCH LA English DT Article ID COLORECTAL CANCERS; CLINICAL-IMPLICATIONS; MOLECULAR PORTRAITS; TARGETED THERAPIES; PROTEIN-KINASES; TUMOR-GROWTH; RNA-SEQ; IN-SITU; COMPLEX; GENES AB Genetically activated kinases have been attractive therapeutic targets in cancer due to the relative ease of developing tumor-specific treatment strategies for them. To discover novel putative oncogenic kinases, we identified 26 genes commonly amplified and overexpressed in breast cancer and subjected them to a lentiviral shRNA cell viability screen in a panel of breast cancer cell lines. Here, we report that CLK2, a kinase that phosphorylates SR proteins involved in splicing, acts as an oncogene in breast cancer. Deregulated alternative splicing patterns are commonly observed in human cancers but the underlying mechanisms and functional relevance are still largely unknown. CLK2 is amplified and overexpressed in a significant fraction of breast tumors. Downregulation of CLK2 inhibits breast cancer growth in cell culture and in xenograft models and it enhances cell migration and invasion. Loss of CLK2 in luminal breast cancer cells leads to the upregulation of epithelial-to-mesenchymal transition (EMT)-related genes and a switch to mesenchymal splice variants of several genes, including ENAH (MENA). These results imply that therapeutic targeting of CLK2 may be used to modulate EMT splicing patterns and to inhibit breast tumor growth. (C)2015 AACR. C1 [Yoshida, Taku; Kim, Jee Hyun; Carver, Kristopher; Su, Ying; Mulvey, Laura; Yamamoto, Shoji; Yao, Jun; Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Yoshida, Taku; Kim, Jee Hyun; Carver, Kristopher; Su, Ying; Yamamoto, Shoji; Yao, Jun; Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Yoshida, Taku; Kim, Jee Hyun; Carver, Kristopher; Su, Ying; Yamamoto, Shoji; Yao, Jun; Polyak, Kornelia] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Kim, Jee Hyun] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Weremowicz, Stanislawa] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Weremowicz, Stanislawa] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Brennan, Cameron] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Mei, Shenglin; Long, Henry; Polyak, Kornelia] Dana Farber Canc Inst, Ctr Funct Epigenet, Boston, MA 02215 USA. [Mei, Shenglin] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. [Yao, Jun] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Polyak, Kornelia] Harvard Stem Cell Inst, Cambridge, MA USA. [Polyak, Kornelia] Broad Inst, Cambridge, MA USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, 450 Brookline Ave D740C, Boston, MA 02215 USA. EM Kornelia_polyak@dfci.harvard.edu OI Brennan, Cameron/0000-0003-4064-8891 FU Susan G. Komen Foundation; Tisch Family Fund FX This work was supported by the Susan G. Komen Foundation and the Tisch Family Fund (to K. Polyak). NR 65 TC 8 Z9 8 U1 0 U2 3 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 APR 1 PY 2015 VL 75 IS 7 BP 1516 EP 1526 DI 10.1158/0008-5472.CAN-14-2443 PG 11 WC Oncology SC Oncology GA CE6LW UT WOS:000351948900036 PM 25670169 ER PT J AU Neskey, DM Osman, AA Ow, TJ Katsonis, P McDonald, T Hicks, SC Hsu, TK Pickering, CR Ward, A Patel, A Yordy, JS Skinner, HD Giri, U Sano, D Story, MD Beadlel, BM El-Naggar, AK Kies, MS William, WN Caulin, C Frederick, M Kimmel, M Myers, JN Lichtarge, O AF Neskey, David M. Osman, Abdullah A. Ow, Thomas J. Katsonis, Panagiotis McDonald, Thomas Hicks, Stephanie C. Hsu, Teng-Kuei Pickering, Curtis R. Ward, Alexandra Patel, Ameeta Yordy, John S. Skinner, Heath D. Giri, Uma Sano, Daisuke Story, Michael D. Beadlel, Beth M. El-Naggar, Adel K. Kies, Merrill S. William, William N. Caulin, Carlos Frederick, Mitchell Kimmel, Marek Myers, Jeffrey N. Lichtarge, Olivier TI Evolutionary Action Score of TP53 Identifies High-Risk Mutations Associated with Decreased Survival and Increased Distant Metastases in Head and Neck Cancer SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; MUTANT P53; GENE-EXPRESSION; PROTEIN; GAIN; IMPACT; SUBSTITUTION; STATISTICS; PHENOTYPE; RESIDUES AB TP53 is the most frequently altered gene in head and neck squamous cell carcinoma, with mutations occurring in over two-thirds of cases, but the prognostic significance of these mutations remains elusive. In the current study, we evaluated a novel computational approach termed evolutionary action (EAp53) to stratify patients with tumors harboring TP53 mutations as high or low risk, and validated this system in both in vivo and in vitro models. Patients with high-risk TP53 mutations had the poorest survival outcomes and the shortest time to the development of distant metastases. Tumor cells expressing high-risk TP53 mutations were more invasive and tumorigenic and they exhibited a higher incidence of lung metastases. We also documented an association between the presence of high-risk mutations and decreased expression of TP53 target genes, highlighting key cellular pathways that are likely to be dysregulated by this subset of p53 mutations that confer particularly aggressive tumor behavior. Overall, our work validated EAp53 as a novel computational tool that may be useful in clinical prognosis of tumors harboring p53 mutations. (C)2015 AACR. C1 [Neskey, David M.] Med Univ S Carolina, Hollings Canc Ctr, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Osman, Abdullah A.; Pickering, Curtis R.; Ward, Alexandra; Patel, Ameeta; Caulin, Carlos; Frederick, Mitchell; Myers, Jeffrey N.] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA. [Ow, Thomas J.] Yeshiva Univ, Albert Einstein Sch Med, Dept Otolaryngol Head & Neck Surg, New York, NY 10033 USA. [Katsonis, Panagiotis; Hsu, Teng-Kuei; Lichtarge, Olivier] Baylor Coll Med, Dept Human & Mol Genet, Houston, TX 77030 USA. [McDonald, Thomas; Kimmel, Marek] Rice Univ, Dept Stat, Houston, TX 77251 USA. [Hicks, Stephanie C.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Yordy, John S.; Story, Michael D.] UT Southwestern Med Ctr, Radiat Oncol, Dallas, TX USA. [Skinner, Heath D.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Radiat Oncol, Houston, TX 77030 USA. [Giri, Uma] Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA. [Sano, Daisuke] Yokahama Univ, Dept Otolaryngol Head & Neck Surg, Yokohama, Japan. [Beadlel, Beth M.] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Radiat Oncol, Houston, TX 77030 USA. [El-Naggar, Adel K.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Kies, Merrill S.; William, William N.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. [Story, Michael D.] UT Southwestern Med Ctr, Dept Radiat Oncol, Dallas, TX USA. RP Myers, JN (reprint author), Univ Texas MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM jmyers@mdanderson.org OI Hicks, Stephanie/0000-0002-7858-0231 FU UTMDACC PANTHEON program; UTMDACC Sisters Institution Network Fund; National Institute of Health Specialized Program of Research Excellence Grant [P50CA097007]; NIH [R01 DE14613, R01 GM079656, R01 GM066099]; Cancer Prevention and Research Institute of Texas [RP120258]; National Research Science Award Institutional Research Training Grant [T32CA60374]; National Institute of Health Program Project Grant [CA06294]; Cancer Center Support Grant [CA016672]; NSF [DBI 1356569, DBI 0851393]; Pharmacoinformatics Training Program of the Neck Center of the Gulf Coast Consortia (NIH) [5 R90 DKO71505] FX This work was supported by the UTMDACC PANTHEON program, the UTMDACC Sisters Institution Network Fund, the National Institute of Health Specialized Program of Research Excellence Grant (P50CA097007), the NIH (R01 DE14613), Cancer Prevention and Research Institute of Texas (RP120258), National Research Science Award Institutional Research Training Grant (T32CA60374), the National Institute of Health Program Project Grant (CA06294), and the Cancer Center Support Grant (CA016672). O. Lichtarge gratefully acknowledges support from NIH R01 GM079656 and R01 GM066099, and NSF DBI 1356569 and DBI 0851393. P. Katsonis was supported by the Pharmacoinformatics Training Program of the Neck Center of the Gulf Coast Consortia (NIH grant no. 5 R90 DKO71505). NR 36 TC 15 Z9 15 U1 1 U2 5 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 APR 1 PY 2015 VL 75 IS 7 BP 1527 EP 1536 DI 10.1158/0008-5472.CAN-14-2735 PG 10 WC Oncology SC Oncology GA CE6LW UT WOS:000351948900037 PM 25634208 ER PT J AU Schainfeld, RM Rajachandran, M AF Schainfeld, Robert M. Rajachandran, Manu TI What's Past is Prologue SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material ID OCCLUSIVE DISEASE; BYPASS GRAFTS; METAANALYSIS C1 [Schainfeld, Robert M.] Massachusetts Gen Hosp, Div Cardiol, Sect Vasc Med, Boston, MA 02114 USA. [Rajachandran, Manu] Mem Hosp, Dept Cardiol, York, PA 17403 USA. RP Schainfeld, RM (reprint author), Massachusetts Gen Hosp, Sect Vasc Med, 55 Fruit St, Boston, MA 02114 USA. EM rschainfeld@partners.org NR 5 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 EI 1522-726X J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD APR PY 2015 VL 85 IS 5 BP 868 EP 869 DI 10.1002/ccd.25883 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CE0UU UT WOS:000351523800022 PM 25789732 ER PT J AU Gelber, RD Gelber, S AF Gelber, Richard D. Gelber, Shari TI Marvin Zelen, 1927-2014 SO CLINICAL TRIALS LA English DT Biographical-Item C1 [Gelber, Richard D.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Gelber, Richard D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. [Gelber, Shari] Harvard Univ, Sch Med, Boston, MA USA. [Gelber, Shari] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. RP Gelber, RD (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM gelber@jimmy.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 EI 1740-7753 J9 CLIN TRIALS JI Clin. Trials PD APR PY 2015 VL 12 IS 2 BP 89 EP 90 DI 10.1177/1740774515569013 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CE9OQ UT WOS:000352173700020 ER PT J AU Lok, J Wang, XS Xing, CH Maki, TK Wu, LM Guo, SZ Noviski, N Arai, K Whalen, MJ Lo, EH Wang, XY AF Lok, Josephine Wang, Xiao-Shu Xing, Chang-Hong Maki, Taka-Kuni Wu, Li-Min Guo, Shu-Zhen Noviski, Natan Arai, Ken Whalen, Michael J. Lo, Eng H. Wang, Xiao-Ying TI Targeting the Neurovascular Unit in Brain Trauma SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Review DE Endothelial; Glia; Neuron; Neuroprotection; Traumatic brain injury ID CEREBRAL-BLOOD-FLOW; OLIGODENDROCYTE PRECURSOR CELLS; MICROGLIAL ACTIVATION; REACTIVE ASTROCYTES; ENDOTHELIAL-CELLS; CORTICAL IMPACT; INJURY MODEL; HEAD-INJURY; BARRIER; STROKE AB Although the neurovascular unit was originally developed as a conceptual framework for stroke, it is now recognized that these cell-cell interactions play critical roles in many other CNS disorders as well. In brain trauma, perturbations within the neurovascular unit may be especially important. Changes in neurovascular coupling may disrupt blood flow and metabolic regulation. Disruption of transmitter release-reuptake kinetics in neurons and astrocytes may augment excitotoxicity. Alterations in gliovascular signaling may underlie blood-brain barrier disruptions and traumatic edema. Perturbations in cell-cell signaling between all neuronal, glial, and vascular compartments may increase susceptibility to cell death. Finally, repairing the brain after trauma requires the integrated restoration of all neural, glial, and vascular connectivity for effective functional recovery. Just as in stroke, saving neurons alone may also be insufficient for treating brain trauma. In this minireview, we attempt to briefly highlight some of these pathways to underscore the importance of rescuing the entire neurovascular unit in brain trauma. C1 [Lok, Josephine; Wang, Xiao-Ying] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02129 USA. [Lok, Josephine; Wang, Xiao-Ying] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02129 USA. [Lok, Josephine; Wang, Xiao-Ying] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02129 USA. RP Lok, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02129 USA. EM jlok1@mgh.harvard.edu; wangxi@helix.mgh.harvard.edu FU NIH; AHA; Rappaport Foundation FX The study is based in part on ideas and sections drawn from Lok et al., Neurochem Res 2006; Xing et al., Neurol Res 2012; Lok et al., Vasc Mech CNS Trauma 2014; and Wang et al., Vasc Mech CNS Trauma 2014 and supported in part by grants from NIH, AHA and the Rappaport Foundation. NR 61 TC 5 Z9 5 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-5930 EI 1755-5949 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PD APR PY 2015 VL 21 IS 4 SI SI BP 304 EP 308 DI 10.1111/cns.12359 PG 5 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CE5JX UT WOS:000351870400002 PM 25475543 ER PT J AU Kim, JY Kim, N Yenari, MA AF Kim, Jong-Youl Kim, Nuri Yenari, Midori A. TI Mechanisms and Potential Therapeutic Applications of Microglial Activation after Brain Injury SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Review DE Brain injury; Inflammation; Microglia; Neurotoxic mediator ID FOCAL CEREBRAL-ISCHEMIA; NITRIC-OXIDE SYNTHASE; CENTRAL-NERVOUS-SYSTEM; TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; MICROGLIA/MACROPHAGE POLARIZATION DYNAMICS; INTRACEREBRAL INFLAMMATORY RESPONSE; RECEPTOR-GAMMA AGONISTS; CELL-ADHESION MOLECULES; TRANSGENIC MOUSE MODEL AB As the resident immune cells of the central nervous system, microglia rapidly respond to brain insults, including stroke and traumatic brain injury. Microglial activation plays a major role in neuronal cell damage and death by releasing a variety of inflammatory and neurotoxic mediators. Their activation is an early response that may exacerbate brain injury and many other stressors, especially in the acute stages, but are also essential to brain recovery and repair. The full range of microglial activities is still not completely understood, but there is accumulating knowledge about their role following brain injury. We review recent progress related to the deleterious and beneficial effects of microglia in the setting of acute neurological insults and the current literature surrounding pharmacological interventions for intervention. C1 [Kim, Jong-Youl; Kim, Nuri; Yenari, Midori A.] Univ Calif San Francisco, Dept Neurol, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. RP Yenari, MA (reprint author), Univ Calif San Francisco, Dept Neurol, San Francisco Vet Affairs Med Ctr, 4150 Clement,MS 127, San Francisco, CA 94121 USA. EM yenari@alum.mit.edu FU National Institutes of Health (NIH) [NS40516]; Veteran's Merit Awards; American Hearts Association [13POST14810019]; Veterans Affairs Medical Center, San Francisco, California FX This work was supported by grants from the National Institutes of Health (NIH) (NS40516 to MY), the Veteran's Merit Awards to MY, and American Hearts Association (13POST14810019) to JYK. Grants to MY and JYK were administered by the Northern California Institute for Research and Education and supported by resources of the Veterans Affairs Medical Center, San Francisco, California. NR 217 TC 11 Z9 11 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-5930 EI 1755-5949 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PD APR PY 2015 VL 21 IS 4 SI SI BP 309 EP 319 DI 10.1111/cns.12360 PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CE5JX UT WOS:000351870400003 PM 25475659 ER PT J AU Hershenberg, R Olino, TM Dyson, MW Davila, J Kleine, DN AF Hershenberg, Rachel Olino, Thomas M. Dyson, Margaret W. Davila, Joanne Kleine, Daniel N. TI Are personality disorder dimensions related over time? An examination over the course of ten years using multivariate growth modeling SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID 5-FACTOR MODEL; PATTERNS; COOCCURRENCE; COMORBIDITY; OUTPATIENTS; STABILITY AB Objective: Despite the well-documented literature on cross-sectional comorbidity, there is a paucity of data on the associations between personality disorders (PDs) over time. Using multivariate growth modeling, the present study examined the inter-relationships between pairs of PD disorder dimensions. Methods: We tested these associations in a sample of 142 depressed outpatients followed-up five times over the course of 10 years. Results: We found cross-sectional associations between the initial levels of severity of many pairs of PD dimensions. However, there was limited support for longitudinal associations between PD dimensions. Conclusion: These findings suggest that the course of PD dimensions is fairly independent of each other, and that initial levels of PD dimensions have relatively little prognostic value for predicting the course of other PD dimensions. Published by Elsevier Inc. C1 [Hershenberg, Rachel] Philadelphia VA Med Ctr, VISN MIRECC 4, Philadelphia, PA 19104 USA. [Hershenberg, Rachel] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Olino, Thomas M.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. [Dyson, Margaret W.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Davila, Joanne; Kleine, Daniel N.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. RP Hershenberg, R (reprint author), Philadelphia VA Med Ctr, VISN MIRECC 4, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM rhersh@mail.med.upenn.edu; thomas.olino@temple.edu; mdyson@ucsd.edu; joanne.davila@stonybrook.edu; Daniel.klein@stonybrook.edu FU VISN 4 Mental Illness Research, Education, and Clinical Center, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA; NIH [K01 MH09263, RO1 MH45757] FX This paper was prepared with the support of the VISN 4 Mental Illness Research, Education, and Clinical Center, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA. The views expressed in the article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. Dr. Olino was supported by NIH grant K01 MH09263. Dr. Klein was supported by NIH grant RO1 MH45757. There were no conflicts of interest related to this project or its authors. NR 29 TC 0 Z9 0 U1 1 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 0010-440X EI 1532-8384 J9 COMPR PSYCHIAT JI Compr. Psychiat. PD APR PY 2015 VL 58 BP 11 EP 17 DI 10.1016/j.comppsych.2014.12.002 PG 7 WC Psychiatry SC Psychiatry GA CE4NR UT WOS:000351807800002 PM 25659664 ER PT J AU Badour, CL Gros, DF Szafranski, DD Acierno, R AF Badour, Christal L. Gros, Daniel F. Szafranski, Derek D. Acierno, Ron TI Problems in sexual functioning among male OEF/OIF veterans seeking treatment for posttraumatic stress SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID ADMINISTERED PTSD SCALE; IRAQI FREEDOM VETERANS; MALE VIETNAM VETERANS; SOCIAL SUPPORT; DISORDER SYMPTOMS; ENDURING FREEDOM; COMBAT VETERANS; AFGHANISTAN; IMPAIRMENT; DYSFUNCTION AB Objective: Few studies have examined sexual dysfunction among Operations Enduring/Iraqi Freedom (OEF/OIF) veterans with posttraumatic stress disorder (PTSD). The present study investigated predictors of erectile dysfunction [ED] and self-reported sexual problems among 150 male combat veterans seeking outpatient treatment for PTSD within the Veterans Affairs healthcare system. Method: Participants completed clinical interviews and several questionnaires including measures of sexual arousal and sexual desire. A medical records review was also conducted to document evidence of an ED diagnosis or associated medication use. Results: An ED diagnosis was present for 12% of the sample, and 10% were taking associated medications. Sexual arousal problems were reported by sixty-two percent of partnered veterans. Sexual desire problems were endorsed by 63% of the total sample, and by 72% of partnered veterans. Age was the only significant predictor of ED diagnosis or medication use. Age, race, PTSD diagnosis (versus subclinical symptoms), depression, and social support predicted self-reported sexual arousal problems; while race, combat exposure, social support, and avoidance/numbing symptoms of PTSD predicted self-reported sexual desire problems. Conclusions: Sexual problems are common among male OEF/OIF combat veterans seeking treatment for PTSD. Moreover, avoidance/numbing symptoms robustly predicted sexual desire problems. These findings highlight the importance of expanding assessment of sexual dysfunction and support the need for additional research in this area. (C) 2014 Elsevier Inc. All rights reserved. C1 [Badour, Christal L.; Gros, Daniel F.; Acierno, Ron] Med Univ S Carolina, Charleston, SC 29425 USA. [Badour, Christal L.; Gros, Daniel F.; Acierno, Ron] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. [Szafranski, Derek D.] Vet Affairs Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. RP Badour, CL (reprint author), 67 President St,MSC 861,2nd Fl IOP South Bldg, Charleston, SC 29425 USA. EM badour@musc.edu FU Department of Defense [W81XWH-07-PTSD-IIRA]; Veterans Affairs Health Services Research and Development [NCT01102764]; Department of Veteran Affairs Clinical Sciences Research and Development Career Development Award [CX000845]; South Carolina Clinical & Translational Research Institute; academic home at the Medical University of South Carolina (NIH) [UL1 TR000062] FX This publication was supported, in part, by grants from the Department of Defense (W81XWH-07-PTSD-IIRA [PI: Acierno]), Veterans Affairs Health Services Research and Development (NCT01102764 [PI: Acierno]), Department of Veteran Affairs Clinical Sciences Research and Development Career Development Award (CX000845 [PI: Gros]) and the South Carolina Clinical & Translational Research Institute, with an academic home at the Medical University of South Carolina (NIH Grant Number UL1 TR000062 [PI: Brady]). Several authors are also core and affiliate members of the Ralph H Johnson VA Centers of Innovation (PI: Egede), Charleston Health Equity and Rural Outreach Innovation Center. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. There are no conflicts of interest to disclose. NR 51 TC 2 Z9 2 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 0010-440X EI 1532-8384 J9 COMPR PSYCHIAT JI Compr. Psychiat. PD APR PY 2015 VL 58 BP 74 EP 81 DI 10.1016/j.comppsych.2014.12.012 PG 8 WC Psychiatry SC Psychiatry GA CE4NR UT WOS:000351807800010 PM 25596624 ER PT J AU Slavin-Mulford, J Perkey, H Blais, M Stein, M Sinclair, SJ AF Slavin-Mulford, Jenelle Perkey, Hana Blais, Mark Stein, Michelle Sinclair, Samuel Justin TI External validity of the Symptom Assessment-45 Questionnaire (SA-45) in a clinical sample SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID PERSONALITY-ASSESSMENT INVENTORY; SELF-REPORT; DISCIPLINARY ADJUSTMENT; MAJOR DEPRESSION; MENTAL-DISORDERS; YOUNG ADULTHOOD; PAI; SCL-90; VALIDATION; SCALE AB This study seeks to evaluate the construct validity of the Symptom Assessment-45 by investigating the instrument's correlation with selected scales from the Personality Assessment Inventory and life-event data in a sample of 93 psychiatric patients. The life-event data used in the study included: education and employment, as well as history of suicide attempts, psychiatric hospitalizations, medical problems, hallucinations, and paranoid ideation. Bivariate correlations were computed to explore the associations among the SA-45 scales and the validity criteria. The results indicated that the SA-45 scales demonstrated adequate convergent and divergent validity with target scales from the PAI. They were also found to be meaningfully associated with a variety of life event variables. These findings add to the emerging body of evidence corroborating the convergent and discriminant validity of the SA-45. (C) 2015 Elsevier Inc. All rights reserved. C1 [Slavin-Mulford, Jenelle; Perkey, Hana] Georgia Regents Univ, Augusta, GA 30904 USA. [Blais, Mark; Stein, Michelle; Sinclair, Samuel Justin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Blais, Mark; Stein, Michelle; Sinclair, Samuel Justin] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Slavin-Mulford, J (reprint author), Georgia Regents Univ, Dept Psychol, Summerville Campus,2500 Walton Way, Augusta, GA 30904 USA. EM jslavinm@gru.edu; hperkey@gmail.com; MBLAIS@mgh.harvard.edu; MSTE1N3@mgh.harvard.edu; SJSINCLAIR@mgh.harvard.edu NR 47 TC 0 Z9 0 U1 11 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 0010-440X EI 1532-8384 J9 COMPR PSYCHIAT JI Compr. Psychiat. PD APR PY 2015 VL 58 BP 205 EP 212 DI 10.1016/j.comppsych.2014.12.007 PG 8 WC Psychiatry SC Psychiatry GA CE4NR UT WOS:000351807800028 PM 25612902 ER PT J AU Ghatalia, P Morgan, CJ Choueiri, TK Rocha, P Naik, G Sonpavde, G AF Ghatalia, Pooja Morgan, Charity J. Choueiri, Toni K. Rocha, Pedro Naik, Gurudatta Sonpavde, Guru TI Pancreatitis with vascular endothelial growth factor receptor tyrosine kinase inhibitors SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE Vascular endothelial growth factor receptor; Tyrosine kinase inhibitors; Approved; Pancreatitis; Meta-analysis ID PHASE-III TRIAL; CELL LUNG-CANCER; RANDOMIZED CONTROLLED-TRIALS; ADVANCED BREAST-CANCER; DOUBLE-BLIND; 1ST-LINE TREATMENT; THYROID-CANCER; SORAFENIB; SUNITINIB; COMBINATION AB A trial-level meta-analysis was conducted to determine the relative risk (RR) of pancreatitis associated with multi-targeted vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI). Eligible studies included randomized phase 2 and 3 trials comparing arms with and without an FDA-approved VEGFR TKI (sunitinib, sorafenib, pazopanib, axitinib, vandetanib, cabozantinib, ponatinib, regorafenib). Statistical analyses calculated the RR and 95% confidence intervals (CI). A total of 10,578 patients from 16 phase III trials and 6 phase II trials were selected. The RR for all grade and high-grade pancreatitis for the TKI vs. no TKI- arms was 1.95 (p = 0.042, 95% CI: 1.02 to 3.70) and 1.89 (p = 0.069, 95% CI: 0.95 to 373), respectively. No differential impact of malignancy type or specific TKI agent was seen on RR of all grade of high grade pancreatitis. Better patient selection and monitoring may mitigate the risk of severe pancreatitis. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Ghatalia, Pooja] UAB, Dept Internal Med, Birmingham, AL USA. [Morgan, Charity J.] UAB, Dept Biostat, Sch Publ Hlth, Birmingham, AL USA. [Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Choueiri, Toni K.] Harvard Univ, Sch Med, Boston, MA USA. [Rocha, Pedro] Univ Autonoma Barcelona, Hosp Mar, Dept Med, E-08003 Barcelona, Spain. [Naik, Gurudatta; Sonpavde, Guru] UAB, Med Ctr, Dept Internal Med, Sect Med Oncol, Birmingham, AL 35233 USA. RP Sonpavde, G (reprint author), UAB, Med Ctr, Dept Internal Med, Sect Med Oncol, Birmingham, AL 35233 USA. EM gsonpavde@uabmc.edu FU Pfizer; Novartis; Onyx FX Toni K. Choueiri: Advisory board/Consultant: Bayer, Pfizer, GSK, Novartis, Aveo. Research support from Pfizer.; Guru Sonpavde: Research support and advisory board for Novartis; Advisory board for GSK, Sanofi-Aventis, Merck and Bayer; Research support from Onyx. NR 41 TC 6 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 1040-8428 EI 1879-0461 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD APR PY 2015 VL 94 IS 1 BP 136 EP 145 DI 10.1016/j.critrevonc.2014.11.008 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA CE4IP UT WOS:000351794600013 PM 25541349 ER PT J AU Tapp, A Wood, AE Kennedy, A Sylvers, P Kilzieh, N Saxon, AJ AF Tapp, Andre Wood, Amanda Ernst Kennedy, Annette Sylvers, Patrick Kilzieh, Nael Saxon, Andrew J. TI Quetiapine for the treatment of cocaine use disorder SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Cocaine use disorder; Quetiapine; Treatment trial ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND TRIAL; OPEN-LABEL TRIAL; DEPENDENT PATIENTS; TIMELINE FOLLOWBACK; ALCOHOL DEPENDENCE; BIPOLAR DISORDER; SUBSTANCE USE; PILOT TRIAL; RISPERIDONE AB Background: Cocaine addiction continues to be a significant healthcare issue, yet there are no FDA approved medications for the treatment of cocaine use disorder within the United States. Methods: This 12-week, prospective, double-blind, randomized, placebo-controlled study examined the effectiveness of quetiapine (Seroquel XR (TM)) versus matched placebo for the treatment of DSM-IV cocaine dependence in non-psychotic individuals. Subjects randomized to quetiapine (N = 29) were titrated up to a target dose of 400 mg/day of quetiapine, while those in the placebo arm (N = 31) were given a matched placebo. All subjects had weekly clinic visits and a cognitive-behavioral therapy group session. Outcome measures included self-report of cocaine use and money spent on cocaine as well as urine drug screens (UDS). Results: The drop-out rate was substantial at 68%. Logistic regression analysis did not find significant differences between groups in predicting end-of trial abstinence, defined as three consecutive weekly negative UDS (13.7% in the quetiapine group versus 12.9% in the placebo group; p = .92). Based upon a repeated measures analysis of variance, subjects in this study, as a whole, demonstrated reductions in their self-reported use of cocaine, self-reported money spent on cocaine, and number of days per week using cocaine. However, the quetiapine group did not differ significantly from the placebo group. Conclusions: This study did not find group differences between the quetiapine and placebo arms, suggesting that quetiapine is not an efficacious treatment for DSM-IV cocaine dependence. Published by Elsevier Ireland Ltd. C1 [Tapp, Andre] Univ Washington, Amer Lake Div A 116, VA Puget Sound Hlth Care Syst, Tacoma, WA 98493 USA. [Wood, Amanda Ernst; Sylvers, Patrick; Kilzieh, Nael; Saxon, Andrew J.] Univ Washington, VA Puget Sound Hlth Care Syst, Tacoma, WA 98493 USA. [Kennedy, Annette] Univ Wyoming, Sheridan VAMC, Laramie, WY 82071 USA. RP Tapp, A (reprint author), Univ Washington, Amer Lake Div A 116, VA Puget Sound Hlth Care Syst, 9600 Vet Dr SW, Tacoma, WA 98493 USA. EM Andre.Tapp@va.gov FU AstraZeneca Pharmaceuticals FX Funding for this study was provided by an investigator initiated grant from AstraZeneca Pharmaceuticals; AstraZeneca Pharmaceuticals had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 47 TC 3 Z9 3 U1 1 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD APR 1 PY 2015 VL 149 BP 18 EP 24 DI 10.1016/j.drugalcdep.2014.12.037 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA CE4KJ UT WOS:000351799200003 PM 25682480 ER PT J AU Hoerster, KD Jakupcak, M Hanson, R McFall, M Reiber, G Hall, KS Nelson, KM AF Hoerster, Katherine D. Jakupcak, Matthew Hanson, Robert McFall, Miles Reiber, Gayle Hall, Katherine S. Nelson, Karin M. TI PTSD and depression symptoms are associated with binge eating among US Iraq and Afghanistan veterans SO EATING BEHAVIORS LA English DT Article DE Veterans; Post-traumatic stress disorder; Depression; Obesity; Binge eating ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH; OBESE VETERANS; CARE; OVERWEIGHT; MILITARY; BEHAVIOR AB Objective: US Iraq and Afghanistan Veterans with post-traumatic stress disorder (PTSD) and depression are at increased risk for obesity. Understanding the contribution of health behaviors to this relationship will enhance efforts to prevent and reduce obesity. Therefore, we examined the association of PTSD and depression symptoms with binge eating, a risk factor for obesity, among Iraq/Afghanistan Veterans. Method: Iraq/Afghanistan Veterans were assessed at intake to the VA Puget Sound Healthcare System-Seattle post-deployment clinic (May 2004-January 2007). The Patient Health Questionnaire was used to measure depression and binge eating symptoms, and the PTSD Checklist-Military Version assessed PTSD symptoms. Results: The majority of the sample (N = 332) was male (91.5%) and Caucasian (72.6%), with an average age of 31.1 (SD = 8.5) years; 16.3% met depression screening criteria, 37.8% met PTSD screening criteria, and 8.4% met binge eating screening criteria. In adjusted models, those meeting depression (odds ratio (OR) = 7.53; 95% CI = 2.69, 21.04; p < .001) and PTSD (OR = 3.37; 95% CI = 1.34, 8.46; p = .01) screening criteria were more likely to meet binge eating screening criteria. Continuous measures of PTSD and depression symptom severity were also associated with meeting binge eating screening criteria (ps < .05). Conclusion: PTSD and depression are common conditions among Iraq/Afghanistan Veterans. In the present study, PTSD and depression symptoms were associated with meeting binge eating screening criteria, identifying a possible pathway by which psychiatric conditions lead to disproportionate burden of overweight and obesity in this Veteran cohort. Tailored dietary behavior interventions may be needed for Iraq/Afghanistan Veterans with co-morbid obesity and psychiatric conditions. Published by Elsevier Ltd. C1 [Hoerster, Katherine D.; Jakupcak, Matthew; McFall, Miles] VA Puget Sound Healthcare Syst, Seattle Div, Mental Hlth Serv, Seattle, WA 98108 USA. [Hoerster, Katherine D.; Jakupcak, Matthew; McFall, Miles] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Hanson, Robert; Reiber, Gayle; Nelson, Karin M.] VA Puget Sound Healthcare Syst, Res & Dev Serv, Seattle, WA 98108 USA. [Reiber, Gayle] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Reiber, Gayle] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Hall, Katherine S.] Durham Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC 27705 USA. [Hall, Katherine S.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Nelson, Karin M.] VA Puget Sound Healthcare Syst, Gen Internal Med Serv, Seattle, WA 98108 USA. [Nelson, Karin M.] Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Hoerster, KD (reprint author), 1660 S Columbian Way S-116, Seattle, WA 98108 USA. EM Katherine.Hoerster@va.gov; Matthew.Jakupcak@va.gov; Robert.Hanson@va.gov; Miles.McFall@va.gov; Gayle.Reiber@va.gov; katherine.hall@duke.edu; Karin.Nelson@va.gov FU Career Development Award from the Rehabilitation Research and Development Service of the Department of Veterans Affairs [2RX001316] FX There was no funding for this paper. This material is the result of work supported by resources from VA Puget Sound Healthcare System. Dr. Hall is funded by a Career Development Award from the Rehabilitation Research and Development Service of the Department of Veterans Affairs (2RX001316). The funders 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 22 TC 7 Z9 7 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1471-0153 EI 1873-7358 J9 EAT BEHAV JI Eat. Behav. PD APR PY 2015 VL 17 BP 115 EP 118 DI 10.1016/j.eatbeh.2015.01.005 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CE4XP UT WOS:000351834000025 PM 25687231 ER PT J AU Boyle, FM Smith, IE O'Shaughnessy, J Ejlertsen, B Buzdar, AU Fumoleau, P Gradishar, W Martin, M Moy, B Piccart-Gebhart, M Pritchard, KI Lindquist, D Amonkar, M Huang, YJ Rappold, E Williams, LS Wang-Silvanto, J Kaneko, T Finkelstein, DM Goss, PE AF Boyle, Frances M. Smith, Ian E. O'Shaughnessy, Joyce Ejlertsen, Bent Buzdar, Aman U. Fumoleau, Pierre Gradishar, William Martin, Miguel Moy, Beverly Piccart-Gebhart, Martine Pritchard, Kathleen I. Lindquist, Deborah Amonkar, Mayur Huang, Yingjie Rappold, Erica Williams, Lisa S. Wang-Silvanto, Jing Kaneko, Tomomi Finkelstein, Dianne M. Goss, Paul E. CA TEACH Investigators TI Health related quality of life of women in TEACH, a randomised placebo controlled adjuvant trial of lapatinib in early stage Human Epidermal Growth Factor Receptor (HER2) overexpressing breast cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Tykerb/Tyverb; Evaluation After; Chemotherapy (TEACH) trial; Health related quality of life; HRQOL; Adjuvant breast cancer; Human Epidermal Growth Factor Receptor (HER2); HER2 positive; Early breast cancer; Lapatinib; Placebo; SF-36 ID THERAPY AB Background: To evaluate health related quality of life (HRQOL) in TEACH, a phase III randomized placebo controlled trial of 12 months of adjuvant lapatinib in HER2 positive (HER2+) early breast cancer which demonstrated marginal benefit in disease-free survival. Methods: Women on TEACH completed the Short Form 36-item health survey (version2; SF-36v2) at the baseline, six and 12 months after therapy initiation and six monthly thereafter. Mean changes were compared between treatment groups for two summary measures (Physical and Mental Component Summary scores; PCS and MCS) and eight domain measures (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health), and in patients discontinuing therapy. A five-point change was deemed a Minimally Clinically Important Difference (MCID). Response analysis compared the proportion of patients demonstrating a MCID in HRQOL, and a regression analysis identified predictors of worsening HRQOL. Findings: 3074 (97%) subjects completed baseline SF-36v2. During the initial 12 months, summary SF-36v2 scores decreased in both arms but did not reach Minimally Clinically Important Difference (MCID) despite significant incidences of diarrhoea and rash in lapatinib treated patients. At six months, women receiving lapatinib had more significant reductions (p < 0.01 versus placebo) in social functioning. Early treatment discontinuations were more frequent on lapatinib (32% versus 18%), and were associated with more substantial decrements of HRQOL in both arms. For those discontinuing primarily due to adverse events, decrements in HRQOL reached MCID in Mental Summary scores (MCS) only. Lower baseline HRQOL was a significant predictor of worsening HRQOL (p < 0.05). Interpretation: Despite frequent but usually mild toxicities, adjuvant lapatinib is not associated with clinically significant decreases in overall HRQOL. These placebo-controlled results may also help to inform physicians and patients using lapatinib in metastatic HER2 positive breast cancer. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Boyle, Frances M.] Mater Hosp, Sydney, NSW, Australia. [Moy, Beverly; Finkelstein, Dianne M.; Goss, Paul E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Smith, Ian E.] Royal Marsden Hosp, London SW3 6JJ, England. [O'Shaughnessy, Joyce] US Oncol, Texas Oncol, Baylor Sammons Canc Ctr, Dallas, TX USA. [Ejlertsen, Bent] Rigshosp, DBCG Secretariat, DK-2100 Copenhagen, Denmark. [Buzdar, Aman U.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Fumoleau, Pierre] Ctr GF Leclerc, Dijon, France. [Gradishar, William] Northwestern Univ, Chicago, IL 60611 USA. [Martin, Miguel] Univ Complutense Madrid, Hosp Univ Gregorio Maranon, Madrid, Spain. [Piccart-Gebhart, Martine] Univ Libre Bruxelles, Inst Jules Bordet, Brussels, Belgium. [Pritchard, Kathleen I.] Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Lindquist, Deborah] US Oncol, Arizona Oncol, Sedona, AZ USA. [Amonkar, Mayur; Huang, Yingjie; Rappold, Erica; Williams, Lisa S.; Wang-Silvanto, Jing; Kaneko, Tomomi] GlaxoSmithKline, Collegeville, PA USA. [Amonkar, Mayur; Huang, Yingjie; Rappold, Erica; Williams, Lisa S.; Wang-Silvanto, Jing; Kaneko, Tomomi] GlaxoSmithKline, Uxbridge, Middx, England. RP Boyle, FM (reprint author), Mater Hosp, Patricia Ritchie Ctr Canc Care & Res, 25 Rocklands Rd, Sydney, NSW 2060, Australia. EM frances.boyle@sydney.edu.au OI MARTIN, MIGUEL/0000-0001-9237-3231; Brunet, Joan/0000-0003-1945-3512 NR 18 TC 1 Z9 1 U1 2 U2 6 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 APR PY 2015 VL 51 IS 6 BP 685 EP 696 DI 10.1016/j.ejca.2015.02.005 PG 12 WC Oncology SC Oncology GA CE4YA UT WOS:000351835200001 PM 25752740 ER PT J AU Flores-Blanco, PJ Lopez-Cuenca, A Januzzi, JL Marin, F Sanchez-Martinez, M Quintana-Giner, M Romero-Aniorte, AI Valdes, M Manzano-Fernandez, S AF Flores-Blanco, Pedro J. Lopez-Cuenca, Angel Januzzi, James L. Marin, Francisco Sanchez-Martinez, Marianela Quintana-Giner, Miriam Romero-Aniorte, Ana I. Valdes, Mariano Manzano-Fernandez, Sergio TI Major bleeding risk prediction using Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease equations in acute coronary syndrome SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE Acute coronary syndrome; haemorrhage; kidney; prognosis ID GLOMERULAR-FILTRATION-RATE; PLATELET GLYCOPROTEIN IIB/IIIA; SUPPRESS ADVERSE OUTCOMES; BETA-TRACE-PROTEIN; SERUM CYSTATIN-C; UNSTABLE ANGINA; MYOCARDIAL-INFARCTION; EARLY IMPLEMENTATION; GLOBAL REGISTRY; ESTIMATING GFR AB BackgroundChronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular filtration rate more accurately than the Modification of Diet in Renal Disease (MDRD) Study equation. Our aim was to evaluate whether CKD-EPI equations based on serum creatinine and/or cystatin C (CysC) predict risk for major bleeding (MB) more accurately than the MDRD Study equation in patients with non-ST-segment elevation acute coronary syndromes (ACS). Materials and methodsThree hundred and fifty consecutive subjects with non-ST-segment elevation ACS (6812years, 70% male) were studied. Glomerular filtration rate was estimated using the CKD-EPI and MDRD Study equations. The primary endpoint was the occurrence of MB during the follow-up, which was defined according to the Bleeding Academic Research Consortium Definition criteria as bleeding types 3-5. ResultsDuring the median follow-up of 589days (interquartile range, 390-986), 27 patients had MB (004% events per person year). Patients with MB had worse kidney function parameters, regardless of the estimating equation used (P<0001). After multivariate Cox regression adjustment, both CysC-based CKD-EPI equations were independent predictors of MB (CKD-EPIcreatinine-cystatin (C) per mL/min/173m(2), HR=0973 (95%CI 0955-0991; P=0003) and CKD-EPIcystatin (C) per mL/min/173m(2), HR=0976 (95%CI 0976-0992; P=0003), while the CKD-EPIcreatinine and MDRD equations did not achieve statistical significance. Both CKD-EPIcreatine-cystatin (C) and CKD-EPIcystatin (C) were associated with a significant improvement in MB risk reclassification. ConclusionsIn this cohort of non-ST-segment elevation ACS patients with relatively preserved renal function, both CysC-based CKD-EPI equations improved ability to predict risk for MB and were superior to other equations for this application. C1 [Flores-Blanco, Pedro J.; Marin, Francisco; Sanchez-Martinez, Marianela; Quintana-Giner, Miriam; Romero-Aniorte, Ana I.; Valdes, Mariano; Manzano-Fernandez, Sergio] Hosp Clin Univ Virgen de la Arrixaca, Dept Cardiol, Murcia 30120, Spain. [Lopez-Cuenca, Angel] Hosp Vega Lorenzo Guirao, Dept Cardiol, Murcia 30530, Spain. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Marin, Francisco; Valdes, Mariano; Manzano-Fernandez, Sergio] Univ Murcia, Sch Med, Dept Cardiol, E-30100 Murcia, Spain. RP Flores-Blanco, PJ (reprint author), Univ Murcia, Univ Hosp Virgen de la Arrixaca, Div Cardiol, Sch Med, Carretera Madrid Cartagena S-N, Murcia 30120, Spain. EM pedrofb1986@gmail.com OI Flores-Blanco, Pedro J/0000-0002-6394-9841 NR 39 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2972 EI 1365-2362 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD APR PY 2015 VL 45 IS 4 BP 385 EP 393 DI 10.1111/eci.12418 PG 9 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA CE7GZ UT WOS:000352008100003 PM 25661774 ER PT J AU Chi, W Wu, E Morgan, BA AF Chi, Woo Wu, Eleanor Morgan, Bruce A. TI Earlier- born secondary hair follicles exhibit phenotypic plasticity SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE dermal papilla; hair type conversion; Sox2 ID DERMAL PAPILLA CELLS; MOUSE SKIN; SOX2; REGENERATION; EXPRESSION; MUTATIONS; GROWTH; MICE; SIZE AB The mouse pelage is composed of four distinct hair types. The fact that the follicles that generate these hair types form in successive waves during late embryonic development suggested the model that distinct epigenetic states of the inductive mesenchyme fixed when the follicles are formed specify the distinctive hair morphologies. This model is inconsistent with the observation that many follicles produce different hair types in successive hair cycles. In this study, the characteristics of the hair follicles that switch between the production of different hair types were examined. These follicles were born earlier than those that do not switch between hair types and made longer hairs. They also expressed a higher level of Sox2 in the dermal papilla and had more DP cells per follicle. These observations are consistent with the hypothesis that different birthdates specify the potential of different follicles. However, rather than directly specifying hair type, birthdate correlates with three types: guard hairs, a plastic population that can make awl, auchene or zigzag hairs, and a population that normally makes only zigzag hairs. Although Sox2 expression levels in the DP identify this subset during the morphogenetic cycle, Sox2 expression is not a fixed epigenetic state specified when the follicle is first formed. C1 [Chi, Woo; Wu, Eleanor; Morgan, Bruce A.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. [Chi, Woo; Morgan, Bruce A.] Harvard Univ, Sch Med, Boston, MA USA. RP Morgan, BA (reprint author), Cutaneous Biol Res Ctr, 149 13th St, Charlestown, MA 02119 USA. EM bmorgan@mgh.harvard.edu FU NIAMS [5R01AR055256] FX The authors thank R. Czyzewski for technical assistance. This work was funded by grant 5R01AR055256 from the NIAMS to BAM. W.C. and B.A.M. designed the study, W.C. and E.W. collected data, and W.C. and B.A.M. analysed data and wrote the manuscript. All procedures were approved by the Massachusetts General Hospital Subcommittee on Research Animal Care. NR 16 TC 2 Z9 2 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0906-6705 EI 1600-0625 J9 EXP DERMATOL JI Exp. Dermatol. PD APR PY 2015 VL 24 IS 4 BP 265 EP 268 DI 10.1111/exd.12608 PG 4 WC Dermatology SC Dermatology GA CE6GZ UT WOS:000351936100009 PM 25431314 ER PT J AU Guze, K Pawluk, HC Short, M Zeng, HS Lorch, J Norris, C Sonis, S AF Guze, Kevin Pawluk, Hanna C. Short, Michael Zeng, Haishan Lorch, Jochen Norris, Charles Sonis, Stephen TI Pilot study: Raman spectroscopy in differentiating premalignant and malignant oral lesions from normal mucosa and benign lesions in humans SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE Raman; oral cancer; squamous cell carcinoma (SCC); diagnostics; spectroscopy ID CANCER DIAGNOSIS; OPTICAL DIAGNOSIS; MICROENDOSCOPE; IDENTIFICATION; FLUORESCENCE; DYSPLASIA; NEOPLASIA; TISSUES; PROBE AB BackgroundCurrent practice for differentiating tissue lesions are based on histopathological criteria. This process is subject to error. The purpose of this study was to test whether an alternative, tissue-based molecular signatures Raman spectra could be used to differentiate premalignant and malignant lesions from normal mucosa or benign lesions. MethodsEighteen treatment naive subjects with histologically diagnosed oral disease were studied by comparing the Raman spectra of lesions with contralateral healthy sites. Principle component and multivariate analysis were used to predict which of the tissue groups the average spectrum of each lesion or normal tissue belonged. ResultsThe average spectra were clearly different between premalignant and malignant lesions and those derived from normal, benign tissues. Premalignant and malignant lesions could be predicted with 100% sensitivity and 77% specificity. ConclusionRaman spectroscopy (RS) offers the potential to provide point of care diagnosis of oral disease using a noninvasive, convenient, and relatively inexpensive technology. (c) 2014 Wiley Periodicals, Inc. Head Neck, 2014 (c) 2014 Wiley Periodicals, Inc. Head Neck37: 511-517, 2015 C1 [Guze, Kevin; Sonis, Stephen] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Pawluk, Hanna C.; Short, Michael; Zeng, Haishan] British Columbia Canc Agcy, Res Ctr, Integrat Oncol Dept, Imaging Unit, Vancouver, BC V5Z 4E6, Canada. [Lorch, Jochen; Norris, Charles] Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. [Guze, Kevin; Sonis, Stephen] Dana Farber Canc Inst, Div Oral Med, Boston, MA 02115 USA. [Guze, Kevin; Sonis, Stephen] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Guze, K (reprint author), Harvard Univ, Sch Dent Med, Dept Periodontol, Longwood Campus,188 Longwood Ave, Boston, MA 02115 USA. EM Kevin_guze@hsdm.harvard.edu NR 43 TC 11 Z9 11 U1 2 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1043-3074 EI 1097-0347 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD APR PY 2015 VL 37 IS 4 BP 511 EP 517 DI 10.1002/hed.23629 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CE2ZB UT WOS:000351690800011 PM 24677300 ER PT J AU Urken, ML Milas, M Randolph, GW Tufano, R Bergman, D Bernet, V Brett, EM Brierley, JD Cobin, R Doherty, G Klopper, J Lee, S Machac, J Mechanick, JI Orloff, LA Ross, D Smallridge, RC Terris, DJ Clain, JB Tuttle, M AF Urken, Mark L. Milas, Mira Randolph, Gregory W. Tufano, Ralph Bergman, Donald Bernet, Victor Brett, Elise M. Brierley, James D. Cobin, Rhoda Doherty, Gerard Klopper, Joshua Lee, Stephanie Machac, Josef Mechanick, Jeffrey I. Orloff, Lisa A. Ross, Douglas Smallridge, Robert C. Terris, David J. Clain, Jason B. Tuttle, Michael TI Management of recurrent and persistent metastatic lymph nodes in well-differentiated thyroid cancer: A multifactorial decision-making guide for the Thyroid Cancer Care Collaborative SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Review DE persistent thyroid cancer; recurrent thyroid cancer; thyroid cancer care collaborative (TCCC); clinical decision-making modules (CDMMs); reoperation ID CENTRAL COMPARTMENT DISSECTION; UNDERWENT TOTAL THYROIDECTOMY; EXTERNAL-BEAM RADIOTHERAPY; CENTRAL NECK DISSECTION; RADIOACTIVE IODINE; SERUM THYROGLOBULIN; REMNANT ABLATION; CASTLEMANS-DISEASE; NODAL METASTASES; PAPILLARY AB BackgroundWell-differentiated thyroid cancer (WDTC) recurs in up to 30% of patients. Guidelines from the American Thyroid Association (ATA) and the National Comprehensive Cancer Network (NCCN) provide valuable parameters for the management of recurrent disease, but fail to guide the clinician as to the multitude of factors that should be taken into account. The Thyroid Cancer Care Collaborative (TCCC) is a web-based repository of a patient's clinical information. Ten clinical decision-making modules (CDMMs) process this information and display individualized treatment recommendations. MethodsWe conducted a review of the literature and analysis of the management of patients with recurrent/persistent WDTC. ResultsSurgery remains the most common treatment in recurrent/persistent WDTC and can be performed with limited morbidity in experienced hands. However, careful observation may be the recommended course in select patients. Reoperation yields biochemical remission rates between 21% and 66%. There is a reported 1.2% incidence of permanent unexpected nerve paralysis and a 3.5% incidence of permanent hypoparathyroidism. External beam radiotherapy and percutaneous ethanol ablation have been reported as therapeutic alternatives. Radioactive iodine as a primary therapy has been reported previously for metastatic lymph nodes, but is currently advocated by the ATA as an adjuvant to surgery. ConclusionThe management of recurrent lymph nodes is a multifactorial decision and is best determined by a multidisciplinary team. The CDMMs allow for easy adoption of contemporary knowledge, making this information accessible to both patient and clinician. (c) 2014 Wiley Periodicals, Inc. Head Neck37: 605-614, 2015 C1 [Urken, Mark L.] Beth Israel Deaconess Med Ctr, Dept Otolaryngol Head & Neck Surg, New York, NY 10003 USA. [Milas, Mira] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97201 USA. [Randolph, Gregory W.] Massachusetts Eye & Ear, Dept Otolaryngol, Boston, MA USA. [Tufano, Ralph] Johns Hopkins Sch Med, Dept Otolaryngol Head & Neck Surg, Outpatient Ctr, Baltimore, MD USA. [Bergman, Donald; Brett, Elise M.; Mechanick, Jeffrey I.] Mt Sinai Sch Med, Dept Endocrinol, New York, NY USA. [Bernet, Victor; Smallridge, Robert C.] Mayo Clin, Dept Endocrinol, Jacksonville, FL 32224 USA. [Brierley, James D.] Univ Toronto, Dept Radiat Oncol, Toronto, ON, Canada. [Cobin, Rhoda] Mt Sinai Sch Med, Dept Med, Ridgewood, NJ USA. [Doherty, Gerard] Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. [Klopper, Joshua] Univ Colorado, Sch Med, Dept Endocrinol, Denver, CO USA. [Lee, Stephanie] Boston Univ, Sch Med, Dept Endocrinol, Boston, MA 02118 USA. [Machac, Josef] Mt Sinai Sch Med, Dept Radiol, New York, NY USA. [Orloff, Lisa A.] Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, Med Ctr, San Francisco, CA USA. [Ross, Douglas] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Terris, David J.] Georgia Regents Univ, Dept Otolaryngol, Augusta, GA, Rep of Georgia. [Clain, Jason B.] Thyroid Head & Neck Canc Fdn, Head & Neck Oncol, New York, NY 10003 USA. [Tuttle, Michael] Mem Sloan Kettering Canc Ctr, Dept Endocrinol, New York, NY 10021 USA. RP Clain, JB (reprint author), Thyroid Head & Neck Canc Fdn, Head & Neck Oncol, 10 Union Sq East,Suite 5B, New York, NY 10003 USA. EM Jclain@thancfoundation.org FU Continuum Health Partners FX Contract grant sponsor: This study was conducted with the generous support of Continuum Health Partners. NR 64 TC 13 Z9 13 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1043-3074 EI 1097-0347 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD APR PY 2015 VL 37 IS 4 BP 605 EP 614 DI 10.1002/hed.23615 PG 10 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CE2ZB UT WOS:000351690800024 PM 24436291 ER PT J AU Murray, RJ Debbane, M Fox, PT Bzdok, D Eickhoff, SB AF Murray, Ryan J. Debbane, Martin Fox, Peter T. Bzdok, Danilo Eickhoff, Simon B. TI Functional Connectivity Mapping of Regions Associated with Self- and Other-Processing SO HUMAN BRAIN MAPPING LA English DT Review DE self-concept; rostral anterior cingulate; social value; posterior cingulate; precuneus; social cognition; connectivity ID ANTERIOR CINGULATE CORTEX; COORDINATE-BASED METAANALYSIS; CORTICAL MIDLINE STRUCTURES; TEMPORO-PARIETAL JUNCTION; MEDIAL PREFRONTAL CORTEX; DEFAULT-MODE NETWORK; SOCIAL COGNITION; DECISION-MAKING; TEMPOROPARIETAL JUNCTION; HUMAN BRAIN AB Neuroscience literature increasingly suggests a conceptual self composed of interacting neural regions, rather than independent local activations, yet such claims have yet to be investigated. We, thus, combined task-dependent meta-analytic connectivity modeling (MACM) with task-independent resting-state (RS) connectivity analysis to delineate the neural network of the self, across both states. Given psychological evidence implicating the self's interdependence on social information, we also delineated the neural network underlying conceptual other-processing. To elucidate the relation between the self-/other-networks and their function, we mined the MACM metadata to generate a cognitive-behavioral profile for an empirically identified region specific to conceptual self, the pregenual anterior cingulate (pACC), and conceptual other, posterior cingulate/precuneus (PCC/PC). Mining of 7,200 published, task-dependent, neuroimaging studies, using healthy human subjects, yielded 193 studies activating the self-related seed and were conjoined with RS connectivity analysis to delineate a differentiated self-network composed of the pACC (seed) and anterior insula, relative to other functional connectivity. Additionally, 106 studies activating the other-related seed were conjoined with RS connectivity analysis to delineate a differentiated other-network of PCC/PC (seed) and angular gyrus/temporoparietal junction, relative to self-functional connectivity. The self-network seed related to emotional conflict resolution and motivational processing, whereas the other-network seed related to socially oriented processing and contextual information integration. Notably, our findings revealed shared RS connectivity between ensuing self-/other-networks within the ventromedial prefrontal cortex and medial orbitofrontal cortex, suggesting self-updating via integration of self-relevant social information. We, therefore, present initial neurobiological evidence corroborating the increasing claims of an intricate self-network, the architecture of which may promote social value processing. Hum Brain Mapp 36:1304-1324, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Murray, Ryan J.; Debbane, Martin] Univ Geneva, Fac Psychol & Educ Sci, Dev Clin Psychol Res Unit, Geneva, Switzerland. [Murray, Ryan J.] Univ Geneva, Swiss Ctr Affect Sci, Geneva, Switzerland. [Debbane, Martin] Univ Geneva, Geneva Fac Med, Dept Psychiat, Off Med Pedagog, Geneva, Switzerland. [Debbane, Martin] UCL, Res Dept Clin Educ & Hlth Psychol, London WC1E 6BT, England. [Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Fox, Peter T.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Bzdok, Danilo; Eickhoff, Simon B.] Res Ctr Julich, Inst Neurosci & Med INM 1, Julich, Germany. [Bzdok, Danilo; Eickhoff, Simon B.] Univ Dusseldorf, Inst Clin Neurosci & Med Psychol, Dusseldorf, Germany. RP Murray, RJ (reprint author), CISA Univ Geneva, Campus Biotech,Case Postale 60, CH-1211 Geneva 20, Switzerland. EM ryan.murray@unige.ch RI Eickhoff, Simon/K-2061-2013 OI Eickhoff, Simon/0000-0001-6363-2759 FU National Institute of Mental Health 907 [R01-MH074457]; Initiative and Networking Fund of the Helmholtz Association within the Helmholtz Alliance on Systems Biology (Human Brain Model); Swiss National Science Foundation [100014-135311/1] FX Contract grant sponsor: the National Institute of Mental Health 907; Contract grant number: R01-MH074457; Contract grant sponsor: the Initiative and Networking Fund of the Helmholtz Association within the Helmholtz Alliance on Systems Biology (Human Brain Model); Contract grant sponsor: the Swiss National Science Foundation; Contract grant number: 100014-135311/1 NR 151 TC 14 Z9 14 U1 5 U2 33 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD APR PY 2015 VL 36 IS 4 BP 1304 EP 1324 DI 10.1002/hbm.22703 PG 21 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CE3OX UT WOS:000351737800006 PM 25482016 ER PT J AU Persson, J Rieckmann, A Kalpouzos, G Fischer, H Backman, L AF Persson, Jonas Rieckmann, Anna Kalpouzos, Gregoria Fischer, Hakan Backman, Lars TI Influences of a DRD2 Polymorphism on Updating of Long-Term Memory Representations and Caudate BOLD Activity: Magnification in Aging SO HUMAN BRAIN MAPPING LA English DT Article DE functional magnetic resonance imaging (fMRI); memory; aging; dopamine; DRD2; updating; striatum ID DOPAMINE-RECEPTOR GENE; STRIATAL DOPAMINE; WORKING-MEMORY; COGNITIVE PERFORMANCE; HEALTHY-VOLUNTEERS; CEREBRAL-CORTEX; HUMAN BRAIN; A1 ALLELE; OLD-AGE; CAPACITY AB A number of genetic polymorphisms are related to individual differences in cognitive performance. Striatal dopamine (DA) functions, associated with cognitive performance, are linked to the TaqIA polymorphism of the DRD2/ANKK1 gene. In humans, presence of an A1 allele of the DRD2/ANKK1-TaqIA polymorphism is related to reduced density of striatal DA D2 receptors. The resource-modulation hypothesis assumes that aging-related losses of neurochemical and structural brain resources modulate the extent to which genetic variations affect cognitive functioning. Here, we tested this hypothesis using functional MRI during long-term memory (LTM) updating in younger and older carriers and noncarriers of the A1-allele of the TaqIa polymorphism. We demonstrate that older A1-carriers have worse memory performance, specifically during LTM updating, compared to noncarriers. Moreover, A1-carriers exhibited less blood oxygen level-dependent (BOLD) activation in left caudate nucleus, a region critical to updating. This effect was only seen in older adults, suggesting magnification of genetic effects on functional brain activity in aging. Further, a positive relationship between caudate BOLD activation and updating performance among non-A1 carriers indicated that caudate activation was behaviorally relevant. These results demonstrate a link between the DRD2/ANKK1-TaqIA polymorphism and neurocognitive deficits related to LTM updating, and provide novel evidence that this effect is magnified in aging. Hum Brain Mapp 36:1325-1334, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Persson, Jonas; Kalpouzos, Gregoria; Fischer, Hakan; Backman, Lars] Karolinska Inst, ARC, S-11330 Stockholm, Sweden. [Persson, Jonas; Kalpouzos, Gregoria; Fischer, Hakan; Backman, Lars] Stockholm Univ, S-11330 Stockholm, Sweden. [Persson, Jonas; Fischer, Hakan] Stockholm Univ, Dept Psychol, S-11330 Stockholm, Sweden. [Persson, Jonas; Rieckmann, Anna] Umea Univ, Umea Ctr Funct Brain Imaging UFBI, SE-90187 Umea, Sweden. [Rieckmann, Anna] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Persson, J (reprint author), Karolinska Inst, ARC, Gavlegatan 16, S-11330 Stockholm, Sweden. EM jonas.persson.1@ki.se OI Persson, Jonas/0000-0001-9143-3730 FU Swedish Research Council; Swedish Brain Power; Alexander von Humboldt Research Award; af Jochnick Foundation FX Contract grant sponsors: Swedish Research Council and Swedish Brain Power; Alexander von Humboldt Research Award; af Jochnick Foundation (L.B.); Swedish Research Council (H.F.) NR 50 TC 4 Z9 4 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD APR PY 2015 VL 36 IS 4 BP 1325 EP 1334 DI 10.1002/hbm.22704 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CE3OX UT WOS:000351737800007 PM 25486867 ER PT J AU Wachinger, C Golland, P Magnain, C Fischl, B Reuter, M AF Wachinger, Christian Golland, Polina Magnain, Caroline Fischl, Bruce Reuter, Martin TI Multi-Modal Robust Inverse-Consistent Linear Registration SO HUMAN BRAIN MAPPING LA English DT Article DE computer-assisted image analysis; rigid and affine image alignment; statistical model; magnetic resonance imaging; optical coherence tomography; histology ID MEDICAL IMAGE REGISTRATION; OPTICAL COHERENCE TOMOGRAPHY; MUTUAL INFORMATION; NONPARAMETRIC WINDOWS; CROSS-CORRELATION; LEAST-SQUARES; BRAIN; ACCURATE; ALIGNMENT; REPRESENTATIONS AB Registration performance can significantly deteriorate when image regions do not comply with model assumptions. Robust estimation improves registration accuracy by reducing or ignoring the contribution of voxels with large intensity differences, but existing approaches are limited to monomodal registration. In this work, we propose a robust and inverse-consistent technique for cross-modal, affine image registration. The algorithm is derived from a contextual framework of image registration. The key idea is to use a modality invariant representation of images based on local entropy estimation, and to incorporate a heteroskedastic noise model. This noise model allows us to draw the analogy to iteratively reweighted least squares estimation and to leverage existing weighting functions to account for differences in local information content in multimodal registration. Furthermore, we use the nonparametric windows density estimator to reliably calculate entropy of small image patches. Finally, we derive the Gauss-Newton update and show that it is equivalent to the efficient second-order minimization for the fully symmetric registration approach. We illustrate excellent performance of the proposed methods on datasets containing outliers for alignment of brain tumor, full head, and histology images. Hum Brain Mapp 36:1365-1380, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Wachinger, Christian; Golland, Polina; Fischl, Bruce; Reuter, Martin] MIT, Dept Elect Engn & Comp Sci, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Wachinger, Christian; Reuter, Martin] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Magnain, Caroline; Fischl, Bruce; Reuter, Martin] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Wachinger, C (reprint author), MIT, 32 Vassar St, Cambridge, MA 02139 USA. EM wachinge@mit.edu RI Christian, Wachinger/L-7358-2016; OI Christian, Wachinger/0000-0002-3652-1874; Reuter, Martin/0000-0002-2665-9693 FU Humboldt foundation; National Cancer Institute [K25-CA181632-01A1]; National Center for Research Resources [P41-RR13218, P41-RR14075, U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering [R01EB006758, NAMIC U54-EB005149]; National Institute on Aging [AG022381, 5R01AG008122-22]; National Center for Alternative Medicine [RC1 AT005728-01]; National Institute for Neurological Disorders and Stroke [R01 NS052585-01, 1R21NS072652-01, 1R01NS070963]; Shared Instrumentation Grants [1S10RR023401, 1S10RR019307, 1S10RR023043]; Autism & Dyslexia Project (Ellison Medical Foundation); NIH Blueprint for Neuroscience Research (part of the multi-institutional Human Connectome Project) [5U01-MH093765] FX Contract grant sponsor: Humboldt foundation; Contract grant sponsor: National Cancer Institute; Contract grant number: K25-CA181632-01A1; Contract grant sponsor: National Center for Research Resources; Contract grant numbers: P41-RR13218, P41-RR14075, and U24 RR021382; Contract grant sponsor: National Institute for Biomedical Imaging and Bioengineering; Contract grant numbers: R01EB006758 and NAMIC U54-EB005149; Contract grant sponsor: National Institute on Aging; Contract grant numbers: AG022381 and 5R01AG008122-22; Contract grant sponsor: National Center for Alternative Medicine; Contract grant number: RC1 AT005728-01; Contract grant sponsor: National Institute for Neurological Disorders and Stroke; Contract grant numbers: R01 NS052585-01, 1R21NS072652-01, and 1R01NS070963; Contract grant sponsor: Shared Instrumentation Grants; Contract grant numbers: 1S10RR023401, 1S10RR019307, and 1S10RR023043; Contract grant sponsor: The Autism & Dyslexia Project (Ellison Medical Foundation); Contract grant sponsor: NIH Blueprint for Neuroscience Research (part of the multi-institutional Human Connectome Project); Contract grant number: 5U01-MH093765 NR 57 TC 1 Z9 1 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD APR PY 2015 VL 36 IS 4 BP 1365 EP 1380 DI 10.1002/hbm.22707 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CE3OX UT WOS:000351737800010 PM 25470798 ER PT J AU Belkind-Gerson, J Hotta, R Nagy, N Thomas, AR Graham, H Cheng, L Solorzano, J Nguyen, D Kamionek, M Dietrich, J Cherayil, BJ Goldstein, AM AF Belkind-Gerson, Jaime Hotta, Ryo Nagy, Nandor Thomas, Alyssa R. Graham, Hannah Cheng, Lily Solorzano, Juan Nguyen, Deanna Kamionek, Michal Dietrich, Jorg Cherayil, Bobby J. Goldstein, Allan M. TI Colitis Induces Enteric Neurogenesis Through a 5-HT4-dependent Mechanism SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE enteric nervous system; neurogenesis; enteric glial cells; serotonin; colitis ID NEURAL STEM-CELLS; NERVOUS-SYSTEM; INTESTINAL INFLAMMATION; GLIAL-CELLS; RADIAL GLIA; MOUSE; NEURONS; MICE; GUT; REGENERATION AB Background:The intestine is known to contain enteric neuronal progenitors, but their precise identity and the mechanisms that activate them remain unknown. Based on the evidence for the neurogenic role of serotonin (5-HT) in the postnatal gut and the observation of enteric neuronal hyperplasia in inflammatory bowel disease, we hypothesized that colitis induces a neurogenic response through 5-HT4 receptor signaling.Methods:We examined the effects of 5-HT4 agonism on colonic neurogenesis and gliogenesis in vitro and in vivo in adult mice using dextran sodium sulfate to experimentally induce colitis.Results:In vitro, 5-HT4 agonism led to increased neuronal proliferation and density. Induction of experimental colitis in vivo similarly resulted in increased numbers of myenteric neurons, and this was inhibited by 5-HT4 antagonism. Interestingly, both in vitro and in vivo, 5-HT4 signaling increased glial cell proliferation but did not increase glial cell numbers, leading us to hypothesize that glia may give rise to neurons. After induction of colitis in normal, Nestin-GFP and Sox2-GFP transgenic mice, it was revealed that multiple glial markers (Sox2, Nestin, and CD49b) became strongly expressed by enteric neurons. Immunoselected enteric glia were found to give rise to neurons in culture, and this was inhibited in the presence of 5-HT4 blockade. Finally, isolated glia gave rise to a neuronal network upon transplantation into aganglionic embryonic avian hindgut.Conclusions:These results show that colitis promotes enteric neurogenesis in the adult colon through a serotonin-dependent mechanism that drives glial cells to transdifferentiate into neurons. C1 [Belkind-Gerson, Jaime] Massachusetts Gen Hosp, Dept Pediat, Mucosal Immunol & Biol Res Ctr, Boston, MA 02114 USA. [Belkind-Gerson, Jaime; Goldstein, Allan M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Neurogastroenterol Program, Boston, MA USA. [Hotta, Ryo; Nagy, Nandor; Thomas, Alyssa R.; Graham, Hannah; Cheng, Lily; Solorzano, Juan; Goldstein, Allan M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA USA. [Nagy, Nandor] Semmelweis Univ, Dept Human Morphol & Dev Bio, Fac Med, H-1085 Budapest, Hungary. [Nguyen, Deanna] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Kamionek, Michal] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Dietrich, Jorg] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Cherayil, Bobby J.] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Goldstein, AM (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Warren 1153, Boston, MA 02114 USA. EM agoldstein@partners.org NR 36 TC 9 Z9 9 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD APR PY 2015 VL 21 IS 4 BP 870 EP 878 DI 10.1097/MIB.0000000000000326 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CE2TM UT WOS:000351671500020 PM 25742399 ER PT J AU Cruz, S Crego, A Ribeiro, E Goncalves, O Sampaio, A AF Cruz, Sara Crego, Alberto Ribeiro, Eugenia Goncalves, Oscar Sampaio, Adriana TI A VEP study in sleeping and awake one-month-old infants and its relation with social behavior SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Infancy; State; VEPs; Neurobehavioral assessment; NBAS; Development ID VISUAL-EVOKED POTENTIALS; EVENT-RELATED POTENTIALS; PRETERM INFANTS; NEWBORN; RESPONSES; STATES; AGE AB With the present study we aimed to analyze the relationship between infants' behavior and their visual evoked-potential (VEPs) response. Specifically, we want to verify differences regarding the VEP response in sleeping and awake infants and if an association between VEP components, in both groups, with neuro-behavioral outcome could be identified. To do so, thirty-two full-term and healthy infants, approximately 1-month of age, were assessed through a VEP unpatterned flashlight stimuli paradigm, offered in two different intensities, and were assessed using a neurobehavioral scale. However, only 18 infants have both assessments, and therefore, these is the total included in both analysis. Infants displayed a mature neurobehavioral outcome, expected for their age. We observed that P2 and N3 components were present in both sleeping and awake infants. Differences between intensities were found regarding the P2 amplitude, but only in awake infants. Regression analysis showed that N3 amplitude predicted an adequate social interactive and internal regulatory behavior in infants who were awake during the stimuli presentation. Taking into account that social orientation and regulatory behaviors are fundamental keys for social-like behavior in 1-month-old infants, this study provides an important approach for assessing physiological biomarkers (VEPs) and its relation with social behavior, very early in postnatal development. Moreover, we evidence the importance of the infant's state when studying differences regarding visual threshold processing and its association with behavioral outcome. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Cruz, Sara; Crego, Alberto; Goncalves, Oscar; Sampaio, Adriana] Univ Minho, CIPsi Sch Psychol, Neuropsychophysiol Lab, Braga, Portugal. [Ribeiro, Eugenia] Univ Minho, CIPsi Sch Psychol, Braga, Portugal. [Goncalves, Oscar] Northeastern Univ, Bouve Coll Hlth Sci, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. [Goncalves, Oscar] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Spaulding Ctr Neuromodulat,Dept Phys Med & Rehabi, Boston, MA USA. [Goncalves, Oscar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Cruz, S (reprint author), Univ Minho, Sch Psychol, Neuropsychophysiol Lab, Campus Gualtar, P-4710057 Braga, Portugal. EM saracruz@psi.uminho.pt RI Goncalves, Oscar/G-5278-2010; Ribeiro, Eugenia/A-1574-2011; Sampaio, Adriana/C-8361-2011; Crego, Alberto/O-4035-2016 OI Goncalves, Oscar/0000-0003-2735-9155; Ribeiro, Eugenia/0000-0002-8749-7130; Sampaio, Adriana/0000-0001-7347-1282; Crego, Alberto/0000-0002-6621-690X FU Fundacao Bial [42/08]; Fundacao para a Ciencia e Tecnologia (FCT) [SFRH/BD/68263/2010] FX We would like to thank the families and infants who participated in this study. Also, we would like to thank Pedro Hispano Hospital, particularly to Dr. J. Lopes dos Santos, for all the kindness throughout the time that we were there for the data collection process. We thank to Maria de Gois-Eanes for all the help and knowledge entailed throughout this study. Furthermore, we thank Associacao Viver a Ciencia for the Simbiontes prize in 2013. This work was supported by Fundacao Bial (grant number 42/08) and financed by Fundacao para a Ciencia e Tecnologia (FCT) under a PhD grant (reference SFRH/BD/68263/2010). NR 43 TC 1 Z9 1 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 EI 1873-474X J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD APR PY 2015 VL 41 BP 37 EP 43 DI 10.1016/j.ijdevneu.2014.12.006 PG 7 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA CE4IJ UT WOS:000351794000005 PM 25522889 ER PT J AU Zhuo, YJ Xi, M Wan, YP Hua, W Liu, YL Wan, S Zhou, YL Luo, HW Wu, SL Zhong, WD Wu, CL AF Zhuo, Yang-Jia Xi, Ming Wan, Yue-Ping Hua, Wei Liu, Yuan-Ling Wan, Song Zhou, Yu-Lin Luo, Hong-Wei Wu, Shu-Lin Zhong, Wei-De Wu, Chin-Lee TI Enhanced expression of centromere protein F predicts clinical progression and prognosis in patients with prostate cancer SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE prostate cancer; centromere protein F; clinicopathological characteristic; biochemical recurrence-free survival ID CENP-F; THERAPEUTIC IMPLICATIONS; CHROMOSOMAL INSTABILITY; RADICAL PROSTATECTOMY; GENE-EXPRESSION; POOR-PROGNOSIS; BREAST-CANCER; CARCINOMA; MITOSIS; TUMORS AB Centromere protein F (CENPF) is a protein associated with the centromere-kinetochore complex and chromosomal segregation during mitosis. Previous studies have demonstrated that the upregulation of CENPF may be used as a proliferation marker of malignant cell growth in tumors. The overexpression of CENPF has also been reported to be associated with a poor prognosis in human cancers. However, the clinical significance of CENPF in prostate cancer (PCa) has not yet been fully elucidated. Thus, the aim of the present study was to determine the association of CENPF with tumor progression and prognosis in patients with PCa. The expression of CENPF at the protein level in human PCa and non-cancerous prostate tissues was detected by immunohistochemical analysis, which was further validated using a microarray-based dataset (NCBI GEO accession no: GSE21032) at the mRNA level. Subsequently, the association of CENPF expression with the clinicopathological characteristics of the patients with PCa was statistically analyzed. Immunohistochemistry and dataset analysis revealed that CENPF expression was significantly increased in the PCa tissues compared with the non-cancerous prostate tissues [immunoreactivity score (IRS): PCa, 177.98 +/- 94.096 vs. benign, 121.30 +/- 89.596, P < 0.001; mRNA expression in the dataset: PCa, 5.67 +/- 0.47 vs. benign, 5.40 +/- 0.11; P < 0.001]. Additionally, as revealed by the dataset, the upregulation of CENPF mRNA expression in the PCa tissues significantly correlated with a higher Gleason score (GS, P = 0.005), an advanced pathological stage (P = 0.008), the presence of metastasis (P < 0.001), a shorter overall survival (P = 0.003) and prostate-specific antigen (PSA) failure (P < 0.001). Furthermore, both univariate and multivariate analyses revealed that the upregulation of CENPF was an independent predictor of poor biochemical recurrence (BCR)-free survival (P < 0.001 and P = 0.012, respectively). Our data suggest that the increased expression of CENPF plays an important role in the progression of PCa. More importantly, the increased expression of CENPF may efficiently predict poor BCR-free survival in patients with PCa. C1 [Zhuo, Yang-Jia; Xi, Ming; Wan, Yue-Ping; Hua, Wei; Liu, Yuan-Ling; Wan, Song; Zhou, Yu-Lin; Zhong, Wei-De] Southern Med Univ, Dept Urol, Huadu Dist Peoples Hosp, Guangzhou 510800, Guangdong, Peoples R China. [Luo, Hong-Wei] Southern Med Univ, Guangdong Prov Inst Nephrol, Guangzhou 510515, Guangdong, Peoples R China. [Zhuo, Yang-Jia; Zhong, Wei-De] Guangzhou Med Univ, Guangzhou Peoples Hosp 1, Dept Urol, Guangdong Key Lab Clin Mol Med & Diagnost, Guangzhou 510180, Guangdong, Peoples R China. [Wu, Shu-Lin; Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wu, Shu-Lin; Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Zhong, WD (reprint author), Guangzhou Med Univ, Guangzhou Peoples Hosp 1, Dept Urol, Guangdong Key Lab Clin Mol Med & Diagnost, 1 Panfu Rd, Guangzhou 510180, Guangdong, Peoples R China. EM zhongwd2009@live.cn FU National Natural Science Foundation of China [81170699, 81272813]; Guangdong Provincial Science and Technology Project [2012B031800008]; Guangzhou Municipal Science and the Technology Key Project [11C23150711] FX The present study was supported by grants from the National Natural Science Foundation of China (81170699, 81272813), the Guangdong Provincial Science and Technology Project (2012B031800008), Guangzhou Municipal Science and the Technology Key Project (11C23150711). NR 34 TC 4 Z9 5 U1 0 U2 3 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 EI 1791-244X J9 INT J MOL MED JI Int. J. Mol. Med. PD APR PY 2015 VL 35 IS 4 BP 966 EP 972 DI 10.3892/ijmm.2015.2086 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CE3YA UT WOS:000351764800014 PM 25647485 ER PT J AU Soukup, K Wang, XH AF Soukup, Klara Wang, Xinhui TI Radiation meets immunotherapy - a perfect match in the era of combination therapy? SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Review DE Radiation; radiotherapy; immunotherapy; cancer; combination therapy ID CD8(+) T-CELLS; LOW-DOSE IRRADIATION; CANCER-IMMUNOTHERAPY; TUMOR-CELLS; METASTATIC MELANOMA; COMBINING RADIOTHERAPY; CALRETICULIN EXPOSURE; ANTI-CTLA-4 ANTIBODY; IONIZING-RADIATION; PROSTATE-CANCER AB Purpose : This review focuses on recent advances in the field of combining radiation with immunotherapy for the treatment of malignant diseases, since various combinatorial cancer therapy approaches have lately proven highly successful. Results : With initial case reports and anecdotes progressively converting into solid clinical data, interest in cancer immunotherapy (CIT) has risen steeply. Especially immune checkpoint blockade therapies have recently celebrated tremendous successes in the treatment of severe malignancies resistant to conventional treatment strategies. Nevertheless, the high variability of patient responses to CIT remains a major hurdle, clearly indicating an urgent need for improvement. It has been suggested that successful cancer therapy most probably involves combinatorial treatment approaches. Radiotherapy (RT) has been proposed as a powerful partner for CIT due to its broad spectrum of immune modulatory characteristics. Several preclinical studies, supported by an increasing number of clinical observations, have demonstrated synergistic interactions between RT and CIT resulting in significantly improved therapy outcomes. Conclusions : Numerous reports have shown that radiation is capable of tipping the scales from tumor immune evasion to elimination in different tumor types. The next puzzle to be solved is the question of logistics - including types, schedule and dosage of combinatorial RT and CIT strategies. C1 [Soukup, Klara; Wang, Xinhui] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol,Dept Surg, Boston, MA 02114 USA. [Soukup, Klara] St Anna Kinderkrebsforschung, Dept Tumor Immunol, CCRI, Vienna, Austria. RP Wang, XH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Surg Oncol, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM xwang30@mgh.harvard.edu FU Department of Surgery, Massachusetts General Hospital; NIH [RO3 CA141086]; Austrian Science Funds (FWF) [P23271-B11]; PhD program "BioToP - Biomolecular Technology of Proteins" (Austrian Science Funds, FWF project) [W1224] FX This study was supported by Department of Surgery, Massachusetts General Hospital (X.W.), NIH grant RO3 CA141086 (X.W.), the Austrian Science Funds (FWF) project P23271-B11 (K.S.) as well as the PhD program "BioToP - Biomolecular Technology of Proteins" (Austrian Science Funds, FWF project W1224) (K.S.). NR 86 TC 4 Z9 4 U1 1 U2 11 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0955-3002 EI 1362-3095 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD APR PY 2015 VL 91 IS 4 BP 299 EP 305 DI 10.3109/09553002.2014.995383 PG 7 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA CE3XU UT WOS:000351764200001 PM 25630486 ER PT J AU Paganetti, H AF Paganetti, Harald TI Relating Proton Treatments to Photon Treatments via the Relative Biological Effectiveness-Should We Revise Current Clinical Practice? SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material ID LINEAR-ENERGY-TRANSFER; EFFECTIVENESS RBE VALUES; BEAM THERAPY; MEDULLOBLASTOMA C1 [Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA USA. RP Paganetti, H (reprint author), Massachusetts Gen Hosp, 30 Fruit St, Boston, MA 02114 USA. EM hpaganetti@partners.org OI Paganetti, Harald/0000-0002-6257-2413 NR 11 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD APR 1 PY 2015 VL 91 IS 5 BP 892 EP 894 DI 10.1016/j.ijrobp.2014.11.021 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CE3NR UT WOS:000351734000003 PM 25832682 ER PT J AU Liu, Q Ghosh, P Magpayo, N Testa, M Tang, SK Gheorghiu, L Biggs, P Paganetti, H Efstathiou, JA Lu, HM Held, KD Willers, H AF Liu, Qi Ghosh, Priyanjali Magpayo, Nicole Testa, Mauro Tang, Shikui Gheorghiu, Liliana Biggs, Peter Paganetti, Harald Efstathiou, Jason A. Lu, Hsiao-Ming Held, Kathryn D. Willers, Henning TI Lung Cancer Cell Line Screen Links Fanconi Anemia/BRCA Pathway Defects to Increased Relative Biological Effectiveness of Proton Radiation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID DOUBLE-STRAND BREAKS; HOMOLOGOUS RECOMBINATION REPAIR; EFFECTIVENESS RBE VALUES; IONIZING-RADIATION; HUMAN FIBROBLASTS; HIGH-LET; X-RAYS; DNA; SENSITIVITY; THERAPY AB Purpose: Growing knowledge of genomic heterogeneity in cancer, especially when it results in altered DNA damage responses, requires re-examination of the generic relative biological effectiveness (RBE) of 1.1 of protons. Methods and Materials: For determination of cellular radiosensitivity, we irradiated 17 lung cancer cell lines at the mid-spread-out Bragg peak of a clinical proton beam (linear energy transfer, 2.5 keV/mu m). For comparison, 250-kVp X rays and Cs-137 gamma-rays were used. To estimate the RBE of protons relative to Co-60 (Co60eq), we assigned an RBE(Co60Eq) of 1.1 to X rays to correct the physical dose measured. Standard DNA repair foci assays were used to monitor damage responses. FANCD2 was depleted using RNA interference. Results: Five lung cancer cell lines (29.4%) exhibited reduced clonogenic survival after proton irradiation compared with X-irradiation with the same physical doses. This was confirmed in a 3-dimensional sphere assay. Corresponding proton RBE(Co60Eq) estimates were statistically significantly different from 1.1 (P <= .05): 1.31 to 1.77 (for a survival fraction of 0.5). In 3 of these lines, increased RBE was correlated with alterations in the Fanconi anemia (FA)/BRCA pathway of DNA repair. In Calu-6 cells, the data pointed toward an FA pathway defect, leading to a previously unreported persistence of proton-induced RAD51 foci. The FA/BRCA-defective cells displayed a 25% increase in the size of subnuclear 53BP1 foci 18 hours after proton irradiation. Conclusions: Our cell line screen has revealed variations in proton RBE that are partly due to FA/BRCA pathway defects, suggesting that the use of a generic RBE for cancers should be revisited. We propose that functional biomarkers, such as size of residual 53BP1 foci, may be used to identify cancers with increased sensitivity to proton radiation. (C) 2015 Elsevier Inc. All rights reserved. C1 [Liu, Qi; Ghosh, Priyanjali; Magpayo, Nicole; Gheorghiu, Liliana; Efstathiou, Jason A.; Held, Kathryn D.; Willers, Henning] Massachusetts Gen Hosp, Dept Radiat Oncol, Lab Cellular & Mol Radiat Oncol, Boston, MA 02114 USA. [Testa, Mauro; Tang, Shikui; Biggs, Peter; Paganetti, Harald; Lu, Hsiao-Ming] Massachusetts Gen Hosp, Dept Radiat Oncol, Div Radiat Phys, Boston, MA 02114 USA. RP Willers, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM hwillers@mgh.harvard.edu FU Massachusetts General Hospital [C06 CA059267] FX Federal share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center (H.P., J.A.E., H-M.L., K.D.H., H.W.). NR 37 TC 11 Z9 11 U1 1 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 APR 1 PY 2015 VL 91 IS 5 BP 1081 EP 1089 DI 10.1016/j.ijrobp.2014.12.046 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CE3NR UT WOS:000351734000027 PM 25832698 ER PT J AU Farkas, AH Vanderberg, R Sucato, GS Miller, E Akers, AY Borrero, S AF Farkas, Amy H. Vanderberg, Rachel Sucato, Gina S. Miller, Elizabeth Akers, Aletha Y. Borrero, Sonya TI Racial and Ethnic Differences in Young Men's Sex and Contraceptive Education SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Race; Disparities; Men; Sex education; Contraceptive education ID BEHAVIORS AB Purpose: Racial/ethnic disparities exist in young men's contraceptive knowledge. This study examines whether the likelihood of receiving sexual health education varies by race/ethnicity. Methods: We examined racial/ethnic differences in sex and contraceptive education both in school and from parents with multivariable logistic regression models among 4,104 men aged 15-24 years using data from the 2006-2010 National Survey of Family Growth. Results: Nearly all respondents (96.6%) reported formal sex education. Fewer reported formal birth control education (66.6%), parental sex discussions (66.8%), and parental discussions specifically about birth control (49.2%). In multivariable analysis, black men were less likely than white men to report receiving formal contraceptive education (adjusted odds ratio [aOR],.70; 95% CI, .51-.96). Both black and U.S.-born Hispanic men reported more parental sex discussions than white men (aOR, 1.44; 95% CI, 1.07-1.94, aOR, 1.47; 95% CI, 1.09-1.99, respectively). Conclusions: Nearly all respondents reported having received formal sexual health education. Fewer reported receiving education about birth control either at school or at home. Black men were less likely to report receiving formal contraceptive education. Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine. C1 [Farkas, Amy H.; Vanderberg, Rachel; Borrero, Sonya] Univ Pittsburgh, Div Gen Internal Med, Dept Internal Med, Pittsburgh, PA 15213 USA. [Sucato, Gina S.; Miller, Elizabeth] UPMC, Childrens Hosp Pittsburgh, Dept Pediat, Div Adolescent Med, Pittsburgh, PA USA. [Akers, Aletha Y.] Childrens Hosp Philadelphia, Craig Dalsimer Div Adolescent Med, Gynecol Consultat Serv, Philadelphia, PA 19104 USA. [Borrero, Sonya] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. RP Borrero, S (reprint author), Univ Pittsburgh, Ctr Res Hlth Care, 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM borrerosp@upmc.edu FU NIH [UL1-TR-000005] FX We thank Dan Winger, at the Clinical and Translation Science Institute, University of Pittsburgh supported by NIH grant UL1-TR-000005, for his assistance with statistical analysis. NR 9 TC 0 Z9 0 U1 1 U2 9 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 APR PY 2015 VL 56 IS 4 BP 464 EP 467 DI 10.1016/j.jadohealth.2014.12.014 PG 4 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA CE3BC UT WOS:000351698100018 PM 25797633 ER PT J AU Rosenblau, G Kliemann, D Heekeren, HR Dziobek, I AF Rosenblau, Gabriela Kliemann, Dorit Heekeren, Hauke R. Dziobek, Isabel TI Approximating Implicit and Explicit Mentalizing with Two Naturalistic Video-Based Tasks in Typical Development and Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Cognition; Mentalizing; Behavioral assessment; Implicit ID HIGH-FUNCTIONING AUTISM; COMPLEX EMOTION RECOGNITION; SOCIAL COGNITION RESEARCH; ASPERGER-SYNDROME; FALSE BELIEF; DIAGNOSTIC INTERVIEW; FIXATION PATTERNS; BRAIN MECHANISMS; REVISED VERSION; SEX-DIFFERENCES AB Individuals with autism spectrum disorder (ASD) have been proposed to show greater impairments in implicit than explicit mentalizing. To test this proposition, we developed two comparable naturalistic tasks for a performance-based approximation of implicit and explicit mentalizing in 28 individuals with ASD and 23 matched typically developed (TD) participants. Although both tasks were sensitive to the social impairments of individuals with ASD, implicit mentalizing was not more dysfunctional than explicit mentalizing. In TD participants, performance on the tasks did not correlate with each other, whereas in individuals with ASD they were highly correlated. These findings suggest that implicit and explicit mentalizing processes are separable in typical development. In contrast, in individuals with ASD implicit and explicit mentalizing processes are similarly impaired and closely linked suggesting a lack of developmental specification of these processes in ASD. C1 [Rosenblau, Gabriela; Kliemann, Dorit; Heekeren, Hauke R.; Dziobek, Isabel] Free Univ Berlin, Cluster Excellence Languages Emot, D-14195 Berlin, Germany. [Rosenblau, Gabriela; Kliemann, Dorit; Heekeren, Hauke R.] Free Univ Berlin, Dept Educ & Psychol, D-14195 Berlin, Germany. [Rosenblau, Gabriela] Yale Univ, Yale Child Study Ctr, Ctr Translat Dev Neurosci, New Haven, CT 06519 USA. [Kliemann, Dorit] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Kliemann, Dorit] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Dziobek, Isabel] Humboldt Univ, Berlin Sch Mind & Brain, D-10099 Berlin, Germany. RP Rosenblau, G (reprint author), Free Univ Berlin, Cluster Excellence Languages Emot, Habelschwerdter Allee 45, D-14195 Berlin, Germany. EM gabriela.rosenblau@yale.edu OI Heekeren, Hauke/0000-0001-7912-6826 FU German Research Foundation (DFG) [EXC 302] FX We thank Joerg Schulze, member of the Computer and Media Service team (CMS) at the Humboldt University, for his advice and support with the production and postproduction of the film stimuli and the actors. We also thank our student research assistants for their help with the stimulus production and data acquisition. In addition, we would like especially our participants on the autism spectrum for their participation in the study. This work was supported by a Grant from the German Research Foundation (DFG; EXC 302). NR 69 TC 5 Z9 5 U1 4 U2 20 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD APR PY 2015 VL 45 IS 4 BP 953 EP 965 DI 10.1007/s10803-014-2249-9 PG 13 WC Psychology, Developmental SC Psychology GA CE1BO UT WOS:000351546800007 PM 25267068 ER PT J AU Bunchorntavakul, C Jones, LM Kikuchi, M Valiga, ME Kaplan, DE Nunes, FA Aytaman, A Reddy, KR Chang, KM AF Bunchorntavakul, Chalermrat Jones, Lisa M. Kikuchi, Masahiro Valiga, Mary E. Kaplan, David E. Nunes, Frederick A. Aytaman, Ayse Reddy, K. Rajender Chang, Kyong-Mi TI Distinct Features in Natural History and Outcomes of Acute Hepatitis C SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE hepatitis C virus; acute hepatitis; RNA fluctuation; clinical presentation; autoantibody ID HIV-INFECTED MEN; INJECTION-DRUG USERS; T-CELL RESPONSES; VIRUS-INFECTION; FIBROSIS PROGRESSION; VIRAL CLEARANCE; LIVER FIBROSIS; UNITED-STATES; RISK-FACTORS; COHORT AB Background: Acute hepatitis C (AHCV) provides a diagnostic challenge with diverse clinical presentations. Goals: This study was aimed to examine the clinical and demographic features as well as outcomes in AHCV patients identified from inpatient and outpatient hospital settings. Study: Patients with suspected AHCV were recruited from Philadelphia VA Medical Center, Hospital of University of Pennsylvania and Brooklyn VA Medical Center between 2000 and 2010. AHCV was diagnosed by acute serum alanine aminotransferase elevation with anti-hepatitis C virus (HCV) sero-conversion, HCV-RNA fluctuations above 1 log, and/or recent high-risk exposure without prior HCV infection, excluding those with human immunodeficiency virus infection. Clinical and therapeutic outcomes were monitored for at least 6 months. Results: A total of 40 AHCV patients were enrolled with a median follow-up of 129 weeks. They were mostly men (68%) and whites (73%) with median age of 43 years, diverse risk factors (33% injection drugs, 20% health care-associated, 3% sexual, and 45% unknown), and wide variations in peak alanine aminotransferase (143 to 3435 U/L) and total bilirubin levels (0.4 to 19.3 mg/dL). Viremia resolved spontaneously in 23% and persisted without therapy in 27%, whereas 50% received interferon a-based therapy with 90% cure (18/20). Distinct clinical scenarios included: (1) wide viremic fluctuations > 1log (65%) and intermittent HCV-RNA negativity; (2) autoantibodies (25% antinuclear antibodies, 69% antismooth muscle antibodies) or autoimmune features; (3) delayed spontaneous viral clearance in 2 patients; (4) rapid cirrhosis progression in 2 patients. Conclusions: AHCV is a heterogenous disease that requires careful monitoring. The lack of apparent risk factor in high proportion of patients and its diverse presentations warrant diagnostic vigilance. C1 [Bunchorntavakul, Chalermrat; Jones, Lisa M.; Kikuchi, Masahiro; Valiga, Mary E.; Kaplan, David E.; Reddy, K. Rajender; Chang, Kyong-Mi] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Jones, Lisa M.; Kikuchi, Masahiro; Valiga, Mary E.; Kaplan, David E.; Chang, Kyong-Mi] Philadelphia VA Med Ctr, Div Gastroenterol & Hepatol, Dept Med, Philadelphia, PA 19104 USA. [Nunes, Frederick A.] Penn Hosp, Philadelphia, PA 19107 USA. [Bunchorntavakul, Chalermrat] Rangsit Univ, Rajavithi Hosp, Coll Med, Bangkok, Thailand. [Aytaman, Ayse] VA New York Harbor Healthcare Syst, Brooklyn, NY USA. RP Chang, KM (reprint author), Philadelphia VA Med Ctr, A424,Med Res Bldg, Philadelphia, PA 19104 USA. EM kmchang@mail.med.upenn.edu FU Office of Research and Development, Department of Veterans Affairs [IOBX000649]; NIH [R01-AI-47519, R01-AA-12849, T32 DK 07066, K12-RR-017625]; Philadelphia VA Medical Research; NIH/NIDDK Center of Molecular Studies in Digestive and Liver Diseases [P30DK50306]; NIH Public Health Service Research [M01-RR00040]; NIH Loan Repayment Program; AASLD/Schering Advanced Hepatology Fellowship; VA Career Development Award; VA Stars and Stripes Award FX This material is based upon work supported in part by the Office of Research and Development, Department of Veterans Affairs with VA Merit Review IOBX000649 and with the resources and the use of facilities at the Philadelphia VA Medical Center. This study was also supported by NIH Grants R01-AI-47519 and R01-AA-12849; the Philadelphia VA Medical Research; NIH/NIDDK Center of Molecular Studies in Digestive and Liver Diseases P30DK50306 and its Molecular Biology and Cell Culture Core Facilities; the NIH Public Health Service Research Grant M01-RR00040. D.E.K. was supported by the NIH T32 DK 07066, NIH Loan Repayment Program, AASLD/Schering Advanced Hepatology Fellowship, NIH K12-RR-017625, and the VA Career Development Award and the VA Stars and Stripes Award. NR 53 TC 3 Z9 3 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0192-0790 EI 1539-2031 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD APR PY 2015 VL 49 IS 4 BP E31 EP E40 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CE2GJ UT WOS:000351632400001 PM 24457946 ER PT J AU Marcus, DK Bell, EC Mercer, SH AF Marcus, David K. Bell, Erin C. Mercer, Sterett H. TI Adding Components Improves Treatment Outcomes: Reply to Fluckiger et al. (2015) SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Editorial Material DE specific ingredients; component studies; additive studies; psychotherapy research; sleeper effect ID DODO BIRD; METAANALYSIS AB In our article "Are the Parts as Good as the Whole? A Meta-Analysis of Component Treatment Studies" (Bell, Marcus, & Goodlad, 2013), we found that adding a component to an existing treatment resulted in better outcomes than the standard treatment for targeted problems at both termination and follow-up. The effect size at follow-up was twice as large as at termination, suggesting a "sleeper effect," but we did not test whether this increase was statistically significant. In their commentary on our article, Fluckiger, Del Re, and Wampold (2015) tested whether this difference was significant, and they found that it was not. The lack of support for a sleeper effect should not, however, distract from our central findings that specific ingredients can make a modest contribution to targeted treatment outcomes. The implications of these findings for the common factors versus specific ingredients debate are discussed. C1 [Marcus, David K.] Washington State Univ, Dept Psychol, Pullman, WA 99164 USA. [Bell, Erin C.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Bell, Erin C.] Ralph H Johnson Vet Affairs Med Ctr, Psychol Serv, Charleston, SC USA. [Mercer, Sterett H.] Univ British Columbia, Dept Educ & Counselling Psychol & Special Educ, Vancouver, BC V5Z 1M9, Canada. RP Marcus, DK (reprint author), Washington State Univ, Dept Psychol, Pullman, WA 99164 USA. EM david.marcus@wsu.edu NR 13 TC 1 Z9 1 U1 2 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X EI 1939-2117 J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD APR PY 2015 VL 83 IS 2 BP 443 EP 444 DI 10.1037/ccp0000012 PG 2 WC Psychology, Clinical SC Psychology GA CE6KL UT WOS:000351945200020 ER PT J AU Zhao, X Bichara, DA Zhou, L Kulig, KM Tseng, A Bowley, CM Vacanti, JP Pomerantseva, I Sundback, CA Randolph, MA AF Zhao, Xing Bichara, David A. Zhou, Libin Kulig, Katherine M. Tseng, Alan Bowley, Christopher M. Vacanti, Joseph P. Pomerantseva, Irina Sundback, Cathryn A. Randolph, Mark A. TI Conditions for seeding and promoting neo-auricular cartilage formation in a fibrous collagen scaffold SO JOURNAL OF CRANIO-MAXILLOFACIAL SURGERY LA English DT Article DE Cartilage; Ear; Auricle; Tissue engineering; Collagen; Scaffold ID TISSUE-ENGINEERED CARTILAGE; MESENCHYMAL STEM-CELLS; 3-DIMENSIONAL ALGINATE SCAFFOLD; EAR-SHAPED CARTILAGE; IN-VITRO; RIB CARTILAGE; RECONSTRUCTION; CHONDROCYTES; MODEL; IMPLANTS AB Background: Carved autologous costal cartilage and porous polyethylene implants (Medpor) are the most common approaches for total ear reconstruction, but these approaches may have inconsistent cosmetic outcomes, a high risk of extrusion, or other surgical complications. Engineering ear cartilage to emulate native auricular tissue is an appealing approach, but often the cell-seeded scaffolds are susceptible to shrinkage and architectural changes when placed in vivo. The aim of this study was to assess the most favorable conditions for in vitro pre-culture of cell-seeded type I collagen scaffolds prior to in vivo implantation. Methods: Sheep auricular chondrocytes were seeded into this type I collagen scaffold. The cell-seeded constructs were cultured in either static or dynamic conditions for two days or two weeks and then implanted into nude mice for another six weeks. The harvested constructs were evaluated histologically, immunohistochemically, and biochemically. Results: Robust neo-cartilage formation was found in these collagen scaffolds seeded with auricular chondrocytes, which was comparable to native cartilage morphologically, histologically, and biochemically. Culture under dynamic conditions prior to implantation improved the neo-cartilage formation histologically and biochemically. Conclusion: Dynamic culture of this cell-seeded fibrous collagen material could permit predictable engineered auricular cartilage and a promising approach for external ear reconstruction. (C) 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved. C1 [Zhao, Xing; Bichara, David A.; Randolph, Mark A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Plast Surg Res Lab, Boston, MA USA. [Zhou, Libin; Kulig, Katherine M.; Tseng, Alan; Vacanti, Joseph P.; Pomerantseva, Irina; Sundback, Cathryn A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Tissue Engn & Organ Fabricat, Boston, MA USA. [Zhou, Libin] PLA, Hosp 513, Dept Stomatol, Lanzhou 732750, Gansu, Peoples R China. [Bowley, Christopher M.] Kensey Nash Corp, Exton, PA USA. [Zhao, Xing] Univ Med Ctr Utrecht, Dept Orthopaed, Utrecht, Netherlands. RP Randolph, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Room WAC 435,15 Parkman St, Boston, MA 02163 USA. EM marandolph@partners.org FU Armed Forces Institute of Regenerative Medicine award [W81XWH-08-2-0034] FX This research was sponsored by the Armed Forces Institute of Regenerative Medicine award number W81XWH-08-2-0034. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. The sponsor was not involved in the study design, data collection or analyses and interpretation of the data. The content of the manuscript does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred. NR 50 TC 4 Z9 4 U1 3 U2 18 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1010-5182 EI 1878-4119 J9 J CRANIO MAXILL SURG JI J. Cranio-MaxilloFac. Surg. PD APR PY 2015 VL 43 IS 3 BP 382 EP 389 DI 10.1016/j.jcms.2014.12.007 PG 8 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA CE9NS UT WOS:000352171300016 PM 25600627 ER PT J AU Huang, G Wharton, W Travison, TG Ho, MH Gleason, C Asthana, S Bhasin, S Basaria, S AF Huang, G. Wharton, W. Travison, T. G. Ho, M. H. Gleason, C. Asthana, S. Bhasin, S. Basaria, S. TI Effects of testosterone administration on cognitive function in hysterectomized women with low testosterone levels: a dose-response randomized trial SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Article DE Testosterone; Menopause; Cognition; Androgen deficiency ID HEALTH INITIATIVE MEMORY; POSTMENOPAUSAL WOMEN; SEX-HORMONES; REPLACEMENT THERAPY; SPATIAL COGNITION; MENSTRUAL-CYCLE; DOUBLE-BLIND; ESTROGEN; ABILITIES AB Purpose To determine the dose-dependent effects of testosterone administration on cognition in women with low testosterone levels. Methods 71 hysterectomized women with or without oophorectomy with total testosterone <31 ng/dl and/or free testosterone <3.5 pg/ml received a standardized transdermal estradiol regimen during the 12-week run-in period and were then randomized to receive weekly intramuscular injections of placebo, 3, 6.25, 12.5, or 25 mg testosterone enanthate for 24 weeks. Total testosterone was measured in serum by LC-MS/MS, and free testosterone levels were measured by equilibrium dialysis. Cognitive function was evaluated using a comprehensive battery of standardized neuropsychological tests at baseline and 24 weeks. Results 46 women who had baseline and end-of-treatment cognitive function data constituted the analytic sample. The five groups were similar at baseline. Mean on-treatment nadir total testosterone concentrations were 15, 89, 98, 134, and 234 ng/dl in the placebo, 3, 6.25, 12.5, and 25 mg groups, respectively. No significant changes in spatial ability, verbal fluency, verbal memory, or executive function were observed in any treatment arm compared to placebo even after adjustment for baseline cognitive function, age, and education. Multiple regression analysis did not show any significant relation between changes in testosterone concentrations and change in cognitive function scores. Conclusion Short-term testosterone administration over a wide range of doses for 24 weeks in women with low testosterone levels was neither associated with improvements nor worsening of cognitive function. C1 [Huang, G.; Travison, T. G.; Bhasin, S.; Basaria, S.] Harvard Univ, Brigham & Womens Hosp, Sect Mens Hlth Aging & Metab, Sch Med, Boston, MA 02115 USA. [Wharton, W.] Emory Univ, Dept Neurol, Atlanta, GA 30329 USA. [Ho, M. H.] Charles R Drew Univ Med & Sci, Div Endocrinol Metab & Mol Med, Los Angeles, CA 90059 USA. [Gleason, C.; Asthana, S.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53792 USA. [Gleason, C.; Asthana, S.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI 53705 USA. [Gleason, C.; Asthana, S.] Wisconsin Alzheimers Dis Res Ctr, Madison, WI 53792 USA. RP Huang, G (reprint author), Harvard Univ, Brigham & Womens Hosp, Sect Mens Hlth Aging & Metab, Sch Med, BLI-5,221 Longwood Ave, Boston, MA 02115 USA. EM ghuang7@partners.org FU National Institute of Child Health and Human Development [2008 TF D2274G]; Boston Claude D. Pepper Older Americans Independence Center Grant from the National Institute of Aging [5P30AG031679] FX This study was supported by Grants 5U54HD041748-04 (to Charles Drew University of Medicine and Science) and 2008 TF D2274G (sub award to Boston University) from the National Institute of Child Health and Human Development and the Boston Claude D. Pepper Older Americans Independence Center Grant #5P30AG031679 from the National Institute of Aging. Watson Pharmaceuticals provided the transdermal estradiol patch for this trial. ENDO Pharmaceuticals provided testosterone injections for this trial. NR 23 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1720-8386 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD APR PY 2015 VL 38 IS 4 BP 455 EP 461 DI 10.1007/s40618-014-0213-3 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CE3CQ UT WOS:000351702500010 PM 25430996 ER PT J AU Tangelder, MJD Nwachuku, CE Jaff, M Baumgartner, I Duggal, A Adams, G Ansel, G Grosso, M Mercuri, M Shi, MG Minar, E Moll, FL AF Tangelder, Marco J. D. Nwachuku, Chuke E. Jaff, Michael Baumgartner, Iris Duggal, Anil Adams, George Ansel, Gary Grosso, Michael Mercuri, Michele Shi, Minggao Minar, Erich Moll, Frans L. TI A Review of Antithrombotic Therapy and the Rationale and Design of the Randomized Edoxaban in Patients With Peripheral Artery Disease (ePAD) Trial Adding Edoxaban or Clopidogrel to Aspirin After Femoropopliteal Endovascular Intervention SO JOURNAL OF ENDOVASCULAR THERAPY LA English DT Article DE peripheral artery disease; endovascular therapy; antithrombotic therapy; aspirin; clopidogrel; edoxaban; antiplatelet therapy; factor Xa inhibitor; randomized controlled trial; bleeding; femoropopliteal segment; angioplasty; stent; restenosis ID PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; DUAL ANTIPLATELET THERAPY; ATRIAL-FIBRILLATION; PLATELET INHIBITION; BALLOON ANGIOPLASTY; DIPYRIDAMOLE; RESTENOSIS; WARFARIN; PREVENTION; GUIDELINES AB Compared with the coronary setting, knowledge about antithrombotic therapies after endovascular treatment (EVT) is inadequate in patients with peripheral artery disease (PAD). Based on a review of trials and guidelines, which is summarized in this article, there is scant evidence that antithrombotic drugs improve outcome after peripheral EVT. To address this knowledge gap, the randomized, open-label, multinational edoxaban in patients with Peripheral Artery Disease (ePAD) study (ClinicalTrials.gov identifier NCT01802775) was designed to explore the safety and efficacy of a combined regimen of antiplatelet therapy with clopidogrel and anticoagulation with edoxaban, a selective and direct factor Xa inhibitor, both combined with aspirin. As of July 2014, 203 patients (144 men; mean age 67 years) from 7 countries have been enrolled. These patients have been allocated to once-daily edoxaban [60 mg for 3 months (or 30 mg in the presence of factors associated with increased exposure)] or clopidogrel (75 mg/d for 3 months). All patients received aspirin (100 mg/d) for the 6-month duration of the study. The primary safety endpoint is major or clinically relevant nonmajor bleeding; the primary efficacy endpoint is restenosis or reocclusion at the treated segment(s) measured at 1, 3, and 6 months using duplex ultrasound scanning. All outcomes will be assessed and adjudicated centrally in a masked fashion. The ePAD study is the first of its kind to investigate a combined regimen of antiplatelet therapy and anticoagulation through factor Xa inhibition with edoxaban. C1 [Tangelder, Marco J. D.; Moll, Frans L.] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Nwachuku, Chuke E.; Duggal, Anil; Grosso, Michael; Mercuri, Michele; Shi, Minggao] Daiichi Sankyo Pharma Dev, Edison, NJ USA. [Jaff, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jaff, Michael] Harvard Univ, Sch Med, Boston, MA USA. [Baumgartner, Iris] Univ Hosp Bern, Swiss Cardiovasc Ctr, Bern, Switzerland. [Adams, George] Univ North Carolina Hlth Syst, Rex Healthcare, Raleigh, NC USA. [Ansel, Gary] Riverside Methodist Hosp, Columbus, OH 43214 USA. [Minar, Erich] Med Univ Vienna, Vienna Gen Hosp, Vienna, Austria. RP Tangelder, MJD (reprint author), Univ Med Ctr Utrecht, Dept Vasc Surg, Utrecht, Netherlands. EM m.tangelder@umcutrecht.nl FU Daiichi Sankyo Pharma Development FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study is sponsored by Daiichi Sankyo Pharma Development. NR 29 TC 3 Z9 3 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1526-6028 EI 1545-1550 J9 J ENDOVASC THER JI J. Endovascular Ther. PD APR PY 2015 VL 22 IS 2 BP 261 EP 268 DI 10.1177/1526602815574687 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA CE6OQ UT WOS:000351958000022 PM 25809373 ER PT J AU Rich, JD Allen, SA Williams, BA AF Rich, Josiah D. Allen, Scott A. Williams, Brie A. TI The Need for Higher Standards in Correctional Healthcare to Improve Public Health SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article ID CRIMINAL-JUSTICE SYSTEM; HEPATITIS-C; HIGH-RISK; EPIDEMIC; INMATES; INCARCERATION; FACILITIES; RELEASE; AGENDA; PRISON C1 [Rich, Josiah D.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Rich, Josiah D.; Allen, Scott A.] Miriam Hosp, Ctr Prisoner Hlth & Human Rights, Providence, RI 02906 USA. [Allen, Scott A.] Univ Calif Riverside, Sch Med, Riverside, CA 92521 USA. [Williams, Brie A.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA. [Williams, Brie A.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Rich, JD (reprint author), Miriam Hosp, Ctr Prisoner Hlth & Human Rights, 164 Summit Ave, Providence, RI 02906 USA. EM jrich@lifespan.org FU National Institute on Drug Abuse [K24DA022112]; National Institute on Allergy and Infectious Diseases [P30A142853]; National Institute on Aging [K23AG033102]; Jacob & Valeria Langeloth Foundation; UCSF Program for the Aging Century; UCSF Claude D. Pepper Older Americans Independence Center FX Dr. Rich is supported by the National Institute on Drug Abuse (K24DA022112) and the National Institute on Allergy and Infectious Diseases (P30A142853). Dr. Williams is an employee of the Department of Veterans Affairs and is supported by the National Institute on Aging (K23AG033102), The Jacob & Valeria Langeloth Foundation, the UCSF Program for the Aging Century, and the UCSF Claude D. Pepper Older Americans Independence Center. Dr. Rich participated in a single meeting of the Gilead advisory board in 2012 and is a stockholder in Alkermes. Drs. Rich, Allen, and Williams have all offered expert testimony in cases (12 cumulatively) involving the health care of prisoners. The opinions expressed in this manuscript may not represent those of the supporting agencies. NR 32 TC 1 Z9 1 U1 3 U2 11 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 APR PY 2015 VL 30 IS 4 BP 503 EP 507 DI 10.1007/s11606-014-3142-0 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CE2RO UT WOS:000351664000030 PM 25523471 ER PT J AU Chiovaro, J AF Chiovaro, Joseph TI Capsule commentary on Turner, et al. Chronic opioid therapy urine drug testing in primary care: prevalence and predictors of aberrant results (vol 30, pg 241, 2015) SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Correction C1 Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. RP Chiovaro, J (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. EM jchiovaro@gmail.com 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 APR PY 2015 VL 30 IS 4 BP 534 EP 534 DI 10.1007/s11606-015-3232-7 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CE2RO UT WOS:000351664000037 PM 25701048 ER PT J AU Rhee, EP Clish, CB Pierce, KA Saad, A Lerman, LO Textor, SC AF Rhee, Eugene P. Clish, Clary B. Pierce, Kerry A. Saad, Ahmed Lerman, Lilach O. Textor, Stephen C. TI Metabolomics of renal venous plasma from individuals with unilateral renal artery stenosis and essential hypertension SO JOURNAL OF HYPERTENSION LA English DT Article DE hypertension; metabolism; metabolomics; renal artery stenosis ID RENOVASCULAR DISEASE; GENERAL-POPULATION; MEDICAL THERAPY; KIDNEY-FUNCTION; UREMIC SOLUTES; INJURY; CKD; METABOANALYST; OXYGENATION; METABOLISM AB Objective: To compare the metabolite profiles of venous effluent from both kidneys of individuals with unilateral atherosclerotic renal artery stenosis (ARAS) in order to directly examine how impaired renal blood flow impacts small-molecule handling in humans. Methods: We applied liquid chromatography-mass spectrometry based metabolite profiling to venous plasma obtained from the stenotic (STK) and contralateral (CLK) kidneys of ARAS patients (n = 16), and both the kidneys of essential hypertensive controls (n = 11). Study samples were acquired during a 3-day protocol that included iothalamate clearance measurements, radiographic kidney phenotyping (Duplex ultrasound, multidetector computed tomography, and blood-oxygen-level-dependent MRI), and controlled sodium and caloric intake and antihypertensive treatment. Results: Partial least squares-discriminant analysis demonstrated clear separation of essential hypertensive kidney metabolite profiles versus STK and CLK metabolite profiles, but no separation between metabolite profiles of STK and CLK samples. All of the discriminating metabolites were similarly elevated in the STK and CLK samples, likely reflecting the lower glomerular filtration rate in the ARAS versus essential hypertensive individuals (mean 66.1 versus 89.2 ml/min per 1.73 m(2)). In a paired analysis within the ARAS group, no metabolite was significantly altered in STK compared with CLK samples; notably, creatinine was the same in STK and CLK samples (STK/CLK ratio = 1.0, P = 0.9). Results were unchanged in an examination of ARAS patients in the bottom half of renal tissue perfusion or oxygenation. Conclusion: Metabolite profiling does not differentiate venous effluent from STKs or CLKs in individuals with unilateral ARAS, despite the measurable loss of kidney volume and blood flow on the affected side. These findings are consistent with the kidney's ability to adapt to ARAS to maintain a range of metabolic functions. C1 [Rhee, Eugene P.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Rhee, Eugene P.; Clish, Clary B.; Pierce, Kerry A.] Broad Inst, Metabolite Profiling, Cambridge, MA USA. [Saad, Ahmed; Lerman, Lilach O.; Textor, Stephen C.] Mayo Clin, Div Nephrol & Hypertens, Rochester, MN USA. RP Rhee, EP (reprint author), Simches Res Bldg,Room 3212,185 Cambridge St, Boston, MA 02114 USA. EM eprhee@partners.org FU Extramural Grant Program by Satellite Healthcare, a not-for-profit renal care provider; NIH [K08-DK-090142, P01-HL-085307, RO1-DK100081, UL1-RR-024150] FX This study was supported by the Extramural Grant Program by Satellite Healthcare, a not-for-profit renal care provider, and NIH grants K08-DK-090142, P01-HL-085307, RO1-DK100081, and UL1-RR-024150. NR 34 TC 3 Z9 3 U1 3 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0263-6352 EI 1473-5598 J9 J HYPERTENS JI J. Hypertens. PD APR PY 2015 VL 33 IS 4 BP 836 EP 842 DI 10.1097/HJH.0000000000000470 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CE6OD UT WOS:000351956700024 PM 25490710 ER PT J AU Toniolo, PA Liu, SH Yeh, JE Moraes-Vieira, PM Walker, SR Vafaizadeh, V Barbuto, JAM Frank, DA AF Toniolo, Patricia A. Liu, Suhu Yeh, Jennifer E. Moraes-Vieira, Pedro M. Walker, Sarah R. Vafaizadeh, Vida Barbuto, Jose Alexandre M. Frank, David A. TI Inhibiting STAT5 by the BET Bromodomain Inhibitor JQ1 Disrupts Human Dendritic Cell Maturation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNE-RESPONSES; FAMILY PROTEINS; T-CELLS; GM-CSF; C-MYC; DIFFERENTIATION; ACTIVATION; EXPRESSION; CANCER; INFLAMMATION AB Maturation of dendritic cells (DCs) is required to induce T cell immunity, whereas immature DCs can induce immune tolerance. Although the transcription factor STAT5 is suggested to participate in DC maturation, its role in this process remains unclear. In this study, we investigated the effect of STAT5 inhibition on LPS-induced maturation of human monocyte-derived DCs (Mo-DCs). We inhibited STAT5 by treating Mo-DCs with JQ1, a selective inhibitor of BET epigenetic readers, which can suppress STAT5 function. We found that JQ1 inhibits LPS-induced STAT5 phosphorylation and nuclear accumulation, thereby attenuating its transcriptional activity in Mo-DCs. The diminished STAT5 activity results in impaired maturation of Mo-DCs, as indicated by defective upregulation of costimulatory molecules and CD83, as well as reduced secretion of IL-12p70. Expression of constitutively activated STAT5 in JQ1-treated Mo-DCs overcomes the effects of JQ1 and enhances the expression of CD86, CD83, and IL-12. The activation of STAT5 in Mo-DCs is mediated by GM-CSF produced following LPS stimulation. Activated STAT5 then leads to increased expression of both GM-CSF and GM-CSFR, triggering an autocrine loop that further enhances STAT5 signaling and enabling Mo-DCs to acquire a more mature phenotype. JQ1 decreases the ability of Mo-DCs to induce allogeneic CD4(+) and CD8(+) T cell proliferation and production of proinflammatory cytokines. Furthermore, JQ1 leads to a reduced generation of inflammatory CD8(+) T cells and decreased Th1 differentiation. Thus, JQ1 impairs LPS-induced Mo-DC maturation by inhibiting STAT5 activity, thereby generating cells that can only weakly stimulate an adaptive-immune response. Therefore, JQ1 could have beneficial effects in treating T cell-mediated inflammatory diseases. C1 [Toniolo, Patricia A.; Liu, Suhu; Yeh, Jennifer E.; Walker, Sarah R.; Frank, David A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Toniolo, Patricia A.; Liu, Suhu; Yeh, Jennifer E.; Walker, Sarah R.; Frank, David A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. [Toniolo, Patricia A.; Liu, Suhu; Yeh, Jennifer E.; Walker, Sarah R.; Frank, David A.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Toniolo, Patricia A.; Barbuto, Jose Alexandre M.] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, BR-05508900 Sao Paulo, Brazil. [Moraes-Vieira, Pedro M.] Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Dept Med, Boston, MA 02215 USA. [Moraes-Vieira, Pedro M.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Vafaizadeh, Vida] Georg Speyer Haus, Inst Biomed Res, D-60956 Frankfurt, Germany. RP Frank, DA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM david_frank@dfci.harvard.edu RI Moraes-Vieira, Pedro/C-8701-2014; Barbuto, Jose Alexandre/H-5299-2011 OI Barbuto, Jose Alexandre/0000-0001-9526-6781 FU National Cancer Institute [R01-CA160979]; Lymphoma Research Foundation; Brent Leahey Fund; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [09/54599-5, 12/01623-9]; Conselho Nacional de Pesquisa FX This work was supported by the National Cancer Institute (Grant R01-CA160979), the Lymphoma Research Foundation, the Brent Leahey Fund, the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (Grants 09/54599-5 and 12/01623-9), and Conselho Nacional de Pesquisa. NR 36 TC 8 Z9 9 U1 8 U2 13 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 APR 1 PY 2015 VL 194 IS 7 BP 3180 EP 3190 DI 10.4049/jimmunol.1401635 PG 11 WC Immunology SC Immunology GA CE2RK UT WOS:000351663400024 PM 25725100 ER PT J AU Yoo, EM Trinh, KR Tran, D Vasuthasawat, A Zhang, J Hoang, B Lichtenstein, A Morrison, SL AF Yoo, Esther M. Trinh, Kham R. Danh Tran Vasuthasawat, Alex Zhang, Juan Hoang, Bao Lichtenstein, Alan Morrison, Sherie L. TI Anti-CD138-Targeted Interferon Is a Potent Therapeutic Against Multiple Myeloma SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID ALPHA-INDUCED APOPTOSIS; B-CELL LYMPHOMA; MAMMALIAN TARGET; ANTITUMOR ACTIVITIES; IFN-ALPHA; RAPAMYCIN; 3-KINASE; FUSION; LINES; EXPRESSION AB Multiple myeloma (MM), a plasma cell malignancy, is the second most prevalent hematologic malignancy in the US. Although much effort has been made trying to understand the etiology and the complexities of this disease with the hope of developing effective therapies, MM remains incurable at this time. Because of their antiproliferative and proapoptotic activities, interferons (IFNs) have been used to treat various malignancies, including MM. Although some success has been observed, the inherent toxicities of IFNs limit their efficacy. To address this problem, we produced anti-CD138 antibody fusion proteins containing either IFN alpha 2 or a mutant IFN alpha 2 (IFN alpha 2(YNS)) with the goal of targeting IFN to CD138-expressing cells, thereby achieving effective IFN concentrations at the site of the tumor in the absence of toxicity. The fusion proteins inhibited the proliferation and induced apoptosis of U266, ANBL-6, NCI-H929, and MM1-144 MM cell lines. The fusion proteins decreased the expression of IFN regulatory factor 4 (IRF4) in U266. In addition, the fusion proteins were effective against primary cells from MM patients, and treatment with fusion proteins prolonged survival in the U266 murine model of MM. These studies show that IFN alpha antibody fusion proteins can be effective novel therapeutics for the treatment of MM. C1 [Yoo, Esther M.; Trinh, Kham R.; Danh Tran; Vasuthasawat, Alex; Zhang, Juan; Morrison, Sherie L.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. [Zhang, Juan] China Pharmaceut Univ, State Key Lab Nat Med, Sch Life Sci & Technol, Nanjing, Jiangsu, Peoples R China. [Hoang, Bao; Lichtenstein, Alan] Greater Los Angeles Vet Adm Healthcare Ctr, Los Angeles, CA USA. [Hoang, Bao; Lichtenstein, Alan] Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA. [Hoang, Bao; Lichtenstein, Alan] Univ Calif Los Angeles, Div Hematol Oncol, Los Angeles, CA 90095 USA. [Morrison, Sherie L.] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. RP Morrison, SL (reprint author), Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, 247 BSRB 615 Charles E Young Dr East, Los Angeles, CA 90095 USA. EM sheriem@microbio.ucla.edu FU Senior Research Award; Dean Assink/Multiple Myeloma Research Foundation Senior Research Award; National Institutes of Health [2RO1CA111448, 1RO1CA132778, 1R21CA168491]; Multiple Myeloma Research Foundation; Veteran's Administration FX This work was supported by the Senior Research Award (S.L.M.), the Dean Assink/Multiple Myeloma Research Foundation Senior Research Award (S.L.M.), the National Institutes of Health (grants 2RO1CA111448, 1RO1CA132778 and 1R21CA168491 to A.L.), and grants from the Multiple Myeloma Research Foundation (A.L.), and the Veteran's Administration (A.L.). NR 34 TC 5 Z9 5 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 EI 1557-7465 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD APR 1 PY 2015 VL 35 IS 4 BP 281 EP 291 DI 10.1089/jir.2014.0125 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA CF1PW UT WOS:000352321000006 PM 25353626 ER PT J AU Ko, F Isoda, F Mobbs, C AF Ko, Fred Isoda, Fumiko Mobbs, Charles TI Laparotomy in Mice Induces Blood Cell Expression of Inflammatory and Stress Genes SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; MULTIPLE ORGAN FAILURE; OXIDATIVE STRESS; REACTIVE OXYGEN; SURGICAL TRAUMA; GLUTATHIONE DEPLETION; SIGNALING PATHWAYS; IMMUNE-RESPONSE; ONCOSTATIN-M; SURGERY AB Surgical trauma induces immune and stress responses although its effects on postsurgical inflammatory and stress gene expression remain poorly characterized. This study sought to improve current scientific knowledge by investigating the effects of laparotomy on mouse blood cell inflammatory and stress gene expression. Three-month-old male C57BL/6J mice were subjected to 2% isoflurane or 2% isoflurane with laparotomy and sacrificed 4 h postintervention. Blood was collected and blood cell expression of 158 genes central to inflammatory and stress responses was assayed using quantitative polymerase chain reaction arrays. Mice subjected to isoflurane with laparotomy, compared with mice receiving isoflurane alone, had >2-fold upregulation of genes in inflammation (Osm, IL1rn, IL1b, and Csf1), oxidative stress (Hmox1), heat shock (Hspa1b), growth arrest (Cdkn1a), and DNA repair (Ugt1a2). These genes demonstrated similar expression patterns by Pearson correlation and cluster analysis. Thus, laparotomy induces coordinated, postsurgical blood cell expression of unique inflammatory and stress genes whose roles in influencing surgical outcomes need further investigation. C1 [Ko, Fred; Mobbs, Charles] Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Ko, Fred] James J Peters VA Med Ctr, GRECC, Bronx, NY USA. [Isoda, Fumiko; Mobbs, Charles] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. RP Ko, F (reprint author), Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, One Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM fred.ko@mssm.edu FU NIH [P30 AG028741-01A2, 5KL2RR029885-03]; Hartford Foundation National Center of Excellence Award FX This work was supported by grants from the NIH (P30 AG028741-01A2 and 5KL2RR029885-03) and The Hartford Foundation National Center of Excellence Award. The authors wish to thank Dr. Christopher Cardozo's critical reading of this article and Qingling Du's assistance with statistical analysis. NR 58 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 EI 1557-7465 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD APR 1 PY 2015 VL 35 IS 4 BP 302 EP 312 DI 10.1089/jir.2014.0031 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA CF1PW UT WOS:000352321000008 PM 25406893 ER PT J AU Sidhu, M Uthamalingam, S Engel, L Lee, AM Ghoshhajra, B AF Sidhu, M. Uthamalingam, S. Engel, L. Lee, A. M. Ghoshhajra, B. TI DUAL - ENERGY CT MYOCARDIAL PERFUSION IMAGING OF VASODIALATOR INDUCED MYOCARDIAL ISCHEMIA SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Combined Annual Meeting of the Central-Society-for-Clinical-and-Translational-Research and Midwestern-Section of American-Federation-for-Medical-Research CY APR 23-24, 2015 CL Chicago, IL SP Cent Soc Clin & Translat Res, Amer Federat Med Res, Midwestern Sect C1 [Sidhu, M.] Univ Missouri, Cardiovasc Med, Columbia, MO USA. [Uthamalingam, S.; Engel, L.; Lee, A. M.; Ghoshhajra, B.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Uthamalingam, S.; Engel, L.; Lee, A. M.; Ghoshhajra, B.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD APR PY 2015 VL 63 IS 4 MA 19 BP 664 EP 664 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA CE3EZ UT WOS:000351710300041 ER PT J AU Linnemann, AK Battiola, TJ Kimple, ME Davis, DB Neuman, JC Davis, DB AF Linnemann, A. K. Battiola, T. J. Kimple, M. E. Davis, D. B. Neuman, J. C. Davis, D. B. TI PANCREATIC ISLET GLP-1 SECRETION IS INCREASED IN NON-DIABETIC OBESITY AND GLP-1 DIRECTLY REGULATES BETA-CELL CHOLECYSTOKININ PRODUCTION SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Combined Annual Meeting of the Central-Society-for-Clinical-and-Translational-Research and Midwestern-Section of American-Federation-for-Medical-Research CY APR 23-24, 2015 CL Chicago, IL SP Cent Soc Clin & Translat Res, Amer Federat Med Res, Midwestern Sect C1 [Linnemann, A. K.; Battiola, T. J.; Kimple, M. E.; Davis, D. B.] Univ Wisconsin, Med Endocrinol, Madison, WI USA. [Neuman, J. C.] Univ Wisconsin, Nutr Sci, Madison, WI USA. [Davis, D. B.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD APR PY 2015 VL 63 IS 4 MA 26 BP 667 EP 667 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA CE3EZ UT WOS:000351710300048 ER PT J AU Ren, B Silverstein, R Best, B Ramakrishnan, D Walcott, B Storz, P AF Ren, B. Silverstein, R. Best, B. Ramakrishnan, D. Walcott, B. Storz, P. TI ENDOTHELIAL CELL CD36 TRANSCRIPTION IS DOWNREGULATED BY LPA/PKD-1-HDAC7-FOXO1 SIGNALING AXIS AND IS ASSOCIATED WITH PROANGIOGENIC REPROGRAMMING SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Combined Annual Meeting of the Central-Society-for-Clinical-and-Translational-Research and Midwestern-Section of American-Federation-for-Medical-Research CY APR 23-24, 2015 CL Chicago, IL SP Cent Soc Clin & Translat Res, Amer Federat Med Res, Midwestern Sect C1 [Ren, B.; Silverstein, R.] Med Coll Wisconsin, BloodCtr Wisconsin, Blood Res Inst, Milwaukee, WI 53226 USA. [Best, B.; Ramakrishnan, D.] Blood Ctr Wisconsin, Blood Res Inst, Milwaukee, WI USA. [Walcott, B.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Storz, P.] Mayo Clin, Canc Biol, Jacksonville, FL 32224 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD APR PY 2015 VL 63 IS 4 MA 126 BP 690 EP 690 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA CE3EZ UT WOS:000351710300112 ER PT J AU Vranceanu, AM Merker, VL Park, ER Plotkin, SR AF Vranceanu, Ana-Maria Merker, Vanessa L. Park, Elyse R. Plotkin, Scott R. TI Quality of life among children and adolescents with neurofibromatosis 1: a systematic review of the literature SO JOURNAL OF NEURO-ONCOLOGY LA English DT Review DE Neurofibromatosis 1; Quality of life; Children; Adolescents ID SCHWANNOMATOSIS; TYPE-1; VALIDITY; RELIABILITY; POPULATION; PREVALENCE; DISORDERS; OUTCOMES; DISEASE; COHORT AB The aim of this research is to identify, within a systematic review, aspects of quality of life (QoL) that are adversely affected in children and adolescents with neurofibromatosis (NF), and to report predictors of quality of life in this population. Published reports of original research were included if they described QoL in children and/or adolescents with NF, and met methodological quality according to a list of predefined criteria. Seven studies conducted between 2006 and 2013 met inclusion criteria. All seven studies examined patients with NF1 and reported that these patients have lower general QoL compared to population norms. Parents' proxy ratings of QoL were generally lower than children's self-report ratings. By parent proxy, familial NF1 was a strong protective factor for QoL, while the opposite was found by child report. By parent proxy, male sex was significantly associated with lower scores on the parental time impact of QoL. Skin-related QoL was only slightly altered in this population, vision-specific QoL was impacted only in patients with vision loss. The majority of findings regarding predictors of QoL in children with NF1 were weak, due to a lack of studies, heterogeneity of samples, and heterogeneity of measurements/predictors assessed. Future studies should examine more comprehensively the psychosocial factors affecting the NF population, especially in young patients with NF2 and schwannomatosis, who have been neglected in prior research. The use of consistent QoL measures is preferred to allow better comparison among studies and conditions. Interventions, including comprehensive mind-body treatments, are warranted to address impaired QoL in children and adolescents with NF1. C1 [Vranceanu, Ana-Maria; Park, Elyse R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Merker, Vanessa L.; Plotkin, Scott R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Merker, Vanessa L.; Plotkin, Scott R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. RP Vranceanu, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Ne Bowdoin Sq, Boston, MA 02114 USA. EM avranceanu@mgh.harvard.edu OI Merker, Vanessa/0000-0002-4542-5227 NR 33 TC 5 Z9 5 U1 1 U2 9 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 APR PY 2015 VL 122 IS 2 BP 219 EP 228 DI 10.1007/s11060-015-1725-1 PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CE5FL UT WOS:000351856300001 PM 25663248 ER PT J AU Perez, SE He, B Nadeem, M Wuu, J Ginsberg, SD Ikonomovic, MD Mufson, EJ AF Perez, Sylvia E. He, Bin Nadeem, Muhammad Wuu, Joanne Ginsberg, Stephen D. Ikonomovic, Milos D. Mufson, Elliott J. TI Hippocampal Endosomal, Lysosomal, and Autophagic Dysregulation in Mild Cognitive Impairment: Correlation With A beta and Tau Pathology SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer disease; Autophagy; Cathepsin D; Endosomallysosomal proteins; Hippocampus; Mild cognitive impairment; mTOR; Rabaptin5 ID AMYLOID PRECURSOR PROTEIN; FRONTOTEMPORAL LOBAR DEGENERATION; SPORADIC ALZHEIMERS-DISEASE; CATHEPSIN-D; UP-REGULATION; ENDOCYTIC PATHWAY; SIGNALING PATHWAY; MAMMALIAN TARGET; NEURODEGENERATIVE DISEASES; NEUROTROPHIN RECEPTOR AB Endosomal-lysosomal and autophagic dysregulation occurs in the hippocampus in prodromal Alzheimer disease (AD), but its relationship with A-amyloid (AA) and tau pathology remains unclear. To investigate this issue, we performed immunoblot analysis of hippocampal homogenates from cases with an antemortem clinical diagnosis of no cognitive impairment, mild cognitive impairment (MCI), and AD. Western blot analysis revealed significant increases in the acid hydrolase cathepsin D and early endosome marker rabaptin5 in the MCI group compared with AD, whereas levels of phosphorylated mammalian target of rapamycin proteins (pmTOR), total mammalian target of rapamycin (mTOR), p62, traf6, and LilrB2 were comparable across clinical groups. Hippocampal A beta 1 (40) and A beta(1) (42) concentrations and AT8-immunopositive neurofibrillary tangle density were not significantly different across the clinical groups. Greater cathepsin D expression was associated with global cognitive score and episodic memory score but not with mini mental state examination or advanced neuropathology criteria. These results indicate that alterations in hippocampal endosomal-lysosomal proteins in MCI are independent of tau or AA pathology. C1 [Perez, Sylvia E.; Mufson, Elliott J.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [He, Bin; Nadeem, Muhammad; Mufson, Elliott J.] Barrow Neurol Inst, Alzheimers Dis Res Lab, Phoenix, AZ 85013 USA. [Wuu, Joanne] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. [Ginsberg, Stephen D.] Nathan S Kline Inst Psychiat Res, Ctr Dementia Res, Orangeburg, NY USA. [Ginsberg, Stephen D.] NYU Langone Med Ctr, Dept Psychiat, New York, NY USA. [Ginsberg, Stephen D.] NYU Langone Med Ctr, Dept Physiol, New York, NY USA. [Ginsberg, Stephen D.] NYU Langone Med Ctr, Dept Neurosci, New York, NY USA. [Ikonomovic, Milos D.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Ikonomovic, Milos D.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. [Ikonomovic, Milos D.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Mufson, EJ (reprint author), Barrow Neurol Inst, Alzheimers Dis Res Lab, 350 W Thomas St, Phoenix, AZ 85013 USA. EM elliott.mufson@dignityhealth.org FU NIA [PO1AG14449, RO1AG043375, P30AG010161, RO1AG042210, PO1AG025204, PO1AG107617]; Alzheimer's Association; Brinson Foundation FX Supported by NIA Grants PO1AG14449, RO1AG043375, P30AG010161, RO1AG042210, PO1AG025204, PO1AG107617, Alzheimer's Association, and Brinson Foundation. NR 110 TC 10 Z9 12 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD APR PY 2015 VL 74 IS 4 BP 345 EP 358 PG 14 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA CE2UV UT WOS:000351676100005 PM 25756588 ER PT J AU Jadvar, H Subramaniam, RM Berman, CG Boada, F Colletti, PM Guimaraes, AR McConathy, J Meltzer, CC Noto, RB Packard, AB Rohren, EM Oates, ME AF Jadvar, Hossein Subramaniam, Rathan M. Berman, Claudia G. Boada, Fernando Colletti, Patrick M. Guimaraes, Alexander R. McConathy, Jonathan Meltzer, Carolyn C. Noto, Richard B. Packard, Alan B. Rohren, Eric M. Oates, M. Elizabeth TI American College of Radiology and Society of Nuclear Medicine and Molecular Imaging Joint Credentialing Statement for PET/MR Imaging: Brain SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article C1 [Jadvar, Hossein; Colletti, Patrick M.] Univ So Calif, Los Angeles, CA 90033 USA. [Subramaniam, Rathan M.] Johns Hopkins Univ, Baltimore, MD USA. [Berman, Claudia G.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Boada, Fernando] NYU, New York, NY USA. [Guimaraes, Alexander R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McConathy, Jonathan] Washington Univ, St Louis, MO USA. [Meltzer, Carolyn C.] Emory Univ, Atlanta, GA 30322 USA. [Noto, Richard B.] Brown Univ, Providence, RI 02912 USA. [Packard, Alan B.] Boston Childrens Hosp, Boston, MA USA. [Rohren, Eric M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Oates, M. Elizabeth] Univ Kentucky, Lexington, KY USA. RP Jadvar, H (reprint author), Univ So Calif, 2250 Alcazar St,CSC 102, Los Angeles, CA 90033 USA. EM jadvar@med.usc.edu FU NIBIB NIH HHS [P41 EB017183] NR 11 TC 2 Z9 2 U1 0 U2 9 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 APR PY 2015 VL 56 IS 4 BP 642 EP 645 DI 10.2967/jnumed.115.155218 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CE9NL UT WOS:000352170600052 PM 25745088 ER PT J AU Scanzello, CR Markova, DZ Chee, A Xiu, Y Adams, SL Anderson, G Zgonis, M Qin, L An, HS Zhang, YJ AF Scanzello, Carla R. Markova, Dessislava Z. Chee, Ana Xiu, Yan Adams, Sherrill L. Anderson, Greg Zgonis, Miltiadis Qin, Ling An, Howard S. Zhang, Yejia TI Fibronectin Splice Variation in Human Knee Cartilage, Meniscus and Synovial Membrane: Observations in Osteoarthritic Knee SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE fibronectin; alternative splicing; cartilage; synovium; degeneration ID B-CONTAINING FIBRONECTIN; RHEUMATOID-ARTHRITIS; ARTICULAR-CARTILAGE; EXTRA-DOMAIN; MESSENGER-RNA; EIIIA SEGMENT; CELL-ADHESION; NERVE GROWTH; ED-A; EXPRESSION AB Fibronectin (FN) is a widely expressed molecule that can participate in development of osteoarthritis (OA) affecting cartilage, meniscus, and synovial membrane (SM). The alternatively spliced isoforms of FN in joint tissues other than cartilage have not been extensively studied previously. The present study compares FN splice variation in patients with varying degrees of osteoarthritic change. Joint tissues were collected from asymptomatic donors and patients undergoing arthroscopic procedures. Total RNA was amplified by PCR using primers flanking alternatively spliced Extra Domain A (EDA), Extra Domain B (EDB) and Variable (V) regions. EDB+, EDB- and EDA(-) and V+ variants were present in all joint tissues, while the EDA(+) variant was rarely detected. Expression levels of EDB+ and EDV+ variants were similar in cartilage, synovium, and meniscal tissues. Synovial expression of V+ FN in arthroscopy patients varied with degree of cartilage degeneration. Two V- isoforms, previously identified in cartilage, were also present in SM and meniscus. Fibronectin splicing in meniscus and SM bears striking resemblance to that of cartilage. Expression levels of synovial V+ FN varied with degree of cartilage degeneration. V+ FN should be investigated as a potential biomarker of disease stage or progression in larger populations. (c) 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:556-562, 2015. C1 [Scanzello, Carla R.] Univ Penn, Philadelphia Vet Affairs Med Ctr, Div Rheumatol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Markova, Dessislava Z.; Anderson, Greg] Thomas Jefferson Univ, Dept Orthoped Surg, Philadelphia, PA 19107 USA. [Chee, Ana; An, Howard S.; Zhang, Yejia] Rush Univ, Dept Orthoped Surg, Med Ctr, Chicago, IL 60612 USA. [Adams, Sherrill L.] Univ Penn, Sch Dent Med, Dept Biochem, Philadelphia, PA 19104 USA. [Xiu, Yan; Zgonis, Miltiadis; Qin, Ling] Univ Penn, Perelman Sch Med, Dept Orthoped Surg, Philadelphia, PA 19104 USA. [Zhang, Yejia] Univ Penn, Perelman Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Zhang, Yejia] Univ Penn, Perelman Sch Med, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA. RP Zhang, YJ (reprint author), Rush Univ, Dept Orthoped Surg, Med Ctr, Chicago, IL 60612 USA. EM yejia.zhang@uphs.upenn.edu FU National Institute of Child Health and Human Development [1K08 HD049598]; National Institute of Arthritis, Musculoskeletal and Skin Diseases [1K08 AR057859]; NIH [AR060991] FX Grant sponsor: National Institute of Child Health and Human Development; Grant number: 1K08 HD049598; Grant sponsor: National Institute of Arthritis, Musculoskeletal and Skin Diseases; Grant number: 1K08 AR057859; Grant sponsor: NIH; Grant number: AR060991. NR 38 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 EI 1554-527X J9 J ORTHOP RES JI J. Orthop. Res. PD APR PY 2015 VL 33 IS 4 BP 556 EP 562 DI 10.1002/jor.22787 PG 7 WC Orthopedics SC Orthopedics GA CE2YE UT WOS:000351687400016 PM 25410897 ER PT J AU Feng, Y Tsai, TY Li, JS Wang, SB Hu, H Zhang, CQ Rubash, HE Li, GA AF Feng, Yong Tsai, Tsung-Yuan Li, Jing-Sheng Wang, Shaobai Hu, Hai Zhang, Changqing Rubash, Harry E. Li, Guoan TI Motion of the Femoral Condyles in Flexion and Extension During a Continuous Lunge SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE condylar motion; continuous flexion-extension; gender difference; in vivo knee kinematics ID SINGLE-PLANE FLUOROSCOPY; TOTAL KNEE ARTHROPLASTY; IN-VIVO KINEMATICS; WEIGHT-BEARING; GENDER-DIFFERENCES; LIVING KNEE; DESIGN; DIFFERENCE; STIFFNESS; MOVEMENT AB Numerous studies have reported on in-vivo posterior femoral condyle translations during various activities of the knee. However, no data has been reported on the knee motion during a continuous flexion-extension cycle. Further, few studies have investigated the gender variations on the knee kinematics. This study quantitatively determined femoral condylar motion of 10 male and 10 female knees during a continuous weightbearing flexion-extension cycle using two-dimensional to three-dimensional fluoroscopic tracking technique. The knees were CT-scanned to create three-dimensional models of the tibia and femur. Continuous images of each subject were taken using a single-fluoroscopic imaging system. The knee kinematics were measured along the motion path using geometric center axis of the femur. The results indicated that statistical differences between the flexion and extension motions were only found in internal-external tibial rotation and lateral femoral condylar motion at the middle range of flexion angles. At low flexion angles, male knees have greater external tibial rotation and more posteriorly positioned medial femoral condyle than females. The knee did not show a specific pivoting type of rotation with flexion. Axial rotation center varied from lateral to medial compartments of the knee. These data could provide useful information for understanding physiological motion of normal knees. (c) 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:591-597, 2015. C1 [Feng, Yong; Hu, Hai; Zhang, Changqing] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Orthopaed Surg, Shanghai 200233, Peoples R China. [Feng, Yong; Tsai, Tsung-Yuan; Li, Jing-Sheng; Wang, Shaobai; Rubash, Harry E.; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab Med Sch, Boston, MA 02114 USA. RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab Med Sch, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM Li.Guoan@mgh.harvard.edu OI Tsai, Tsung-Yuan/0000-0003-1522-2987 FU National Key Clinical Specialist Construction Project of China; National Institutes of Health [R01 AR055612] FX This study has been supported by National Key Clinical Specialist Construction Project of China and National Institutes of Health Grant (R01 AR055612). NR 33 TC 4 Z9 4 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 EI 1554-527X J9 J ORTHOP RES JI J. Orthop. Res. PD APR PY 2015 VL 33 IS 4 BP 591 EP 597 DI 10.1002/jor.22826 PG 7 WC Orthopedics SC Orthopedics GA CE2YE UT WOS:000351687400020 PM 25641056 ER PT J AU LeBlanc, TW Nipp, RD Rushing, CN Samsa, GP Locke, SC Kamal, AH Cella, DF Abernethy, AP AF LeBlanc, Thomas W. Nipp, Ryan D. Rushing, Christel N. Samsa, Greg P. Locke, Susan C. Kamal, Arif H. Cella, David F. Abernethy, Amy P. TI Correlation Between the International Consensus Definition of the Cancer Anorexia-Cachexia Syndrome (CACS) and Patient-Centered Outcomes in Advanced Non-Small Cell Lung Cancer SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Patient outcome assessment; health services research; carcinoma; non-small cell lung ID QUALITY-OF-LIFE; COOPERATIVE-ONCOLOGY-GROUP; FUNCTIONAL ASSESSMENT; DOUBLE-BLIND; MISSING DATA; WEIGHT-LOSS; CLINICAL-TRIALS; THERAPY; CARE; SYMPTOMS AB Context. The cancer anorexia-cachexia syndrome (CACS) is common in patients with advanced solid tumors and is associated with adverse outcomes including poor quality of life (QOL), impaired functioning, and shortened survival. Objectives. To apply the recently posed weight-based international consensus CACS definition to a population of patients with advanced non-small cell lung cancer (NSCLC) and explore its impact on patient-reported outcomes. Methods. Ninety-nine patients participated in up to four study visits over a six-month period. Longitudinal assessments included measures of physical function, QOL, and other clinical variables such as weight and survival. Results. Patients meeting the consensus CACS criteria at Visit 1 had a significantly shorter median survival (239.5 vs. 446 days; hazard ratio, 2.06, P < 0.05). Physical function was worse in the CACS group (mean Karnofsky Performance Status score 68 vs. 77, Eastern Cooperative Oncology Group Performance Status score 1.8 vs. 1.3, P < 0.05 for both), as was QOL (Functional Assessment of Cancer Therapy-General [FACT-G] Lung Cancer subscale of 17.2 vs. 19.9, Anorexia/Cachexia subscale of 31.4 vs. 37.9, P < 0.05 for both). Differences in the FACT-G and the Functional Assessment of Chronic Illness Therapy-Fatigue subscale approached but did not reach statistical significance. Longitudinally, all measures of physical function and QOL worsened regardless of CACS status, but the rate of decline was more rapid in the CACS group. Conclusion. The weight-based component of the recently proposed international consensus CACS definition is useful in identifying patients with advanced NSCLC who are likely to have significantly inferior survival and who will develop more precipitous declines in physical function and QOL. This definition may be useful for clinical screening purposes and identify patients with high palliative care needs. (C) 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved. C1 [LeBlanc, Thomas W.; Kamal, Arif H.; Abernethy, Amy P.] Duke Univ, Sch Med, Duke Canc Inst, Durham, NC USA. [LeBlanc, Thomas W.; Rushing, Christel N.; Samsa, Greg P.; Locke, Susan C.; Kamal, Arif H.; Abernethy, Amy P.] Duke Clin Res Inst, Ctr Learning Hlth, Durham, NC USA. [LeBlanc, Thomas W.] Duke Univ, Sch Med, Dept Med, Div Hematol Malignancies & Cellular Therapy, Durham, NC 27706 USA. [Kamal, Arif H.; Abernethy, Amy P.] Duke Univ, Sch Med, Dept Med, Div Med Oncol, Durham, NC 27706 USA. [Nipp, Ryan D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cella, David F.] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA. RP Abernethy, AP (reprint author), DUMC, Box 3436, Durham, NC 27710 USA. EM amy.abernethy@duke.edu OI LeBlanc, Thomas/0000-0002-0546-7895 FU Helsinn Therapeutics; Junior Career Development Award grant from the National Palliative Care Research Center; DARA Biosciences; Glaxo Smith Kline; Celgene; Dendreon; Kanglaite; Bristol Myers Squibb; Pfizer; NINR [U24 NR014637-02, UC4-12584]; Galena Biopharma; Insys Therapeutics; NIH/AHRQ [R18-HS-022763-01]; North Carolina Oncology Society, Association of Community Cancer Centers, American Academy of Hospice and Palliative Medicine; American Society of Clinical Oncology FX This work was funded in part via a research grant from Helsinn Therapeutics to Duke University Medical Center. Dr. LeBlanc receives research funding from a Junior Career Development Award grant from the National Palliative Care Research Center. Dr. Abernethy has research funding from DARA Biosciences, Glaxo Smith Kline, Celgene, Helsinn Therapeutics, Dendreon, Kanglaite, Bristol Myers Squibb and Pfizer, as well as federal sources (NINR U24 NR014637-02; UC4-12584); these funds are all distributed to Duke University Medical Center to support research including salary support for Dr. Abernethy. Pending industry funded projects include: Galena Biopharma and Insys Therapeutics. She has consulting agreements with or received honoraria from Novartis and from Pfizer (<$5,000 annually) and from Bristol-Myers Squibb (>$5,000 annually). Dr. Abernethy has corporate leadership responsibility in Flatiron Health Inc. (health information technology [HIT] company; Chief Medical Officer & Senior Vice President), athenahealth Inc. (HIT company; Director), Advoset LLC(education company; Owner), and Orange Leaf Associates LLC (IT development company; Owner). Dr. Kamal reports grant support from NIH/AHRQ R18-HS-022763-01 and speaker support from the North Carolina Oncology Society, Association of Community Cancer Centers, American Academy of Hospice and Palliative Medicine, and American Society of Clinical Oncology. The other authors have no disclosures to report. NR 48 TC 9 Z9 9 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 APR PY 2015 VL 49 IS 4 BP 680 EP 689 DI 10.1016/j.jpainsymman.2014.09.008 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA CE4ZU UT WOS:000351840100008 PM 25461669 ER PT J AU McDonald, JC Spruyt, O Alhatem, A AF McDonald, Julie Clare Spruyt, Odette Alhatem, Albert TI Control of Intractable Pruritus in a Patient With Cutaneous T-Cell Lymphoma Using a Continuous Subcutaneous Infusion of Lidocaine SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Letter ID EFFICACY; ITCH C1 [McDonald, Julie Clare] Univ Hlth Network, Princess Margaret Canc Ctr, Dept Psychosocial Oncol & Palliat Care, Toronto, ON, Canada. [Spruyt, Odette] Univ Melbourne, Peter MacCallum Canc Ctr, Pain & Palliat Care, Melbourne, Vic, Australia. [Alhatem, Albert] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA USA. RP McDonald, JC (reprint author), Univ Hlth Network, Princess Margaret Canc Ctr, Dept Psychosocial Oncol & Palliat Care, Toronto, ON, Canada. EM Julie.clare4@gmail.com OI mcdonald, julie/0000-0003-4115-7875 NR 10 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD APR PY 2015 VL 49 IS 4 BP E1 EP E3 DI 10.1016/j.jpainsymman.2014.12.005 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA CE4ZU UT WOS:000351840100001 PM 25623922 ER PT J AU Yawn, J Lawrence, LA Carroll, WW Mulligan, JK AF Yawn, James Lawrence, Lauren A. Carroll, William W. Mulligan, Jennifer K. TI Vitamin D for the treatment of respiratory diseases: Is it the end or just the beginning? SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Review DE Vitamin D; Sinusitis; Asthma; Rhinitis; Supplementation ID AIRWAY SMOOTH-MUSCLE; 25-HYDROXYVITAMIN D LEVELS; BRONCHIAL EPITHELIAL-CELLS; REGULATORY T-CELLS; ALLERGIC FUNGAL RHINOSINUSITIS; 1,25-DIHYDROXYVITAMIN D-3; DENDRITIC CELLS; IN-VITRO; D DEFICIENCY; D SUPPLEMENTATION AB A large number of human, animal and in vitro studies have suggested that vitamin D3 (VD3) plays a critical role in inflammatory airway diseases such as asthma, chronic rhinosinusitis, and allergic rhinitis. VD3 acts upon a broad range of immune cells involved in the pathogenesis of these diseases including T-cells, dendritic cells (DCs), macrophages, and B-cells. In addition, VD3 can also regulate the functions of a number of non-immune cells including epithelial cells, fibroblasts, and smooth muscle cells. Given that VD3 has known effects on the immune system, it seems logical that supplementation with VD3 would prove efficacious in the treatment of these three diseases. While many studies, most of which are observational, have suggested that VD3 deficiency is associated with more severe disease, VD3 supplementation trials in humans have resulted in varied outcomes in terms of efficacy. In this review article we will discuss the role of VD3 in these three commonly associated respiratory diseases. We will explore the literature describing associations of VD3 deficiency with patient outcomes, cells in the respiratory microenvironment susceptible to VD3 regulation, conflicting results of VD3 supplementation trials, and potential gaps in our knowledge that may be limiting the widespread use of VD3 for the treatment of respiratory diseases such asthma, chronic rhinosinusitis and allergic rhinitis. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Yawn, James; Lawrence, Lauren A.; Carroll, William W.; Mulligan, Jennifer K.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Mulligan, Jennifer K.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Mulligan, Jennifer K.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Mulligan, JK (reprint author), 135 Rutledge Ave,MSC 550, Charleston, SC 29425 USA. EM konopa@musc.edu FU American Academy of Otolaryngology - Head & Neck Surgery Foundation; Flight Attendant Medical Research Institute; Department of Veterans Affairs; W.K. Kellogg Foundation; National Institute of Health; American Society of Pediatric Otolaryngology FX Dr. Carroll has received grant funding from the American Academy of Otolaryngology - Head & Neck Surgery Foundation. Dr. Mulligan has received research grant funding from the Flight Attendant Medical Research Institute, Department of Veterans Affairs,W.K. Kellogg Foundation, National Institute of Health and the American Society of Pediatric Otolaryngology. NR 173 TC 9 Z9 9 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD APR PY 2015 VL 148 SI SI BP 326 EP 337 DI 10.1016/j.jsbmb.2015.01.017 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA CE4FJ UT WOS:000351786200049 PM 25625665 ER PT J AU Walcott, BP Stapleton, CJ Koch, MJ Ogilvy, CS AF Walcott, Brian P. Stapleton, Christopher J. Koch, Matthew J. Ogilvy, Christopher S. TI Diffuse Patterns of Nonaneurysmal Subarachnoid Hemorrhage Originating from the Basal Cisterns Have Predictable Vasospasm Rates Similar to Aneurysmal Subarachnoid Hemorrhage SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Aneurysm; vasospasm; subarachnoid hemorrhage; hydrocephalus ID SYMPTOMATIC VASOSPASM; CATHETER ANGIOGRAPHY; CEREBRAL ANEURYSMS; CLINICAL-COURSE; FISHER SCALE AB Background: Nonaneurysmal subarachnoid hemorrhage (SAH) has been historically associated with a benign clinical course. However, recent studies have suggested that nonaneurysmal SAH can present with different hemorrhage patterns that may be associated with differential rates of morbidity. Herein, we analyze a retrospective consecutive cohort of patients with nonaneurysmal SAH to determine outcomes. We also seek to evaluate a validated radiographic grading scale to determine its utility in predicting vasospasm in the setting of different hemorrhage patterns. Methods: After institutional review board approval, the records of 563 consecutive patients admitted with spontaneous SAH between January 2007 and 2014 were retrospectively reviewed. A total of 138 of these patients had no identifiable source of hemorrhage and were further divided into 2 groups depending on their pattern of hemorrhage: perimesencephalic or diffuse. Clinical characteristics and outcomes were assessed. Results: In nonaneurysmal SAH, 70 patients (50.7%) had a perimesencephalic pattern of hemorrhage, whereas 68 (49.3%) experienced diffuse SAH. Radiographic vasospasm developed in 6 patients (8.6%) with perimesencephalic SAH and in 14 patients (20.6%) with a diffuse SAH pattern. When comparing historical rates of vasospasm based on the Barrow Neurological Institute (BNI) scale and rates in the nonaneurysmal diffuse pattern in this series, there was no significant difference in distribution (chi-square; P = .149), compared with a difference seen with the perimesencephalic group (P < .00001). Conclusions: Nonaneurysmal SAH is associated with the potential for vasospasm, with higher rates in the diffuse versus perimesencephalic SAH patterns. The BNI grading scale for aneurysmal SAH can be used to predict the risk of vasospasm in diffuse, nonaneurysmal SAH. C1 [Walcott, Brian P.; Stapleton, Christopher J.; Koch, Matthew J.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Walcott, Brian P.; Stapleton, Christopher J.; Koch, Matthew J.; Ogilvy, Christopher S.] Harvard Univ, Sch Med, Boston, MA USA. [Ogilvy, Christopher S.] Beth Israel Deaconess Med Ctr, Dept Surg, Div Neurosurg, Boston, MA 02215 USA. [Ogilvy, Christopher S.] Beth Israel Deaconess Med Ctr, Brain Aneurysm Inst, Boston, MA 02215 USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 15 Parkman St,ACC 021, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu NR 30 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 EI 1532-8511 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD APR PY 2015 VL 24 IS 4 BP 795 EP 801 DI 10.1016/j.jstrokecerebrovasdis.2014.11.011 PG 7 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CE5FP UT WOS:000351856700019 PM 25680661 ER PT J AU Fairweather, M Raut, CP AF Fairweather, Mark Raut, Chandrajit P. TI Surgical Management of GIST and Intra-Abdominal Visceral Leiomyosarcomas SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Review DE intra-abdominal sarcoma; visceral sarcoma; leiomyosarcoma; gastrointestinal stromal tumor; surgery ID GASTROINTESTINAL STROMAL TUMORS; SOFT-TISSUE SARCOMAS; PHASE-II TRIAL; NEOADJUVANT/ADJUVANT IMATINIB MESYLATE; TERM-FOLLOW-UP; PROGNOSTIC-FACTORS; RADIATION-THERAPY; LAPAROSCOPIC RESECTION; INTRAMURAL LEIOMYOMAS; ADJUVANT CHEMOTHERAPY AB Intra-abdominal visceral sarcomas are a rare group of mesenchymal tumors that require the use of distinct surgical principles and a multidisciplinary approach in order to optimize treatment. Surgery remains the only potentially curative treatment. Management and outcomes vary for the different sarcomas arising from viscera. This review will summarize the current treatment strategies for the two most common visceral sarcomas, leiomyosarcomas, and gastrointestinal stromal tumors. J. Surg. Oncol. 2015 111:562-569. (c) 2014 Wiley Periodicals, Inc. C1 [Fairweather, Mark; Raut, Chandrajit P.] Brigham & Womens Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02115 USA. [Fairweather, Mark; Raut, Chandrajit P.] Harvard Univ, Sch Med, Boston, MA USA. [Raut, Chandrajit P.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. RP Raut, CP (reprint author), Brigham & Womens Hosp, Dept Surg, Div Surg Oncol, 75 Francis St, Boston, MA 02115 USA. EM craut@partners.org NR 74 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4790 EI 1096-9098 J9 J SURG ONCOL JI J. Surg. Oncol. PD APR 1 PY 2015 VL 111 IS 5 SI SI BP 562 EP 569 DI 10.1002/jso.23803 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA CE2YH UT WOS:000351687700011 PM 25335830 ER PT J AU Bernstein, KD Delaney, TF AF Bernstein, Karen De Amorim Delaney, Thomas F. TI Role of Radiation Therapy for Non-Extremity Soft Tissue Sarcomas SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Review DE Head and neck sarcomas; paraspinal sarcomas; chest wall sarcomas; abdominal wall sarcomas; retroperitoneal sarcomas ID COMBINED-MODALITY TREATMENT; ELECTRON-BEAM RADIOTHERAPY; CHEST-WALL SARCOMAS; TERM-FOLLOW-UP; PROGNOSTIC-FACTORS; SURGICAL RESECTION; RETROPERITONEAL SARCOMA; POSTOPERATIVE RADIOTHERAPY; SINGLE INSTITUTION; DOSE-ESCALATION AB BackgroundNegative surgical margins are uncommon for non-extremity soft tissue sarcomas. Radiation therapy is usually recommended to improve local control; however, appropriate RT dosing is challenging due to nearby dose-limiting normal structures. Material and MethodsComprehensive literature search using PubMed (March 2014). ResultsData suggest radiation therapy is an important modality in maximizing local tumor control in non-extremity sarcomas. ConclusionThe literature supports the use of RT to improve local control for non-extremity soft tissue sarcomas. J. Surg. Oncol. 2015 111:604-614. (c) 2014 Wiley Periodicals, Inc. C1 [Bernstein, Karen De Amorim] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Delaney, Thomas F.] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Dept Radiat Oncol, Boston, MA 02114 USA. RP Bernstein, KD (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM kbernstein2@partners.org NR 71 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4790 EI 1096-9098 J9 J SURG ONCOL JI J. Surg. Oncol. PD APR 1 PY 2015 VL 111 IS 5 SI SI BP 604 EP 614 DI 10.1002/jso.23863 PG 11 WC Oncology; Surgery SC Oncology; Surgery GA CE2YH UT WOS:000351687700016 ER PT J AU Jortberg, B Myers, E Gigliotti, L Ivens, BJ Lebre, M March, SB Nogueira, I Nwankwo, R Parkinson, MR Paulsen, B Turner, T AF Jortberg, Bonnie Myers, Eileen Gigliotti, Linda Ivens, Barbara J. Lebre, Monica March, Susan Burke Nogueira, Isadora Nwankwo, Robin Parkinson, Meredith R. Paulsen, Barbara Turner, Tonya TI Academy of Nutrition and Dietetics: Standards of Practice and Standards of Professional Performance for Registered Dietitian Nutritionists (Competent, Proficient, and Expert) in Adult Weight Management SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS LA English DT Article AB Weight management encompasses the inter-relationship of nutrition, physical activity, and health behavior change. Nutrition is key for the prevention and treatment of obesity and chronic disease and maintenance of overall health. Thus, the Weight Management Dietetic Practice Group, with guidance from the Academy of Nutrition and Dietetics Quality Management Committee, has developed Standards of Practice and Standards of Professional Performance for Registered Dietitian Nutritionists (RDNs) in Adult Weight Management as a resource for RDNs working in weight management. This document allows RDNs to assess their current skill levels and to identify areas for further professional development in this expanding practice area. This document describes the current standards for weight management practice for RDNs. The Standards of Practice represent the four steps in the Nutrition Care Process as applied to the care of patients/clients. The Standards of Professional Performance consist of six domains of professionalism: Quality in Practice, Competence and Accountability, Provision of Services, Application of Research, Communication and Application of Knowledge, and Utilization and Management of Resources. Within each standard, specific indicators provide measurable action statements that illustrate how the standard can be applied to practice. The indicators describe three skill levels ( competent, proficient, and expert) for RDNs working in weight management. The Standards of Practice and Standards of Professional Performance are complementary resources for the Registered Dietitian Nutritionist in weight management. C1 [Jortberg, Bonnie] Univ Colorado, Sch Med, Dept Family Med, Aurora, CO 80045 USA. [Myers, Eileen] Little Clin, Nashville, TN USA. [Gigliotti, Linda] Univ Calif Irvine, Weight Management Program, Irvine, CA 92717 USA. [Ivens, Barbara J.] ConAgra Foods, Nutr, Omaha, NE USA. [Lebre, Monica] Northeastern Univ, Boston, MA 02115 USA. [Nogueira, Isadora] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nwankwo, Robin] Univ Michigan, Sch Med, Dept Learning Serv, Ann Arbor, MI USA. [Parkinson, Meredith R.] Christiana Care Hlth Syst, Newark, DE USA. [Turner, Tonya] Med Univ S Carolina, Weight Management Ctr, Charleston, SC USA. RP Jortberg, B (reprint author), Univ Colorado, Sch Med, Dept Family Med, Mail Stop F496,AO1,12631 E 17th Ave,Room 3519, Aurora, CO 80045 USA. EM bonnie.jortberg@ucdenver.edu NR 26 TC 1 Z9 1 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-2672 EI 2212-2680 J9 J ACAD NUTR DIET JI J. Acad. Nutr. Diet. PD APR PY 2015 VL 115 IS 4 BP 609 EP U412 DI 10.1016/j.jand.2014.12.018 PG 50 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CE4CS UT WOS:000351779000014 PM 25819519 ER PT J AU Win, AZ AF Win, Aung Zaw TI Telehealth Can Bridge the Gap for Rural, Disabled, and Elderly Patients SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Editorial Material ID QUALITY-OF-LIFE; HEALTH-CARE; TELEMEDICINE; AMERICA; IMPACT; MODEL C1 San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Win, AZ (reprint author), San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM aungzwin@gmail.com NR 16 TC 3 Z9 3 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 EI 1538-9375 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD APR 1 PY 2015 VL 16 IS 4 BP 268 EP 269 DI 10.1016/j.jamda.2015.01.077 PG 2 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA CE6KT UT WOS:000351946000002 PM 25687928 ER PT J AU Romanus, D Cardarella, S Cutler, D Landrum, MB Lindeman, NI Gazelle, GS AF Romanus, Dorothy Cardarella, Stephanie Cutler, David Landrum, Mary Beth Lindeman, Neal I. Gazelle, G. Scott TI Cost-Effectiveness of Multiplexed Predictive Biomarker Screening in Non-Small-Cell Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Multiplexed test; Non-small-cell; Lung cancer; Targeted therapy; Cost-effectiveness ID CHEMOTHERAPY-NAIVE PATIENTS; KINASE INHIBITOR THERAPY; 1ST-LINE TREATMENT; MAINTENANCE THERAPY; SUPPORTIVE CARE; UNITED-STATES; PHASE-III; EGFR; ERLOTINIB; GEFITINIB AB Introduction: Population-wide screening for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements to inform cancer therapy in non-small-cell lung cancer (NSCLC) is recommended by guidelines. We estimated cost-effectiveness of multiplexed predictive biomarker screening in metastatic NSCLC from a societal perspective in the United States. Methods: We constructed a microsimulation model to compare the life expectancy and costs of multiplexed testing and molecularly guided therapy versus treatment with cisplatin-pemetrexed (CisPem). All testing interventions included a two-step algorithm of concurrent EGFR mutation and ALK overexpression testing with immunohistochemistry followed by ALK rearrangement confirmation with a fluorescence in situ hybridization assay for immunohistochemistry-positive results. Three strategies were included: "Test-treat" approach, where molecularly guided therapy was initiated after obtainment of test results; "Empiric switch therapy," with concurrent initiation of CisPem and testing and immediate switch to test-result conditional treatment after one cycle of CisPem; and "Empiric therapy" approach in which CisPem was continued for four cycles before start of a tyrosine kinase inhibitor. Results: The incremental cost-effectiveness ratio for "Test-treat" compared with treatment with CisPem was $136,000 per quality-adjusted life year gained. Both empiric treatment approaches had less favorable incremental cost-effectiveness ratios. "Test-treat" and "Empiric switch therapy" yielded higher expected outcomes in terms of quality-adjusted life years and life-years than "Empiric therapy." These results were robust across plausible ranges of model inputs. Conclusion: From a societal perspective, our cost-effectiveness results support the value of multiplexed genetic screening and molecularly guided therapy in metastatic NSCLC. C1 [Romanus, Dorothy] Harvard Univ, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02115 USA. [Cardarella, Stephanie] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Cutler, David] Harvard Univ, Dept Econ, Cambridge, MA 02138 USA. [Landrum, Mary Beth] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Lindeman, Neal I.] Harvard Univ, Sch Med, Dept Pathol, Brigham & Women Hosp, Boston, MA 02115 USA. [Gazelle, G. Scott] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. RP Romanus, D (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimack St,10th Floor, Boston, MA 02114 USA. EM dorothy.romanus@mail.harvard.edu FU National Cancer Institute Program in Cancer Outcomes Research Training [R25CA092203] FX This work was supported by the National Cancer Institute Program in Cancer Outcomes Research Training (R25CA092203). NR 35 TC 6 Z9 6 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD APR PY 2015 VL 10 IS 4 BP 586 EP 594 DI 10.1097/JTO.0000000000000474 PG 9 WC Oncology; Respiratory System SC Oncology; Respiratory System GA CE2UQ UT WOS:000351675400010 PM 25590606 ER PT J AU Tompkins, RG AF Tompkins, Ronald G. TI Genomics of injury: The Glue Grant experience SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Editorial Material ID STANDARD OPERATING PROCEDURES; SCALE COLLABORATIVE PROJECT; ORIENTED RESEARCH CORE; VENOUS THROMBOEMBOLISM PROPHYLAXIS; DYNAMIC-RANGE CHARACTERIZATION; HUMAN INFLAMMATORY DISEASES; GENE-EXPRESSION ANALYSIS; TRAUMA PATIENT; CLINICAL CARE; HOST RESPONSE C1 [Tompkins, Ronald G.] Harvard Univ, Dept Surg, Sch Med, Boston, MA 02114 USA. [Tompkins, Ronald G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Tompkins, RG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Surg Innovat & Bioengn, 55 Fruit St,GRB 1401, Boston, MA 02114 USA. EM rtompkins@mgh.harvard.edu FU NIGMS NIH HHS [U54GM62119, U54 GM062119, R24 GM102656] NR 71 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD APR PY 2015 VL 78 IS 4 BP 671 EP 686 DI 10.1097/TA.0000000000000568 PG 16 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA CE8EJ UT WOS:000352074000002 PM 25742245 ER PT J AU Sourbeer, KN Howard, LE Moreira, DM Amarasekara, HS Chow, LD Cockrell, DC Hanyok, BT Pratson, CL Kane, CJ Terris, MK Aronson, WJ Cooperberg, MR Amling, CL Hernandez, RK Freedland, SJ AF Sourbeer, Katharine N. Howard, Lauren E. Moreira, Daniel M. Amarasekara, Hiruni S. Chow, Lydia D. Cockrell, Dillon C. Hanyok, Brian T. Pratson, Connor L. Kane, Christopher J. Terris, Martha K. Aronson, William J. Cooperberg, Matthew R. Amling, Christopher L. Hernandez, Rohini K. Freedland, Stephen J. TI Practice Patterns and Predictors of Followup Imaging after a Negative Bone Scan in Men with Castration Resistant Prostate Cancer: Results from the SEARCH Database SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; prostate specific antigen; radionuclide imaging; neoplasm metastasis; physician's practice patterns ID BIOCHEMICAL RECURRENCE; RADICAL PROSTATECTOMY; SURVIVAL; ANTIGEN; RISK AB Purpose: We investigated imaging practice patterns in men with nonmetastatic (M0) castration resistant prostate cancer. Materials and Methods: We analyzed data on 247 patients with documented M0 CRPC from the SEARCH database. Patients were selected regardless of primary treatment modality and all had a negative bone scan after a castration resistant prostate cancer diagnosis. Cox models were used to test associations of time to a second imaging test with several demographic and clinical factors. Results: During a median followup of 29.0 months (IQR 12.9-43.5) after a postcastration resistant prostate cancer bone scan was negative, 190 patients (77%) underwent a second imaging test. On univariable analysis patients with higher prostate specific antigen (HR 1.13, p = 0.016), shorter prostate specific antigen doubling time (HR 0.79, p < 0.001) and faster prostate specific antigen velocity (HR 1.01, p < 0.001) were more likely to undergo a second imaging test. Treatment center was also a significant predictor of a second imaging test (p - 0.010). No other factor was a significant predictor. Results were similar on multivariable analysis. It was estimated that approximately 20% of men with a prostate specific antigen doubling time of less than 3 months did not undergo an imaging test in the first year after a post-castration resistant prostate cancer negative bone scan. However, 50% of patients with prostate specific antigen doubling time 15 months or greater underwent a second imaging test in the first year. Conclusions: Clinicians use some known predictors of positive imaging tests to determine which patients with M0 castration resistant prostate cancer undergo a second imaging test. However, there may be under imaging in those at high risk and over imaging in those at low risk. Further studies are needed to identify risk factors for metastasis and form clear imaging guidelines in patients with M0 castration resistant prostate cancer. C1 [Sourbeer, Katharine N.; Howard, Lauren E.; Amarasekara, Hiruni S.; Chow, Lydia D.; Cockrell, Dillon C.; Hanyok, Brian T.; Pratson, Connor L.; Freedland, Stephen J.] Duke Univ, Sch Med, Durham Vet Affairs Med Ctr, Urol Sect, Durham, NC USA. [Sourbeer, Katharine N.; Howard, Lauren E.; Amarasekara, Hiruni S.; Chow, Lydia D.; Cockrell, Dillon C.; Hanyok, Brian T.; Pratson, Connor L.; Freedland, Stephen J.] Duke Univ, Sch Med, Div Urol, Duke Prostate Ctr,Dept Surg, Durham, NC USA. [Howard, Lauren E.] Duke Univ, Sch Med, Dept Biostat, Durham, NC USA. [Freedland, Stephen J.] Duke Univ, Sch Med, Dept Pathol, Durham, NC 27706 USA. [Moreira, Daniel M.] Mayo Clin, Dept Urol, Rochester, MN USA. [Kane, Christopher J.] Univ Calif San Diego Hlth Syst, Dept Urol, San Diego, CA USA. [Aronson, William J.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, Urol Sect, Los Angeles, CA USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. [Cooperberg, Matthew R.] Univ Calif San Francisco, Dept Urol, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Hernandez, Rohini K.] Amgen Inc, Ctr Observat Res, Thousand Oaks, CA 91320 USA. [Terris, Martha K.] Vet Affairs Med Ctr, Urol Sect, Augusta, GA USA. [Terris, Martha K.] Med Coll Georgia, Augusta, GA 30912 USA. [Amling, Christopher L.] Oregon Hlth & Sci Univ, Div Urol, Portland, OR USA. RP Freedland, SJ (reprint author), Cedars Sinai Med Ctr, Dept Surg, Div Urol, 8635 West 3rd,Suite 1070W, Los Angeles, CA 90048 USA. EM Stephen.freedland@cshs.org OI Terris, Martha/0000-0002-3843-7270 FU Amgen FX Supported by Amgen. NR 18 TC 4 Z9 4 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD APR PY 2015 VL 193 IS 4 BP 1232 EP 1238 DI 10.1016/j.juro.2014.11.014 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA CE8OO UT WOS:000352102900028 PM 25463986 ER PT J AU Deipolyi, AR Oklu, R Al-Ansari, S Zhu, AX Goyal, L Ganguli, S AF Deipolyi, Amy R. Oklu, Rahmi Al-Ansari, Shehab Zhu, Andrew X. Goyal, Lipika Ganguli, Suvranu TI Safety and Efficacy of 70-150 mu m and 100-300 mu m Drug-Eluting Bead Transarterial Chemoembolization for Hepatocellular Carcinoma SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID TRANSCATHETER ARTERIAL EMBOLIZATION; HEPATIC-TUMORS; LIVER-CANCER; MODEL; DOXORUBICIN; COMPLICATIONS; PARTICLES; SURVIVAL AB Purpose: To compare the safety and efficacy of using 70-150 mu m drug-eluting beads (DEBs) (LC BeadM1; Biocompatibles UK Ltd, Farnham, Surrey, United Kingdom) in addition to 100-300 mu m DEBs with 100-300 mu m DEBs alone in transarterial chemoembolization for treatment of hepatocellular carcinoma (HCC). Materials and Methods: A cohort of patients with HCC who underwent transarterial chemoembolization with two vials of 100-300 mu m DEBs (group 1, 55 procedures among 42 patients, 33 men, average Model for End-Stage Liver Disease score 10 +/- 0.6, 67% Child-Pugh A, 33% Child-Pugh B) was retrospectively compared with a cohort of patients who underwent transarterial chemoembolization with one vial of 70-150 mu m DEBs followed by one vial of 100-300 mu m DEBs (group 2, 51 procedures among 42 patients, 29 men, average Model for End-Stage Liver Disease score 9 +/- 0.6; 73% Child-Pugh A, 27% Child-Pugh B) in regard to adverse events and response on 1-month follow-up imaging using modified Response Evaluation Criteria In Solid Tumors criteria. Results: There was no difference in 1-month imaging response (P= .3). Patients in group 2 were readmitted more often within 1 month for hepatobiliary adverse events (group 2, 25%; group 1, 9%; P < .0001), including ascites, gastrointestinal hemorrhage, biliary dilatation, and cholecystitis. Conclusions: Despite similar efficacy based on short-term follow-up imaging, transarterial chemoembolization with smaller DEBs (70-150 mu m) followed by larger DEBs (100-300 mu m) may cause more hepatobiliary adverse events. C1 [Deipolyi, Amy R.] NYU Med Ctr, Dept Radiol, Div Vasc & Intervent Radiol, New York, NY 10016 USA. [Oklu, Rahmi; Al-Ansari, Shehab; Ganguli, Suvranu] Massachusetts Gen Hosp, Dept Radiol, Div Intervent Radiol, Boston, MA 02114 USA. [Zhu, Andrew X.; Goyal, Lipika] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Zhu, Andrew X.; Goyal, Lipika] Massachusetts Gen Hosp, Dept Internal Med, Ctr Canc, Boston, MA 02114 USA. RP Ganguli, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Intervent Radiol, 55 Fruit St,GRB 293, Boston, MA 02114 USA. EM sganguli@partners.org OI Deipolyi, Amy/0000-0003-3144-386X NR 18 TC 6 Z9 6 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD APR PY 2015 VL 26 IS 4 BP 516 EP 522 DI 10.1016/j.jvir.2014.12.020 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA CE5OE UT WOS:000351884200007 PM 25704226 ER PT J AU Madigan, M Entabi, F Zuckerbraun, B Loughran, P Tzeng, E AF Madigan, Michael Entabi, Fateh Zuckerbraun, Brian Loughran, Patricia Tzeng, Edith TI Delayed inhaled carbon monoxide mediates the regression of established neointimal lesions SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID BARE-METAL STENTS; INHIBITS INTIMAL HYPERPLASIA; SMOOTH-MUSCLE-CELLS; BALLOON ANGIOPLASTY; HEME OXYGENASE-1; ELUTING STENTS; NITRIC-OXIDE; VEIN GRAFTS; APOPTOSIS; AUTOPHAGY AB Objective: Intimal hyperplasia (IH) contributes to the failure of vascular interventions. While many investigational therapies inhibit the development of IH in animal models, few of these potential therapies can reverse established lesions. Inhaled carbon monoxide (CO) dramatically inhibits IH in both rats and pigs when given perioperatively. It also prevented the development of pulmonary arterial hypertension in rodents. Interestingly, CO could reverse pulmonary artery structural changes and right heart hemodynamic changes when administered after the establishment of pulmonary hypertension. Thus, we hypothesize that inhaled CO may mediate the regression of established neointimal lesions. Methods: Rats underwent carotid artery balloon angioplasty injury. Carotid arteries were collected at 2 and 4 weeks after injury for morphometric analysis of the neointima. Another group was treated with inhaled CO (250 parts per million) for 1 hour daily from week 2 until week 4. Additional rats were sacrificed 3 days after initiating CO treatment, and the carotid arteries were examined for apoptosis by terminal deoxynucleotidyl transferase dUTP nick end-labeling, proliferation by Ki67 staining, and autophagy by microtubule-associated protein light chain 3 I/II staining. Results: At 2 weeks following injury, sizable neointimal lesions had developed (intimal/media [0.92 +/- 0.22). By 4 weeks, lesion size remained stable (0.80 +/- 0.09). Delayed inhaled CO treatment greatly reduced neointimal lesion size vs the 2-and 4-week control mice (0.38 +/- 0.05; P < .05). Arteries from the CO-treated rats exhibited significantly reduced apoptosis compared with control vessels (3.18% +/- 1.94% vs 16.26% +/- 5.91%; P = .036). Proliferation was also dramatically reduced in the CO-treated animals (2.98 +/- 1.55 vs 10.37 +/- 2.80; P = .036). No difference in autophagy between control and CO-treated rats was detected. Conclusions: Delayed administration of inhaled CO reduced established neointimal lesion size. This effect was mediated by the antiproliferative effect of CO on medial and intimal smooth muscle cells without increases in arterial wall apoptosis or autophagy. Future studies will examine additional time points to determine if there is temporal variation in the rates of apoptosis and autophagy. C1 [Madigan, Michael; Entabi, Fateh; Zuckerbraun, Brian; Tzeng, Edith] Univ Pittsburgh, Dept Vet Affairs Med Ctr, Pittsburgh, PA 15213 USA. [Madigan, Michael; Entabi, Fateh; Tzeng, Edith] Univ Pittsburgh, Div Vasc Surg, Pittsburgh, PA 15213 USA. [Zuckerbraun, Brian] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. [Loughran, Patricia] Univ Pittsburgh, Ctr Biol Imaging, Pittsburgh, PA 15213 USA. RP Tzeng, E (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Vasc Surg, A1010 PUH,200 Lothrop St, Pittsburgh, PA 15213 USA. EM tzenge@upmc.edu FU Department of Veterans Affairs, Veterans Health Administration [BX000635]; Office of Biomedical Laboratory Research and Development; NIH [T32 HL098036] FX This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration (VA Merit Grant BX000635), Office of Biomedical Laboratory Research and Development (E.T.), and through funding from NIH T32 HL098036 (E.T.). NR 35 TC 3 Z9 3 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD APR PY 2015 VL 61 IS 4 BP 1026 EP 1033 DI 10.1016/j.jvs.2013.11.072 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA CE4BP UT WOS:000351776100029 PM 24418641 ER PT J AU Economopoulos, KP Tzani, A Reifsnyder, T AF Economopoulos, Konstantinos P. Tzani, Aspasia Reifsnyder, Thomas TI Adjunct endovascular interventions in carotid body tumors SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID DIRECT PERCUTANEOUS EMBOLIZATION; PREOPERATIVE EMBOLIZATION; SURGICAL-TREATMENT; NECK PARAGANGLIOMAS; ONYX EMBOLIZATION; SINGLE-CENTER; MANAGEMENT; EXPERIENCE; OUTCOMES; SURGERY AB Objective: Most patients presenting with carotid body tumors (CBTs) seek medical attention when tumors have grown to exceed Shamblin I stage, rendering surgery a challenging undertaking and the associated morbidity a continuing threat to the clinical outcome. This study examined the availability, applicability, and overall clinical efficacy of adjunct endovascular interventions performed alongside CBT surgery and their potential in clinical decision making and clinical practice. Methods: Studies reporting the feasibility, applicability, and clinical efficacy of adjunct endovascular interventions in the surgical management of CBTs were thoroughly searched using the Medline database from January 1967 to August 2013. Results: There were no randomized studies on the efficacy of endovascular interventions in CBT surgery. Sixty studies met our inclusion criteria, reporting 465 patients (526 CBTs) with a mean age of 39.8 years. The treated CBTs were a mean size of 4.9 cm. Patients treated with surgery with the use of adjunct endovascular interventions had a mean blood loss of 368.4 mL (range, 25-to 2000 mL). There were 57 cranial nerve injuries, of which 28 (49.1%) were permanent. Cerebrovascular accident occurred in nine patients, of which one died. Hospital stay was a mean of 4.4 days (range, 2-17 days). Conclusions: Preoperative selective endovascular embolization in patients with Shamblin II and Shamblin III CBTs may be beneficial when competently performed by interventional physicians proficient in neurovascular microcatheterization/embolization procedures. C1 [Economopoulos, Konstantinos P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Economopoulos, Konstantinos P.; Tzani, Aspasia] Soc Jr Doctors, Surg Working Grp, Athens, Greece. [Reifsnyder, Thomas] Johns Hopkins Med Inst, Johns Hopkins Bayview Med Ctr, Div Vasc Surg, Baltimore, MD 21205 USA. RP Economopoulos, KP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, 101 Merrimac St, Boston, MA 02114 USA. EM keconomopoulos@mgh.harvard.edu OI Economopoulos, Konstantinos/0000-0003-4856-0405 NR 52 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD APR PY 2015 VL 61 IS 4 BP 1081 EP + DI 10.1016/j.jvs.2015.01.035 PG 13 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA CE4BP UT WOS:000351776100039 PM 25814372 ER PT J AU Lynch, CP Baker, N Korte, JE Mauldin, JG Mayorga, ME Hunt, KJ AF Lynch, Cheryl P. Baker, Nathaniel Korte, Jeffrey E. Mauldin, Jill G. Mayorga, Maria E. Hunt, Kelly J. TI Increasing Prevalence of Diabetes During Pregnancy in South Carolina SO JOURNAL OF WOMENS HEALTH LA English DT Article ID OF-THE-LITERATURE; RISK-FACTORS; MELLITUS; WOMEN; POPULATION; METAANALYSIS; PREDICTORS; COHORT; TRENDS; US AB Background: The objective of our study was to examine the prevalence of diabetes during pregnancy at the population level in SC from January 1996 through December 2008. Methods: The study included 387,720 non-Hispanic white (NHW), 232,278 non-Hispanic black (NHB), and 43,454 Hispanic live singleton births. Maternal inpatient hospital discharge codes from delivery (91.59%) and prenatal information (i.e., Medicaid [42.91%] and SC State Health Plan [SHP] [5.98%]) were linked to birth certificate data. Diabetes during pregnancy included gestational and preexisting, defined by prenatal and maternal inpatient International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes (i.e., 64801-64802, 64881-64882, or 25000-25092) or report on the birth certificate. Results: Diabetes prevalence from any source increased from 5.02% (95% confidence interval [CI]: 4.82-5.22) in 1996 to 8.37% (95% CI: 8.15-8.60) in 2008. Diabetes prevalence, standardized for maternal age and race/ethnicity from 1996 through 2008, increased from 3.38% (95% CI: 3.29-3.47) to 5.81% (95% CI: 5.71-5.91) using birth certificate data, from 3.99% (95% CI: 3.89-4.10) to 6.69% (95% CI: 6.58-6.80) using hospital discharge data, and from 4.74% (95% CI: 4.52-4.96) to 8.82% (95% CI: 8.61-9.03) using Medicaid data. Comparing birth certificate to hospital discharge, Medicaid, and SHP data, Cohen's kappa in 2008 was 0.73 (95% CI: 0.72-0.75), 0.64 (95% CI: 0.62-0.66), and 0.59 (95% CI: 0.54-0.65), respectively. Conclusions: An increasing prevalence of diabetes during pregnancy is reported, as well as substantial lack of agreement in reporting of diabetes prevalence across administrative databases. Prevalence of reported diabetes during pregnancy is impacted by screening, diagnostic, and reporting practices across different data sources, as well as by actual changes in prevalence over time. C1 [Lynch, Cheryl P.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Lynch, Cheryl P.; Hunt, Kelly J.] Ralph H Johnson Dept Vet Affairs Med Ctr, Hlth Equity & Rural Outreach Innovat Ctr, Charleston, SC USA. [Baker, Nathaniel; Korte, Jeffrey E.; Hunt, Kelly J.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Mauldin, Jill G.] Med Univ S Carolina, Dept Obstet & Gynecol, Charleston, SC 29425 USA. [Mayorga, Maria E.] N Carolina State Univ, Dept Ind & Syst Engn, Raleigh, NC 27695 USA. RP Hunt, KJ (reprint author), Med Univ S Carolina, Dept Publ Hlth Sci, 135 Cannon St,Suite 302, Charleston, SC 29425 USA. EM huntke@musc.edu FU National Institutes of Health [R01 MD004251] FX This work was supported by National Institutes of Health grant R01 MD004251 (PI Mayorga/Hunt). The funding agency did not participate in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the article. The article represents the views of the authors and not those of the Veterans Health Administration or Health Services Research and Development Service. NR 28 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD APR 1 PY 2015 VL 24 IS 4 BP 316 EP 323 DI 10.1089/jwh.2014.4968 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA CF5YG UT WOS:000352632700008 PM 25786128 ER PT J AU Schwamm, LH AF Schwamm, Lee H. TI Breaking up is hard to do: tenecteplase in acute stroke SO LANCET NEUROLOGY LA English DT Editorial Material ID ACUTE ISCHEMIC-STROKE; RANDOMIZED-TRIAL; ALTEPLASE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke Serv, Boston, MA 02114 USA. RP Schwamm, LH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke Serv, Boston, MA 02114 USA. EM lschwamm@mgh.harvard.edu NR 11 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 EI 1474-4465 J9 LANCET NEUROL JI Lancet Neurol. PD APR PY 2015 VL 14 IS 4 BP 343 EP 345 DI 10.1016/S1474-4422(15)70036-0 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA CE5RD UT WOS:000351892400003 PM 25726503 ER PT J AU Heneka, MT Carson, MJ El Khoury, J Landreth, GE Brosseron, F Feinstein, DL Jacobs, AH Wyss-Coray, T Vitorica, J Ransohoff, RM Herrup, K Frautschy, SA Finsen, B Brown, GC Verkhratsky, A Yamanaka, K Koistinaho, J Latz, E Halle, A Petzold, GC Town, T Morgan, D Shinohara, ML Perry, VH Holmes, C Bazan, NG Brooks, DJ Hunot, S Joseph, B Deigendesch, N Garaschuk, O Boddeke, E Dinarello, CA Breitner, JC Cole, GM Golenbock, DT Kummer, MP AF Heneka, Michael T. Carson, Monica J. El Khoury, Joseph Landreth, Gary E. Brosseron, Frederic Feinstein, Douglas L. Jacobs, Andreas H. Wyss-Coray, Tony Vitorica, Javier Ransohoff, Richard M. Herrup, Karl Frautschy, Sally A. Finsen, Bente Brown, Guy C. Verkhratsky, Alexei Yamanaka, Koji Koistinaho, Jari Latz, Eicke Halle, Annett Petzold, Gabor C. Town, Terrence Morgan, Dave Shinohara, Mari L. Perry, V. Hugh Holmes, Clive Bazan, Nicolas G. Brooks, David J. Hunot, Stephane Joseph, Bertrand Deigendesch, Nikolaus Garaschuk, Olga Boddeke, Erik Dinarello, Charles A. Breitner, John C. Cole, Greg M. Golenbock, Douglas T. Kummer, Markus P. TI Neuroinflammation in Alzheimer's disease SO LANCET NEUROLOGY LA English DT Review ID MILD COGNITIVE IMPAIRMENT; RANDOMIZED CONTROLLED-TRIAL; TRAUMATIC BRAIN-INJURY; TRANSGENIC MOUSE MODEL; ANTIINFLAMMATORY PREVENTION TRIAL; NITRIC-OXIDE SYNTHASE; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL AMYLOID ANGIOPATHY; GENOME-WIDE ASSOCIATION; CENTRAL-NERVOUS-SYSTEM AB Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease. C1 [Heneka, Michael T.; Petzold, Gabor C.] Univ Bonn, Dept Neurol, Univ Hosp Bonn, D-53127 Bonn, Germany. [Heneka, Michael T.; Brosseron, Frederic; Latz, Eicke; Petzold, Gabor C.] German Ctr Neurodegnerat Dis DZNE, Bonn, Germany. [Carson, Monica J.] Univ Calif Riverside, Div Biomed Sci, Ctr Glial Neuronal Interact, Riverside, CA 92521 USA. [El Khoury, Joseph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Charlestown, MA USA. [Landreth, Gary E.] Case Western Reserve Univ, Sch Med, Dept Neurosci, Alzheimer Res Lab, Cleveland, OH 44106 USA. [Feinstein, Douglas L.] Univ Illinois, Dept Anesthesiol, Chicago, IL USA. [Jacobs, Andreas H.] Johanniter Hosp, Dept Geriatr, Bonn, Germany. [Jacobs, Andreas H.] Westfalian Wilhelms Univ WWU, European Inst Mol Imaging EIMI, Munster, Germany. [Wyss-Coray, Tony] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. [Wyss-Coray, Tony] VA Palo Alto Hlth Care Syst, Ctr Tissue Regenerat Repair & Restorat, Palo Alto, CA USA. [Vitorica, Javier] Univ Seville, Inst Biomed Sevilla IBIS, Hosp Univ Virgen del Rocio, Consejo Super Invest Cient, Seville, Spain. [Ransohoff, Richard M.] Cleveland Clin, Lerner Res Inst, Neuroinflammat Res Ctr, Dept Neurosci, Cleveland, OH 44106 USA. [Herrup, Karl] Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China. [Frautschy, Sally A.; Cole, Greg M.] Univ Calif Los Angeles, David Geffen Sch Med, Geriatr Res & Clin Ctr, Dept Neurol,Greater Los Angeles Vet Affairs Healt, Los Angeles, CA 90095 USA. [Finsen, Bente] Univ Southern Denmark, Inst Mol Med, Odense, Denmark. [Brown, Guy C.] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England. [Verkhratsky, Alexei] Univ Manchester, Fac Life Sci, Manchester, Lancs, England. [Verkhratsky, Alexei] Basque Fdn Sci IKERBASQUE, Achucarro Ctr Neurosci, Bilbao, Spain. [Verkhratsky, Alexei] Univ Basque Country, Univ Basque Country UPV, Dept Neurosci,EHU Euskal Herriko Unibertsitatea, CIBERNED Ctr Invest Biomed Red Enfermedades Neuro, Leioa, Spain. [Yamanaka, Koji] Nagoya Univ, RIKEN Brain Sci Inst, Environm Med Res Inst, Wako, Saitama, Japan. [Koistinaho, Jari] Univ Eastern Finland, Al Virtanen Inst Mol Sci, Dept Neurobiol, Kuopio, Finland. [Latz, Eicke] Univ Bonn, Inst Innate Immun, D-53127 Bonn, Germany. [Latz, Eicke; Golenbock, Douglas T.] Univ Massachusetts, Sch Med, Dept Infect Dis & Immunol, Worcester, MA USA. [Halle, Annett] Ctr Adv European Studies & Res CAESAR, Max Planck Res Grp Neuroimmunol, Bonn, Germany. [Town, Terrence] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Los Angeles, CA 90033 USA. [Morgan, Dave] Univ S Florida, Coll Med, Dept Mol Pharmacol & Physiol, Byrd Alzheimers Inst, Tampa, FL USA. [Shinohara, Mari L.] Duke Univ, Med Ctr, Dept Immunol, Durham, NC USA. [Perry, V. Hugh] Southampton Gen Hosp, Sch Biol Sci, Southampton SO9 4XY, Hants, England. [Holmes, Clive] Univ Southampton, Clin & Expt Sci, Southampton, Hants, England. [Holmes, Clive] Southern Hlth Fdn Trust, Moorgreen Hosp, Memory Assessment & Res Ctr, Southampton, Hants, England. [Bazan, Nicolas G.] Louisiana State Univ, Neurosci Ctr Excellence, Sch Med, New Orleans, LA USA. [Brooks, David J.] Univ London Imperial Coll Sci Technol & Med, Div Expt Med, Hammersmith Hosp, London, England. [Hunot, Stephane] CNRS, UMR 7225, Expt Therapeut Neurodegenerat, Paris, France. [Joseph, Bertrand] Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Stockholm, Sweden. [Deigendesch, Nikolaus] Max Planck Inst Infect Biol, Dept Cellular Microbiol, Berlin, Germany. [Garaschuk, Olga] Univ Tubingen, Inst Physiol 2, Tubingen, Germany. [Boddeke, Erik] Univ Groningen, Univ Med Ctr Groningen, Dept Neurosci, Groningen, Netherlands. [Dinarello, Charles A.] Univ Colorado Denver, Dept Med, Aurora, CO USA. [Breitner, John C.] Douglas Mental Hlth Univ Inst, Ctr Studies Prevent Alzheimers Dis, Montreal, PQ, Canada. [Breitner, John C.] McGill Univ, Fac Med, Montreal, PQ, Canada. RP Heneka, MT (reprint author), Univ Bonn, Dept Neurol, Univ Hosp Bonn, D-53127 Bonn, Germany. EM michael.heneka@ukb.uni-bonn.de RI Garaschuk, Olga/G-5633-2015; Verkhratsky, Alexei/J-4527-2013; Yamanaka, Koji/H-5806-2011; IBIS, ALZHEIMER/O-9867-2015 OI Verkhratsky, Alexei/0000-0003-2592-9898; Yamanaka, Koji/0000-0003-4655-0035; FU Boehringer Ingelheim Pharma; Veterans Affairs; US National Institutes of Health (NIH) [WO 2007103435 A3]; UK National MS Society; MEXT, Japan; Baxter; NIH FX MTH and MPK have a patent pending on nitration of amyloid 13 peptides (WO 2011006871 A1). GEL has a patent pending on an RXR agonist in Alzheimer's disease (WO 2011006157 A2). AH reports grants from Boehringer Ingelheim Pharma during the preparation of the Review. SAF reports grants from Veterans Affairs and the US National Institutes of Health (NIH) during the preparation of the Review, and a patent for curcumin formulation (application no. 60,779,817 [WO 2007103435 A3]) with royalties paid. RMR reports grants from the UK National MS Society during the preparation of the Review. CV reports grants from Pfizer, outside the submitted work. KY reports grants from MEXT, Japan, during the preparation of the Review. JK reports grants from Baxter, and personal fees from Medeia Therapeutics, outside the submitted work. CH reports grants from Pfizer, outside the submitted work. GMC reports grants from Veterans Affairs and NIH during the preparation of the Review. All other authors declare no competing interests. NR 232 TC 304 Z9 309 U1 102 U2 294 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 EI 1474-4465 J9 LANCET NEUROL JI Lancet Neurol. PD APR PY 2015 VL 14 IS 4 BP 388 EP 405 PG 18 WC Clinical Neurology SC Neurosciences & Neurology GA CE5RD UT WOS:000351892400014 PM 25792098 ER PT J AU Fried, MP Kleefied, J Gopal, H Reardon, E Ho, BT Kuhn, FA AF Fried, Marvin P. Kleefied, Jonathan Gopal, Harsha Reardon, Edward Ho, Bryan T. Kuhn, Frederick A. TI Image-Guided Endoscopic Surgery: Results of Accuracy and Performance in a Multicenter Clinical Study Using an Electromagnetic Tracking System SO LARYNGOSCOPE LA English DT Editorial Material ID SINUS SURGERY; COMPLICATIONS C1 [Fried, Marvin P.; Gopal, Harsha] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Fried, Marvin P.; Gopal, Harsha] Beth Israel Deaconess Med Ctr, Joint Ctr Otolaryngol, Boston, MA USA. [Fried, Marvin P.; Gopal, Harsha] Beth Israel Deaconess Med Ctr, Div Otolaryngol, Boston, MA USA. [Fried, Marvin P.; Gopal, Harsha] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kleefied, Jonathan] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Reardon, Edward; Ho, Bryan T.] Carney Hosp, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. [Kuhn, Frederick A.] Mem Med Ctr, Dept Otolaryngol, Georgia Ear Inst, Savannah, GA USA. RP Fried, MP (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. NR 11 TC 0 Z9 0 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 APR PY 2015 VL 125 IS 4 BP 774 EP 781 DI 10.1002/lary.25217 PG 8 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA CE2YB UT WOS:000351686900009 PM 25809338 ER PT J AU Chambers, KJ Creighton, F Abdul-Aziz, D Cheney, M Randolph, GW AF Chambers, Kyle J. Creighton, Francis Abdul-Aziz, Dunia Cheney, Mack Randolph, Gregory W. TI Global Health-Related Publications in Otolaryngology Are Increasing SO LARYNGOSCOPE LA English DT Article DE Global health; global health research; otolaryngology; international otolaryngology ID ACADEMIC TRACK; SURGERY; INITIATIVES; CHALLENGES; COUNTRY; AFRICA; AGENDA AB Objectives/HypothesisDetermine trends in global health-related publication in otolaryngology. Study DesignA review of research databases. MethodsA search of publications available on PubMed and nine additional databases was undertaken reviewing two time periods 10 years apart for the timeframes 1998 to 2002 (early time period) and 2008 to 2012 (recent time period) using specific search terms to identify global health-related publications in otolaryngology. Publications were examined for region of origin, subspecialty, type of publication, and evidence of international collaboration. and t test analyses were used to identify trends. ResultsIn the 1998 to 2002 time period, a total of 26 publications met inclusion criteria for the study, with a mean of 5.22.8 publications per year. In the 2008 to 2012 time period, a total of 61 publications met inclusion criteria, with a mean of 12.35.6 publications per year. The 235% increase in global health-related publications identified between the two study periods was statistically significant (P=.02). The absolute number of publications in which collaboration occurred between countries increased from three in the early time period to nine the recent time period. ConclusionsThere has been a significant increase in the volume of global health-related publications in English language otolaryngology journals over the past decade, providing strong evidence of the increasing trend of global health as an academic pursuit within the field of otolaryngology. Level of EvidenceNA Laryngoscope, 125:848-851, 2015 C1 [Chambers, Kyle J.; Creighton, Francis; Abdul-Aziz, Dunia; Cheney, Mack; Randolph, Gregory W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Chambers, Kyle J.; Creighton, Francis; Abdul-Aziz, Dunia; Cheney, Mack; Randolph, Gregory W.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Randolph, Gregory W.] Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA. RP Chambers, KJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM kyle_chambers@meei.harvard.edu NR 24 TC 1 Z9 1 U1 0 U2 0 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 APR PY 2015 VL 125 IS 4 BP 848 EP 851 DI 10.1002/lary.24906 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA CE2YB UT WOS:000351686900024 PM 25155277 ER PT J AU Remenschneider, AK Dilger, AE Wang, YB Palmer, EL Scott, JA Emerick, KS AF Remenschneider, Aaron K. Dilger, Amanda E. Wang, Yingbing Palmer, Edwin L. Scott, James A. Emerick, Kevin S. TI The Predictive Value of Single-Photon Emission Computed Tomography/Computed Tomography for Sentinel Lymph Node Localization in Head and Neck Cutaneous Malignancy SO LARYNGOSCOPE LA English DT Article DE Single-photon emission computed tomography; computed tomography; sentinel lymph node biopsy; predictive value; cutaneous malignancy; skin cancer ID NEUROENDOCRINE TUMORS; BREAST-CANCER; SPECT/CT; MELANOMA; BIOPSY; ACCURATE AB Objectives/HypothesisPreoperative localization of sentinel lymph nodes in head and neck cutaneous malignancies can be aided by single-photon emission computed tomography/computed tomography (SPECT/CT); however, its true predictive value for identifying lymph nodes intraoperatively remains unquantified. This study aims to understand the sensitivity, specificity, and positive and negative predictive values of SPECT/CT in sentinel lymph node biopsy for cutaneous malignancies of the head and neck. Study DesignBlinded retrospective imaging review with comparison to intraoperative gamma probe confirmed sentinel lymph nodes. MethodsA consecutive series of patients with a head and neck cutaneous malignancy underwent preoperative SPECT/CT followed by sentinel lymph node biopsy with a gamma probe. Two nuclear medicine physicians, blinded to clinical data, independently reviewed each SPECT/CT. Activity within radiographically defined nodal basins was recorded and compared to intraoperative gamma probe findings. Sensitivity, specificity, and negative and positive predictive values were calculated with subgroup stratification by primary tumor site. ResultsNinety-two imaging reads were performed on 47 patients with cutaneous malignancy who underwent SPECT/CT followed by sentinel lymph node biopsy. Overall sensitivity was 73%, specificity 92%, positive predictive value 54%, and negative predictive value 96%. The predictive ability of SPECT/CT to identify the basin or an adjacent basin containing the single hottest node was 92%. SPECT/CT overestimated uptake by an average of one nodal basin. In the head and neck, SPECT/CT has higher reliability for primary lesions of the eyelid, scalp, and cheek. ConclusionsSPECT/CT has high sensitivity, specificity, and negative predictive value, but may overestimate relevant nodal basins in sentinel lymph node biopsy. Level of Evidence4 Laryngoscope, 125:877-882, 2015 C1 [Remenschneider, Aaron K.; Dilger, Amanda E.; Emerick, Kevin S.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Remenschneider, Aaron K.; Dilger, Amanda E.; Emerick, Kevin S.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Wang, Yingbing; Palmer, Edwin L.; Scott, James A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Nucl Med & Mol Imaging, Boston, MA USA. RP Remenschneider, AK (reprint author), 243 Charles St, Boston, MA 02114 USA. EM aaron_remenschneider@meei.harvard.edu 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 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD APR PY 2015 VL 125 IS 4 BP 877 EP 882 DI 10.1002/lary.25024 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA CE2YB UT WOS:000351686900029 PM 25388656 ER PT J AU Chambers, KJ Aswani, J Patel, A Fundakowski, C Mannion, K Lin, DT Netterville, J AF Chambers, Kyle J. Aswani, Joyce Patel, Asmeeta Fundakowski, Christopher Mannion, Kyle Lin, Derrick T. Netterville, James TI The Value of a Collaborative Course for Advanced Head and Neck Surgery in East Africa SO LARYNGOSCOPE LA English DT Article DE Head and neck surgery; surgical training; global otolaryngology; global health AB Objectives/HypothesisTo determine the value of a collaborative course for advanced head and neck surgery in East Africa. Study DesignSurvey of participants. MethodsA 3-day course in head and neck surgery was designed for otolaryngologists and trainees from Kenya and surrounding countries through a collaborative effort between Kenyatta National Hospital, the University of Nairobi, and the Head and Neck Divisions from the Vanderbilt Bill Wilkerson Center and the Massachusetts Eye and Ear Infirmary. Topics included neck dissection, parotidectomy, total laryngectomy, parapharyngeal space tumors excision, and pectoralis myocutaneous flaps. A pre- and postcourse self-evaluation survey was administered to measure course impact. ResultsEighteen otolaryngologists and trainees participated in the course, with 17 completing course surveys. The majority of participants (72%) were from Kenya. Prior to the start of the course, 41%, 71%, 23%, 12%, and 0% of participants indicated they could complete a neck dissection, parotidectomy, parapharyngeal space mass excision, total laryngectomy, and pectoralis myocutaneous flap, respectively. Following the course, 50%, 94%, 69%, 25%, and 38% of participants indicated they could complete a neck dissection, parotidectomy, total laryngectomy, parapharyngeal space tumors excision, respectively, with a statistically significant increase identified for pectoralis myocutaneous flaps (P<.001) and total laryngectomy (P=.009). There was also a trend toward an increase in the number of participants indicating an ability to complete parotidectomy following the course (P=.085). ConclusionsThis survey demonstrates the potential value of a collaborative course in advanced head and neck surgery as one useful model for increasing the number of well-trained head and neck surgeons in East Africa. Level of EvidenceNA Laryngoscope, 125:883-887, 2015 C1 [Chambers, Kyle J.; Lin, Derrick T.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA USA. [Chambers, Kyle J.; Lin, Derrick T.] Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02115 USA. [Patel, Asmeeta] Kenyatta Natl Hosp, Dept Surg, Nairobi, Kenya. [Aswani, Joyce] Univ Nairobi, Sch Med, Dept Surg, Nairobi, Kenya. [Aswani, Joyce; Patel, Asmeeta] Kenya Ear Nose & Throat Soc, Nairobi, Kenya. [Fundakowski, Christopher; Mannion, Kyle; Netterville, James] Vanderbilt Univ, Med Ctr, Div Head & Neck Surg, Vanderbilt Bill Wilkerson Ctr, Nashville, TN USA. [Fundakowski, Christopher; Mannion, Kyle; Netterville, James] Vanderbilt Univ, Med Ctr, Vanderbilt Dept Otolaryngol, Nashville, TN USA. [Fundakowski, Christopher; Mannion, Kyle; Netterville, James] Vanderbilt Univ, Med Ctr, Bill Wilkerson Ctr, Nashville, TN USA. RP Chambers, KJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM kyle_chambers@meei.harvard.edu NR 13 TC 1 Z9 1 U1 0 U2 0 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 APR PY 2015 VL 125 IS 4 BP 883 EP 887 DI 10.1002/lary.25028 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA CE2YB UT WOS:000351686900030 PM 25417971 ER PT J AU Puram, SV Kozin, ED Sethi, R Alkire, B Lee, DJ Gray, ST Shrime, MG Cohen, M AF Puram, Sidharth V. Kozin, Elliott D. Sethi, Rosh Alkire, Blake Lee, Daniel J. Gray, Stacey T. Shrime, Mark G. Cohen, Michael TI Impact of Resident Surgeons on Procedure Length Based on Common Pediatric Otolaryngology Cases SO LARYNGOSCOPE LA English DT Article DE residency; education; training; procedure length; operative time; cost ID OPERATIVE TIME; SURGICAL-PROCEDURES; COST; PARTICIPATION; ROOM; CARE AB Objectives/HypothesisSurgical education remains an important mission of academic medical centers. Financial pressures may favor improved operating room (OR) efficiency at the expense of teaching in the OR. We aim to evaluate factors, such as resident participation, associated with duration of total OR, as well as procedural time of common pediatric otolaryngologic cases. Study DesignRetrospective cohort study. MethodsWe reviewed resident and attending surgeon total OR and procedural times for isolated tonsillectomy, adenoidectomy, tonsillectomy with adenoidectomy (T&A), and bilateral myringotomy with tube insertion between 2009 and 2013. We included cases supervised or performed by one of four teaching surgeons in children with American Society of Anesthesiology classification<3. Regression analyses were used to identify predictors of procedural time. ResultsWe identified 3,922 procedures. Residents had significantly longer procedure times for all procedures compared to an attending surgeon (4.9-12.8 minutes, P < 0.001). Differences were proportional to case complexity. In T&A patients, older patient age and attending surgeon identity were also significant predictors of increased mean procedural time (P < 0.05). ConclusionsResident participation contributes to increased procedure time for common otolaryngology procedures. We found that differences in operative time between resident surgeons and attending surgeons are proportional to the complexity of the case, with additional factors, such as attending surgeon identity and older patient age, also influencing procedure times. Despite the increased procedural time, our investigation shows that resident education does not result in excessive operative times beyond what may be reasonably expected at a teaching institution. Level of Evidence4. Laryngoscope, 125:991-997, 2015 C1 [Puram, Sidharth V.; Kozin, Elliott D.; Alkire, Blake; Lee, Daniel J.; Gray, Stacey T.; Shrime, Mark G.; Cohen, Michael] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Puram, Sidharth V.; Kozin, Elliott D.; Sethi, Rosh; Alkire, Blake; Lee, Daniel J.; Gray, Stacey T.; Shrime, Mark G.; Cohen, Michael] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Cohen, M (reprint author), 243 Charles St, Boston, MA 02114 USA. EM Michael_cohen@meei.harvard.edu RI Kozin, Elliott/J-1225-2014 OI Kozin, Elliott/0000-0002-0305-0682 FU NIDCD NIH HHS [T32 DC000020] NR 22 TC 6 Z9 6 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD APR PY 2015 VL 125 IS 4 BP 991 EP 997 DI 10.1002/lary.24912 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA CE2YB UT WOS:000351686900049 PM 25251257 ER PT J AU Gooi, Z Ward, BK Mener, DJ Ozgursoy, OB Pai, SI AF Gooi, Zhen Ward, Bryan K. Mener, David J. Ozgursoy, Ozan B. Pai, Sara I. TI A Staged Thyroidectomy Approach for Gastric Bypass Patients SO LARYNGOSCOPE LA English DT Article DE Head and neck cancer; papillary thyroid cancer; gastric bypass; obesity; hypocalcemia ID NEAR-TOTAL THYROIDECTOMY; BILIOPANCREATIC DIVERSION; HYPOCALCEMIA C1 [Gooi, Zhen; Ward, Bryan K.; Mener, David J.; Pai, Sara I.] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA. [Ozgursoy, Ozan B.] Ankara Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, TR-06100 Ankara, Turkey. [Pai, Sara I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Laryngeal Surg,Dept Surg, Boston, MA 02114 USA. RP Pai, SI (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, One Bowdoin Sq,11th Floor, Boston, MA 02114 USA. EM sara.pai@mgh.harvard.edu NR 10 TC 1 Z9 1 U1 0 U2 0 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 APR PY 2015 VL 125 IS 4 BP 1028 EP 1030 DI 10.1002/lary.24835 PG 3 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA CE2YB UT WOS:000351686900055 PM 25043176 ER PT J AU Soukos, NS Stultz, J Abernethy, AD Goodson, JM AF Soukos, Nikolaos S. Stultz, Jacyn Abernethy, Abraham D. Goodson, J. Max TI Phototargeting human periodontal pathogens in vivo SO LASERS IN MEDICAL SCIENCE LA English DT Article DE Phototherapy; Blue light; Dental plaque; Black-pigmented bacteria ID PHOTODYNAMIC THERAPY; VISIBLE-LIGHT; PORPHYROMONAS-GINGIVALIS; HELICOBACTER-PYLORI; BLUE-LIGHT; ORAL BACTERIA; ARGON-LASER; DISEASE; SUBGINGIVAL; PLAQUE AB The effects of blue light at 455 nm were investigated on the bacterial composition of human dental plaque in vivo. Eleven subjects who refrained from brushing for 3 days before and during phototherapy participated in the study. Light with a power density of 70 mW/cm(2) was applied to the buccal surfaces of premolar and molar teeth on one side of the mouth twice daily for 2 min over a period of 4 days. Dental plaque was harvested at baseline and again at the end of 4 days from eight posterior teeth on both the exposed side and unexposed sides of the mouth. Microbiological changes were monitored by checkerboard DNA probe analysis of 40 periodontal bacteria. The proportions of black-pigmented species Porphyromonas gingivalis and Prevotella intermedia were significantly reduced on the exposed side from their original proportions by 25 and 56 %, respectively, while no change was observed to the unexposed side. Five other species showed the greatest proportional reduction of the light-exposed side relative to the unexposed side. These species were Streptococcus intermedius, Fusobacterium nucleatum ss. vincentii, Fusobacterium nucleatum ss. polymorphum, Fusobacterium periodonticum, and Capnocytophaga sputigena. At the same time, the percentage of gingival areas scored as being red decreased on the side exposed to light from 48 to 42 %, whereas the percentage scored as red increased on the unexposed side from 53 to 56 %. No adverse effects were found or reported in this study. The present study proposes a new method to modify the ecosystem in dental plaque by phototherapy and introduces a new avenue of prophylactic treatment for periodontal diseases. C1 [Soukos, Nikolaos S.; Abernethy, Abraham D.] Forsyth Inst, Appl Mol Photomed Lab, Dept Appl Oral Sci, Cambridge, MA 02142 USA. [Stultz, Jacyn; Goodson, J. Max] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA 02142 USA. [Stultz, Jacyn] Mt IDA Coll, Dent Hyg, Newton, MA USA. [Abernethy, Abraham D.] Univ Hosp Cleveland, Cleveland, OH 44106 USA. RP Soukos, NS (reprint author), Forsyth Inst, Appl Mol Photomed Lab, Dept Appl Oral Sci, 245 First St, Cambridge, MA 02142 USA. EM nsoukos@forsyth.org; jstultz@mountida.edu; abraham.abernethy@UHHospitals.org; mgoodson@forsyth.org FU BriteSmile, Inc. FX We thank Gordon Row, Healthcare and Bioscience Practice, IDEO, Lexington, MA, USA for making the prototype used in this study. This work was supported by BriteSmile, Inc. NR 49 TC 0 Z9 0 U1 2 U2 5 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0268-8921 EI 1435-604X J9 LASER MED SCI JI Lasers Med. Sci. PD APR PY 2015 VL 30 IS 3 BP 943 EP 952 DI 10.1007/s10103-013-1497-9 PG 10 WC Engineering, Biomedical; Surgery SC Engineering; Surgery GA CE5IB UT WOS:000351863700001 PM 24346334 ER PT J AU Jurczyszyn, A Czepiel, J Gdula-Argasinska, J Pasko, P Czapkiewicz, A Librowski, T Perucki, W Butrym, A Castillo, JJ Skotnicki, AB AF Jurczyszyn, Artur Czepiel, Jacek Gdula-Argasinska, Joanna Pasko, Pawel Czapkiewicz, Anna Librowski, Tadeusz Perucki, William Butrym, Aleksandra Castillo, Jorge J. Skotnicki, Aleksander B. TI Plasma fatty acid profile in multiple myeloma patients SO LEUKEMIA RESEARCH LA English DT Article DE Multiple myeloma; Fatty acids; Plasma; Gas chromatography; Desaturase activity ID NON-HODGKINS-LYMPHOMA; ERYTHROCYTE-MEMBRANE; THERAPEUTIC TARGET; DIABETES-MELLITUS; ARACHIDONIC-ACID; UNITED-STATES; LINOLEIC-ACID; CANCER; RISK; DIET AB membrane formation in the proliferating tumor cells consequently results in hypermetabolism of fatty acids (FA), as seen in many cancer patients, including multiple myeloma (MM). The FA composition of plasma reflects both endogenous synthesis as well as the dietary supply of these compounds. Additionally, obesity is a risk factor for the development of MM. The aim of this study was to compare the FA composition of plasma in 60 MM patients and 60 healthy controls. We noted significant differences in the FA profile of plasma from patients with MM when compared to the control group. Increased levels of saturated and n-6 polyunsaturated fatty acids in MM patients suggest that there may be increased endogenous synthesis of these fatty acids, likely due to increased expression of desaturase and elongase. Furthermore, cluster analysis showed differences in the distribution of FA in plasma from MM patients compared to controls. Dietary fat and a deranged endogenous FA metabolism may contribute to cancer-associated inflammation through an abnormal arachidonic acid metabolism, caused by pro-inflammatory derivatives. Our study supports further research on the biochemistry of lipids in patients with MM. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Jurczyszyn, Artur; Skotnicki, Aleksander B.] Univ Hosp, Dept Hematol, PL-31501 Krakow, Poland. [Czepiel, Jacek] Jagiellonian Univ, Coll Med, Dept Infect Dis, Krakow, Poland. [Gdula-Argasinska, Joanna; Librowski, Tadeusz] Jagiellonian Univ, Coll Med, Fac Pharm, Dept Radioligands, Krakow, Poland. [Pasko, Pawel] Jagiellonian Univ, Coll Med, Fac Pharm, Dept Food Chem & Nutr, Krakow, Poland. [Czapkiewicz, Anna] AGH Univ Sci & Technol, Fac Management, PL-30059 Krakow, Poland. [Perucki, William] Univ Connecticut, Dept Med, John Dempsey Hosp, Farmington, CT 06032 USA. [Butrym, Aleksandra] Med Univ, Dept Hematol Blood Neoplasms & Bone Marrow Transp, Wroclaw, Poland. [Butrym, Aleksandra] Med Univ, Dept Physiol, Wroclaw, Poland. [Castillo, Jorge J.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Jurczyszyn, A (reprint author), Univ Hosp, Dept Hematol, Ul Kopernika 17, PL-31501 Krakow, Poland. EM mmjurczy@cyf-kr.edu.pl RI Czapkiewicz, Anna/K-9242-2015; OI Gdula-Argasinska, Joanna/0000-0003-3501-8350; Castillo, Jorge/0000-0001-9490-7532 FU National Science Centre, Poland [DEC-2011/01/B/NZ7/00038] FX This project was partially supported by National Science Centre, Poland to the author Joanna Gdula-Argasinska DEC-2011/01/B/NZ7/00038. NR 48 TC 2 Z9 2 U1 2 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 EI 1873-5835 J9 LEUKEMIA RES JI Leuk. Res. PD APR PY 2015 VL 39 IS 4 BP 400 EP 405 DI 10.1016/j.leukres.2014.12.010 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA CE3GK UT WOS:000351714500003 PM 25666255 ER PT J AU Rangachari, D Yamaguchi, N VanderLaan, PA Folch, E Mahadevan, A Floyd, SR Uhlmann, EJ Wong, ET Dahlberg, SE Huberman, MS Costa, DB AF Rangachari, Deepa Yamaguchi, Norihiro VanderLaan, Paul A. Folch, Erik Mahadevan, Anand Floyd, Scott R. Uhlmann, Erik J. Wong, Eric T. Dahlberg, Suzanne E. Huberman, Mark S. Costa, Daniel B. TI Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers SO LUNG CANCER LA English DT Article DE Lung cancer; NSCLC; Brain metastases; EGFR; ALK; Mutation; Rearrangement; Central nervous system; CNS ID CHEMOTHERAPY; ERLOTINIB; SYSTEM; CRIZOTINIB; MUTATIONS; GEFITINIB AB Introduction: Brain metastases (BM) are common in non-small-cell lung cancer (NSCLC). However, the baseline incidence and evolution of BM over time in oncogene-driven NSCLCs are seldom reported. In this study, we evaluated the frequency of BM in patients with epidermal growth factor receptor (EGFR)-mutated or anaplastic lymphoma kinase (ALK)-rearranged NSCLC. Methods: The presence of BM, clinicopathologic data, and tumor genotype were retrospectively compiled and analyzed from a cohort of 381 patients. Results: We identified 86 EGFR-mutated (90.7% with metastatic disease; 85.9% received an EGFR inhibitor) and 23 ALK-rearranged (91.3% with metastatic disease; 85.7% received an ALK inhibitor) NSCLCs. BM were present in 24.4% of EGFR-mutated and 23.8% of ALK-rearranged NSCLCs at the time of diagnosis of advanced disease. This study did not demonstrate a difference in the cumulative incidence of BM over time between the two cohorts (EGFR/ALK cohort competing risk regression [CRR] coefficient of 0.78[95% CI 0.44-1.39], p= 0.41). In still living patients with advanced EGFR-mutated NSCLC, 34.2% had BM at 1 year, 38.4% at 2 years, 46.7% at 3 years, 48.7% at 4 years, and 52.9% at 5 years. In still living patients with advanced ALK-rearranged NSCLC, 23.8% had BM at 1 year, 45.5% at 2 years, and 58.4% at 3 years. Conclusions: BM are frequent in advanced EGFR-mutated or ALK-rearranged NSCLCs, with an estimated >45% of patients with CNS involvement by three years of survival with the use of targeted therapies. These data point toward the CNS as an important unmet clinical need in the evolving schema for personalized care in NSCLC. (c) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Rangachari, Deepa; Yamaguchi, Norihiro; Folch, Erik; Huberman, Mark S.; Costa, Daniel B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. [VanderLaan, Paul A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Folch, Erik] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Surg, Boston, MA 02215 USA. [Mahadevan, Anand; Floyd, Scott R.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiat Oncol, Boston, MA 02215 USA. [Uhlmann, Erik J.; Wong, Eric T.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Dahlberg, Suzanne E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Dahlberg, Suzanne E.] Harvard Univ, Sch Med, Sch Publ Hlth, Boston, MA USA. RP Costa, DB (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol Oncol, 330 Brookline Ave, Boston, MA 02215 USA. EM dbcosta@bidmc.harvard.edu OI Folch, Erik/0000-0001-7076-7328; Costa, Daniel/0000-0002-0689-395X; VanderLaan, Paul/0000-0002-7234-5652 FU American Society of Clinical Oncology Conquer Cancer Foundation; American Cancer Society [RSG 11-186]; Lung Cancer Foundation of America-International Association for the Study of Lung Cancer; National Institutes of Health (NIH) [CA090578]; Gallup Funds from the Thoracic Oncology Program at the Dana-Farber Cancer Institute FX This work was funded in part through a fellowship from the American Society of Clinical Oncology Conquer Cancer Foundation (DBC), an American Cancer Society grant (RSG 11-186 to DBC), a Lung Cancer Foundation of America-International Association for the Study of Lung Cancer grant (to DBC), National Institutes of Health (NIH) grant CA090578 (to DBC), and Gallup Funds from the Thoracic Oncology Program at the Dana-Farber Cancer Institute (to SED). NR 16 TC 30 Z9 32 U1 0 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 EI 1872-8332 J9 LUNG CANCER JI Lung Cancer PD APR PY 2015 VL 88 IS 1 BP 108 EP 111 DI 10.1016/j.lungcan.2015.01.020 PG 4 WC Oncology; Respiratory System SC Oncology; Respiratory System GA CE4IS UT WOS:000351794900018 PM 25682925 ER PT J AU Eryaman, Y Guerin, B Keil, B Mareyam, A Herraiz, JL Kosior, RK Martin, A Torrado-Carvajal, A Malpica, N Hernandez-Tamames, JA Schiavi, E Adalsteinsson, E Wald, LL AF Eryaman, Yigitcan Guerin, Bastien Keil, Boris Mareyam, Azma Herraiz, Joaquin L. Kosior, Robert K. Martin, Adrian Torrado-Carvajal, Angel Malpica, Norberto Hernandez-Tamames, Juan A. Schiavi, Emanuele Adalsteinsson, Elfar Wald, Lawrence L. TI SAR Reduction in 7T C-Spine Imaging Using a "Dark Modes" Transmit Array Strategy SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE parallel transmit; local SAR; global SAR; radiative dipole; loop-dipole arrays; excitation fidelity ID PARALLEL TRANSMIT; COIL ARRAY; EXCITATION; DESIGN; MRI; POWER; TESLA AB PurposeLocal specific absorption rate (SAR) limits many applications of parallel transmit (pTx) in ultra high-field imaging. In this Note, we introduce the use of an array element, which is intentionally inefficient at generating spin excitation (a dark mode) to attempt a partial cancellation of the electric field from those elements that do generate excitation. We show that adding dipole elements oriented orthogonal to their conventional orientation to a linear array of conventional loop elements can lower the local SAR hotspot in a C-spine array at 7 T. MethodsWe model electromagnetic fields in a head/torso model to calculate SAR and excitation B-1(+) patterns generated by conventional loop arrays and loop arrays with added electric dipole elements. We utilize the dark modes that are generated by the intentional and inefficient orientation of dipole elements in order to reduce peak 10g local SAR while maintaining excitation fidelity. ResultsFor B-1(+) shimming in the spine, the addition of dipole elements did not significantly alter the B-1(+) spatial pattern but reduced local SAR by 36%. ConclusionThe dipole elements provide a sufficiently complimentary B-1(+) and electric field pattern to the loop array that can be exploited by the radiofrequency shimming algorithm to reduce local SAR. Magn Reson Med 73:1533-1539, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Eryaman, Yigitcan; Herraiz, Joaquin L.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Eryaman, Yigitcan; Guerin, Bastien; Keil, Boris; Mareyam, Azma; Wald, Lawrence L.] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Eryaman, Yigitcan; Herraiz, Joaquin L.; Kosior, Robert K.; Martin, Adrian; Torrado-Carvajal, Angel; Malpica, Norberto; Hernandez-Tamames, Juan A.; Schiavi, Emanuele; Adalsteinsson, Elfar] Madrid MIT M Vis Consortium, Madrid, Spain. [Adalsteinsson, Elfar] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Adalsteinsson, Elfar; Wald, Lawrence L.] MIT, Harvard MIT Hlth Sci & Technol, Cambridge, MA 02139 USA. [Adalsteinsson, Elfar] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. [Torrado-Carvajal, Angel; Malpica, Norberto; Hernandez-Tamames, Juan A.] Rey Juan Carlos Univ, Dept Elect Technol, Madrid, Spain. [Martin, Adrian; Schiavi, Emanuele] Rey Juan Carlos Univ, Dept Appl Math, Madrid, Spain. [Kosior, Robert K.] Univ Calgary, Fac Med, Calgary, AB, Canada. [Keil, Boris] Harvard Univ, Sch Med, Boston, MA USA. RP Eryaman, Y (reprint author), MIT, Elect Res Lab, Cambridge, MA 02139 USA. EM yigitcan@mit.edu RI LOPEZ HERRAIZ, JOAQUIN/E-9234-2010; Keil, Boris/P-1411-2014; Martin Fernandez, Adrian/H-7802-2015; Malpica, Norberto/I-2090-2015; Schiavi, Emanuele/H-9840-2012; Wald, Lawrence/D-4151-2009; Hernandez-Tamames, Juan /N-5319-2014 OI LOPEZ HERRAIZ, JOAQUIN/0000-0001-7208-8863; Martin Fernandez, Adrian/0000-0001-7127-0073; Malpica, Norberto/0000-0003-4618-7459; Schiavi, Emanuele/0000-0002-2790-307X; Hernandez-Tamames, Juan /0000-0003-0027-9518 FU National Institutes of Health NIBIB [R01EB006847, R01EB007942]; Comunidad de Madrid, Madrid-MIT M+Vision Consortium FX Grant sponsor: National Institutes of Health NIBIB; grant numbers: R01EB006847; R01EB007942; Grant sponsor: Comunidad de Madrid, Madrid-MIT M+Vision Consortium. NR 19 TC 5 Z9 5 U1 2 U2 5 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 APR PY 2015 VL 73 IS 4 BP 1533 EP 1539 DI 10.1002/mrm.25246 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CE2XS UT WOS:000351685900018 PM 24753012 ER PT J AU Huang, C Galons, JP Graff, CG Clarkson, EW Bilgin, A Kalb, B Martin, DR Altbach, MI AF Huang, Chuan Galons, Jean-Philippe Graff, Christian G. Clarkson, Eric W. Bilgin, Ali Kalb, Bobby Martin, Diego R. Altbach, Maria I. TI Correcting Partial Volume Effects in Biexponential T-2 Estimation of Small Lesions SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE T-2 estimation; MR parameter estimation; partial volume effect; lesion classification ID CONVENTIONAL SPIN-ECHO; FOCAL LIVER-LESIONS; T2 RELAXATION-TIMES; MR-IMAGES; RECONSTRUCTION; HEMANGIOMAS; RELAXOMETRY; EXCITATION; NOISE; DIFFERENTIATION AB PurposeT(2) mapping provides a quantitative approach for focal liver lesion characterization. For small lesions, a biexponential model should be used to account for partial volume effects (PVE). However, conventional biexponential fitting suffers from large uncertainty of the fitted parameters when noise is present. The purpose of this work is to develop a more robust method to correct for PVE affecting small lesions. MethodsWe developed a region of interest-based joint biexponential fitting (JBF) algorithm to estimate the T-2 of lesions affected by PVE. JBF takes advantage of the lesion fraction variation among voxels within a region of interest. JBF is compared to conventional approaches using Cramer-Rao lower bound analysis, numerical simulations, phantom, and in vivo data. ResultsJBF provides more accurate and precise T-2 estimates in the presence of PVE. Furthermore, JBF is less sensitive to region of interest drawing. Phantom and in vivo results show that JBF can be combined with a reconstruction method for highly undersampled data, enabling the characterization of small abdominal lesions from data acquired in a single breath hold. ConclusionThe JBF algorithm provides more accurate and stable T-2 estimates for small structures than conventional techniques when PVE is present. It should be particularly useful for the characterization of small abdominal lesions. Magn Reson Med 73:1632-1642, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Huang, Chuan] Univ Arizona, Dept Math, Tucson, AZ 85724 USA. [Huang, Chuan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Imaging,Ctr Adv Med Imaging Sci, Boston, MA USA. [Galons, Jean-Philippe; Kalb, Bobby; Martin, Diego R.; Altbach, Maria I.] Univ Arizona, Dept Med Imaging, Tucson, AZ 85724 USA. [Graff, Christian G.] US FDA, Div Imaging & Appl Math, Silver Spring, MD USA. [Clarkson, Eric W.] Univ Arizona, Coll Opt Sci, Tucson, AZ 85724 USA. [Bilgin, Ali] Univ Arizona, Dept Elect & Comp Engn, Tucson, AZ 85724 USA. [Bilgin, Ali] Univ Arizona, Dept Biomed Engn, Tucson, AZ 85724 USA. RP Altbach, MI (reprint author), Univ Arizona, Dept Med Imaging, Tucson, AZ 85724 USA. EM maltbach@email.arizona.edu FU NIH [HL085385] FX Grant sponsor: NIH; Grant number: HL085385. NR 35 TC 1 Z9 1 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD APR PY 2015 VL 73 IS 4 BP 1632 EP 1642 DI 10.1002/mrm.25250 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CE2XS UT WOS:000351685900030 PM 24753061 ER PT J AU Ramos, EM Kovalenko, M Guide, JR St Claire, J Gillis, T Mysore, JS Sequeiros, J Wheeler, VC Alonso, I MacDonald, ME AF Ramos, Eliana Marisa Kovalenko, Marina Guide, Jolene R. St Claire, Jason Gillis, Tammy Mysore, Jayalakshmi S. Sequeiros, Jorge Wheeler, Vanessa C. Alonso, Isabel MacDonald, Marcy E. TI Chromosome substitution strain assessment of a Huntington's disease modifier locus SO MAMMALIAN GENOME LA English DT Article ID KNOCK-IN MOUSE; AGE-OF-ONSET; CAG REPEAT INSTABILITY; STRIATAL NEURONAL LOSS; TRINUCLEOTIDE REPEAT; WEIGHT-LOSS; HD MAPS; MICE; LENGTH; GENE AB Huntington's disease (HD) is a dominant neurodegenerative disorder that is due to expansion of an unstable HTT CAG repeat for which genome-wide genetic scans are now revealing chromosome regions that contain disease-modifying genes. We have explored a novel human-mouse cross-species functional prioritisation approach, by evaluating the HD modifier 6q23-24 linkage interval. This unbiased strategy employs C57BL/6J (B6J) Hdh(Q111) knock-in mice, replicates of the HD mutation, and the C57BL/6J-chr10(A/J)/NaJ chromosome substitution strain (CSS10), in which only chromosome 10 (chr10), in synteny with the human 6q23-24 region, is derived from the A/J (AJ) strain. Crosses were performed to assess the possibility of dominantly acting chr10 AJ-B6J variants of strong effect that may modulate CAG-dependent Hdh(Q111/+) phenotypes. Testing of F1 progeny confirmed that a single AJ chromosome had a significant effect on the rate of body weight gain and in Hdh(Q111) mice the AJ chromosome was associated subtle alterations in somatic CAG instability in the liver and the formation of intra-nuclear inclusions, as well as DARPP-32 levels, in the striatum. These findings in relatively small cohorts are suggestive of dominant chr10 AJ-B6 variants that may modify effects of the CAG expansion, and encourage a larger study with CSS10 and sub-strains. This cross-species approach may therefore be suited to functional in vivo prioritisation of genomic regions harbouring genes that can modify the early effects of the HD mutation. C1 [Ramos, Eliana Marisa; Kovalenko, Marina; Guide, Jolene R.; St Claire, Jason; Gillis, Tammy; Mysore, Jayalakshmi S.; Wheeler, Vanessa C.; MacDonald, Marcy E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Ramos, Eliana Marisa; Sequeiros, Jorge; Alonso, Isabel] Univ Porto, Inst Mol & Cell Biol IBMC, UnIGENe, P-4150180 Oporto, Portugal. [Sequeiros, Jorge; Alonso, Isabel] Univ Porto, Inst Mol & Cell Biol IBMC, CGPP, P-4150180 Oporto, Portugal. [Sequeiros, Jorge; Alonso, Isabel] Univ Porto, Inst Ciencias Biomed Abel Salazar ICBAS, P-4050313 Oporto, Portugal. RP MacDonald, ME (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Simches Res Bldg,Room 5414,185 Cambridge St, Boston, MA 02114 USA. EM macdonam@helix.mgh.harvard.edu RI Alonso, Isabel/I-4307-2013 OI Alonso, Isabel/0000-0001-8549-6903 FU Fundacao para a Ciencia e a Tecnologia of Portugal [SFRH/BD/44335/2008]; NIH from the NINDS [NS32765] FX EMR is the recipient of a scholarship from the Fundacao para a Ciencia e a Tecnologia of Portugal (SFRH/BD/44335/2008). Study funding supported by NIH Grant from the NINDS NS32765. NR 43 TC 2 Z9 2 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-8990 EI 1432-1777 J9 MAMM GENOME JI Mamm. Genome PD APR PY 2015 VL 26 IS 3-4 BP 119 EP 130 DI 10.1007/s00335-014-9552-9 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA CE3CW UT WOS:000351703200001 PM 25645993 ER PT J AU Zhang, R Chomistek, AK Dimitrakoff, JD Giovannucci, EL Willett, WC Rosner, BA Wu, KN AF Zhang, Ran Chomistek, Andrea K. Dimitrakoff, Jordan D. Giovannucci, Edward L. Willett, Walter C. Rosner, Bernard A. Wu, Kana TI Physical Activity and Chronic Prostatitis/Chronic Pelvic Pain Syndrome SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE EXERCISE; EPIDEMIOLOGY; PROSTATE; RISK FACTORS; CHRONIC PAIN; WALKING ID QUALITY-OF-LIFE; SYMPTOM INDEX; RISK-FACTORS; EXERCISE; HEALTH; PREVALENCE; MEN; POPULATION; CLASSIFICATION; OVERLAP AB Purpose Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent urologic disorder among men, but its etiology is still poorly understood. Our objective was to examine the relation between physical activity and incidence of CP/CPPS in a large cohort of male health professionals. Methods We conducted a prospective cohort study among men in the Health Professionals Follow-up Study followed from 1986 to 2008. The study population included 20,918 men who completed all CP/CPPS questions on the 2008 questionnaire. Leisure-time physical activity, including type and intensity of activity, was measured by questionnaire in 1986. A National Institute of Health Chronic Prostatitis Symptom Index pain score was calculated on the basis of the responses on the 2008 questionnaire. Participants with pain scores 8 were considered CP/CPPS cases (n = 689). Results Higher leisure-time physical activity was associated with lower risk of CP/CPPS. The multivariable-adjusted odds ratio comparing >35.0 to 3.5 METhwk(-1) of physical activity was 0.72 (95% confidence interval, 0.56-0.92; P for trend <0.001). Observed inverse associations between physical activity and CP/CPPS were similar for both moderate- and vigorous-intensity activities. Sedentary behavior, measured as time spent watching television, was not associated with risk of CP/CPPS (P for trend = 0.64). Conclusions Findings from this study, the first large scale and most comprehensive study to date on this association, suggest that higher levels of leisure-time physical activity may lower risk of CP/CPPS in middle-age and older men. C1 [Zhang, Ran; Giovannucci, Edward L.; Willett, Walter C.; Wu, Kana] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Zhang, Ran; Giovannucci, Edward L.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chomistek, Andrea K.] Indiana Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Bloomington, IN 47405 USA. [Dimitrakoff, Jordan D.] Beth Israel Deaconess Med Ctr, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02215 USA. [Dimitrakoff, Jordan D.; Giovannucci, Edward L.; Willett, Walter C.; Rosner, Bernard A.] Harvard Univ, Sch Med, Boston, MA USA. [Dimitrakoff, Jordan D.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Giovannucci, Edward L.; Willett, Walter C.; Rosner, Bernard A.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Rosner, Bernard A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Zhang, R (reprint author), Indiana Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Room C101,1025 E 7th St, Bloomington, IN 47405 USA. EM achomist@indiana.edu RI Chomistek, Andrea/A-2104-2017 OI Chomistek, Andrea/0000-0002-8764-1446 FU NIH [UM1 CA167552, P01 CA055075, R01 CA133891] FX This study was supported by NIH grants UM1 CA167552, P01 CA055075, and R01 CA133891. NR 39 TC 7 Z9 7 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD APR PY 2015 VL 47 IS 4 BP 757 EP 764 DI 10.1249/MSS.0000000000000472 PG 8 WC Sport Sciences SC Sport Sciences GA CE1QU UT WOS:000351587800011 PM 25116086 ER PT J AU Matheny, RW Riddle-Kottke, MA Leandry, LA Lynch, CM Abdalla, MN Geddis, AV Piper, DR Zhao, JJ AF Matheny, Ronald W., Jr. Riddle-Kottke, Melissa A. Leandry, Luis A. Lynch, Christine M. Abdalla, Mary N. Geddis, Alyssa V. Piper, David R. Zhao, Jean J. TI Role of Phosphoinositide 3-OH Kinase p110 beta in Skeletal Myogenesis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MYOSIN HEAVY-CHAIN; PHOSPHATIDYLINOSITOL 3-KINASE; MUSCLE DIFFERENTIATION; METABOLIC-REGULATION; P110-ALPHA ISOFORM; GENE-TRANSCRIPTION; PI3K P110-ALPHA; SATELLITE CELLS; DRUG DISCOVERY; GROWTH AB Phosphoinositide 3-OH kinase (PI3K) regulates a number of developmental and physiologic processes in skeletal muscle; however, the contributions of individual PI3K p110 catalytic subunits to these processes are not well-defined. To address this question, we investigated the role of the 110-kDa PI3K catalytic subunit beta (p110 beta) in myogenesis and metabolism. In C2C12 cells, pharmacological inhibition of p110 beta delayed differentiation. We next generated mice with conditional deletion of p110 beta in skeletal muscle (p110 beta muscle knockout [ p110 beta-mKO] mice). While young p110 beta-mKO mice possessed a lower quadriceps mass and exhibited less strength than control littermates, no differences in muscle mass or strength were observed between genotypes in old mice. However, old p110 beta-mKO mice were less glucose tolerant than old control mice. Overexpression of p110 beta accelerated differentiation in C2C12 cells and primary human myoblasts through an Akt-dependent mechanism, while expression of kinase-inactive p110 beta had the opposite effect. p110 beta overexpression was unable to promote myoblast differentiation under conditions of p110 beta inhibition, but expression of p110 beta was able to promote differentiation under conditions of p110 beta inhibition. These findings reveal a role for p110 beta during myogenesis and demonstrate that long-term reduction of skeletal muscle p110 beta impairs whole-body glucose tolerance without affecting skeletal muscle size or strength in old mice. C1 [Matheny, Ronald W., Jr.; Riddle-Kottke, Melissa A.; Leandry, Luis A.; Lynch, Christine M.; Abdalla, Mary N.; Geddis, Alyssa V.] US Army Res Inst Environm Med, Mil Performance Div, Natick, MA 01760 USA. [Piper, David R.] Thermo Fisher Sci, Life Sci Solut, Biosci Div, Madison, WI USA. [Zhao, Jean J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Zhao, Jean J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Matheny, RW (reprint author), US Army Res Inst Environm Med, Mil Performance Div, Natick, MA 01760 USA. EM ronald.w.matheny.civ@mail.mil FU Research Area Directorate III; Medical Research and Materiel Command; NIH [R01 CA172461-02, U24-DK092993]; U.S. Army Research Institute of Environmental Medicine FX This work was supported by funding from Research Area Directorate III, Medical Research and Materiel Command (to R.W.M.), and by NIH grants R01 CA172461-02 (to J.J.Z.) and U24-DK092993 (University of California, Davis, Mouse Metabolic Phenotyping Center). C.M.L., A.V.G., and M.N.A. were supported by appointments to the Postgraduate Research Participation Program at the U.S. Army Research Institute of Environmental Medicine, administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Army Medical Research and Materiel Command. NR 59 TC 6 Z9 6 U1 0 U2 6 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 APR PY 2015 VL 35 IS 7 BP 1182 EP 1196 DI 10.1128/MCB.00550-14 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CE3PG UT WOS:000351739200009 PM 25605332 ER PT J AU Bouamar, H Jiang, DF Wang, L Lin, AP Ortega, M Aguiar, RCT AF Bouamar, Hakim Jiang, Daifeng Wang, Long Lin, An-Ping Ortega, Manoela Aguiar, Ricardo C. T. TI MicroRNA 155 Control of p53 Activity Is Context Dependent and Mediated by Aicda and Socs1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INDUCED CYTIDINE DEAMINASE; B-CELL LYMPHOMA; SOMATIC HYPERMUTATION; BREAST-CANCER; EXPRESSION; MIR-155; GENE; AID; PATHWAY; PROTEIN AB In biological processes, the balance between positive and negative inputs is critical for an effective physiological response and to prevent disease. A case in point is the germinal center (GC) reaction, wherein high mutational and proliferation rates are accompanied by an obligatory suppression of the DNA repair machinery. Understandably, when the GC reaction goes awry, loss of immune cells or lymphoid cancer ensues. Here, we detail the functional interactions that make microRNA 155 (miR-155) a key part of this process. Upon antigen exposure, miR-155(-/-) mature B cells displayed significantly higher double-strand DNA break (DSB) accumulation and p53 activation than their miR-155(+/+) counterparts. Using B cell-specific knockdown strategies, we confirmed the role of the miR-155 target Aicda (activation-induced cytidine deaminase) in this process and, in combination with a gain-of-function model, unveiled a previously unappreciated role for Socs1 in directly modulating p53 activity and the DNA damage response in B lymphocytes. Thus, miR-155 controls the outcome of the GC reaction by modulating its initiation (Aicda) and termination (Socs1/p53 response), suggesting a mechanism to explain the quantitative defect in germinal center B cells found in mice lacking or overexpressing this miRNA. C1 [Bouamar, Hakim; Jiang, Daifeng; Wang, Long; Lin, An-Ping; Ortega, Manoela; Aguiar, Ricardo C. T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hematol & Med Oncol, San Antonio, TX 78229 USA. [Aguiar, Ricardo C. T.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. [Aguiar, Ricardo C. T.] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA. [Aguiar, Ricardo C. T.] Audie Murphy VA Hosp, South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Aguiar, RCT (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hematol & Med Oncol, San Antonio, TX 78229 USA. EM aguiarr@uthscsa.edu FU National Cancer Institute [R01-CA138747]; Young Investigator Award from the Voelcker Fund; Veterans Administration Merit Award [I01-BX001882]; National Cancer Institute Cancer Center Support Grant [P30 CA054174] FX This work was supported by a grant from the National Cancer Institute (R01-CA138747) (R.C.T.A), a Young Investigator Award from the Voelcker Fund (R.C.T. A), a Veterans Administration Merit Award (I01-BX001882), and a National Cancer Institute Cancer Center Support Grant (P30 CA054174). NR 37 TC 7 Z9 8 U1 2 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 APR PY 2015 VL 35 IS 8 BP 1329 EP 1340 DI 10.1128/MCB.01446-14 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CE3PX UT WOS:000351741500002 PM 25645925 ER PT J AU Maudsley, S Martin, B Gesty-Palmer, D Cheung, H Johnson, C Patel, S Becker, KG Wood, WH Zhang, YQ Lehrmann, E Luttrell, LM AF Maudsley, Stuart Martin, Bronwen Gesty-Palmer, Diane Cheung, Huey Johnson, Calvin Patel, Shamit Becker, Kevin G. Wood, William H., III Zhang, Yongqing Lehrmann, Elin Luttrell, Louis M. TI Delineation of a Conserved Arrestin-Biased Signaling Repertoire In Vivo SO MOLECULAR PHARMACOLOGY LA English DT Article ID BETA-ARRESTIN; PARATHYROID-HORMONE; FUNCTIONAL SELECTIVITY; RECEPTOR; EFFICACY; PATHWAYS; CANCER; BETA-ARRESTIN2; ACTIVATION; TOPOLOGY AB Biased G protein-coupled receptor agonists engender a restricted repertoire of downstream events from their cognate receptors, permitting them to produce mixed agonist-antagonist effects in vivo. While this opens the possibility of novel therapeutics, it complicates rational drug design, since the in vivo response to a biased agonist cannot be reliably predicted from its in cellula efficacy. We have employed novel informatic approaches to characterize the in vivo transcriptomic signature of the arrestin pathway-selective parathyroid hormone analog [D-Trp(12), Tyr(34)] bovine PTH(7-34) in six different murine tissues after chronic drug exposure. We find that [D-Trp(12), Tyr(34)] bovine PTH(7-34) elicits a distinctive arrestin-signaling focused transcriptomic response that is more coherently regulated across tissues than that of the pluripotent agonist, human PTH(1-34). This arrestin-focused network is closely associated with transcriptional control of cell growth and development. Our demonstration of a conserved arrestin-dependent transcriptomic signature suggests a framework within which the in vivo outcomes of arrestin-biased signaling may be generalized. C1 [Maudsley, Stuart; Martin, Bronwen; Patel, Shamit; Becker, Kevin G.; Wood, William H., III; Zhang, Yongqing; Lehrmann, Elin] NIA, NIH, Baltimore, MD 21224 USA. [Gesty-Palmer, Diane] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Cheung, Huey; Johnson, Calvin] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. [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 USA. RP Maudsley, S (reprint author), Univ Antwerp VIB, Dept Mol Genet, Univ Pl 1,Bldg V, B-2610 Antwerp, Belgium. EM stuart.maudsley@molgen.vib-ua.be FU Intramural Research Program of the National Institutes of Health National Institute on Aging; National Institutes of Health National Institute of General Medical Sciences [R01-GM095497]; National Institutes of Health National Institute of Diabetes, Digestive and Kidney Diseases [R01-DK055524]; National Institutes of Health National Institute of Child Health and Human Development [T32-HD043446]; Arthritis Foundation; Research Service of the Charleston, SC Veterans Affairs Medical Center FX This research was supported by the Intramural Research Program of the National Institutes of Health National Institute on Aging; the National Institutes of Health National Institute of General Medical Sciences [Grant R01-GM095497]; the National Institutes of Health National Institute of Diabetes, Digestive and Kidney Diseases [Grant R01-DK055524]; the National Institutes of Health National Institute of Child Health and Human Development [Grant T32-HD043446]; the Arthritis Foundation; and the Research Service of the Charleston, SC Veterans Affairs Medical Center. The contents of this article do not represent the views of the Department of Veterans Affairs or the United States Government. NR 48 TC 10 Z9 10 U1 1 U2 3 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 APR PY 2015 VL 87 IS 4 BP 706 EP 717 DI 10.1124/mol.114.095224 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CE7FT UT WOS:000352004100014 PM 25637603 ER PT J AU Fridman, V Oaklander, AL David, WS Johnson, EA Pan, J Novak, P Brown, RH Eichler, FS AF Fridman, Vera Oaklander, Anne Louise David, William S. Johnson, Elise A. Pan, Jessica Novak, Peter Brown, Robert H., Jr. Eichler, Florian S. TI NATURAL HISTORY AND BIOMARKERS IN HEREDITARY SENSORY NEUROPATHY TYPE 1 SO MUSCLE & NERVE LA English DT Article DE hereditary neuropathy; neurogenetics; peripheral neuropathy; skin biopsy; small fiber neuropathy ID SKIN BIOPSY; RELIABILITY; DIAGNOSIS; SPTLC1; SCORE AB Introduction: Hereditary sensory and autonomic neuropathy type 1 (HSAN1) is most commonly caused by missense mutations in SPTLC1. In this study we mapped symptom progression and compared the utility of outcomes. Methods: We administered retrospective surveys of symptoms and analyzed results of nerve conduction, autonomic function testing (AFT), and PGP9.5-immunolabeled skin biopsies. Results: The first symptoms were universally sensory and occurred at a median age of 20 years (range 14-54 years). The onset of weakness, ulcers, pain, and balance problems followed sequentially. Skin biopsies revealed universally absent epidermal innervation at the distal leg with relative preservation in the thigh. Neurite density was highly correlated with total Charcot-Marie-Tooth Examination Score (CMTES; r(2)=-0.8) and median motor amplitude (r(2)=-0.75). Conclusions: These results confirm sensory loss as the initial symptom of HSAN1 and suggest that skin biopsy may be the most promising biomarker for future clinical trials. Muscle Nerve, 2015 Muscle Nerve 51: 489-495, 2015 C1 [Fridman, Vera; Oaklander, Anne Louise; David, William S.; Johnson, Elise A.; Pan, Jessica; Eichler, Florian S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02114 USA. [Novak, Peter; Brown, Robert H., Jr.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA. RP Eichler, FS (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. EM feichler@partners.org FU Deater Foundation FX The authors thank the families for their participation and the Deater Foundation for support. Heather Downs provided technical assistance. We also thank Dr. April Eichler for careful review of the manuscript. NR 17 TC 5 Z9 5 U1 0 U2 5 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 APR PY 2015 VL 51 IS 4 BP 489 EP 495 DI 10.1002/mus.24336 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CE2VU UT WOS:000351679400004 PM 25042817 ER PT J AU Morris, N Lynch, K Greenberg, SA AF Morris, Nicholas Lynch, Karen Greenberg, Steven A. TI SEVERE MOTOR NEUROPATHY OR NEURONOPATHY DUE TO NITROUS OXIDE TOXICITY AFTER CORRECTION OF VITAMIN B12 DEFICIENCY SO MUSCLE & NERVE LA English DT Article DE nitrous oxide; vitamin B12; B12 deficiency; cobalamin; myeloneuropathy; motor neuropathy ID MYELOPATHY; MYELONEUROPATHY AB Introduction: Nitrous oxide (N2O) toxicity can cause a sensory predominant myeloneuropathy identical to subacute combined degeneration caused by vitamin B12 deficiency. We describe a patient with a typical vitamin B12 deficiency syndrome after N2O abuse who recovered and then developed a severe lower motor neuron syndrome following vitamin B12 correction. This suggests N2O toxicity independent of functional vitamin B12 deficiency. Methods: Electrophysiological, serological, and clinical evaluations were undertaken in the evaluation of this patient. Results: A 22-year-old man abused N2O and presented with a dorsal column syndrome with low vitamin B12 and high homocysteine serum levels. He recovered with treatment but presented later with profound motor axonal degeneration and normal vitamin B12, homocysteine, and methlymalonic acid levels. Conclusions: This case illustrates that N2O-associated severe motor neuropathy or neuronopathy can develop separately from typical vitamin B12 deficiency dorsal column myelopathy. This syndrome can present when functional measures of vitamin B12 deficiency have normalized. Muscle Nerve 51: 614-616, 2015 C1 [Morris, Nicholas] Massachusetts Gen Hosp, Brigham & Womens Hosp, Partners Neurol Residency, Boston, MA 02114 USA. [Morris, Nicholas; Lynch, Karen] Harvard Univ, Sch Med, Boston, MA USA. [Lynch, Karen] Massachusetts Gen Hosp, Brigham & Womens Hosp, Partners Neurol Neuromuscular Fellowship, Boston, MA 02114 USA. [Greenberg, Steven A.] Harvard Univ, Sch Med, Dept Neurol, Div Neuromuscular Dis,Brigham & Womens Hosp,Child, Boston, MA 02115 USA. [Greenberg, Steven A.] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Boston, MA USA. RP Greenberg, SA (reprint author), Harvard Univ, Sch Med, Dept Neurol, Div Neuromuscular Dis,Brigham & Womens Hosp,Child, 75 Francis St, Boston, MA 02115 USA. EM sagreenberg@partners.org NR 13 TC 4 Z9 4 U1 0 U2 4 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 APR PY 2015 VL 51 IS 4 BP 614 EP 616 DI 10.1002/mus.24482 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CE2VU UT WOS:000351679400023 PM 25297001 ER PT J AU Chen, CW Koche, RP Sinha, AU Deshpande, AJ Zhu, N Eng, R Doench, JG Xu, HM Chu, SH Qi, J Wang, X Delaney, C Bernt, KM Root, DE Hahn, WC Bradner, JE Armstrong, SA AF Chen, Chun-Wei Koche, Richard P. Sinha, Amit U. Deshpande, Aniruddha J. Zhu, Nan Eng, Rowena Doench, John G. Xu, Haiming Chu, Scott H. Qi, Jun Wang, Xi Delaney, Christopher Bernt, Kathrin M. Root, David E. Hahn, William C. Bradner, James E. Armstrong, Scott A. TI DOT1L inhibits SIRT1-mediated epigenetic silencing to maintain leukemic gene expression in MLL-rearranged leukemia SO NATURE MEDICINE LA English DT Article ID MIXED-LINEAGE LEUKEMIA; LENTIVIRAL RNAI LIBRARY; ACUTE MYELOID-LEUKEMIA; H3K79 METHYLATION; HISTONE H3; FACULTATIVE HETEROCHROMATIN; TRANSCRIPTIONAL ELONGATION; METHYLTRANSFERASE DOT1L; MAMMALIAN-CELLS; SIRT1 AB Rearrangements of MLL (encoding lysine-specific methyltransferase 2A and officially known as KMT2A; herein referred to as MLL to denote the gene associated with mixed-lineage leukemia) generate MLL fusion proteins that bind DNA and drive leukemogenic gene expression. This gene expression program is dependent on the disruptor of telomeric silencing 1-like histone 3 lysine 79 (H3K79) methyltransferase DOT1L, and small-molecule DOT1L inhibitors show promise as therapeutics for these leukemias. However, the mechanisms underlying this dependency are unclear. We conducted a genome-scale RNAi screen and found that the histone deacetylase SIRT1 is required for the establishment of a heterochromatin-like state around MLL fusion target genes after DOT1L inhibition. DOT1L inhibits chromatin localization of a repressive complex composed of SIRT1 and the H3K9 methyltransferase SUV39H1, thereby maintaining an open chromatin state with elevated H3K9 acetylation and minimal H3K9 methylation at MLL fusion target genes. Furthermore, the combination of SIRT1 activators and DOT1L inhibitors shows enhanced antiproliferative activity against MLL-rearranged leukemia cells. These results indicate that the dynamic interplay between chromatin regulators controlling the activation and repression of gene expression could provide novel opportunities for combination therapy. C1 [Chen, Chun-Wei; Koche, Richard P.; Sinha, Amit U.; Deshpande, Aniruddha J.; Zhu, Nan; Eng, Rowena; Xu, Haiming; Chu, Scott H.; Wang, Xi; Delaney, Christopher; Armstrong, Scott A.] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10021 USA. [Doench, John G.; Root, David E.; Hahn, William C.; Bradner, James E.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA. [Qi, Jun; Hahn, William C.; Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bernt, Kathrin M.] Univ Colorado, Sch Med, Childrens Hosp Colorado, Dept Pediat, Aurora, CO USA. RP Armstrong, SA (reprint author), Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, 1275 York Ave, New York, NY 10021 USA. EM Armstros@mskcc.org RI Bernt, Kathrin/L-1826-2016; OI Bernt, Kathrin/0000-0002-5400-0482; Chu, S. Haihua/0000-0002-8333-5409; Doench, John/0000-0002-3707-9889 FU Leukemia and Lymphoma Society; Gabrielle's Angel Research Foundation; US National Institutes of Health [CA66996, CA140575, CA176745] FX We would like to thank J. Bradner for providing EPZ4777, and J. Brady and Z. Feng for administrative assistance. This work was supported by the Leukemia and Lymphoma Society, by Gabrielle's Angel Research Foundation and by US National Institutes of Health grant nos. CA66996, CA140575 and CA176745 (to S.A.A.). NR 63 TC 33 Z9 34 U1 2 U2 20 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 APR PY 2015 VL 21 IS 4 BP 335 EP + DI 10.1038/nm.3832 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CF4BO UT WOS:000352493600015 PM 25822366 ER PT J AU Shinoda, K Luijten, IHN Hasegawa, Y Hong, H Sonne, SB Kim, M Xue, R Chondronikola, M Cypess, AM Tseng, YH Nedergaard, J Sidossis, LS Kajimura, S AF Shinoda, Kosaku Luijten, Ineke H. N. Hasegawa, Yutaka Hong, Haemin Sonne, Si B. Kim, Miae Xue, Ruidan Chondronikola, Maria Cypess, Aaron M. Tseng, Yu-Hua Nedergaard, Jan Sidossis, Labros S. Kajimura, Shingo TI Genetic and functional characterization of clonally derived adult human brown adipocytes SO NATURE MEDICINE LA English DT Article ID ADIPOSE-TISSUE; INSULIN SENSITIVITY; BEIGE ADIPOCYTES; FAT DEVELOPMENT; EXPRESSION; NECK; CELL; THERMOGENESIS; STIMULATION; TEMPERATURE AB Brown adipose tissue (BAT) acts in mammals as a natural defense system against hypothermia, and its activation to a state of increased energy expenditure is believed to protect against the development of obesity. Even though the existence of BAT in adult humans has been widely appreciated(1-8), its cellular origin and molecular identity remain elusive largely because of high cellular heterogeneity within various adipose tissue depots. To understand the nature of adult human brown adipocytes at single cell resolution, we isolated clonally derived adipocytes from stromal vascular fractions of adult human BAT from two individuals and globally analyzed their molecular signatures. We used RNA sequencing followed by unbiased genome-wide expression analyses and found that a population of uncoupling protein 1 (UCP1)-positive human adipocytes possessed molecular signatures resembling those of a recruitable form of thermogenic adipocytes (that is, beige adipocytes). In addition, we identified molecular markers that were highly enriched in UCP1-positive human adipocytes, a set that included potassium channel K3 (KCNK3) and mitochondrial tumor suppressor 1 (MTUS1). Further, we functionally characterized these two markers using a loss-of-function approach and found that KCNK3 and MTUS1 were required for beige adipocyte differentiation and thermogenic function. The results of this study present new opportunities for human BAT research, such as facilitating cell-based disease modeling and unbiased screens for thermogenic regulators. C1 [Shinoda, Kosaku; Luijten, Ineke H. N.; Hasegawa, Yutaka; Hong, Haemin; Sonne, Si B.; Kim, Miae; Kajimura, Shingo] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA. [Shinoda, Kosaku; Luijten, Ineke H. N.; Hasegawa, Yutaka; Hong, Haemin; Sonne, Si B.; Kim, Miae; Kajimura, Shingo] UCSF, Dept Cell & Tissue Biol, San Francisco, CA USA. [Shinoda, Kosaku; Luijten, Ineke H. N.; Hasegawa, Yutaka; Hong, Haemin; Sonne, Si B.; Kim, Miae; Kajimura, Shingo] UCSF, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA USA. [Luijten, Ineke H. N.; Nedergaard, Jan] Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, S-10691 Stockholm, Sweden. [Xue, Ruidan; Cypess, Aaron M.; Tseng, Yu-Hua] Joslin Diabet Ctr, Boston, MA 02215 USA. [Xue, Ruidan; Cypess, Aaron M.; Tseng, Yu-Hua] Harvard Univ, Sch Med, Boston, MA USA. [Chondronikola, Maria; Sidossis, Labros S.] Shriners Hosp Children, Metab Unit, Galveston, TX 77550 USA. [Chondronikola, Maria; Sidossis, Labros S.] Univ Texas Med Branch, Dept Internal Med, Galveston, TX 77555 USA. [Chondronikola, Maria; Sidossis, Labros S.] Univ Texas Med Branch, Dept Surg, Galveston, TX 77555 USA. [Chondronikola, Maria; Sidossis, Labros S.] Univ Texas Med Branch, Dept Nutr & Metab, Galveston, TX 77555 USA. RP Kajimura, S (reprint author), Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA. EM skajimura@diabetes.ucsf.edu RI Sonne, Si/A-4851-2012; OI Sonne, Si/0000-0003-3194-3805; Nedergaard, Jan/0000-0003-2070-1587 FU National Institutes of Health (NIH) [DK087853, DK097441]; UCSF Diabetes Research Center grant [DK63720]; UCSF Program for Breakthrough Biomedical Research program; Pew Charitable Trust; Japan Science and Technology Agency; NIH [P50-GM60338]; American Dental Association [1-14-TS-35]; Japan Society for the Promotion of Science; Manpei Suzuki Diabetes Foundation; Dutch Heart Foundation FX We acknowledge support from the National Institutes of Health (NIH) (DK087853 and DK097441), the UCSF Diabetes Research Center grant (DK63720), the UCSF Program for Breakthrough Biomedical Research program, the Pew Charitable Trust, and the Japan Science and Technology Agency (all to S.K.); and from the NIH (P50-GM60338) and the American Dental Association (1-14-TS-35) (both to L.S.S.). K.S. is supported by a fellowship from the Japan Society for the Promotion of Science. Y.H. is supported by the Manpei Suzuki Diabetes Foundation. I.H.N.L. is supported by the Dutch Heart Foundation. NR 41 TC 72 Z9 74 U1 6 U2 27 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 APR PY 2015 VL 21 IS 4 BP 389 EP + DI 10.1038/nm.3819 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CF4BO UT WOS:000352493600021 PM 25774848 ER PT J AU Bachireddy, P Burkhardt, UE Rajasagi, M Wu, CJ AF Bachireddy, Pavan Burkhardt, Ute E. Rajasagi, Mohini Wu, Catherine J. TI Haematological malignancies: at the forefront of immunotherapeutic innovation SO NATURE REVIEWS CANCER LA English DT Review ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; STEM-CELL TRANSPLANTATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; REGULATORY T-CELLS; NON-HODGKINS-LYMPHOMA; PHASE-II TRIAL; WT1 PEPTIDE VACCINATION; COLONY-STIMULATING FACTOR; NATURAL-KILLER-CELLS AB The recent successes of cancer immunotherapies have stimulated interest in the potential widespread application of these approaches; haematological malignancies have provided both initial proofs of concept and an informative testing ground for various immune-based therapeutics. The immune-cell origin of many of the blood malignancies provides a unique opportunity both to understand the mechanisms of cancer immune responsiveness and immune evasion, and to exploit these mechanisms for therapeutic purposes. C1 [Bachireddy, Pavan; Burkhardt, Ute E.; Rajasagi, Mohini; Wu, Catherine J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Bachireddy, Pavan; Burkhardt, Ute E.; Rajasagi, Mohini; Wu, Catherine J.] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02215 USA. [Bachireddy, Pavan; Rajasagi, Mohini; Wu, Catherine J.] Broad Inst, Cambridge, MA 02142 USA. [Bachireddy, Pavan; Wu, Catherine J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Wu, CJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM cwu@partners.org FU US National Cancer Institute [T32CA009172]; German Research Foundation (Deutsche Forschungsgemeinschaft) [BU 3028/1-1]; NHGRI [U54HG003067]; NCI [1RO1CA155010-02]; NHLBI [5R01HL103532-03]; Blavatinik Family Foundation; Leukaemia and Lymphoma Translational Research Program; Innovative Research Grant for Stand Up to Cancer/AACR FX P.B. was supported by the US National Cancer Institute under award number T32CA009172. U.E.B. acknowledges support from the German Research Foundation (Deutsche Forschungsgemeinschaft; BU 3028/1-1). C.J.W. is supported in parts by grants NHGRI (U54HG003067), NCI (1RO1CA155010-02) and NHLBI (5R01HL103532-03); the Blavatinik Family Foundation; and the Leukaemia and Lymphoma Translational Research Program. C.J.W. is a recipient of an Innovative Research Grant for Stand Up to Cancer/AACR. The authors thank E. Fritsch, J. Ritz, R. Soiffer and P. Ott for valuable feedback on and discussion of this manuscript. NR 212 TC 16 Z9 16 U1 4 U2 23 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X EI 1474-1768 J9 NAT REV CANCER JI Nat. Rev. Cancer PD APR PY 2015 VL 15 IS 4 BP 201 EP 215 DI 10.1038/nrc3907 PG 15 WC Oncology SC Oncology GA CE3WI UT WOS:000351760300007 PM 25786696 ER PT J AU Greene, SJ Fonarow, GC Vaduganathan, M Khan, SS Butler, J Gheorghiade, M AF Greene, Stephen J. Fonarow, Gregg C. Vaduganathan, Muthiah Khan, Sadiya S. Butler, Javed Gheorghiade, Mihai TI The vulnerable phase after hospitalization for heart failure SO NATURE REVIEWS CARDIOLOGY LA English DT Review ID NATIONAL REGISTRY ADHERE; 30-DAY READMISSION RATES; EVEREST TRIAL; HIGH-RISK; POSTDISCHARGE OUTCOMES; SCIENTIFIC STATEMENT; IDENTIFYING PATIENTS; THERAPEUTIC TARGET; DISEASE MANAGEMENT; EUROPEAN-SOCIETY AB Despite available therapy, mortality and readmission rates within 60-90 days of discharge for patients hospitalized with heart failure (HF) approach 15% and 30%, respectively. This early postdischarge period has been termed the 'vulnerable phase' and accounts for a disproportionate amount of the >US$30 billion spent annually on HF care in the USA. The pathophysiology underlying these early adverse events is likely associated with persistently elevated filling pressures at time of discharge and subsequent acute or subacute worsening of postdischarge haemodynamics. Despite limited proven strategies to reduce early adverse events, hospitals in the USA face penalties for 30-day readmission rates that exceed current expectations, and an urgent need exists for novel approaches to improve early postdischarge outcomes. The objective of this Review is to describe the early postdischarge problem among patients hospitalized for HF, the associated patient profile and pathophysiology, and the limitations of current postdischarge treatment strategies. We also identify therapeutic targets and outline a progressive management approach that should be considered by clinicians for reducing early postdischarge morbidity and mortality. Although these strategies require prospective validation, they are practical, affordable, and have the potential to improve patient outcomes substantially after HF hospitalization. C1 [Greene, Stephen J.; Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Ronald Reagan Med Ctr, Ahmanson Cardiomyopathy Ctr, Los Angeles, CA 90095 USA. [Vaduganathan, Muthiah] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Khan, Sadiya S.] Northwestern Univ, Feinberg Sch Med, Div Cardiol, Chicago, IL 60611 USA. [Butler, Javed] SUNY Stony Brook, Div Cardiol, Stony Brook, NY 11794 USA. RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, 201 East Huron St,Galter 3-150, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu FU Agency for Healthcare Research and Quality; NIH; European Union; Health Resources Service Administration FX G.C.F. declares research support from the Agency for Healthcare Research and Quality and has been a consultant for Gambro, Medtronic, and Novartis. J.B. has received research support from the NIH, European Union, and Health Resources Service Administration, and is or has been a consultant for Amgen, Bayer, BG Medicine, Cardiocell, Celladon, Gambro, GE Healthcare, Medtronic, Novartis, Ono Pharma, Takeda, Trevena, and Zensun. M.G. is a consultant for Abbott Laboratories, Astellas, AstraZeneca, Bayer Schering Pharma AG, Cardiorentis, CorThera, Cytokinetics, CytoPherx Inc, DebioPharm SA, Errekappa Terapeutici, GlaxoSmithKline, Ikaria, Intersection Medical Inc, Johnson & Johnson, Medtronic, Merck, Novartis Pharma AG, Ono Pharmaceuticals USA, Otsuka Pharmaceuticals, Palatin Technologies, Pericor Therapeutics, Protein Design Laboratories, Sanofi-Aventis, Sigma Tau, Solvay Pharmaceuticals, Sticares InterACT, Takeda Pharmaceuticals North America, and Trevena Therapeutics. The other authors declare no competing interests. NR 82 TC 17 Z9 17 U1 5 U2 11 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 APR PY 2015 VL 12 IS 4 BP 220 EP 229 DI 10.1038/nrcardio.2015.14 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CE2YO UT WOS:000351688900007 PM 25666406 ER PT J AU Tang, YY Holzel, BK Posner, MI AF Tang, Yi-Yuan Hoelzel, Britta K. Posner, Michael I. TI The neuroscience of mindfulness meditation SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID SHORT-TERM MEDITATION; RANDOMIZED CONTROLLED-TRIAL; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; OVERLAPPING MENTAL OPERATIONS; ANTERIOR CINGULATE CORTEX; SCALE BRAIN NETWORKS; DEFAULT MODE NETWORK; WHITE-MATTER CHANGES; EMOTION REGULATION; STRESS REDUCTION AB Research over the past two decades broadly supports the claim that mindfulness meditation - practiced widely for the reduction of stress and promotion of health - exerts beneficial effects on physical and mental health, and cognitive performance. Recent neuroimaging studies have begun to uncover the brain areas and networks that mediate these positive effects. However, the underlying neural mechanisms remain unclear, and it is apparent that more methodologically rigorous studies are required if we are to gain a full understanding of the neuronal and molecular bases of the changes in the brain that accompany mindfulness meditation. C1 [Tang, Yi-Yuan] Texas Tech Univ, Dept Psychol Sci, Lubbock, TX 79409 USA. [Tang, Yi-Yuan; Posner, Michael I.] Univ Oregon, Dept Psychol, Eugene, OR 97403 USA. [Hoelzel, Britta K.] Tech Univ Munich, Dept Neuroradiol, D-81675 Munich, Germany. [Hoelzel, Britta K.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Tang, YY (reprint author), Texas Tech Univ, Dept Psychol Sci, Lubbock, TX 79409 USA. EM yiyuan.tang@ttu.edu FU US Office of Naval Research FX This work was supported by the US Office of Naval Research. We thank E. Luders for her contributions to an earlier version of this manuscript. We benefited from discussions with R. Davidson and A. Chiesa. We thank four anonymous reviewers for their constructive comments and R. Tang for manuscript preparation. NR 181 TC 114 Z9 117 U1 82 U2 310 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-003X EI 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD APR PY 2015 VL 16 IS 4 BP 213 EP U80 DI 10.1038/nrn3916 PG 13 WC Neurosciences SC Neurosciences & Neurology GA CE2YR UT WOS:000351689400008 PM 25783612 ER PT J AU Fenves, AZ Shchelochkov, OA Mehta, A AF Fenves, Andrew Z. Shchelochkov, Oleg A. Mehta, Ankit TI Hyperammonemic Syndrome After Roux-En-Y Gastric Bypass SO OBESITY LA English DT Article ID UREA CYCLE DISORDERS; BARIATRIC-SURGERY; LONGITUDINAL ASSESSMENT; ENCEPHALOPATHY; DEFICIENCY; THERAPY; SAFETY AB ObjectiveHyperammonemic encephalopathy is an uncommon but severe complication of the Roux-en-Y gastric bypass surgery for obesity. Mechanisms underlying this complication are incompletely understood, resulting in delayed recognition and management. This study evaluated common laboratory findings and possible etiology of hyperammonemic encephalopathy after successful Roux-en-Y gastric bypass surgery. MethodsA retrospective review of 20 patients identified through our own clinical practice was conducted, with the addition of similar cases from other institutions identified through the review of literature. ResultsPatients presenting with hyperammonemic encephalopathy after Roux-en-Y gastric bypass surgery presented with overlapping clinical and laboratory findings. Common features included: (1) weight loss following successful Roux-en-Y gastric bypass for obesity; (2) hyperammonemic encephalopathy accompanied by elevated plasma glutamine levels; (3) absence of cirrhosis; (4) hypoalbuminemia; and (5) low plasma zinc levels. The mortality rate was 50%. Ninety-five percent of patients were women. Three patients were diagnosed with proximal urea cycle disorders. One patient experienced improvement in the hyperammonemia after surgical correction of spontaneous splenorenal shunt. ConclusionsHyperammonemic encephalopathy after Roux-en-Y gastric bypass surgery is a newly recognized, potentially fatal syndrome with diverse pathophysiologic mechanisms encompassing genetic and nongenetic causes. C1 [Fenves, Andrew Z.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02138 USA. [Shchelochkov, Oleg A.] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. [Mehta, Ankit] Baylor Univ, Med Ctr, Dallas, TX USA. RP Fenves, AZ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02138 USA. EM AFENVES@partners.org NR 15 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD APR PY 2015 VL 23 IS 4 BP 746 EP 749 DI 10.1002/oby.21037 PG 4 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CE4XA UT WOS:000351832400007 PM 25754921 ER PT J AU Patti, ME Li, P Goldfine, AB AF Patti, Mary Elizabeth Li, Ping Goldfine, Allison B. TI Insulin Response to Oral Stimuli and Glucose Effectiveness Increased in Neuroglycopenia Following Gastric Bypass SO OBESITY LA English DT Article ID BETA-CELL FUNCTION; HYPERINSULINEMIC HYPOGLYCEMIA; POSTPRANDIAL HYPOGLYCEMIA; ISLET HYPERPLASIA; MINIMAL MODEL; MIXED-MEAL; BILE-ACIDS; SENSITIVITY; SECRETION; SURGERY AB ObjectiveHyperinsulinemic hypoglycemia with neuroglycopenia is a rare complication following Roux-en-Y gastric bypass (RYGB) surgery for weight management. Insulin secretion and action in response to oral and intravenous stimuli in persons with and without neuroglycopenia following RYGB are evaluated in this study. MethodsCross-sectional cohort studies were performed at a single academic institution to assess insulin secretion and action during oral mixed meal tolerance test and intravenous glucose tolerance test (IVGTT). ResultsInsulin secretion was increased more following oral mixed meal than intravenous glucose in individuals with neuroglycopenia compared to the asymptomatic group. Reduced insulin clearance did not contribute to higher insulinemia. Glucose effectiveness at zero insulin, estimated during the IVGTT, was also higher in those with neuroglycopenia. Insulin sensitivity did not differ between groups. ConclusionsIncreased beta-cell response to oral stimuli and insulin-independent glucose disposal may both contribute to severe hypoglycemia after RYGB. C1 [Patti, Mary Elizabeth; Li, Ping; Goldfine, Allison B.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Patti, Mary Elizabeth; Li, Ping; Goldfine, Allison B.] Harvard Univ, Sch Med, Boston, MA USA. [Li, Ping] China Med Univ, Shengjing Hosp, Dept Endocrinol, Shenyang 110001, Liaoning Provin, Peoples R China. RP Goldfine, AB (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM allison.goldfine@joslin.harvard.edu FU American Society of Metabolic and Bariatric Surgery (ASMBS); NIH [P30-DK036836]; National Natural Science Foundation of China [81170779] FX This work was supported by an unrestricted research grant from the American Society of Metabolic and Bariatric Surgery (ASMBS) to MEP, NIH P30-DK036836, and support for the Joslin Clinical Research Center from its philanthropic donors. Ping Li receives support from National Natural Science Foundation of China (grant number 81170779). NR 39 TC 12 Z9 12 U1 0 U2 1 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 APR PY 2015 VL 23 IS 4 BP 798 EP 807 DI 10.1002/oby.21043 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CE4XA UT WOS:000351832400014 PM 25755084 ER PT J AU Lin, SW Freedman, ND Shi, JX Gail, MH Vogtmann, E Yu, GQ Klepac-Ceraj, V Paster, BJ Dye, BA Wang, GQ Wei, WQ Fan, JH Qiao, YL Dawsey, SM Abnet, CC AF Lin, Shih-Wen Freedman, Neal D. Shi, Jianxin Gail, Mitchell H. Vogtmann, Emily Yu, Guoqin Klepac-Ceraj, Vanja Paster, Bruce J. Dye, Bruce A. Wang, Guo-Qing Wei, Wen-Qiang Fan, Jin-Hu Qiao, You-Lin Dawsey, Sanford M. Abnet, Christian C. TI Beta-Diversity Metrics of the Upper Digestive Tract Microbiome Are Associated with Body Mass Index SO OBESITY LA English DT Article ID HUMAN GUT MICROBIOTA; OBESITY; ECOLOGY; DISEASE; LACTOBACILLUS; PERIODONTITIS; OVERWEIGHT; CHILDREN; LINXIAN; CANCER AB ObjectiveStudies of the fecal microbiome have implicated the gut microbiota in obesity, but few studies have examined the microbial diversity at other sites. The association between obesity and the upper gastrointestinal (UGI) microbial diversity was explored. MethodsThe UGI microbiome of 659 healthy Chinese adults with a measured body mass index (BMI) range of 15.0 to 35.7 was characterized using the 16S rRNA gene DNA microarray (HOMIM). ResultsIn multivariate-adjusted models, alpha diversity was not associated with BMI. However, beta diversity, assessed by principal coordinate vectors generated from an unweighted UniFrac distance matrix of pairwise comparisons, was associated with BMI (third and fourth vectors, P=0.01 and P=0.03, respectively). Moreover, beta diversity, assessed by cluster membership (three clusters), was also associated with BMI; individuals in the first cluster [median BMI 22.35, odds ratio (OR)=0.48, 95% confidence interval (CI) = 0.05-4.34] and second cluster [median BMI 22.55, OR=0.26, 95% CI=0.09-0.75] were significantly less likely to be obese (BMI27.5) than those in the third cluster (median BMI 23.59). ConclusionsA beta-diversity metric of the UGI microbiome is associated with a four fold difference in obesity risk in this Asian population. Future studies should address whether the UGI microbiome plays a causal role in obesity. C1 [Lin, Shih-Wen; Freedman, Neal D.; Shi, Jianxin; Gail, Mitchell H.; Vogtmann, Emily; Yu, Guoqin; Dawsey, Sanford M.; Abnet, Christian C.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Klepac-Ceraj, Vanja; Paster, Bruce J.] Forsyth Inst, Dept Microbiol, Boston, MA USA. [Klepac-Ceraj, Vanja] Wellesley Coll, Dept Biol Sci, Wellesley, MA 02181 USA. [Dye, Bruce A.] Ctr Dis Control & Prevent, Hyattsville, MD USA. [Wang, Guo-Qing; Wei, Wen-Qiang; Fan, Jin-Hu; Qiao, You-Lin] Chinese Acad Med Sci, Canc Inst & Hosp, Beijing 100730, Peoples R China. RP Lin, SW (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM lins4@mail.nih.gov RI Freedman, Neal/B-9741-2015; Abnet, Christian/C-4111-2015; Qiao, You-Lin/B-4139-2012 OI Freedman, Neal/0000-0003-0074-1098; Abnet, Christian/0000-0002-3008-7843; Qiao, You-Lin/0000-0001-6380-0871 FU Intramural Research Program, Division of Cancer Epidemiology & Genetics, National Cancer Institute FX Supported by the Intramural Research Program, Division of Cancer Epidemiology & Genetics, National Cancer Institute. NR 40 TC 1 Z9 1 U1 1 U2 12 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 APR PY 2015 VL 23 IS 4 BP 862 EP 869 DI 10.1002/oby.21020 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CE4XA UT WOS:000351832400022 PM 25755147 ER PT J AU LeardMann, CA Woodall, KA Littman, AJ Jacobson, IG Boyko, EJ Smith, B Wells, TS Crum-Cianflone, NF AF LeardMann, Cynthia A. Woodall, Kelly A. Littman, Alyson J. Jacobson, Isabel G. Boyko, Edward J. Smith, Besa Wells, Timothy S. Crum-Cianflone, Nancy F. TI Post-Traumatic Stress Disorder Predicts Future Weight Change in the Millennium Cohort Study SO OBESITY LA English DT Article ID NATIONALLY REPRESENTATIVE SAMPLE; BODY-MASS INDEX; MILITARY SERVICE; PRIMARY-CARE; FOLLOW-UP; PRIME-MD; HEALTH; OBESITY; PTSD; US AB ObjectiveTo prospectively examine the association between post-traumatic stress disorder (PTSD) and weight change. MethodsLongitudinal analysis techniques were used to examine data (2001-2008) from Millennium Cohort Study participants, consisting of U.S. service members and veterans. Using the PTSD Checklist-Civilian Version, PTSD was assessed as none, resolved, new onset, or persistent. Subsequent weight change was assessed as stable (loss or gain), >3% weight loss, >3% but <10% weight gain, and 10% weight gain. ResultsOf the 38,352 participants, 2391 (6.2%) had PTSD (838 resolved, 1024 new onset, and 529 persistent), and 11% of participants subsequently had 10% weight gain. In multivariable models, PTSD was associated with higher odds of 10% weight gain (new onset OR: 1.44 [95% CI: 1.20-1.73]; persistent OR: 1.51 [CI: 1.17-1.96]; resolved OR: 1.30 [CI: 1.05-1.60]) compared with those without PTSD. New-onset and persistent PTSD were also associated with higher odds of >3% weight loss (OR: 1.41 [CI: 1.17-1.71]; OR: 1.42 [CI: 1.09-1.86], respectively). ConclusionsPTSD is independently associated with a higher risk of weight gain and loss, the former of which leads to a higher prevalence of overweight and obesity and a higher risk of comorbidities associated with excessive body adiposity. C1 [LeardMann, Cynthia A.; Woodall, Kelly A.; Jacobson, Isabel G.; Smith, Besa; Wells, Timothy S.; Crum-Cianflone, Nancy F.] Naval Hlth Res Ctr, Deployment Hlth Res Dept, San Diego, CA 92106 USA. [Littman, Alyson J.; Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. RP LeardMann, CA (reprint author), Naval Hlth Res Ctr, Deployment Hlth Res Dept, San Diego, CA 92106 USA. EM cynthia.leardmann@med.navy.mil FU Military Operational Medicine Research Program of the U.S. Army Medical Research and Materiel Command, Fort Detrick, Maryland; Veterans Affairs Puget Sound Health Care System; Rehabilitation Research VA Career Development Award [6982]; Department of Defense [60002] FX The Millennium Cohort Study is funded through the Military Operational Medicine Research Program of the U.S. Army Medical Research and Materiel Command, Fort Detrick, Maryland. Drs. Boyko and Littman's efforts in this project were supported by Veterans Affairs Puget Sound Health Care System. Dr. Littman's time was also supported in part through a Rehabilitation Research VA Career Development Award (#6982). This research represents Naval Health Research Center report 14-06, supported by the Department of Defense, under work unit no. 60002. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of the Army, Department of the Air Force, Department of Defense, Department of Veterans Affairs, or the U.S. Government. The funding organizations had no role in the design and conduct of the study; collection, analysis, or preparation of data; or preparation, review, or approval of the manuscript. Approved for public release; distribution is unlimited. NR 39 TC 4 Z9 4 U1 1 U2 2 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 APR PY 2015 VL 23 IS 4 BP 886 EP 892 DI 10.1002/oby.21025 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CE4XA UT WOS:000351832400025 PM 25776806 ER PT J AU Chen, YF Lubitz, CC Shikora, SA Hodin, RA Gaz, RD Moore, FD McKenzie, TJ AF Chen, Yufei Lubitz, Carrie C. Shikora, Scott A. Hodin, Richard A. Gaz, Randall D. Moore, Francis D., Jr. McKenzie, Travis J. TI Primary Hyperparathyroidism After Roux-en-Y Gastric Bypass SO OBESITY SURGERY LA English DT Article DE Hyperparathyroidism; Primary hyperparathyroidism; Gastric bypass; Roux-en-Y; Hypercalcemia ID POST-PARATHYROIDECTOMY HYPOCALCEMIA; INTRAOPERATIVE PTH DETERMINATIONS; BONE-MINERAL DENSITY; SURGICAL-MANAGEMENT; VITAMIN-D; INITIAL-EXPERIENCE; RISK-FACTORS; HORMONE; CALCIUM; SURGERY AB Primary hyperparathyroidism (PHPT) in the setting of previous roux-en-Y gastric bypass (RYGBP) is not well described. The diagnosis can be difficult, as secondary hyperparathyroidism (SHPT) commonly occurs in patients after RYGBP due to calcium malabsorption and vitamin D deficiency. All patients from 2000 to 2012 who underwent cervical exploration for diagnosis of primary hyperparathyroidism with history of preceding RYGBP were identified and analyzed retrospectively. Ten patients were identified. The average age was 58.4 and all patients were female. Time interval between RYGBP and cervical exploration was 67 months with median follow-up of 19 months. Average preoperative calcium was 10.8 mg/dL, PTH 155 pg/mL, and 25-vitamin-D 32 ng/mL. Eighty percent of patients presented with symptoms and 90 % underwent preoperative imaging. Seventy percent underwent initial focused parathyroidectomy with 20 % being converted to four-gland exploration. Seventy percent of patients had a single adenoma with two patients having multi-gland disease. Intraoperative PTH was used in seven patients with successful drop to 50 % of baseline in all. Ninety percent of patients had greater then 6-month follow-up without evidence of persistent or recurrent PHPT. Average 6-month calcium was 9.3 mg/dL, PTH 73 pg/mL, and 25-vitamin-D 44 ng/ML. Four patients had evidence of persistently elevated PTH despite normalization of calcium. PHPT after RYGBP is rare but surgery with either a focused approach following successful localization or four-gland exploration is indicated when the biochemical diagnosis holds true. The presence of SHPT can make diagnosis and follow-up difficult and may predispose them to severe post-operative hypocalcemia. C1 [Chen, Yufei; Lubitz, Carrie C.; Hodin, Richard A.; Gaz, Randall D.; McKenzie, Travis J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shikora, Scott A.; Moore, Francis D., Jr.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Chen, YF (reprint author), Massachusetts Gen Hosp, GRB 425,55 Fruit St, Boston, MA 02114 USA. EM ychen49@partners.org; clubitz@mgh.harvard.edu; sshikora@partners.org; rhodin@mgh.harvard.edu; gaz.randall@mgh.harvard.edu; fmoore@partners.org; tjmckenzie@partners.org NR 32 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0960-8923 EI 1708-0428 J9 OBES SURG JI Obes. Surg. PD APR PY 2015 VL 25 IS 4 BP 700 EP 704 DI 10.1007/s11695-014-1444-2 PG 5 WC Surgery SC Surgery GA CE4AD UT WOS:000351771500015 PM 25248510 ER PT J AU Kheirkhah, A Dohlman, TH Amparo, F Arnoldner, MA Jamali, A Hamrah, P Dana, R AF Kheirkhah, Ahmad Dohlman, Thomas H. Amparo, Francisco Arnoldner, Michael A. Jamali, Arsia Hamrah, Pedram Dana, Reza TI Effects of Corneal Nerve Density on the Response to Treatment in Dry Eye Disease SO OPHTHALMOLOGY LA English DT Article ID DEXAMETHASONE 0.1-PERCENT/TOBRAMYCIN 0.3-PERCENT; PRIMARY SJOGRENS-SYNDROME; KERATOCONJUNCTIVITIS SICCA; 0.5-PERCENT/TOBRAMYCIN 0.3-PERCENT; NEUROTROPHIC KERATITIS; CONFOCAL MICROSCOPY; WORKSHOP 2007; SENSITIVITY; MULTICENTER; INNERVATION AB Purpose: To evaluate whether levels of corneal subbasal nerve fiber length (SNFL) in dry eye disease (DED) could prognosticate the level of improvement in signs and symptoms after treatment. Design: Phase IV, double-masked, randomized clinical trial. Participants: Sixty patients with meibomian gland dysfunction-associated DED and 27 age-matched controls. Methods: Patients with DED were randomized to receive topical artificial tears, loteprednol etabonate 0.5%, or loteprednol etabonate 0.5%/ tobramycin 0.3% twice daily for 4 weeks. At baseline, in vivo confocal microscopy of central cornea was performed in both eyes. Patients with DED were divided into 2 subgroups: those with low baseline SNFL and those with near-normal baseline SNFL for this purpose (the cutoff point: the mean SNFL in controls minus 2 standard deviations). Clinical signs and symptoms at baseline and after 4 weeks of treatment were compared between the subgroups with low and near-normal SNFL for all therapeutic groups. Main Outcome Measures: Symptom questionnaires, corneal fluorescein staining (CFS), conjunctival staining with lissamine green, tear break-up time, Schirmer's test, and SNFL. Results: In patients with DED, baseline SNFL (17.06 +/- 5.78 mm/mm(2)) was significantly lower than in controls (23.68 +/- 3.42 mm/mm(2), P = 0.001). In the artificial tear and loteprednol groups, although no significant improvement in any sign or symptom was noted in patients with low baseline SNFL (<16.84 mm/mm(2)), subjects with near-normal baseline SNFL (>= 16.84 mm/mm(2)) showed significant improvement in both symptoms and CFS score (all P < 0.05). In the loteprednol/tobramycin group, no significant change was evident for any sign or symptom in either subgroup of low or near-normal baseline SNFL. Conclusions: Significant improvements in CFS and patient symptomatology after DED treatment were evident only in the subgroup with near-normal corneal SNFL. Consideration of SNFL may assist in explaining the variability of patients' response to DED therapy. (C) 2015 by the American Academy of Ophthalmology. C1 [Kheirkhah, Ahmad; Dohlman, Thomas H.; Amparo, Francisco; Arnoldner, Michael A.; Jamali, Arsia; Hamrah, Pedram; Dana, Reza] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Cornea & Refract Surg Serv, Boston, MA 02115 USA. RP Dana, R (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Reza_Dana@meei.harvard.edu FU Bausch Lomb, Inc; National Institutes of Health [K24-EY019098]; Falk Medical Research Trust FX Funded by Bausch & Lomb, Inc, National Institutes of Health K24-EY019098, Falk Medical Research Trust. NR 37 TC 4 Z9 4 U1 1 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 APR PY 2015 VL 122 IS 4 BP 662 EP 668 DI 10.1016/j.ophtha.2014.11.006 PG 7 WC Ophthalmology SC Ophthalmology GA CE3EX UT WOS:000351710100011 PM 25542519 ER PT J AU Margulis, AV Mittleman, MA Glynn, RJ Holmes, LB Hernandez-Diaz, S AF Margulis, Andrea V. Mittleman, Murray A. Glynn, Robert J. Holmes, Lewis B. Hernandez-Diaz, Sonia TI Effects of gestational age at enrollment in pregnancy exposure registries SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE pregnancy registries; left truncation; anticonvulsants; spontaneous abortions; major congenital malformations; pharmacoepidemiology ID SPONTANEOUS-ABORTION; LEFT TRUNCATION; ANTIEPILEPTIC DRUGS; EXCLUSION CRITERIA; BIAS; EPILEPSY; MALFORMATIONS; INCLUSION; OUTCOMES AB PurposeThis study aims to explore the influence of gestational age at enrollment, and enrollment before or after prenatal screening, on the estimation of drug effects in pregnancy exposure registries. MethodsWe assessed the associations between first trimester antiepileptic drug (AED) exposure and risk of spontaneous abortion and major congenital malformations in the North American AED Registry (1996-2013). We performed logistic regression analyses, conditional or unconditional on gestational age at enrollment, to estimate relative risk (RR) for first trimester AED users compared with non-users. We also compared first trimester users of valproic acid and lamotrigine. Analyses were repeated in women who enrolled before prenatal screening. ResultsEnrollment occurred earlier among 7029 AED users than among 581 non-users; it was similar among AEDs. Comparing AED users with non-users, RR (95% confidence interval) of spontaneous abortion (n=359) decreased from 5.1 (2.3-14.1) to 2.0 (0.9-5.6) after conditioning on gestational week at enrollment and to 1.9 (0.8-5.4) upon further restriction to before-screening enrollees. RR of congenital malformations (n=216) changed from 3.1 (1.4-8.5) to 3.2 (1.4-9.0) after conditioning on gestational week at enrollment and to 2.0 (0.7-10.1) upon further restriction to before-screening enrollees. When comparing valproic acid users and lamotrigine users, the RR of congenital malformations was not substantially changed by conditioning or restricting. ConclusionsSpontaneous abortion rates were sensitive to gestational age at enrollment. Estimates of congenital malformation risks for AED users relative to non-users were sensitive to before/after-screening enrollment. This difference was not apparent between active drugs, likely due to similar gestational age at enrollment. Copyright (c) 2015 John Wiley & Sons, Ltd. C1 [Margulis, Andrea V.; Mittleman, Murray A.; Glynn, Robert J.; Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mittleman, Murray A.] Beth Israel Deaconess Med Ctr, Cardiovasc Epidemiol Res Unit, Boston, MA 02215 USA. [Glynn, Robert J.] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Holmes, Lewis B.] MassGen Hosp Children, Med Genet Unit, North Amer AED Pregnancy Registry, Boston, MA USA. RP Margulis, AV (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,Kresge Bldg, Boston, MA 02115 USA. EM andreamargulis@post.harvard.edu OI Margulis, Andrea/0000-0001-7388-6082 FU Pfizer; Millennium; Bayer; PhRMA; Abbvie; Eisai; Novartis; Ortho-McNeil; Sunovion; UCB Pharmaceuticals; North American AED Pregnancy Registry; AstraZeneca FX The Pharmacoepidemiology program at Harvard School of Public Health is supported by training grants from Pfizer, Millennium, Bayer, and PhRMA. The North American AED Pregnancy Registry has been supported by funds provided by Abbvie, Eisai, Novartis, Ortho-McNeil, Pfizer, Sunovion, and UCB Pharmaceuticals. Contributors to the North American AED Pregnancy Registry include Aurobindo Pharma, Dr Reddy's Labs, GlaxoSmithKline, Sandoz, and Teva. S. H. D. is partially supported by the North American AED Pregnancy Registry. She has consulted on unrelated issues for Novartis, AstraZeneca, and GSK Biologics in the last 5 years. R. J. G. has received grant support through his employer (Brigham and Women's Hospital) from AstraZeneca and Novartis for research unrelated to this topic. NR 31 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD APR PY 2015 VL 24 IS 4 BP 343 EP 352 DI 10.1002/pds.3731 PG 10 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA CE5AE UT WOS:000351841300002 PM 25702683 ER PT J AU Phiri, K Hernandez-Diaz, S Tsen, LC Puopolo, KM Seeger, JD Bateman, BT AF Phiri, Kelesitse Hernandez-Diaz, Sonia Tsen, Lawrence C. Puopolo, Karen M. Seeger, John D. Bateman, Brian T. TI Accuracy of ICD-9-CM coding to identify small for gestational age newborns SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE healthcare records; sensitivity; specificity; gestational age; small for gestational age; ICD-9-CM codes; pharmacoepidemiology ID HOSPITAL DISCHARGE DATA; HIV-INFECTED WOMEN; BIRTH-WEIGHT; ANTIRETROVIRAL THERAPY; PREGNANCY; RISK; COMPLICATIONS; OUTCOMES; SMOKING; HEALTH AB PurposeThis study aimed to evaluate the accuracy of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis code for small for gestational age (SGA) recorded in administrative healthcare records using birthweight and gestational age information recorded in electronic medical records. MethodsWe used billing and medical records from women aged 13-55years who delivered at a tertiary care center in the USA between 2004 and 2011. Information on birthweight, gestational age at birth, and ICD-9-CM code for SGA, 656.5x, was abstracted from the database. Each infant's birthweight percentile for gestational age was calculated on the basis of published US references; infants below the 10th percentile were classified as SGA. The performance characteristics of SGA ICD-9-CM diagnosis code against SGA classification based on birthweight and gestational age were calculated, for all deliveries and by strata of demographic and delivery characteristics. ResultsWe identified 51292 singleton live birth deliveries. The prevalence of SGA infants calculated from birthweight and gestational age at birth was higher (13%) than the prevalence based on ICD-9-CM code (2%). Sensitivity of the SGA ICD-9-CM code was 14.2%, specificity was 99.7%, positive predictive value was 86.8%, and negative predictive value was 88.4%. Stratification by demographic and delivery characteristics yielded similar results. ConclusionsIdentification of SGA infants using ICD-9-CM code, 656.5x, from administrative healthcare records has low sensitivity but high specificity; the accuracy did not differ across demographic and delivery characteristics. Thus, although this source of information would underestimate the prevalence of SGA, it could produce valid relative risk estimates. Copyright (c) 2015 John Wiley & Sons, Ltd. C1 [Phiri, Kelesitse; Hernandez-Diaz, Sonia; Seeger, John D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Tsen, Lawrence C.] Brigham & Womens Hosp, Dept Anesthesia Perioperat & Pain Med, Boston, MA 02115 USA. [Puopolo, Karen M.] Brigham & Womens Hosp, Dept Newborn Med, Boston, MA 02115 USA. [Seeger, John D.; Bateman, Brian T.] Harvard Univ, Sch Med, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Phiri, K (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM kphiri@hsph.harvard.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health [K08HD075831] FX Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (Award Number K08HD075831). NR 29 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD APR PY 2015 VL 24 IS 4 BP 381 EP 388 DI 10.1002/pds.3740 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA CE5AE UT WOS:000351841300006 PM 25656656 ER PT J AU Tritos, NA Biller, BMK AF Tritos, Nicholas A. Biller, Beverly M. K. TI Update on radiation therapy in patients with Cushing's disease SO PITUITARY LA English DT Article DE Cushing's disease; Cushing's syndrome; Nelson's syndrome; Pituitary adenoma; Radiation therapy ID FRACTIONATED STEREOTACTIC RADIOTHERAPY; LINEAR-ACCELERATOR LINAC; NELSONS-SYNDROME; PITUITARY-ADENOMAS; SURGERY; ADRENALECTOMY; RADIOSURGERY; MANAGEMENT AB Introduction Radiation therapy is an important therapy for patients with Cushing's disease who are not in remission or relapse after transsphenoidal pituitary surgery and are not considered surgical candidates. The development of stereotactic radiation therapy, using gamma knife, linear accelerators or proton beam based methods, has enabled selective radiation delivery to the target while minimizing exposure of healthy tissues. In patients whose tumors are sufficiently distant from the optic apparatus, stereotactic radiation therapy can be delivered in a single session, a procedure termed radiosurgery, which significantly improves patient convenience. Methods Original articles on radiation therapy in Cushing's disease, published during the past 12 months (2013-2014), were identified and pertinent data extracted. Results Recent studies have reported on the outcomes of patients with Cushing's disease who received mostly stereotactic radiation therapy. While tumor control has been excellent, biochemical remission was less consistently achieved. Some studies suggested that stereotactic radiation may lead to biochemical remission faster than conventional radiation therapy. In addition, retrospective data have suggested that withdrawing medical therapy around the time stereotactic radiation therapy is administered might lead to a faster biochemical response. Regardless of the radiation therapy method, biochemical recurrences may develop and these patients are at long-term risk of developing anterior hypopituitarism and require lifelong periodic endocrine follow-up. Other, less frequent complications may include cranial neuropathies, secondary tumor formation or temporal lobe necrosis. It is plausible that complications may be less frequent after stereotactic radiation therapy, but this requires confirmation. Conclusions Radiation therapy is an effective second line therapy in patients with Cushing's disease. Ongoing refinements in delivery of radiation therapy are anticipated to lead to improved patient outcomes, but long-term follow-up data, including adequate control groups, are needed to fully investigate this possibility. C1 [Tritos, Nicholas A.; Biller, Beverly M. K.] Massachusetts Gen Hosp, Neuroendocrine & Pituitary Tumor Clin Ctr, Neuroendocrine Unit, Boston, MA 02114 USA. [Tritos, Nicholas A.; Biller, Beverly M. K.] Harvard Univ, Sch Med, Boston, MA USA. RP Tritos, NA (reprint author), Massachusetts Gen Hosp, Neuroendocrine & Pituitary Tumor Clin Ctr, Neuroendocrine Unit, Zero Emerson Pl 112, Boston, MA 02114 USA. EM ntritos@partners.org FU Ipsen; Pfizer; Novartis; Cortendo FX Dr. Tritos has served as the PI of research grants to MGH from Ipsen and Pfizer and has received occasional consulting honoraria from Pfizer and Corcept. Dr. Biller has served as the PI of research grants to MGH from Novartis and Cortendo and received occasional consulting honoraria from Novartis and Cortendo. NR 13 TC 5 Z9 5 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1386-341X EI 1573-7403 J9 PITUITARY JI Pituitary PD APR PY 2015 VL 18 IS 2 BP 263 EP 268 DI 10.1007/s11102-014-0615-4 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CE1IO UT WOS:000351565500014 PM 25359445 ER PT J AU Bueno, A Dong, H Damasceno, DC Loeken, MR AF Bueno, A. Dong, H. Damasceno, D. C. Loeken, M. R. TI HYPERGLYCEMIA EFFECTS ON EPIGENETIC REGULATION OF PAX3 DURING THE EARLY EMBRYONIC DEVELOPMENT SO PLACENTA LA English DT Meeting Abstract CT 6th Latin American Symposium on Maternal-Fetal Interaction and Placenta / 5th Latin American Symposium on Reproductive Immunology CY APR 13-16, 2015 CL Mar del Plata, ARGENTINA C1 [Bueno, A.; Damasceno, D. C.] Univ Estadual Paulista Unesp, Lab Expt Res Gynecol & Obstet, Grad Program Gynecol Obstet & Mastol, Botucatu Med Sch, Sao Paulo, Brazil. [Dong, H.; Loeken, M. R.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 EI 1532-3102 J9 PLACENTA JI Placenta PD APR PY 2015 VL 36 IS 4 MA PA.22 BP 494 EP 495 PG 2 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA CE4JI UT WOS:000351796500106 ER PT J AU Reish, RG Lin, A Phillips, NA Winograd, J Liao, EC Cetrulo, CL Smith, BL Austen, WG Colwell, AS AF Reish, Richard G. Lin, Alex Phillips, Nicole A. Winograd, Jonathan Liao, Eric C. Cetrulo, Curtis L., Jr. Smith, Barbara L. Austen, William G., Jr. Colwell, Amy S. TI Breast Reconstruction Outcomes after Nipple-Sparing Mastectomy and Radiation Therapy SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID IMPLANT RECONSTRUCTION; CANCER; COMPLICATIONS; TRENDS AB Background: Few studies in the literature examine outcomes of immediate breast reconstruction after mastectomy with nipple preservation and radiation therapy. Methods: Retrospective analysis of multisurgeon consecutive implant-based reconstructions after nipple-sparing mastectomy from June of 2007 to December of 2012 was conducted at a single institution. Results: Six hundred five immediate breast reconstructions were performed following nipple-sparing mastectomy, of which 88 were treated with radiation therapy. There was a trend toward more complications in patients with radiation (19.3 percent versus 12.8 percent; p = 0.099) associated with a higher rate of implant loss (6.8 percent versus 1.0 percent; p = 0.001). Preoperative radiotherapy had a higher risk of total complications (p = 0.04; OR, 2.225; 95 percent CI, 1.040 to 4.758) and postoperative radiotherapy had a higher risk of explantation (p = 0.015; OR, 5.634; 95 percent CI, 1.405 to 22.603). There were no significant differences in nipple removal secondary to malposition or positive oncologic margins in patients with radiation compared to those without radiation. Patients with radiation did have a higher incidence of secondary procedures for capsular contracture (12.5 percent versus 2.3 percent; p < 0.001) and fat grafting (13.6 percent versus 3.9 percent; p < 0.001). The total nipple retention rate in patients with radiation therapy was 90 percent (79 of 88), and the reconstruction failure rate was 8 percent. Conclusions: Nipple-sparing mastectomy and immediate reconstruction in patients who had or will receive radiation therapy is associated with a higher incidence of complications and operative revisions compared with patients without radiation. However, most patients have successful reconstructions with nipple retention and no recurrences. C1 [Reish, Richard G.; Lin, Alex; Phillips, Nicole A.; Winograd, Jonathan; Liao, Eric C.; Cetrulo, Curtis L., Jr.; Smith, Barbara L.; Austen, William G., Jr.; Colwell, Amy S.] Harvard Univ, Div Plast Surg, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. RP Colwell, AS (reprint author), Massachusetts Gen Hosp, Div Plast Surg, 55 Fruit St,WACC 435, Boston, MA 02114 USA. EM acolwell@partners.org NR 14 TC 16 Z9 16 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD APR PY 2015 VL 135 IS 4 BP 959 EP 966 DI 10.1097/PRS.0000000000001129 PG 8 WC Surgery SC Surgery GA CE5XU UT WOS:000351910200031 PM 25811561 ER PT J AU Ghasemi, M Hadipour-Niktarash, A AF Ghasemi, Mehdi Hadipour-Niktarash, Arash TI Pathologic role of neuronal nicotinic acetylcholine receptors in epileptic disorders: implication for pharmacological interventions SO REVIEWS IN THE NEUROSCIENCES LA English DT Article DE acetylcholine; autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE); epilepsy; juvenile myoclonic epilepsy (JME); neuronal nicotinic acetylcholine receptor (nAChR); nicotinic receptor antagonist; seizure ID FRONTAL-LOBE EPILEPSY; JUVENILE MYOCLONIC EPILEPSY; IDIOPATHIC GENERALIZED EPILEPSY; MESSENGER-RNA EXPRESSION; CENTRAL-NERVOUS-SYSTEM; ANTICONVULSIVE DRUG LAMOTRIGINE; MAJOR SUSCEPTIBILITY LOCUS; ADRENAL CHROMAFFIN CELLS; INDUCED SEIZURE ACTIVITY; DORSAL RAPHE NUCLEUS AB Accumulating evidence suggests that neuronal nicotinic acetylcholine receptors (nAChRs) may play a key role in the pathophysiology of some neurological diseases such as epilepsy. Based on genetic studies in patients with epileptic disorders worldwide and animal models of seizure, it has been demonstrated that nAChR activity is altered in some specific types of epilepsy, including autosomal dominant nocturnal frontal lobe epilepsy (ADN-FLE) and juvenile myoclonic epilepsy (JME). Neuronal nAChR antagonists also have antiepileptic effects in preclinical studies. There is some evidence that conventional antiepileptic drugs may affect neuronal nAChR function. In this review, we re-examine the evidence for the involvement of nAChRs in the pathophysiology of some epileptic disorders, especially ADNFLE and JME, and provide an overview of nAChR antagonists that have been evaluated in animal models of seizure. C1 [Ghasemi, Mehdi] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA. [Ghasemi, Mehdi] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Ghasemi, Mehdi] NeurExpand Brain Ctr, Lutherville Timonium, MD 21093 USA. [Hadipour-Niktarash, Arash] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Ghasemi, M (reprint author), Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA. EM m82.ghasemi@gmail.com NR 213 TC 2 Z9 2 U1 2 U2 5 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0334-1763 EI 1607-8470 J9 REV NEUROSCIENCE JI Rev. Neurosci. PD APR PY 2015 VL 26 IS 2 BP 199 EP 223 DI 10.1515/revneuro-2014-0044 PG 25 WC Neurosciences SC Neurosciences & Neurology GA CE6CW UT WOS:000351924800006 PM 25565544 ER PT J AU Maestre, JM Rudolph, JW AF Maestre, Jose M. Rudolph, Jenny W. TI Theories and Styles of Debriefing: the Good Judgment Method as a Tool for Formative Assessment in Healthcare SO REVISTA ESPANOLA DE CARDIOLOGIA LA English DT Editorial Material ID MEDICAL-EDUCATION; SIMULATION; FEEDBACK C1 [Maestre, Jose M.] Hosp Virtual Valdecilla, Santander 39008, Cantabria, Spain. [Maestre, Jose M.] Hosp Univ Marques de Valdecilla, Serv Anestesiol & Reanimac, Santander, Cantabria, Spain. [Rudolph, Jenny W.] Massachusetts Gen Hosp, Ctr Med Simulat, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Maestre, JM (reprint author), Hosp Virtual Valdecilla, Avda Valdecilla S-N, Santander 39008, Cantabria, Spain. EM jmmaestre@hvvaldecilla.es NR 12 TC 1 Z9 3 U1 2 U2 4 PU EDICIONES DOYMA S A PI BARCELONA PA TRAV DE GRACIA 17-21, 08021 BARCELONA, SPAIN SN 0300-8932 EI 1579-2242 J9 REV ESP CARDIOL JI Rev. Esp. Cardiol. PD APR PY 2015 VL 68 IS 4 BP 282 EP 285 DI 10.1016/j.rec.2014.05.018 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CE5BO UT WOS:000351845100002 PM 25239179 ER PT J AU Gur, RC Braff, DL Calkins, ME Dobie, DJ Freedman, R Green, MF Greenwood, TA Lazzeroni, LC Light, GA Nuechterlein, KH Olincy, A Radant, AD Seidman, LJ Siever, LJ Silverman, JM Sprock, J Stone, WS Sugar, CA Swerdlow, NR Tsuang, DW Tsuang, MT Turetsky, BI Gur, RE AF Gur, Ruben C. Braff, David L. Calkins, Monica E. Dobie, Dorcas J. Freedman, Robert Green, Michael F. Greenwood, Tiffany A. Lazzeroni, Laura C. Light, Gregory A. Nuechterlein, Keith H. Olincy, Ann Radant, Allen D. Seidman, Larry J. Siever, Larry J. Silverman, Jeremy M. Sprock, Joyce Stone, William S. Sugar, Catherine A. Swerdlow, Neal R. Tsuang, Debby W. Tsuang, Ming T. Turetsky, Bruce I. Gur, Raquel E. TI Neurocognitive performance in family-based and case-control studies of schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Neurocognition; Schizophrenia; Family-based; Case-control; Ascertainment ID COGNITIVE DEFICITS; 12 ENDOPHENOTYPES; SEX-DIFFERENCES; YOUNG-ADULTS; HIGH-RISK; GENETICS; CONSORTIUM; BATTERY; HERITABILITY; VALIDATION AB Background: Neurocognitive deficits in schizophrenia (SZ) are established and the Consortium on the Genetics of Schizophrenia (COGS) investigated such measures as endophenotypes in family-based (COGS-1) and case-control (COGS-2) studies. By requiring family participation, family-based sampling may result in samples that vary demographically and perform better on neurocognitive measures. Methods: The Penn computerized neurocognitive battery (CNB) evaluates accuracy and speed of performance for several domains and was administered across sites in COGS-1 and COGS-2. Most tests were included in both studies. COGS-1 included 328 patients with SZ and 497 healthy comparison subjects (HCS) and COGS-2 included 1195 patients and 1009 HCS. Results: Demographically, COGS-1 participants were younger, more educated, with more educated parents and higher estimated IQ compared to COGS-2 participants. After controlling for demographics, the two samples produced very similar performance profiles compared to their respective controls. As expected, performance was better and with smaller effect sizes compared to controls in COGS-1 relative to COGS-2. Better performance was most pronounced for spatial processing while emotion identification had large effect sizes for both accuracy and speed in both samples. Performance was positively correlated with functioning and negatively with negative and positive symptoms in both samples, but correlations were attenuated in COGS-2, especially with positive symptoms. Conclusions: Patients ascertained through family-based design have more favorable demographics and better performance on some neurocognitive domains. Thus, studies that use case-control ascertainment may tap into populations with more severe forms of illness that are exposed to less favorable factors compared to those ascertained with family-based designs. Published by Elsevier B.V. C1 [Gur, Ruben C.; Calkins, Monica E.; Turetsky, Bruce I.; Gur, Raquel E.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Braff, David L.; Greenwood, Tiffany A.; Light, Gregory A.; Sprock, Joyce; Swerdlow, Neal R.; Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Braff, David L.; Greenwood, Tiffany A.; Light, Gregory A.; Sprock, Joyce; Swerdlow, Neal R.; Tsuang, Ming T.] VA San Diego Healthcare Syst, VISN 22 Mental Illness Res Educ & Clin Ctr MIRECC, San Diego, CA USA. [Dobie, Dorcas J.; Radant, Allen D.; Tsuang, Debby W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Dobie, Dorcas J.; Radant, Allen D.; Tsuang, Debby W.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Freedman, Robert; Olincy, Ann] Univ Colorado Denver, Dept Psychiat, Aurora, CO USA. [Green, Michael F.; Nuechterlein, Keith H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Green, Michael F.; Nuechterlein, Keith H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Lazzeroni, Laura C.] Stanford Univ, Dept Psychiat, Palo Alto, CA 94304 USA. [Seidman, Larry J.; Stone, William S.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Seidman, Larry J.; Stone, William S.] Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div, Boston, MA 02215 USA. [Siever, Larry J.; Silverman, Jeremy M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Siever, Larry J.; Silverman, Jeremy M.] James J Peters VA Med Ctr, New York, NY USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. RP Gur, RC (reprint author), Univ Penn, Dept Psychiat, Neuropsychiat Sect, Perelman Sch Med, 3400 Spruce, Philadelphia, PA 19104 USA. EM gur@upenn.edu RI Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Lazzeroni, Laura/0000-0002-1846-6920; Greenwood, Tiffany/0000-0002-6080-6503 FU National Institute of Mental Health; COGS-1 [MH065571 UCSD, MH065707 UCLA, MH065554 MSSM]; COGS-2 [MH065571 UCSD, MH065707 UCLA, MH065554 MSSM]; COGS-1, Penn [MH065578]; COGS-2, Penn [MH065578]; COGS-1, Washington [MH065558]; COGS-2, Washington [MH065558]; COGS-1, Colorado [MH065588]; COGS-1, Harvard [MH065562]; COGS-1, Seidman; COGS-1, Stone; COGS-2, Stanford [MH86135] FX This work was supported by collaborative R01 grants from the National Institute of Mental Health. COGS-1 and COGS-2: MH065571 UCSD, MH065707 UCLA, MH065554 MSSM, MH065578 Penn, MH065558 Washington; COGS-1 Only: MH065588 Colorado, MH065562 Harvard; Seidman and Stone are on a subcontract for COGS-2; COGS-2 Only: MH86135 Stanford. NR 43 TC 7 Z9 7 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2015 VL 163 IS 1-3 BP 17 EP 23 DI 10.1016/j.schres.2014.10.049 PG 7 WC Psychiatry SC Psychiatry GA CE6EE UT WOS:000351928600003 PM 25432636 ER PT J AU Lee, J Green, MF Calkins, ME Greenwood, TA Gur, RE Gur, RC Lazzeroni, LC Light, GA Nuechterlein, KH Radant, AD Seidman, LJ Siever, LJ Silverman, JM Sprock, J Stone, WS Sugar, CA Swerdlow, NR Tsuang, DW Tsuang, MT Turetsky, BI Braff, DL AF Lee, Junghee Green, Michael F. Calkins, Monica E. Greenwood, Tiffany A. Gur, Raquel E. Gur, Ruben C. Lazzeroni, Laura C. Light, Gregory A. Nuechterlein, Keith H. Radant, Allen D. Seidman, Larry J. Siever, Larry J. Silverman, Jeremy M. Sprock, Joyce Stone, William S. Sugar, Catherine A. Swerdlow, Neal R. Tsuang, Debby W. Tsuang, Ming T. Turetsky, Bruce I. Braff, David L. TI Verbal working memory in schizophrenia from the Consortium on the Genetics of Schizophrenia (COGS) Study: The moderating role of smoking status and antipsychotic medications SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Verbal working memory; Letter-Number span; Moderators; Smoking; Antipsychotic medication ID CIGARETTE-SMOKING; 1ST-EPISODE SCHIZOPHRENIA; COGNITIVE FUNCTION; 12 ENDOPHENOTYPES; DOPAMINE RELEASE; CLINICAL-TRIALS; BRAIN-FUNCTION; SUBSTANCE USE; NICOTINE; DEFICITS AB Objectives: Working memory impairment has been extensively studied in schizophrenia, but less is known about moderators of the impairment. Using the Consortium on the Genetics of Schizophrenia case-control study (COGS-2), we examined smoking status, types of antipsychotic medication, and history of substance as moderators for working memory impairment in schizophrenia. Methods: From 5 sites, 1377 patients with schizophrenia or schizoaffective, depressed type and 1037 healthy controls completed the letter-number span (LNS) task. The LNS uses intermixed letter and digit stimuli that increase from 2 up to 8 stimuli. In the forward condition, participants repeated the letters and numbers in the order they were presented. In the reorder condition, participants repeated the digits in ascending order followed by letters in alphabetical order. Results: Schizophrenia patients performed more poorly than controls, with a larger difference on reorder than forward conditions. Deficits were associated with symptoms, functional capacity, and functional outcome. Patients who smoked showed larger impairment than nonsmoking patients, primarily due to deficits on the reorder condition. The impairing association of smoking was more pronounced among patients taking first-generation than those taking second-generation antipsychotic medications. Correlations between working memory and community functioning were stronger for nonsmokers. History of substance use did not moderate working memory impairment. Conclusions: Results confirm the working memory impairment in schizophrenia, and indicate smoking status as an important moderator for these deficits. The greater impairment in smokers may reflect added burden of smoking on general health or that patients with greater deficits are more likely to smoke. (C) 2014 Elsevier B.V. All rights reserved. C1 [Lee, Junghee; Green, Michael F.; Nuechterlein, Keith H.; Sugar, Catherine A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Lee, Junghee; Green, Michael F.; Sugar, Catherine A.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Calkins, Monica E.; Gur, Raquel E.; Gur, Ruben C.; Turetsky, Bruce I.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Greenwood, Tiffany A.; Light, Gregory A.; Sprock, Joyce; Swerdlow, Neal R.; Tsuang, Ming T.; Braff, David L.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Lazzeroni, Laura C.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Lazzeroni, Laura C.] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. [Light, Gregory A.; Sprock, Joyce; Braff, David L.] VA San Diego Healthcare Syst, Mental Illness Res Educ & Clin Ctr MIREC, VISN22, San Diego, CA USA. [Radant, Allen D.; Tsuang, Debby W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Radant, Allen D.; Tsuang, Debby W.] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Seidman, Larry J.; Stone, William S.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Seidman, Larry J.; Stone, William S.] Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Devis, Boston, MA 02215 USA. [Siever, Larry J.; Silverman, Jeremy M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Siever, Larry J.; Silverman, Jeremy M.] James J Peters VA Med Ctr, New York, NY USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90024 USA. [Tsuang, Ming T.] Univ Calif San Diego, Inst Genom Med, San Diego, CA 92103 USA. [Tsuang, Ming T.] Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. RP Lee, J (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza,77-361, Los Angeles, CA 90024 USA. EM jungheelee@ucla.edu RI Lee, Junghee/C-5226-2014; Tsuang, Debby/L-7234-2016; OI Lee, Junghee/0000-0001-9567-8700; Tsuang, Debby/0000-0002-4716-1894; Lazzeroni, Laura/0000-0002-1846-6920; Greenwood, Tiffany/0000-0002-6080-6503 FU National Institute of Health FX Other than providing support, the National Institute of Health does not have any further role in this manuscript. NR 64 TC 8 Z9 8 U1 3 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2015 VL 163 IS 1-3 BP 24 EP 31 DI 10.1016/j.schres.2014.08.014 PG 8 WC Psychiatry SC Psychiatry GA CE6EE UT WOS:000351928600004 PM 25248939 ER PT J AU Stone, WS Mesholam-Gately, RI Braff, DL Calkins, ME Freedman, R Green, MF Greenwood, TA Gur, RE Gur, RC Lazzeroni, LC Light, GA Nuechterlein, KH Olincy, A Radant, AD Siever, LJ Silverman, JM Sprock, J Sugar, CA Swerdlow, NR Tsuang, DW Tsuang, MT Turetsky, BI Seidman, LJ AF Stone, William S. Mesholam-Gately, Raquelle I. Braff, David L. Calkins, Monica E. Freedman, Robert Green, Michael F. Greenwood, Tiffany A. Gur, Raquel E. Gur, Ruben C. Lazzeroni, Laura C. Light, Gregory A. Nuechterlein, Keith H. Olincy, Ann Radant, Allen D. Siever, Larry J. Silverman, Jeremy M. Sprock, Joyce Sugar, Catherine A. Swerdlow, Neal R. Tsuang, Debby W. Tsuang, Ming T. Turetsky, Bruce I. Seidman, Larry J. TI California Verbal Learning Test-II performance in schizophrenia as a function of ascertainment strategy: Comparing the first and second phases of the Consortium on the Genetics of Schizophrenia (COGS) SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Endophenotype; Verbal learning; Memory; Schizophrenia; California Verbal Learning Test ID COGNITIVE DEFICITS; 1ST-EPISODE SCHIZOPHRENIA; 1ST-DEGREE RELATIVES; 12 ENDOPHENOTYPES; FAMILIAL RISK; MEMORY; NEUROCOGNITION; HERITABILITY; DISORDER AB The first phase of the Consortium on the Genetics of Schizophrenia (COGS-1) showed performance deficits in learning and memory on the California Verbal Learning Test, Second Edition (CVLT-II) in individuals with schizophrenia (SZ), compared to healthy comparison subjects (HCS). A question is whether the COGS-1 study, which used a family study design (i.e. studying relatively intact families), yielded "milder" SZ phenotypes than those acquired subsequently in the COGS-2 case-control design that did not recruit unaffected family members. CVLT-II performance was compared for the COGS-1 and COGS-2 samples. Analyses focused on learning, recall and recognition variables, with age, gender and education as covariates. Analyses of COGS-2 data explored effects of additional covariates and moderating factors in CVLT-II performance. 324 SZ subjects and 510 HCS had complete CVLT-II and covariate data in COGS-1, while 1356 SZ and 1036 HCS had complete data in COGS-2. Except for recognition memory, analysis of covariance showed significantly worse performance in COGS-2 on all CVLT-II variables for SZ and HCS, and remained significant in the presence of the covariates. Performance in each of the 5 learning trials differed significantly. However, effect sizes comparing cases and controls were comparable across the two studies. COGS-2 analyses confirmed SZ performance deficits despite effects of multiple significant covariates and moderating factors. CVLT-II performance was worse in COGS-2 than in COGS-1 for both the SZ and the HCS in this large cohort, likely due to cohort effects. Demographically corrected data yield a consistent pattern of performance across the two studies in SZ. (C) 2014 Published by Elsevier B.V. C1 [Stone, William S.; Mesholam-Gately, Raquelle I.; Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Stone, William S.; Mesholam-Gately, Raquelle I.; Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div, Boston, MA 02215 USA. [Braff, David L.; Greenwood, Tiffany A.; Light, Gregory A.; Sprock, Joyce; Swerdlow, Neal R.; Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Calkins, Monica E.; Gur, Raquel E.; Gur, Ruben C.; Turetsky, Bruce I.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Green, Michael F.; Nuechterlein, Keith H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. [Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Lazzeroni, Laura C.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Radant, Allen D.; Tsuang, Debby W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Radant, Allen D.; Tsuang, Debby W.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Siever, Larry J.; Silverman, Jeremy M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Siever, Larry J.; Silverman, Jeremy M.] James J Peters VA Med Ctr, New York, NY USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. [Tsuang, Debby W.] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA. [Tsuang, Ming T.] Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. [Braff, David L.; Light, Gregory A.; Tsuang, Ming T.] VA San Diego Healthcare Syst, VISN 22 Mental Illness Res Educ & Clin Ctr MIRECC, San Diego, CA USA. [Freedman, Robert; Olincy, Ann] Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. [Lazzeroni, Laura C.] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. RP Stone, WS (reprint author), Massachusetts Mental Hlth Ctr, 75 Fenwood Rd, Boston, MA 02115 USA. EM wstone@bidmc.harvard.edu RI Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Lazzeroni, Laura/0000-0002-1846-6920; Greenwood, Tiffany/0000-0002-6080-6503 FU NIH FX Other than providing support, the NIH had no further role in this manuscript. NR 38 TC 3 Z9 3 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2015 VL 163 IS 1-3 BP 32 EP 37 DI 10.1016/j.schres.2014.10.029 PG 6 WC Psychiatry SC Psychiatry GA CE6EE UT WOS:000351928600005 PM 25497440 ER PT J AU Nuechterlein, KH Green, MF Calkins, ME Greenwood, TA Gur, RE Gur, RC Lazzeroni, LC Light, GA Radant, AD Seidman, LJ Siever, LJ Silverman, JM Sprock, J Stone, WS Sugar, CA Swerdlow, NR Tsuang, DW Tsuang, MT Turetsky, BI Braff, DL AF Nuechterlein, Keith H. Green, Michael F. Calkins, Monica E. Greenwood, Tiffany A. Gur, Raquel E. Gur, Ruben C. Lazzeroni, Laura C. Light, Gregory A. Radant, Allen D. Seidman, Larry J. Siever, Larry J. Silverman, Jeremy M. Sprock, Joyce Stone, William S. Sugar, Catherine A. Swerdlow, Neal R. Tsuang, Debby W. Tsuang, Ming T. Turetsky, Bruce I. Braff, David L. TI Attention/vigilance in schizophrenia: Performance results from a large multi-site study of the Consortium on the Genetics of Schizophrenia (COGS) SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Endophenotype; Attention; Continuous Performance Test; Cognition; Functional capacity; Genetics ID SUSTAINED ATTENTION DEFICITS; IDENTICAL PAIRS VERSION; REMITTED SCHIZOPHRENICS; NONPSYCHOTIC RELATIVES; 1ST-DEGREE RELATIVES; IMPAIRED ATTENTION; COGNITIVE FUNCTION; 12 ENDOPHENOTYPES; SIGNAL-DETECTION; SUBSTANCE USE AB Attention/vigilance impairments are present in individuals with schizophrenia across psychotic and remitted states and in their first-degree relatives. An important question is whether deficits in attention/vigilance can be consistently and reliably measured across sites varying in many participant demographic, clinical, and functional characteristics, as needed for large-scale genetic studies of endophenotypes. We examined Continuous Performance Test (CPT) data from phase 2 of the Consortium on the Genetics of Schizophrenia (COGS-2), the largest-scale assessment of cognitive and psychophysiological endophenotypes relevant to schizophrenia. The CPT data from 2251 participants from five sites were examined. A perceptual-load vigilance task (the Degraded Stimulus CPT or DS-CPT) and a memory-load vigilance task (CPT-Identical Pairs or CPT-IP) were utilized. Schizophrenia patients performed more poorly than healthy comparison subjects (HCS) across sites, despite significant site differences in participant age, sex, education, and racial distribution. Patient-HCS differences in signal/noise discrimination (d') in the DS-CPT varied significantly across sites, but averaged a medium effect size. CPT-IP performance showed large patient-HCS differences across sites. Poor CPT performance was independent of or weakly correlated with symptom severity, but was significantly associated with lower educational achievement and functional capacity. Current smoking was associated with poorer CPT-IP d'. Patients taking both atypical and typical antipsychotic medication performed more poorly than those on no or atypical antipsychotic medications, likely reflecting their greater severity of illness. We conclude that CPT deficits in schizophrenia can be reliably detected across sites, are relatively independent of current symptom severity, and are related to functional capacity. (C) 2015 Elsevier B.V. All rights reserved. C1 [Nuechterlein, Keith H.; Green, Michael F.; Sugar, Catherine A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. [Green, Michael F.; Sugar, Catherine A.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Calkins, Monica E.; Gur, Raquel E.; Gur, Ruben C.; Turetsky, Bruce I.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Greenwood, Tiffany A.; Light, Gregory A.; Sprock, Joyce; Swerdlow, Neal R.; Tsuang, Ming T.; Braff, David L.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Lazzeroni, Laura C.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Lazzeroni, Laura C.] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. [Light, Gregory A.; Sprock, Joyce; Braff, David L.] VA San Diego Healthcare Syst, Mental Illness Res Educ & Clin Ctr MIRECC, VISN22, San Diego, CA USA. [Radant, Allen D.; Tsuang, Debby W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Radant, Allen D.; Tsuang, Debby W.] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Seidman, Larry J.; Stone, William S.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Seidman, Larry J.; Stone, William S.] Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div, Boston, MA 02215 USA. [Siever, Larry J.; Silverman, Jeremy M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Siever, Larry J.; Silverman, Jeremy M.] James J Peters VA Med Ctr, New York, NY USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA USA. [Tsuang, Ming T.] Univ Calif San Diego, Inst Genom Med, San Diego, CA 92103 USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, San Diego, CA 92103 USA. [Tsuang, Ming T.] Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. RP Nuechterlein, KH (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, 300 UCLA Med Plaza,Room 2240, Los Angeles, CA 90095 USA. EM keithn@ucla.edu RI Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Nuechterlein, Keith/0000-0002-8179-8952; Lazzeroni, Laura/0000-0002-1846-6920; Greenwood, Tiffany/0000-0002-6080-6503 FU National Institutes of Health FX Beyond providing funding support, the National Institutes of Health does not have any further role in this manuscript. NR 66 TC 5 Z9 5 U1 2 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2015 VL 163 IS 1-3 BP 38 EP 46 DI 10.1016/j.schres.2015.01.017 PG 9 WC Psychiatry SC Psychiatry GA CE6EE UT WOS:000351928600006 PM 25749017 ER PT J AU Radant, AD Steven, PM Braff, DL Calkins, ME Dobie, DJ Freedman, R Green, MF Greenwood, TA Gur, RE Gur, RC Lazzeroni, LC Light, GA Meichle, SP Nuechterlein, KH Olincy, A Seidman, LJ Siever, LJ Silverman, JM Stone, WS Swerdlow, NR Sugar, CA Tsuang, MT Turetsky, BI Tsuang, DW AF Radant, Allen D. Millard, Steven P. Braff, David L. Calkins, Monica E. Dobie, Dorcas J. Freedman, Robert Green, Michael F. Greenwood, Tiffany A. Gur, Raquel E. Gur, Ruben C. Lazzeroni, Laura C. Light, Gregory A. Meichle, Sean P. Nuechterlein, Keith H. Olincy, Ann Seidman, Larry J. Siever, Larry J. Silverman, Jeremy M. Stone, William S. Swerdlow, Neal R. Sugar, Catherine A. Tsuang, Ming T. Turetsky, Bruce I. Tsuang, Debby W. TI Robust differences in antisaccade performance exist between COGS schizophrenia cases and controls regardless of recruitment strategies SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Antisaccade task; Recruitment ID 12 ENDOPHENOTYPES; CONSORTIUM; GENETICS; TASK AB The impaired ability to make correct antisaccades (i.e., antisaccade performance) is well documented among schizophrenia subjects, and researchers have successfully demonstrated that antisaccade performance is a valid schizophrenia endophenotype that is useful for genetic studies. However, it is unclear how the ascertainment biases that unavoidably result from recruitment differences in schizophrenia subjects identified in family versus case-control studies may influence patient-control differences in antisaccade performance. To assess the impact of ascertainment bias, researchers from the Consortium on the Genetics of Schizophrenia (COGS) compared antisaccade performance and antisaccade metrics (latency and gain) in schizophrenia and control subjects from COGS-1, a family-based schizophrenia study, to schizophrenia and control subjects from COGS-2, a corresponding case-control study. COGS-2 schizophrenia subjects were substantially older; had lower education status, worse psychosocial function, and more severe symptoms; and were three times more likely to be a member of a multiplex family than COGS-1 schizophrenia subjects. Despite these variations, which were likely the result of ascertainment differences (as described in the introduction to this special issue), the effect sizes of the control-schizophrenia differences in antisaccade performance were similar in both studies (Cohen's d effect size of 1.06 and 1.01 in COGS-1 and COGS-2, respectively). This suggests that, in addition to the robust, state-independent schizophrenia-related deficits described in endophenotype studies, group differences in antisaccade performance do not vary based on subject ascertainment and recruitment factors. Published by Elsevier B.V. C1 [Radant, Allen D.; Dobie, Dorcas J.; Tsuang, Debby W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Radant, Allen D.] Mental Hlth Serv, Dept Vet Affairs DVA, VISN 20, Seattle, WA USA. [Millard, Steven P.; Dobie, Dorcas J.; Meichle, Sean P.] Mental Illness Res Educ & Clin Ctr MIRECC, DVA, VISN 20, Seattle, WA USA. [Braff, David L.; Greenwood, Tiffany A.; Light, Gregory A.; Swerdlow, Neal R.; Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Calkins, Monica E.; Gur, Raquel E.; Gur, Ruben C.; Turetsky, Bruce I.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Freedman, Robert; Olincy, Ann] Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Aurora, CO USA. [Green, Michael F.; Nuechterlein, Keith H.; Sugar, Catherine A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. [Lazzeroni, Laura C.] Stanford Univ, Dept Biostat, Palo Alto, CA 94304 USA. [Seidman, Larry J.; Stone, William S.] Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr,Dept Psychiat,Publ, Beth Israel Deaconess Med Ctr,Harvard Inst Psychi, Boston, MA 02115 USA. [Siever, Larry J.; Silverman, Jeremy M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Siever, Larry J.; Silverman, Jeremy M.] James J Peters VA Med Ctr, MIRECC, DVA, VISN 3, Bronx, NY USA. [Braff, David L.] San Diego Healthcare Syst, DVA, VISN 22 MIRECC, San Diego, CA USA. [Tsuang, Debby W.] Geriatr Res Educ & Clin Ctr, DVA, VISN 20, Seattle, WA USA. RP Tsuang, DW (reprint author), VA Puget Sound Hlth Care Syst, GRECC 182,1660 S Columbian Way, Seattle, WA 98108 USA. RI Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Lazzeroni, Laura/0000-0002-1846-6920; Greenwood, Tiffany/0000-0002-6080-6503 FU Office of Research and Development Medical Research Service, Department of Veterans Affairs; Office of Health Services R&D Service, Department of Veterans Affairs; NIMH [R01 MH65571, R01 MH65588, R01 MH65562, R01 MH65707, R01 MH65554, R01 MH65578, R01 MH65558] FX This material is based upon work supported (or supported in part) by the Office of Research and Development Medical Research Service (or) Health Services R&D Service, Department of Veterans Affairs. This study was supported by NIMH grants R01 MH65571, R01 MH65588, R01 MH65562, R01 MH65707, R01 MH65554, R01 MH65578, and R01 MH65558. NR 26 TC 2 Z9 2 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2015 VL 163 IS 1-3 BP 47 EP 52 DI 10.1016/j.schres.2014.12.016 PG 6 WC Psychiatry SC Psychiatry GA CE6EE UT WOS:000351928600007 PM 25553977 ER PT J AU Turetsky, BI Dress, EM Braff, DL Calkins, ME Green, MF Greenwood, TA Gur, RE Gur, RC Lazzeroni, LC Nuechterlein, KH Radant, AD Seidman, LJ Siever, LJ Silverman, JM Sprock, J Stone, WS Sugar, CA Swerdlow, NR Tsuang, DW Tsuang, MT Light, G AF Turetsky, Bruce I. Dress, Erich M. Braff, David L. Calkins, Monica E. Green, Michael F. Greenwood, Tiffany A. Gur, Raquel E. Gur, Ruben C. Lazzeroni, Laura C. Nuechterlein, Keith H. Radant, Allen D. Seidman, Larry J. Siever, Larry J. Silverman, Jeremy M. Sprock, Joyce Stone, William S. Sugar, Catherine A. Swerdlow, Neal R. Tsuang, Debby W. Tsuang, Ming T. Light, Gregory TI The utility of P300 as a schizophrenia endophenotype and predictive biomarker: Clinical and socio-demographic modulators in COGS-2 SO SCHIZOPHRENIA RESEARCH LA English DT Article DE P300; Schizophrenia; Endophenotype; Biomarker; Event-related potential ID EVENT-RELATED POTENTIALS; SUBCOMPONENT ABNORMALITIES; AUDITORY ODDBALL; HIGH-RISK; FUNCTIONAL-CAPACITY; MENTAL STATE; AMPLITUDE; PSYCHOSIS; BRAIN; TOPOGRAPHY AB Reduced auditory P300 amplitude is a robust schizophrenia deficit exhibiting the qualities of a viable genetic endophenotype. These include heritability, test-retest reliability, and trait-like stability. Recent evidence suggests that P300 may also serve as a predictive biomarker for transition to psychosis during the schizophrenia prodrome. Historically, the utility of the P300 has been limited by its clinical nonspecificity, cross-site measurement variability, and required EEG expertise. The Consortium on the Genetics of Schizophrenia (COGS-2) study provided an opportunity to examine the consistency of the measure across multiple sites with varying degrees of EEG experience, and to identify important modulating factors that contribute to measurement variability. Auditory P300 was acquired from 649 controls and 587 patients at 5 sites. An overall patient deficit was observed with effect size 0.62. Each site independently observed a significant patient deficit, but site differences also existed. In patients, site differences reflected clinical differences in positive symptomatology and functional capacity. In controls, site differences reflected differences in racial stratification, smoking and substance use history. These factors differentially suppressed the P300 response, but only in control subjects. This led to an attenuated patient-control difference among smokers and among African Americans with history of substance use. These findings indicate that the P300 can be adequately assessed quantitatively, across sites, without substantial EEG expertise. Measurements are suitable for both genetic endophenotype analyses and studies of psychosis risk and conversion. However, careful attention must be given to selection of appropriate comparison samples to avoid misleading false negative results. (C) 2014 Elsevier B.V. All rights reserved. C1 [Turetsky, Bruce I.; Dress, Erich M.; Calkins, Monica E.; Gur, Raquel E.; Gur, Ruben C.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Braff, David L.; Greenwood, Tiffany A.; Sprock, Joyce; Tsuang, Ming T.; Light, Gregory] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Braff, David L.; Light, Gregory] VA San Diego Healthcare Syst, Mental Illness Res Educ & Clin Ctr MIRECC, VISN 22, San Diego, CA USA. [Green, Michael F.; Nuechterlein, Keith H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Lazzeroni, Laura C.] Stanford Univ, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. [Radant, Allen D.; Tsuang, Debby W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Radant, Allen D.; Tsuang, Debby W.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Seidman, Larry J.; Stone, William S.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Seidman, Larry J.; Stone, William S.] Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div, Boston, MA 02215 USA. [Siever, Larry J.; Silverman, Jeremy M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Siever, Larry J.; Silverman, Jeremy M.] James J Peters VA Med Ctr, New York, NY USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. [Tsuang, Ming T.] Univ Calif San Diego, Ctr Behav Genom, La Jolla, CA 92093 USA. [Tsuang, Ming T.] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA. [Tsuang, Ming T.] Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. RP Turetsky, BI (reprint author), Univ Penn, Dept Psychiat, Perelman Sch Med, 10th Floor,Gates Bldg,3400 Spruce, Philadelphia, PA 19104 USA. EM turetsky@upenn.edu RI Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Lazzeroni, Laura/0000-0002-1846-6920; Greenwood, Tiffany/0000-0002-6080-6503 FU National Institute of Mental Health [MH065571, MH065707, MH065554, MH065578, MH065558, MH86135]; NIMH FX This work was supported by collaborative R01 grants from the National Institute of Mental Health: MH065571, MH065707, MH065554, MH065578, MH065558, MH86135. Other than providing financial support, the NIMH had no further role in this manuscript. NR 64 TC 12 Z9 15 U1 1 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 APR PY 2015 VL 163 IS 1-3 BP 53 EP 62 DI 10.1016/j.schres.2014.09.024 PG 10 WC Psychiatry SC Psychiatry GA CE6EE UT WOS:000351928600008 PM 25306203 ER PT J AU Light, GA Swerdlowa, NR Thomas, ML Calkins, ME Green, MF Greenwood, TA Gur, RE Gur, RC Lazzeroni, LC Nuechterlein, KH Pela, M Radant, AD Seidman, LJ Sharp, RF Siever, LJ Silverman, JM Sprock, J Stone, WS Sugar, CA Tsuang, DW Tsuang, MT Braff, DL Turetsky, BI AF Light, Gregory A. Swerdlowa, Neal R. Thomas, Michael L. Calkins, Monica E. Green, Michael F. Greenwood, Tiffany A. Gur, Raquel E. Gur, Ruben C. Lazzeroni, Laura C. Nuechterlein, Keith H. Pela, Marlena Radant, Allen D. Seidman, Larry J. Sharp, Richard F. Siever, Larry J. Silverman, Jeremy M. Sprock, Joyce Stone, William S. Sugar, Catherine A. Tsuang, Debby W. Tsuang, Ming T. Braff, David L. Turetsky, Bruce I. TI Validation of mismatch negativity and P3a for use inmulti-site studies of schizophrenia: Characterization of demographic, clinical, cognitive, and functional correlates in COGS-2 SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Mismatch negativity; P300; P3a; Cognition; Function; EEG ID EVENT-RELATED POTENTIALS; AUDITORY SENSORY MEMORY; HIGH-RISK; 1ST-EPISODE PSYCHOSIS; PROCESSING DEFICITS; HEALTHY-VOLUNTEERS; DURATION; NICOTINE; BRAIN; ATTENTION AB Mismatch negativity (MMN) and P3a are auditory event-related potential (ERP) components that show robust deficits in schizophrenia (SZ) patients and exhibit qualities of endophenotypes, including substantial heritability, test-retest reliability, and trait-like stability. These measures also fulfill criteria for use as cognition and function-linked biomarkers in outcome studies, but have not yet been validated for use in large-scale multi-site clinical studies. This study tested the feasibility of adding MMN and P3a to the ongoing Consortium on the Genetics of Schizophrenia (COGS) study. The extent to which demographic, clinical, cognitive, and functional characteristics contribute to variability in MMN and P3a amplitudes was also examined. Participants (HCS n=824, SZ n=966) underwent testing at 5 geographically distributed COGS laboratories. Valid ERP recordings were obtained from 91% of HCS and 91% of SZ patients. Highly significant MMN (d=0.96) and P3a (d=0.93) amplitude reductions were observed in SZ patients, comparable in magnitude to those observed in single-lab studies with no appreciable differences across laboratories. Demographic characteristics accounted for 26% and 18% of the variance in MMN and P3a amplitudes, respectively. Significant relationships were observed among demographically adjusted MMN and P3a measures and medication status as well as several clinical, cognitive, and functional characteristics of the SZ patients. This study demonstrates that MMN and P3a ERP biomarkers can be feasibly used in multi-site clinical studies. As with many clinical tests of brain function, demographic factors contribute to MMN and P3a amplitudes and should be carefully considered in future biomarker-informed clinical studies. Published by Elsevier B.V. C1 [Light, Gregory A.; Swerdlowa, Neal R.; Thomas, Michael L.; Greenwood, Tiffany A.; Pela, Marlena; Sharp, Richard F.; Sprock, Joyce; Tsuang, Ming T.; Braff, David L.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Light, Gregory A.] VA San Diego Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 22, San Diego, CA USA. [Calkins, Monica E.; Gur, Raquel E.; Gur, Ruben C.; Turetsky, Bruce I.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Green, Michael F.; Nuechterlein, Keith H.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. [Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Lazzeroni, Laura C.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Radant, Allen D.; Tsuang, Debby W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Radant, Allen D.; Tsuang, Debby W.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Seidman, Larry J.; Stone, William S.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Seidman, Larry J.; Stone, William S.] Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div, Boston, MA 02215 USA. [Seidman, Larry J.; Sharp, Richard F.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Siever, Larry J.; Silverman, Jeremy M.] James J Peters VA Med Ctr, New York, NY USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. [Tsuang, Ming T.] Univ Calif San Diego, Ctr Behav Genom, La Jolla, CA 92093 USA. [Tsuang, Ming T.] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA. [Tsuang, Ming T.] Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. RP Light, GA (reprint author), 9500 Gilman Dr, La Jolla, CA 92093 USA. EM glight@ucsd.edu RI Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Lazzeroni, Laura/0000-0002-1846-6920; Greenwood, Tiffany/0000-0002-6080-6503 FU National Institute of Health FX Other than providing support, the National Institute of Health does not have any further role in this manuscript. NR 83 TC 18 Z9 18 U1 3 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2015 VL 163 IS 1-3 BP 63 EP 72 DI 10.1016/j.schres.2014.09.042 PG 10 WC Psychiatry SC Psychiatry GA CE6EE UT WOS:000351928600009 PM 25449710 ER PT J AU Seidman, LJ Hellemann, G Nuechterlein, KH Greenwood, TA Braff, DL Cadenhead, KS Calkins, ME Freedman, R Gur, RE Gur, RC Lazzeroni, LC Light, GA Olincy, A Radant, AD Siever, LJ Silverman, JM Sprock, J Stone, WS Sugar, C Swerdlowe, NR Tsuang, DW Tsuang, MT Turetsky, BI Green, MF AF Seidman, Larry J. Hellemann, Gerhard Nuechterlein, Keith H. Greenwood, Tiffany A. Braff, David L. Cadenhead, Kristin S. Calkins, Monica E. Freedman, Robert Gur, Raquel E. Gur, Ruben C. Lazzeroni, Laura C. Light, Gregory A. Olincy, Ann Radant, Allen D. Siever, Larry J. Silverman, Jeremy M. Sprock, Joyce Stone, William S. Sugar, Catherine Swerdlowe, Neal R. Tsuang, Debby W. Tsuang, Ming T. Turetsky, Bruce I. Green, Michael F. TI Factor structure and heritability of endophenotypes in schizophrenia: Findings from the Consortium on the Genetics of Schizophrenia (COGS-1) SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Endophenotype; Neurocognition; Neurophysiology; Genetics ID TRAIT LINKAGE ANALYSIS; PREPULSE INHIBITION; 1ST-DEGREE RELATIVES; ACOUSTIC STARTLE; P50 SUPPRESSION; WORKING-MEMORY; PERFORMANCE; PROBANDS; FAMILIES AB Background: Although many endophenotypes for schizophrenia have been studied individually, few studies have examined the extent to which common neurocognitive and neurophysiological measures reflect shared versus unique endophenotypic factors. It may be possible to distill individual endophenotypes into composite measures that reflect dissociable, genetically informative elements. Methods: The first phase of the Consortium on the Genetics of Schizophrenia (COGS-1) is a multisite family study that collected neurocognitive and neurophysiological data between 2003 and 2008. For these analyses, participants included schizophrenia probands (n = 83), their nonpsychotic siblings (n = 151), and community comparison subjects (n = 209) with complete data on a battery of 12 neurocognitive tests (assessing domains of working memory, declarative memory, vigilance, spatial ability, abstract reasoning, facial emotion processing, and motor speed) and 3 neurophysiological tasks reflecting inhibitory processing (P50 gating, prepulse inhibition and antisaccade tasks). Factor analyses were conducted on the measures for each subject group and across the entire sample. Heritability analyses of factors were performed using SOLAR. Results: Analyses yielded 5 distinct factors: 1) Episodic Memory, 2) Working Memory, 3) Perceptual Vigilance, 4) Visual Abstraction, and 5) Inhibitory Processing. Neurophysiological measures had low associations with these factors. The factor structure of endophenotypes was largely comparable across probands, siblings and controls. Significant heritability estimates for the factors ranged from 22% (Episodic Memory) to 39% (Visual Abstraction). Conclusions: Neurocognitive measures reflect a meaningful amount of shared variance whereas the neurophysiological measures reflect largely unique contributions as endophenotypes for schizophrenia. Composite endophenotype measures may inform our neurobiological and genetic understanding of schizophrenia. (C) 2015 Elsevier B.V. All rights reserved. C1 [Seidman, Larry J.; Stone, William S.] Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Publ Psychiat Div,Dept Psychiat, Boston, MA 02115 USA. [Seidman, Larry J.; Stone, William S.; Tsuang, Ming T.] Harvard Inst Psychiat Epidemiol & Genet s, Boston, MA USA. [Hellemann, Gerhard; Nuechterlein, Keith H.; Sugar, Catherine; Green, Michael F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Nuechterlein, Keith H.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Greenwood, Tiffany A.; Braff, David L.; Cadenhead, Kristin S.; Sprock, Joyce; Swerdlowe, Neal R.; Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Braff, David L.; Light, Gregory A.] Mental Illness Res Educ & Clin Ctr MIRE, VA San Diego Healthcare Syst VISN 22, San Diego, CA USA. [Calkins, Monica E.; Gur, Raquel E.; Gur, Ruben C.; Turetsky, Bruce I.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Freedman, Robert; Olincy, Ann] Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. [Lazzeroni, Laura C.] Stanford Univ, Med Ctr, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Radant, Allen D.; Tsuang, Debby W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Radant, Allen D.; Tsuang, Debby W.] Mental Illness Res Educ & Clin Ctr, Dept Vet Affairs VISN 20, Seattle, WA USA. [Siever, Larry J.; Silverman, Jeremy M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Siever, Larry J.] Mental Illness Res Educ & Clin Ctr, James J Peters VA & VISN3, Bronx, NY USA. [Sugar, Catherine] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA USA. [Sugar, Catherine; Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, La Jolla, CA 92093 USA. [Tsuang, Ming T.] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA. RP Seidman, LJ (reprint author), Commonwealth Res Ctr, Massachusetts Mental Hlth Ctr, Neuropsychol Lab, Room 542,75 Fenwood Rd, Boston, MA 02115 USA. EM lseidman@bidmc.harvard.edu; dbraff@ucsd.edu RI Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Lazzeroni, Laura/0000-0002-1846-6920; Greenwood, Tiffany/0000-0002-6080-6503 FU Harvard University [RO1-MH065562, MH43518]; Commonwealth Research Center of the Massachusetts Department of Mental Health; Mount Sinai School of Medicine [RO1-MH065554]; University of California Los Angeles [RO1-MH65707]; University of California San Diego [R01-MH065571]; University of Colorado [RO1-MH65588]; University of Pennsylvania [RO1-MH65578]; University of Washington [R01-MH65558] FX Harvard University RO1-MH065562; MH43518; Commonwealth Research Center of the Massachusetts Department of Mental Health; Mount Sinai School of Medicine RO1-MH065554; University of California Los Angeles RO1-MH65707); University of California San Diego R01-MH065571); University of Colorado RO1-MH65588; University of Pennsylvania RO1-MH65578; University of Washington R01-MH65558 NR 42 TC 12 Z9 12 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2015 VL 163 IS 1-3 BP 73 EP 79 DI 10.1016/j.schres.2015.01.027 PG 7 WC Psychiatry SC Psychiatry GA CE6EE UT WOS:000351928600010 PM 25682549 ER PT J AU Li, QY Berry, RB Goetting, MG Staley, B Soto-Calderon, H Tsai, SC Jasko, JG Pack, AI Kuna, ST AF Li, Qing Yun Berry, Richard B. Goetting, Mark G. Staley, Bethany Soto-Calderon, Haideliza Tsai, Sheila C. Jasko, Jeffrey G. Pack, Allan I. Kuna, Samuel T. TI Detection of Upper Airway Status and Respiratory Events by a Current Generation Positive Airway Pressure Device SO SLEEP LA English DT Article DE central sleep apnea; obstructive sleep apnea; positive airway pressure; respiratory event related arousal; upper airway ID APNEA-HYPOPNEA SYNDROME; CENTRAL SLEEP-APNEA; CPAP; POLYSOMNOGRAPHY; ACCURACY; ADULTS; INDEX AB Study Objectives: To compare a positive airway pressure (PAP) device's detection of respiratory events and airway status during device-detected apneas with events scored on simultaneous polysomnography (PSG). Design: Prospective PSGs of patients with sleep apnea using a new-generation PAP device. Settings: Four clinical and academic sleep centers. Patients: Forty-five patients with obstructive sleep apnea (OSA) and complex sleep apnea (Comp SA) performed a PSG on PAP levels adjusted to induce respiratory events. Interventions: None. Measurements and Results: PAP device data identifying the type of respiratory event and whether the airway during a device-detected apnea was open or obstructed were compared to time-synced, manually scored respiratory events on simultaneous PSG recording. Intraclass correlation coefficients between device-detected and PSG scored events were 0.854 for apnea-hypopnea index (AHI), 0.783 for apnea index, 0.252 for hypopnea index, and 0.098 for respiratory event-related arousals index. At a device AHI (AHI(Flow))of 10 events/h, area under the receiver operating characteristic curve was 0.98, with sensitivity 0.92 and specificity 0.84. AHI(Flow) tended to overestimate AHI on PSG at values less than 10 events/h. The device detected that the airway was obstructed in 87.4% of manually scored obstructive apneas. Of the device-detected apneas with clear airway, a minority (15.8%) were manually scored as obstructive apneas. Conclusions: A device-detected apnea-hypopnea index (AHI(Flow)) <10 events/h on a positive airway pressure device is strong evidence of good treatment efficacy. Device-detected airway status agrees closely with the presumed airway status during polysomnography scored events, but should not be equated with a specific type of respiratory event. C1 [Li, Qing Yun] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Resp Med, Shanghai 200025, Peoples R China. [Li, Qing Yun; Staley, Bethany; Soto-Calderon, Haideliza; Pack, Allan I.; Kuna, Samuel T.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Berry, Richard B.] Univ Florida, Dept Med, Gainesville, FL USA. [Goetting, Mark G.] Bronson Sleep Hlth, Kalamazoo, MI USA. [Tsai, Sheila C.] Natl Jewish Hlth, Dept Med, Denver, CO USA. [Jasko, Jeffrey G.] Philips Respiron Inc, Monroeville, PA USA. [Kuna, Samuel T.] Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. RP Li, QY (reprint author), Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Resp Med, 197 Ruijin Er Rd, Shanghai 200025, Peoples R China. EM liqingyun68@hotmail.com FU NIH [1P01-1HL094307]; Philips Respironics, Inc. FX This study was supported by NIH 1P01-1HL094307 and Philips Respironics, Inc. Mr. Jasko is employed by Philips Respironics. The other authors have indicated no conflicts of interest. NR 14 TC 1 Z9 1 U1 0 U2 9 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 APR 1 PY 2015 VL 38 IS 4 DI 10.5665/sleep.4578 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CE7CC UT WOS:000351993600010 ER PT J AU Shen, M Roopchand, R Mananga, ES Amoureux, JP Chen, Q Boutis, GS Hu, BW AF Shen, Ming Roopchand, Rabia Mananga, Eugene S. Amoureux, Jean-Paul Chen, Qun Boutis, Gregory S. Hu, Bingwen TI Revisiting NMR composite pulses for broadband H-2 excitation SO SOLID STATE NUCLEAR MAGNETIC RESONANCE LA English DT Article DE Quadrupolar echo; Deuterium; Composite pulses; Phase cycling ID SOLID-STATE NMR; SUPPRESSION; PATTERNS AB Quadrupolar echo NMR spectroscopy of static solids often requires RF excitation that covers spectral widths exceeding 100 kHz, which is difficult to obtain due to instrumental limitations. In this work we revisit four well-known composite pulses (COM-I, II, III and IV) for broadband excitation in deuterium quadrupolar echo spectroscopy. These composite pulses are combined with several phase cycling schemes that were previously shown to decrease finite pulse width distortions in deuterium solid echo experiments performed with two single pulses. The simulations and experiments show that COM-II and IV composite pulses combined with an 8-step phase cycling aid in achieving broadband excitation with limited pulse width distortions. (C) 2014 Elsevier Inc. All rights reserved. C1 [Shen, Ming; Amoureux, Jean-Paul; Chen, Qun; Hu, Bingwen] E China Normal Univ, Dept Phys, Shanghai 200062, Peoples R China. [Shen, Ming; Amoureux, Jean-Paul; Chen, Qun; Hu, Bingwen] E China Normal Univ, Shanghai Key Lab Magnet Resonance, Shanghai 200062, Peoples R China. [Roopchand, Rabia] CUNY Hunter Coll, Dept Phys, New York, NY 10065 USA. [Mananga, Eugene S.] Harvard Univ, Sch Med, Ctr Adv Radiol Sci, Div Nucl Med & Mol Imaging Phys,Dept Radiol, Boston, MA 02114 USA. [Mananga, Eugene S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Boutis, Gregory S.] CUNY Brooklyn Coll, Dept Phys, Brooklyn, NY 11210 USA. [Amoureux, Jean-Paul] Univ Lille North France, UCCS, F-59652 Villeneuve Dascq, France. [Mananga, Eugene S.] CUNY, Dept Phys & Technol, New York, NY 10453 USA. RP Mananga, ES (reprint author), Harvard Univ, Sch Med, Ctr Adv Radiol Sci, Div Nucl Med & Mol Imaging Phys,Dept Radiol, Boston, MA 02114 USA. RI Hu, Bingwen/G-8930-2011; Shen, Ming/C-8922-2012 OI Shen, Ming/0000-0003-1343-2761 FU Key Project of Shanghai Committee of Science and Technology [11JC1403600]; National Natural Science Foundation of China [21103050, 21373086]; National Key Basic Research Program of China [2013C B921800]; China Scholarship Council; National Institute of General Medical Science of the National Institutes of Health [SC1 GM086268-07] FX The authors are grateful to the Key Project of Shanghai Committee of Science and Technology (11JC1403600), National Natural Science Foundation of China (21103050 and 21373086) and National Key Basic Research Program of China (2013C B921800). MS is grateful for financial support from the China Scholarship Council. Research performed at Brooklyn College of the City University of New York was supported by Award no. SC1 GM086268-07 from the National Institute of General Medical Science of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences or the National Institutes of Health. The authors acknowledge Dr. Alicia Reid for reading the manuscript and providing useful feedbacks. NR 19 TC 1 Z9 2 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0926-2040 EI 1527-3326 J9 SOLID STATE NUCL MAG JI Solid State Nucl. Magn. Reson. PD APR-MAY PY 2015 VL 66-67 BP 45 EP 48 DI 10.1016/j.ssnmr.2014.12.004 PG 4 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical; Physics, Condensed Matter; Spectroscopy SC Chemistry; Physics; Spectroscopy GA CE2SC UT WOS:000351665800007 PM 25583576 ER PT J AU Motiei-Langroudi, R Sadeghian, H AF Motiei-Langroudi, Rouzbeh Sadeghian, Homa TI Assessment of pedicle screw placement accuracy in thoracolumbosacral spine using freehand technique aided by lateral fluoroscopy: results of postoperative computed tomography in 114 patients SO SPINE JOURNAL LA English DT Article DE Pedicle screw; Spine; Accuracy; Computed tomography; Freehand; Fluoroscopy ID HEALTH STROKE SCALE; FREE-HAND; NAVIGATION TECHNIQUES; C-ARM; MORTALITY; INSERTION; BRAIN; SCORE; RISK AB BACKGROUND CONTEXT: Pedicle screw fixation is currently widely used in spine surgery for various pathologies. Increasing screw placement accuracy would improve the outcomes. PURPOSE: To determine the accuracy rate of screw placement in a group of patients who underwent pedicle screw fixation with conventional techniques. STUDY DESIGN: A case series. PATIENT SAMPLE: It includes patients undergoing posterior spinal fixation with pedicle screw insertion. Outcome measures include the accuracy of screw placement in pedicles defined by postoperative computed tomography (CT). METHODS: After surgery, an axial thin-cut CT scan was performed in all patients. Screw position was classified as correct when the screw was completely surrounded by the pedicle cortex and incorrect when any part of the screw was outside the pedicle boundaries. RESULTS: Seven hundred seventy screws were inserted at vertebral levels T7-S1 of 114 patients between March 2012 and December 2012. There were three wound infections and one death. Eighteen screws were diagnosed as having an incorrect position (2.3%). The highest accuracy was observed in levels L4 and L5 (0.8% inaccuracy rate for each), whereas the highest inaccuracy rate was observed in T9. The mean inaccuracy rate was 10.5% for levels T7-T9, 3.5% for levels T10-L2, and 0.9% for levels L3-S1. The differences were statistically significant. Only one screw (5%) needed revision. CONCLUSIONS: The results of our study show that conventional methods for pedicle screw placement remain safe and accurate, with best results obtained in the lumbosacral spine, followed by the thoracolumbar junction. Nonetheless, results are less accurate in the midthoracic spine. (C) 2015 Elsevier Inc. All rights reserved. C1 [Motiei-Langroudi, Rouzbeh] Shahid Beheshti Univ Med Sci, Shohada Tajrish Hosp, Dept Neurosurg, Tehran, Iran. [Sadeghian, Homa] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurovasc Res Lab,Dept Radiol, Charlestown, MA 02129 USA. RP Motiei-Langroudi, R (reprint author), Shahid Beheshti Univ Med Sci, Shohada Tajrish Hosp, Dept Neurosurg, Funct Neurosurg Res Ctr, Tehran, Iran. EM r_motiei@yahoo.com NR 23 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 1529-9430 EI 1878-1632 J9 SPINE J JI Spine Journal PD APR 1 PY 2015 VL 15 IS 4 BP 700 EP 704 DI 10.1016/j.spinee.2014.12.012 PG 5 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA CE2UX UT WOS:000351676400023 PM 25523377 ER PT J AU Boyers, LN Schultz, A Baceviciene, R Blaney, S Marvi, N Dellavalle, RP Dunnick, CA AF Boyers, Lindsay N. Schultz, Amanda Baceviciene, Rasa Blaney, Susan Marvi, Natasha Dellavalle, Robert P. Dunnick, Cory A. TI Teledermatology as an Educational Tool for Teaching Dermatology to Residents and Medical Students SO TELEMEDICINE AND E-HEALTH LA English DT Article DE education; teledermatology; telemedicine; dermatology AB Although teledermatology (TD) is regarded as a tool to improve patient access to specialty healthcare, little has been done to evaluate its role in medical education. We describe the TD program at the Denver (CO) Department of Veterans Affairs Medical Center and evaluate its use as an educational tool for teaching dermatology to dermatology residents and medical students. Dermatology residents manage TD consultations and review all cases with a faculty preceptor; medical students participate as observers when possible. This study assessed dermatology resident (n=14) and medical student (n=16) perceptions of TD and its usefulness in teaching six core clinical competencies. Both residents (79%) and medical students (88%) "strongly agree" or "agree" that TD is an important educational tool. In general, medical students were slightly more satisfied than residents across all of the core competencies assessed except for patient care. Medical students and residents were most satisfied with the competencies of practice-based learning and improvement and medical knowledge, whereas they were least satisfied with those of interpersonal and communication skills and professionalism. Overall, TD is valued as a teaching tool for dermatology in the areas of patient care, medical knowledge, practice-based learning and improvement, and systems-based practice. C1 [Boyers, Lindsay N.] Georgetown Univ, Sch Med, Washington, DC USA. [Schultz, Amanda; Dellavalle, Robert P.; Dunnick, Cory A.] Eastern Colorado Hlth Care Syst, Dermatol Serv, US Dept Vet Affairs, Denver, CO USA. [Baceviciene, Rasa; Marvi, Natasha] Univ Colorado, Sch Med, Aurora, CO USA. [Blaney, Susan] Rocky Mt Network, Vet Integrated Serv Network 19, Telehlth Program, Denver, CO USA. [Dellavalle, Robert P.; Dunnick, Cory A.] Univ Colorado Anschutz Med Campus, Dept Dermatol, Aurora, CO USA. [Dellavalle, Robert P.] Univ Colorado Anschutz Med Campus, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA. RP Dunnick, CA (reprint author), Univ Colorado Denver, Dept Dermatol, 1665 Aurora Court,MS 703, Aurora, CO 80045 USA. EM cory.dunnick@ucdenver.edu FU Centers for Disease Control and Prevention; National Institutes of Health FX L.N.B., A.S., S.B., R.P.D., and C.A.D. were employed by the U.S. Department of Veterans Affairs during the preparation of this manuscript. R.P.D. chairs the Colorado Skin Cancer Prevention Task Force and is supported by grants from the Centers for Disease Control and Prevention and the National Institutes of Health. R.B. and N.M. declare no competing financial interests exist. NR 11 TC 3 Z9 3 U1 1 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 EI 1556-3669 J9 TELEMED E-HEALTH JI Telemed. e-Health PD APR 1 PY 2015 VL 21 IS 4 BP 312 EP 314 DI 10.1089/tmj.2014.0101 PG 3 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CF1DT UT WOS:000352284600012 PM 25635528 ER PT J AU Ma, RS Latif, R Davies, TF AF Ma, Risheng Latif, Rauf Davies, Terry F. TI Human Embryonic Stem Cells Form Functional Thyroid Follicles SO THYROID LA English DT Article ID TRANSGENE EXPRESSION; FOLLICULAR CELLS; GENE-TRANSFER; DIFFERENTIATION; REQUIRES; PROTEIN; LUNG; PAX8 AB Objective: The molecular events that lead to human thyroid cell speciation remain incompletely characterized. It has been shown that overexpression of the regulatory transcription factors Pax8 and Nkx2-1 (ttf-1) directs murine embryonic stem (mES) cells to differentiate into thyroid follicular cells by initiating a transcriptional regulatory network. Such cells subsequently organized into three-dimensional follicular structures in the presence of extracellular matrix. In the current study, human embryonic stem (hES) cells were studied with the aim of recapitulating this scenario and producing functional human thyroid cell lines. Methods: Reporter gene tagged pEZ-lentiviral vectors were used to express human PAX8-eGFP and NKX2-1-mCherry in the H9 hES cell line followed by differentiation into thyroid cells directed by Activin A and thyrotropin (TSH). Results: Both transcription factors were expressed efficiently in hES cells expressing either PAX8, NKX2-1, or in combination in the hES cells, which had low endogenous expression of these transcription factors. Further differentiation of the double transfected cells showed the expression of thyroid-specific genes, including thyroglobulin (TG), thyroid peroxidase (TPO), the sodium/iodide symporter (NIS), and the TSH receptor (TSHR) as assessed by reverse transcription polymerase chain reaction and immunostaining. Most notably, the Activin/TSH-induced differentiation approach resulted in thyroid follicle formation and abundant TG protein expression within the follicular lumens. On stimulation with TSH, these hES-derived follicles were also capable of dose-dependent cAMP generation and radioiodine uptake, indicating functional thyroid epithelial cells. Conclusion: The induced expression of PAX8 and NKX2-1 in hES cells was followed by differentiation into thyroid epithelial cells and their commitment to form functional three-dimensional neo-follicular structures. The data provide proof of principal that hES cells can be committed to thyroid cell speciation under appropriate conditions. C1 Icahn Sch Med Mt Sinai, Thyroid Res Unit, Dept Med, New York, NY 10029 USA. James J Peters VA Med Ctr, New York, NY USA. RP Ma, RS (reprint author), VA Med Ctr, Room 2F-27,130 West Kingsbridge Rd, New York, NY 10468 USA. EM risheng.ma@mssm.edu OI latif, rauf/0000-0002-4226-3728 FU National Institutes of Health [DK069713]; VA Merit Review Program FX Supported in part by DK069713 from the National Institutes of Health and the VA Merit Review Program. NR 19 TC 9 Z9 9 U1 1 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD APR 1 PY 2015 VL 25 IS 4 BP 455 EP 461 DI 10.1089/thy.2014.0537 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CF1HJ UT WOS:000352295100011 PM 25585054 ER PT J AU Bale, SS Golberg, I Jindal, R McCarty, WJ Luitje, M Hegde, M Bhushan, A Usta, OB Yarmush, ML AF Bale, Shyam Sundhar Golberg, Inna Jindal, Rohit McCarty, William J. Luitje, Martha Hegde, Manjunath Bhushan, Abhinav Usta, Osman Berk Yarmush, Martin L. TI Long-Term Coculture Strategies for Primary Hepatocytes and Liver Sinusoidal Endothelial Cells SO TISSUE ENGINEERING PART C-METHODS LA English DT Article ID IN-VITRO; KUPFFER CELLS; SANDWICH CONFIGURATION; NONPARENCHYMAL CELLS; EXTRACELLULAR-MATRIX; COLLAGEN SANDWICH; HEPATOTOXICITY; TOXICITY; MODEL; COMMUNICATION AB Hepatocytes and their in vitro models are essential tools for preclinical screening studies for drugs that affect the liver. Most of the current models primarily focus on hepatocytes alone and lack the contribution of non-parenchymal cells (NPCs), which are significant through both molecular and the response of the NPCs themselves. Models that incorporate NPCs alongside hepatocytes hold the power to enable more realistic recapitulation and elucidation of cell interactions and cumulative drug response. Hepatocytes and liver sinusoidal endothelial cells (LSECs) account for similar to 80% of the liver mass where the LSECs line the walls of blood vessels, and act as a barrier between hepatocytes and blood. Culturing LSECs with hepatocytes to generate multicellular physiologically relevant in vitro liver models has been a major hurdle since LSECs lose their phenotype rapidly after isolation. To this end, we describe the application of collagen gel (1) in a sandwich and (2) as an intervening extracellular matrix layer to coculture hepatocytes with LSECs for extended periods. These coculture configurations provide environments wherein hepatocyte and LSECs, through cell-cell contacts and/or secretion factors, lead to enhanced function and stability of the cocultures. Our results show that in these configurations, hepatocytes and LSECs maintained their phenotypes when cultured together as a mixture, and showed stable secretion and metabolic activity for up to 4 weeks. Immunostaining for sinusoidal endothelial 1 (SE-1) antibody demonstrated retention of LSEC phenotype during the culture period. In addition, LSECs cultured alone maintained high viability and SE-1 expression when cultured within a collagen sandwich configuration up to 4 weeks. Albumin production of the cocultures was 10-15 times higher when LSECs were cultured as a bottom layer (with an intervening collagen layer) and as a mixture in a sandwich configuration, and native CYP 1A1/2 activity was at least 20 times higher than monoculture controls. Together, these data suggest that collagen gel-based hepatocyte-LSEC cocultures are highly suitable models for stabilization and long-term culture of both cell types. In summary, these results indicate that collagen gel-based hepatocyte-LSEC coculture models are promising for in vitro toxicity testing, and liver model development studies. C1 [Bale, Shyam Sundhar; Golberg, Inna; Jindal, Rohit; McCarty, William J.; Luitje, Martha; Hegde, Manjunath; Bhushan, Abhinav; Usta, Osman Berk; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, CEM,Shriners Hosp Children, Boston, MA 02114 USA. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. RP Yarmush, ML (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, CEM,Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org RI Hegde, Manjunath/M-3038-2014 OI McCarty, William/0000-0002-3671-0616; Hegde, Manjunath/0000-0002-5396-2241 FU National Institutes of Health [NIH-5UH2TR000503, NIH-K99DK095984, NIH-F32DK098905]; Shriners Hospital Postdoctoral Fellowship [84202] FX This work was supported by grants from the National Institutes of Health NIH-5UH2TR000503, NIH-K99DK095984 for A.B., NIH-F32DK098905 for W.J.M., and the Shriners Hospital Postdoctoral Fellowship number 84202 for B.U. NR 53 TC 8 Z9 8 U1 4 U2 20 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3384 EI 1937-3392 J9 TISSUE ENG PART C-ME JI Tissue Eng. Part C-Methods PD APR 1 PY 2015 VL 21 IS 4 BP 413 EP 422 DI 10.1089/ten.tec.2014.0152 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CF1KE UT WOS:000352303200009 PM 25233394 ER PT J AU Asmal, M Luedemann, C Lavine, CL Mach, LV Balachandran, H Brinkley, C Denny, TN Lewis, MG Anderson, H Pal, R Sok, D Le, K Pauthner, M Hahn, BH Shaw, GM Seaman, MS Letvin, NL Burton, DR Sodroski, JG Haynes, BF Santra, S AF Asmal, Mohammed Luedemann, Corinne Lavine, Christy L. Mach, Linh V. Balachandran, Harikrishnan Brinkley, Christie Denny, Thomas N. Lewis, Mark G. Anderson, Hanne Pal, Ranajit Sok, Devin Le, Khoa Pauthner, Matthias Hahn, Beatrice H. Shaw, George M. Seaman, Michael S. Letvin, Norman L. Burton, Dennis R. Sodroski, Joseph G. Haynes, Barton F. Santra, Sampa TI Infection of monkeys by simian-human immunodeficiency viruses with transmitted/founder clade C HIV-1 envelopes (vol 475, pg 37, 2015) SO VIROLOGY LA English DT Correction C1 [Asmal, Mohammed; Luedemann, Corinne; Lavine, Christy L.; Mach, Linh V.; Balachandran, Harikrishnan; Seaman, Michael S.; Letvin, Norman L.; Santra, Sampa] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA. [Hahn, Beatrice H.; Shaw, George M.] Univ Penn, Dept Med & Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Sodroski, Joseph G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Brinkley, Christie; Denny, Thomas N.; Haynes, Barton F.] Duke Univ, Sch Med, Duke Human Vaccine Inst, Durham, NC 27710 USA. [Lewis, Mark G.; Anderson, Hanne] BIOQUAL Inc, Rockville, MD 20852 USA. [Pal, Ranajit] Adv BioSci Labs Inc, Rockville, MD 20850 USA. [Sok, Devin; Le, Khoa; Pauthner, Matthias; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbiol, La Jolla, CA 92037 USA. RP Santra, S (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA. EM ssantra@bidmc.harvard.edu NR 1 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR PY 2015 VL 478 BP 149 EP 152 DI 10.1016/j.virol.2015.01.023 PG 4 WC Virology SC Virology GA CE8TK UT WOS:000352116800016 ER PT J AU Fung, LK Akil, M Widge, A Roberts, LW Etkin, A AF Fung, Lawrence K. Akil, Mayada Widge, Alik Roberts, Laura Weiss Etkin, Amit TI Attitudes Toward Neuroscience Education in Psychiatry: a National Multi-stakeholder Survey SO ACADEMIC PSYCHIATRY LA English DT Article DE Neuroscience; Education; Psychiatry; Attitudes ID RESIDENCY CURRICULUM; METAANALYSIS; CLASSIFICATION; PERSPECTIVE; DISORDERS; INTERNET; FUTURE AB Objective The objective of this study is to assess the attitudes of chairs of psychiatry departments, psychiatrists, and psychiatry trainees toward neuroscience education in residency programs and beyond in order to inform future neuroscience education approaches. Method This multi-stakeholder survey captured data on demographics, self-assessments of neuroscience knowledge, attitudes toward neuroscience education, preferences in learning modalities, and interests in specific neuroscience topics. In 2012, the authors distributed the surveys: by paper to 133 US psychiatry department chairs and electronically through the American Psychiatric Association to 3,563 of its members (1,000 psychiatrists and 2,563 trainees). Results The response rates for the chair, psychiatrist, and trainee surveys were 53, 9, and 18 %, respectively. A large majority of respondents agreed with the need for more neuroscience education in general and with respect to their own training. Most respondents believed that neuroscience will help destigmatize mental illness and begin producing new treatments or personalized medicines in 5-10 years. Only a small proportion of trainees and psychiatrists, however, reported a strong knowledge base in neuroscience. Respondents also reported broad enthusiasm for transdiagnostic topics in neuroscience (such as emotion regulation and attention/cognition) and description at the level of neural circuits. Conclusions This study demonstrates the opportunity and enthusiasm for teaching more neuroscience in psychiatry among a broad range of stakeholder groups. A high level of interest was also found for transdiagnostic topics and approaches. We suggest that a transdiagnostic framework may be an effective way to deliver neuroscience education to the psychiatric community and illustrate this through a case example, drawing the similarity between this neuroscience approach and problem-based formulations familiar to clinicians. C1 [Fung, Lawrence K.; Roberts, Laura Weiss; Etkin, Amit] Stanford Univ, Stanford, CA USA. [Akil, Mayada] Georgetown Univ, Washington, DC USA. [Widge, Alik] Massachusetts Gen Hosp, Boston, MA USA. RP Etkin, A (reprint author), Stanford Univ, Stanford, CA 94305 USA. EM amitetkin@stanford.edu OI Roberts, Laura Weiss/0000-0003-4270-253X; Fung, Lawrence/0000-0002-5738-0396 FU Sierra-Pacific Mental Illness Research, Education and Clinical Center (MIRECC) at the Palo Alto VA; T32 research fellowship at Stanford University FX The authors thank Dr. John Oldham, Dr. Dilip Jeste, Dr. Eve Moscicki, Ms. Shelly Cohen and Ms. Janet Kuramoto of the American Psychiatric Association for coordinating the invitation of its members to complete the on-line survey, as well as the 2013 graduating class of general psychiatry at Stanford for their feedback in the pilot study. We thank Dr. Jane Kim for her input on the preparation of the illustrations of this manuscript. Finally, we thank all participants of this study for completing the survey. AE was funded by the Sierra-Pacific Mental Illness Research, Education and Clinical Center (MIRECC) at the Palo Alto VA; LKF was funded by a T32 research fellowship at Stanford University. NR 25 TC 2 Z9 2 U1 2 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1042-9670 EI 1545-7230 J9 ACAD PSYCHIATR JI Acad. Psych. PD APR PY 2015 VL 39 IS 2 BP 139 EP 146 DI 10.1007/s40596-014-0183-y PG 8 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA CD9QU UT WOS:000351433800003 PM 25001432 ER PT J AU Olar, A Wani, KM Alfaro-Munoz, KD Heathcock, LE van Thuijl, HF Gilbert, MR Armstrong, TS Sulman, EP Cahill, DP Vera-Bolanos, E Yuan, Y Reijneveld, JC Ylstra, B Wesseling, P Aldape, KD AF Olar, Adriana Wani, Khalida M. Alfaro-Munoz, Kristin D. Heathcock, Lindsey E. van Thuijl, Hinke F. Gilbert, Mark R. Armstrong, Terri S. Sulman, Erik P. Cahill, Daniel P. Vera-Bolanos, Elizabeth Yuan, Ying Reijneveld, Jaap C. Ylstra, Bauke Wesseling, Pieter Aldape, Kenneth D. TI IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas SO ACTA NEUROPATHOLOGICA LA English DT Article DE Diffuse glioma; IDH; 1p/19q; Outcome; WHO grade; pHH3 ID ANAPLASTIC OLIGODENDROGLIAL TUMORS; MOLECULAR CLASSIFICATION; ADJUVANT PROCARBAZINE; EUROPEAN ORGANIZATION; PROGNOSTIC-FACTORS; 1P/19Q LOSS; INFILTRATING ASTROCYTOMAS; VINCRISTINE CHEMOTHERAPY; RADIATION-THERAPY; HISTONE H3 AB Diffuse gliomas are up till now graded based upon morphology. Recent findings indicate that isocitrate dehydrogenase (IDH) mutation status defines biologically distinct groups of tumors. The role of tumor grade and mitotic index in patient outcome has not been evaluated following stratification by IDH mutation status. To address this, we interrogated 558 WHO grade II-III diffuse gliomas for IDH1/2 mutations and investigated the prognostic impact of WHO grade within IDH-mutant and IDH-wild type tumor subsets independently. The prognostic impact of grade was modest in IDH-mutant [hazard ratio (HR) = 1.21, 95 % confidence interval (CI) = 0.91-1.61] compared to IDH-wild type tumors (HR = 1.74, 95 % CI = 0.95-3.16). Using a dichotomized mitotic index cut-off of 4/1000 tumor cells, we found that while mitotic index was significantly associated with outcome in IDH-wild type tumors (log-rank p < 0.0001, HR = 4.41, 95 % CI = 2.55-7.63), it was not associated with outcome in IDH-mutant tumors (log-rank p = 0.5157, HR = 1.10, 95 % CI = 0.80-1.51), and could demonstrate a statistical interaction (p < 0.0001) between IDH mutation and mitotic index (i.e., suggesting that the effect of mitotic index on patient outcome is dependent on IDH mutation status). Patient age, an established prognostic factor in diffuse glioma, was significantly associated with outcome only in the IDH-wild type subset, and consistent with prior data, 1p/19q co-deletion conferred improved outcome in the IDH-mutant cohort. These findings suggest that stratification of grade II-III gliomas into subsets defined by the presence or absence of IDH mutation leads to subgroups with distinct prognostic characteristics. Further evaluation of grading criteria and prognostic markers is warranted within IDH-mutant versus IDH-wild type diffuse grade II-III gliomas as independent entities. C1 [Olar, Adriana; Wani, Khalida M.; Aldape, Kenneth D.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Alfaro-Munoz, Kristin D.; Gilbert, Mark R.; Armstrong, Terri S.; Vera-Bolanos, Elizabeth] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Heathcock, Lindsey E.] Baylor Coll Med, Houston, TX 77030 USA. [van Thuijl, Hinke F.; Reijneveld, Jaap C.] Vrije Univ Amsterdam Med Ctr, Dept Neurol, NL-1007 MB Amsterdam, Netherlands. [van Thuijl, Hinke F.; Ylstra, Bauke; Wesseling, Pieter] Vrije Univ Amsterdam Med Ctr, Dept Pathol, NL-1007 MB Amsterdam, Netherlands. [Armstrong, Terri S.] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [Sulman, Erik P.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Cahill, Daniel P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Yuan, Ying] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Wesseling, Pieter] Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6500 HB Nijmegen, Netherlands. [Aldape, Kenneth D.] Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada. [Aldape, Kenneth D.] Ontario Canc Inst, Toronto, ON M5G 2M9, Canada. RP Olar, A (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Pathol, G1-3510,1515 Holcombe Blvd, Houston, TX 77030 USA. EM adriana_olar@yahoo.com; ken.aldape@uhnresearch.ca RI Wesseling, P./H-8114-2014; Gilbert, Mark/J-7494-2016; Ylstra, Bauke/D-2906-2012; OI Wesseling, P./0000-0001-5453-5201; Gilbert, Mark/0000-0003-2556-9722; Ylstra, Bauke/0000-0001-9479-3010; Cahill, Daniel/0000-0003-2552-6546 FU National Institutes of Health/National Cancer Institute (SPORE) [P50CA127001, 5P50CA165962]; Burroughs Wellcome Career Award; Koch Institute-Dana Farber Harvard Cancer Center Bridge Foundation; Dutch Cancer Society (KWF) [VU 2009-4470]; foundation 'STOPHersentumoren'; Edli foundation; National Institutes of Health/National Cancer Institute [5T32CA163185] FX Funding was provided by the National Institutes of Health/National Cancer Institute (SPORE Grant No. P50CA127001) (to KDA, EPS), and the Burroughs Wellcome Career Award, the Koch Institute-Dana Farber Harvard Cancer Center Bridge Foundation, and the National Institutes of Health/National Cancer Institute (SPORE Grant No. 5P50CA165962) (to DPC); the Dutch Cancer Society (KWF grant VU 2009-4470) to JCR, BY, the foundation 'STOPHersentumoren' to JCR, BY, the Edli foundation to BY, PW. AO was supported by the National Institutes of Health/National Cancer Institute (Training Grant No. 5T32CA163185). Material and clinical information obtained via the VU University Medical Center was kindly provided by the Elisabeth Hospital Tilburg, the Isala Klinieken Zwolle, the Radboud University Medical Center, Nijmegen, and the Academic Medical Center, Amsterdam, The Netherlands. NR 72 TC 31 Z9 34 U1 2 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 EI 1432-0533 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD APR PY 2015 VL 129 IS 4 BP 585 EP 596 DI 10.1007/s00401-015-1398-z PG 12 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA CE0ST UT WOS:000351517200007 PM 25701198 ER PT J AU Awan, M Dyer, BA Kalpathy-Cramer, J Bongers, E Dahele, M Yang, JZ Walker, GV Thaker, NG Holliday, E Bishop, AJ Thomas, CR Rosenthal, DI Fuller, CD AF Awan, Musaddiq Dyer, Brandon Alan Kalpathy-Cramer, Jayashree Bongers, Eva Dahele, Max Yang, Jinzhong Walker, Gary V. Thaker, Nikhil G. Holliday, Emma Bishop, Andrew J. Thomas, Charles R., Jr. Rosenthal, David I. Fuller, Clifton David TI Auto-segmentation of the brachial plexus assessed with TaCTICS - A software platform for rapid multiple-metric quantitative evaluation of contours SO ACTA ONCOLOGICA LA English DT Letter ID TARGET VOLUME DELINEATION; PERFORMANCE PARAMETERS; RADIATION-THERAPY; NECK-CANCER; RADIOTHERAPY; VALIDATION; HEAD; ATLAS; PROSTATE; STAPLE C1 [Awan, Musaddiq; Yang, Jinzhong; Walker, Gary V.; Thaker, Nikhil G.; Holliday, Emma; Bishop, Andrew J.; Rosenthal, David I.; Fuller, Clifton David] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Dyer, Brandon Alan; Kalpathy-Cramer, Jayashree; Thomas, Charles R., Jr.; Fuller, Clifton David] Oregon Hlth & Sci Univ, Dept Radiat Med, Portland, OR 97201 USA. [Kalpathy-Cramer, Jayashree] Harvard Univ, Sch Med, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. [Kalpathy-Cramer, Jayashree] Massachusetts Gen Hosp, Dept Radiol & Neurosci, Charlestown, MA USA. [Bongers, Eva; Dahele, Max] Vrije Univ Amsterdam, Dept Radiat Oncol, Med Ctr, Amsterdam, Netherlands. RP Fuller, CD (reprint author), Univ Texas MD Anderson Canc Ctr, Head & Neck Sect, Div Radiat Oncol, Dept Radiat Oncol, 1515 Holcombe Blvd,Unit 97, Houston, TX 77030 USA. EM cdfuller@mdanderson.org OI Kalpathy-Cramer, Jayashree/0000-0001-8906-9618; Fuller, Clifton/0000-0002-5264-3994; Yang, Jinzhong/0000-0002-9254-4501 FU NCI NIH HHS [K12 CA088084, K12 CA088084-14, L30 CA136381, L30 CA136381-02, U01 CA154601]; NLM NIH HHS [4R00LM009889, R00 LM009889] NR 25 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 0284-186X EI 1651-226X J9 ACTA ONCOL JI Acta Oncol. PD APR PY 2015 VL 54 IS 4 BP 556 EP 560 DI 10.3109/0284186X.2014.953638 PG 5 WC Oncology SC Oncology GA CE0XH UT WOS:000351533600018 PM 25279958 ER PT J AU Saxon, AJ AF Saxon, Andrew J. TI Commentary on Burns et al. (2015): Retention in buprenorphine treatment SO ADDICTION LA English DT Editorial Material DE Buprenorphine; medication assisted treatment; methadone; opioid use disorder; pharmacogenetics; treatment retention ID PRESCRIPTION OPIOID DEPENDENCE; MAINTENANCE THERAPY; METHADONE; TRIAL; MULTISITE; OPRD1 C1 Univ Washington, Dept Psychiat & Behav Sci, Addict Psychiat Residency Program, CESATE,VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Saxon, AJ (reprint author), Univ Washington, Dept Psychiat & Behav Sci, Addict Psychiat Residency Program, CESATE,VA Puget Sound Hlth Care Syst, 1660 South Columbian Way, Seattle, WA 98108 USA. EM asaxon@uw.edu FU Janssen FX Andrew J. Saxon has received honoraria or worked as a consultant for Alkermes, Inc. and ReckittBenckiser, Inc. and has received research support from Janssen. Alkermes and ReckittBenckiser have supplied study medications for several clinical trials on which Andrew J. Saxon has been an investigator. Andrew J. Saxon also serves as a section editor for UpToDate for which he has received royalties. NR 17 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0965-2140 EI 1360-0443 J9 ADDICTION JI Addiction PD APR PY 2015 VL 110 IS 4 BP 656 EP 657 DI 10.1111/add.12865 PG 2 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA CD6PK UT WOS:000351211200015 PM 25771691 ER PT J AU Kumbhani, DJ Fonarow, GC Cannon, CP Hernandez, AF Peterson, ED Peacock, WF Laskey, WK Deedwania, P Grau-Sepulveda, M Schwamm, LH Bhatt, DL AF Kumbhani, Dharam J. Fonarow, Gregg C. Cannon, Christopher P. Hernandez, Adrian F. Peterson, Eric D. Peacock, W. Frank Laskey, Warren K. Deedwania, Prakash Grau-Sepulveda, Maria Schwamm, Lee H. Bhatt, Deepak L. CA Get Guidelines Steering Comm TI Temporal Trends for Secondary Prevention Measures Among Patients Hospitalized with Coronary Artery Disease SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Angioplasty; Bypass; Coronary Disease; Registries; Surgery ID AMERICAN-HEART-ASSOCIATION; ELEVATION MYOCARDIAL-INFARCTION; BYPASS GRAFT-SURGERY; QUALITY-OF-CARE; TASK-FORCE; PERFORMANCE-MEASURES; PRACTICE GUIDELINES; OUTCOMES; ADHERENCE; MEDICATIONS AB BACKGROUND: Prior studies have noted that in-hospital adherence to secondary prevention measures varied among patients undergoing coronary artery bypass graft surgery, percutaneous coronary revascularization, or no intervention. We sought to study contemporary temporal trends in the in-hospital management of patients with coronary artery disease. METHODS: By using data from the Get With The Guidelines-Coronary Artery Disease registry, we compared adherence to 6 performance measures (aspirin within 24 hours, discharge on aspirin, discharge on beta-blockers, patients with low ejection fraction discharged on angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, smoking cessation counseling, and use of lipid-lowering medications) in eligible patients with coronary artery disease who underwent coronary artery bypass graft surgery, percutaneous coronary intervention, or no intervention between 2003 and 2008. RESULTS: A total of 113,971 patients with coronary artery disease were treated at 193 hospitals. Overall adherence to all 6 quality of care measures improved over time in all 3 treatment groups, but was highest at all time periods in the percutaneous coronary intervention group compared with the coronary artery bypass graft surgery group, whereas the no intervention group had the lowest use of prevention measures at all time points (P < .0001). Likewise, 100% adherence to all 6 measures was superior in the percutaneous coronary intervention group at all time points (P < .0001). On multivariable adjustment for case-mix of patients, the majority of these differences persisted. CONCLUSIONS: Over the last decade, overall adherence with secondary prevention measures improved significantly in patients hospitalized with coronary artery disease regardless of revascularization strategy. However, there still exist select opportunities for improving adherence, particularly among patients undergoing coronary artery bypass graft surgery or no intervention. (C) 2015 Elsevier Inc. All rights reserved. C1 [Kumbhani, Dharam J.] Univ Texas SW Med Ctr Dallas, Div Cardiol, Dallas, TX 75390 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA. [Cannon, Christopher P.; Bhatt, Deepak L.] Brigham & Womens Hosp, Heart & Vasc Ctr, Boston, MA 02115 USA. [Cannon, Christopher P.; Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Hernandez, Adrian F.; Peterson, Eric D.; Grau-Sepulveda, Maria] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Peacock, W. Frank] Baylor Coll Med, Emergency Med, Houston, TX 77030 USA. [Laskey, Warren K.] Univ New Mexico, Div Cardiol, Albuquerque, NM 87131 USA. [Deedwania, Prakash] Univ Calif San Francisco, Div Cardiol, San Francisco, CA USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Kumbhani, DJ (reprint author), Univ Texas SW Med Ctr Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM dharam@post.harvard.edu RI Hernandez, Adrian F./A-7818-2016 OI Hernandez, Adrian F./0000-0003-3387-9616 FU Merck/Schering-Plough Pharmaceutical; American Heart Association FX Get With The Guidelines-Coronary Artery Disease is a program of the American Heart Association and is supported by an unrestricted educational grant from Merck/Schering-Plough Pharmaceutical. Data collection and management were performed by Outcome, Inc (Cambridge, Mass). The analysis of registry data was performed at Duke Clinical Research Institute (Durham, NC), which also receives funding from the American Heart Association. The sponsor was not involved in the management, analysis, or interpretation of data or the preparation of the manuscript. NR 31 TC 7 Z9 7 U1 0 U2 5 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 APR PY 2015 VL 128 IS 4 DI 10.1016/j.amjmed.2014.11.013 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CD8SH UT WOS:000351365600033 ER PT J AU Levy, CE Halan, S Silverman, EP Marsiske, M Lehman, L Omura, D Lok, BC AF Levy, Charles E. Halan, Shivashankar Silverman, Erin P. Marsiske, Michael Lehman, Leigh Omura, David Lok, Benjamin C. TI Virtual Environments and Virtual Humans for Military Mild Traumatic Brain Injury and Posttraumatic Stress Disorder: An Emerging Concept SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article C1 [Levy, Charles E.; Silverman, Erin P.; Lehman, Leigh] North Florida South Georgia Vet Hlth Syst, US Dept Vet Affairs, Gainesville, FL USA. [Levy, Charles E.] Univ Florida, Dept Occupat Therapy, Gainesville, FL 32610 USA. [Halan, Shivashankar; Lok, Benjamin C.] Univ Florida, Dept Comp & Informat Sci & Engn, Coll Engn, Gainesville, FL 32610 USA. [Silverman, Erin P.] Univ Florida, Coll Vet Med, Dept Physiol Sci, Gainesville, FL 32610 USA. [Marsiske, Michael] Univ Florida, Dept Clin & Hlth Psychol, Coll Publ Hlth & Hlth Profess, Gainesville, FL 32610 USA. [Lehman, Leigh] Univ Florida, Dept Occupat Therapy, Coll Publ Hlth & Hlth Profess, Gainesville, FL 32610 USA. [Omura, David] US Dept Vet Affairs, Charlotte, NC USA. RP Silverman, EP (reprint author), Univ Florida, Coll Vet Med, Dept Physiol Sci, POB 100144, Gainesville, FL 32610 USA. OI Marsiske, Michael/0000-0001-5973-2116 FU [W81XWH-08-2-0194 PT073664]; [CDMRP/DoD 9.15.08-9.14.09]; [1I01RX000339-01A3] FX Supported by (1) W81XWH-08-2-0194 PT073664 Design of Effective Therapeutic Interventions for Mild TBI/PTSD using Interactive Virtual World Environments, CDMRP/DoD 9.15.08-9.14.09; (2) Development of Virtual Humans For PTSD and mTBI: Rehabilitation Outcomes Research Center 2010-2011; and (3) 1I01RX000339-01A3, Virtual Environments for Therapuetic Solutions (VETS) mTBI/PTSD Phase II, VA RR&D, $824,835, 4.1.13-3.30.16. NR 2 TC 0 Z9 1 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0894-9115 EI 1537-7385 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD APR PY 2015 VL 94 IS 4 BP E31 EP E32 DI 10.1097/PHM.0000000000000248 PG 2 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA CE1BQ UT WOS:000351547000002 PM 25741622 ER PT J AU Mahon, JN Rohan, KJ Nillni, YI Zvolensky, MJ AF Mahon, Jennifer N. Rohan, Kelly J. Nillni, Yael I. Zvolensky, Michael J. TI The role of perceived control over anxiety in prospective symptom reports across the menstrual cycle SO ARCHIVES OF WOMENS MENTAL HEALTH LA English DT Article DE Perceived control; Anxiety sensitivity; Premenstrual symptoms; Menstrual cycle ID DIOXIDE-ENRICHED AIR; PANIC DISORDER; PREMENSTRUAL EXACERBATION; PSYCHOMETRIC PROPERTIES; CONTROL QUESTIONNAIRE; OFFSET CONTROL; SENSITIVITY; WOMEN; PREDICTION; REACTIVITY AB The present investigation tested the role of psychological vulnerabilities to anxiety in reported menstrual symptom severity. Specifically, the current study tested the incremental validity of perceived control over anxiety-related events in predicting menstrual symptom severity, controlling for the effect of anxiety sensitivity, a documented contributor to menstrual distress. It was expected that women with lower perceived control over anxiety-related events would report greater menstrual symptom severity, particularly in the premenstrual phase. A sample of 49 normally menstruating women, aged 18-47 years, each prospectively tracked their menstrual symptoms for one cycle and completed the Anxiety Control Questionnaire (Rapee, Craske, Brown, & Barlow Behav Ther 27:279-293. doi:10.1016/S0005-7894(96)80018-9, 1996) in their follicular and premenstrual phases. A mixed model analysis revealed perceived control over anxiety-related events was a more prominent predictor of menstrual symptom severity than anxiety sensitivity, regardless of the current cycle phase. This finding provides preliminary evidence that perceived control over anxiety-related events is associated with the perceived intensity of menstrual symptoms. This finding highlights the role of psychological vulnerabilities in menstrual distress. Future research should examine whether psychological interventions that target cognitive vulnerabilities to anxiety may help reduce severe menstrual distress. C1 [Mahon, Jennifer N.; Rohan, Kelly J.; Nillni, Yael I.] Univ Vermont, Dept Psychol, Burlington, VT 05405 USA. [Nillni, Yael I.] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. [Nillni, Yael I.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Zvolensky, Michael J.] Univ Houston, Houston, TX 77004 USA. [Zvolensky, Michael J.] Univ Texas MD Anderson Canc Ctr, Dept Behav Sci, Austin, TX USA. RP Mahon, JN (reprint author), Univ Vermont, Dept Psychol, John Dewey Hall,2 Colchester Ave, Burlington, VT 05405 USA. EM Jennifer.mahon@uvm.edu; Kelly.rohan@uvm.edu; Yael.nillni2@va.gov; mjzvolen@central.uh.edu FU National Institute of Mental Health [1R36MH086170-01A1] FX This project was conducted as part of a larger study funded under Yael I. Nillni by the National Institute of Mental Health-1R36MH086170-01A1. NR 47 TC 1 Z9 1 U1 4 U2 5 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 1434-1816 EI 1435-1102 J9 ARCH WOMEN MENT HLTH JI Arch. Womens Ment. Health PD APR PY 2015 VL 18 IS 2 BP 239 EP 246 DI 10.1007/s00737-014-0456-1 PG 8 WC Psychiatry SC Psychiatry GA CE0ED UT WOS:000351476400010 PM 25269759 ER PT J AU Cavusoglu, E Marmur, JD Chhabra, S Hojjati, MR Yanamadala, S Chopra, V Eng, C Jiang, XC AF Cavusoglu, Erdal Marmur, Jonathan D. Chhabra, Sandeep Hojjati, Mohammad R. Yanamadala, Sunitha Chopra, Vineet Eng, Calvin Jiang, Xian-Cheng TI Elevated baseline plasma phospholipid protein (PLTP) levels are an independent predictor of long-term all-cause mortality in patients with diabetes mellitus and known or suspected coronary artery disease SO ATHEROSCLEROSIS LA English DT Article DE PLTP; Phospholipid transfer protein; Biomarkers; Acute coronary syndrome; Prognosis; Mortality; Diabetes mellitus; Atherosclerosis; Myocardial infarction ID APOLIPOPROTEIN-B; LIPOPROTEIN METABOLISM; INSULIN-RESISTANCE; RISK-FACTOR; VITAMIN-E; ATHEROSCLEROSIS; DETERMINANT; DEFICIENCY; MICE; HDL AB Objectives: To investigate the long-term prognostic significance of baseline plasma PLTP levels in a group of well-characterized male patients with diabetes mellitus and known or suspected coronary artery disease referred for coronary angiography. Background: PLTP is a plasma protein that mediates the net transfer and exchange of phospholipids between lipoproteins. It has been implicated in the pathogenesis of atherosclerosis and elevated plasma levels have been reported in patients with diabetes mellitus. Methods: Baseline plasma PLTP levels were measured in 154 male patients with diabetes mellitus who were referred for coronary angiography and followed prospectively for 5 years for the development of all-cause mortality. Results: After adjustment for a variety of baseline clinical, angiographic and laboratory parameters, plasma PLTP levels (analyzed as a continuous variable) were an independent predictor of all-cause mortality at 5 years (HR, 1.55; 95% CI, 1.22-2.00; P = 0.0009). Furthermore, in 3 additional multivariate models that also included a wide variety of contemporary biomarkers with established prognostic efficacy (i.e., ST2, GDF-15, Cystatin C, Fibrinogen, and NT-proBNP), PLTP remained an independent predictor of all-cause mortality at 5 years. Conclusions: Elevated baseline plasma levels of PLTP are associated with an increased risk of long-term all-cause mortality in patients with diabetes and known or suspected coronary disease. Furthermore, this association is independent of a variety of clinical, angiographic, and laboratory variables, including a whole host of contemporary biomarkers with established prognostic efficacy. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Cavusoglu, Erdal; Chopra, Vineet; Eng, Calvin] Bronx Vet Affairs Med Ctr, Dept Med, Div Cardiol, Bronx, NY USA. [Cavusoglu, Erdal; Marmur, Jonathan D.; Chhabra, Sandeep; Hojjati, Mohammad R.; Yanamadala, Sunitha] Suny Downstate Med Ctr, Dept Med, Div Cardiol, Brooklyn, NY 11203 USA. [Jiang, Xian-Cheng] Suny Downstate Med Ctr, Dept Anat & Cell Biol, Brooklyn, NY 11203 USA. RP Cavusoglu, E (reprint author), Suny Downstate Med Ctr, 450 Clarkson Ave,Box 1199, Brooklyn, NY 11203 USA. EM ECavusoglu@aol.com FU American Heart Association [10GRNT3700003]; NIH-NHLBI [5R21HL098661-02] FX This study was sponsored, in part, by grants related to biomarkers from the American Heart Association (Grant-in-Aid 10GRNT3700003) and the NIH-NHLBI (5R21HL098661-02). NR 32 TC 4 Z9 6 U1 0 U2 0 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 APR PY 2015 VL 239 IS 2 BP 503 EP 508 DI 10.1016/j.atherosclerosis.2015.02.017 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CD4NZ UT WOS:000351061600032 PM 25710294 ER PT J AU Tandon, V Kang, WS Spencer, AJ Kim, ES Pararas, EEL McKenna, MJ Kujawa, SG Mescher, MJ Fiering, J Sewell, WF Borenstein, JT AF Tandon, Vishal Kang, Woo Seok Spencer, Abigail J. Kim, Ernest S. Pararas, Erin E. L. McKenna, Michael J. Kujawa, Sharon G. Mescher, Mark J. Fiering, Jason Sewell, William F. Borenstein, Jeffrey T. TI Microfabricated infuse-withdraw micropump component for an integrated inner-ear drug-delivery platform SO BIOMEDICAL MICRODEVICES LA English DT Article DE Drug Delivery; Microfluidics; Inner Ear; Intracochlear; CAP; DPOAE; Micropump ID GUINEA-PIG COCHLEA; ROUND WINDOW MEMBRANE; HEARING-LOSS; HAIR CELL; EVOKED-POTENTIALS; AUDITORY-NERVE; STEM-CELLS; PRESSURE; THERAPY; SYSTEM AB One of the major challenges in treatment of auditory disorders is that many therapeutic compounds are toxic when delivered systemically. Local intracochlear delivery methods are becoming critical in emerging treatments and in drug discovery. Direct infusion via cochleostomy, in particular, is attractive from a pharmacokinetics standpoint, as there is potential for the kinetics of delivery to be well-controlled. Direct infusion is compatible with a large number of drug types, including large, complex molecules such as proteins and unstable molecules such as siRNA. In addition, hair-cell regeneration therapy will likely require long-term delivery of a timed series of agents. This presents unknown risks associated with increasing the volume of fluid within the cochlea and mechanical damage caused during delivery. There are three key requirements for an intracochlear drug delivery system: (1) a high degree of miniaturization (2) a method for pumping precise and small volumes of fluid into the cochlea in a highly controlled manner, and (3) a method for removing excess fluid from the limited cochlear fluid space. To that end, our group is developing a head-mounted microfluidics-based system for long-term intracochlear drug delivery. We utilize guinea pig animal models for development and demonstration of the device. Central to the system is an infuse-withdraw micropump component that, unlike previous micropump-based systems, has fully integrated drug and fluid storage compartments. Here we characterize the infuse-withdraw capabilities of our micropump, and show experimental results that demonstrate direct drug infusion via cochleostomy in animal models. We utilized DNQX, a glutamate receptor antagonist that suppresses CAPs, as a test drug. We monitored the frequency-dependent changes in auditory nerve CAPs during drug infusion, and observed CAP suppression consistent with the expected drug transport path based on the geometry and tonotopic organization of the cochlea. C1 [Tandon, Vishal; Spencer, Abigail J.; Kim, Ernest S.; Pararas, Erin E. L.; McKenna, Michael J.; Fiering, Jason; Borenstein, Jeffrey T.] Charles Stark Draper Lab Inc, Cambridge, MA 02139 USA. [Tandon, Vishal; Kang, Woo Seok; McKenna, Michael J.; Kujawa, Sharon G.; Sewell, William F.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. [Tandon, Vishal; Kang, Woo Seok; McKenna, Michael J.; Kujawa, Sharon G.; Sewell, William F.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Borenstein, JT (reprint author), Charles Stark Draper Lab Inc, Cambridge, MA 02139 USA. EM William_Sewell@meei.harvard.edu; jborenstein@draper.com RI Tandon, Vishal/F-5699-2016 OI Tandon, Vishal/0000-0002-6618-7846 FU National Institute on Deafness and Other Communication Disorders [R01DC006848] FX The project described was supported by Award Number R01DC006848 from the National Institute on Deafness and Other Communication Disorders. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institute on Deafness and other Communication Disorders or the National Institutes of Health. We would also like to thank Transon Nguyen for his assistance with laser machining. NR 60 TC 1 Z9 1 U1 1 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1387-2176 EI 1572-8781 J9 BIOMED MICRODEVICES JI Biomed. Microdevices PD APR PY 2015 VL 17 IS 2 DI 10.1007/s10544-014-9923-8 PG 16 WC Engineering, Biomedical; Nanoscience & Nanotechnology SC Engineering; Science & Technology - Other Topics GA CD8TT UT WOS:000351369600013 PM 25686902 ER PT J AU Figueiras, M Coelho, L Wicht, KJ Santos, SA Lavrado, J Gut, J Rosenthal, PJ Nogueira, F Egan, TJ Moreira, R Paulo, A AF Figueiras, Marta Coelho, Lis Wicht, Kathryn J. Santos, Sofia A. Lavrado, Joao Gut, Jiri Rosenthal, Philip J. Nogueira, Fatima Egan, Timothy J. Moreira, Rui Paulo, Alexandra TI N10,N11-di-alkylamine indolo[3,2-b]quinolines as hemozoin inhibitors: Design, synthesis and antiplasmodial activity SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE Indolo[3,2-b]quinolines; Hemozoin; Malaria; Vacuolar accumulation; Resistance ID BETA-HEMATIN INHIBITION; PLASMODIUM-FALCIPARUM; CYTOCIDAL ACTIVITIES; DRUG DISCOVERY; BIS-ALKYLAMINE; ANTIMALARIAL; ANALOGS; HEME; CRYSTALLIZATION; CRYSTAL AB We recently reported that potent N10,O11-bis-alkylamine indolo[3,2-b]quinoline antimalarials act as hemozoin (Hz) growth inhibitors. To improve access and binding to the target we have now designed novel N10,N11-di-alkylamine bioisosteres. 3-Chloro derivatives (10a-f) showed selectivity for malaria parasite compared to human cells, high activity against Plasmodium falciparum chloroquine (CQ)-resistant strain W2 (IC(50)s between 20 and 158 nM), good correlation with beta-hematin inhibition and improved vacuolar accumulation ratios, thus suggesting inhibition of Hz growth as one possible mechanism of action for these compounds. Moreover, our studies show that Hz is a valid target for the development of new antimalarials able to overcome CQ resistance. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Figueiras, Marta; Santos, Sofia A.; Lavrado, Joao; Moreira, Rui; Paulo, Alexandra] Univ Lisbon, Fac Pharm, Res Inst Med iMed ULisboa, P-1649003 Lisbon, Portugal. [Coelho, Lis; Nogueira, Fatima] Univ Nova Lisboa, IHMT, Ctr Malaria & Doencas Tropicais, UEI Malaria, P-1349008 Lisbon, Portugal. [Wicht, Kathryn J.; Egan, Timothy J.] Univ Cape Town, Dept Chem, ZA-7701 Rondebosch, South Africa. [Santos, Sofia A.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Gut, Jiri; Rosenthal, Philip J.; Paulo, Alexandra] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, San Francisco, CA 94143 USA. RP Paulo, A (reprint author), Univ Lisbon, Fac Pharm, Res Inst Med iMed ULisboa, Ave Prof Gama Pinto, P-1649003 Lisbon, Portugal. EM mapaulo@ff.ulisboa.pt RI Paulo, Alexandra/M-6683-2013; Lavrado, Joao Paulo/D-6757-2011; PTMS, RNEM/C-1589-2014; nogueira, fatima/I-2148-2012; iMed.ULisboa, iMed.ULisboa/C-6292-2014; iMed.ULisboa, MedChem /B-4834-2014; Moreira, Rui/G-7485-2011 OI Paulo, Alexandra/0000-0003-1433-5402; Lavrado, Joao Paulo/0000-0001-7746-5808; nogueira, fatima/0000-0003-0313-0778; Moreira, Rui/0000-0003-0727-9852 FU Fundacao para a Ciencia e Tecnologia (FCT) [PTDC/SAU-FAR/114864/2009, PEst-OE/SAU/UI4013/2014, SFRH/BPD/72903/2010, SFRH/BD/80162/2011]; National Research Foundation (NRF); South African Medical Research Council (SAMRC); University of Capetown FX This work was supported by Fundacao para a Ciencia e Tecnologia (FCT) project grants: PTDC/SAU-FAR/114864/2009 and PEst-OE/SAU/UI4013/2014. J.L. and S.A.S. acknowledge FCT grants (SFRH/BPD/72903/2010) and (SFRH/BD/80162/2011). T.J.E. acknowledges the National Research Foundation (NRF), the South African Medical Research Council (SAMRC) and the University of Capetown for financial support. NR 28 TC 1 Z9 1 U1 2 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 EI 1464-3391 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD APR 1 PY 2015 VL 23 IS 7 BP 1530 EP 1539 DI 10.1016/j.bmc.2015.02.007 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA CD3QV UT WOS:000350995500019 PM 25725608 ER PT J AU Girnius, SK Lee, S Kambhampati, S Rose, MG Mohiuddin, A Houranieh, A Zimelman, A Grady, T Mehta, P Behler, C Hayes, TG Efebera, YA Prabhala, RH Han, A Yellapragada, SV Klein, CE Roodman, GD Lichtenstein, A Munshi, NC AF Girnius, Saulius K. Lee, Saem Kambhampati, Suman Rose, Michal G. Mohiuddin, Abid Houranieh, Antoun Zimelman, Abraham Grady, Terrence Mehta, Paulette Behler, Caroline Hayes, Teresa G. Efebera, Yvonne A. Prabhala, Rao H. Han, Andrew Yellapragada, Sarvari V. Klein, Catherine E. Roodman, Garson D. Lichtenstein, Alan Munshi, Nikhil C. TI A Phase II trial of weekly bortezomib and dexamethasone in veterans with newly diagnosed multiple myeloma not eligible for or who deferred autologous stem cell transplantation SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE multiple myeloma; bortezomib; transplant ineligible; co-morbidities ID INDUCTION TREATMENT PRIOR; TWICE-WEEKLY BORTEZOMIB; PERIPHERAL NEUROPATHY; PLUS DEXAMETHASONE; RENAL IMPAIRMENT; EFFICACY; REVERSIBILITY; PREDNISONE; MELPHALAN; THERAPY AB Once-weekly administration of bortezomib has reduced bortezomib-induced peripheral neuropathy without affecting response rates, but this has only been demonstrated prospectively in three- and four- drug combinations. We report a phase II trial of alternate dosing and schedule of bortezomib and dexamethasone in newly diagnosed multiple myeloma patients who are not eligible for or refused autologous stem cell transplantation. Bortezomib 16mg/m(2) intravenously was given once-weekly for six cycles, together with dexamethasone 40mg on the day of and day after bortezomib. Fifty patients were enrolled; 58% did not require any dose modification. The majority of patients had multiple co-morbidities, including cardiovascular (76%) and renal insufficiency (54%), and the median number of medications prior to enrollment was 13. Of all evaluable patients, the overall response rate was 79% and at least 45% had at least a very good partial response. The median time to first response was 13months (range, 025-24months). The progression-free and overall survivals were 8months and 465months, respectively. Twenty-four percent developed worsening neuropathy. We conclude that alternate dosing and scheduling of bortezomib and dexamethasone is both safe and effective for management of newly diagnosed multiple myeloma in frail patients. (ClinicalTrials.gov number, NCT01090921). C1 [Girnius, Saulius K.; Lee, Saem; Houranieh, Antoun; Zimelman, Abraham; Efebera, Yvonne A.; Prabhala, Rao H.; Han, Andrew; Munshi, Nikhil C.] VA Boston Healthcare Syst, Boston, MA USA. [Girnius, Saulius K.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Lee, Saem] Boston Univ, Sch Med, Boston, MA 02215 USA. [Lee, Saem; Prabhala, Rao H.; Han, Andrew; Munshi, Nikhil C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kambhampati, Suman] Kansas City Vet Affairs Med Ctr, Kansas City, MO USA. [Rose, Michal G.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Mohiuddin, Abid] Atlanta VA Med Ctr, Decatur, GA USA. [Mohiuddin, Abid; Grady, Terrence] James A Haley Vet Hosp, Tampa, FL 33612 USA. [Mehta, Paulette] John L McClellan Mem Vet Adm Med Ctr, Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. [Behler, Caroline] San Francisco VA Med Ctr, San Francisco, CA USA. [Hayes, Teresa G.; Yellapragada, Sarvari V.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Hayes, Teresa G.; Yellapragada, Sarvari V.] Baylor Coll Med, Houston, TX 77030 USA. [Efebera, Yvonne A.] Ohio State Univ, Med Ctr, James Canc Hosp, Columbus, OH 43210 USA. [Prabhala, Rao H.; Munshi, Nikhil C.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. [Klein, Catherine E.] VA Eastern Colorado Hlth Care Syst, Denver, CO USA. [Roodman, Garson D.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Roodman, Garson D.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Roodman, Garson D.] Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. [Lichtenstein, Alan] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Munshi, NC (reprint author), Dana Farber Canc Inst, Dept Hematol, 450 Brookline Ave,M230, Boston, MA 02215 USA. EM nikhil_munshi@dfci.harvard.edu RI Efebera, Yvonne/E-3012-2011 FU Takeda Pharmaceuticals/Millenium FX Takeda Pharmaceuticals/Millenium. NR 20 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2015 VL 169 IS 1 BP 36 EP 43 DI 10.1111/bjh.13243 PG 8 WC Hematology SC Hematology GA CD9VF UT WOS:000351446400006 PM 25572917 ER PT J AU Castillo, JJ Olszewski, AJ Kanan, S Meid, K Hunter, ZR Treon, SP AF Castillo, Jorge J. Olszewski, Adam J. Kanan, Sandra Meid, Kirsten Hunter, Zachary R. Treon, Steven P. TI Overall survival and competing risks of death in patients with Waldenstrom macroglobulinaemia: an analysis of the Surveillance, Epidemiology and End Results database SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Waldenstrom macroglobulinaemia; survival; competing risks; epidemiology; outcomes ID B-CELL LYMPHOMA; LYMPHOPLASMACYTIC LYMPHOMA; RACIAL-DIFFERENCES; RANDOMIZED-TRIAL; UNITED-STATES; RITUXIMAB; DEXAMETHASONE; DISPARITIES; INFECTION; PATTERNS AB Waldenstrom macroglobulinaemia (WM) is a rare and incurable lymphoma. Given that the survival of WM patients can be prolonged, our objective was to describe trends in overall survival (OS) and analyse competing risks of death in patients with WM. The analysis included 5784 patients diagnosed with WM between 1991 and 2010 from the Surveillance, Epidemiology and End Results (SEER) database. Multivariate hazard models for OS and cumulative incidence of death were fitted according to epoch of diagnosis (1991-2000 vs. 2001-10) while adjusting for age, sex, race, histology, site of involvement and registry. Median OS for the 1991-2000 and the 2001-10 cohorts was 6 and 8years, respectively (P<0001). In the multivariate analysis, better OS [hazard ratio (HR) 073, 95% confidence interval (CI) 067-079; P<0001] was seen in the 2001-10 cohort. Survival benefits were identified, for the 2001-10 cohort, in almost every stratum analysed, with the exception of patients aged <50years and blacks. In the multivariate competing-risk analysis, the 2001-10 cohort experienced lower rates of WM-related (HR 057, 95% CI 049-066; P<0001) and non-WM-related deaths (HR 072, 95% CI 066-079; P<0001). In conclusion, there have been significant improvements in OS, WM-related and non-WM-related mortality in patients with WM diagnosed in the last decade. C1 [Castillo, Jorge J.; Kanan, Sandra; Meid, Kirsten; Hunter, Zachary R.; Treon, Steven P.] Dana Farber Canc Inst, Bing Ctr Waldenstrom Macroglobulinemia, Boston, MA 02115 USA. [Castillo, Jorge J.; Treon, Steven P.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Olszewski, Adam J.] Brown Univ, Mem Hosp Rhode Isl, Div Hematol & Oncol, Warren Alpert Med Sch, Pawtucket, RI 02860 USA. RP Castillo, JJ (reprint author), 450 Brookline Ave,M221, Boston, MA 02215 USA. EM jorgej_castillo@dfci.harvard.edu OI Olszewski, Adam/0000-0002-6472-6658; Castillo, Jorge/0000-0001-9490-7532; Hunter, Zachary/0000-0002-1689-1691 NR 33 TC 19 Z9 19 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2015 VL 169 IS 1 BP 81 EP 89 DI 10.1111/bjh.13264 PG 9 WC Hematology SC Hematology GA CD9VF UT WOS:000351446400011 PM 25521528 ER PT J AU Vogtmann, E Flores, R Yu, GQ Freedman, ND Shi, JX Gail, MH Dye, BA Wang, GQ Klepac-Ceraj, V Paster, BJ Wei, WQ Guo, HQ Dawsey, SM Qiao, YL Abnet, CC AF Vogtmann, Emily Flores, Roberto Yu, Guoqin Freedman, Neal D. Shi, Jianxin Gail, Mitchell H. Dye, Bruce A. Wang, Guo-Qing Klepac-Ceraj, Vanja Paster, Bruce J. Wei, Wen-Qiang Guo, Hui-Qin Dawsey, Sanford M. Qiao, You-Lin Abnet, Christian C. TI Association between tobacco use and the upper gastrointestinal microbiome among Chinese men SO CANCER CAUSES & CONTROL LA English DT Article DE China; Microbiome; Tobacco; Upper gastrointestinal tract ID BIOFILM FORMATION; ORAL BACTERIA; SMOKING; PERIODONTITIS; SMOKERS; MICROARRAY; NONSMOKERS; PROFILES; CANCER; ADULTS AB Tobacco causes many adverse health conditions and may alter the upper gastrointestinal (UGI) microbiome. However, the few studies that studied the association between tobacco use and the microbiome were small and underpowered. Therefore, we investigated the association between tobacco use and the UGI microbiome in Chinese men. We included 278 men who underwent esophageal cancer screening in Henan Province, China. Men were categorized as current, former, or never smokers from questionnaire data. UGI tract bacterial cells were characterized using the Human Oral Microbial Identification Microarray. Counts of unique bacterial species and genera estimated alpha diversity. For beta diversity, principal coordinate (PCoA) vectors were generated from an unweighted UniFrac distance matrix. Polytomous logistic regression models were used for most analyses. Of the 278 men in this study, 46.8 % were current smokers and 12.6 % were former smokers. Current smokers tended to have increased alpha diversity (mean 42.3 species) compared to never smokers (mean 38.9 species). For a 10 species increase, the odds ratio (OR) for current smoking was 1.29 (95 % CI 1.04-1.62). Beta diversity was also associated with current smoking. The first two PCoA vectors were strongly associated with current smoking (PCoA1 OR 0.66; 95 % CI 0.51-0.87; PCoA2 OR 0.73; 95 % CI 0.56-0.95). Furthermore, Dialister invisus and Megasphaera micronuciformis were more commonly detected in current smokers than in never smokers. Current smoking was associated with both alpha and beta diversity in the UGI tract. Future work should consider how the UGI microbiome is associated with smoking-related diseases. C1 [Vogtmann, Emily; Yu, Guoqin; Freedman, Neal D.; Shi, Jianxin; Gail, Mitchell H.; Dawsey, Sanford M.; Abnet, Christian C.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Vogtmann, Emily; Flores, Roberto] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Vogtmann, Emily] NCI, Nutr Epidemiol Branch, DCEG, Bethesda, MD 20892 USA. [Dye, Bruce A.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. [Wang, Guo-Qing; Wei, Wen-Qiang; Guo, Hui-Qin; Qiao, You-Lin] Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China. [Klepac-Ceraj, Vanja; Paster, Bruce J.] Forsyth Inst, Cambridge, MA USA. [Klepac-Ceraj, Vanja] Wellesley Coll, Wellesley, MA 02181 USA. [Paster, Bruce J.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Vogtmann, E (reprint author), NCI, Nutr Epidemiol Branch, DCEG, 9609 Med Ctr Dr,6E404,MSC 9768, Bethesda, MD 20892 USA. EM emily.vogtmann@nih.gov RI Freedman, Neal/B-9741-2015; Abnet, Christian/C-4111-2015; Qiao, You-Lin/B-4139-2012 OI Freedman, Neal/0000-0003-0074-1098; Abnet, Christian/0000-0002-3008-7843; Qiao, You-Lin/0000-0001-6380-0871 FU Intramural Research Program of the National Institutes of Health; Cancer Prevention Fellowship Program of the National Institutes of Health; National Cancer Institute FX We would like to thank the staff in Linzhou, China. This work was supported by the Intramural Research Program and the Cancer Prevention Fellowship Program of the National Institutes of Health and the National Cancer Institute. NR 34 TC 3 Z9 3 U1 1 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD APR PY 2015 VL 26 IS 4 BP 581 EP 588 DI 10.1007/s10552-015-0535-2 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CE0YG UT WOS:000351536400008 PM 25701246 ER PT J AU Pilon, JL Clausen, DJ Hansen, RJ Lunghofer, PJ Charles, B Rose, BJ Thamm, DH Gustafson, DL Bradner, JE Williams, RM AF Pilon, John L. Clausen, Dane J. Hansen, Ryan J. Lunghofer, Paul J. Charles, Brad Rose, Barbara J. Thamm, Douglas H. Gustafson, Daniel L. Bradner, James E. Williams, Robert M. TI Comparative pharmacokinetic properties and antitumor activity of the marine HDACi Largazole and Largazole peptide isostere SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Largazole; Histone deacetylase inhibitor; Peptide isostere; Prodrug; Depsipeptide ID HISTONE DEACETYLASE INHIBITOR; IN-VITRO; FK228; PANOBINOSTAT; FR901228; ANALOGS; CANCER; AGENT; VIVO AB Largazole is a potent class I-selective HDACi natural product isolated from the marine cyanobacteria Symploca sp. The purpose of this study was to test synthetic analogs of Largazole to identify potential scaffold structural modifications that would improve the drug-like properties of this clinically relevant natural product. The impact of Largazole scaffold replacements on in vitro growth inhibition, cell cycle arrest, induction of apoptosis, pharmacokinetic properties, and in vivo activity using a xenograft model was investigated. In vitro studies in colon, lung, and pancreatic cancer cell lines showed that pyridyl-substituted Largazole analogs had low-nanomolar/high-picomolar antiproliferative activity, and induced apoptosis and cell cycle arrest at concentrations equivalent to or lower than the parent compound Largazole. Using IV bolus delivery at 5 mg/kg, two compartmental pharmacokinetic modeling on the peptide isostere analog of Largazole indicated improved pharmacokinetic parameters. In an A549 non-small cell lung carcinoma xenograft model using a dosage of 5 mg/kg administered intraperitoneally every other day, Largazole, Largazole thiol, and Largazole peptide isostere demonstrated tumor growth inhibition (TGI %) of 32, 44, and 66 %, respectively. Largazole peptide isostere treatment was statistically superior to control (p = 0.002) and to Largazole (p = 0.006). Surprisingly, tumor growth inhibition was not observed with the potent pyridyl-based analogs. These results establish that replacing the depsipeptide linkage in Largazole with an amide may impart pharmacokinetic and therapeutic advantage and that alternative prodrug forms of Largazole are feasible. C1 [Pilon, John L.] Cetya Therapeut, Ft Collins, CO 80523 USA. [Clausen, Dane J.; Williams, Robert M.] Colorado State Univ, Dept Chem, Ft Collins, CO 80523 USA. [Hansen, Ryan J.; Lunghofer, Paul J.; Charles, Brad; Rose, Barbara J.; Thamm, Douglas H.; Gustafson, Daniel L.] Colorado State Univ, Flint Anim Canc Ctr, Ft Collins, CO 80523 USA. [Thamm, Douglas H.; Gustafson, Daniel L.; Williams, Robert M.] Univ Colorado, Ctr Canc, Aurora, CO 80045 USA. [Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Williams, RM (reprint author), Colorado State Univ, Dept Chem, 1301 Ctr Ave, Ft Collins, CO 80523 USA. EM rmw@lamar.colostate.edu RI Thamm, Douglas/I-5976-2013 OI Thamm, Douglas/0000-0002-8914-7767 FU National Institutes of Health [RO1 CA152314]; National Cancer Institute [1K08CA128972]; Burroughs-Wellcome Foundation (CAMS); State of Colorado Bioscience Development Program Grant; University of Colorado Cancer Center Shared Resource (Pharmacology) [P30CA046934] FX This work was supported by the National Institutes of Health (RO1 CA152314, to R.M.W and J.E.B.). J.E.B. acknowledges support by Grants from the National Cancer Institute (1K08CA128972) and the Burroughs-Wellcome Foundation (CAMS). JLP acknowledges support from the State of Colorado Bioscience Development Program Grant. This work was also supported by University of Colorado Cancer Center Shared Resource (Pharmacology) support Grant (P30CA046934). NR 25 TC 4 Z9 4 U1 0 U2 22 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 APR PY 2015 VL 75 IS 4 BP 671 EP 682 DI 10.1007/s00280-015-2675-1 PG 12 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA CE1CI UT WOS:000351549100002 PM 25616967 ER PT J AU Chan, E Kwak, EL Hwang, J Heiskala, M de La Bourdonnaye, G Mita, M AF Chan, Emily Kwak, Eunice L. Hwang, Jimmy Heiskala, Marja de La Bourdonnaye, Guillaume Mita, Monica TI Open-label phase 1b study of FOLFIRI plus cetuximab plus IMO-2055 in patients with colorectal cancer who have progressed following chemotherapy for advanced or metastatic disease SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Cetuximab; Colorectal cancer (CRC); FOLFIRI; IMO-2055 (EMD 1201081); Toll-like receptor 9 agonist (TLR9) ID RECEPTOR 9 AGONIST; CELL LUNG-CANCER; 1ST-LINE TREATMENT; IMMUNOMODULATORY OLIGONUCLEOTIDES; TLR9 AGONIST; COLON-CANCER; THERAPY; PF-3512676; CARCINOMA; CISPLATIN AB The immune modulatory oligonucleotide IMO-2055 (EMD 1201081) is a phosphorothioate oligodeoxynucleotide agonist of Toll-like receptor 9. In preclinical studies, IMO-2055 was shown to activate natural killer cells and to support the antitumor activity of monoclonal antibodies. This phase 1b, open-label, 3 + 3 dose-escalation trial was performed to determine the recommended phase 2 dose of IMO-2055 combined with FOLFIRI/cetuximab in patients with previously treated, advanced/metastatic colorectal cancer (NCT00719199). Patients received 14-day cycles of cetuximab (days 1/8; 400 mg/m(2) day 1 cycle 1, 250 mg/m(2) for subsequent days/cycles), irinotecan (day 1; 180 mg/m(2)), folinic acid (day 1; 400 mg/m(2) racemic or 200 mg/m(2) l-form), 5-fluorouracil (day 1; 400 mg/m(2) intravenous bolus, followed by 2,400 mg/m(2) as 46-h infusion), and escalating IMO-2055 doses (days 1/8; 0.16, 0.32, 0.48 mg/kg). Fifteen patients received IMO-2055, including six, three, and six patients who were treated at the dose levels 0.16, 0.32, and 0.48 mg/kg, respectively. One dose-limiting toxicity was observed (grade 3 fatigue; at dose level 0.16 mg/kg). The most common adverse events were injection site reactions, diarrhea, fatigue, hypomagnesemia, and stomatitis. One patient achieved a confirmed partial response; 12 had stable disease, including five with stable disease a parts per thousand yen4.0 months. IMO-2055 combined with FOLFIRI/cetuximab was well tolerated at all dose levels tested. IMO-2055 0.48 mg/kg was considered as the recommended phase 2 dose. C1 [Chan, Emily] Vanderbilt Ingram Canc Ctr, Div Hematol Oncol, Nashville, TN 37232 USA. [Kwak, Eunice L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hwang, Jimmy] Georgetown Univ Hosp, Washington, DC 20007 USA. [Heiskala, Marja; de La Bourdonnaye, Guillaume] Merck KGaA, Darmstadt, Germany. [Mita, Monica] Canc Therapy & Res Ctr UTHSCSA, Inst Drug Dev, San Antonio, TX USA. RP Chan, E (reprint author), Vanderbilt Ingram Canc Ctr, Div Hematol Oncol, 2220 Pierce Ave,777 Preston Res Bldg, Nashville, TN 37232 USA. EM Emily.Chan@Vanderbilt.Edu FU Merck KGaA, Darmstadt, Germany; EMD Serono Inc.; US Affiliate of Merck KGaA, Darmstadt, Germany; National Center for Research Resources [UL1 RR024975-01]; National Center for Advancing Translational Sciences [2 UL1 TR000445-06] FX The authors would like to thank Alice S. Bexon, MBChB, Bexon Clinical Consulting, Montclair, NJ, USA, for her input provided for the study design and her contribution to the initiation of this trial. Editorial and medical writing support in the preparation of this manuscript was provided by Marianne Jenal-Eyholzer, PhD CMPP, TRM Oncology, The Hague, The Netherlands, funded by Merck KGaA, Darmstadt, Germany. The clinical trial was sponsored by EMD Serono Inc., the US Affiliate of Merck KGaA, Darmstadt, Germany. At Vanderbilt, this study was also supported by the National Center for Research Resources, Grant UL1 RR024975-01, and is now at the National Center for Advancing Translational Sciences, Grant 2 UL1 TR000445-06. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 26 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 EI 1432-0843 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD APR PY 2015 VL 75 IS 4 BP 701 EP 709 DI 10.1007/s00280-015-2682-2 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA CE1CI UT WOS:000351549100005 PM 25627002 ER PT J AU Lacouture, ME Morris, JC Lawrence, DP Tan, AR Olencki, TE Shapiro, GI Dezube, BJ Berzofsky, JA Hsu, FJ Guitart, J AF Lacouture, Mario E. Morris, John C. Lawrence, Donald P. Tan, Antoinette R. Olencki, Thomas E. Shapiro, Geoffrey I. Dezube, Bruce J. Berzofsky, Jay A. Hsu, Frank J. Guitart, Joan TI Cutaneous keratoacanthomas/squamous cell carcinomas associated with neutralization of transforming growth factor beta by the monoclonal antibody fresolimumab (GC1008) SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Transforming growth factor beta; GC1008; Fresolimumab; Keratoacanthoma; Squamous cell cancer ID TGF-BETA; RAS MUTATIONS; EXPRESSION; MELANOMA; BRAF; SKIN; MANIFESTATIONS; INHIBITORS; SORAFENIB; TISSUES AB Fresolimumab is an antibody capable of neutralizing all human isoforms of transforming growth factor beta (TGF beta) and has demonstrated anticancer activity in investigational studies. Inhibition of TGF beta by fresolimumab can potentially result in the development of cutaneous lesions. The aim of this study was to investigate the clinical, histological, and immunohistochemical characteristics of cutaneous neoplasms associated with fresolimumab. Skin biopsies (n = 24) were collected and analyzed from patients (n = 5) with treatment-emergent, cutaneous lesions arising during a phase 1 study of multiple doses of fresolimumab in patients (n = 29) with melanoma or renal cell carcinoma. Blinded, independent histological review and measurements of Ki-67, p53, and HPV integration were performed. Based on central review, four patients developed lesions with histological characteristics of keratoacanthomas, and of these patients, a single case of well-differentiated squamous cell carcinoma was also found. Expression of Ki-67, no evidence of p53 overexpression, and only focal positivity for human papillomavirus RNA by in situ hybridization in 4/18 cases were consistent with these findings. Following completion of fresolimumab, lesions spontaneously resolved. Therefore, benign, reversible keratoacanthomas were the most common cutaneous neoplasms observed, a finding of importance for adverse event monitoring, patient care, and optimization of therapies targeting TGF beta. C1 [Lacouture, Mario E.] Mem Sloan Kettering Canc Ctr, Dept Med, Dermatol Serv, Outpatient Ctr, New York, NY 10065 USA. [Morris, John C.; Berzofsky, Jay A.] NCI, Metab Branch & Vaccine Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Lawrence, Donald P.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Tan, Antoinette R.] Canc Inst New Jersey, Dept Med, New Brunswick, NJ USA. [Olencki, Thomas E.] Ohio State Univ, Dept Med, Columbus, OH 43210 USA. [Shapiro, Geoffrey I.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Dezube, Bruce J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Hsu, Frank J.] Genzyme Corp, Cambridge, MA USA. [Guitart, Joan] Northwestern Univ, Dept Dermatol, Chicago, IL 60611 USA. [Guitart, Joan] Northwestern Univ, Dept Pathol, Chicago, IL 60611 USA. RP Lacouture, ME (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Dermatol Serv, Outpatient Ctr, MSK 60th St,Suite 302, New York, NY 10065 USA. EM lacoutum@mskcc.org FU Genzyme Corporation; Intramural Research Program of the Center for Cancer Research, National Cancer Institute (NCI) FX This work was supported by Genzyme Corporation and in part by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute (NCI). NR 32 TC 13 Z9 13 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 EI 1432-0851 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD APR PY 2015 VL 64 IS 4 BP 437 EP 446 DI 10.1007/s00262-015-1653-0 PG 10 WC Oncology; Immunology SC Oncology; Immunology GA CE0SA UT WOS:000351514500005 PM 25579378 ER PT J AU Murphy, JM Guzman, J McCarthy, AE Squicciarini, A George, M Canenguez, K Dunn, E Baer, L Simonsohn, A Smoller, J Jellinek, M AF Murphy, J. Michael Guzman, Javier McCarthy, Alyssa E. Maria Squicciarini, Ana George, Myriam Canenguez, Katia M. Dunn, Erin C. Baer, Lee Simonsohn, Ariela Smoller, Jordan W. Jellinek, Michael S. TI Mental Health Predicts Better Academic Outcomes: A Longitudinal Study of Elementary School Students in Chile SO CHILD PSYCHIATRY & HUMAN DEVELOPMENT LA English DT Article DE Children; Mental health; Screening; School-based services; Low-income population ID PEDIATRIC SYMPTOM CHECKLIST; EDUCATIONAL-ATTAINMENT; PSYCHOSOCIAL DYSFUNCTION; BEHAVIORAL-PROBLEMS; MIDDLE SCHOOL; ADOLESCENTS; ACHIEVEMENT; DISORDERS; CHILDREN; CONSEQUENCES AB The world's largest school-based mental health program, Habilidades para la Vida [Skills for Life (SFL)], has been operating on a national scale in Chile for 15 years. SFL's activities include using standardized measures to screen elementary school students and providing preventive workshops to students at risk for mental health problems. This paper used SFL's data on 37,397 students who were in first grade in 2009 and third grade in 2011 to ascertain whether first grade mental health predicted subsequent academic achievement and whether remission of mental health problems predicted improved academic outcomes. Results showed that mental health was a significant predictor of future academic performance and that, overall, students whose mental health improved between first and third grade made better academic progress than students whose mental health did not improve or worsened. Our findings suggest that school-based mental health programs like SFL may help improve students' academic outcomes. C1 [Murphy, J. Michael; McCarthy, Alyssa E.; Canenguez, Katia M.; Baer, Lee; Jellinek, Michael S.] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. [Murphy, J. Michael; Dunn, Erin C.; Baer, Lee; Smoller, Jordan W.; Jellinek, Michael S.] Harvard Univ, Sch Med, Psychiat, Boston, MA USA. [Guzman, Javier; Maria Squicciarini, Ana; Simonsohn, Ariela] Junta Nacl Auxilio Escolar & Becas, Sch Hlth, Santiago, Chile. [Guzman, Javier] Univ Desarrollo, Psychol, Santiago, Chile. [George, Myriam] Univ Chile, Psychol, Santiago, Chile. [Dunn, Erin C.; Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Dunn, Erin C.; Smoller, Jordan W.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Smoller, Jordan W.] Harvard Univ, Ctr Dev Child, Cambridge, MA 02138 USA. [Jellinek, Michael S.] Harvard Univ, Sch Med, Pediat, Boston, MA USA. RP Murphy, JM (reprint author), Massachusetts Gen Hosp, Psychiat, Yawkey 6A, Boston, MA 02114 USA. EM mmurphy6@partners.org RI Guzman, Javier /E-8170-2016; OI Guzman, Javier /0000-0002-8194-039X; McCarthy, Anne/0000-0001-7195-6366 FU NIMH NIH HHS [K01 MH102403, L40 MH098379] NR 39 TC 4 Z9 4 U1 1 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-398X EI 1573-3327 J9 CHILD PSYCHIAT HUM D JI Child Psychiat. Hum. Dev. PD APR PY 2015 VL 46 IS 2 BP 245 EP 256 DI 10.1007/s10578-014-0464-4 PG 12 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA CD7QX UT WOS:000351287100008 PM 24771270 ER PT J AU Moradi, B Rosshirt, N Tripel, E Kirsch, J Barie, A Zeifang, F Gotterbarm, T Hagmann, S AF Moradi, B. Rosshirt, N. Tripel, E. Kirsch, J. Barie, A. Zeifang, F. Gotterbarm, T. Hagmann, S. TI Unicompartmental and bicompartmental knee osteoarthritis show different patterns of mononuclear cell infiltration and cytokine release in the affected joints SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE bicompartmental; inflammation; osteoarthritis; synovial membrane; unicompartmental ID HUMAN ARTICULAR CHONDROCYTES; SYNOVIAL-FLUID; RHEUMATOID-ARTHRITIS; T-CELLS; MATRIX METALLOPROTEINASES; CARTILAGE DEGRADATION; INNATE PRODUCTION; RECEPTOR 4; INFLAMMATION; MEMBRANE AB It is still controversial which cell types are responsible for synovial inflammation in osteoarthritic (OA) joints. The aim of this study was to quantify the mononuclear cell populations and their cytokines in patients with different knee OA subtypes. Synovial membrane (SM), synovial fluid (SF) and peripheral blood (PB) were harvested from patients with unicompartmental (UC) and bicompartmental (BC) knee OA. Frequencies of mononuclear cells were assessed by flow cytometry in PB and SM. Naive SF samples were analysed for a broad variety of cytokines by multiplex analysis. SM of both groups displayed a distinct mononuclear cell infiltration, with CD14(+) macrophages being the major cell population, followed by CD4(+) T cells and only small numbers of CD8(+) T, CD19(+) B and CD16(+)CD56(+) natural killer (NK) cells. Between the two groups, SM of BC OA showed significantly higher amounts of mononuclear cells (1357 +/- 180 versus 805 +/- 675 cells/mg, P=00009) and higher CD4(+) T cell presence (34 +/- 46 versus 91 +/- 75%, P=00267). SF of BC OA displayed significantly higher concentrations for a number of proinflammatory cytokines [CXCL1, eotaxin, interferon (IFN)-, interleukin (IL)-7, IL-8, IL-9, IL-12]. UC and BC OA show significant differences in their synovial inflammatory pattern. Whereas in UC OA CD14(+) macrophages are the predominant cell population, BC OA has a higher inflammatory profile and seems to be driven by CD14(+) macrophages and CD4(+) T cells. Inclusion of clinical information into the analysis of cellular and molecular results is pivotal in understanding the pathophysiology of OA. C1 [Moradi, B.; Rosshirt, N.; Tripel, E.; Kirsch, J.; Barie, A.; Zeifang, F.; Gotterbarm, T.; Hagmann, S.] Heidelberg Univ, Clin Orthoped & Traumatol, Heidelberg, Germany. [Hagmann, S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Hagmann, S (reprint author), Univ Heidelberg Hosp, Clin Orthoped & Traumatol, Schlierbacher Landstr 200a, D-69118 Heidelberg, Germany. EM sebastien.hagmann@med.uni-heidelberg.de OI Moradi, Babak/0000-0003-1714-2171 FU University of Heidelberg FX The University of Heidelberg funded this study. We are grateful for the technical support of Patrick Gothlich. NR 51 TC 10 Z9 10 U1 3 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9104 EI 1365-2249 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD APR PY 2015 VL 180 IS 1 BP 143 EP 154 DI 10.1111/cei.12486 PG 12 WC Immunology SC Immunology GA CD7BS UT WOS:000351245800015 PM 25393692 ER PT J AU Chak, A Buttar, NS Foster, NR Seisler, DK Marcon, NE Schoen, R Cruz-Correa, MR Falk, GW Sharma, P Hur, C Katzka, DA Rodriguez, LM Richmond, E Sharma, AN Smyrk, TC Mandrekar, SJ Limburg, PJ AF Chak, Amitabh Buttar, Navtej S. Foster, Nathan R. Seisler, Drew K. Marcon, Norman E. Schoen, Robert Cruz-Correa, Marcia R. Falk, Gary W. Sharma, Prateek Hur, Chin Katzka, David A. Rodriguez, Luz M. Richmond, Ellen Sharma, Anamay N. Smyrk, Thomas C. Mandrekar, Sumithra J. Limburg, Paul J. CA Canc Prevention Network TI Metformin Does Not Reduce Markers of Cell Proliferation in Esophageal Tissues of Patients With Barrett's Esophagus SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE HOMA-IR; Diabetes Drug; Cancer Development; Tumorigenesis ID CANCER STATISTICS; CENTRAL ADIPOSITY; INCREASED RISK; OBESITY; ADENOCARCINOMA; ASSOCIATION; INSULIN; METAANALYSIS; ADIPONECTIN; MORTALITY AB BACKGROUND & AIMS: Obesity is associated with neoplasia, possibly via insulin-mediated cell pathways that affect cell proliferation. Metformin has been proposed to protect against obesity-associated cancers by decreasing serum insulin. We conducted a randomized, double-blind, placebo-controlled, phase 2 study of patients with Barrett's esophagus (BE) to assess the effect of metformin on phosphorylated S6 kinase (pS6K1), a biomarker of insulin pathway activation. METHODS: Seventy-four subjects with BE (mean age, 58.7 years; 58 men [78%; 52 with BE >2 cm [70%]) were recruited through 8 participating organizations of the Cancer Prevention Network. Participants were randomly assigned to groups given metformin daily (increasing to 2000 mg/day by week 4, n = 38) or placebo (n = 36) for 12 weeks. Biopsy specimens were collected at baseline and at week 12 via esophagogastroduodenoscopy. We calculated and compared percent changes in median levels of pS6K1 between subjects given metformin vs placebo as the primary end point. RESULTS: The percent change in median level of pS6K1 did not differ significantly between groups (1.4% among subjects given metformin vs -14.7% among subjects given placebo; 1-sided P = .80). Metformin was associated with an almost significant reduction in serum levels of insulin (median -4.7% among subjects given metformin vs 23.6% increase among those given placebo, P = .08) as well as in homeostatic model assessments of insulin resistance (median -7.2% among subjects given metformin vs 38% increase among those given placebo, P = .06). Metformin had no effects on cell proliferation (on the basis of assays for KI67) or apoptosis (on the basis of levels of caspase 3). CONCLUSIONS: In a chemoprevention trial of patients with BE, daily administration of metformin for 12 weeks, compared with placebo, did not cause major reductions in esophageal levels of pS6K1. Although metformin reduced serum levels of insulin and insulin resistance, it did not discernibly alter epithelial proliferation or apoptosis in esophageal tissues. These findings do not support metformin as a chemopreventive agent for BE-associated carcinogenesis. C1 [Chak, Amitabh] Univ Hosp Case Med Ctr, Dept Gastroenterol & Hepatol, Cleveland, OH 44106 USA. [Buttar, Navtej S.; Katzka, David A.; Sharma, Anamay N.; Limburg, Paul J.] Mayo Clin, Dept Gastroenterol & Hepatol, Rochester, MN USA. [Foster, Nathan R.; Seisler, Drew K.; Mandrekar, Sumithra J.] Mayo Clin, Biomed Stat & Informat, Rochester, MN USA. [Smyrk, Thomas C.] Mayo Clin, Anat Pathol, Rochester, MN USA. [Marcon, Norman E.] St Michaels Hosp, Dept Med, Gastroenterol, Toronto, ON M5B 1W8, Canada. [Schoen, Robert] Univ Pittsburgh, Dept Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. [Cruz-Correa, Marcia R.] Univ Puerto Rico, UPR Canc Ctr, Dept Gastroenterol Oncol, San Juan, PR 00936 USA. [Falk, Gary W.] Univ Penn, Dept Gastroenterol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Sharma, Prateek] Kansas City VA, Dept Gastroenterol Hepatol & Motil, Kansas City, MO USA. [Hur, Chin] Massachusetts Gen Hosp, Dept Med, Gastroenterol, Boston, MA 02114 USA. [Rodriguez, Luz M.; Richmond, Ellen] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. RP Chak, A (reprint author), Univ Hosp Case Med Ctr, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM amitabh.chak@UHhospitals.org OI Falk, Gary/0000-0002-7143-1436; Hur, Chin/0000-0002-2819-7576 FU National Cancer Institute, Division of Cancer Prevention [N01-CN-35000]; National Center for Research Resources (NCRR) [1 UL1 RR024150-01]; National Institutes of Health (NIH); NIH Roadmap for Medical Research FX Supported by the National Cancer Institute, Division of Cancer Prevention, contract N01-CN-35000. The project was supported at the Mayo Clinic by grant number 1 UL1 RR024150-01 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and the NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. NR 44 TC 10 Z9 10 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD APR PY 2015 VL 13 IS 4 BP 665 EP + DI 10.1016/j.cgh.2014.08.040 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CD7UL UT WOS:000351299300012 PM 25218668 ER PT J AU Malhotra, R Turner, K Sonnenberg, A Genta, RM AF Malhotra, Reenu Turner, Kevin Sonnenberg, Amnon Genta, Robert M. TI High Prevalence of Inflammatory Bowel Disease in United States Residents of Indian Ancestry SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Ethnic Studies; Indian Immigrants; Lifestyle; Western; Latino ID REGIONAL DIFFERENCES; BARRETTS-ESOPHAGUS; POPULATION; EPIDEMIOLOGY; MANAGEMENT; RISK AB BACKGROUND & AIMS: It is unclear whether the reported low prevalence of inflammatory bowel disease (IBD) in Southern and Eastern Asia is real (caused by genetic or environmental factors) or spurious (because of differences in awareness of the condition among physicians or different interpretations of endoscopic and histologic features). We aimed to estimate the prevalence of IBD in patients of different ethnicities who underwent endoscopy in the United States, with ileocolonic biopsies evaluated by a single group of gastrointestinal pathologists. METHODS: We used a national pathology database to collect data on 1,027,977 subjects who underwent colonoscopy with ileocolonic biopsies from January 2008 through December 2013 throughout the United States; mucosal biopsy specimens were evaluated and reported by 1 group of 35 histopathologists. Patients were stratified into the following ancestries: Indian (persons with ancestry in the Indian subcontinent), East Asian (China, Korea, Japan, and Vietnam), Hispanic, Jewish, and Other. The prevalence of ulcerative colitis (UC), Crohn's disease (CD), and indeterminate colitis was determined for each ethnic group. RESULTS: In the study population, 30,812 patients were diagnosed with IBD (20,308 with UC, 7706 with CD, and 2798 with indeterminate colitis). UC was more commonly associated with Indian and Jewish ethnicity and less commonly associated with East Asian and Hispanic ethnicity. Similar patterns also applied to CD and to all types of IBD analyzed jointly. Among Indian patients, 11.7% of those of Gujarati origins had IBD, compared with 7.9% of other Indians (odds ratio, 1.5; 95% confidence interval, 1.14-2.11). CONCLUSIONS: Patients of Indian origin living in the United States have a greater risk for all types of IBD than other American populations. East Asians and Hispanics have a lower risk, possibly similar to that of the populations still living in their original countries. These findings may have relevance to the practice of gastroenterology in countries where there are sizable portions of the population with roots in the Indian subcontinent. C1 [Malhotra, Reenu; Turner, Kevin; Genta, Robert M.] Miraca Life Sci, Res Inst, Irving, TX 75039 USA. [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Genta, Robert M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Genta, Robert M.] Dallas VA Med Ctr, Dallas, TX USA. RP Genta, RM (reprint author), Miraca Life Sci, 6655 North MacArthur Blvd, Irving, TX 75039 USA. EM robert.genta@utsouthwestern.edu NR 22 TC 8 Z9 8 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD APR PY 2015 VL 13 IS 4 BP 683 EP 689 DI 10.1016/j.cgh.2014.06.035 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CD7UL UT WOS:000351299300014 PM 25083563 ER PT J AU Ananthakrishnan, AN AF Ananthakrishnan, Ashwin N. TI Association Between Reduced Plasma 25-Hydroxyvitamin D and Increased Risk of Cancer in Patients With Inflammatory Bowel Disease Reply SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Letter ID CROHNS-DISEASE; VITAMIN-D C1 [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.] Harvard Univ, Sch Med, Boston, MA USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD APR PY 2015 VL 13 IS 4 BP 814 EP 814 DI 10.1016/j.cgh.2015.01.001 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CD7UL UT WOS:000351299300035 PM 25576688 ER PT J AU Longoni, M Russell, MK High, FA Darvishi, K Maalouf, FI Kashani, A Tracy, AA Coletti, CM Loscertales, M Lage, K Ackerman, KG Woods, SA Ward-Melver, C Andrews, D Lee, C Pober, BR Donahoe, PK AF Longoni, M. Russell, M. K. High, F. A. Darvishi, K. Maalouf, F. I. Kashani, A. Tracy, A. A. Coletti, C. M. Loscertales, M. Lage, K. Ackerman, K. G. Woods, S. A. Ward-Melver, C. Andrews, D. Lee, C. Pober, B. R. Donahoe, P. K. TI Prevalence and penetrance of ZFPM2 mutations and deletions causing congenital diaphragmatic hernia SO CLINICAL GENETICS LA English DT Article DE congenital diaphragmatic hernia; DNA copy number variation; exome; FOG2; penetrance; ZFPM2 ID TETRALOGY; VARIANTS; DEFECTS; FALLOT; FOG2; GENE AB Zinc finger protein, FOG2 family member 2 (ZFPM2) (previously named FOG2) gene defects result in the highly morbid congenital diaphragmatic hernia (CDH) in humans and animal models. In a cohort of 275 CDH patient exomes, we estimated the prevalence of damaging ZFPM2 mutations to be almost 5%. Genetic analysis of a multigenerational family identified a heritable intragenic ZFPM2 deletion with an estimated penetrance of 37.5%, which has important implications for genetic counseling. Similarly, a low penetrance ZFPM2 frameshift mutation was observed in a second multiplex family. Isolated CDH was the predominant phenotype observed in our ZFPM2 mutation patients. Findings from the patients described herein indicate that ZFPM2 point mutations or deletions are a recurring cause of CDH. C1 [Longoni, M.; Russell, M. K.; High, F. A.; Maalouf, F. I.; Kashani, A.; Tracy, A. A.; Coletti, C. M.; Loscertales, M.; Lage, K.; Pober, B. R.; Donahoe, P. K.] Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. [Longoni, M.; Russell, M. K.; Loscertales, M.; Lage, K.; Donahoe, P. K.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [High, F. A.; Pober, B. R.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [High, F. A.] Boston Childrens Hosp, Div Genet, Dept Med, Boston, MA USA. [Darvishi, K.; Lee, C.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Darvishi, K.; Lee, C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Kashani, A.; Lage, K.; Donahoe, P. K.] Broad Inst, Cambridge, MA USA. [Ackerman, K. G.] Univ Rochester, Sch Med & Dent, Dept Pediat, Rochester, NY 14642 USA. [Ackerman, K. G.] Univ Rochester, Sch Med & Dent, Dept Biomed Genet, Rochester, NY USA. [Woods, S. A.; Ward-Melver, C.; Andrews, D.] Akron Childrens Hosp, Genet Ctr, Dept Pediat, Akron, OH USA. [Ward-Melver, C.] Northeast Ohio Med Univ, Rootstown, OH USA. [Lee, C.] Jackson Lab Genom Med, Farmington, CT USA. [Pober, B. R.] Boston Childrens Hosp, Dept Surg, Boston, MA USA. RP Longoni, M (reprint author), MassGen Hosp Children, Pediat Surg Res Labs, 185 Cambridge St, Boston, MA 02114 USA. EM mlongoni@partners.org FU NIH/NICHD [1 R01-HD055150, 1 P01-HD068250]; U.S. Federal Government from the NHLBI [HHSN268201100037C] FX Funding provided by NIH/NICHD 1 R01-HD055150 and 1 P01-HD068250. Resequencing was partially provided through the RS&G Service by the Northwest Genomics Center at the University of Washington, under U.S. Federal Government contract number HHSN268201100037C from the NHLBI. We thank the patients and their families for their support; Alison J. Pfeister, JD, for logistical assistance; Steve DePalma, PhD and Michael E. Talkowski, PhD, for bioinformatics guidance. NR 16 TC 4 Z9 4 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9163 EI 1399-0004 J9 CLIN GENET JI Clin. Genet. PD APR PY 2015 VL 87 IS 4 BP 362 EP 367 DI 10.1111/cge.12395 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA CE0ZN UT WOS:000351540700011 PM 24702427 ER PT J AU Courtney, KD Manola, JB Elfiky, AA Ross, R Oh, WK Yap, JT Van den Abbeele, AD Ryan, CW Beer, TM Loda, M Priolo, C Kantoff, P Taplin, ME AF Courtney, Kevin D. Manola, Judith B. Elfiky, Aymen A. Ross, Robert Oh, William K. Yap, Jeffrey T. Van den Abbeele, Annick D. Ryan, Christopher W. Beer, Tomasz M. Loda, Massimo Priolo, Carmen Kantoff, Philip Taplin, Mary-Ellen TI A Phase I Study of Everolimus and Docetaxel in Patients With Castration-Resistant Prostate Cancer SO CLINICAL GENITOURINARY CANCER LA English DT Article DE mTOR; PI3K; Positron emission tomography; Prostatic adenocarcinoma; PTEN ID POSITRON-EMISSION-TOMOGRAPHY; MAMMALIAN TARGET; TUMOR-SUPPRESSOR; RAPAMYCIN; MTOR; PATHWAY; INHIBITION; PTEN; AKT; GROWTH AB Activation of the phosphoinositide 3-kinase signaling cascade, often through loss of the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor, is frequent in castration-resistant prostate cancer (CRPC). We assessed the safety and efficacy of combining the mammalian target of rapamycin (mTOR) inhibitor everolimus with docetaxel in a phase I clinical trial of men with metastatic CRPC, and evaluated the ability of fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) to predict response to treatment. The observed clinical activity of tolerable dose levels of everolimus with docetaxel was low. FDG-PET might serve as a biomarker for target inhibition by mTOR inhibitors in metastatic CRPC. Background: The PTEN tumor suppressor is frequently lost in CRPC, with activation of Akt-mTOR signaling, driving growth. We conducted a phase 1 trial of the mTOR inhibitor, everolimus, and docetaxel in CRPC. Patients and Methods: Eligible patients had progressive, metastatic, chemotherapy-naive CRPC. Patients received everolimus 10 mg daily for 2 weeks and underwent a restaging FDG-PET/computed tomography scan. Patient cohorts were subsequently treated at 3 dose levels of everolimus with docetaxel: 5 mg to 60 mg/m(2), 10 mg to 60 mg/m(2), and 10 mg to 70 mg/m(2). The primary end point was the safety and tolerability of combination therapy. Results: Accrual was 4 patients at level 1, 3 patients at level 2, and 8 patients at level 3. Common toxicities were hematologic and fatigue. Serum concentrations of everolimus when administered with docetaxel were 1.5 to 14.8 ng/mL in patients receiving 5 mg everolimus and 4.5 to 55.4 ng/mL in patients receiving 10 mg everolimus. Four patients had partial metabolic response (PMR) using FDG-PET, 12 had stable metabolic disease, and 2 had progressive metabolic disease after a 2-week treatment with everolimus alone. Five of 12 evaluable patients experienced a prostate-specific antigen (PSA) reduction >= 50% during treatment with everolimus together with docetaxel. All 4 patients with a PMR according to PET imaging experienced a PSA reduction in response to everolimus with docetaxel, and 3 of 4 had PSA declines >= 50%. Conclusion: Everolimus 10 mg daily and docetaxel 60 mg/m(2) was safe in CRPC patients and these were the recommended doses in combination. FDG-PET response might serve as a biomarker for target inhibition by mTOR inhibitors. C1 [Courtney, Kevin D.; Elfiky, Aymen A.; Ross, Robert; Oh, William K.; Loda, Massimo; Priolo, Carmen; Kantoff, Philip; Taplin, Mary-Ellen] Harvard Univ, Sch Med, Dana Farber Canc Inst & Internal Med, Med Oncol, Boston, MA 02115 USA. [Manola, Judith B.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Manola, Judith B.; Yap, Jeffrey T.; Van den Abbeele, Annick D.; Loda, Massimo] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Yap, Jeffrey T.; Van den Abbeele, Annick D.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiol, Dept Imaging, Boston, MA 02115 USA. [Ryan, Christopher W.; Beer, Tomasz M.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Loda, Massimo] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Taplin, ME (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. EM Mary_Taplin@dfci.harvard.edu FU Novartis [CRAD001C2427]; Prostate Cancer Foundation [612200]; Sanofi [16176] FX Financial support was provided by Novartis (CRAD001C2427), Prostate Cancer Foundation (PS#612200) and Sanofi (IST#16176). NR 42 TC 9 Z9 11 U1 0 U2 4 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 EI 1938-0682 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD APR PY 2015 VL 13 IS 2 BP 113 EP 123 DI 10.1016/j.clgc.2014.08.007 PG 11 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA CD8GL UT WOS:000351333100002 PM 25450031 ER PT J AU Fay, AP Xie, WLL Lee, JL Harshman, LC Bjarnason, GA Knox, JJ Ernst, S Wood, L Vaishamayan, UN Yuasa, T Tan, MH Rha, SY Donskov, F Agarwal, N Kollmannsberger, CK North, SA Rini, BI Choueiri, TK Heng, DYC AF Fay, Andre P. Xie, Wanlin L. Lee, Jae-Lyn Harshman, Lauren C. Bjarnason, Georg A. Knox, Jennifer J. Ernst, Scott Wood, Lori Vaishamayan, Ulka N. Yuasa, Takeshi Tan, Mm-Han Rha, Sun-Young Donskov, Frede Agarwal, Neeraj Kollmannsberger, Christian K. North, Scott A. Rini, Brian I. Choueiri, Toni K. Heng, Daniel Y. C. TI Characteristics of Long-Term and Short-Term Survivors of Metastatic Renal Cell Carcinoma Treated With Targeted Therapies: Results From the International mRCC Database Consortium SO CLINICAL GENITOURINARY CANCER LA English DT Article DE Long-term survival; Overall survival; Primary refractory disease; Prognostic factors; Renal cell carcinoma; Targeted therapies ID INTERFERON-ALPHA; CLINICAL-TRIALS; SUNITINIB; PAZOPANIB AB Patients with mRCC may have variable clinical courses when treated with targeted therapy. The two extremes of the survival spectrum need to be characterized. Analyzing data from a large database (International Metastatic Renal Cell Carcinoma Database Consortium - IMDC) we found that baseline prognostic criteria and absence of PD after first- and second-line targeted therapy may discriminate long-term survival. Background: Targeted therapies improve survival in metastatic renal cell carcinoma (mRCC). However, survival patterns can be divergent, and patients at the 2 extremes of the survival spectrum need to be characterized. Patients and Methods: Data from 2161 patients included in the International mRCC Database Consortium (IMDC) were analyzed. We identified patients on the basis of their duration of survival. Long-term survival (LTS) was defined as overall survival (OS) of >= 4 years, and short-term survival (STS) was defined as OS of <= 6 months from the start of targeted therapy. Baseline characteristics, including demographic, clinicopathologic, and laboratory data, were compared between LTS and STS. Treatment response by the RECIST criteria was summarized for the 2 survival groups. Results: A total of 152 patients experienced LTS and 218 experienced STS. Adverse clinical and laboratory prognostic factors previously described in the IMDC prognostic model were significantly more frequent in the STS group (P < .0001). In the LTS group, 138 patients (91%) had nonprogressive disease (non-PD) as best response to first-line targeted therapy, and 56 (60%) of 94 patients who received second-line therapy had non-PD. In the STS group, only 51 patients (23%) had non-PD on first-line therapy. None of 21 the patients who received secondline therapy had non-PD as best response. In LTS, the median duration of therapy was 23.6 months (range 0.4 to 81.8+ months) for first-line therapy and 11.5 months (range 0.6 to 45.7 months) for second-line therapy, compared to 2.0 and 0.8 months for the STS group, respectively. Conclusion: Baseline prognostic criteria and absence of PD after. first and second-line targeted therapy may characterize long-term survival. C1 [Fay, Andre P.; Xie, Wanlin L.; Harshman, Lauren C.; Choueiri, Toni K.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Lee, Jae-Lyn] Univ Ulsan, Coll Med, Asan, South Korea. [Harshman, Lauren C.] Stanford Canc Inst, Stanford, CA USA. [Bjarnason, Georg A.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Knox, Jennifer J.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Ernst, Scott] London Hlth Sci Ctr, London, ON, Canada. [Wood, Lori] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [Vaishamayan, Ulka N.] Karmanos Canc Ctr, Detroit, MI USA. [Yuasa, Takeshi] Canc Inst Hosp, Japanese Fdn Canc Res, Tokyo, Japan. [Tan, Mm-Han] Natl Canc Ctr, Singapore, Singapore. [Rha, Sun-Young] Yonsei Univ, Coll Med, Yonsei Canc Ctr, Seoul 120749, South Korea. [Donskov, Frede] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. [Agarwal, Neeraj] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Kollmannsberger, Christian K.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [North, Scott A.] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. [Rini, Brian I.] Taussig Canc Inst, Cleveland Clin, Cleveland, OH USA. [Heng, Daniel Y. C.] Tom Baker Canc Clin, Calgary, AB, Canada. [Heng, Daniel Y. C.] Univ Calgary, Calgary, AB, Canada. RP Heng, DYC (reprint author), Univ Calgary, Tom Baker Canc Ctr, 1331 29th St NW, Calgary, AB T2N 4N2, Canada. EM daniel.heng@albertahealthservices.ca OI Donskov, Frede/0000-0002-8449-863X; Bjarnason, Georg Arnold/0000-0001-6903-5357 FU DF/HCC Kidney Cancer SPORE [P50 CA101942-01]; DF/HCC Kidney Cancer SPORE Fund; Trust Family Fund; Michael Brigham Fund FX This work was conducted as part of the IMDC database. We thank the DF/HCC Kidney Cancer SPORE, Trust Family, and the Michael Brigham Funds for Kidney Cancer Research (T.K.C.). This work was supported in part by DF/HCC Kidney Cancer SPORE P50 CA101942-01. NR 21 TC 1 Z9 2 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 EI 1938-0682 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD APR PY 2015 VL 13 IS 2 BP 150 EP 155 DI 10.1016/j.clgc.201.4.09.003 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA CD8GL UT WOS:000351333100007 PM 25458371 ER PT J AU Necchi, A Pond, GR Giannatempo, P Di Lorenzo, G Eigl, BJ Locke, J Pal, SK Agarwal, N Poole, A Vaishampayan, UN Niegisch, G Hussain, SA Singh, P Bellmunt, J Sonpavde, G AF Necchi, Andrea Pond, Gregory R. Giannatempo, Patrizia Di Lorenzo, Giusepe Eigl, Bernhard J. Locke, Jenn Pal, Sumanta K. Agarwal, Neeraj Poole, Austin Vaishampayan, Ulka N. Niegisch, Guenter Hussain, Syed A. Singh, Parminder Bellmunt, Joaquim Sonpavde, Guru TI Cisplatin-Based First-Line Therapy for Advanced Urothelial Carcinoma After Previous Perioperative Cisplatin-Based Therapy SO CLINICAL GENITOURINARY CANCER LA English DT Article DE Cisplatin; First-line; Pen-operative; Urothelial carcinoma ID INVASIVE BLADDER-CANCER; TRANSITIONAL-CELL CARCINOMA; PHASE-III TRIAL; LONG-TERM-SURVIVAL; NEOADJUVANT CHEMOTHERAPY; ADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIAL; PREDICTING SURVIVAL; PROGNOSTIC-FACTORS; PLUS CISPLATIN AB Longer time from previous perioperative chemotherapy (TFPC) >= 78 weeks and Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 0 were independently prognostic for better survival with cisplatin-based first-line chemotherapy for advanced urothelial carcinoma (UC) after previous perioperative cisplatin-based chemotherapy. Because of particularly poor outcomes in those with TFPC < 52 weeks, the data support using TFPC >= 52 weeks to rechallenge with cisplatin-based first-line chemotherapy for metastatic disease. Background: Outcomes with cisplatin-based first-line therapy for advanced UC after previous perioperative cisplatin-based chemotherapy are unclear. In this study we evaluated outcomes with a focus on the effect of time from previous cisplatin-based perioperative chemotherapy. Patients and Methods: Data were collected for patients who received cisplatin-based first-line therapy for advanced UC after previous perioperative cisplatin-based therapy. Cox proportional hazards models were used to investigate the prognostic ability of visceral metastasis, ECOG PS, TFPC, anemia, leukocytosis, and albumin on overall survival (OS). Results: Data were available for 41 patients from 8 institutions including 31 men (75.6%). The median age was 61 (range, 41-77) years, most received gemcitabine plus cisplatin (n = 26; 63.4%), and the median number of cycles was 4 (range, 1-8). The median OS was 68 weeks (95% confidence interval [CI], 48.0-81.0). Multivariable Cox regression analysis results showed an independent prognostic effect on OS for PS > 0 versus 0 (hazard ratio [HR], 4.56 [95% CI, 1.66-12.52]; P = .003) and TFPC >= 78 weeks versus < 78 weeks (HR, 0.48 [95% CI, 0.21-1.07]; P = .072). The prognostic model for OS was internally validated with c-index = 0.68. Patients with TFPC < 52 weeks, 52 to 104 weeks, and >= 104 weeks had median survival of 42, 70, and 162 weeks, respectively. Conclusion: Longer TFPC >= 78 weeks and ECOG PS = 0 were independently prognostic for better survival with cisplatin-based first-line chemotherapy for advanced UC after previous perioperative cisplatin-based chemotherapy. The data support using TFPC >= 52 weeks to rechallenge with cisplatin-based first-line chemotherapy for metastatic disease. C1 [Necchi, Andrea; Giannatempo, Patrizia] Fdn IRCCS Ist Nazl Tumori, Dept Med, Milan, Italy. [Pond, Gregory R.] McMaster Univ, Dept Stat, Hamilton, ON, Canada. [Di Lorenzo, Giusepe] Univ Naples Federico II, Dept Med, Naples, Italy. [Eigl, Bernhard J.; Locke, Jenn] British Columbia Canc Agcy, Dept Med, Vancouver, BC V5Z 4E6, Canada. [Pal, Sumanta K.] City Hope Canc Ctr, Dept Med, Duarte, CA USA. [Agarwal, Neeraj; Poole, Austin] Univ Utah, Huntsman Canc Inst, Dept Med, Salt Lake City, UT USA. [Vaishampayan, Ulka N.] Wayne State Univ, Ctr Canc, Dept Med, Detroit, MI USA. [Niegisch, Guenter] Univ Dusseldorf, Dept Urol, Dusseldorf, Germany. [Hussain, Syed A.] Univ Liverpool, Dept Med, Liverpool L69 3BX, Merseyside, England. [Singh, Parminder] Univ Arizona, Dept Med, Tucson, AZ USA. [Bellmunt, Joaquim] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Sonpavde, Guru] UAB, Comprehens Canc Ctr, Dept Med, Birmingham, AL 35294 USA. RP Sonpavde, G (reprint author), UAB, Comprehens Canc Ctr, 1802 6th Ave S,NP2540B, Birmingham, AL 35294 USA. EM gsonpavde@uabmc.edu OI Niegisch, Gunter/0000-0001-6929-8691; Necchi, Andrea/0000-0002-3007-2756 FU NCI NIH HHS [P30 CA022453] NR 33 TC 3 Z9 3 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 EI 1938-0682 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD APR PY 2015 VL 13 IS 2 BP 178 EP 184 DI 10.1016/j.clgc.2014.08.010 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA CD8GL UT WOS:000351333100011 PM 25450035 ER PT J AU Sonpavde, G Pond, GR Rosenberg, JE Bajorin, DF Regazzi, AM Choueiri, TK Qu, AQ Niegisch, G Albers, P Necchi, A Di Lorenzo, G Fougeray, R Dreicer, R Chen, YH Wong, YN Sridhar, SS Ko, YJ Milowsky, MI Galsky, MD Bellmunt, J AF Sonpavde, Guru Pond, Gregory R. Rosenberg, Jonathan E. Bajorin, Dean F. Regazzi, Ashley M. Choueiri, Toni K. Qu, Angela Q. Niegisch, Guenter Albers, Peter Necchi, Andrea Di Lorenzo, Giuseppe Fougeray, Ronan Dreicer, Robert Chen, Yu-Hui Wong, Yu-Ning Sridhar, Srikala S. Ko, Yoo-Joung Milowsky, Matthew I. Galsky, Matthew D. Bellmunt, Joaquim TI Complete Response as an Intermediate End Point in Patients Receiving Salvage Systemic Therapy for Urothelial Carcinoma sdfhzdfh SO CLINICAL GENITOURINARY CANCER LA English DT Article DE Advanced urothelial carcinoma; Complete response; Overall survival; Partial response; Progression-free survival; Salvage systemic therapy ID BLADDER-CANCER PATIENTS; TRANSITIONAL-CELL CARCINOMA; PLATINUM-CONTAINING REGIMEN; PHASE-III TRIAL; PRIOR CHEMOTHERAPY; 2ND-LINE TREATMENT; SOLID TUMORS; SINGLE GROUP; PACLITAXEL; VINFLUNINE AB In this retrospective analysis, complete remission (CR) of disease occurred in 1.8% of patients receiving salvage systemic therapy for advanced urothelial carcinoma. CR was strongly associated with longer survival, prior cisplatin therapy, and time from prior chemotherapy of 3 months. Agents inducing CR as salvage therapy should undergo further development, and tumors of patients showing CR should be selected for molecular profiling. Background: The complete remission (CR) rate with salvage systemic therapy for urothelial carcinoma (UC) is unclear, and its value as an intermediate end point and association with survival are unknown. Materials and Methods: Data from phase II trials of salvage chemotherapy and/or biologic agents were pooled. Data regarding response, overall survival (OS), progression-free survival (PFS), time from prior chemotherapy, hemoglobin, performance status, and liver metastasis status were collected. Cox proportional hazards regression was used to evaluate the association of CR and other prognostic factors with outcomes. Results: A total of 789 of 818 patients enrolled in 12 phase II trials had evaluable data. CR and partial response were seen in 14 (1.8%) and 109 (13.8%) patients. Median (95% confidence interval) OS for those with a CR was 21.5 (14.2-34.3) months, compared with 6.7 (6.0-7.0) months in those without a CR (P < .001). Median (95% confidence interval) PFS for those with a CR was 15.7 (8.2-27.1) months, compared with 2.6 (2.4-2.8) months for those without a CR (P < .001). Prior cisplatin and time from prior chemotherapy of >= 3 months were associated with CR (P < .05). The presence of poor prognostic factors and suboptimal response to prior therapy did not preclude CR. Conclusion: CR occurs in 1.8% of patients receiving salvage therapy for advanced UC and is strongly associated with durable OS and PFS. CR warrants validation as an intermediate end point and may help select agents for further investigation and tumors for molecular interrogation. C1 [Sonpavde, Guru] UAB, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Pond, Gregory R.] McMaster Univ, Hamilton, ON L8S 4L8, Canada. [Rosenberg, Jonathan E.; Bajorin, Dean F.; Regazzi, Ashley M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Choueiri, Toni K.; Qu, Angela Q.; Chen, Yu-Hui; Bellmunt, Joaquim] Dana Farber Canc Inst, Boston, MA 02115 USA. [Choueiri, Toni K.; Qu, Angela Q.; Chen, Yu-Hui] Harvard Univ, Sch Med, Boston, MA USA. [Niegisch, Guenter; Albers, Peter] Univ Dusseldorf, Dusseldorf, Germany. [Necchi, Andrea] Fdn IRCCS Ist Nazl Tumori, Milan, Italy. [Di Lorenzo, Giuseppe] Univ Naples Federico II, Naples, Italy. [Fougeray, Ronan] Inst Rech Pierre Fabre, Boulogne, France. [Dreicer, Robert] Cleveland Clin, Cleveland, OH 44106 USA. [Wong, Yu-Ning] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Sridhar, Srikala S.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Ko, Yoo-Joung] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Milowsky, Matthew I.] Univ N Carolina, Chapel Hill, NC USA. [Galsky, Matthew D.] Mt Sinai Sch Med, Tisch Canc Ctr Inst, New York, NY USA. [Bellmunt, Joaquim] Univ Hosp Mar IMIM, Barcelona, Spain. RP Sonpavde, G (reprint author), UAB, Ctr Comprehens Canc, 1802-6th Ave S,NP2540B, Birmingham, AL 35294 USA. EM gsonpavde@uabmc.edu RI Mendez, Pedro /J-8955-2016 OI Mendez, Pedro /0000-0001-6713-7907 FU Boehringer-Ingelheim; Onyx; Sanofi-Aventis; Novartis; Astrazeneca; Pierre-Fabre; BMS; Celgene; GSK; Eli-Lilly FX G.S. received research support to institution from Boehringer-Ingelheim, Onyx, Sanofi-Aventis; J.E.R., D.F.B., A.M.R., and M.I.M. received research support to institution from Novartis; R.F. is an employee of Pierre-Fabre; T.K.C. and A.Q.Q. received research support to institution from Astrazeneca; J.M.B. received research support to institution from Pierre-Fabre; Y.N.W. received research support from BMS; S.S. received research support to institution from Celgene; Y.J.K. received research support to institution from Celgene; A.N. received research support and consultant for GSK; M.D.G. received research support to institution from Eli-Lilly; G.N. received research support to institution from Eli Lilly and BMS; and P.A. received research support to institution from Eli Lilly and BMS. G.R.P., G.D.L., R.D., and Y.H.C. declare that they have no conflict of interest. NR 31 TC 2 Z9 2 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 EI 1938-0682 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD APR PY 2015 VL 13 IS 2 BP 185 EP 192 DI 10.1016/j.clgc.2014.09.004 PG 8 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA CD8GL UT WOS:000351333100012 PM 25458370 ER PT J AU Hoge, EA Bui, E Goetter, E Robinaugh, DJ Ojserkis, RA Fresco, DM Simon, NM AF Hoge, Elizabeth A. Bui, Eric Goetter, Elizabeth Robinaugh, Donald J. Ojserkis, Rebecca A. Fresco, David M. Simon, Naomi M. TI Change in Decentering Mediates Improvement in Anxiety in Mindfulness-Based Stress Reduction for Generalized Anxiety Disorder SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE Mindfulness-based stress reduction; Mindfulness meditation; Generalized anxiety disorder; Decentering ID RANDOMIZED CONTROLLED-TRIAL; PSYCHOMETRIC PROPERTIES; CHRONIC PAIN; DEPRESSION; QUESTIONNAIRE; THERAPY; METAANALYSIS; MEDITATION; REACTIVITY; PROGRAM AB We sought to examine psychological mechanisms of treatment outcomes of a mindfulness meditation intervention for generalized anxiety disorder (GAD). We examined mindfulness and decentering as two potential therapeutic mechanisms of action of GAD symptom reduction in patients randomized to receive either mindfulness-based stress reduction (MBSR) or an attention control class (N = 38). Multiple mediation analyses were conducted using a non-parametric cross product of the coefficients approach that employs bootstrapping. Analyses revealed that change in decentering and change in mindfulness significantly mediated the effect of MBSR on anxiety. When both mediators were included in the model, the multiple mediation analysis revealed a significant indirect effect through increases in decentering, but not mindfulness. Furthermore, the direct effect of MBSR on decrease in anxiety was not significant, suggesting that decentering fully mediated the relationship. Results also suggested that MBSR reduces worry through an increase in mindfulness, specifically by increases in awareness and nonreactivity. Improvements in GAD symptoms resulting from MBSR are in part explained by increased levels of decentering. C1 [Hoge, Elizabeth A.; Bui, Eric; Goetter, Elizabeth; Robinaugh, Donald J.; Ojserkis, Rebecca A.; Simon, Naomi M.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. [Fresco, David M.] Kent State Univ, Dept Psychol, Kent, OH 44242 USA. RP Hoge, EA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. EM ehoge@partners.org RI Bui, Eric/J-8347-2015; Hoge, Elizabeth/H-5879-2012; OI Bui, Eric/0000-0002-1413-6473; Hoge, Elizabeth/0000-0002-5513-2292; Fresco, David/0000-0001-6736-3912 FU National Center on Complementary and Alternative Medicine, National Institutes of Health [K23AT4432]; Highland Street Foundation FX This study was primarily supported by Grant K23AT4432 from the National Center on Complementary and Alternative Medicine, National Institutes of Health (Hoge, P.I.). The Highland Street Foundation provided additional support to Drs. Simon and Bui. NR 41 TC 11 Z9 11 U1 0 U2 30 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 EI 1573-2819 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD APR PY 2015 VL 39 IS 2 BP 228 EP 235 DI 10.1007/s10608-014-9646-4 PG 8 WC Psychology, Clinical SC Psychology GA CD9BW UT WOS:000351392500012 PM 28316355 ER PT J AU Farris, SG Langdon, KJ DiBello, AM Zvolensky, MJ AF Farris, Samantha G. Langdon, Kirsten J. DiBello, Angelo M. Zvolensky, Michael J. TI Why Do Anxiety Sensitive Smokers Perceive Quitting as Difficult? The Role of Expecting "Interoceptive Threat" During Acute Abstinence SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE Anxiety sensitivity; Abstinence; Expectancies; Cessation ID SMOKING-CESSATION; NEGATIVE AFFECT; DISTRESS TOLERANCE; BODILY SENSATIONS; SYMPTOM SEVERITY; PANIC DISORDER; EXPECTANCIES; QUESTIONNAIRE; VALIDATION; PREDICTION AB There is a growing literature that documents the direct and indirect effects of anxiety sensitivity in terms of the maintenance of cigarette smoking and cessation problems, as maintained, at least in part, by affective-regulatory expectancies effects and motives for smoking. Yet, the role of expectancies about the interoceptive-specific consequences of smoking abstinence has yet to be empirically examined. Participants (N = 110) were daily tobacco smokers recruited as part of a self-guided tobacco cessation study. Baseline (pre-treatment) data were utilized. A structural equation model was constructed to examine the relations between anxiety sensitivity in terms of interoceptively-relevant smoking abstinence expectancies (somatic symptoms and harmful consequences) in regard to perceived barriers to smoking cessation, number of problematic symptoms experienced during past quit attempts, and the number of prior quit attempts. Anxiety sensitivity was significantly related to interoceptive threat abstinence expectancies (beta = .56, p < .001). Expectancies were directly related to perceived barriers to smoking cessation (beta = .39, p < .001) and number of problematic symptoms experienced during past quit attempts (beta = .41, p < .001), but not the number of prior quit attempts. Mediational results indicated indirect (but not direct) effects of anxiety sensitivity on perceived barriers to smoking cessation and problems during prior quit attempts; effects that occurred through interoceptive threat smoking abstinence expectancies. The present findings suggest that one's expectancies about the negative interoceptive consequences of smoking abstinence may be an explanatory mechanism between anxiety sensitivity and certain quit-relevant smoking processes. C1 [Farris, Samantha G.; DiBello, Angelo M.; Zvolensky, Michael J.] Univ Houston, Dept Psychol, Houston, TX 77204 USA. [Langdon, Kirsten J.] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Langdon, Kirsten J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Zvolensky, Michael J.] Univ Texas MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77030 USA. RP Farris, SG (reprint author), Univ Houston, Dept Psychol, 126 Fred J Heyne Bldg,Suite 104, Houston, TX 77204 USA. EM sgfarris@uh.edu FU pre-doctoral National Research Service Award from the National Institute of Drug Abuse [F31-DA026634, F31-DA035564] FX This work was supported by a pre-doctoral National Research Service Award from the National Institute of Drug Abuse awarded to Dr. Langdon (F31-DA026634). Ms. Farris acknowledges support from a pre-doctoral National Research Service Award from the National Institute of Drug Abuse (F31-DA035564). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the Department of Veterans Affairs, or the United States Government, and the funding sources had no other role than financial support. NR 42 TC 5 Z9 5 U1 1 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 EI 1573-2819 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD APR PY 2015 VL 39 IS 2 BP 236 EP 244 DI 10.1007/s10608-014-9644-6 PG 9 WC Psychology, Clinical SC Psychology GA CD9BW UT WOS:000351392500013 ER PT J AU Aloi, JA Mulla, C Ullal, J Lieb, DC AF Aloi, Joseph A. Mulla, Christopher Ullal, Jagdeesh Lieb, David C. TI Improvement in Inpatient Glycemic Care: Pathways to Quality SO CURRENT DIABETES REPORTS LA English DT Article DE Inpatient; Glycemic control; Hyperglycemia; Hypoglycemia; Insulin dosing algorithms; Glucometrics ID SLIDING-SCALE INSULIN; SUBCUTANEOUS INSULIN; GLUCOSE MANAGEMENT; MEDICAL RESIDENTS; DIABETES CARE; PROTOCOL; CONFIDENCE; EDUCATION; IMPLEMENTATION; HYPERGLYCEMIA AB The management of inpatient hyperglycemia is a focus of quality improvement projects across many hospital systems while remaining a point of controversy among clinicians. The association of inpatient hyperglycemia with suboptimal hospital outcomes is accepted by clinical care teams; however, the clear benefits of targeting hyperglycemia as a mechanism to improve hospital outcomes remain contentious. Glycemic management is also frequently confused with efforts aimed at intensive glucose control, further adding to the confusion. Nonetheless, several regulatory agencies assign quality rankings based on attaining specified glycemic targets for selected groups of patients (Surgical Care Improvement Project (SCIP) measures). The current paper reviews the data supporting the benefits associated with inpatient glycemic control projects, the components of a successful glycemic control intervention, and utilization of the electronic medical record in implementing an inpatient glycemic control project. C1 [Aloi, Joseph A.; Ullal, Jagdeesh; Lieb, David C.] Eastern Virginia Med Sch, Div Endocrinol & Metab, Norfolk, VA 23510 USA. [Mulla, Christopher] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. RP Aloi, JA (reprint author), Eastern Virginia Med Sch, Div Endocrinol & Metab, 855 W Brambleton Ave, Norfolk, VA 23510 USA. EM aloija@evms.edu; mullacm@gmail.com; ullalj@evms.edu; liebdc@evms.edu OI Ullal, Jagdeesh/0000-0001-6475-5240 NR 37 TC 0 Z9 0 U1 1 U2 5 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 EI 1539-0829 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD APR PY 2015 VL 15 IS 4 AR 18 DI 10.1007/s11892-015-0587-4 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CD7TV UT WOS:000351296800004 PM 25715828 ER PT J AU Segre, AV Wei, N Altshuler, D Florez, JC AF Segre, Ayellet V. Wei, Nancy Altshuler, David Florez, Jose C. CA DIAGRAM Consortium MAGIC Investigators TI Pathways Targeted by Antidiabetes Drugs Are Enriched for Multiple Genes Associated With Type 2 Diabetes Risk SO DIABETES LA English DT Article ID LARGE-SCALE ASSOCIATION; GENOME-WIDE ASSOCIATION; COMMON VARIANTS; SUSCEPTIBILITY LOCI; INSULIN-RESISTANCE; GLYCEMIC TRAITS; PPAR-GAMMA; GLUCOSE; METFORMIN; MECHANISM AB Genome-wide association studies (GWAS) have uncovered >65 common variants associated with type 2 diabetes (T2D); however, their relevance for drug development is not yet clear. Of note, the first two T2D-associated loci (PPARG and KCNJ11/ABCC8) encode known targets of antidiabetes medications. We therefore tested whether other genes/pathways targeted by antidiabetes drugs are associated with T2D. We compiled a list of 102 genes in pathways targeted by marketed antidiabetic medications and applied Gene Set Enrichment Analysis (MAGENTA [Meta-Analysis Gene-set Enrichment of variaNT Associations]) to this gene set, using available GWAS meta-analyses for T2D and seven quantitative glycemic traits. We detected a strong enrichment of drug target genes associated with T2D (P = 2 x 10(-5); 14 potential new associations), primarily driven by insulin and thiazolidinedione (TZD) targets, which was replicated in an independent meta-analysis (Metabochip). The glycemic traits yielded no enrichment. The T2D enrichment signal was largely due to multiple genes of modest effects (P = 4 x 10(-4), after removing known loci), highlighting new associations for follow-up (ACSL1, NFKB1, SLC2A2, incretin targets). Furthermore, we found that TZD targets were enriched for LDL cholesterol associations, illustrating the utility of this approach in identifying potential side effects. These results highlight the potential biomedical relevance of genes revealed by GWAS and may provide new avenues for tailored therapy and T2D treatment design. C1 [Segre, Ayellet V.; Altshuler, David; Florez, Jose C.] Broad Inst Harvard & Massachusetts Inst Technol, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Segre, Ayellet V.; Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Wei, Nancy; Altshuler, David; Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA. [Wei, Nancy; Altshuler, David; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Altshuler, David; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Altshuler, David] MIT, Dept Biol, Cambridge, MA USA. RP Florez, JC (reprint author), Broad Inst Harvard & Massachusetts Inst Technol, Program Med & Populat Genet, Cambridge, MA 02142 USA. EM jcflorez@partners.org FU American Diabetes Association; National Institute of Diabetes and Digestive and Kidney Diseases [T32-DK-007028]; Doris Duke Clinical Scientist Development Award; Massachusetts General Hospital FX For this project, A.V.S. and D.A. were supported by the American Diabetes Association Mentor-Based Postdoctoral Fellowship, N.W. by the National Institute of Diabetes and Digestive and Kidney Diseases training grant T32-DK-007028, and J.C.F. by a Doris Duke Clinical Scientist Development Award, a Massachusetts General Hospital Physician-Scientist Development Award, and the Massachusetts General Hospital Research Scholars Award. NR 49 TC 10 Z9 10 U1 2 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD APR PY 2015 VL 64 IS 4 BP 1470 EP 1483 DI 10.2337/db14-0703 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CE2CA UT WOS:000351619300039 PM 25368101 ER PT J AU Welch, G Zagarins, SE Santiago-Kelly, P Rodriguez, Z Bursell, SE Rosal, MC Gabbay, RA AF Welch, Garry Zagarins, Sofija E. Santiago-Kelly, Paula Rodriguez, Zoraida Bursell, Sven-Erik Rosal, Milagros C. Gabbay, Robert A. TI An Internet-Based Diabetes Management Platform Improves Team Care and Outcomes in an Urban Latino Population SO DIABETES CARE LA English DT Article ID COMMUNITY-HEALTH WORKERS; DECISION-SUPPORT; PROGRAM; PEOPLE AB OBJECTIVETo compare usual diabetes care (UDC) to a comprehensive diabetes care intervention condition (IC) involving an Internet-based diabetes dashboard management tool used by clinicians.RESEARCH DESIGN AND METHODSWe used a parallel-group randomized design. Diabetes nurses, diabetes dietitians, and providers used the diabetes dashboard as a clinical decision support system to deliver a five-visit, 6-month intervention to 199 poorly controlled (HbA(1c) >7.5% [58 mmol/mol]) Latino type 2 diabetic (T2D) patients (mean age 55 years, 60% female) at urban community health centers. We compared this intervention to an established, in-house UDC program (n = 200) for its impact on blood glucose control and psychosocial outcomes.RESULTSRecruitment and retention rates were 79.0 and 88.5%, respectively. Compared with UDC, more IC patients reached HbA(1c) targets of <7% (53 mmol/mol; 15.8 vs. 7.0%, respectively, P < 0.01) and <8% (64 mmol/mol; 45.2 vs. 25.3%, respectively, P < 0.001). In multiple linear regression adjusting for baseline HbA(1c), adjusted mean SE HbA(1c) at follow-up was significantly lower in the IC compared with the UDC group (P < 0.001; IC 8.4 +/- 0.10%; UDC 9.2 +/- 0.10%). The results showed lower diabetes distress at follow-up for IC patients (40.4 +/- 2.1) as compared with UDC patients (48.3 +/- 2.0) (P < 0.01), and also lower social distress (32.2 +/- 1.3 vs. 27.2 +/- 1.4, P < 0.01). There was a similar, statistically significant (P < 0.01) improvement for both groups in the proportion of patients moving from depressed status at baseline to nondepressed at follow-up (41.8 vs. 40%; no significance between groups).CONCLUSIONSThe diabetes dashboard intervention significantly improved diabetes-related outcomes among Latinos with poorly controlled T2D compared with a similar diabetes team condition without access to the diabetes dashboard. C1 [Welch, Garry; Zagarins, Sofija E.; Santiago-Kelly, Paula; Rodriguez, Zoraida] Baystate Med Ctr, Behav Med Res, Springfield, MA 01199 USA. [Bursell, Sven-Erik] Univ Hawaii Manoa, Honolulu, HI 96822 USA. [Rosal, Milagros C.] Univ Massachusetts, Sch Med, Div Prevent & Behav Med, Worcester, MA USA. [Gabbay, Robert A.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Welch, G (reprint author), Baystate Med Ctr, Behav Med Res, Springfield, MA 01199 USA. EM garry@silverfernhealthcare.com FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health [5R01-DK-084325-04] FX This project was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, through grant 5R01-DK-084325-04. NR 35 TC 2 Z9 2 U1 1 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD APR PY 2015 VL 38 IS 4 BP 561 EP 567 DI 10.2337/dc14-1412 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CE2FX UT WOS:000351630900016 PM 25633661 ER PT J AU Thorpe, CT Gellad, WF Good, CB Zhang, SJ Zhao, XH Mor, M Fine, MJ AF Thorpe, Carolyn T. Gellad, Walid F. Good, Chester B. Zhang, Sijian Zhao, Xinhua Mor, Maria Fine, Michael J. TI Tight Glycemic Control and Use of Hypoglycemic Medications in Older Veterans With Type 2 Diabetes and Comorbid Dementia SO DIABETES CARE LA English DT Article ID ADMINISTRATIVE DATA; MELLITUS; COHORT; ADULTS; SURVIVAL; RISK; OVERTREATMENT; PREVALENCE; DIAGNOSIS; DISEASE AB OBJECTIVEOlder adults with diabetes and dementia are at increased risk for hypoglycemia and other adverse events associated with tight glycemic control and are unlikely to experience long-term benefits. We examined risk factors for tight glycemic control in this population and use of medications associated with a high risk of hypoglycemia in the subset with tight control.RESEARCH DESIGN AND METHODSThis retrospective cohort study of national Veterans Affairs (VA) administrative/clinical data and Medicare claims for fiscal years (FYs) 2008-2009 included 15,880 veterans aged 65 years with type 2 diabetes and dementia and prescribed antidiabetic medication. Multivariable regression analyses were used to identify sociodemographic and clinical predictors of hemoglobin A(1c) (HbA(1c)) control (tight, moderate, poor, or not monitored) and, in patients with tight control, subsequent use of medication associated with a high risk of hypoglycemia (sulfonylureas, insulin).RESULTSFifty-two percent of patients had tight glycemic control (HbA(1c) <7% [53 mmol/mol]). Specific comorbidities, older age, and recent weight loss were associated with greater odds of tight versus moderate control, whereas Hispanic ethnicity and obesity were associated with lower odds of tight control. Among tightly controlled patients, 75% used sulfonylureas and/or insulin, with higher odds in patients who were male, black, or aged 75 years; had a hospital or nursing home stay in FY2008; or had congestive heart failure, renal failure, or peripheral vascular disease.CONCLUSIONSMany older veterans with diabetes and dementia are at high risk for hypoglycemia associated with intense diabetes treatment and may be candidates for deintensification or alteration of diabetes medications. C1 [Thorpe, Carolyn T.; Gellad, Walid F.; Good, Chester B.; Zhang, Sijian; Zhao, Xinhua; Mor, Maria; Fine, Michael J.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Thorpe, Carolyn T.; Good, Chester B.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Gellad, Walid F.; Good, Chester B.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. [Good, Chester B.; Zhao, Xinhua] Vet Affairs Pharm Benefits Management, Chicago, IL USA. [Mor, Maria] Univ Pittsburgh, Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15260 USA. RP Thorpe, CT (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. EM ctthorpe@pitt.edu FU VA Health Services Research Development [CIN 13-405]; VA Health Services Research & Development Career Development Award [CDA 09-207] FX C.T.T., S.Z., M.M., and M.J.F. are supported by VA Health Services Research & Development (CIN 13-405). W.F.G. is supported by a VA Health Services Research & Development Career Development Award (CDA 09-207). NR 32 TC 8 Z9 8 U1 3 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD APR PY 2015 VL 38 IS 4 BP 588 EP 595 DI 10.2337/dc14-0599 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CE2FX UT WOS:000351630900020 PM 25592195 ER PT J AU Ardestani, A Rhoads, D Tavakkoli, A AF Ardestani, Ali Rhoads, David Tavakkoli, Ali TI Insulin Cessation and Diabetes Remission After Bariatric Surgery in Adults With Insulin-Treated Type 2 Diabetes SO DIABETES CARE LA English DT Article ID Y GASTRIC BYPASS; OUTCOMES LONGITUDINAL DATABASE; METABOLIC SYNDROME; MEDICAL THERAPY; MELLITUS; WEIGHT; OBESITY; HYPERTENSION AB OBJECTIVEThe impact of bariatric surgeries on insulin-treated type 2 diabetes (I-T2D) in the general population is largely undocumented. We assessed changes in insulin treatment after bariatric surgery in a large cohort of I-T2D patients, comparing Roux-en-Y gastric bypass surgery (RYGB) with laparoscopic adjustable gastric banding (LAGB), controlling for differences in weight loss between procedures.RESEARCH DESIGN AND METHODSOf 113,638 adult surgical patients in the Bariatric Outcomes Longitudinal Database (BOLD), 10% had I-T2D. Analysis was restricted to 5,225 patients with I-T2D and at least 1 year of postoperative follow-up. Regression models were used to identify factors that predict cessation of insulin therapy. To control for differences in weight loss patterns between RYGB and LAGB, a case-matched analysis was also performed.RESULTSOf I-T2D patients who underwent RYGB (n = 3,318), 62% were off insulin at 12 months compared with 34% (n = 1,907) after LAGB (P < 0.001). Regression analysis indicated that RYGB strongly predicted insulin cessation at both 1 and 12 months postoperatively. In the case-matched analysis at 3 months, the proportion of insulin cessation was significantly higher in the RYGB group than in the LAGB group (P = 0.03), and the diabetes remission rate was higher at all time points after this surgery. RYGB was a weight-independent predictor of insulin therapy cessation early after surgery, whereas insulin cessation after LAGB was linked to weight loss.CONCLUSIONSI-T2D patients have a greater probability of stopping insulin after RYGB than after LAGB (62% vs. 34%, respectively, at 1 year), with weight-independent effects in the early months after surgery. These findings support RYGB as the procedure of choice for reversing I-T2D. C1 [Ardestani, Ali; Tavakkoli, Ali] Harvard Univ, Sch Med, Dept Surg, Brigham & Womens Hosp, Boston, MA 02115 USA. [Rhoads, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Endocrine Unit, Boston, MA USA. [Tavakkoli, Ali] Harvard Univ, Brigham & Womens Hosp, Ctr Weight Management & Metab Surg, Boston, MA 02115 USA. RP Tavakkoli, A (reprint author), Harvard Univ, Sch Med, Dept Surg, Brigham & Womens Hosp, Boston, MA 02115 USA. EM atavakkoli@partners.org NR 36 TC 9 Z9 10 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD APR PY 2015 VL 38 IS 4 BP 659 EP 664 DI 10.2337/dc14-1751 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CE2FX UT WOS:000351630900029 PM 25573879 ER PT J AU Udell, JA Bhatt, DL Braunwald, E Cavender, MA Mosenzon, O Steg, PG Davidson, JA Nicolau, JC Corbalan, R Hirshberg, B Frederich, R Im, K Umez-Eronini, AA He, P McGuire, DK Leiter, LA Raz, I Scirica, BM AF Udell, Jacob A. Bhatt, Deepak L. Braunwald, Eugene Cavender, Matthew A. Mosenzon, Ofri Steg, Ph. Gabriel Davidson, Jaime A. Nicolau, Jose C. Corbalan, Ramon Hirshberg, Boaz Frederich, Robert Im, KyungAh Umez-Eronini, Amarachi A. He, Ping McGuire, Darren K. Leiter, Lawrence A. Raz, Itamar Scirica, Benjamin M. CA SAVOr-TIMI 53 Steering Comm TI Saxagliptin and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Moderate or Severe Renal Impairment: Observations From the SAVOR-TIMI 53 Trial SO DIABETES CARE LA English DT Article ID CHRONIC KIDNEY-DISEASE; CLINICAL-PRACTICE GUIDELINE; REGRESSION-MODELS; HEART-FAILURE; MORTALITY; METFORMIN; MELLITUS; EVENTS; POPULATION; HYPERGLYCEMIA AB OBJECTIVEThe glycemic management of patients with type 2 diabetes mellitus (T2DM) and renal impairment is challenging, with few treatment options. We investigated the effect of saxagliptin in the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR)-Thrombolysis in Myocardial Infarction (TIMI) 53 trial according to baseline renal function.RESEARCH DESIGN AND METHODSPatients with T2DM at risk for cardiovascular events were stratified as having normal or mildly impaired renal function (estimated glomerular filtration rate [eGFR] >50 mL/min/1.73 m(2); n = 13,916), moderate renal impairment (eGFR 30-50 mL/min/1.73 m(2); n = 2,240), or severe renal impairment (eGFR <30 mL/min/1.73 m(2); n = 336) and randomized to receive saxagliptin or placebo. The primary end point was cardiovascular death, myocardial infarction, or ischemic stroke.RESULTSAfter a median duration of 2 years, saxagliptin neither increased nor decreased the risk of the primary and secondary composite end points compared with placebo, irrespective of renal function (all P for interactions 0.19). Overall, the risk of hospitalization for heart failure among the three eGFR groups of patients was 2.2% (referent), 7.4% (adjusted hazard ratio [HR] 2.38 [95% CI 1.95-2.91], P < 0.001), and 13.0% (adjusted HR 4.59 [95% CI 3.28-6.28], P < 0.001), respectively. The relative risk of hospitalization for heart failure with saxagliptin was similar (P for interaction = 0.43) in patients with eGFR >50 mL/min/1.73 m(2) (HR 1.23 [95% CI 0.99-1.55]), eGFR 30-50 mL/min/1.73 m(2) (HR 1.46 [95% CI 1.07-2.00]), and in patients with eGFR <30 (HR 0.94 [95% CI 0.52-1.71]). Patients with renal impairment achieved reductions in microalbuminuria with saxagliptin (P = 0.041) that were similar to those of the overall trial population.CONCLUSIONSSaxagliptin did not affect the risk of ischemic cardiovascular events, increased the risk of heart failure hospitalization, and reduced progressive albuminuria, irrespective of baseline renal function. C1 [Udell, Jacob A.] Univ Toronto, Womens Coll Hosp, Cardiovasc Div, Toronto, ON, Canada. [Bhatt, Deepak L.; Braunwald, Eugene; Cavender, Matthew A.; Im, KyungAh; Umez-Eronini, Amarachi A.; He, Ping; Scirica, Benjamin M.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Bhatt, Deepak L.; Braunwald, Eugene; Cavender, Matthew A.; Im, KyungAh; Umez-Eronini, Amarachi A.; He, Ping; Scirica, Benjamin M.] Harvard Univ, Sch Med, Boston, MA USA. [Mosenzon, Ofri; Raz, Itamar] Hadassah Hebrew Univ Hosp, Div Internal Med, Diabet Unit, Jerusalem, Israel. [Steg, Ph. Gabriel] Univ Paris Diderot, Dept Hospitalouniv Fibrosis Inflammat Remodelling, INSERM, U1148, Paris, France. [Steg, Ph. Gabriel] Hop Bichat Claude Bernard, AP HP, F-75877 Paris, France. [Steg, Ph. Gabriel] Univ London Imperial Coll Sci Technol & Med, Royal Brompton Hosp, London, England. [Davidson, Jaime A.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Endocrinol, Dallas, TX 75390 USA. [Nicolau, Jose C.] Univ Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo, Brazil. [Corbalan, Ramon] Pontificia Univ Catolica Chile, Div Cardiovasc, Santiago, Chile. [Hirshberg, Boaz] AstraZeneca Res & Dev, Wilmington, DE USA. [Frederich, Robert] Bristol Myers Squibb Co, Princeton, NJ USA. [McGuire, Darren K.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Cardiovasc Med, Dallas, TX 75390 USA. [Leiter, Lawrence A.] Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, Div Endocrinol & Metab,Keenan Res Ctr, Toronto, ON, Canada. RP Scirica, BM (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM bscirica@partners.org RI Nicolau, Jose/E-1487-2012; davidson, josy/F-2415-2014 OI davidson, josy/0000-0003-4004-1889 FU AstraZeneca/Bristol-Myers Squibb; AstraZeneca; Bristol-Myers Squibb; Amarin; Eisai; Ethicon; Medtronic; Roche; Sanofi; Medicines Company; TIMI Study Group; Merck Sharp Dohme; Hadassah Hebrew University Hospital from AstraZeneca; Eli Lilly; Novartis; Novo Nordisk; Bayer; Pfizer; Daiichi-Sankyo; Servier; Vivus; Janssen; Johnson Johnson; President of WorldWIDE Diabetes; Executive Committee CME of The University of Texas Southwestern Medical Center; editorial boards of The Journal of Diabetes and ALAD; Journal of the Latin American Diabetes Association; Heart Institute (InCor) at the University of Sao Paulo Medical School from AstraZeneca; Brigham and Women's Hospital; Boehringer Ingelheim; Janssen Research and Development LLC; Duke Clinical Research Institute; Cleveland Clinic Coordinating Center for Clinical Research; University of Oxford; Eli Lilly USA; F. Hoffmann-La Roche; GlaxoSmithKline; Takeda Pharmaceuticals North America; Omthera; Regeneron; Gilead Sciences; Takeda; Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael's Hospital; University of Toronto, from AstraZeneca; Brigham and Women's Hospital from AstraZeneca; Bayer Healthcare; Gilead; Lexicon; Arena; St. Jude's Medical; Forest Pharmaceuticals; Boston Clinical Research Institute; Decision Resources; University of Calgary; Elsevier Practice Update Cardiology FX The SAVOR-TIMI 53 trial was funded by AstraZeneca/Bristol-Myers Squibb. J.A.U., M.A.C., K.I., A.A.U.-E., and P.H. report they are or were members of the TIMI Study Group, which received research grant support from AstraZeneca and Bristol-Myers Squibb. D.L.B. discloses the following relationships: advisory board for Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; board of directors for Boston VA Research Institute and Society of Cardiovascular Patient Care; chair of the American Heart Association Get With The Guidelines Steering Committee; data monitoring committees for Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, Population Health Research Institute; honoraria from the American College of Cardiology (editor, Clinical Trials, Cardiosource), Belvoir Publications (editor in chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (editor in chief, Journal of Invasive Cardiology), Population Health Research Institute (clinical trial steering committee), Slack Publications (chief medical editor, Cardiology Today's Intervention), and WebMD (continuing medical education steering committees); Clinical Cardiology (associate editor); Journal of the American College of Cardiology (section editor, pharmacology); research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Roche, Sanofi, and The Medicines Company; and unfunded research for FlowCo, PLx Pharma, and Takeda. E.B. discloses research grants through the TIMI Study Group and Brigham and Women's Hospital from AstraZeneca and Bristol-Myers Squibb. M.A.C. has received consulting fees from AstraZeneca and Merck Sharp & Dohme. O.M. discloses the following relationships: research grants through Hadassah Hebrew University Hospital from AstraZeneca and Bristol-Myers Squibb; consulting fees from AstraZeneca and Bristol-Myers Squibb; travel support for attendance at scientific meetings from AstraZeneca and Bristol-Myers Squibb; advisory board for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Novartis, Novo Nordisk, and Sanofi; and speaker fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, and Sanofi. P.G.S. discloses the following relationships: speaker fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Pfizer, Roche, and The Medicines Company; consulting fees from Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Sanofi, Servier, and Vivus; honoraria for clinical trial steering committee participation from AstraZeneca, Amarin, GlaxoSmithKline, Otsuka, Sanofi, Servier, and Vivus; and honoraria for preparation of educational material from Boehringer Ingelheim. J.A.D. discloses the following relationships: honoraria for advisory board participation from Aspire Bariatrics, AstraZeneca, Eli Lilly, Janssen, and Novo Nordisk; speaker fees from AstraZeneca, Janssen, Johnson & Johnson, and Novo Nordisk; President of WorldWIDE Diabetes, a not-for-profit foundation; The Executive Committee CME of The University of Texas Southwestern Medical Center; the editorial boards of The Journal of Diabetes and ALAD, the Journal of the Latin American Diabetes Association. J.C.N.; discloses the following relationships: research grants through the Heart Institute (InCor) at the University of Sao Paulo Medical School from AstraZeneca, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Johnson & Johnson, and Sanofi; advisory boards for AstraZeneca, Bayer, and Sanofi; consulting fees from AstraZeneca; travel support for attendance at scientific meetings from AstraZeneca; speaker fees from AstraZeneca, Bayer, and Sanofi; and honoraria for the preparation of educational material from AstraZeneca and Bayer. R.C. discloses honoraria through the Pontificia Universidad Catolica de Chile from Brigham and Women's Hospital during the conduct of this study and served on the Latin American Advisory Board. B.H. is employed by AstraZeneca. R.F. is employed by Bristol-Myers Squibb. D.K.M. discloses the following relationships: research grants and honoraria from Brigham and Women's Hospital during the conduct of this study; personal fees from Boehringer Ingelheim, Janssen Research and Development LLC, Merck Sharp & Dohme, Brigham and Women's Hospital, Duke Clinical Research Institute, Cleveland Clinic Coordinating Center for Clinical Research, University of Oxford, Eli Lilly USA, Novo Nordisk, F. Hoffmann-La Roche, GlaxoSmithKline, Takeda Pharmaceuticals North America, Bristol-Myers Squibb, Omthera, AstraZeneca, and Regeneron; and nonfinancial research support from Gilead Sciences. L.A.L. discloses the following relationships: consulting fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Merck Sharp & Dohme, Novo Nordisk, Roche, Sanofi, Servier, and Takeda; research grants through the Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Merck Sharp & Dohme, Novo Nordisk, Roche, and Sanofi; speaker fees from Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Roche, Sanofi, and Takeda; and honoraria for the preparation of educational material from AstraZeneca and Bristol-Myers Squibb. I. R. discloses the following relationships: consulting fees from Andromeda, AstraZeneca, Bristol-Myers Squibb, and Insuline; travel support for attendance at scientific meetings from AstraZeneca; advisory boards for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Medscape, Merck Sharp & Dohme, Novartis, Novo Nordisk, and Sanofi; speaker fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Johnson & Johnson, Merck Sharp & Dohme, Novartis, Novo Nordisk, and Sanofi; and equity stock ownership in Insuline. B.M.S. discloses the following relationships: research grants through the TIMI Study Group and Brigham and Women's Hospital from AstraZeneca and Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Johnson & Johnson, Bayer Healthcare, Gilead, Eisai, and Merck Sharp & Dohme and consulting fees from Gilead, Lexicon, Arena, Eisai, St. Jude's Medical, Bristol-Myers Squibb, Forest Pharmaceuticals, Boston Clinical Research Institute, Decision Resources, University of Calgary, and Elsevier Practice Update Cardiology. No other potential conflicts of interest relevant to this article were reported. NR 37 TC 40 Z9 42 U1 1 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD APR PY 2015 VL 38 IS 4 BP 696 EP 705 DI 10.2337/dc14-1850 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CE2FX UT WOS:000351630900035 PM 25552421 ER PT J AU Guerrero-Berroa, E Ravona-Springer, R Heymann, A Schmeidler, J Levy, A Leroith, D Beeri, MS AF Guerrero-Berroa, Elizabeth Ravona-Springer, Ramit Heymann, Anthony Schmeidler, James Levy, Andrew Leroith, Derek Beeri, Michal S. TI Haptoglobin genotype modulates the relationships of glycaemic control with cognitive function in elderly individuals with type 2 diabetes SO DIABETOLOGIA LA English DT Article DE Cognition; Cognitive domains; Diabetes; Glucose; Glycaemia; Haptoglobin; HbA(1c) ID SMALL VESSEL DISEASE; ALZHEIMERS-DISEASE; CARDIOVASCULAR-DISEASE; NEUROPSYCHOLOGICAL BATTERY; HBA(1C) VARIABILITY; GLOBAL PREVALENCE; PROCESSING SPEED; OLDER-ADULTS; DEMENTIA; RISK AB The purpose of this study was to investigate whether the association of glycaemic control with cognitive function is modulated by the haptoglobin 1-1 (Hp 1-1) genotype in cognitively normal elderly individuals with type 2 diabetes. In this cross-sectional study, we examined 793 participants who were genotyped for Hp (80 Hp 1-1 carriers and 713 Hp 1-1 non-carriers) enrolled in the Israel Diabetes and Cognitive Decline (IDCD) study. Glycaemic control was operationally defined by HbA(1c) level. The outcome measures were performance in four cognitive domains (episodic memory, attention/working memory, language/semantic categorisation, executive function) and overall cognition, a composite of the domains. Effect sizes were obtained from hierarchical linear regression analyses for each outcome measure, controlling for demographics, type 2 diabetes-related characteristics, cardiovascular risk factors, and their interactions with Hp genotype. Interaction analyses showed significantly stronger associations of HbA(1c) with poorer cognitive function among Hp 1-1 carriers than non-carriers; attention/working memory (p < 0.001) and overall cognition (p = 0.003). For these two cognitive domains, associations were significant for Hp 1-1 carriers despite the small sample size (p < 0.00001 and p = 0.001, respectively), but not for non-carriers. Our findings suggest that patients with type 2 diabetes and poor glycaemic control carrying the Hp 1-1 genotype may be at increased risk of cognitive impairment, particularly in the attention/working memory domain. The association of glycaemic control with this domain may indicate cerebrovascular mechanisms. C1 [Guerrero-Berroa, Elizabeth; Schmeidler, James; Beeri, Michal S.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Guerrero-Berroa, Elizabeth] James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Ravona-Springer, Ramit; Beeri, Michal S.] Chaim Sheba Med Ctr, Joseph Sagol Neurosci Ctr, Ramat Gan, Israel. [Ravona-Springer, Ramit; Heymann, Anthony] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Heymann, Anthony] Maccabi Healthcare Serv, Tel Aviv, Israel. [Levy, Andrew] Technion Israel Inst Technol, Technion Fac Med, Haifa, Israel. [Leroith, Derek] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Beeri, Michal S.] Interdisciplinary Ctr, Sch Psychol, Hertzlia, Israel. RP Guerrero-Berroa, E (reprint author), James J Peters VA Med Ctr, 130 West Kingsbridge Rd,Room 1F-01, Bronx, NY 10468 USA. EM elizabeth.guerrero-berroa@mssm.edu FU NIA NIH HHS [P50 AG005138, R01 AG034087] NR 52 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2015 VL 58 IS 4 BP 736 EP 744 DI 10.1007/s00125-014-3487-2 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CD2BK UT WOS:000350878400013 PM 25628235 ER PT J AU Bottcher, A Kucher, S Knecht, R Jowett, N Krotz, P Reimer, R Schumacher, U Anders, S Munscher, A Dalchow, CV Miller, RJD AF Boettcher, Arne Kucher, Stanislav Knecht, Rainald Jowett, Nathan Kroetz, Peter Reimer, Rudolph Schumacher, Udo Anders, Sven Muenscher, Adrian Dalchow, Carsten V. Miller, R. J. Dwayne TI Reduction of thermocoagulative injury via use of a picosecond infrared laser (PIRL) in laryngeal tissues SO EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY LA English DT Article DE Laryngeal surgery; Er:YAG laser; CO2 laser; PIRL; Damage zones; Electron microscopy; Thermography ID SURGERY; ABLATION AB The carbon dioxide (CO2) laser is routinely used in glottic microsurgery for the treatment of benign and malignant disease, despite significant collateral thermal damage secondary to photothermal vaporization without thermal confinement. Subsequent tissue response to thermal injury involves excess collagen deposition resulting in scarring and functional impairment. To minimize collateral thermal injury, short-pulse laser systems such as the microsecond pulsed erbium:yttrium-aluminium-garnet (Er:YAG) laser and picosecond infrared laser (PIRL) have been developed. This study compares incisions made in ex vivo human laryngeal tissues by CO2 and Er:YAG lasers versus PIRL using light microscopy, environmental scanning electron microscopy (ESEM), and infrared thermography (IRT). In comparison to the CO2 and Er:YAG lasers, PIRL incisions showed significantly decreased mean epithelial (59.70 A mu m) and subepithelial (22.15 A mu m) damage zones (p < 0.05). Cutting gaps were significantly narrower for PIRL (133.70 A mu m) compared to Er:YAG and CO2 lasers (p < 0.05), which were more than 5 times larger. ESEM revealed intact collagen fibers along PIRL cutting edges without obvious carbonization, in comparison to diffuse carbonization and tissue melting seen for CO2 and Er:YAG laser incisions. IRT demonstrated median temperature rise of 4.1 K in PIRL vocal fold incisions, significantly less than for Er:YAG laser cuts (171.85 K; p < 0.001). This study has shown increased cutting precision and reduced lateral thermal damage zones for PIRL ablation in comparison to conventional CO2 and Er:YAG lasers in human glottis and supraglottic tissues. C1 [Boettcher, Arne; Kucher, Stanislav; Knecht, Rainald; Jowett, Nathan; Muenscher, Adrian; Dalchow, Carsten V.] Univ Med Ctr Hamburg Eppendorf, Dept Otorhinolaryngol Head & Neck Surg, Hamburg, Germany. [Boettcher, Arne] Campus Virchow Klinikum, Charite Univ Med Ctr Berlin, Dept Otorhinolaryngol Head & Neck Surg, D-13353 Berlin, Germany. [Kucher, Stanislav] Univ Med Ctr Hamburg Eppendorf, Dept Prosthet Dent, Hamburg, Germany. [Jowett, Nathan] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Jowett, Nathan] Harvard Univ, Sch Med, Boston, MA USA. [Kroetz, Peter; Miller, R. J. Dwayne] Max Planck Inst Struct & Dynam Matter, Atomically Resolved Dynam Div, Hamburg, Germany. [Reimer, Rudolph] Univ Hamburg, Heinrich Pette Inst, Leibniz Inst Expt Virol, Hamburg, Germany. [Schumacher, Udo] Univ Med Ctr Hamburg Eppendorf, Dept Anat & Expt Morphol, Hamburg, Germany. [Anders, Sven] Univ Med Ctr Hamburg Eppendorf, Dept Legal Med, Hamburg, Germany. RP Bottcher, A (reprint author), Campus Virchow Klinikum, Charite Univ Med Ctr Berlin, Dept Otorhinolaryngol Head & Neck Surg, Augustenburger Pl 1, D-13353 Berlin, Germany. EM arne.boettcher@charite.de FU European Research Council [ERC-AdG-2011-291630] FX This study was funded by the European Research Council Advanced Investigator Grant "Miller: ERC-AdG-2011-291630: SUREPIRL, Picosecond Infrared Laser for Scar Free Surgery with Preservation of Tissue Structure and Recognition of Tissue Type and Boundaries''. NR 16 TC 2 Z9 2 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0937-4477 EI 1434-4726 J9 EUR ARCH OTO-RHINO-L JI Eur. Arch. Oto-Rhino-Laryn. PD APR PY 2015 VL 272 IS 4 BP 941 EP 948 DI 10.1007/s00405-015-3501-4 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA CE0SY UT WOS:000351517900024 PM 25575843 ER PT J AU Evins, AE Hong, LE Kelly, DL AF Evins, A. Eden Hong, L. Elliot Kelly, Deanna L. TI T. Kishi and N. Iwata: Varenicline for smoking cessation in people with schizophrenia: systematic review meta-analysis SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Letter ID SCHIZOAFFECTIVE DISORDER; BIPOLAR DISORDER; DOUBLE-BLIND; TRIAL C1 [Evins, A. Eden] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Evins, A. Eden] Harvard Univ, Sch Med, Boston, MA USA. [Hong, L. Elliot; Kelly, Deanna L.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Evins, AE (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM a_eden_evins@hms.harvard.edu FU NIDA NIH HHS [R01 DA021245, K24 DA030443] NR 9 TC 1 Z9 1 U1 1 U2 3 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0940-1334 EI 1433-8491 J9 EUR ARCH PSY CLIN N JI Eur. Arch. Psych. Clin. Neurosci. PD APR PY 2015 VL 265 IS 3 BP 269 EP 270 DI 10.1007/s00406-014-0556-y PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CD9IT UT WOS:000351412500011 PM 25377170 ER PT J AU Kurdziel, LBF Dempsey, K Zahara, M Valera, E Spencer, RMC AF Kurdziel, Laura B. F. Dempsey, Katherine Zahara, Mackenzie Valera, Eve Spencer, Rebecca M. C. TI Impaired visuomotor adaptation in adults with ADHD SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE ADHD; Adaptation; Cerebellum; Reaching ID DEFICIT-HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; POSTERIOR PARIETAL CORTEX; SELF-REPORT SCALE; PRISM ADAPTATION; CEREBELLAR DEGENERATION; RESPONSE-INHIBITION; PRESCHOOL-CHILDREN; BRAIN ACTIVITY; MOTOR CORTEX AB Attention-deficit hyperactivity disorder (ADHD) is a prevalent psychiatric disorder in children that often continues into adulthood. It has been suggested that motor impairments in ADHD are associated with underlying cerebellar pathology. If such is the case, individuals with ADHD should be impaired on motor tasks requiring healthy cerebellar function. To test this, we compared performance of individuals with ADHD and ADHD-like symptoms with non-ADHD controls on a visuomotor adaptation task known to be impaired following cerebellar lesions. Participants adapted reaching movements to a visual representation that was rotated by 30A degrees. Individuals with ADHD and those with ADHD-like symptoms took longer to correct the angle of movement once the rotation was applied relative to controls. However, post-adaptation residual effect did not differ for individuals with ADHD and ADHD-like symptoms compared to the control group. These results are consistent with the hypothesis that mild cerebellar deficits are evident in the motor performance of adults with ADHD. C1 [Kurdziel, Laura B. F.; Spencer, Rebecca M. C.] Univ Massachusetts, Neurosci & Behav Program, Amherst, MA 01003 USA. [Dempsey, Katherine; Zahara, Mackenzie; Spencer, Rebecca M. C.] Univ Massachusetts, Dept Psychol & Brain Sci, Amherst, MA 01003 USA. [Valera, Eve] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. RP Spencer, RMC (reprint author), Univ Massachusetts, Dept Psychol & Brain Sci, Amherst, MA 01003 USA. EM rspencer@psych.umass.edu FU National Institutes of Health [R01 HD067744]; Honors Research Grant from Commonwealth Honors College at the University of Massachusetts, Amherst FX This work was supported in part by R01 HD067744 (PI: Valera) from the National Institutes of Health and an Honors Research Grant from Commonwealth Honors College at the University of Massachusetts, Amherst. NR 58 TC 1 Z9 1 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 EI 1432-1106 J9 EXP BRAIN RES JI Exp. Brain Res. PD APR PY 2015 VL 233 IS 4 BP 1145 EP 1153 DI 10.1007/s00221-014-4190-8 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CD5XP UT WOS:000351162400013 PM 25567090 ER PT J AU Fernandez-del Castillo, C Tanaka, M AF Fernandez-del Castillo, Carlos Tanaka, Masao TI Management of Pancreatic Cysts: The Evidence Is Not Here Yet SO GASTROENTEROLOGY LA English DT Editorial Material ID PAPILLARY MUCINOUS NEOPLASMS; INTERNATIONAL-CONSENSUS-GUIDELINES; RESECTION; CARCINOMA; IPMN C1 [Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Tanaka, Masao] Kyushu Univ, Grad Sch Med Sci, Dept Surg & Oncol, Kyushu, Japan. RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 17 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2015 VL 148 IS 4 BP 685 EP 687 DI 10.1053/j.gastro.2015.02.034 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CE2IJ UT WOS:000351639000008 PM 25724457 ER PT J AU Stollenwerk, B Lhachimi, SK Briggs, A Fenwick, E Caro, JJ Siebert, U Danner, M Gerber-Grote, A AF Stollenwerk, Bjoern Lhachimi, Stefan K. Briggs, Andrew Fenwick, Elisabeth Caro, Jaime J. Siebert, Uwe Danner, Marion Gerber-Grote, Andreas TI COMMUNICATING THE PARAMETER UNCERTAINTY IN THE IQWIG EFFICIENCY FRONTIER TO DECISION-MAKERS SO HEALTH ECONOMICS LA English DT Article DE efficiency frontier; economic evaluation; decision-making; uncertainty; Germany ID WILLINGNESS-TO-PAY; ECONOMIC-EVALUATION; INFORMATION AB The Institute for Quality and Efficiency in Health Care (IQWiG) developed-in a consultation process with an international expert panel-the efficiency frontier (EF) approach to satisfy a range of legal requirements for economic evaluation in Germany's statutory health insurance system. The EF approach is distinctly different from other health economic approaches. Here, we evaluate established tools for assessing and communicating parameter uncertainty in terms of their applicability to the EF approach. Among these are tools that perform the following: (i) graphically display overall uncertainty within the IQWiG EF (scatter plots, confidence bands, and contour plots) and (ii) communicate the uncertainty around the reimbursable price. We found that, within the EF approach, most established plots were not always easy to interpret. Hence, we propose the use of price reimbursement acceptability curves-a modification of the well-known cost-effectiveness acceptability curves. Furthermore, it emerges that the net monetary benefit allows an intuitive interpretation of parameter uncertainty within the EF approach. This research closes a gap for handling uncertainty in the economic evaluation approach of the IQWiG methods when using the EF. However, the precise consequences of uncertainty when determining prices are yet to be defined. (C) 2014 The Authors. Health Economics published by John Wiley & Sons Ltd. C1 [Stollenwerk, Bjoern] Helmholtz Zentrum Munchen, German Res Ctr Environm, Inst Hlth Econ & Hlth Care Management, Neuherberg, Germany. [Lhachimi, Stefan K.; Gerber-Grote, Andreas] IQWiG, Inst Qual & Efficiency Hlth Care, Dept Hlth Econ, Cologne, Germany. [Lhachimi, Stefan K.] Leibniz Inst Prevent Res & Epidemiol, Cooperat Res Grp Evidence Based Publ Hlth, Bremen, Germany. [Lhachimi, Stefan K.] Univ Bremen, Inst Publ Hlth & Nursing Res, D-28359 Bremen, Germany. [Briggs, Andrew; Fenwick, Elisabeth] Univ Glasgow, Inst Hlth & Wellbeing, Hlth Econ & Hlth Technol Assessment, Glasgow, Lanark, Scotland. [Caro, Jaime J.] McGill Univ, Div Gen Internal Med, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada. [Caro, Jaime J.] United BioSource Corp, Lexington, MA USA. [Siebert, Uwe] UMIT Univ Hlth Sci Med Informat & Technol, Inst Publ Hlth Med Decis Making & Hlth Technol As, Dept Publ Hlth & Hlth Technol Assessment, EWZ 1, Tyrol, Austria. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. [Siebert, Uwe] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Hlth Decis Sci, Boston, MA 02115 USA. [Siebert, Uwe] ONCOTYROL Ctr Personalized Canc Med, Div Publ Hlth Decis Modelling Hlth Technol Assess, Innsbruck, Austria. [Danner, Marion] Univ Colgone, Inst Hlth Econ & Clin Epidemiol, Cologne, Germany. RP Lhachimi, SK (reprint author), IQWiG, Inst Qual & Efficiency Hlth Care, Dept Hlth Econ, Cologne, Germany. EM stefan.Lhachimi@iqwig.de RI Lhachimi, Stefan/D-9227-2014; OI Caro, Jaime/0000-0001-5470-3754; Lhachimi, Stefan/0000-0001-8597-0935 NR 17 TC 3 Z9 3 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9230 EI 1099-1050 J9 HEALTH ECON JI Health Econ. PD APR PY 2015 VL 24 IS 4 BP 481 EP 490 DI 10.1002/hec.3041 PG 10 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA CD6DS UT WOS:000351180300007 PM 24590819 ER PT J AU Palombo, DJ Keane, MM Verfaellie, M AF Palombo, Daniela J. Keane, Margaret M. Verfaellie, Mieke TI How Do Lesion Studies Elucidate the Role of the Hippocampus in Intertemporal Choice? SO HIPPOCAMPUS LA English DT Letter ID EPISODIC FUTURE THINKING; MENTAL TIME-TRAVEL; DECISION-MAKING; ORBITOFRONTAL CORTEX; VENTRAL HIPPOCAMPUS; IMPULSIVE CHOICE; RATS C1 [Palombo, Daniela J.; Keane, Margaret M.; Verfaellie, Mieke] VA Boston Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02130 USA. [Palombo, Daniela J.; Keane, Margaret M.; Verfaellie, Mieke] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Keane, Margaret M.] Wellesley Coll, Dept Psychol, Wellesley, MA 02181 USA. RP Palombo, DJ (reprint author), VA Boston Healthcare Syst, Memory Disorders Res Ctr, 150 South Huntington Ave,151-A, Boston, MA 02130 USA. EM palombo@bu.edu NR 13 TC 4 Z9 4 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1050-9631 EI 1098-1063 J9 HIPPOCAMPUS JI Hippocampus PD APR PY 2015 VL 25 IS 4 BP 407 EP 408 DI 10.1002/hipo.22433 PG 2 WC Neurosciences SC Neurosciences & Neurology GA CE0VQ UT WOS:000351527400001 PM 25708726 ER PT J AU Vranceanu, AM Hageman, M Strooker, J ter Meulen, D Vrahas, M Ring, D AF Vranceanu, Ana-Maria Hageman, Michiel Strooker, Joost ter Meulen, Dirk Vrahas, Mark Ring, David TI A preliminary RCT of a mind body skills based intervention addressing mood and coping strategies in patients with acute orthopaedic trauma SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE Musculoskeletal trauma; Mind body intervention; Disability; Pain ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; SATISFACTION 12 MONTHS; CHRONIC PAIN; GENERAL HEALTH; RECOVERY PROJECT; MAJOR TRAUMA; WORK STATUS; BACK-PAIN; ARM PAIN AB Objective: To test the acceptability and feasibility of a mind body skills-based intervention (RRCB) and estimate its preliminary effect in reducing disability and pain intensity as compared to standard care (SC) in patients with acute musculoskeletal trauma. Design: Randomised controlled trial. Setting: Level I trauma centre. Patients: Adult patients with acute fractures at risk for chronic pain and disability based on scores on two coping with pain measures who presented to an orthopedic trauma center and met inclusion and exclusion criteria. Intervention: Participants were randomied to either RRCB with SC or SC alone. Main outcome measurement: Disability (short musculoskeletal functional assessment, SMFA) and pain (Numerical Analogue Scale). Secondary outcome measures: coping strategies (Pain Catastrophizing Scale, PCS and Pain Anxiety Scale, PAS) and mood (CESD Depression and PTSD checklist). Results: Among the 50 patients consented, two did not complete the initial assessment. Of these, the first four received the intervention as part of an open pilot and the next 44 were randomised (24 RRCBT and 20 UC) and completed initial assessment. We combined the patients who received RRCB into one group, N = 28. Of the entire sample, 34 completed time two assessments (24 RRCBT and 10 SC). The RRCB proved to be feasible and accepted (86% retention, 28 out of 24 completers). Analyses of covariance ANCOVA showed a significant (p < 05) improvement and large effect sizes for all time two main study variables (.2-.5) except pain with activity where the effect size was medium (.08). Improvement for pain at rest was not significantly higher in the RRCB as compared to the control, for a small effect size (.03). Conclusion: The RRCB is feasible, acceptable and potentially efficacious. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Vranceanu, Ana-Maria] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Behav Med, Boston, MA 02114 USA. [Hageman, Michiel; Strooker, Joost; ter Meulen, Dirk] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Vrahas, Mark] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthoped Trauma Serv, Boston, MA 02114 USA. [Ring, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Vranceanu, AM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Behav Med, Boston, MA 02114 USA. EM avranceanu@mgh.harvard.edu; dring@mgh.harvard.edu FU Orthopaedic Trauma Association (OTA) FX This research was supported by a clinical research grant from Orthopaedic Trauma Association (OTA) awarded to Ana-Maria Vranceanu. We thank Neil Wicks, Mark van Suchtelen, Niels Bosma, and Arjan Bot for their help with patient recruitment. NR 47 TC 7 Z9 7 U1 1 U2 3 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 APR PY 2015 VL 46 IS 4 BP 552 EP 557 DI 10.1016/j.injury.2014.11.001 PG 6 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA CD7MZ UT WOS:000351275900007 PM 25435134 ER PT J AU Mulder, FJ van Suchtelen, M Menendez, ME Gradl, G Neuhaus, V Ring, D AF Mulder, Frans J. van Suchtelen, Mark Menendez, Mariano E. Gradl, Gertraud Neuhaus, Valentin Ring, David TI A comparison of actual and theoretical treatments of glenoid fractures SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE 3D computed tomography; Glenoid fracture; Indications for surgery; Operative treatment; Radiographs ID SCAPULAR FRACTURES; FOLLOW-UP; CLASSIFICATION; DISLOCATION; MANAGEMENT; OUTCOMES AB Background: There is no consensus on the operative treatment of glenoid fractures. The purpose of this study was to see whether there was a difference between how patients with a glenoid fracture would receive treatment according to theoretical operative indications based on the measurement of computed tomography (CT) scans and radiographs and the treatment they actually received in our institutions. Methods: A total of 457 patients with a scapular fracture were treated in two level 1 trauma centres between January 2002 and August 2011. Ninety-eight patients with a glenoid fracture were retrospectively analyzed. Intra-articular gap, medial or lateral (M/L) displacement, angular deformity, and glenopolar angle (GPA) were measured on CT scans or radiographs to determine theoretical indications for operative treatment. Results: Twenty-four patients (25%) actually had operative treatment, while 35 patients (36%) fulfilled at least one theoretical criterion to proceed with operative treatment with a medium correlation between theoretical indications for surgery and the actual operative treatment. All the patients with a theoretical indication for surgery had an intra-articular gap with a step-off of >4 mm. A bony Bankart lesion with shoulder dislocation and injury in sports was retained in the best multivariable model as indications for the actual surgery. Conclusion: Theoretical guidelines for surgery on glenoid fractures may not have much influence on the current treatment. Level of evidence: Therapeutic, level III. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Mulder, Frans J.; van Suchtelen, Mark; Menendez, Mariano E.; Gradl, Gertraud; Ring, David] Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Neuhaus, Valentin] Univ Zurich Hosp, Div Trauma Surg, CH-8091 Zurich, Switzerland. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Ring, David/0000-0002-6506-4879; Neuhaus, Valentin/0000-0003-4012-5628 NR 15 TC 4 Z9 4 U1 0 U2 1 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 APR PY 2015 VL 46 IS 4 BP 699 EP 702 DI 10.1016/j.injury.2015.01.037 PG 4 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA CD7MZ UT WOS:000351275900032 PM 25697856 ER PT J AU Chebib, I Desphande, V Nielsen, GP AF Chebib, Ivan Desphande, Vikram Nielsen, G. Petur TI Sclerosing Muc-4-Positive Sarcoma With Glandular Differentiation Resembling Sclerosing Epithelioid Fibrosarcoma SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE sclerosing; epithelioid; fibrosarcoma; Muc-4 ID GRADE FIBROMYXOID SARCOMA; SERIES; TUMOR AB Sclerosing epithelioid fibrosarcoma is a rare soft tissue tumor that is composed of epithelioid fibroblasts embedded in an abundant extracellular collagenous matrix. They have been shown to be weakly epithelial membrane antigen (EMA) positive by immunohistochemistry and may contain intercellular junctions ultrastructurally. We present a case of a 52-year-old female who presented with a sclerosing Muc-4-positive sarcoma with glandular differentiation of the sciatic nerve, resembling sclerosing epithelioid fibrosarcoma. The glandular component showed strong expression of keratin and EMA and ultrastructurally showed numerous intercellular junctions and intraluminal microvilli, supportive of true glandular differentiation. The patient received preoperative radiotherapy (50 Gray) and subsequent resection of the mass with negative margins. She is currently disease free at 20-month follow-up. This case report describes an unusual sclerosing Muc-4-positive sarcoma with glandular differentiation, distinctive expression of epithelial immunohistochemical markers, and glandular differentiation by electron microscopy. C1 [Chebib, Ivan; Desphande, Vikram; Nielsen, G. Petur] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chebib, Ivan; Desphande, Vikram; Nielsen, G. Petur] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Chebib, I (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, 55 Fruit St,WRN3, Boston, MA 02114 USA. EM ichebib@partners.org NR 12 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 1066-8969 EI 1940-2465 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD APR PY 2015 VL 23 IS 2 BP 144 EP 148 DI 10.1177/1066896914558263 PG 5 WC Pathology; Surgery SC Pathology; Surgery GA CE1UJ UT WOS:000351597500012 PM 25411219 ER PT J AU Janssen, SJ Teunis, T Hornicek, FJ Bramer, JAM Schwab, JH AF Janssen, Stein J. Teunis, Teun Hornicek, Francis J. Bramer, Jos A. M. Schwab, Joseph H. TI Outcome of operative treatment of metastatic fractures of the humerus: a systematic review of twenty three clinical studies SO INTERNATIONAL ORTHOPAEDICS LA English DT Review DE Pathological; Impending; Metastatic bone disease; Humeral; Upper extremity ID PATHOLOGICAL FRACTURES; SURGICAL-TREATMENT; BONE METASTASES; SHAFT FRACTURES; LONG BONES; DISEASE; PLATE; NAIL; OSTEOSYNTHESIS; STABILIZATION AB Purpose This systematic review aims to provide an overview of functional outcome and complications after surgery for metastatic humerus fractures. Methods A literature search was performed in September 2013 using the Pubmed, Embase and Cochrane database. We included 23 studies reporting on 29 treatment arms: intramedullary nailing (19 studies, 596 cases), plate-screw fixation (five studies, 150 cases), endoprosthetic reconstruction (three studies, 81 cases), and diaphysis prosthesis (two studies, 82 cases), totalling 909 fractures. There were 414 pathological and 56 impending fractures. In 439 cases the type of fracture was not specified. Four studies reported functional outcome. Results Average Musculoskeletal Tumor Society score ranged from 64 to 79 (three studies, 100 patients) after intramedullary nailing, was 90 (one study, 24 patients) after plate-screw fixation, and 73 (one study, 30 patients) after endoprosthetic reconstruction. Re-operation rate varied from 0 to 10 % after intramedullary nailing (overall 4.4 %), 5-14 % after plate-screw fixation (overall 9.3 %), 14-16 % after diaphysis prosthesis (overall 14.6 %), and 0-6 % after endoprosthetic reconstruction (overall 2.5 %). Systemic complication rate varied between 0 and 26 % after intramedullary nailing (overall 2.2 %), between 0 and 6 % after plate-screw fixation (overall 4.8 %), was 0 % after endoprosthetic reconstruction, and varied between 0 and 16 % after diaphysis prosthesis (overall 9.7 %). Conclusions Reported complication rates help surgeons inform their patients and could aid in surgical decision making. Functional outcome, pain and quality of life were poorly reported. Patient reported outcomes are therefore an important direction for future research. C1 [Janssen, Stein J.; Teunis, Teun; Hornicek, Francis J.; Schwab, Joseph H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Orthopaed Oncol Serv, Boston, MA 02114 USA. [Bramer, Jos A. M.] Univ Amsterdam, Acad Med Ctr, Dept Orthopaed Surg, NL-1105 AZ Amsterdam, Netherlands. RP Janssen, SJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Orthopaed Oncol Serv, Room 3-946,Yawkey Bldg,55 Fruit St, Boston, MA 02114 USA. EM steinjanssen@gmail.com; teunteunis@gmail.com; fhornicek@mgh.harvard.edu; jhschwab@mgh.harvard.edu; j.a.bramer@amc.uva.nl FU Stichting Anna Fonds; Stichting Michael van Vloten Fonds FX Dr. Janssen received funding from Stichting Anna Fonds and the Stichting Michael van Vloten Fonds during the conduct of the study. Dr. Schwab has received payments or benefits from Stryker and Biom'up, outside the submitted work. The other authors have nothing to disclose. NR 48 TC 2 Z9 2 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2695 EI 1432-5195 J9 INT ORTHOP JI Int. Orthop. PD APR PY 2015 VL 39 IS 4 BP 735 EP 746 DI 10.1007/s00264-014-2584-7 PG 12 WC Orthopedics SC Orthopedics GA CE0SL UT WOS:000351516200017 PM 25398471 ER PT J AU Menendez, ME Memtsoudis, SG Opperer, M Boettner, F Della Valle, AG AF Menendez, Mariano E. Memtsoudis, Stavros G. Opperer, Marion Boettner, Friedrich Della Valle, Alejandro Gonzalez TI A nationwide analysis of risk factors for in-hospital myocardial infarction after total joint arthroplasty SO INTERNATIONAL ORTHOPAEDICS LA English DT Article DE Myocardial infarction; Knee arthroplasty; Hip arthroplasty; Risk factors; Epidemiology ID TOTAL KNEE ARTHROPLASTY; TOTAL HIP-ARTHROPLASTY; OBSTRUCTIVE SLEEP-APNEA; UNITED-STATES; 30-DAY MORTALITY; COMPLICATIONS; OUTCOMES; TRENDS; DEATH; REPLACEMENT AB Purpose Despite acute myocardial infarction (AMI) being a feared medical complication and currently a major cause of death after total hip and knee arthroplasty (THA/TKA), little is known about its peri-operative associated factors. Methods Data for this retrospective cohort study were extracted from the Nationwide Inpatient Sample for 2008-2011. Multivariate logistic regression modeling was performed to determine peri-operative factors associated with the development of inpatient AMI following THA/TKA. Results An estimated 3,096,791 procedures were identified. Perioperative AMI rates were 0.25 % for THA and 0.18 % for TKA. Patients with AMI had significantly greater comorbidity burden, higher peri-operative mortality rates, longer length of hospital stay and increased complication rates. Independent risk factors for the development of AMI comprised advance age, male gender [odds ratio (OR) 1.4, 95 % confidence interval (CI) 1.4-1.5], THA surgery (OR 1.3, 95 % CI 1.3-1.4), low household income (OR 1.3, 95 % CI 1.2-1.4), history of cardiac disease (coronary artery disease: OR 4.9, 95 % CI 4.6-5.2; congestive heart failure: OR 2.6, 95 % CI 2.4-2.8; valvular disease: OR 1.2, 95 % CI 1.1-1.3), diabetes (OR 1.1, 95 % CI 1.1-1.2), pulmonary circulation disorders (OR 1.4, 95 % CI 1.2-1.6), cerebrovascular disease (OR 2.3, 95 % CI 2.0-2.6), peripheral vascular disorders (OR 1.5, 95 % CI 1.4-1.7), coagulopathy (OR 1.4, 95 % CI 1.2-1.5), AIDS/HIV infection (OR 7.9, 95 % CI 4.5-13.9), deficiency anaemia (OR 1.4, 95 % CI 1.3-1.5), fluid and electrolyte disorders (OR 1.9, 95 % CI 1.8-2.0) and the occurrence of concomitant postoperative complications. Conclusion Our findings can be used to better identify patients at high risk of AMI and to develop strategies aimed at diminishing its incidence, which could in turn translate to improved hospital efficiency and quality of care. C1 [Menendez, Mariano E.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkey Ctr, Boston, MA 02114 USA. [Memtsoudis, Stavros G.] Hosp Special Surg, Dept Anesthesiol, New York, NY 10021 USA. [Opperer, Marion; Boettner, Friedrich; Della Valle, Alejandro Gonzalez] Hosp Special Surg, Dept Orthopaed Surg, New York, NY 10021 USA. RP Menendez, ME (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkey Ctr, 55 Fruit St,Suite 2100, Boston, MA 02114 USA. EM memenendez@partners.org RI Boettner, Friedrich/C-2153-2016 OI Boettner, Friedrich/0000-0002-7906-9486 FU Sidney Milton and Leoma Simon Foundation FX This study was partially funded by the generous donation of Mr. Glenn Bergenfield and the Sidney Milton and Leoma Simon Foundation. NR 47 TC 14 Z9 15 U1 0 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2695 EI 1432-5195 J9 INT ORTHOP JI Int. Orthop. PD APR PY 2015 VL 39 IS 4 BP 777 EP 786 DI 10.1007/s00264-014-2502-z PG 10 WC Orthopedics SC Orthopedics GA CE0SL UT WOS:000351516200022 PM 25172363 ER PT J AU Eliyahu Greenblatt, E Winkler, T Harris, RS Kelly, VJ Kone, M Venegas, J AF Greenblatt, Elliot Eliyahu Winkler, Tilo Harris, Robert Scott Kelly, Vanessa Jane Kone, Mamary Venegas, Jose TI Analysis of Three-Dimensional Aerosol Deposition in Pharmacologically Relevant Terms: Beyond Black or White ROIs SO JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY LA English DT Article DE partial volume effect; mucocilliary transport; spillover effect; ROIs; PET-CT; heterogeneity; tissue dosing; motion correction; surface concentration ID IMAGE REGISTRATION; LUNG; PULMONARY; LANDMARK; AIRWAY; MODEL; TOMOGRAPHY; VALIDATION; ACCURACY; DELIVERY AB Background: This article presents a novel methodological approach to evaluate images of aerosol deposition taken with PET-CT cameras. Traditionally, Black-or-White (BW) Regions of Interest (ROIs) are created to cover Anatomical Regions (ARs) segmented from the high-resolution CT. Such ROIs do not usually consider blurring effects due to limited spatial resolution or breathing motion, and do not consider uncertainty in the AR position within the PET image. The new methodology presented here (Grayscale) addresses these issues, allows estimates of aerosol deposition within ARs, and expresses the deposition in terms of Tissue Dosing (in the lung periphery) and Inner Surface Concentration (in the larger airways). Methods: Imaging data included a PET deposition image acquired during breathing and two CT scans acquired during breath holds at different lung volumes. The lungs were segmented into anatomically consistent ARs to allow unbiased comparisons across subjects and across lobes. The Grayscale method involves defining Voxel Influence Matrices (VIMs) to consider how average activity within each AR influences the measured activity within each voxel. The BW and Grayscale methods were used to analyze aerosol deposition in 14 bronchoconstricted asthmatics. Results: Grayscale resulted in a closer description of the PET image than BW (p<0.0001) and exposed a seven-fold underestimation in measures of specific deposition. The Average Tissue Dosing was 2.11x10(-6) Total Lung Dose/mg. The average Inner Surface Concentration was 45x10(-6) Total Lung Dose/mm(2), with the left lower lobe having a lower ISC than lobes of the right lung (p<0.05). There was a strong lobar heterogeneity in these measures (COV=0.3). Conclusion: The Grayscale approach is an improvement over the BW approach and provides a closer description of the PET image. It can be used to characterize heterogeneous concentrations throughout the lung and may be important in translational research and in the evaluation of aerosol delivery systems. C1 [Greenblatt, Elliot Eliyahu] MIT, Dept Mech Engn, Cambridge, MA 02142 USA. [Greenblatt, Elliot Eliyahu; Winkler, Tilo; Venegas, Jose] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. [Harris, Robert Scott; Kelly, Vanessa Jane; Kone, Mamary] Massachusetts Gen Hosp, Dept Crit Care Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Venegas, J (reprint author), Massachusetts Gen Hosp, Edwards 410A,55 Fruit St, Boston, MA 02114 USA. EM jvenegas@alum.mit.edu RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 FU NIH [HL68011]; American Air Liquide Inc. FX This work was sponsored by NIH grant HL68011, and by support from American Air Liquide Inc. Aerogen is thanked for providing the vibrating mesh nebulizers. NR 30 TC 0 Z9 0 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1941-2711 EI 1941-2703 J9 J AEROSOL MED PULM D JI J. Aerosol Med. Pulm. Drug Deliv. PD APR 1 PY 2015 VL 28 IS 2 BP 116 EP 129 DI 10.1089/jamp.2013.1120 PG 14 WC Respiratory System SC Respiratory System GA CE7YP UT WOS:000352058200006 ER PT J AU Chirinos, DA Medina-Lezama, J Salinas-Najarro, B Arguelles, W Llabre, MM Schneiderman, N Paz-Manrique, R Bolanos, JF Khan, Z Chirinos, JA AF Chirinos, Diana A. Medina-Lezama, Josefina Salinas-Najarro, Belissa Arguelles, William Llabre, Maria M. Schneiderman, Neil Paz-Manrique, Roberto Bolanos, Juan F. Khan, Zubair Chirinos, Julio A. TI Depressive symptoms and carotid intima-media thickness in South American Hispanics: results from the PREVENCION study SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE Depression; Carotid intima-media thickness; Gender moderation; South American Hispanics; Cardiovascular disease ID CORONARY-ARTERY-DISEASE; HEART-RATE-VARIABILITY; C-REACTIVE PROTEIN; 1966 BIRTH COHORT; CARDIOVASCULAR-DISEASE; METABOLIC SYNDROME; MYOCARDIAL-INFARCTION; RISK-FACTORS; SUBCLINICAL ATHEROSCLEROSIS; HOSPITAL ANXIETY AB This study aimed to: (1) examine the relationship between depressive symptoms and subclinical atherosclerosis, measured by carotid intima-media thickness (IMT); and, (2) Determine the moderating effect of gender in this relationship among South American Hispanics. We studied 496 adults enrolled in the population-based PREVENCION study. Carotid IMT was measured with high-resolution ultrasonography. Depressive symptoms were assessed using the Hospital Anxiety and Depression Scale. Mean carotid IMT was 0.66 mm. (SD = 0.17) and mean depression score was 5.6 (SD = 3.5). Depressive symptoms were not associated with carotid IMT (beta = 0.04, p = 0.222) in multivariate analyses. A significant moderating effect of gender was found (beta for interaction = 0.10, p = 0.030), resulting from a significant association between depressive symptoms and carotid IMT in men but not women. Depressive symptoms were associated with subclinical atherosclerosis in South American Hispanic men but not women after controlling for demographic characteristics and traditional cardiovascular risk factors. C1 [Chirinos, Diana A.; Arguelles, William; Llabre, Maria M.; Schneiderman, Neil] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. [Chirinos, Diana A.; Medina-Lezama, Josefina; Salinas-Najarro, Belissa; Paz-Manrique, Roberto; Bolanos, Juan F.] Santa Maria Catholic Univ, Res Inst, Arequipa, Peru. [Khan, Zubair; Chirinos, Julio A.] Univ Penn, Philadelphia, PA 19104 USA. [Chirinos, Julio A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Chirinos, DA (reprint author), Univ Miami, Dept Psychol, POB 248185, Coral Gables, FL 33124 USA. EM dchirinos-medina@psy.miami.edu OI Khan, Zubair/0000-0002-0451-9155 FU Santa Maria Research Institute in Arequipa, Peru FX The PREVENCION study was supported by the Santa Maria Research Institute in Arequipa, Peru. NR 60 TC 2 Z9 2 U1 0 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0160-7715 EI 1573-3521 J9 J BEHAV MED JI J. Behav. Med. PD APR PY 2015 VL 38 IS 2 BP 284 EP 293 DI 10.1007/s10865-014-9599-9 PG 10 WC Psychology, Clinical SC Psychology GA CD5NV UT WOS:000351135900010 PM 25267357 ER PT J AU Magidson, JF Listhaus, A Seitz-Brown, CJ Safren, SA Lejuez, CW Daughters, SB AF Magidson, Jessica F. Listhaus, Alyson Seitz-Brown, C. J. Safren, Steven A. Lejuez, C. W. Daughters, Stacey B. TI Can behavioral theory inform the understanding of depression and medication nonadherence among HIV-positive substance users? SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE Depression; HIV/AIDS; Medication adherence; Substance use; Behavioral theory ID SELF-REPORTED ADHERENCE; ACTIVE ANTIRETROVIRAL THERAPY; ILLICIT DRUG-USE; NEW-YORK-CITY; HEALTH LOCUS; PROTEASE INHIBITORS; DISEASE PROGRESSION; INFECTED PATIENTS; EXTERNAL CONTROL; LIFE EVENTS AB Medication adherence is highly predictive of health outcomes across chronic conditions, particularly HIV/AIDS. Depression is consistently associated with worse adherence, yet few studies have sought to understand how depression relates to adherence. This study tested three components of behavioral depression theory-goal-directed activation, positive reinforcement, and environmental punishment-as potential indirect effects in the relation between depressive symptoms and medication nonadherence among low-income, predominantly African American substance users (n = 83). Medication nonadherence was assessed as frequency of doses missed across common reasons for nonadherence. Non-parametric bootstrapping was used to evaluate the indirect effects. Of the three intermediary variables, there was only an indirect effect of environmental punishment; depressive symptoms were associated with greater nonadherence through greater environmental punishment. Goal-directed activation and positive reinforcement were unrelated to adherence. Findings suggest the importance of environmental punishment in the relation between depression and medication adherence and may inform future intervention efforts for this population. C1 [Magidson, Jessica F.; Safren, Steven A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Magidson, Jessica F.; Listhaus, Alyson; Seitz-Brown, C. J.; Lejuez, C. W.] Univ Maryland, College Pk, MD 20742 USA. [Listhaus, Alyson] Columbia Univ, New York, NY USA. [Daughters, Stacey B.] Univ N Carolina, Chapel Hill, NC USA. RP Magidson, JF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, One Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM jmagidson@partners.org FU [R01DA022974]; [R36DA034513]; [T32MH093310]; [K24MH094214] FX This study was supported by Grants R01DA022974 (PI: Daughters) and R36DA034513 (PI: Magidson). Dr. Magidson's work on this manuscript was also supported by T32MH093310 (PIs: Henderson and Fricchione). Dr. Safren is supported by Grant K24MH094214. NR 73 TC 1 Z9 1 U1 4 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0160-7715 EI 1573-3521 J9 J BEHAV MED JI J. Behav. Med. PD APR PY 2015 VL 38 IS 2 BP 337 EP 347 DI 10.1007/s10865-014-9606-1 PG 11 WC Psychology, Clinical SC Psychology GA CD5NV UT WOS:000351135900015 PM 25381605 ER PT J AU Mayberry, LS Egede, LE Wagner, JA Osborn, CY AF Mayberry, Lindsay Satterwhite Egede, Leonard E. Wagner, Julie A. Osborn, Chandra Y. TI Stress, depression and medication nonadherence in diabetes: test of the exacerbating and buffering effects of family support SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE Stress/stressors; Depression; Family support; Social support; Medication adherence; Diabetes ID SOCIAL SUPPORT; GLYCEMIC CONTROL; SUPPRESSOR VARIABLES; REGIMEN ADHERENCE; PATIENT-ADHERENCE; PHARMACY RECORDS; HEALTH LITERACY; SELF-CARE; ADULTS; MORTALITY AB Stressors and depressive symptoms have been associated with medication nonadherence among adults with type 2 diabetes (T2DM). We tested whether these associations were exacerbated by obstructive family behaviors or buffered by supportive family behaviors in a sample of 192 adults with T2DM and low socioeconomic status using unadjusted and adjusted regression models. We found support for the exacerbating hypothesis. Stressors and nonadherence were only associated at higher levels of obstructive family behaviors (interaction AOR = 1.12, p = .002). Similarly, depressive symptoms and nonadherence were only associated at higher levels of obstructive family behaviors (interaction AOR = 3.31, p = .002). When participants reported few obstructive family behaviors, neither stressors nor depressive symptoms were associated with nonadherence. We did not find support for the buffering hypothesis; stressors and depressive symptoms were associated with nonadherence regardless of supportive family behaviors. Nonadherent patients experiencing stressors and/or major depressive symptoms may benefit from interventions that reduce obstructive family behaviors. C1 [Mayberry, Lindsay Satterwhite; Osborn, Chandra Y.] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37235 USA. [Mayberry, Lindsay Satterwhite; Osborn, Chandra Y.] Vanderbilt Univ, Med Ctr, Ctr Diabet Translat Res, Nashville, TN USA. [Mayberry, Lindsay Satterwhite; Osborn, Chandra Y.] Vanderbilt Univ, Med Ctr, Ctr Hlth Behav & Hlth Educ, Nashville, TN USA. [Egede, Leonard E.] Ralph H Johnson Dept Vet Affairs Med Ctr, Hlth Equ & Rural Outreach Innovat Ctr, Charleston, SC USA. [Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Div Gen Internal Med, Charleston, SC 29425 USA. [Wagner, Julie A.] Univ Connecticut, Ctr Hlth, Div Behav Sci & Community Hlth, Farmington, CT USA. [Osborn, Chandra Y.] Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN USA. RP Mayberry, LS (reprint author), Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37235 USA. EM Lindsay.mayberry@vanderbilt.edu FU National Center for Research Resources at the National Center for Advancing Translational Sciences [UL1 RR024975-01, 2 UL1 TR000445-06]; NIH/NIDDK Career Development Award [K01DK087894]; NIH/NIDDK National Research Service Award [F32DK097880]; AHRQ [K12 HS022990]; NIH/NIMHD [R01 MD005879]; NIH/NIDDK [DP3 DK097705, K24DK093699, R01DK098529]; American Diabetes Association [7-13-TS-31]; Chicago Center for Diabetes Translation Research; [P30DK092986]; [R01 (R01DK100694-01A1)] FX The authors would like to acknowledge Cecilia C. Quintero, Sahbina Ebba, Karen Calderon, Leo Cortes, Anne Crook, Carmen Mekhail, the Vine Hill Community Clinic personnel, and the participants for their contributions to this research. This research study was funded with support the National Center for Research Resources, Grant UL1 RR024975-01, which is now at the National Center for Advancing Translational Sciences, Grant 2 UL1 TR000445-06. This study was supported in part by grant P30DK092986 (PI: Elasy). C. Y. O. was supported by an NIH/NIDDK Career Development Award (K01DK087894) and R01 (R01DK100694-01A1). L. S. M. was supported by an NIH/NIDDK National Research Service Award (F32DK097880) and AHRQ (K12 HS022990). J. A. W. was supported by the NIH/NIMHD (R01 MD005879), the NIH/NIDDK (DP3 DK097705), the American Diabetes Association (7-13-TS-31), and the Chicago Center for Diabetes Translation Research. L. E. E. was supported by NIH/NIDDK (K24DK093699) and NIH/NIDDK (R01DK098529). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 64 TC 4 Z9 4 U1 3 U2 10 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0160-7715 EI 1573-3521 J9 J BEHAV MED JI J. Behav. Med. PD APR PY 2015 VL 38 IS 2 BP 363 EP 371 DI 10.1007/s10865-014-9611-4 PG 9 WC Psychology, Clinical SC Psychology GA CD5NV UT WOS:000351135900017 PM 25420694 ER PT J AU Trackman, PC Kantarci, A AF Trackman, P. C. Kantarci, A. TI Molecular and Clinical Aspects of Drug-induced Gingival Overgrowth SO JOURNAL OF DENTAL RESEARCH LA English DT Review DE gingiva; cell signaling; connective tissue biology; inflammation; collagen(s); innate immunity ID TISSUE GROWTH-FACTOR; SQUAMOUS-CELL CARCINOMA; NEUROFIBROMATOSIS TYPE-I; CYCLOSPORINE-A; TGF-BETA; MAST-CELLS; EXTRACELLULAR-MATRIX; PERIODONTAL THERAPY; LYSYL OXIDASE; EXPRESSION AB Drug-induced gingival overgrowth is a tissue-specific condition and is estimated to affect approximately one million North Americans. Lesions occur principally as side-effects from phenytoin, nifedipine, or ciclosporin therapy in approximately half of the people who take these agents. Due to new indications for these drugs, their use continues to grow. Here, we review the molecular and cellular characteristics of human gingival overgrowth lesions and highlight how they differ considerably as a function of the causative drug. Analyses of molecular signaling pathways in cultured human gingival fibroblasts have provided evidence for their unique aspects compared with fibroblasts from the lung and kidney. These findings provide insights into both the basis for tissue specificity and into possible therapeutic opportunities which are reviewed here. Although ciclosporin-induced gingival overgrowth lesions exhibit principally the presence of inflammation and little fibrosis, nifedipine- and especially phenytoin-induced lesions are highly fibrotic. The increased expression of markers of gingival fibrosis, particularly CCN2 [also known as connective tissue growth factor (CTGF)], markers of epithelial to mesenchymal transition, and more recently periostin and members of the lysyl oxidase family of enzymes have been documented in phenytoin or nifedipine lesions. Some oral fibrotic conditions such as leukoplakia and oral submucous fibrosis, after subsequent additional genetic damage, can develop into oral cancer. Since many pathways are shared, the study of gingival fibrosis and comparisons with characteristics and molecular drivers of oral cancer would likely enhance understandings and functional roles of molecular drivers of these oral pathologies. C1 [Trackman, P. C.] Boston Univ, Dept Mol & Cell Biol, Henry M Goldman Sch Dent Med, Boston, MA 02118 USA. [Kantarci, A.] Ctr Periodontol, Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA USA. RP Trackman, PC (reprint author), Boston Univ, Dept Mol & Cell Biol, Henry M Goldman Sch Dent Med, 700 Albany St W-201, Boston, MA 02118 USA. EM trackman@bu.edu FU National Institutes of Health (NIH)/National Institute of Dental and Craniofacial Research (NIDCR) [R01DE011004]; Boston University Henry M. Goldman School of Dental Medicine FX This work was supported by National Institutes of Health (NIH)/National Institute of Dental and Craniofacial Research (NIDCR) R01DE011004 and support from the Boston University Henry M. Goldman School of Dental Medicine. The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 69 TC 9 Z9 9 U1 3 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD APR PY 2015 VL 94 IS 4 BP 540 EP 546 DI 10.1177/0022034515571265 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CE2HO UT WOS:000351636500005 PM 25680368 ER PT J AU Murphy, SN Herrick, C Wang, YB Wang, TD Sack, D Andriole, KP Wei, J Reynolds, N Plesniak, W Rosen, BR Pieper, S Gollub, RL AF Murphy, Shawn N. Herrick, Christopher Wang, Yanbing Wang, Taowei David Sack, Darren Andriole, Katherine P. Wei, Jesse Reynolds, Nathaniel Plesniak, Wendy Rosen, Bruce R. Pieper, Steven Gollub, Randy L. TI High Throughput Tools to Access Images from Clinical Archives for Research SO JOURNAL OF DIGITAL IMAGING LA English DT Article DE Medical images; Informatics; Secondary research use of medical records ID INTEGRATING BIOLOGY; ACUTE STROKE; INFORMATICS; PREDICTS; BRAIN; THROMBOLYSIS; ANNOTATION; MATURATION; CHILDHOOD; BEDSIDE AB Historically, medical images collected in the course of clinical care have been difficult to access for secondary research studies. While there is a tremendous potential value in the large volume of studies contained in clinical image archives, Picture Archiving and Communication Systems (PACS) are designed to optimize clinical operations and workflow. Search capabilities in PACS are basic, limiting their use for population studies, and duplication of archives for research is costly. To address this need, we augment the Informatics for Integrating Biology and the Bedside (i2b2) open source software, providing investigators with the tools necessary to query and integrate medical record and clinical research data. Over 100 healthcare institutions have installed this suite of software tools that allows investigators to search medical record metadata including images for specific types of patients. In this report, we describe a new Medical Imaging Informatics Bench to Bedside (mi2b2) module (www.mi2b2.org), available now as an open source addition to the i2b2 software platform that allows medical imaging examinations collected during routine clinical care to be made available to translational investigators directly from their institution's clinical PACS for research and educational use in compliance with the Health Insurance Portability and Accountability Act (HIPAA) Omnibus Rule. Access governance within the mi2b2 module is customizable per institution and PACS minimizing impact on clinical systems. Currently in active use at our institutions, this new technology has already been used to facilitate access to thousands of clinical MRI brain studies representing specific patient phenotypes for use in research. C1 [Murphy, Shawn N.; Herrick, Christopher; Wang, Yanbing; Wang, Taowei David] Partners HealthCare, Res IS & Comp, Charlestown, MA 02129 USA. [Murphy, Shawn N.] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. [Rosen, Bruce R.; Gollub, Randy L.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Andriole, Katherine P.; Plesniak, Wendy] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Wei, Jesse] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Reynolds, Nathaniel; Gollub, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Pieper, Steven] Isomics, Cambridge, MA USA. [Rosen, Bruce R.] Kyung Hee Univ, East West Med Res Inst, Dept Meridian & Acupuncture, Collaborating Ctr Tradit Med, Seoul 130701, South Korea. [Rosen, Bruce R.] Kyung Hee Univ, Sch Korean Med, Seoul 130701, South Korea. [Sack, Darren] Partners HealthCare, Informat Syst, Charlestown, MA USA. RP Murphy, SN (reprint author), Partners HealthCare, Res IS & Comp, Charlestown, MA 02129 USA. EM snmurphy@partners.org FU National Institutes of Health, National Center for Research Resources (NIH-NCRR) as an ARRA [1 UL1 RR 025758-01]; Biomedical Informatics Research Network [1 U24 RR 025736-01]; Partners HealthCare System Inc; National Institute for Biomedical Imaging and Bioengineering [R01 EB014947-01] FX This work was funded by National Institutes of Health, National Center for Research Resources (NIH-NCRR) as an ARRA supplement to Harvard Medical School's Clinical Translational Science Award (the Harvard Catalyst) under the Medical Imaging Informatics Bench to Bedside (mi2b2) grant NCRR (1 UL1 RR 025758-01), the Biomedical Informatics Research Network (1 U24 RR 025736-01) and Partners HealthCare System Inc, and by the National Institute for Biomedical Imaging and Bioengineering R01 EB014947-01 (PIs: Murphy/Grant/Gollub) "mi2bi2 Enabled Pediatric Radiological Decision Support." NR 38 TC 2 Z9 2 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0897-1889 EI 1618-727X J9 J DIGIT IMAGING JI J. Digit. Imaging PD APR PY 2015 VL 28 IS 2 BP 194 EP 204 DI 10.1007/s10278-014-9733-9 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CD7AL UT WOS:000351242500010 PM 25316195 ER PT J AU Rachidi, S Sun, SL Wu, BX Jones, E Drake, RR Ogretmen, B Cowart, LA Clarke, CJ Hannun, YA Chiosis, G Liu, B Li, ZH AF Rachidi, Saleh Sun, Shaoli Wu, Bill X. Jones, Elizabeth Drake, Richard R. Ogretmen, Besim Cowart, L. Ashley Clarke, Christopher J. Hannun, Yusuf A. Chiosis, Gabriela Liu, Bei Li, Zihai TI Endoplasmic reticulum heat shock protein gp96 maintains liver homeostasis and promotes hepatocellular carcinogenesis SO JOURNAL OF HEPATOLOGY LA English DT Article DE grp94; Molecular chaperone; Liver cancer; gp96 ID TOLL-LIKE RECEPTORS; GLUCOSE-REGULATED PROTEINS; HEPATIC STEATOSIS; MOLECULAR-MECHANISMS; SIGNAL-TRANSDUCTION; THERAPEUTIC-TARGET; MASTER CHAPERONE; MOUSE MODEL; ER STRESS; CERAMIDE AB Background & Aims: gp96, or grp94, is an endoplasmic reticulum (ER)-localized heat shock protein 90 paralog that acts as a protein chaperone and plays an important role for example in ER homeostasis, ER stress, Wnt and integrin signaling, and calcium homeostasis, which are vital processes in oncogenesis. However, the cancer-intrinsic function of gp96 remains controversial. Methods: We studied the roles of gp96 in liver biology in mice via an Albumin promoter-driven Cre recombinase-mediated disruption of gp96 gene, hsp90b1. The impact of gp96 status on hepatic carcinogenesis in response to diethyl-nitrosoamine (DENA) was probed. The roles of gp96 on human hepatocellular carcinoma cells (HCC) were also examined pharmacologically with a targeted gp96 inhibitor. Results: We demonstrated that gp96 maintains liver development and hepatocyte function in vivo, and its loss genetically promotes adaptive accumulation of long chain ceramides, accompanied by steatotic regeneration of residual gp96+ hepatocytes. The need for compensatory expansion of gp96+ cells in the gp96- background predisposes mice to develop carcinogen-induced hepatic hyperplasia and cancer from gp96+ but not gp96- hepatocytes. We also found that genetic and pharmacological inhibition of gp96 in human HCCs perturbed multiple growth signals, and attenuated proliferation and expansion. Conclusions: gp96 is a pro-oncogenic chaperone and an attractive therapeutic target for HCC. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 [Rachidi, Saleh; Wu, Bill X.; Liu, Bei; Li, Zihai] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Rachidi, Saleh; Wu, Bill X.; Liu, Bei; Li, Zihai] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Sun, Shaoli] Med Univ S Carolina, Dept Pathol, Charleston, SC 29425 USA. [Jones, Elizabeth; Drake, Richard R.] Med Univ S Carolina, Dept Cell & Mol Pharmacol, Charleston, SC 29425 USA. [Ogretmen, Besim; Cowart, L. Ashley] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Cowart, L. Ashley] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Clarke, Christopher J.; Hannun, Yusuf A.] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. [Chiosis, Gabriela] Mem Sloan Kettering Canc Ctr, Program Mol Pharmacol & Chem, New York, NY 10021 USA. RP Li, ZH (reprint author), Hollings Canc Ctr, Dept Microbiol & Immunol, Charleston, SC 29425 USA. EM zihai@musc.edu FU NIH [AI070603, AI077283, CA97132]; VA Merit Award [2I0BX000200-04]; Lipidomics Shared Resource, Hollings Cancer Center, Medical University of South Carolina [P30 CA138313]; Lipidomics Core in the SC Lipidomics and Pathobiology COBRE, Department of Biochemistry and Molecular Biology, MUSC [P20 RR017677] FX This study was supported in part by NIH grants AI070603, AI077283 (to ZL), CA97132 (to YAH), and a VA Merit Award 2I0BX000200-04 (to LAC). It was also supported by the Lipidomics Shared Resource, Hollings Cancer Center, Medical University of South Carolina (P30 CA138313) and the Lipidomics Core in the SC Lipidomics and Pathobiology COBRE, Department of Biochemistry and Molecular Biology, MUSC (P20 RR017677). NR 55 TC 11 Z9 12 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD APR PY 2015 VL 62 IS 4 BP 879 EP 888 DI 10.1016/j.jhep.2014.11.010 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CD7WH UT WOS:000351305300019 PM 25463537 ER PT J AU Katiyar, SK AF Katiyar, Santosh K. TI Hsp90 Inhibitor Can Inhibit UV Carcinogenesis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material ID PROTEIN-KINASE-C; SQUAMOUS-CELL CARCINOMAS; INDUCED CUTANEOUS DAMAGE; PHASE-II TRIAL; CANCER; 17-ALLYLAMINO-17-DEMETHOXYGELDANAMYCIN; EPSILON; TARGET; SKIN AB Extensive exposure to solar UVR is a well-recognized etiologic factor for cutaneous non-melanoma skin cancer. In this issue of the Journal, Singh et al. show that topical treatment of the skin with 17-[allylamino]-17-demethoxygeldanamycin (17AAG), a heat-shock protein 90 (Hsp90) inhibitor, prevents UVR-induced squamous cell carcinomas (SCCs) in mice. The inhibitory effect of 17AAG on SCC was associated with the inhibition of the UVR-induced (i) hyperplastic response, (ii) Hsp90 beta-PKC epsilon interaction, and (iii) pStat3 and pAkt expression in mouse skin. C1 [Katiyar, Santosh K.] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Dept Dermatol, Birmingham, AL USA. RP Katiyar, SK (reprint author), Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU BLRD VA [I01 BX001410]; NCI NIH HHS [CA140197, CA140832, R01 CA140197, R21 CA140832] NR 12 TC 1 Z9 1 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2015 VL 135 IS 4 BP 945 EP 947 DI 10.1038/jid.2014.504 PG 3 WC Dermatology SC Dermatology GA CD6GW UT WOS:000351188600006 PM 25785948 ER PT J AU Gilchrest, BA Campisi, J Chang, HY Fisher, GJ Kulesz-Martin, MF AF Gilchrest, Barbara A. Campisi, Judith Chang, Howard Y. Fisher, Gary J. Kulesz-Martin, Molly F. TI Montagna Symposium 2014-Skin Aging: Molecular Mechanisms and Tissue Consequences SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article C1 [Gilchrest, Barbara A.] Massachusetts Gen Hosp, Dermatol Serv, Boston, MA 02114 USA. [Campisi, Judith] Buck Inst Res Aging, Novato, CA USA. [Campisi, Judith] Lawrence Berkeley Natl Lab, Novato, CA USA. [Chang, Howard Y.] Stanford Univ, Dept Dermatol, Stanford, CA 94305 USA. [Fisher, Gary J.] Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA. [Kulesz-Martin, Molly F.] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97239 USA. RP Kulesz-Martin, MF (reprint author), Oregon Hlth & Sci Univ, Dept Dermatol, L468R,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM kuleszma@ohsu.edu FU National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institute of Aging [R13 AR009431]; Estee Lauder Companies; Galderma International; Advancing Innovation in Dermatology; DUSA Pharmaceuticals; Johnson and Johnson Consumer and Personal Products Worldwide; KYTHERA Bio-pharmaceuticals; Living Proof; Procter and Gamble Company; Valeant Pharmaceuticals North America LLC; Maruho Company; Orentreich Family Foundation FX The Montagna Symposium on the Biology of Skin is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute of Aging (R13 AR009431). Other 2014 supporters included the following: The Estee Lauder Companies; Galderma International; Advancing Innovation in Dermatology; DUSA Pharmaceuticals; Johnson and Johnson Consumer and Personal Products Worldwide; KYTHERA Bio-pharmaceuticals; Living Proof; The Procter and Gamble Company; Curtis T. Thompson; Valeant Pharmaceuticals North America LLC; Maruho Company; The Orentreich Family Foundation; and Joel S. Gordon. Loa Nowina-Sapinski and Clara Stemwedel assisted in the preparation of this manuscript. The Montagna Symposium on the Biology of Skin, directed by Molly F. KuleszMartin, is an annual nonprofit scientific meeting, inaugurated in 1950 by William Montagna, that gathers leading cutaneous biologists and dermatologists to discuss new findings, techniques, and goals in skin biology. Podcast interviews of Symposium invited speakers are available at http://www.nature.com/jid/skinpod/index.html, and blog posts from the meeting may be found at http://www.scilogs.com/jid/category/meeting-notes/. NR 0 TC 2 Z9 2 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2015 VL 135 IS 4 BP 950 EP 953 DI 10.1038/jid.2014.546 PG 4 WC Dermatology SC Dermatology GA CD6GW UT WOS:000351188600008 PM 25785950 ER PT J AU Kumar, R Taylor, M Miao, BC Ji, ZY Njauw, JCN Jonsson, G Frederick, DT Tsao, HS AF Kumar, Raj Taylor, Michael Miao, Benchun Ji, Zhenyu Njauw, Jenny C-N Jonsson, Goran Frederick, Dennie T. Tsao, Hensin TI BAP1 Has a Survival Role in Cutaneous Melanoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID UVEAL MELANOMA; MUTATIONS; GROWTH; MESOTHELIOMA; PREDISPOSE; EXPRESSION; REGULATOR; HYDROLASE; CANCER; FORMS AB Although the pattern of BAP1 inactivation in ocular melanoma specimens and in the BAP1 cutaneous melanoma (CM)/ocular melanoma predisposition syndrome suggests a tumor suppressor function, the specific role of this gene in the pathogenesis of CM is not fully understood. We thus set out to characterize BAP1 in CM and discovered an unexpected pro-survival effect of this protein. Tissue and cell lines analysis showed that BAP1 expression was maintained, rather than lost, in primary melanomas compared with nevi and normal skin. Genetic depletion of BAP1 in melanoma cells reduced proliferation and colony-forming capability induced apoptosis, and inhibited melanoma tumor growth in vivo. On the molecular level, suppression of BAP1 led to a concomitant drop in the protein levels of survivin, a member of anti-apoptotic proteins and a known mediator of melanoma survival. Restoration of survivin in melanoma cells partially rescued the growth-retarding effects of BAP1 loss. In contrast to melanoma cells, stable overexpression of BAP1 into immortalized but non-transformed melanocytes did suppress proliferation and reduce survivin. Taken together, these studies demonstrate that BAP1 may have a growth-sustaining role in melanoma cells, but that its impact on ubiquitination underpins a complex physiology, which is context and cell dependent. C1 [Kumar, Raj; Taylor, Michael; Miao, Benchun; Ji, Zhenyu; Njauw, Jenny C-N; Tsao, Hensin] Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Jonsson, Goran] Lund Univ, Dept Oncol, Clin Sci, Lund, Sweden. [Frederick, Dennie T.] Massachusetts Gen Hosp, MGH Canc Ctr, Dept Surg Oncol, Boston, MA 02466 USA. RP Tsao, HS (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Dept Dermatol, Edwards 211,48 Blossom St, Boston, MA 02466 USA. EM htsao@partners.org FU NIH [K24 CA149202] FX This work was supported in part by the generous donors of the Massachusetts General Hospital, the American Skin Association (to HT), and the Swedish Cancer Society and Swedish Research Council (both to GJ). Mentorship during the performance of this research was supported by an NIH K24 CA149202 award (to HT). Cell line maintenance manipulation was done with support from NIH P01CA163222. NR 24 TC 7 Z9 7 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2015 VL 135 IS 4 BP 1089 EP 1097 DI 10.1038/jid.2014.528 PG 9 WC Dermatology SC Dermatology GA CD6GW UT WOS:000351188600025 PM 25521456 ER PT J AU Yeon, SB Salton, CJ Gona, P Chuang, ML Blease, SJ Han, YC Tsao, CW Danias, PG Levy, D O'Donnell, CJ Manning, WJ AF Yeon, Susan B. Salton, Carol J. Gona, Philimon Chuang, Michael L. Blease, Susan J. Han, Yuchi Tsao, Connie W. Danias, Peter G. Levy, Daniel O'Donnell, Christopher J. Manning, Warren J. TI Impact of Age, Sex, and Indexation Method on MR Left Ventricular Reference Values in the Framingham Heart Study Offspring Cohort SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE magnetic resonance imaging; left ventricle; aging; sex differences; population study; reference values ID CARDIOVASCULAR MAGNETIC-RESONANCE; FAT-FREE MASS; BODY-SIZE; GENDER-DIFFERENCES; AMERICAN-INDIANS; ADULTS; ATHEROSCLEROSIS; REPRODUCIBILITY; HYPERTENSION; HYPERTROPHY AB PurposeTo determine normative values for left ventricular (LV) volumes, mass, concentricity, and ejection fraction (EF) and investigate associations between sex, age, and body size with LV parameters in community-dwelling adults. Materials and MethodsIn all, 1794 Framingham Heart Study Offspring cohort members underwent LV short-axis oriented, contiguous multislice cine steady-state free precession MR of the left ventricle; from these a healthy referent group (n=852, 619 years, 40% men) free of clinical cardiac disease and hypertension (SBP<140, DBP<90 mmHg, never used antihypertensive medication 30 years prior to scanning) was identified. Referent participants were stratified by sex and age group (55, 56-65, >65 years); LV parameters were indexed to measures of body size. ResultsMen have greater LV volumes and mass than women both before and after indexation to height, powers of height, and body surface area (P<0.01 all), but indexation to fat-free mass yielded greater LV volume and mass in women. In both sexes, LV volumes and mass decrease with advancing age, although indexation attenuates this association. LVEF is greater in women than men (68 +/- 5% vs. 66 +/- 5%, P<0.01) and increases with age in both sexes (P<0.05). ConclusionAmong nonhypertensive adults free of cardiac disease, men have greater LV volumes and mass with sex differences generally persisting after indexation to body size. LV volumes and mass tend to decrease with greater age in both sexes. Female sex and advanced age were both associated with greater LVEF. J. Magn. Reson. Imaging 2015;41:1038-1045. (c) 2014 Wiley Periodicals, Inc. C1 [Yeon, Susan B.; Salton, Carol J.; Tsao, Connie W.; Danias, Peter G.; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA. [Yeon, Susan B.; Tsao, Connie W.; O'Donnell, Christopher J.; Manning, Warren J.] Harvard Univ, Sch Med, Boston, MA USA. [Gona, Philimon; Chuang, Michael L.; Blease, Susan J.; Tsao, Connie W.; Levy, Daniel; O'Donnell, Christopher J.] NHLBIs Framingham Heart Study, Framingham, MA USA. [Han, Yuchi] Univ Penn, Sch Med, Dept Med, Div Cardiovasc, Philadelphia, PA 19104 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. RP Chuang, ML (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM mlc48104@gmail.com FU National Institutes of Health [R01 AG17509, N01-HC-38038, N01-HC-025195]; National Institute of Arthritis Musculoskeletal and Skin Diseases; National Institute of Aging [R01 AR/AG 41398] FX Contract grant sponsor: National Institutes of Health; Contract grant numbers: R01 AG17509, N01-HC-38038, and N01-HC-025195; Contract grant sponsor: National Institute of Arthritis Musculoskeletal and Skin Diseases and the National Institute of Aging; Contract grant number: R01 AR/AG 41398 (for DXA scanning). NR 36 TC 10 Z9 10 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-1807 EI 1522-2586 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD APR PY 2015 VL 41 IS 4 BP 1038 EP 1045 DI 10.1002/jmri.24649 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CE0UD UT WOS:000351521700021 PM 24817313 ER PT J AU Wang, CH Chan, ED Perng, CL Chian, CF Chen, CW Perng, WC Su, WL AF Wang, Ching-Hsun Chan, Edward D. Perng, Cherng-Lih Chian, Chih-Feng Chen, Chien-Wen Perng, Wann-Cherng Su, Wen-Lin TI Intravenous immunoglobulin replacement therapy to prevent pulmonary infection in a patient with Good's syndrome SO JOURNAL OF MICROBIOLOGY IMMUNOLOGY AND INFECTION LA English DT Article DE Cytomegalovirus infections; Immunodeficiency; Pneumonia; Thymoma ID IMMUNODEFICIENCY; DISEASE; COMMITTEE; THYMOMA AB Good's syndrome is an acquired immunodeficiency state associated with thymoma and characterized by recurrent pulmonary infections. We describe a 67-year-old woman who presented with respiratory symptoms caused by concomitant disseminated cytomegalovirus infection and Pneumocystis jiroveci pneumonia 38 months after thymectomy for a thymoma. Immunologic analysis revealed hypogammaglobulinemia with absent B-cell population as demonstrated by flow cytometry, consistent with Good's syndrome. Following treatment with sulfamethoxazole/trimethoprim and ganciclovir, the patient improved with resolution of her respiratory symptoms. However, the patient subsequently experienced additional infections, necessitating additional subsequent hospital admissions. During the last admission, intravenous immunoglobulin (IVIG) replacement therapy was initiated and continued after discharge. Infection has been prevented for one year after beginning IVIG replacement therapy. This case reveals that in patients with combined humoral and cell-mediated immune deficiency, concomitant infection with different pathogens is not unusual, and immediate specific therapy is important. Periodic IVIG infusion, to maintain adequate Ig levels, is recommended. Copyright (C) 2012, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. All rights reserved. C1 [Wang, Ching-Hsun] Tri Serv Gen Hosp, Dept Internal Med, Taipei 114, Taiwan. [Chan, Edward D.] Univ Colorado, Anschutz Med Ctr, Div Pulm Sci & Crit Care Med, Denver, CO 80045 USA. [Chan, Edward D.] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. [Chan, Edward D.] Natl Jewish Hlth, Dept Med, Div Mycobacterial & Resp Infect, Denver, CO 80206 USA. [Perng, Cherng-Lih] Tri Serv Gen Hosp, Dept Pathol, Div Clin Pathol, Taipei 114, Taiwan. [Perng, Cherng-Lih] Natl Def Med Ctr, Grad Inst Pathol, Taipei, Taiwan. [Chian, Chih-Feng; Chen, Chien-Wen; Perng, Wann-Cherng; Su, Wen-Lin] Tri Serv Gen Hosp, Div Pulm & Crit Care Med, Dept Internal Med, Taipei 114, Taiwan. [Perng, Wann-Cherng; Su, Wen-Lin] Natl Def Med Ctr, Taipei, Taiwan. RP Su, WL (reprint author), Tri Serv Gen Hosp, Div Pulm & Crit Care Med, 325,Sect 2,Cheng Kung Rd, Taipei 114, Taiwan. EM soa@mail.ndmctsgh.edu.tw NR 10 TC 4 Z9 4 U1 1 U2 4 PU ELSEVIER TAIWAN PI TAIPEI PA RM N-412, 4F, CHIA HSIN BUILDING 11, NO 96, ZHONG SHAN N ROAD SEC 2, TAIPEI, 10449, TAIWAN SN 1684-1182 EI 1995-9133 J9 J MICROBIOL IMMUNOL JI J. Microbiol. Immunol. Infect. PD APR PY 2015 VL 48 IS 2 BP 229 EP 232 DI 10.1016/j.jmii.2012.09.003 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CD4PY UT WOS:000351067100016 PM 23200552 ER PT J AU Zhang, Z Yang, XQ Zhang, LL Duan, ZF Jia, LT Wang, P Shi, Y Li, Y Gao, JJ AF Zhang, Zhan Yang, Xiaoqian Zhang, Linlin Duan, Zhenfeng Jia, Liting Wang, Peng Shi, Ying Li, Ying Gao, Junjun TI Decreased expression and activation of Stat3 in severe preeclampsia SO JOURNAL OF MOLECULAR HISTOLOGY LA English DT Article DE Severe preeclampsia; Stat3 signal pathway; Placenta; Apoptosis; Invasion ID MATRIX-METALLOPROTEINASE (MMP)-2; PLACENTAL APOPTOSIS; INFLAMMATORY CYTOKINES; TROPHOBLAST APOPTOSIS; ABNORMAL PREGNANCIES; INTERLEUKIN-6; INVASION; CYTOTROPHOBLASTS; GROWTH; CELLS AB Severe preeclampsia (PE) is a major cause of maternal mortality and morbidity worldwide. Signal transducer and activator of transcription 3 (Stat3) signal pathway can modulate various fundamental cellular processes. However, whether Stat3 plays a role in the pathogenesis of severe PE is unknown. Therefore, in this study, the expression levels of Stat3 pathway-related genes and proteins, Stat3, pStat3, IL-6, Mcl-1L, Bcl-xL, survivin, MMP-2, and MMP-9, were evaluated by immunohistochemistry (IHC), Western blot analysis and real-time PCR in the severe preeclamptic placentas. Our results showed that Stat3 and pStat3 immunoreactivity were localized in both extravillous cytotrophoblast cells and villous trophoblast cells in the placentas. As compared with normotensive pregnancies, significantly decreased expressions of Stat3 and pStat3 proteins were observed in extravillous cytotrophoblast cells, villous trophoblast cells and entire placentas in patients with severe PE. The expression levels of Stat3, IL-6, survivin and MMP-2 mRNA were significantly decreased in severe preeclamptic placentas, while Mcl-1L, Bcl-xL and MMP-9 mRNA levels were unchanged. IHC results further confirmed that there was a significant decrease of IL-6, survivin and MMP-2 proteins expression in the severe preeclamptic placentas compared with the normal specimens. These findings suggested that decreased expression and activation of the Stat3 may be caused by decreased expression of a Stat3 upstream gene, such as IL-6. Decreased Stat3 expression and activation may play an important role in the pathogenesis of PE through regulation of the transcription of the Stat3 targeted genes survivin and MMP-2 to modulate apoptosis and invasion of placental trophoblastic cells. C1 [Zhang, Zhan; Yang, Xiaoqian] Zhengzhou Univ, Affiliated Hosp 3, Dept Obstet & Gynecol, Zhengzhou 450052, Henan Province, Peoples R China. [Zhang, Zhan; Zhang, Linlin; Jia, Liting; Wang, Peng; Shi, Ying; Gao, Junjun] Zhengzhou Univ, Affiliated Hosp 3, Dept Clin Lab, Zhengzhou 450052, Henan Province, Peoples R China. [Zhang, Zhan; Zhang, Linlin; Jia, Liting; Li, Ying] Zhengzhou Univ, Affiliated Hosp 3, Henan Prov Engn Res Ctr Perinatal Med, Zhengzhou 450052, Henan Province, Peoples R China. [Zhang, Zhan; Zhang, Linlin; Jia, Liting; Li, Ying] Zhengzhou Univ, Affiliated Hosp 3, Henan Translat Med Engn Lab Maternal & Childrens, Zhengzhou 450052, Henan Province, Peoples R China. [Duan, Zhenfeng] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. [Duan, Zhenfeng] Harvard Univ, Sch Med, Boston, MA USA. RP Zhang, Z (reprint author), Zhengzhou Univ, Affiliated Hosp 3, Dept Obstet & Gynecol, 7 Kangfuqian St, Zhengzhou 450052, Henan Province, Peoples R China. EM zhangzhanzdsfy@126.com FU Science and Technology Fund for Innovative Talents of Henan Province [124200510005]; Key Scientific and Technological Project of Henan Province [112102310089]; Science and Technology Fund for Innovation Leading Research Team of Zhengzhou City [131PCXTD624] FX This work was supported by Grants from the Science and Technology Fund for Innovative Talents of Henan Province (No. 124200510005), the Key Scientific and Technological Project of Henan Province (No. 112102310089), and the Science and Technology Fund for Innovation Leading Research Team of Zhengzhou City (No. 131PCXTD624). NR 53 TC 4 Z9 4 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1567-2379 EI 1567-2387 J9 J MOL HISTOL JI J. Mol. Histol. PD APR PY 2015 VL 46 IS 2 BP 205 EP 219 DI 10.1007/s10735-015-9613-8 PG 15 WC Cell Biology SC Cell Biology GA CE1CK UT WOS:000351549300008 PM 25752465 ER PT J AU Hirsch, JA Leslie-Mazwi, TM Nicola, GN Barr, RM Bello, JA Donovan, WD Tu, R Alson, MD Manchikanti, L AF Hirsch, Joshua A. Leslie-Mazwi, Thabele M. Nicola, Gregory N. Barr, Robert M. Bello, Jacqueline A. Donovan, William D. Tu, Raymond Alson, Mark D. Manchikanti, Laxmaiah TI Current procedural terminology; a primer SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Review AB In 1966, The American Medical Association (AMA) working with multiple major medical specialty societies developed an iterative coding system for describing medical procedures and services using uniform language, the Current Procedural Terminology (CPT) system. The current code set, CPT IV, forms the basis of reporting most of the services performed by healthcare providers, physicians and non-physicians as well as facilities allowing effective, reliable communication among physician and other providers, third parties and patients. This coding system and its maintenance has evolved significantly since its inception, and now goes well beyond its readily perceived role in reimbursement. Additional roles include administrative management, tracking new and investigational procedures, and evolving aspects of 'pay for performance'. The system also allows for local, regional and national utilization comparisons for medical education and research. Neurointerventional specialists use CPT category I codes regularly-for example, 36 215 for first-order cerebrovascular angiography, 36 216 for second-order vessels, and 37 184 for acute stroke treatment by mechanical means. Additionally, physicians add relevant modifiers to the CPT codes, such as '-26' to indicate 'professional charge only,' or '-59' to indicate a distinct procedural service performed on the same day. C1 [Hirsch, Joshua A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroendovasc Program, Boston, MA 02114 USA. [Leslie-Mazwi, Thabele M.] Massachusetts Gen Hosp, Neuroendovasc Program, Boston, MA 02114 USA. [Nicola, Gregory N.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Barr, Robert M.] Mecklenburg Radiol Associates PA, Charlotte, NC USA. [Bello, Jacqueline A.] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. [Donovan, William D.] Norwich Diagnost Imaging Associates, Norwich, CT USA. [Tu, Raymond] George Washington Univ, Dept Progress Radiol, Falls Church, VA USA. [Alson, Mark D.] Sierra Imaging Associates, Clovis, CA USA. [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. RP Hirsch, JA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroendovasc Program, Boston, MA 02114 USA. EM Hirsch@snisonline.org NR 9 TC 12 Z9 12 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 APR PY 2015 VL 7 IS 4 BP 309 EP 312 DI 10.1136/neurintsurg-2014-011156 PG 4 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA CE2CB UT WOS:000351619400020 PM 24589819 ER PT J AU Mills, KA Markun, LC San Luciano, M Rizk, R Allen, IE Racine, CA Starr, PA Alberts, JL Ostrem, JL AF Mills, Kelly A. Markun, Leslie C. San Luciano, Marta Rizk, Rami Allen, I. Elaine Racine, Caroline A. Starr, Philip A. Alberts, Jay L. Ostrem, Jill L. TI Effect of subthalamic nucleus deep brain stimulation on dual-task cognitive and motor performance in isolated dystonia SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID QUALITY-OF-LIFE; PARKINSONS-DISEASE; PALLIDAL STIMULATION; CERVICAL DYSTONIA; RANDOMIZED-TRIAL; WORKING-MEMORY; FORCE CONTROL; FOLLOW-UP; GAIT; AGE AB Objective Subthalamic nucleus (STN) deep brain stimulation (DBS) can improve motor complications of Parkinson's disease (PD) but may worsen specific cognitive functions. The effect of STN DBS on cognitive function in dystonia patients is less clear. Previous reports indicate that bilateral STN stimulation in patients with PD amplifies the decrement in cognitive-motor dual-task performance seen when moving from a single-task to dual-task paradigm. We aimed to determine if the effect of bilateral STN DBS on dual-task performance in isolated patients with dystonia, who have less cognitive impairment and no dementia, is similar to that seen in PD. Methods Eight isolated predominantly cervical patients with dystonia treated with bilateral STN DBS, with average dystonia duration of 10.5 years and Montreal Cognitive Assessment score of 26.5, completed working memory (n-back) and motor (forced-maintenance) tests under single-task and dual-task conditions while on and off DBS. Results A multivariate, repeated-measures analysis of variance showed no effect of stimulation status (On vs Off) on working memory (F=0.75, p=0.39) or motor function (F=0.22, p=0.69) when performed under single-task conditions, though as working memory task difficulty increased, stimulation disrupted the accuracy of force-tracking. There was a very small worsening in working memory performance (F=9.14, p=0.019) when moving from single-task to dual-tasks when using the 'dual-task loss' analysis. Conclusions This study suggests the effect of STN DBS on working memory and attention may be much less consequential in patients with dystonia than has been reported in PD. C1 [Mills, Kelly A.; Markun, Leslie C.; San Luciano, Marta; Ostrem, Jill L.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Mills, Kelly A.; Ostrem, Jill L.] San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, San Francisco, CA USA. [Rizk, Rami; Alberts, Jay L.] Cleveland Clin, Dept Biomed Engn, Cleveland, OH 44106 USA. [Allen, I. Elaine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Racine, Caroline A.; Starr, Philip A.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. RP Ostrem, JL (reprint author), Univ Calif San Francisco, Surg Movement Disorders Ctr, 1635 Divisadero St,Suite 520,UCSF Box 1838, San Francisco, CA 94143 USA. EM jill.ostrem@ucsf.edu FU NIH/NCRR UCSF-CTSI [UL1RR024131] FX This project was supported by NIH/NCRR UCSF-CTSI Grant Number UL1RR024131. NR 38 TC 4 Z9 4 U1 0 U2 6 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 APR PY 2015 VL 86 IS 4 BP 404 EP 409 DI 10.1136/jnnp-2014-307942 PG 6 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA CD3SK UT WOS:000351000800011 PM 25012202 ER PT J AU Rizk, DV Riad, S Hage, FG AF Rizk, Dana V. Riad, Samy Hage, Fadi G. TI Screening for Coronary Artery Disease in Kidney Transplant Candidates SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Editorial Material ID STAGE RENAL-DISEASE; DIABETIC-PATIENTS; SURVIVAL; ASSOCIATION; RECIPIENTS; MORTALITY; FAILURE; DEATH C1 [Rizk, Dana V.] Univ Alabama Birmingham, Dept Med, Div Nephrol, Birmingham, AL 35294 USA. [Riad, Samy] CHRISTUS Transplant Inst, South Texas Renal Care Grp, San Antonio, TX USA. [Hage, Fadi G.] Univ Alabama Birmingham, Div Cardiovasc Dis, Dept Med, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Cardiol Sect, Birmingham, AL USA. RP Hage, FG (reprint author), Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Lyons Harrison Res Bldg 314,1900 Univ BLVD, Birmingham, AL 35294 USA. EM fadihage@uab.edu OI Hage, Fadi/0000-0002-1397-4942 NR 23 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 EI 1532-6551 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD APR PY 2015 VL 22 IS 2 BP 297 EP 300 DI 10.1007/s12350-014-0006-2 PG 4 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CD4YJ UT WOS:000351092200007 PM 25294435 ER PT J AU AlJaroudi, WA Einstein, AJ Chaudhry, FA Lloyd, SG Hage, FG AF AlJaroudi, Wael A. Einstein, Andrew J. Chaudhry, Farooq A. Lloyd, Steven G. Hage, Fadi G. TI Multi-modality imaging: Bird's-eye view from the 2014 American Heart Association Scientific Sessions SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Review DE SPECT; CT; echocardiography; MRI ID HEINZ NIXDORF RECALL; FRACTIONAL FLOW RESERVE; CORONARY-ARTERY-DISEASE; COMPUTED-TOMOGRAPHY ANGIOGRAPHY; POSITRON-EMISSION-TOMOGRAPHY; DIAGNOSTIC PERFORMANCE; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; TREADMILL EXERCISE; GENERAL-POPULATION AB A large number of studies were presented at the 2014 American Heart Association Scientific Sessions. In this review, we will summarize key studies in nuclear cardiology, computed tomography, echocardiography, and cardiac magnetic resonance imaging. This brief review will be helpful for readers of the Journal who are interested in being updated on the latest research covering these imaging modalities. C1 [AlJaroudi, Wael A.] Amer Univ Beirut, Med Ctr, Beirut, Lebanon. [Einstein, Andrew J.] Columbia Univ, New York Presbyterian Hosp, Med Ctr, New York, NY USA. [Chaudhry, Farooq A.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Lloyd, Steven G.; Hage, Fadi G.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Lloyd, Steven G.; Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Hage, FG (reprint author), Univ Alabama Birmingham, Lyons Harrison Res Bldg 314,1900 Univ BLVD, Birmingham, AL 35294 USA. EM fadihage@uab.edu OI Hage, Fadi/0000-0002-1397-4942 FU GE Healthcare; Phillips Healthcare; Astellas Pharma USA. FX Dr. Einstein reports grant support from GE Healthcare and Phillips Healthcare. Dr. Hage reports grant support from Astellas Pharma USA. NR 41 TC 1 Z9 1 U1 3 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 EI 1532-6551 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD APR PY 2015 VL 22 IS 2 BP 364 EP 371 DI 10.1007/s12350-015-0076-9 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CD4YJ UT WOS:000351092200015 PM 25698480 ER PT J AU Farag, AA Hage, FG AF Farag, Ayman A. Hage, Fadi G. TI Incidentally found giant thymomas by SPECT myocardial perfusion imaging SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Editorial Material C1 [Farag, Ayman A.; Hage, Fadi G.] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Cardiol Sect, Birmingham, AL USA. RP Farag, AA (reprint author), Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, THT 311,1900 Univ BLVD, Birmingham, AL 35294 USA. EM afarag@uab.edu OI Hage, Fadi/0000-0002-1397-4942 NR 7 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 EI 1532-6551 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD APR PY 2015 VL 22 IS 2 BP 385 EP 387 DI 10.1007/s12350-014-0028-9 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CD4YJ UT WOS:000351092200017 PM 25367454 ER PT J AU Gary, JL Paryavi, E Gibbons, SD Weaver, MJ Morgan, JH Ryan, SP Starr, AJ O'Toole, RV AF Gary, Joshua L. Paryavi, Ebrahim Gibbons, Steven D. Weaver, Michael J. Morgan, Jordan H. Ryan, Scott P. Starr, Adam J. O'Toole, Robert V. TI Effect of Surgical Treatment on Mortality After Acetabular Fracture in the Elderly: A Multicenter Study of 454 Patients SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE geriatric; acetabulum; mortality; nonoperative; percutaneous; total hip arthroplasty; open reduction internal fixation; trauma ID TOTAL HIP-ARTHROPLASTY; REDUCTION INTERNAL-FIXATION; OLDER POPULATION; OUTCOMES AB Objectives: Controversy exists regarding the effect of operative treatment on mortality after acetabular fracture in elderly patients. Our hypothesis was that operative treatment would confer a mortality benefit compared with nonoperative treatment even after adjusting for comorbidities associated with death. Design: Retrospective study. Setting: Three University Level I Trauma Centers. Patients/Participants: All patients aged 60 years and older with acetabular fractures treated from 2002 to 2009 were included in the study. Four hundred fifty-four patients were identified with an average age of 74 years. Sixty-seven percent of the study group was male and 33% female. Intervention: One of 4 treatments: nonoperative management with early mobilization, percutaneous reduction and fixation, open reduction and internal fixation, acute total hip arthroplasty. Main Outcome Measurements: Kaplan-Meier survival curves were created, and Cox proportional hazards models were used to calculate unadjusted and adjusted hazard ratios (HRs) for covariates of interest. Results: In contrast to previous smaller studies, the overall mortality was relatively low at 16% at 1 year [95% confidence interval (CI), 13-19]. Unadjusted survivorship curves suggested higher 1-year mortality rates for nonoperatively treated patients (21% vs. 13%, P < 0.001); however, nonoperative treatment was associated with other risk factors for higher mortality. By accounting for these patient risk factors, our final multivariate model of survival demonstrated no significant difference in hazard of death for non-operative treatment (0.92, P = 0.6) nor for any of the 3 operative treatment subgroups (P range, 0.4-0.8). As expected, we did find a significantly increased hazard for factors such as the Charlson comorbidity index [HR, 1.25 per point (95% CI, 1.16-1.34)] and age [HR, 1.08 per year of age more than 70 years (95% CI, 1.05-1.11)]. In addition, associated fracture patterns (compared with elementary patterns) significantly increased the hazard of death with a ratio of 1.51 (95% CI, 1.10-2.06). Conclusions: The operative treatment of acetabular fractures does not increase or decrease mortality, once comorbidities are taken into account. The reasons for this are unknown. Regardless of the causes, the decision for operative versus nonoperative treatment of geriatric acetabular fractures should not be justified based on the concern for increased or decreased mortality alone. C1 [Gary, Joshua L.] Univ Texas Hlth Sci Ctr Houston, Dept Orthopaed Surg, Houston, TX 77030 USA. [Paryavi, Ebrahim; O'Toole, Robert V.] Univ Maryland, Div Orthopaed Trauma, R Adams Cowley Shock Trauma Ctr, Baltimore, MD 21201 USA. [Gibbons, Steven D.; Starr, Adam J.] Univ Texas SW Med Ctr Dallas, Dept Orthopaed Surg, Dallas, TX 75390 USA. [Weaver, Michael J.; Morgan, Jordan H.] Brigham & Womens Hosp, Partners Orthopaed Trauma, Boston, MA 02115 USA. [Weaver, Michael J.; Morgan, Jordan H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ryan, Scott P.] Tufts Med Ctr, Dept Orthopaed Surg, Boston, MA USA. RP Gary, JL (reprint author), Univ Texas Hlth Sci Ctr Houston, Dept Orthopaed Surg, 6400 Fannin St,Suite 1700, Houston, TX 77030 USA. EM joshgary14@gmail.com NR 31 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0890-5339 EI 1531-2291 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD APR PY 2015 VL 29 IS 4 BP 202 EP 208 PG 7 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA CE1ED UT WOS:000351554000016 PM 25233162 ER PT J AU Zhao, YL Zhou, P Liu, BL Bambakidis, T Mazitschek, R Alam, HB Li, YQ AF Zhao, Yili Zhou, Peter Liu, Baoling Bambakidis, Ted Mazitschek, Ralph Alam, Hasan B. Li, Yongqing TI Protective effect of suberoylanilide hydroxamic acid against lipopolysaccharide-induced liver damage in rodents SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Histone deacetylase inhibitor; LPS; Liver; Inflammation; Apoptosis ID NITRIC-OXIDE PATHWAY; REACTIVE OXYGEN; SEPTIC SHOCK; OXIDATIVE MODIFICATION; L-ARGININE; APOPTOSIS; ACTIVATION; SEPSIS; CELLS; PEROXYNITRITE AB Background: Lipopolysaccharide (LPS) has a deleterious effect on several organs, including the liver, and eventually leads to endotoxic shock and death. LPS-induced hepatotoxicity is characterized by disturbed intracellular redox balance and excessive reactive oxygen species (ROS) accumulation, leading to liver injury. We have shown that treatment with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, improves survival in a murine model of LPS-induced shock, but the protective effect of SAHA against liver damage remains unknown. The goal of this study was to investigate the mechanism underlying SAHA action in murine livers. Method: Male C57BL/6J mice (6-8 wk), weighing 20-25 g, were randomly divided into three groups: (A) a sham group was given isotonic sodium chloride solution (10 mu L/g body weight, intraperitoneal, i.p.) with dimethyl sulfoxide (DMSO; 1 mL/g body weight, i.p.); (B) an LPS group was challenged with LPS (20 mg/kg, i.p.) dissolved in isotonic sodium chloride solution with DMSO; (C) and an LPS plus SAHA group was treated with SAHA (50 mg/kg, i.p.) dissolved in DMSO immediately after injection of LPS (20 mg/kg, i.p.). Mice were anesthetized, and their livers were harvested 6 or 24 h after injection to analyze whether SAHA affected production of ROS and activation of apoptotic proteins in the liver cells of challenged mice. Results: SAHA counteracted LPS-induced production of ROS (thiobarbituric acid reactive substances and nitrite) and reversed an LPS-induced decrease in antioxidant enzyme, glutathione. SAHA also attenuated LPS-induced hepatic apoptosis. Moreover, SAHA inhibited activation of the redox-sensitive kinase, apoptosis signal-regulating kinase-1, and the mitogen-activated protein kinases, p38 and Jun N-terminal kinase. Conclusions: Our data indicate, for the first time, that SAHA is capable of alleviating LPS-induced hepatotoxicity and suggest that a blockade of the upstream events required for apoptosis signal-regulating kinase-1 action may serve as a new therapeutic option in the treatment of LPS-induced inflammatory conditions. (C) 2015 Elsevier Inc. All rights reserved. C1 [Zhao, Yili] Tufts Univ, Sch Arts & Sci, Medford, MA 02155 USA. [Zhou, Peter] Harvard Univ, Cambridge, MA 02138 USA. [Liu, Baoling; Bambakidis, Ted; Alam, Hasan B.; Li, Yongqing] Univ Michigan Hosp, Sect Gen Surg, Trauma Translat & Clin Res, Ann Arbor, MI 48109 USA. [Mazitschek, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Alam, HB (reprint author), Univ Michigan, Gen Surg, North Campus Res Complex,Rm 363N,Bldg 26, Ann Arbor, MI 48109 USA. EM alamh@med.umich.edu; yqli@med.umich.edu FU NIH [RO1 GM084127] FX This work was supported by NIH RO1 GM084127 to H.B.A. NR 35 TC 4 Z9 4 U1 1 U2 14 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 APR PY 2015 VL 194 IS 2 BP 544 EP 550 DI 10.1016/j.jss.2014.10.056 PG 7 WC Surgery SC Surgery GA CD4OC UT WOS:000351061900031 PM 25479907 ER PT J AU Seliverstov, I Oertel, L Moulaison, W AF Seliverstov, Irina Oertel, Lynn Moulaison, Walter TI Monitoring patient compliance with INR testing using and automated telephone reminder call process in the Anticoagulation Management Service (AMS) SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Meeting Abstract C1 [Seliverstov, Irina; Oertel, Lynn; Moulaison, Walter] Massachusetts Gen Hosp, Anticoagulat Management Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 EI 1573-742X J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD APR PY 2015 VL 39 IS 3 SI SI MA A6 BP 413 EP 413 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CD6OX UT WOS:000351209800024 ER PT J AU Oertel, LB O'Leary, C Ronin, J AF Oertel, Lynn B. O'Leary, Christine Ronin, Jamie TI Improving patient and family education in the Anticoagulation Management Service (AMS) SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Meeting Abstract C1 [Oertel, Lynn B.; O'Leary, Christine; Ronin, Jamie] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 EI 1573-742X J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD APR PY 2015 VL 39 IS 3 SI SI MA E2 BP 417 EP 417 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CD6OX UT WOS:000351209800039 ER PT J AU DeTour, D Oertel, L Moulaison, W AF DeTour, Diane Oertel, Lynn Moulaison, Walter TI Promoting patient safety during transitions of care in the Anticoagulation Management Service (AMS) SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Meeting Abstract C1 [DeTour, Diane; Oertel, Lynn; Moulaison, Walter] Massachusetts Gen Hosp, Anticoagulat Management Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 EI 1573-742X J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD APR PY 2015 VL 39 IS 3 SI SI MA G1 BP 423 EP 423 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CD6OX UT WOS:000351209800058 ER PT J AU Sherman, O Baruch, L AF Sherman, Olga Baruch, Lawrence TI Activated partial thromboplastin time guided dabigatran dose reduction and switch to alternative novel anticoagulant SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Meeting Abstract C1 [Sherman, Olga; Baruch, Lawrence] James J Peters VA Med Ctr, Bronx, NY USA. [Baruch, Lawrence] Mt Sinai Med Ctr, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 EI 1573-742X J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD APR PY 2015 VL 39 IS 3 SI SI MA F15 BP 423 EP 423 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CD6OX UT WOS:000351209800057 ER PT J AU Tramontano, AC Schrag, DL Malin, JK Miller, MC Weeks, JC Swan, JS McMahon, PM AF Tramontano, Angela C. Schrag, Deborah L. Malin, Jennifer K. Miller, Melecia C. Weeks, Jane C. Swan, J. Shannon McMahon, Pamela M. TI Catalog and Comparison of Societal Preferences (Utilities) for Lung Cancer Health States: Results from the Cancer Care Outcomes Research and Surveillance (CanCORS) Study SO MEDICAL DECISION MAKING LA English DT Article DE lung cancer; utilities; quality-of-life; EQ5D; SF6D ID QUALITY-OF-LIFE; UNITED-STATES; US VALUATION; EQ-5D; SCORES; INDEXES; VALIDATION; QLQ-C30; BURDEN; TRIALS AB Background. The EQ-5D and SF-6D are 2 health-related quality-of-life indexes that provide preference-weighted measures for use in cost-effectiveness analyses. Methods. The National Cancer Institute's Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium included the EQ-5D and SF-12v2 in their survey of newly diagnosed lung cancer patients. Utilities were calculated from patient-provided scores for each domain of the EQ-5D or the SF-6D. Utilities were calculated for categories of cancer type, stage, and treatment. Results. There were 5015 enrolled lung cancer patients with a baseline survey in CanCORS; 2396 (47.8%) completed the EQ-5D, and 2344 (46.7%) also completed the SF-12v2. The mean (standard deviation) utility from the EQ-5D was 0.78 (0.18), and from the SF-6D (derived from SF-12v2) was 0.68 (0.14). The EQ-5D demonstrated a ceiling effect, with 20% of patients reporting perfect scores, translating to a utility of 1.0. No substantial SF-6D floor effects were noted. Utilities increased with age and decreased with stage and comorbidities. Patient-reported (EQ-5D) visual analog scale scores for health status had a moderate (r = 0.48, p < 0.0001) positive correlation with utilities. A subset (n = 1474) completed follow-up EQ-5D questionnaires 11-13 months after diagnosis. Among these patients, there was a nonsignificant decrease in mean utility for stage IV and an increase in mean utility for stages I, II, and III. Conclusion. This study generated a catalog of community-weighted utilities applicable to societal-perspective cost-effectiveness analyses of lung cancer interventions and compared utilities based on the EQ-5D and SF-6D. Potential users of these scores should be aware of the limitations and think carefully about their use in specific studies. C1 [Tramontano, Angela C.; Miller, Melecia C.; Swan, J. Shannon; McMahon, Pamela M.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Schrag, Deborah L.; Weeks, Jane C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Malin, Jennifer K.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Schrag, Deborah L.; Swan, J. Shannon; McMahon, Pamela M.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Tramontano, AC (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,Fl 10, Boston, MA 02114 USA. EM angela@mgh-ita.org FU American Cancer Society [2008A060554]; National Cancer Institute's Cancer Intervention and Surveillance Modeling Network (CISNET) Lung Group [1U01CA152956] FX Financial support for this study was provided in part by the American Cancer Society (2008A060554, ACT, PMM) and by the National Cancer Institute's Cancer Intervention and Surveillance Modeling Network (CISNET) Lung Group (1U01CA152956, PMM, MM, ACT). The funding agreement ensured the authors' independence in designing the study, interpreting the data, and writing and publishing the report. Revision accepted for publication 9 January 2015. NR 37 TC 2 Z9 2 U1 5 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X EI 1552-681X J9 MED DECIS MAKING JI Med. Decis. Mak. PD APR PY 2015 VL 35 IS 3 BP 371 EP 387 DI 10.1177/0272989X15570364 PG 17 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA CE0ZY UT WOS:000351542100009 PM 25670839 ER PT J AU Desbordes, G Gard, T Hoge, EA Holzel, B Kerr, C Lazar, SW Olendzki, A Vago, DR AF Desbordes, Gaelle Gard, Tim Hoge, Elizabeth A. Hoelzel, Britta K. Kerr, Catherine Lazar, Sara W. Olendzki, Andrew Vago, David R. TI Moving Beyond Mindfulness: Defining Equanimity as an Outcome Measure in Meditation and Contemplative Research SO MINDFULNESS LA English DT Article DE Equanimity; Mindfulness; Emotion regulation; Meditation; Acceptance ID HEART-RATE-VARIABILITY; COMPASSION MEDITATION; EMOTION REGULATION; NEGATIVE EMOTION; PSYCHOMETRIC PROPERTIES; FOCUSED ATTENTION; COGNITIVE THERAPY; NEURAL MECHANISMS; ANXIETY DISORDER; STRESS MEDIATORS AB In light of a growing interest in contemplative practices such as meditation, the emerging field of contemplative science has been challenged to describe and objectively measure how these practices affect health and well-being. While "mindfulness" itself has been proposed as a measurable outcome of contemplative practices, this concept encompasses multiple components, some of which, as we review here, may be better characterized as equanimity. Equanimity can be defined as an even-minded mental state or dispositional tendency toward all experiences or objects, regardless of their origin or their affective valence (pleasant, unpleasant, or neutral). In this article, we propose that equanimity be used as an outcome measure in contemplative research. We first define and discuss the inter-relationship between mindfulness and equanimity from the perspectives of both classical Buddhism and modern psychology and present existing meditation techniques for cultivating equanimity. We then review psychological, physiological, and neuroimaging methods that have been used to assess equanimity either directly or indirectly. In conclusion, we propose that equanimity captures potentially the most important psychological element in the improvement of well-being, and therefore should be a focus in future research studies. C1 [Desbordes, Gaelle] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Gard, Tim] Maastricht Univ, Fac Psychol & Neurosci, NL-6200 MD Maastricht, Netherlands. [Hoge, Elizabeth A.; Lazar, Sara W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02129 USA. [Hoelzel, Britta K.] Charite, Inst Med Psychol, D-13353 Berlin, Germany. [Kerr, Catherine] Brown Univ, Alpert Med Sch, Dept Family Med, Providence, RI 02912 USA. [Olendzki, Andrew] Barre Ctr Buddhist Studies, Barre, MA USA. [Vago, David R.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Desbordes, G (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 149 Thirteenth St, Boston, MA 02129 USA. EM desbordes@gmail.com RI Lazar, Sara/G-3809-2012; Desbordes, Gaelle/B-5924-2008; Hoge, Elizabeth/H-5879-2012 OI Lazar, Sara/0000-0003-1126-8363; Desbordes, Gaelle/0000-0002-6117-2880; Vago, David/0000-0002-6269-9027; Hoge, Elizabeth/0000-0002-5513-2292 FU National Institutes of Health [K23 AT004432]; European Community FX This work was supported in part by the National Institutes of Health (grant number K23 AT004432 to Elizabeth Hoge) and the 7th European Community Framework Programme (Marie Curie International Outgoing Fellowship to Britta K. Holzel). The authors would like to thank Andrea Grabovac for helpful comments on an earlier version of this manuscript. All authors contributed equally to this work and are listed alphabetically. NR 156 TC 23 Z9 24 U1 20 U2 53 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1868-8527 EI 1868-8535 J9 MINDFULNESS JI Mindfulness PD APR PY 2015 VL 6 IS 2 BP 356 EP 372 DI 10.1007/s12671-013-0269-8 PG 17 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CD7YI UT WOS:000351311400022 ER PT J AU Robinson, EB Kirby, A Ruparel, K Yang, J McGrath, L Anttila, V Neale, BM Merikangas, K Lehner, T Sleiman, PMA Daly, MJ Gur, R Gur, R Hakonarson, H AF Robinson, E. B. Kirby, A. Ruparel, K. Yang, J. McGrath, L. Anttila, V. Neale, B. M. Merikangas, K. Lehner, T. Sleiman, P. M. A. Daly, M. J. Gur, R. Gur, R. Hakonarson, H. TI The genetic architecture of pediatric cognitive abilities in the Philadelphia Neurodevelopmental Cohort SO MOLECULAR PSYCHIATRY LA English DT Article ID AUTISM SPECTRUM DISORDERS; GENERALIST GENES; COMMON SNPS; SCHIZOPHRENIA; HERITABILITY; INTELLIGENCE; TRAITS; AGE; ASSOCIATION; CHILDHOOD AB The objective of this analysis was to examine the genetic architecture of diverse cognitive abilities in children and adolescents, including the magnitude of common genetic effects and patterns of shared and unique genetic influences. Subjects included 3689 members of the Philadelphia Neurodevelopmental Cohort, a general population sample comprising those aged 8-21 years who completed an extensive battery of cognitive tests. We used genome-wide complex trait analysis to estimate the SNP-based heritability of each domain, as well as the genetic correlation between all domains that showed significant genetic influence. Several of the individual domains suggested strong influence of common genetic variants (for example, reading ability, h(g)(2) = 0.43, P = 4e - 06; emotion identification, h(g)(2) = 0.36, P= 1e - 05; verbal memory, h(g)(2) = 0.24, P = 0.005). The genetic correlations highlighted trait domains that are candidates for joint interrogation in future genetic studies (for example, language reasoning and spatial reasoning, r(g) = 0.72, P = 0.007). These results can be used to structure future genetic and neuropsychiatric investigations of diverse cognitive abilities. C1 [Robinson, E. B.; Kirby, A.; Anttila, V.; Neale, B. M.; Daly, M. J.] Harvard Univ, Sch Med, Analyt & Translat Genet Unit, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Robinson, E. B.; Kirby, A.; Anttila, V.; Neale, B. M.; Daly, M. J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Robinson, E. B.; Kirby, A.; Anttila, V.; Neale, B. M.; Daly, M. J.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Robinson, E. B.; Kirby, A.; Anttila, V.; Neale, B. M.; Daly, M. J.] Broad Inst MIT & Harvard, Med & Populat Genet Program, Cambridge, MA USA. [Ruparel, K.; Gur, R.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Yang, J.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. [McGrath, L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [McGrath, L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Anttila, V.] Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland. [Merikangas, K.] NIMH, Genet Epidemiol Res Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Lehner, T.] NIMH, Off Genom Res Coordinat, NIH, Bethesda, MD 20892 USA. [Sleiman, P. M. A.] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. RP Robinson, EB (reprint author), Harvard Univ, Sch Med, Analyt & Translat Genet Unit, Massachusetts Gen Hosp, 6th Floor,185 Cambridge St, Boston, MA 02114 USA. EM erobinson@atgu.mgh.harvard.edu RI Yang, Jian/A-5852-2010; OI Yang, Jian/0000-0003-2001-2474; Anttila, Verneri/0000-0002-0073-4675; Robinson, Elise/0000-0003-2314-2792 FU NIH [MH089983, MH089924]; National Institutes of Mental Health [1K01MH099286-01A1] FX We greatly appreciate the efforts of the participants and families involved in the Philadelphia Neurodevelopmental Cohort. The PNC was supported by NIH RC2 grants MH089983 and MH089924. EBR was funded by grant 1K01MH099286-01A1 from the National Institutes of Mental Health. NR 31 TC 7 Z9 7 U1 0 U2 8 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 APR PY 2015 VL 20 IS 4 BP 454 EP 458 DI 10.1038/mp.2014.65 PG 5 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA CE4DK UT WOS:000351780800006 PM 25023143 ER PT J AU Rauh-Hain, JA Buskwofie, A Clemmer, J Boruta, DM Schorge, JO del Carmen, MG AF Rauh-Hain, J. Alejandro Buskwofie, Ama Clemmer, Joel Boruta, David M. Schorge, John O. del Carmen, Marcela G. TI Racial Disparities in Treatment of High-Grade Endometrial Cancer in the Medicare Population SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID BREAST-CANCER; AFRICAN-AMERICANS; WHITE WOMEN; SURVIVAL; DIAGNOSIS; COMORBIDITY; STATISTICS; VALIDATION; CARCINOMA; BLACKS AB OBJECTIVE: To examine the patterns of care and survival for African American and white women with high-grade endometrial cancer. METHODS: The linked Surveillance, Epidemiology, and End Results and Medicare databases were queried to identify patients diagnosed with grade 3 endometrioid endometrial adenocarcinoma, uterine carcinosarcoma, uterine clear cell carcinoma, and uterine serous carcinoma between 1992 and 2009. The effect of treatment modality on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model. RESULTS: A total of 9,042 patients met study eligibility criteria. African Americans had definitive surgery (76.8% compared with 88.7%; P<.001) less frequently. There was no difference in the rate of adjuvant treatment between the groups. In the crude models for both all-cause mortality and cancer-specific mortality, African American women had an increased overall and disease-specific hazard of death compared with white women. The overall hazard ratio for African American women was 1.6 (95% confidence interval [CI] 1.5-1.7), and the disease-specific hazard ratio was 1.5 (95% CI 1.3-1.6). Over the entire study period, after adjusting for stage, age, period of diagnosis, registry region, urban compared with rural setting, marital status, treatment, surgery, socioeconomic status, and comorbidities, there was no association between race and lower disease-specific survival (hazard ratio 1.1, 95% CI 1-1.2; P=.06). CONCLUSION: African American women had lower cancer-specific and all-cause survival compared with white women. Controlling for treatment, sociodemographics, comorbidities, and histopathologic variables eliminated the difference between African American and white women in the disease-specific analysis. C1 [Rauh-Hain, J. Alejandro; Buskwofie, Ama; Clemmer, Joel; Boruta, David M.; Schorge, John O.; del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA USA. RP del Carmen, MG (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, Vincent Obstet & Gynecol, 55 Fruit St,Yawkey 9 E, Boston, MA 02114 USA. EM mdelcarmen@partners.org FU Deborah Kelly Center for Outcomes Research, Massachusetts General Hospital FX Supported by The Deborah Kelly Center for Outcomes Research, Massachusetts General Hospital. NR 29 TC 13 Z9 13 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2015 VL 125 IS 4 BP 843 EP 851 DI 10.1097/AOG.0000000000000605 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CE1TP UT WOS:000351595200013 PM 25751197 ER PT J AU Uchiyama, E Faez, S Nasir, H Unizony, SH Plenge, R Papaliodis, GN Sobrin, L AF Uchiyama, Eduardo Faez, Sepideh Nasir, Humzah Unizony, Sebastian H. Plenge, Robert Papaliodis, George N. Sobrin, Lucia TI Accuracy of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) As a Research Tool for Identification of Patients with Uveitis and Scleritis SO OPHTHALMIC EPIDEMIOLOGY LA English DT Article DE Epidemiology; ICD-9-CM; polymyalgia rheumatica; scleritis; uveitis ID OF-DISEASES; 9TH-REVISION; CODES AB Purpose: To report on the accuracy of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for identifying patients with polymyalgia rheumatica (PMR) and concurrent noninfectious inflammatory ocular conditions in a large healthcare organization database. Methods: Queries for patients with PMR and uveitis or scleritis were executed in two general teaching hospitals' databases. Patients with ocular infections or other rheumatologic conditions were excluded. Patients with PMR and ocular inflammation were identified, and medical records were reviewed to confirm accuracy. Results: The query identified 10,697 patients with the ICD-9-CM code for PMR and 4154 patients with the codes for noninfectious inflammatory ocular conditions. The number of patients with both PMR and noninfectious uveitis or scleritis by ICD-9-CM codes was 66. On detailed review of the charts of these 66 patients, 31 (47%) had a clinical diagnosis of PMR, 43 (65%) had noninfectious uveitis or scleritis, and only 20 (30%) had PMR with concurrent noninfectious uveitis or scleritis confirmed based on clinical notes. Conclusions: While the use of ICD-9-CM codes has been validated for medical research of common diseases, our results suggest that ICD-9-CM codes may be of limited value for epidemiological investigations of diseases which can be more difficult to diagnose. The ICD-9-CM codes for rarer diseases (PMR, uveitis and scleritis) did not reflect the true clinical problem in a large proportion of our patients. This is particularly true when coding is performed by physicians outside the area of specialty of the diagnosis. C1 [Uchiyama, Eduardo; Faez, Sepideh; Nasir, Humzah; Papaliodis, George N.; Sobrin, Lucia] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Uveitis & Ocular Immunol Div, Boston, MA USA. [Unizony, Sebastian H.] Massachusetts Gen Hosp, Dept Internal Med, Div Rheumatol, Boston, MA 02114 USA. [Plenge, Robert] Brigham & Womens Hosp, Dept Internal Med, Div Rheumatol, Boston, MA 02115 USA. [Plenge, Robert] Genet & Pharmacogen GpGx, Merck Res Labs, Boston, MA USA. RP Sobrin, L (reprint author), Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. EM Lucia_Sobrin@meei.harvard.edu NR 7 TC 1 Z9 1 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0928-6586 EI 1744-5086 J9 OPHTHAL EPIDEMIOL JI Ophthalmic Epidemiol. PD APR PY 2015 VL 22 IS 2 BP 139 EP 141 DI 10.3109/09286586.2015.1012274 PG 3 WC Ophthalmology SC Ophthalmology GA CD9EO UT WOS:000351400700009 PM 25777314 ER PT J AU Hughes, HK Korthuis, PT Saha, S Eggly, S Sharp, V Cohn, J Moore, R Beach, MC AF Hughes, Helen Kinsman Korthuis, Philip Todd Saha, Somnath Eggly, Susan Sharp, Victoria Cohn, Jonathan Moore, Richard Beach, Mary Catherine TI A mixed methods study of patient-provider communication about opioid analgesics SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Communication; Pain; Mixed methods ID AMBULATORY AIDS PATIENTS; CHRONIC PAIN; CARE; EMPATHY; ENCOUNTERS; MANAGEMENT; ATTITUDES; MEDICINE; QUALITY; RATES AB Objective: To describe patient-provider communication about opioid pain medicine and explore how these discussions affect provider attitudes toward patients. Methods: We audio-recorded 45 HIV providers and 423 patients in routine outpatient encounters at four sites across the country. Providers completed post-visit questionnaires assessing their attitudes toward patients. We identified discussions about opioid pain management and analyzed them qualitatively. We used logistic regression to assess the association between opioid discussion and providers' attitudes toward patients. Results: 48 encounters (11% of the total sample) contained substantive discussion of opioid-related pain management. Most conversations were initiated by patients (n = 28, 58%) and ended by the providers (n = 36, 75%). Twelve encounters (25%) contained dialog suggesting a difference of opinion or conflict. Providers more often agreed than disagreed to give the prescription (50% vs. 23%), sometimes reluctantly; in 27% (n = 13) of encounters, no decision was made. Fewer than half of providers (n = 20, 42%) acknowledged the patient's experience of pain. Providers had a lower odds of positive regard for the patient (adjusted OR =.0.51, 95% Cl: 0.27-0.95) when opioids were discussed. Conclusions: Pain management discussions are common in routine outpatient HIV encounters and providers may regard patients less. favorably if opioids are discussed during visits. The sometimes-adversarial nature of these discussions may negatively affect provider attitudes toward patients. Practice implications: Empathy and pain acknowledgment are tools that clinicians can use to facilitate productive discussions of pain management. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Hughes, Helen Kinsman; Moore, Richard; Beach, Mary Catherine] Johns Hopkins Univ, Baltimore, MD 21287 USA. [Korthuis, Philip Todd; Saha, Somnath] Oregon Hlth & Sci Univ, Portland, OR USA. [Saha, Somnath] Portland VA Med Ctr, Portland, OR USA. [Eggly, Susan; Cohn, Jonathan] Wayne State Univ, Detroit, MI USA. [Sharp, Victoria] St Lukes Roosevelt, New York, NY USA. RP Beach, MC (reprint author), Johns Hopkins Univ, Baltimore, MD 21287 USA. EM mcbeach@jhmi.edu OI Eggly, Susan/0000-0002-8137-6098 FU Health Resources Service Administration; Agency for Healthcare Research and Quality [AHRQ290-01-0012, K08 HS013903-05]; National Institute of Drug Abuse [K23 DA019808]; Department of Veterans Affairs; Robert Wood Johnson Generalist Physician Faculty Scholars Awards; Predoctoral Clinical Research Training Program at Johns Hopkins [UL1-RR025005] FX Funders: This research was supported by a contract from the Health Resources Service Administration and the Agency for Healthcare Research and Quality (AHRQ290-01-0012). In addition, Dr. Korthuis was supported by the National Institute of Drug Abuse (K23 DA019808), Dr. Beach was supported by the Agency for Healthcare Research and Quality (K08 HS013903-05), Dr. Saha was supported by the Department of Veterans Affairs, and both Drs. Beach and Saha were supported by Robert Wood Johnson Generalist Physician Faculty Scholars Awards. Dr. Hughes's was supported by the Predoctoral Clinical Research Training Program at Johns Hopkins (UL1-RR025005) NR 35 TC 2 Z9 2 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD APR PY 2015 VL 98 IS 4 BP 453 EP 461 DI 10.1016/j.pec.2014.12.003 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA CE2LP UT WOS:000351647400006 PM 25601279 ER PT J AU Ritschel, F King, JA Geisler, D Flohr, L Neidel, F Boehm, I Seidel, M Zwipp, J Ripke, S Smolka, MN Roessner, V Ehrlich, S AF Ritschel, F. King, J. A. Geisler, D. Flohr, L. Neidel, F. Boehm, I. Seidel, M. Zwipp, J. Ripke, S. Smolka, M. N. Roessner, V. Ehrlich, S. TI Temporal delay discounting in acutely ill and weight-recovered patients with anorexia nervosa SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Anorexia nervosa; delay discounting; impulsivity; intertemporal choice; self-control; weight-recovered anorexia nervosa ID BODY-MASS INDEX; INTERTEMPORAL CHOICE; EATING-DISORDERS; PHYSICAL-ACTIVITY; POTENTIALLY REAL; AGE-DIFFERENCES; REWARD; ADOLESCENTS; PERSONALITY; IMPULSIVITY AB Background. Patients with anorexia nervosa (AN) are characterized by a very low body weight but readily give up immediate rewards (food) for long-term goals (slim figure), which might indicate an unusual level of self-control. This everyday clinical observation may be quantifiable in the framework of the anticipation-discounting dilemma. Method. Using a cross-sectional design, this study compared the capacity to delay reward in 34 patients suffering from acute AN (acAN), 33 weight-recovered AN patients (recAN) and 54 healthy controls. We also used a longitudinal study to reassess 21 acAN patients after short-term weight restoration. A validated intertemporal choice task and a hyperbolic model were used to estimate temporal discounting rates. Results. Confirming the validity of the task used, decreased delay discounting was associated with age and low self-reported impulsivity. However, no group differences in key measures of temporal discounting of monetary rewards were found. Conclusions. Increased cognitive control, which has been suggested as a key characteristic of AN, does not seem to extend the capacity to wait for delayed monetary rewards. Differences between our study and the only previous study reporting decreased delay discounting in adult AN patients may be explained by the different age range and chronicity of acute patients, but the fact that weight recovery was not associated with changes in discount rates suggests that discounting behavior is not a trait marker in AN. Future studies using paradigms with disorder-specific stimuli may help to clarify the role of delay discounting in AN. C1 [Ritschel, F.; King, J. A.; Geisler, D.; Flohr, L.; Neidel, F.; Boehm, I.; Seidel, M.; Zwipp, J.; Roessner, V.; Ehrlich, S.] Tech Univ Dresden, Fac Med Carl Gustav Carus, Dept Child & Adolescent Psychiat, D-01062 Dresden, Germany. [Ripke, S.; Smolka, M. N.] Tech Univ Dresden, Dept Psychiat, D-01062 Dresden, Germany. [Ripke, S.; Smolka, M. N.] Tech Univ Dresden, Neuroimaging Ctr, D-01062 Dresden, Germany. [Ehrlich, S.] Massachusetts Gen Hosp, MGH MIT HMS Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Ehrlich, S.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 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 FU Deutsche Forschungsgemeinschaft (DFG) [SM 80/5-2, SM 80/7-1, EH 367/5-1, SFB 940/1]; Bundesministerium fur Bildung und Forschung (BMBF) [01EV0711]; Swiss Anorexia Nervosa Foundation FX This work was supported by the Deutsche Forschungsgemeinschaft (DFG grants SM 80/5-2, SM 80/7-1, EH 367/5-1 and SFB 940/1), the Bundesministerium fur Bildung und Forschung (BMBF grant 01EV0711) and the Swiss Anorexia Nervosa Foundation. We thank all junior researchers and student workers for their assistance with data collection and all participants for their time and cooperation. NR 69 TC 15 Z9 15 U1 3 U2 10 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 EI 1469-8978 J9 PSYCHOL MED JI Psychol. Med. PD APR PY 2015 VL 45 IS 6 BP 1229 EP 1239 DI 10.1017/S0033291714002311 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA CE0AA UT WOS:000351462600011 PM 25579471 ER PT J AU Zhang, JH AF Zhang, Jianhua TI Teaching the basics of autophagy and mitophagy to redox biologists-Mechanisms and experimental approaches SO REDOX BIOLOGY LA English DT Review DE mTOR; Beclin; LC3; Mitochondria; Neurodegenerative diseases; Aging ID ISOLATED RAT HEPATOCYTES; MICROAUTOPHAGIC VACUOLE INVAGINATION; MITOCHONDRIAL QUALITY-CONTROL; PARKIN-MEDIATED MITOPHAGY; CENTRAL-NERVOUS-SYSTEM; EXTENDS LIFE-SPAN; SELECTIVE AUTOPHAGY; PROTEIN-DEGRADATION; OXIDATIVE STRESS; LYSOSOME FUSION AB Autophagy is a lysosomal mediated degradation activity providing an essential mechanism for recycling cellular constituents, and clearance of excess or damaged lipids, proteins and organelles. Autophagy involves more than 30 proteins and is regulated by nutrient availability, and various stress sensing signaling pathways. This article provides an overview of the mechanisms and regulation of autophagy, its role in health and diseases, and methods for its measurement. Hopefully this teaching review together with the graphic illustrations will be helpful for instructors teaching graduate students who are interested in grasping the concepts and major research areas and introducing recent developments in the held (C) 2015 The Authors. Published by Elsevier B.V. C1 [Zhang, Jianhua] Univ Alabama Birmingham, Ctr Free Rad Biol, Birmingham, AL 35294 USA. [Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Zhang, Jianhua] Birmingham VA Med Ctr, Dept Vet Affairs, Birmingham, AL USA. RP Zhang, JH (reprint author), Univ Alabama Birmingham, Dept Pathol, Biomed Res Bldg 2,901 19th St South, Birmingham, AL 35294 USA. EM zhanja@uab.edu OI Zhang, Jianhua/0000-0002-2128-9574 FU NIH [R01-NS064090] FX This work was supported by NIH R01-NS064090 (to J.Z.). NR 207 TC 18 Z9 18 U1 3 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2317 J9 REDOX BIOL JI Redox Biol. PD APR PY 2015 VL 4 BP 242 EP 259 DI 10.1016/j.redox.2015.01.003 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CD1DI UT WOS:000350813800028 PM 25618581 ER PT J AU Velez, MI Nambiar, AM AF Velez, Maria I. Nambiar, Anoop M. TI Combination pirfenidone and inhaled N-acetylcysteine therapy for IPF: Does it take these two to tango? SO RESPIROLOGY LA English DT Editorial Material DE acetylcysteine; combination drug therapy; disease progression; idiopathic pulmonary fibrosis; pirfenidone ID IDIOPATHIC PULMONARY-FIBROSIS; MANAGEMENT; EFFICACY; TRIAL C1 [Velez, Maria I.; Nambiar, Anoop M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Pulm Dis & Crit Care Med, San Antonio, TX 78229 USA. [Velez, Maria I.; Nambiar, Anoop M.] South Texas Vet Hlth Care Syst, Audie L Murphy VA Hosp, San Antonio, TX USA. RP Velez, MI (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Pulm Dis & Crit Care Med, San Antonio, TX 78229 USA. NR 10 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1323-7799 EI 1440-1843 J9 RESPIROLOGY JI Respirology PD APR PY 2015 VL 20 IS 3 BP 359 EP 360 DI 10.1111/resp.12487 PG 2 WC Respiratory System SC Respiratory System GA CD6CE UT WOS:000351175700002 PM 25678074 ER PT J AU Calderon, V Mejia, Y Lara-Munoz, MD Segoviano, J Castro, Q Casados, A Lopez, SR AF Calderon, Vanessa Mejia, Yesenia del Carmen Lara-Munoz, Maria Segoviano, Joanna Castro, Quetzalli Casados, Ava Lopez, Steven Regeser TI Towards the sustainability of information campaigns: training Promotores to increase the psychosis literacy of Spanish-speaking communities SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY LA English DT Article DE Psychosis literacy; Spanish language; Community lay workers; Promotores ID UNTREATED PSYCHOSIS; DURATION; LATINO AB To assess the acceptability and efficacy of training community health workers (promotores) in Mexico to both recognize psychosis and to teach others to recognize psychosis. Two studies were carried out utilizing a single-group design. In Study 1, promotores watched a DVD-based psychosis literacy training. In Study 2, promotores were trained to administer a flip-chart version of the program and they then administered it to community residents. Significant increases in the post-training assessment of psychosis literacy were observed. Promotores can be an important resource in identifying psychosis early and enhancing the sustainability of psychosis literacy information campaigns. C1 [Calderon, Vanessa] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mejia, Yesenia; Lopez, Steven Regeser] Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. [del Carmen Lara-Munoz, Maria] Benemerita Univ Autonoma Puebla, Puebla, Mexico. [Segoviano, Joanna] San Diego State Univ, San Diego, CA 92182 USA. [Castro, Quetzalli] Univ Illinois, Chicago, IL USA. [Casados, Ava] Yale Univ, New Haven, CT USA. RP Lopez, SR (reprint author), Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. EM lopezs@usc.edu FU National Institute of Minority Health and Health Disparities [T37 MD003405]; National Institute of Mental Health [R01 MH103830] FX The research was funded by the National Institute of Minority Health and Health Disparities, T37 MD003405, and the National Institute of Mental Health, R01 MH103830. We acknowledge the collaboration of the Department of Health, Puebla, Mexico. There is no conflict of interest and the studies were approved by the USC Institutional Review Board. NR 14 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0933-7954 EI 1433-9285 J9 SOC PSYCH PSYCH EPID JI Soc. Psychiatry Psychiatr. Epidemiol. PD APR PY 2015 VL 50 IS 4 BP 665 EP 669 DI 10.1007/s00127-014-0992-z PG 5 WC Psychiatry SC Psychiatry GA CD9RU UT WOS:000351436700018 PM 25520238 ER PT J AU Menon, BK Saver, JL Goyal, M Nogueira, R Prabhakaran, S Liang, L Xian, Y Hernandez, AF Fonarow, GC Schwamm, L Smith, EE AF Menon, Bijoy K. Saver, Jeffrey L. Goyal, Mayank Nogueira, Raul Prabhakaran, Shyam Liang, Li Xian, Ying Hernandez, Adrian F. Fonarow, Gregg C. Schwamm, Lee Smith, Eric E. TI Trends in Endovascular Therapy and Clinical Outcomes Within the Nationwide Get With The Guidelines-Stroke Registry SO STROKE LA English DT Article DE endovascular procedures; outcome assessment; stroke ID ACUTE ISCHEMIC-STROKE; MECHANICAL THROMBECTOMY; RANDOMIZED-TRIAL; MERCI TRIAL; REVASCULARIZATION; PROUROKINASE; MANAGEMENT; FATALITY; DISEASE; SAFETY AB Background and Purpose-We sought to determine hospital and patient characteristics associated with the use of endovascular therapy for acute ischemic stroke and to analyze trends in clinical outcome. Methods-Data were from Get With The Guidelines-Stroke hospitals from April 1, 2003, to June 30, 2013. We looked at trends in number of hospitals providing endovascular therapy, the use of endovascular therapy in these hospitals and clinical outcomes. We analyzed hospital and patient characteristics associated with endovascular therapy use. Results-Of 1087 hospitals, 454 provided endovascular therapy to >= 1 patient in the study period. From 2003 to 2012, proportion of hospitals providing endovascular therapy increased by 1.6% per year (from 12.9% to 28.9%; P<0.0001), with a modest drop to 23.4% in 2013. Utilization of endovascular therapy increased from 0.7% to 2% (P<0.001) with a modest drop to 1.9% in 2013. The overall rate of symptomatic intracerebral hemorrhage among endovascular therapy treated patients was 9.7%. In multivariable analyses, patient outcomes after endovascular therapy improved over time, with reductions in in-hospital mortality (29.6% in 2004 to 16.2% in 2013; P=0.002); and from late 2010, reduction in symptomatic intracerebral hemorrhage (11% in 2010 to 5% in 2013; P<0.0001), increased independent ambulation at discharge (24.5% in 2010 to 33% in 2013; P<0.0001) and discharge home (17.7% in 2010 to 26.1% in 2013; P<0.0001). Trends for these outcomes persist in the analyses adjusted for baseline National Institutes of Health Stroke Scale. Conclusion-The use of endovascular therapy increased modestly nationally from 2003 to 2012 and decreased in 2013. Clinical outcomes improved notably from 2010 to 2013, coincident with more experience and newer thrombectomy devices. C1 [Menon, Bijoy K.; Goyal, Mayank; Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary Stroke Program, Hotchkiss Brain Inst, Calgary, AB, Canada. [Menon, Bijoy K.; Goyal, Mayank; Smith, Eric E.] Univ Calgary, Dept Radiol, Calgary, AB, Canada. [Saver, Jeffrey L.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Nogueira, Raul] Emory Univ, Sch Med, Dept Neurol, Marcus Stroke & Neurosci Ctr,Grady Mem Hosp, Atlanta, GA 30322 USA. [Prabhakaran, Shyam] Northwestern Univ, Dept Neurol, Evanston, IL USA. [Liang, Li; Xian, Ying; Hernandez, Adrian F.] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Schwamm, Lee] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Menon, BK (reprint author), 1079 A,29th St NW, Calgary, AB T3H 4J2, Canada. EM Bijoy.Menon@Albertahealthservices.ca RI Hernandez, Adrian F./A-7818-2016 OI Hernandez, Adrian F./0000-0003-3387-9616 FU Pfizer, Inc., New York, NY; Merck-Schering Plough Partnership (North Wales, PA) FX The American Heart Association and the American Stroke Association fund Get With The Guidelines-Stroke. The program is also supported, in part, by unrestricted educational grants to the American Heart Association by Pfizer, Inc., New York, NY, and the Merck-Schering Plough Partnership (North Wales, PA), who did not participate in the design, analysis, article preparation or approval. NR 30 TC 21 Z9 22 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD APR PY 2015 VL 46 IS 4 BP 989 EP + DI 10.1161/STROKEAHA.114.007542 PG 17 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CE2SW UT WOS:000351669000025 PM 25681065 ER PT J AU Urday, S Beslow, LA Goldstein, DW Vashkevich, A Ayres, AM Battey, TWK Selim, MH Kimberly, WT Rosand, J Sheth, KN AF Urday, Sebastian Beslow, Lauren A. Goldstein, David W. Vashkevich, Anastasia Ayres, Alison M. Battey, Thomas W. K. Selim, Magdy H. Kimberly, W. Taylor Rosand, Jonathan Sheth, Kevin N. TI Measurement of Perihematomal Edema in Intracerebral Hemorrhage SO STROKE LA English DT Article DE computed tomography; intracerebral hemorrhage ID PERIHAEMATOMAL EDEMA; BRAIN EDEMA; VOLUME; ASSOCIATION; TRIAL; MRI AB Background and Purpose-Perihematomal edema (PHE) is a marker of secondary injury in intracerebral hemorrhage (ICH). PHE measurement on computed tomography (CT) is challenging, and the principles used to detect PHE have not been described fully. We developed a systematic approach for CT-based measurement of PHE. Methods-Two independent raters measured PHE volumes on baseline and 24-hour post-ICH CT scans of 20 primary supratentorial ICH subjects. Boundaries were outlined with an edge-detection tool and adjusted after inspection of the 3 orthogonal planes. PHE was delineated with the additional principle that it should be (a) more hypodense than the corresponding area in the contralateral hemisphere and (b) most hypodense immediately surrounding the hemorrhage. We examined intra-and interrater reliability using intraclass correlation coefficients and Bland-Altman plots for interrater consistency. CT-based PHE was also compared using magnetic resonance imaging-based PHE detection for 18 subjects. Results-Median PHE volumes were 22.7 cc at baseline and 20.4 cc at 24 hours post-ICH. There were no statistically significant differences in PHE measurements between raters. Interrater and intrarater reliability for PHE were excellent. At baseline and 24 hours, interrater intraclass correlation coefficients were 0.98 (0.96-1.00) and 0.98 (0.97-1.00); intrarater intraclass correlation coefficients were 0.99 (0.99-1.00) and 0.99 (0.98-1.00). Bland-Altman analysis showed the bias for PHE measurements at baseline and 24 hours, -0.5 cc (SD, 5.4) and -3.2 cc (SD, 5.0), was acceptably small. PHE volumes determined by CT and magnetic resonance imaging were similar (23.9 +/- 16.9 cc versus 23.9 +/- 16.0 cc, R-2 = 0.98, P<0.0001). Conclusions-Our method measures PHE with excellent reliability at baseline and 24 hours post-ICH. C1 [Urday, Sebastian; Beslow, Lauren A.; Goldstein, David W.; Sheth, Kevin N.] Yale Univ, Sch Med, Dept Neurol, Div Neurocrit Care & Emergency Neurol, New Haven, CT 06510 USA. [Vashkevich, Anastasia; Ayres, Alison M.; Battey, Thomas W. K.; Kimberly, W. Taylor; Rosand, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Ctr Human Genet Res,Dept Neurol,Med Sch, Boston, MA USA. [Selim, Magdy H.] Beth Israel Deaconess Med Ctr, Dept Neurol, Stroke Div, Boston, MA 02215 USA. RP Sheth, KN (reprint author), Yale Univ, Sch Med, Dept Neurol, Div Neurocrit Care & Emergency Neurol, 15 York St,LCI 1003, New Haven, CT 06510 USA. EM kevin.sheth@yale.edu FU NINDS [K23NS076597]; [NIH-K12-NS049453] FX S. Urday received Leon Rosenberg, MD Medical Student Research Fund in Genetics (Yale School of Medicine) and 2014 Student Scholarship in Cerebrovascular Disease and Stroke (American Heart Association's Stroke Council). L.A. Beslow was supported by NIH-K12-NS049453. W.T. Kimberly was supported by NINDS K23NS076597. NR 19 TC 6 Z9 7 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD APR PY 2015 VL 46 IS 4 BP 1116 EP + DI 10.1161/STROKEAHA.114.007565 PG 16 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CE2SW UT WOS:000351669000045 PM 25721012 ER PT J AU Arai, K AF Arai, Ken TI Stroke Literature Synopses: Basic Science SO STROKE LA English DT Editorial Material C1 [Arai, Ken] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA USA. [Arai, Ken] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Arai, Ken] Harvard Univ, Sch Med, Charlestown, MA USA. RP Arai, K (reprint author), Neuroprotect Res Lab, MGH East 149-2401, Charlestown, MA 02129 USA. EM karai@mgh.harvard.edu FU NINDS NIH HHS [P01 NS055104, R01 NS065089] NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD APR PY 2015 VL 46 IS 4 BP E78 EP E78 DI 10.1161/STROKEAHA.115.008759 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CE2SW UT WOS:000351669000002 PM 25744515 ER PT J AU Wu, LM Walas, S Leung, W Sykes, DB Wu, J Lo, EH Lok, J AF Wu, Limin Walas, Samantha Leung, Wendy Sykes, David B. Wu, Jiang Lo, Eng H. Lok, Josephine TI Neuregulin1-beta Decreases IL-1 beta-Induced Neutrophil Adhesion to Human Brain Microvascular Endothelial Cells SO TRANSLATIONAL STROKE RESEARCH LA English DT Article DE Neuroinflammation; IL-1 beta; NRG1-beta; Neutrophil; VCAM-1; E-selectin ID RECEPTOR SUBUNIT; ERBB RECEPTORS; INJURY; SCHIZOPHRENIA; INFLAMMATION; PROMOTES; LEADS; INTERLEUKIN-1-BETA; MICRODIALYSIS; ANGIOGENESIS AB Neuroinflammation contributes to the pathophysiology of diverse diseases including stroke, traumatic brain injury, Alzheimer's disease, Parkinson's disease, and multiple sclerosis, resulting in neurodegeneration and loss of neurological function. The response of the microvascular endothelium often contributes to neuroinflammation. One such response is the upregulation of endothelial adhesion molecules which facilitate neutrophil adhesion to the endothelium and their migration from blood to tissue. Neuregulin-1 (NRG1) is an endogenous growth factor which has been reported to have anti-inflammatory effects in experimental stroke models. We hypothesized that NRG1 would decrease the endothelial response to inflammation and result in a decrease in neutrophil adhesion to endothelial cells. We tested this hypothesis in an in vitro model of cytokine-induced endothelial injury, in which human brain microvascular endothelial cells (BMECs) were treated with IL-1 beta, along with co-incubation with vehicle or NRG1-beta. Outcome measures included protein levels of endothelial ICAM-1, VCAM-1, and E-selectin, as well as the number of neutrophils that adhere to the endothelial monolayer. Our data show that NRG1-beta decreased the levels of VCAM-1, E-selectin, and neutrophil adhesion to brain microvascular endothelial cells activated by IL1-beta. These findings open new possibilities for investigating NRG1 in neuroprotective strategies in brain injury. C1 [Wu, Limin; Walas, Samantha; Leung, Wendy; Lo, Eng H.; Lok, Josephine] Harvard Univ, Sch Med, Neuroprotect Res Lab, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Wu, Limin; Wu, Jiang] Jilin Univ, Hosp 1, Dept Neurol, Changchun 130021, Jilin, Peoples R China. [Lok, Josephine] Harvard Univ, Sch Med, Dept Pediat, Div Pediat Crit Care,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Sykes, David B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Hematol Oncol, Boston, MA 02115 USA. [Sykes, David B.] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA USA. RP Lok, J (reprint author), Harvard Univ, Sch Med, Neuroprotect Res Lab, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. EM jlok1@mgh.harvard.edu FU China Scholarship Council [201206170107]; [R37NS037074-13]; [R01NS076694-02]; [P01NS055104-05]; [K08N5057339-04] FX This work is supported by the following grants:; R37NS037074-13 (EHL); R01NS076694-02(EHL); P01NS055104-05 (EHL); K08N5057339-04 (JL); China Scholarship Council (#201206170107; LW) NR 44 TC 5 Z9 6 U1 2 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1868-4483 EI 1868-601X J9 TRANSL STROKE RES JI Transl. Stroke Res. PD APR PY 2015 VL 6 IS 2 BP 116 EP 124 DI 10.1007/s12975-014-0347-9 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CD8AH UT WOS:000351317000004 PM 24863743 ER PT J AU Schlunk, F Schulz, E Lauer, A Yigitkanli, K Pfeilschifter, W Steinmetz, H Lo, EH Foerch, C AF Schlunk, Frieder Schulz, Elena Lauer, Arne Yigitkanli, Kazim Pfeilschifter, Waltraud Steinmetz, Helmuth Lo, Eng H. Foerch, Christian TI Warfarin Pretreatment Reduces Cell Death and MMP-9 Activity in Experimental Intracerebral Hemorrhage SO TRANSLATIONAL STROKE RESEARCH LA English DT Article DE Intracerebral hemorrhage; Warfarin; Animal model; Cell death; Edema; Blood-brain barrier ID BRAIN-INJURY; HEMATOMA EXPANSION; MOUSE MODEL; THROMBIN; ANTICOAGULATION; APOPTOSIS; THERAPY; EDEMA; MATRIX-METALLOPROTEINASE-9; MECHANISMS AB Little is known about the pathophysiology of oral anticoagulation-associated intracerebral hemorrhage (OAC-ICH). We compared hematoma volume, number of terminal deoxynucleotidyl dUTP nick-end labeling (TUNEL)-positive cells (indicating cell death), MMP-9 levels, and perilesional edema formation between warfarin-treated mice and controls. Intracerebral hemorrhage was induced by an injection of collagenase into the right striatum. Twenty-four hours later, hematoma volume was measured using a photometric hemoglobin assay. Cell death was quantified using TUNEL staining. MMP-9 levels were determined by zymography, and edema formation was assessed via the wet-dry method. Warfarin increased hematoma volume by 2.6-fold. The absolute number of TUNEL-positive cells in the perihematomal zone was lower in warfarin-treated animals (300.5 +/- 39.8 cells/mm(2)) than in controls (430.5 +/- 38.9 cells/mm(2); p = 0.034), despite the larger bleeding volume. MMP-9 levels were reduced in anticoagulated mice as compared to controls (p = 0.018). Perilesional edema formation was absent in warfarin mice and modestly present in controls. Our results suggest differences in the pathophysiology of OAC-ICH compared to intracerebral hemorrhage occurring under normal coagulation. A likely explanation is that thrombin, a strong inductor of apoptotic cell death and blood-brain barrier disruption, is produced to a lesser extent in OAC-ICH. In humans, however, we assume that the detrimental effects of a larger hematoma volume in OAC-ICH by far outweigh potential protective effects of thrombin deficiency. C1 [Schlunk, Frieder; Schulz, Elena; Lauer, Arne; Pfeilschifter, Waltraud; Steinmetz, Helmuth; Foerch, Christian] Goethe Univ Frankfurt, Dept Neurol, D-60054 Frankfurt, Germany. [Schlunk, Frieder; Schulz, Elena; Lauer, Arne; Yigitkanli, Kazim; Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab, Charlestown, MA USA. RP Schlunk, F (reprint author), Goethe Univ Frankfurt, Dept Neurol, D-60054 Frankfurt, Germany. EM fschlunk@gmail.com NR 28 TC 9 Z9 9 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1868-4483 EI 1868-601X J9 TRANSL STROKE RES JI Transl. Stroke Res. PD APR PY 2015 VL 6 IS 2 BP 133 EP 139 DI 10.1007/s12975-014-0377-3 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CD8AH UT WOS:000351317000006 PM 25424451 ER PT J AU Cetas, JS McFarlane, R Kronfeld, K Smitasin, P Liu, JJ Raskin, JS AF Cetas, Justin S. McFarlane, Robin Kronfeld, Kassi Smitasin, Phoebe Liu, Jesse J. Raskin, Jeffrey S. TI Brainstem Opioidergic System Is Involved in Early Response to Experimental SAH SO TRANSLATIONAL STROKE RESEARCH LA English DT Article DE Subarachnoid hemorrhage; Rostral ventromedial medulla; Brainstem; Cerebral blood flow; Modulation; Stroke ID ROSTRAL VENTROMEDIAL MEDULLA; CEREBRAL-BLOOD-FLOW; LIGHTLY ANESTHETIZED RAT; CAUDAL MIDLINE MEDULLA; SUBARACHNOID HEMORRHAGE; CORTICAL PERFUSION; NEURONS; INJURY; PAIN; STIMULATION AB Subarachnoid hemorrhage (SAH) is a form of stroke with high rates of mortality and permanent disability for patients who survive the initial event. Previous research has focused on delayed cerebral vasospasm of large conduit arteries as the cause of poor long-term outcomes after SAH. New evidence suggests that acute failure to restore cerebral blood flow (CBF) after SAH may be setting the stage for delayed ischemic neurological deficits. Our lab previously demonstrated that the rostral ventromedial medulla (RVM), an autonomic and sensorimotor integration center, is important for maintaining CBF after experimental SAH. In this study, we have demonstrated that ablation of mu-opioid receptor containing cells with dermorphin conjugates in the RVM results in a high mortality rate after experimental SAH and, in survivors, causes a dramatic decrease in CBF. Further, locally blocking the mu-opioid receptor with the antagonist naltrexone attenuated the reduction in CBF secondary to experimental SAH. Saturating mu-opioid receptors with the agonist [d-Ala(2),NMe-Phe(4),Gly-ol(5)]-encephalin (DAMGO) had no effect. Taken together, these results suggest that SAH activates opioidergic signaling in the RVM with a resultant reduction in CBF. Further, cells in the RVM that contain mu-opioid receptors are important for survival after acute SAH. We propose that failure of the RVM mu-opioid receptor cells to initiate the compensatory CBF response sets the stage for acute and delayed ischemic injury following SAH. C1 [Cetas, Justin S.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97239 USA. [Cetas, Justin S.; McFarlane, Robin; Kronfeld, Kassi; Smitasin, Phoebe; Liu, Jesse J.; Raskin, Jeffrey S.] Oregon Hlth & Sci Univ, Dept Neurol Surg, Portland, OR 97239 USA. RP Cetas, JS (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97239 USA. EM cetasj@ohsu.edu NR 39 TC 5 Z9 5 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1868-4483 EI 1868-601X J9 TRANSL STROKE RES JI Transl. Stroke Res. PD APR PY 2015 VL 6 IS 2 BP 140 EP 147 DI 10.1007/s12975-014-0378-2 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CD8AH UT WOS:000351317000007 PM 25417789 ER PT J AU Moses, R Pais, VM Ursiny, M Prien, EL Miller, N Eisner, BH AF Moses, Rachel Pais, Vernon M., Jr. Ursiny, Michal Prien, Edwin L., Jr. Miller, Nicole Eisner, Brian H. TI Changes in stone composition over two decades: evaluation of over 10,000 stone analyses SO UROLITHIASIS LA English DT Article DE Stone composition; Epidemiology; Change ID UNITED-STATES; KIDNEY-STONES; EPIDEMIOLOGY; PREVALENCE; UROLITHIASIS; CYSTINURIA; MINNESOTA; ROCHESTER; NUTRITION; PHOSPHATE AB To examine the changes in stone composition from 1990 to 2010. A retrospective review was performed of all renal and ureteral stones submitted from the state of Massachusetts to a single laboratory (Laboratory for Stone Research, Newton, MA) for the years 1990 and 2010. Stone composition was determined by infrared spectroscopy and/or polarizing microscopy. A total of 11,099 stones were evaluated (56.7 % from 1990, 43.3 % from 2010). From 1990 to 2010, the percentage of stones from females (i.e., female/male ratio) increased significantly (29.8 % in 1990 to 39.1 % in 2010, p < 0.001). Among women, from 1990 to 2010, there was a significant increase in stones which were > 50 % uric acid (7.6-10.2 %, p < 0.005) and a significant decrease in struvite stones (7.8-3.0 %, p < 0.001). Among women with calcium stones, the % apatite per stone decreased significantly (20.0 vs. 11.7 %, p < 0.001). Among men, there were no changes in stones which were majority uric acid (11.7-10.8 %, p = 0.2). Among men with calcium stones, the % apatite per stone increased significantly (9.8 vs. 12.5 %, p < 0.001). Males also demonstrated a significant increase in both cystine (0.1-0.6 %, p < 0.001) and struvite stones (2.8-3.7 %, p = 0.02). The epidemiology of stone disease continues to evolve and appears to vary according to gender. While some of these findings may be related to population changes in body mass index and obesity, the etiology of others remains unclear. C1 [Moses, Rachel; Pais, Vernon M., Jr.] Dartmouth Hitchcock Med Ctr, Dept Urol, Lebanon, NH 03766 USA. [Ursiny, Michal; Eisner, Brian H.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Prien, Edwin L., Jr.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Miller, Nicole] Vanderbilt Univ Sch Med, Dept Urol, Nashville, TN USA. RP Eisner, BH (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org NR 23 TC 8 Z9 9 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 2194-7228 EI 2194-7236 J9 UROLITHIASIS JI Urolithiasis PD APR PY 2015 VL 43 IS 2 BP 135 EP 139 DI 10.1007/s00240-015-0756-6 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA CE1QO UT WOS:000351587200005 PM 25689875 ER PT J AU Petroze, RT Byiringiro, JC Ntakiyiruta, G Briggs, SM Deckelbaum, DL Razek, T Riviello, R Kyamanywa, P Reid, J Sawyer, RG Calland, JF AF Petroze, Robin T. Byiringiro, Jean Claude Ntakiyiruta, Georges Briggs, Susan M. Deckelbaum, Dan L. Razek, Tarek Riviello, Robert Kyamanywa, Patrick Reid, Jennifer Sawyer, Robert G. Calland, J. Forrest TI Can Focused Trauma Education Initiatives Reduce Mortality or Improve Resource Utilization in a Low-Resource Setting? SO WORLD JOURNAL OF SURGERY LA English DT Article ID SERVICE DATA UNDERESTIMATE; FORMAL MEDICAL-SERVICES; STRENGTHENING TRAUMA; DEVELOPING-NATION; INJURED PERSONS; HEALTH; CARE; REGISTRY; PROGRAM; AFRICA AB Over 90 % of injury deaths occur in low-income countries. Evaluating the impact of focused trauma courses in these settings is challenging. We hypothesized that implementation of a focused trauma education initiative in a low-income country would result in measurable differences in injury-related outcomes and resource utilization. Two 3-day trauma education courses were conducted in the Rwandan capital over a one-month period (October-November, 2011). An ATLS provider demonstration course was delivered to 24 faculty surgeons and 15 Rwandan trauma nurse auditors, and a Canadian Network for International Surgery Trauma Team Training (TTT) course was delivered to 25 faculty, residents, and nurses. Trauma registry data over the 6 months prior to the courses were compared to the 6 months afterward with emergency department (ED) mortality as the primary endpoint. Secondary endpoints included radiology utilization and early procedural interventions. Univariate analyses were conducted using chi (2) and Fisher's exact test. A total of 798 and 575 patients were prospectively studied during the pre-intervention and post-intervention periods, respectively. Overall mortality of injured patients decreased after education implementation from 8.8 to 6.3 %, but was not statistically significant (p = 0.09). Patients with an initial Glasgow Coma Score (GCS) of 3-8 had the highest injury-related mortality, which significantly decreased from 58.5 % (n = 55) to 37.1 % (n = 23), (p = 0.009, OR 0.42, 95 % CI 0.22-0.81). There was no statistical difference in the rates of early intubation, cervical collar use, imaging studies, or transfusion in the overall cohort or the head injury subset. When further stratified by GCS, patients with an initial GCS of 3-5 in the post-intervention period had higher utilization of head CT scans and chest X-rays. The mortality of severely injured patients decreased after initiation of focused trauma education courses, but no significant increase in resource utilization was observed. The explanation may be complex and multi-factorial. Long-term multidisciplinary efforts that pair training with changes in resources and mentorship may be needed to produce broad and lasting changes in the overall care system. C1 [Petroze, Robin T.; Sawyer, Robert G.; Calland, J. Forrest] Univ Virginia Hlth Syst, Dept Surg, Charlottesville, VA 22908 USA. [Byiringiro, Jean Claude] Kigali Univ, Teaching Hosp, Dept Accid & Emergency, Butare, Rwanda. [Byiringiro, Jean Claude] Univ Rwanda, Sch Med, Butare, Rwanda. [Ntakiyiruta, Georges; Kyamanywa, Patrick] Univ Rwanda, Dept Surg, Coll Med & Hlth Sci, Butare, Rwanda. [Briggs, Susan M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Deckelbaum, Dan L.; Razek, Tarek] McGill Univ, Ctr Hlth, Ctr Global Surg, Montreal, PQ, Canada. [Razek, Tarek] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Reid, Jennifer] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. RP Calland, JF (reprint author), Univ Virginia Hlth Syst, Dept Surg, Charlottesville, VA 22908 USA. EM rtp3z@virgina.edu; jcbyiringiro@yahoo.fr; georgentakiyiruta@yahoo.co.uk; Briggs.Susan@mgh.harvard.edu; dan.deckelbaum@muhc.mcgill.ca; tarek.razek@muhc.mcgill.ca; robertriviello@gmail.com; pkyamanywa@nur.ac.rw; jer4zf@virginia.edu; rws2k@virginia.edu; calland@virginia.edu FU Fogarty International Clinical Research Fellowship; NIH; International Clinical Research Fellows Program at Vanderbilt University, USA [R24 TW007988]; University of Virginia Department of Surgery; NIH [5-T32-AI-078875-03] FX Support for the Rwanda Injury Registry (local staff stipends, training, and registry printing) comes from a Fogarty International Clinical Research Fellowship, NIH and International Clinical Research Fellows Program at Vanderbilt University, USA (R24 TW007988) from February 2011-August 2012. Maintenance of the Rwanda Injury Registry is currently funded by the University of Virginia Department of Surgery. Salary for RTP (author) was funded by NIH 5-T32-AI-078875-03, PI: Robert G. Sawyer from July 1, 2012, to June 30, 2013. NR 29 TC 5 Z9 5 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 EI 1432-2323 J9 WORLD J SURG JI World J.Surg. PD APR PY 2015 VL 39 IS 4 BP 926 EP 933 DI 10.1007/s00268-014-2899-y PG 8 WC Surgery SC Surgery GA CD6WN UT WOS:000351231100015 PM 25479817 ER PT J AU Moye, J AF Moye, Jennifer TI Evidence-Based Treatment of Neurocognitive Disorders: Measured Optimism About Select Outcomes SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Editorial Material ID CLINICAL-PRACTICE; DEMENTIA; DISEASE C1 [Moye, Jennifer] VA Boston Healthcare Syst, Boston, MA USA. [Moye, Jennifer] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. RP Moye, J (reprint author), VA Boston Healthcare Syst, Brockton Campus,940 Belmont St, Brockton, MA 02301 USA. EM Jennifer.moye@va.gov RI Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X NR 14 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD APR PY 2015 VL 23 IS 4 BP 331 EP 334 DI 10.1016/j.jagp.2015.01.002 PG 4 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA CD1IW UT WOS:000350829600001 PM 25747404 ER PT J AU Ferrone, CR AF Ferrone, Cristina R. TI FOLFIRINOX: Desert, Oasis, or Mirage? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material ID UNDERSTANDING HOSPITAL READMISSIONS; ADVANCED PANCREATIC-CANCER; NEOADJUVANT FOLFIRINOX; PANCREATICODUODENECTOMY; ADENOCARCINOMA; BORDERLINE; GEMCITABINE; PREVENT C1 Massachusetts Gen Hosp, Surg, Boston, MA 02114 USA. RP Ferrone, CR (reprint author), Massachusetts Gen Hosp, Surg, Boston, MA 02114 USA. EM cFERRONE@mgh.harvard.edu NR 14 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2015 VL 22 IS 4 BP 1059 EP 1060 DI 10.1245/s10434-014-4260-y PG 2 WC Oncology; Surgery SC Oncology; Surgery GA CC7MY UT WOS:000350553300004 PM 25490873 ER PT J AU Inamura, K Yamauchi, M Nishihara, R Kim, SA Mima, K Sukawa, Y Li, TT Yasunari, M Zhang, XH Wu, KN Meyerhardt, JA Fuchs, CS Harris, CC Qian, ZR Ogino, S AF Inamura, Kentaro Yamauchi, Mai Nishihara, Reiko Kim, Sun A. Mima, Kosuke Sukawa, Yasutaka Li, Tingting Yasunari, Mika Zhang, Xuehong Wu, Kana Meyerhardt, Jeffrey A. Fuchs, Charles S. Harris, Curtis C. Qian, Zhi Rong Ogino, Shuji TI Prognostic Significance and Molecular Features of Signet-Ring Cell and Mucinous Components in Colorectal Carcinoma SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID ISLAND METHYLATOR PHENOTYPE; POPULATION-BASED SAMPLE; III COLON-CANCER; MICROSATELLITE INSTABILITY; BRAF MUTATION; PIK3CA MUTATION; CLINICOPATHOLOGICAL FEATURES; PATHOLOGICAL EPIDEMIOLOGY; LINE-1 HYPOMETHYLATION; KRAS MUTATION AB Colorectal carcinoma (CRC) represents a group of histopathologically and molecularly heterogeneous diseases, which may contain signet-ring cell component and/or mucinous component to a varying extent under pathology assessment. However, little is known about the prognostic significance of those components, independent of various tumor molecular features. Utilizing a molecular pathological epidemiology database of 1,336 rectal and colon cancers in the Nurses' Health Study and the Health Professionals Follow-up Study, we examined patient survival according to the proportion of signet-ring cell and mucinous components in CRCs. Cox proportional hazards models were used to compute hazard ratio (HR) for mortality, adjusting for potential confounders including stage, microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and KRAS, BRAF, and PIK3CA mutations. Compared to CRC without signet-ring cell component, 1-50 % signet-ring cell component was associated with multivariate CRC-specific mortality HR of 1.40 [95 % confidence interval (CI) 1.02-1.93], and > 50 % signet-ring cell component was associated with multivariate CRC-specific mortality HR of 4.53 (95 % CI 2.53-8.12) (P (trend) < 0.0001). Compared to CRC without mucinous component, neither 1-50 % mucinous component (multivariate HR 1.04; 95 % CI 0.81-1.33) nor > 50 % mucinous component (multivariate HR 0.82; 95 % CI 0.54-1.23) was significantly associated with CRC-specific mortality (P (trend) < 0.57). Even a minor (50 % or less) signet-ring cell component in CRC was associated with higher patient mortality, independent of various tumor molecular and other clinicopathological features. In contrast, mucinous component was not associated with mortality in CRC patients. C1 [Inamura, Kentaro; Yamauchi, Mai; Nishihara, Reiko; Kim, Sun A.; Mima, Kosuke; Sukawa, Yasutaka; Li, Tingting; Yasunari, Mika; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Qian, Zhi Rong; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Inamura, Kentaro; Yamauchi, Mai; Nishihara, Reiko; Kim, Sun A.; Mima, Kosuke; Sukawa, Yasutaka; Li, Tingting; Yasunari, Mika; Zhang, Xuehong; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Harris, Curtis C.; Qian, Zhi Rong; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA. [Inamura, Kentaro; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. [Nishihara, Reiko; Wu, Kana] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Li, Tingting] Chinese Peoples Liberat Army Gen Hosp, Dept Geriatr Gastroenterol, Beijing 100853, Peoples R China. [Zhang, Xuehong; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Inamura, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM kentaro_inamura@dfci.harvard.edu; shuji_ogino@dfci.harvard.edu FU U.S. National Institutes of Health (NIH) [P01 CA87969, P01 CA55075, UM1 CA167552, P50 CA127003, R01 CA151993]; Bennett Family Fund; Entertainment Industry Foundation through National Colorectal Cancer Research Alliance; Japan Society for the Promotion of Science Postdoctoral Fellowship for Research Abroad; Takashi Tsuruo Memorial Fund; Asan medical center; Uehara Memorial Foundation FX This work was supported by U.S. National Institutes of Health (NIH) grants (P01 CA87969 to S.E. Hankinson; P01 CA55075 to W.C. Willett; UM1 CA167552 to W.C. Willett; P50 CA127003 to C.S.F.; and R01 CA151993 to S.O.); and by grants from the Bennett Family Fund and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance. K.I. was supported by a Japan Society for the Promotion of Science Postdoctoral Fellowship for Research Abroad and by Takashi Tsuruo Memorial Fund. S.A.K. is supported by an early exchange postdoctoral fellowship grant from Asan medical center. K.M. is supported by a fellowship grant from the Uehara Memorial Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 59 TC 8 Z9 8 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2015 VL 22 IS 4 BP 1226 EP 1235 DI 10.1245/s10434-014-4159-7 PG 10 WC Oncology; Surgery SC Oncology; Surgery GA CC7MY UT WOS:000350553300030 PM 25326395 ER PT J AU Mao, YL Du, SD Ba, JT Li, F Yang, HY Lu, X Sang, XT Li, SH Che, L Tong, JX Xu, YY Xu, HF Zhao, HT Chi, TY Liu, F Du, YR Zhang, XZ Wang, XB Dong, JH Zhong, SX Huang, JF Yu, YM Wang, JP AF Mao, Yilei Du, Shunda Ba, Jiantao Li, Fang Yang, Huayu Lu, Xin Sang, Xinting Li, Shaohua Che, Lu Tong, Junxiang Xu, Yiyao Xu, Haifeng Zhao, Haitao Chi, Tianyi Liu, Fang Du, Yanrong Zhang, Xianzhong Wang, Xuebin Dong, Jiahong Zhong, Shouxian Huang, Jiefu Yu, Yongming Wang, Jiping TI Using Dynamic T-99m(c)-GSA SPECT/CT Fusion Images for Hepatectomy Planning and Postoperative Liver Failure Prediction SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID MAJOR HEPATIC RESECTION; HUMAN SERUM-ALBUMIN; HEPATOCELLULAR-CARCINOMA; ASIALOGLYCOPROTEIN RECEPTOR; REMNANT LIVER; RISK-FACTORS; SCINTIGRAPHY; CIRRHOSIS; VOLUME AB Available tools in liver surgery planning rely on the future remnant liver (FRL) volume. Inappropriate decision might be made since the same FRL volume might represent different liver functions depending on the severity of underlying liver damage. This study developed an alternative system to estimate FRL function and to predict the risk of postoperative liver failure. Current study recruited 71 prehepatectomy patients and 71 healthy volunteers. A technetium-99-labelled asialoglycoproteins was given to participants and SPECT was used to capture the intensity of the signal, represented by uptake index (UI). The agreement between preoperative UI values, liver function tests, and Child scores were evaluated. Linear regression was used to evaluate the agreement between predicted UI for FRL and postoperative UI values. Area under the receiver operating characteristic (AUC) curve was used to evaluate the discriminative performance of UI in differentiating patient with high risk of liver failure. Preoperative UIs are highly correlated with Child score (P < 0.0001), especially to identify patients with ascites and elevated bilirubin. The predicted UIs were in close agreement with the actual postoperative UI values (r = 0.95 P < 0.001). The AUC analysis indicated that UI values had a high accuracy in predicting the risk of liver failure (AUC = 0.95, P < 0.0001). The best cut-off point was 0.9 and the corresponding sensitivity was 100 % and specificity was 92 %. The new methodology reliably estimates FRL function and predicts the risk of liver failure. It provides a visual aid for liver surgeon in surgery planning and risk assessment. C1 [Mao, Yilei; Du, Shunda; Yang, Huayu; Lu, Xin; Sang, Xinting; Li, Shaohua; Che, Lu; Xu, Yiyao; Xu, Haifeng; Zhao, Haitao; Chi, Tianyi; Liu, Fang; Zhong, Shouxian; Huang, Jiefu] Chinese Acad Med Sci, Peking Union Med Coll PUMC Hosp, Dept Liver Surg, Beijing 100730, Peoples R China. [Mao, Yilei; Du, Shunda; Ba, Jiantao; Li, Fang; Yang, Huayu; Lu, Xin; Sang, Xinting; Li, Shaohua; Che, Lu; Xu, Yiyao; Xu, Haifeng; Zhao, Haitao; Chi, Tianyi; Liu, Fang; Du, Yanrong; Zhong, Shouxian; Huang, Jiefu] PUMC, Beijing, Peoples R China. [Ba, Jiantao; Li, Fang; Du, Yanrong] Chinese Acad Med Sci, Peking Union Med Coll PUMC Hosp, Dept Nucl Med, Beijing 100730, Peoples R China. [Tong, Junxiang; Dong, Jiahong] Chinese Peoples Liberat Army Gen Hosp, Dept Hepatobiliary Surg, Beijing 100853, Peoples R China. [Zhang, Xianzhong; Wang, Xuebin] Beijing Normal Univ, Coll Chem, Minist Educ, Key Lab Radiopharmaceut, Beijing 100875, Peoples R China. [Yu, Yongming] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Wang, Jiping] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Wang, Jiping] Brigham & Womens Hosp, Div Surg Oncol, Boston, MA 02115 USA. RP Mao, YL (reprint author), Chinese Acad Med Sci, Peking Union Med Coll PUMC Hosp, Dept Liver Surg, Beijing 100730, Peoples R China. EM yileimao@126.com; jwang39@partners.org RI Zhang, Xianzhong/A-7754-2012 OI Zhang, Xianzhong/0000-0002-1001-1884 FU China Medical Board of New York (CMB) [06-837, 11-045]; National Natural Science Foundation of China [30901453, 81201566]; National Key Technology Research and Development Program of China [BAI06B01] FX The authors thank EDDA Technique Corp, Ltd. for their collaboration and assistance in the computerization and image development of our system. This work was supported by the China Medical Board of New York (CMB) (06-837 and 11-045), National Natural Science Foundation of China (30901453 and 81201566) and National Key Technology Research and Development Program of China (BAI06B01). NR 28 TC 6 Z9 6 U1 3 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2015 VL 22 IS 4 BP 1301 EP 1307 DI 10.1245/s10434-014-4117-4 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA CC7MY UT WOS:000350553300040 PM 25294018 ER PT J AU Elias, KM Kang, S Liu, XX Horowitz, NS Berkowitz, RS Frendl, G AF Elias, Kevin M. Kang, Stephanie Liu, Xiaoxia Horowitz, Neil S. Berkowitz, Ross S. Frendl, Gyorgy TI Anesthetic Selection and Disease-Free Survival Following Optimal Primary Cytoreductive Surgery for Stage III Epithelial Ovarian Cancer SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID EPIDURAL ANALGESIA; NEOADJUVANT CHEMOTHERAPY; RADICAL PROSTATECTOMY; NEURAXIAL ANESTHESIA; GENERAL-ANESTHESIA; RECURRENCE; METASTASIS; SEVOFLURANE; POPULATION; DESFLURANE AB Previous studies have offered conflicting results regarding an association between perioperative epidural analgesia and disease-free survival (DFS) following optimal primary cytoreductive surgery for stage III epithelial ovarian cancer. A possible separate role for inhalational anesthetics has not been assessed. We conducted a historical cohort study of all women undergoing optimal primary cytoreduction (< 1 cm residual disease) for Stage III epithelial ovarian cancer between January 1, 2007, and December 31, 2011, at Brigham and Women's Hospital. Cohorts were defined by exposure to perioperative epidural analgesia or exposure to specific volatile anesthetics. The primary outcome was DFS. A total of 194 patients met study inclusion criteria. Addition of epidural analgesia was associated with a lower overall rate of ovarian cancer recurrence compared with general anesthesia alone (72 vs. 85 %, p = 0.028). Longer median DFS was associated with more than 48 h of epidural use (14.9 months) compared with fewer than 24 h (10.9 months) or 24-48 h of epidural use (10.0 months; p = 0.025). Use of desflurane was associated with a lower overall rate of ovarian cancer recurrence compared with sevoflurane (63 vs. 84 %, p = 0.01). In multivariate analysis, use of desflurane was independently associated with improved DFS (hazards ratio 0.563; 95% confidence interval 0.33-0.962). For patients with Stage III ovarian cancer, use of desflurane is associated with improved DFS following primary cytoreductive surgery compared with other volatile anesthetics. If epidural analgesia offers additional benefit, this effect appears limited to patients with more than 48 h of postoperative epidural use. C1 [Elias, Kevin M.; Horowitz, Neil S.; Berkowitz, Ross S.] Brigham & Womens Hosp, Dept Obstet & Gynecol & Reprod Biol, Div Gynecol Oncol, Boston, MA 02115 USA. [Elias, Kevin M.; Kang, Stephanie; Liu, Xiaoxia; Frendl, Gyorgy] Brigham & Womens Hosp, Surg ICU Translat Res Ctr, Boston, MA 02115 USA. [Elias, Kevin M.; Frendl, Gyorgy] Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Elias, Kevin M.; Horowitz, Neil S.; Berkowitz, Ross S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Elias, Kevin M.; Horowitz, Neil S.; Berkowitz, Ross S.; Frendl, Gyorgy] Harvard Univ, Sch Med, Boston, MA USA. RP Elias, KM (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol & Reprod Biol, Div Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA. EM kelias1@partners.org OI Elias, Kevin/0000-0003-1502-5553 FU Ruth N. White Gynecologic Oncology Research Fellowship FX Supported by the Ruth N. White Gynecologic Oncology Research Fellowship. NR 35 TC 2 Z9 2 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2015 VL 22 IS 4 BP 1341 EP 1348 DI 10.1245/s10434-014-4112-9 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA CC7MY UT WOS:000350553300045 PM 25287437 ER PT J AU De Souza, P Smith, MR Fizazi, K Saad, F Mulders, PFA Sternberg, CN Miller, K Logothetis, CJ Shore, N Small, EJ Carles, J Flaig, TW Taplin, ME Higano, CS De Bono, JS Griffin, TW De Porre, P Yu, MK Park, YC Li, J Kheoh, T Naini, V Molina, A Rathkopf, DE Ryan, CJ AF De Souza, P. Smith, M. R. Fizazi, K. Saad, F. Mulders, P. F. A. Sternberg, C. N. Miller, K. Logothetis, C. J. Shore, N. Small, E. J. Carles, J. Flaig, T. W. Taplin, M-E. Higano, C. S. De Bono, J. S. Griffin, T. W. De Porre, P. Yu, M. K. Park, Y. C. Li, J. Kheoh, T. Naini, V. Molina, A. Rathkopf, D. E. Ryan, C. J. TI Final analysis of the randomised, phase 3, COU-AA-302 study of abiraterone acetate (AA) in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (mCRPC) SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Urological-Society-of-Australia-and-New Zealand CY APR 11-14, 2015 CL Adelaide, AUSTRALIA SP Urol Soc Australia & New Zealand C1 [De Souza, P.] Univ Western Sydney, Sch Med, Liverpool, Merseyside, Australia. [De Souza, P.] Ingham Inst, Liverpool, Merseyside, Australia. [Smith, M. R.] Harvard Univ, Sch Med, Boston, MA USA. [Smith, M. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fizazi, K.] Univ Paris Sud, Inst Gustave Roussy, Villejuif, France. [Saad, F.] Univ Montreal, Montreal, PQ, Canada. [Mulders, P. F. A.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Sternberg, C. N.] San Camillo & Forlanini Hosp, Rome, Italy. [Miller, K.] Charite, Berlin, Germany. [Logothetis, C. J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Shore, N.] Atlantic Urol Clin, Carolina Urol Res Ctr, Myrtle Beach, SC USA. [Small, E. J.; Ryan, C. J.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Carles, J.] Vall dHebron Univ Hosp, Barcelona, Spain. [Carles, J.] Vall dHebron Inst Oncol, Barcelona, Spain. [Flaig, T. W.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Flaig, T. W.] Univ Colorado, Sch Med, Aurora, CO USA. [Taplin, M-E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Higano, C. S.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [De Bono, J. S.] Inst Canc Res, Sutton, Surrey, England. [De Bono, J. S.] Royal Marsden Hosp, Sutton, Surrey, England. [Griffin, T. W.; Yu, M. K.; Kheoh, T.; Naini, V.] Janssen Res & Dev, Los Angeles, CA USA. [De Porre, P.; Park, Y. C.] Janssen Res & Dev, Beerse, Belgium. [Li, J.] Johnson & Johnson Med China, Shanghai, Peoples R China. [Molina, A.] Janssen Res & Dev, Menlo Pk, CA USA. [Rathkopf, D. E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RI Mulders, Peter/H-8076-2014 NR 0 TC 0 Z9 0 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD APR PY 2015 VL 115 SU 4 SI SI MA 41 BP 21 EP 22 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA CD9CQ UT WOS:000351395100042 ER PT J AU Mainwaring, P Liu, G Lee, JY Semenov, A Tejwani, S Lara, P Trudel, GC Sosa, A Kheoh, T Yu, MK Rooney, B Espina, B Smith, MR Small, EJ AF Mainwaring, P. Liu, G. Lee, J. Y. Semenov, A. Tejwani, S. Lara, P., Jr. Trudel, G. C. Sosa, A. Kheoh, T. Yu, M. K. Rooney, B. Espina, B. Smith, M. R. Small, E. J. TI SPARTAN - a randomised double-blind, comparative study of ARN-509 plus androgen deprivation therapy (ADT) vs ADT alone in non-metastatic castration-resistant prostate cancer (M0-CRPC) SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Urological-Society-of-Australia-and-New Zealand CY APR 11-14, 2015 CL Adelaide, AUSTRALIA SP Urol Soc Australia & New Zealand C1 [Mainwaring, P.] ICON Canc Care, Brisbane, Qld, Australia. [Liu, G.] Univ Wisconsin, Madison, WI 53706 USA. [Lee, J. Y.] Catholic Univ Korea, Seoul St Marys Hosp, Seoul, South Korea. [Semenov, A.] Ivanovo Reg Canc Ctr, Ivanovo, Russia. [Tejwani, S.] Henry Ford Hosp, Detroit, MI 48202 USA. [Lara, P., Jr.] Univ Calif Davis, Davis, CA 95616 USA. [Trudel, G. C.; Sosa, A.; Kheoh, T.; Yu, M. K.; Espina, B.] Janssen Res & Dev, Los Angeles, CA USA. [Rooney, B.] Janssen Res & Dev, High Wycombe, Bucks, England. [Smith, M. R.] Harvard Univ, Sch Med, Boston, MA USA. [Smith, M. R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Small, E. J.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD APR PY 2015 VL 115 SU 4 SI SI MA 204 BP 97 EP 97 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA CD9CQ UT WOS:000351395100205 ER PT J AU Baumann, O Borra, RJ Bower, JM Cullen, KE Habas, C Ivry, RB Leggio, M Mattingley, JB Molinari, M Moulton, EA Paulin, MG Pavlova, MA Schmahmann, JD Sokolov, AA AF Baumann, Oliver Borra, Ronald J. Bower, James M. Cullen, Kathleen E. Habas, Christophe Ivry, Richard B. Leggio, Maria Mattingley, Jason B. Molinari, Marco Moulton, Eric A. Paulin, Michael G. Pavlova, Marina A. Schmahmann, Jeremy D. Sokolov, Arseny A. TI Consensus Paper: The Role of the Cerebellum in Perceptual Processes SO CEREBELLUM LA English DT Article DE Audition; Biological motion; Cerebellum; Connectivity; Evolution; fMRI; Pain; Perception; Prediction; Single-unit recording; Self-motion; Sequencing; State estimation; Timing; Vision ID AUTISM SPECTRUM DISORDER; SUPERIOR TEMPORAL SULCUS; INTRINSIC FUNCTIONAL CONNECTIVITY; TRANSCRANIAL MAGNETIC STIMULATION; INDEPENDENT COMPONENT ANALYSIS; CONDITIONED EYELID RESPONSES; BIOLOGICAL MOTION PERCEPTION; TACTILE PROJECTION PATTERNS; RHESUS-MONKEY; MOTOR CONTROL AB Various lines of evidence accumulated over the past 30 years indicate that the cerebellum, long recognized as essential for motor control, also has considerable influence on perceptual processes. In this paper, we bring together experts from psychology and neuroscience, with the aim of providing a succinct but comprehensive overview of key findings related to the involvement of the cerebellum in sensory perception. The contributions cover such topics as anatomical and functional connectivity, evolutionary and comparative perspectives, visual and auditory processing, biological motion perception, nociception, self-motion, timing, predictive processing, and perceptual sequencing. While no single explanation has yet emerged concerning the role of the cerebellum in perceptual processes, this consensus paper summarizes the impressive empirical evidence on this problem and highlights diversities as well as commonalities between existing hypotheses. In addition to work with healthy individuals and patients with cerebellar disorders, it is also apparent that several neurological conditions in which perceptual disturbances occur, including autism and schizophrenia, are associated with cerebellar pathology. A better understanding of the involvement of the cerebellum in perceptual processes will thus likely be important for identifying and treating perceptual deficits that may at present go unnoticed and untreated. This paper provides a useful framework for further debate and empirical investigations into the influence of the cerebellum on sensory perception. C1 [Baumann, Oliver; Mattingley, Jason B.] Univ Queensland, Queensland Brain Inst, St Lucia, Qld, Australia. [Borra, Ronald J.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. [Borra, Ronald J.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Borra, Ronald J.] Harvard Univ, Sch Med, Charlestown, MA USA. [Borra, Ronald J.] Turku Univ Hosp, Med Imaging Ctr Southwest Finland, Dept Diagnost Radiol, FIN-20520 Turku, Finland. [Bower, James M.] Numedon Inc, Pasadena, CA USA. [Cullen, Kathleen E.] McGill Univ, Dept Physiol, Montreal, PQ, Canada. [Habas, Christophe] UPMC Paris 6, CHNO Quinze Vingts, Serv NeuroImagerie, Paris, France. [Ivry, Richard B.] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. [Leggio, Maria] Univ Roma La Sapienza, Dept Psychol, I-00185 Rome, Italy. [Leggio, Maria; Molinari, Marco] IRCCS Santa Lucia Fdn, Rome, Italy. [Moulton, Eric A.] Harvard Univ, Ctr Pain & Brain, Pain Analgesia Imaging Neurosci PIN Grp, Dept Anesthesia,Boston Childrens Hosp,Sch Med, Waltham, MA USA. [Paulin, Michael G.] Univ Otago, Dept Zool, Otago, New Zealand. [Pavlova, Marina A.] Univ Tubingen, Sch Med, Dept Biomed Magnet Resonance, Tubingen, Germany. [Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Dept Neurol, Lab Neuroanat & Cerebellar Neurobiol, Ataxia Unit,Cognit Behav Neurol Unit, Boston, MA 02114 USA. [Schmahmann, Jeremy D.] Harvard Univ, Sch Med, Boston, MA USA. [Sokolov, Arseny A.] Ctr Hosp Univ Vaudois CHUV, Dept Neurosci Clin, Lausanne, Switzerland. RP Baumann, O (reprint author), Univ Queensland, Queensland Brain Inst, St Lucia, Qld, Australia. EM o.baumann@uq.edu.au RI Mattingley, Jason/J-1537-2014; Molinari, Marco/A-9624-2010; OI Mattingley, Jason/0000-0003-0929-9216; Molinari, Marco/0000-0001-9808-9688; Borra, Ronald/0000-0001-8072-1243; Leggio, Maria /0000-0003-3750-2760 FU MINDlink Foundation; Birmingham Foundation; Australian Research Council (ARC) Discovery Early Career Researcher Award [DE120100535]; ARC Australian Laureate Fellowship [FL110100103]; ARC-SRI Science of Learning Research Centre [SR120300015]; ARC Centre of Excellence for Integrative Brain Function (ARC Centre Grant) [CE140100007]; Else Kroner Fresenius Foundation [P2013_127]; Reinhold-Beitlich Foundation; Berthold Leibinger Foundation; Heidehof Foundation [59073.01.1/3.13]; Sigrid Juselius Foundation; Instrumentarium Research Foundation; Finnish Medical Foundation; Paulo Foundation; Academy of Finland [270352]; National Institute of Health, USA [NIH/NCI R21CA185870, NS084948, NS074917] FX (1) Dr. Schmahmann's work was supported in part by the MINDlink and Birmingham Foundations. (2) Dr. Baumann was supported by an Australian Research Council (ARC) Discovery Early Career Researcher Award (DE120100535) and Dr. Mattingley by an ARC Australian Laureate Fellowship (FL110100103), the ARC-SRI Science of Learning Research Centre (SR120300015), and the ARC Centre of Excellence for Integrative Brain Function (ARC Centre Grant CE140100007). (3) Dr. Pavlova was supported by Else Kroner Fresenius Foundation (Grant P2013_127), the Reinhold-Beitlich Foundation, the Berthold Leibinger Foundation, and the Heidehof Foundation (Grant 59073.01.1/3.13). (4) Dr. Borra was supported by funding from the Sigrid Juselius Foundation, the Instrumentarium Research Foundation, the Finnish Medical Foundation, the Paulo Foundation and the Academy of Finland (270352). Dr. Moulton was supported by the National Institute of Health, USA (NIH/NCI R21CA185870). (5) Dr. Ivry was supported by the National Institute of Health, USA (NS084948 and NS074917). NR 246 TC 26 Z9 27 U1 9 U2 51 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1473-4222 EI 1473-4230 J9 CEREBELLUM JI Cerebellum PD APR PY 2015 VL 14 IS 2 BP 197 EP 220 DI 10.1007/s12311-014-0627-7 PG 24 WC Neurosciences SC Neurosciences & Neurology GA CD2HU UT WOS:000350897800014 PM 25479821 ER PT J AU Mananga, ES Charpentier, T AF Mananga, Eugene Stephane Charpentier, Thibault TI Floquet-Magnus expansion for general N-coupled spins systems in magic-angle spinning nuclear magnetic resonance spectra SO CHEMICAL PHYSICS LA English DT Article DE Floquet theory; Floquet-Magnus expansion; Magic-angle spinning; Gamma encoding; Nuclear magnetic resonance ID SOLID-STATE NMR; AVERAGE HAMILTONIAN THEORY; CHEMICAL-SHIFT ANISOTROPY; ROTATING SOLIDS; CROSS-POLARIZATION; SPECTROSCOPY; SIMULATION; SEQUENCES; ORDER; DYNAMICS AB In this paper we present a theoretical perturbative approach for describing the NMR spectrum of strongly dipolar-coupled spin systems under fast magic-angle spinning. Our treatment is based on two approaches: the Floquet approach and the Floquet-Magnus expansion. The Floquet approach is well known in the NMR community as a perturbative approach to get analytical approximations. Numerical procedures are based on step-by-step numerical integration of the corresponding differential equations. The Floquet-Magnus expansion is a perturbative approach of the Floquet theory. Furthermore, we address the "gamma-encoding'' effect using the Floquet-Magnus expansion approach. We show that the average over "gamma'' angle can be performed for any Hamiltonian with gamma symmetry. (C) 2015 Elsevier B.V. All rights reserved. C1 [Mananga, Eugene Stephane] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Mananga, Eugene Stephane] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging Phys, Dept Radiol, Boston, MA 02114 USA. [Charpentier, Thibault] CEA CNRS UMR 3299, IRAMIS, Serv Interdisciplinaire Syst Mol & Mat, Commissariat Energie Atom, F-91191 Gif Sur Yvette, France. [Mananga, Eugene Stephane] CUNY, Dept Phys & Technol, BCC, New York, NY 10453 USA. RP Mananga, ES (reprint author), CUNY, Dept Phys & Technol, BCC, 2155 Univ Ave,CPH 118, New York, NY 10453 USA. EM esm041@mail.harvard.edu RI Charpentier, Thibault/A-3557-2010 OI Charpentier, Thibault/0000-0002-3034-1389 FU National Institute of Health (NIH) of the US [R01-HL110241, T32 EB013180] FX This work was supported by the National Institute of Health (NIH) of the US, under Grants R01-HL110241 and T32 EB013180. The contents of this paper are solely the responsibility of the authors and do not represent the official views of NIH. NR 68 TC 5 Z9 5 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0104 EI 1873-4421 J9 CHEM PHYS JI Chem. Phys. PD APR 1 PY 2015 VL 450 BP 83 EP 90 DI 10.1016/j.chemphys.2015.02.006 PG 8 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA CD1XP UT WOS:000350868100009 ER PT J AU Scioli-Salter, ER Forman, DE Otis, JD Gregor, K Valovski, I Rasmusson, AM AF Scioli-Salter, Erica R. Forman, Daniel E. Otis, John D. Gregor, Kristin Valovski, Ivan Rasmusson, Ann M. TI The Shared Neuroanatomy and Neurobiology of Comorbid Chronic Pain and PTSD Therapeutic Implications SO CLINICAL JOURNAL OF PAIN LA English DT Review DE chronic pain; posttraumatic stress disorder; neuropeptide Y; allopregnanolone; exercise ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMATIC BRAIN-INJURY; PITUITARY-ADRENAL AXIS; LOW-BACK-PAIN; NEUROPEPTIDE-Y CONCENTRATIONS; INTIMATE PARTNER VIOLENCE; MENSTRUAL-CYCLE; ALLOPREGNANOLONE LEVELS; FIBROMYALGIA SYNDROME; BASOLATERAL AMYGDALA AB Chronic pain and posttraumatic stress disorder (PTSD) are disabling conditions that affect biological, psychological, and social domains of functioning. Clinical research demonstrates that patients who are affected by chronic pain and PTSD in combination experience greater pain, affective distress, and disability than patients with either condition alone. Additional research is needed to delineate the interrelated pathophysiology of chronic pain and PTSD, with the goal of facilitating more effective therapies to treat both conditions more effectively; current treatment strategies for chronic pain associated with PTSD have limited efficacy and place a heavy burden on patients, who must visit various specialists to manage these conditions separately. This article focuses on neurobiological factors that may contribute to the coprevalence and synergistic interactions of chronic pain and PTSD. First, we outline how circuits that mediate emotional distress and physiological threat, including pain, converge. Secondly, we discuss specific neurobiological mediators and modulators of these circuits that may contribute to chronic pain and PTSD symptoms. For example, neuropeptide Y, and the neuroactive steroids allopregnanolone and pregnanolone (together termed ALLO) have antistress and antinociceptive properties. Reduced levels of neuropeptide Y and ALLO have been implicated in the pathophysiology of both chronic pain and PTSD. The potential contribution of opioid and cannabinoid system factors also will be discussed. Finally, we address potential novel methods to restore the normal function of these systems. Such novel perspectives regarding disease and disease management are vital to the pursuit of relief for the many individuals who struggle with these disabling conditions. C1 [Scioli-Salter, Erica R.; Otis, John D.; Gregor, Kristin] VA Boston Healthcare Syst, Div Res, Jamaica Plain, MA USA. [Valovski, Ivan] VA Boston Healthcare Syst, Dept Anesthesiol, Jamaica Plain, MA USA. [Scioli-Salter, Erica R.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Otis, John D.] Boston Univ, Sch Med, Dept Psychiat & Psychol, Boston, MA 02118 USA. [Forman, Daniel E.] Harvard Univ, Brigham & Womens Hosp, New England Geriatr Res Educ & Clin Ctr, Sch Med,Div Cardiovasc Med, Boston, MA 02115 USA. [Rasmusson, Ann M.] Boston Univ, Sch Med, Dept Psychiat,VA Boston Healtcare Syst, Natl Ctr PTSD,Womens Hlth Sci Div, Boston, MA 02118 USA. RP Scioli-Salter, ER (reprint author), VA Boston Healthcare Syst, Div Res, 12C-5,150 South Huntington Ave, Boston, MA 02130 USA. EM ericarose.scioli@va.gov FU Career Development Award through VA Rehabilitation, Research and Development Service (VARRD) [CDA-2] FX This publication was, in part, based on the grant narrative of my Career Development Award (CDA-2) through the VA Rehabilitation, Research and Development Service (VARR&D). The authors declare no conflict of interest. NR 135 TC 15 Z9 15 U1 3 U2 11 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 APR PY 2015 VL 31 IS 4 BP 363 EP 374 DI 10.1097/AJP.0000000000000115 PG 12 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA CD3NR UT WOS:000350986000010 PM 24806468 ER PT J AU Karim, SM Colman, MW Lozano-Calderon, SA Raskin, KA Schwab, JH Hornicek, FJ AF Karim, S. Mohammed Colman, Matthew W. Lozano-Calderon, Santiago A. Raskin, Kevin A. Schwab, Joseph H. Hornicek, Francis J. TI What Are the Functional Results and Complications From Allograft Reconstruction After Partial Hemipelvectomy of the Pubis? SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID PELVIC RECONSTRUCTION; TUMORS; RESECTIONS; BONE AB In patients undergoing hemipelvectomies including resection either of a portion of the pubis or the entire pubis from the symphysis to the lateral margin of the obturator foramen while sparing the hip (so-called Dunham Type III hemipelvectomies), reconstructions typically are not performed given the preserved continuity of the weightbearing axis and the potential complications associated with reconstruction. Allograft reconstruction of the pelvic ring may, however, offer benefits for soft tissue reconstruction of the pelvic floor and hip stability, but little is known about these reconstructions. (1) What is the postoperative functional status after allograft reconstruction of Type III pelvic defects? (2) What are the rates of hernia, infection, and hip instability? In this case series, we reviewed all patients with Type III pelvic resections (with or without anterior acetabular wall resections) who underwent allograft reconstruction between 2005 and 2013 at one center (N = 14). During the period in question, reconstruction was the general approach used in patients undergoing these resections; during that time, three other patients were treated without reconstruction as a result of either surgeon preference or the patient choosing to not have reconstruction after a discussion of the risks and benefits. Of the 14 patients treated with reconstruction, complete followup was available at a minimum of 1 year in 11 (other than those who died before the end of the first year; median, 19 months; range 16-70 months among those surviving), one was lost to followup before a year, and two others had partial telephone or email followup. Patient demographics, disease status, functional status, and complications were recorded. For a portion of the cohort (four patients) later in the series, we used a novel technique for anterior acetabular wall reconstruction using the concave cartilaginous surface of a proximal fibula allograft; the others received either a long bone (humerus or femur) or hemipelvis graft. Seven patients died of disease; two had local recurrence, and five died of metastatic disease. All patients remained ambulatory Pain at 12 months after surgery was reported as none in five, mild in two, moderate in two, and severe in one. Operative complications included infection in two, symptomatic hernia in one, hip instability in one, dislocated total hip arthroplasty on the first postoperative day in one, and graft failure in one. Allograft reconstruction after Type III pelvic resections can provide functional reconstruction of the pelvic ring, pelvic floor, and, in certain patients with partial anterior acetabular resections, the resected anterior acetabulum. This has implications in preventing the occurrence of hernia and hip instability in this patient population that is classically not reconstructed, although longer-term outcomes in a larger number of patients would help to better delineate this because infection, hernia, hip instability, and graft nonunion still remain concerns with this approach. The most important unanswered question remains whether, on balance, any benefits that may accrue to these patients as the result of reconstruction are offset by a relatively high likelihood of undergoing secondary or revision surgery. Level IV, therapeutic study. C1 [Karim, S. Mohammed; Colman, Matthew W.; Lozano-Calderon, Santiago A.; Raskin, Kevin A.; Schwab, Joseph H.; Hornicek, Francis J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Colman, Matthew W.] Rush Univ, Midwest Orthoped, Chicago, IL 60612 USA. RP Colman, MW (reprint author), Rush Univ, Midwest Orthoped, 1611 West Harrison St,Suite 300, Chicago, IL 60612 USA. EM matthew.colman@rushortho.com NR 18 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD APR PY 2015 VL 473 IS 4 BP 1442 EP 1448 DI 10.1007/s11999-014-4009-8 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CD2DY UT WOS:000350885600039 PM 25337979 ER PT J AU Strooker, JA Nota, SPFT Hageman, MGJS Ring, DC AF Strooker, Joost A. Nota, Sjoerd P. F. T. Hageman, Michiel G. J. S. Ring, David C. TI Patients With Greater Symptom Intensity and More Disability are More Likely to be Surprised by a Hand Surgeon's Advice SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID ARM PAIN; COMMUNICATION; PHYSICIAN AB A clash between a patient's assumptions and a doctor's advice can feel adversarial which might influence satisfaction ratings and compliance with treatment recommendations. A better understanding of sources of patients' bewilderment might lead to improved strategies for conveying counterintuitive information that improve patient comfort and wellbeing. This study addressed the following questions: (1) Are magnitude of disability, pain intensity, symptoms of depression, or health anxiety associated with a higher level of surprise when a patient is presented with diagnostic information and/or therapeutic recommendations? (2) Does the surgeon accurately perceive the patient's bewilderment? (3) Does the surgeon's perception of patient bewilderment correlate with diagnosis or a patient's magnitude of disability, pain intensity, symptoms of depression, or health anxiety? In this prospective cohort study, we invited new patients who met prespecified criteria during a 3-month period in one hand-surgery practice to enroll; of 93 patients invited, 84 (90%) agreed to participate. Patients reported demographics and completed the short versions of the DASH questionnaire (QuickDASH), the Patient Health Questionnaire, the Pain Self-Efficacy Questionnaire, and the Short Health Anxiety Inventory; rated their pain intensity; and rated the degree to which the information given by the surgeon was unexpected or surprising on an 11-point ordinal scale. The surgeon also rated his impression of the patient's surprise on an 11-point ordinal scale. Only greater symptom intensity and magnitude of disability (QuickDASH) correlated with greater unexpected information when rated by the patient ( = 0.058; p < 0.001). There was a correlation between patient surprise and the surgeon's perception of the patient's surprise (r = 0.58; p < 0.001). Greater surgeon-perceived patient surprise correlated with nonspecific illness (p = 0.007; = 3.0). Patients with greater symptom intensity and magnitude of disability, and perhaps also patients with nonspecific diagnoses, are more likely to be surprised by a hand surgeon's advice. Future research might address the ability of previsit preparation (using decision aids or other alternative means of education) to ameliorate the discordance between patient assumptions and hand surgeon advice. C1 [Strooker, Joost A.; Nota, Sjoerd P. F. T.; Hageman, Michiel G. J. S.; Ring, David C.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand Surg Serv, Yawkey Ctr, Boston, MA 02114 USA. RP Ring, DC (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand Surg Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 13 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD APR PY 2015 VL 473 IS 4 BP 1478 EP 1483 DI 10.1007/s11999-014-3971-5 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CD2DY UT WOS:000350885600045 PM 25280552 ER PT J AU Tiberi, JV Hansen, V El-Abbadi, N Bedair, H AF Tiberi, John V., III Hansen, Viktor El-Abbadi, Naglaa Bedair, Hany TI Reply to the Letter to the Editor: Increased Complication Rates After Hip and Knee Arthroplasty in Patients With Cirrhosis of the Liver SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Letter C1 [Tiberi, John V., III] South Bay Orthopaed Specialists Med Ctr, Torrance, CA 90505 USA. [Hansen, Viktor] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. [El-Abbadi, Naglaa] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Bedair, Hany] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Tiberi, JV (reprint author), South Bay Orthopaed Specialists Med Ctr, 23560 Crenshaw Blvd Suite 102, Torrance, CA 90505 USA. EM jvtiberi@gmail.com 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 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD APR PY 2015 VL 473 IS 4 BP 1534 EP 1535 DI 10.1007/s11999-015-4144-x PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CD2DY UT WOS:000350885600055 PM 25645261 ER PT J AU Jeschke, MG Pinto, R Kraft, R Nathens, AB Finnerty, CC Gamelli, RL Gibran, NS Klein, MB Arnoldo, BD Tompkins, RG Herndon, DN AF Jeschke, Marc G. Pinto, Ruxandra Kraft, Robert Nathens, Avery B. Finnerty, Celeste C. Gamelli, Richard L. Gibran, Nicole S. Klein, Matthew B. Arnoldo, Brett D. Tompkins, Ronald G. Herndon, David N. CA Inflammation Host Response Injury TI Morbidity and Survival Probability in Burn Patients in Modern Burn Care SO CRITICAL CARE MEDICINE LA English DT Article DE burns; cutoff; morbidity; outcomes; survival ID MULTIPLE ORGAN FAILURE; RISK-FACTORS; BAUX SCORE; INJURY; MORTALITY; DEATH; ASSOCIATION; MULTICENTER; PREDICTION; COHORT AB Objective: Characterizing burn sizes that are associated with an increased risk of mortality and morbidity is critical because it would allow identifying patients who might derive the greatest benefit from individualized, experimental, or innovative therapies. Although scores have been established to predict mortality, few data addressing other outcomes exist. The objective of this study was to determine burn sizes that are associated with increased mortality and morbidity after burn. Design and Patients: Burn patients were prospectively enrolled as part of the multicenter prospective cohort study, Inflammation and the Host Response to Injury Glue Grant, with the following inclusion criteria: 0-99 years old, admission within 96 hours after injury, and more than 20% total body surface area burns requiring at least one surgical intervention. Setting: Six major burn centers in North America. Measurements and Main Results: Burn size cutoff values were determined for mortality, burn wound infection (at least two infections), sepsis (as defined by American Burn Association sepsis criteria), pneumonia, acute respiratory distress syndrome, and multiple organ failure (Denver 2 score > 3) for both children (< 16 yr) and adults (16-65 yr). Five hundred seventy-three patients were enrolled, of which 226 patients were children. Twenty-three patients were older than 65 years and were excluded from the cutoff analysis. In children, the cutoff burn size for mortality, sepsis, infection, and multiple organ failure was approximately 60% total body surface area burned. In adults, the cutoff for these outcomes was lower, at approximately 40% total body surface area burned. Conclusions: In the modern burn care setting, adults with over 40% total body surface area burned and children with over 60% total body surface area burned are at high risk for morbidity and mortality, even in highly specialized centers. C1 [Jeschke, Marc G.; Nathens, Avery B.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Surg, Ross Tilley Burn Ctr,Div Plast Surg, Toronto, ON, Canada. [Pinto, Ruxandra] Sunnybrook Hlth Sci Ctr, Programme Trauma Emergency & Crit Care, Toronto, ON M4N 3M5, Canada. [Pinto, Ruxandra] Sunnybrook Hlth Sci Ctr, Dept Crit Care Med, Toronto, ON M4N 3M5, Canada. [Kraft, Robert; Finnerty, Celeste C.; Herndon, David N.] Shriners Hosp Children, Galveston, TX 77550 USA. [Kraft, Robert; Finnerty, Celeste C.; Herndon, David N.] Univ Texas Med Branch, Dept Surg, Galveston, TX 77555 USA. [Finnerty, Celeste C.] Univ Texas Med Branch, Sealy Ctr Mol Med, Galveston, TX 77555 USA. [Finnerty, Celeste C.] Univ Texas Med Branch, Inst Translat Sci, Galveston, TX 77555 USA. [Gamelli, Richard L.] Loyola Univ, Stritch Sch Med, Dept Surg, Maywood, IL 60153 USA. [Gibran, Nicole S.; Klein, Matthew B.] Univ Washington, Sch Med, Dept Surg, Harborview Med Ctr, Seattle, WA 98195 USA. [Arnoldo, Brett D.] Univ Texas SW Med Ctr Dallas, Dept Surg, Dallas, TX 75390 USA. [Tompkins, Ronald G.] Massachusetts Gen Hosp, Dept Surg, Shriners Hosp Children, Boston, MA 02114 USA. [Tompkins, Ronald G.] Harvard Univ, Sch Med, Boston, MA USA. RP Jeschke, MG (reprint author), Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Surg, Ross Tilley Burn Ctr,Div Plast Surg, Toronto, ON, Canada. EM marc.jeschke@sunnybrook.ca FU Institute for Translational Science at the University of Texas Medical Branch; Clinical and Translational Science Award from the National Center for Advancing Translational Science, National Institutes of Health [UL1TR000071]; National Institute of General Medical Sciences [R01 GM087285, P50 GM060338, R01 GM056687, T32 GM0008256, U54 GM62119]; Canadian Institutes of Health Research [123336]; Ganda Foundation for Innovation Leader's Opportunity Fund [25407]; National Institute of General Medical Sciences at the Massachusetts General Hospital, Boston, MA [U54 GM62119]; Shriners Hospitals for Children at the University of Texas Medical Branch, Galveston, TX [71008, 84080]; National Institutes of Health (NIH); NIH [UL1TR000071, R01 GM087285, P50 GM060338, R01 GM056687, U54 GM062119, T32 GM008256]; Institute for Translational Science at the University of Texas Medical Branch (NIH funds) [KL2RR029875, UL1RR029876]; Shriners Hospitals for Children [71008, 84080]; CFI Leader's Opportunity Fund [25407]; National Center for Advancing Translational Science, NIH [UL1TR000071] FX Supported, in part, by the Institute for Translational Science at the University of Texas Medical Branch and the Clinical and Translational Science Award (UL1TR000071) from the National Center for Advancing Translational Science, National Institutes of Health.; Dr. Jeschke was supported by the National Institute of General Medical Sciences (R01 GM087285), Canadian Institutes of Health Research (#123336), and Ganda Foundation for Innovation Leader's Opportunity Fund (Project #25407). Dr. Tompkins received Large-Scale Collaborative Research Grant from the National Institute of General Medical Sciences (U54 GM62119) at the Massachusetts General Hospital, Boston, MA. Dr. Herndon received research grants from the National Institute of General Medical Sciences (P50 GM060338, R01 GM056687, and T32 GM0008256) and Shriners Hospitals for Children (71008, 84080) at the University of Texas Medical Branch, Galveston, TX. Dr. Finnerty is an Institute for Translational Sciences Career Development Scholar supported, in part, by KL2RR029875 and UL1RR029876. The authors received support for article research from the National Institutes of Health (NIH) and received grant support from the NIH (U54 GM062119, P50 GM060338, R01 GM056687, T32 GM008256, R01 GM087285, UL1TR000071), Institute for Translational Science at the University of Texas Medical Branch (NIH funds; KL2RR029875, UL1RR029876), Shriners Hospitals for Children (71008, 84080), Canadian Institutes of Health Research (123336), and CFI Leader's Opportunity Fund (Project #25407). This study was supported by a Large-Scale Collaborative Research Grant from the National Institute of General Medical Sciences (U54 GM62119) awarded to Ronald G. Tompkins at the Massachusetts General Hospital, Boston, MA and by research grants awarded to David N. Herndon at the University of Texas Medical Branch, Galveston, TX by the National Institute of General Medical Sciences (P50 GM060338, R01 GM056687, T32 GM0008256) and Shriners Hospitals for Children (71008, 84080) as well as to Marc G. Jeschke by the National Institute of General Medical Sciences (R01 GM087285), Canadian Institutes of Health Research (#123336), and CFI Leader's Opportunity Fund (Project #25407). CCF is an Institute for Translational Sciences Career Development Scholar supported, in part, by KL2RR029875 and UL1RR029876. This study was conducted with the support of the Institute for Translational Science at the University of Texas Medical Branch, supported in part by a Clinical and Translational Science Award (UL1TR000071) from the. National Center for Advancing Translational Science, NIH. NR 22 TC 15 Z9 16 U1 2 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2015 VL 43 IS 4 BP 808 EP 815 DI 10.1097/CCM.0000000000000790 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA CD3TI UT WOS:000351004100018 PM 25559438 ER PT J AU Elias, KM Moromizato, T Gibbons, FK Christopher, KB AF Elias, Kevin M. Moromizato, Takuhiro Gibbons, Fiona K. Christopher, Kenneth B. TI Derivation and Validation of the Acute Organ Failure Score to Predict Outcome in Critically Ill Patients: A Cohort Study SO CRITICAL CARE MEDICINE LA English DT Article DE acute organ failure; intensive care; mortality prediction ID CRITICAL-CARE INITIATION; NEIGHBORHOOD POVERTY RATE; BLOOD-STREAM INFECTIONS; HOSPITAL MORTALITY; PROGNOSTIC MODEL; CRITICAL ILLNESS; RISK PREDICTION; LIVER-DISEASE; APACHE-II; ASSOCIATION AB Objectives: Prediction models for ICU mortality rely heavily on physiologic variables that may not be available in large retrospective studies. An alternative approach when physiologic variables are absent stratifies mortality risk by acute organ failure classification. Design: Retrospective cohort study. Setting: Two large teaching hospitals in Boston, MA. Subjects: Ninety-two thousand eight hundred eighty-six patients aged 18 years old or older admitted between November 3, 1997, and February 25, 2011, who received critical care. Interventions: None. Measurements and Main Results: The derivation cohort consisted of 35,566 patients from Brigham and Women's Hospital, and the validation cohort comprised 57,320 patients from Massachusetts General Hospital. Acute organ failure was determined for each patient based on International Classification of Diseases, 9th Revision, Clinical Modification code combinations. The main outcome measure was 30-day mortality. A clinical prediction model was created based on a logistic regression model describing the risk of 30-day mortality as a function of age, medical versus surgical patient type, Deyo-Charlson index, sepsis, and type acute organ failure (respiratory, renal, hepatic, hematologic, metabolic, and neurologic) after ICU admission. We computed goodness-of fit statistics and c-statistics as measures of model calibration and 30-day mortality discrimination, respectively. Thirty-day mortality occurred in 5,228 of 35,566 patients (14.7%) assigned to the derivation cohort. The clinical prediction model was predictive for 30-day mortality. The c-statistic for the clinical prediction model was 0.7447 (95% CI, 0.74-0.75) in the derivation cohort and 0.7356 (95% CI, 0.73-0.74) in the validation cohort. For both the derivation and validation cohorts, the Hosmer-Lemeshow chi-square p values indicated good model fit. In a smaller cohort of 444 patients with Acute Physiologic and Chronic Health Evaluation II scores determined, differences in model discrimination of 30-day mortality between the clinical prediction model and Acute Physiologic and Chronic Health Evaluation II were not significant (chi-square = 0.76; p = 0.38). Conclusions: An acute organ failure-based clinical prediction model shows good calibration and discrimination for 30-day mortality in the critically ill. The clinical prediction model compares favorably to Acute Physiologic and Chronic Health Evaluation II score in the prediction of 30-day mortality in the critically ill. This score may be useful for severity of illness risk adjustment in observational studies where physiologic data are unavailable. C1 [Elias, Kevin M.] Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Moromizato, Takuhiro] Okinawa Hokubu Prefectural Hosp, Dept Med, Okinawa, Japan. [Gibbons, Fiona K.] Massachusetts Gen Hosp, Pulm & Crit Care Div, Boston, MA 02114 USA. [Christopher, Kenneth B.] Brigham & Womens Hosp, Div Renal, Nathan E Hellman Mem Lab, Boston, MA 02115 USA. RP Christopher, KB (reprint author), Brigham & Womens Hosp, Div Renal, Nathan E Hellman Mem Lab, Boston, MA 02115 USA. EM kbchristopher@partners.org OI Elias, Kevin/0000-0003-1502-5553 FU White Foundation FX Dr. Elias consulted for Firefly Bioworks; is employed by Brigham and Women's Hospital; and received support for travel from Tracon Pharmaceuticals. His institution received grant support from the White Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest. NR 48 TC 11 Z9 11 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2015 VL 43 IS 4 BP 856 EP 864 DI 10.1097/CCM.0000000000000858 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA CD3TI UT WOS:000351004100024 PM 25746746 ER PT J AU Hess, DR AF Hess, Dean R. TI The Evidence Is In: Noninvasive Ventilation Saves Lives SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE mechanical ventilation; noninvasive ventilation; outcomes ID ACUTE RESPIRATORY-FAILURE C1 [Hess, Dean R.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [Hess, Dean R.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. RP Hess, DR (reprint author), Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. FU NHLBI NIH HHS [1R01HL113933-01A1, P01 HL108801, 5P01HL108801-03, R01 HL113933] NR 13 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2015 VL 43 IS 4 BP 927 EP 928 DI 10.1097/CCM.0000000000000845 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA CD3TI UT WOS:000351004100043 PM 25768364 ER PT J AU Brautbar, A Leary, E Rasmussen, K Wilson, DP Steiner, RD Virani, S AF Brautbar, Ariel Leary, Emili Rasmussen, Kristen Wilson, Don P. Steiner, Robert D. Virani, Salim TI Genetics of Familial Hypercholesterolemia SO CURRENT ATHEROSCLEROSIS REPORTS LA English DT Article DE Familial hypercholesterolemia (FH); Low-density lipoprotein receptor (LDLR); Apolipoprotein B (APOB); Familial defective apolipoprotein B-100 (FDB); Proprotein convertase subtilisin/kexin type 9 (PCSK9); Autosomal recessive hypercholesterolemia (ARH); LDL receptor adapter protein 1 (LDLRAP1); Genetic counseling (GC); Cascade testing; Penetrance; Cerebrotendinous xanthomatosis (CTX); Sitosterolemia; Cholesterol ester storage disease (CESD) ID AUTOSOMAL-DOMINANT HYPERCHOLESTEROLEMIA; LYSOSOMAL ACID LIPASE; ESTER STORAGE DISEASE; CORONARY-HEART-DISEASE; LDL-RECEPTOR GENE; DEFECTIVE APOLIPOPROTEIN B-100; APOE P.LEU167DEL MUTATION; CEREBROTENDINOUS-XANTHOMATOSIS; RECESSIVE HYPERCHOLESTEROLEMIA; MOLECULAR-GENETICS AB Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein (LDL) cholesterol and premature cardiovascular disease, with a prevalence of approximately 1 in 200-500 for heterozygotes in North America and Europe. Monogenic FH is largely attributed to mutations in the LDLR, APOB, and PCSK9 genes. Differential diagnosis is critical to distinguish FH from conditions with phenotypically similar presentations to ensure appropriate therapeutic management and genetic counseling. Accurate diagnosis requires careful phenotyping based on clinical and biochemical presentation, validated by genetic testing. Recent investigations to discover additional genetic loci associated with extreme hypercholesterolemia using known FH families and population studies have met with limited success. Here, we provide a brief overview of the genetic determinants, differential diagnosis, genetic testing, and counseling of FH genetics. C1 [Brautbar, Ariel] Cook Childrens Med Ctr, Div Genet, Ft Worth, TX 76104 USA. [Brautbar, Ariel] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Brautbar, Ariel] Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI USA. [Leary, Emili] Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA. [Leary, Emili] Marshfield Clin Fdn Med Res & Educ, Clin Pharm Serv, Marshfield, WI USA. [Rasmussen, Kristen] Marshfield Clin Fdn Med Res & Educ, Ctr Human Genet, Marshfield, WI USA. [Wilson, Don P.] Cook Childrens Med Ctr, Div Pediat Endocrinol & Diabet, Ft Worth, TX USA. [Steiner, Robert D.] Marshfield Clin Res Fdn, Marshfield, WI USA. [Steiner, Robert D.] Univ Wisconsin, Dept Pediat, Madison, WI USA. [Virani, Salim] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Virani, Salim] Baylor Coll Med, Dept Med, Sect Cardiovasc Res, Houston, TX 77030 USA. RP Brautbar, A (reprint author), Cook Childrens Med Ctr, Div Genet, Ft Worth, TX 76104 USA. EM ariel.brautbar@cookchildrens.org; ejwatts@wisc.edu; Rasmussen.kristen@marshfieldclinic.org; don.wilson@cookchildrens.org; steiner.robert@mcrf.mfldclin.edu; virani@bcm.edu OI Virani, Salim/0000-0001-9541-6954 NR 125 TC 10 Z9 10 U1 2 U2 15 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1523-3804 EI 1534-6242 J9 CURR ATHEROSCLER REP JI Curr. Atheroscleros. Rep. PD APR PY 2015 VL 17 IS 4 AR 20 DI 10.1007/s11883-015-0491-z PG 17 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CD2EM UT WOS:000350887100001 PM 25712136 ER PT J AU Russell, SJ AF Russell, Steven J. TI Progress of artificial pancreas devices towards clinical use: the first outpatient studies SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Review DE artificial pancreas; bionic pancreas; continuous glucose monitoring; glucagon insulin; sensor-augmented pump ID LOOP INSULIN DELIVERY; DEPENDENT DIABETES-MELLITUS; RANDOMIZED CROSSOVER TRIAL; SEVERE HYPOGLYCEMIA; INTENSIVE TREATMENT; GLUCOSE CONTROL; GLYCEMIC CONTROL; HOME-USE; TYPE-1; REGISTRY AB Purpose of review This article describes recent progress in the automated control of glycemia in type 1 diabetes with artificial pancreas devices that combine continuous glucose monitoring with automated decision-making and insulin delivery. Recent findings After a gestation period of closely supervised feasibility studies in research centers, the last 2 years have seen publication of studies testing these devices in outpatient environments, and many more such studies are ongoing. The most basic form of automation, suspension of insulin delivery for actual or predicted hypoglycemia, has been shown to be effective and well tolerated, and a first-generation device has actually reached the market. Artificial pancreas devices that actively dose insulin fall into two categories, those that dose insulin alone and those that also use glucagon to prevent and treat hypoglycemia (bihormonal artificial pancreas). Initial outpatient clinical trials have shown that both strategies can improve glycemic management in comparison with patient-controlled insulin pump therapy, but only the bihormonal strategy has been tested without restrictions on exercise. Summary Artificial pancreas technology has the potential to reduce acute and chronic complications of diabetes and mitigate the burden of diabetes self-management. Successful outpatient studies bring these technologies one step closer to availability for patients. C1 Massachusetts Gen Hosp, Diabet Res Ctr, Boston, MA 02114 USA. RP Russell, SJ (reprint author), Massachusetts Gen Hosp, Diabet Res Ctr, 50 Staniford St,Suite 301, Boston, MA 02114 USA. EM sjrussell@mgh.harvard.edu FU National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease; Helmsley Charitable Trust; American Diabetes Association; Massachusetts General Hospital Diabetes Research Center, Boston, Massachusetts, USA FX This work was supported by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease, Helmsley Charitable Trust, the American Diabetes Association, and Massachusetts General Hospital Diabetes Research Center, Boston, Massachusetts, USA. NR 39 TC 7 Z9 7 U1 2 U2 24 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1752-296X EI 1752-2978 J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD APR PY 2015 VL 22 IS 2 BP 106 EP 111 DI 10.1097/MED.0000000000000142 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CD0LQ UT WOS:000350764800006 PM 25692927 ER PT J AU Schmitt, NC Duvvuri, U AF Schmitt, Nicole C. Duvvuri, Umamaheswar TI Transoral robotic surgery for oropharyngeal squamous cell carcinoma SO CURRENT OPINION IN OTOLARYNGOLOGY & HEAD AND NECK SURGERY LA English DT Review DE oropharyngeal squamous cell carcinoma; transoral robotic surgery; unknown primary carcinoma ID QUALITY-OF-LIFE; UNKNOWN PRIMARY; FUNCTIONAL OUTCOMES; HUMAN-PAPILLOMAVIRUS; PRIMARY HEAD; CANCER; NECK; TORS; EXPERIENCE; THERAPY AB Purpose of review This article reviews recent information on outcomes, indications, techniques, and cost of transoral robotic surgery (TORS) for oropharyngeal squamous cell carcinoma (OPSCC). New information on comparisons between TORS, conventional surgery techniques, and chemoradiation is also highlighted. Recent findings Consistent with prior reports, recent studies show excellent oncologic and functional outcomes with TORS for OPSCC. As surgeon experience with this relatively new technique has increased, outcomes continue to improve and complications are rare. TORS may also have a role in management of carcinoma of unknown primary site. Compared with other treatment modalities, TORS for OPSCC may result in similar oncologic outcomes, improved functional outcomes, and decreased cost. Summary TORS for OPSCC results in excellent functional and oncologic outcomes. Randomized clinical trials are needed to compare TORS with adjuvant therapy to definitive chemoradiation and will determine whether adjuvant therapy and associated morbidity can be decreased without compromising survival. C1 [Duvvuri, Umamaheswar] Univ Pittsburgh, Med Ctr, Inst Eye & Ear, Dept Otolaryngol, Pittsburgh, PA 15213 USA. VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. RP Duvvuri, U (reprint author), Univ Pittsburgh, Med Ctr, Inst Eye & Ear, Dept Otolaryngol, 200 Lothrop St,Suite 519, Pittsburgh, PA 15213 USA. EM duvvuriu@upmc.edu FU Department of Veterans Affairs, BLSRD; PNC Foundation FX This work was supported in part by funds from the Department of Veterans Affairs, BLSR&D, and the PNC Foundation (U.D.) The views represented in this manuscript do not reflect the views of the United States Government. NR 31 TC 2 Z9 2 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1068-9508 EI 1531-6998 J9 CURR OPIN OTOLARYNGO JI Curr. Opin. Otolaryngol. Head Neck Surg. PD APR PY 2015 VL 23 IS 2 BP 127 EP 131 DI 10.1097/MOO.0000000000000136 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA CD3VL UT WOS:000351010900008 PM 25692632 ER PT J AU Reynolds, DB Walker, RJ Campbell, JA Egede, LE AF Reynolds, D. Brice Walker, Rebekah J. Campbell, Jennifer A. Egede, Leonard E. TI Differential Effect of Race, Education, Gender, and Language Discrimination on Glycemic Control in Adults with Type 2 Diabetes SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID OLDER AFRICAN-AMERICAN; SOCIAL DETERMINANTS; HEALTH; MELLITUS; OUTCOMES; DISPARITIES; RACISM; WOMEN; CARE AB Background: Discrimination has been linked to negative health outcomes, but little research has investigated different types of discrimination to determine if some have a greater impact on outcomes. We examined the differential effect of discrimination based on race, level of education, gender, and language on glycemic control in adults with type 2 diabetes. Patients and Methods: Six hundred two patients with type 2 diabetes from two adult primary care clinics in the southeastern United States completed validated questionnaires. Questions included perceived discrimination because of race/ethnicity, level of education, sex/gender, or language. A multiple linear regression model assessed the differential effect of each type of perceived discrimination on glycemic control while adjusting for relevant covariates, including race, site, gender, marital status, duration of diabetes, number of years in school, number of hours worked per week, income, and health status. Results: The mean age was 61.5 years, and the mean duration of diabetes was 12.3 years. Of the sample, 61.6% were men, and 64.9% were non-Hispanic black. In adjusted models, education discrimination remained significantly associated with glycemic control (beta=0.47; 95% confidence interval, 0.03, 0.92). Race, gender and language discrimination were not significantly associated with poor glycemic control in either unadjusted or adjusted analyses. Conclusions: Discrimination based on education was found to be significantly associated with poor glycemic control. The findings suggest that education discrimination may be an important social determinant to consider when providing care to patients with type 2 diabetes and should be assessed separate from other types of discrimination, such as that based on race. C1 [Reynolds, D. Brice; Walker, Rebekah J.; Campbell, Jennifer A.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Dept Med, Charleston, SC 29425 USA. [Walker, Rebekah J.; Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Hlth Equ & Rural Outreach Innovat Ctr, Charleston Vet Affairs Hlth Serv Res & Dev Ctr In, Charleston, SC USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu FU National Institute of Diabetes and Digestive and Kidney Disease [K24DK093699-01] FX This study was supported by grant K24DK093699-01 from the National Institute of Diabetes and Digestive and Kidney Disease (Principal Investigator L.E.E.). NR 26 TC 3 Z9 3 U1 2 U2 12 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 EI 1557-8593 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD APR 1 PY 2015 VL 17 IS 4 BP 243 EP 247 DI 10.1089/dia.2014.0285 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CD4MO UT WOS:000351057300004 PM 25549154 ER PT J AU Krall, J Gabbay, R Zickmund, S Hamm, ME Williams, KR Siminerio, L AF Krall, Jodi Gabbay, Robert Zickmund, Susan Hamm, Megan E. Williams, Kelly R. Siminerio, Linda TI Current Perspectives on Psychological Insulin Resistance: Primary Care Provider and Patient Views SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID NATIONAL DIABETES ATTITUDES; RANDOMIZED CONTROLLED-TRIAL; SELF-MANAGEMENT SUPPORT; NEEDS DAWN; CLINICAL INERTIA; BARRIERS; THERAPY; WISHES; RECOMMENDATIONS; ADHERENCE AB Background: Psychological insulin resistance (PIR) refers to reluctance of providers to prescribe and patients to take insulin. Processes and tools have been developed to address PIR. The purpose of this qualitative study was to examine current understanding and opinions of insulin therapy of primary care providers (PCPs) and patients with type 2 diabetes (both naive to insulin and insulin users). Subjects and Methods: Providers (n=23 PCPs) and patients (n=96) participated in 1:1 interviews and 12 racially/ethnically diverse focus groups, respectively, conducted by trained qualitative researchers using pilot-tested scripts. Participants examined insulin devices and needles while specific questions were asked about insulin therapy. Recorded sessions were transcribed and analyzed. Results: Salient themes related to injection resistance, patient adherence, health system barriers, and education emerged during the sessions. Provider knowledge about insulin injection devices and approaches varied and was often limited, particularly regarding needle sizes, which influenced prescribing practices and patient education. Other barriers included limited time and personnel. However, PCPs placed priority on continuing education on devices, needles, insulin adjustment, educational approaches, and cost. Patient focus groups revealed a strong desire for knowledge on injection logistics, particularly by insulin users who felt that they had received inadequate education. Most patients had limited experience with tools like shorter needles but would consider injecting if presented. Those who had self-injection experience were more willing to accept insulin. Cost concerns and need for information were frequently reported. Conclusions: Findings reveal that programs and tools designed to address problems associated with PIR have yet to be fully realized. C1 [Krall, Jodi] Univ Pittsburgh, Inst Diabet, Pittsburgh, PA 15203 USA. [Gabbay, Robert] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Zickmund, Susan; Hamm, Megan E.; Williams, Kelly R.] Univ Pittsburgh, Dept Med, Qualitat Serv, Ctr Res Hlth Care Data Ctr, Pittsburgh, PA 15203 USA. [Zickmund, Susan; Hamm, Megan E.; Williams, Kelly R.] Univ Pittsburgh, Dept Med, Evaluat Serv, Ctr Res Hlth Care Data Ctr, Pittsburgh, PA 15203 USA. [Zickmund, Susan; Hamm, Megan E.; Williams, Kelly R.] Univ Pittsburgh, Dept Med, Stakeholder Engagement Serv, Ctr Res Hlth Care Data Ctr, Pittsburgh, PA 15203 USA. [Siminerio, Linda] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15203 USA. RP Siminerio, L (reprint author), Univ Pittsburgh, Dept Med, 2 Hot Met St,Suite E290, Pittsburgh, PA 15203 USA. EM simineriol@upmc.edu FU Becton, Dickinson and Company FX This article represents independent research supported by a grant from Becton, Dickinson and Company. We thank the providers and patients who participated in this study and Justin Kanter and the diabetes educators and coordinators who assisted with recruitment and facilitation of the study. NR 31 TC 3 Z9 3 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 EI 1557-8593 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD APR 1 PY 2015 VL 17 IS 4 BP 268 EP 274 DI 10.1089/dia.2014.0268 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CD4MO UT WOS:000351057300007 PM 25551737 ER PT J AU Barnard, KD Hood, KK Weissberg-Benchell, J Aldred, C Oliver, N Laffel, L AF Barnard, Katharine D. Hood, Korey K. Weissberg-Benchell, Jill Aldred, Chris Oliver, Nick Laffel, Lori TI Psychosocial Assessment of Artificial Pancreas (AP): Commentary and Review of Existing Measures and Their Applicability in AP Research SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Review ID QUALITY-OF-LIFE; RANDOMIZED CLINICAL-TRIAL; OVERNIGHT GLUCOSE CONTROL; LOOP INSULIN DELIVERY; GLYCEMIC CONTROL; DIABETES CAMP; CHILDREN; ADULTS; PARTICIPANTS; METAANALYSIS AB Aim: This study aimed to systematically review the evidence base for the use of existing psychological and psychosocial measures suitable for use in artificial pancreas (AP) research. Materials and Methods: This systematic review of published literature, gray literature, previous systematic reviews, and qualitative and economic studies was conducted using terms and abbreviations synonymous with diabetes, AP, and quality of life (QoL). Results: Two hundred ninety-two abstracts were identified that reported psychosocial assessment of diabetes-related technologies. Of these, nine met the inclusion criteria and were included. Only four of 103 ongoing trials evaluated psychosocial aspects as an outcome in the trial. Of these, treatment satisfaction, acceptance and use intention of AP, fear of hypoglycemia episodes, satisfaction with AP, and an unspecified QoL measure were used. Conclusions: A better understanding of the psychosocial side of AP systems and the extent to which human factors play a role in the uptake and efficient use of these systems will ultimately lead to the most benefit for people with diabetes. C1 [Barnard, Katharine D.; Aldred, Chris] Univ Southampton, Human Dev & Hlth Acad Unit, Fac Med, Southampton SO16 6YD, Hants, England. [Hood, Korey K.] Stanford Univ, Pediat Psychiat & Behav Sci, Sch Med, Stanford, CA 94305 USA. [Weissberg-Benchell, Jill] Northwestern Univ, Feinberg Sch Med, Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. [Oliver, Nick] Univ London Imperial Coll Sci Technol & Med, London, England. [Laffel, Lori] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Barnard, KD (reprint author), Univ Southampton, Human Dev & Hlth, Fac Med, Southampton Gen Hosp, IDS Bldg,Tremona Rd, Southampton SO16 6YD, Hants, England. EM k.barnard@soton.ac.uk RI Oliver, Nick/G-9109-2016 OI Oliver, Nick/0000-0003-3525-3633 NR 37 TC 6 Z9 6 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 EI 1557-8593 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD APR 1 PY 2015 VL 17 IS 4 BP 295 EP 300 DI 10.1089/dia.2014.0305 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CD4MO UT WOS:000351057300011 PM 25549042 ER PT J AU Ruderfer, DM Lim, ET Genovese, G Moran, JL Hultman, CM Sullivan, PF McCarroll, SA Holmans, P Sklar, P Purcell, SM AF Ruderfer, Douglas M. Lim, Elaine T. Genovese, Giulio Moran, Jennifer L. Hultman, Christina M. Sullivan, Patrick F. McCarroll, Steven A. Holmans, Peter Sklar, Pamela Purcell, Shaun M. TI No evidence for rare recessive and compound heterozygous disruptive variants in schizophrenia SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; LOCI; HOMOZYGOSITY; RUNS; MUTATIONS; DISORDER; GENES; RISK AB Recessive inheritance of gene disrupting alleles, either through homozygosity at a specific site or compound heterozygosity, have been demonstrated to underlie many Mendelian diseases and some complex psychiatric disorders. On the basis of exome sequencing data, an increased burden of complete knockout (homozygous or compound heterozygous) variants has been identified in autism. In addition, using single-nucleotide polymorphism microarray data, an increased rate of homozygosity by descent, or autozygosity, has been linked to the risk of schizophrenia (SCZ). Here, in a large Swedish case-control SCZ sample (11244 individuals, 5079 of whom have exome sequence data available), we survey the contribution of both autozygosity and complete knockouts to disease risk. We do not find evidence for association with SCZ, either genome wide or at specific loci. However, we note the possible impact of sample size and population genetic factors on the power to detect and quantify any burden that may exist. C1 [Ruderfer, Douglas M.; Sklar, Pamela; Purcell, Shaun M.] Icahn Sch Med Mt Sinai, Dept Psychiat, Div Psychiat Genom, New York, NY 10029 USA. [Ruderfer, Douglas M.; Purcell, Shaun M.] Icahn Sch Med Mt Sinai, Inst Genom & Multiscale Biol, New York, NY 10029 USA. [Ruderfer, Douglas M.; Genovese, Giulio; Moran, Jennifer L.; McCarroll, Steven A.; Purcell, Shaun M.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Lim, Elaine T.; Purcell, Shaun M.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Hultman, Christina M.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [McCarroll, Steven A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Holmans, Peter] Cardiff Univ, Med Res Council Ctr Neuropsychiat Genet & Genom, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales. [Sklar, Pamela] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. RP Purcell, SM (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM shaun.purcell@mssm.edu RI Holmans, Peter/F-4518-2015; Ruderfer, Douglas/M-5795-2016; OI Holmans, Peter/0000-0003-0870-9412; Ruderfer, Douglas/0000-0002-2365-386X; Moran, Jennifer/0000-0002-5664-4716 FU Medical Research Council [MR/L010305/1]; NIMH NIH HHS [R01 MH095034] NR 20 TC 3 Z9 3 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 EI 1476-5438 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD APR PY 2015 VL 23 IS 4 BP 555 EP 557 DI 10.1038/ejhg.2014.228 PG 3 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CD2BI UT WOS:000350878200023 PM 25370044 ER PT J AU Graff, JN Gordon, MJ Beer, TM AF Graff, Julie N. Gordon, Max J. Beer, Tomasz M. TI Safety and effectiveness of enzalutamide in men with metastatic, castration-resistant prostate cancer SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE androgen receptor; castration-resistant prostate cancer; enzalutamide; MDV3100 ID ANDROGEN-RECEPTOR; INCREASED SURVIVAL; CHEMOTHERAPY; MITOXANTRONE; ABIRATERONE; PREDNISONE; DOCETAXEL; ANTIANDROGEN; VARIANTS; TRIAL AB Introduction: Enzalutamide (MDV3100) is a second-generation androgen receptor antagonist that improves survival in metastatic, castration-resistant prostate cancer (mCRPC). Alternatives include chemotherapy, radiation, immunotherapy and abiraterone. Areas covered: The Phase I/II study showed early evidence of efficacy and determined that fatigue is the dose-limiting toxicity. Two randomized, placebo-controlled trials have demonstrated superiority of enzalutamide 160 mg by mouth daily over placebo in terms of overall survival, radiographic progression-free survival as well as a broad range of secondary and exploratory end points in men who had received previous chemotherapy (AFFIRM) and in those who were chemotherapy naive (PREVAIL). Common side effects include fatigue, arthralgias and constipation. A post hoc analysis from AFFIRM found that enzalutamide is safe and effective in men aged >= 75 years. The Phase I/II studies as well as AFFIRM and PREVAIL are described in this review. Expert opinion: Enzalutamide extends overall and progression-free survival and is associated with robust response rates and quality of life benefits in men with mCRPC. Enzalutamide has not been proven to be effective in biochemically relapsed disease or in castration-sensitive prostate cancer. It should not be used in men at high risk for seizure, and patients should be counseled about the increased risk of falls. C1 [Graff, Julie N.] OHSU Knight Canc Inst, Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. [Gordon, Max J.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Beer, Tomasz M.] OHSU Knight Canc Inst, Portland, OR 97239 USA. RP Graff, JN (reprint author), OHSU Knight Canc Inst, Portland Vet Affairs Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM graffj@ohsu.edu FU Astellas Pharma Global; Medivation; Janssen Research Development; Janssen Japan; Research to Practice FX TM Beer has received research funding from Astellas Pharma Global; Medivation; Janssen Research & Development. Acts as paid consultant for Astellas Pharma Global; Janssen Japan; and received payment from Research to Practice for participation in a Certified Nursing Education program which was supported in part by Astellas Pharma Global and Medivation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 25 TC 1 Z9 1 U1 0 U2 5 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 APR PY 2015 VL 16 IS 5 BP 749 EP 754 DI 10.1517/14656566.2015.1016911 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CD3IA UT WOS:000350970500012 PM 25687355 ER PT J AU Berkowitz, SA Traore, CY Singer, DE Atlas, SJ AF Berkowitz, Seth A. Traore, Carine Y. Singer, Daniel E. Atlas, Steven J. TI Evaluating Area-Based Socioeconomic Status Indicators for Monitoring Disparities within Health Care Systems: Results from a Primary Care Network SO HEALTH SERVICES RESEARCH LA English DT Article DE Socioeconomic status; delivery of health care; quality of health care; health care disparities; geographic mapping ID TYPE-2 DIABETES-MELLITUS; GEOCODING PROJECT; NEIGHBORHOOD DEPRIVATION; GEOGRAPHIC AREAS; LIFE-STYLE; INEQUALITIES; US; MORTALITY; TRENDS; LEVEL AB ObjectiveTo determine which area-based socioeconomic status (SES) indicator is best suited to monitor health care disparities from a delivery system perspective. Data Sources/Study Setting142,659 adults seen in a primary care network from January 1, 2009 to December 31, 2011. Study DesignCross-sectional, comparing associations between area-based SES indicators and patient outcomes. Data CollectionAddress data were geocoded to construct area-based SES indicators at block group (BG), census tract (CT), and ZIP code (ZIP) levels. Data on health outcomes were abstracted from electronic records. Relative indices of inequality (RIIs) were calculated to quantify disparities detected by area-based SES indicators and compared to RIIs from self-reported educational attainment. Principal FindingsZIP indicators had less missing data than BG or CT indicators (p<.0001). Area-based SES indicators were strongly associated with self-report educational attainment (p<.0001). ZIP, BG, and CT indicators all detected expected SES gradients in health outcomes similarly. Single-item, cut point defined indicators performed as well as multidimensional indices and quantile indicators. ConclusionsArea-based SES indicators detected health outcome differences well and may be useful for monitoring disparities within health care systems. Our preferred indicator was ZIP-level median household income or percent poverty, using cut points. C1 [Traore, Carine Y.; Singer, Daniel E.; Atlas, Steven J.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Singer, Daniel E.; Atlas, Steven J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Berkowitz, SA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Internal Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM saberkowitz@partners.org OI Berkowitz, Seth/0000-0003-1030-4297 FU Institutional National Research Service Award [T32HP10251]; Ryoichi Sasakawa Fellowship Fund; Division of General Internal Medicine at Massachusetts General Hospital; Johnson Johnson FX Joint Acknowledgment/Disclosure Statement: Seth A. Berkowitz was supported by an Institutional National Research Service Award #T32HP10251, the Ryoichi Sasakawa Fellowship Fund, and by the Division of General Internal Medicine at Massachusetts General Hospital. Dr. Singer reports research grant support from Johnson & Johnson and consultant/advisory board support from Bayer HealthCare, Boehringer Ingelheim, Bristol-Myers Squibb, Johnson & Johnson, Pfizer, and Daiichi Sankyo. All other authors declare that they have no conflict of interest. The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of data; or preparation, review, or approval of the manuscript. The authors thank Charlotte Ward for her assistance in preparing CAHPS score data. NR 33 TC 9 Z9 9 U1 2 U2 23 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 EI 1475-6773 J9 HEALTH SERV RES JI Health Serv. Res. PD APR PY 2015 VL 50 IS 2 BP 398 EP 417 DI 10.1111/1475-6773.12229 PG 20 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CD5ZL UT WOS:000351167600005 PM 25219917 ER PT J AU Joynt, KE Chan, DC Zheng, J Orav, EJ Jha, AK AF Joynt, Karen E. Chan, David C. Zheng, Jie Orav, E. John Jha, Ashish K. TI The Impact of Massachusetts Health Care Reform on Access, Quality, and Costs of Care for the Already-Insured SO HEALTH SERVICES RESEARCH LA English DT Article DE Insurance expansion; costs; quality; outpatient care ID MEDICAID; OUTCOMES AB ObjectiveTo assess the impact of Massachusetts Health Reform (MHR) on access, quality, and costs of outpatient care for the already-insured. Data Sources/Study SettingMedicare data from before (2006) and after (2009) MHR implementation. Study DesignWe performed a retrospective difference-in-differences analysis of quantity of outpatient visits, proportion of outpatient quality metrics met, and costs of care for Medicare patients with 1 chronic disease in 2006 versus 2009. We used the remaining states in New England as controls. Data Collection/Extraction MethodsWe used existing Medicare claims data provided by the Centers for Medicare and Medicaid Services. Principal FindingsMHR was not associated with a decrease in outpatient visits per year compared to controls (9.4 prereform to 9.6 postreform in MA vs. 9.4-9.5 in controls, p=.32). Quality of care in MA improved more than controls for hemoglobin A1c monitoring, mammography, and influenza vaccination, and similarly to controls for diabetic eye examination, colon cancer screening, and pneumococcal vaccination. Average costs for patients in Massachusetts increased from $9,389 to $10,668, versus $8,375 to $9,114 in control states (p<.001). ConclusionsMHR was not associated with worsening in access or quality of outpatient care for the already-insured, and it had modest effects on costs. This has implications for other states expanding insurance coverage under the Affordable Care Act. C1 [Chan, David C.; Orav, E. John; Jha, Ashish K.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Chan, David C.] MIT, Dept Econ, Boston, MA USA. [Chan, David C.] Beth Israel Deaconess Med Ctr, Div Gen Internal Med, Boston, MA 02215 USA. [Zheng, Jie; Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Brigham & Womens Hosp, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA. RP Joynt, KE (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM kjoynt@partners.org FU Rx Foundation in Cambridge, MA FX Joint Acknowledgment/Disclosure Statement: Funding was provided by the Rx Foundation in Cambridge, MA. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. NR 9 TC 1 Z9 1 U1 2 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 EI 1475-6773 J9 HEALTH SERV RES JI Health Serv. Res. PD APR PY 2015 VL 50 IS 2 BP 599 EP 613 DI 10.1111/1475-6773.12228 PG 15 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CD5ZL UT WOS:000351167600014 PM 25219772 ER PT J AU Helfand, B Roehl, K Cooper, P McGuire, B Fitzgerald, L Cancel-Tassin, G Cornu, JN Bauer, S Blarigan, E Chen, X Duggan, D Ostrander, E Gwo-Shu, M Zhang, ZF Chang, SC Jeong, S Fontham, E Smith, G Mohler, J Berndt, S McDonnell, S Kittles, R Rybicki, B Freedman, M Kantoff, P Pomerantz, M Breyer, J Smith, J Rebbeck, T Mercola, D Isaacs, W Wiklund, F Cussenot, O Thibodeau, S Schaid, D Cannon-Albright, L Cooney, K Chanock, S Stanford, J Chan, J Witte, J Xu, J Bensen, J Taylor, J Catalona, W AF Helfand, Brian T. Roehl, Kimberly A. Cooper, Phillip R. McGuire, Barry B. Fitzgerald, Liesel M. Cancel-Tassin, Geraldine Cornu, Jean-Nicolas Bauer, Scott Blarigan, Erin L. Van Chen, Xin Duggan, David Ostrander, Elaine A. Gwo-Shu, Mary Zhang, Zuo-Feng Chang, Shen-Chih Jeong, Somee Fontham, Elizabeth T. H. Smith, Gary Mohler, James L. Berndt, Sonja I. McDonnell, Shannon K. Kittles, Rick Rybicki, Benjamin A. Freedman, Matthew Kantoff, Philip W. Pomerantz, Mark Breyer, Joan P. Smith, Jeffrey R. Rebbeck, Timothy R. Mercola, Dan Isaacs, William B. Wiklund, Fredrick Cussenot, Olivier Thibodeau, Stephen N. Schaid, Daniel J. Cannon-Albright, Lisa Cooney, Kathleen A. Chanock, Stephen J. Stanford, Janet L. Chan, June M. Witte, John Xu, Jianfeng Bensen, Jeannette T. Taylor, Jack A. Catalona, William J. TI Associations of prostate cancer risk variants with disease aggressiveness: results of the NCI-SPORE Genetics Working Group analysis of 18,343 cases SO HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; LINKAGE SCAN; CHROMOSOME 19Q; GLEASON SCORE; PSA LEVELS; MEN; MORTALITY; POLYMORPHISM; REPLICATION AB Genetic studies have identified single nucleotide polymorphisms (SNPs) associated with the risk of prostate cancer (PC). It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score (Gleason a parts per thousand currency sign6, 7, a parts per thousand yen8) and aggressiveness (non-aggressive, intermediate, and aggressive disease). Statistical analyses were used to compare the frequency of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 (G) was significantly and inversely associated with aggressive (OR = 0.77; 95 % CI 0.69-0.87) and high-grade disease (OR = 0.77; 95 % CI 0.68-0.86) in European men. Similar associations with aggressive (OR = 0.72; 95 % CI 0.58-0.89) and high-grade disease (OR = 0.69; 95 % CI 0.54-0.87) were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels (< 4.0 ng/mL) in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness. C1 [Helfand, Brian T.] NorthShore Univ Hlth Syst, Div Urol, Dept Surg, John & Carol Walter Ctr Urol Hlth, Evanston, IL USA. [Roehl, Kimberly A.; Cooper, Phillip R.; McGuire, Barry B.; Catalona, William J.] NW Univ Feinberg Sch Med, Dept Urol, Chicago, IL USA. [Fitzgerald, Liesel M.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3004, Australia. [Cancel-Tassin, Geraldine; Cornu, Jean-Nicolas; Cussenot, Olivier] Assistance Publ Hopitaux Paris, CeRePP ICPCG Grp, Hop Tenon, F-75020 Paris, France. [Bauer, Scott; Blarigan, Erin L. Van; Chan, June M.; Witte, John] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Genome Anal Core Facil, San Francisco, CA USA. [Chen, Xin; Mercola, Dan] Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA USA. [Duggan, David] Integrated Canc Genom Div, TGen, Phoenix, AZ USA. [Ostrander, Elaine A.] Natl Human Genome Res Inst, Canc Genet Branch, Bethesda, MD USA. [Gwo-Shu, Mary] Dana Farber Canc Inst & Harvard Med Sch, Dept Med Oncol, Boston, MA USA. [Zhang, Zuo-Feng; Chang, Shen-Chih; Jeong, Somee] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA USA. [Fontham, Elizabeth T. H.] Louisiana State Univ Hlth Sci Ctr, Sch Publ Hlth, New Orleans, LA USA. [Smith, Gary; Mohler, James L.] Roswell Pk Canc Inst, Dept Urol, Buffalo, NY USA. [Berndt, Sonja I.] Natl Canc Inst, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, Bethesda, MD USA. [McDonnell, Shannon K.; Schaid, Daniel J.] Dept Hlth Sci Res, Mayo Clin, Rochester, MN USA. [Kittles, Rick] Univ Arizona, Div Urol, Dept Surg, Tucson, AZ USA. [Rybicki, Benjamin A.] Dept Publ Hlth Sci, Henry Ford Hlth Syst, Detroit, MI USA. [Freedman, Matthew; Kantoff, Philip W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Pomerantz, Mark] Dana Farber Canc Inst & Harvard Med Sch, Lank Ctr Genitourinary Oncol, Boston, MA USA. [Breyer, Joan P.; Smith, Jeffrey R.] Vanderbilt Univ Sch Med, Dept Med, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Rebbeck, Timothy R.] Univ Pennsylvania Sch Med, Dept Biostatist & Epidemiol, Ctr Clin Epidemiol & Biostatist, Philadelphia, PA USA. [Isaacs, William B.] Johns Hopkins Univ, Dept Urol, Baltimore, MD USA. [Wiklund, Fredrick] Univ UmeAyen ICPCG Grp, UmeAyen, Sweden. [Thibodeau, Stephen N.] Dept Lab Med & Pathol, Mayo Clin, Rochester, MN USA. [Cannon-Albright, Lisa] Univ Utah Sch Med, Div Genet Epidemiol, Dept Med, Salt Lake City, UT USA. [Cooney, Kathleen A.] Univ Michigan Med Sch, Dept Urol, Dept Internal Med, Ann Arbor, MI USA. [Chanock, Stephen J.] Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD USA. [Stanford, Janet L.] Div Publ Hlth Sci, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Xu, Jianfeng] NorthShore Univ Hlth Syst, Program Personalized Canc Care & Dept Surg, Evanston, IL USA. [Bensen, Jeannette T.] Univ N Carolina, Gillings Sch Global Publ Hlth Dept Epidemiol & Li, Chapel Hill, NC USA. [Taylor, Jack A.] Natl Inst Environm Hlth Sci, Epidemiol Branch & Lab Mol Carcinogenesis, Durham, NC USA. RP Catalona, W (reprint author), NW Univ Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA. EM WCatalona@nmff.org OI Cancel-Tassin, Geraldine/0000-0002-9583-6382; , dan/0000-0002-0281-9840; albright, lisa/0000-0003-2602-3668; taylor, jack/0000-0001-5303-6398; Ostrander, Elaine/0000-0001-6075-9738 FU BLRD VA [I01 BX002502]; Intramural NIH HHS [Z01 ES049032-12, Z01 ES049033-11]; NCI NIH HHS [P30 CA016042, P30 CA060553]; NIEHS NIH HHS [P30 ES010126] NR 62 TC 13 Z9 13 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 EI 1432-1203 J9 HUM GENET JI Hum. Genet. PD APR PY 2015 VL 134 IS 4 BP 439 EP 450 DI 10.1007/s00439-015-1534-9 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA CD5OB UT WOS:000351136600006 PM 25715684 ER PT J AU Kinard, BE Chuang, SK August, M Dodson, TB AF Kinard, Brian E. Chuang, Sung-Kiang August, Meredith Dodson, Thomas B. TI For Treatment of Odontogenic Keratocysts, Is Enucleation, When Compared to Decompression, a Less Complex Management Protocol? SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID TERM-FOLLOW-UP; RECURRENCE; MARSUPIALIZATION; CRYOTHERAPY; CYSTS AB Purpose: To determine whether the clinical management of odontogenic keratocysts (OKCs) is more complex in patients who undergo enucleation with or without adjuvant therapy than in patients who undergo decompression with or without residual cystectomy. Materials and Methods: The authors implemented a retrospective cohort study and enrolled a sample composed of patients presenting for the evaluation and management of OKCs. The predictor variable was treatment group, classified as decompression with or without residual cystectomy versus enucleation with or without adjuvant therapy (Carnoy solution, cryotherapy, or peripheral ostectomy). The outcome variables were measurements of complexity of management, including total number of procedures, venue of procedure (operating room vs office), type of anesthesia, hospital admissions, and total number of follow-up visits. Data analyses were performed using univariate and bivariate statistics and a multiple linear regression model. Results: The study sample was composed of 45 patients (66 OKC lesions) with a mean age of 43.3 years. Of the 66OKCs treated, 34 (51.5%) were treated with decompression with or without residual cystectomy and 32 (48.5%) were treated with enucleation with or without adjunctive therapy. Larger lesions and lesions with radiographic evidence of cortical perforation were treated more often with decompression with or without residual cystectomy. Based on the multiple linear regression model, patients who underwent enucleation with or without adjuvant therapy compared with those who underwent decompression with or without residual cystectomy had on average 1) 1.1 fewer total procedures (P < .01), 2) 0.8 fewer total office procedures (P < .01), 3) 0.6 fewer local anesthesia procedures (P < .01), and 4) 4.8 fewer postoperative visits (P < .01). There was no difference in the number of general anesthesia procedures, office sedation procedures, or hospital admissions. Conclusion: Given comparable recurrence rates, the increased complexity of managing OKCs with decompression with or without residual cystectomy might not be warranted. Enucleation with or without adjunctive therapy could be the more efficient treatment option. (C) 2015 American Association of Oral and Maxillofacial Surgeons C1 [Kinard, Brian E.] Emory Univ, Sch Med, Dept Surg, Div Oral & Maxillofacial Surg, Atlanta, GA 30322 USA. [Kinard, Brian E.] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Chuang, Sung-Kiang; August, Meredith] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Dodson, Thomas B.] Dept Oral & Maxillofacial Surg, Seattle, WA USA. [Dodson, Thomas B.] Univ Washington, Sch Dent, Hosp Affairs, Seattle, WA 98195 USA. RP Kinard, BE (reprint author), Emory Univ, Sch Med, Dept Surg, Div Oral & Maxillofacial Surg, 1365 Clifton Rd NE,Suite 2300 B, Atlanta, GA 30322 USA. EM bkinard@Emory.edu FU Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund; Center for Applied Clinical Investigation; Massachusetts General Physicians Organization FX This project was supported in part by the Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund (to B.E.K.), the Center for Applied Clinical Investigation (to S.-K.C. and T.B.D.), and the Massachusetts General Physicians Organization (to S.-K.C, M.A., and T.B.D.). NR 34 TC 3 Z9 3 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 0278-2391 EI 1531-5053 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD APR PY 2015 VL 73 IS 4 BP 641 EP 648 DI 10.1016/j.joms.2014.11.001 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CD6ZN UT WOS:000351240100013 PM 25649015 ER PT J AU Lee, SH Kaban, LB Lahey, ET AF Lee, Sang Hwa Kaban, Leonard B. Lahey, Edward T. TI Skeletal Stability of Patients Undergoing Maxillomandibular Advancement for Treatment of Obstructive Sleep Apnea SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID TERM SURGICAL STABILITY; UPPER AIRWAY; SURGERY; FIXATION; EFFICACY; ADULTS AB Purpose: To determine the long-term stability of maxillomandibular advancement (MMA) in patients with obstructive sleep apnea (OSA). Materials and Methods: This was a retrospective cohort study of patients who underwent MMA and genial tubercle advancement (GTA) for treatment of OSA. Patients were included if they 1) were older than 19 years; 2) had a confirmatory polysomnogram; 3) underwent a Le Fort I osteotomy, bilateral sagittal split osteotomies, and GTA; 4) had adequate radiographic documentation; and 5) at least 11 months of follow-up. Exclusion criteria included previous orthognathic or other maxillofacial surgery. Predictor variables were the presence of OSA treated by MMA, pre- and postoperative orthodontia or no orthodontia, length of follow-up, and magnitude of advancement. The outcome variable was the stability of MMA judged by clinical examination and cephalometric measurements. Standardized lateral cephalometric measurements were performed preoperatively (T0), immediately postoperatively (T1), and at the latest follow-up beyond 11 months (T2). Differences in cephalometric measurements were calculated between time points (T0 to T1 and T1 to T2) for the overall group and for patients who had orthodontia (group 1) and those who did not (group 2). A correlation analysis using length of follow-up and magnitude of advancement as predictor variables of stability was completed. For all analyses, a P value less than .05 was considered statistically significant. Results: During the 9-year study period, 120 patients with OSA were evaluated and 112 had operative treatment; 25 patients specifically had MMA and GTA, met the inclusion criteria, and formed the study sample. The mean maxillary and mandibular advancements (T1 vs T0) were 9.48 mm (range, 1.6 to 15.2 mm) and 10.85 mm (range, 6.3 to 15.8 mm), respectively. From T1 to T2, no occlusal changes occurred. Changes in the subgroup analyses included a decrease in the angle formed by the sella, nasion, and A point (SNA) and the angle formed by the nasion and A and B points (ANB) and an increase in the angle formed by the mandibular plane (gnathion and gonion) to a line from the sella to the nasion in group 1 and a decrease in ANB in group 2. The only statistical mean difference in cephalometric measurements between groups was in the distance between the condylion and the gnathion. There was no correlation between length of follow-up (mean, 27.84 months) and changes in cephalometric measurements. Conclusion: Results of this study indicate that although there were changes in the SNA and ANB from T1 to T2 suggesting maxillary relapse, the mean difference was no greater than 1 degrees and no patients developed a malocclusion; therefore, the changes were considered clinically minor. Advancement of the maxillomandibular complex by 10 mm for treatment of OSA remains stable at a mean follow-up period longer than 2 years and preoperative orthodontic treatment does not appear to influence skeletal stability. (C) 2015 American Association of Oral and Maxillofacial Surgeons C1 [Lee, Sang Hwa; Kaban, Leonard B.; Lahey, Edward T.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Kaban, Leonard B.; Lahey, Edward T.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Lahey, Edward T.] Massachusetts Gen Hosp, Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Lahey, ET (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Warren Bldg,55 Fruit St,Suite 1201, Boston, MA 02114 USA. EM elahey@mgh.harvard.edu FU Harvard Catalyst; Harvard Clinical and Translational Science Center [1UL1TR001102-01]; Harvard University FX This work was conducted with support from the Harvard Catalyst and the Harvard Clinical and Translational Science Center (National Center for Research Resources and National Center for Advancing Translational Sciences, National Institutes of Health Award 1UL1TR001102-01) and financial contributions from Harvard University and its affiliated academic health care centers and the Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund. NR 23 TC 2 Z9 2 U1 3 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 EI 1531-5053 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD APR PY 2015 VL 73 IS 4 BP 694 EP 700 DI 10.1016/j.joms.2014.10.018 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CD6ZN UT WOS:000351240100023 PM 25622883 ER PT J AU Balkin, EM Wolfe, J Ziniel, SI Lang, P Thiagarajan, R Dillis, S Fynn-Thompson, F Blume, ED AF Balkin, Emily M. Wolfe, Joanne Ziniel, Sonja I. Lang, Peter Thiagarajan, Ravi Dillis, Shay Fynn-Thompson, Francis Blume, Elizabeth D. TI Physician and Parent Perceptions of Prognosis and End-of-Life Experience in Children with Advanced Heart Disease SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID PALLIATIVE CARE; CANCER; PERSPECTIVES AB Background: Little is known about how physician and parent perspectives compare regarding the prognosis and end-of-life (EOL) experience of children with advanced heart disease (AHD). Objective: The study's objective was to describe and compare parent and physician perceptions regarding prognosis and EOL experience in children with AHD. Methods: This was a cross-sectional survey study of cardiologists and bereaved parents. Study subjects were parents and cardiologists of children with primary cardiac diagnoses who died in a tertiary care pediatric hospital between January 2007 and December 2009. Inclusion required both physician and parent to have completed surveys respective to the same patient. A total of 31 parent/physician pairs formed the analytic sample. Perceptions were measured of cardiologists and bereaved parents regarding the EOL experience of children with AHD. Results: Nearly half of parents and physicians felt that patients suffered 'a great deal,' 'a lot,' or 'somewhat' at EOL, but there was no agreement between them. At diagnosis, parents more often expected complete repair and normal lifespan while the majority of physicians expected shortened lifespan without normal quality of life. Parents who expected complete repair with normal life were more likely to report 'a lot' of suffering at EOL (p=0.002). In 43% of cases, physicians reported that the parents were prepared for the way in which their child died, while the parents reported feeling unprepared. Conclusion: Both parents and physicians perceive suffering at EOL in patients who die of AHD. Moreover, parent expectations at diagnosis may influence perceptions of suffering at EOL. Physicians overestimate the degree of parent preparedness for their child's death. C1 [Balkin, Emily M.] Univ Calif San Francisco, Benioff Childrens Hosp, Dept Pediat, San Francisco, CA 94143 USA. [Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Ziniel, Sonja I.] Boston Childrens Hosp, Ctr Patient Safety & Qual Res, Program Patient Safety & Qual, Boston, MA USA. [Ziniel, Sonja I.] Boston Childrens Hosp, Div Adolescent & Young Adult Med, Boston, MA USA. [Lang, Peter; Thiagarajan, Ravi; Dillis, Shay; Blume, Elizabeth D.] Boston Childrens Hosp, Dept Cardiol, Boston, MA USA. [Fynn-Thompson, Francis] Boston Childrens Hosp, Dept Cardiac Surg, Boston, MA USA. RP Balkin, EM (reprint author), Univ Calif San Francisco, Benioff Childrens Hosp, 505 Parnassus Ave,Moffitt Room 691B, San Francisco, CA 94143 USA. EM Emily.balkin@ucsf.edu NR 10 TC 4 Z9 4 U1 1 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD APR 1 PY 2015 VL 18 IS 4 BP 318 EP 323 DI 10.1089/jpm.2014.0305 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CD7ML UT WOS:000351274500005 PM 25493354 ER PT J AU Perez, GK Haime, V Jackson, V Chittenden, E Mehta, DH Park, ER AF Perez, Giselle K. Haime, Vivian Jackson, Vicki Chittenden, Eva Mehta, Darshan H. Park, Elyse R. TI Promoting Resiliency among Palliative Care Clinicians: Stressors, Coping Strategies, and Training Needs SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID BURNOUT; PHYSICIANS; MEDICINE; HOSPICE; WORK AB Background: Palliative care clinicians (PCCs) are susceptible to burnout, as they regularly witness immense patient and family suffering; however, little is known about their specific challenges and training needs to enhance their long-term sustainability. Objective: The purpose of this qualitative study was to explore common stressors, coping strategies, and training needs among PCCs in efforts to inform the development of a targeted Resiliency Program. Methods: Utilizing a semistructured interview guide, we conducted a series of in-depth interviews with 15 PCCs at the Massachusetts General Hospital. Results: Content analysis highlighted three main areas of stressors: (1) systematic challenges related to managing large, emotionally demanding caseloads within time constraints; (2) patient factors, such as addressing patients' mutable needs, managing family dynamics, and meeting patient and family demands and expectations; and (3) personal challenges of delineating emotional and professional boundaries. Engaging in healthy behaviors and hobbies and seeking emotional support from colleagues and friends were among the most common methods of coping with stressors. In terms of programmatic topics, PCCs desired training in mind-body skills (e.g., breathing, yoga, meditation), health education about the effects of stress, and cognitive strategies to help reduce ruminative thoughts and negative self-talk. A majority of clinicians stressed the need for brief strategies that could be readily integrated in the workplace. Conclusions: These results suggest that an intervention aimed to enhance PCC sustainability should focus on utilizing a skill-building approach to stress reduction that imparts strategies that can be readily utilized during work hours. C1 [Perez, Giselle K.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Haime, Vivian; Mehta, Darshan H.; Park, Elyse R.] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. [Jackson, Vicki; Chittenden, Eva] Massachusetts Gen Hosp, Div Palliat Med, Boston, MA 02114 USA. RP Perez, GK (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM gperez@mgh.harvard.edu OI Mehta, Darshan/0000-0003-0457-4717 NR 13 TC 8 Z9 8 U1 6 U2 30 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD APR 1 PY 2015 VL 18 IS 4 BP 332 EP 337 DI 10.1089/jpm.2014.0221 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CD7ML UT WOS:000351274500007 PM 25715108 ER PT J AU Roza, KA Lee, EJ Meier, DE Goldstein, NE AF Roza, Katherine A. Lee, Eric J. Meier, Diane E. Goldstein, Nathan E. TI A Survey of Bereaved Family Members To Assess Quality of Care on a Palliative Care Unit SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID LIFE CARE; ILL PATIENTS; END; CONSULTATION; PERCEPTIONS; OUTCOMES; EXPERIENCE; DEATH; COST AB Background: More U.S. hospitals are adopting palliative care programs, prompting inquiry about the relationship of palliative care to patient and family satisfaction. This study compares the impact of palliative care units, palliative care consultation, and usual care on bereaved families' perceptions of care quality. Methods: Using the Bereaved Family Survey we conducted interviews with family members of patients who died at Mount Sinai Medical Center between March 2012 and March 2013. Results: Of 108 completed surveys, 31 were in the palliative care unit group, 28 in the consultation service group, and 49 in the usual care group. Family members of patients who died on the palliative care unit were more likely to report that their loved one's end-of-life medical care had been "excellent" as compared to family members of patients who received palliative care consultation or usual care (adjusted OR, 2.06; 95% CI, 1.17-3.61). Family members of palliative care unit patients also reported greater satisfaction with emotional support before the patient's death (adjusted OR, 1.71; 95% CI, 1.01-2.90). We found no significant differences between the consultation service and usual care. Conclusion: Family members of patients who died while receiving care in a dedicated palliative care unit report higher overall satisfaction and emotional support before death as compared to the consultation service or usual care. C1 [Roza, Katherine A.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Lee, Eric J.; Meier, Diane E.; Goldstein, Nathan E.] Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, Lilian & Benjamin Hertzberg Palliat Care Inst, New York, NY 10029 USA. [Goldstein, Nathan E.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. RP Goldstein, NE (reprint author), Dept Geriatr & Palliat Med, One Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM nathan.goldstein@mssm.edu FU Doris Duke Charitable Foundation Clinical Research Fellowship FX Katherine Roza is the recipient of a Doris Duke Charitable Foundation Clinical Research Fellowship. The manuscript's contents are solely the responsibility of the authors and do not necessarily represent the official views of the Doris Duke Charitable Foundation or the Department of Veterans Affairs. The funding body had no role in the collection, analysis, and interpretation of the data or in the writing of the manuscript, or in the decision to submit the manuscript for publication. NR 24 TC 2 Z9 2 U1 0 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD APR 1 PY 2015 VL 18 IS 4 BP 358 EP 365 DI 10.1089/jpm.2014.0172 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CD7ML UT WOS:000351274500010 PM 25793359 ER PT J AU Walling, AM Schreibeis-Baum, H Pimstone, N Asch, SM Robinson, L Korlekar, S Lorenz, K Nwajuaku, T Rosenfeld, K AF Walling, Anne M. Schreibeis-Baum, Hannah Pimstone, Neville Asch, Steven M. Robinson, Linda Korlekar, Sheri Lorenz, Karl Nwajuaku, Tracy Rosenfeld, Kenneth TI Proactive Case Finding To Improve Concurrently Curative and Palliative Care in Patients with End-Stage Liver Disease SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID LUNG-CANCER; HEALTH-CARE; OF-LIFE AB Background: Palliative care and preparation for liver transplantation are often perceived as conflicting for patients with end-stage liver disease (ESLD). We sought to improve both simultaneously through a case finding and care coordination quality improvement intervention. Methods: We identified patients with cirrhosis using validated ICD-9 codes and screened them for ESLD by assessing medical records at a VA hospital for either a model for end-stage liver disease (MELD) >= 14 or a diagnosis of hepatocellular carcinoma (HCC) between October 2012 and January 2013. A care coordinator followed veterans from the index hospitalization through April 2013 and encouraged treating physicians to submit liver transplant evaluation consults for all veterans with a MELD >= 14 and palliative care consults for all veterans with a MELD >= 20 or inoperable HCC. Results: We compared rates of consultation for 49 hospitalized veterans and compared their outcomes to 61 pre-intervention veterans. Veterans were more likely to be considered for liver transplantation (77.6% versus 31.1%, p<0.001) and receive palliative care consultation during the intervention period, although the latter finding did not reach statistical significance (62.5% versus 47.1%, p=0.38). Conclusions: Active case finding improved consideration for liver transplantation without decreasing palliative care consultation. C1 [Walling, Anne M.; Schreibeis-Baum, Hannah; Pimstone, Neville; Korlekar, Sheri; Lorenz, Karl; Nwajuaku, Tracy] Univ Calif Los Angeles, David Geffen Sch Med, Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90095 USA. [Walling, Anne M.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Asch, Steven M.] VA Palo Alto Healthcare Syst, Palo Alto, CA USA. [Asch, Steven M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Rosenfeld, Kenneth] Sutter Hlth, Res Dev & Disseminat RD&D, Walnut Creek, CA USA. [Robinson, Linda] St Peters Hosp, Helena, MT USA. RP Walling, AM (reprint author), Univ Calif Los Angeles, Dept Gen Internal Med & Hlth Serv Res, 911 Broxton,3D, Los Angeles, CA 90095 USA. EM awalling@mednet.ucla.edu FU quality improvement award through VA HIV, Hepatitis, and Public Health Pathogens, Office of Public Health/Clinical Public Health; NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI Grant [UL1TR000124]; NIH loan repayment program FX This project was funded by a quality improvement award through VA HIV, Hepatitis, and Public Health Pathogens, Office of Public Health/Clinical Public Health. Dr. Walling also is currently supported by a career development award from NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI Grant Number UL1TR000124 and the NIH loan repayment program. NR 17 TC 2 Z9 2 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD APR 1 PY 2015 VL 18 IS 4 BP 378 EP 381 DI 10.1089/jpm.2014.0265 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CD7ML UT WOS:000351274500013 PM 25493552 ER PT J AU Wang, ZH Butner, JD Cristini, V Deisboeck, TS AF Wang, Zhihui Butner, Joseph D. Cristini, Vittorio Deisboeck, Thomas S. TI Integrated PK-PD and agent-based modeling in oncology SO JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS LA English DT Review DE Chemotherapy; Computer simulation; Mathematical modeling; Multiscale; Tumor growth and invasion; Translational research ID CELLULAR-AUTOMATON MODEL; LYMPHATIC VASCULAR SYSTEMS; NONLINEAR TUMOR-GROWTH; LUNG-CANCER MODEL; CARCINOMA IN-SITU; BREAST-CANCER; INTERSTITIAL PRESSURE; SENSITIVITY-ANALYSIS; ANTITUMOR-ACTIVITY; DRUG RESPONSE AB Mathematical modeling has become a valuable tool that strives to complement conventional biomedical research modalities in order to predict experimental outcome, generate new medical hypotheses, and optimize clinical therapies. Two specific approaches, pharmacokinetic-pharmacodynamic (PK-PD) modeling, and agent-based modeling (ABM), have been widely applied in cancer research. While they have made important contributions on their own (e.g., PK-PD in examining chemotherapy drug efficacy and resistance, and ABM in describing and predicting tumor growth and metastasis), only a few groups have started to combine both approaches together in an effort to gain more insights into the details of drug dynamics and the resulting impact on tumor growth. In this review, we focus our discussion on some of the most recent modeling studies building on a combined PK-PD and ABM approach that have generated experimentally testable hypotheses. Some future directions are also discussed. C1 [Wang, Zhihui; Cristini, Vittorio] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA. [Butner, Joseph D.; Cristini, Vittorio] Univ New Mexico, Dept Chem Engn, Albuquerque, NM 87131 USA. [Butner, Joseph D.; Cristini, Vittorio] Univ New Mexico, Ctr Biomed Engn, Albuquerque, NM 87131 USA. [Cristini, Vittorio] King Abdulaziz Univ, Dept Math, Fac Sci, Jeddah 21589, Saudi Arabia. [Deisboeck, Thomas S.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. [Deisboeck, Thomas S.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Deisboeck, TS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. EM deisboec@helix.mgh.harvard.edu RI Cristini, Vittorio/N-3540-2013 FU National Science Foundation (NSF) [DMS-1263742]; National Institutes of Health (NIH) [1U54CA149196, 1U54CA143837, 1U54CA151668, 1U54CA143907]; King Abdulaziz University (KAU) [54-130-35-HiCi]; University of New Mexico Cancer Center Victor and Ruby Hansen Surface Professorship in Molecular Modeling of Cancer; Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging; Department of Radiology at Massachusetts General Hospital FX This work has been supported in part by the National Science Foundation (NSF) Grant DMS-1263742 (Z.W., V.C.), the National Institutes of Health Grant (NIH) 1U54CA149196, 1U54CA143837, 1U54CA151668, 1U54CA143907 (V.C.), King Abdulaziz University (KAU) Grant No. 54-130-35-HiCi (V.C.), the University of New Mexico Cancer Center Victor and Ruby Hansen Surface Professorship in Molecular Modeling of Cancer (V.C.), and the Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging and the Department of Radiology at Massachusetts General Hospital (T.S.D.). Finally, we apologize to those of our colleagues whose works could not be cited due to space limitations. NR 98 TC 8 Z9 8 U1 2 U2 17 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1567-567X EI 1573-8744 J9 J PHARMACOKINET PHAR JI J. Pharmacokinet. Pharmacodyn. PD APR PY 2015 VL 42 IS 2 BP 179 EP 189 DI 10.1007/s10928-015-9403-7 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CD6BB UT WOS:000351172300007 PM 25588379 ER PT J AU Upshur, C Weinreb, L Bharel, M Reed, G Frisard, C AF Upshur, Carole Weinreb, Linda Bharel, Monica Reed, George Frisard, Christine TI A Randomized Control Trial of a Chronic Care Intervention for Homeless Women With Alcohol Use Problems SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE Alcohol abuse; Homeless women; Chronic care model; Primary care; Randomized trial ID POSTTRAUMATIC-STRESS-DISORDER; SUBSTANCE-ABUSE TREATMENT; SERIOUS MENTAL-ILLNESS; LINE FOLLOW-BACK; HEALTH-SERVICES; DRUG-USE; AUDIT-C; ADULTS; PREVALENCE; RISK AB A clinician-randomized trial was conducted using the chronic care model for disease management for alcohol use problems among n = 82 women served in a health care for the homeless clinic. Women with problem alcohol use received either usual care or an intervention consisting of a primary care provider (PCP) brief intervention, referral to addiction services, and on-going support from a care manager (CM) for 6 months. Both groups significantly reduced their alcohol consumption, with a small effect size favoring intervention at 3 months, but there were no significant differences between groups in reductions in drinking or in housing stability, or mental or physical health. However, intervention women had significantly more frequent participation in substance use treatment services. Baseline differences and small sample size limit generalizability, although substantial reductions in drinking for both groups suggest that screening and PCP brief treatment are promising interventions for homeless women with alcohol use problems. (C) 2015 Elsevier Inc. All rights reserved. C1 [Upshur, Carole; 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 02215 USA. [Bharel, Monica] Massachusetts Gen Hosp, Boston Hlth Care Homeless Program, Boston, MA 02114 USA. [Reed, George] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA 01655 USA. [Frisard, Christine] Univ Massachusetts, Sch Med, Dept Med, Div Prevent & Behav Med, Worcester, MA 01655 USA. RP Upshur, C (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 National Institute of Alcohol Abuse and Alcoholism [R21AA018311] FX This study was supported by grant # R21AA018311 from the National Institute of Alcohol Abuse and Alcoholism. The authors wish to acknowledge the research and clinical staff of the Boston Health Care for the Homeless Program who participated in the study: Jim O'Connell, MD, President; research office: Erin Stringfellow, MSW, Julie Marston, MPH, Jess Hoy, Leah Isquith, and Stacy Swain, MHD, MDiv.; clinical staff: Erline Destra and Kim Herman, care managers; Rita Chapman, BSN,RN, LADC1, clinic director; Barbara Cocci, LICSW, director and Ester Valdez, MD, medical director for behavioral health services; Toni Abraham, NP, Assnt Medical Director; Barry Bock, RN, Director, clinical operations; Pooja Bhalla, RN, Asst. Dir, clinical operations; Ava Cherloff and Joan Nordberg, information services. We also wish to thank the project staff from the Department of Family Medicine and Community Health, Susan Van Buskirk, MEd, and Gail Sawosik. NR 58 TC 2 Z9 2 U1 8 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD APR PY 2015 VL 51 BP 19 EP 29 DI 10.1016/j.jsat.2014.11.001 PG 11 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA CD0RM UT WOS:000350781600002 PM 25488504 ER PT J AU Shorey, RC Martino, S Lamb, KE LaRowe, SD Ana, EJS AF Shorey, Ryan C. Martino, Steve Lamb, Kayla E. LaRowe, Steven D. Ana, Elizabeth J. Santa TI Change Talk and Relatedness in Group Motivational Interviewing: A Pilot Study SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE Change talk; Motivational interviewing; Group motivational interviewing; Substance use; Relatedness ID SUBSTANCE USE DISORDERS; NEGATIVE CONSEQUENCES; ACTIVE INGREDIENTS; DRINKING OUTCOMES; COLLEGE-STUDENTS; CLIENT LANGUAGE; INTERVENTIONS; PSYCHOTHERAPY; MECHANISMS; THERAPY AB Background: Change talk (CT), or client speech in favor of change, is a hypothesized mechanism of action in motivational interviewing (MI) for substance use disorders. Although group-based treatment is the primary treatment modality for the majority of clients seeking substance use treatment, limited research has examined group motivational interviewing (GMI) among this population, and no study has examined CT within GMI. Therefore, in the current study we examined both standard CT (e.g., desire, ability, reason, need) and a novel phenomenon involving CT which we termed 'relatedness,' or the synergistic exchange of CT between and among group members. Method: Data were utilized from an ongoing randomized controlled trial (RCT) examining the effectiveness of GMI relative to a treatment control condition (TCC) among U.S. veteran outpatients with a primary alcohol use disorder at a Veterans Affairs hospital. A subsample of participants (n = 52) from the RCT were randomly assigned to receive GM! or TCC. The majority of participants in the subsample had co-existing psychiatric (88%) and dual diagnosis drug use disorders (38%). Two of four treatment sessions were coded by trained raters for CT and relatedness. Results: Analyses demonstrated that CT and relatedness occurred with greater frequency in GMI compared to TCC, with effect sizes in the large range for each difference. Results held after controlling for number of group members in treatment sessions. Conclusions: Findings suggest that GMI is associated with more frequent CT and relatedness than TCC, consistent with the broader literature demonstrating the influence of MI on CT. (C) 2015 Elsevier Inc. All rights reserved. C1 [Shorey, Ryan C.] Ohio Univ, Athens, OH 45701 USA. [Martino, Steve] Yale Univ, Sch Med, New Haven, CT USA. [Martino, Steve] VA Connecticut Healthcare Syst, West Haven, CT USA. [Lamb, Kayla E.; LaRowe, Steven D.; Ana, Elizabeth J. Santa] Ralph H Johnson VAMC, Charleston, SC USA. [LaRowe, Steven D.; Ana, Elizabeth J. Santa] Med Univ S Carolina, Charleston, SC 29425 USA. RP Shorey, RC (reprint author), Ohio Univ, Dept Psychol, 239 Porter Hall, Athens, OH 45701 USA. EM shorey@ohio.edu FU Clinical Science Research and Development Career Development Award (CDA-2) from the United States (U.S.) Department of Veterans Affairs (Clinical Sciences Research and Development) [CDA-2-016-08S] FX This work was supported by a Clinical Science Research and Development Career Development Award (CDA-2) to Dr. Santa Ana (CDA-2-016-08S) from the United States (U.S.) Department of Veterans Affairs (Clinical Sciences Research and Development). The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. Dr. Santa Ana is Evidence-Based Training Program Coordinator; VISN 7 Homeless Program; Charleston VA Medical Center, Charleston, SC. NR 44 TC 4 Z9 4 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD APR PY 2015 VL 51 BP 75 EP 81 DI 10.1016/j.jsat.2014.11.003 PG 7 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA CD0RM UT WOS:000350781600010 PM 25488505 ER PT J AU Coates, SJ Kvedar, J Granstein, RD AF Coates, Sarah J. Kvedar, Joseph Granstein, Richard D. TI Teledermatology: From historical perspective to emerging techniques of the modern era Part I: History, rationale, and current practice SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE dermatology workforce; Internet; smartphone; store-and-forward; teledermatology telemedicine ID RANDOMIZED-CONTROLLED-TRIAL; LIVE INTERACTIVE TELEDERMATOLOGY; DERMATOLOGY WORKFORCE SHORTAGE; PAY STATED PREFERENCES; CHRONIC LEG ULCERS; FORWARD TELEDERMATOLOGY; SKIN-CANCER; WOUND CARE; MOBILE TELEDERMATOLOGY; PATIENT SATISFACTION AB Telemedicine is the use of telecommunications technology to support health care at a distance. Technological advances have progressively increased the ability of clinicians to care for diverse patient populations in need of skin expertise. Dermatology relies on visual cues that are easily captured by imaging technologies, making it ideally suited for this care model. Moreover, there is a shortage of medical dermatologists in the United States, where skin disorders account for 1 in 8 primary care visits and specialists tend to congregate in urban areas. Even in regions where dermatologic expertise is readily accessible, teledermatology may serve as an alternative that streamlines health care delivery by triaging chief complaints and reducing unnecessary in-person visits. In addition, many patients in the developing world have no access to dermatologic expertise, rendering it possible for teledermatologists to make a significant contribution to patient health outcomes. Teledermatology also affords educational benefits to primary care providers and dermatologists, and enables patients to play a more active role in the health care process by promoting direct communication with dermatologists. C1 [Coates, Sarah J.; Granstein, Richard D.] Weill Cornell Med Coll, Dept Dermatol, New York, NY 10021 USA. [Kvedar, Joseph] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kvedar, Joseph] Harvard Univ, Sch Med, Boston, MA USA. RP Granstein, RD (reprint author), Weill Cornell Med Coll, Dept Dermatol, 1305 York Ave,9th Fl, New York, NY 10021 USA. EM rdgranst@med.cornell.edu NR 125 TC 16 Z9 16 U1 1 U2 14 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 APR PY 2015 VL 72 IS 4 BP 563 EP 576 DI 10.1016/j.jaad.2014.07.061 PG 14 WC Dermatology SC Dermatology GA CD6FE UT WOS:000351184200010 PM 25773407 ER PT J AU Coates, SJ Kvedar, J Granstein, RD AF Coates, Sarah J. Kvedar, Joseph Granstein, Richard D. TI Teledermatology: From historical perspective to emerging techniques of the modern era Part II: Emerging technologies in teledermatology, limitations and future directions SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE Internet; smartphone; store-and-forward; teledermatology; teledermatopathology; teledermoscopy ID STORE-AND-FORWARD; COST-MINIMIZATION ANALYSIS; MULTIMEDIA MESSAGING SERVICE; MELANOCYTIC SKIN-LESIONS; HIGH-NEED PATIENTS; TO-FACE DIAGNOSIS; OF-THE-ART; MOBILE TELEDERMATOLOGY; ECONOMIC-EVALUATION; PIGMENTED LESIONS AB Telemedicine is the use of telecommunications technology to support health care at a distance. Dermatology relies on visual cues that are easily captured by imaging technologies, making it ideally suited for this care model. Advances in telecommunications technology have made it possible to deliver high-quality skin care when patient and provider are separated by both time and space. Most recently, mobile devices that connect users through cellular data networks have enabled teledermatologists to instantly communicate with primary care providers throughout the world. The availability of teledermoscopy provides an additional layer of visual information to enhance the quality of teleconsultations. Teledermatopathology has become increasingly feasible because of advances in digitization of entire microscopic slides and robot-assisted microscopy. Barriers to additional expansion of these services include underdeveloped infrastructure in remote regions, fragmented electronic medical records, and varying degrees of reimbursement. Teleconsultants also confront special legal and ethical challenges as they work toward building a global network of practicing physicians. C1 [Coates, Sarah J.; Granstein, Richard D.] Weill Cornell Med Coll, Dept Dermatol, New York, NY 10021 USA. [Kvedar, Joseph] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kvedar, Joseph] Harvard Univ, Sch Med, Boston, MA USA. RP Granstein, RD (reprint author), Weill Cornell Med Coll, Dept Dermatol, 1305 York Ave,9th Fl, New York, NY 10021 USA. EM rdgranst@med.cornell.edu NR 103 TC 16 Z9 16 U1 1 U2 11 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 APR PY 2015 VL 72 IS 4 BP 577 EP 588 DI 10.1016/j.jaad.2014.08.014 PG 12 WC Dermatology SC Dermatology GA CD6FE UT WOS:000351184200011 PM 25773408 ER PT J AU Tsao, H Olazagasti, JM Cordoro, KM Brewer, JD Taylor, SC Bordeaux, JS Chren, MM Sober, AJ Tegeler, C Bhushan, R Begolka, WS AF Tsao, Hensin Olazagasti, Jeannette M. Cordoro, Kelly M. Brewer, Jerry D. Taylor, Susan C. Bordeaux, Jeremy S. Chren, Mary-Margaret Sober, Arthur J. Tegeler, Connie Bhushan, Reva Begolka, Wendy Smith TI Early detection of melanoma: Reviewing the ABCDEs SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE ABCDE; criteria; detection; diagnosis; melanoma; screening ID CUTANEOUS MALIGNANT-MELANOMA; PRIMARY-CARE PHYSICIANS; PIGMENTED LESIONS; 7-POINT CHECKLIST; SELF-EXAMINATION; EARLY-DIAGNOSIS; SKIN; CHILDREN; CRITERIA; FEATURES AB Over the course of their nearly 30-year history, the ABCD(E) criteria have been used globally in medical education and in the lay press to provide simple parameters for assessment of pigmented lesions that need to be further evaluated by a dermatologist. In this article, the efficacy and limitations of the ABCDE criteria as both a clinical tool and a public message will be reviewed. C1 [Tsao, Hensin; Sober, Arthur J.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Tsao, Hensin; Sober, Arthur J.] Harvard Univ, Sch Med, Dept Dermatol, Cambridge, MA 02138 USA. [Olazagasti, Jeannette M.; Brewer, Jerry D.] Mayo Clin, Dept Dermatol, Rochester, MN USA. [Olazagasti, Jeannette M.; Brewer, Jerry D.] Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA. [Cordoro, Kelly M.; Chren, Mary-Margaret] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Taylor, Susan C.] Soc Hill Dermatol & Cosmet Ctr, Philadelphia, PA USA. [Bordeaux, Jeremy S.] Univ Hosp Case Med Ctr, Dept Dermatol, Cleveland, OH USA. [Bordeaux, Jeremy S.] Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. [Chren, Mary-Margaret] San Francisco VA Med Ctr, Dermatol Serv, San Francisco, CA USA. [Tegeler, Connie; Bhushan, Reva; Begolka, Wendy Smith] Amer Acad Dermatol, Schaumburg, IL 60173 USA. RP Begolka, WS (reprint author), Amer Acad Dermatol, 930 East Woodfield Rd, Schaumburg, IL 60173 USA. EM wsmithbegolka@aad.org FU Genentech FX Dr Tsao served as an investigator for MelaScience receiving equipment, and served as a consultant to Scibase receiving honoraria. Dr Taylor served as a speaker, investigator, and advisory board member for Allergan receiving honoraria and grants; served as a speaker and advisory board member for Bieresdorf and Galderma receiving honoraria; served as the founder of T2 Skin Care receiving other financial benefits; served as an investigator for Teoxane receiving grants; served as a consultant and speaker for Unilever receiving honoraria; and served as an advisory board member for Valeant receiving honoraria. Dr Chren served as a consultant for Genentech receiving salary. Dr Sober served as a consultant for MelaScience and Worldcare receiving other financial benefits. Ms Olazagasti, Drs Cordoro, Brewer, Bordeaux, and Bhushan, Ms Tegeler, and Ms Smith Begolka have no conflicts of interest to declare. NR 60 TC 15 Z9 16 U1 1 U2 12 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 APR PY 2015 VL 72 IS 4 BP 717 EP 723 DI 10.1016/j.jaad.2015.01.025 PG 7 WC Dermatology SC Dermatology GA CD6FE UT WOS:000351184200029 ER PT J AU Horner, ME Kourosh, AS Menter, MA AF Horner, Mary E. Kourosh, A. Shadi Menter, M. Alan TI Awareness and engagement in political advocacy among dermatology residents: A needs assessment SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter C1 [Horner, Mary E.; Menter, M. Alan] Baylor Univ, Med Ctr, Div Dermatol, Dallas, TX 75246 USA. [Kourosh, A. Shadi] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Horner, ME (reprint author), Baylor Univ, Med Ctr, Div Dermatol, 3900 Junius St 145, Dallas, TX 75246 USA. EM maryehorner@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD APR PY 2015 VL 72 IS 4 BP 730 EP 732 DI 10.1016/j.jaad.2014.12.011 PG 4 WC Dermatology SC Dermatology GA CD6FE UT WOS:000351184200033 PM 25773414 ER PT J AU Smith, GP AF Smith, Gideon P. TI The readability of patient education materials designed for patients with psoriasis: What have we learned in 20 years? SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Smith, GP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 50 Staniford St,Suite 200, Boston, MA 02114 USA. EM gpsmith@mgh.harvard.edu NR 3 TC 1 Z9 1 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD APR PY 2015 VL 72 IS 4 BP 737 EP 738 DI 10.1016/j.jaad.2014.12.018 PG 3 WC Dermatology SC Dermatology GA CD6FE UT WOS:000351184200037 PM 25773418 ER PT J AU Das, S Nambudiri, VE Kroshinsky, D AF Das, Shinjita Nambudiri, Vinod E. Kroshinsky, Daniela TI Waxing and waning eczematous dermatitis and glossitis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Editorial Material C1 [Das, Shinjita; Nambudiri, Vinod E.; Kroshinsky, Daniela] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Kroshinsky, D (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 55 Fruit St,Bartlett Hall,6th Fl, Boston, MA 02114 USA. EM dkroshinsky@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD APR PY 2015 VL 72 IS 4 BP E89 EP E90 DI 10.1016/j.jaad.2014.09.043 PG 2 WC Dermatology SC Dermatology GA CD6FE UT WOS:000351184200001 PM 25773429 ER PT J AU Hosseinbor, AP Chung, MK Wu, YC Bendlin, BB Alexander, AL AF Hosseinbor, A. Pasha Chung, Moo K. Wu, Yu-Chien Bendlin, Barbara B. Alexander, Andrew L. TI A 4D hyperspherical interpretation of q-space SO MEDICAL IMAGE ANALYSIS LA English DT Article DE Hyperspherical harmonics; Diffusion propagator; ODF; q-Space indices; Diffusion MRI ID ORIENTATION DISTRIBUTION FUNCTION; DIFFUSION-WEIGHTED MRI; HUMAN BRAIN; SPHERICAL DECONVOLUTION; MODEL-FREE; RECONSTRUCTION; TISSUE; TENSOR; ATTENUATION; COMPUTATION AB 3D q-space can be viewed as the surface of a 40 hypersphere. In this paper, we seek to develop a 4D hyperspherical interpretation of q-space by projecting it onto a hypersphere and subsequently modeling the q-space signal via 40 hyperspherical harmonics (HSH). Using this orthonormal basis, we derive several well-established q-space indices and numerically estimate the diffusion orientation distribution function (dODF). We also derive the integral transform describing the relationship between the diffusion signal and propagator on a hypersphere. Most importantly, we will demonstrate that for hybrid diffusion imaging (HYDI) acquisitions low order linear expansion of the HSH basis is sufficient to characterize diffusion in neural tissue. In fact, the HSH basis achieves comparable signal and better dODF reconstructions than other well-established methods, such as Bessel Fourier orientation reconstruction (BFOR), using fewer fitting parameters. All in all, this work provides a new way of looking at q-space. (C) 2014 Elsevier B.V. All rights reserved. C1 [Hosseinbor, A. Pasha; Chung, Moo K.; Alexander, Andrew L.] Univ Wisconsin, Waisman Lab Brain Imaging & Behav, Madison, WI 53718 USA. [Chung, Moo K.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. [Wu, Yu-Chien] Indiana Univ, Ctr Neuroimaging, Indianapolis, IN 46204 USA. [Bendlin, Barbara B.] Univ Wisconsin, William S Middleton Mem Vet Hosp, GRECC, Madison, WI USA. [Alexander, Andrew L.] Univ Wisconsin, Dept Med Phys, Madison, WI 53706 USA. [Alexander, Andrew L.] Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA. RP Hosseinbor, AP (reprint author), Univ Wisconsin, Waisman Lab Brain Imaging & Behav, Madison, WI 53718 USA. EM hosseinbor@wisc.edu OI Bendlin, Barbara/0000-0002-0580-9875 FU National Institute of Aging [R01 AG037639]; National Institute of Child Health and Human Development [P-30 HD03352]; National Institute of Dental and Craniofacial Research [5T15LM007359]; UW-Madison FX This research was supported by the National Institute of Aging (R01 AG037639), National Institute of Child Health and Human Development (P-30 HD03352), National Institute of Dental and Craniofacial Research (5T15LM007359), and Vilas Associate Award from UW-Madison. NR 50 TC 0 Z9 0 U1 2 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1361-8415 EI 1361-8423 J9 MED IMAGE ANAL JI Med. Image Anal. PD APR PY 2015 VL 21 IS 1 BP 15 EP 28 DI 10.1016/j.media.2014.11.013 PG 14 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA CD0PU UT WOS:000350777200002 ER PT J AU Wu, C Sun, DD AF Wu, Connie Sun, Dandan TI GABA receptors in brain development, function, and injury SO METABOLIC BRAIN DISEASE LA English DT Review DE gamma-aminobutyric acid receptors; Chloride transporters; Anoxic-ischemic injury; Periventricular leukomalacia; Schizophrenia; Stroke ID GAMMA-AMINOBUTYRIC-ACID; NEOCORTICAL INHIBITORY SYSTEM; CORTICAL PROGENITOR CELLS; CENTRAL-NERVOUS-SYSTEM; WHITE-MATTER INJURY; GABAERGIC NEURONS; PREFRONTAL CORTEX; VISUAL-CORTEX; PERIVENTRICULAR LEUKOMALACIA; SCHIZOPHRENIC SUBJECTS AB This review presents a brief overview of the gamma-aminobutyric acid (GABA) system in the developing and mature central nervous system (CNS) and its potential connections to pathologies of the CNS. gamma-aminobutyric acid (GABA) is a major neurotransmitter expressed from the embryonic stage and throughout life. At an early developmental stage, GABA acts in an excitatory manner and is implicated in many processes of neurogenesis, including neuronal proliferation, migration, differentiation, and preliminary circuit-building, as well as the development of critical periods. In the mature CNS, GABA acts in an inhibitory manner, a switch mediated by chloride/cation transporter expression and summarized in this review. GABA also plays a role in the development of interstitial neurons of the white matter, as well as in oligodendrocyte development. Although the underlying cellular mechanisms are not yet well understood, we present current findings for the role of GABA in neurological diseases with characteristic white matter abnormalities, including anoxic-ischemic injury, periventricular leukomalacia, and schizophrenia. Development abnormalities of the GABAergic system appear particularly relevant in the etiology of schizophrenia. This review also covers the potential role of GABA in mature brain injury, namely transient ischemia, stroke, and traumatic brain injury/post-traumatic epilepsy. C1 [Wu, Connie] Univ Wisconsin, Dept Neurosci, Madison, WI 53706 USA. [Sun, Dandan] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. [Sun, Dandan] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15213 USA. RP Sun, DD (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S-598 South Biomed Sci Tower BST,3500 Terrace St, Pittsburgh, PA 15213 USA. EM sund@upmc.edu FU NIH [R01NS38118, R01NS075995] FX This work was supported in part by NIH grant R01NS38118, R01NS075995 (D. Sun). NR 93 TC 10 Z9 11 U1 3 U2 31 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 APR PY 2015 VL 30 IS 2 BP 367 EP 379 DI 10.1007/s11011-014-9560-1 PG 13 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA CD2HA UT WOS:000350894800003 PM 24820774 ER PT J AU Kawabori, M Yenari, MA AF Kawabori, Masahito Yenari, Midori A. TI The role of the microglia in acute CNS injury SO METABOLIC BRAIN DISEASE LA English DT Review DE Microglia; Inflammation; Brain; Spinal cord; Stroke; Trauma ID TRAUMATIC BRAIN-INJURY; SPINAL-CORD-INJURY; FOCAL CEREBRAL-ISCHEMIA; TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE SYNTHASE; ACTIVATED PARENCHYMAL MICROGLIA/MACROPHAGES; INTRACEREBRAL INFLAMMATORY RESPONSE; BLOOD-DERIVED MACROPHAGES; CENTRAL-NERVOUS-SYSTEM; GROWTH-FACTOR-BETA AB Microglia are considered the brain's resident immune cell involved in immune defense, immunocompetence, and phagocytosis. They maintain tissue homeostasis within the brain and spinal cord under normal condition and serves as its initial host defense system. However, when the central nervous system (CNS) faces injury, microglia respond through signaling molecules expressed or released by neighboring cells. Microglial responses are dual in nature. They induce a nonspecific immune response that may exacerbate CNS injury, especially in the acute stages, but are also essential to CNS recovery and repair. The full range of microglial mechanisms have yet to be clarified, but there is accumulating knowledge about microglial activation in acute CNS injury. Microglial responses require hours to days to fully develop, and may present a therapeutic target for intervention with a much longer window of opportunity compare to other neurological treatments. The challenge will be to find ways to selectively suppress the deleterious effects of microglial activation without compromising its beneficial functions. This review aims to provide an overview of the recent progress relating on the deleterious and beneficial effect of microglia in the setting of acute CNS injury and the potential therapeutic intervention against microglial activation to CNS injury. C1 [Kawabori, Masahito; Yenari, Midori A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Kawabori, Masahito; Yenari, Midori A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Yenari, MA (reprint author), Univ Calif San Francisco, Dept Neurol, 4150 Clement St, San Francisco, CA 94121 USA. EM yenari@alum.mit.edu FU National Institutes of Health [NS40516]; Veteran's Merit Award; Uehara Foundation; Veterans Affairs Medical Center, San Francisco, California FX This work was supported by grants from the National Institutes of Health (NS40516, to MY), the Veteran's Merit Award (MY), the Uehara Foundation (2013 Research Fellowship, to MK). Grants to MY were administered by the Northern California Institute for Research and Education, and supported by resources of the Veterans Affairs Medical Center, San Francisco, California. NR 164 TC 8 Z9 10 U1 4 U2 25 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 APR PY 2015 VL 30 IS 2 BP 381 EP 392 DI 10.1007/s11011-014-9531-6 PG 12 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA CD2HA UT WOS:000350894800004 PM 24682762 ER PT J AU Yu, ZY Liu, N Zhao, JH Li, YD McCarthy, TJ Tedford, CE Lo, EH Wang, XY AF Yu, Zhanyang Liu, Ning Zhao, Jianhua Li, Yadan McCarthy, Thomas J. Tedford, Clark E. Lo, Eng H. Wang, Xiaoying TI Near infrared radiation rescues mitochondrial dysfunction in cortical neurons after oxygen-glucose deprivation SO METABOLIC BRAIN DISEASE LA English DT Article DE Near infrared radiation; Oxygen-glucose deprivation; Primary cortical neurons; MTT reduction; Mitochondrial membrane potential; ATP ID LEVEL LASER THERAPY; TERM NEUROLOGICAL DEFICITS; TRAUMATIC BRAIN-INJURY; OXIDATIVE STRESS; PROMOTES REGENERATION; FUNCTIONAL RECOVERY; LIGHT; MICE; PHOTOBIOMODULATION; ACTIVATION AB Near infrared radiation (NIR) is known to penetrate and affect biological systems in multiple ways. Recently, a series of experimental studies suggested that low intensity NIR may protect neuronal cells against a wide range of insults that mimic diseases such as stroke, brain trauma and neurodegeneration. However, the potential molecular mechanisms of neuroprotection with NIR remain poorly defined. In this study, we tested the hypothesis that low intensity NIR may attenuate hypoxia/ischemia-induced mitochondrial dysfunction in neurons. Primary cortical mouse neuronal cultures were subjected to 4 h oxygen-glucose deprivation followed by reoxygenation for 2 h, neurons were then treated with a 2 min exposure to 810-nm NIR. Mitochondrial function markers including MTT reduction and mitochondria membrane potential were measured at 2 h after treatment. Neurotoxicity was quantified 20 h later. Our results showed that 4 h oxygen-glucose deprivation plus 20 h reoxygenation caused 33.8 +/- 3.4 % of neuron death, while NIR exposure significantly reduced neuronal death to 23.6 +/- 2.9 %. MTT reduction rate was reduced to 75.9 +/- 2.7 % by oxygen-glucose deprivation compared to normoxic controls, but NIR exposure significantly rescued MTT reduction to 87.6 +/- 4.5 %. Furthermore, after oxygen-glucose deprivation, mitochondria membrane potential was reduced to 48.9 +/- 4.39 % of normoxic control, while NIR exposure significantly ameliorated this reduction to 89.6 +/- 13.9 % of normoxic control. Finally, NIR significantly rescued OGD-induced ATP production decline at 20 min after NIR. These findings suggest that low intensity NIR can protect neurons against oxygen-glucose deprivation by rescuing mitochondrial function and restoring neuronal energetics. C1 [Yu, Zhanyang; Liu, Ning; Zhao, Jianhua; Li, Yadan; Lo, Eng H.; Wang, Xiaoying] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA 02129 USA. [Yu, Zhanyang; Liu, Ning; Zhao, Jianhua; Li, Yadan; Lo, Eng H.; Wang, Xiaoying] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA 02129 USA. [Yu, Zhanyang; Liu, Ning; Zhao, Jianhua; Li, Yadan; Lo, Eng H.; Wang, Xiaoying] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [McCarthy, Thomas J.] Sequent Med Inc, Aliso Viejo, CA 92656 USA. [Tedford, Clark E.] Solentix Biosci Inc, Poulsbo, WA 98370 USA. RP Yu, ZY (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA 02129 USA. EM Yu.Zhanyang@mgh.harvard.edu; wangxi@helix.mgh.harvard.edu FU NINDS NIH HHS [R01 NS065998, P01 NS055104, R01 NS076694, R37 NS037074] NR 31 TC 0 Z9 0 U1 1 U2 5 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 APR PY 2015 VL 30 IS 2 BP 491 EP 496 DI 10.1007/s11011-014-9515-6 PG 6 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA CD2HA UT WOS:000350894800015 PM 24599760 ER PT J AU Katsiki, N Rizzo, M Mikhailidis, DP Mantzoros, CS AF Katsiki, Niki Rizzo, Manfredi Mikhailidis, Dimitri P. Mantzoros, Christos S. TI New-Onset Diabetes and Statins: Throw the Bath Water Out, But, Please, Keep the Baby! SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Editorial Material ID DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY-ARTERY-DISEASE; ALL-CAUSE MORTALITY; PRIMARY PREVENTION; CARDIOVASCULAR-DISEASE; SECONDARY PREVENTION; GLUCOSE-METABOLISM; HEART-DISEASE; RISK; METAANALYSIS C1 [Katsiki, Niki] Aristotle Univ Thessaloniki, Hippocrat Hosp, Sch Med, Propedeut Dept Internal Med 2, GR-54006 Thessaloniki, Greece. [Rizzo, Manfredi] Univ Palermo, Biomed Dept Internal Med & Med Specialties, I-90133 Palermo, Italy. [Rizzo, Manfredi] Euromediterranean Inst Sci & Technol, Palermo, Italy. UCL, Sch Med, Univ Coll, Dept Clin Biochem,Vasc Prevent Clin,Royal Free Ho, London W1N 8AA, England. [Mantzoros, Christos S.] Harvard Univ, Sch Med, VA Healthcare Syst, Beth Israel Deaconess Med Ctr,Div Endocrinol Diab, Boston, MA 02115 USA. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA 02115 USA. RP Katsiki, N (reprint author), Aristotle Univ Thessaloniki, Hippocrat Hosp, Sch Med, Propedeut Dept Internal Med 2, GR-54006 Thessaloniki, Greece. EM cmantzor@bidmc.harvard.edu OI RIZZO, Manfredi/0000-0002-9549-8504 NR 56 TC 12 Z9 12 U1 2 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD APR PY 2015 VL 64 IS 4 BP 471 EP 475 DI 10.1016/j.metabol.2014.11.001 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CC8IZ UT WOS:000350613000001 PM 25484289 ER PT J AU Shoup, TM Bonab, AA Wilson, AA Vasdev, N AF Shoup, Timothy M. Bonab, Ali A. Wilson, Alan A. Vasdev, Neil TI Synthesis and Preclinical Evaluation of [F-18]FCHC for Neuroimaging of Fatty Acid Amide Hydrolase SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE [F-18]FCHC; Fatty acid amide hydrolase; FAAH; Positron emission tomography; PET; Rodents ID POSITRON-EMISSION-TOMOGRAPHY; CANNABINOID CB1 RECEPTORS; SELECTIVE FAAH INHIBITOR; IN-VIVO EVALUATION; HUMAN BRAIN; INFLAMMATORY PAIN; NERVOUS-SYSTEM; PET; ANANDAMIDE; ENZYME AB Fatty acid amide hydrolase (FAAH), a catabolic enzyme which regulates lipid transmitters in the endocannabinoid system, is an avidly sought therapeutic and positron emission tomography (PET) imaging target for studies involving addiction and neurological disorders. We report the synthesis of a new fluorine-18-labeled FAAH inhibitor, trans-3-(4, 5-dihydrooxazol-2-yl)phenyl-4-[F-18]fluorocyclohexylcarbamate ([F-18]FCHC), and its evaluation in rat brain. The synthesis of [F-18]FCHC was conducted via a 3-step, 1-pot reaction, resulting in uncorrected radiochemical yields between 10 and 20 % (n = 5) relative to [F-18]fluoride, with specific activities of > 5 Ci/mu mol at the end of the synthesis. The radiosynthesis was seamlessly automated using a commercial radiofluorination apparatus. Ex vivo biodistribution and preliminary PET imaging studies were carried out in male Sprague-Dawley rats. Rat brain biodistribution at 2 min post-injection showed a standard uptake value of 4.6 +/- 0.1 in the cortex, which increased to 7.8 +/- 0.1 at 40 min. Pretreatment with the selective FAAH inhibitor URB597 reduced uptake of radioactivity in all brain regions by > 90 %, with 98 % blockade in the FAAH-rich cortex. PET imaging was consistent with biodistribution studies. [F-18]FCHC appears to be a highly sensitive F-18-labeled radiotracer for imaging FAAH in the central nervous system, and these results warrant further imaging in nonhuman primates. C1 [Shoup, Timothy M.; Bonab, Ali A.; Vasdev, Neil] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. [Shoup, Timothy M.; Bonab, Ali A.; Vasdev, Neil] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Wilson, Alan A.] Univ Toronto, Res Imaging Ctr, Ctr Addict & Mental Hlth, Toronto, ON M5T 1R8, Canada. [Wilson, Alan A.] Univ Toronto, Dept Psychiat, Toronto, ON M5T 1R8, Canada. RP Vasdev, N (reprint author), Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. EM vasdev.neil@mgh.harvard.edu FU NIH [1R21MH094424] FX This work was supported by the NIH Grant No. 1R21MH094424 to AAW. We would like to thank Dr. Jun Parkes for her assistance with the radiochemistry and animal dissection experiments. NR 45 TC 3 Z9 3 U1 5 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 EI 1860-2002 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD APR PY 2015 VL 17 IS 2 BP 257 EP 263 DI 10.1007/s11307-014-0789-1 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CD4YO UT WOS:000351092900013 PM 25273322 ER PT J AU Puram, SV Tward, AD Jung, DH Dilger, AE Herrmann, BS Duhaime, AC Barker, FG Lee, DJ AF Puram, Sidharth V. Tward, Aaron D. Jung, David H. Dilger, Amanda E. Herrmann, Barbara S. Duhaime, Ann-Christine Barker, Fred G., II Lee, Daniel J. TI Auditory Brainstem Implantation in a 16-Month-Old Boy With Cochlear Hypoplasia SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Auditory brainstem implant; Infant, non-NF2; Pediatric ID CHILDREN; MALFORMATIONS; NERVE AB Objective: To determine the safety and feasibility of auditory brainstem implantation in children younger than 5 years. Patient(s): Patients younger than 5 years who were not candidates for cochlear implantation because of anatomic considerations were included in the analyses. Intervention(s): Auditory brainstem implantation via retrosigmoid craniotomy. Main Outcome Measure(s): Audiologic, speech, quality of life, and safety outcomes were assessed. Results: Auditory brainstem implantation was performed in a 16-month-old male infant with bilateral cochlear hypoplasia and cochlear nerve hypoplasia after a prior aborted attempt at cochlear implantation. Intraoperatively, multiphasic evoked auditory brainstem responses (EABRs) characteristic of synchronized responses of central auditory pathways were obtained on multiple electrodes. There were no complications in the immediate postoperative period, and the child was discharged home on Postoperative Day 4. Audiologic testing 2 and 4 months after activation indicated sound detection between 45 and 70 dB HL for warble tones, improvements in Infant Meaningful Auditory Integration Scale scores, and subjective gains in sound awareness, as well as quality of life measures. There were no major or minor complications of the procedure. Conclusion: Based on our experience in combination with the work of others internationally, auditory brainstem implantation is feasible and safe in children younger than 5 years. C1 [Puram, Sidharth V.; Tward, Aaron D.; Jung, David H.; Dilger, Amanda E.; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Puram, Sidharth V.; Tward, Aaron D.; Jung, David H.; Dilger, Amanda E.; Herrmann, Barbara S.; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Herrmann, Barbara S.] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. [Duhaime, Ann-Christine] Massachusetts Gen Hosp, Dept Pediat Neurosurg, Boston, MA 02114 USA. [Duhaime, Ann-Christine; Barker, Fred G., II] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Duhaime, Ann-Christine; Barker, Fred G., II] Harvard Univ, Sch Med, Dept Surg Neurosurg, Boston, MA USA. RP Lee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Daniel_Lee@meei.harvard.edu NR 13 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD APR PY 2015 VL 36 IS 4 BP 618 EP 624 PG 7 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA CD3SI UT WOS:000351000600010 PM 25473959 ER PT J AU Murphy, TM O'Donovan, A Mullins, N O'Farrelly, C McCann, A Malone, K AF Murphy, Therese M. O'Donovan, Aoife Mullins, Niamh O'Farrelly, Cliona McCann, Amanda Malone, Kevin TI Anxiety is associated with higher levels of global DNA methylation and altered expression of epigenetic and interleukin-6 genes SO PSYCHIATRIC GENETICS LA English DT Article DE anxiety; DNA methylation; DNA methyltransferase; inflammation; interleukin-6 ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; DEPRESSION SCALE; HOSPITAL ANXIETY; UP-REGULATION; CANCER CELLS; METHYLTRANSFERASE; STRESS; BLOOD; PROTEIN; GROWTH AB ObjectivesAnxiety is associated with elevated levels of the inflammatory cytokine interleukin-6 (IL-6) and an increased risk for diseases with an inflammatory aetiology. In cancer, higher levels of IL-6 have been associated with increased expression of the epigenetic enzymes DNMT1 and Enhancer of Zeste Homolog 2 (EZH2). However, the relationship between IL-6 and DNA methyltransferases (DNMTs) and EZH2 expression has not previously been examined in anxious individuals.MethodsGlobal DNA methylation levels were measured using the Methylflash Methylated DNA Quantification Kit and gene expression levels of the DNMT and EZH2 genes in anxious (n=25) and nonanxious individuals (n=22) were compared using quantitative real-time PCR. Specifically, we investigated whether global DNA methylation or aberrant expression of these genes was correlated with IL-6 mRNA and protein serum levels in anxious individuals.ResultsAnxious participants had significantly higher levels of global DNA methylation compared with controls (P=0.001). There were no differences in the mean mRNA expression levels of the DNMT1/3A/3B, EZH2 and IL-6 genes in anxious individuals compared with controls. However, the expression of DNMT1/3A, EZH2 and IL-6 genes increases with increasing Hospital Anxiety and Depression Scale-Anxiety scores in the anxious cohort only. Interestingly, IL-6 gene expression was correlated strongly with DNMT1/3A/3B and EZH2 expression, highlighting a potential relationship between IL-6 and important epigenetic regulatory enzymes.ConclusionThis study provides novel insight into the relationship between anxiety, epigenetics and IL-6. Moreover, our findings support the hypothesis that changes in DNA methylation profiles may contribute to the biology of anxiety. C1 [Murphy, Therese M.] Univ Exeter, Sch Med, Royal Devon & Exeter Hosp, Exeter EX2 5DW, Devon, England. [O'Donovan, Aoife] Dept Psychiat, San Francisco, CA USA. [O'Donovan, Aoife] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA USA. [Mullins, Niamh; Malone, Kevin] St Vincents Univ Hosp, Educ & Res Ctr, Dept Psychiat & Mental Hlth Res, Dublin, Ireland. [McCann, Amanda] Univ Coll Dublin, UCD Sch Med & Med Sci, UCD Conway Inst Biomol & Biomed Res, Dublin 2, Ireland. [O'Farrelly, Cliona] Trinity Coll Dublin, Sch Biochem & Immunol, Dublin, Ireland. RP Murphy, TM (reprint author), Univ Exeter, Sch Med, Royal Devon & Exeter Hosp, Exeter EX2 5DW, Devon, England. EM murphyth@tcd.ie RI Murphy, Therese/C-7481-2014; OI Mullins, Niamh/0000-0001-8021-839X; Murphy, Therese/0000-0002-7647-2798; Malone, Kevin M/0000-0001-5665-4706 FU Craig-Dobbin Newman Fellowship in Mental Health; Society in Science - The Branco Weiss Fellowship FX Funding for this study was provided by the Craig-Dobbin Newman Fellowship in Mental Health (T.M. and A.O'D), Society in Science - The Branco Weiss Fellowship (A.O'D). NR 37 TC 7 Z9 7 U1 3 U2 26 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0955-8829 EI 1473-5873 J9 PSYCHIAT GENET JI Psychiatr. Genet. PD APR PY 2015 VL 25 IS 2 BP 71 EP 78 DI 10.1097/YPG.0000000000000055 PG 8 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA CD0GW UT WOS:000350749700003 PM 25350786 ER PT J AU Hendriksen, E Williams, E Sporn, N Greer, J DeGrange, A Koopman, C AF Hendriksen, Ellen Williams, Emma Sporn, Nora Greer, Joseph DeGrange, Alexandra Koopman, Cheryl TI Worried together: a qualitative study of shared anxiety in patients with metastatic non-small cell lung cancer and their family caregivers SO SUPPORTIVE CARE IN CANCER LA English DT Article DE Lung cancer; Patients; Caregivers; Anxiety; Uncertainty; Loss ID INFORMAL CARERS; SURVIVORS; HEALTH; DEPRESSION; DISORDERS; CONTEXTS; PARTNERS; SYMPTOMS; ILLNESS AB Anxiety is prevalent, distressing, and understudied among patients with advanced lung cancer and their family caregivers. Preliminary evidence suggests that anxiety is not only present in both patients and caregivers but shared by the dyad. Few studies have examined the nature of shared anxiety and its impact on patient-caregiver dyads. This study was developed to identify shared causes and manifestations of anxiety experienced by patients with stage IV non-small cell lung cancer (NSCLC) and their primary caregivers. Data were collected through in-depth semi-structured interviews with ten matched patient-caregiver dyads and one unmatched patient (N = 21) recruited from two comprehensive cancer care centers. Using grounded theory, eight themes emerged characterizing shared causes and manifestations of anxiety: (1) uncertainty, (2) loss and impending loss, (3) changing roles, (4) conflict outside the dyad, (5) finances, (6) physical symptoms, (7) fears of decline and dying, and (8) life after the patient's passing. All themes were shared by patients and caregivers. Implications for future research include the development and evaluation of interventions to reduce anxiety in cancer patient-caregiver dyads. C1 [Hendriksen, Ellen; Koopman, Cheryl] Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, Stanford, CA 94305 USA. [Williams, Emma; DeGrange, Alexandra] PGSP Stanford Psy D Consortium, Palo Alto, CA USA. [Sporn, Nora] Univ Kansas, Dept Psychol, Lawrence, KS 66045 USA. [Greer, Joseph] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Greer, Joseph] Harvard Univ, Sch Med, Boston, MA USA. RP Hendriksen, E (reprint author), Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, MC 5718, Stanford, CA 94305 USA. EM ehendrik@stanford.edu OI Rivera, Alexandra/0000-0001-6649-9615 FU National Cancer Institute [5R03CA159707-02] FX This study was supported by grant number 5R03CA159707-02 from the National Cancer Institute. The authors would like to thank the patients and caregivers who participated in this study and the thoracic oncology teams at the Massachusetts General Hospital Cancer Center and the Stanford Cancer Center. NR 34 TC 4 Z9 4 U1 0 U2 10 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 APR PY 2015 VL 23 IS 4 BP 1035 EP 1041 DI 10.1007/s00520-014-2431-9 PG 7 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA CC6RY UT WOS:000350496500019 PM 25277959 ER PT J AU Redeker, NS Pigeon, WR Boudreau, EA AF Redeker, Nancy S. Pigeon, Wilfred R. Boudreau, Eilis A. TI Incorporating measures of sleep quality into cancer studies SO SUPPORTIVE CARE IN CANCER LA English DT Review DE Sleep quality; Sleep-wake cycle; Sleep measurement methods; Insomnia; Cancer; Sleep apnea ID COGNITIVE-BEHAVIOR THERAPY; CLOCK GENE-EXPRESSION; STAGE BREAST-CANCER; DAYTIME SLEEPINESS; PROSTATE-CANCER; RADIATION-THERAPY; INFLAMMATORY MARKERS; CLINICAL ONCOLOGY; FAMILY CAREGIVERS; FATIGUE INVENTORY AB Sleep disturbance may influence the development of cancer and responses to treatment. It is also closely tied to recovery and quality of life in cancer patients, survivors, and caregivers, and recent studies have begun to show beneficial effects of sleep-promoting interventions. Despite the importance of sleep to cancer and its treatment and the availability of numerous tools for measuring sleep quality and quantity, sleep measurements are underutilized in cancer studies. This review, written for cancer researchers interested in incorporating sleep measures into their studies, is designed to raise awareness about the importance of sleep and suggests strategies for including sleep evaluation in cancer studies. Inclusion of readily available sleep measures may ultimately improve cancer care by facilitating studies that lead to a greater understanding of how sleep and sleep disturbance influence all aspects of cancer care and the patient experience. C1 [Redeker, Nancy S.] Yale Univ, Sch Nursing, West Haven, CT 06516 USA. [Pigeon, Wilfred R.] Canandaigua VA Med Ctr, Canandaigua, NY 14424 USA. [Pigeon, Wilfred R.] Univ Rochester, Sleep & Neurophysiol Res Lab, Med Ctr, Rochester, NY 14642 USA. [Boudreau, Eilis A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Boudreau, Eilis A.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA. [Boudreau, Eilis A.] Portland VA Med Ctr, Epilepsy Ctr Excellence, Portland, OR 97239 USA. RP Redeker, NS (reprint author), Yale Univ, Sch Nursing, West Campus,POB 27399, West Haven, CT 06516 USA. EM nancy.redeker@yale.edu RI Redeker, Nancy/Q-8252-2016 OI Redeker, Nancy/0000-0001-7817-2708 FU Sleep Research Network; [5P20NR014126]; [RR028183]; [TR000172] FX This work was funded by 5P20NR014126 (Redeker), RR028183 and TR000172 (Kupfer), and the Sleep Research Network, a consortium of sleep researchers representing the CTSA program. NR 106 TC 2 Z9 2 U1 6 U2 23 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 APR PY 2015 VL 23 IS 4 BP 1145 EP 1155 DI 10.1007/s00520-014-2537-0 PG 11 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA CC6RY UT WOS:000350496500034 PM 25510361 ER PT J AU Ullery, BW Kalapatapu, V AF Ullery, Brant W. Kalapatapu, Venkat TI Bilateral reperfusion injury after carotid endarterectomy with contralateral carotid occlusion SO VASCULAR LA English DT Article DE Reperfusion injury; carotid endarterectomy; contralateral carotid occlusion; hyperperfusion syndrome; high risk ID CEREBRAL HYPERPERFUSION SYNDROME; INTRACEREBRAL HEMORRHAGE; INTRACRANIAL HEMORRHAGE; ARTERY OCCLUSION; RISK; REVASCULARIZATION; PREVENTION; STENOSIS; EXPERIENCE; STROKES AB Cerebral hyperperfusion syndrome represents a clinical spectrum characterized by severe unilateral headache, acute changes in mental status, vomiting, seizures, focal neurologic deficits, and, in its most severe form, intracranial hemorrhage. With the exception of one early case report, reperfusion injury to the brain following carotid endarterectomy has been reported only ipsilateral to the side of surgery. We report the unique case of a patient with symptomatic severe right internal carotid artery stenosis and contralateral carotid occlusion who underwent carotid endarterectomy complicated by cerebral hyperperfusion syndrome and associated bilateral intracranial hemorrhage. C1 [Ullery, Brant W.] Stanford Univ, Div Vasc Surg, Stanford, CA 94305 USA. [Kalapatapu, Venkat] Philadelphia Vet Affairs Med Ctr, Dept Surg, Philadelphia, PA USA. RP Ullery, BW (reprint author), Stanford Univ, Med Ctr, Div Vasc Surg, 300 Pasteur Dr,Suite H3600, Stanford, CA 94305 USA. EM ullery@gmail.com NR 36 TC 0 Z9 0 U1 1 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1708-5381 EI 1708-539X J9 VASCULAR JI Vascular PD APR PY 2015 VL 23 IS 2 BP 188 EP 192 DI 10.1177/1708538114538254 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CD3EP UT WOS:000350961000015 PM 24903528 ER PT J AU Arpino, PA Goeller, AJ Fatalo, A Van Cott, EM AF Arpino, Paul A. Goeller, Adrienne J. Fatalo, Anthony Van Cott, Elizabeth M. TI Evaluation of 2 Nomogram-Based Strategies for Dosing Argatroban in Patients With Known or Suspected Heparin-Induced Thrombocytopenia SO CLINICAL AND APPLIED THROMBOSIS-HEMOSTASIS LA English DT Article DE argatroban; direct thrombin inhibitors; sliding scale; nomogram; anticoagulants ID THROMBOSIS; THERAPY AB No study has compared 2 different dosing strategies for argatroban titration nor has any published nomogram demonstrated improvement in outcomes. This study was conducted to evaluate the effectiveness of 2 argatroban nomograms on reaching therapeutic anticoagulation. Patients treated with argatroban were separated into 2 sliding scale groups, percentage adjustments (PAs) and predefined dose increments (PDIs). The primary outcome was the time to reach a therapeutic activated partial thromboplastin time (aPTT). The average initial dose and dose to achieve a therapeutic aPTT were similar between the groups. There was also no difference in the number of dose changes. The time to reach a therapeutic aPTT was 2 hours shorter in the PDI compared to the PA group, 8 +/- 4 hours versus 10 +/- 4 hours, P = .015. This study demonstrates a significant time advantage associated with a PDI nomogram compared to a PA nomogram but no difference with respect to the number of rate changes. C1 [Arpino, Paul A.; Goeller, Adrienne J.; Fatalo, Anthony] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. [Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Arpino, PA (reprint author), Massachusetts Gen Hosp, Dept Pharm, 55 Fruit St, Boston, MA 02114 USA. EM parpino@partners.org NR 18 TC 2 Z9 2 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1076-0296 EI 1938-2723 J9 CLIN APPL THROMB-HEM JI Clin. Appl. Thromb.-Hemost. PD APR PY 2015 VL 21 IS 3 BP 260 EP 265 DI 10.1177/1076029613501542 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CC6QV UT WOS:000350492800011 PM 23965335 ER PT J AU Stover, DG Wagle, N AF Stover, Daniel G. Wagle, Nikhil TI Precision Medicine in Breast Cancer: Genes, Genomes, and the Future of Genomically Driven Treatments SO CURRENT ONCOLOGY REPORTS LA English DT Article DE Breast cancer; Genomics; Sequencing; Precision cancer medicine; Personalized medicine ID ESTROGEN-RECEPTOR-ALPHA; CLINICAL TUMOR SAMPLES; CELL LUNG-CANCER; MUTATIONAL PROCESSES; EXPRESSION PATTERNS; MOLECULAR PORTRAITS; ACQUIRED-RESISTANCE; PATHWAY ALTERATIONS; SOMATIC MUTATIONS; ENDOCRINE-THERAPY AB Remarkable progress in sequencing technology over the past 20 years has made it possible to comprehensively profile tumors and identify clinically relevant genomic alterations. In breast cancer, the most common malignancy affecting women, we are now increasingly able to use this technology to help specify the use of therapies that target key molecular and genetic dependencies. Large sequencing studies have confirmed the role of well-known cancer-related genes and have also revealed numerous other genes that are recurrently mutated in breast cancer. This growing understanding of patient-to-patient variability at the genomic level in breast cancer is advancing our ability to direct the appropriate treatment to the appropriate patient at the appropriate time-a hallmark of "precision cancer medicine." This review focuses on the technological advances that have catalyzed these developments, the landscape of mutations in breast cancer, the clinical impact of genomic profiling, and the incorporation of genomic information into clinical care and clinical trials. C1 [Stover, Daniel G.; Wagle, Nikhil] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Wagle, Nikhil] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Wagle, Nikhil] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Wagle, N (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM NWAGLE@PARTNERS.ORG OI Stover, Daniel/0000-0001-9003-8165 FU Susan G. Komen Breast Cancer Foundation; Foundation Medicine FX Daniel G. Stover has received a grant from The Susan G. Komen Breast Cancer Foundation.; Nikhil Wagle has received consultancy fees from and has stock options in Foundation Medicine. NR 94 TC 5 Z9 5 U1 1 U2 20 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3790 EI 1534-6269 J9 CURR ONCOL REP JI Curr. Oncol. Rep. PD APR PY 2015 VL 17 IS 4 AR 15 DI 10.1007/s11912-015-0438-0 PG 11 WC Oncology SC Oncology GA CC3GV UT WOS:000350235700002 PM 25708799 ER PT J AU Omobono, MA Zhao, X Furlong, MA Kwon, CH Gill, TJ Randolph, MA Redmond, RW AF Omobono, Mark A. Zhao, Xing Furlong, Michael A. Kwon, Chi-Heon Gill, Thomas J. Randolph, Mark A. Redmond, Robert W. TI Enhancing the stiffness of collagen hydrogels for delivery of encapsulated chondrocytes to articular lesions for cartilage regeneration SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE collagen; cartilage tissue engineering; crosslinking; hydrogel; scaffold ID CROSS-LINKED COLLAGEN; MESENCHYMAL STEM-CELLS; DERMAL SHEEP COLLAGEN; TENDON TISSUE; CARBODIIMIDE; LINKING; SCAFFOLDS; MEMBRANES AB This study investigated a dual crosslinking paradigm, consisting of (a) photocrosslinking with Rose Bengal (RB) and green light followed by (b) chemical crosslinking with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), and N-hydroxysuccinimide (NHS) to enhance collagen gel stiffness. In group 1, 50 L collagen constructs of 2% (w/v) type I collagen containing 10 M RB were allowed to gel spontaneously at 37 degrees C. In group 2, the spontaneous gels were exposed to green light (532 nm). In group 3, the photochemically crosslinked gels were subsequently treated with a 1-h exposure to 33 mM EDC/6 mM NHS. Samples (n=18) were subjected to 0.08% (w/v) collagenase digestion, and the storage modulus of samples was measured by rheometry. Viability of encapsulated chondrocytes was measured by live/dead assay. Chondrocytes were 95% viable in all constructs at 10 days in vitro. Resistance to collagenase digestion increased as; spontaneous gels (2 h)24 h). The storage modulus of dual-crosslinked constructs was increased 5-fold over both photocrosslinked and spontaneous gels. As the dual crosslinking paradigm did not reduce encapsulated chondrocyte viability, these crosslinked collagen hydrogels could be a useful tool for the practical delivery of encapsulated chondrocytes to articular defects. (c) 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1332-1338, 2015. C1 [Omobono, Mark A.; Randolph, Mark A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Plast Surg Res Lab, Boston, MA 02114 USA. [Omobono, Mark A.; Furlong, Michael A.; Kwon, Chi-Heon; Redmond, Robert W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Zhao, Xing; Gill, Thomas J.; Randolph, Mark A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped, Boston, MA 02114 USA. [Zhao, Xing] Univ Med Ctr Utrecht, Dept Orthopaed, Utrecht, Netherlands. RP Redmond, RW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. EM redmond@helix.mgh.harvard.edu RI Randolph, Mark/A-4406-2009 FU AO/ASIF Foundation; U.S. Department of Defense [W81XWH-10-1-0791] FX Contract grant sponsor: AO/ASIF Foundation and the U.S. Department of Defense; contract grant number: W81XWH-10-1-0791 NR 30 TC 2 Z9 2 U1 5 U2 45 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1549-3296 EI 1552-4965 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD APR PY 2015 VL 103 IS 4 BP 1332 EP 1338 DI 10.1002/jbm.a.35266 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA CC5JQ UT WOS:000350395300005 PM 25044419 ER PT J AU Segawa, JA Tourville, JA Beal, DS Guenther, FH AF Segawa, Jennifer A. Tourville, Jason A. Beal, Deryk S. Guenther, Frank H. TI The Neural Correlates of Speech Motor Sequence Learning SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID AUDITORY-FEEDBACK CONTROL; SURFACE-BASED ANALYSIS; EVENT-RELATED FMRI; CORTICAL SURFACE; DEVELOPMENTAL DYSLEXIA; CONSONANT CLUSTERS; COORDINATE SYSTEM; ANTERIOR INSULA; FRONTAL-CORTEX; BASAL GANGLIA AB Speech is perhaps the most sophisticated example of a species-wide movement capability in the animal kingdom, requiring split-second sequencing of approximately 100 muscles in the respiratory, laryngeal, and oral movement systems. Despite the unique role speech plays in human interaction and the debilitating impact of its disruption, little is known about the neural mechanisms underlying speech motor learning. Here, we studied the behavioral and neural correlates of learning new speech motor sequences. Participants repeatedly produced novel, meaningless syllables comprising illegal consonant clusters (e.g., GVAZF) over 2 days of practice. Following practice, participants produced the sequences with fewer errors and shorter durations, indicative of motor learning. Using fMRI, we compared brain activity during production of the learned illegal sequences and novel illegal sequences. Greater activity was noted during production of novel sequences in brain regions linked to non-speech motor sequence learning, including the BG and pre-SMA. Activity during novel sequence production was also greater in brain regions associated with learning and maintaining speech motor programs, including lateral premotor cortex, frontal operculum, and posterior superior temporal cortex. Measures of learning success correlated positively with activity in left frontal operculum and white matter integrity under left posterior superior temporal sulcus. These findings indicate speech motor sequence learning relies not only on brain areas involved generally in motor sequencing learning but also those associated with feedback-based speech motor learning. Furthermore, learning success is modulated by the integrity of structural connectivity between these motor and sensory brain regions. C1 [Segawa, Jennifer A.; Tourville, Jason A.; Beal, Deryk S.; Guenther, Frank H.] Boston Univ, Boston, MA 02215 USA. [Beal, Deryk S.] Univ Alberta, Edmonton, AB T6G 2M7, Canada. [Guenther, Frank H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Segawa, JA (reprint author), Boston Univ, Ctr Computat Neurosci & Neural Technol, 677 Beacon St, Boston, MA 02215 USA. EM jsegawa@bu.edu OI Beal, Deryk/0000-0001-9488-4326 FU National Institute on Deafness and Other Communication Disorders of the National Institutes of Health [R01DC007683] FX Research reported in this publication was supported by the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health under award number R01DC007683. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 84 TC 3 Z9 3 U1 3 U2 16 PU MIT PRESS PI CAMBRIDGE PA ONE ROGERS ST, CAMBRIDGE, MA 02142-1209 USA SN 0898-929X EI 1530-8898 J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD APR PY 2015 VL 27 IS 4 BP 819 EP 831 DI 10.1162/jocn_a_00737 PG 13 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA CC7YO UT WOS:000350585000014 PM 25313656 ER PT J AU Hemingway, MW O'Malley, C Silvestri, S AF Hemingway, Maureen White O'Malley, Catherine Silvestri, Sandra TI Safety Culture and Care: A Program to Prevent Surgical Errors SO AORN JOURNAL LA English DT Article DE safety culture; quality assurance; safety program; preventing surgical errors; process improvement ID HEALTH-CARE AB Surgical errors are under scrutiny in health care as part of ensuring a culture of safety in which patients receive quality care. Hospitals use safety measures to compare their performance against industry benchmarks. To understand patient safety issues, health care providers must have processes in place to analyze and evaluate the quality of the care they provide. At one facility, efforts made to improve its quality and safety led to the development of a robust safety program with resources devoted to enhancing the culture of safety in the Perioperative Services department. Improvement initiatives included changing processes for safety reporting and performance improvement plans, adding resources and nurse roles, and creating communication strategies around adverse safety events and how to improve care. One key outcome included a 54% increase in the percentage of personnel who indicated in a survey that they would speak up if they saw something negatively affecting patient care. (C) AORN, Inc, 2015. C1 [Hemingway, Maureen White; O'Malley, Catherine; Silvestri, Sandra] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hemingway, MW (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 11 TC 1 Z9 2 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0001-2092 J9 ASSOC OPER ROOM NURS JI AORN J. PD APR PY 2015 VL 101 IS 4 BP 404 EP 412 DI 10.1016/j.aorn.2015.01.002 PG 9 WC Nursing SC Nursing GA DI4BR UT WOS:000373445700007 PM 25835006 ER PT J AU Kehl, KL Landrum, MB Arora, NK Ganz, PA van Ryn, M Mack, JW Keating, NL AF Kehl, Kenneth L. Landrum, Mary Beth Arora, Neeraj K. Ganz, Patricia A. van Ryn, Michelle Mack, Jennifer W. Keating, Nancy L. TI Association of Actual and Preferred Decision Roles With Patient-Reported Quality of Care Shared Decision Making in Cancer Care SO JAMA ONCOLOGY LA English DT Article ID BREAST-CANCER; OUTCOMES RESEARCH; SURVEILLANCE CONSORTIUM; PREFERENCES; WOMEN; SATISFACTION; INVOLVEMENT; EXPERIENCE; PLAY AB IMPORTANCE Shared decision making is associated with improved patient-reported outcomes of cancer treatment, but not all patients prefer to participate in medical decisions. Results from studies of the effect of matching between actual and preferred medical decision roles on patients' perceptions of care quality have been conflicting. OBJECTIVES To determine whether shared decision making was associated with patient ratings of care quality and physician communication and whether patients' preferred decision roles modified those associations. DESIGN, SETTING, AND PARTICIPANTS We performed a population-and health system-based survey of participants in the Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) study diagnosed with lung and/or colorectal cancer between 2003 and 2005 (56% with colorectal cancer, 40% with non-small-cell lung cancer, and 5% with small-cell lung cancer). The CanCORS study included 9737 patients (cooperation rate among patients contacted, 59.9%) treated in integrated care delivery systems, academic institutions, private offices, and Veterans Affairs hospitals. The medical records were abstracted between October 11, 2005, and April 30, 2009; all analyses were conducted between 2013 and 2014. INTERVENTIONS We surveyed patients specifically about their preferred roles in cancer treatment decisions and their actual roles in decisions about surgery, chemotherapy, and radiation therapy. We analyzed the responses of 5315 patients who completed baseline surveys and reported decision roles for a total of 10 817 treatment decisions and assessed associations of patients' decision roles with patient-reported quality of care and physician communication. MAIN OUTCOMES AND MEASURES The outcomes (identified before data collection) included patient-reported excellent quality of care and top ratings (highest score) on a physician communication scale. RESULTS After adjustment, patients describing physician-controlled (vs shared) decisions were less likely to report excellent quality of care (odds ratio [OR], 0.64; 95% CI, 0.54-0.75; P <.001). Patients' preferred decision roles did not modify this effect (P =.29 for the interaction). Patients describing either actual or preferred physician-controlled (vs shared) roles were less likely to provide a top rating of physician communication (OR, 0.55; 95% CI, 0.45-0.66; P <.001, and OR, 0.67; 95% CI, 0.51-0.87; P =.002, respectively). The preferred role did not modify the effect of the actual role (P =.76 for interaction). CONCLUSIONS AND RELEVANCE Physician-controlled decisions regarding lung or colorectal cancer treatment were associated with lower ratings of care quality and physician communication. These effects were independent of patients' preferred decision roles, underscoring the importance of seeking to involve all patients in decision making about their treatment. C1 [Kehl, Kenneth L.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Houston, TX 77030 USA. [Landrum, Mary Beth; Keating, Nancy L.] Harvard Med Sch, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. [Arora, Neeraj K.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [van Ryn, Michelle] Mayo Clin, Div Hlth Care Policy & Res, Rochester, MN USA. [Mack, Jennifer W.] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. RP Keating, NL (reprint author), Harvard Med Sch, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM keating@hcp.med.harvard.edu FU National Cancer Institute (NCI) [U01 CA093344, U01 CA093332, U01 CA093324, U01 CA093348, U01 CA093329, U01 CA093339, U01 CA093326]; Department of Veterans Affairs [CRS 02-164]; NCI grant [1R01CA164021-01A1] FX This work of the CanCORS Consortium was supported by grants from the National Cancer Institute (NCI) to the Statistical Coordinating Center (U01 CA093344) and to the following NCI-supported Primary Data Collection and Research Centers: Dana Farber Cancer Institute/Cancer Research Network (U01 CA093332), Harvard Medical School/Northern California Cancer Center (U01 CA093324), RAND Corporation/University of California, Los Angeles (U01 CA093348), University of Alabama at Birmingham (U01 CA093329), University of Iowa (U01 CA093339), and University of North Carolina (U01 CA093326); it was also supported by a Department of Veterans Affairs grant to the Durham VA Medical Center (CRS 02-164). Drs Keating and Landrum were supported by NCI grant 1R01CA164021-01A1. NR 30 TC 16 Z9 16 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA EI 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD APR PY 2015 VL 1 IS 1 BP 50 EP 58 DI 10.1001/jamaoncol.2014.112 PG 9 WC Oncology SC Oncology GA DW0RR UT WOS:000383349900009 PM 26182303 ER PT J AU Brooks, GA Jacobson, JO Schrag, D AF Brooks, Gabriel A. Jacobson, Joseph O. Schrag, Deborah TI Clinician Perspectives on Potentially Avoidable Hospitalizations in Patients With Cancer SO JAMA ONCOLOGY LA English DT Letter C1 [Brooks, Gabriel A.; Jacobson, Joseph O.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Schrag, Deborah] Harvard Med Sch, Boston, MA USA. RP Brooks, GA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM gabriel_brooks@dfci.harvard.edu FU NCI NIH HHS [R25 CA092203] NR 0 TC 5 Z9 5 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA EI 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD APR PY 2015 VL 1 IS 1 BP 109 EP 110 DI 10.1001/jamaoncol.2014.155 PG 2 WC Oncology SC Oncology GA DW0RR UT WOS:000383349900019 PM 26146663 ER PT J AU Dietzek, A Connelly, K Cotugno, M Bartel, S McDonnell, AM AF Dietzek, Amanda Connelly, Kelly Cotugno, Michael Bartel, Sylvia McDonnell, Anne M. TI Denosumab in hypercalcemia of malignancy: A case series SO JOURNAL OF ONCOLOGY PHARMACY PRACTICE LA English DT Article ID ZOLEDRONIC ACID; BONE METASTASES; BREAST-CANCER; TRIALS AB Background Denosumab is a nuclear factor-kappa ligand monoclonal antibody whose FDA-approved indications include treatment of osteoporosis, bone loss with certain anticancer hormonal agents, and prevention of skeletal-related events in patients with bone metastases from solid tumors. In clinical trials, the incidence of severe hypocalcemia has been reported as 3.1-10.8%. To date, case reports and two clinical trials have reported the use of denosumab in the management of hypercalcemia of malignancy. No reports of denosumab-induced hypocalcemia have been reported for the hypercalcemia of malignancy population. Methods We performed a retrospective chart review of all patients who received denosumab for hypercalcemia of malignancy to describe the effects of denosumab on calcium levels at our institution. Results Seven patients received doses of denosumab for hypercalcemia of malignancy. The most common tumor types were breast cancer (n=3) and hematologic malignancies (n=2). All patients had bone involvement. Two patients received single doses of 60mg. The other five patients received 120mg. The mean corrected calcium levels were 13.7mg/dL and 12.24mg/dL for the days of admission and denosumab administration, respectively (p=0.1889). The mean corrected calcium level for the last known value was 9.92mg/dL, while in house (p=0.0016). Supportive care prior to denosumab included hydration (n=7), bisphosphonates (n=6), and calcitonin (n=5). One patient had a calcium level of 6.6mg/dL on day 4 after denosumab, requiring calcium supplementation and telemetry. Of the seven patients treated with denosumab for hypercalcemia of malignancy at our institution, six patients were discharged alive. Of these, one patient died two days after discharge. Last-known follow-up was a median of 26 days, range, 3-195, for all patients. Conclusions Denosumab helped decrease calcium in patients with hypercalcemia of malignancy. However, symptomatic hypocalcemia may result from denosumab in hypercalcemia of malignancy. C1 [Dietzek, Amanda; Bartel, Sylvia] Dana Farber Canc Inst, Div Pharm, Boston, MA 02215 USA. [Connelly, Kelly] Smilow Canc Hosp Yale New Haven, New Haven, CT USA. [Cotugno, Michael; Bartel, Sylvia; McDonnell, Anne M.] Brigham & Womens Hosp, Dept Pharm, Boston, MA 02115 USA. RP Dietzek, A (reprint author), Dana Farber Canc Inst, Div Pharm, 450 Brookline Ave, Boston, MA 02215 USA. EM amanda_dietzek@dfci.harvard.edu NR 20 TC 2 Z9 2 U1 0 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1078-1552 EI 1477-092X J9 J ONCOL PHARM PRACT JI J. Oncol. Pharm. Pract. PD APR PY 2015 VL 21 IS 2 BP 143 EP 147 DI 10.1177/1078155213518361 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA CC3KS UT WOS:000350248000009 PM 24415364 ER PT J AU Dohner, H Seymour, JF Butrym, A Wierzbowska, A Selleslag, D Jang, JH Cavenagh, JD Kumar, R Schuh, AC Candoni, A Recher, C Sandhu, I del Castillo, TB Al-Ali, HK Martinelli, G Falantes, J Nopenney, R Stone, RM Minden, MD McIntyre, H Songer, S Lucy, LM Beach, CL Dombret, H AF Doehner, H. Seymour, J. F. Butrym, A. Wierzbowska, A. Selleslag, D. Jang, J. H. Cavenagh, J. D. Kumar, R. Schuh, A. C. Candoni, A. Recher, C. Sandhu, I. Bernal del Castillo, T. Al-Ali, H. K. Martinelli, G. Falantes, J. Nopenney, R. Stone, R. M. Minden, M. D. McIntyre, H. Songer, S. Lucy, L. M. Beach, C. L. Dombret, H. TI OVERALL SURVIVAL IN OLDER PATIENTS WITH NEWLY DIAGNOSED AML WITH > 30% BONE MARROW BLASTS AND POOR-RISK CYTOGENETICS TREATED WITH AZACITIDINE: SUBANALYSIS OF THE AZA-AML-001 STUDY SO LEUKEMIA RESEARCH LA English DT Meeting Abstract CT 13th International Symposium on Myelodysplastic Syndromes (MDS) CY APR 29-MAY 02, 2015 CL Washington, DC C1 [Doehner, H.] Univ Ulm Klinikum, Dept Internal Med 3, Ulm, Germany. [Seymour, J. F.] PeterMacCallum Canc Ctr, Dept Haematol, East Melbourne, Vic, Australia. [Butrym, A.] Wroclaw Med Univ, Dept Haematol Blood Neoplasms & Bone Marrow Trans, Wroclaw, Poland. [Wierzbowska, A.] Med Univ Lodz, Dept Hematol, Lodz, Poland. [Selleslag, D.] AZ Sint Jan Brugge Oostende, Div Hematol, Brugge, Belgium. [Jang, J. H.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Hematol Oncol, Seoul, South Korea. [Cavenagh, J. D.] St Bartholomews Hosp, Dept Hematol, London, England. [Kumar, R.] Canc Care Manitoba, Dept Med Oncol & Haematol, Winnipeg, MB, Canada. [Schuh, A. C.; Minden, M. D.] Princess Margaret Canc Ctr, Malignant Hematol, Toronto, ON, Canada. [Candoni, A.] Azienda Osped Univ S Maria Misericordia Udine, Div Hematol, Udine, Italy. [Candoni, A.] Azienda Osped Univ S Maria Misericordia Udine, Bone Marrow Transplantat Unit, Udine, Italy. [Recher, C.] Inst Univ Canc Toulouse Oncopole, Dept Hematol, Toulouse, France. [Sandhu, I.] Univ Alberta Hosp, Dept Oncol, Edmonton, AB T6G 2B7, Canada. [Bernal del Castillo, T.] Univ Oviedo, Hosp Cent Asturias, Dept Hematol, E-33080 Oviedo, Spain. [Al-Ali, H. K.] Univ Hosp Leipzig, Div Hematol & Oncol, Leipzig, Germany. [Martinelli, G.] Inst Hematol & Med Oncol LA Seragnoli, Dept Hematol & Oncol, Bologna, Italy. [Falantes, J.] Hosp Univ Virgen Rocio, Inst BioMed Sevilla, Dept Hematol, Seville, Spain. [Nopenney, R.] Univ Klinikum Essen, Klin Hamatol, Dept Hematol, Essen, Germany. [Stone, R. M.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [McIntyre, H.; Songer, S.; Beach, C. L.] Hoechst Celanese Corp, Clin Dev, Summit, NJ 07901 USA. [Lucy, L. M.] Hoechst Celanese Corp, Dept Biostat, Summit, NJ 07901 USA. [Dombret, H.] Hop St Louis, Dept Hematol, Paris, France. RI Wierzbowska, Agnieszka/S-9449-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 EI 1873-5835 J9 LEUKEMIA RES JI Leuk. Res. PD APR PY 2015 VL 39 SU 1 MA 96 BP S48 EP S49 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA DI0JY UT WOS:000373183500097 ER PT J AU Garcia-Manero, G Fenaux, P Al-Kali, A Baer, MR Sekeres, M Roboz, G Gaidano, G Scott, B Greenberg, P Platzbecker, U Steensma, DP Kambhampati, S Kreuzer, KA Godley, L Collins, R Atallah, E Azarnia, N Petrone, ME Snyder, BR Maniar, M Silverman, LR AF Garcia-Manero, G. Fenaux, P. Al-Kali, A. Baer, M. R. Sekeres, M. Roboz, G. Gaidano, G. Scott, B. Greenberg, P. Platzbecker, U. Steensma, D. P. Kambhampati, S. Kreuzer, K. A. Godley, L. Collins, R. Atallah, E. Azarnia, N. Petrone, M. E. Snyder, B. R. Maniar, M. Silverman, L. R. TI RANDOMIZED PHASE III STUDY OF IV RIGOSERTIB VERSUS BEST SUPPORTIVE CARE (BSC) IN PATIENTS WITH HIGHER-RISK MDS (HR-MDS) AFTER FAILURE OF HYPOMETHYLATING AGENTS (HMAS) SO LEUKEMIA RESEARCH LA English DT Meeting Abstract CT 13th International Symposium on Myelodysplastic Syndromes (MDS) CY APR 29-MAY 02, 2015 CL Washington, DC C1 [Garcia-Manero, G.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Fenaux, P.] Hosp St Louis, Serv Hematol Seniors, Paris, France. [Al-Kali, A.] Mayo Clin, Dept Hematol, Rochester, MN USA. [Baer, M. R.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Sekeres, M.] Cleveland Clin, Dept Hematol Oncol & Blood Disorders, Cleveland, OH 44106 USA. [Roboz, G.] Weill Cornell Med Coll, Leukemia Serv, New York, NY USA. [Gaidano, G.] Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Novara, Italy. [Scott, B.] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA. [Greenberg, P.] Stanford Med Sch, Dept Med Hematol, Stanford, CA USA. [Platzbecker, U.] Univ Klinikum Dresden, Med Klin & Poliklin 1, Dresden, Germany. [Steensma, D. P.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Kambhampati, S.] Univ Kansas, Med Ctr, Dept Internal Med, Westwood, KS USA. [Kreuzer, K. A.] Univ Klinikum Koln, Dept Internal Med, Cologne, Germany. [Godley, L.] Univ Chicago, Med Ctr, Dept Med, Chicago, IL 60637 USA. [Collins, R.] Univ Texas Dallas, Dept Internal Med, Dallas, TX 75230 USA. [Atallah, E.] Med Coll Wisconsin, Froedtert Mem Lutheran Hosp, Div Hematol & Oncol, Milwaukee, WI 53226 USA. [Atallah, E.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Azarnia, N.] Onconova Therapeut Inc, Dept Biometr, Newtown, PA USA. [Petrone, M. E.] Onconova Therapeut Inc, Dept Pharmacovigilance & Med & Sci Commun, Newtown, PA USA. [Snyder, B. R.] Onconova Therapeut Inc, Dept Med & Sci Commun, Newtown, PA USA. [Maniar, M.] Onconova Therapeut Inc, Prod Dev Dept, Newtown, PA USA. [Silverman, L. R.] Icahn Sch Med Mt Sinai, Dept Leukemia, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 EI 1873-5835 J9 LEUKEMIA RES JI Leuk. Res. PD APR PY 2015 VL 39 SU 1 MA 112 BP S57 EP S58 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA DI0JY UT WOS:000373183500113 ER PT J AU Gjini, E Mansour, MARC He, S Nguyen, A Ko, M Sander, J Joung, JK Zhou, Y Zon, LI Rao, A Look, AT AF Gjini, E. Mansour, M. A. R. C. He, S. Nguyen, A. Ko, M. Sander, J. Joung, J. K. Zhou, Y. Zon, L. I. Rao, A. Look, A. T. TI A ZEBRAFISH MODEL OF MYELODYSPLASTIC SYNDROME PRODUCED THROUGH TET2 GENOMIC EDITING SO LEUKEMIA RESEARCH LA English DT Meeting Abstract CT 13th International Symposium on Myelodysplastic Syndromes (MDS) CY APR 29-MAY 02, 2015 CL Washington, DC C1 [Gjini, E.; Mansour, M. A. R. C.; He, S.; Nguyen, A.; Look, A. T.] Dana Farber Canc Inst, Pediat Oncol, Boston, MA 02115 USA. [Ko, M.; Rao, A.] La Jolla Inst Allergy & Immunol, Signaling & Gene Express, La Jolla, CA USA. [Sander, J.; Joung, J. K.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Zhou, Y.; Zon, L. I.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 EI 1873-5835 J9 LEUKEMIA RES JI Leuk. Res. PD APR PY 2015 VL 39 SU 1 MA 25 BP S11 EP S11 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA DI0JY UT WOS:000373183500026 ER PT J AU Komrokji, R Zeidan, A Al Ali, N Padron, E Lancet, J Steensma, D Dezern, A Roboz, G Jabbour, E Sekeres, M Garcia-Manero, G List, A AF Komrokji, R. Zeidan, A. Al Ali, N. Padron, E. Lancet, J. Steensma, D. Dezern, A. Roboz, G. Jabbour, E. Sekeres, M. Garcia-Manero, G. List, A. TI RISK STRATIFICATION OF THERAPY-RELATED MYELODYSPLASTIC SYNDROMES (T-MDS): A REPORT ON BEHALF OF THE MDS CLINICAL RESEARCH CONSORTIUM SO LEUKEMIA RESEARCH LA English DT Meeting Abstract CT 13th International Symposium on Myelodysplastic Syndromes (MDS) CY APR 29-MAY 02, 2015 CL Washington, DC C1 [Komrokji, R.; Al Ali, N.; Padron, E.; Lancet, J.; List, A.] Univ S Florida, H Lee Moffitt Canc Ctr, Malignant Hematol, Tampa, FL 33682 USA. [Zeidan, A.] Yale Univ, Yale Sch Med, New Haven, CT USA. [Steensma, D.] Dana Farber Canc Inst, Med, Boston, MA 02115 USA. [Dezern, A.] Johns Hopkins Univ, Oncol, Baltimore, MD USA. [Roboz, G.] Cornell Univ, Weill Cornell Med Coll, New York, NY 10021 USA. [Jabbour, E.; Garcia-Manero, G.] Univ Texas MD Anderson Canc Ctr, Leukemia, Houston, TX 77030 USA. [Sekeres, M.] Cleveland Clin, Leukemia, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 EI 1873-5835 J9 LEUKEMIA RES JI Leuk. Res. PD APR PY 2015 VL 39 SU 1 MA 320 BP S158 EP S159 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA DI0JY UT WOS:000373183500321 ER PT J AU Komrokji, R Garcia-Manero, G Ades, L Laadem, A Vo, B Prebet, T Stamatoullas, A Boyd, T Delaunay, J Steensma, DP Sekeres, MA Beyne-Rauzy, O Zou, J Attie, KM Sherman, ML Fenaux, P List, AF AF Komrokji, R. Garcia-Manero, G. Ades, L. Laadem, A. Vo, B. Prebet, T. Stamatoullas, A. Boyd, T. Delaunay, J. Steensma, D. P. Sekeres, M. A. Beyne-Rauzy, O. Zou, J. Attie, K. M. Sherman, M. L. Fenaux, P. List, A. F. TI A PHASE 2, DOSE-FINDING STUDY OF SOTATERCEPT (ACE-011) IN PATIENTS WITH LOWER-RISK MYELODYSPLASTIC SYNDROMES (MDS) OR NON-PROLIFERATIVE CHRONIC MYELOMONOCYTIC LEUKEMIA (CMML) AND ANEMIA REQUIRING TRANSFUSION SO LEUKEMIA RESEARCH LA English DT Meeting Abstract CT 13th International Symposium on Myelodysplastic Syndromes (MDS) CY APR 29-MAY 02, 2015 CL Washington, DC C1 [Komrokji, R.; List, A. F.] H Lee Moffitt Canc Ctr & Res Inst, Dept Malignant Hematol, Tampa, FL USA. [Garcia-Manero, G.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Ades, L.; Fenaux, P.] Univ Paris 07, Hop St Louis, Serv Hematol Seniors, Paris, France. [Laadem, A.; Vo, B.] Celgene Corp, Hematol & Oncol, Summit, NJ USA. [Prebet, T.] Inst J Paoli I Calmettes, Dept Oncohematol, F-13009 Marseille, France. [Stamatoullas, A.] Ctr Henri Becquerel, Serv Hematol, F-76038 Rouen, France. [Boyd, T.] Yakima Valley Mem Hosp, North Star Lodge Canc Ctr, Yakima, WA USA. [Delaunay, J.] CHU Nantes, Hotel Dieu, Serv Hematol Clin, F-44035 Nantes 01, France. [Steensma, D. P.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Sekeres, M. A.] Cleveland Clin, Taussig Canc Inst, Leukemia Program, Hematol & Oncol, Cleveland, OH 44106 USA. [Beyne-Rauzy, O.] Ctr Hosp Univ Purpan Pavill Med, Dept Hematol Med Interne, Toulouse, France. [Zou, J.] Celgene Corp, Biostats, Summit, NJ USA. [Attie, K. M.; Sherman, M. L.] Acceleron Pharma, Cambridge, MA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 EI 1873-5835 J9 LEUKEMIA RES JI Leuk. Res. PD APR PY 2015 VL 39 SU 1 MA 14 BP S5 EP S6 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA DI0JY UT WOS:000373183500015 ER PT J AU Lindsley, RC Mar, BG Mazzola, E Grauman, PG Lindeman, N Steensma, DP DeAngelo, DJ Wadleigh, M Neuberg, D Stone, RM Ebert, BL AF Lindsley, R. C. Mar, B. G. Mazzola, E. Grauman, P. G. Lindeman, N. Steensma, D. P. DeAngelo, D. J. Wadleigh, M. Neuberg, D. Stone, R. M. Ebert, B. L. TI AN OBJECTIVE GENETIC ONTOGENY CLASSIFICATION IDENTIFIES TRUE BIOLOGICAL SECONDARY AML AMONG DE NOVO AML PATIENTS >= 60 YEARS OLD SO LEUKEMIA RESEARCH LA English DT Meeting Abstract CT 13th International Symposium on Myelodysplastic Syndromes (MDS) CY APR 29-MAY 02, 2015 CL Washington, DC C1 [Lindsley, R. C.; Steensma, D. P.; DeAngelo, D. J.; Wadleigh, M.; Stone, R. M.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Mar, B. G.] Dana Farber Canc Inst, Pediat Oncol, Boston, MA 02115 USA. [Mazzola, E.; Neuberg, D.] Dana Farber Canc Inst, Biostat, Boston, MA 02115 USA. [Grauman, P. G.; Ebert, B. L.] Brigham & Womens Hosp, Hematol, Boston, MA 02115 USA. [Lindeman, N.] Brigham & Womens Hosp, Pathol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 EI 1873-5835 J9 LEUKEMIA RES JI Leuk. Res. PD APR PY 2015 VL 39 SU 1 MA 19 BP S8 EP S8 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA DI0JY UT WOS:000373183500020 ER PT J AU Seymour, JF Dohner, H Butrym, A Wierzbowska, A Selleslag, D Jang, JH Cavenagh, JD Kumar, R Schuh, AC Candoni, A Recher, C Sandhu, I del Castillo, TB Al-Ali, HK Martinelli, G Falantes, J Nopenney, R Stone, RM Minden, MD McIntyre, H Songer, S Lucy, LM Beach, CL Dombret, H AF Seymour, J. F. Doehner, H. Butrym, A. Wierzbowska, A. Selleslag, D. Jang, J. H. Cavenagh, J. D. Kumar, R. Schuh, A. C. Candoni, A. Recher, C. Sandhu, I. del Castillo, T. Bernal Al-Ali, H. K. Martinelli, G. Falantes, J. Nopenney, R. Stone, R. M. Minden, M. D. McIntyre, H. Songer, S. Lucy, L. M. Beach, C. L. Dombret, H. TI AZACITIDINE VERSUS CONVENTIONAL CARE REGIMENS (CCR) IN OLDER PATIENTS WITH NEWLY DIAGNOSED AML (> 30% MARROW BLASTS) WITH MYELODYSPLASIA-RELATED CHANGES: SUBGROUP ANALYSIS OF THE AZA-AML-001 STUDY SO LEUKEMIA RESEARCH LA English DT Meeting Abstract CT 13th International Symposium on Myelodysplastic Syndromes (MDS) CY APR 29-MAY 02, 2015 CL Washington, DC C1 [Seymour, J. F.] PeterMacCallum Canc Ctr, Dept Haematol, East Melbourne, Vic, Australia. [Doehner, H.] Univ Ulm Klinikum, Dept Internal Med 3, Ulm, Germany. [Butrym, A.] Wroclaw Med Univ, Dept Haematol Blood Neoplasms & Bone Marrow Trans, Wroclaw, Poland. [Wierzbowska, A.] Med Univ Lodz, Dept Hematol, Lodz, Poland. [Selleslag, D.] AZ Sint Jan Brugge Oostende, Div Hematol, Brugge, Belgium. [Jang, J. H.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Hematol Oncol, Seoul, South Korea. [Cavenagh, J. D.] St Bartholomews Hosp, Dept Haematol, London, England. [Kumar, R.] CancerCare Manitoba, Dept Med Oncol & Haematol, Winnipeg, MB, Canada. [Schuh, A. C.; Minden, M. D.] Princess Margaret Canc Ctr, Malignant Hematol, Toronto, ON, Canada. [Candoni, A.] Azienda Osped Univ S Maria della Misericordia Udi, Div Hematol & Bone Marrow Transplantat, Udine, Italy. [Recher, C.] Inst Univ Canc Toulouse Oncopole, Dept Hematol, Toulouse, France. [Sandhu, I.] Univ Alberta Hosp, Dept Oncol, Edmonton, AB T6G 2B7, Canada. [del Castillo, T. Bernal] Univ Oviedo, Hosp Cent Asturias, Dept Hematol, E-33080 Oviedo, Spain. [Al-Ali, H. K.] Univ Hosp Leipzig, Div Hematol & Oncol, Leipzig, Germany. [Martinelli, G.] Inst Hematol & Med Oncol L & A Seragnoli, Div Hematol & Oncol, Bologna, Italy. [Falantes, J.] Hosp Univ Virgen del Rocio, Inst BioMed Sevilla, Dept Hematol, Seville, Spain. [Nopenney, R.] Univ Klinikum Essen Klin Hamatol, Dept Hematol, Essen, Germany. [Stone, R. M.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [McIntyre, H.; Songer, S.; Beach, C. L.] Celgene Corp, Clin Dev, Summit, NJ USA. [Lucy, L. M.] Celgene Corp, Dept Biostat, Summit, NJ USA. [Dombret, H.] Hop St Louis, Serv Hematol Seniors, Paris, France. RI Wierzbowska, Agnieszka/S-9449-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 EI 1873-5835 J9 LEUKEMIA RES JI Leuk. Res. PD APR PY 2015 VL 39 SU 1 MA 124 BP S63 EP S64 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA DI0JY UT WOS:000373183500125 ER PT J AU Silverman, LR Fenaux, P Al-Kali, A Baer, MR Sekeres, M Roboz, G Gaidano, G Scott, B Greenberg, P Platzbecker, U Steensma, DP Kambhampati, S Kreuzer, KA Godley, L Collins, R Atallah, E Navada, SC Azarnia, N Garcia-Manero, G AF Silverman, L. R. Fenaux, P. Al-Kali, A. Baer, M. R. Sekeres, M. Roboz, G. Gaidano, G. Scott, B. Greenberg, P. Platzbecker, U. Steensma, D. P. Kambhampati, S. Kreuzer, K. A. Godley, L. Collins, R. Atallah, E. Navada, S. C. Azarnia, N. Garcia-Manero, G. TI BONE MARROW BLAST (BMBL) RESPONSE CORRELATES WITH OVERALL SURVIVAL IN RIGOSERTIB-TREATED PATIENTS WITH HIGHER-RISK MDS AFTER FAILURE OF HYPOMETHYLATING AGENTS (HMAS): A NEW RESPONSE CRITERION? SO LEUKEMIA RESEARCH LA English DT Meeting Abstract CT 13th International Symposium on Myelodysplastic Syndromes (MDS) CY APR 29-MAY 02, 2015 CL Washington, DC C1 [Silverman, L. R.; Navada, S. C.] Icahn Sch Med Mt Sinai, Div Hematol Oncol, New York, NY 10029 USA. [Fenaux, P.] Hosp St Louis, Serv Hematol Seniors, Paris, France. [Al-Kali, A.] Mayo Clin, Dept Hematol, Rochester, MN USA. [Baer, M. R.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Sekeres, M.] Cleveland Clin, Dept Hematol Oncol & Blood Disorders, Cleveland, OH 44106 USA. [Roboz, G.] Weill Cornell Med Coll, Leukemia Serv, New York, NY USA. [Gaidano, G.] Amedeo Avogadro Univ Eastern Piedmont Novara, Dept Translat Med, Novara, Italy. [Scott, B.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Greenberg, P.] Stanford Med Sch, Dept Med Hematol, Stanford, CA USA. [Platzbecker, U.] Univ Klinikum Dresden, Med Klin & Poliklin 1, Dresden, Germany. [Steensma, D. P.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Kambhampati, S.] Univ Kansas, Med Ctr, Dept Internal Med, Westwood, KS USA. [Kreuzer, K. A.] Univ Klinikum Koln, Dept Internal Med, Cologne, Germany. [Godley, L.] Univ Chicago, Med Ctr, Dept Med, Chicago, IL 60637 USA. [Collins, R.] Univ Texas Dallas, Dept Internal Med, Dallas, TX 75230 USA. [Atallah, E.] Froedtert Hosp, Div Hematol & Oncol, Milwaukee, WI USA. [Atallah, E.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Azarnia, N.] Onconova Therapeut Inc, Dept Biometr, Newtown, PA USA. [Garcia-Manero, G.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 EI 1873-5835 J9 LEUKEMIA RES JI Leuk. Res. PD APR PY 2015 VL 39 SU 1 MA 88 BP S44 EP S45 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA DI0JY UT WOS:000373183500089 ER PT J AU Steensma, D Abedi, M Bejar, R Cogle, C Foucar, K Garcia-Manero, G George, T Grinblatt, D Komrokji, R Maciejewski, J Pollyea, D Roboz, G Savona, M Scott, B Sekeres, M Thompson, M Sugrue, M Swern, A Nifenecker, M Erba, H AF Steensma, D. Abedi, M. Bejar, R. Cogle, C. Foucar, K. Garcia-Manero, G. George, T. Grinblatt, D. Komrokji, R. Maciejewski, J. Pollyea, D. Roboz, G. Savona, M. Scott, B. Sekeres, M. Thompson, M. Sugrue, M. Swern, A. Nifenecker, M. Erba, H. TI CONNECT MDS AND AML: THE MYELODYSPLASTIC SYNDROMES (MDS) AND ACUTE MYELOID LEUKEMIA (AML) DISEASE REGISTRY SO LEUKEMIA RESEARCH LA English DT Meeting Abstract CT 13th International Symposium on Myelodysplastic Syndromes (MDS) CY APR 29-MAY 02, 2015 CL Washington, DC C1 [Steensma, D.] Dana Farber Canc Inst, Hematol Oncol, Boston, MA 02115 USA. [Abedi, M.] Univ Calif Davis, Ctr Comprehens Canc, Div Hematol & Oncol, Sacramento, CA 95817 USA. [Bejar, R.] Univ Calif San Diego, Moores Canc Ctr, Div Hematol & Oncol, La Jolla, CA 92093 USA. [Cogle, C.] Univ Florida, Dept Med, Div Hematol & Oncol, Gainesville, FL USA. [Foucar, K.; George, T.] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA. [Garcia-Manero, G.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Leukemia, Houston, TX 77030 USA. [Grinblatt, D.] North Shore Univ Hlth Syst, Hematol, Evanston, IL USA. [Komrokji, R.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Med Oncol, Tampa, FL 33612 USA. [Maciejewski, J.] Cleveland Clin Fdn, Dept Translat Hematol & Oncol Res, Cleveland, OH 44195 USA. [Pollyea, D.] Univ Colorado, Ctr Canc, Div Hematol, Aurora, CO USA. [Roboz, G.] Cornell Univ, Weill Med Coll, Weill Dept Med, New York, NY 10021 USA. [Savona, M.] Vanderbilt Ingram Canc Ctr, Div Hematol Oncol, Nashville, TN USA. [Scott, B.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Sekeres, M.] Cleveland Clin Fdn, Dept Hematol & Oncol, Cleveland, OH 44195 USA. [Thompson, M.] Aurora Hlth Care, Aurora Res Inst, Aurora, CO USA. [Sugrue, M.] Celgene Corp, Med Affairs, Summit, NJ USA. [Swern, A.] Celgene Corp, Biometr, Summit, NJ USA. [Erba, H.] Univ Alabama Birmingham, Div Hematol & Oncol, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 EI 1873-5835 J9 LEUKEMIA RES JI Leuk. Res. PD APR PY 2015 VL 39 SU 1 MA 249 BP S124 EP S124 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA DI0JY UT WOS:000373183500250 ER PT J AU Bastian, LA Mattocks, KM Rosen, AK Hamilton, AB Bean-Mayberry, B Sadler, AG Klap, RS Yano, EM AF Bastian, Lori A. Mattocks, Kristin M. Rosen, Amy K. Hamilton, Alison B. Bean-Mayberry, Bevanne Sadler, Anne G. Klap, Ruth S. Yano, Elizabeth M. TI Informing Policy to Deliver Comprehensive Care for Women Veterans SO MEDICAL CARE LA English DT Editorial Material C1 [Bastian, Lori A.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Bastian, Lori A.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. [Mattocks, Kristin M.] VA Cent Western Massachusetts, Leeds, W Yorkshire, England. [Mattocks, Kristin M.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci & Psychiat, Worcester, MA USA. [Rosen, Amy K.] VA Boston Healthcare Syst, Boston, MA USA. [Rosen, Amy K.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Hamilton, Alison B.; Bean-Mayberry, Bevanne; Klap, Ruth S.; Yano, Elizabeth M.] VA Greater Los Angeles HSR&D Ctr Study Healthcare, Los Angeles, CA USA. [Hamilton, Alison B.; Bean-Mayberry, Bevanne] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [Sadler, Anne G.] Iowa City Vet Affairs Hlth Care Syst, Iowa City, IA USA. [Sadler, Anne G.] Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA. RP Bastian, LA (reprint author), VA Connecticut Healthcare Syst, 555 Willard Ave, Newington, CT 06111 USA. EM lori.bastian@va.gov FU Department of Veteran Affairs Health Service Research Development [SDR 10-012] FX Supported by the Department of Veteran Affairs Health Service Research & Development SDR 10-012. NR 28 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD APR PY 2015 VL 53 IS 4 SU 1 BP S1 EP S4 PG 4 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DS3BL UT WOS:000380657800001 PM 25767961 ER PT J AU Bean-Mayberry, B Bastian, L Trentalange, M Murphy, TE Skanderson, M Allore, H Reyes-Harvey, E Maisel, NC Gaetano, V Wright, S Haskell, S Brandt, C AF Bean-Mayberry, Bevanne Bastian, Lori Trentalange, Mark Murphy, Terrence E. Skanderson, Melissa Allore, Heather Reyes-Harvey, Evelyn Maisel, Natalya C. Gaetano, Vera Wright, Steven Haskell, Sally Brandt, Cynthia TI Associations Between Provider Designation and Female-specific Cancer Screening in Women Veterans SO MEDICAL CARE LA English DT Article DE cancer screening; prevention; women; veterans; primary-care providers ID FORCE RECOMMENDATION STATEMENT; HEALTH-CARE-DELIVERY; QUALITY-OF-CARE; PREVENTIVE SERVICES; CERVICAL-CANCER; UNITED-STATES; AMBULATORY-CARE; MENTAL-ILLNESS; BREAST; MAMMOGRAPHY AB Background: In 2010, the Department of Veterans Affairs Healthcare System (VA) implemented policy to provide Comprehensive Primary Care (for acute, chronic, and female-specific care) from designated Women's Health providers (DWHPs) at all VA sites. However, since that time no comparisons of quality measures have been available to assess the level of care for women Veterans assigned to these providers. Objectives: To evaluate the associations between cervical and breast cancer screening rates among age-appropriate women Veterans and designation of primary-care provider (DWHP vs. non-DWHP). Research Design: Cross-sectional analyses using the fiscal year 2012 data on VA women's health providers, administrative files, and patient-specific quality measures. Subjects: The sample included 37,128 women Veterans aged 21 through 69 years. Measures: Variables included patient demographic and clinical factors (ie, age, race, ethnicity, mental health diagnoses, obesity, and site), and provider factors (ie, DWHP status, sex, and panel size). Screening measures were defined by age-appropriate subgroups using VA national guidelines. Results: Female-specific cancer screening rates were higher among patients assigned to DWHPs (cervical cytology 94.4% vs. 91.9%, P < 0.0001; mammography 86.3% vs. 83.3%, P < 0.0001). In multivariable models with adjustment for patient and provider characteristics, patients assigned to DWHPs had higher odds of cervical cancer screening (odds ratio, 1.26; 95% confidence interval, 1.07-1.47; P < 0.0001) and breast cancer screening (odds ratio, 1.24; 95% CI, 1.10-1.39; P < 0.0001). Conclusions: As the proportion of women Veterans increases, assignment to DWHPs may raise rate of female-specific cancer screening within VA. Separate evaluation of sex neutral measures is needed to determine whether other measures accrue benefits for patients with DWHPs. C1 [Bean-Mayberry, Bevanne] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles HSR&D Ctr Study Healthcare, Los Angeles, CA 90095 USA. [Bean-Mayberry, Bevanne] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Bastian, Lori; Haskell, Sally; Brandt, Cynthia] VA Connecticut Healthcare Syst, West Haven, CT USA. [Bastian, Lori] Univ Connecticut, Ctr Hlth, Dept Internal Med, Farmington, CT USA. [Trentalange, Mark; Murphy, Terrence E.; Allore, Heather; Haskell, Sally] Sch Med, Dept Internal Med, New Haven, CT USA. [Skanderson, Melissa] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Reyes-Harvey, Evelyn] VHA Off Informat & Analyt 10P2, Durham, NC USA. [Maisel, Natalya C.] VA Palo Alto Hlth Care Syst, HSR&D Ctr Innovat Implementat Ci2i, Palo Alto, CA USA. [Gaetano, Vera] VA Connecticut HSR&D Pain Res Informat Multimorbi, West Haven, CT USA. [Wright, Steven] Off Analyt & Business Intelligence 10P2B, Durham, NC USA. [Haskell, Sally] VA Cent Off, Womens Hlth Serv, Patient Care Serv, Washington, DC USA. [Brandt, Cynthia] Yale Univ, Sch Med, Yale Ctr Med Informat, West Haven, CT 06516 USA. RP Bean-Mayberry, B (reprint author), VA Greater Los Angeles HSR&D Ctr Study Healthcare, 16111 Plummer St 152, Sepulveda, CA 91343 USA. EM bevanne.bean-mayberry@va.gov FU VA Central Office Operations Funds; Yale Claude D. Pepper Older Americans Independence Center [P30AG21342] FX Supported by VA Central Office Operations Funds. This work was partially funded by the Yale Claude D. Pepper Older Americans Independence Center (P30AG21342) to co-authors H.A., T.M., and M.T. NR 47 TC 4 Z9 4 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD APR PY 2015 VL 53 IS 4 SU 1 BP S47 EP S54 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DS3BL UT WOS:000380657800009 PM 25767975 ER PT J AU Cordasco, KM Huynh, AK Zephyrin, L Hamilton, AB Lau-Herzberg, AE Kessler, CS Yano, EM AF Cordasco, Kristina M. Huynh, Alexis K. Zephyrin, Laurie Hamilton, Alison B. Lau-Herzberg, Amy E. Kessler, Chad S. Yano, Elizabeth M. TI Building Capacity in VA to Provide Emergency Gynecology Services for Women SO MEDICAL CARE LA English DT Article DE Veterans; women's health; emergency care; qualitative methods ID HIDDEN POPULATIONS; VETERANS; IMPLEMENTATION; HEALTH AB Background: Visits to Veterans Administration (VA) emergency departments (EDs) are increasingly being made by women. A 2011 national inventory of VA emergency services for women revealed that many EDs have gaps in their resources and processes for gynecologic emergency care. Objectives: To guide VA in addressing these gaps, we sought to understand factors acting as facilitators and/or barriers to improving VA ED capacity for, and quality of, emergency gynecology care. Research Design: Semistructured interviews with VA emergency and women's health key informants. Subjects: ED directors/providers (n = 14), ED nurse managers (n = 13), and Women Veteran Program Managers (n = 13) in 13 VA facilities. Results: Leadership, staff, space, demand, funding, policies, and community were noted as important factors influencing VA EDs building capacity and improving emergency gynecologic care for women Veterans. These factors are intertwined and cross multiple organizational levels so that each ED's capacity is a reflection not only of its own factors, but also those of its local medical center and non-VA community context as well as VA regional and national trends and policies. Conclusions: Policies and quality improvement initiatives aimed at building VA's emergency gynecologic services for women need to be multifactorial and aimed at multiple organizational levels. Policies need to be flexible to account for wide variations across EDs and their medical center and community contexts. Approaches that build and encourage local leadership engagement, such as evidence-based quality improvement methodology, are likely to be most effective. C1 [Cordasco, Kristina M.; Huynh, Alexis K.; Hamilton, Alison B.; Lau-Herzberg, Amy E.; Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Study Healthcare Innovat Implementat, North Hills, CA USA. [Cordasco, Kristina M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Cordasco, Kristina M.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Zephyrin, Laurie] Vet Hlth Adm, VA Womens Hlth Serv, Off Patient Care Serv, Washington, DC USA. [Zephyrin, Laurie] VA New York Harbor Healthcare Syst, New York, NY USA. [Zephyrin, Laurie] NYU, Dept Obstet & Gynecol, Langone Sch Med, New York, NY 10016 USA. [Hamilton, Alison B.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Kessler, Chad S.] Durham VA Med Ctr, Durham, NC USA. [Kessler, Chad S.] Duke Univ, Sch Med, Dept Emergency Med, Durham, NC USA. [Kessler, Chad S.] Duke Univ, Sch Med, Dept Internal Med, Durham, NC USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90024 USA. RP Cordasco, KM (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd 111 G, Los Angeles, CA 90073 USA. EM kristina.cordasco@va.gov FU VA Women's Health Services; VA Health Services Research & Development Senior Research Career Scientist Award (RCS) [05-195] FX This work was funded by VA Women's Health Services. Dr. Elizabeth Yano's contribution was also funded by a VA Health Services Research & Development Senior Research Career Scientist Award (RCS #05-195). NR 20 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD APR PY 2015 VL 53 IS 4 SU 1 BP S81 EP S87 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DS3BL UT WOS:000380657800014 PM 25767982 ER PT J AU Cordasco, KM Zuchowski, JL Hamilton, AB Kirsh, S Veet, L Saavedra, JO Altman, L Knapp, H Canning, M Washington, DL AF Cordasco, Kristina M. Zuchowski, Jessica L. Hamilton, Alison B. Kirsh, Susan Veet, Laure Saavedra, Joann O. Altman, Lisa Knapp, Herschel Canning, Mark Washington, Donna L. TI Early Lessons Learned in Implementing a Women's Health Educational and Virtual Consultation Program in VA SO MEDICAL CARE LA English DT Article DE veterans; women's health; Continuing Medical Education; qualitative methods ID PRIMARY-CARE; VETERANS; DELIVERY; CLINICS AB Background: Many Veterans Health Administration primary care providers (PCPs) have small female patient caseloads, making it challenging for them to build and maintain their women's health (WH) knowledge and skills. To address this issue, we implemented a longitudinal WH-focused educational and virtual consultation program using televideo conferencing. Objective: To perform a formative evaluation of the program's development and implementation. Research Design: We used mixed methods including participant surveys, semi-structured interviews, stakeholder meeting field notes, and participation logs. We conducted qualitative content analysis for interviews and field notes, and quantitative tabulation for surveys and logs. Subjects: Veterans Health Administration WH PCPs. Results: In 53 postsession surveys received, 47(89%) agreed with the statement, "The information provided in the session would influence my patient care." Among 18 interviewees, all reported finding the program useful for building and maintaining WH knowledge. All interviewees also reported that sessions being conducted during their lunch hour limited consistent participation. Logs showed that PCPs participated more consistently in the 1 health care system that provided time specifically allocated for this program. Key stakeholder discussions revealed that rotating specialists and topics across the breadth of WH limited submission of cases. Conclusions: Our WH education and virtual consultation program is a promising modality for building and maintaining PCP knowledge of WH, and influencing patient care. However, allocated time for PCPs to participate is essential for robust and consistent participation. Narrowing the modality's focus to gynecology, rather than covering the breadth WH topics, may facilitate PCPs having active cased-based questions for sessions. C1 [Cordasco, Kristina M.; Zuchowski, Jessica L.; Hamilton, Alison B.; Canning, Mark; Washington, Donna L.] VA HSR&D Ctr Study Healthcare Innovat Implementat, North Hills, CA USA. [Cordasco, Kristina M.; Zuchowski, Jessica L.; Hamilton, Alison B.; Saavedra, Joann O.; Altman, Lisa; Knapp, Herschel; Canning, Mark; Washington, Donna L.] VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd 111G, Los Angeles, CA 90073 USA. [Cordasco, Kristina M.; Altman, Lisa; Washington, Donna L.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Hamilton, Alison B.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Kirsh, Susan] Vet Hlth Adm, Off Patient Care Serv, VHA Specialty Care Serv, Washington, DC USA. [Kirsh, Susan] Louis Stokes Cleveland VA Med Ctr, Cleveland, OH USA. [Kirsh, Susan] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Veet, Laure] Vet Hlth Adm, Off Patient Care Serv, VHA Womens Hlth Serv, Washington, DC USA. [Veet, Laure] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Cordasco, KM (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd 111G, Los Angeles, CA 90073 USA. EM kristina.cordasco@va.gov FU Veterans Health Administration (VHA) Health Services Research & Development (HSR&D) CREATE project [CRE-12-031]; VHA HSR&D Center for the Study of Healthcare Implementation, Innovation Policy (CSHIP); VHA Patient Care Services, Office of Specialty Care Transformation (a VHA T-21 Transformational Initiative) FX Supported by Veterans Health Administration (VHA) Health Services Research & Development (HSR&D) CREATE project CRE-12-031; VHA HSR&D Center for the Study of Healthcare Implementation, Innovation & Policy (CSHIP); and VHA Patient Care Services, Office of Specialty Care Transformation (a VHA T-21 Transformational Initiative). NR 16 TC 5 Z9 5 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD APR PY 2015 VL 53 IS 4 SU 1 BP S88 EP S92 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DS3BL UT WOS:000380657800015 PM 25767983 ER PT J AU deKleijn, M Lagro-Janssen, ALM Canelo, I Yano, EM AF deKleijn, Miriam Lagro-Janssen, Antoine L. M. Canelo, Ismelda Yano, Elizabeth M. TI Creating a Roadmap for Delivering Gender-sensitive Comprehensive Care for Women Veterans Results of a National Expert Panel SO MEDICAL CARE LA English DT Article DE comprehensive care; women's health; sex sensitivity; Veterans ID HEALTH-CARE; SEXUAL TRAUMA; PATCHWORK QUILT; CLINICS; SATISFACTION; ASSOCIATION; AFGHANISTAN; DISPARITIES; INNOVATION; QUALITY AB Background: Women Veterans are a significant minority of users of the VA healthcare system, limiting provider and staff experience meeting their needs in environments historically designed for men. The VA is nonetheless committed to ensuring that women Veterans have access to comprehensive care in environments sensitive to their needs. Objectives: We sought to determine what aspects of care need to be tailored to the needs of women Veterans in order for the VA to deliver gender-sensitive comprehensive care. Research Design: Modified Delphi expert panel process. Subjects: Eleven clinicians and social scientists with expertise in women's health, primary care, and mental health. Measures: Importance of tailoring over 100 discrete aspects of care derived from the Institute of Medicine's definition of comprehensive care and literature-based domains of sex-sensitive care on a 5-point scale. Results: Panelists rated over half of the aspects of care as very-to-extremely important (median score 4+) to tailor to the needs of women Veterans. The panel arrived at 14 priority recommendations that broadly encompassed the importance of (1) the design/delivery of services sensitive to trauma histories, (2) adapting to women's preferences and information needs, and (3) sex awareness and cultural transformation in every facet of VA operations. Conclusions: We used expert panel methods to arrive at consensus on top priority recommendations for improving delivery of sex-sensitive comprehensive care in VA settings. Accomplishment of their breadth will require national, regional, and local strategic action and multilevel stakeholder engagement, and will support VA's national efforts at improving customer service for all Veterans. C1 [deKleijn, Miriam; Lagro-Janssen, Antoine L. M.] Radboud Univ Nijmegen, Med Ctr, Gender & Womens Hlth Unit, Dept Primary & Community Care, Nijmegen, Netherlands. [Canelo, Ismelda; Yano, Elizabeth M.] VA Greater Los Angeles, VA HSR&D Ctr Study Healthcare Innovat Implementat, Sepulveda, CA USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, Los Angeles, CA USA. RP Yano, EM (reprint author), VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Study Healthcare Innovat Implementat, 16111 Plummer St,Mailcode 152, Sepulveda, CA 91343 USA. EM elizabeth.yano@va.gov RI Lagro, A.L.M./H-8066-2014 FU Women's Health Services, Office of Patient Care Services, Veterans Health Administration, Washington, DC; Radboud University Medical Center, Njimegen, The Netherlands; Dutch Society of Female Doctors; VA Health Services Research & Development Senior Research Career Scientist Award [RCS 05-195] FX Supported by Women's Health Services, Office of Patient Care Services, Veterans Health Administration, Washington, DC. M.d.K.'s effort was covered through a Gender Sensitive Medicine Postdoctoral Fellowship at Radboud University Medical Center, Njimegen, The Netherlands and the Hilly de Roever-Bonnet fund of The Dutch Society of Female Doctors. E.M.Y.'s effort was funded by a VA Health Services Research & Development Senior Research Career Scientist Award (Project # RCS 05-195). NR 48 TC 6 Z9 6 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD APR PY 2015 VL 53 IS 4 SU 1 BP S156 EP S164 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DS3BL UT WOS:000380657800025 PM 25767971 ER PT J AU Foynes, MM Smith, BN Shipherd, JC AF Foynes, Melissa M. Smith, Brian N. Shipherd, Jillian C. TI Associations Between Race-based and Sex-based Discrimination, Health, and Functioning A Longitudinal Study of Marines SO MEDICAL CARE LA English DT Article DE discrimination; health disparities; women's health; minority health; veterans ID PERCEIVED SOCIAL SUPPORT; POSTTRAUMATIC-STRESS-DISORDER; SELF-ESTEEM; MULTIDIMENSIONAL SCALE; MILITARY CULTURE; PSYCHOMETRIC PROPERTIES; PSYCHOLOGICAL DISTRESS; IRAQ RANDOMIZATION; GENDER-DIFFERENCES; VETERANS AB Background: Only a few studies have examined race-based discrimination (RBD) and sex-based discrimination (SBD) in military samples and all are cross-sectional. Objectives: The current study examined associations between both RBD and SBD experienced during Marine recruit training and several health and functioning outcomes 11 years later in a racially/ethnically diverse sample of men and women. Research Design: Linear multiple regression models were used to examine associations between sex, race/ethnicity, RBD and SBD, and later outcomes (physical health, self-esteem, and occupational/vocational functioning), accounting for baseline levels and covariates. Subjects: Data were drawn from a larger longitudinal investigation of US Marine Corps recruits. The sample (N = 471) was comprised of white men (34.6%), white women (37.6%), racial/ethnic minority men (12.7%), and racial/ethnic minority women (15.1%). Measures: Self-report measures of sex and race (T1), RBD and SBD (T2), social support (T2), mental health (T2), physical health (T2 and T5), self-esteem (T2 and T5), and occupational/vocational functioning (T5) were included. Results: Over a decade later, experiences of RBD were negatively associated with physical health and self-esteem. Social support was the strongest predictor of occupational/vocational functioning. Effects of sex, SBD, and minority status were not significant in regressions after accounting for other variables. Conclusions: Health care providers can play a key role in tailoring care to the needs of these important subpopulations of veterans by assessing and acknowledging experiences of discrimination and remaining aware of the potential negative associations between discrimination and health and functioning above and beyond the contributions of sex and race/ethnicity. C1 [Foynes, Melissa M.; Smith, Brian N.; Shipherd, Jillian C.] Boston Univ, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02215 USA. [Foynes, Melissa M.; Smith, Brian N.; Shipherd, Jillian C.] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. [Foynes, Melissa M.; Smith, Brian N.; Shipherd, Jillian C.] VA Boston Healthcare Syst 116B 3, 150 South Huntington Ave, Boston, MA 02130 USA. [Shipherd, Jillian C.] VHA Cent Off, Patient Care Serv, Washington, DC USA. RP Foynes, MM (reprint author), VA Boston Healthcare Syst 116B 3, 150 South Huntington Ave, Boston, MA 02130 USA. EM melissa.foynes2@va.gov FU Department of Defense; U.S. Army Medical Research and Material Command [MIPR 96MM6746]; Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development [IIR 04-420-2] FX Supported by the Department of Defense, Women's Defense Health Research Program, and was administered by both the U.S. Army Medical Research and Material Command under Grant MIPR 96MM6746 (PI Jessica Wolfe) and the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (IIR 04-420-2; PI J.C.S.). NR 49 TC 1 Z9 1 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD APR PY 2015 VL 53 IS 4 SU 1 BP S128 EP S135 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DS3BL UT WOS:000380657800021 PM 25767966 ER PT J AU Friedman, SA Frayne, SM Berg, E Hamilton, AB Washington, DL Saechao, F Maisel, NC Lin, JY Hoggatt, KJ Phibbs, CS AF Friedman, Sarah A. Frayne, Susan M. Berg, Eric Hamilton, Alison B. Washington, Donna L. Saechao, Fay Maisel, Natalya C. Lin, Julia Y. Hoggatt, Katherine J. Phibbs, Ciaran S. TI Travel Time and Attrition From VHA Care Among Women Veterans How Far is Too Far? SO MEDICAL CARE LA English DT Article; Proceedings Paper CT VA HSR and D Women's Health Research Meeting CY JUL, 2014 CL Arlington, VA DE women veterans; access to health care; rural communities ID VA HEALTH-CARE; MEDICAL-CARE; DISTANCE; ACCESS; LEVEL AB Background: Travel time, an access barrier, may contribute to attrition of women veterans from Veterans Health Administration (VHA) care. Objective: We examined whether travel time influences attrition: (a) among women veterans overall, (b) among new versus established patients, and (c) among rural versus urban patients. Research Design: This retrospective cohort study used logistic regression to estimate the association between drive time and attrition, overall and for new/established and rural/urban patients. Subjects: In total, 266,301 women veteran VHA outpatients in the Fiscal year 2009. Measures: An "attriter" did not return for VHA care during the second through third years after her first 2009 visit (T-0). Drive time (log minutes) was between the patient's residence and her regular source of VHA care. "New" patients had no VHA visits within 3 years before T-0. Models included age, service-connected disability, health status, and utilization as covariates. Results: Overall, longer drive times were associated with higher odds of attrition: drive time adjusted odds ratio = 1.11 (99% confidence interval, 1.09-1.14). The relationship between drive time and attrition was stronger among new patients but was not modified by rurality. Conclusions: Attrition among women veterans is sensitive to longer drive time. Linking new patients to VHA services designed to reduce distance barriers (telemedicine, community-based clinics, mobile clinics) may reduce attrition among women new to VHA. C1 [Friedman, Sarah A.; Frayne, Susan M.; Berg, Eric; Saechao, Fay; Maisel, Natalya C.; Phibbs, Ciaran S.] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat Ci2i, Palo Alto, CA USA. [Friedman, Sarah A.] Univ Calif Los Angeles, Dept Hlth Policy & Management, Los Angeles, CA USA. [Frayne, Susan M.] VA Palo Alto Hlth Care Syst, Womens Hlth Sect, Med Serv, Palo Alto, CA USA. [Frayne, Susan M.] Stanford Univ, Sch Med, Div Gen Med Disciplines, Stanford, CA 94305 USA. [Frayne, Susan M.; Phibbs, Ciaran S.] Stanford Univ, Sch Med, Ctr Primary Care & Outcomes Res, Stanford, CA 94305 USA. [Hamilton, Alison B.; Washington, Donna L.; Hoggatt, Katherine J.] VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Study Healthcare Innovat Implementat, Los Angeles, CA USA. [Hamilton, Alison B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Washington, Donna L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Lin, Julia Y.] VA Palo Alto Hlth Care Syst, VA Cooperat Studies Program Coordinating Ctr, Palo Alto, CA USA. [Hoggatt, Katherine J.] Univ Calif Los Angeles, Dept Epidemiol, Los Angeles, CA USA. [Phibbs, Ciaran S.] VA Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, Palo Alto, CA USA. [Phibbs, Ciaran S.] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA. RP Friedman, SA (reprint author), VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat Ci2i, 795 Willow Rd 152 MPD, Menlo Pk, CA 94025 USA. EM safriedman@mednet.ucla.edu FU Department of Veterans Affairs (VA) Health Services Research & Development Service [CRE 12-019]; VA Women's Health Services; Ms. Friedman's NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI Grant [TL1TR000121]; Dr Hoggatt's VA HSR&D/QUERI Career Development Award [CDA 11-261] FX Supported in part by the Department of Veterans Affairs (VA) Health Services Research & Development Service (CRE 12-019), by VA Women's Health Services, and by Ms. Friedman's NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI Grant (TL1TR000121), by Dr Hoggatt's VA HSR&D/QUERI Career Development Award (CDA 11-261). NR 29 TC 5 Z9 5 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD APR PY 2015 VL 53 IS 4 SU 1 BP S15 EP S22 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DS3BL UT WOS:000380657800005 PM 25767970 ER PT J AU Hamilton, AB Williams, L Washington, DL AF Hamilton, Alison B. Williams, Lindsay Washington, Donna L. TI Military and Mental Health Correlates of Unemployment in a National Sample of Women Veterans SO MEDICAL CARE LA English DT Article DE women Veterans; unemployment; depression; military experiences ID POSTTRAUMATIC-STRESS-DISORDER; INTIMATE PARTNER VIOLENCE; SHORT SCREENING SCALE; OF-THE-LITERATURE; SUPPORTED EMPLOYMENT; PRECARIOUS EMPLOYMENT; DEPRESSIVE SYMPTOMS; PRIMARY-CARE; IMPACT; SERVICES AB Background: The unemployment rate is currently higher among women Veterans than among male Veterans and civilian women. Employment is a key social determinant of health, with unemployment being strongly associated with adverse health. Objective: To identify military-related and health-related characteristics associated with unemployment in women Veterans. Research Design and Subjects: Secondary analysis of workforce participants (n = 1605) in the National Survey of Women Veterans telephone survey. Measures: Demographics, mental health conditions, health care utilization, and military experiences and effects. Unemployment was defined as being in the labor force but unemployed and looking for work. Analysis: The chi(2) analyses to identify characteristics of unemployed women Veterans; logistic regression to identify independent factors associated with unemployment. Results: Ten percent of women Veterans were unemployed. Independent correlates of unemployment were screening positive for depression [odds ratio (OR) = 4.7; 95% confidence interval [CI], 1.8-12.4], military service during wartime (OR = 2.9; 95%, CI 1.1-7.3), and service in the regular military (vs. in the National Guards/Reserves only) (OR = 6.8; 95% CI, 2.2-20.5). Two postactive duty perceptions related to not being respected and understood as a Veteran were each independently associated with unemployment. Conclusions: Whether depression underlies unemployment, is exacerbated by unemployment, or both, it is critical to identify and treat depression among women Veterans, and also to investigate women Veterans' experiences and identities in civilian life. Community-based employers may need education regarding women Veterans' unique histories and strengths. Women who served in the regular military and during wartime may benefit from job assistance before and after they leave the military. Gender-specific adaptation of employment services may be warranted. C1 [Hamilton, Alison B.; Washington, Donna L.] VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Study Healthcare Innovat Implementat, 11301 Wilshire Blvd 210A, Los Angeles, CA 90073 USA. [Hamilton, Alison B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Williams, Lindsay] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. [Washington, Donna L.] 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 Study Healthcare Innovat Implementat, 11301 Wilshire Blvd 210A, Los Angeles, CA 90073 USA. EM alison.hamilton@va.gov FU Department of Veterans Affairs (VA), Women's Health Services within the Office of Patient Care Services; VA Health Services Research and Development (HSRD) Service [SDR-08-270]; VA Health Services Research and Development Service FX The National Survey of Women Veterans was funded by the Department of Veterans Affairs (VA), Women's Health Services within the Office of Patient Care Services, and the VA Health Services Research and Development (HSR&D) Service (SDR-08-270).; A.B.H. and D.L.W. are employed by the Department of Veterans Affairs. A.B.H. and D.L.W. receive research funding from the VA Health Services Research and Development Service. NR 48 TC 2 Z9 2 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD APR PY 2015 VL 53 IS 4 SU 1 BP S32 EP S38 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DS3BL UT WOS:000380657800007 PM 25767973 ER PT J AU Iverson, KM Pogoda, TK AF Iverson, Katherine M. Pogoda, Terri K. TI Traumatic Brain Injury Among Women Veterans An Invisible Wound of Intimate Partner Violence SO MEDICAL CARE LA English DT Article DE Veterans health administration; concussion; abuse; domestic violence; strangulation ID INTERPERSONAL VIOLENCE; HEALTH CONSEQUENCES; PHYSICAL HEALTH; RISK-FACTOR; STRANGULATION; VALIDITY; GENDER; SCALES; POLICY AB Background: Intimate partner violence (IPV) is prevalent among women Veterans and is known to increase women's risk for traumatic brain injury (TBI). IPV-related TBI has not been examined in the women Veteran population. Objectives: To identify the occurrence of IPV-related TBI in a sample of women Veterans and examine the associations of IPV-related TBI with sociodemographic characteristics, health symptoms, health care utilization, and IPV experiences. Research Design: Cross-sectional mail survey conducted in 2013. Subjects: The sample comprised 176 New England Department of Veterans Affairs (VA) women Veteran patients. Measures: Self-reported IPV-related TBI was assessed with a modified VA TBI screening tool. The survey included validated measures of depression (Center for Epidemiologic Studies Depression Scale) and posttraumatic stress disorder (PTSD; Posttraumatic Disorder Checklist) symptoms, as well as overall mental and physical health (SF-12), and IPV (Conflict Tactics Scales-Revised-2). Questions assessed past-year VA and non-VA health care use. Results: A total of 18.8% (n = 33) met screening criteria for IPV-related TBI history. Women who experienced IPV-related TBI reported significantly higher depression (mean Center for Epidemiologic Studies Depression Scale scores: 26.6 vs. 20.7, P < 0.0001) and PTSD (mean Posttraumatic Disorder Checklist scores: 53.2 vs. 34.1, P < 0.0001) symptoms, and poorer perceptions of physical health (mean SF-12 34.6 vs. 42.3, P < 0.01) than women who experienced IPV to the head without TBI. IPV-related TBI was also associated with poorer perceptions of mental health, as well as more frequent VA health care utilization and overall IPV. Conclusions: IPV-related TBI is associated with poorer mental and physical health in women Veterans. This invisible injury is associated with greater VA health care utilization and IPV exposure. Implications for VA practice and policy are discussed. C1 [Iverson, Katherine M.] VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, 150 South Huntington Ave 116B-3, Boston, MA 02130 USA. [Iverson, Katherine M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Iverson, Katherine M.; Pogoda, Terri K.] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA USA. [Pogoda, Terri K.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. RP Iverson, KM (reprint author), VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, 150 South Huntington Ave 116B-3, Boston, MA 02130 USA. EM katherine.iverson@va.gov FU Department of Veterans Affairs, Office of Research and Development, Health Services Research & Development (HSRD) Service [CDA 10-029] FX Supported by the Department of Veterans Affairs, Office of Research and Development, Health Services Research & Development (HSR&D) Service as part of KMI's HSR&D Career Development Award (CDA 10-029). NR 45 TC 1 Z9 2 U1 6 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD APR PY 2015 VL 53 IS 4 SU 1 BP S112 EP S119 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DS3BL UT WOS:000380657800019 PM 25767964 ER PT J AU Katon, JG Hoggatt, KJ Balasubramanian, V Saechao, FS Frayne, SM Mattocks, KM Feibus, KB Galvan, IV Hickman, R Hayes, PM Haskell, SG Yano, EM Phibbs, CS Zephyrin, LC AF Katon, Jodie G. Hoggatt, Katherine J. Balasubramanian, Vidhya Saechao, Fay S. Frayne, Susan M. Mattocks, Kristin M. Feibus, Karen B. Galvan, Ileana V. Hickman, Renee Hayes, Patricia M. Haskell, Sally G. Yano, Elizabeth M. Phibbs, Ciaran S. Zephyrin, Laurie C. TI Reproductive Health Diagnoses of Women Veterans Using Department of Veterans Affairs Health Care SO MEDICAL CARE LA English DT Article DE women veterans; reproductive health; life course; health care needs ID SEXUAL VIOLENCE; MENTAL-HEALTH; AVAILABILITY; AFGHANISTAN; SERVICES; GENDER; IRAQ AB Background: Little is known regarding the reproductive health needs of women Veterans using Department of Veterans Affairs (VA) health care. Objective: To describe the reproductive health diagnoses of women Veterans using VA health care, how these diagnoses differ across age groups, and variations in sociodemographic and clinical characteristics by presence of reproductive health diagnoses. Research Design: This study is a cross-sectional analysis of VA administrative and clinical data. Subjects: The study included women Veterans using VA health care in FY10. Measures: Reproductive health diagnoses were identified through presence of International Classification of Disease, 9th Revision (ICD-9) codes in VA clinical and administrative records. The prevalence of specific diagnosis categories were examined by age group (18-44, 45-64, >= 65 y) and the most frequent diagnoses for each age group were identified. Sociodemographic and clinical characteristics were compared by presence of at least 1 reproductive health diagnosis. Results: The most frequent reproductive health diagnoses were menstrual disorders and endometriosis among those aged 18-44 years (n = 16,658, 13%), menopausal disorders among those aged 45-64 years (n = 20,707, 15%), and osteoporosis among those aged >= 65 years (n = 8365, 22%). Compared with women without reproductive health diagnoses, those with such diagnoses were more likely to have concomitant mental health (46% vs. 37%, P < 0.001) and medical conditions (75% vs. 63%, P < 0.001). Conclusions: Women Veterans using VA health care have diverse reproductive health diagnoses. The high prevalence of comorbid medical and mental health conditions among women Veterans with reproductive health diagnoses highlights the importance of integrating reproductive health expertise into all areas of VA health care, including primary, mental health, and specialty care. C1 [Katon, Jodie G.] Puget Sound Hlth Care Syst, Dept Vet Affairs VA, HSR&D, Seattle, WA USA. [Katon, Jodie G.; Feibus, Karen B.; Galvan, Ileana V.; Hickman, Renee; Hayes, Patricia M.; Haskell, Sally G.; Zephyrin, Laurie C.] VA Off Patient Care Serv, Womens Hlth Serv, Washington, DC USA. [Katon, Jodie G.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Hoggatt, Katherine J.; Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Study Healthcare Innovat Implementat, Los Angeles, CA USA. [Hoggatt, Katherine J.; Yano, Elizabeth M.] Univ Calif Los Angeles, Jonathan & Karin Fielding Sch Publ Hlth, Los Angeles, CA 90024 USA. [Balasubramanian, Vidhya; Saechao, Fay S.; Frayne, Susan M.; Phibbs, Ciaran S.] VA Palo Alto Hlth Care Syst, VA HSR&D Ctr Innovat Implementat Ci2i, Palo Alto, CA USA. [Frayne, Susan M.; Phibbs, Ciaran S.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Mattocks, Kristin M.] VA Cent Western Massachusetts, Leeds, MA USA. [Mattocks, Kristin M.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Haskell, Sally G.] Yale Sch Med, Med, New Haven, CT USA. [Haskell, Sally G.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Phibbs, Ciaran S.] VA Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, Palo Alto, CA USA. [Zephyrin, Laurie C.] NYU, Langone Med Ctr, New York, NY USA. RP Katon, JG (reprint author), VA Med Ctr, 1660S Columbian Way S-152, Seattle, WA 98108 USA. EM jkaton@u.washington.edu FU Women's Health Services in the Veterans Health Administration of the U.S. Department of Veteran Affairs (VA); VA Office of Academic Affiliations' Associated Health Postdoctoral Fellowship [TPP 61-026]; VA HSR&D Career Scientist Award [RCS 05-195]; VA HSR&D Career Development Award [CDA 11-261] FX Data for this study was originally compiled for the VA State of Reproductive Health Report in Women Veterans. This program evaluation work was supported by Women's Health Services in the Veterans Health Administration of the U.S. Department of Veteran Affairs (VA), and includes program evaluation data from the Women's Health Evaluation Initiative (WHEI) of Women's Health Services. Additional support included a VA Office of Academic Affiliations' Associated Health Postdoctoral Fellowship to J.G.K. (TPP 61-026), a VA HSR&D Career Scientist Award to E.M.Y. (grant RCS 05-195), and a VA HSR&D Career Development Award to K.J.H. (CDA 11-261). NR 28 TC 2 Z9 2 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD APR PY 2015 VL 53 IS 4 SU 1 BP S63 EP S67 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DS3BL UT WOS:000380657800011 PM 25767978 ER PT J AU Mattocks, K Kroll-Desrosiers, A Zephyrin, L Katon, J Weitlauf, J Bastian, L Haskell, S Brandt, C AF Mattocks, Kristin Kroll-Desrosiers, Aimee Zephyrin, Laurie Katon, Jodie Weitlauf, Julie Bastian, Lori Haskell, Sally Brandt, Cynthia TI Infertility Care Among OEF/OIF/OND Women Veterans in the Department of Veterans Affairs SO MEDICAL CARE LA English DT Article DE women's health; Veterans; infertility ID SELF-REPORTED INFERTILITY; GULF-WAR VETERANS; SEXUAL ASSAULT; MENTAL-HEALTH; AVAILABILITY; PREGNANCY; AFGHANISTAN; POPULATION; OUTCOMES; IRAQ AB Background: An increasing number of young women Veterans seek reproductive health care through the VA, yet little is known regarding the provision of infertility care for this population. The VA provides a range of infertility services for Veterans including artificial insemination, but does not provide in vitro fertilization. This study will be the first to characterize infertility care among OEF/OIF/OND women Veterans using VA care. Methods: We analyzed data from the OEF/OIF/OND roster file from the Defense Manpower Data Center (DMDC)-Contingency Tracking System Deployment file of military discharges from October 1, 2001-December 30, 2010, which includes 68,442 women Veterans between the ages of 18 and 45 who utilized VA health care after separating from military service. We examined the receipt of infertility diagnoses and care using ICD-9 and CPT codes. Results: Less than 2% (n = 1323) of OEF/OIF/OND women Veterans received an infertility diagnosis during the study period. Compared with women VA users without infertility diagnosis, those with infertility diagnosis were younger, obese, black, or Hispanic, have a service-connected disability rating, a positive screen for military sexual trauma, and a mental health diagnosis. Overall, 22% of women with an infertility diagnosis received an infertility assessment or treatment. Thirty-nine percent of women Veterans receiving infertility assessment or treatment received this care from non-VA providers. Conclusions: Overall, a small proportion of OEF/OIF/OND women Veterans received infertility diagnoses from the VA during the study period, and an even smaller proportion received infertility treatment. Nearly 40% of those who received infertility treatments received these treatments from non-VA providers, indicating that the VA may need to examine the training and resources needed to provide this care within the VA. Understanding women's use of VA infertility services is an important component of understanding VA's commitment to comprehensive medical care for women Veterans. C1 [Mattocks, Kristin] VA Cent Western Massachusetts Healthcare Syst, 421 N Main St, Leeds, MA 01053 USA. [Mattocks, Kristin; Kroll-Desrosiers, Aimee] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Kroll-Desrosiers, Aimee] Clin & Populat Hlth Res Program, Worcester, MA USA. [Zephyrin, Laurie] VA Cent Off, Reprod Hlth Women Vet Hlth Strateg Healthcare Grp, Washington, DC USA. [Katon, Jodie] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Katon, Jodie] VA Off Patient Serv, Off Womens Hlth, Washington, DC USA. [Katon, Jodie] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Weitlauf, Julie] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Weitlauf, Julie] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Bastian, Lori] Univ Connecticut, Dept Med, Mansfield, CT USA. [Bastian, Lori] VA Connecticut Healthcare Syst, West Haven, CT USA. [Haskell, Sally] VHA, Comprehens Womens Hlth, Washington, DC USA. [Haskell, Sally] Yale Univ, Sch Med, New Haven, CT USA. [Brandt, Cynthia] VA Connecticut, New Haven, CT USA. [Brandt, Cynthia] Yale Univ, Sch Med, Dept Emergency Med, New Haven, CT USA. RP Mattocks, K (reprint author), VA Cent Western Massachusetts Healthcare Syst, 421 N Main St, Leeds, MA 01053 USA. EM kristin.mattocks@va.gov FU Veteran Affairs Health Services Research and Development FX Supported by Veteran Affairs Health Services Research and Development. NR 23 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD APR PY 2015 VL 53 IS 4 SU 1 BP S68 EP S75 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DS3BL UT WOS:000380657800012 PM 25767979 ER PT J AU Washington, DL Farmer, MM Mor, SS Canning, M Yano, EM AF Washington, Donna L. Farmer, Melissa M. Mor, Su Sun Canning, Mark Yano, Elizabeth M. TI Assessment of the Healthcare Needs and Barriers to VA Use Experienced by Women Veterans Findings From the National Survey of Women Veterans SO MEDICAL CARE LA English DT Article DE women Veterans; health services need; access to care; VA healthcare; health services utilization ID POSTTRAUMATIC-STRESS-DISORDER; SHORT SCREENING SCALE; QUALITY; RELIABILITY; POPULATION; MORTALITY; VALIDITY; ACCESS; LIFE AB Background: Prior regional studies of women Veterans identified barriers to Veterans Affairs (VA) healthcare use. However, these studies do not reflect the demographic profile of women Veterans nationally, recent advances in VA women's healthcare, and the national context of expanded healthcare alternatives. Objective: To characterize health, VA perceptions, barriers, healthcare delivery preferences, and reasons for VA or non-VA healthcare use in a national women Veteran sample. Methods: Cross-sectional, population-based 2008-2009 National Survey of Women Veterans (n = 3611). Results: VA users had worse physical and mental health than non-VA-only users and healthcare nonusers. Older women Veterans had worse physical health, whereas younger groups had worse mental health. Healthcare use was highest for dual users, followed by VA-only users, but did not differ by age group. Healthcare nonusers were most likely to lack a regular source for healthcare. Perceptions of VA care quality and sex-appropriateness were highest for VA-only, followed by dual, then non-VA-only users. VA perceptions were guided by personal experience for 90% of VA users, versus media or other second-hand sources for 70% of other groups. Non-VA-only users and healthcare nonusers had more knowledge gaps about VA and misperceptions about VA eligibility and services; non-VA-only users more likely encountered VA enrollment barriers. Conclusions: Many nonusers had healthcare needs that were not met. Positive VA perceptions by women with first-hand VA experience, contrasted with VA knowledge gaps by those without such exposure, suggests the need for more education about available VA healthcare services. VA planning should account for mental health needs and healthcare use by younger women Veterans. C1 [Washington, Donna L.; Farmer, Melissa M.; Mor, Su Sun; Canning, Mark; Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, VA Greater Los Angeles Hlth Serv Res & Dev HSR&D, Sepulveda, CA USA. [Washington, Donna L.; Farmer, Melissa M.; Mor, Su Sun; Canning, Mark; Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, VA Greater Los Angeles Hlth Serv Res & Dev HSR&D, Los Angeles, CA USA. [Washington, Donna L.] Univ Calif Los Angeles, Dept Med, Geffen Sch Med, Los Angeles, CA 90024 USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, Los Angeles, CA USA. RP Washington, DL (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,111 G, Los Angeles, CA 90073 USA. EM donna.washington@va.gov FU Department of Veterans Affairs (VA) Women's Health Services, Office of Patient Care Services; VA Health Services Research and Development (HSRD) Service [SDR-08-270]; VA HSR&D Senior Research Career Scientist award [RCS-05-195]; VA Health Services Research and Development Service; VA Office of Patient Care Services FX Supported by the Department of Veterans Affairs (VA) Women's Health Services, Office of Patient Care Services, and the VA Health Services Research and Development (HSR&D) Service (#SDR-08-270). Dr. Yano is supported by a VA HSR&D Senior Research Career Scientist award (#RCS-05-195). Drs Washington, Farmer, and Yano receive research funding from the VA Health Services Research and Development Service. Drs Washington and Yano receive funding from the VA Office of Patient Care Services. NR 34 TC 12 Z9 12 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD APR PY 2015 VL 53 IS 4 SU 1 BP S23 EP S31 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DS3BL UT WOS:000380657800006 PM 25767972 ER PT J AU Yano, EM AF Yano, Elizabeth M. TI A Partnered Research Initiative to Accelerate Implementation of Comprehensive Care for Women Veterans The VA Women's Health CREATE SO MEDICAL CARE LA English DT Editorial Material ID SERVICES RESEARCH; TRANSLATION C1 [Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Study Healthcare Innovat Implementat, 16111 Plummer St,Mailcode 152, Sepulveda, CA 91343 USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, Los Angeles, CA USA. RP Yano, EM (reprint author), VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Study Healthcare Innovat Implementat, 16111 Plummer St,Mailcode 152, Sepulveda, CA 91343 USA. EM elizabeth.yano@va.gov FU VA HSR&D Service, Veterans Health Administration through the CREATE initiative [CRE 12-019, CRE 12-038, CRE 12-026, CRE 12-031, CRE-12-008]; VA HSR&D Senior Research Career Scientist Award [RCS 05-195]; VA Women's Health Services in the Office of Patient Care Services, Veterans Health Administration, Washington, DC; VA HSR&D Women's Health Research Network (WHRN) [SDR 10-012] FX Supported by VA HSR&D Service, Veterans Health Administration through the CREATE initiative, comprised of 5 interrelated projects (CRE 12-019: Susan Frayne, MD, MPH; Alison Hamilton, PhD, PIs; CRE 12-038: Elizabeth M. Yano, PhD, MSPH, PI; Danielle Rose, PhD, Co-PI; CRE 12-026: Elizabeth M. Yano, PhD, MSPH, PI; Lisa V. Rubenstein, MD, MSPH, Co-PI; CRE 12-031: Donna L. Washington, MD, MPH, PI; Kristina Cordasco, MD, MPH, Co-PI; and CRE-12-008: Lori Bastian, MD, MPH; Kristin Mattocks, PhD, PIs). E.M.Y. effort was funded by a VA HSR&D Senior Research Career Scientist Award (Project #RCS 05-195). CREATE management was funded by VA Women's Health Services (Chief Consultant, Patricia Hayes, PhD) in the Office of Patient Care Services, Veterans Health Administration, Washington, DC. Also supported by the VA HSR&D Women's Health Research Network (WHRN) (SDR 10-012). NR 25 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD APR PY 2015 VL 53 IS 4 SU 1 BP S10 EP S14 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DS3BL UT WOS:000380657800004 PM 25767962 ER PT J AU Luan, T Liu, XH Easley, JT Ravishankar, B Puttlitz, C Feeley, BT AF Luan, Tammy Liu, Xuhui Easley, Jeremiah T. Ravishankar, Bharat Puttlitz, Christian Feeley, Brian T. TI Muscle atrophy and fatty infiltration after an acute rotator cuff repair in a sheep model SO MLTJ-MUSCLES LIGAMENTS AND TENDONS JOURNAL LA English DT Article DE acute rotator cuff repair; fatty infiltration; fibrosis; SREBP-1; PPAR gamma ID SUPRASCAPULAR NERVE INJURY; ARTHROSCOPIC REPAIR; SKELETAL-MUSCLE; GENE-EXPRESSION; INTERVAL SLIDES; RAT MODEL; TEARS; DEGENERATION; IMPROVE; RELEASE AB Introduction: rotator cuff tears (RCTs) are the most common tendon injury seen in orthopedic patients. Muscle atrophy and fatty infiltration of the muscle are crucial factors that dictate the outcome following rotator cuff surgery. Though less studied in humans, rotator cuff muscle fibrosis has been seen in animal models as well and may influence outcomes as well. The purpose of this study was to determine if the rotator cuff would develop muscle changes even in the setting of an acute repair in a sheep model. We hypothesized that fatty infiltration and fibrosis would be present even after an acute repair six months after initial surgery. Methods: twelve female adult sheep underwent an acute rotator cuff tear and immediate repair on the right shoulder. The left shoulder served as a control and did not undergo a tear or a repair. Six months following acute rotator cuff repairs, sheep muscles were harvested to study atrophy, fatty infiltration, and fibrosis by histological analysis, western blotting, and reverse transcription polymerase chain reaction (RT-PCR). Results: the repair group demonstrated an increase expression of muscle atrophy, fatty infiltration, and fibrosis related genes. Significantly increased adipocytes, muscle fatty infiltration, and collagen deposition was observed in rotator cuff muscles in the tendon repair group compared to the control group. Conclusions: rotator cuff muscle undergoes degradation changes including fatty infiltration and fibrosis even after the tendons are repair immediately after rupture. Level of Evidence: Basic Science Study. C1 [Luan, Tammy; Liu, Xuhui; Ravishankar, Bharat] San Francisco VA Med Ctr, Dept Vet Affairs, San Francisco, CA USA. [Liu, Xuhui; Ravishankar, Bharat; Feeley, Brian T.] Univ Calif San Francisco, Dept Orthopaed Surg, 1500 Owens Ave,Box 3004, San Francisco, CA 94158 USA. [Easley, Jeremiah T.; Puttlitz, Christian] Colorado State Univ, Ft Collins, CO 80523 USA. RP Feeley, BT (reprint author), Univ Calif San Francisco, Dept Orthopaed Surg, 1500 Owens Ave,Box 3004, San Francisco, CA 94158 USA. EM feeleyb@orthosurg.ucsf.edu NR 46 TC 5 Z9 5 U1 0 U2 2 PU CIC EDIZIONI INT PI ROME PA CORSO TRIESTE 42, ROME, 00198, ITALY SN 2240-4554 J9 MLTJ-MUSCLE LIGAMENT JI MLTJ-Muscles Ligaments Tendons J. PD APR-JUN PY 2015 VL 5 IS 2 BP 106 EP 112 DI 10.11138/mltj/2015.5.2.106 PG 7 WC Orthopedics SC Orthopedics GA DZ2TT UT WOS:000385695200010 PM 26261789 ER PT J AU Liu, XH Joshi, S Ravishankar, B Laron, D Kim, HT Feeley, BT AF Liu, Xuhui Joshi, Sunil Ravishankar, Bharat Laron, Dominique Kim, Hubert T. Feeley, Brian T. TI Bone morphogenetic protein signaling in rotator cuff muscle atrophy and fatty infiltration SO MLTJ-MUSCLES LIGAMENTS AND TENDONS JOURNAL LA English DT Article DE atrophy; BMP; fatty infiltration; muscle; rotator cuff tear ID INDUCED HETEROTOPIC OSSIFICATION; SUPRASCAPULAR NERVE INJURY; MOUSE MODEL; REPAIR; TEARS; MASS; AUTOPHAGY AB Background: reduced mass (atrophy) and increased fat content (fatty infiltration) of rotator cuff muscles are common complications of large or massive rotator cuff (RC) tears, and are believed to be irreversible even after tendon repairs. Clinically, both muscle atrophy and fatty infiltration are important factors contributing to poor functional outcomes after tendon repairs. The molecular mechanism of RC muscle atrophy and FI remains undefined. In this study, we investigated the role of bone morphogenetic proteins (BMP) signaling in RC muscle atrophy and fatty infiltration using a rat model. Methods: unilateral massive RC tears was induced in adult rats. RC muscles were harvested at 2 and 6 weeks after injury for BMP signaling analysis. In a separate experiment, BMP inhibitor (LDN-193189) was injected to rats through daily intraperitoneal injection. RC muscles from rats in the treated and control groups were harvested at 6 weeks after injury for biochemistry and histology analysis. Results: we found significantly increased BMP-14 and BMP-7 expression in rotator cuff muscles after RCT. Inhibiting BMP signaling resulted in increased muscle atrophy and reduced fatty infiltration in rotator cuff muscle after RC tears. Conclusion: this result suggests that BMP signaling inhibits RC muscle atrophy but promotes fatty infiltration. C1 [Liu, Xuhui; Joshi, Sunil; Ravishankar, Bharat; Kim, Hubert T.; Feeley, Brian T.] San Francisco VA Med Ctr, Dept Vet Affairs, San Francisco, CA USA. [Liu, Xuhui; Ravishankar, Bharat; Laron, Dominique; Kim, Hubert T.; Feeley, Brian T.] Univ Calif San Francisco, Dept Orthopaed Surg, 1500 Owens Ave,Box 3004, San Francisco, CA 94158 USA. RP Feeley, BT (reprint author), Univ Calif San Francisco, Dept Orthopaed Surg, 1500 Owens Ave,Box 3004, San Francisco, CA 94158 USA. EM feeleyb@orthosurg.ucsf.edu FU NIAMS NIH HHS [R03 AR060871]; RRD VA [I01 RX000195] NR 21 TC 2 Z9 2 U1 0 U2 0 PU CIC EDIZIONI INT PI ROME PA CORSO TRIESTE 42, ROME, 00198, ITALY SN 2240-4554 J9 MLTJ-MUSCLE LIGAMENT JI MLTJ-Muscles Ligaments Tendons J. PD APR-JUN PY 2015 VL 5 IS 2 BP 113 EP 119 DI 10.11138/mltj/2015.5.2.113 PG 7 WC Orthopedics SC Orthopedics GA DZ2TT UT WOS:000385695200011 PM 26261790 ER PT J AU Kuhn, H Banthiya, S van Leyen, K AF Kuhn, Hartmut Banthiya, Swathi van Leyen, Klaus TI Mammalian lipoxygenases and their biological relevance SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Review DE Eicosanoid; Inflammation; Atherosclerosis; Cancer; Stroke; Infection ID PLATELET-TYPE 12-LIPOXYGENASE; PROSTATE-CANCER CELLS; E-DEFICIENT MICE; ACTIVATED RECEPTOR-GAMMA; X-RAY-SCATTERING; ARACHIDONIC-ACID METABOLISM; FUNCTIONAL TUMOR-SUPPRESSOR; SMOOTH-MUSCLE-CELLS; NF-KAPPA-B; ENHANCES 15-LIPOXYGENASE-MEDIATED VASORELAXATION AB Lipoxygenases (LOXs) form a heterogeneous class of lipid peroxidizing enzymes, which have been implicated not only in cell proliferation and differentiation but also in the pathogenesis of various diseases with major public health relevance. As other fatty acid dioxygenases LOXs oxidize polyunsaturated fatty adds to their corresponding hydroperoxy derivatives, which are further transformed to bioactive lipid mediators (eicosanoids and related substances). On the other hand, lipoxygenases are key players in the regulation of the cellular redox homeostasis, which is an important element in gene expression regulation. Although the first mammalian lipoxygenases were discovered 40 years ago and although the enzymes have been well characterized with respect to their structural and functional properties the biological roles of the different lipoxygenase isoforms are not completely understood. This review is aimed at summarizing the current knowledge on the physiological roles of different mammalian LOX-isoforms and their patho-physiological function in inflammatory, metabolic, hyperproliferative, neurodegenerative and infectious disorders. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance". (C) 2014 Elsevier B.V. All rights reserved. C1 [Kuhn, Hartmut; Banthiya, Swathi] Charite, Inst Biochem, D-10117 Berlin, Germany. [van Leyen, Klaus] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA USA. [van Leyen, Klaus] Harvard Univ, Sch Med, Charlestown, MA USA. RP Kuhn, H (reprint author), Charite, Inst Biochem, Charitepl 1,CCO Bldg,Virchowweg 6, D-10117 Berlin, Germany. EM hartmut.kuehn@charite.de FU Deutsche Forschungsgemeinschaft [GRK1673/1, GRK 1673/1]; U.S. National Institutes of Health [R01 NS49430, R01 NS069939] FX Financial support for this work was provided by GRK1673/1 granted by Deutsche Forschungsgemeinschaft (GRK 1673/1 to H.K.) and by the U.S. National Institutes of Health (R01 NS49430 and R01 NS069939 to K.v.L). NR 416 TC 47 Z9 52 U1 13 U2 44 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 EI 0006-3002 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD APR PY 2015 VL 1851 IS 4 SI SI BP 308 EP 330 DI 10.1016/j.bbalip.2014.10.002 PG 23 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA CC2PJ UT WOS:000350186800002 PM 25316652 ER PT J AU Stanley, TL Grinspoon, SK AF Stanley, Takara L. Grinspoon, Steven K. TI Effects of growth hormone-releasing hormone on visceral fat, metabolic, and cardiovascular indices in human studies SO GROWTH HORMONE & IGF RESEARCH LA English DT Review DE Growth hormone; Visceral obesity; Obesity; Growth hormone-releasing hormone; Cardiovascular risk ID HIV-INFECTED PATIENTS; RANDOMIZED CONTROLLED-TRIAL; CARDIOMETABOLIC RISK-FACTORS; HEPATIC-STEROID METABOLISM; CORONARY-HEART-DISEASE; EXCESS ABDOMINAL FAT; GH-DEFICIENT ADULTS; OBESE SUBJECTS; BODY-COMPOSITION; ADIPOSE-TISSUE AB Increased visceral adipose tissue (VAT) is associated with reductions in endogenous GH secretion, possibly as a result of hyperinsulinemia, increased circulating free fatty acid, increased somatostatin tone, and reduced ghrelin. Reduced GH may, in turn, further exacerbate visceral fat accumulation because of decreased hormone-sensitive lipolysis in this depot. Data from multiple populations demonstrate that both reduced GH and increased VAT appear to contribute independently to dyslipidemia, increased systemic inflammation, and increased cardiovascular risk. The reductions in GH in states of visceral adiposity are characterized by reduced basal and pulsatile GH secretion with intact pulse frequency. Treatment with GH-releasing hormone (GHRH) provides a means to reverse these abnormalities, increasing endogenous basal and pulsatile GH secretion without altering pulse frequency. This review describes data from HIV-infected individuals and individuals with general obesity showing that treatment with GHRH significantly reduces visceral fat, ameliorates dyslipidemia, and reduces markers of cardiovascular risk Further research is needed regarding the long-term efficacy and safety of this treatment modality. (C) 2014 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Program Nutr Metab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Grinspoon, SK (reprint author), MGH Program Nutr Metab, LON5-207,55 Fruit St, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU National Institutes of Health [K23 DK089910, R01DK063639, R01HL85268]; Nutrition Obesity Research Center, Harvard University (National Institutes of Health) [P30 DK40561]; National Center for Research Resources [M01RR01066, UL1RR025758] FX This work was supported in part by the National Institutes of Health [grants K23 DK089910 to T.LS. and R01DK063639 and R01HL85268 to S.KG.]. The work was also supported in part by the Nutrition Obesity Research Center, Harvard University (National Institutes of Health grant P30 DK40561) and by M01RR01066 and UL1RR025758 to the Harvard Clinical and Translational Science Center from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NR 81 TC 7 Z9 9 U1 2 U2 15 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1096-6374 EI 1532-2238 J9 GROWTH HORM IGF RES JI Growth Horm. IGF Res. PD APR PY 2015 VL 25 IS 2 BP 59 EP 65 DI 10.1016/j.ghir.2014.12.005 PG 7 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA CC1KG UT WOS:000350099000002 PM 25555516 ER PT J AU Arnold, RM Back, AL Barnato, AE Prendergast, TJ Emlet, LL Karpov, I White, PH Nelson, JE AF Arnold, Robert M. Back, Anthony L. Barnato, Amber E. Prendergast, Thomas J. Emlet, Lillian L. Karpov, Irina White, Patrick H. Nelson, Judith E. TI The Critical Care Communication project: Improving fellows' communication skills SO JOURNAL OF CRITICAL CARE LA English DT Article DE Communication; Critical care; Palliative care; Intensive care unit; Standardized patient; End-of-life care ID OF-LIFE CARE; STANDARDIZED FAMILY-MEMBERS; INTENSIVE-CARE; UNIT PATIENTS; PALLIATIVE CARE; HEALTH-CARE; END; CONFERENCES; SATISFACTION; SYMPTOMS AB Purpose: The aimof this study was to develop an evidence-based communication skills training workshop to improve the communication skills of critical care fellows. Materials and methods: Pulmonary and critical care fellows (N = 38) participated in a 3-day communication skills workshop between 2008 and 2010 involving brief didactic talks, faculty demonstration of skills, and facultysupervised small group skills practice sessions with simulated families. Skills included the following: giving bad news, achieving consensus on goals of therapy, and discussing the limitations of life-sustaining treatment. Participants rated their skill levels in a pre-post survey in 11 core communication tasks using a 5-point Likert scale. Results: Of 38 fellows, 36 (95%) completed all 3 days of the workshop. We compared pre and post scores using the Wilcoxon signed rank test. Overall, self-rated skills increased for all 11 tasks. In analyses by participant, 95% reported improvement in at least 1 skill; with improvement in amedian of 10 of 11 skills. Ninety-two percent rated the course as either very good/excellent, and 80% recommended that it be mandatory for future fellows. Conclusions: This 3-day communication skills training program increased critical care fellows' self-reported family meeting communication skills. (C) 2014 Elsevier Inc. All rights reserved. C1 [Arnold, Robert M.; Barnato, Amber E.] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Arnold, Robert M.] Univ Pittsburgh, Med Ctr, UPMC Support & Palliat Care Program, Pittsburgh, PA 15213 USA. [Back, Anthony L.] Univ Washington, Dept Med Oncol, Seattle, WA 98195 USA. [Prendergast, Thomas J.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR USA. [Prendergast, Thomas J.] Portland VA Med Ctr, Sect Pulm & Crit Care, Portland, OR USA. [Emlet, Lillian L.] Univ Pittsburgh, Dept Crit Care Med & Emergency Med, Pittsburgh, PA 15213 USA. [Karpov, Irina] Univ Pittsburgh, Ctr Res Hlth Care, Ctr Data, Pittsburgh, PA 15213 USA. [White, Patrick H.] Univ Pittsburgh, Clin & Translat Sci Program, Pittsburgh, PA 15213 USA. [Nelson, Judith E.] Icahn Sch Med Mt Sinai, Dept Med, Div Pulm Crit Care & Sleep Med, New York, NY 10029 USA. RP Arnold, RM (reprint author), Univ Pittsburgh, 200 Lothrop St, Pittsburgh, PA 15213 USA. EM rabob@pitt.edu OI Arnold, Bob/0000-0003-1610-8932 FU National Palliative Care Research Center; Jewish Healthcare Foundation; Arthur Vining Davis Foundation; National Institutes of Health [TL-1, 8TL1R000145] FX This program was supported by grants from the National Palliative Care Research Center, Jewish Healthcare Foundation, and Arthur Vining Davis Foundation. Dr Arnold receives support from the Jewish Healthcare Foundation. Dr White was supported by the National Institutes of Health TL-1 Award # 8TL1R000145. NR 25 TC 14 Z9 14 U1 3 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0883-9441 EI 1557-8615 J9 J CRIT CARE JI J. Crit. Care PD APR PY 2015 VL 30 IS 2 BP 250 EP 254 DI 10.1016/j.jcrc.2014.11.016 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA CB8WV UT WOS:000349913800006 PM 25535029 ER PT J AU Wachinger, C Golland, P Kremen, W Fischl, B Reuter, M AF Wachinger, Christian Golland, Polina Kremen, William Fischl, Bruce Reuter, Martin CA Alzheimer's Dis Neuroimaging Initi TI BrainPrint: A discriminative characterization of brain morphology SO NEUROIMAGE LA English DT Article DE Brain shape; Large brain datasets; Brain similarity; Subject identification; Brain asymmetry; Morphological heritability ID SURFACE-BASED ANALYSIS; CORTICAL SURFACE; ALZHEIMERS-DISEASE; SPECTRAL-ANALYSIS; ENVIRONMENTAL-INFLUENCES; CEREBRAL LATERALIZATION; GENETIC INFLUENCES; COORDINATE SYSTEM; SHAPE-ANALYSIS; TWIN AB We introduce BrainPrint, a compact and discriminative representation of brain morphology. BrainPrint captures shape information of an ensemble of cortical and subcortical structures by solving the eigenvalue problem of the 2D and 3D Laplace-Beltrami operator on triangular (boundary) and tetrahedral (volumetric) meshes. This discriminative characterization enables new ways to study the similarity between brains; the focus can either be on a specific brain structure of interest or on the overall brain similarity. We highlight four applications for BrainPrint in this article: (i) subject identification, (ii) age and sex prediction, (iii) brain asymmetry analysis, and (iv) potential genetic influences on brain morphology. The properties of BrainPrint require the derivation of new algorithms to account for the heterogeneous mix of brain structures with varying discriminative power. We conduct experiments on three datasets, including over 3000 MRI scans from the ADNI database, 436 MRI scans from the OASIS dataset, and 236 MRI scans from the VETSA twin study. All processing steps for obtaining the compact representation are fully automated, making this processing framework particularly attractive for handling large datasets. (C) 2015 Elsevier Inc. All rights reserved. C1 [Wachinger, Christian; Golland, Polina; Fischl, Bruce; Reuter, Martin] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Wachinger, Christian; Fischl, Bruce; Reuter, Martin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. [Kremen, William] Univ Calif San Diego, San Diego, CA 92103 USA. [Kremen, William] VA San Diego, Ctr Excellence Stress & Mental Hlth, San Diego, CA USA. RP Wachinger, C (reprint author), 32 Vassar St,D462, Cambridge, MA 02139 USA. EM wachinger@csail.mit.edu RI Christian, Wachinger/L-7358-2016 OI Christian, Wachinger/0000-0002-3652-1874 FU Humboldt Foundation; National Cancer Institute [1K25-CA181632-01]; Martinos Center for Biomedical Imaging [P41-RR014075, P41-EB015896]; National Alliance for Medical Image Computing [U54-EB005149]; NeuroImaging Analysis Center [P41-EB015902]; National Center for Research Resources [U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering [5P41EB015896-15, R01EB006758]; National Institute on Aging [AG022381, 5R01AG008122-22, AG018344, AG018386]; National Center for Alternative Medicine [RC1 AT005728-01]; National Institute for Neurological Disorders and Stroke [R01 NS052585-01, 1R21NS072652-01, 1R01NS070963, R01NS083534]; Autism & Dyslexia Project - Ellison Medical Foundation; NIH Blueprint for Neuroscience Research [5U01-MH093765]; Massachusetts Alzheimer's Disease Research Center [5 P50 AG005134]; MGH Neurology Clinical Trials Unit; Harvard NeuroDiscovery Center; Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; DOD ADNI (Department of Defense) [W81XWH-12-2-0012]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Canadian Institutes of Health Research; [1S10RR023401]; [1S10RR019307]; [1S10RR023043] FX We thank the reviewers for their helpful suggestions to improve the manuscript. Support for this research was provided in part by the Humboldt Foundation, the National Cancer Institute (1K25-CA181632-01), the Martinos Center for Biomedical Imaging (P41-RR014075, P41-EB015896), the National Alliance for Medical Image Computing (U54-EB005149), the NeuroImaging Analysis Center (P41-EB015902), the National Center for Research Resources (U24 RR021382), the National Institute for Biomedical Imaging and Bioengineering (5P41EB015896-15, R01EB006758), the National Institute on Aging (AG022381, 5R01AG008122-22, AG018344, AG018386), the National Center for Alternative Medicine (RC1 AT005728-01), the National Institute for Neurological Disorders and Stroke (R01 NS052585-01, 1R21NS072652-01, 1R01NS070963, R01NS083534), and was made possible by the resources provided by Shared Instrumentation Grants 1S10RR023401, 1S10RR019307, and 1S10RR023043. Additional support was provided by The Autism & Dyslexia Project funded by the Ellison Medical Foundation, and by the NIH Blueprint for Neuroscience Research (5U01-MH093765), part of the multi-institutional Human Connectome Project. MR was additionally supported by a grant from the Massachusetts Alzheimer's Disease Research Center (5 P50 AG005134), the MGH Neurology Clinical Trials Unit, and the Harvard NeuroDiscovery Center. In addition, BF has a financial interest in CorticoMetrics, a company whose medical pursuits focus on brain imaging and measurement technologies. BF's interests were reviewed and are managed by the Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies.; Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development, LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. NR 85 TC 14 Z9 14 U1 2 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD APR 1 PY 2015 VL 109 BP 232 EP 248 DI 10.1016/j.neuroimage.2015.01.032 PG 17 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CB9SB UT WOS:000349971600022 PM 25613439 ER PT J AU Ge, T Nichols, TE Ghosh, D Mormino, EC Smoller, JW Sabuncu, MR AF Ge, Tian Nichols, Thomas E. Ghosh, Debashis Mormino, Elizabeth C. Smoller, Jordan W. Sabuncu, Mert R. CA Alzheimer's Dis Neuroimaging Initi TI A kernel machine method for detecting effects of interaction between multidimensional variable sets: An imaging genetics application SO NEUROIMAGE LA English DT Article DE Interaction; Kernel machines; Alzheimer's disease; Cardiovascular disease; Imaging genetics ID GENOME-WIDE ASSOCIATION; VASCULAR RISK-FACTORS; LONGITUDINAL NEUROIMAGE DATA; INCIDENT ALZHEIMER-DISEASE; SURFACE-BASED ANALYSIS; COMMON SNPS; IDENTIFIES VARIANTS; APOE GENOTYPE; ENVIRONMENT; MODELS AB Measurements derived from neuroimaging data can serve as markers of disease and/or healthy development, are largely heritable, and have been increasingly utilized as (intermediate) phenotypes in genetic association studies. To date, imaging genetic studies have mostly focused on discovering isolated genetic effects, typically ignoring potential interactions with non-genetic variables such as disease risk factors, environmental exposures, and epigenetic markers. However, identifying significant interaction effects is critical for revealing the true relationship between genetic and phenotypic variables, and shedding light on disease mechanisms. In this paper, we present a general kernel machine based method for detecting effects of the interaction between multidimensional variable sets. This method can model the joint and epistatic effect of a collection of single nucleotide polymorphisms (SNPs), accommodate multiple factors that potentially moderate genetic influences, and test for nonlinear interactions between sets of variables in a flexible framework. As a demonstration of application, we applied the method to the data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to detect the effects of the interactions between candidate Alzheimer's disease (AD) risk genes and a collection of cardiovascular disease (CVD) risk factors, on hippocampal volume measurements derived from structural brain magnetic resonance imaging (MRI) scans. Our method identified that two genes, CR1 and EPHA1, demonstrate significant interactions with CVD risk factors on hippocampal volume, suggesting that CR1 and EPHA1 may play a role in influencing AD-related neurodegeneration in the presence of CVD risks. (C) 2015 Elsevier Inc. All rights reserved. C1 [Ge, Tian; Sabuncu, Mert R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Ge, Tian; Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Nichols, Thomas E.] Univ Warwick, Dept Stat, Coventry CV4 7AL, W Midlands, England. [Nichols, Thomas E.] Univ Warwick, Warwick Mfg Grp, Coventry CV4 7AL, W Midlands, England. [Ghosh, Debashis] Penn State Univ, Dept Stat, University Pk, PA 16802 USA. [Mormino, Elizabeth C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Smoller, Jordan W.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02138 USA. [Sabuncu, Mert R.] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. RP Sabuncu, MR (reprint author), Athinoula A Martinos Ctr Biomed Imaging, 149 Thirteenth St,Suite 2301, Charlestown, MA 02129 USA. EM tge1@nmr.mgh.harvard.edu; msabuncu@nmr.mgh.harvard.edu FU Alzheimer's Disease Neuroimaging Initiative (ADNI) [U01 AG024904]; DOD ADNI [W81XWH-12-2-0012]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Canadian Institutes of Health Research; Center for Functional Neuroimaging Technologies [P41EB015896]; National Institute of Biomedical Imaging and Bioengineering (NIBIB) [P41]; National Institutes of Health (NIH); NIH [R01 EB01561101, U54 MH091657-03, R01 NS083534, R01 NS070963]; NIH NIBIB [1K25EB013649-01, K24MH094614, R01 MH101486]; Wellcome Trust [100309/Z/12/Z, 098369/Z/12/Z]; BrightFocus Foundation [AHAF-A2012333]; National Institute on Aging [R01 AG008122, R01 AG016495] FX Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, and the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N. V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www. fnih. org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.; This research was carried out in whole or in part at Athinoula A. Martinos Center for Biomedical Imaging atMassachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41EB015896, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), and the National Institutes of Health (NIH).; This research was also funded in part by NIH grants R01 EB01561101 and U54 MH091657-03 (TEN), R01 NS083534, and R01 NS070963, and NIH NIBIB 1K25EB013649-01 (MRS), K24MH094614 and R01 MH101486 (JWS), Wellcome Trust grants 100309/Z/12/Z and 098369/ Z/12/Z (TEN), and a BrightFocus Foundation grant AHAF-A2012333 (MRS). Two additional R01 grants from the National Institute on Aging (R01 AG008122 and R01 AG016495) provided partial support for this research. NR 81 TC 3 Z9 3 U1 81 U2 87 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 APR 1 PY 2015 VL 109 BP 505 EP 514 DI 10.1016/j.neuroimage.2015.01.029 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CB9SB UT WOS:000349971600045 PM 25600633 ER PT J AU Gardella, TJ Vilardaga, JP AF Gardella, Thomas J. Vilardaga, Jean-Pierre TI International Union of Basic and Clinical Pharmacology. XCIII. The Parathyroid Hormone Receptors-Family B G Protein-Coupled Receptors SO PHARMACOLOGICAL REVIEWS LA English DT Review ID (PTH)/PTH-RELATED PEPTIDE RECEPTOR; PTH-RELATED PEPTIDE; JANSENS METAPHYSEAL CHONDRODYSPLASIA; PHOTOAFFINITY CROSS-LINKING; CORTICOTROPIN-RELEASING-FACTOR; BETA-ADRENERGIC-RECEPTOR; N-TERMINAL REGION; REGULATED KINASE ACTIVATION; EXTRACELLULAR LOOP REGIONS; AMINO ACID SEQUENCE AB The type-1 parathyroid hormone receptor (PTHR1) is a family B G protein-coupled receptor (GPCR) that mediates the actions of two polypeptide ligands; parathyroid hormone (PTH), an endocrine hormone that regulates the levels of calcium and inorganic phosphate in the blood by acting on bone and kidney, and PTH-related protein (PTHrP), a paracrine-factor that regulates cell differentiation and proliferation programs in developing bone and other tissues. The type-2 parathyroid hormone receptor (PTHR2) binds a peptide ligand, called tuberoinfundibular peptide-39 (TIP39), and while the biologic role of the PTHR2/TIP39 system is not as defined as that of the PTHR1, it likely plays a role in the central nervous system as well as in spermatogenesis. Mechanisms of action at these receptors have been explored through a variety of pharmacological and biochemical approaches, and the data obtained support a basic "two-site" mode of ligand binding now thought to be used by each of the family B peptide hormone GPCRs. Recent crystallographic studies on the family B GPCRs are providing new insights that help to further refine the specifics of the overall receptor architecture and modes of ligand docking. One intriguing pharmacological finding for the PTHR1 is that it can form surprisingly stable complexes with certain PTH/PTHrP ligand analogs and thereby mediate markedly prolonged cell signaling responses that persist even when the bulk of the complexes are found in internalized vesicles. The PTHR1 thus appears to be able to activate the Gas/cAMP pathway not only from the plasma membrane but also from the endosomal domain. The cumulative findings could have an impact on efforts to develop new drug therapies for the PTH receptors. C1 [Gardella, Thomas J.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Vilardaga, Jean-Pierre] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Lab GPCR Biol, Pittsburgh, PA USA. RP Gardella, TJ (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 10,50 Blossom St, Boston, MA 02114 USA. EM Gardella@Helix.MGH.Harvard.edu FU National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [P01-DK11794, R01-DK087688, R01-DK102495]; Wellcome Trust [099156/Z/12/Z] FX Grant support to conduct research related to this work was provided by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grants P01-DK11794 (project I; to T.J.G.) and R01-DK087688 and R01-DK102495 (to J.P.V.)]. NC-IUPHAR is supported in part by Wellcome Trust Grant 099156/Z/12/Z. NR 265 TC 7 Z9 7 U1 1 U2 23 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0031-6997 EI 1521-0081 J9 PHARMACOL REV JI Pharmacol. Rev. PD APR PY 2015 VL 67 IS 2 BP 310 EP 337 DI 10.1124/pr.114.009464 PG 28 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CC2WS UT WOS:000350206300003 PM 25713287 ER PT J AU Bechard, LJ Gordon, C Feldman, HA Venick, R Gura, K Guinan, EC Duggan, C AF Bechard, Lori J. Gordon, Catherine Feldman, Henry A. Venick, Robert Gura, Kathleen Guinan, Eva C. Duggan, Christopher TI Bone Loss and Vitamin D Deficiency in Children Undergoing Hematopoietic Cell Transplantation SO PEDIATRIC BLOOD & CANCER LA English DT Article DE bone density; bone demineralization; hematopoietic cell transplantation; vitamin D ID LONG-TERM SURVIVORS; MINERAL DENSITY; MARROW-TRANSPLANTATION; YOUNG-ADULTS; RISK-FACTORS; CHILDHOOD; TURNOVER; LEUKEMIA; HEALTH; SCT AB BackgroundHematopoietic cell transplantation (HCT) may be detrimental to bone health and vitamin D status in children. ProcedureWe conducted a prospective, multicenter cohort study to identify changes in bone health markers during the first 100 days after allogeneic HCT in 26 children. Bone mineral density (BMD), bone mineral content (BMC), and serum 25-hydroxyvitamin D (25OHD) concentrations were measured at baseline, 30 days, and 100 days after HCT. ResultsMean (SD) BMD and BMC Z-scores (-0.48 1.09 and -0.98 +/- 1.26, respectively) were normal at baseline. Repeated-measures analysis revealed significant declines in BMD and BMC Z-scores over the 100 day study period, when adjusted for age, sex, Tanner stage, lean mass, fat mass, resting energy expenditure, total energy intake, insulin sensitivity, serum phosphorus, and inpatient steroid intake. Adjusted mean (SE) 25OHD concentrations declined from 29.2 (3.1)ng/ml at baseline, to 17.7 (1.8)ng/ml at 100 days after HCT. Vitamin D deficiency (25OHD <20ng/ml) was present in 50% of patients 100 days after HCT. ConclusionsSignificant bone loss and vitamin D deficiency occur in children in the first 100 days following allogeneic HCT. Strategies to diminish acute bone loss during HCT in children are needed. Pediatr Blood Cancer 2015;62:687-692. (c) 2015 Wiley Periodicals, Inc. C1 [Bechard, Lori J.; Feldman, Henry A.; Gura, Kathleen; Duggan, Christopher] Boston Childrens Hosp, Ctr Nutr, Boston, MA 02115 USA. [Bechard, Lori J.; Guinan, Eva C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gordon, Catherine] Hasbro Childrens Hosp, Providence, RI USA. [Venick, Robert] Univ Calif Los Angeles, Mattel Childrens Hosp, Los Angeles, CA USA. RP Bechard, LJ (reprint author), Boston Childrens Hosp, Ctr Nutr, 333 Longwood Ave, Boston, MA 02115 USA. EM lori.bechard@childrens.harvard.edu FU Massachusetts Vitamin Litigation Grant; NIH NCRR grant [M01-RR02172]; NIH [K24 HD 058795]; [UL1 RR025758-01]; [M01-RR00865] FX Grant sponsor: Supported by the Massachusetts Vitamin Litigation Grant; NIH NCRR grant M01-RR02172 to Children's Hospital, Boston General Clinical Research Center; grant UL1 RR025758-01 to the Harvard Catalyst CTSA 1; grant M01-RR00865 to the General Clinical Research Centers Program at UCLA; and NIH K24 HD 058795 (to CD) NR 29 TC 2 Z9 2 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD APR PY 2015 VL 62 IS 4 BP 687 EP 692 DI 10.1002/pbc.25370 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA CB9WS UT WOS:000349985300024 PM 25630874 ER PT J AU Simeone, FJ Huang, AJ Chang, CY Smith, M Gill, TJ Bredella, MA Torriani, M AF Simeone, F. Joseph Huang, Ambrose J. Chang, Connie Y. Smith, Maximilian Gill, Thomas J. Bredella, Miriam A. Torriani, Martin TI Posteromedial knee friction syndrome: an entity with medial knee pain and edema between the femoral condyle, sartorius and gracilis SO SKELETAL RADIOLOGY LA English DT Article DE Knee; Gracilis; Sartorius; Femoral condyle; MR imaging; Friction syndrome, edema ID ILIOTIBIAL BAND SYNDROME; SNAPPING PES SYNDROME; IMAGING FINDINGS; TENDON AB To describe MRI features of an entity consisting of medial knee pain and edema between the posteromedial femoral condyle (PMFC), sartorius and/or gracilis tendons and determine whether reduced tendon-bone distances may account for these findings. We retrospectively identified MRI cases of edema between the PMFC, sartorius and/or gracilis tendons (25 subjects, 26 knees). Two musculoskeletal radiologists independently graded edema and measured the sartorius- and gracilis-PMFC distances and knee flexion angle. Age- and gender-matched subjects with normal knee MRIs (27 subjects, 27 knees) served as controls for measurements. Statistical analyses compared abnormal to control subjects. Sartorius-PMFC and gracilis-PMFC spaces were narrower in abnormal compared to control subjects (1.6 +/- 1.0 vs. 2.1 +/- 1.2 mm, P = 0.04; 2.3 +/- 2.0 vs. 4.6 +/- 3.0 mm, P = 0.002, respectively). The knee flexion angle was similar between groups (P > 0.05). In subjects with clinical information, medial knee pain was the main complaint in 58 % (15/26) of abnormal subjects, with 42 % (11/26) having clinical suspicion of medial meniscal tear. Edema between the PMFC, sartorius and/or gracilis was mild in 54 % (14/26), moderate in 35 % (9/26) and severe in 12 % (3/26), and it was most frequent deep to both the sartorius and gracilis (50 %, 13/26). Edema between the PMFC, sartorius and/or gracilis tendons identified on knee MRI may be associated with medial knee pain and may represent a friction syndrome. C1 [Simeone, F. Joseph; Huang, Ambrose J.; Chang, Connie Y.; Smith, Maximilian; Bredella, Miriam A.; Torriani, Martin] Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. [Simeone, F. Joseph; Huang, Ambrose J.; Chang, Connie Y.; Smith, Maximilian; Bredella, Miriam A.; Torriani, Martin] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Gill, Thomas J.] Boston Sports Med & Res Inst, Boston, MA USA. RP Torriani, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, 55 Fruit Str YAW 6048, Boston, MA 02114 USA. EM mtorriani@mgh.harvard.edu NR 16 TC 1 Z9 1 U1 2 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 EI 1432-2161 J9 SKELETAL RADIOL JI Skeletal Radiol. PD APR PY 2015 VL 44 IS 4 BP 557 EP 563 DI 10.1007/s00256-014-2081-5 PG 7 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA CB1FQ UT WOS:000349372800011 PM 25527466 ER PT J AU Tian, HJ Li, CS Zhao, KW Wang, JC Duarte, MEL David, CL Phan, K Atti, E Brochmann, EJ Murray, SS AF Tian, Haijun Li, Chen-Shuang Zhao, Ke-Wei Wang, Jeffrey C. Duarte, M. Eugenia L. David, Cynthia L. Phan, Kevin Atti, Elisa Brochmann, Elsa J. Murray, Samuel S. TI A Carboxy Terminal BMP/TGF-beta Binding Site in Secreted Phosphoprotein 24 kD Independently Affects BMP-2 Activity SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE SECRETED PHOSPHOPROTEIN 24 kD; BONE MORPHOGENETIC PROTEIN 2; BONE RESEARCH ID RODENT MODEL; PROTEIN; PEPTIDE; SPP24; GROWTH AB Secreted phosphoprotein 24kD (spp24) is a bone matrix protein isolated during attempts to identify osteogenic proteins. It is not osteogenic but performs other important roles in the regulation of bone metabolism, at least in part, by binding to and affecting the activity of members of the BMP/TGF- family of cytokines. Spp24 exists in a number of forms that preserve the N-terminus and are truncated at the C-terminus. The hypothesized cytokine binding domain is present within the cystatin domain which is preserved in all of the N-terminal products. In this report, we describe a C-terminal fragment that is distinct from the cystatin domain and which independently binds to BMP-2 and TGF-. This fragment inhibited BMP-2 activity in an ectopic bone forming assay. A shorter C-terminal product did not inhibit BMP-2 activity but improved bone quality induced by BMP-2 and produced increased calcium deposition outside of bone. Spp24 has been used to develop several potential therapeutic proteins. These results provide more information on the function of spp24 and provide other materials that can be exploited for clinical interventions. J. Cell. Biochem. 116: 667-676, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Tian, Haijun] Second Mil Med Univ, Shanghai Changzheng Hosp, Dept Orthopaed Surg, Shanghai 200003, Peoples R China. [Tian, Haijun; Wang, Jeffrey C.; Phan, Kevin] Univ Calif Los Angeles, Dept Orthopaed Surg, Los Angeles, CA 90024 USA. [Li, Chen-Shuang] Peking Univ Sch & Hosp Stomatol, Dept Orthodont, Beijing 100081, Peoples R China. [Zhao, Ke-Wei; Brochmann, Elsa J.; Murray, Samuel S.] VA Greater Los Angeles Healthcare Syst, Res Serv, North Hills, CA 91343 USA. [Duarte, M. Eugenia L.] Univ Fed Rio de Janeiro, Natl Inst Traumatol & Orthopaed, BR-21941 Rio De Janeiro, Brazil. [David, Cynthia L.] Univ Arizona, Ctr Toxicol, Tucson, AZ 85721 USA. [Atti, Elisa] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. [Brochmann, Elsa J.; Murray, Samuel S.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, North Hills, CA 91343 USA. [Brochmann, Elsa J.; Murray, Samuel S.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Tian, HJ (reprint author), Second Mil Med Univ, Shanghai Changzheng Hosp, Dept Orthopaed Surg, 415 Fengyang Rd, Shanghai 200003, Peoples R China. EM haijuntianmd@gmail.com FU Research Service of the Department of Veterans Affairs [1I01BX000511]; NIEHS [ES06694]; NIH/NCI [CA023074] FX Grant sponsor: Research Service of the Department of Veterans Affairs; Grant number: 1I01BX000511; Grant sponsor: NIEHS; Grant number: ES06694; Grant sponsor: NIH/NCI; Grant number: CA023074. NR 17 TC 3 Z9 3 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0730-2312 EI 1097-4644 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR PY 2015 VL 116 IS 4 BP 667 EP 676 DI 10.1002/jcb.25023 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CA8IU UT WOS:000349163000020 PM 25418420 ER PT J AU Wang, J Freire, D Knable, L Zhao, W Gong, B Mazzola, P Ho, L Levine, S Pasinetti, GM AF Wang, Jun Freire, Daniel Knable, Lindsay Zhao, Wei Gong, Bing Mazzola, Paolo Ho, Lap Levine, Samara Pasinetti, Giulio M. TI Childhood and Adolescent Obesity and Long-Term Cognitive Consequences During Aging SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE obesity; insulin resistance; aging; synaptic plasticity; cognitive function ID IMPAIR SYNAPTIC PLASTICITY; METABOLIC SYNDROME; ALZHEIMERS-DISEASE; MOUSE MODEL; BETA OLIGOMERS; OVERWEIGHT; CHILDREN; RISK; RATS; DIET AB The prevalence of childhood/adolescent obesity and insulin resistance has reached an epidemic level. Obesity's immediate clinical impacts have been extensively studied; however, current clinical evidence underscores the long-term implications. The current study explored the impacts of brief childhood/adolescent obesity and insulin resistance on cognitive function in later life. To mimic childhood/adolescent obesity and insulin resistance, we exposed 9-week-old C57BL/6J mice to a high-fat diet for 15 weeks, after which the mice exhibited diet-induced obesity and insulin resistance. We then put these mice back on a normal low-fat diet, after which the mice exhibited normal body weight and glucose tolerance. However, a spatial memory test in the forms of the Morris water maze (MWM) and contextual fear conditioning at 85 weeks of age showed that these mice had severe deficits in learning and long-term memory consolidation. Mechanistic investigations identified increased expression of histone deacetylases 5, accompanied by reduced expression of brain-derived neurotrophic factor, in the brains 61 weeks after the mice had been off the high-fat diet. Electrophysiology studies showed that hippocampal slices isolated from these mice are more susceptible to synaptic impairments compared with slices isolated from the control mice. We demonstrated that a 15-week occurrence of obesity and insulin resistance during childhood/adolescence induces irreversible epigenetic modifications in the brain that persist following restoration of normal metabolic homeostasis, leading to brain synaptic dysfunction during aging. Our study provides experimental evidence that limited early-life exposure to obesity and insulin resistance may have long-term deleterious consequences in the brain, contributing to the onset/progression of cognitive dysfunction during aging. J. Comp. Neurol. 523:757-768, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Wang, Jun; Freire, Daniel; Knable, Lindsay; Zhao, Wei; Gong, Bing; Mazzola, Paolo; Ho, Lap; Levine, Samara; Pasinetti, Giulio M.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Wang, Jun; Pasinetti, Giulio M.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY 10468 USA. [Mazzola, Paolo] Univ Milano Bicocca, Dept Hlth Sci, I-20900 Monza, MB, Italy. [Mazzola, Paolo] San Gerardo Univ Hosp, Geriatr Clin, I-20900 Monza, MB, Italy. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Dept Neurol, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu OI Mazzola, Paolo/0000-0002-0484-1136 FU Mount Sinai School of Medicine FX Grant sponsor: Mount Sinai School of Medicine. NR 47 TC 8 Z9 10 U1 6 U2 94 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9967 EI 1096-9861 J9 J COMP NEUROL JI J. Comp. Neurol. PD APR 1 PY 2015 VL 523 IS 5 BP 757 EP 768 DI 10.1002/cne.23708 PG 12 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA CA0AM UT WOS:000348576500004 PM 25380530 ER PT J AU Stefater, JA Borkar, DS Chodosh, J AF Stefater, James A. Borkar, Durga S. Chodosh, James TI Pink hypopyon in a patient with Serratia marcescens corneal ulceration SO JOURNAL OF OPHTHALMIC INFLAMMATION AND INFECTION LA English DT Letter DE Corneal ulcer; Pink hypopyon; Serratia marcescens AB A 65-year-old woman presented to the emergency ward at the Massachusetts Eye and Ear Infirmary with 2 days of redness, irritation, photophobia, and diminished vision in her left eye. She was found to have a large central corneal ulcer with a small hypopyon. On the following day, after initiation of broad-spectrum antibiotics, the patient had improved symptoms but now had a 2-mm hypopyon that was distinctly pink in color. Cultures were positive for Serratia marcescens. A pink hypopyon, a rare occurrence, alerted the authors to a causative agent of Enterobacteriacae, either Klebsiella or Serratia. Immediate and intensive treatment was subsequently initiated. C1 [Stefater, James A.; Borkar, Durga S.; Chodosh, James] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Chodosh, J (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM James_Chodosh@meei.harvard.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1869-5760 J9 J OPHTHALMIC INFLAMM JI J. Ophthalmic Inflamm. Infect. PD MAR 31 PY 2015 VL 5 AR 9 DI 10.1186/s12348-015-0041-4 PG 2 WC Ophthalmology SC Ophthalmology GA CZ2JZ UT WOS:000366932800001 PM 25861400 ER PT J AU Lyratzopoulos, G Vedsted, P Singh, H AF Lyratzopoulos, G. Vedsted, P. Singh, H. TI Understanding missed opportunities for more timely diagnosis of cancer in symptomatic patients after presentation SO BRITISH JOURNAL OF CANCER LA English DT Article DE neoplasm; diagnosis; missed opportunities; patient safety; general practice; system factors; errors; quality ID HEALTH-CARE-SYSTEMS; GENERAL-PRACTICE; LUNG-CANCER; ALARM SYMPTOMS; ERRORS; EXPERIENCE; COHORT; RECORD; SAFETY; MODEL AB The diagnosis of cancer is a complex, multi-step process. In this paper, we highlight factors involved in missed opportunities to diagnose cancer more promptly in symptomatic patients and discuss responsible mechanisms and potential strategies to shorten intervals from presentation to diagnosis. Missed opportunities are instances in which post-hoc judgement indicates that alternative decisions or actions could have led to more timely diagnosis. They can occur in any of the three phases of the diagnostic process (initial diagnostic assessment; diagnostic test performance and interpretation; and diagnostic follow-up and coordination) and can involve patient, doctor/care team, and health-care system factors, often in combination. In this perspective article, we consider epidemiological 'signals' suggestive of missed opportunities and draw on evidence from retrospective case reviews of cancer patient cohorts to summarise factors that contribute to missed opportunities. Multi-disciplinary research targeting such factors is important to shorten diagnostic intervals post presentation. Insights from the fields of organisational and cognitive psychology, human factors science and informatics can be extremely valuable in this emerging research agenda. We provide a conceptual foundation for the development of future interventions to minimise the occurrence of missed opportunities in cancer diagnosis, enriching current approaches that chiefly focus on clinical decision support or on widening access to investigations. C1 [Lyratzopoulos, G.] UCL, Dept Epidemiol & Publ Hlth, Hlth Behav Res Ctr, London WC1E 6BT, England. [Lyratzopoulos, G.] Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge Ctr Hlth Serv Res, Cambridge CB2 0SR, England. [Vedsted, P.] Aarhus Univ, Res Ctr Canc Diag Primary Care CaP, Res Unit Gen Practice, Dept Publ Hlth, DK-8000 Aarhus, Denmark. [Singh, H.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston Vet Affairs Ctr Innovat Qual Effectivenes, Houston, TX 77030 USA. [Singh, H.] Baylor Coll Med, Sect Hlth Serv Res, Dept Med, Houston, TX 77030 USA. RP Lyratzopoulos, G (reprint author), UCL, Dept Epidemiol & Publ Hlth, Hlth Behav Res Ctr, 1-19 Torrington Pl, London WC1E 6BT, England. EM gl290@medschl.cam.ac.uk RI Vedsted, Peter/C-2583-2008; OI Vedsted, Peter/0000-0003-2113-5599; Lyratzopoulos, Georgios/0000-0002-2873-7421 FU National Institute for Health Research [PDF-2011-04-047]; Cancer Research UK Clinician Scientist Fellowship [A18180]; VA Health Services Research and Development Service [CRE 12-033, USA 14-274]; VA National Center for Patient Safety; Agency for Health Care Research and Quality [R01HS022087]; Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety [CIN 13-413]; CaP; Danish Cancer Society; Novo Nordisk Foundation FX We acknowledge the helpful and incisive comments by Dr Rikke Sand Andersen (Aarhus University, Denmark) in conceptualising this piece and in drafts of the manuscript. The work is independent research supported by different funding schemes. GL was supported by a Post-Doctoral Fellowship by the National Institute for Health Research (PDF-2011-04-047) until the end of 2014 and by a Cancer Research UK Clinician Scientist Fellowship award (A18180) from 2015. HS is supported by the VA Health Services Research and Development Service (CRE 12-033; Presidential Early Career Award for Scientists and Engineers USA 14-274), the VA National Center for Patient Safety, the Agency for Health Care Research and Quality (R01HS022087) and in part by the Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413). PV was supported by CaP, funded by The Danish Cancer Society and the Novo Nordisk Foundation. NR 72 TC 13 Z9 13 U1 5 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD MAR 31 PY 2015 VL 112 SU 1 BP S84 EP S91 DI 10.1038/bjc.2015.47 PG 8 WC Oncology SC Oncology GA CJ3GV UT WOS:000355372300013 PM 25734393 ER PT J AU Xu, CF Johnson, T Garcia-Donas, J Choueiri, TK Sternberg, CN Davis, ID Bing, N Deen, KC Xue, Z McCann, L Esteban, E Whittaker, JC Spraggs, CF Rodriguez-Antona, C Pandite, LN Motzer, RJ AF Xu, C-F Johnson, T. Garcia-Donas, J. Choueiri, T. K. Sternberg, C. N. Davis, I. D. Bing, N. Deen, K. C. Xue, Z. McCann, L. Esteban, E. Whittaker, J. C. Spraggs, C. F. Rodriguez-Antona, C. Pandite, L. N. Motzer, R. J. TI IL8 polymorphisms and overall survival in pazopanib- or sunitinib-treated patients with renal cell carcinoma SO BRITISH JOURNAL OF CANCER LA English DT Article ID CLINICAL-PRACTICE GUIDELINES; PHASE-III TRIAL; INTERFERON-ALPHA; 1ST-LINE SUNITINIB; CANCER-CELLS; DOUBLE-BLIND; END-POINTS; INTERLEUKIN-8; BIOMARKERS; THERAPY AB Background: We evaluated germline single nucleotide polymorphisms (SNPs) for association with overall survival (OS) in pazopanib- or sunitinib-treated patients with advanced renal cell carcinoma (aRCC). Methods: The discovery analysis tested 27 SNPs within 13 genes from a phase III pazopanib trial (N = 241, study 1). Suggestive associations were then pursued in two independent datasets: a phase III trial (COMPARZ) comparing pazopanib vs sunitinib (N = 729, study 2) and an observational study of sunitinib-treated patients (N = 89, study 3). Results: In study 1, four SNPs showed nominally significant association (P <= 0.05) with OS; two of these SNPs (rs1126647, rs4073) in IL8 were associated (P <= 0.05) with OS in study 2. Because rs1126647 and rs4073 were highly correlated, only rs1126647 was evaluated in study 3, which also showed association (P <= 0.05). In the combined data, rs1126647 was associated with OS after conservative multiple-test adjustment (P = 8.8 x 10(-5); variant vs reference allele hazard ratio 1.32, 95% confidence interval: 1.15-1.52), without evidence for heterogeneity of effects between studies or between pazopanib-and sunitinib-treated patients. Conclusions: Variant alleles of IL8 polymorphisms are associated with poorer survival outcomes in pazopanib- or sunitinib-treated patients with aRCC. These findings provide insight in aRCC prognosis and may advance our thinking in development of new therapies. C1 [Xu, C-F; Johnson, T.; Whittaker, J. C.; Spraggs, C. F.] GlaxoSmithKline, Stevenage SG1 2NY, Herts, England. [Garcia-Donas, J.; Esteban, E.] Ctr Integral Oncol Clara Campal, Dept Med Oncol, Madrid 28050, Spain. [Garcia-Donas, J.] Spanish Oncol Genitourinary Grp SOGUG, Madrid, Spain. [Choueiri, T. K.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Sternberg, C. N.] San Camillo & Forlanini Hosp, Dept Med Oncol, I-00152 Rome, Italy. [Davis, I. D.] Monash Univ, Eastern Hlth Clin Sch, Clayton, Vic 3128, Australia. [Bing, N.; Xue, Z.; Pandite, L. N.] GlaxoSmithKline, Res Triangle Pk, NC 27709 USA. [Deen, K. C.; McCann, L.] GlaxoSmithKline, Collegeville, PA 19426 USA. [Esteban, E.] Hosp Univ Cent Asturias, Oviedo 33011, Spain. [Rodriguez-Antona, C.] Spanish Natl Canc Res Ctr, Madrid 28029, Spain. [Rodriguez-Antona, C.] ISCIII Ctr Biomed Res Rare Dis CIBERER, Madrid 28029, Spain. [Motzer, R. J.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA. RP Xu, CF (reprint author), GlaxoSmithKline, Gunnels Wood Rd, Stevenage SG1 2NY, Herts, England. EM chun-fang.2.xu@gsk.com RI Rodriguez-Antona, Cristina/E-1073-2011; OI Rodriguez-Antona, Cristina/0000-0001-8750-7338; Garcia-Donas, Jesus/0000-0001-7731-3601; Johnson, Toby/0000-0002-5998-3270 FU GlaxoSmithKline; Pfizer; GlaxoSmithKline, Philadelphia, Pennsylvania FX This study was funded by GlaxoSmithKline. Pfizer provided funding for the Spanish Oncology Genitourinary Group (SOGUG) sunitinib study. We thank the investigators and their patients who made this study possible. We thank Karen King and Sandy Stinnett for their help in generation and management of the genetic data. We also thank Dr Enrique Grande for his support, and all members of SOGUG for their commitment to the project. Medical editorial assistance for the manuscript was provided by Joan Hudson and Jerome F. Sah, PhD, of ProEd Communications, Inc., Beachwood, Ohio, and was funded by GlaxoSmithKline, Philadelphia, Pennsylvania. NR 37 TC 10 Z9 10 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD MAR 31 PY 2015 VL 112 IS 7 BP 1190 EP 1198 DI 10.1038/bjc.2015.64 PG 9 WC Oncology SC Oncology GA CE9DZ UT WOS:000352145300006 PM 25695485 ER PT J AU Zurita, AJ Khajavi, M Wu, HK Tye, L Huang, X Kulke, MH Lenz, HJ Meropol, NJ Carley, W DePrimo, SE Lin, E Wang, X Harmon, CS Heymach, JV AF Zurita, A. J. Khajavi, M. Wu, H-K Tye, L. Huang, X. Kulke, M. H. Lenz, H-J Meropol, N. J. Carley, W. DePrimo, S. E. Lin, E. Wang, X. Harmon, C. S. Heymach, J. V. TI Circulating cytokines and monocyte subpopulations as biomarkers of outcome and biological activity in sunitinib-treated patients with advanced neuroendocrine tumours SO BRITISH JOURNAL OF CANCER LA English DT Article ID VASCULAR ENDOTHELIAL GROWTH; PANCREATIC ENDOCRINE TUMORS; RENAL-CELL CARCINOMA; PROGNOSTIC-FACTORS; BREAST-CANCER; PHASE-3 TRIAL; VEGF-C; EXPRESSION; PROGRESSION; RESISTANCE AB Background: Sunitinib is approved worldwide for treatment of advanced pancreatic neuroendocrine tumours (pNET), but no validated markers exist to predict response. This analysis explored biomarkers associated with sunitinib activity and clinical benefit in patients with pNET and carcinoid tumours in a phase II study. Methods: Plasma was assessed for vascular endothelial growth factor (VEGF)-A, soluble VEGF receptor (sVEGFR)-2, sVEGFR-3, interleukin (IL)-8 (n = 105), and stromal cell-derived factor (SDF)-1 alpha (n = 28). Pre-treatment levels were compared between tumour types and correlated with response, progression-free (PFS), and overall survival (OS). Changes in circulating myelomonocytic and endothelial cells were also analysed. Results: Stromal cell-derived factor-1 alpha and sVEGFR-2 levels were higher in pNET than in carcinoid (P 0.003 and 0.041, respectively). High (above-median) baseline SDF-1 alpha was associated with worse PFS, OS, and response in pNET, and high sVEGFR-2 with longer OS (P <= 0.05). For carcinoid, high IL-8, sVEGFR-3, and SDF-1 alpha were associated with shorter PFS and OS, and high IL-8 and SDF-1 alpha with worse response (P <= 0.05). Among circulating cell types, monocytes showed the largest on-treatment decrease, particularly CD14+ monocytes co-expressing VEGFR-1 or CXCR4. Conclusions: Interleukin-8, sVEGFR-3, and SDF-1 alpha were identified as predictors of sunitinib clinical outcome. Putative protumorigenic CXCR4+ and VEGFR-1+ monocytes represent novel candidate markers and biologically relevant targets explaining the activity of sunitinib. C1 [Zurita, A. J.; Khajavi, M.; Wu, H-K; Lin, E.; Wang, X.; Heymach, J. V.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Tye, L.; Huang, X.; Carley, W.; DePrimo, S. E.; Harmon, C. S.] Pfizer Inc, La Jolla, CA USA. [Kulke, M. H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lenz, H-J] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Meropol, N. J.] Case Comprehens Canc Ctr, Univ Hosp Case Med Ctr Seidman Canc Ctr, Cleveland, OH USA. [Meropol, N. J.] Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Zurita, AJ (reprint author), Univ Texas MD Anderson Canc Ctr, 1515 Holcombe Blvd,Unit 1374, Houston, TX 77030 USA. EM azurita@mdanderson.org; jheymach@mdanderson.org FU Pfizer Inc. FX We thank Dr James C Yao for valuable insights. This study was sponsored by Pfizer Inc. Editorial assistance was provided by Susanne Gilbert and Emily Seidman at ACUMED (New York, NY, USA) and was funded by Pfizer Inc. NR 37 TC 7 Z9 7 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD MAR 31 PY 2015 VL 112 IS 7 BP 1199 EP 1205 DI 10.1038/bjc.2015.73 PG 7 WC Oncology SC Oncology GA CE9DZ UT WOS:000352145300007 PM 25756398 ER PT J AU Li, N Hauser, R Holford, T Zhu, Y Zhang, Y Bassig, BA Honig, S Chen, C Boyle, P Dai, M Schwartz, SM Morey, P Sayward, H Hu, Z Shen, H Gomery, P Zheng, T AF Li, N. Hauser, R. Holford, T. Zhu, Y. Zhang, Y. Bassig, B. A. Honig, S. Chen, C. Boyle, P. Dai, M. Schwartz, S. M. Morey, P. Sayward, H. Hu, Z. Shen, H. Gomery, P. Zheng, T. TI Muscle-building supplement use and increased risk of testicular germ cell cancer in men from Connecticut and Massachusetts SO BRITISH JOURNAL OF CANCER LA English DT Article DE Muscle-building supplements; testicular cancer; epidemiology ID PERFORMANCE; CRYPTORCHIDISM; CREATINE AB Background: No analytic epidemiological study has examined the relationship between use of muscle-building supplements (MBSs) and testicular germ cell cancer (TGCC) risk. Methods: We conducted a population-based case-control study including 356 TGCC cases and 513 controls from Connecticut and Massachusetts. Results: The odds ratio (OR) for ever use of MBSs in relation to risk of TGCC was significantly elevated (OR = 1.65, 95% confidence interval (CI): 1.11-2.46). The associations were significantly stronger among early users, men with more types of MBSs used, and longer periods of use. Conclusions: MBS use is a potentially modifiable risk factor that may be associated with TGCC. C1 [Li, N.; Holford, T.; Zhu, Y.; Zhang, Y.; Bassig, B. A.; Sayward, H.; Zheng, T.] Yale Univ, Sch Publ Hlth, Dept Environm Hlth Sci, New Haven, CT 06520 USA. [Li, N.; Dai, M.] Chinese Acad Med Sci, China Canc Inst & Hosp, Natl Off Canc Prevent & Control, Beijing 100021, Peoples R China. [Hauser, R.; Morey, P.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth Sci, Boston, MA 02115 USA. [Honig, S.] Yale Univ, Sch Med, Dept Urol, New Haven, CT 06510 USA. [Chen, C.; Schwartz, S. M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 19024 USA. [Boyle, P.] Int Prevent & Res Inst, F-69006 Lyon, France. [Hu, Z.; Shen, H.] Nanjing Med Univ, Sch Publ Hlth, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Ctr Canc, Nanjing 210029, Jiangsu, Peoples R China. [Gomery, P.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Zheng, T (reprint author), Yale Univ, Sch Publ Hlth, Dept Environm Hlth Sci, 60 Coll St,LEPH 440, New Haven, CT 06520 USA. EM tongzhang.zheng@yale.edu FU National Cancer Institute [CA104786]; Fogarty training grants from the National Institutes of Health [D43TW 008323, D43TW 007864-01]; National Natural Science Fund from the National Natural Science Foundation of China [81172757]; Beijing Natural Science Foundation [7123225]; Beijing Nova Program [xx2012067] FX This work was partly supported by the National Cancer Institute (grant CA104786); Fogarty training grants from the National Institutes of Health (D43TW 008323, D43TW 007864-01); The National Natural Science Fund from the National Natural Science Foundation of China (grant 81172757); The Beijing Natural Science Foundation (grant 7123225); and the Beijing Nova Program (grant xx2012067). NR 17 TC 4 Z9 4 U1 3 U2 22 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD MAR 31 PY 2015 VL 112 IS 7 BP 1247 EP 1250 DI 10.1038/bjc.2015.26 PG 4 WC Oncology SC Oncology GA CE9DZ UT WOS:000352145300013 PM 25826226 ER PT J AU McGlynn, KA Sahasrabuddhe, VV Campbell, PT Graubard, BI Chen, J Schwartz, LM Petrick, JL Alavanja, MC Andreotti, G Boggs, DA Buring, JE Chan, AT Freedman, ND Gapstur, SM Hollenbeck, AR Hou, L King, LY Koshiol, J Linet, M Palmer, JR Poynter, JN Purdue, M Robien, K Schairer, C Sesso, HD Sigurdson, A Wactawski-Wende, J Zeleniuch-Jacquotte, A AF McGlynn, K. A. Sahasrabuddhe, V. V. Campbell, P. T. Graubard, B. I. Chen, J. Schwartz, L. M. Petrick, J. L. Alavanja, M. C. Andreotti, G. Boggs, D. A. Buring, J. E. Chan, A. T. Freedman, N. D. Gapstur, S. M. Hollenbeck, A. R. Hou, L. King, L. Y. Koshiol, J. Linet, M. Palmer, J. R. Poynter, J. N. Purdue, M. Robien, K. Schairer, C. Sesso, H. D. Sigurdson, A. Wactawski-Wende, J. Zeleniuch-Jacquotte, A. TI Reproductive factors, exogenous hormone use and risk of hepatocellular carcinoma among US women: results from the Liver Cancer Pooling Project SO BRITISH JOURNAL OF CANCER LA English DT Article DE hepatocellular carcinoma; oophorectomy; oral contraceptives; menopausal hormone therapy ID PLACEBO-CONTROLLED TRIAL; REPLACEMENT THERAPY; ORAL-CONTRACEPTIVES; YOUNG-WOMEN; PARITY; HEPATOCARCINOGENESIS; DIETHYLNITROSAMINE; MORTALITY; COHORT; AGE AB Background: Hepatocellular carcinoma (HCC) occurs less commonly among women than men in almost all regions of the world. The disparity in risk is particularly notable prior to menopause suggesting that hormonal exposures during reproductive life may be protective. Exogenous oestrogenic exposures such as oral contraceptives (OCs), however, have been reported to increase risk, suggesting that estrogens may be hepatocarcinogenic. To examine the effects of reproductive factors and exogenous hormones on risk, we conducted a prospective analysis among a large group of US women. Methods: In the Liver Cancer Pooling Project, a consortium of US-based cohort studies, data from 799 500 women in 11 cohorts were pooled and harmonised. Cox proportional hazards regression models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of reproductive factors and exogenous hormones with HCC (n = 248). Results: Bilateral oophorectomy was associated with a significantly increased risk of HCC (HR = 2.67, 95% CI = 1.22-5.85), which did not appear to be related to a shorter duration of exposure to endogenous hormones or to menopausal hormone therapy use. There was no association between OC use and HCC (HR = 1.12, 95% CI = 0.82-1.55). Nor were there associations with parity, age at first birth, age at natural menopause, or duration of fertility. Conclusions: The current study suggests that bilateral oophorectomy increases the risk of HCC but the explanation for the association is unclear. There was no association between OC use and HCC risk. Examination of endogenous hormone levels in relation to HCC may help to clarify the findings of the current study. C1 [McGlynn, K. A.; Sahasrabuddhe, V. V.; Graubard, B. I.; Chen, J.; Schwartz, L. M.; Petrick, J. L.; Alavanja, M. C.; Andreotti, G.; Freedman, N. D.; Koshiol, J.; Linet, M.; Purdue, M.; Schairer, C.; Sigurdson, A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Campbell, P. T.; Gapstur, S. M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Boggs, D. A.; Palmer, J. R.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. [Buring, J. E.; Chan, A. T.; King, L. Y.; Sesso, H. D.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Buring, J. E.; Sesso, H. D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chan, A. T.; King, L. Y.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Chan, A. T.; King, L. Y.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, A. T.; King, L. Y.] Harvard Univ, Sch Med, Boston, MA USA. [Hollenbeck, A. R.] AARP, Washington, DC USA. [Hou, L.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Poynter, J. N.] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. [Robien, K.] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Epidemiol & Biostat, Washington, DC USA. [Wactawski-Wende, J.] SUNY Buffalo, Dept Epidemiol & Environm Hlth, Buffalo, NY 14260 USA. [Zeleniuch-Jacquotte, A.] NYU, Sch Med, Dept Populat Hlth, New York, NY USA. RP McGlynn, KA (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM mcglynnk@mail.nih.gov RI Freedman, Neal/B-9741-2015; OI Freedman, Neal/0000-0003-0074-1098; Robien, Kim/0000-0002-2120-2280; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303 FU National Institutes of Health Intramural Research Program FX This study was funded by the National Institutes of Health Intramural Research Program. NR 38 TC 9 Z9 9 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD MAR 31 PY 2015 VL 112 IS 7 BP 1266 EP 1272 DI 10.1038/bjc.2015.58 PG 7 WC Oncology SC Oncology GA CE9DZ UT WOS:000352145300016 PM 25742475 ER PT J AU Bornigen, D Moon, YS Rahnavard, G Waldron, L McIver, L Shafquat, A Franzosa, EA Miropolsky, L Sweeney, C Morgan, XC Garrett, WS Huttenhower, C AF Boernigen, Daniela Moon, Yo Sup Rahnavard, Gholamali Waldron, Levi McIver, Lauren Shafquat, Afrah Franzosa, Eric A. Miropolsky, Larissa Sweeney, Christopher Morgan, Xochitl C. Garrett, Wendy S. Huttenhower, Curtis TI A reproducible approach to high-throughput biological data acquisition and integration SO PEERJ LA English DT Article DE High-throughput data; Data integration; Data acquisition; Meta-analysis; Heterogeneous data; Reproducibility ID NF-KAPPA-B; RETRACTED ARTICLE. SEE; PROTEIN-INTERACTION DATABASE; BACTERIAL OUTER-MEMBRANE; PSEUDOMONAS-AERUGINOSA; ESCHERICHIA-COLI; GUT MICROBIOTA; FUNCTIONAL GENOMICS; SECRETION SYSTEMS; VI SECRETION AB Modern biological research requires rapid, complex, and reproducible integration of multiple experimental results generated both internally and externally (e.g., from public repositories). Although large systematic meta-analyses are among the most effective approaches both for clinical biomarker discovery and for computational inference of biomolecular mechanisms, identifying, acquiring, and integrating relevant experimental results from multiple sources for a given study can be time-consuming and error-prone. To enable efficient and reproducible integration of diverse experimental results, we developed a novel approach for standardized acquisition and analysis of high-throughput and heterogeneous biological data. This allowed, first, novel biomolecular network reconstruction in human prostate cancer, which correctly recovered and extended the NF kappa B signaling pathway. Next, we investigated host-microbiome interactions. In less than an hour of analysis time, the system retrieved data and integrated six germ-free murine intestinal gene expression datasets to identify the genes most influenced by the gut microbiota, which comprised a set of immune-response and carbohydrate metabolism processes. Finally, we constructed integrated functional interaction networks to compare connectivity of peptide secretion pathways in the model organisms Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa. C1 [Boernigen, Daniela; Moon, Yo Sup; Rahnavard, Gholamali; Waldron, Levi; McIver, Lauren; Shafquat, Afrah; Franzosa, Eric A.; Miropolsky, Larissa; Morgan, Xochitl C.; Huttenhower, Curtis] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Boernigen, Daniela; Rahnavard, Gholamali; Franzosa, Eric A.; Morgan, Xochitl C.; Garrett, Wendy S.; Huttenhower, Curtis] Broad Inst MIT & Harvard, Cambridge, MA USA. [Sweeney, Christopher] Dana Farber Canc Inst, Boston, MA 02115 USA. [Garrett, Wendy S.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Garrett, Wendy S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Garrett, Wendy S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Waldron, Levi] CUNY Hunter Coll, City Univ New York Sch Publ Hlth, New York, NY 10021 USA. RP Huttenhower, C (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM chuttenh@hsph.harvard.edu OI Morgan, Xochitl/0000-0002-6264-6961; Waldron, Levi/0000-0003-2725-0694 FU National Science Foundation award CAREER [DBI-1053486]; National Science Foundation grant [MCB-1453942] FX This work was supported by National Science Foundation award CAREER DBI-1053486, and a National Science Foundation grant (MCB-1453942) to Curtis Huttenhower. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 136 TC 2 Z9 2 U1 3 U2 18 PU PEERJ INC PI LONDON PA 341-345 OLD ST, THIRD FLR, LONDON, EC1V 9LL, ENGLAND SN 2167-8359 J9 PEERJ JI PeerJ PD MAR 31 PY 2015 VL 3 AR e791 DI 10.7717/peerj.791 PG 35 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF1IU UT WOS:000352299200001 PM 26157642 ER PT J AU Atkinson, C Qiao, F Yang, XF Zhu, P Reaves, N Kulik, L Goddard, M Holers, VM Tomlinson, S AF Atkinson, Carl Qiao, Fei Yang, Xiaofeng Zhu, Peng Reaves, Nicholas Kulik, Liudmila Goddard, Martin Holers, V. Michael Tomlinson, Stephen TI Targeting Pathogenic Postischemic Self-Recognition by Natural IgM to Protect Against Posttransplantation Cardiac Reperfusion Injury SO CIRCULATION LA English DT Article DE antibodies; complement system proteins; inflammation; ischemia; transplantation ID EPSTEIN-BARR-VIRUS; COMPLEMENT INHIBITION; ISCHEMIA/REPERFUSION INJURY; MYOCARDIAL-ISCHEMIA; ENDOTHELIAL-CELLS; RECEPTOR; ACTIVATION; ANTIBODIES; MICE; DISEASE AB Background-Natural IgM antibodies represent a class of innate pattern recognition receptors that recognize danger-associated molecular patterns expressed on stressed or dying cells. They play important roles in tissue homeostasis by disposing of prenecrotic cells and suppressing inflammation. However, ischemic insult leads to a pathogenic level of IgM binding and complement activation, resulting in inflammation and injury. We investigate the role of self-reactive IgM in the unique setting of transplantation where the donor organ undergoes both cold and warm ischemia and global ischemic insult. Methods and Results-By transplanting hearts from wild-type donor mice into antibody-deficient mice reconstituted with specific self-reactive IgM monoclonal antibodies, we identified neoepitopes expressed after transplantation and demonstrated a key role for IgM recognition of these epitopes in graft injury. With this information, we developed and characterized a therapeutic strategy that exploited the postischemia recognition system of natural antibodies. On the basis of neoepitope identification, we constructed an anti-annexin IV single-chain antibody (scFv) and an scFv linked to Crry, an inhibitor of C3 activation (scFv-Crry). In an allograft transplantation model in which recipients contain a full natural antibody repertoire, both constructs blocked graft IgM binding and complement activation and significantly reduced graft inflammation and injury. Furthermore, scFv-Crry specifically targeted to the transplanted heart and, unlike complement deficiency, did not affect immunity to infection, an important consideration for immunosuppressed transplant recipients. Conclusions-We identified pathophysiologically important epitopes expressed within the heart after transplantation and described a novel translatable strategy for targeted complement inhibition that has several advantages over currently available approaches. C1 [Atkinson, Carl; Qiao, Fei; Yang, Xiaofeng; Zhu, Peng; Reaves, Nicholas; Tomlinson, Stephen] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Kulik, Liudmila; Holers, V. Michael] Univ Colorado Denver, Dept Med & Immunol, Aurora, CO USA. [Goddard, Martin] Papworth Hosp, Dept Pathol, Papworth Everard, Cambs, England. [Tomlinson, Stephen] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Tomlinson, S (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. EM tomlinss@musc.edu FU National Institutes of Health [RO1 HL 86576, RO1 HL091944]; Veteran's Affairs [1BX001218, 1RX001141]; American Heart Association [SDG AHA 065100]; South Carolina Clinical & Translational Research Institute, Medical University of South Carolina's CTSA, National Institutes of Health/National Center for Advancing Translational Sciences [UL1TR000062] FX This study was supported by grants from the National Institutes of Health (RO1 HL 86576 to Dr Tomlinson, RO1 HL091944 to Dr Atkinson), the Veteran's Affairs (1BX001218 and 1RX001141 to Dr Tomlinson), and the American Heart Association (SDG AHA 065100 to Dr Atkinson). Statistical support was provided through the South Carolina Clinical & Translational Research Institute, Medical University of South Carolina's CTSA, National Institutes of Health/National Center for Advancing Translational Sciences grant UL1TR000062. NR 38 TC 8 Z9 8 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD MAR 31 PY 2015 VL 131 IS 13 BP 1171 EP + DI 10.1161/CIRCULATIONAHA.114.010482 PG 17 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CE6NE UT WOS:000351953300011 PM 25825397 ER PT J AU Subramanian, K Gianni, D Balla, C Assenza, GE Joshi, M Semigran, MJ Macgillivray, TE Van Eyk, JE Agnetti, G Paolocci, N Bamburg, JR Agrawal, PB del Monte, F AF Subramanian, Khaushik Gianni, Davide Balla, Cristina Assenza, Gabriele Egidy Joshi, Mugdha Semigran, Marc J. Macgillivray, Thomas E. Van Eyk, Jennifer E. Agnetti, Giulio Paolocci, Nazareno Bamburg, James R. Agrawal, Pankaj B. del Monte, Federica TI Cofilin-2 Phosphorylation and Sequestration in Myocardial Aggregates Novel Pathogenetic Mechanisms for Idiopathic Dilated Cardiomyopathy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID DEPENDENT ACTIN DYNAMICS; ADF/COFILIN; PROTEIN; REORGANIZATION; MITOCHONDRIA; PHOSPHATASES; MIGRATION; DISEASE; BINDING; FAMILY AB BACKGROUND Recently, tangles and plaque-like aggregates have been identified in certain cases of dilated cardiomyopathy (DCM). This suggests a potential underlying cause for the one-third of cases, traditionally labeled idiopathic (iDCM), where there is no specific diagnostic test or targeted therapy. OBJECTIVES This study sought to identify the make-up of myocardial aggregates to understand the molecular mechanisms of these cases of DCM; this strategy has been central to understanding Alzheimer's disease. METHODS Aggregates were extracted from human iDCM samples with high congophilic reactivity (an indication of plaque presence), and the findings were validated in a larger cohort of samples. We tested the expression, distribution, and activity of cofilin in human tissue and generated a cardiac-specific knockout mouse model to investigate the functional impact of the human findings. We also modeled cofilin inactivity in vitro by using pharmacological and genetic gain-and loss-of-function approaches. RESULTS Aggregates in human myocardium were enriched for cofilin-2, an actin-depolymerizing protein known to participate in neurodegenerative diseases and nemaline myopathy. Cofilin-2 was predominantly phosphorylated, rendering it inactive. Cardiac-specific haploinsufficiency of cofilin-2 in mice recapitulated the human disease's morphological, functional, and structural phenotype. Pharmacological stimulation of cofilin-2 phosphorylation and genetic overexpression of the phosphomimetic protein promoted the accumulation of "stress-like" fibers and severely impaired cardiomyocyte contractility. CONCLUSIONS Our study provides the first biochemical characterization of prefibrillar myocardial aggregates in humans and the first report to link cofilin-2 to cardiomyopathy. The findings suggest a common pathogenetic mechanism connecting certain iDCMs and other chronic degenerative diseases, laying the groundwork for new therapeutic strategies. (C) 2015 by the American College of Cardiology Foundation. C1 [Subramanian, Khaushik; Gianni, Davide; Balla, Cristina; del Monte, Federica] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA. [Balla, Cristina; Assenza, Gabriele Egidy] Univ Roma La Sapienza, Div Cardiol, I-00185 Rome, Italy. [Joshi, Mugdha; Agrawal, Pankaj B.] Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA. [Joshi, Mugdha; Agrawal, Pankaj B.] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Joshi, Mugdha; Agrawal, Pankaj B.] Childrens Hosp, Program Genom, Boston, MA 02115 USA. [Semigran, Marc J.; del Monte, Federica] Massachusetts Gen Hosp, Heart Ctr, Boston, MA 02114 USA. [Macgillivray, Thomas E.] Massachusetts Gen Hosp, Cardiovasc Surg, Boston, MA 02114 USA. [Van Eyk, Jennifer E.; Agnetti, Giulio] Johns Hopkins Univ, Sch Med, Prote Ctr, Natl Heart Lung Blood Inst, Baltimore, MD USA. [Paolocci, Nazareno] Johns Hopkins Univ, Sch Med, Inst Heart & Vasc, Baltimore, MD USA. [Bamburg, James R.] Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA. RP del Monte, F (reprint author), Beth Israel Deaconess Med Ctr, Cardiovasc Intitute, 3 Blackfan Circle,E-CLS9-911, Boston, MA 02215 USA. EM fdelmont@bidmc.harvard.edu OI Egidy Assenza, Gabriele/0000-0001-6591-002X; Paolocci, Nazareno/0000-0001-7011-997X FU Beth Israel Deaconess Medical Center departmental funds; National Institutes of Health [R21HL102716, R01HL098468, K08 AR055072]; America Heart Association [IRG18980028] FX This study was supported by Beth Israel Deaconess Medical Center departmental funds and by National Institutes of Health grants R21HL102716 and R01HL098468, and America Heart Association grant IRG18980028 to Dr. del Monte and by National Institutes of Health grant K08 AR055072 to Dr. Agrawal. Dr. Gianni is currently working for Biogen. Dr. Bamburg is a member of the Scientific Advisory Board of Rapid Pharmaceuticals. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 37 TC 9 Z9 9 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 31 PY 2015 VL 65 IS 12 BP 1199 EP 1214 DI 10.1016/j.jacc.2015.01.031 PG 16 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CE4ZM UT WOS:000351839300007 PM 25814227 ER PT J AU Drachman, DE AF Drachman, Douglas E. TI The American College of Cardiology's In-Training Examination SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Drachman, DE (reprint author), Massachusetts Gen Hosp, Div Cardiol, Gray Bigelow 800,55 Fruit St, Boston, MA 02114 USA. EM DDRACHMAN@PARTNERS.ORG NR 3 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 31 PY 2015 VL 65 IS 12 BP 1229 EP 1230 DI 10.1016/j.jacc.2015.02.008 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CE4ZM UT WOS:000351839300010 PM 25814230 ER PT J AU Hambright, HG Meng, P Kumar, AP Ghosh, R AF Hambright, Heather G. Meng, Peng Kumar, Addanki P. Ghosh, Rita TI Inhibition of PI3K/AKT/mTOR axis disrupts oxidative stress-mediated survival of melanoma cells SO ONCOTARGET LA English DT Article DE Reactive oxygen species; oxidative stress; mTORC1; melanoma; Nexrutine(R) ID AMURENSE BARK EXTRACT; PROSTATE-CANCER; SIGNALING PATHWAY; TRANSGENIC ADENOCARCINOMA; METASTATIC MELANOMA; MALIGNANT-MELANOMA; PANCREATIC-CANCER; REDOX REGULATION; ACTIVATION; NEXRUTINE AB Elevated oxidative stress in cancer cells contributes to hyperactive proliferation and enhanced survival, which can be exploited using agents that increase reactive oxygen species (ROS) beyond a threshold level. Here we show that melanoma cells exhibit an oxidative stress phenotype compared with normal melanocytes, as evidenced by increased total cellular ROS, KEAP1/NRF2 pathway activity, protein damage, and elevated oxidized glutathione. Our overall objective was to test whether augmenting this high oxidative stress level in melanoma cells would inhibit their dependence on oncogenic PI3K/AKT/mTOR-mediated survival. We report that Nexrutine(R) augmented the constitutively elevated oxidative stress markers in melanoma cells, which was abrogated by N-acetyl cysteine (NAC) pre-treatment. Nexrutine(R) disrupted growth homeostasis by inhibiting proliferation, survival, and colony formation in melanoma cells without affecting melanocyte cell viability. Increased oxidative stress in melanoma cells inhibited PI3K/AKT/mTOR pathway through disruption of mTORC1 formation and phosphorylation of downstream targets p70S6K, 4EBP1 and rpS6. NAC pre-treatment reversed inhibition of mTORC1 targets, demonstrating a ROS-dependent mechanism. Overall, our results illustrate the importance of disruption of the intrinsically high oxidative stress in melanoma cells to selectively inhibit their survival mediated by PI3K/AKT/mTOR. C1 [Hambright, Heather G.; Meng, Peng; Kumar, Addanki P.; Ghosh, Rita] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Kumar, Addanki P.; Ghosh, Rita] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Kumar, Addanki P.; Ghosh, Rita] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Kumar, Addanki P.; Ghosh, Rita] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. [Kumar, Addanki P.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Meng, Peng] Lawrence Berkley Natl Lab, Div Life Sci, Berkeley, CA 94710 USA. RP Ghosh, R (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. EM ghoshr@uthscsa.edu FU VA Merit [I01BX000-766]; Cancer Therapy and Research Center at the University of Texas Health Science Center at San Antonio [2P30 CA054174-17]; [1R21CA125719] FX This work was funded in part by 1R21CA125719 (RG); VA Merit I01BX000-766 (APK); and through the Cancer Therapy and Research Center at the University of Texas Health Science Center at San Antonio (2P30 CA054174-17). NR 48 TC 16 Z9 17 U1 3 U2 7 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD MAR 30 PY 2015 VL 6 IS 9 BP 7195 EP 7208 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CF8GI UT WOS:000352793800052 PM 25749517 ER PT J AU Mitsuhashi, K Nosho, K Sukawa, Y Matsunaga, Y Ito, M Kurihara, H Kanno, S Igarashi, H Naito, T Adachi, Y Tachibana, M Tanuma, T Maguchi, H Shinohara, T Hasegawa, T Imamura, M Kimura, Y Hirata, K Maruyama, R Suzuki, H Imai, K Yamamoto, H Shinomura, Y AF Mitsuhashi, Kei Nosho, Katsuhiko Sukawa, Yasutaka Matsunaga, Yasutaka Ito, Miki Kurihara, Hiroyoshi Kanno, Shinichi Igarashi, Hisayoshi Naito, Takafumi Adachi, Yasushi Tachibana, Mami Tanuma, Tokuma Maguchi, Hiroyuki Shinohara, Toshiya Hasegawa, Tadashi Imamura, Masafumi Kimura, Yasutoshi Hirata, Koichi Maruyama, Reo Suzuki, Hiromu Imai, Kohzoh Yamamoto, Hiroyuki Shinomura, Yasuhisa TI Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis SO ONCOTARGET LA English DT Article DE Fusobacterium; microbiota; pancreas; miR-31; survival ID DUCTAL ADENOCARCINOMA; COLORECTAL-CANCER; PERIODONTAL-DISEASE; ULCERATIVE-COLITIS; BRAF MUTATION; EXPRESSION; MICRORNA; NUCLEATUM; ABSCESS; CELLS AB Recently, bacterial infection causing periodontal disease has attracted considerable attention as a risk factor for pancreatic cancer. Fusobacterium species is an oral bacterial group of the human microbiome. Some evidence suggests that Fusobacterium species promote colorectal cancer development; however, no previous studies have reported the association between Fusobacterium species and pancreatic cancer. Therefore, we examined whether Fusobacterium species exist in pancreatic cancer tissue. Using a database of 283 patients with pancreatic ductal adenocarcinoma (PDAC), we tested cancer tissue specimens for Fusobacterium species. We also tested the specimens for KRAS, NRAS, BRAF and PIK3CA mutations and measured microRNA-21 and microRNA-31. In addition, we assessed epigenetic alterations, including CpG island methylator phenotype (CIMP). Our data showed an 8.8% detection rate of Fusobacterium species in pancreatic cancers; however, tumor Fusobacterium status was not associated with any clinical and molecular features. In contrast, in multivariate Cox regression analysis, compared with the Fusobacterium species- negative group, we observed significantly higher cancer-specific mortality rates in the positive group (p = 0.023). In conclusion, Fusobacterium species were detected in pancreatic cancer tissue. Tumor Fusobacterium species status is independently associated with a worse prognosis of pancreatic cancer, suggesting that Fusobacterium species may be a prognostic biomarker of pancreatic cancer. C1 [Mitsuhashi, Kei; Nosho, Katsuhiko; Matsunaga, Yasutaka; Ito, Miki; Kurihara, Hiroyoshi; Kanno, Shinichi; Igarashi, Hisayoshi; Naito, Takafumi; Adachi, Yasushi; Tachibana, Mami; Tanuma, Tokuma] Sapporo Med Univ, Sch Med, Dept Gastroenterol Rheumatol & Clin Immunol, Sapporo, Hokkaido, Japan. [Sukawa, Yasutaka] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sukawa, Yasutaka] Harvard Univ, Sch Med, Boston, MA USA. [Tanuma, Tokuma; Maguchi, Hiroyuki] Teine Keijinkai Hosp, Dept Gastroenterol, Sapporo, Hokkaido, Japan. [Shinohara, Toshiya] Teine Keijinkai Hosp, Dept Pathol, Sapporo, Hokkaido, Japan. [Hasegawa, Tadashi] Sapporo Med Univ, Sch Med, Dept Surg Pathol, Sapporo, Hokkaido, Japan. [Imamura, Masafumi; Kimura, Yasutoshi; Hirata, Koichi] Sapporo Med Univ, Sch Med, Dept Surg Surg Oncol & Sci, Sapporo, Hokkaido, Japan. [Maruyama, Reo; Suzuki, Hiromu] Sapporo Med Univ, Sch Med, Dept Mol Biol, Sapporo, Hokkaido, Japan. [Imai, Kohzoh] Univ Tokyo, Inst Med Sci, Tokyo, Japan. [Yamamoto, Hiroyuki; Shinomura, Yasuhisa] St Marianna Univ, Sch Med, Dept Gastroenterol & Hepatol, Kawasaki, Kanagawa, Japan. RP Nosho, K (reprint author), Sapporo Med Univ, Sch Med, Dept Gastroenterol Rheumatol & Clin Immunol, Sapporo, Hokkaido, Japan. EM nosho@sapmed.ac.jp FU Japan Society for the Promotion of Science (JSPS) Challenging Exploratory Research [25670371]; Ono Cancer Research Foundation; Takeda Science Foundation; Suhara Memorial Foundation; Yuasa Memorial Foundation; Pancreas Research Foundation of Japan; Daiwa Securities Health Foundation FX This work was supported by the Japan Society for the Promotion of Science (JSPS) Challenging Exploratory Research (grant number 25670371 to Y.S.), Ono Cancer Research Foundation (to K.N.), Takeda Science Foundation (to K.N.), The Suhara Memorial Foundation (to K.N.), Yuasa Memorial Foundation (to K.N.), Pancreas Research Foundation of Japan (to K.N.) and Daiwa Securities Health Foundation (to H.I.). NR 50 TC 10 Z9 10 U1 0 U2 7 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD MAR 30 PY 2015 VL 6 IS 9 BP 7209 EP 7220 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CF8GI UT WOS:000352793800053 PM 25797243 ER PT J AU Bruinsma, BG Wu, W Ozer, S Farmer, A Markmann, JF Yeh, H Uygun, K AF Bruinsma, Bote G. Wu, Wilson Ozer, Sinan Farmer, Adam Markmann, James F. Yeh, Heidi Uygun, Korkut TI Warm Ischemic Injury Is Reflected in the Release of Injury Markers during Cold Preservation of the Human Liver SO PLOS ONE LA English DT Article ID SUBNORMOTHERMIC MACHINE PERFUSION; HUMAN DONOR LIVERS; CARDIAC DEATH; UNITED-STATES; RAT LIVERS; TRANSPLANTATION; DONATION; VIABILITY; STORAGE; GRAFTS AB Background Liver transplantation plays a pivotal role in the treatment of patients with end-stage liver disease. Despite excellent outcomes, the field is strained by a severe shortage of viable liver grafts. To meet high demands, attempts are made to increase the use of suboptimal livers by both pretransplant recovery and assessment of donor livers. Here we aim to assess hepatic injury in the measurement of routine markers in the post-ischemic flush effluent of discarded human liver with a wide warm ischemic range. Methods Six human livers discarded for transplantation with variable warm and cold ischemia times were flushed at the end of preservation. The liver grafts were flushed with NaCl or Lactated Ringer's, 2 L through the portal vein and 1 L through the hepatic artery. The vena caval effluent was sampled and analyzed for biochemical markers of injury; lactate dehydrogenase (LDH), alanine transaminase (ALT), and alkaline phosphatase (ALP). Liver tissue biopsies were analyzed for ATP content and histologically (H&E) examined. Results The duration of warm ischemia in the six livers correlated significantly to the concentration of LDH, ALT, and ALP in the effluent from the portal vein flush. No correlation was found with cold ischemia time. Tissue ATP content at the end of preservation correlated very strongly with the concentration of ALP in the arterial effluent (P<0.0007, R-2 = 0.96). Conclusion Biochemical injury markers released during the cold preservation period were reflective of the duration of warm ischemic injury sustained prior to release of the markers, as well as the hepatic energy status. As such, assessment of the flush effluent at the end of cold preservation may be a useful tool in evaluating suboptimal livers prior to transplantation, particularly in situations with undeterminable ischemic durations. C1 [Bruinsma, Bote G.; Wu, Wilson; Ozer, Sinan; Farmer, Adam; Uygun, Korkut] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Dept Surg, Boston, MA 02163 USA. [Bruinsma, Bote G.] Univ Amsterdam, Acad Med Ctr, Dept Surg, Surg Lab, NL-1105 AZ Amsterdam, Netherlands. [Markmann, James F.; Yeh, Heidi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Ctr, Boston, MA USA. RP Uygun, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Dept Surg, Boston, MA 02163 USA. EM korkut.uygun@mgh.harvard.edu FU National Institutes of Health [R00DK080942, R01DK096075]; Organ Solutions FX This work was supported from the National Institutes of Health (R00DK080942, R01DK096075) (KU) www.nih.gov. Organ Solutions provided support in the form of salaries for author KU. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 35 TC 1 Z9 3 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 30 PY 2015 VL 10 IS 3 AR e0123421 DI 10.1371/journal.pone.0123421 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE9AD UT WOS:000352134700224 PM 25822248 ER PT J AU Yucel, MA Aasted, CM Petkov, MP Borsook, D Boas, DA Becerra, L AF Yuecel, Meryem A. Aasted, Christopher M. Petkov, Mihayl P. Borsook, David Boas, David A. Becerra, Lino TI Specificity of Hemodynamic Brain Responses to Painful Stimuli: A functional near-infrared spectroscopy study SO SCIENTIFIC REPORTS LA English DT Article ID DIFFUSE OPTICAL TOMOGRAPHY; LASER-EVOKED-POTENTIALS; ELECTRICAL-STIMULATION; SOMATOSENSORY CORTEX; HABITUATION; ACTIVATION; FMRI; SENSITIVITY; PERCEPTION; SYSTEM AB Assessing pain in individuals not able to communicate (e.g. infants, under surgery, or following stroke) is difficult due to the lack of non-verbal objective measures of pain. Near-infrared spectroscopy (NIRS) being a portable, non-invasive and inexpensive method of monitoring cerebral hemodynamic activity has the potential to provide such a measure. Here we used functional NIRS to evaluate brain activation to an innocuous and a noxious electrical stimulus on healthy human subjects (n = 11). For both innocuous and noxious stimuli, we observed a signal change in the primary somatosensory cortex contralateral to the stimulus. The painful and non-painful stimuli can be differentiated based on their signal size and profile. We also observed that repetitive noxious stimuli resulted in adaptation of the signal. Furthermore, the signal was distinguishable from a skin sympathetic response to pain that tended to mask it. Our results support the notion that functional NIRS has a potential utility as an objective measure of pain. C1 [Yuecel, Meryem A.; Borsook, David; Boas, David A.; Becerra, Lino] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, MGH HST Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Aasted, Christopher M.; Petkov, Mihayl P.; Borsook, David; Becerra, Lino] Boston Childrens Hosp, Dept Anaesthesia, Ctr Pain & Brain, Boston, MA USA. [Aasted, Christopher M.; Petkov, Mihayl P.; Borsook, David; Becerra, Lino] Boston Childrens Hosp, Dept Radiol, Ctr Pain & Brain, Boston, MA USA. [Borsook, David; Becerra, Lino] MGH, Dept Psychiat, Boston, MA USA. [Borsook, David; Becerra, Lino] MGH, Dept Radiol, Boston, MA USA. RP Yucel, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, MGH HST Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM mayucel@nmr.mgh.harvard.edu FU NIH [R01-GM104986, K24] FX We acknowledge support from NIH R01-GM104986 (NIGMS, DAB and DB) and K24 (DB). NR 44 TC 13 Z9 13 U1 1 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD MAR 30 PY 2015 VL 5 AR 9469 DI 10.1038/srep09469 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE6IA UT WOS:000351938900001 PM 25820289 ER PT J AU Balevich, EC Haznedar, MM Wang, E Newmark, RE Bloom, R Schneiderman, JS Aronowitz, J Tang, CY Chu, KW Byne, W Buchsbaum, MS Hazlett, EA AF Balevich, Emily C. Haznedar, M. Mehmet Wang, Eugene Newmark, Randall E. Bloom, Rachel Schneiderman, Jason S. Aronowitz, Jonathan Tang, Cheuk Y. Chu, King-Wai Byne, William Buchsbaum, Monte S. Hazlett, Erin A. TI Corpus callosum size and diffusion tensor anisotropy in adolescents and adults with schizophrenia SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Diffusion tensor imaging; White matter; Schizophrenia spectrum; Magnetic resonance imaging (MRI) ID CORTICAL BRODMANNS AREAS; WHITE-MATTER; MAGNETIC-RESONANCE; ONSET SCHIZOPHRENIA; 1ST-EPISODE SCHIZOPHRENIA; FRACTIONAL ANISOTROPY; IMAGING FINDINGS; MRI; ABNORMALITIES; CONNECTIVITY AB The corpus callosum has been implicated as a region of dysfunctional connectivity in schizophrenia, but the association between age and callosal pathology is unclear. Magnetic resonance imaging (MRO and diffusion-tensor imaging (DTI) were performed on adults (n=34) and adolescents (n=17) with schizophrenia and adult (n=33) and adolescent (n=15) age- and sex-matched healthy controls. The corpus callosum was manually traced on each participant's MRL and the DTI scan was co-registered to the MRL The corpus callosum was divided into five anteroposterior segments. Area and anisotropy were calculated for each segment. Both patient groups demonstrated reduced callosal anisotropy; however, the adolescents exhibited reductions mostly in anterior regions while the reductions were more prominent in posterior regions of the adults. The adolescent patients showed greater decreases in absolute area as compared with the adult patients, particularly in the anterior segments. However, the adults showed greater reductions when area was considered relative to whole brain white matter volume. Our results suggest that the initial stages of the illness are characteiized by deficiencies in frontal connections, and the chronic phase is characterized by deficits in the posterior corpus callosum; or, alternatively, adolescent-onset schizophrenia may represent a different or more severe form of the illness. Published by Elsevier Ireland Ltd. C1 [Balevich, Emily C.; Haznedar, M. Mehmet; Wang, Eugene; Newmark, Randall E.; Bloom, Rachel; Schneiderman, Jason S.; Aronowitz, Jonathan; Byne, William; Hazlett, Erin A.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Balevich, Emily C.] CUNY, Grad Ctr, New York, NY 10016 USA. [Haznedar, M. Mehmet; Byne, William] James J Peters VA Med Ctr, Outpatient Psychiat Care Ctr, Bronx, NY 10468 USA. [Tang, Cheuk Y.] Icahn Sch Med Mt Sinai, Dept Radiol, New York, NY 10029 USA. [Chu, King-Wai; Byne, William; Hazlett, Erin A.] James J Peters VA Med Ctr, Res & Dev, Bronx, NY 10468 USA. [Chu, King-Wai; Byne, William; Hazlett, Erin A.] James J Peters VA Med Ctr, VISN Mental Illness Res Educ & Clin Ctr 3, Bronx, NY 10468 USA. [Buchsbaum, Monte S.] Univ Calif San Diego, San Diego Sch Med, Dept Psychiat, La Jolla, CA 92093 USA. [Buchsbaum, Monte S.] Univ Calif San Diego, San Diego Sch Med, Dept Radiol, La Jolla, CA 92093 USA. RP Hazlett, EA (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. EM erin.hazlett@mssm.edu FU National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) [UL1TR000067]; NIH [R01MH60023, R01MH56489, R01MH603845]; Eli Lilly and Company; U.S. Department of Veterans Affairs (VA Merit Award) [101CX00026] FX Funding for this study was provided in part by Grants from the National Center for Advancing Translational Sciences (NCATS) (UL1TR000067), a component of the National Institutes of Health (NIH), NIH Grants (R01MH60023, R01MH56489, and R01MH603845 to MSB), Eli Lilly and Company (adolescent MRI and clinical assessment), and the U.S. Department of Veterans Affairs (VA Merit Award 101CX00026 to EAH). NR 60 TC 6 Z9 7 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 EI 1872-7506 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD MAR 30 PY 2015 VL 231 IS 3 BP 244 EP 251 DI 10.1016/j.psychresns.2014.12.005 PG 8 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CD7YE UT WOS:000351311000008 PM 25637358 ER PT J AU Chodos, AH Lee, SJ AF Chodos, Anna H. Lee, Sei J. TI Journalists, district attorneys and researchers: why IRBs should get in the middle SO BMC MEDICAL ETHICS LA English DT Article ID ACCOUNTABILITY AB Background: Federal regulations in the United States have shaped Institutional Review Boards (IRBs) to focus on protecting individual human subjects. Health services research studies focusing on healthcare institutions such as hospitals or clinics do not have individual human subjects. Since U.S. federal regulations are silent on what type of review, if any, these studies require, different IRBs may approach similar studies differently, resulting in undesirable variation in the review of studies focusing on healthcare institutions. Further, although these studies do not focus on individual human subjects, they may pose risks to participating institutions, as well as individuals who work at those institutions, if identifying information becomes public. Discussion: Using two recent health services research studies conducted in the U.S. as examples, we discuss variations in the level of IRB oversight for studies focusing on institutions rather than individual human subjects. We highlight how lack of IRB guidance poses challenges for researchers who wish to both protect their subjects and work appropriately with the public, journalists or the legal system in the U.S. Competing interests include the public's interest in transparency, the researcher's interest in their science, and the research participants' interests in confidentiality. Potential solutions that may help guide health services researchers to balance these competing interests include: 1) creating consensus guidelines and standard practices that address confidentiality risk to healthcare institutions and their employees; and 2) expanding the IRB role to conduct a streamlined review of health services research studies focusing on healthcare institutions to balance the competing interest of stakeholders on a case-by-case basis. Summary: For health services research studies focusing on healthcare institutions, we outline the competing interests of researchers, healthcare institutions and the public. We propose solutions to decrease undesirable variations in the review of these studies. C1 [Chodos, Anna H.] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco Gen Hosp, San Francisco, CA 94143 USA. [Chodos, Anna H.; Lee, Sei J.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Chodos, Anna H.; Lee, Sei J.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Chodos, AH (reprint author), Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco Gen Hosp, 1001 Potrero Ave, San Francisco, CA 94143 USA. EM anna.chodos@ucsf.edu FU National Institute on Aging [T32AG000212-20]; Paul Beeson Career Development Award from the National Institute on Aging [K23AG040779] FX Dr. Chodos was supported by a training grant to the Division of Geriatrics at the University of California, San Francisco from the National Institute on Aging (T32AG000212-20). Dr. Lee was supported through the Paul Beeson Career Development Award from the National Institute on Aging (K23AG040779). NR 6 TC 0 Z9 0 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6939 J9 BMC MED ETHICS JI BMC Med. Ethics PD MAR 29 PY 2015 VL 16 AR 19 DI 10.1186/s12910-015-0015-y PG 3 WC Ethics; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Biomedical Social Sciences GA CO8IR UT WOS:000359412300001 PM 25889147 ER PT J AU Santiago, M Matano, LM Moussa, SH Gilmore, MS Walker, S Meredith, TC AF Santiago, Marina Matano, Leigh M. Moussa, Samir H. Gilmore, Michael S. Walker, Suzanne Meredith, Timothy C. TI A new platform for ultra-high density Staphylococcus aureus transposon libraries SO BMC GENOMICS LA English DT Article DE Staphylococcus aureus; Functional genomics; Transposon library; Temperature-sensitivity; Small colony variants; Essential genes ID SMALL-COLONY VARIANTS; GRAM-POSITIVE BACTERIA; YYCFG 2-COMPONENT SYSTEM; BETA-LACTAM ANTIBIOTICS; WALL TEICHOIC-ACIDS; BACILLUS-SUBTILIS; METHICILLIN RESISTANCE; HEAT-SHOCK; CELL-DIVISION; RECURRENT INFECTIONS AB Background: Staphylococcus aureus readily develops resistance to antibiotics and achieving effective therapies to overcome resistance requires in-depth understanding of S. aureus biology. High throughput, parallel-sequencing methods for analyzing transposon mutant libraries have the potential to revolutionize studies of S. aureus, but the genetic tools to take advantage of the power of next generation sequencing have not been fully developed. Results: Here we report a phage-based transposition system to make ultra-high density transposon libraries for genome-wide analysis of mutant fitness in any phi 11-transducible S. aureus strain. The high efficiency of the delivery system has made it possible to multiplex transposon cassettes containing different regulatory elements in order to make libraries in which genes are over- or under-expressed as well as deleted. By incorporating transposon-specific barcodes into the cassettes, we can evaluate how null mutations and changes in gene expression levels affect fitness in a single sequencing data set. Demonstrating the power of the system, we have prepared a library containing more than 690,000 unique insertions. Because one unique feature of the phage-based approach is that temperature-sensitive mutants are retained, we have carried out a genome-wide study of S. aureus genes involved in withstanding temperature stress. We find that many genes previously identified as essential are temperature sensitive and also identify a number of genes that, when disrupted, confer a growth advantage at elevated temperatures. Conclusions: The platform described here reliably provides mutant collections of unparalleled genotypic diversity and will enable a wide range of functional genomic studies in S. aureus. C1 [Santiago, Marina; Matano, Leigh M.; Moussa, Samir H.; Gilmore, Michael S.; Walker, Suzanne; Meredith, Timothy C.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Gilmore, Michael S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Meredith, Timothy C.] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. RP Walker, S (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. EM suzanne_walker@hms.harvard.edu; txm50@psu.edu FU NIH [U19AI109764, P01AI083214, F32AI118160] FX We would like to thank Terry Roemer (Merck Research Laboratories) for strains and plasmids and Eric Rubin as well as members of his lab Yanjia Zhang and Karen Kieser (Harvard School of Public Health) for providing python and EL-ARTIST scripts used in NGS data analysis. This work was funded by NIH grants U19AI109764 to SW and TCM, P01AI083214 to MSG and SW, and F32AI118160 to SHM. NR 126 TC 7 Z9 7 U1 2 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD MAR 29 PY 2015 VL 16 AR 252 DI 10.1186/s12864-015-1361-3 PG 18 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA CF3XD UT WOS:000352481500001 PM 25888466 ER PT J AU Saleh, F AF Saleh, F. TI Adolescent Sexual Behavior and the Digital Revolution SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 [Saleh, F.] Harvard Univ, Sch Med, BIDMC, Psychiat, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 EI 1778-3585 J9 EUR PSYCHIAT JI Eur. Psychiat. PD MAR 28 PY 2015 VL 30 SU 1 MA 0439 PG 1 WC Psychiatry SC Psychiatry GA CR1WS UT WOS:000361116601132 ER PT J AU Wanderer, JP Ehrenfeld, JM Epstein, RH Kor, DJ Bartz, RR Fernandez-Bustamante, A Melo, MFV Blum, JM AF Wanderer, Jonathan P. Ehrenfeld, Jesse M. Epstein, Richard H. Kor, Daryl J. Bartz, Raquel R. Fernandez-Bustamante, Ana Melo, Marcos F. Vidal Blum, James M. TI Temporal trends and current practice patterns for intraoperative ventilation at US academic medical centers: a retrospective study SO BMC ANESTHESIOLOGY LA English DT Article DE Intraoperative ventilation; Lung protective ventilation; Practice patterns ID TIDAL-VOLUME VENTILATION; RESPIRATORY-DISTRESS-SYNDROME; LUNG-PROTECTIVE VENTILATION; SURGICAL-PATIENTS; PULMONARY COMPLICATIONS; ABDOMINAL-SURGERY; INJURY; RISK; INFLAMMATION; STRATEGY AB Background: Lung protective ventilation strategies utilizing lower tidal volumes per predicted body weight (PBW) and positive end-expiratory pressure (PEEP) have been suggested to be beneficial in a variety of surgical populations. Recent clinical studies have used control groups ventilated with high tidal volumes without PEEP based on the assumption that this reflects current clinical practice. We hypothesized that ventilation strategies have changed over time, that most anesthetics in U.S. academic medical centers are currently performed with lower tidal volumes, and that most receive PEEP. Methods: Intraoperative data were pooled for adults undergoing general anesthesia with tracheal intubation. Median tidal volumes per kilogram of PBW were categorized as > 10, 8-10 and < 8 mL per kg of PBW. The percentages of cases in 2013 that were performed with median tidal volumes < 8 mL per kg of PBW and PEEP were determined. As a secondary analysis, a proportional odds model using institution, year, height, weight and gender determined the relative associations of these factors using categorical and interquartile odds ratios. Results: 295,540 cases were analyzed from 5 institutions over a period of 10 years. In 2013, 59.3% of cases used median tidal volumes < 8 mL per kg of PBW, 83.3% used PEEP, and 51.0% used both. Of those cases with PEEP, 60.9% used a median pressure of >= 5 cmH(2)O. Predictors of lower categories of tidal volumes included height (odds ratio (OR) 10.83, 95% confidence interval [10.50, 11.16]), institution (lowest OR 0.98 [0.96, 1.00], highest OR 9.63 [9.41, 9.86]), year (lowest OR 1.32 [1.21, 1.44], highest OR 6.31 [5.84, 6.82]), male gender (OR 1.10 [1.07, 1.12]), and weight (OR 0.30 [0.29, 0.31]). Conclusion: Most general anesthetics with tracheal intubation at the institutions surveyed are currently performed with a median tidal volume < 8 mL per kg of PBW, most are managed with PEEP of >= 5 cmH(2)O and approximately half utilize both. Given the diversity of the institutions included, this is likely reflective of practice in U.S. academic medical centers. The utilization of higher tidal volumes without PEEP in control groups for clinical research studies should be reconsidered. C1 [Wanderer, Jonathan P.] Vanderbilt Univ, Dept Anesthesiol, Vanderbilt Clin, Nashville, TN 37235 USA. [Wanderer, Jonathan P.] Vanderbilt Univ, Dept Biomed Informat, Vanderbilt Clin, Nashville, TN 37235 USA. [Ehrenfeld, Jesse M.] Vanderbilt Univ, Dept Anesthesiol, Nashville, TN 37235 USA. [Ehrenfeld, Jesse M.] Vanderbilt Univ, Dept Biomed Informat, Nashville, TN 37235 USA. [Ehrenfeld, Jesse M.] Vanderbilt Univ, Dept Hlth Policy & Surg, Nashville, TN 37235 USA. [Epstein, Richard H.] Thomas Jefferson Univ, Sidney Kimmel Coll Med, Dept Anesthesiol, Philadelphia, PA 19107 USA. [Kor, Daryl J.] Mayo Clin, Dept Anesthesiol, Rochester, MN USA. [Bartz, Raquel R.] Duke Univ, Sch Med, Dept Anesthesiol, Durham, NC USA. [Fernandez-Bustamante, Ana] Univ Colorado, Sch Med, Dept Anesthesiol, Colorado City, CO USA. [Melo, Marcos F. Vidal] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Blum, James M.] Emory Univ Hosp, Dept Anesthesiol, Atlanta, GA 30322 USA. RP Wanderer, JP (reprint author), Vanderbilt Univ, Dept Anesthesiol, Vanderbilt Clin, 1301 Med Ctr Dr,Suite 4648, Nashville, TN 37235 USA. EM jonathan.p.wanderer@vanderbilt.edu OI Fernandez-Bustamante, Ana/0000-0002-2996-7704 FU Foundation for Anesthesia Education and Research (FAER); Anesthesia Quality Institution; NHLBI Grant [R01 HL121228] FX The authors would like to thank Milcho Niklov and Geoff Counihan at Massachusetts General Hospital, Betsy Hale at Duke University, Nageswar R. Madde at Mayo Clinic, Ken Bullard at University of Colorado School of Medicine, and Michaelene Johnson and Karen McCarthy at Vanderbilt University, for their collective technical assistance in data retrieval. This perioperative medical investigation was funded by departmental sources and, in part, the Foundation for Anesthesia Education and Research (FAER) (to Drs. Wanderer and Fernandez-Bustamante), the Anesthesia Quality Institution (Dr. Wanderer) and NHLBI Grant R01 HL121228 (Dr. Vidal Melo). NR 19 TC 6 Z9 7 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2253 J9 BMC ANESTHESIOL JI BMC Anesthesiol. PD MAR 28 PY 2015 VL 15 AR 40 DI 10.1186/s12871-015-0010-3 PG 10 WC Anesthesiology SC Anesthesiology GA CF0SY UT WOS:000352255700001 PM 25852301 ER PT J AU Fonyad, L Shinoda, K Farkash, EA Groher, M Sebastian, DP Szasz, AM Colvin, RB Yagi, Y AF Fonyad, Laszlo Shinoda, Kazunobu Farkash, Evan A. Groher, Martin Sebastian, Divya P. Szasz, A. Marcell Colvin, Robert B. Yagi, Yukako TI 3-dimensional digital reconstruction of the murine coronary system for the evaluation of chronic allograft vasculopathy SO DIAGNOSTIC PATHOLOGY LA English DT Article DE Digital slides; 3D; CAV; Serial sectioning; Neointimal volume index ID TRANSPLANT ARTERIOPATHY; MORPHOMETRIC-ANALYSIS; NEOINTIMAL FORMATION; CARDIAC ALLOGRAFTS; VIRTUAL MICROSCOPY; MIXED CHIMERISM; NK CELLS; MICE; ALLOANTIBODY; REJECTION AB Background: Chronic allograft vasculopathy (CAV) is a major mechanism of graft failure of transplanted organs in humans. Morphometric analysis of coronary arteries enables the quantitation of CAV in mouse models of heart transplantation. However, conventional histological procedures using single 2-dimensional sections limit the accuracy of CAV quantification. The aim of this study is to improve the accuracy of CAV quantification by reconstructing the murine coronary system in 3-dimensions (3D) and using virtual reconstruction and volumetric analysis to precisely assess neointimal thickness. Methods: Mouse tissue samples, native heart and transplanted hearts with chronic allograft vasculopathy, were collected and analyzed. Paraffin embedded samples were serially sectioned, stained and digitized using whole slide digital imaging techniques under normal and ultraviolet lighting. Sophisticated software tools were used to generate and manipulate 3D reconstructions of the major coronary arteries and branches. Results: The 3D reconstruction provides not only accurate measurements but also exact volumetric data of vascular lesions. This virtual coronary arteriography demonstrates that the vasculopathy lesions in this model are localized to the proximal coronary segments. In addition, virtual rotation and volumetric analysis enabled more precise measurements of CAV than single, randomly oriented histologic sections, and offer an improved readout for this important experimental model. Conclusions: We believe 3D reconstruction of 2D histological slides will provide new insights into pathological mechanisms in which structural abnormalities play a role in the development of a disease. The techniques we describe are applicable to the analysis of arteries, veins, bronchioles and similar sized structures in a variety of tissue types and disease model systems. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3772457541477230. C1 [Fonyad, Laszlo] Semmelweis Univ, Dept Pathol & Expt Canc Res 1, H-1085 Budapest, Hungary. [Shinoda, Kazunobu; Farkash, Evan A.; Sebastian, Divya P.; Colvin, Robert B.; Yagi, Yukako] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Groher, Martin] MicroDimens GmbH, Munich, Germany. [Szasz, A. Marcell] Semmelweis Univ, Dept Pathol 2, H-1085 Budapest, Hungary. RP Fonyad, L (reprint author), Semmelweis Univ, Dept Pathol & Expt Canc Res 1, H-1085 Budapest, Hungary. EM fonyadla@gmail.com FU NIAID NIH HHS [K23 AI108951] NR 22 TC 2 Z9 2 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1746-1596 J9 DIAGN PATHOL JI Diagn. Pathol. PD MAR 28 PY 2015 VL 10 AR 16 DI 10.1186/s13000-015-0248-6 PG 8 WC Pathology SC Pathology GA CE8DE UT WOS:000352070600001 PM 25884689 ER PT J AU Rennie, S Siedner, M Tucker, JD Moodley, K AF Rennie, Stuart Siedner, Mark Tucker, Joseph D. Moodley, Keymanthri TI The ethics of talking about 'HIV cure' SO BMC MEDICAL ETHICS LA English DT Article DE HIV/AIDS; Ethics; HIV cure; Biomedical research ID ANTIRETROVIRAL THERAPY; MODEL AB Background: In 2008, researchers reported that Timothy Brown (the 'Berlin Patient'), a man with HIV infection and leukemia, received a stem-cell transplant that removed HIV from his body as far as can be detected. In 2013, an infant born with HIV infection received anti-retroviral treatment shortly after birth, but was then lost to the health care system for the next six months. When tested for HIV upon return, the child (the 'Mississippi Baby') had no detectable viral load despite cessation of treatment. These remarkable clinical developments have helped reinvigorate the field of 'HIV cure' research. Discussion: Although this research field is largely in a pre-clinical phase, talk about curing HIV has become a regular feature in the global mass media. This paper explores the language of HIV cure from philosophical, ethical and historical perspectives. Examination of currently influential definitions of 'functional' and 'sterilizing' HIV cure reveal that these conceptualizations are more complicated than they seem. Cure is often understood in narrowly biomedical terms in isolation from the social and psychological dimensions of illness. Contemporary notions of HIV cure also inherit some of the epistemic problems traditionally associated with cures for other health conditions, such as cancer. Efforts to gain greater conceptual clarity about cure lead to the normative question of how 'HIV cure research' ought to be talked about. Summary: We argue that attention to basic concepts ethically matter in this context, and identify advantages as well as potential pitfalls of how different HIV/AIDS stakeholders may make use of the concept of cure. While concepts other than cure (such as remission) may be appropriate in clinical contexts, use of the word cure may be justified for other important purposes in the struggle against HIV/AIDS. C1 [Rennie, Stuart] Univ N Carolina, Dept Social Med, Ctr Bioeth, Chapel Hill, NC 27599 USA. [Siedner, Mark] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Siedner, Mark] Harvard Univ, Sch Med, Boston, MA USA. [Tucker, Joseph D.] Univ N Carolina, Inst Global Hlth & Infect Dis, Chapel Hill, NC USA. [Tucker, Joseph D.] Guangdong Prov Dermatol STD Hosp, UNC Project China, Guangzhou, Guangdong, Peoples R China. [Moodley, Keymanthri] Univ Stellenbosch, Dept Med, Ctr Med Eth & Law, ZA-7505 Tygerberg, South Africa. RP Rennie, S (reprint author), Univ N Carolina, Dept Social Med, Ctr Bioeth, Chapel Hill, NC 27599 USA. EM stuart_rennie@med.unc.edu OI Rennie, Stuart/0000-0003-3844-972X FU NIH/NIAID [R01A108366-01] FX Stuart Rennie, Joe Tucker, Keymanthri Moodley and Mark Siedner are members of the Social and Ethical Aspects of Research on Curing HIV (searcHIV) Working Group, which is supported by a NIH/NIAID grant (R01A108366-01: 'Unintended and Intended Implications of HIV Cure: A Social and Ethical Analysis'). The Working Group's composition and rationale is explained at http://searchiv.web.unc.edu/. NR 29 TC 6 Z9 6 U1 1 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6939 J9 BMC MED ETHICS JI BMC Med. Ethics PD MAR 27 PY 2015 VL 16 AR 18 DI 10.1186/s12910-015-0013-0 PG 8 WC Ethics; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Biomedical Social Sciences GA CO8IP UT WOS:000359412100001 PM 25885856 ER PT J AU Balan, M Teran, EMY Waaga-Gasser, AM Gasser, M Choueiri, TK Freeman, G Pal, S AF Balan, Murugabaskar Mier y Teran, Eduardo Waaga-Gasser, Ana Maria Gasser, Martin Choueiri, Toni K. Freeman, Gordon Pal, Soumitro TI Novel Roles of c-Met in the Survival of Renal Cancer Cells through the Regulation of HO-1 and PD-L1 Expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POTENTIAL THERAPEUTIC TARGET; HEME OXYGENASE-1; TYROSINE KINASE; T-CELLS; CARCINOMA PATIENTS; TUMOR PROGRESSION; DENDRITIC CELLS; GROWTH; IMMUNITY; RECEPTOR AB The receptor tyrosine kinase c-Met is overexpressed in renal cancer cells and can play major role in the growth and survival of tumor. We investigated how the c-Met-mediated signaling through binding to its ligand hepatocyte growth factor (HGF) can modulate the apoptosis and immune escape mechanism(s) of renal cancer cells by the regulations of novel molecules heme oxygenase-1 (HO-1) and programmed death-1 ligand 1 (PD-L1). We found that HGF/c-Met-mediated signaling activated the Ras/Raf pathway and down-regulated cancer cell apoptosis; and it was associated with the overexpression of cytoprotective HO-1 and anti-apoptotic Bcl-2/Bcl-xL. c-Met-induced HO-1 overexpression was regulated at the transcriptional level. Next, we observed that c-Met induction markedly up-regulated the expression of the negative co-stimulatory molecule PD-L1, and this can be prevented following treatment of the cells with pharmacological inhibitors of c-Met. Interestingly, HGF/c-Met-mediated signaling could not induce PD-L1 at the optimum level when either Ras or HO-1 was knocked down. To study the functional significance of c-Met-induced PD-L1 expression, we performed a co-culture assay using mouse splenocytes (expressing PD-L1 receptor PD-1) and murine renal cancer cells (RENCA, expressing high PD-L1). We observed that the splenocyte-mediated apoptosis of cancer cells during co-culture was markedly increased in the presence of either c-Met inhibitor or PD-L1 neutralizing antibody. Finally, we found that both c-Met and PD-L1 are significantly up-regulated and co-localized in human renal cancer tissues. Together, our study suggests a novel mechanism(s) by which c-Met can promote increased survival of renal cancer cells through the regulation of HO-1 and PD-L1. C1 [Balan, Murugabaskar; Mier y Teran, Eduardo; Pal, Soumitro] Boston Childrens Hosp, Div Nephrol, Boston, MA 02115 USA. [Balan, Murugabaskar; Choueiri, Toni K.; Freeman, Gordon; Pal, Soumitro] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Choueiri, Toni K.; Freeman, Gordon] Dana Farber Canc Inst, Boston, MA 02115 USA. [Waaga-Gasser, Ana Maria; Gasser, Martin] Univ Wurzburg, Dept Surg Mol Oncol & Immunol, D-97080 Wurzburg, Germany. RP Pal, S (reprint author), Childrens Hosp, Div Nephrol, 300 Longwood Ave, Boston, MA 02115 USA. EM soumitro.pal@childrens.harvard.edu FU National Institutes of Health [R01 CA131145, R21 CA172946] FX This work was supported by National Institutes of Health Grants R01 CA131145 and R21 CA172946 (to S. P.). NR 49 TC 12 Z9 13 U1 0 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 27 PY 2015 VL 290 IS 13 BP 8110 EP 8120 DI 10.1074/jbc.M114.612689 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CE2RE UT WOS:000351662600009 PM 25645920 ER PT J AU Dutta, S Ryan, J Chen, TS Kougentakis, C Letai, A Keating, AE AF Dutta, Sanjib Ryan, Jeremy Chen, T. Scott Kougentakis, Christos Letai, Anthony Keating, Amy E. TI Potent and Specific Peptide Inhibitors of Human Pro-Survival Protein Bcl-x(L) SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE Bcl-2 proteins; BH3 peptides; yeast-surface display; BH3 profiling; peptide design ID YEAST SURFACE DISPLAY; BCL-2 FAMILY; CELL-DEATH; ANTIAPOPTOTIC BCL-2; BH3-ONLY LIGANDS; CANCER-THERAPY; APOPTOSIS; ACTIVATION; LEUKEMIA; ABT-737 AB The Bcl-2 family of proteins plays a critical role regulating apoptosis, and pro-survival Bcl-2 family members are important therapeutic targets due to their overexpression in different cancers. Pro-apoptotic Bcl-2 homology 3 (BH3)-only proteins antagonize pro-survival Bcl-2 protein functions by binding directly to them, and a sub-class of BH3-only proteins termed sensitizers can initiate apoptosis via this mechanism in response to diverse signals. The five pro-survival proteins Bcl-x(L), Mcl-1, Bcl-2, Bcl-w and Bfl-1 differ in their binding preferences, with Bcl-x(L), Bcl-2 and Bcl-w sharing similar interaction profiles for many natural sensitizers and small molecules. Peptides that bind selectively to just one or a subset of family members have shown utility in assays that diagnose apoptotic blockades in cancer cells and as reagents for dissecting apoptotic mechanism. Combining computational design, combinatorial library screening and rational mutagenesis, we designed a series of BH3 sensitizer peptides that bind Bcl-x(L) with sub-nanomolar affinity and selectivity up to 1000-fold over each of the four competing pro-survival proteins. We demonstrate the efficacy of our designed BH3 peptides in assays that differentiate between cancer cells that are dependent on different pro-survival proteins. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Dutta, Sanjib; Chen, T. Scott; Kougentakis, Christos; Keating, Amy E.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Ryan, Jeremy; Letai, Anthony] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Keating, AE (reprint author), 77 Massachusetts Ave,Bldg 68-622, Cambridge, MA 02139 USA. EM keating@mit.edu FU National Institute of General Medical Sciences [P50-GM068762, GM110048, CA129974] FX We thank the Koch Institute Biopolymers and Proteomics Facilities for peptide synthesis and the Swanson Biotechnology Center Flow Cytometry Facility at Massachusetts Institute of Technology for cell sorting. We also thank members of the Keating laboratory for critical reading of the manuscript and helpful suggestions. This work was funded by National Institute of General Medical Sciences awards P50-GM068762 and GM110048 to A.E.K. and award CA129974 to A.L. NR 44 TC 9 Z9 9 U1 1 U2 16 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD MAR 27 PY 2015 VL 427 IS 6 BP 1241 EP 1253 DI 10.1016/j.jmb.2014.09.030 PN B PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CE4KE UT WOS:000351798700002 PM 25451027 ER PT J AU Shih, WM AF Shih, William M. TI Exploiting weak interactions in DNA self-assembly SO SCIENCE LA English DT Editorial Material ID NANOSCALE SHAPES; FOLDING DNA; ORIGAMI C1 [Shih, William M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Shih, William M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Shih, WM (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM william.shih@wyss.harvard.edu NR 14 TC 2 Z9 2 U1 9 U2 93 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD MAR 27 PY 2015 VL 347 IS 6229 BP 1417 EP 1418 DI 10.1126/science.aaa9483 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE9AT UT WOS:000352136400021 PM 25814568 ER PT J AU Cirulli, ET Lasseigne, BN Petrovski, S Sapp, PC Dion, PA Leblond, CS Couthouis, J Lu, YF Wang, QL Krueger, BJ Ren, Z Keebler, J Han, YJ Levy, SE Boone, BE Wimbish, JR Waite, LL Jones, AL Carulli, JP Day-Williams, AG Staropoli, JF Xin, WW Chesi, A Raphael, AR McKenna-Yasek, D Cady, J de Jong, JMBV Kenna, KP Smith, BN Topp, S Miller, J Gkazi, A Al-Chalabi, A van den Berg, LH Veldink, J Silani, V Ticozzi, N Shaw, CE Baloh, RH Appel, S Simpson, E Lagier-Tourenne, C Pulst, SM Gibson, S Trojanowski, JQ Elman, L McCluskey, L Grossman, M Shneider, NA Chung, WK Ravits, JM Glass, JD Sims, KB Van Deerlin, VM Maniatis, T Hayes, SD Ordureau, A Swarup, S Landers, J Baas, F Allen, AS Bedlack, RS Harper, JW Gitler, AD Rouleau, GA Brown, R Harms, MB Cooper, GM Harris, T Myers, RM Goldstein, DB AF Cirulli, Elizabeth T. Lasseigne, Brittany N. Petrovski, Slave Sapp, Peter C. Dion, Patrick A. Leblond, Claire S. Couthouis, Julien Lu, Yi-Fan Wang, Quanli Krueger, Brian J. Ren, Zhong Keebler, Jonathan Han, Yujun Levy, Shawn E. Boone, Braden E. Wimbish, Jack R. Waite, Lindsay L. Jones, Angela L. Carulli, John P. Day-Williams, Aaron G. Staropoli, John F. Xin, Winnie W. Chesi, Alessandra Raphael, Alya R. McKenna-Yasek, Diane Cady, Janet de Jong, J. M. B. Vianney Kenna, Kevin P. Smith, Bradley N. Topp, Simon Miller, Jack Gkazi, Athina Al-Chalabi, Ammar van den Berg, Leonard H. Veldink, Jan Silani, Vincenzo Ticozzi, Nicola Shaw, Christopher E. Baloh, Robert H. Appel, Stanley Simpson, Ericka lagier-Tourenne, ClotilDe Pulst, Stefan M. Gibson, Summer Trojanowski, John Q. Elman, Lauren McCluskey, Leo Grossman, Murray Shneider, Neil A. Chung, Wendy K. Ravits, John M. Glass, Jonathan D. Sims, Katherine B. Van Deerlin, Vivianna M. Maniatis, Tom Hayes, Sebastian D. Ordureau, Alban Swarup, Sharan Landers, John Baas, Frank Allen, Andrew S. Bedlack, Richard S. Harper, J. Wade Gitler, Aaron D. Rouleau, Guy A. Brown, Robert Harms, Matthew B. Cooper, Gregory M. Harris, Tim Myers, Richard M. Goldstein, David B. CA FALS Sequencing Consortium TI Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways SO SCIENCE LA English DT Article ID AUTOPHAGY RECEPTOR; SPASTIN GENE; D-SERINE; OPTINEURIN; MUTATIONS; ALS; GRANULES; DISEASE; BINDING; PROTEIN AB Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease with no effective treatment. We report the results of a moderate-scale sequencing study aimed at increasing the number of genes known to contribute to predisposition for ALS. We performed whole-exome sequencing of 2869 ALS patients and 6405 controls. Several known ALS genes were found to be associated, and TBK1 (the gene encoding TANK-binding kinase 1) was identified as an ALS gene. TBK1 is known to bind to and phosphorylate a number of proteins involved in innate immunity and autophagy, including optineurin (OPTN) and p62 (SQSTM1/sequestosome), both of which have also been implicated in ALS. These observations reveal a key role of the autophagic pathway in ALS and suggest specific targets for therapeutic intervention. C1 [Cirulli, Elizabeth T.] Duke Univ, Sch Med, Ctr Appl Genom & Precis Med, Durham, NC 27708 USA. [Lasseigne, Brittany N.; Levy, Shawn E.; Boone, Braden E.; Wimbish, Jack R.; Waite, Lindsay L.; Jones, Angela L.; Cooper, Gregory M.; Myers, Richard M.] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA. [Petrovski, Slave; Lu, Yi-Fan; Wang, Quanli; Krueger, Brian J.; Ren, Zhong; Goldstein, David B.] Columbia Univ, Inst Genom Med, New York, NY 10032 USA. [Sapp, Peter C.; McKenna-Yasek, Diane; Landers, John; Brown, Robert] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA. [Dion, Patrick A.; Leblond, Claire S.; Rouleau, Guy A.] McGill Univ, Dept Neurol & Neurosurg, Montreal Neurol Inst, Montreal, PQ H3A 2B4, Canada. [Couthouis, Julien; Chesi, Alessandra; Raphael, Alya R.; Gitler, Aaron D.] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA. [Keebler, Jonathan; Han, Yujun] Duke Univ, Sch Med, Durham, NC 27708 USA. [Carulli, John P.; Day-Williams, Aaron G.; Staropoli, John F.; Hayes, Sebastian D.; Harris, Tim] Biogen Inc, Cambridge, MA 02142 USA. [Xin, Winnie W.; Sims, Katherine B.] Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Neurogenet DNA Diagnost Lab, Boston, MA 02114 USA. [Cady, Janet; Harms, Matthew B.] Washington Univ, Sch Med, Neurol, St Louis, MO 63110 USA. [de Jong, J. M. B. Vianney; Baas, Frank] Univ Amsterdam, Acad Med Ctr, Dept Genome Anal, NL-1105 AZ Amsterdam, Netherlands. [Kenna, Kevin P.] Univ Dublin Trinity Coll, Trinity Biomed Sci Inst, Acad Unit Neurol, Dublin, Ireland. [Smith, Bradley N.; Topp, Simon; Miller, Jack; Gkazi, Athina; Al-Chalabi, Ammar; Shaw, Christopher E.] Kings Coll London, Dept Basic & Clin Neurosci, Inst Psychiat, London SE5 8AF, England. [van den Berg, Leonard H.; Veldink, Jan] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Neurol, NL-3508 GA Utrecht, Netherlands. [Silani, Vincenzo; Ticozzi, Nicola] IRCCS Ist Auxol ltaliano, Dept Neurol, I-20149 Milan, Italy. [Silani, Vincenzo; Ticozzi, Nicola] IRCCS Ist Auxol ltaliano, Lab Neurosci, I-20149 Milan, Italy. [Silani, Vincenzo; Ticozzi, Nicola] Univ Milan, Dino Ferrari Ctr, Dept Pathophysiol & Transplantat, I-20122 Milan, Italy. [Baloh, Robert H.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Appel, Stanley; Simpson, Ericka] Houston Methodist Hosp, Houston, TX 77030 USA. [Appel, Stanley; Simpson, Ericka] Cornell Univ, Weill Cornell Med Coll, New York, NY 10065 USA. [lagier-Tourenne, ClotilDe] Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. [lagier-Tourenne, ClotilDe; Ravits, John M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Pulst, Stefan M.; Gibson, Summer] Univ Utah, Sch Med, Dept Neurol, Salt Lake City, UT 84112 USA. [Trojanowski, John Q.; Van Deerlin, Vivianna M.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Elman, Lauren; McCluskey, Leo] Univ Penn, Perelman Sch Med, Penn ALS Ctr, Dept Neurol, Philadelphia, PA 19104 USA. [Grossman, Murray] Univ Penn, Perelman Sch Med, Penn Frontotemporal Degenerat Ctr, Dept Neurol, Philadelphia, PA 19104 USA. [Shneider, Neil A.] Columbia Univ, Ctr Motor Neuron Biol & Dis, Dept Neurol, New York, NY 10032 USA. [Chung, Wendy K.] Columbia Univ, Dept Pediat & Med, New York, NY 10032 USA. [Glass, Jonathan D.] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. [Maniatis, Tom] Columbia Univ, Dept Biochem Mol Biophys, New York, NY 10027 USA. [Hayes, Sebastian D.; Ordureau, Alban; Swarup, Sharan; Harper, J. Wade] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Allen, Andrew S.] Duke Univ, Sch Med, Dept Biostat & Bioinformat, Durham, NC 27708 USA. [Bedlack, Richard S.] Duke ALS Clin, Durham, NC 27708 USA. [Bedlack, Richard S.] Durham VA Med Ctr, Durham, NC 27708 USA. RP Harris, T (reprint author), Biogen Inc, 14 Cambridge Ctr, Cambridge, MA 02142 USA. EM tim.harris@biogenidec.com RI CEREDA, CRISTINA/G-8208-2011; Ordureau, Alban/C-7558-2012; COUTHOUIS, Julien/G-3895-2012; Vance, Caroline/C-3047-2012; Williams, Kelly/A-5545-2010; Troakes, Claire/K-4346-2015; ceroni, mauro/G-7080-2011; CASTELLOTTI, BARBARA/J-4939-2016; Pensato, Viviana/J-6533-2016; Ticozzi, Nicola/K-8094-2016; Baas, Frank/F-9574-2010 OI McLaughlin, Russell/0000-0003-3915-2135; Petrovski, Slave/0000-0002-1527-961X; topp, simon/0000-0002-5200-3284; Hardiman, Orla/0000-0003-2610-1291; putchakatla, venkateswarlu/0000-0002-5045-9819; Lasseigne, Brittany/0000-0002-1642-8904; Turner, Martin/0000-0003-0267-3180; CEREDA, CRISTINA/0000-0001-9571-0862; Ordureau, Alban/0000-0002-4924-8520; COUTHOUIS, Julien/0000-0002-2378-4595; Vance, Caroline/0000-0001-5780-6951; Williams, Kelly/0000-0001-6319-9473; Shneider, Neil/0000-0002-3223-7366; ceroni, mauro/0000-0002-8947-5007; Shaw, Pamela/0000-0002-8925-2567; CASTELLOTTI, BARBARA/0000-0002-9098-3041; Pensato, Viviana/0000-0001-9798-2669; Ticozzi, Nicola/0000-0001-5963-7426; Baas, Frank/0000-0003-3912-5428 FU Medical Research Council [MR/L501529/1, G0500289, G0900688, MC_G1000733, MR/L021803/1]; NCATS NIH HHS [TL1 TR001066, UL1 TR001067]; NIA NIH HHS [P01 AG017586, P01 AG032953, P50 AG025688]; NIGMS NIH HHS [T32 GM007754]; NINDS NIH HHS [K08 NS075094, R01 NS073873, R37 NS033123, R37 NS083524]; Wellcome Trust [089701] NR 52 TC 146 Z9 149 U1 13 U2 63 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD MAR 27 PY 2015 VL 347 IS 6229 BP 1436 EP 1441 DI 10.1126/science.aaa3650 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE9AT UT WOS:000352136400031 PM 25700176 ER PT J AU Evans, CL AF Evans, Conor L. TI Three-dimensional in vitro cancer spheroid models for photodynamic therapy: strengths and opportunities SO FRONTIERS IN PHYSICS LA English DT Review DE 3D cultures; spheroids; oxygenation; imaging; advanced microscopy ID MULTICELL TUMOR SPHEROIDS; HUMAN GLIOMA SPHEROIDS; 5-AMINOLEVULINIC ACID; OVARIAN-CANCER; TISSUE-CULTURE; OXYGEN; PDT; INVASIVENESS; MODULATION; MECHANISMS AB Three dimensional, in vitro spheroid cultures offer considerable utility for the development and testing of anticancer photodynamic therapy regimens. More complex than monolayer cultures, three-dimensional spheroid systems replicate many of the important cell-cell and cell-matrix interactions that modulate treatment response in vivo. Simple enough to be grown by the thousands and small enough to be optically interrogated, spheroid cultures lend themselves to high-content and high-throughput imaging approaches. These advantages have enabled studies investigating photosensitizer uptake, spatiotemporal patterns of therapeutic response, alterations in oxygen diffusion and consumption during therapy, and the exploration of mechanisms that underlie therapeutic synergy. The use of quantitative imaging methods, in particular, has accelerated the pace of three-dimensional in vitro photodynamic therapy studies, enabling the rapid compilation of multiple treatment response parameters in a single experiment. Improvements in model cultures, the creation of new molecular probes of cell state and function, and innovations in imaging toolkits will be important for the advancement of spheroid culture systems for future photodynamic therapy studies. C1 [Evans, Conor L.] Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA. RP Evans, CL (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, CNY149-3,13th St, Charlestown, MA 02129 USA. EM evans.conor@mgh.harvard.edu NR 50 TC 4 Z9 4 U1 1 U2 1 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA EPFL SCIENCE PARK, BLDG D, LAUSANNE, 1015, SWITZERLAND SN 2296-424X J9 FRONT PHYS JI Front. Physics PD MAR 27 PY 2015 VL 3 AR 15 DI 10.3389/fphy.2015.00015 PG 7 WC Physics, Multidisciplinary SC Physics GA EB2FE UT WOS:000387172400001 ER PT J AU Lee, J Meyerhardt, JA Giovannucci, E Jeon, JY AF Lee, Junga Meyerhardt, Jeffrey A. Giovannucci, Edward Jeon, Justin Y. TI Association between Body Mass Index and Prognosis of Colorectal Cancer: A Meta-Analysis of Prospective Cohort Studies SO PLOS ONE LA English DT Article ID LIFE-STYLE FACTORS; TREATMENT-RELATED TOXICITY; COLON-CANCER; PHYSICAL-ACTIVITY; ADJUVANT CHEMOTHERAPY; RECTAL-CANCER; SURVIVAL; RISK; DIAGNOSIS; OBESITY AB Studies have reported conflicting results on the association between body mass index (BMI) and prognosis of colorectal cancer. Therefore, we have conducted a meta-analysis of prospective studies, which examined the association of pre- and post-diagnostic BMI with colorectal cancer-specific mortality and all-cause mortality in patients with colorectal cancer. We searched Medline and EMBASE database published between 1970 and September 2014. A total of 508 articles were identified, of which 16 prospective cohort studies were included for the current meta-analysis. The analysis included 58,917 patients who were followed up over a period ranging from 4.9 to 20 years (median: 9.9 years). We found that being underweight before cancer diagnosis was associated with increased all-cause mortality (Relative risk [RR]: 1.63, 95% CI: 1.18-2.23, p < 0.01) and being obese (BMI >= 30 kg/m(2)) before cancer diagnosis was associated with increased colorectal cancer-specific mortality (RR: 1.22, 95% CI: 1.003-1.35, p < 0.01) and all-cause mortality (RR: 1.25, 95% CI: 1.14-1.36, p < 0.01). On the other hand, being underweight (RR: 1.33, 95% CI: 1.20-1.47, p < 0.01), obese (RR: 1.08, 95% CI: 1.03-1.3, p < 0.01), and class II/III obese (BMI >= 35 kg/m(2); RR: 1.13, 95% CI: 1.04-1.23, p < 0.01) after diagnosis were associated with significantly increased all-cause mortality. Being obese prior to diagnosis of colorectal cancer was associated with increased colorectal cancer-specific mortality and all-cause mortality, whereas being obese after diagnosis was associated with increased all-cause mortality. The associations with being underweight may reflect reverse causation. Maintaining a healthy body weight should be discussed with colorectal cancer survivors. C1 [Lee, Junga; Jeon, Justin Y.] Yonsei Univ, Dept Sport & Leisure Studies, Seoul 120749, South Korea. [Lee, Junga; Jeon, Justin Y.] Yonsei Univ, Exercise Med Ctr Diabet & Canc Patients, Seoul 120749, South Korea. [Meyerhardt, Jeffrey A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Giovannucci, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. EM egiovann@hsph.harvard.edu; jjeon@yonsei.ac.kr FU NCI NIH HHS [R01 CA118553, R01 CA169141] NR 39 TC 11 Z9 11 U1 2 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 26 PY 2015 VL 10 IS 3 AR e0120706 DI 10.1371/journal.pone.0120706 PG 25 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CK6QW UT WOS:000356353700056 PM 25811460 ER PT J AU Moreno, LO Salvemini, L Mendonca, C Copetti, M De Bonis, C De Cosmo, S Doria, A Trischitta, V Menzaghi, C AF Moreno, Lorena Ortega Salvemini, Lucia Mendonca, Christine Copetti, Massimiliano De Bonis, Concetta De Cosmo, Salvatore Doria, Alessandro Trischitta, Vincenzo Menzaghi, Claudia TI Serum Resistin and Glomerular Filtration Rate in Patients with Type 2 Diabetes SO PLOS ONE LA English DT Article ID CHRONIC KIDNEY-DISEASE; GENERAL JAPANESE POPULATION; CIRCULATING ADIPONECTIN; INSULIN-RESISTANCE; ALL-CAUSE; RISK; ASSOCIATION; BIOMARKERS; PLASMA; ATHEROSCLEROSIS AB Background High serum levels of the pro-inflammatory adipokine resistin have been associated with decreased renal function in the general population. The goal of this study was to investigate whether such association is also present among diabetic subjects, who are at increased risk of renal function loss. Methods The cross-sectional association between serum resistin levels and estimated glomerular filtration rate (eGFR) was investigated in 1,560 type 2 diabetic (T2D) patients of European ancestry comprised in two different cohorts: 762 patients from San Giovanni Rotondo (SGR; Italy) and 798 patients from Boston (US). Results Serum resistin was inversely associated with eGFR in SGR [beta (SE) for one SD of resistin increment = -1.01 (0.70) ml/min/1.73m(2), p = 0.019] and in Boston [beta (SE) = -5.31 (0.74) ml/min/1.73m(2), p < 0.001] samples, as well as in the two studies combined [beta (SE) = -3.42 (0.52) ml/min/1.73m(2), p < 0.001]. The association was unaffected by adjustment for smoking habits, BMI, waist circumference, diabetes duration, HbA1c, insulin treatment, hypertension and lipid-lowering therapy: beta (SE) for one SD of resistin increment = -1.07 (0.70), p = 0.02; -5.50 (0.88), p < 0.001; and -2.81 (0.55) ml/min/1.73m(2), p <.001, in SGR, Boston and the two studies combined, respectively. The association was significantly stronger in men than in women (p for resistin-by-gender interaction = 0.003). For each resistin SD increment, the odds of having eGFR < 0 ml/min/1.73m(2) increased by 22% (OR = 1.22; 95% CI 1.02-1.44; p = 0.025) in SGR sample, 69% (OR = 1.69; 95% CI 1.38-2.07; p < 0.001) in Boston sample, and 47% (OR = 1.47; 95% CI 1.29-1.68; p < 0.001) in the two studies considered together. Similar associations were observed in the adjusted model: OR 95% CI for each SD resistin increment being 1.23 (1.03-1.46), p = 0.021; 1.52 (1.20-1.92), p < 0.001; 1.33 (1.16-1.53), p < 0.001, in SGR, Boston and the two studies combined, respectively. Conclusions This is the first report of an association between high serum resistin and low eGFR in patients with T2D of European ancestry. C1 [Moreno, Lorena Ortega; Salvemini, Lucia; De Bonis, Concetta; Trischitta, Vincenzo; Menzaghi, Claudia] IRCCS Casa Sollievo Sofferenza, Res Unit Diabet & Endocrine Dis, San Giovanni Rotondo, Italy. [Mendonca, Christine; Doria, Alessandro] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Copetti, Massimiliano] IRCCS Casa Sollievo Sofferenza, Biostat Unit, San Giovanni Rotondo, Italy. [De Cosmo, Salvatore] IRCCS Casa Sollievo Sofferenza, Div Internal Med, Dept Med Sci, San Giovanni Rotondo, Italy. [Doria, Alessandro] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Trischitta, Vincenzo] Univ Roma La Sapienza, Dept Expt Med, I-00185 Rome, Italy. RP Trischitta, V (reprint author), IRCCS Casa Sollievo Sofferenza, Res Unit Diabet & Endocrine Dis, San Giovanni Rotondo, Italy. EM vincenzo.trischitta@uniroma1.it; c.menzaghi@operapadrepio.it RI De Cosmo, Salvatore/J-7420-2016; Trischitta, Vincenzo/K-1487-2016; Salvemini, Lucia/K-2121-2016; Copetti, Massimiliano/K-3186-2016; OI De Cosmo, Salvatore/0000-0001-8787-8286; Trischitta, Vincenzo/0000-0003-1174-127X; Salvemini, Lucia/0000-0001-8776-9477; Copetti, Massimiliano/0000-0002-7960-5947; Menzaghi, Claudia/0000-0002-7438-8955 FU Accordo Programma Quadro in Materia di Ricerca Scientifica nella Regione Puglia-PST; Accordo Programma Quadro in Materia di Ricerca Scientifica nella Regione Puglia-PO Puglia FESR; Italian Ministry of Health [RC2014, RC2015]; European Foundation for the Study of Diabetes/Pfizer; Societa Italiana di Diabetologia-Fondazione Diabete Ricerca; National Institutes of Health [R01 DK073168, DK110400] FX This study was supported by Accordo Programma Quadro in Materia di Ricerca Scientifica nella Regione Puglia-PST 2006 and PO Puglia FESR 2007-2013, Italian Ministry of Health grants RC2014 and RC2015, European Foundation for the Study of Diabetes/Pfizer grant and Societa Italiana di Diabetologia-Fondazione Diabete Ricerca (CM) and National Institutes of Health grants R01 DK073168 and DK110400 (AD). Dr. Ortega Moreno is supported by grant Societa Italiana di Diabetologia-Fondazione Diabete Ricerca. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 3 Z9 3 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 26 PY 2015 VL 10 IS 3 AR e0119529 DI 10.1371/journal.pone.0119529 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CK6QW UT WOS:000356353700018 PM 25811174 ER PT J AU Walford, GA Colomo, N Todd, JN Billings, LK Fernandez, M Chamarthi, B Warner, AS Davis, J Littleton, KR Hernandez, AM Fanelli, RR Lanier, A Barbato, C Ackerman, RJ Khan, SQ Bui, R Garber, L Stolerman, ES Moore, AF Huang, CM Kaur, V Harden, M Taylor, A Chen, L Manning, AK Huang, P Wexler, D McCarthy, RM Lo, J Thomas, MK Grant, RW Goldfine, A Hudson, MS Florez, JC AF Walford, Geoffrey A. Colomo, Natalia Todd, Jennifer N. Billings, Liana K. Fernandez, Marlene Chamarthi, Bindu Warner, A. Sofia Davis, Jaclyn Littleton, Katherine R. Hernandez, Alicia M. Fanelli, Rebecca R. Lanier, Amelia Barbato, Corinne Ackerman, Rachel J. Khan, Sabina Q. Bui, Rosa Garber, Laurel Stolerman, Elliot S. Moore, Allan F. Huang, Chunmei Kaur, Varinderpal Harden, Maegan Taylor, Andrew Chen, Ling Manning, Alisa K. Huang, Paul Wexler, Deborah McCarthy, Rita M. Lo, Janet Thomas, Melissa K. Grant, Richard W. Goldfine, Allison Hudson, Margo S. Florez, Jose C. TI The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH): Design of a pharmacogenetic Resource for Type 2 Diabetes SO PLOS ONE LA English DT Article ID EUROPEAN ASSOCIATION; INSULIN-RESISTANCE; GLYCEMIC CONTROL; GLUCOSE; RISK; HYPERGLYCEMIA; MANAGEMENT; STATEMENT; MELLITUS; HOMEOSTASIS AB Objective Genome-wide association studies have uncovered a large number of genetic variants associated with type 2 diabetes or related phenotypes. In many cases the causal gene or polymorphism has not been identified, and its impact on response to anti-hyperglycemic medications is unknown. The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH, NCT01762046) is a novel resource of genetic and biochemical data following glipizide and metformin administration. We describe recruitment, enrollment, and phenotyping procedures and preliminary results for the first 668 of our planned 1,000 participants enriched for individuals at risk of requiring anti-diabetic therapy in the future. Methods All individuals are challenged with 5 mg glipizide x 1; twice daily 500 mg metformin x 2 days; and 75-g oral glucose tolerance test following metformin. Genetic variants associated with glycemic traits and blood glucose, insulin, and other hormones at baseline and following each intervention are measured. Results Approximately 50% of the cohort is female and 30% belong to an ethnic minority group. Following glipizide administration, peak insulin occurred at 60 minutes and trough glucose at 120 minutes. Thirty percent of participants experienced non-severe symptomatic hypoglycemia and required rescue with oral glucose. Following metformin administration, fasting glucose and insulin were reduced. Common genetic variants were associated with fasting glucose levels. Conclusions SUGAR-MGH represents a viable pharmacogenetic resource which, when completed, will serve to characterize genetic influences on pharmacological perturbations, and help establish the functional relevance of newly discovered genetic loci to therapy of type 2 diabetes. C1 [Walford, Geoffrey A.; Colomo, Natalia; Todd, Jennifer N.; Billings, Liana K.; Fernandez, Marlene; Warner, A. Sofia; Davis, Jaclyn; Littleton, Katherine R.; Hernandez, Alicia M.; Fanelli, Rebecca R.; Lanier, Amelia; Ackerman, Rachel J.; Khan, Sabina Q.; Stolerman, Elliot S.; Moore, Allan F.; Kaur, Varinderpal; Taylor, Andrew; Chen, Ling; Manning, Alisa K.; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Walford, Geoffrey A.; Billings, Liana K.; Moore, Allan F.; Wexler, Deborah; Thomas, Melissa K.; Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Boston, MA 02114 USA. [Walford, Geoffrey A.; Todd, Jennifer N.; Billings, Liana K.; Moore, Allan F.; Huang, Chunmei; Huang, Paul; Wexler, Deborah; Lo, Janet; Thomas, Melissa K.; Goldfine, Allison; Florez, Jose C.] Harvard Univ, Sch Med, Boston, MA USA. [Colomo, Natalia] Hosp Univ Reg Malaga, Dept Endocrinol & Nutr, Inst Invest Biomed Malaga IBIMA, Malaga, Spain. [Todd, Jennifer N.] Boston Childrens Hosp, Boston, MA USA. [Billings, Liana K.] NorthShore Univ Hlth Syst, Div Endocrinol & Metab, Evanston, IL USA. [Chamarthi, Bindu] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Chamarthi, Bindu; McCarthy, Rita M.; Hudson, Margo S.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Barbato, Corinne; Bui, Rosa; Garber, Laurel; Goldfine, Allison] Joslin Diabet Ctr, Boston, MA 02215 USA. [Harden, Maegan] Broad Inst, Genom Platform, Cambridge, MA USA. [Grant, Richard W.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM jcflorez@partners.org FU National Institutes of Health/NIDDK [R01 DK088214, R03 DK077675, P30 DK036836]; Joslin Clinical Research Center; 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, NIH) [M01-RR-01066, 1 UL1 RR025758-04, 8UL1TR000170-05]; Harvard University and its affiliated academic health care centers FX This work was conducted with support from National Institutes of Health/NIDDK awards R01 DK088214, R03 DK077675, and P30 DK036836; from the Joslin Clinical Research Center from its philanthropic donors; and the Harvard Catalyst: The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH Awards M01-RR-01066, 1 UL1 RR025758-04 and 8UL1TR000170-05 and financial contributions from Harvard University and its affiliated academic health care centers). The funders had no role in study design, data collection and analysis, decision to publish, or preparations of the manuscript. NR 30 TC 2 Z9 2 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 26 PY 2015 VL 10 IS 3 AR e0121553 DI 10.1371/journal.pone.0121553 PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CK6QW UT WOS:000356353700115 PM 25812009 ER PT J AU Yukl, SA Shergill, AK Girling, V Li, QS Killian, M Epling, L Li, PL Kaiser, P Haase, A Havlir, DV McQuaid, K Sinclair, E Wong, JK AF Yukl, Steven A. Shergill, Amandeep K. Girling, Valerie Li, Qingsheng Killian, Maudi Epling, Lorrie Li, Peilin Kaiser, Philipp Haase, Ashley Havlir, Diane V. McQuaid, Kenneth Sinclair, Elizabeth Wong, Joseph K. TI Site-Specific Differences in T Cell Frequencies and Phenotypes in the Blood and Gut of HIV-Uninfected and ART-Treated HIV plus Adults SO PLOS ONE LA English DT Article ID IMMUNODEFICIENCY VIRUS-INFECTION; ACTIVE ANTIRETROVIRAL THERAPY; MUCOSAL IMMUNE RECONSTITUTION; PERIPHERAL-BLOOD; LYMPHOID-TISSUE; GASTROINTESTINAL-TRACT; COLLAGEN DEPOSITION; DISEASE PROGRESSION; POSITIVE PATIENTS; SIV INFECTION AB Gastrointestinal T lymphocytes are critical for mucosal immunity and HIV pathogenesis, yet little is known about normal T cell numbers and phenotypes in different regions of the gut, or the degree to which ART can restore levels to those of HIV-uninfected individuals. To investigate these questions, we measured T cell frequencies and markers of memory, activation, anergy, and homing in the blood, ileum, and rectum of HIV- and ART-suppressed HIV+ adults. In HIV-individuals, T cell frequencies and phenotypes differed significantly between sites. Compared to HIV-adults, HIV+ adults had lower absolute CD4+T cell counts in the ileal lamina propria and lower relative CD4+T cell counts in the blood and ileum. In the gut, HIV+ adults had a higher proportion of CD38+CD4+ T cells, a lower proportion of terminally-differentiated effector cells, and, in the rectum, a higher proportion of CTLA-4+ CD4+T cells. In HIV+ individuals, relative CD4+T cell numbers in the ileum correlated with the proportion of CTLA-4+ CD4+T cells, whereas in the rectum, they tended to correlate with the proportion of circulating CD4+T cells expressing alpha 4 beta 7 or CCR6. Mechanisms of T cell reconstitution may differ throughout the gut, with homing contributing more in the rectum while ileal reconstitution is associated with mucosal CD4+T cell anergy. C1 [Yukl, Steven A.; Shergill, Amandeep K.; Li, Peilin; Kaiser, Philipp; McQuaid, Kenneth; Wong, Joseph K.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA. [Yukl, Steven A.; Shergill, Amandeep K.; Girling, Valerie; Killian, Maudi; Epling, Lorrie; Li, Peilin; Kaiser, Philipp; Havlir, Diane V.; McQuaid, Kenneth; Sinclair, Elizabeth; Wong, Joseph K.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Li, Qingsheng] Univ Nebraska, Sch Biol Sci, Lincoln, NE USA. [Haase, Ashley] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA. RP Yukl, SA (reprint author), San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA. EM steven.yukl@ucsf.edu FU U.S. Department of Veterans Affairs [1 IK2 CX000520-01, I01 BX000192]; UCSF-Gladstone Center for AIDS Research (CFAR) [P30-AI027763]; National Institute of Allergy and Infectious Diseases at the National Institutes of Health [R56AI091573, U19AI096109, 1R21AI104445-01A1]; Swiss National Science Foundation [PBZHP3_147260] FX This work was supported by the U.S. Department of Veterans Affairs [1 IK2 CX000520-01 (SY), I01 BX000192 (JW)]; the UCSF-Gladstone Center for AIDS Research (CFAR) [P30-AI027763 (SY)]; the National Institute of Allergy and Infectious Diseases at the National Institutes of Health [R56AI091573 (JW, SY, AS, DH), U19AI096109 (JW), 1R21AI104445-01A1 (PL)]; and the Swiss National Science Foundation [PBZHP3_147260 (PK)]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 8 Z9 8 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 26 PY 2015 VL 10 IS 3 AR e0121290 DI 10.1371/journal.pone.0121290 PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CK6QW UT WOS:000356353700091 PM 25811360 ER PT J AU Palumbo, A Bringhen, S Mateos, MV Larocca, A Facon, T Kumar, SK Offidani, M McCarthy, P Evangelista, A Lonial, S Zweegman, S Musto, P Terpos, E Belch, A Hajek, R Ludwig, H Stewart, AK Moreau, P Anderson, K Einsele, H Durie, BGM Dimopoulos, MA Landgren, O San Miguel, JF Richardson, P Sonneveld, P Rajkumar, SV AF Palumbo, Antonio Bringhen, Sara Mateos, Maria-Victoria Larocca, Alessandra Facon, Thierry Kumar, Shaji K. Offidani, Massimo McCarthy, Philip Evangelista, Andrea Lonial, Sagar Zweegman, Sonja Musto, Pellegrino Terpos, Evangelos Belch, Andrew Hajek, Roman Ludwig, Heinz Stewart, A. Keith Moreau, Philippe Anderson, Kenneth Einsele, Hermann Durie, Brian G. M. Dimopoulos, Meletios A. Landgren, Ola San Miguel, Jesus F. Richardson, Paul Sonneveld, Pieter Rajkumar, S. Vincent TI Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report SO BLOOD LA English DT Article ID DIAGNOSED MULTIPLE-MYELOMA; RANDOMIZED-TRIALS; FRAILTY; OLDER; AGE; DEXAMETHASONE; LENALIDOMIDE; METAANALYSIS; BORTEZOMIB; CANCER AB We conducted a pooled analysis of 869 individual newly diagnosed elderly patient data from 3 prospective trials. At diagnosis, a geriatric assessment had been performed. An additive scoring system (range 0-5), based on age, comorbidities, and cognitive and physical conditions, was developed to identify 3 groups: fit (score = 0, 39%), intermediate fitness (score = 1,31%), and frail (score >= 2, 30%). The 3-year overall survival was 84% in fit, 76% in intermediate-fitness (hazard ratio [HR], 1.61; P = .042), and 57% in frail (HR, 3.57; P<.001) patients. The cumulative incidence of grade >= 3 nonhematologic adverse events at 12 months was 22.2% in fit, 26.4% in intermediate-fitness (HR, 1.23; P = .217), and 34.0% in frail (HR, 1.74; P < .001) patients. The cumulative incidence of treatment discontinuation at 12 months was 16.5% in fit, 20.8% in intermediate-fitness (HR, 1.41; P = .052), and 31.2% in frail (HR, 2.21; P < .001) patients. Our frailty score predicts mortality and the risk of toxicity in elderly myeloma patients. The International Myeloma Working group proposes this score for the measurement of frailty in designing future clinical trials. C1 [Palumbo, Antonio; Bringhen, Sara; Larocca, Alessandra] Univ Turin, Div Hematol, Myeloma Unit, Azienda Osped Univ Citta Salute & Sci Torino, Turin, Italy. [Mateos, Maria-Victoria] Univ Salamanca, CSIC, Hosp Univ Salamanca, Serv Hematol,Ctr Invest Canc,Inst Biol Mol & Celu, E-37008 Salamanca, Spain. [Facon, Thierry] Univ Hosp, Dept Hematol, Lille, France. [Kumar, Shaji K.; Rajkumar, S. Vincent] Mayo Clin, Div Hematol, Coll Med, Rochester, MN USA. [Offidani, Massimo] Azienda Osped Univ Osped Ancona, Clin Ematol, Ancona, Italy. [McCarthy, Philip] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [Evangelista, Andrea] Azienda Osped Citta Salute & Sci Torino, Clin Epidemiol Unit, I-10126 Turin, Italy. [Lonial, Sagar] Emory Univ, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA. [Zweegman, Sonja] Vrije Univ Amsterdam, Med Ctr, Dept Hematol, Amsterdam, Netherlands. [Musto, Pellegrino] Referral Canc Ctr Basilicata, Ist Ricovero & Cura Carattere Sci, Sci Direct, Rionero In Vulture, Italy. [Terpos, Evangelos; Dimopoulos, Meletios A.] Univ Athens, Sch Med, Dept Clin Therapeut, Athens 11528, Greece. [Belch, Andrew] Univ Alberta, Dept Oncol, Cross Canc Inst, Edmonton, AB, Canada. [Hajek, Roman] Univ Ostrava, Dept Haematooncol, CZ-70103 Ostrava, Czech Republic. [Hajek, Roman] Univ Ostrava, Fac Med, Ostrava, Czech Republic. [Ludwig, Heinz] Wilhelminen, Dept Oncol Hematol & Palliat Care, Vienna, Austria. [Stewart, A. Keith] Mayo Clin, Div Hematol Oncol, Scottsdale, AZ USA. [Moreau, Philippe] Univ Hosp Hotel Dieu, Dept Hematol, Nantes, France. [Anderson, Kenneth] Dana Farber Canc Inst, Dept Hematol Oncol, Boston, MA 02115 USA. [Einsele, Hermann] Univ Hosp, Dept Internal Med 2, Med Clin & Polyclin 2, Wurzburg, Germany. [Durie, Brian G. M.] Cedars Sinai Comprehens Canc Ctr, Dept Hematol Oncol, Los Angeles, CA USA. [Landgren, Ola] NCI, Multiple Myeloma sect, Bethesda, MD 20892 USA. [San Miguel, Jesus F.] Univ Navarra Clin, Ctr Invest Med Aplicadas, Pamplona, Spain. [Richardson, Paul] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sonneveld, Pieter] Erasmus MC, Dept Hematol, Rotterdam, Netherlands. [Sonneveld, Pieter] HOVON Data Ctr, Rotterdam, Netherlands. RP Palumbo, A (reprint author), Azienda Osped Citta Salute & Sci Torino, Dipartimento Oncol & Ematol, Via Genova 3, I-10126 Turin, Italy. EM appalumbo@yahoo.com RI richard, chrystelle/K-8595-2015; FACON, THIERRY/M-9736-2014; evangelista, andrea/A-7802-2013; OI FACON, THIERRY/0000-0001-7705-8460; Musto, Pellegrino/0000-0003-3277-6594 FU Amgen; Bristol-Myers Squibb; Genmab A/S; Celgene; Janssen-Cilag; Millennium Pharmaceuticals Inc; Onyx Pharmaceuticals; Onyx; Novartis; Millennium; Cephalon; Merck; Abbott; Janssen; Sanofi; Array Pharmaceuticals; Millennium Pharmaceuticals FX Conflict-of-interest disclosure: A.P. has received honoraria from Amgen, Array BioPharma, Bristol-Myers Squibb, Genmab A/S, Celgene, Janssen-Cilag, Millennium Pharmaceuticals Inc, Onyx Pharmaceuticals, and Sanofi Aventis, and consultancy fees from Amgen, Bristol-Myers Squibb, Genmab A/S, Celgene, Janssen-Cilag, Millennium Pharmaceuticals Inc, and Onyx Pharmaceuticals. S.B. has received honoraria from Celgene, Janssen-Cilag, and Novartis, consultancy fees from Onyx, and has served on the advisory committee of Merck Sharp & Dohme. M.-V.M. has received honoraria from Celgene and Janssen-Cilag, and served on the speakers bureau of Celgene, Millennium, and Ortho-Biotech. A.L. has received honoraria from Celgene and Janssen-Cilag. T.F. has received honoraria from Celgene and Janssen. S.K.K. has received institutional clinical trial funding from Celgene, Novartis, Onyx, Millennium, Cephalon, Merck, and Abbott. M.O. has received honoraria from Celgene and Janssen. P. McCarthy has served on the advisory board and received honoraria from Celgene, Millennium, and Janssen. S.L. is a consultant for Millennium, Celgene, Novartis, BMS, Onyx, and Janssen. S.Z. has served on the advisory board and received a research grant from Celgene, Janssen-Cilag, and Millennium. P. Musto has received research funds from Celgene and honoraria from Celgene, Janssen, Sanofi, and Novartis. E.T. has received honoraria from Novartis, Amgen, Celgene, and Onyx, advisory fees from Amgen, has been on the Steering Committee of Amgen and Janssen-Cilag, and received educational grants from Amgen, Janssen-Cilag, and Celgene. R.H. has received consultancy fees from Celgene, Janssen, and Merck. A.K.S. has received consultancy fees and honoraria from Celgene, Array Pharmaceuticals, Millennium Pharmaceuticals, and Novartis. P. Moreau has served on the advisory board of Janssen, Millennium, Onyx, and Celgene, and received honoraria from Janssen, Celgene, and Mundipharma. K.A. has served on the advisory board of Millennium, Gilead, Sanofi Aventis, and Onyx. H.E. has received consultancy fees and honoraria from Celgene and Janssen-Cilag. B.G.M.D. has received honoraria from Celgene. M.A.D. has received honoraria from Celgene, Ortho-Biotech, and Onyx. J.F.S.M. has received consultancy fees and honoraria from Janssen-Cilag, Millennium Pharmaceuticals, Celgene, Onyx Pharmaceuticals, and Novartis. P.R. is a member of the advisory board for Celgene Corporation. P.S. has received research support from Celgene, Janssen, Onyx, and Millennium. The remaining authors declare no competing financial interests. NR 38 TC 67 Z9 70 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAR 26 PY 2015 VL 125 IS 13 BP 2068 EP 2074 DI 10.1182/blood-2014-12-615187 PG 7 WC Hematology SC Hematology GA CI3CX UT WOS:000354626300012 PM 25628469 ER PT J AU Stewart, MH Albert, M Sroczynska, P Cruickshank, VA Guo, YP Rossi, DJ Helin, K Enver, T AF Stewart, Morag H. Albert, Mareike Sroczynska, Patrycja Cruickshank, V. Adam Guo, Yanping Rossi, Derrick J. Helin, Kristian Enver, Tariq TI The histone demethylase Jarid1b is required for hematopoietic stem cell self-renewal in mice SO BLOOD LA English DT Article ID TRANSCRIPTIONAL REPRESSOR; EXPRESSION; DIFFERENTIATION; PROLIFERATION; LEUKEMIA; PATTERN; PLU-1 AB Jarid1b/KDM5bis a histone demethylase that regulates self-renewal and differentiation in stem cells and cancer; however, its function in hematopoiesis is unclear. Here, we find that Jarid1b is highly expressed in primitive hematopoietic compartments and is over-expressed in acute myeloid leukemias. Constitutive genetic deletion of Jarid1b did not impact steady-state hematopoiesis. In contrast, acute deletion of Jarid1b from bone marrow increased peripheral blood T cells and, following secondary transplantation, resulted in loss of bone marrow reconstitution. Our results reveal that deletion of Jarid1b compromises hematopoietic stem cell (HSC) self-renewal capacity and suggest that Jarid1b is a positive regulator of HSC potential. C1 [Stewart, Morag H.; Rossi, Derrick J.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Stewart, Morag H.; Rossi, Derrick J.] Harvard Univ, Dept Stem Cell & Regenerat Med, Cambridge, MA 02138 USA. [Albert, Mareike; Sroczynska, Patrycja; Cruickshank, V. Adam; Helin, Kristian] Univ Copenhagen, Ctr Epigenet, Biotech Res & Innovat Ctr, Copenhagen, Denmark. [Albert, Mareike; Sroczynska, Patrycja; Cruickshank, V. Adam; Helin, Kristian] Univ Copenhagen, Danish Stem Cell Ctr, Copenhagen, Denmark. [Guo, Yanping; Enver, Tariq] UCL, UCL Canc Inst, Stem Cell Grp, London WC1E 6BT, England. RP Enver, T (reprint author), UCL, UCL Canc Inst, Stem Cell Grp, 72 Huntley St,Paul OGorman Bldg, London WC1E 6BT, England. EM t.enver@ucl.ac.uk OI Helin, Kristian/0000-0003-1975-6097 FU Kay Kendall Leukaemia Fund; Merton College Oxford; EMBO; Danish Medical Research Council; Leukaemia and Lymphoma Research; Cancer Research UK FX This work was supported by junior research fellowships from Kay Kendall Leukaemia Fund and Merton College Oxford (M.H.S.), an EMBO long-term postdoctoral fellowship (M.A.), a grant from the Danish Medical Research Council (K.H.), and program grants from Leukaemia and Lymphoma Research and Cancer Research UK (T.E.). NR 19 TC 9 Z9 10 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAR 26 PY 2015 VL 125 IS 13 BP 2075 EP 2078 DI 10.1182/blood-2014-08-596734 PG 4 WC Hematology SC Hematology GA CI3CX UT WOS:000354626300013 PM 25655602 ER PT J AU Hebraud, B Magrangeas, F Cleynen, A Lauwers-Cances, V Chretien, ML Hulin, C Leleu, X Yon, E Marit, G Karlin, L Roussel, M Stoppa, AM Belhadj, K Voillat, L Garderet, L Macro, M Caillot, D Mohty, M Facon, T Moreau, P Attal, M Munshi, N Corre, J Minvielle, S Avet-Loiseau, H AF Hebraud, Benjamin Magrangeas, Florence Cleynen, Alice Lauwers-Cances, Valerie Chretien, Marie-Lorraine Hulin, Cyrille Leleu, Xavier Yon, Edwige Marit, Gerald Karlin, Lionel Roussel, Murielle Stoppa, Anne-Marie Belhadj, Karim Voillat, Laurent Garderet, Laurent Macro, Margaret Caillot, Denis Mohty, Mohamad Facon, Thierry Moreau, Philippe Attal, Michel Munshi, Nikhil Corre, Jill Minvielle, Stephane Avet-Loiseau, Herve TI Role of additional chromosomal changes in the prognostic value of t(4;14) and del(17p) in multiple myeloma: the IFM experience SO BLOOD LA English DT Article ID GENETIC ABNORMALITIES; FGFR3 EXPRESSION; SURVIVAL; T(4/14)(P16,Q32); CYTOGENETICS AB In multiple myeloma, cytogenetic changes are important predictors of patient outcome. In this setting, the most important changes are deletion 17p, del(17p), and translocation of chromosomes 4 and 14, t(4; 14), conferring a poor outcome. However, a certain degree of heterogeneity is observed in the survival of these high-risk patients. We hypothesized that other chromosomal changes may impact the outcome. We retrospectively analyzed a large series of 242 patients displaying either t(4; 14) (157 patients) or del(17p) (110 patients), 25 patients presenting both abnormalities, using single nucleotide polymorphism array. In patients with t(4; 14), del(1p32), del22q, and >30 chromosomal structural changes negatively impacted progression-free survival (PFS). For overall survival (OS), del(13q14), del(1p32), and the number of chromosomal structural changes worsened the prognosis of patients. For patients with del(17p), del6q worsened the prognosis of patients, whereas trisomy 15 and monosomy 14 were found to have a protective effect on PFS. For OS, del(1p32) worsened the prognosis of patients, whereas having >8 numerical changes was found to have a protective effect on survival. This study, which is the largest series of high-risk patients analyzed with the most modern genomic technique, identified 1 main factor negatively impacting survival: del(1p32). C1 [Hebraud, Benjamin; Cleynen, Alice; Corre, Jill; Avet-Loiseau, Herve] Inst Univ Canc, Lab Genom Myeloma, Toulouse, France. [Hebraud, Benjamin; Cleynen, Alice; Corre, Jill; Avet-Loiseau, Herve] Univ Hosp, Toulouse, France. [Hebraud, Benjamin; Cleynen, Alice; Corre, Jill; Avet-Loiseau, Herve] Fac Med Toulouse, INSERM, Ctr Rech Canc Toulouse, U1037, F-31073 Toulouse, France. [Magrangeas, Florence; Minvielle, Stephane] Univ Hosp, Unite Mixte Genom Canc, Nantes, France. [Magrangeas, Florence; Minvielle, Stephane] INSERM, U892, Nantes, France. [Lauwers-Cances, Valerie; Yon, Edwige] Univ Hosp, Serv Epidemiol, Toulouse, France. [Chretien, Marie-Lorraine; Caillot, Denis] Univ Hosp, Dept Hematol, Dijon, France. [Hulin, Cyrille] Univ Hosp, Dept Hematol, Nancy, France. [Leleu, Xavier; Facon, Thierry] Univ Hosp, Dept Hematol, Lille, France. [Marit, Gerald] Univ Hosp, Dept Hematol, Bordeaux, France. [Karlin, Lionel] Univ Hosp, Dept Hematol, Lyon, France. [Roussel, Murielle; Attal, Michel] Univ Hosp, Dept Hematol, Toulouse, France. [Stoppa, Anne-Marie] Inst J Paoli I Calmettes, Dept Hematol, F-13009 Marseille, France. [Belhadj, Karim] Henri Mondor Univ Hosp, Dept Hematol, Creteil, France. [Voillat, Laurent] Gen Hosp, Dept Hematol, Chalon Sur Saone, France. [Garderet, Laurent; Mohty, Mohamad] St Antoine Univ Hosp, Dept Hematol, Paris, France. [Macro, Margaret] Univ Hosp, Dept Hematol, Caen, France. [Moreau, Philippe] Univ Hosp, Dept Hematol, Nantes, France. [Munshi, Nikhil] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Munshi, Nikhil] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Avet-Loiseau, H (reprint author), IUC T Oncopole, Unite Genom Myelome, 1 Ave Irene Joliot Curie, F-31059 Toulouse, France. EM avet-loiseau.h@chu-toulouse.fr RI Minvielle, Stephane/K-8251-2015; richard, chrystelle/K-8595-2015; Magrangeas, Florence/L-3080-2015; FACON, THIERRY/M-9736-2014; corre, jill/Q-2460-2015 OI FACON, THIERRY/0000-0001-7705-8460; FU National Institutes of Health, National Cancer Institute (Dana-Farber Cancer Institute) [PO1 CA100707-12]; CAPTOR program (French government); Onyx FX This study was supported by a grant from the National Institutes of Health, National Cancer Institute (Dana-Farber Cancer Institute) (PO1 CA100707-12), the CAPTOR program (French government), and a dedicated grant from Onyx. NR 19 TC 16 Z9 17 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAR 26 PY 2015 VL 125 IS 13 BP 2095 EP 2100 DI 10.1182/blood-2014-07-587964 PG 6 WC Hematology SC Hematology GA CI3CX UT WOS:000354626300016 PM 25636340 ER PT J AU Weinstock, DM Dalla-Favera, R Gascoyne, RD Leonard, JP Levy, R Lossos, IS Melnick, AM Nowakowski, GS Press, OW Savage, KJ Shipp, MA Staudt, LM AF Weinstock, David M. Dalla-Favera, Riccardo Gascoyne, Randy D. Leonard, John P. Levy, Ronald Lossos, Izidore S. Melnick, Ari M. Nowakowski, Grzegorz S. Press, Oliver W. Savage, Kerry J. Shipp, Margaret A. Staudt, Louis M. TI A roadmap for discovery and translation in lymphoma SO BLOOD LA English DT Letter ID T-LYMPHOCYTES C1 [Weinstock, David M.; Shipp, Margaret A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Weinstock, David M.; Shipp, Margaret A.] Harvard Univ, Sch Med, Boston, MA USA. [Dalla-Favera, Riccardo] Columbia Univ, Inst Canc Genet, New York, NY USA. [Dalla-Favera, Riccardo] Columbia Univ, Dept Pathol & Cell Biol, New York, NY USA. [Gascoyne, Randy D.; Savage, Kerry J.] British Columbia Canc Agcy, Ctr Lymphoid Canc, Div Med Oncol, Vancouver, BC V5Z 4E6, Canada. [Gascoyne, Randy D.] British Columbia Canc Agcy, Ctr Lymphoid Canc, Dept Pathol, Vancouver, BC V5Z 4E6, Canada. [Gascoyne, Randy D.; Savage, Kerry J.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Leonard, John P.; Melnick, Ari M.] Weill Cornell Med Coll, Div Hematol & Med Oncol, New York, NY USA. [Levy, Ronald] Stanford Univ, Dept Med, Div Oncol, Palo Alto, CA 94304 USA. [Lossos, Izidore S.] Univ Miami, Miller Sch Med, Dept Med, Div Hematol Oncol, Miami, FL 33136 USA. [Nowakowski, Grzegorz S.] Mayo Clin, Div Hematol, Rochester, MN USA. [Press, Oliver W.] Fred Hutchinson Canc Res Ctr, Dept Med, Div Hematol, Seattle, WA 98104 USA. [Press, Oliver W.] Fred Hutchinson Canc Res Ctr, Dept Med, Div Oncol, Seattle, WA 98104 USA. [Press, Oliver W.] Univ Washington, Seattle, WA 98195 USA. [Staudt, Louis M.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Weinstock, DM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Dana 510B, Boston, MA 02215 USA. EM dweinstock@partners.org NR 8 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAR 26 PY 2015 VL 125 IS 13 BP 2175 EP 2177 DI 10.1182/blood-2015-01-623777 PG 5 WC Hematology SC Hematology GA CI3CX UT WOS:000354626300027 PM 25814490 ER PT J AU Traeger, LL Volkening, JD Moffett, H Gallant, JR Chen, PH Novina, CD Phillips, GN Anand, R Wells, GB Pinch, M Guth, R Unguez, GA Albert, JS Zakon, H Sussman, MR Samanta, MP AF Traeger, Lindsay L. Volkening, Jeremy D. Moffett, Howell Gallant, Jason R. Chen, Po-Hao Novina, Carl D. Phillips, George N., Jr. Anand, Rene Wells, Gregg B. Pinch, Matthew Gueth, Robert Unguez, Graciela A. Albert, James S. Zakon, Harold Sussman, Michael R. Samanta, Manoj P. TI Unique patterns of transcript and miRNA expression in the South American strong voltage electric eel (Electrophorus electricus) SO BMC GENOMICS LA English DT Article DE Electric eel; Genome; Transcriptome; miRNA; Gene ontology ID SKELETAL-MUSCLE; DIFFERENTIAL EXPRESSION; COLOR-VISION; MICRORNAS; EVOLUTION; ORGAN; GENES; CONTRIBUTES; COMPLEXITY; ZEBRAFISH AB Background: With its unique ability to produce high-voltage electric discharges in excess of 600 volts, the South American strong voltage electric eel (Electrophorus electricus) has played an important role in the history of science. Remarkably little is understood about the molecular nature of its electric organs. Results: We present an in-depth analysis of the genome of E. electricus, including the transcriptomes of eight mature tissues: brain, spinal cord, kidney, heart, skeletal muscle, Sachs' electric organ, main electric organ, and Hunter's electric organ. A gene set enrichment analysis based on gene ontology reveals enriched functions in all three electric organs related to transmembrane transport, androgen binding, and signaling. This study also represents the first analysis of miRNA in electric fish. It identified a number of miRNAs displaying electric organ-specific expression patterns, including one novel miRNA highly over-expressed in all three electric organs of E. electricus. All three electric organ tissues also express three conserved miRNAs that have been reported to inhibit muscle development in mammals, suggesting that miRNA-dependent regulation of gene expression might play an important role in specifying an electric organ identity from its muscle precursor. These miRNA data were supported using another complete miRNA profile from muscle and electric organ tissues of a second gymnotiform species. Conclusions: Our work on the E. electricus genome and eight tissue-specific gene expression profiles will greatly facilitate future research on determining the coding and regulatory sequences that specify the function, development, and evolution of electric organs. Moreover, these data and future studies will be informed by the first comprehensive analysis of miRNA expression in an electric fish presented here. C1 [Traeger, Lindsay L.] Univ Wisconsin, Dept Genet, Madison, WI 53706 USA. [Traeger, Lindsay L.; Volkening, Jeremy D.; Sussman, Michael R.] Univ Wisconsin, Ctr Biotechnol, Madison, WI 53706 USA. [Volkening, Jeremy D.; Sussman, Michael R.] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA. [Moffett, Howell; Chen, Po-Hao; Novina, Carl D.] Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. [Moffett, Howell; Chen, Po-Hao; Novina, Carl D.] Dana Farber Canc Inst, AIDS, Boston, MA 02115 USA. [Moffett, Howell; Chen, Po-Hao; Novina, Carl D.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA. [Gallant, Jason R.] Michigan State Univ, Dept Zool, E Lansing, MI USA. [Gallant, Jason R.; Zakon, Harold] BEACON Ctr Study Evolut Act, Lansing, MI USA. [Chen, Po-Hao; Novina, Carl D.] Broad Inst Harvard, Cambridge, MA 02141 USA. [Chen, Po-Hao; Novina, Carl D.] MIT, Cambridge, MA 02141 USA. [Phillips, George N., Jr.] Rice Univ, Biosci Rice, Houston, TX 77005 USA. [Phillips, George N., Jr.] Rice Univ, Dept Chem, Houston, TX 77005 USA. [Anand, Rene] Ohio State Univ, Wexner Med Ctr, Dept Pharmacol, Columbus, OH 43210 USA. [Anand, Rene] Ohio State Univ, Wexner Med Ctr, Dept Neurosci, Columbus, OH 43210 USA. [Wells, Gregg B.] Texas A&M Univ, Dept Mol & Cellular Med, College Stn, TX 77843 USA. [Pinch, Matthew; Gueth, Robert; Unguez, Graciela A.] New Mexico State Univ, Dept Biol, Las Cruces, NM 88003 USA. [Albert, James S.] Dept Biol, Lafayette, LA 70503 USA. [Zakon, Harold] Univ Texas Austin, Austin, TX 78712 USA. [Zakon, Harold] Marine Biol Lab, Josephine Bay Paul Ctr Comparat Mol Biol & Evolut, Woods Hole, MA 02543 USA. [Samanta, Manoj P.] Systemix Inst, Redmond, WA 98053 USA. RP Zakon, H (reprint author), Marine Biol Lab, Josephine Bay Paul Ctr Comparat Mol Biol & Evolut, Woods Hole, MA 02543 USA. EM h.zakon@austin.utexas.edu; msussman@wisc.edu; manoj.samanta@systemix.org RI Gallant, Jason/A-9629-2015; OI Gallant, Jason/0000-0002-6528-090X; Volkening, Jeremy/0000-0002-8892-7155 FU NSF [1144012, 0741450, 1248109]; W.M. Keck Foundation Distinguished Young Scholars in Medical Research; NIH [R01 GM084879, R01 GM088670, 1SC1GM092297-01A1]; Morgridge Graduate Fellowship; University of Wisconsin Genetics NIH Graduate Training Grant; Cornell University Center for Vertebrate Genomics FX This project has been funded in part by NSF Grant MCB No. 1144012 (MRS), NSF Grant DEB No. 0741450 (JSA), NSF Grant CNS No. 1248109 (GAU), W.M. Keck Foundation Distinguished Young Scholars in Medical Research (CDN), NIH R01 GM084879 (HZ), NIH grant R01 GM088670 (RA), NIH grant 1SC1GM092297-01A1 (GAU), the Morgridge Graduate Fellowship (JDV and LLT), University of Wisconsin Genetics NIH Graduate Training Grant (LLT); and the Cornell University Center for Vertebrate Genomics (JRG). Susan B. McKay assisted with data analysis. MPS acknowledges useful discussions with Rayan Chukhi, Ruibang Luo and Jared Simpson. LLT and MRS thank the DNA Sequencing Facility at UW Madison for their assistance. The help of Jeffrey Bayliss in dissection of E. electricus and Richard Amasino in preparing this manuscript are gratefully acknowledged. NR 57 TC 5 Z9 5 U1 5 U2 29 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD MAR 26 PY 2015 VL 16 AR 243 DI 10.1186/s12864-015-1288-8 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA CF5QO UT WOS:000352612200001 PM 25887781 ER PT J AU Chen, Z Zierath, J Kahn, CR Spiegelman, B O'Rahilly, S Bruning, JC AF Chen, Zhu Zierath, Juleen Kahn, C. Ronald Spiegelman, Bruce O'Rahilly, Stephen Bruning, Jens C. TI How to Stop the Obesity Epidemic? SO CELL LA English DT News Item C1 [Chen, Zhu] Shanghai Jiao Tong Univ, Shanghai 200030, Peoples R China. [Zierath, Juleen] Karolinska Inst, S-10401 Stockholm, Sweden. [Kahn, C. Ronald] Joslin Diabet Ctr, Boston, MA USA. [Spiegelman, Bruce] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [O'Rahilly, Stephen] Univ Cambridge, Cambridge CB2 1TN, England. RP Chen, Z (reprint author), Shanghai Jiao Tong Univ, Shanghai 200030, Peoples R China. NR 0 TC 1 Z9 1 U1 5 U2 20 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD MAR 26 PY 2015 VL 161 IS 1 BP 173 EP 174 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CE6MW UT WOS:000351952200017 ER PT J AU Mannan, AA Elmardi, KA Idris, YA Spector, JM Ali, NA Malik, EM AF Mannan, Abeer A. Elmardi, Khalid A. Idris, Yassir A. Spector, Jonathan M. Ali, Nahid A. Malik, Elfatih M. TI Do frontline health care providers know enough about artemisinin-based combination therapy to rationally treat malaria? A cross-sectional survey in Gezira State, Sudan SO MALARIA JOURNAL LA English DT Article ID INTERVENTIONS; QUALITY; WORKERS; PERFORMANCE; GUIDELINES; KNOWLEDGE; TANZANIA; ACTS AB Background: In 2004, artemisinin-based combination therapy (ACT) was introduced in Sudan for the treatment of malaria. The role of health care providers working in first-level health care facilities is central for the effective implementation of this revised malaria treatment policy. However, information about their level of ACT knowledge is inadequate. This study sought to describe frontline health care providers' knowledge about the formulations and dose regimens of nationally recommended ACT in Sudan. Methods: This cross-sectional study took place in Gezira State, Sudan. Data were gathered from five localities comprising forty primary health care facilities. A total of 119 health care providers participated in the study (72 prescribers and 47 dispensers). The primary outcome was the proportion of health care providers who were ACT knowledgeable, a composite indicator of health care providers' ability to (1) define what combination therapy is; (2) identify the recommended first-and second-line treatments; and (3) correctly state the dose regimens for each. Results: All prescribers and 95.7% (46/47) of dispensers were aware of the new national malaria treatment policy. However, 93.1% (67/72) of prescribers compared to 87.2% (41/47) of dispensers recognized artesunate-sulphadoxine/pyrimethamine as the recommended first-line treatment in Sudan. Only a small number of prescribers and dispensers (9.4% and 13.6%, respectively) were able to correctly define the meaning of a combination therapy. Overall, only 22% (26/119, 95% CI 14.6-29.4) of health care providers were found to be ACT knowledgeable with no statistically significant difference between prescribers and dispensers. Conclusion: Overall, ACT knowledge among frontline health care providers is very poor. This finding suggests that efforts are needed to improve knowledge of prescribers and dispensers working in first-level health care facilities, perhaps through implementing focused, provider-oriented training programmes. Additionally, a system for regularly monitoring and evaluating the quality of in-service training may be beneficial to ensure its responsiveness to the needs of the target health care providers. C1 [Mannan, Abeer A.] Al Neelain Univ, Khartoum 11123, Sudan. [Elmardi, Khalid A.; Ali, Nahid A.] Fed Minist Hlth, Khartoum, Sudan. [Idris, Yassir A.; Malik, Elfatih M.] Gezira State Minist Hlth, Gezira, Sudan. [Spector, Jonathan M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mannan, AA (reprint author), Al Neelain Univ, Steen St,POB 7294, Khartoum 11123, Sudan. EM abeeratta@gmail.com FU National Fund for Promoting Medical Services; National Malaria Control programme; Al Neelain University in Sudan FX We wish to acknowledge the financial support received from the National Fund for Promoting Medical Services, the National Malaria Control programme, and Al Neelain University in Sudan. We are thankful to Dr. Sakhr Omer, the Coordinator of malaria programme in Gezira state for facilitating field work, and to the field teams who participated in data collection. We are also indebted to all health care providers who participated in this study. NR 30 TC 0 Z9 0 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD MAR 26 PY 2015 VL 14 AR 131 DI 10.1186/s12936-015-0652-0 PG 7 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA CE4SC UT WOS:000351819400001 PM 25889428 ER PT J AU Traverso, G Langer, R AF Traverso, Giovanni Langer, Robert TI PERSPECTIVE Special delivery for the gut SO NATURE LA English DT Editorial Material C1 [Traverso, Giovanni] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Traverso, Giovanni] Harvard Univ, Sch Med, Boston, MA USA. [Langer, Robert] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. RP Traverso, G (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ctraverso@partners.org; rlanger@mit.edu NR 7 TC 11 Z9 11 U1 7 U2 37 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD MAR 26 PY 2015 VL 519 IS 7544 BP S19 EP S19 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE1WF UT WOS:000351602800007 PM 25806494 ER PT J AU Wells, JA Glassman, AR Ayala, AR Jampol, LM Aiello, LP Antoszyk, AN Arnold-Bush, B Baker, CW Bressler, NM Browning, DJ Elman, MJ Ferris, FL Friedman, SM Melia, M Pieramici, DJ Sun, JK Beck, RW AF Wells, John A. Glassman, Adam R. Ayala, Allison R. Jampol, Lee M. Aiello, Lloyd Paul Antoszyk, Andrew N. Arnold-Bush, Bambi Baker, Carl W. Bressler, Neil M. Browning, David J. Elman, Michael J. Ferris, Frederick L. Friedman, Scott M. Melia, Michele Pieramici, Dante J. Sun, Jennifer K. Beck, Roy W. CA Diabet Retinopathy Clinical TI Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; RETINA STUDY-GROUP; INTRAVITREAL BEVACIZUMAB; LASER; RETINOPATHY; TRIAL; PREVALENCE; RISK AB BACKGROUND The relative efficacy and safety of intravitreous aflibercept, bevacizumab, and ranibizumab in the treatment of diabetic macular edema are unknown. METHODS At 89 clinical sites, we randomly assigned 660 adults (mean age, 61 +/- 10 years) with diabetic macular edema involving the macular center to receive intravitreous aflibercept at a dose of 2.0 mg (224 participants), bevacizumab at a dose of 1.25 mg (218 participants), or ranibizumab at a dose of 0.3 mg (218 participants). The study drugs were administered as often as every 4 weeks, according to a protocol-specified algorithm. The primary outcome was the mean change in visual acuity at 1 year. RESULTS From baseline to 1 year, the mean visual-acuity letter score (range, 0 to 100, with higher scores indicating better visual acuity; a score of 85 is approximately 20/20) improved by 13.3 with aflibercept, by 9.7 with bevacizumab, and by 11.2 with ranibizumab. Although the improvement was greater with aflibercept than with the other two drugs (P<0.001 for aflibercept vs. bevacizumab and P = 0.03 for aflibercept vs. ranibizumab), it was not clinically meaningful, because the difference was driven by the eyes with worse visual acuity at baseline (P<0.001 for interaction). When the initial visual-acuity letter score was 78 to 69 (equivalent to approximately 20/32 to 20/40) (51% of participants), the mean improvement was 8.0 with aflibercept, 7.5 with bevacizumab, and 8.3 with ranibizumab (P>0.50 for each pairwise comparison). When the initial letter score was less than 69 (approximately 20/50 or worse), the mean improvement was 18.9 with aflibercept, 11.8 with bevacizumab, and 14.2 with ranibizumab (P<0.001 for aflibercept vs. bevacizumab, P = 0.003 for aflibercept vs. ranibizumab, and P = 0.21 for ranibizumab vs. bevacizumab). There were no significant differences among the study groups in the rates of serious adverse events (P = 0.40), hospitalization (P = 0.51), death (P = 0.72), or major cardiovascular events (P = 0.56). CONCLUSIONS Intravitreous aflibercept, bevacizumab, or ranibizumab improved vision in eyes with center-involved diabetic macular edema, but the relative effect depended on baseline visual acuity. When the initial visual-acuity loss was mild, there were no apparent differences, on average, among study groups. At worse levels of initial visual acuity, aflibercept was more effective at improving vision. C1 [Wells, John A.] Palmetto Retina Ctr, W Columbia, SC USA. [Glassman, Adam R.; Ayala, Allison R.; Arnold-Bush, Bambi; Melia, Michele; Beck, Roy W.] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA. [Jampol, Lee M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Aiello, Lloyd Paul; Sun, Jennifer K.] Harvard Univ, Sch Med, Beetham Eye Inst, Joslin Diabet Ctr, Boston, MA USA. [Antoszyk, Andrew N.; Browning, David J.] Charlotte Eye Ear Nose & Throat Associates, Charlotte, NC USA. [Baker, Carl W.] Paducah Retinal Ctr, Paducah, KY USA. [Bressler, Neil M.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. [Elman, Michael J.] Elman Retina Grp, Baltimore, MD USA. [Ferris, Frederick L.] NEI, NIH, Bethesda, MD 20892 USA. [Friedman, Scott M.] Florida Retina Consultants, Lakeland, FL USA. [Pieramici, Dante J.] Calif Retina Consultants, Santa Barbara, CA USA. RP Glassman, AR (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA. EM drcrstat2@jaeb.org FU National Institutes of Health FX Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01627249. NR 34 TC 180 Z9 182 U1 9 U2 25 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 26 PY 2015 VL 372 IS 13 BP 1193 EP 1203 DI 10.1056/NEJMoa1414264 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CE1QD UT WOS:000351585900005 ER PT J AU Hazen, EP Sherry, NA Parangi, S Rabito, CA Sadow, PM AF Hazen, Eric P. Sherry, Nicole A. Parangi, Sareh Rabito, Carlos A. Sadow, Peter M. TI Case 10-2015: A 15-Year-Old Girl with Graves' Disease and Psychotic Symptoms SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID THYROID-SURGERY; HYPERTHYROIDISM; CHILDREN; MANIFESTATIONS; THYROTOXICOSIS; COMPLAINTS C1 [Hazen, Eric P.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Sherry, Nicole A.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Parangi, Sareh] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Rabito, Carlos A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Sadow, Peter M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hazen, Eric P.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Sherry, Nicole A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Parangi, Sareh] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Rabito, Carlos A.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Sadow, Peter M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hazen, EP (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. FU Novo Nordisk FX Dr. Sherry reports receiving consulting fees from Novo Nordisk. No other potential conflict of interest relevant to this article was reported. NR 19 TC 2 Z9 2 U1 0 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 26 PY 2015 VL 372 IS 13 BP 1250 EP 1258 DI 10.1056/NEJMcpc1314239 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CE1QD UT WOS:000351585900012 PM 25806918 ER PT J AU El Saleeby, CM Kaplan, JL Nelson, BA AF El Saleeby, Chadi M. Kaplan, Jess L. Nelson, Benjamin A. TI Case 39-2014: A Girl with Crohn's Disease and Pulmonary Nodules REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID CHRONIC GRANULOMATOUS-DISEASE C1 [El Saleeby, Chadi M.; Kaplan, Jess L.; Nelson, Benjamin A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP El Saleeby, CM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM celsaleeby@mgh.harvard.edu NR 3 TC 1 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 26 PY 2015 VL 372 IS 13 BP 1273 EP 1273 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CE1QD UT WOS:000351585900029 PM 25806932 ER PT J AU Wagner, MJ Amodu, LI Duh, MS Korves, C Solleza, F Manson, SC Diaz, J Neary, MP Demetri, GD AF Wagner, Michael J. Amodu, Leo Ismaila Duh, Mei Sheng Korves, Caroline Solleza, Franco Manson, Stephanie C. Diaz, Jose Neary, Maureen P. Demetri, George D. TI A retrospective chart review of drug treatment patterns and clinical outcomes among patients with metastatic or recurrent soft tissue sarcoma refractory to one or more prior chemotherapy treatments SO BMC CANCER LA English DT Review DE Anthracycline; Chemotherapy; Doxorubicin; Gemcitabine; Metastatic; Soft tissue sarcoma ID RANDOMIZED PHASE-II; SURVIVAL; REGIMENS; TRIAL AB Background: Limited clinical data on real-world practice patterns are available for patients with metastatic/relapsed soft tissue sarcomas (STS). The primary objective of this study was to evaluate treatment patterns in patients with metastatic/relapsed STS following failure of prior chemotherapy by examining data collected from 2000 to 2011 from a major tertiary academic cancer center in the United States. Methods: Medical records, including community-based referral records, from a tertiary cancer center for adult patients with metastatic/relapsed STS with confirmed disease progression who commenced second-line treatment between January 1, 2000 and February 4, 2011, and with at least 3 months of follow-up data following second-line treatment initiation, were retrospectively reviewed. Overall survival, time to progression, and clinician-reported tumor response were collected. Results: A total of 99 patients (leiomyosarcoma, n = 48; synovial cell sarcoma, n = 7; liposarcoma, n = 5; or other histological subtypes, n = 39) received an average of four lines of treatment (maximum of 10). No consistent or dominant regimens were used in each treatment line beyond the second line. Median second-line treatment duration was 4.1 months (95% confidence interval, 3.0-5.0). Overall, 72 of 99 patients (73%) discontinued second-line treatment due to progressive disease. Median progression-free survival from initiation of second-line treatment varied across regimens from 2.0 to 6.6 months (overall median, 5.4 months). Conclusions: Wide variations in treatment were evident, with no single standard of care for patients with metastatic/relapsed STS. Most patients discontinued second-line treatment due to progressive disease, often receiving additional systemic therapy with other drugs. These data suggest a high unmet need for more efficacious treatment options and improved data collection to guide practice among patients with relapsed/refractory STS. C1 [Wagner, Michael J.; Amodu, Leo Ismaila; Demetri, George D.] Harvard Univ, Ludwig Ctr, Dana Farber Canc Inst, Boston, MA 02215 USA. [Duh, Mei Sheng; Korves, Caroline; Solleza, Franco] Anal Grp Inc, Boston, MA 02199 USA. [Manson, Stephanie C.; Diaz, Jose] GlaxoSmithKline, Value Evidence & Outcomes, Uxbridge UB11 1BT, Middx, England. [Neary, Maureen P.] GlaxoSmithKline, Value Evidence & Outcomes, Collegeville, PA 19426 USA. [Wagner, Michael J.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Amodu, Leo Ismaila] North Shore LIJ Hlth Syst, Manhasset, NY 10030 USA. [Neary, Maureen P.] Novartis Pharmaceut, E Hanover, NJ 07936 USA. [Manson, Stephanie C.; Diaz, Jose] Novartis Pharmaceut, Uxbridge UB11 1BT, Middx, England. RP Demetri, GD (reprint author), Harvard Univ, Ludwig Ctr, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM george_demetri@dfci.harvard.edu OI AMODU, LEO/0000-0002-5188-9466 FU GlaxoSmithKline, Philadelphia, Pennsylvania; Ludwig Center at Harvard; Dana-Farber Cancer Institute FX All listed authors meet the criteria for authorship set forth by the International Committee for Medical Journal Editors. The authors wish to acknowledge Nancy Price, PhD, of AOI Communications, L.P., for medical writing and editorial assistance. The authors are also grateful to Francis Vekeman, MS, and Rajeev Ayyagari, PhD, at Analysis Group, Inc. for their assistance in data quality assurance and analysis. This work was supported in part by GlaxoSmithKline, Philadelphia, Pennsylvania, through a research grant to Analysis Group, Inc. and the Dana-Farber Cancer Institute. The Ludwig Center at Harvard also provided partial support for this work. NR 20 TC 4 Z9 4 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD MAR 25 PY 2015 VL 15 AR 175 DI 10.1186/s12885-015-1182-4 PG 7 WC Oncology SC Oncology GA CF8UM UT WOS:000352837400001 PM 25885530 ER PT J AU McDonald-Hyman, C Turka, LA Blazar, BR AF McDonald-Hyman, Cameron Turka, Laurence A. Blazar, Bruce R. TI Advances and challenges in immunotherapy for solid organ and hematopoietic stem cell transplantation SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Review ID GRAFT-VERSUS-HOST; REGULATORY T-CELLS; BONE-MARROW-TRANSPLANTATION; HISTONE METHYLTRANSFERASE EZH2; JAK3 INHIBITOR CP-690,550; ANTI-HLA ANTIBODIES; LONG-TERM SURVIVAL; PHASE 1/2 TRIAL; IN-VIVO; RENAL-TRANSPLANTATION AB Although major advances have been made in solid organ and hematopoietic stem cell transplantation in the last 50 years, big challenges remain. This review outlines the current immunological limitations for hematopoietic stem cell and solid organ transplantation and discusses new immune-modulating therapies in preclinical development and in clinical trials that may allow these obstacles to be overcome. C1 [McDonald-Hyman, Cameron; Blazar, Bruce R.] Univ Minnesota, Dept Pediat, Div Blood & Marrow Transplantat, Minneapolis, MN 55455 USA. [Turka, Laurence A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Transplantat Sci,Dept Surg, Boston, MA 02115 USA. [Turka, Laurence A.] Massachusetts Gen Hosp, Immune Tolerance Network, Boston, MA 02114 USA. RP Blazar, BR (reprint author), Univ Minnesota, Dept Pediat, Div Blood & Marrow Transplantat, Minneapolis, MN 55455 USA. EM lturka@partners.org; blaza001@umn.edu FU National Institute of Allergy and Infectious Diseases of the NIH [UM1AI109565, R01 AI-037691, P01 AI056299, R01 HL56067, AI112613, AI34495, P01 CA142106, T32 AI007313, F30 HL121873] FX The authors are supported by the National Institute of Allergy and Infectious Diseases of the NIH under award numbers UM1AI109565 and R01 AI-037691 (L.A.T.); P01 AI056299 (L.A.T. and B.R.B.); R01 HL56067, AI112613, AI34495, and P01 CA142106 (B.R.B.); and T32 AI007313 and F30 HL121873 (C.M.-H.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 122 TC 26 Z9 26 U1 3 U2 13 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD MAR 25 PY 2015 VL 7 IS 280 AR 280rv2 DI 10.1126/scitranslmed.aaa6853 PG 14 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CE4AM UT WOS:000351772700005 PM 25810312 ER PT J AU Smucny, J Visani, A Tregells, JR AF Smucny, Jason Visani, Adrienne Tregells, Jason R. TI Could vagus nerve stimulation target hippocampal hyperactivity to improve cognition in schizophrenia? SO FRONTIERS IN PSYCHIATRY LA English DT Editorial Material DE vagus nerve stimulation; schizophrenia patients; hippocampus; cognition; acetylcholine ID NICOTINIC ACETYLCHOLINE-RECEPTORS; TREATMENT-RESISTANT DEPRESSION; PURSUIT EYE-MOVEMENT; BLOOD-FLOW; PARTIAL EPILEPSY; EPILEPTIFORM ACTIVITY; HEMODYNAMIC-RESPONSE; REFRACTORY EPILEPSY; PREFRONTAL CORTEX; STABLE MEDICATION C1 [Smucny, Jason; Tregells, Jason R.] Univ Colorado, Neurosci Program, Aurora, CO 80045 USA. [Smucny, Jason; Tregells, Jason R.] Denver Vet Affairs Med Ctr, Res Serv, Denver, CO USA. [Smucny, Jason; Visani, Adrienne; Tregells, Jason R.] Univ Colorado, Dept Psychiat, Aurora, CO USA. RP Smucny, J (reprint author), Univ Colorado, Neurosci Program, Anschutz Med Campus, Aurora, CO 80045 USA. EM jason.smucny@ucdenver.edu OI Smucny, Jason/0000-0001-5656-7987 FU CSRD VA [I01 CX000459]; NIDDK NIH HHS [R01 DK089095, R21 DK102052]; NIMH NIH HHS [R01 MH102224, F31 MH102879] NR 85 TC 3 Z9 3 U1 5 U2 8 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-0640 J9 FRONT PSYCHIATRY JI Front. Psychiatry PD MAR 24 PY 2015 VL 6 AR 43 DI 10.3389/fpsyt.2015.00043 PG 5 WC Psychiatry SC Psychiatry GA CV4CF UT WOS:000364212300001 PM 25852579 ER PT J AU Koudriavtseva, T Renna, R Plantone, D Mainero, C AF Koudriavtseva, Tatiana Renna, Rosaria Plantone, Domenico Mainero, Caterina TI Demyelinating and thrombotic disease of the central nervous system: common pathogenic and triggering factors SO FRONTIERS IN NEUROLOGY LA English DT Editorial Material DE multiple sclerosis; acute disseminated encephalomyelitis; neuromyelitis optica; antiphospholipid syndrome; cerebral venous thrombosis; thrombosis ID ACUTE DISSEMINATED ENCEPHALOMYELITIS; CEREBRAL VENOUS THROMBOSIS; MULTIPLE-SCLEROSIS PATIENTS; ANTIPHOSPHOLIPID ANTIBODIES; NEUROMYELITIS-OPTICA; UPDATE; AUTOIMMUNITY; COAGULATION; INFECTION; DIAGNOSIS C1 [Koudriavtseva, Tatiana; Renna, Rosaria; Plantone, Domenico] IFO, Regina Elena Natl Canc Inst, Multiple Sclerosis Ctr, Neurol Unit, Rome, Italy. [Mainero, Caterina] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Mainero, Caterina] Harvard Univ, Sch Med, Boston, MA USA. RP Koudriavtseva, T (reprint author), IFO, Regina Elena Natl Canc Inst, Multiple Sclerosis Ctr, Neurol Unit, Rome, Italy. EM koudriavtseva@ifo.it NR 48 TC 7 Z9 7 U1 0 U2 1 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-2295 J9 FRONT NEUROL JI Front. Neurol. PD MAR 24 PY 2015 VL 6 AR UNSP 63 DI 10.3389/fneur.2015.00063 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CU8EQ UT WOS:000363774500001 PM 25852641 ER PT J AU Pooler, AM Polydoro, M Maury, EA Nicholls, SB Reddy, SM Wegmann, S William, C Saqran, L Cagsal-Getkin, O Pitstick, R Beier, DR Carlson, GA Spires-Jones, TL Hyman, BT AF Pooler, Amy M. Polydoro, Manuela Maury, Eduardo A. Nicholls, Samantha B. Reddy, Snigdha M. Wegmann, Susanne William, Christopher Saqran, Lubna Cagsal-Getkin, Ozge Pitstick, Rose Beier, David R. Carlson, George A. Spires-Jones, Tara L. Hyman, Bradley T. TI Amyloid accelerates tau propagation and toxicity in a model of early Alzheimer's disease SO ACTA NEUROPATHOLOGICA COMMUNICATIONS LA English DT Article DE Neurofibrillary tangles; Amyloid plaques; Alzheimer's disease; Tauopathy; Aggregation ID TRANSGENIC MICE; NEUROFIBRILLARY TANGLES; NEURONAL-ACTIVITY; BETA-DEPOSITION; RTGTAUEC MODEL; PATHOLOGY; BRAIN; AD AB Introduction: In early stages of Alzheimer's disease (AD), neurofibrillary tangles (NFT) are largely restricted to the entorhinal cortex and medial temporal lobe. At later stages, when clinical symptoms generally occur, NFT involve widespread limbic and association cortices. At this point in the disease, amyloid plaques are also abundantly distributed in the cortex. This observation from human neuropathological studies led us to pose two alternative hypotheses: that amyloid in the cortex is permissive for the spread of tangles from the medial temporal lobe, or that these are co-occurring but not causally related events simply reflecting progression of AD pathology. Results: We now directly test the hypothesis that cortical amyloid acts as an accelerant for spreading of tangles beyond the medial temporal lobe. We crossed rTgTauEC transgenic mice that demonstrate spread of tau from entorhinal cortex to other brain structures at advanced age with APP/PS1 mice, and examined mice with either NFTs, amyloid pathology, or both. We show that concurrent amyloid deposition in the cortex 1) leads to a dramatic increase in the speed of tau propagation and an extraordinary increase in the spread of tau to distal brain regions, and 2) significantly increases tau-induced neuronal loss. Conclusions: These data strongly support the hypothesis that cortical amyloid accelerates the spread of tangles throughout the cortex and amplifies tangle-associated neural system failure in AD. C1 [Pooler, Amy M.; Polydoro, Manuela; Maury, Eduardo A.; Nicholls, Samantha B.; Reddy, Snigdha M.; Wegmann, Susanne; William, Christopher; Saqran, Lubna; Cagsal-Getkin, Ozge; Spires-Jones, Tara L.; Hyman, Bradley T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Pooler, Amy M.] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Basic & Clin Neurosci, London SE5 8AF, England. [Pitstick, Rose; Carlson, George A.] McLaughlin Res Inst, Great Falls, MT 59405 USA. [Beier, David R.] Seattle Childrens Res Inst, Ctr Dev Biol & Regenerat Med, Seattle, WA USA. [Spires-Jones, Tara L.] Univ Edinburgh, Ctr Cognit & Neural Syst, Edinburgh EH8 9JZ, Midlothian, Scotland. RP Hyman, BT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, 114 16th St, Charlestown, MA 02129 USA. EM bhyman@mgh.harvard.edu FU Alzheimer's Society [195]; NIA NIH HHS [5T32AG00022222, P50 AG005134, R00 AG033670, R00AG033670, R01 AG026249, R01AG026249-07, R21AG03885, T32 AG000222] NR 29 TC 19 Z9 19 U1 3 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 2051-5960 J9 ACTA NEUROPATHOL COM JI Acta Neuropathol. Commun. PD MAR 24 PY 2015 VL 3 AR 14 DI 10.1186/s40478-015-0199-x PG 11 WC Neurosciences SC Neurosciences & Neurology GA CP9UZ UT WOS:000360241800002 PM 25853174 ER PT J AU Daniel, CL Armstrong, GT Keske, RR Davine, JA McDonald, AJ Sprunck-Harrild, KM Coleman, C Haneuse, SJ Mertens, AC Emmons, KM Marghoob, AA Elkin, EB Dusza, SW Robison, LL Geller, AC AF Daniel, Casey L. Armstrong, Gregory T. Keske, Robyn R. Davine, Jessica A. McDonald, Aaron J. Sprunck-Harrild, Kim M. Coleman, Catherine Haneuse, Sebastien J. Mertens, Ann C. Emmons, Karen M. Marghoob, Ashfaq A. Elkin, Elena B. Dusza, Stephen W. Robison, Leslie L. Geller, Alan C. TI Advancing Survivors' Knowledge (ASK) about skin cancer study: study protocol for a randomized controlled trial SO TRIALS LA English DT Article DE Skin cancer; Early detection; Melanoma; Childhood cancer; Survivor; Dermoscopy; Skin self-examination; Health communication ID PATIENT ACTIVATION MEASURE; BASAL-CELL CARCINOMA; CHILDHOOD-CANCER; ADULT SURVIVORS; TRANSPLANT RECIPIENTS; SELF-EXAMINATION; RADIATION-EXPOSURE; ADOLESCENT CANCER; HEALTH OUTCOMES; CHRONIC DISEASE AB Background: Advances in treatment have increased childhood cancer 5-year survival rates to greater than 80%. However, children previously treated with radiation are at significantly increased risk of developing subsequent neoplasms, the most common of which are skin cancers. The National Cancer Institute and Children's Oncology Group have issued recommendations for survivors treated with radiation to perform monthly skin self-examinations and receive a physician skin examination at least annually, as early detection has demonstrated markedly improved outcomes in the diagnosis and treatment of skin cancers. The goal of the present study is to increase rates of skin self-examinations and clinical skin examinations among adult survivors of childhood cancer treated with radiation. Methods/Design: This randomized controlled trial uses a 3-group comparative effectiveness design comparing: (1) Patient Activation and Education (PAE) including text messaging, print and web-based tutorials over 12 months; (2) PAE plus physician activation (PAE + MD) adding physician activation/educational materials about survivors' increased skin cancer risk and conducting full-body skin exams; and (3) PAE plus physician activation, plus teledermoscopy (PAE + MD + TD) adding participant receipt of a dermatoscope intended to empower them to photograph suspect moles or lesions for review by the study dermatologist. Discussion: The current study addresses barriers to screening in this population by providing educational and motivational information for both survivors and physicians regarding the value of periodic skin examinations. It also utilizes innovative mobile health technology to encourage and motivate (that is activate) survivors to conduct skin self-examinations, request physician exams, and obtain treatment when worrisome lesions are found. Finally, as a comparative effectiveness trial, this study isolates the effects of adding specific components to the patient activation intervention to test the most effective intervention for enhancing skin examination vigilance among this high-risk group. C1 [Daniel, Casey L.; Keske, Robyn R.; Davine, Jessica A.; Geller, Alan C.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Armstrong, Gregory T.; McDonald, Aaron J.; Robison, Leslie L.] St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. [Sprunck-Harrild, Kim M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Coleman, Catherine] Dana Farber Canc Inst, Dept Populat Sci, Boston, MA 02215 USA. [Haneuse, Sebastien J.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Mertens, Ann C.] Emory Univ, Emory Childrens Ctr, Dept Pediat, Atlanta, GA 30322 USA. [Emmons, Karen M.] Kaiser Permanente, Oakland, CA 94612 USA. [Marghoob, Ashfaq A.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Elkin, Elena B.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA. [Elkin, Elena B.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA. [Dusza, Stephen W.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10022 USA. RP Geller, AC (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, 677 Huntington Ave,Kresge 718, Boston, MA 02115 USA. EM ageller@hsph.harvard.edu FU NCI grant [R01 CA175231, R25 CA057711]; National Cancer Institute [CA55727]; Cancer Center Support (CORE) grant [CA21765]; American Lebanese-Syrian Associated Charities (ALSAC); NCI Cancer Center Support Grant [NIH 5 P30 CA06516] FX This study is funded by NCI grant R01 CA175231 (A Geller, Principal Investigator, Reducing Skin Cancer Risk among Childhood Cancer Survivors, 2013 to 2018). This work was supported by the National Cancer Institute (CA55727, GT Armstrong, Principal Investigator). Support to St. Jude Children's Research Hospital also provided by the Cancer Center Support (CORE) grant (CA21765, R Gilbertson, Principal Investigator) and the American Lebanese-Syrian Associated Charities (ALSAC). The first author is supported by NCI grant R25 CA057711 (G Sorensen, Principal Investigator). We thank Dana-Farber/Harvard Cancer Center in Boston, MA for the services of the Health Communication Core (www.healthcommcore.org), which provided assistance with planning, writing, designing, and developing the print and online components of the study materials. Dana-Farber/Harvard Cancer Center is supported in part by an NCI Cancer Center Support Grant #NIH 5 P30 CA06516. NR 62 TC 1 Z9 1 U1 3 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6215 J9 TRIALS JI Trials PD MAR 24 PY 2015 VL 16 AR 109 DI 10.1186/s13063-015-0637-x PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CF6TN UT WOS:000352689300001 PM 25873142 ER PT J AU Scheffer, DI Zhang, DS Shen, J Indzhykulian, A Karavitaki, KD Xu, YJ Wang, QC Lin, JJC Chen, ZY Corey, DP AF Scheffer, Deborah I. Zhang, Duan-Sun Shen, Jun Indzhykulian, Artur Karavitaki, K. Domenica Xu, Yichao Joy Wang, Qinchuan Lin, Jim Jung-Ching Chen, Zheng-Yi Corey, David P. TI XIRP2, an Actin-Binding Protein Essential for Inner Ear Hair-Cell Stereocilia SO CELL REPORTS LA English DT Article ID CUTICULAR PLATE; CROSS-LINKER; HEARING-LOSS; XIN-REPEATS; FILAMENTS; COCHLEA; GENE; CARDIOMYOPATHY; LOCALIZATION; CHANNELS AB Hair cells of the inner ear are mechanoreceptors for hearing and balance, and proteins highly enriched in hair cells may have specific roles in the development and maintenance of the mechanotransduction apparatus. We identified XIRP2/mXin beta as an enriched protein likely to be essential for hair cells. We found that different isoforms of this protein are expressed and differentially located: short splice forms (also called XEPLIN) are targeted more to stereocilia, whereas two long isoforms containing a XIN-repeat domain are in both stereocilia and cuticular plates. Mice lacking the Xirp2 gene developed normal stereocilia bundles, but these degenerated with time: stereocilia were lost and long membranous protrusions emanated from the nearby apical surfaces. At an ultrastructural level, the paracrystalline actin filaments became disorganized. XIRP2 is apparently involved in the maintenance of actin structures in stereocilia and cuticular plates of hair cells, and perhaps in other organs where it is expressed. C1 [Scheffer, Deborah I.; Zhang, Duan-Sun; Shen, Jun; Indzhykulian, Artur; Karavitaki, K. Domenica; Corey, David P.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Scheffer, Deborah I.; Zhang, Duan-Sun; Shen, Jun; Indzhykulian, Artur; Karavitaki, K. Domenica; Corey, David P.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Scheffer, Deborah I.; Chen, Zheng-Yi] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. [Scheffer, Deborah I.; Chen, Zheng-Yi] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Shen, Jun] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Shen, Jun] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Xu, Yichao Joy] Harvard Univ, Sch Med, Image & Data Anal Core, Boston, MA 02115 USA. [Wang, Qinchuan; Lin, Jim Jung-Ching] Univ Iowa, Dept Biol, Iowa City, IA 52242 USA. RP Corey, DP (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. EM dcorey@hms.harvard.edu RI Wang, Qinchuan/G-4536-2011; OI Scheffer, Deborah/0000-0002-6066-5907; Wang, Qinchuan/0000-0002-2359-3262; Indzhykulian, Artur/0000-0002-2076-6818; Corey, David/0000-0003-4497-6016 FU NINDS P30 Core Center [NS072030]; NIH [R01-DC000304, R01-DC002281, R01-DC006908, P30-DC05209, RO1-HL107383]; Frederick and Ines Yeatts Hair Cell Regeneration grant FX We appreciate help with FM1-43 loading from Paul Niksch at Harvard Medical School, help with initial auditory brainstem response tests on another XIRP2 mutant from Sharon Kujawa at Massachusetts Eye and Ear, advice on image analysis from Hunter Elliott and Tiao Xie at the Harvard Medical School Image and Data Analysis Core, and electron microscopy support from Louise Trakimas at Harvard Medical School and William Fowle at Northeastern University. We appreciate a PMCA2 antibody from Peter Barr-Gillespie at Oregon Health & Science University and a XIRP2 antibody from Francisco Naya at Boston University. We thank Andy Sharpe and Chris Bennet at the University of Leeds (UK) for providing us with the DFNB27 family DNAs. We thank the Harvard Neurobiology Imaging Facility (a part of the Neural Imaging Center supported by NINDS P30 Core Center grant NS072030) for consultation and instrumentation. This research was supported by NIH grants R01-DC000304 and R01-DC002281 (to D.P.C.), R01-DC006908 (to Z.-Y.C.), P30-DC05209 to the Massachusetts Eye and Ear, RO1-HL107383 (to J.J.-C.L.), and a Frederick and Ines Yeatts Hair Cell Regeneration grant (to Z.-Y.C.). D.P.C. is an investigator and K.D.K. and D.-S.Z. were associates of the Howard Hughes Medical Institute. We thank Dr. Lisa Goodrich for helpful comments on the manuscript. NR 31 TC 12 Z9 12 U1 2 U2 3 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 24 PY 2015 VL 10 IS 11 BP 1811 EP 1818 DI 10.1016/j.celrep.2015.02.042 PG 8 WC Cell Biology SC Cell Biology GA CE4CY UT WOS:000351779600003 PM 25772365 ER PT J AU Cavender, MA Scirica, BM Bonaca, MP Angiolillo, DJ Dalby, AJ Dellborg, M Morais, J Murphy, SA Ophuis, TO Tendera, M Braunwald, E Morrow, DA AF Cavender, Matthew A. Scirica, Benjamin M. Bonaca, Marc P. Angiolillo, Dominick J. Dalby, Anthony J. Dellborg, Mikael Morais, Joao Murphy, Sabina A. Ophuis, Ton Oude Tendera, Michal Braunwald, Eugene Morrow, David A. TI Vorapaxar in Patients With Diabetes Mellitus and Previous Myocardial Infarction Findings From the Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-TIMI 50 Trial SO CIRCULATION LA English DT Article DE coronary disease; diabetes mellitus; myocardial infarction; secondary prevention ID ACUTE CORONARY SYNDROMES; ANTIPLATELET THERAPY; PLATELET INHIBITION; MORTALITY; DISEASE; CLOPIDOGREL; RISK; INTERVENTION; DETERMINANTS; OUTCOMES AB Background-Vorapaxar reduces cardiovascular death, myocardial infarction (MI), or stroke in patients with previous MI while increasing bleeding. Patients with diabetes mellitus (DM) are at high risk of recurrent thrombotic events despite standard therapy and may derive particular benefit from antithrombotic therapies. The Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-TIMI 50 trial was a randomized, double-blind, placebo-controlled trial of vorapaxar in patients with stable atherosclerosis. Methods and Results-We examined the efficacy of vorapaxar in patients with and without DM who qualified for the trial with a previous MI. Because vorapaxar is contraindicated in patients with a history of stroke or transient ischemic attack, the analysis (n=16 896) excluded such patients. The primary end point of cardiovascular death, MI, or stroke occurred more frequently in patients with DM than in patients without DM (rates in placebo group: 14.3% versus 7.6%; adjusted hazard ratio, 1.47; P<0.001). In patients with DM (n=3623), vorapaxar significantly reduced the primary end point (11.4% versus 14.3%; hazard ratio, 0.73 [95% confidence interval, 0.60-0.89]; P=0.002) with a number needed to treat to avoid 1 major cardiovascular event of 29. The incidence of moderate/severe bleeding was increased with vorapaxar in patients with DM (4.4% versus 2.6%; hazard ratio, 1.60 [95% confidence interval, 1.07-2.40]). However, net clinical outcome integrating these 2 end points (efficacy and safety) was improved with vorapaxar (hazard ratio, 0.79 [95% confidence interval, 0.67-0.93]). Conclusions-In patients with previous MI and DM, the addition of vorapaxar to standard therapy significantly reduced the risk of major vascular events with greater potential for absolute benefit in this group at high risk of recurrent ischemic events. C1 [Cavender, Matthew A.; Scirica, Benjamin M.; Bonaca, Marc P.; Murphy, Sabina A.; Braunwald, Eugene; Morrow, David A.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Cavender, Matthew A.; Scirica, Benjamin M.; Bonaca, Marc P.; Murphy, Sabina A.; Braunwald, Eugene; Morrow, David A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Angiolillo, Dominick J.] Univ Florida, Coll Med, Jacksonville, FL USA. [Dalby, Anthony J.] Milpk Hosp, Johannesburg, South Africa. [Dellborg, Mikael] Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden. [Dellborg, Mikael] Sahlgrens Univ Hosp, Gothenburg, Sweden. [Morais, Joao] Santo Andres Hosp, Leiria, Portugal. [Ophuis, Ton Oude] Canisius Wilhelmina Ziekenhuis, Dept Cardiol, Nijmegen, Netherlands. [Tendera, Michal] Med Univ Silesia, Div Cardiol 3, Katowice, Poland. RP Morrow, DA (reprint author), Brigham & Womens Hosp, 350 Longwood Ave,First Floor Off, Boston, MA 02115 USA. EM dmorrow@partners.org FU Merck and Co. FX The TRA2 degrees P-TIMI 50 Trial was sponsored by Merck and Co. NR 20 TC 23 Z9 23 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD MAR 24 PY 2015 VL 131 IS 12 BP 1047 EP + DI 10.1161/CIRCULATIONAHA.114.013774 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CE2TA UT WOS:000351669900009 PM 25681464 ER PT J AU Joynt, KE AF Joynt, Karen E. TI Health Policy and Cardiovascular Medicine Rapid Changes, Immense Opportunities SO CIRCULATION LA English DT Article DE health care reform; health policy; quality of health care ID PERCUTANEOUS CORONARY INTERVENTION; QUALITY-OF-CARE; ACUTE MYOCARDIAL-INFARCTION; IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; BYPASS GRAFT-SURGERY; INSURANCE DESIGN; ACCOUNTABLE CARE; RANDOMIZED-TRIAL; US HOSPITALS; UNINTENDED CONSEQUENCES C1 [Joynt, Karen E.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Joynt, Karen E.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Joynt, Karen E.] VA Boston Healthcare Syst, Dept Med, Cardiol & Vasc Med Sect, Boston, MA USA. RP Joynt, KE (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. EM kjoynt@partners.org NR 79 TC 4 Z9 4 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD MAR 24 PY 2015 VL 131 IS 12 BP 1098 EP 1105 DI 10.1161/CIRCULATIONAHA.114.013606 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CE2TA UT WOS:000351669900014 PM 25802255 ER PT J AU Neuwelt, EA Schiff, D AF Neuwelt, Edward A. Schiff, David TI Primary CNS lymphoma A landmark trial and the next steps SO NEUROLOGY LA English DT Editorial Material ID WHOLE-BRAIN RADIOTHERAPY; HIGH-DOSE METHOTREXATE; RITUXIMAB; CHEMOTHERAPY; THERAPY C1 [Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurosurg, Portland, OR 97201 USA. [Neuwelt, Edward A.] Portland VA Med Ctr, Portland, OR USA. [Schiff, David] Univ Virginia, Neurooncol Ctr, Charlottesville, VA USA. RP Neuwelt, EA (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. EM neuwelte@ohsu.edu NR 10 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD MAR 24 PY 2015 VL 84 IS 12 BP 1194 EP 1195 DI 10.1212/WNL.0000000000001407 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA CE2RI UT WOS:000351663200008 PM 25716361 ER PT J AU Charidimou, A Martinez-Ramirez, S Shoamanesh, A Oliveira, J Frosch, M Vashkevich, A Ayres, A Rosand, J Gurol, ME Greenberg, SM Viswanathan, A AF Charidimou, Andreas Martinez-Ramirez, Sergi Shoamanesh, Ashkan Oliveira-Filho, Jamary Frosch, Matthew Vashkevich, Anastasia Ayres, Alison Rosand, Jonathan Gurol, Mahmut Edip Greenberg, Steven M. Viswanathan, Anand TI Cerebral amyloid angiopathy with and without hemorrhage Evidence for different disease phenotypes SO NEUROLOGY LA English DT Article ID CORTICAL SUPERFICIAL SIDEROSIS; SMALL VESSEL DISEASE; APOLIPOPROTEIN-E; ALZHEIMERS-DISEASE; INTRACEREBRAL HEMORRHAGE; PERIVASCULAR SPACES; CLINICAL SPECTRUM; METAANALYSIS; MICROBLEEDS; PREVALENCE AB Objective: To gain insight into different cerebral amyloid angiopathy (CAA) phenotypes and mechanisms, we investigated cortical superficial siderosis (CSS), a new imaging marker of the disease, and its relation with APOE genotype in patients with pathologically proven CAA, who presented with and without intracerebral hemorrhage (ICH). Methods: MRI scans of 105 patients with CAA pathologic confirmation and MRI were analyzed for CSS (focal, <3 sulci; disseminates, <4 sulci) and other imaging markers. We compared pathologic, imaging, and APOE genotype data between subjects with vs without ICH, and investigated associations between CSS and APOE genotype. Results: Our cohort consisted of 54 patients with CAA with symptomatic lobar ICH and 51 without ICH. APOE genotype was available in 53 patients. More than 90% of pathology samples in both groups had neuritic plaques, whereas neurofibrillary tangles were more commonly present in the patients without ICH (87% vs 42%, p < 0.0001). There was a trend for patients with CAA with ICH to more commonly have APOE epsilon 2 (48.7% vs 21.4%, p = 0.075), whereas patients without ICH were more likely to be APOE epsilon 4 carriers (85.7% vs 53.9%, p = 0.035). Disseminated CSS was considerably commoner in patients with ICH (33.3% vs 5.9%, p < 0.0001). In logistic regression, disseminated CSS was associated with APOE epsilon 2 (but not APOE epsilon 4) (odds ratio 5.83; 95% confidence interval 1.49-22.82, p = 0.011). Conclusions: This neuropathologically defined CAA cohort suggests that CSS and APOE epsilon 2 are related to the hemorrhagic expression of the disease; APOE epsilon 4 is enriched in nonhemorrhagic CAA. Our study emphasizes the concept of different CAA phenotypes, suggesting divergent pathophysiologic mechanisms. C1 [Charidimou, Andreas] UCL Inst Neurol, Dept Brain Repair & Rehabil, London, England. [Charidimou, Andreas] Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England. [Charidimou, Andreas; Martinez-Ramirez, Sergi; Shoamanesh, Ashkan; Oliveira-Filho, Jamary; Vashkevich, Anastasia; Ayres, Alison; Rosand, Jonathan; Gurol, Mahmut Edip; Greenberg, Steven M.; Viswanathan, Anand] Harvard Univ, Sch Med, Dept Neurol,Stroke Res Ctr, Hemorrhag Stroke Res Program,Massachusetts Gen Ho, Boston, MA 02115 USA. [Frosch, Matthew] Harvard Univ, Massachusetts Gen Hosp, Sch Med, CS Kubik Lab Neuropathol, Boston, MA USA. [Rosand, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neurocrit Care & Emergency Neurol, Boston, MA USA. [Rosand, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. RP Charidimou, A (reprint author), UCL Inst Neurol, Dept Brain Repair & Rehabil, London, England. EM acharidimou@mgh.harvard.edu OI Beiser, Alexa/0000-0001-8551-7778 FU NIH [K23AG028726-05, P50AG005134-30, 2R01AG26484, 5R01AG026484-10, 5K23AG028726-05] FX Supported by NIH grants K23AG028726-05, P50AG005134-30, 2R01AG26484, 5R01AG026484-10, and 5K23AG028726-05. NR 38 TC 16 Z9 17 U1 5 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD MAR 24 PY 2015 VL 84 IS 12 BP 1206 EP 1212 DI 10.1212/WNL.0000000000001398 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA CE2RI UT WOS:000351663200010 PM 25716356 ER PT J AU Waldo, SW McCabe, JM O'Brien, C Kennedy, KF Joynt, KE Yeh, RW AF Waldo, Stephen W. McCabe, James M. O'Brien, Cashel Kennedy, Kevin F. Joynt, Karen E. Yeh, Robert W. TI Association Between Public Reporting of Outcomes With Procedural Management and Mortality for Patients With Acute Myocardial Infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE acute coronary syndromes(s); percutaneous coronary intervention; public reporting ID PERCUTANEOUS CORONARY INTERVENTION; NEW-YORK-STATE; HEART-ASSOCIATION; CARDIOTHORACIC SURGEONS; PRACTICE GUIDELINES; SURGICAL MORTALITY; CARDIOGENIC-SHOCK; FOCUSED UPDATE; TASK-FORCE; REVASCULARIZATION AB BACKGROUND Public reporting of procedural outcomes may create disincentives to provide percutaneous coronary intervention (PCI) for critically ill patients. OBJECTIVES This study evaluated the association between public reporting with procedural management and outcomes among patients with acute myocardial infarction (AMI). METHODS Using the Nationwide Inpatient Sample, we identified all patients with a primary diagnosis of AMI in states with public reporting (Massachusetts and New York) and regionally comparable states without public reporting (Connecticut, Maine, Maryland, New Hampshire, Rhode Island, and Vermont) between 2005 and 2011. Procedural management and in-hospital outcomes were stratified by public reporting. RESULTS Among 84,121 patients hospitalized with AMI, 57,629 (69%) underwent treatment in a public reporting state. After multivariate adjustment, percutaneous revascularization was performed less often in public reporting states than in nonreporting states (odds ratio [OR]: 0.81, 95% confidence interval [CI]: 0.67 to 0.96), especially among older patients (OR: 0.75, 95% CI: 0.62 to 0.91), those with Medicare insurance (OR: 0.75, 95% CI: 0.62 to 0.91), and those presenting with ST-segment elevation myocardial infarction (OR: 0.63, 95% CI: 0.56 to 0.71) or concomitant cardiac arrest or cardiogenic shock (OR: 0.58, 95% CI: 0.47 to 0.70). Overall, patients with AMI in public reporting states had higher adjusted in-hospital mortality rates (OR: 1.21, 95% CI: 1.06 to 1.37) than those in nonreporting states. This was observed predominantly in patients who did not receive percutaneous revascularization in public reporting states (adjusted OR: 1.30, 95% CI: 1.13 to 1.50), whereas those undergoing the procedure had lower mortality (OR: 0.71, 95% CI: 0.62 to 0.83). CONCLUSIONS Public reporting is associated with reduced percutaneous revascularization and increased in-hospital mortality among patients with AMI, particularly among patients not selected for PCI. (C) 2015 by the American College of Cardiology Foundation. C1 [Waldo, Stephen W.; O'Brien, Cashel; Yeh, Robert W.] Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA. [McCabe, James M.] Univ Washington, Dept Med, Div Cardiol, Seattle, WA USA. [Kennedy, Kevin F.] St Lukes Mid Amer Heart Inst, Kansas City, MO USA. [Joynt, Karen E.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. RP Yeh, RW (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,GRB 8-843, Boston, MA 02114 USA. EM ryeh@partners.org FU Hassenfeld Scholars Program; National Heart, Lung, and Blood Institute career development award [1K23HL118138] FX The study was supported by the Hassenfeld Scholars Program. Dr. Yeh was supported by National Heart, Lung, and Blood Institute career development award 1K23HL118138. Dr. McCabe receives speaking honoraria from Abbott Vascular and Edwards LifeSciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 19 TC 22 Z9 22 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 24 PY 2015 VL 65 IS 11 BP 1119 EP 1126 DI 10.1016/j.jacc.2015.01.008 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CD3GS UT WOS:000350967000009 PM 25790884 ER PT J AU Mi, LZ Brown, CT Gao, YJ Tian, Y Le, VQ Walz, T Springer, TA AF Mi, Li-Zhi Brown, Christopher T. Gao, Yijie Tian, Yuan Le, Viet Q. Walz, Thomas Springer, Timothy A. TI Structure of bone morphogenetic protein 9 procomplex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CRYSTAL-STRUCTURE; PRO-REGION; TGF-BETA; GROWTH; PRODOMAIN; IDENTIFICATION; PURIFICATION; ACTIVATION; RECEPTORS; SIGNALS AB Bone morphogenetic proteins (BMPs) belong to the TGF-beta family, whose 33 members regulate multiple aspects of morphogenesis. TGF-beta family members are secreted as procomplexes containing a small growth factor dimer associated with two larger prodomains. As isolated procomplexes, some members are latent, whereas most are active; what determines these differences is unknown. Here, studies on pro-BMP structures and binding to receptors lead to insights into mechanisms that regulate latency in the TGF-beta family and into the functions of their highly divergent prodomains. The observed open-armed, nonlatent conformation of pro-BMP9 and pro-BMP7 contrasts with the cross-armed, latent conformation of pro-TGF-beta 1. Despite markedly different arm orientations in pro-BMP and pro-TGF-beta, the arm domain of the prodomain can similarly associate with the growth factor, whereas prodomain elements N-and C-terminal to the arm associate differently with the growth factor and may compete with one another to regulate latency and stepwise displacement by type I and II receptors. Sequence conservation suggests that pro-BMP9 can adopt both cross-armed and open-armed conformations. We propose that interactors in the matrix stabilize a cross-armed pro-BMP conformation and regulate transition between cross-armed, latent and open-armed, nonlatent pro-BMP conformations. C1 [Mi, Li-Zhi; Tian, Yuan; Le, Viet Q.; Springer, Timothy A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Mi, Li-Zhi; Tian, Yuan; Le, Viet Q.; Springer, Timothy A.] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Mi, Li-Zhi] Tianjin Univ, Sch Life Sci, Dept Mol & Struct Biol, Tianjin 300072, Peoples R China. [Brown, Christopher T.; Gao, Yijie] Pfizer Worldwide Res & Dev, Global BioTherapeut Technol, Cambridge, MA 02139 USA. [Walz, Thomas] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Walz, Thomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM timothy.springer@childrens.harvard.edu RI Mi, Li-Zhi/B-1371-2016 OI Mi, Li-Zhi/0000-0001-9907-5245 NR 26 TC 22 Z9 22 U1 2 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 24 PY 2015 VL 112 IS 12 BP 3710 EP 3715 DI 10.1073/pnas.1501303112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE0EJ UT WOS:000351477000045 PM 25751889 ER PT J AU Ji, X Dadon, DB Abraham, BJ Lee, TI Jaenisch, R Bradner, JE Young, RA AF Ji, Xiong Dadon, Daniel B. Abraham, Brian J. Lee, Tong Ihn Jaenisch, Rudolf Bradner, James E. Young, Richard A. TI Chromatin proteomic profiling reveals novel proteins associated with histone-marked genomic regions SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chromatin; genomics; proteomics ID RNA-POLYMERASE-II; MESSENGER-RNA; TRANSCRIPTION FACTORS; MASS SPECTROMETRY; SUPER-ENHANCERS; CELL IDENTITY; DEMETHYLATION; PLURIPOTENCY; CANCER; STATE AB More than a thousand proteins are thought to contribute to mammalian chromatin and its regulation, but our understanding of the genomic occupancy and function of most of these proteins is limited. Here we describe an approach, which we call "chromatin proteomic profiling," to identify proteins associated with genomic regions marked by specifically modified histones. We used ChIP-MS to identify proteins associated with genomic regions marked by histones modified at specific lysine residues, including H3K27ac, H3K4me3, H3K79me2, H3K36me3, H3K9me3, and H4K20me3, in ES cells. We identified 332 known and 114 novel proteins associated with these histone-marked genomic segments. Many of the novel candidates have been implicated in various diseases, and their chromatin association may provide clues to disease mechanisms. More than 100 histone modifications have been described, so similar chromatin proteomic profiling studies should prove to be valuable for identifying many additional chromatin-associated proteins in a broad spectrum of cell types. C1 [Ji, Xiong; Dadon, Daniel B.; Abraham, Brian J.; Lee, Tong Ihn; Jaenisch, Rudolf; Young, Richard A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Dadon, Daniel B.; Jaenisch, Rudolf; Young, Richard A.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bradner, James E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Young, RA (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM young@wi.mit.edu RI Young, Richard/F-6495-2012 OI Young, Richard/0000-0001-8855-8647 FU National Institutes of Health [HG002668, HG006046, HD045022] FX We thank Eric Spooner at the Whitehead Proteomics Core for mass spectrometry; Tom Volkert and Sumeet Gupta at the Whitehead Genome Technology Core for sequencing; Zi Peng Fan and Violaine Saint-Andre for protein domain analysis; Jessica Reddy and Lyndon Zhang for helpful bioinformatics discussions; and Jill Dowen, Denes Hnisz, and Jurian Schuijers for comments on the manuscript. This work was supported by National Institutes of Health Grants HG002668 (to R.A.Y.), HG006046 (to R.A.Y.), and HD045022 (to R.J.). NR 45 TC 12 Z9 12 U1 1 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 24 PY 2015 VL 112 IS 12 BP 3841 EP 3846 DI 10.1073/pnas.1502971112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE0EJ UT WOS:000351477000067 PM 25755260 ER PT J AU Lieberman, J Sharp, PA AF Lieberman, Judy Sharp, Philip A. TI Harnessing RNA Interference for Therapy The Silent Treatment SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Lieberman, Judy] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Sharp, Philip A.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. RP Lieberman, J (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, 200 Longwood Ave, Boston, MA 02115 USA. EM judy.lieberman@childrens.harvard.edu NR 6 TC 4 Z9 4 U1 2 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 24 PY 2015 VL 313 IS 12 BP 1207 EP 1208 DI 10.1001/jama.2015.1241 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CD9RJ UT WOS:000351435500013 PM 25803342 ER PT J AU Cohen, DM Ellison, DH AF Cohen, David M. Ellison, David H. TI Evaluating Hyponatremia SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID WATER C1 [Cohen, David M.; Ellison, David H.] Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Dept Med, Portland, OR 97239 USA. [Cohen, David M.] Oregon Hlth & Sci Univ, Dept Cell & Dev Biol, Portland, OR 97239 USA. [Cohen, David M.; Ellison, David H.] Portland VA Med Ctr, Portland, OR USA. [Ellison, David H.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. RP Ellison, DH (reprint author), Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, CH12R,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM ellisond@ohsu.edu OI Ellison, David/0000-0003-2915-265X FU NIDDK NIH HHS [R01 DK084004] NR 5 TC 0 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 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 24 PY 2015 VL 313 IS 12 BP 1260 EP 1261 DI 10.1001/jama.2014.13967 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CD9RJ UT WOS:000351435500027 PM 25803349 ER PT J AU Azroyan, A Cortez-Retamozo, V Bouley, R Liberman, R Ruan, YC Kiselev, E Jacobson, KA Pittet, MJ Brown, D Breton, S AF Azroyan, Anie Cortez-Retamozo, Virna Bouley, Richard Liberman, Rachel Ruan, Ye Chun Kiselev, Evgeny Jacobson, Kenneth A. Pittet, Mikael J. Brown, Dennis Breton, Sylvie TI Renal Intercalated Cells Sense and Mediate Inflammation via the P2Y(14) Receptor SO PLOS ONE LA English DT Article ID VACUOLAR H+-ATPASE; LYSOPHOSPHATIDIC ACID RECEPTOR; PROTEIN-COUPLED RECEPTOR; EPIDIDYMAL CLEAR CELLS; DUCT EPITHELIAL-CELLS; V-ATPASE; COLLECTING DUCT; UDP-GLUCOSE; RAT-KIDNEY; FUNCTIONAL EXPRESSION AB Uncontrolled inflammation is one of the leading causes of kidney failure. Pro-inflammatory responses can occur in the absence of infection, a process called sterile inflammation. Here we show that the purinergic receptor P2Y(14) (GPR105) is specifically and highly expressed in collecting duct intercalated cells (ICs) and mediates sterile inflammation in the kidney. P2Y(14) is activated by UDP-glucose, a damage-associated molecular pattern molecule (DAMP) released by injured cells. We found that UDP-glucose increases pro-inflammatory chemokine expression in ICs as well as MDCK-C11 cells, and UDP-glucose activates the MEK1/2-ERK1/2 pathway in MDCK-C11 cells. These effects were prevented following inhibition of P2Y(14) with the small molecule PPTN. Tail vein injection of mice with UDP-glucose induced the recruitment of neutrophils to the renal medulla. This study identifies ICs as novel sensors, mediators and effectors of inflammation in the kidney via P2Y(14). C1 [Azroyan, Anie; Cortez-Retamozo, Virna; Bouley, Richard; Liberman, Rachel; Ruan, Ye Chun; Pittet, Mikael J.; Brown, Dennis; Breton, Sylvie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Azroyan, Anie; Bouley, Richard; Liberman, Rachel; Ruan, Ye Chun; Brown, Dennis; Breton, Sylvie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Membrane Biol,Nephrol Div, Boston, MA USA. [Kiselev, Evgeny; Jacobson, Kenneth A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Breton, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. EM Breton.Sylvie@MGH.Harvard.edu RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU NIH [HD040793, DK097124, DK042956]; Boston Area Diabetes and Endocrinology Research Center [DK57521]; Center for the Study of Inflammatory Bowel Disease [DK43351]; Charles and Ann Sanders Research Scholar Award at MGH; Intramural Research Program of the NIH, NIDDK; PRAT Program, NIGMS FX This work was supported by NIH grants HD040793 and DK097124 (to S.B.) and NIH grant DK042956 (to D.B.). The Microscopy Core facility of the MGH Program in Membrane Biology receives support from the Boston Area Diabetes and Endocrinology Research Center (DK57521) and the Center for the Study of Inflammatory Bowel Disease (DK43351). S.B. is a recipient of the Charles and Ann Sanders Research Scholar Award at MGH. K.A.J. is funded by the Intramural Research Program of the NIH, NIDDK. E.K. is funded by the PRAT Program, NIGMS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 77 TC 4 Z9 4 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 23 PY 2015 VL 10 IS 3 AR e0121419 DI 10.1371/journal.pone.0121419 PG 24 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE6ZS UT WOS:000351987300250 PM 25799465 ER PT J AU Butt, H Yetisen, AK Ahmed, R Yun, SH Dai, Q AF Butt, Haider Yetisen, Ali K. Ahmed, Rajib Yun, Seok Hyun Dai, Qing TI Carbon nanotube biconvex microcavities SO APPLIED PHYSICS LETTERS LA English DT Article ID MICRO-CAVITY; CRYSTAL; METAMATERIALS; SENSORS; ARRAYS; INDEX AB Developing highly efficient microcavities with predictive narrow-band resonance frequencies using the least amount of material will allow the applications in nonlinear photonic devices. We have developed a microcavity array that comprised multi-walled carbon nanotubes (MWCNT) organized in a biconvex pattern. The finite element model allowed designing microcavity arrays with predictive transmission properties and assessing the effects of the microarray geometry. The microcavity array demonstrated negative index and produced high Q factors. 2-3 mu m tall MWCNTs were patterned as biconvex microcavities, which were separated by 10 mu m in an array. The microcavity was iridescent and had optical control over the diffracted elliptical patterns with a far-field pattern, whose properties were predicted by the model. It is anticipated that the MWCNT biconvex microcavities will have implications for the development of highly efficient lenses, metamaterial antennas, and photonic circuits. (C) 2015 AIP Publishing LLC. C1 [Butt, Haider; Ahmed, Rajib] Univ Birmingham, Sch Mech Engn, Nanotechnol Lab, Birmingham B15 2TT, W Midlands, England. [Yetisen, Ali K.; Yun, Seok Hyun] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Yetisen, Ali K.; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Dai, Qing] Natl Ctr Nanosci & Technol, Beijing 100190, Peoples R China. RP Butt, H (reprint author), Univ Birmingham, Sch Mech Engn, Nanotechnol Lab, Birmingham B15 2TT, W Midlands, England. EM h.butt@bham.ac.uk OI Butt, Haider/0000-0003-2434-9525 FU Leverhulme Trust FX H.B. thanks the Leverhulme Trust for the research funding. NR 19 TC 10 Z9 10 U1 1 U2 27 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 0003-6951 EI 1077-3118 J9 APPL PHYS LETT JI Appl. Phys. Lett. PD MAR 23 PY 2015 VL 106 IS 12 AR 121108 DI 10.1063/1.4916236 PG 5 WC Physics, Applied SC Physics GA CE5LM UT WOS:000351876700008 ER PT J AU Ablain, J Durand, EM Yang, S Zhou, Y Zon, LI AF Ablain, Julien Durand, Ellen M. Yang, Song Zhou, Yi Zon, Leonard I. TI A CRISPR/Cas9 Vector System for Tissue-Specific Gene Disruption in Zebrafish SO DEVELOPMENTAL CELL LA English DT Article ID RNA-GUIDED ENDONUCLEASE; HUMAN-CELLS; CAS SYSTEMS; EXPRESSION; RECOMBINATION; MUTATIONS; NUCLEASES; GENOMES; P53 AB CRISPR/Cas9 technology of genome editing has greatly facilitated the targeted inactivation of genes in vitro and in vivo in a wide range of organisms. In zebrafish, it allows the rapid generation of knockout lines by simply injecting a guide RNA (gRNA) and Cas9 mRNA into one-cell stage embryos. Here, we report a simple and scalable CRISPR-based vector system for tissue-specific gene inactivation in zebrafish. As proof of principle, we used our vector with the gata1 promoter driving Cas9 expression to silence the urod gene, implicated in heme biosynthesis, specifically in the erythrocytic lineage. Urod targeting yielded red fluorescent erythrocytes in zebrafish embryos, recapitulating the phenotype observed in the yquem mutant. While F0 embryos displayed mosaic gene disruption, the phenotype appeared very penetrant in stable F1 fish. This vector system constitutes a unique tool to spatially control gene knockout and greatly broadens the scope of loss-of-function studies in zebrafish. C1 [Ablain, Julien; Durand, Ellen M.; Yang, Song; Zhou, Yi; Zon, Leonard I.] Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Ablain, Julien; Durand, Ellen M.; Yang, Song; Zhou, Yi; Zon, Leonard I.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Ablain, Julien; Durand, Ellen M.; Yang, Song; Zhou, Yi; Zon, Leonard I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zhou, Yi; Zon, Leonard I.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Zon, Leonard I.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Zon, LI (reprint author), Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu FU NIH [R01 CA103846, R01 HL04880, R01 DK53298, PO1 HL32262, P30 DK49216, U01 HL10001, R24 DK092760]; European Molecular Biology Organization (EMBO) Long-Term Fellowship [EMBO ALTF 263-2013] FX We thank Charles K. Kaufman and Elliott J. Hagedorn for critical reading of the manuscript. This work was supported by NIH grants R01 CA103846, R01 HL04880, R01 DK53298, PO1 HL32262, P30 DK49216, U01 HL10001, and R24 DK092760. In addition, L.I.Z. is a Howard Hughes Medical Institute Investigator and J. A. is supported by a European Molecular Biology Organization (EMBO) Long-Term Fellowship (EMBO ALTF 263-2013). L.I.Z. is a founder and stockholder of Fate, Inc. and Scholar Rock. NR 31 TC 68 Z9 71 U1 10 U2 75 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 EI 1878-1551 J9 DEV CELL JI Dev. Cell PD MAR 23 PY 2015 VL 32 IS 6 BP 756 EP 764 DI 10.1016/j.devcel.2015.01.032 PG 9 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA CE5AK UT WOS:000351841900013 PM 25752963 ER PT J AU Yang, T O'Malley, TT Kanmert, D Jerecic, J Zieske, LR Zetterberg, H Hyman, BT Walsh, DM Selkoe, DJ AF Yang, Ting O'Malley, Tiernan T. Kanmert, Daniel Jerecic, Jasna Zieske, Lynn R. Zetterberg, Henrik Hyman, Bradley T. Walsh, Dominic M. Selkoe, Dennis J. TI A highly sensitive novel immunoassay specifically detects low levels of soluble A beta oligomers in human cerebrospinal fluid SO ALZHEIMERS RESEARCH & THERAPY LA English DT Article ID ALZHEIMERS-DISEASE; PROTEIN; BRAIN; CSF; PURIFICATION; ASSEMBLIES AB Introduction: Amyloid beta-protein oligomers play a key role in Alzheimer's disease (AD), but well-validated assays that routinely detect them in cerebrospinal fluid (CSF) are just emerging. We sought to confirm and extend a recent study using the Singulex Erenna platform that reported increased mean CSF oligomer levels in AD. Methods: We tested four antibody pairs and chose one pair that was particularly sensitive, using 1C22, our new oligomer-selective monoclonal antibody, for capture. We applied this new assay to extracts of human brain and CSF. Results: A combination of 1C22 for capture and 3D6 for detection yielded an Erenna immunoassay with a lower limit of quantification of approximately 0.15 pg/ml that was highly selective for oligomers over monomers and detected a wide size-range of oligomers. Most CSFs we tested had detectable oligomer levels but with a large overlap between AD and controls and a trend for higher mean levels in mild cognitive impairment (MCI) than controls. Conclusion: A beta oligomers are detectable in most human CSFs, but AD and controls overlap. MCI CSFs may have a modest elevation in mean value by this assay. C1 [Yang, Ting; O'Malley, Tiernan T.; Kanmert, Daniel; Walsh, Dominic M.; Selkoe, Dennis J.] Brigham & Womens Hosp, Ann Romney Ctr Neurol Dis, Boston, MA 02115 USA. [Yang, Ting; O'Malley, Tiernan T.; Kanmert, Daniel; Walsh, Dominic M.; Selkoe, Dennis J.] Harvard Univ, Sch Med, Harvard Inst Med, Boston, MA 02115 USA. [Jerecic, Jasna] Acumen Pharmaceut Inc, Beverly Hills, CA 90210 USA. [Zieske, Lynn R.] Singulex Inc, Alameda, CA USA. [Zetterberg, Henrik] Univ Gothenburg, Sahlgrenska Acad, Dept Psychiat & Neurochem, Clin Neurochem Lab,Inst Neurosci & Physiol, S-43180 Molndal, Sweden. [Zetterberg, Henrik] UCL Inst Neurol, London WC1N 3BG, England. [Hyman, Bradley T.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Walsh, DM (reprint author), Brigham & Womens Hosp, Ann Romney Ctr Neurol Dis, 77 Ave Louis Pasteur,Room 730, Boston, MA 02115 USA. EM dwalsh3@partners.org; dselkoe@partners.org FU National Institutes of Health [R01AG046275, RO1 AG06173]; BrightFocus [A2013059S] FX This work was supported by grants from the National Institutes of Health: R01AG046275 to DMW and DJS, RO1 AG06173 to DJS, and BrightFocus grant A2013059S. NR 26 TC 15 Z9 15 U1 2 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-9193 J9 ALZHEIMERS RES THER JI Alzheimers Res. Ther. PD MAR 22 PY 2015 VL 7 AR 14 DI 10.1186/s13195-015-0100-y PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CD8KV UT WOS:000351344600001 PM 25802556 ER PT J AU Giantsoudi, D Schuemann, J Jia, X Dowdell, S Jiang, S Paganetti, H AF Giantsoudi, Drosoula Schuemann, Jan Jia, Xun Dowdell, Stephen Jiang, Steve Paganetti, Harald TI Validation of a GPU-based Monte Carlo code (gPMC) for proton radiation therapy: clinical cases study SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE Monte Carlo; GPU; gPMC; clinical validation; proton radiation therapy ID RANGE UNCERTAINTIES; DOSE CALCULATION; ELECTRON-TRANSPORT; DISTRIBUTIONS; SIMULATION; ALGORITHM; GEANT4; TOPAS AB Monte Carlo (MC) methods are recognized as the gold-standard for dose calculation, however they have not replaced analytical methods up to now due to their lengthy calculation times. GPU-based applications allow MC dose calculations to be performed on time scales comparable to conventional analytical algorithms. This study focuses on validating our GPU-based MC code for proton dose calculation (gPMC) using an experimentally validated multi-purpose MC code (TOPAS) and compare their performance for clinical patient cases. Clinical cases from five treatment sites were selected covering the full range from very homogeneous patient geometries (liver) to patients with high geometrical complexity (air cavities and density heterogeneities in head-and-neck and lung patients) and from short beam range (breast) to large beam range (prostate). Both gPMC and TOPAS were used to calculate 3D dose distributions for all patients. Comparisons were performed based on target coverage indices (mean dose, V-95, D-98, D-50, D-02) and gamma index distributions. Dosimetric indices differed less than 2% between TOPAS and gPMC dose distributions for most cases. Gamma index analysis with 1%/1 mm criterion resulted in a passing rate of more than 94% of all patient voxels receiving more than 10% of the mean target dose, for all patients except for prostate cases. Although clinically insignificant, gPMC resulted in systematic underestimation of target dose for prostate cases by 1-2% compared to TOPAS. Correspondingly the gamma index analysis with 1%/1 mm criterion failed for most beams for this site, while for 2%/1 mm criterion passing rates of more than 94.6% of all patient voxels were observed. For the same initial number of simulated particles, calculation time for a single beam for a typical head and neck patient plan decreased from 4 CPU hours per million particles (2.8-2.9 GHz Intel X5600) for TOPAS to 2.4 s per million particles (NVIDIA TESLA C2075) for gPMC. Excellent agreement was demonstrated between our fast GPU-based MC code (gPMC) and a previously extensively validated multi-purpose MC code (TOPAS) for a comprehensive set of clinical patient cases. This shows that MC dose calculations in proton therapy can be performed on time scales comparable to analytical algorithms with accuracy comparable to state-of-the-art CPU-based MC codes. C1 [Giantsoudi, Drosoula; Schuemann, Jan; Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Giantsoudi, Drosoula; Schuemann, Jan; Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA USA. [Jia, Xun; Jiang, Steve] Univ Texas SW Med Ctr Dallas, Dept Radiat Oncol, Dallas, TX 75390 USA. [Dowdell, Stephen] Shoalhaven Canc Care Ctr, Nowra, NSW, Australia. RP Giantsoudi, D (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM giantsoudi@livemail.uthscsa.edu FU Federal Share of program by Massachusetts General Hospital, Proton Therapy Research and Treatment Center [C06 CA059267] FX This project was supported by the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center. The authors thank Jonathan Jackson, PhD and Tao Song of the Enterprise Research Infrastructure and Services (ERIS) at Partners HealthCare for their in-depth support and delivery of the high-performance computing (HPC) clusters. NR 20 TC 7 Z9 7 U1 1 U2 7 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAR 21 PY 2015 VL 60 IS 6 BP 2257 EP 2269 DI 10.1088/0031-9155/60/6/2257 PG 13 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA CI6OV UT WOS:000354880900001 PM 25715661 ER PT J AU Byrne, HL Domanova, W McNamara, AL Incerti, S Kuncic, Z AF Byrne, H. L. Domanova, W. McNamara, A. L. Incerti, S. Kuncic, Z. TI The cytoplasm as a radiation target: an in silico study of microbeam cell irradiation SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE microbeam; cytoplasmic irradiation; Monte-Carlo; bystander effect; alpha particle; soft x-ray ID TRACK STRUCTURE CALCULATIONS; INDUCED GENOMIC INSTABILITY; MONTE-CARLO-SIMULATION; X-RAY; MICRODOSIMETRIC MODEL; BYSTANDER EXPERIMENTS; IONIZING-RADIATION; MAMMALIAN-CELLS; CENBG MICROBEAM; REPAIR MODEL AB We performed in silico microbeam cell irradiation modelling to quantitatively investigate ionisations resulting from soft x-ray and alpha particle microbeams targeting the cytoplasm of a realistic cell model. Our results on the spatial distribution of ionisations show that as x-rays are susceptible to scatter within a cell that can lead to ionisations in the nucleus, soft x-ray microbeams may not be suitable for investigating the DNA damage response to radiation targeting the cytoplasm alone. In contrast, ionisations from an ideal alpha microbeam are tightly confined to the cytoplasm, but a realistic alpha microbeam degrades upon interaction with components upstream of the cellular target. Thus it is difficult to completely rule out a contribution from alpha particle hits to the nucleus when investigating DNA damage response to cytoplasmic irradiation. We find that although the cytoplasm targeting efficiency of an alpha microbeam is better than that of a soft x-ray microbeam (the probability of stray alphas hitting the nucleus is 0.2% compared to 3.6% for x-rays), stray alphas produce more ionisations in the nucleus and thus have greater potential for initiating damage responses therein. Our results suggest that observed biological responses to cytoplasmic irradiation include a small component that can be attributed to stray ionisations in the nucleus resulting from the stochastic nature of particle interactions that cause out-of-beam scatter. This contribution is difficult to isolate experimentally, thus demonstrating the value of the in silico approach. C1 [Byrne, H. L.; Domanova, W.; Kuncic, Z.] Univ Sydney, Sch Phys, Inst Med Phys, Sydney, NSW 2006, Australia. [McNamara, A. L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [McNamara, A. L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Incerti, S.] Univ Bordeaux, CNRS IN2P3, CENBG, F-33175 Gradignan, France. RP Byrne, HL (reprint author), Univ Sydney, Sch Phys, Inst Med Phys, Sydney, NSW 2006, Australia. EM h.byrne@physics.usyd.edu.au RI McNamara, Aimee/C-9432-2009; OI McNamara, Aimee/0000-0001-8792-0464; Byrne, Hilary/0000-0001-7023-7976; Incerti, Sebastien/0000-0002-0619-2053 FU Australian Postgraduate Award; Cancer Institute of NSW FX H L Byrne, acknowledges funding from an Australian Postgraduate Award. The authors acknowledge the Cancer Institute of NSW for funding the Advanced Computing Facility for Cancer Research, which was used for these simulations. NR 57 TC 3 Z9 3 U1 0 U2 5 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAR 21 PY 2015 VL 60 IS 6 BP 2325 EP 2337 DI 10.1088/0031-9155/60/6/2325 PG 13 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA CI6OV UT WOS:000354880900005 PM 25715947 ER PT J AU Singh, JA Ramachandran, R AF Singh, Jasvinder A. Ramachandran, Rekha TI Racial disparities in total ankle arthroplasty utilization and outcomes SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID TOTAL KNEE ARTHROPLASTY; TOTAL HIP-ARTHROPLASTY; COUNTY OSTEOARTHRITIS PROJECT; PATIENT-REPORTED OUTCOMES; TOTAL JOINT ARTHROPLASTY; INPATIENT SAMPLE NIS; REVISION TOTAL HIP; QUALITY-OF-LIFE; UNITED-STATES; SHOULDER ARTHROPLASTY AB Introduction: The objective of this study was to examine the racial disparities in total ankle arthroplasty (TAA) utilization and outcomes. Methods: We used the National Inpatient Sample (NIS) to study the time-trends. Race was categorized as White and Black. Utilization rates were calculated for the U.S. general population per 100,000. Hospital length of stay, discharge disposition and mortality after TAA were assessed. We used the Cochran Armitage trend test to assess time-trends from 1998 to 2011 and chi-square test to compare TAA utilization. We used analysis of variance or chi-squared test to compare the characteristics of Whites and Blacks undergoing TAA and logistic regression to compare mortality, length of stay and discharge to home versus medical facility. Results: The mean ages for Whites undergoing TAA were 62 years and for Blacks was 52 years. Significant racial disparities were noted in TAA utilization rates (/100,000) in 1998, 0.14 in Whites vs. 0.07 in Blacks (P < 0.0001; 2-fold) and in 2011, 1.17 in Whites vs. 0.33 in Blacks (P < 0.0001; 4-fold). Racial disparities in TAA utilization increased significantly from 1998 to 2011 (P < 0.0001). There was a trend towards statistical significance for the difference in the length of hospital stay in Blacks vs. Whites (52.9% vs. 44.3% with length of hospital stay higher than the median; P = 0.08). Differences in the proportion discharged to an inpatient medical facility after TAA, 16.6% Blacks vs. 13.4% Whites, were not significant (P = 0.36). Conclusions: This study demonstrated significant racial disparities with lower TAA utilization and suboptimal outcomes in Blacks compared to Whites. Further studies are needed to understand the mediators of these disparities and to assess whether these mediators can be targeted to reduce racial disparities in TAA. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Ramachandran, Rekha] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Ramachandran, Rekha] Univ Alabama Birmingham, Div Epidemiol, Sch Publ Hlth, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Dept Orthoped Surg, Coll Med, Rochester, MN 55905 USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Med Serv, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM jassingh@uab.edu FU Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs); National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS); National Institute of Aging; National Cancer Institute FX This material is the result of work supported by the resources and use of facilities at the Birmingham VA Medical Center, AL, USA. JAS is also supported by grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs), the National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), the National Institute of Aging and the National Cancer Institute. NR 55 TC 1 Z9 1 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PD MAR 21 PY 2015 VL 17 AR 70 DI 10.1186/s13075-015-0589-2 PG 8 WC Rheumatology SC Rheumatology GA CF5QE UT WOS:000352611200001 PM 25889569 ER PT J AU Naggie, S Kim, AY AF Naggie, Susanna Kim, Arthur Y. TI PHOTON-2: hope for patients with HIV and HCV co-infection? SO LANCET LA English DT Editorial Material ID HEPATITIS-C; SOFOSBUVIR; RIBAVIRIN C1 [Naggie, Susanna] Duke Clin Res Inst, Durham, NC USA. [Kim, Arthur Y.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Kim, Arthur Y.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Kim, AY (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM akim1@mgh.harvard.edu FU NIAID NIH HHS [K23 AI096913, P30 AI064518] NR 14 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 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD MAR 21 PY 2015 VL 385 IS 9973 BP 1052 EP 1054 DI 10.1016/S0140-6736(15)60122-2 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA CD7KX UT WOS:000351270400008 PM 25659286 ER PT J AU Tung, NM Winer, EP AF Tung, Nadine M. Winer, Eric P. TI Tumor-Infiltrating Lymphocytes and Response to Platinum in Triple-Negative Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID PATHOLOGICAL COMPLETE RESPONSE; NEOADJUVANT CISPLATIN; GENOMIC INSTABILITY; ANTITUMOR IMMUNITY; ESTROGEN-RECEPTOR; PROGNOSTIC VALUE; CHEMOTHERAPY; EXPRESSION; TRIAL; CARBOPLATIN C1 [Tung, Nadine M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Tung, NM (reprint author), Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. EM ntung@bidmc.harvard.edu NR 38 TC 10 Z9 11 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 20 PY 2015 VL 33 IS 9 BP 969 EP + DI 10.1200/JCO.2014.59.6031 PG 5 WC Oncology SC Oncology GA CK2QP UT WOS:000356056400002 PM 25559817 ER PT J AU Redig, AJ Janne, PA AF Redig, Amanda J. Jaenne, Pasi A. TI Basket Trials and the Evolution of Clinical Trial Design in an Era of Genomic Medicine SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID CELL LUNG-CANCER; THYROID-CANCER; BRAF MUTATIONS; PHASE-II; GEFITINIB; INHIBITION; EVEROLIMUS; EGFR C1 [Redig, Amanda J.; Jaenne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Redig, Amanda J.; Jaenne, Pasi A.] Harvard Univ, Sch Med, Boston, MA USA. [Jaenne, Pasi A.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Redig, AJ (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM pasi_janne@dfci.harvard.edu FU NCI NIH HHS [T32 CA009172] NR 18 TC 48 Z9 50 U1 1 U2 7 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 20 PY 2015 VL 33 IS 9 BP 975 EP + DI 10.1200/JCO.2014.59.8433 PG 4 WC Oncology SC Oncology GA CK2QP UT WOS:000356056400004 PM 25667288 ER PT J AU Petereit, DG Frank, SJ Viswanathan, AN Erickson, B Eifel, P Nguyen, PL Wazer, DE AF Petereit, Daniel G. Frank, Steven J. Viswanathan, Akila N. Erickson, Beth Eifel, Patricia Nguyen, Paul L. Wazer, David E. TI Brachytherapy: Where Has It Gone? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID LOCALIZED PROSTATE-CANCER; CERVICAL-CANCER; RADIATION-THERAPY; RADICAL PROSTATECTOMY; UNITED-STATES; DATA-BASE; RADIOTHERAPY; ONCOLOGY; RISK; TRENDS C1 [Petereit, Daniel G.] Rapid City Reg Canc Ctr, Rapid City, SD 57701 USA. [Frank, Steven J.; Eifel, Patricia] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Viswanathan, Akila N.; Nguyen, Paul L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Viswanathan, Akila N.; Nguyen, Paul L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Viswanathan, Akila N.; Nguyen, Paul L.] Harvard Univ, Sch Med, Boston, MA USA. [Erickson, Beth] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Wazer, David E.] Tufts Univ, Sch Med, Tufts Med Ctr, Boston, MA 02111 USA. [Wazer, David E.] Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Providence, RI 02903 USA. RP Petereit, DG (reprint author), Rapid City Reg Canc Ctr, Rapid City, SD 57701 USA. EM dpetereit@regionalhealth.com FU NCI NIH HHS [P30 CA016672] NR 22 TC 18 Z9 18 U1 1 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 20 PY 2015 VL 33 IS 9 BP 980 EP + DI 10.1200/JCO.2014.59.8128 PG 4 WC Oncology SC Oncology GA CK2QP UT WOS:000356056400006 PM 25667278 ER PT J AU Chen, JY Tibroni, N Sauter, D Galaski, J Miura, T Alter, G Mueller, B Haller, C Walker, BD Kirchhoff, F Brumme, ZL Ueno, T Fackler, OT AF Chen, Jingyan Tibroni, Nadine Sauter, Daniel Galaski, Johanna Miura, Toshiyuki Alter, Galit Mueller, Birthe Haller, Claudia Walker, Bruce D. Kirchhoff, Frank Brumme, Zabrina L. Ueno, Takamasa Fackler, Oliver T. TI Modest Attenuation of HIV-1 Vpu Alleles Derived from Elite Controller Plasma SO PLOS ONE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CELL-MEDIATED CYTOTOXICITY; CLASS-I MOLECULES; PARTICLE RELEASE; KAPPA-B; TETHERIN ANTAGONISM; RESTRICTION FACTOR; NEF PROTEIN; BETA-TRCP; NTB-A AB In the absence of antiretroviral therapy, infection with human immunodeficiency virus type 1 (HIV-1) can typically not be controlled by the infected host and results in the development of acquired immunodeficiency. In rare cases, however, patients spontaneously control HIV-1 replication. Mechanisms by which such elite controllers (ECs) achieve control of HIV-1 replication include particularly efficient immune responses as well as reduced fitness of the specific virus strains. To address whether polymorphisms in the accessory HIV-1 protein Vpu are associated with EC status we functionally analyzed a panel of plasma-derived vpu alleles from 15 EC and 16 chronic progressor (CP) patients. Antagonism of the HIV particle release restriction by the intrinsic immunity factor CD317/tetherin was well conserved among EC and CP Vpu alleles, underscoring the selective advantage of this Vpu function in HIV-1 infected individuals. In contrast, interference with CD317/tetherin induced NF-kappa B activation was little conserved in both groups. EC Vpus more frequently displayed reduced ability to downregulate cell surface levels of CD4 and MHC class I (MHC-I) molecules as well as of the NK cell ligand NTB-A. Polymorphisms potentially associated with high affinity interactions of the inhibitory killer immunoglobulin-like receptor (KIR) KIR2DL2 were significantly enriched among EC Vpus but did not account for these functional differences. Together these results suggest that in a subgroup of EC patients, some Vpu functions are modestly reduced, possibly as a result of host selection. C1 [Chen, Jingyan; Tibroni, Nadine; Galaski, Johanna; Mueller, Birthe; Haller, Claudia; Fackler, Oliver T.] Univ Heidelberg Hosp, Integrat Virol, Dept Infect Dis, Heidelberg, Germany. [Chen, Jingyan; Tibroni, Nadine; Galaski, Johanna; Mueller, Birthe; Haller, Claudia; Fackler, Oliver T.] Heidelberg Univ, German Ctr Infect Res, Heidelberg, Germany. [Sauter, Daniel; Kirchhoff, Frank] Univ Ulm, Inst Mol Virol, Med Ctr, D-89069 Ulm, Germany. [Miura, Toshiyuki] Nagasaki Univ, Inst Trop Med, Nagasaki 852, Japan. [Alter, Galit; Walker, Bruce D.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Alter, Galit; Walker, Bruce D.] Harvard Univ, Boston, MA USA. [Walker, Bruce D.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Brumme, Zabrina L.] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. [Brumme, Zabrina L.] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Ueno, Takamasa] Kumamoto Univ, Ctr AIDS Res, Kumamoto, Japan. [Ueno, Takamasa] Kumamoto Univ, Int Res Ctr Med Sci IRCMS, Kumamoto 860, Japan. RP Fackler, OT (reprint author), Univ Heidelberg Hosp, Integrat Virol, Dept Infect Dis, INF 324, Heidelberg, Germany. EM oliver.fackler@med.uni-heidelberg.de RI Ueno, Takamasa/F-5788-2013 OI Ueno, Takamasa/0000-0003-4852-4236 FU German Center for Infection Research [8.2 TTU HIV]; German Center for Infection Research (MD student fellowship); Deutsche Forschungsgemeinschaft; Ministry of Education, Science, Sports, and Culture of Japan; Ministry of Health, Labor, and Welfare of Japan FX This study was supported by the German Center for Infection Research (project 8.2 TTU HIV to OTF and MD student fellowship to JG), the Deutsche Forschungsgemeinschaft (grants to OTF, DS and FK) and grants-in-aid for scientific research from the Ministry of Education, Science, Sports, and Culture of Japan and the Ministry of Health, Labor, and Welfare of Japan (to TU). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 66 TC 3 Z9 3 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 20 PY 2015 VL 10 IS 3 AR e0120434 DI 10.1371/journal.pone.0120434 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE8HY UT WOS:000352083900034 PM 25793728 ER PT J AU Closson, EF Mimiaga, MJ Sherman, SG Tangmunkongvorakul, A Friedman, RK Limbada, M Moore, AT Srithanaviboonchai, K Alves, CA Roberts, S Oldenburg, CE Elharrar, V Mayer, KH Safren, SA AF Closson, Elizabeth F. Mimiaga, Matthew J. Sherman, Susan G. Tangmunkongvorakul, Arunrat Friedman, Ruth K. Limbada, Mohammed Moore, Ayana T. Srithanaviboonchai, Kriengkrai Alves, Carla A. Roberts, Sarah Oldenburg, Catherine E. Elharrar, Vanessa Mayer, Kenneth H. Safren, Steven A. CA HPTN063 Study Team TI Intimacy versus Isolation: A Qualitative Study of Sexual Practices among Sexually Active HIV-Infected Patients in HIV Care in Brazil, Thailand, and Zambia SO PLOS ONE LA English DT Article ID ANTIRETROVIRAL THERAPY; POSITIVE MEN; TRANSMISSION RISK; PREVENTION; WOMEN; BEHAVIOR; PARTNERS; PEOPLE; DISCLOSURE; SEROSTATUS AB The success of global treatment as prevention (TasP) efforts for individuals living with HIV/AIDS (PLWHA) is dependent on successful implementation, and therefore the appropriate contribution of social and behavioral science to these efforts. Understanding the psychosocial context of condomless sex among PLWHA could shed light on effective points of intervention. HPTN 063 was an observational mixed-methods study of sexually active, in-care PLWHA in Thailand, Zambia, and Brazil as a foundation for integrating secondary HIV prevention into HIV treatment. From 2010-2012, 80 qualitative interviews were conducted with PLWHA receiving HIV care and reported recent sexual risk. Thirty men who have sex with women (MSW) and 30 women who have sex with men (WSM) participated in equal numbers across the sites. Thailand and Brazil also enrolled 20 biologically-born men who have sex with men (MSM). Part of the interview focused on the impact of HIV on sexual practices and relationships. Interviews were recorded, transcribed, translated into English and examined using qualitative descriptive analysis. The mean age was 25 (SD = 3.2). There were numerous similarities in experiences and attitudes between MSM, MSW and WSM across the three settings. Participants had a high degree of HIV transmission risk awareness and practiced some protective sexual behaviors such as reduced sexual activity, increased use of condoms, and external ejaculation. Themes related to risk behavior can be categorized according to struggles for intimacy and fears of isolation, including: fear of infecting a sex partner, guilt about sex, sexual communication difficulty, HIV-stigma, and worry about sexual partnerships. Emphasizing sexual health, intimacy and protective practices as components of nonjudgmental sex-positive secondary HIV prevention interventions is recommended. For in-care PLWHA, this approach has the potential to support TasP. The overlap of themes across groups and countries indicates that similar intervention content may be effective for a range of settings. C1 [Closson, Elizabeth F.; Mimiaga, Matthew J.; Oldenburg, Catherine E.; Mayer, Kenneth H.; Safren, Steven A.] Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. [Mimiaga, Matthew J.; Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Mimiaga, Matthew J.; Oldenburg, Catherine E.; Mayer, Kenneth H.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Sherman, Susan G.] Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. [Tangmunkongvorakul, Arunrat; Srithanaviboonchai, Kriengkrai] Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai 50000, Thailand. [Friedman, Ruth K.; Alves, Carla A.] Fundacao Oswaldo Cruz Fiocruz, Inst Pesquisa Clin Evandro Chagas, Rio De Janeiro, Brazil. [Limbada, Mohammed; Roberts, Sarah] Ctr Infect Dis Res Zambia, Lusaka, Zambia. [Moore, Ayana T.] FHI360, Durham, NC USA. [Srithanaviboonchai, Kriengkrai] Chiang Mai Univ, Fac Med, Chiang Mai 50000, Thailand. [Elharrar, Vanessa] NIAID, Bethesda, MD 20892 USA. [Mayer, Kenneth H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Mimiaga, MJ (reprint author), Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. EM mmimiaga@mgh.harvard.edu OI Srithanaviboonchai, Kriengkrai/0000-0002-1683-4259 FU Division of AIDS, National Institute of Allergy and Infectious Disease (NIAID); National Institute on Drug Abuse (NIDA); National Institute of Mental Health (NIMH) of the U.S. National Institutes of Health (NIH), U.S. Department of Health and Human Services [UM1 AI068619, UM1 AI068617, UM1 AI068613]; NIAID [T32AI007535] FX The study HPTN 063 was funded by the Division of AIDS, National Institute of Allergy and Infectious Disease (NIAID); National Institute on Drug Abuse (NIDA); and the National Institute of Mental Health (NIMH) of the U.S. National Institutes of Health (NIH), U.S. Department of Health and Human Services, under Cooperative Agreements #UM1 AI068619, UM1 AI068617, and UM1 AI068613. CEO is supported by a NIAID T32 NRSA grant (T32AI007535; PI: Seage). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health (NIH) or The HIV Prevention Trials Network (HPTN). NR 43 TC 1 Z9 1 U1 6 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 20 PY 2015 VL 10 IS 3 AR e0120957 DI 10.1371/journal.pone.0120957 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE8HY UT WOS:000352083900093 PM 25793283 ER PT J AU Herting, MM Gautam, P Spielberg, JM Dahl, RE Sowell, ER AF Herting, Megan M. Gautam, Prapti Spielberg, Jeffrey M. Dahl, Ronald E. Sowell, Elizabeth R. TI A Longitudinal Study: Changes in Cortical Thickness and Surface Area during Pubertal Maturation SO PLOS ONE LA English DT Article ID HUMAN CEREBRAL-CORTEX; BRAIN-DEVELOPMENT; PREFRONTAL CORTEX; STEROID-HORMONES; SEX-DIFFERENCES; VOLUME CHANGES; GRAY-MATTER; ADOLESCENCE; TESTOSTERONE; CELLS AB Sex hormones have been shown to contribute to the organization and function of the brain during puberty and adolescence. Moreover, it has been suggested that distinct hormone changes in girls versus boys may contribute to the emergence of sex differences in internalizing and externalizing behavior during adolescence. In the current longitudinal study, the influence of within-subject changes in puberty (physical and hormonal) on cortical thickness and surface area was examined across a 2-year span, while controlling for age. Greater increases in Tanner Stage predicted less superior frontal thinning and decreases in precuneus surface area in both sexes. Significant Tanner Stage and sex interactions were also seen, with less right superior temporal thinning in girls but not boys, as well as greater decreases in the right bank of the superior temporal sulcus surface area in boys compared to girls. In addition, within-subject changes in testosterone over the 2-year follow-up period were found to relate to decreases in middle superior frontal surface area in boys, but increases in surface area in girls. Lastly, larger increases in estradiol in girls predicted greater middle temporal lobe thinning. These results show that within-subject physical and hormonal markers of puberty relate to region and sex-specific changes in cortical development across adolescence. C1 [Herting, Megan M.; Gautam, Prapti; Sowell, Elizabeth R.] Childrens Hosp Los Angeles, Keck Sch Med USC, Dept Pediat, Los Angeles, CA 90027 USA. [Spielberg, Jeffrey M.] VA Boston Hlth Care Syst, Neuroimaging Res Vet Ctr, Boston, MA USA. [Dahl, Ronald E.] Univ Calif Berkeley, Inst Human Dev, Berkeley, CA 94720 USA. RP Herting, MM (reprint author), Childrens Hosp Los Angeles, Keck Sch Med USC, Dept Pediat, Los Angeles, CA 90027 USA. EM mherting@chla.usc.edu; esowell@chla.usc.edu OI Spielberg, Jeffrey/0000-0001-8348-7157 FU National Institute of Drug Abuse Grant [R01 DA018910]; National Institute of Mental Health Grant [R01 MH087563]; National Institute of Child Development Health Grant [F32 HD078084] FX This work was supported by the National Institute of Drug Abuse Grant R01 DA018910 awarded to Dr. Dahl. Support for this research was also provided by the National Institute of Mental Health Grant R01 MH087563 awarded to Dr. Sowell and the National Institute of Child Development Health Grant F32 HD078084 awarded to Dr. Herting. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 13 Z9 13 U1 2 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 20 PY 2015 VL 10 IS 3 AR e0119774 DI 10.1371/journal.pone.0119774 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE8IA UT WOS:000352084200114 PM 25793383 ER PT J AU Reveles, KR Juday, TR Labreche, MJ Mortensen, EM Koeller, JM Seekins, D Oramasionwu, CU Bollinger, M Copeland, LA Jones, X Frei, CR AF Reveles, Kelly R. Juday, Timothy R. Labreche, Matthew J. Mortensen, Eric M. Koeller, Jim M. Seekins, Daniel Oramasionwu, Christine U. Bollinger, Mary Copeland, Laurel A. Jones, Xavier Frei, Christopher R. TI Comparative Value of Four Measures of Retention in Expert Care in Predicting Clinical Outcomes and Health Care Utilization in HIV Patients SO PLOS ONE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; QUALITY-OF-LIFE; UNITED-STATES; VETERANS-AFFAIRS; INFECTION; ADHERENCE; ENGAGEMENT; PREVENTION; MORTALITY; ADULTS AB This study compared the ability of four measures of patient retention in HIV expert care to predict clinical outcomes. This retrospective study examined Veterans Health Administration (VHA) beneficiaries with HIV (ICD-9-CM codes 042 or V08) receiving expert care (defined as HIV-1 RNA viral load and CD4 cell count tests occurring within one week of each other) at VHA facilities from October 1, 2006, to September 30, 2008. Patients were >= 18 years old and continuous VHA users for at least 24 months after entry into expert care. Retention measures included: Annual Appointments (>= 2 appointments annually at least 60 days apart), Missed Appointments (missed >= 25% of appointments), Infrequent Appointments (> 6 months without an appointment), and Missed or Infrequent Appointments (missed >= 25% of appointments or > 6 months without an appointment). Multivariable nominal logistic regression models were used to determine associations between retention measures and outcomes. Overall, 8,845 patients met study criteria. At baseline, 64% of patients were virologically suppressed and 37% had a CD4 cell count > 500 cells/mm(3). At 24 months, 82% were virologically suppressed and 46% had a CD4 cell count > 500 cells/mm(3). During follow-up, 13% progressed to AIDS, 48% visited the emergency department (ED), 28% were hospitalized, and 0.3% died. All four retention measures were associated with virologic suppression and antiretroviral therapy initiation at 24 months follow-up. Annual Appointments correlated positively with CD4 cell count > 500 cells/mm(3). Missed Appointments was predictive of all primary and secondary outcomes, including CD4 cell count <= 500 cells/mm(3), progression to AIDS, ED visit, and hospitalization. Missed Appointments was the only measure to predict all primary and secondary outcomes. This finding could be useful to health care providers and public health organizations as they seek ways to optimize the health of HIV patients. C1 [Reveles, Kelly R.; Koeller, Jim M.; Frei, Christopher R.] Univ Texas Austin, Austin, TX 78712 USA. [Reveles, Kelly R.; Koeller, Jim M.; Frei, Christopher R.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Juday, Timothy R.; Seekins, Daniel] Bristol Myers Squibb Co, Plainsboro, NJ USA. [Labreche, Matthew J.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Mortensen, Eric M.] VA North Texas Hlth Care Syst, Dallas, TX USA. [Mortensen, Eric M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Oramasionwu, Christine U.] Univ N Carolina, Chapel Hill, NC USA. [Bollinger, Mary; Jones, Xavier] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Copeland, Laurel A.] Cent Texas Vet Hlth Care Syst, Temple, TX USA. [Copeland, Laurel A.] Scott & White Healthcare, Ctr Appl Hlth Res, Temple, TX USA. RP Frei, CR (reprint author), Univ Texas Austin, Austin, TX 78712 USA. EM freic@uthscsa.edu OI Mortensen, Eric/0000-0002-3880-5563; Copeland, Laurel/0000-0002-9478-0209 FU Bristol-Myers Squibb Company, Plainsboro, NJ FX This work was supported by Bristol-Myers Squibb Company, Plainsboro, NJ (http://www.bms.com/pages/default.aspx). The funders assisted with the study design and preparation of the manuscript. This work was partially supported with the resources of the Department of Veterans Affairs. The views are those of the authors and do not necessarily reflect the views of the Department of Veterans Affairs. NR 45 TC 2 Z9 2 U1 2 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 20 PY 2015 VL 10 IS 3 AR e0120953 DI 10.1371/journal.pone.0120953 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE8HY UT WOS:000352083900092 PM 25794182 ER PT J AU Sampaio, AS Hounie, AG Petribu, K Cappi, C Morais, I Vallada, H do Rosario, MC Stewart, SE Fargeness, J Mathews, C Arnold, P Hanna, GL Richter, M Kennedy, J Fontenelle, L Pereira, CAD Pauls, DL Miguel, EC AF Sampaio, Aline Santos Hounie, Ana Gabriela Petribu, Katia Cappi, Carolina Morais, Ivanil Vallada, Homero do Rosario, Maria Conceicao Stewart, S. Evelyn Fargeness, Jesen Mathews, Carol Arnold, Paul Hanna, Gregory L. Richter, Margaret Kennedy, James Fontenelle, Leonardo de Braganca Pereira, Carlos Alberto Pauls, David L. Miguel, Euripedes Constantino TI COMT and MAO-A Polymorphisms and Obsessive-Compulsive Disorder: A Family-Based Association Study SO PLOS ONE LA English DT Article ID CATECHOL-O-METHYLTRANSFERASE; MONOAMINE-OXIDASE-A; MAJOR DEPRESSIVE DISORDER; LA-TOURETTE-SYNDROME; HIGH-ACTIVITY ALLELE; FUNCTIONAL POLYMORPHISM; BIPOLAR DISORDER; PREFERENTIAL TRANSMISSION; GENETIC ASSOCIATION; ANXIETY DISORDERS AB Objective Obsessive-compulsive disorder (OCD) is a common and debilitating psychiatric illness. Although a genetic component contributes to its etiology, no single gene or mechanism has been identified to the OCD susceptibility. The catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAO-A) genes have been investigated in previous OCD studies, but the results are still unclear. More recently, Taylor (2013) in a comprehensive meta-analysis of genetic association studies has identified COMT and MAO-A polymorphisms involved with OCD. In an effort to clarify the role of these two genes in OCD vulnerability, a family-based association investigation was performed as an alternative strategy to the classical case-control design. Methods Transmission disequilibrium analyses were performed after genotyping 13 single-nucleotide polymorphisms (eight in COMT and five in MAO-A) in 783 OCD trios (probands and their parents). Four different OCD phenotypes (from narrow to broad OCD definitions) and a SNP x SNP epistasis were also analyzed. Results OCD, broad and narrow phenotypes, were not associated with any of the investigated COMT and MAO-A polymorphisms. In addition, the analyses of gene-gene interaction did not show significant epistatic influences on phenotype between COMT and MAO-A. Conclusions The findings do not support an association between DSM-IV OCD and the variants of COMT or MAO-A. However, results from this study cannot exclude the contribution of these genes in the manifestation of OCD. The evaluation of broader spectrum phenotypes could help to understand the role of these and other genes in the pathophysiology of OCD and its spectrum disorders. C1 [Sampaio, Aline Santos; Hounie, Ana Gabriela; Cappi, Carolina; Morais, Ivanil; Vallada, Homero; Miguel, Euripedes Constantino] Univ Sao Paulo, Fac Med, Dept & Inst Psychiat, Sao Paulo, SP, Brazil. [Sampaio, Aline Santos] Univ Fed Bahia, Serv Med Univ, Salvador, BA, Brazil. [Petribu, Katia] Univ Pernambuco, Fac Ciencias Med, Recife, PE, Brazil. [do Rosario, Maria Conceicao] Univ Fed Sao Paulo, Sao Paulo, SP, Brazil. [Stewart, S. Evelyn] British Columbia Mental Hlth & Addict Res Inst, Vancouver, BC, Canada. [Stewart, S. Evelyn; Pauls, David L.] Massachusetts Gen Hosp, PNGU, Boston, MA 02114 USA. [Fargeness, Jesen] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Mathews, Carol] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Arnold, Paul] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada. [Hanna, Gregory L.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Richter, Margaret] Sunnybrook Hlth Sci Ctr, Frederick W Thompson Anxiety Disorders Ctr, Toronto, ON M4N 3M5, Canada. [Kennedy, James] Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON, Canada. [Fontenelle, Leonardo] Univ Fed Rio de Janeiro, Inst Psiquiatria, IPUB, Programa Ansiedade & Depressao, Rio De Janeiro, Brazil. [de Braganca Pereira, Carlos Alberto] Univ Sao Paulo, Inst Math & Stat, Dept Stat, Sao Paulo, SP, Brazil. RP Sampaio, AS (reprint author), Univ Sao Paulo, Fac Med, Dept & Inst Psychiat, Sao Paulo, SP, Brazil. EM alinestsampaio@gmail.com RI Miguel, Euripedes/B-2871-2008; Vallada, Homero/D-1333-2014; OI Vallada, Homero/0000-0001-5123-8295; Hanna, Gregory/0000-0002-0742-6990 FU Brazilian governmental agencies; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, National Council for Scientific and Technological Development) [573974/2008-0]; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Foundation for the Support of Research in the State of Sao Paulo) [2005/55628-08, 2008/57896-8]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES -Coordination for Education of Graduated People), Brazil; Fundo de Aprimoramento Academico (FUAA-Grant for Academic Improvement); Department of Psychiatry University of Sao Paulo School of Medicine FX This study received financial support in the form of grants provided by the following Brazilian governmental agencies to Dr. Miguel: the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, National Council for Scientific and Technological Development, Grant number: 573974/2008-0) and the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Foundation for the Support of Research in the State of Sao Paulo, Grant number: 2005/55628-08 and 2008/57896-8); to Dr. Sampaio: by Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES -Coordination for Education of Graduated People), Brazil, Fundo de Aprimoramento Academico (FUAA-Grant for Academic Improvement), Department of Psychiatry University of Sao Paulo School of Medicine. Genotyping expenses were paid by Obsessive-Compulsive Foundation Genetics Collaborative Study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 62 TC 4 Z9 4 U1 2 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 20 PY 2015 VL 10 IS 3 AR e0119592 DI 10.1371/journal.pone.0119592 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE8IA UT WOS:000352084200098 PM 25793616 ER PT J AU Liu, YY Ayers, S Milanesi, A Teng, XC Rabi, S Akiba, Y Brent, GA AF Liu, Yan-Yun Ayers, Stephen Milanesi, Anna Teng, Xiaochun Rabi, Sina Akiba, Ysutada Brent, Gregory A. TI Thyroid Hormone Receptor Sumoylation Is Required for Preadipocyte Differentiation and Proliferation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Adipogenesis; Cell Proliferation; Peroxisome Proliferator-activated Receptor (PPAR); Sumoylation; Wnt Signaling; 3T3L1; Human Primary Preadipocytes; NCoR; Perilipin1; TR ID PPAR-GAMMA; IN-VIVO; ADIPOCYTE DIFFERENTIATION; TRANSCRIPTIONAL REGULATION; LIPID DROPLETS; SUMO CHAINS; NUCLEAR RECEPTOR; PERILIPIN-GENE; STEM-CELLS; ALPHA-GENE AB Background: Thyroid hormone receptor (TR) sumoylation is essential for thyroid hormone regulation of gene expression. Results: TR sumoylation mutants impair differentiation though down-regulation of C/EBPs, constitutive interaction with NCoR, interference with PPAR signaling, and disruption of the Wnt canonical signaling pathway important for preadipocyte proliferation. Conclusion: TR sumoylation site mutations impair preadipocyte proliferation and differentiation. Significance: TR sumoylation is required for adipogenesis. Thyroid hormone and thyroid hormone receptor (TR) play an essential role in metabolic regulation. However, the role of TR in adipogenesis has not been established. We reported previously that TR sumoylation is essential for TR-mediated gene regulation and that mutation of either of the two sites in TR or any of the three sites in TR reduces TR sumoylation. Here, we transfected TR sumoylation site mutants into human primary preadiocytes and the mouse 3T3L1 preadipocyte cell line to determine the role of TR sumoylation in adipogenesis. Reduced sumoylation of TR or TR resulted in fewer and smaller lipid droplets and reduced proliferation of preadipocytes. TR sumoylation mutations, compared with wild-type TR, results in reduced C/EBP expression and reduced PPAR(2) mRNA and protein levels. TR sumoylation mutants recruited NCoR and disrupted PPAR-mediated perilipin1 (Plin1) gene expression, associated with impaired lipid droplet formation. Expression of NCoRID, a mutant NCoR lacking the TR interaction domain, partially rescued the delayed adipogenesis and restored Plin1 gene expression and adipogenesis. TR sumoylation site mutants impaired Wnt/-catenin signaling pathways and the proliferation of primary human preadipocytes. Expression of the TR K146Q sumoylation site mutant down-regulated the essential genes required for canonical Wnt signal-mediated proliferation, including Wnt ligands, Fzds, -catenin, LEF1, and CCND1. Additionally, the TR K146Q mutant enhanced the canonical Wnt signaling inhibitor Dickkopf-related protein 1 (DKK1). Our data demonstrate that TR sumoylation is required for activation of the Wnt canonical signaling pathway during preadipocyte proliferation and enhances the PPAR signaling that promotes differentiation. C1 [Liu, Yan-Yun; Milanesi, Anna; Rabi, Sina; Akiba, Ysutada; Brent, Gregory A.] Vet Affairs Greater Los Angeles Healthcare Syst, Mol Endocrinol Lab, Los Angeles, CA 90073 USA. [Liu, Yan-Yun; Milanesi, Anna; Rabi, Sina; Akiba, Ysutada; Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA. [Liu, Yan-Yun; Milanesi, Anna; Rabi, Sina; Akiba, Ysutada; Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90073 USA. [Ayers, Stephen] Methodist Hosp, Res Inst, Genom Med Program, Houston, TX 77030 USA. [Teng, Xiaochun] China Med Univ, Inst Endocrinol, Shenyang 110001, Peoples R China. RP Liu, YY (reprint author), VA Greater Los Angeles Healthcare Syst, Bldg 114,Rm 230,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM yyl@ucla.edu; gbrent@ucla.edu FU National Institutes of Health [R01DK098576] FX This research was supported, in whole or in part, by National Institutes of Health Grant R01DK098576 (to G. A. B.). NR 67 TC 4 Z9 4 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 20 PY 2015 VL 290 IS 12 BP 7402 EP 7415 DI 10.1074/jbc.M114.600312 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CE2AC UT WOS:000351613600009 PM 25572392 ER PT J AU Peng, B Zhang, CH Marutani, E Pacheco, A Chen, W Ichinose, F Xian, M AF Peng, Bo Zhang, Caihong Marutani, Eizo Pacheco, Armando Chen, Wei Ichinose, Fumito Xian, Ming TI Trapping Hydrogen Sulfide (H2S) with Diselenides: The Application in the Design of Fluorescent Probes SO ORGANIC LETTERS LA English DT Article ID SMALL-MOLECULE DISELENIDES; CHEMICAL BIOLOGY; IN-VIVO; CHEMISTRY; BIOCHEMISTRY; SELECTIVITY; SELENIUM; TOOLS; WATER AB Here we report a unique reaction between phenyl diselenide-ester substrates and H2S to form 1,2-benzothiaselenol-3-one. This reaction proceeded rapidly under mild conditions. Thiols could also react with the diselenide substrates. However, the resulted S-Se intermediate retained high reactivity toward H2S and eventually led to the same cyclized product 1,2-benzothiaselenol-3-one. Based on this reaction two fluorescent probes were developed and showed high selectivity and sensitivity for H2S. The presence of thiols was found not to interfere with the detection process. C1 [Peng, Bo; Zhang, Caihong; Pacheco, Armando; Chen, Wei; Xian, Ming] Washington State Univ, Dept Chem, Pullman, WA 99164 USA. [Zhang, Caihong] Shanxi Univ, Ctr Environm Sci & Engn Res, Sch Chem & Chem Engn, Taiyuan 030006, Peoples R China. [Marutani, Eizo; Ichinose, Fumito] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Marutani, Eizo; Ichinose, Fumito] Harvard Univ, Sch Med, Boston, MA USA. RP Xian, M (reprint author), Washington State Univ, Dept Chem, Pullman, WA 99164 USA. EM mxian@wsu.edu FU American Chemical Society Teva USA Scholar Grant; NIH [R01HL101930, R01HL116571] FX This work is supported by an American Chemical Society Teva USA Scholar Grant and the NIH (R01HL101930 and R01HL116571). NR 37 TC 13 Z9 13 U1 6 U2 78 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 EI 1523-7052 J9 ORG LETT JI Org. Lett. PD MAR 20 PY 2015 VL 17 IS 6 BP 1541 EP 1544 DI 10.1021/acs.orglett.5b00431 PG 4 WC Chemistry, Organic SC Chemistry GA CE1FS UT WOS:000351558100049 PM 25723840 ER PT J AU Corre, J Munshi, N Avet-Loiseau, H AF Corre, Jill Munshi, Nikhil Avet-Loiseau, Herve TI Genetics of multiple myeloma: another heterogeneity level? SO BLOOD LA English DT Review ID IN-SITU HYBRIDIZATION; PLASMA-CELL LEUKEMIA; ADVERSE PROGNOSTIC-FACTOR; MONOCLONAL GAMMOPATHY; CHROMOSOMAL TRANSLOCATIONS; UNDETERMINED SIGNIFICANCE; MOLECULAR CLASSIFICATION; INTERGROUPE FRANCOPHONE; FGFR3 EXPRESSION; C-MAF AB Our knowledge of myeloma genetics remained limited and lagged behind many other hematologic malignancies because of the inherent difficulties in generating metaphases within the malignant plasma cell clone. With the development of molecular techniques (microarrays and next-generation sequencing), our understanding has been highly improved in the past 5 years. These studies have not only confirmed the prevalence of wide heterogeneity in myeloma at the molecular level, but has also provided a much clearer picture of the disease pathogenesis and progression. Whether these data will enable improvements in the therapeutic approach is still a matter of debate. The next improvement will come from detailed analyses of these molecular features to try to move from a treatment fitted to every patient to individualized therapies, taking into account the complexity of the chromosomal changes, the mutation spectrum, and subclonality evolution. C1 [Corre, Jill; Avet-Loiseau, Herve] CHU, IUCT Oncopole, Unit Genom Myeloma, F-31059 Toulouse, France. [Corre, Jill; Avet-Loiseau, Herve] Inst Natl Sante & Rech Med, Ctr Rech Cancerol Toulouse, U1037, Toulouse, France. [Munshi, Nikhil] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Munshi, Nikhil] Boston Vet Adm Healthcare Syst, West Roxbury, MA USA. RP Avet-Loiseau, H (reprint author), CHU, IUCT Oncopole, F-31059 Toulouse, France. EM avet-loiseau.h@chu-toulouse.fr RI corre, jill/Q-2460-2015 FU CAPTOR program; National Institutes of Health, National Cancer Institute [CA 100707-12] FX This work was partially supported by the CAPTOR program, and a National Institutes of Health, National Cancer Institute PO1 grant (CA 100707-12). NR 63 TC 12 Z9 14 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAR 19 PY 2015 VL 125 IS 12 BP 1870 EP 1876 DI 10.1182/blood-2014-10-567370 PG 7 WC Hematology SC Hematology GA CI3BY UT WOS:000354623700009 PM 25628468 ER PT J AU Martinod, K Fuchs, TA Zitomersky, NL Wong, SL Demers, M Gallant, M Wang, YM Wagner, DD AF Martinod, Kimberly Fuchs, Tobias A. Zitomersky, Naamah L. Wong, Siu Ling Demers, Melanie Gallant, Maureen Wang, Yanming Wagner, Denisa D. TI PAD4-deficiency does not affect bacteremia in polymicrobial sepsis and ameliorates endotoxemic shock SO BLOOD LA English DT Article ID NEUTROPHIL EXTRACELLULAR TRAPS; CITRULLINATED HISTONE H3; INNATE IMMUNE-RESPONSE; GROUP-A STREPTOCOCCUS; DEEP-VEIN THROMBOSIS; DNA TRAPS; IN-VIVO; CHROMATIN DECONDENSATION; CECAL LIGATION; SEPTIC SHOCK AB Neutrophil extracellular traps (NETs), consisting of nuclear DNA with histones and microbicidal proteins, are expelled from activated neutrophils during sepsis. NETs were shown to trap microbes, but they also fuel cardiovascular, thrombotic, and autoimmune disease. The role of NETs in sepsis, particularly the balance between their antimicrobial and cytotoxic actions, remains unclear. Neutrophils from peptidylarginine deiminase 4-(PAD4(-/-)) deficient mice, which lack the enzyme allowing for chromatin decondensation and NET formation, were evaluated. We found that neutrophil functions involved in bacterial killing, other than NETosis, remained intact. Therefore, we hypothesized that prevention of NET formation might not have devastating consequences in sepsis. To test this, we subjected the PAD4(-/-) mice to mild and severe polymicrobial sepsis produced by cecal ligation and puncture. Surprisingly, under septic conditions, PAD4(-/-) mice did not fare worse than wild-type mice and had comparable survival. In the presence of antibiotics, PAD4-deficiency resulted in slightly accelerated mortality but bacteremia was unaffected. PAD4(-/-) mice were partially protected from lipopolysaccharide-induced shock, suggesting that PAD4/NETs may contribute to the toxic inflammatory and procoagulant host response to endotoxin. We propose that preventing NET formation by PAD4 inhibition in inflammatory or thrombotic diseases is not likely to increase host vulnerability to bacterial infections. C1 [Martinod, Kimberly] Harvard Univ, Sch Med, Div Med Sci, Grad Program Immunol, Boston, MA USA. [Martinod, Kimberly; Fuchs, Tobias A.; Zitomersky, Naamah L.; Wong, Siu Ling; Demers, Melanie; Gallant, Maureen; Wagner, Denisa D.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Martinod, Kimberly; Fuchs, Tobias A.; Zitomersky, Naamah L.; Wong, Siu Ling; Demers, Melanie; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Zitomersky, Naamah L.] Boston Childrens Hosp, Div Gastroenterol Hepatol & Nutr, Boston, MA 02115 USA. [Wang, Yanming] Penn State Univ, Dept Biochem & Mol Biol, Ctr Eukaryot Gene Regulat, University Pk, PA 16802 USA. [Wagner, Denisa D.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Wagner, DD (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, 3 Blackfan Circle,3rd Floor, Boston, MA 02115 USA. EM denisa.wagner@childrens.harvard.edu OI Martinod, Kimberly/0000-0002-1026-6107 FU National Institutes of Health National Heart, Lung, and Blood Institute [R01HL102101]; National Cancer Institute [R01CA136856] FX This study was supported by grants from the National Institutes of Health National Heart, Lung, and Blood Institute (R01HL102101) (D.D.W.) and the National Cancer Institute (R01CA136856) (Y.W.). NR 61 TC 28 Z9 28 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAR 19 PY 2015 VL 125 IS 12 BP 1948 EP 1956 DI 10.1182/blood-2014-07-587709 PG 9 WC Hematology SC Hematology GA CI3BY UT WOS:000354623700018 PM 25624317 ER PT J AU Laurent, B Ruitu, L Murn, J Hempel, K Ferrao, R Xiang, Y Liu, SC Garcia, BA Wu, H Wu, FZ Steen, H Shi, Y AF Laurent, Benoit Ruitu, Lv Murn, Jernej Hempel, Kristina Ferrao, Ryan Xiang, Yang Liu, Shichong Garcia, Benjamin A. Wu, Hao Wu, Feizhen Steen, Hanno Shi, Yang TI A Specific LSD1/KDM1A Isoform Regulates Neuronal Differentiation through H3K9 Demethylation SO MOLECULAR CELL LA English DT Article ID LSD1 HISTONE DEMETHYLASE; ANDROGEN-RECEPTOR; STRUCTURAL BASIS; GENE-EXPRESSION; NANOSCALE CLAMP; STEM-CELLS; SUPERVILLIN; PROTEIN; RECOGNITION; ACTIVATION AB Lysine-specific demethylase 1 (LSD1) has been reported to repress and activate transcription by mediating histone H3K4me1/2 and H3K9me1/2 demethylation, respectively. The molecular mechanism that underlies this dual substrate specificity has remained unknown. Here we report that an isoform of LSD1, LSD1+8a, does not have the intrinsic capability to demethylate H3K4me2. Instead, LSD1+8a mediates H3K9me2 demethylation in collaboration with supervillin (SVIL), a new LSD1+8a interacting protein. LSD1+8a knockdown increases H3K9me2, but not H3K4me2, levels at its target promoters and compromises neuronal differentiation. Importantly, SVIL co-localizes to LSD1+8a-bound promoters, and its knockdown mimics the impact of LSD1+8a loss, supporting SVIL as a cofactor for LSD1+8a in neuronal cells. These findings provide insight into mechanisms by which LSD1 mediates H3K9me demethylation and highlight alternative splicing as a means by which LSD1 acquires selective substrate specificities (H3K9 versus H3K4) to differentially control specific gene expression programs in neurons. C1 [Laurent, Benoit; Murn, Jernej; Xiang, Yang; Shi, Yang] Boston Childrens Hosp, Dept Med, Div Newborn Med, Boston, MA 02115 USA. [Laurent, Benoit; Murn, Jernej; Xiang, Yang; Shi, Yang] Boston Childrens Hosp, Dept Med, Epigenet Program, Boston, MA 02115 USA. [Laurent, Benoit; Murn, Jernej; Xiang, Yang; Shi, Yang] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Ruitu, Lv; Wu, Feizhen] Fudan Univ, Inst Biomed Sci, Dept Biochem, Shanghai 200032, Peoples R China. [Ruitu, Lv; Wu, Feizhen] Fudan Univ, Inst Biomed Sci, Epigenet Lab, Shanghai 200032, Peoples R China. [Hempel, Kristina] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Hempel, Kristina; Steen, Hanno] Boston Childrens Hosp, Prote Ctr, Boston, MA 02115 USA. [Ferrao, Ryan; Wu, Hao] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Ferrao, Ryan; Wu, Hao] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Ferrao, Ryan; Wu, Hao] Weill Cornell Grad Sch Med Sci, New York, NY 10065 USA. [Liu, Shichong; Garcia, Benjamin A.] Univ Penn, Perelman Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. [Steen, Hanno] Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Steen, Hanno] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Shi, Y (reprint author), Boston Childrens Hosp, Dept Med, Div Newborn Med, Boston, MA 02115 USA. EM yang_shi@hms.harvard.edu FU Association pour la Recherche sur le Cancer (ARC); Philippe Foundation; NIH [R01 CA118487] FX We thank members of the Shi lab for helpful discussions. In particular, we wish to thank James Lee (Dana Farber Cancer Institute, Boston) for help with the mass spectrometer and Angeles Fernandez-Gonzalez (Boston Children's Hospital, Boston) for help with immunofluorescence microscopy. We thank Dr. Elizabeth J. Luna (University of Massachusetts Medical School, Worcester) for the pEGFP-SVIL constructs. B.L. was supported by fellowships from Association pour la Recherche sur le Cancer (ARC) and the Philippe Foundation. This work was supported by a grant from the NIH to Y.S. (R01 CA118487). Y.S. is an American Cancer Society Research Professor. NR 40 TC 40 Z9 40 U1 7 U2 23 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD MAR 19 PY 2015 VL 57 IS 6 BP 957 EP 970 DI 10.1016/j.molcel.2015.01.010 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CE3GP UT WOS:000351715000005 PM 25684206 ER PT J AU Papageorgiou, A Rapley, J Mesirov, JP Tamayo, P Avruch, J AF Papageorgiou, Angela Rapley, Joseph Mesirov, Jill P. Tamayo, Pablo Avruch, Joseph TI A Genome-Wide siRNA Screen in Mammalian Cells for Regulators of S6 Phosphorylation SO PLOS ONE LA English DT Article ID RIBOSOMAL-PROTEIN S6; AMINO-ACID SUFFICIENCY; MTOR COMPLEX 1; RAG GTPASES; TRANSFER-RNA; TUMOR-SUPPRESSOR; GROWTH-CONTROL; DNA-DAMAGE; IN-VITRO; RAPAMYCIN AB mTOR complex1, the major regulator of mRNA translation in all eukaryotic cells, is strongly activated in most cancers. We performed a genome-wide RNAi screen in a human cancer cell line, seeking genes that regulate S6 phosphorylation, readout of mTORC1 activity. Applying a stringent selection, we retrieved nearly 600 genes wherein at least two RNAis gave significant reduction in S6-P. This cohort contains known regulators of mTOR complex 1 and is significantly enriched in genes whose depletion affects the proliferation/viability of the large set of cancer cell lines in the Achilles database in a manner paralleling that caused by mTOR depletion. We next examined the effect of RNAi pools directed at 534 of these gene products on S6-P in TSC1 null mouse embryo fibroblasts. 76 RNAis reduced S6 phosphorylation significantly in 2 or 3 replicates. Surprisingly, among this cohort of genes the only elements previously associated with the maintenance of mTORC1 activity are two subunits of the vacuolar ATPase and the CUL4 subunit DDB1. RNAi against a second set of 84 targets reduced S6-P in only one of three replicates. However, an indication that this group also bears attention is the presence of rpS6KB1 itself, Rac1 and MAP4K3, a protein kinase that supports amino acid signaling to rpS6KB1. The finding that S6 phosphorylation requires a previously unidentified, functionally diverse cohort of genes that participate in fundamental cellular processes such as mRNA translation, RNA processing, DNA repair and metabolism suggests the operation of feedback pathways in the regulation of mTORC1 operating through novel mechanisms. C1 [Papageorgiou, Angela; Rapley, Joseph; Avruch, Joseph] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Papageorgiou, Angela; Rapley, Joseph; Avruch, Joseph] Massachusetts Gen Hosp, Med Serv, Diabet Unit, Boston, MA 02114 USA. [Papageorgiou, Angela; Rapley, Joseph; Avruch, Joseph] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Mesirov, Jill P.; Tamayo, Pablo] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM avruch@molbio.mgh.harvard.edu FU NIH [CA73818, DK17776, NIH-R37DK17776, NIH-R01CA73818] FX This study was supported by NIH grants (CA73818 and DK17776) and institutional funds. JA received funding from the NIH (NIH-R37DK17776 and NIH-R01CA73818). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 63 TC 1 Z9 1 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 19 PY 2015 VL 10 IS 3 AR e0116096 DI 10.1371/journal.pone.0116096 PG 26 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CD9NQ UT WOS:000351425400008 PM 25790369 ER PT J AU Rockey, DC Bell, PD Hill, JA AF Rockey, Don C. Bell, P. Darwin Hill, Joseph A. TI Fibrosis - A Common Pathway to Organ Injury and Failure SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID IDIOPATHIC-PULMONARY-FIBROSIS; CHRONIC HEPATITIS-C; CARDIOVASCULAR MAGNETIC-RESONANCE; NEPHROGENIC SYSTEMIC FIBROSIS; CONTROLLED CLINICAL-TRIAL; PLACEBO-CONTROLLED TRIAL; CHRONIC KIDNEY-DISEASE; RENAL FIBROSIS; CARDIAC FIBROSIS; MESENCHYMAL TRANSITION C1 [Rockey, Don C.; Bell, P. Darwin] Med Univ S Carolina, Dept Internal Med, Charleston, SC 29425 USA. [Bell, P. Darwin] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Hill, Joseph A.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Hill, Joseph A.] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA. RP Rockey, DC (reprint author), Med Univ S Carolina, Dept Internal Med, 96 Jonathan Lucas St,Suite 803,MSC 623, Charleston, SC 29425 USA. EM rockey@musc.edu NR 102 TC 83 Z9 87 U1 10 U2 43 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 19 PY 2015 VL 372 IS 12 BP 1138 EP 1149 DI 10.1056/NEJMra1300575 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA CD6EZ UT WOS:000351183600008 PM 25785971 ER PT J AU Miller, BL Dickerson, BC Lucente, DE Larvie, M Frosch, MP AF Miller, Bruce L. Dickerson, Bradford C. Lucente, Diane E. Larvie, Mykol Frosch, Matthew P. TI Case 9-2015: A 31-Year-Old Man with Personality Changes and Progressive Neurologic Decline SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID FRONTOTEMPORAL LOBAR DEGENERATION; AMYOTROPHIC-LATERAL-SCLEROSIS; PICKS-DISEASE; TAU-GENE; ALZHEIMERS-DISEASE; G389R CAUSES; DEMENTIA; MUTATIONS; CHROMOSOME-17; MANAGEMENT C1 [Miller, Bruce L.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Dickerson, Bradford C.; Frosch, Matthew P.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Larvie, Mykol] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lucente, Diane E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Dickerson, Bradford C.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Larvie, Mykol] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Frosch, Matthew P.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Miller, BL (reprint author), Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. FU Massachusetts Alzheimer's Disease Research Center (National Institutes of Health) [P50 AG05134]; Krupp Foundation; National Institutes of Health [NS084156]; Larry L. Hillblom Foundation; John Douglas French Alzheimer's Foundation; Tau Consortium; TauRx; Allon Therapeutics; Bristol-Myers Squibb; Eli Lilly; Merck; Forum; Med Learning Group FX The pathological examination was supported by the Massachusetts Alzheimer's Disease Research Center (National Institutes of Health grant P50 AG05134). Dr. Dickerson was supported by the Krupp Foundation and the National Institutes of Health (grant NS084156). This case was the first in the Betty U. and William F. McNeely Memorial Clinicopathological Conference series, supported by a gift from Dr. Sarah Weinberg and the Hon. John Weinberg.; Dr. Miller reports receiving fees for board membership (paid to his institution) from the Larry L. Hillblom Foundation, the John Douglas French Alzheimer's Foundation, and the Tau Consortium and consulting fees from TauRx, Allon Therapeutics, Bristol-Myers Squibb, and Eli Lilly. Dr. Dickerson reports receiving consulting fees from Merck, Forum, and the Med Learning Group and payment for development of educational presentations from the Med Learning Group. No other potential conflict of interest relevant to this article was reported. NR 45 TC 2 Z9 3 U1 2 U2 7 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 19 PY 2015 VL 372 IS 12 BP 1151 EP 1162 DI 10.1056/NEJMcpc1409839 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA CD6EZ UT WOS:000351183600012 PM 25785973 ER PT J AU Wilhelm, CJ Hashimoto, JG Roberts, ML Bloom, SH Beard, DK Wiren, KM AF Wilhelm, Clare J. Hashimoto, Joel G. Roberts, Melissa L. Bloom, Shelley H. Beard, Douglas K. Wiren, Kristine M. TI Females uniquely vulnerable to alcohol-induced neurotoxicity show altered glucocorticoid signaling SO BRAIN RESEARCH LA English DT Article DE Alcohol; Neurodegeneration; Glucocorticoid signaling; Neurotoxicity; Astrocyte ID TISSUE GROWTH-FACTOR; ANTERIOR CINGULATE CORTEX; HIPPOCAMPAL SLICE CULTURES; NF-KAPPA-B; SEX-DIFFERENCES; ETHANOL WITHDRAWAL; GENDER-DIFFERENCES; PREFRONTAL CORTEX; GENE-EXPRESSION; LIVER-DISEASE AB Women are more sensitive to the harmful effects of alcohol (EtOH) abuse than men, yet the underlying mechanisms remain poorly understood. Previous gene expression analysis of the medial prefrontal cortex (mPFC) following a chronic intoxication paradigm using continuous 72 h vapor inhalation found that females, but not males, exhibit an inflammatory response at peak withdrawal that is associated with cell damage. Given that glucocorticoids can function as anti-inflammatories, are known to increase with EtOH exposure, and influence neurotoxicity, we hypothesized that males and females may exhibit an altered corticosterone (CORT) response following chronic intoxication. Analysis of serum CORT levels revealed the expected increase during withdrawal with no difference between males and females, while control males but not females exhibited higher CORT concentrations than naive animals. Glucocorticoid signaling characterized using focused qPCR arrays identified a sexually dimorphic response in the mPFC during withdrawal, particularly among astrocyte-enriched genes. These genes include aquaporin-1 (Aqp1), sphingosine kinase 1 (Sphk1) and connective tissue growth factor (Ctgf); genes associated with inflammatory signaling, and tissue damage and repair. Bioinformatic analysis also revealed activation of inflammatory signaling and cell death pathways in females. Confirmation studies showed that female mice exhibited significant neuronal degeneration within the anterior cingulate cortex (ACC). By contrast, EtOH exposure lead to a significant reduction in cell death in males. Thus, distinct glucocorticoid signaling pathways are associated with sexually dimorphic neurotoxicity, suggesting one mechanism by which EtOH-exposed females are particularly vulnerable to the damaging effects of alcohol in the CNS. Published by Elsevier B.V. C1 [Wilhelm, Clare J.; Hashimoto, Joel G.; Roberts, Melissa L.; Bloom, Shelley H.; Beard, Douglas K.; Wiren, Kristine M.] VA Portland Hlth Care Syst, Portland, OR 97239 USA. [Wilhelm, Clare J.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA. [Hashimoto, Joel G.; Wiren, Kristine M.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. RP Wilhelm, CJ (reprint author), Portland VA Med Ctr, R&D 17, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM wilhelmc@ohsu.edu FU United States (U.S.) Department of Veterans Affairs Biomedical Laboratory Research and Development [I01 BX001172, IK2 BX001294]; NIH/NIAAA [R01AA021468]; NIAAA [P60AA010760, R24AA020245] FX This research was supported by Merit Review Award #I01 BX001172 (K.M.W.) and Career Development Award #IK2 BX001294 (C.J.W.) from the United States (U.S.) Department of Veterans Affairs Biomedical Laboratory Research and Development and from the NIH/NIAAA (R01AA021468 (K.M.W.)). Additionally, this material is the result of work supported with resources and the use of facilities at the Portland VA Medical Center (K.M.W.) and the Research Career Scientist Program (K.M.W.). We thank Melissa Andrew for assistance with the vapor exposure procedure and acknowledge support from NIAAA for the Portland Alcohol Research Center (P60AA010760) and for the maintenance of colonies of WSR and WSP mice (R24AA020245) used in the present studies. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. NR 132 TC 4 Z9 5 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD MAR 19 PY 2015 VL 1601 BP 102 EP 116 DI 10.1016/j.brainres.2015.01.002 PG 15 WC Neurosciences SC Neurosciences & Neurology GA CD2TD UT WOS:000350931000011 PM 25601008 ER PT J AU Selmecki, AM Maruvka, YE Richmond, PA Guillet, M Shoresh, N Sorenson, AL De, S Kishony, R Michor, F Dowell, R Pellman, D AF Selmecki, Anna M. Maruvka, Yosef E. Richmond, Phillip A. Guillet, Marie Shoresh, Noam Sorenson, Amber L. De, Subhajyoti Kishony, Roy Michor, Franziska Dowell, Robin Pellman, David TI Polyploidy can drive rapid adaptation in yeast SO NATURE LA English DT Article ID SITE-DIRECTED MUTAGENESIS; DNA-SEQUENCING DATA; SACCHAROMYCES-CEREVISIAE; ASEXUAL POPULATIONS; CLONAL INTERFERENCE; CANDIDA-ALBICANS; BUDDING YEAST; BENEFICIAL MUTATIONS; ADAPTIVE EVOLUTION; DRUG-RESISTANCE AB Polyploidy is observed across the tree of life, yet its influence on evolution remains incompletely understood(1-4). Polyploidy, usually whole-genome duplication, is proposed to alter the rate of evolutionary adaptation. This could occur through complex effects on the frequency or fitness of beneficial mutations(2,5-7). For example, in diverse cell types and organisms, immediately after a whole-genome duplication, newly formed polyploids missegregate chromosomes and undergo genetic instability(8-13). The instability following wholegenome duplications is thought to provide adaptive mutations in microorganisms(13,14) and can promote tumorigenesis in mammalian cells(11,15). Polyploidy may also affect adaptation independently of beneficial mutations through ploidy-specific changes in cell physiology(16). Here we perform in vitro evolution experiments to test directly whether polyploidy can accelerate evolutionary adaptation. Compared with haploids and diploids, tetraploids undergo significantly faster adaptation. Mathematical modelling suggests that rapid adaptation of tetraploids is driven by higher rates of beneficial mutations with stronger fitness effects, which is supported by whole-genome sequencing and phenotypic analyses of evolved clones. Chromosome aneuploidy, concerted chromosome loss, and point mutations all provide large fitness gains. We identify several mutations whose beneficial effects are manifest specifically in the tetraploid strains. Together, these results provide direct quantitative evidence that in some environments polyploidy can accelerate evolutionary adaptation. C1 [Selmecki, Anna M.; Guillet, Marie; Pellman, David] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Selmecki, Anna M.; Guillet, Marie; Pellman, David] Harvard Univ, Dept Cell Biol, Sch Med, Boston, MA 02215 USA. [Selmecki, Anna M.; Guillet, Marie; Pellman, David] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Maruvka, Yosef E.; Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Maruvka, Yosef E.; Michor, Franziska] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Richmond, Phillip A.; Sorenson, Amber L.; Dowell, Robin] Univ Colorado, BioFrontiers Inst, Boulder, CO 80303 USA. [Richmond, Phillip A.; Sorenson, Amber L.; Dowell, Robin] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA. [Shoresh, Noam] Broad Inst, Cambridge, MA 02142 USA. [De, Subhajyoti] Univ Colorado Sch Med, Dept Med, Aurora, CO 80045 USA. [De, Subhajyoti] Colorado Sch Publ Hlth, Dept Biostat & Informat, Aurora, CO 80045 USA. [De, Subhajyoti] Univ Colorado Canc Ctr, Mol Oncol Program, Aurora, CO 80045 USA. [Kishony, Roy] Harvard Univ, Dept Syst Biol, Sch Med, Boston, MA 02115 USA. [Kishony, Roy] Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel. [Pellman, David] Childrens Hosp, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. RP Selmecki, AM (reprint author), Creighton Univ Sch Med, Dept Med Microbiol & Immunol, 2500 Calif Plaza, Omaha, NE 68178 USA. EM AnnaSelmecki@creighton.edu; david_pellman@dfci.harvard.edu OI DOWELL, ROBIN/0000-0001-7665-9985 FU Howard Hughes Medical Institute; National Institutes of Health [R37 GM61345, R01 GM081617]; G. Harold & Leila Y. Mathers Charitable Foundation; Dana-Farber Cancer Institute Physical Sciences-Oncology Center [U54CA143798]; Boettcher Foundation's Webb-Waring Biomedical Research Program; National Science Foundation [NSF 1350915]; American Cancer Society Postdoctoral Fellowship FX This work was supported by the Howard Hughes Medical Institute, the National Institutes of Health (R37 GM61345), the G. Harold & Leila Y. Mathers Charitable Foundation, the Dana-Farber Cancer Institute Physical Sciences-Oncology Center (U54CA143798), the Boettcher Foundation's Webb-Waring Biomedical Research Program, the National Science Foundation (NSF 1350915), the National Institutes of Health (R01 GM081617), and an American Cancer Society Postdoctoral Fellowship. NR 68 TC 45 Z9 45 U1 15 U2 74 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD MAR 19 PY 2015 VL 519 IS 7543 BP 349 EP + DI 10.1038/nature14187 PG 21 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CD6AY UT WOS:000351171900040 PM 25731168 ER PT J AU Agarwal-Harding, KJ Meara, JG Greenberg, SLM Hagander, LE Zurakowski, D Dyer, GSM AF Agarwal-Harding, Kiran J. Meara, John G. Greenberg, Sarah L. M. Hagander, Lars E. Zurakowski, David Dyer, George S. M. TI Estimating the Global Incidence of Femoral Fracture from Road Traffic Collisions A Literature Review SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Review ID SYSTEMATIC ANALYSIS; SHAFT FRACTURES; DEVELOPING-COUNTRIES; INTRAMEDULLARY NAIL; PERKINS TRACTION; INJURIES; BURDEN; MORTALITY; DISEASE; FEMUR AB Background: Worldwide, road injuries cause over 1.3 million deaths and many more disabilities annually, disproportionately affecting the young and the poor. Approximately one in ten road injuries involves a femoral shaft fracture that is most effectively treated with surgery. Current femoral shaft fracture incidence according to country and age group is unknown and difficult to measure directly but is critical to designing and evaluating interventions. Methods: We modeled femoral shaft fracture incidence from road traffic collisions with use of World Bank, World Health Organization, and Global Burden of Disease Study data for 176 countries and five age groups. We used road traffic death rates, ratios of road traffic deaths to injuries, and proportions of road traffic injuries that were femoral shaft fractures to calculate the fracture incidence. Results: The worldwide annual femoral shaft fracture incidence from road traffic collisions was between 1.0 and 2.9 million. Incidence rates were significantly higher in low and middle income countries compared with high income countries. Overall, low and middle income countries had a mean femoral shaft fracture incidence between 15.7 and 45.5 per 100,000 people per year, with a rate ratio of 2.08 (95% confidence interval, 2.02 to 2.13; p < 0.001) relative to high income countries. Conclusions: Our results demonstrate a substantial worldwide burden and disparities in femoral shaft fracture incidence between low to middle income and high income countries, and the young are disproportionately affected, underscoring the potential impact of improved access to treatment. We believe that the methodology of this study can be applied to estimate the burden of other diseases, allowing for better direction of global health efforts. C1 [Agarwal-Harding, Kiran J.] Massachusetts Gen Hosp, Harvard Combined Orthopaed Residency Program, Boston, MA 02114 USA. [Meara, John G.; Greenberg, Sarah L. M.] Harvard Univ, Sch Med, Program Global Surg & Social Change, Boston, MA 02115 USA. [Zurakowski, David] Boston Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA. [Zurakowski, David] Boston Childrens Hosp, Dept Surg, Boston, MA 02115 USA. [Hagander, Lars E.] Lund Univ, Childrens Hosp, Dept Clin Sci, Int Pediat & Pediat Surg, SE-22100 Lund, Sweden. [Dyer, George S. M.] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. RP Agarwal-Harding, KJ (reprint author), Massachusetts Gen Hosp, Harvard Combined Orthopaed Residency Program, 55 Fruit St, Boston, MA 02114 USA. EM gdyer@partners.org NR 33 TC 6 Z9 7 U1 1 U2 2 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 EI 1535-1386 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAR 18 PY 2015 VL 97A IS 6 AR e31 DI 10.2106/JBJS.N.00314 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CM4PC UT WOS:000357665900002 PM 25788312 ER PT J AU Wynn, JK Roach, BJ Lee, J Horan, WP Ford, JM Jimenez, AM Green, MF AF Wynn, Jonathan K. Roach, Brian J. Lee, Junghee Horan, William P. Ford, Judith M. Jimenez, Amy M. Green, Michael F. TI EEG Findings of Reduced Neural Synchronization during Visual Integration in Schizophrenia SO PLOS ONE LA English DT Article ID GESTALT PERCEPTION; ILLUSORY CONTOURS; BIPOLAR DISORDER; CORTEX; INTERNEURONS; COMPLETION; MODULATION; FREQUENCY; RESPONSES; COGNITION AB Schizophrenia patients exhibit well-documented visual processing deficits. One area of disruption is visual integration, the ability to form global objects from local elements. However, most studies of visual integration in schizophrenia have been conducted in the context of an active attention task, which may influence the findings. In this study we examined visual integration using electroencephalography (EEG) in a passive task to elucidate neural mechanisms associated with poor visual integration. Forty-six schizophrenia patients and 30 healthy controls had EEG recorded while passively viewing figures comprised of real, illusory, or no contours. We examined visual P100, N100, and P200 event-related potential (ERP) components, as well as neural synchronization in the gamma (30-60 Hz) band assessed by the EEG phase locking factor (PLF). The N100 was significantly larger to illusory vs. no contour, and illusory vs. real contour stimuli while the P200 was larger only to real vs. illusory stimuli; there were no significant interactions with group. Compared to controls, patients failed to show increased phase locking to illusory versus no contours between 40-60 Hz. Also, controls, but not patients, had larger PLF between 30-40 Hz when viewing real vs. illusory contours. Finally, the positive symptom factor of the BPRS was negatively correlated with PLF values between 40-60 Hz to illusory stimuli, and with PLF between 30-40 Hz to real contour stimuli. These results suggest that the pattern of results across visual processing conditions is similar in patients and controls. However, patients have deficits in neural synchronization in the gamma range during basic processing of illusory contours when attentional demand is limited. C1 [Wynn, Jonathan K.; Lee, Junghee; Horan, William P.; Jimenez, Amy M.; Green, Michael F.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Wynn, Jonathan K.; Lee, Junghee; Horan, William P.; Green, Michael F.] Univ Calif Los Angeles, Psychiat & Biobehav Sci, Los Angeles, CA USA. [Roach, Brian J.; Ford, Judith M.] Vet Affairs San Francisco Med Ctr, San Francisco, CA USA. [Ford, Judith M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Wynn, JK (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. EM jkwynn@ucla.edu RI Lee, Junghee/C-5226-2014; Wynn, Jonathan/H-3749-2014 OI Lee, Junghee/0000-0001-9567-8700; Wynn, Jonathan/0000-0002-1763-8540 FU VA Career Development Award; NIMH [MH43292, MH065707] FX Support for this study came from a VA Career Development Award to Jonathan K. Wynn, Ph.D., and NIMH Grants MH43292 and MH065707 (PI: Michael F. Green, Ph.D). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 2 Z9 2 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 18 PY 2015 VL 10 IS 3 AR e0119849 DI 10.1371/journal.pone.0119849 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE9BN UT WOS:000352138500134 PM 25785939 ER PT J AU French, B Small, DS Novak, J Saulsgiver, KA Harhay, MO Asch, DA Volpp, KG Halpern, SD AF French, Benjamin Small, Dylan S. Novak, Julie Saulsgiver, Kathryn A. Harhay, Michael O. Asch, David A. Volpp, Kevin G. Halpern, Scott D. TI Preference-adaptive randomization in comparative effectiveness studies SO TRIALS LA English DT Article DE Adaptive design; Adherence; Comparative effectiveness research; Efficacy; Instrumental variables ID CONTROLLED CLINICAL-TRIAL; PLAY-WINNER RULE; FINANCIAL INCENTIVES; DESIGNS AB Background: Determination of comparative effectiveness in a randomized controlled trial requires consideration of an intervention's comparative uptake (or acceptance) among randomized participants and the intervention's comparative efficacy among participants who use their assigned intervention. If acceptance differs across interventions, then simple randomization of participants can result in post-randomization losses that introduce bias and limit statistical power. Methods: We develop a novel preference-adaptive randomization procedure in which the allocation probabilities are updated based on the inverse of the relative acceptance rates among randomized participants in each arm. In simulation studies, we determine the optimal frequency with which to update the allocation probabilities based on the number of participants randomized. We illustrate the development and application of preference-adaptive randomization using a randomized controlled trial comparing the effectiveness of different financial incentive structures on prolonged smoking cessation. Results: Simulation studies indicated that preference-adaptive randomization performed best with frequent updating, accommodated differences in acceptance across arms, and performed well even if the initial values for the allocation probabilities were not equal to their true values. Updating the allocation probabilities after randomizing each participant minimized imbalances in the number of accepting participants across arms over time. In the smoking cessation trial, unexpectedly large differences in acceptance among arms required us to limit the allocation of participants to less acceptable interventions. Nonetheless, the procedure achieved equal numbers of accepting participants in the more acceptable arms, and balanced the characteristics of participants across assigned interventions. Conclusions: Preference-adaptive randomization, coupled with analysis methods based on instrumental variables, can enhance the validity and generalizability of comparative effectiveness studies. In particular, preference-adaptive randomization augments statistical power by maintaining balanced sample sizes in efficacy analyses, while retaining the ability of randomization to balance covariates across arms in effectiveness analyses. C1 [French, Benjamin; Saulsgiver, Kathryn A.; Harhay, Michael O.; Halpern, Scott D.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Small, Dylan S.; Novak, Julie] Univ Penn, Dept Stat, Philadelphia, PA 19104 USA. [Asch, David A.; Volpp, Kevin G.; Halpern, Scott D.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Asch, David A.; Volpp, Kevin G.] Univ Penn, Dept Hlth Care Management, Philadelphia, PA 19104 USA. [Asch, David A.; Volpp, Kevin G.; Halpern, Scott D.] Univ Penn, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. [Asch, David A.; Volpp, Kevin G.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. RP French, B (reprint author), Univ Penn, Dept Biostat & Epidemiol, 423 Guardian Dr, Philadelphia, PA 19104 USA. EM bcfrench@upenn.edu OI Harhay, Michael/0000-0002-0553-674X FU National Institutes of Health [R01-CA159932, RC2-AG036592] FX This work was supported by the National Institutes of Health (grant numbers R01-CA159932 and RC2-AG036592), which had no role in design; in the collection, analysis or interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. NR 27 TC 3 Z9 3 U1 3 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6215 J9 TRIALS JI Trials PD MAR 18 PY 2015 VL 16 AR 99 DI 10.1186/s13063-015-0592-6 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CF0XL UT WOS:000352267700001 PM 25887045 ER PT J AU Richter, T Bergmann, R Musch, G Pietzsch, J Koch, T AF Richter, Torsten Bergmann, Ralf Musch, Guido Pietzsch, Jens Koch, Thea TI Reduced pulmonary blood flow in regions of injury 2 hours after acid aspiration in rats SO BMC ANESTHESIOLOGY LA English DT Article DE Acute lung injury; Respiratory aspiration; Positron emission tomography; Pulmonary circulation; Pulmonary perfusion; Adult respiratory distress syndrome ID ACUTE LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; PRONE POSITION; PERFUSION; VASOCONSTRICTION; PATHOGENESIS; PNEUMONITIS; VENTILATION; EDEMA AB Background: Aspiration-induced lung injury can decrease gas exchange and increase mortality. Acute lung injury following acid aspiration is characterized by elevated pulmonary blood flow (PBF) in damaged lung areas in the early inflammation stage. Knowledge of PBF patterns after acid aspiration is important for targeting intravenous treatments. We examined PBF in an experimental model at a later stage (2 hours after injury). Methods: Anesthetized Wistar-Unilever rats (n = 5) underwent unilateral endobronchial instillation of hydrochloric acid. The PBF distribution was compared between injured and uninjured sides and with that of untreated control animals (n = 6). Changes in lung density after injury were measured using computed tomography (CT). Regional PBF distribution was determined quantitatively in vivo 2 hours after acid instillation by measuring the concentration of [Ga-68]-radiolabeled microspheres using positron emission tomography. Results: CT scans revealed increased lung density in areas of acid aspiration. Lung injury was accompanied by impaired gas exchange. Acid aspiration decreased the arterial pressure of oxygen from 157 mmHg [139; 165] to 74 mmHg [67; 86] at 20 minutes and tended toward restoration to 109 mmHg [69; 114] at 110 minutes (P < 0.001). The PBF ratio of the middle region of the injured versus uninjured lungs of the aspiration group (0.86 [0.7; 0.9], median [25%; 75%]) was significantly lower than the PBF ratio in the left versus right lung of the control group (1.02 [1.0;1.05]; P = 0.016). Conclusions: The PBF pattern 2 hours after aspiration-induced lung injury showed a redistribution of PBF away from injured regions that was likely responsible for the partial recovery from hypoxemia over time. Treatments given intravenously 2 hours after acid-induced lung injury may not preferentially reach the injured lung regions, contrary to what occurs during the first hour of inflammation. C1 [Richter, Torsten; Koch, Thea] Tech Univ Dresden, Carl Gustav Carus Univ Hosp, Dept Anesthesia & Intens Care, D-01062 Dresden, Germany. [Bergmann, Ralf; Pietzsch, Jens] Helmholtz Zentrum Dresden Rossendorf, Inst Radiopharmaceut Canc Res, Dept Radiopharmaceut & Chem Biol, D-01314 Dresden, Germany. [Musch, Guido] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Musch, Guido] Harvard Univ, Sch Med, Boston, MA USA. [Pietzsch, Jens] Tech Univ Dresden, Dept Chem & Food Chem, D-01062 Dresden, Germany. RP Richter, T (reprint author), Tech Univ Dresden, Carl Gustav Carus Univ Hosp, Dept Anesthesia & Intens Care, D-01062 Dresden, Germany. EM torsten.richter@uniklinikum-dresden.de OI Pietzsch, Jens/0000-0002-1610-1493 FU National Institutes of Health [R01HL094639] FX Funding support was provided by institutional and departmental sources. Guido Musch was supported by grant R01HL094639 from the National Institutes of Health. The study was conducted at Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany. NR 41 TC 1 Z9 1 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2253 J9 BMC ANESTHESIOL JI BMC Anesthesiol. PD MAR 18 PY 2015 VL 15 AR 36 DI 10.1186/s12871-015-0013-0 PG 9 WC Anesthesiology SC Anesthesiology GA CE0KP UT WOS:000351493200001 PM 25805960 ER PT J AU Vanduffel, W Arsenault, JT AF Vanduffel, Wim Arsenault, John T. TI Noisy Neurons, Neat Networks SO NEURON LA English DT Editorial Material ID CORTEX; ORGANIZATION; HUMANS; BRAIN AB In this issue of Neuron, Kiani et al. (2015) show that the correlated activity of multiple simultaneously recorded neurons can be used to identify, in a completely un-biased manner, distinct functional domains within prefrontal and (pre)motor cortex of macaque monkeys. C1 [Vanduffel, Wim; Arsenault, John T.] KU Leuven Med Sch, Dept Neurosci, Lab Neuro & Psychophysiol, B-3000 Leuven, Belgium. [Vanduffel, Wim; Arsenault, John T.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Vanduffel, Wim] Harvard Univ, Dept Radiol, Sch Med, Boston, MA 02144 USA. RP Vanduffel, W (reprint author), KU Leuven Med Sch, Dept Neurosci, Lab Neuro & Psychophysiol, B-3000 Leuven, Belgium. EM wim@nmr.mgh.harvard.edu NR 13 TC 0 Z9 0 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD MAR 18 PY 2015 VL 85 IS 6 BP 1155 EP 1157 DI 10.1016/j.neuron.2015.03.001 PG 3 WC Neurosciences SC Neurosciences & Neurology GA CD8BA UT WOS:000351319000004 PM 25789752 ER PT J AU Bollinger, MJ Schmidt, S Pugh, JA Parsons, HM Copeland, LA Pugh, MJ AF Bollinger, Mary J. Schmidt, Susanne Pugh, Jacqueline A. Parsons, Helen M. Copeland, Laurel A. Pugh, Mary Jo TI Erosion of the healthy soldier effect in veterans of US military service in Iraq and Afghanistan SO POPULATION HEALTH METRICS LA English DT Article DE Veterans/statistics & numerical data; Mortality; Healthy soldier effect ID PERSIAN-GULF-WAR; RISK-FACTORS; MORTALITY; DEPLOYMENT; DISABILITY; CONFLICT; SUICIDE; RATIOS AB Background: This research explores the healthy soldier effect (HSE) - a lower mortality risk among veterans relative to the general population-in United States (US) veterans deployed in support of operations in Iraq and Afghanistan (OEF/OIF/OND). While a HSE has been affirmed in other OEF/OIF/OND populations, US veterans of OEF/OIF/OND have not been systematically studied. Methods: Using US Department of Veterans Affairs (VA) administrative data, we identified veterans who (1) had been deployed in support of OEF/OIF/OND between 2002 and 2011 and (2) were enrolled in the VA health care system. We divided the VA population into VA health care utilizers and non-utilizers. We obtained Department of Defense (DOD) administrative data on the OEF/OIF/OND population and obtained VA and DOD mortality data excluding combat deaths from the analyses. Indirect standardization was used to compare VA and DOD cohorts to the US population using total population at risk to compute the Standardized Mortality Ratio (SMR). A directly standardized relative risk (DSRR) was calculated to enable comparisons between cohorts. To compare VA enrollee mortality on military specific characteristics, we used a DOD population standard. Results: The overall VA SMR of 2.8 (95% Confidence Interval [CI] 2.8-2.9), VA utilizer SMR of 3.2 (95% CI 3.1-3.3), VA non-utilizer SMR of 0.9 (95% CI 0.8-1.1), and DOD SMR of 1.5 (95% CI 1.4-1.5) provide no evidence of a HSE in any cohort relative to the US standard population. Relative to DOD, both the total VA population SMR of 2.1 (95% CI 2.0-2.2) and the SMR for VA utilizers of 2.3 (95% CI 2.3-2.4) indicate mortality twice what would be expected given DOD mortality rates. In contrast, the VA enrollees who had not used clinical services had 40% lower than expected mortality relative to DOD. Conclusions: No support was found for the HSE among US veterans of OEF/OIF/OND. These findings may be attributable to a number of factors including post-deployment risk-taking behavior, an abbreviated follow up period, and the nature of the OEF/OIF/OND conflict. C1 [Bollinger, Mary J.; Pugh, Jacqueline A.; Pugh, Mary Jo] South Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. [Bollinger, Mary J.; Pugh, Jacqueline A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hosp Med, San Antonio, TX 78229 USA. [Schmidt, Susanne; Parsons, Helen M.; Pugh, Mary Jo] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Copeland, Laurel A.] Cent Texas Vet Hlth Care Syst, Dept Vet Affairs, Temple, TX 76504 USA. [Copeland, Laurel A.] Baylor Scott & White Hlth, Ctr Appl Hlth Res, Temple, TX 76502 USA. RP Bollinger, MJ (reprint author), South Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. EM bollinger@uthscsa.edu OI Pugh, Jacqueline/0000-0003-4933-141X; Copeland, Laurel/0000-0002-9478-0209 FU Department of Veterans Affairs, Veterans Administration, Office of Research and Development, VA Health Services Research and Development Service [DHI 09-237]; South Texas Veterans Health care System/Audie L. Murphy Division FX This material is based upon work supported by the Department of Veterans Affairs, Veterans Administration, Office of Research and Development, VA Health Services Research and Development Service (DHI 09-237; Dr. MJ Pugh PI). The funding agency had no role in data collection, analysis, or manuscript development. The authors acknowledge and appreciate support from the South Texas Veterans Health care System/Audie L. Murphy Division. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 34 TC 3 Z9 3 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-7954 J9 POPUL HEALTH METR JI Popul. Health Metr. PD MAR 18 PY 2015 VL 13 AR 8 DI 10.1186/s12963-015-0040-6 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CD7MA UT WOS:000351273300001 PM 25798075 ER PT J AU Watanabe, R Gehad, A Yang, C Scott, LL Teague, JE Schlapbach, C Elco, CP Huang, V Matos, TR Kupper, TS Clark, RA AF Watanabe, Rei Gehad, Ahmed Yang, Chao Scott, Laura L. Teague, Jessica E. Schlapbach, Christoph Elco, Christopher P. Huang, Victor Matos, Tiago R. Kupper, Thomas S. Clark, Rachael A. TI Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID SEZARY-SYNDROME; CYTOKINE PRODUCTION; PERIPHERAL-TISSUES; SUBSETS; LYMPHOMA; PSORIASIS; INFECTION; IMMUNITY; VIRUS; ALEMTUZUMAB AB The skin of an adult human contains about 20 billion memory T cells. Epithelial barrier tissues are infiltrated by a combination of resident and recirculating T cells in mice, but the relative proportions and functional activities of resident versus recirculating T cells have not been evaluated in human skin. We discriminated resident from recirculating T cells in human-engrafted mice and lymphoma patients using alemtuzumab, a medication that depletes recirculating T cells from skin, and then analyzed these T cell populations in healthy human skin. All nonrecirculating resident memory T cells (T-RM) expressed CD69, but most were CD4(+), CD103(-), and located in the dermis, in contrast to studies in mice. Both CD4(+) and CD8(+) CD103(+) T-RM were enriched in the epidermis, had potent effector functions, and had a limited proliferative capacity compared to CD103(-) T-RM. T-RM of both types had more potent effector functions than recirculating T cells. We observed two distinct populations of recirculating T cells, CCR7(+)/L-selectin(+) central memory T cells (T-CM) and CCR7(+)/L-selectin(-) T cells, which we term migratory memory T cells (T-MM). Circulating skin-tropic T-MM were intermediate in cytokine production between T-CM and effector memory T cells. In patients with cutaneous T cell lymphoma, malignant T-CM and T-MM induced distinct inflammatory skin lesions, and T-MM were depleted more slowly from skin after alemtuzumab, suggesting that T-MM may recirculate more slowly. In summary, human skin is protected by four functionally distinct populations of T cells, two resident and two recirculating, with differing territories of migration and distinct functional activities. C1 [Watanabe, Rei; Gehad, Ahmed; Yang, Chao; Scott, Laura L.; Teague, Jessica E.; Huang, Victor; Matos, Tiago R.; Kupper, Thomas S.; Clark, Rachael A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Schlapbach, Christoph] Univ Bern, Inselspital, Dept Dermatol, CH-3010 Bern, Switzerland. [Elco, Christopher P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Matos, Tiago R.] Univ Lisbon, Fac Med, Inst Med Mol, P-1699 Lisbon, Portugal. [Kupper, Thomas S.; Clark, Rachael A.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. RP Clark, RA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA. EM rclark1@partners.org OI Matos, Tiago R./0000-0003-2864-8207 FU NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [R01 AR063962]; NIH/NIAMS [R01 AR056720]; Damon Runyon Clinical Investigator Award; SPORE in Skin Cancer NIH/National Cancer Institute [P50 CA9368305]; National Institute of Allergy and Infectious Diseases [R01 AI097128]; Special Scholar Grant from the Leukemia and Lymphoma Society; Swiss National Science Foundation; Fondation Rene Touraine FX This work was supported by a generous charitable contribution from Edward P. Lawrence, Esq., R01 AR063962 NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (to R.A.C.), R01 AR056720 NIH/NIAMS (to R.A.C.), a Damon Runyon Clinical Investigator Award (to R.A.C.), the SPORE in Skin Cancer P50 CA9368305 NIH/National Cancer Institute (to T.S.K.), and R01 AI097128 National Institute of Allergy and Infectious Diseases (to T.S.K. and R.A.C.). R.W. salary support was provided by a Special Scholar Grant from the Leukemia and Lymphoma Society. Salary support for C.S. was provided by the Swiss National Science Foundation and the Fondation Rene Touraine. NR 35 TC 41 Z9 41 U1 4 U2 13 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD MAR 18 PY 2015 VL 7 IS 279 AR 279ra39 DI 10.1126/scitranslmed.3010302 PG 13 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CD9UH UT WOS:000351443500008 PM 25787765 ER PT J AU Keller, BM McCarthy, AM Chen, J Armstrong, K Conant, EF Domchek, SM Kontos, D AF Keller, Brad M. McCarthy, Anne Marie Chen, Jinbo Armstrong, Katrina Conant, Emily F. Domchek, Susan M. Kontos, Despina TI Associations between breast density and a panel of single nucleotide polymorphisms linked to breast cancer risk: a cohort study with digital mammography SO BMC CANCER LA English DT Article DE Breast density; Breast cancer; Genetic risk factors; Single-nucleotide polymorphisms; Race-stratified; Association study ID GENOME-WIDE ASSOCIATION; AFRICAN-AMERICAN WOMEN; COMMON GENETIC-VARIANTS; SUSCEPTIBILITY LOCI; MULTIPLE IMPUTATION; CONFER SUSCEPTIBILITY; DIGITIZED MAMMOGRAMS; SCREENING POPULATION; PREDICTION MODEL; CHROMOSOME 5P12 AB Background: Breast density and single-nucleotide polymorphisms (SNPs) have both been associated with breast cancer risk. To determine the extent to which these two breast cancer risk factors are associated, we investigate the association between a panel of validated SNPs related to breast cancer and quantitative measures of mammographic density in a cohort of Caucasian and African-American women. Methods: In this IRB-approved, HIPAA-compliant study, we analyzed a screening population of 639 women (250 African American and 389 Caucasian) who were tested with a validated panel assay of 12 SNPs previously associated to breast cancer risk. Each woman underwent digital mammography as part of routine screening and all were interpreted as negative. Both absolute and percent estimates of area and volumetric density were quantified on a per-woman basis using validated software. Associations between the number of risk alleles in each SNP and the density measures were assessed through a race-stratified linear regression analysis, adjusted for age, BMI, and Gail lifetime risk. Results: The majority of SNPs were not found to be associated with any measure of breast density. SNP rs3817198 (in LSP1) was significantly associated with both absolute area (p = 0.004) and volumetric (p = 0.019) breast density in Caucasian women. In African-American women, SNPs rs3803662 (in TNRC9/TOX3) and rs4973768 (in NEK10) were significantly associated with absolute (p = 0.042) and percent (p = 0.028) volume density respectively. Conclusions: The majority of SNPs investigated in our study were not found to be significantly associated with breast density, even when accounting for age, BMI, and Gail risk, suggesting that these two different risk factors contain potentially independent information regarding a woman's risk to develop breast cancer. Additionally, the few statistically significant associations between breast density and SNPs were different for Caucasian versus African American women. Larger prospective studies are warranted to validate our findings and determine potential implications for breast cancer risk assessment. C1 [Keller, Brad M.; Conant, Emily F.; Kontos, Despina] Univ Penn, Dept Radiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [McCarthy, Anne Marie; Armstrong, Katrina] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Chen, Jinbo] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Domchek, Susan M.] Univ Penn, Dept Biostat & Epidemiol, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Kontos, D (reprint author), Univ Penn, Dept Radiol, Perelman Sch Med, 3600 Market St Ste 360, Philadelphia, PA 19104 USA. EM despina.kontos@uphs.upenn.edu FU National Cancer Institute [1U54CA163313-01, UC2CA148310]; American Cancer Society [RSGHP-CPHPS-119586]; Susan G. Komen for the Cure Foundation [SAC100003, PDF14299284] FX This work was supported in part by the National Cancer Institute (1U54CA163313-01 and UC2CA148310), the American Cancer Society (RSGHP-CPHPS-119586), and the Susan G. Komen for the Cure Foundation (SAC100003 and PDF14299284). NR 83 TC 3 Z9 3 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD MAR 18 PY 2015 VL 15 AR 143 DI 10.1186/s12885-015-1159-3 PG 12 WC Oncology SC Oncology GA CD5KU UT WOS:000351127300001 PM 25881232 ER PT J AU Price, RL Chiocca, EA AF Price, Richard Lee Chiocca, Ennio Antonio TI Modeling cytomegalovirus infection in mouse tumor models SO FRONTIERS IN ONCOLOGY LA English DT Article DE cytomegalovirus; malignant glioma; glioblastoma; rhabdomyosarcoma; mouse model; oncomodulatory ID MURINE CYTOMEGALOVIRUS; DNA-SEQUENCE; GLIOBLASTOMA; MICE; GLIOMAS; CARCINOMA; BRAIN; CELLS; ASTROCYTOMAS; LOCALIZATION AB The hypothesis that cytomegalovirus (CMV) modulates cancer is evolving. Originally discovered in glioblastoma in 2002, the number of cancers, where intratumoral CMV antigen is detected, has increased in recent years suggesting that CMV actively affects the pathobiology of certain tumors. These findings are controversial as several groups have also reported inability to replicate these results. Regardless, several clinical trials for glioblastoma are underway or have been completed that target intratumoral CMV with anti-viral drugs or immunotherapy. Therefore, a better understanding of the possible pathobiology of CMV in cancer needs to be ascertained. We have developed genetic, syngeneic, and orthotopic malignant glioma mouse models to study the role of CMV in cancer development and progression. These models recapitulate for the most part intratumoral CMV expression as seen in human tumors. Additionally, we discovered that CMV infection in Trp53-i+ mice promotes pleomorphic rhabdomyosarcomas. These mouse models are not only a vehicle for studying pathobiology of the viral-tumor interaction but also a platform for developing and testing cancer therapeutics. C1 [Price, Richard Lee] Washington Univ, Dept Neurol Surg, St Louis, MO USA. [Chiocca, Ennio Antonio] Brigham & Womens Faulkner Hosp, Dept Neurosurg, Harvard Inst Med, Harvey Cushing Neurooncol Labs, Boston, MA USA. [Chiocca, Ennio Antonio] Brigham & Womens Faulkner Hosp, Inst Neurosci, Boston, MA USA. [Chiocca, Ennio Antonio] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RP Chiocca, EA (reprint author), Brigham & Womens Hosp, Dept Neurosurg, 75 Francis St,PBB-301, Boston, MA 02115 USA. EM eachiocca@partners.org NR 42 TC 1 Z9 1 U1 0 U2 1 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 2234-943X J9 FRONT ONCOL JI Front. Oncol. PD MAR 17 PY 2015 VL 5 AR 61 DI 10.3389/fonc.2015.00061 PG 8 WC Oncology SC Oncology GA CO3TP UT WOS:000359082900001 PM 25853089 ER PT J AU Gounder, K Padayachi, N Mann, JK Radebe, M Mokgoro, M van der Stok, M Mkhize, L Mncube, Z Jaggernath, M Reddy, T Walker, BD Ndung'u, T AF Gounder, Kamini Padayachi, Nagavelli Mann, Jaclyn K. Radebe, Mopo Mokgoro, Mammekwa van der Stok, Mary Mkhize, Lungile Mncube, Zenele Jaggernath, Manjeetha Reddy, Tarylee Walker, Bruce D. Ndung'u, Thumbi TI High Frequency of Transmitted HIV-1 Gag HLA Class I-Driven Immune Escape Variants but Minimal Immune Selection over the First Year of Clade C Infection SO PLOS ONE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; VIRAL LOAD; DISEASE PROGRESSION; REPLICATION CAPACITY; LYMPHOCYTE ESCAPE; MALE CIRCUMCISION; TYPE-1 INFECTION; CONTROLLED-TRIAL; RHESUS-MONKEYS AB In chronic HIV infection, CD8+ T cell responses to Gag are associated with lower viral loads, but longitudinal studies of HLA-restricted CD8+ T cell-driven selection pressure in Gag from the time of acute infection are limited. In this study we examined Gag sequence evolution over the first year of infection in 22 patients identified prior to seroconversion. A total of 310 and 337 full-length Gag sequences from the earliest available samples (median = 14 days after infection [Fiebig stage I/II]) and at one-year post infection respectively were generated. Six of 22 (27%) individuals were infected with multiple variants. There was a trend towards early intra-patient viral sequence diversity correlating with viral load set point (p = 0.07, r = 0.39). At 14 days post infection, 59.7% of Gag CTL epitopes contained non-consensus polymorphisms and over half of these (35.3%) comprised of previously described CTL escape variants. Consensus and variant CTL epitope proportions were equally distributed irrespective of the selecting host HLA allele and most epitopes remained unchanged over 12 months post infection. These data suggest that intrapatient diversity during acute infection is an indicator of disease outcome. In this setting, there is a high rate of transmitted CTL escape variants and limited immune selection in Gag during the first year of infection. These data have relevance for vaccine strategies designed to elicit effective CD8+ T cell immune responses. C1 [Gounder, Kamini; Padayachi, Nagavelli; Mann, Jaclyn K.; Radebe, Mopo; Mokgoro, Mammekwa; van der Stok, Mary; Mkhize, Lungile; Mncube, Zenele; Jaggernath, Manjeetha; Walker, Bruce D.; Ndung'u, Thumbi] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. [Gounder, Kamini; Padayachi, Nagavelli; Mann, Jaclyn K.; Radebe, Mopo; Mokgoro, Mammekwa; van der Stok, Mary; Mkhize, Lungile; Mncube, Zenele; Jaggernath, Manjeetha; Ndung'u, Thumbi] Univ KwaZulu Natal, Nelson R Mandela Sch Med, KwaZulu Natal Res Inst TB & HIV, Durban, South Africa. [Reddy, Tarylee] MRC, Biostat Unit, Durban, South Africa. [Walker, Bruce D.; Ndung'u, Thumbi] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Walker, Bruce D.; Ndung'u, Thumbi] Harvard Univ, Boston, MA 02115 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Ndung'u, Thumbi] Max Planck Inst Infect Biol, Berlin, Germany. RP Ndung'u, T (reprint author), Univ KwaZulu Natal, Nelson R Mandela Sch Med, Doris Duke Med Res Inst, HIV Pathogenesis Programme, 719 Umbilo Rd, Durban, South Africa. EM ndungu@ukzn.ac.za OI Ndung'u, Thumbi/0000-0003-2962-3992 FU National Institutes of Health (NIH) [RO1 AI067073-02]; South African NRF/DST (Ndung'u); Gates Foundation, IAVI; Victor Daitz Chair in HIV/TB Research; International Early Career Scientist Award from the Howard Hughes Medical Institute; NIH Fogarty International Clinical Research Fellows (FICRF); Medical Research Council; K-RITH Collaborative grant award; National Research Foundation; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology; Harvard University; UNESCO/ L'Oreal Corporate Foundation fellowship; Technology Innovation Agency of the Department of Science and Technology of South Africa; Victor Daitz Information Gateway; initiative of the Victor Daitz Foundation; University of KwaZulu-Natal FX This research was supported by National Institutes of Health (NIH) grants RO1 AI067073-02 (Walker), South African NRF/DST (Ndung'u), Gates Foundation, IAVI. Partial funding was also received from the Victor Daitz Chair in HIV/TB Research and an International Early Career Scientist Award from the Howard Hughes Medical Institute to TN. KG was funded by the NIH Fogarty International Clinical Research Fellows (FICRF), Medical Research Council and K-RITH Collaborative grant award. JKM was supported by the National Research Foundation and the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University. MR was funded by a UNESCO/ L'Oreal Corporate Foundation fellowship and the Technology Innovation Agency of the Department of Science and Technology of South Africa. Open Access publication of this article has been made possible through support from the Victor Daitz Information Gateway, an initiative of the Victor Daitz Foundation and the University of KwaZulu-Natal. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 89 TC 2 Z9 2 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 17 PY 2015 VL 10 IS 3 AR e0119886 DI 10.1371/journal.pone.0119886 PG 23 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CD7QC UT WOS:000351284600105 PM 25781986 ER PT J AU Liu, X Zhu, L Liao, S Xu, ZW Zhou, YC AF Liu, Xiao Zhu, Ling Liao, Shan Xu, Zhiwen Zhou, Yuancheng TI The Porcine MicroRNA Transcriptome Response to Transmissible Gastroenteritis Virus Infection SO PLOS ONE LA English DT Article ID HIV-1 TAR ELEMENT; RESPIRATORY CORONAVIRUS; CAENORHABDITIS-ELEGANS; GENE-EXPRESSION; MESSENGER-RNAS; DROSOPHILA; TARGETS; DIFFERENTIATION; PATHOGENESIS; RECOGNITION AB Transmissible gastroenteritis virus (TGEV; Coronaviridae family) causes huge economic losses to the swine industry. MicroRNAs (miRNAs) play a regulatory role in viral infection and may be involved in the mammalian immune response. Here, we report a comprehensive analysis of host miRNA expression in TGEV-infected swine testis (ST) cells. Deep sequencing generated 3,704,353 and 2,763,665 reads from uninfected ST cells and infected ST cells, respectively. The reads were aligned to known Sus scrofa pre-miRNAs in miR-Base 19, identifying 284 annotated miRNAs. Certain miRNAs were differentially regulated during TGEV infection. 59 unique miRNAs displayed significant differentially expression between the normal and TGEV-infected ST cell samples: 15 miRNAs were significantly up-regulated and 44 were significantly down-regulated. Stem-loop RT-PCR was carried out to determine the expression levels of specific miRNAs in the two samples, and the results were consistent with those of sequencing. Gene ontology enrichment analysis of host target genes demonstrated that the differentially expressed miRNAs are involved in regulatory networks, including cellular process, metabolic process, immune system process. This is the first report of the identification of ST cell miRNAs and the comprehensive analysis of the miRNA regulatory mechanism during TGEV infection, which revealed the miRNA molecular regulatory mechanisms for the viral infection, expression of viral genes and the expression of immune-related genes. The results presented here will aid research on the prevention and treatment of viral diseases. C1 [Liu, Xiao; Zhu, Ling; Liao, Shan; Xu, Zhiwen; Zhou, Yuancheng] Sichuan Agr Univ, Coll Vet Med, Anim Biotechnol Ctr, Yaan, Peoples R China. [Xu, Zhiwen] Sichuan Agr Univ, Coll Vet Med, Key Lab Anim Dis & Human Hlth, Yaan, Peoples R China. [Liu, Xiao] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Liver, Boston, MA USA. [Liu, Xiao] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Div,Dept Med, Boston, MA USA. RP Xu, ZW (reprint author), Sichuan Agr Univ, Coll Vet Med, Anim Biotechnol Ctr, Yaan, Peoples R China. EM abtcxzw@126.com OI Zhou, Yuancheng/0000-0001-5295-826X FU Program for New Century Excellent Talents in University of Ministry of Education of China [NCET-11-1059]; program for Changjiang Scholars and Innovative Research Team in University [IRT13083]; Sichuan Youth Waterfowl Disease Control and Prevention Science and Technology Innovative Research Team [2013TD0015]; Excellent Doctoral Dissertation Fostering Foundation of Sichuan Agricultural University FX This study was supported by the Program for New Century Excellent Talents in University of Ministry of Education of China (Project No: NCET-11-1059), program for Changjiang Scholars and Innovative Research Team in University (Project No: IRT13083), Sichuan Youth Waterfowl Disease Control and Prevention Science and Technology Innovative Research Team (Project No: 2013TD0015), and by the Excellent Doctoral Dissertation Fostering Foundation of Sichuan Agricultural University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 1 Z9 1 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 17 PY 2015 VL 10 IS 3 AR e0120377 DI 10.1371/journal.pone.0120377 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CD7QC UT WOS:000351284600157 PM 25781021 ER PT J AU Najafzadeh, M Andersson, K Shrank, WH Krumme, AA Matlin, OS Brennan, T Avorn, J Choudhry, NK AF Najafzadeh, Mehdi Andersson, Karin Shrank, William H. Krumme, Alexis A. Matlin, Olga S. Brennan, Troyen Avorn, Jerry Choudhry, Niteesh K. TI Cost-Effectiveness of Novel Regimens for the Treatment of Hepatitis C Virus SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID GENOTYPE 1 INFECTION; DISCRETE-EVENT SIMULATION; ACTING ANTIVIRAL THERAPY; TREATMENT-NAIVE PATIENTS; UNITED-STATES; CHRONIC HCV; FIBROSIS PROGRESSION; PLUS SOFOSBUVIR; ALCOHOL-USE; RIBAVIRIN AB Background: New regimens for hepatitis C virus (HCV) have shorter treatment durations and increased rates of sustained virologic response compared with existing therapies but are extremely expensive. Objective: To evaluate the cost-effectiveness of these treatments under different assumptions about their price and efficacy. Design: Discrete-event simulation. Data Sources: Published literature. Target Population: Treatment-naive patents infected with chronic HCV genotype 1, 2, or 3. Time Horizon: Lifetime. Perspective: Societal. Intervention: Usual care (boceprevir-ribavirin-pegylated interferon [PEG]) was compared with sofosbuvir-ribavirin-PEG and 3 PEG-free regimens: sofosbuvir-simeprevir, sofosbuvir-daclatasvir, and sofosbuvir-ledipasvir. For genotypes 2 and 3, usual care (ribavirin-PEG) was compared with sofosbuvir-ribavirin, sofosbuvir-daclatasvir, and sofosbuvir-ledipasvir-ribavirin (genotype 3 only). Outcome Measures: Discounted costs (in 2014 U.S. dollars), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Results of Base-Case Analysis: Assuming sofosbuvir, simeprevir, daclatasvir, and ledipasvir cost $7000, $5500, $5500, and $875 per week, respectively, sofosbuvir-ledipasvir was cost-effective for genotype 1 and cost $12 825 more per OALY than usual care. For genotype 2, sofosbuvir-ribavirin and sofosbuvir-daclatasvir cost $110000 and $691 000 per QALY, respectively. For genotype 3, sofosbuvir-ledipasvir-ribavirin cost $73 000 per QALY, sofosbuvir-ribavirin was more costly and less effective than usual care, and sofosbuvir-daclatasvir cost more than $396 000 per QALY at assumed prices. Results of Sensitivity Analysis: Sofosbuvir-ledipasvir was the optimal strategy in most simulations for genotype 1 and would be cost-saving if sofosbuvir cost less than $5500. For genotype 2, sofosbuvir-ribavirin-PEG would be cost-saving if sofosbuvir cost less than $2250 per week. For genotype 3, sofosbuvir-ledipasvir-ribavirin would be cost-saving if sofosbuvir cost less than $1500 per week. Limitation: Data are lacking on real-world effectiveness of new treatments and some prices. Conclusion: From a societal perspective, novel treatments for HCV are cost-effective compared with usual care for genotype 1 and probably genotype 3 but not for genotype 2. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02120 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. CVS Hlth, Woonsocket, RI USA. RP Choudhry, NK (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA. EM mnajafzadeh@partners.org; nchoudhry@partners.org FU CVS Health FX CVS Health. NR 52 TC 77 Z9 77 U1 4 U2 17 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 17 PY 2015 VL 162 IS 6 BP 407 EP U136 DI 10.7326/M14-1152 PG 22 WC Medicine, General & Internal SC General & Internal Medicine GA CD7OH UT WOS:000351279600014 PM 25775313 ER PT J AU Shekelle, P Holty, JEC Denberg, TD Qaseem, A AF Shekelle, Paul Holty, Jon-Erik C. Denberg, Thomas D. Qaseem, Amir TI Diagnosis of Obstructive Sleep Apnea in Adults RESPONSE SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 [Shekelle, Paul] Greater Los Angeles Vet Affairs Hlth Ctr, Los Angeles, CA 90073 USA. [Shekelle, Paul] RAND Corp, Los Angeles, CA USA. [Holty, Jon-Erik C.] Stanford Univ, Stanford, CA 94305 USA. [Denberg, Thomas D.] Caril Clin, Roanoke, VA USA. [Qaseem, Amir] Amer Coll Physicians, Philadelphia, PA USA. RP Shekelle, P (reprint author), Greater Los Angeles Vet Affairs Hlth Ctr, Los Angeles, CA 90073 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 17 PY 2015 VL 162 IS 6 BP 456 EP 457 DI 10.7326/L15-5062-3 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CD7OH UT WOS:000351279600023 PM 25775323 ER PT J AU Maazi, H Patel, N Sankaranarayanan, I Suzuki, Y Rigas, D Soroosh, P Freeman, GJ Sharpe, AH Akbari, O AF Maazi, Hadi Patel, Nisheel Sankaranarayanan, Ishwarya Suzuki, Yuzo Rigas, Diamanda Soroosh, Pejman Freeman, Gordon J. Sharpe, Arlene H. Akbari, Omid TI ICOS:ICOS-Ligand Interaction Is Required for Type 2 Innate Lymphoid Cell Function, Homeostasis, and Induction of Airway Hyperreactivity SO IMMUNITY LA English DT Article ID TRANSCRIPTION FACTOR GATA3; ALLERGIC LUNG INFLAMMATION; REGULATORY T-CELLS; TH2 DIFFERENTIATION; HUMAN INTERLEUKIN-5; ADAPTIVE IMMUNITY; MOLECULE ICOS; EXPRESSION; RESPONSES; RECEPTOR AB Allergic asthma is caused by Th2-cell-type cytokines in response to allergen exposure. Type 2 innate lymphoid cells (ILC2s) are a newly identified subset of immune cells that, along with Th2 cells, contribute to the pathogenesis of asthma by producing copious amounts of IL-5 and IL-13, which cause eosinophilia and airway hyperreactivity (AHR), a cardinal feature of asthma. ILC2s express ICOS, a T cell costimulatory molecule with a currently unknown function. Here we showed that a lack of ICOS on murine ILC2s and blocking the ICOS: ICOS-ligand interaction in human ILC2s reduced AHR and lung inflammation. ILC2s expressed both ICOS and ICOS-ligand, and the ICOS: ICOS-ligand interaction promoted cytokine production and survival in ILC2s through STAT5 signaling. Thus, ICOS: ICOS-ligand signaling pathway is critically involved in ILC2 function and homeostasis. C1 [Maazi, Hadi; Patel, Nisheel; Sankaranarayanan, Ishwarya; Suzuki, Yuzo; Rigas, Diamanda; Akbari, Omid] Univ So Calif, Keck Sch Med, Dept Mol Microbiol & Immunol, Los Angeles, CA 90033 USA. [Soroosh, Pejman] Janssen Res & Dev, San Diego, CA 92121 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med,Dept Med Oncol, Boston, MA 02115 USA. [Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. RP Akbari, O (reprint author), Univ So Calif, Keck Sch Med, Dept Mol Microbiol & Immunol, Los Angeles, CA 90033 USA. EM akbari@usc.edu FU National Institutes of Health public health service [R01 AI 066020, R01 ES 021801, R21 ES 024707, P01 AI 056299]; American Association of Immunology (AAI) Careers in Immunology Fellowship FX Studies described in this article were financially supported by National Institutes of Health public health service grants R01 AI 066020, R01 ES 021801, R21 ES 024707 (O.A.), and P01 AI 056299 (G.J.F. and A.H.S.). H.M. is supported by an American Association of Immunology (AAI) Careers in Immunology Fellowship. NR 44 TC 30 Z9 34 U1 3 U2 15 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD MAR 17 PY 2015 VL 42 IS 3 BP 538 EP 551 DI 10.1016/j.immuni.2015.02.007 PG 14 WC Immunology SC Immunology GA CD7VE UT WOS:000351301900017 PM 25769613 ER PT J AU Filley, CM Bernick, C AF Filley, Christopher M. Bernick, Charles TI Children and football A cautionary tale SO NEUROLOGY LA English DT Editorial Material ID TRAUMATIC BRAIN-INJURY; NEUROPATHOLOGY AB As even any casual American sports enthusiast can attest, the football season occupies a special position in the popular imagination. Fans flock to stadiums and televisions to watch their teams perform in this increasingly violent contact sport, and among these fans, children may come to idolize star players and be almost irresistibly drawn to the gridiron. Parents and coaches may also exert substantial pressure on children to take up the sport. Whereas the benefits of physical exercise are undeniable for the promotion of cardiovascular health and psychological well-being, participation in football may result in neurologic sequelae ranging from mild traumatic brain injury (mTBI)(1) to death,(2) and repetitive mTBI has been associated with a degenerative dementia in later life known as chronic traumatic encephalopathy (CTE).(3) Football has the highest injury rate among team sports, and given that 70% of all football players in the United States are under the age of 14 and that every child aged 9-12 can be exposed to 240 head impacts during a single football season,(4) a better understanding of neurobehavioral sequelae among children who play football is urgently needed. Wide gaps exist in our knowledge, but an area of particularly limited information is the long-term outcome of repetitive mTBI among children in whom recovery from the acute event was apparently complete. C1 [Filley, Christopher M.] Univ Colorado, Sch Med, Dept Psychiat, Aurora, CO 80045 USA. [Filley, Christopher M.] Univ Colorado, Sch Med, Dept Neurol, Aurora, CO USA. [Filley, Christopher M.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Bernick, Charles] Cleveland Clin, Lou Ruvo Ctr Brain Hlth, Cleveland, OH 44106 USA. RP Filley, CM (reprint author), Univ Colorado, Sch Med, Dept Psychiat, Aurora, CO 80045 USA. EM Christopher.filley@ucdenver.edu NR 10 TC 1 Z9 1 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD MAR 17 PY 2015 VL 84 IS 11 BP 1068 EP 1069 DI 10.1212/WNL.0000000000001357 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA CD9YU UT WOS:000351458600005 PM 25632092 ER PT J AU Kim, HJ Paul, F Lana-Peixoto, MA Tenembaum, S Asgari, N Palace, J Klawiter, EC Sato, DK de Seze, J Wuerfel, J Banwell, BL Villoslada, P Saiz, A Fujihara, K Kim, SH AF Kim, Ho Jin Paul, Friedemann Lana-Peixoto, Marco A. Tenembaum, Silvia Asgari, Nasrin Palace, Jacqueline Klawiter, Eric C. Sato, Douglas K. de Seze, Jerome Wuerfel, Jens Banwell, Brenda L. Villoslada, Pablo Saiz, Albert Fujihara, Kazuo Kim, Su-Hyun CA Guthy-Jackson Charitable Fdn NMO TI MRI characteristics of neuromyelitis optica spectrum disorder An international update SO NEUROLOGY LA English DT Review ID EXTENSIVE TRANSVERSE MYELITIS; OLIGODENDROCYTE GLYCOPROTEIN ANTIBODIES; CNS AQUAPORIN-4 AUTOIMMUNITY; SPINAL-CORD LESIONS; MULTIPLE-SCLEROSIS; BRAIN ABNORMALITIES; ANTI-AQUAPORIN-4 ANTIBODY; DIAGNOSTIC-CRITERIA; IGG PREDICTS; GRAY-MATTER AB Since its initial reports in the 19th century, neuromyelitis optica (NMO) had been thought to involve only the optic nerves and spinal cord. However, the discovery of highly specific anti-aquaporin-4 antibody diagnostic biomarker for NMO enabled recognition of more diverse clinical spectrum of manifestations. Brain MRI abnormalities in patients seropositive for anti-aquaporin-4 antibody are common and some may be relatively unique by virtue of localization and configuration. Some seropositive patients present with brain involvement during their first attack and/or continue to relapse in the same location without optic nerve and spinal cord involvement. Thus, characteristics of brain abnormalities in such patients have become of increased interest. In this regard, MRI has an increasingly important role in the differential diagnosis of NMO and its spectrum disorder (NMOSD), particularly from multiple sclerosis. Differentiating these conditions is of prime importance because early initiation of effective immunosuppressive therapy is the key to preventing attack-related disability in NMOSD, whereas some disease-modifying drugs for multiple sclerosis may exacerbate the disease. Therefore, identifying the MRI features suggestive of NMOSD has diagnostic and prognostic implications. We herein review the brain, optic nerve, and spinal cord MRI findings of NMOSD. C1 [Kim, Ho Jin; Kim, Su-Hyun] Natl Canc Ctr, Res Inst & Hosp, Dept Neurol, Goyang, South Korea. [Paul, Friedemann; Wuerfel, Jens] Charite, NeuroCure Clin Res Ctr, Dept Neurol, D-13353 Berlin, Germany. [Paul, Friedemann; Wuerfel, Jens] Charite, Clin & Expt Multiple Sclerosis Res Ctr, Dept Neurol, D-13353 Berlin, Germany. [Lana-Peixoto, Marco A.] Univ Fed Minas Gerais, Sch Med, CIEM MS Res Ctr, Belo Horizonte, MG, Brazil. [Tenembaum, Silvia] Natl Paediat Hosp Dr Juan P Garrahan, Dept Neurol, Buenos Aires, DF, Argentina. [Asgari, Nasrin] Univ Southern Denmark, Inst Mol Med, Neurobiol, Odense, Denmark. [Asgari, Nasrin] Vejle Hosp, Dept Neurol, Vejle, Denmark. [Palace, Jacqueline] John Radcliffe Hosp, Dept Clin Neurol, Oxford OX3 9DU, England. [Klawiter, Eric C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Sato, Douglas K.] Tohoku Univ, Sch Med, Dept Neurol, Sendai, Miyagi 980, Japan. [de Seze, Jerome] Hop Univ Strasbourg, Dept Neurol, Strasbourg, France. [Wuerfel, Jens] Univ Med Goettingen, Inst Neuroradiol, Gottingen, Germany. [Banwell, Brenda L.] Childrens Hosp Philadelphia, Div Neurol, Dept Pediat, Philadelphia, PA USA. [Banwell, Brenda L.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Villoslada, Pablo; Saiz, Albert] Hosp Clin Barcelona, Serv Neurol, Ctr Neuroimmunol, Barcelona, Spain. Inst Biomed Res August Pi Sunyer, Barcelona, Spain. [Fujihara, Kazuo] Tohoku Univ, Grad Sch Med, Dept Multiple Sclerosis Therapeut, Sendai, Miyagi 980, Japan. RP Kim, HJ (reprint author), Natl Canc Ctr, Res Inst & Hosp, Dept Neurol, Goyang, South Korea. EM hojinkim@ncc.re.kr RI Sato, Douglas/F-2508-2013; Aktas, Orhan/B-7623-2009; De Seze, Jerome/M-8316-2016; OI Sato, Douglas/0000-0002-7695-6020; Aktas, Orhan/0000-0002-2020-9210; De Seze, Jerome/0000-0002-7197-7578; paul, friedemann/0000-0002-6378-0070 FU Bayer Schering Pharma; Biogen Idec; Genzyme; Kael-GemVax; Merck Serono; Novartis; Teva-Handok; UCB; German Research Council; German Ministry of Education and Research (Competence Network Multiple Sclerosis "KKNMS"); Guthy-Jackson Charitable Foundation; Biogen; Bayer; Teva; Merck; Sanofi; Bayer Schering; Roche; Bayer Healthcare; Genzyme Corporation; Teva Neuroscience; Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan; Ichiro Kanehara Foundation; German Ministry of Science (BMBF/KKNMS); Canadian MS Research Foundation; Canadian MS Society; CIHR; European Commission; Instituto Salud Carlos III; Marato TV3; Eisai Inc.; Mitsubishi Tanabe Pharma Corporation; Novartis Pharma; Astellas Pharma Inc.; Takeda Pharmaceutical Company Limited; Asahi Kasei Medical Co.; Daiichi Sankyo; Nihon Pharmaceutical; Biogen Idec Japan; Asahi Kasei Medical; Chemo-Sero-Therapeutic Research Institute; Teva Pharmaceutical; Mitsubishi Tanabe Pharma; Teijin Pharma; Chugai Pharmaceutical; Ono Pharmaceutical; Genzyme Japan; Ministry of Education, Science and Technology of Japan [22229008]; Ministry of Health, Welfare and Labor of Japan FX H. Kim has given talks, consulted, and received honoraria and/or research support from Bayer Schering Pharma, Biogen Idec, Genzyme, Kael-GemVax, Merck Serono, Novartis, Teva-Handok, and UCB. He serves on a steering committee for MedImmune. F. Paul has received funding from German Research Council, German Ministry of Education and Research (Competence Network Multiple Sclerosis "KKNMS"), and The Guthy-Jackson Charitable Foundation. He has received travel compensation, speaker honoraria, and research support from Biogen, Bayer, Teva, Merck, Novartis, and Sanofi, and has served as steering committee member of the OCTIMS Study sponsored by Novartis. M. Lana-Peixoto reports no disclosures relevant to the manuscript. S. Tenembaum has provided consulting services to Genzyme Corporation and Biogen Idec and received lecture fees from Merck Serono. N. Asgari reports no disclosures relevant to the manuscript. J. Palace is partly funded by highly specialized services to run a national congenital myasthenia service and a neuromyelitis service. She has received support for scientific meetings and honorariums for advisory work from Merck Serono, Biogen Idec, Novartis, Teva, Chugai Pharma, and Bayer Schering, and unrestricted grants from Merck Serono, Novartis, Biogen Idec, and Bayer Schering. Her hospital trust receives funds for her role as clinical lead for the RSS, and she has received grants from the MS Society and Guthy-Jackson Foundation for unrelated research studies. E. Klawiter has received research funding from Roche. He has received consulting fees and/or speaking honoraria from Biogen Idec, Bayer Healthcare, Genzyme Corporation, and Teva Neuroscience. D. Sato receives scholarship funds from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan and has received research support from Ichiro Kanehara Foundation. J. de Seze has received honoraria from Bayer Schering, Biogen Idec, LFB, Merck Serono, Novartis, Sanofi-Aventis, and Teva. He serves as a consultant for Alexion and Chugai. J. Wuerfel serves on advisory boards for Novartis and Biogen Idec. He received a research grant from Novartis, and speaker honoraria from Bayer, Novartis, and Biogen Idec. He is supported by the German Ministry of Science (BMBF/KKNMS). B. Banwell serves as a senior editor for Multiple Sclerosis and Related Disorders and on the editorial board of Neurology (R). She serves as a consultant for Biogen Idec, Novartis, Teva Neuroscience, and Merck Serono. She has been funded by the Canadian MS Research Foundation, the Canadian MS Society, and CIHR. P. Villoslada serves as a board member for Roche, Novartis, Neurotec Pharma, Bionure Farma, and as a consultant for Novartis, Roche, TFS, Heidelberg Engineering, MedImmune, Digna Biotech, and Neurotec Pharma. He has received research support from European Commission, Instituto Salud Carlos III, Marato TV3, Novartis, and Roche and travel expenses from Novartis. He holds patents with Digna Biotech, Bionure Farma, and stock/stock options of Bionure Farma. A. Saiz has received compensation for consulting services and speaking from Bayer Schering, Merck Serono, Biogen Idec, Sanofi-Aventis, Teva Pharmaceutical Industries, and Novartis. K.; Fujihara serves on scientific advisory boards for Bayer Schering Pharma, Biogen Idec, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, Chugai Pharmaceutical, Ono Pharmaceutical, Nihon Pharmaceutical, Merck Serono, Alexion Pharmaceuticals, MedImmune, and Medical Review; has received funding for travel and speaker honoraria from Bayer Schering Pharma, Biogen Idec, Eisai Inc., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, Astellas Pharma Inc., Takeda Pharmaceutical Company Limited, Asahi Kasei Medical Co., Daiichi Sankyo, and Nihon Pharmaceutical; serves as an editorial board member of Clinical and Experimental Neuroimmunology (2009-present) and an advisory board member of Sri Lanka Journal of Neurology; has received research support from Bayer Schering Pharma, Biogen Idec Japan, Asahi Kasei Medical, The Chemo-Sero-Therapeutic Research Institute, Teva Pharmaceutical, Mitsubishi Tanabe Pharma, Teijin Pharma, Chugai Pharmaceutical, Ono Pharmaceutical, Nihon Pharmaceutical, and Genzyme Japan; and is funded as the secondary investigator (22229008, 2010-2015) by the Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Technology of Japan and as the secondary investigator by the Grants-in-Aid for Scientific Research from the Ministry of Health, Welfare and Labor of Japan (2010-present). S. Kim reports no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures. NR 60 TC 67 Z9 68 U1 3 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD MAR 17 PY 2015 VL 84 IS 11 BP 1165 EP 1173 DI 10.1212/WNL.0000000000001367 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CD9YU UT WOS:000351458600020 PM 25695963 ER PT J AU Sayama, H Sinatra, R AF Sayama, Hiroki Sinatra, Roberta TI Social diffusion and global drift on networks SO PHYSICAL REVIEW E LA English DT Article ID SCALE-FREE NETWORKS; COMPLEX NETWORKS; SYNCHRONIZATION; SPREAD AB We study a mathematical model of social diffusion on a symmetric weighted network where individual nodes' states gradually assimilate to local social norms made by their neighbors' average states. Unlike physical diffusion, this process is not state conservational and thus the global state of the network (i.e., sum of node states) will drift. The asymptotic average node state will be the average of initial node states weighted by their strengths. Here we show that, while the global state is not conserved in this process, the inner product of strength and state vectors is conserved instead, and perfect positive correlation between node states and local averages of their self-neighbor strength ratios always results in upward (or at least neutral) global drift. We also show that the strength assortativity negatively affects the speed of homogenization. Based on these findings, we propose an adaptive link weight adjustment method to achieve the highest upward global drift by increasing the strength-state correlation. The effectiveness of the method was confirmed through numerical simulations and implications for real-world social applications are discussed. C1 [Sayama, Hiroki] SUNY Binghamton, Collect Dynam Complex Syst Res Grp, Binghamton, NY 13902 USA. [Sayama, Hiroki; Sinatra, Roberta] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. [Sayama, Hiroki; Sinatra, Roberta] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Sinatra, Roberta] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. RP Sayama, H (reprint author), SUNY Binghamton, Collect Dynam Complex Syst Res Grp, Binghamton, NY 13902 USA. OI Sinatra, Roberta/0000-0002-7558-1028 FU U.S. National Science Foundation [1027752]; James S. McDonnell Foundation FX We thank Albert-Laszlo Barabasi for valuable comments. This material is based on work supported by the U.S. National Science Foundation under Grant No. 1027752. R.S. acknowledges support from the James S. McDonnell Foundation. NR 28 TC 0 Z9 0 U1 0 U2 5 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1539-3755 EI 1550-2376 J9 PHYS REV E JI Phys. Rev. E PD MAR 17 PY 2015 VL 91 IS 3 AR 032809 DI 10.1103/PhysRevE.91.032809 PG 6 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA CE0RE UT WOS:000351511500004 PM 25871159 ER PT J AU Bateman, BT Hernandez-Diaz, S Fischer, MA Seely, EW Ecker, JL Franklin, JM Desai, RJ Allen-Coleman, C Mogun, H Avorn, J Huybrechts, KF AF Bateman, Brian T. Hernandez-Diaz, Sonia Fischer, Michael A. Seely, Ellen W. Ecker, Jeffrey L. Franklin, Jessica M. Desai, Rishi J. Allen-Coleman, Cora Mogun, Helen Avorn, Jerry Huybrechts, Krista F. TI Statins and congenital malformations: cohort study SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Article ID MATERNAL EXPOSURE; PREGNANCY; RISK; OUTCOMES; WOMEN; SURVEILLANCE; SIMVASTATIN; PRAVASTATIN; LOVASTATIN; ANOMALIES AB OBJECTIVE To examine the teratogenic potential of statins. DESIGN Cohort study. SETTING United States. PARTICIPANTS A cohort of 886 996 completed pregnancies linked to liveborn infants of women enrolled in Medicaid from 2000 to 2007. METHODS We examined the risk of major congenital malformations and organ specific malformations in offspring associated with maternal use of a statin in the first trimester. Propensity score based methods were used to control for potential confounders, including maternal demographic characteristics, obstetric and medical conditions, and use of other drugs. RESULTS 1152 (0.13%) women used a statin during the first trimester. In unadjusted analyses, the prevalence of malformations in the offspring of these women was 6.34% compared with 3.55% in those of women who did not use a statin in the first trimester (relative risk 1.79, 95% confidence interval 1.43 to 2.23). Controlling for confounders, particularly pre-existing diabetes, accounted for this increase in risk (1.07, 0.85 to 1.37). There were also no statistically significant increases in any of the organ specific malformations assessed after accounting for confounders. Results were similar across a range of sensitivity analyses. CONCLUSIONS Our analysis did not find a significant teratogenic effect from maternal use of statins in the first trimester. However, these findings need to be replicated in other large studies, and the long term effects of in utero exposure to statins needs to be assessed, before use of statins in pregnancy can be considered safe. C1 [Bateman, Brian T.; Fischer, Michael A.; Franklin, Jessica M.; Desai, Rishi J.; Allen-Coleman, Cora; Mogun, Helen; Avorn, Jerry; Huybrechts, Krista F.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Bateman, Brian T.; Fischer, Michael A.; Franklin, Jessica M.; Desai, Rishi J.; Allen-Coleman, Cora; Mogun, Helen; Avorn, Jerry; Huybrechts, Krista F.] Harvard Univ, Sch Med, Boston, MA USA. [Bateman, Brian T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Obstet Anesthesia,Dept Anesthesia Crit Care &, Boston, MA USA. [Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Seely, Ellen W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Metab,Dept Med, Boston, MA 02115 USA. [Ecker, Jeffrey L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. RP Bateman, BT (reprint author), Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, Boston, MA 02115 USA. EM bbateman@partners.org FU Eunice Kennedy Shriver National Institute of Child Health & Human Development of the NIH (Bethesda, MD) [K08HD075831]; National Heart Lung and Blood Institute of the NIH [K24HL096141]; National Institute of Mental Health of the NIH [K01MH099141]; Agency for Healthcare Research and Quality (AHRQ) [R01HS018533] FX This study was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the NIH (Bethesda, MD) under award No K08HD075831 (BTB), the National Heart Lung and Blood Institute of the NIH under award No K24HL096141 (EWS), and the National Institute of Mental Health of the NIH under award No K01MH099141 (KFH). Medicaid Analytic eXtract pregnancy cohort creation was supported by the Agency for Healthcare Research and Quality (AHRQ) (grant R01HS018533). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 31 TC 25 Z9 26 U1 0 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD MAR 17 PY 2015 VL 350 AR h1035 DI 10.1136/bmj.h1035 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CE1KO UT WOS:000351570700001 PM 25784688 ER PT J AU Rosetti, F Chen, YF Sen, M Thayer, E Azcutia, V Herter, JM Luscinskas, FW Cullere, X Zhu, C Mayadas, TN AF Rosetti, Florencia Chen, Yunfeng Sen, Mehmet Thayer, Elizabeth Azcutia, Veronica Herter, Jan M. Luscinskas, F. William Cullere, Xavier Zhu, Cheng Mayadas, Tanya N. TI A Lupus-Associated Mac-1 Variant Has Defects in Integrin Allostery and Interaction with Ligands under Force SO CELL REPORTS LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-1; CATCH BONDS; LEUKOCYTE ADHESION; CELL-SURFACES; DYNAMIC CATCH; DOMAIN; ERYTHEMATOSUS; ITGAM; CD11B/CD18; DEFICIENCY AB Leukocyte CD18 integrins increase their affinity for ligand by transmitting allosteric signals to and from their ligand-binding alpha I domain. Mechanical forces induce allosteric changes that paradoxically slow dissociation by increasing the integrin/ligand bond lifetimes, referred to as catch bonds. Mac-1 formed catch bonds with its ligands. However, a Mac-1 gene (ITGAM) coding variant (rs1143679, R77H), which is located in the beta-propeller domain and is significantly associated with systemic lupus erythematosus risk, exhibits a marked impairment in 2D ligand affinity and affinity maturation under mechanical force. Targeted mutations and activating antibodies reveal that the failure in Mac-1 R77H allostery is rescued by induction of cytoplasmic tail separation and full integrin extension. These findings demonstrate roles for R77, and the beta-propeller in which it resides, in force-induced allostery relay and integrin bond stabilization. Defects in these processes may have pathological consequences, as the Mac-1 R77H variant is associated with increased susceptibility to lupus. C1 [Rosetti, Florencia; Thayer, Elizabeth; Azcutia, Veronica; Herter, Jan M.; Luscinskas, F. William; Cullere, Xavier; Mayadas, Tanya N.] Brigham & Womens Hosp, Dept Pathol, Ctr Excellence Vasc Biol, Boston, MA 02115 USA. [Rosetti, Florencia; Thayer, Elizabeth; Azcutia, Veronica; Herter, Jan M.; Luscinskas, F. William; Cullere, Xavier; Mayadas, Tanya N.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Rosetti, Florencia] Harvard Univ, Sch Med, Harvard Grad Sch Arts & Sci, Div Med Sci,Immunol Grad Program, Boston, MA 02115 USA. [Chen, Yunfeng; Zhu, Cheng] Georgia Inst Technol, George W Woodruff Sch Mech Engn, Atlanta, GA 30332 USA. [Chen, Yunfeng; Zhu, Cheng] Georgia Inst Technol, Inst Bioengn & Biosci, Atlanta, GA 30332 USA. [Sen, Mehmet] Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat,Program Cellular & Mol Med, Boston, MA 02115 USA. [Zhu, Cheng] Georgia Inst Technol, Coulter Dept Biomed Engn, Atlanta, GA 30332 USA. RP Zhu, C (reprint author), Georgia Inst Technol, George W Woodruff Sch Mech Engn, Atlanta, GA 30332 USA. EM cheng.zhu@bme.gatech.edu; tmayadas@rics.bwh.harvard.edu RI Azcutia, Veronica/A-7704-2017; OI Azcutia, Veronica/0000-0003-2160-5175; Luscinskas, Francis/0000-0001-7100-4103 FU NIH [HL065095, AI044902, T32 HL007627]; Target Identification in Lupus Grant/Alliance for Lupus Research Foundation; Consejo Nacional de Ciencia y Tecnologia; Fundacion Mexico en Harvard; German Research Foundation [HE-6810/1-1] FX We thank Dr. T. Springer for providing beta2 antibodies. This work was supported by grants from the NIH (HL065095 to T.N.M., AI044902 to C.Z., and T32 HL007627 to F.R.), the Target Identification in Lupus Grant/Alliance for Lupus Research Foundation (to T.M.), the Consejo Nacional de Ciencia y Tecnologia and Fundacion Mexico en Harvard (to F.R.), and the German Research Foundation (HE-6810/1-1 to J.M.H.). NR 36 TC 2 Z9 3 U1 2 U2 7 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 17 PY 2015 VL 10 IS 10 BP 1655 EP 1664 DI 10.1016/j.celrep.2015.02.037 PG 10 WC Cell Biology SC Cell Biology GA CD8AE UT WOS:000351316700003 ER PT J AU Fitamant, J Kottakis, F Benhamouche, S Tian, HS Chuvin, N Parachoniak, CA Nagle, JM Perera, RM Lapouge, M Deshpande, V Zhu, AX Lai, A Min, B Hoshida, Y Avruch, J Sia, D Camprecios, G McClatchey, AI Llovet, JM Morrissey, D Raj, L Bardeesy, N AF Fitamant, Julien Kottakis, Filippos Benhamouche, Samira Tian, Helen S. Chuvin, Nicolas Parachoniak, Christine A. Nagle, Julia M. Perera, Rushika M. Lapouge, Marjorie Deshpande, Vikram Zhu, Andrew X. Lai, Albert Min, Bosun Hoshida, Yujin Avruch, Joseph Sia, Daniela Camprecios, Genis McClatchey, Andrea I. Llovet, Josep M. Morrissey, David Raj, Lakshmi Bardeesy, Nabeel TI YAP Inhibition Restores Hepatocyte Differentiation in Advanced HCC, Leading to Tumor Regression SO CELL REPORTS LA English DT Article ID YES-ASSOCIATED PROTEIN; HEPATOCELLULAR-CARCINOMA; HIPPO PATHWAY; SUPPRESSOR PATHWAY; LIVER-CANCER; SIZE-CONTROL; ORGAN SIZE; ADULT MICE; IN-VIVO; PROLIFERATION AB Defective Hippo/YAP signaling in the liver results in tissue overgrowth and development of hepatocellular carcinoma (HCC). Here, we uncover mechanisms of YAP-mediated hepatocyte reprogramming and HCC pathogenesis. YAP functions as a rheostat in maintaining metabolic specialization, differentiation, and quiescence within the hepatocyte compartment. Increased or decreased YAP activity reprograms subsets of hepatocytes to different fates associated with deregulation of the HNF4A, CTNNB1, and E2F transcriptional programs that control hepatocyte quiescence and differentiation. Importantly, treatment with small interfering RNA-lipid nanoparticles (siRNA-LNPs) targeting YAP restores hepatocyte differentiation and causes pronounced tumor regression in a genetically engineered mouse HCC model. Furthermore, YAP targets are enriched in an aggressive human HCC subtype characterized by a proliferative signature and absence of CTNNB1 mutations. Thus, our work reveals Hippo signaling as a key regulator of the positional identity of hepatocytes, supports targeting of YAP using siRNA-LNPs as a paradigm of differentiation-based therapy, and identifies an HCC subtype that is potentially responsive to this approach. C1 [Fitamant, Julien; Kottakis, Filippos; Benhamouche, Samira; Tian, Helen S.; Chuvin, Nicolas; Parachoniak, Christine A.; Nagle, Julia M.; Perera, Rushika M.; Lapouge, Marjorie; Deshpande, Vikram; Zhu, Andrew X.; McClatchey, Andrea I.; Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Fitamant, Julien; Kottakis, Filippos; Tian, Helen S.; Chuvin, Nicolas; Parachoniak, Christine A.; Nagle, Julia M.; Perera, Rushika M.; Lapouge, Marjorie; Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Avruch, Joseph] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Fitamant, Julien; Kottakis, Filippos; Parachoniak, Christine A.; Perera, Rushika M.; Zhu, Andrew X.; Avruch, Joseph; Bardeesy, Nabeel] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Benhamouche, Samira; Deshpande, Vikram; McClatchey, Andrea I.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Benhamouche, Samira] Univ Bordeaux, INSERM, U1053, F-33076 Bordeaux, France. [Lai, Albert; Min, Bosun; Morrissey, David; Raj, Lakshmi] Novartis Inst Biomed Res Inc, Cambridge, MA 02139 USA. [Hoshida, Yujin; Sia, Daniela; Camprecios, Genis; Llovet, Josep M.] Icahn Sch Med Mt Sinai, Dept Med, Div Liver Dis, Liver Canc Program,Tisch Canc Inst, New York, NY 10029 USA. [Sia, Daniela] Natl Canc Inst, Gastrointestinal Surg & Liver Transplantat Unit, I-20133 Milan, Italy. [Llovet, Josep M.] Univ Barcelona, HCC Translat Res Lab, BCLC Grp, Liver Unit,IDIBAPS,Hosp Clin,CIBERehd, E-08036 Barcelona, Catalonia, Spain. [Llovet, Josep M.] Inst Catalana Recerca & Estudis Avancats, Barcelona 08010, Catalonia, Spain. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 185 Cambridge St, Boston, MA 02114 USA. EM avruch@molbio.mgh.harvard.edu; bardeesy.nabeel@mgh.harvard.edu RI Llovet, Josep M /D-4340-2014 OI Llovet, Josep M /0000-0003-0547-2667 FU NIH/NCI [R01CA136567, P50CA127003]; NIH/NIDDK [R01DK099558]; TargetCancer Foundation; EMBO; International Human Frontiers Science Program; ECOR Fund for Medical Discovery postdoctoral fellowships; CIHR postdoctoral fellowship; Asociacion Espanola Contra el Cancer FX We thank members of the Bardeesy lab, A. Kimmelman, and W. Kimfor helpful comments, and F. Camargo for generously providing the Yapfl mice. We also thank the Novartis siRNA formulation group for preparing the siLNPs, K. Ross for bioinformatics assistance, and D. Zhou for initiation of the mouse cohort. This work was supported by grants from the NIH/NCI (R01CA136567 and P50CA127003 to N.B. and J.A.), NIH/NIDDK (R01DK099558 to Y.H.), and the TargetCancer Foundation (to N.B.). N.B. holds the Gallagher Chair in Gastrointestinal Cancer Research at Massachusetts General Hospital. N.B. and J.M.L. are members of the Waxman Institute without Walls. J.F. and S.B. are recipients of long-term postdoctoral fellowships from EMBO and the International Human Frontiers Science Program, respectively, and both were supported by ECOR Fund for Medical Discovery postdoctoral fellowships. C.P. is the recipient of a CIHR postdoctoral fellowship. J.M.L. and D.S. are supported by the Asociacion Espanola Contra el Cancer. A. L., B.M., D.M., and L.R. are employees of Novartis, and J.M.L. is a consultant with Novartis. This work is dedicated to the bright memory of Rolande Fitamant (1959-2014). NR 51 TC 26 Z9 26 U1 3 U2 20 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 17 PY 2015 VL 10 IS 10 BP 1692 EP 1707 DI 10.1016/j.celrep.2015.02.027 PG 16 WC Cell Biology SC Cell Biology GA CD8AE UT WOS:000351316700007 ER PT J AU Chan, KE Edelman, ER Wenger, JB Thadhani, RI Maddux, FW AF Chan, Kevin E. Edelman, Elazer R. Wenger, Julia B. Thadhani, Ravi I. Maddux, Franklin W. TI Dabigatran and Rivaroxaban Use in Atrial Fibrillation Patients on Hemodialysis SO CIRCULATION LA English DT Article DE atrial fibrillation; dabigatran; dialysis; rivaroxaban; warfarin ID STAGE RENAL-DISEASE; WARFARIN; RISK AB Background-Dabigatran and rivaroxaban are new oral anticoagulants that are eliminated through the kidneys. Their use in dialysis patients is discouraged because these drugs can bioaccumulate to precipitate inadvertent bleeding. We wanted to determine whether prescription of dabigatran or rivaroxaban was occurring in the dialysis population and whether these practices were safe. Methods and Results-Prevalence plots were used to describe the point prevalence (monthly) of dabigatran and rivaroxaban use among 29 977 hemodialysis patients with atrial fibrillation. Poisson regression compared the rate of bleeding, stroke, and arterial embolism in patients who started dabigatran, rivaroxaban, or warfarin. The first record of dabigatran prescription among hemodialysis patients occurred 45 days after the drug became available in the United States. Since then, dabigatran and rivaroxaban use in the atrial fibrillation-end-stage renal disease population has steadily risen where 5.9% of anticoagulated dialysis patients are started on dabigatrian or rivaroxaban. In covariate adjusted Poisson regression, dabigatran (rate ratio, 1.48; 95% confidence interval, 1.21-1.81; P=0.0001) and rivaroxaban (rate ratio, 1.38; 95% confidence interval, 1.03-1.83; P=0.04) associated with a higher risk of hospitalization or death from bleeding when compared with warfarin. The risk of hemorrhagic death was even larger with dabigatran (rate ratio, 1.78; 95% confidence interval, 1.18-2.68; P=0.006) and rivaroxaban (rate ratio, 1.71; 95% confidence interval, 0.94-3.12; P=0.07) relative to warfarin. There were too few events in the study to detect meaningful differences in stroke and arterial embolism between the drug groups. Conclusions-More dialysis patients are being started on dabigatran and rivaroxaban, even when their use is contraindicated and there are no studies to support that the benefits outweigh the risks of these drugs in end-stage renal disease. C1 [Chan, Kevin E.; Wenger, Julia B.; Thadhani, Ravi I.] Massachusetts Gen Hosp, Div Nephrol, Waltham, MA 02451 USA. [Chan, Kevin E.; Maddux, Franklin W.] Fresenius Med Care North Amer, Div Clin Res, Waltham, MA USA. [Edelman, Elazer R.] MIT, Harvard MIT Biomed Engn Ctr, Inst Med Engn & Sci, Cambridge, MA 02139 USA. [Edelman, Elazer R.] Brigham & Womens Hosp, Cardiovasc Med Div, Boston, MA 02115 USA. RP Chan, KE (reprint author), Massachusetts Gen Hosp, Div Clin Res, Fresenius Med Care North Amer, Div Nephrol, 920 Winter St, Waltham, MA 02451 USA. EM kevin.chan@fmc-na.com FU National Institutes of Health [R01 GM 49039] FX Dr Edelman was supported in part by grants from the National Institutes of Health (R01 GM 49039). NR 17 TC 45 Z9 45 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD MAR 17 PY 2015 VL 131 IS 11 BP 972 EP 979 DI 10.1161/CIRCULATIONAHA.114.014113 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CD6CG UT WOS:000351175900008 PM 25595139 ER PT J AU Martinsson, A Li, XJ Andersson, C Nilsson, J Smith, JG Sundquist, K AF Martinsson, Andreas Li, Xinjun Andersson, Charlotte Nilsson, Johan Smith, J. Gustav Sundquist, Kristina TI Temporal Trends in the Incidence and Prognosis of Aortic Stenosis A Nationwide Study of the Swedish Population SO CIRCULATION LA English DT Article DE aortic valve stenosis; epidemiology; heart valves ID ANGIOTENSIN-CONVERTING ENZYME; VALVULAR HEART-DISEASE; HOSPITAL DISCHARGE REGISTRY; ACUTE MYOCARDIAL-INFARCTION; LOW-DENSITY-LIPOPROTEIN; VALVE-REPLACEMENT; EARLY LESION; MORTALITY; FAILURE; ASSOCIATION AB Background-The aging of Western populations is expected to result in increasing occurrence of aortic stenosis (AS), but data are limited. Recent studies have reported declining incidence and mortality for other major heart diseases. We aimed to study temporal trends in the incidence and prognosis for AS in Sweden. Methods and Results-With the use of nationwide registers, all adult patients in the Swedish population with a first diagnosis of AS, heart failure, acute myocardial infarction, and aortic valve replacement for AS between 1989 and 2009 were identified and followed up until the end of 2010 for all-cause and cardiovascular-related mortality. The age-adjusted incidence of AS in Sweden declined from 15.0 to 11.4 in men and 9.8 to 7.1 in women per 100 000 between 1989 to 1991 and 2007 to 2009, and the median age at diagnosis increased by 4 years for both men and women. The age-and sex-adjusted relative risk of 1- and 3-year mortality in 2007 to 2009 was 0.58 (95% confidence interval, 0.53-0.63) and 0.60 (95% confidence interval, 0.56-0.65), respectively, compared with 1989 to 1991. Similar improvements were observed for heart failure and acute myocardial infarction. Findings were broadly consistent across subgroups. Postoperative mortality at 30 days declined despite increased median age at diagnosis. Conclusions-Incidence and mortality rates in AS in Sweden declined between 1989 and 2009 to an extent similar to that observed for heart failure and acute myocardial infarction. These findings could suggest that improved risk factor control and cardiovascular therapy, combined with increased use of aortic valve replacement in the elderly and reduced perioperative mortality in aortic valve replacement, have translated into favorable effects for AS. C1 [Martinsson, Andreas; Smith, J. Gustav] Lund Univ, Dept Cardiol, SE-22185 Lund, Sweden. [Nilsson, Johan] Lund Univ, Dept Cardiothorac Surg, SE-22185 Lund, Sweden. Lund Univ, Dept Clin Sci, SE-22185 Lund, Sweden. Skane Univ Hosp, Lund, Sweden. [Li, Xinjun; Sundquist, Kristina] Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden. [Andersson, Charlotte] Copenhagen Univ Hosp Gentofte, Dept Cardiol, Hellerup, Denmark. [Smith, J. Gustav] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Smith, J. Gustav] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Smith, J. Gustav] Harvard Univ, Sch Med, Boston, MA USA. [Smith, J. Gustav] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Smith, J. Gustav] MIT, Cambridge, MA 02139 USA. RP Martinsson, A (reprint author), Lund Univ, Dept Cardiol, SE-22185 Lund, Sweden. EM andreas.martinsson@med.lu.se RI Martinsson, Andreas/E-5028-2015; Nilsson, Johan/A-4742-2011 OI Martinsson, Andreas/0000-0003-1461-0777; Nilsson, Johan/0000-0001-6860-6090 FU Swedish Heart-Lung Foundation; Swedish National Health Service; Ulla Ekdahl Foundation; Thorsten Westerstrom Foundation; Craaford Foundation; Skane University Hospital in Lund; Swedish Research Council; Danish Research Council FX This work was supported by the Swedish Heart-Lung Foundation, governmental funding of clinical research within the Swedish National Health Service, the Ulla Ekdahl Foundation, the Thorsten Westerstrom Foundation, the Craaford Foundation, Skane University Hospital in Lund (Drs Smith and Martinsson), and the Swedish Research Council (Drs Smith, Sundquist, and Li). Dr Andersson was supported by the Danish Research Council. NR 44 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD MAR 17 PY 2015 VL 131 IS 11 BP 988 EP 994 DI 10.1161/CIRCULATIONAHA.114.012906 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CD6CG UT WOS:000351175900010 PM 25779541 ER PT J AU Murphy, TP Cutlip, DE Regensteiner, JG Mohler, ER Cohen, DJ Reynolds, MR Massaro, JM Lewis, BA Cerezo, J Oldenburg, NC Thum, CC Jaff, MR Comerota, AJ Steffes, MW Abrahamsen, IH Goldberg, S Hirsch, AT AF Murphy, Timothy P. Cutlip, Donald E. Regensteiner, Judith G. Mohler, Emile R., III Cohen, David J. Reynolds, Matthew R. Massaro, Joseph M. Lewis, Beth A. Cerezo, Joselyn Oldenburg, Niki C. Thum, Claudia C. Jaff, Michael R. Comerota, Anthony J. Steffes, Michael W. Abrahamsen, Ingrid H. Goldberg, Suzanne Hirsch, Alan T. TI Supervised Exercise, Stent Revascularization, or Medical Therapy for Claudication Due to Aortoiliac Peripheral Artery Disease The CLEVER Study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE angioplasty; ankle-brachial index; cilostazol; exercise rehabilitation; quality of life; walking ID PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; RANDOMIZED CONTROLLED TRIAL; INTERMITTENT CLAUDICATION; RISK-FACTORS; PREVALENCE; HEALTH; REHABILITATION; PLACEMENT; OUTCOMES; PROGRAM AB BACKGROUND Treatment for claudication that is due to aortoiliac peripheral artery disease (PAD) often relies on stent revascularization (ST). However, supervised exercise (SE) is known to provide comparable short-term (6-month) improvements in functional status and quality of life. Longer-term outcomes are not known. OBJECTIVES The goal of this study was to report the longer-term (18-month) efficacy of SE compared with ST and optimal medical care (OMC). METHODS Of 111 patients with aortoiliac PAD randomly assigned to receive OMC, OMC plus SE, or OMC plus ST, 79 completed the 18-month clinical and treadmill follow-up assessment. SE consisted of 6 months of SE and an additional year of telephone-based exercise counseling. Primary clinical outcomes included objective treadmill-based walking performance and subjective quality of life. RESULTS Peak walking time improved from baseline to 18 months for both SE (5.0 +/- 5.4 min) and ST (3.2 +/- 4.7 min) significantly more than for OMC (0.2 +/- 2.1 min; p < 0.001 and p = 0.04, respectively). The difference between SE and ST was not significant (p = 0.16). Improvement in claudication onset time was greater for SE compared with OMC, but not for ST compared with OMC. Many disease-specific quality-of-life scales demonstrated durable improvements that were greater for ST compared with SE or OMC. CONCLUSIONS Both SE and ST had better 18-month outcomes than OMC. SE and ST provided comparable durable improvement in functional status and in quality of life up to 18 months. The durability of claudication exercise interventions merits its consideration as a primary PAD claudication treatment. (C) 2015 by the American College of Cardiology Foundation. C1 [Murphy, Timothy P.; Cerezo, Joselyn] Rhode Isl Hosp, Vasc Dis Res Ctr, Dept Diagnost Imaging, Providence, RI 02903 USA. [Cutlip, Donald E.] Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. [Cutlip, Donald E.; Reynolds, Matthew R.; Massaro, Joseph M.; Thum, Claudia C.] Harvard Clin Res Inst, Boston, MA USA. [Regensteiner, Judith G.] Univ Colorado, Sch Med Aurora, Ctr Womens Hlth Res, Aurora, CO USA. [Mohler, Emile R., III] Univ Penn, Perelman Sch Med, Div Cardiovasc, Sect Vasc Med, Philadelphia, PA 19104 USA. [Cohen, David J.] Univ Missouri, Div Cardiol, Kansas City, MO 64110 USA. [Massaro, Joseph M.] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Lewis, Beth A.] Univ Minnesota, Sch Kinesiol, Minneapolis, MN USA. [Oldenburg, Niki C.; Steffes, Michael W.; Hirsch, Alan T.] Univ Minnesota, Sch Med, Div Cardiovasc, Lillehei Heart Inst, Minneapolis, MN 55455 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Comerota, Anthony J.] Toledo Hosp, Jobst Vasc Inst, Toledo, OH USA. [Goldberg, Suzanne] NHLBI, Bethesda, MD 20892 USA. RP Murphy, TP (reprint author), Rhode Isl Hosp, Vasc Dis Res Ctr, Gerry 337,593 Eddy St, Providence, RI 02903 USA. EM tmurphy@lifespan.org FU National Heart, Lung, and Blood Institute [HL77221, HL081656]; eV3; Boston Scientific; Abbott Vascular; Cordis/Johnson Johnson; Otsuka Pharmaceuticals; Medtronic; Cardiovascular Systems, Inc.; Aastrom Biosciences; Viromed; AstraZeneca; pedometers FX The CLEVER study was sponsored primarily by the National Heart, Lung, and Blood Institute (grants HL77221 and HL081656), and also received financial support from Cordis/Johnson & Johnson, eV3, and Boston Scientific. Throughout the study, Otsuka America donated cilostazol for all study participants. Omron Healthcare donated pedometers. Krames Stay well donated print materials on exercise and diet for study participants. Dr. Murphy has received research grant support from Abbott Vascular, Cordis/Johnson & Johnson, and Otsuka Pharmaceuticals. Dr. Cutlip has received either a research contract or grant support paid to his institution from Medtronic, Boston Scientific, and Abbott Vascular. Dr. Cohen has received research grant support from Medtronic, Boston Scientific, Abbott Vascular, and Cardiovascular Systems, Inc.; and has served as a consultant to Medtronic, Abbott Vascular, and Cardiovascular Systems, Inc. Dr. Reynolds has served as a consultant to Medtronic, Inc. Dr. Jaff has equity in Micell, Inc. and PQ Bypass; has served on the board of VIVA Physicians, Inc.; and has served as a consultant to Becker Venture Services Group, Abbott Vascular, Boston Scientific, Cordis Corporation, Covidien/eV3, and Medtronic Vascular. Dr. Hirsch has received research grants from Abbott Vascular, Aastrom Biosciences, Viromed, and AstraZeneca; and served as a consultant to Novartis and Merck & Co. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 36 TC 29 Z9 31 U1 2 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 BP 999 EP 1009 DI 10.1016/j.jacc.2014.12.043 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CC8RK UT WOS:000350635600007 PM 25766947 ER PT J AU Braunwald, E AF Braunwald, Eugene TI The Path to an Angiotensin Receptor Antagonist-Neprilysin Inhibitor in the Treatment of Heart Failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review DE hypertension; natriuretic peptide; renin ID NEUTRAL ENDOPEPTIDASE INHIBITION; ATRIAL-NATRIURETIC-PEPTIDE; BRADYKININ-POTENTIATING FACTOR; CONVERTING ENZYME-INHIBITION; BRACHIAL BLOOD-PRESSURE; VASOPEPTIDASE INHIBITION; RANDOMIZED-TRIAL; RENAL-FUNCTION; EXPERIMENTAL-HYPERTENSION; AORTIC STIFFNESS AB The PARADIGM-HF (Prospective comparison of ARNi with ACEi to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial demonstrated that a new angiotensin receptor antagonist-neprilysin inhibitor was superior to an angiotensin-converting enzyme inhibitor in reducing mortality in patients with heart failure and reduced ejection fraction. This paper traces the research path that culminated in the development of this drug. The first phase, elucidation of the renin-angiotensin-aldosterone system, began with Tigerstedt's discovery of renin, followed by isolation of angiotensin, isolation of angiotensin-converting enzyme, and synthesis of its inhibitors and of angiotensin receptor blockers. Phase 2 began with de Bold's discovery of atrial natriuretic peptide, followed by isolation of the enzyme that degrades it (neprilysin) and its inhibitors. Phase 3 consists of blocking both the renin-angiotensin-aldosterone and atrial natriuretic peptide-degrading systems simultaneously. A molecular complex, LCZ696, developed by scientists at Novartis, combines an angiotensin receptor blocker with a neprilysin inhibitor, is well tolerated, and represents an important step in the management of heart failure and reduced ejection fraction. (C) 2015 by the American College of Cardiology Foundation. C1 [Braunwald, Eugene] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Braunwald, Eugene] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Braunwald, E (reprint author), Brigham & Womens Hosp, Dept Med, TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 114 TC 25 Z9 26 U1 5 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 BP 1029 EP 1041 DI 10.1016/j.jacc.2015.01.033 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CC8RK UT WOS:000350635600011 PM 25766951 ER PT J AU Kleinridders, A Cai, WK Cappellucci, L Ghazarian, A Collins, WR Vienberg, SG Pothos, EN Kahn, CR AF Kleinridders, Andre Cai, Weikang Cappellucci, Laura Ghazarian, Armen Collins, William R. Vienberg, Sara G. Pothos, Emmanuel N. Kahn, C. Ronald TI Insulin resistance in brain alters dopamine turnover and causes behavioral disorders SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE insulin receptor; diabetes; mitochondrial function; monoamine oxidase; dopamine signaling ID DB/DB DIABETIC MICE; MITOCHONDRIAL DYSFUNCTION; MONOAMINE-OXIDASE; ALZHEIMERS-DISEASE; MAJOR DEPRESSION; FUNCTIONAL CONNECTIVITY; PARKINSONS-DISEASE; OXIDATIVE STRESS; OBESITY; RECEPTOR AB Diabetes and insulin resistance are associated with altered brain imaging, depression, and increased rates of age-related cognitive impairment. Here we demonstrate that mice with a brain-specific knockout of the insulin receptor (NIRKO mice) exhibit brain mitochondrial dysfunction with reduced mitochondrial oxidative activity, increased levels of reactive oxygen species, and increased levels of lipid and protein oxidation in the striatum and nucleus accumbens. NIRKO mice also exhibit increased levels of monoamine oxidase A and B (MAO A and B) leading to increased dopamine turnover in these areas. Studies in cultured neurons and glia cells indicate that these changes in MAO A and B are a direct consequence of loss of insulin signaling. As a result, NIRKO mice develop age-related anxiety and depressive-like behaviors that can be reversed by treatment with MAO inhibitors, as well as the tricyclic antidepressant imipramine, which inhibits MAO activity and reduces oxidative stress. Thus, insulin resistance in brain induces mitochondrial and dopaminergic dysfunction leading to anxiety and depressive-like behaviors, demonstrating a potential molecular link between central insulin resistance and behavioral disorders. C1 [Kleinridders, Andre; Cai, Weikang; Vienberg, Sara G.; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA. [Cappellucci, Laura; Ghazarian, Armen; Pothos, Emmanuel N.] Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Dept Integrat Physiol & Pathobiol, Boston, MA 02111 USA. [Collins, William R.; Pothos, Emmanuel N.] Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Grad Program Pharmacol & Expt Therapeut, Boston, MA 02111 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu OI Pothos, Emmanuel/0000-0001-8825-7852 FU NIH [R01 DK033201, R01 DK031036]; Mary K. Iacocca Professorship [DK065872, P30 DK036836]; Deutsche Forschungsgesellschaft (DFG) [KL2399/1-1, KL2399/3-1] FX We thank M. Rourk and G. Smyth for animal care; G. Sankaranarayanan [Joslin Diabetes Center's Diabetes and Endocrinology Research Center (DERC) Specialized Assay Core], C. Cahill (Joslin's DERC Advanced Microscopy Core), and Maura Mulvey (Joslin's DERC Physiology Core) for technical assistance; and Elizabeth Hanson and Laura Darnieder for experimental assistance. This work was supported by NIH Grants R01 DK033201 and R01 DK031036 and the Mary K. Iacocca Professorship (to C.R.K.), DK065872 (to E.N.P.), and P30 DK036836 (Joslin's DERC Core Facilities) and Deutsche Forschungsgesellschaft (DFG) Projects KL2399/1-1 and KL2399/3-1 (to A.K.). NR 62 TC 35 Z9 36 U1 7 U2 29 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 17 PY 2015 VL 112 IS 11 BP 3463 EP 3468 DI 10.1073/pnas.1500877112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CD4NM UT WOS:000351060000083 PM 25733901 ER PT J AU Kim, T Thankachan, S McKenna, JT McNally, JM Yang, C Choi, JH Chen, LC Kocsis, B Deisseroth, K Strecker, RE Basheer, R Brown, RE McCarley, RW AF Kim, Tae Thankachan, Stephen McKenna, James T. McNally, James M. Yang, Chun Choi, Jee Hyun Chen, Lichao Kocsis, Bernat Deisseroth, Karl Strecker, Robert E. Basheer, Radhika Brown, Ritchie E. McCarley, Robert W. TI Cortically projecting basal forebrain parvalbumin neurons regulate cortical gamma band oscillations SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ArchT; arousal; auditory steady-state response; channelrhodopsin2; optogenetics ID NUCLEUS BASALIS; CHOLINERGIC NEURONS; EVOKED-POTENTIALS; WAKE STATES; SCHIZOPHRENIA; SLEEP; ACTIVATION; CORTEX; RAT; INTERNEURONS AB Cortical gamma band oscillations (GBO, 30-80 Hz, typically similar to 40 Hz) are involved in higher cognitive functions such as feature binding, attention, and working memory. GBO abnormalities are a feature of several neuropsychiatric disorders associated with dysfunction of cortical fast-spiking interneurons containing the calcium-binding protein parvalbumin (PV). GBO vary according to the state of arousal, are modulated by attention, and are correlated with conscious awareness. However, the subcortical cell types underlying the state-dependent control of GBO are not well understood. Here we tested the role of one cell type in the wakefulness-promoting basal forebrain (BF) region, cortically projecting GABAergic neurons containing PV, whose virally transduced fibers we found apposed cortical PV interneurons involved in generating GBO. Optogenetic stimulation of BF PV neurons in mice preferentially increased cortical GBO power by entraining a cortical oscillator with a resonant frequency of similar to 40 Hz, as revealed by analysis of both rhythmic and nonrhythmic BF PV stimulation. Selective saporin lesions of BF cholinergic neurons did not alter the enhancement of cortical GBO power induced by BF PV stimulation. Importantly, bilateral optogenetic inhibition of BF PV neurons decreased the power of the 40-Hz auditory steady-state response, a read-out of the ability of the cortex to generate GBO used in clinical studies. Our results are surprising and novel in indicating that this presumptively inhibitory BF PV input controls cortical GBO, likely by synchronizing the activity of cortical PV interneurons. BF PV neurons may represent a previously unidentified therapeutic target to treat disorders involving abnormal GBO, such as schizophrenia. C1 [Kim, Tae; Thankachan, Stephen; McKenna, James T.; McNally, James M.; Yang, Chun; Chen, Lichao; Strecker, Robert E.; Basheer, Radhika; Brown, Ritchie E.; McCarley, Robert W.] VA Boston Healthcare Syst, Dept Psychiat, Brockton, MA 02301 USA. [Kim, Tae; Thankachan, Stephen; McKenna, James T.; McNally, James M.; Yang, Chun; Chen, Lichao; Kocsis, Bernat; Strecker, Robert E.; Basheer, Radhika; Brown, Ritchie E.; McCarley, Robert W.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Choi, Jee Hyun] Korea Inst Sci & Technol, Ctr Neurosci, Seoul 130722, South Korea. [Kocsis, Bernat] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Deisseroth, Karl] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA. RP McCarley, RW (reprint author), VA Boston Healthcare Syst, Dept Psychiat, Brockton, MA 02301 USA. EM robert_mccarley@hms.harvard.edu OI Brown, Ritchie/0000-0002-7164-4132 FU Department of Veterans Affairs Awards; National Institutes of Mental Health [R01 MH039683, R21 MH094803, R01 MH100820]; National Institute of Neurological Disorders and Stroke [R21 NS079866-01, P01 HL095491]; Global Frontier Grant [2011-0031525] FX This work was supported by Department of Veterans Affairs Awards (to R.W.M., R.B., and R.E.S.); by National Institutes of Mental Health Grants R01 MH039683 (to R.W.M.), R21 MH094803 (to R.E.B.), and R01 MH100820 (to B.K.); National Institute of Neurological Disorders and Stroke Grants R21 NS079866-01 (to R.B.) and P01 HL095491 (to R.W.M. and B.K.); and Global Frontier Grant 2011-0031525 (to J.H.C.). NR 52 TC 37 Z9 38 U1 4 U2 26 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 17 PY 2015 VL 112 IS 11 BP 3535 EP 3540 DI 10.1073/pnas.1413625112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CD4NM UT WOS:000351060000095 PM 25733878 ER PT J AU Faber, AC Farago, AF Costa, C Dastur, A Gomez-Caraballo, M Robbins, R Wagner, BL Rideout, WM Jakubik, CT Ham, J Edelman, EJ Ebi, H Yeo, AT Hata, AN Song, YC Patel, NU March, RJ Tam, AT Milano, RJ Boisvert, JL Hicks, MA Elmiligy, S Malstrom, SE Rivera, MN Harada, H Windle, BE Ramaswamy, S Benes, CH Jacks, T Engelman, JA AF Faber, Anthony C. Farago, Anna F. Costa, Carlotta Dastur, Anahita Gomez-Caraballo, Maria Robbins, Rebecca Wagner, Bethany L. Rideout, William M., III Jakubik, Charles T. Ham, Jungoh Edelman, Elena J. Ebi, Hiromichi Yeo, Alan T. Hata, Aaron N. Song, Youngchul Patel, Neha U. March, Ryan J. Ah Ting Tam Milano, Randy J. Boisvert, Jessica L. Hicks, Mark A. Elmiligy, Sarah Malstrom, Scott E. Rivera, Miguel N. Harada, Hisashi Windle, Brad E. Ramaswamy, Sridhar Benes, Cyril H. Jacks, Tyler Engelman, Jeffrey A. TI Assessment of ABT-263 activity across a cancer cell line collection leads to a potent combination therapy for small-cell lung cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE small-cell lung cancer; targeted therapies; BH3 mimetics; apoptosis; BIM ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CAP-DEPENDENT TRANSLATION; BCL-2 FAMILY INHIBITOR; ANTAGONIST ABT-737; OBATOCLAX GX15-070; KINASE INHIBITORS; DRUG-SENSITIVITY; PHASE-I; MCL-1; BIM AB BH3 mimetics such as ABT-263 induce apoptosis in a subset of cancer models. However, these drugs have shown limited clinical efficacy as single agents in small-cell lung cancer (SCLC) and other solid tumor malignancies, and rational combination strategies remain underexplored. To develop a novel therapeutic approach, we examined the efficacy of ABT-263 across > 500 cancer cell lines, including 311 for which we had matched expression data for select genes. We found that high expression of the proapoptotic gene Bcl2-interacting mediator of cell death (BIM) predicts sensitivity to ABT-263. In particular, SCLC cell lines possessed greater BIM transcript levels than most other solid tumors and are among the most sensitive to ABT-263. However, a subset of relatively resistant SCLC cell lines has concomitant high expression of the antiapoptotic myeloid cell leukemia 1 (MCL-1). Whereas ABT-263 released BIM from complexes with BCL-2 and BCL-XL, high expression of MCL-1 sequestered BIM released from BCL-2 and BCL-XL, thereby abrogating apoptosis. We found that SCLCs were sensitized to ABT-263 via TORC1/2 inhibition, which led to reduced MCL-1 protein levels, thereby facilitating BIM-mediated apoptosis. AZD8055 and ABT-263 together induced marked apoptosis in vitro, as well as tumor regressions in multiple SCLC xenograft models. In a Tp53; Rb1 deletion genetically engineered mouse model of SCLC, the combination of ABT-263 and AZD8055 significantly repressed tumor growth and induced tumor regressions compared with either drug alone. Furthermore, in a SCLC patient-derived xenograft model that was resistant to ABT-263 alone, the addition of AZD8055 induced potent tumor regression. Therefore, addition of a TORC1/2 inhibitor offers a therapeutic strategy to markedly improve ABT-263 activity in SCLC. C1 [Faber, Anthony C.; Farago, Anna F.; Costa, Carlotta; Dastur, Anahita; Gomez-Caraballo, Maria; Jakubik, Charles T.; Ham, Jungoh; Edelman, Elena J.; Ebi, Hiromichi; Yeo, Alan T.; Hata, Aaron N.; Song, Youngchul; March, Ryan J.; Ah Ting Tam; Milano, Randy J.; Boisvert, Jessica L.; Rivera, Miguel N.; Ramaswamy, Sridhar; Benes, Cyril H.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. [Faber, Anthony C.; Farago, Anna F.; Costa, Carlotta; Dastur, Anahita; Gomez-Caraballo, Maria; Jakubik, Charles T.; Ham, Jungoh; Edelman, Elena J.; Ebi, Hiromichi; Yeo, Alan T.; Hata, Aaron N.; Song, Youngchul; March, Ryan J.; Ah Ting Tam; Milano, Randy J.; Boisvert, Jessica L.; Ramaswamy, Sridhar; Benes, Cyril H.; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Farago, Anna F.; Robbins, Rebecca; Wagner, Bethany L.; Rideout, William M., III; Elmiligy, Sarah; Malstrom, Scott E.; Jacks, Tyler] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02138 USA. [Patel, Neha U.; Hicks, Mark A.; Harada, Hisashi; Windle, Brad E.] Virginia Commonwealth Univ, Sch Dent, Philips Inst Oral Hlth Res, Richmond, VA 23298 USA. [Patel, Neha U.; Hicks, Mark A.; Harada, Hisashi; Windle, Brad E.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA 23298 USA. [Rivera, Miguel N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Faber, AC (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. EM acfaber@vcu.edu; jengelman@partners.org OI Ebi, Hiromichi/0000-0003-3155-7576 FU Dana Farber/Harvard Cancer Center (DF/HCC) Lung Cancer Specialized Program in Research Excellence NIH-National Cancer Institute (NCI) Grant [2P50 CA09057]; NIH Grants [R01CA140594, R01CA137008-01, 1U54HG006097-01]; Department of Defense Grants [W81-XWH-13-1-0323, W81-XWH-13-1-0325]; U.S. Army Medical Research and Material Command Acquisition Activity is the awarding and administering acquisition office; NCI [P30-CA14051]; David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology (Koch Institute)-DF/HCC Bridge Project; Wellcome Trust [086357]; Lung Cancer Research Foundation grant; American Cancer Society Postdoctoral Fellowship; Uniting Against Lung Cancer FX We thank the Koch Institute Swanson Biotechnology Center for technical support, specifically the Hope Babette Tang (1983) Histology Facility and the Applied Therapeutics and Live Animal Imaging facility, and Alex Shoemaker (AbbVie) for helpful suggestions. T.J. is a Howard Hughes Medical Institute Investigator and a Daniel K. Ludwig Scholar. This work was supported by Dana Farber/Harvard Cancer Center (DF/HCC) Lung Cancer Specialized Program in Research Excellence NIH-National Cancer Institute (NCI) Grant 2P50 CA09057 (to J.A.E.); NIH Grants R01CA140594 (to J.A.E.), R01CA137008-01 (to J.A.E.), and 1U54HG006097-01 (to C.H.B.); Department of Defense Grants W81-XWH-13-1-0323 (to T.J.) and W81-XWH-13-1-0325 (to J.A.E.); U.S. Army Medical Research and Material Command Acquisition Activity is the awarding and administering acquisition office (T.J. and J.A.E.); Cancer Center Support Grant P30-CA14051 from the NCI (to T.J.); the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology (Koch Institute)-DF/HCC Bridge Project (T.J. and J.A.E.); Grant 086357 from the Wellcome Trust (to C.H.B.); awards from the Burroughs Wellcome Fund and the Howard Hughes Medical Institute (to M.N.R.); a Lung Cancer Research Foundation grant (to A.C.F.); an American Cancer Society Postdoctoral Fellowship (to A.C.F.); and a grant from Uniting Against Lung Cancer (to A.F.F.). NR 45 TC 17 Z9 17 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 17 PY 2015 VL 112 IS 11 BP E1288 EP E1296 DI 10.1073/pnas.1411848112 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CD4NM UT WOS:000351060000018 PM 25737542 ER PT J AU Frakt, AB AF Frakt, Austin B. TI An Observational Study Goes Where Randomized Clinical Trials Have Not SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 [Frakt, Austin B.] Boston VA Healthcare Syst, Boston, MA 02130 USA. [Frakt, Austin B.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Frakt, Austin B.] Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Frakt, AB (reprint author), Boston VA Healthcare Syst, Boston, MA 02130 USA. EM afrakt@gmail.com NR 0 TC 4 Z9 5 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 17 PY 2015 VL 313 IS 11 BP 1091 EP 1092 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CD5BP UT WOS:000351102500003 PM 25781429 ER PT J AU Kereiakes, DJ Yeh, RW Massaro, JM Driscoll-Shempp, P Cutlip, DE Steg, PG Gershlick, AH Darius, H Meredith, IT Ormiston, J Tanguay, JF Windecker, S Garratt, KN Kandzari, DE Lee, DP Simon, DI Iancu, AC Trebacz, J Mauri, L AF Kereiakes, Dean J. Yeh, Robert W. Massaro, Joseph M. Driscoll-Shempp, Priscilla Cutlip, Donald E. Steg, P. Gabriel Gershlick, Anthony H. Darius, Harald Meredith, Ian T. Ormiston, John Tanguay, Jean Francois Windecker, Stephan Garratt, Kirk N. Kandzari, David E. Lee, David P. Simon, Daniel I. Iancu, Adrian Corneliu Trebacz, Jaroslaw Mauri, Laura CA Dual Antiplatelet Therapy DAPT TI Antiplatelet Therapy Duration Following Bare Metal or Drug-Eluting Coronary Stents The Dual Antiplatelet Therapy Randomized Clinical Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID AMERICAN-COLLEGE; IMPLANTATION; MULTICENTER; OUTCOMES; INTERVENTION; DEFINITIONS; RESTENOSIS; GUIDELINES; EVENTS; IMPACT AB IMPORTANCE Despite antirestenotic efficacy of coronary drug-eluting stents (DES) compared with bare metal stents (BMS), the relative risk of stent thrombosis and adverse cardiovascular events is unclear. Although dual antiplatelet therapy (DAPT) beyond 1 year provides ischemic event protection after DES, ischemic event risk is perceived to be less after BMS, and the appropriate duration of DAPT after BMS is unknown. OBJECTIVE To compare (1) rates of stent thrombosis and major adverse cardiac and cerebrovascular events (MACCE; composite of death, myocardial infarction, or stroke) after 30 vs 12 months of thienopyridine in patients treated with BMS taking aspirin and (2) treatment duration effect within the combined cohorts of randomized patients treated with DES or BMS as prespecified secondary analyses. DESIGN, SETTING, AND PARTICIPANTS International, multicenter, randomized, double-blinded, placebo-controlled trial comparing extended (30-months) thienopyridine vs placebo in patients taking aspirin who completed 12 months of DAPT without bleeding or ischemic events after receiving stents. The study was initiated in August 2009 with the last follow-up visit in May 2014. INTERVENTIONS Continued thienopyridine or placebo at months 12 through 30 after stent placement, in 11 648 randomized patients treated with aspirin, of whom 1687 received BMS and 9961 DES. MAIN OUTCOMES AND MEASURES Stent thrombosis, MACCE, and moderate or severe bleeding. RESULTS Among 1687 patients treated with BMS who were randomized to continued thienopyridine vs placebo, rates of stent thrombosis were 0.5% vs 1.11% (n = 4 vs 9; hazard ratio [HR], 0.49; 95% CI, 0.15-1.64; P = .24), rates of MACCE were 4.04% vs 4.69%(n = 33 vs 38; HR, 0.92; 95% CI, 0.57-1.47; P = .72), and rates of moderate/severe bleeding were 2.03% vs 0.90% (n = 16 vs 7; P = .07), respectively. Among all 11 648 randomized patients (both BMS and DES), stent thrombosis rates were 0.41% vs 1.32%(n = 23 vs 74; HR, 0.31; 95% CI, 0.19-0.50; P < .001), rates of MACCE were 4.29% vs 5.74%(n = 244 vs 323; HR, 0.73; 95% CI, 0.62-0.87; P < .001), and rates of moderate/severe bleeding were 2.45% vs 1.47%(n = 135 vs 80; P < .001). CONCLUSIONS AND RELEVANCE Among patients undergoing coronary stent placement with BMS and who tolerated 12 months of thienopyridine, continuing thienopyridine for an additional 18 months compared with placebo did not result in statistically significant differences in rates of stent thrombosis, MACCE, or moderate or severe bleeding. However, the BMS subset may have been underpowered to identify such differences, and further trials are suggested. C1 [Kereiakes, Dean J.] Christ Hosp Heart & Vasc Ctr, Cincinnati, OH USA. [Kereiakes, Dean J.] Lindner Res Ctr, Cincinnati, OH USA. [Yeh, Robert W.; Massaro, Joseph M.; Driscoll-Shempp, Priscilla; Cutlip, Donald E.; Mauri, Laura] Harvard Clin Res Inst, Boston, MA USA. [Yeh, Robert W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Massaro, Joseph M.] Boston Univ, Boston, MA 02215 USA. [Cutlip, Donald E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Steg, P. Gabriel] Univ Paris Diderot, Paris, France. [Steg, P. Gabriel] Hop Bichat Claude Bernard, Dept Hosp Univ FIRE, F-75877 Paris, France. [Steg, P. Gabriel] Royal Brompton Hosp, Imperial Coll, Natl Heart & Lung Inst, London SW3 6LY, England. [Gershlick, Anthony H.] Univ Hosp Leicester, Leicester, Leics, England. [Darius, Harald] Vivantes Neukoelln Med Ctr, Berlin, Germany. [Meredith, Ian T.] Monash Heart, Clayton, Vic, Australia. [Ormiston, John] Mercy Hosp, Auckland, New Zealand. [Tanguay, Jean Francois] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada. [Windecker, Stephan] Univ Hosp Bern, CH-3010 Bern, Switzerland. [Garratt, Kirk N.] Lenox Hill Hosp, New York, NY 10021 USA. [Kandzari, David E.] Piedmont Heart Inst, Atlanta, GA USA. [Lee, David P.] Stanford Univ, Stanford, CA 94305 USA. [Simon, Daniel I.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Iancu, Adrian Corneliu] Inst Heart, Cluj Napoca, Romania. [Trebacz, Jaroslaw] Jan Pawel II Hosp Krakow, Krakow, Poland. [Mauri, Laura] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Mauri, L (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM lmauri1@partners.org FU Harvard Clinical Research Institute (HCRI); Abbott; Boston Scientific; Cordis; Medtronic; Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership; Eli Lilly; Daiichi Sankyo; US Department of Health and Human Services [1RO1FD003870-01] FX The study was sponsored by the Harvard Clinical Research Institute (HCRI) and funded by Abbott, Boston Scientific, Cordis, Medtronic, Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership, Eli Lilly, and Daiichi Sankyo and the US Department of Health and Human Services (1RO1FD003870-01). NR 22 TC 37 Z9 37 U1 1 U2 20 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 17 PY 2015 VL 313 IS 11 BP 1113 EP 1121 DI 10.1001/jama.2015.1671 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CD5BP UT WOS:000351102500013 PM 25781440 ER PT J AU Nan, HM Hutter, CM Lin, Y Jacobs, EJ Ulrich, CM White, E Baron, JA Berndt, SI Brenner, H Butterbach, K Caan, BJ Campbell, PT Carlson, CS Casey, G Chang-Claude, J Chanock, SJ Cotterchio, M Duggan, D Figueiredo, JC Fuchs, CS Giovannucci, EL Gong, J Haile, RW Harrison, TA Hayes, RB Hoffmeister, M Hopper, JL Hudson, TJ Jenkins, MA Jiao, S Lindor, NM Lemire, M Le Marchand, L Newcomb, PA Ogino, S Pflugeisen, BM Potter, JD Qu, CH Rosse, SA Rudolph, A Schoen, RE Schumacher, FR Seminara, D Slattery, ML Thibodeau, SN Thomas, F Thornquist, M Warnick, GS Zanke, BW Gauderman, WJ Peters, U Hsu, L Chan, AT AF Nan, Hongmei Hutter, Carolyn M. Lin, Yi Jacobs, Eric J. Ulrich, Cornelia M. White, Emily Baron, John A. Berndt, Sonja I. Brenner, Hermann Butterbach, Katja Caan, Bette J. Campbell, Peter T. Carlson, Christopher S. Casey, Graham Chang-Claude, Jenny Chanock, Stephen J. Cotterchio, Michelle Duggan, David Figueiredo, Jane C. Fuchs, Charles S. Giovannucci, Edward L. Gong, Jian Haile, Robert W. Harrison, Tabitha A. Hayes, Richard B. Hoffmeister, Michael Hopper, John L. Hudson, Thomas J. Jenkins, Mark A. Jiao, Shuo Lindor, Noralane M. Lemire, Mathieu Le Marchand, Loic Newcomb, Polly A. Ogino, Shuji Pflugeisen, Bethann M. Potter, John D. Qu, Conghui Rosse, Stephanie A. Rudolph, Anja Schoen, Robert E. Schumacher, Fredrick R. Seminara, Daniela Slattery, Martha L. Thibodeau, Stephen N. Thomas, Fridtjof Thornquist, Mark Warnick, Greg S. Zanke, Brent W. Gauderman, W. James Peters, Ulrike Hsu, Li Chan, Andrew T. CA CCFR GECCO TI Association of Aspirin and NSAID Use With Risk of Colorectal Cancer According to Genetic Variants SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID GENOME-WIDE ASSOCIATION; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PROSTAGLANDIN E-2 BIOSYNTHESIS; COLON-CANCER; PIK3CA MUTATION; METAANALYSIS; CYCLOOXYGENASE-2; CHEMOPREVENTION; INTERLEUKIN-16; POLYMORPHISMS AB IMPORTANCE Use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with lower risk of colorectal cancer. OBJECTIVE To identify common genetic markers that may confer differential benefit from aspirin or NSAID chemoprevention, we tested gene x environment interactions between regular use of aspirin and/or NSAIDs and single-nucleotide polymorphisms (SNPs) in relation to risk of colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS Case-control study using data from 5 case-control and 5 cohort studies initiated between 1976 and 2003 across the United States, Canada, Australia, and Germany and including colorectal cancer cases (n=8634) and matched controls (n=8553) ascertained between 1976 and 2011. Participants were all of European descent. EXPOSURES Genome-wide SNP data and information on regular use of aspirin and/or NSAIDs and other risk factors. MAIN OUTCOMES AND MEASURES Colorectal cancer. RESULTS Regular use of aspirin and/or NSAIDs was associated with lower risk of colorectal cancer (prevalence, 28% vs 38%; odds ratio [OR], 0.69 [95% Cl, 0.64-0.74]; P = 6.2 x 10(-28)) compared with nonregular use. In the conventional logistic regression analysis, the SNP rs2965667 at chromosome 12p12.3 near the MGST1 gene showed a genome-wide significant interaction with aspirin and/or NSAID use (P = 4.6 x 10(-9) for interaction). Aspirin and/or NSAID use was associated with a lower risk of colorectal cancer among individuals with rs2965667-TT genotype (prevalence, 28% vs 38%; OR, 0.66 [95% CI, 0.61-0.70]; P =7.7 x 10(-33)) but with a higher risk among those with rare (4%) TA or AA genotypes (prevalence, 35% vs 29%; OR, 1.89 [95% Cl, 1.27-2.81]; P = .002). In case-only interaction analysis, the SNP rs16973225 at chromosome 15q25.2 near the IL16 gene showed a genome-wide significant interaction with use of aspirin and/or NSAIDs (P = 8.2 x 10(-9) for interaction). Regular use was associated with a lower risk of colorectal cancer among individuals with rs16973225-AA genotype (prevalence, 28% vs 38%; OR, 0.66 [95% CI, 0.62-0.71]; P = 1.9 x 10(-30)) but was not associated with risk of colorectal cancer among those with less common (9%) AC or CC genotypes (prevalence, 36% vs 39%; OR, 0.97 [95% Cl, 0.78-1.20]; P = .76). CONCLUSIONS AND RELEVANCE In this genome-wide investigation of gene x environment interactions, use of aspirin and/or NSAIDs was associated with lower risk of colorectal cancer, and this association differed according to genetic variation at 2 SNPs at chromosomes 12 and 15. Validation of these findings in additional populations may facilitate targeted colorectal cancer prevention strategies. C1 [Nan, Hongmei] Indiana Univ, Richard M Fairbanks Sch Publ Hlth, Dept Epidemiol, Indianapolis, IN 46204 USA. [Nan, Hongmei] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. [Hutter, Carolyn M.; Seminara, Daniela] NHGRI, NIH, Bethesda, MD 20892 USA. [Lin, Yi; Ulrich, Cornelia M.; White, Emily; Carlson, Christopher S.; Gong, Jian; Harrison, Tabitha A.; Jiao, Shuo; Newcomb, Polly A.; Pflugeisen, Bethann M.; Potter, John D.; Qu, Conghui; Rosse, Stephanie A.; Thornquist, Mark; Warnick, Greg S.; Peters, Ulrike; Hsu, Li] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Jacobs, Eric J.; Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Ulrich, Cornelia M.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [White, Emily; Peters, Ulrike] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Baron, John A.] Univ N Carolina, Sch Med, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. [Berndt, Sonja I.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Brenner, Hermann; Butterbach, Katja; Hoffmeister, Michael] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Brenner, Hermann] German Canc Consortium DKTK, Heidelberg, Germany. [Caan, Bette J.] Kaiser Permanente Med Care Program No Calif, Div Res, Oakland, CA USA. [Casey, Graham; Figueiredo, Jane C.; Haile, Robert W.; Schumacher, Fredrick R.; Gauderman, W. James] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Chang-Claude, Jenny; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Cotterchio, Michelle] Canc Care Ontario, Prevent & Canc Control, Toronto, ON, Canada. [Duggan, David] Translat Genom Res Inst TGen, Genet Basis Human Dis Div, Phoenix, AZ USA. [Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Giovannucci, Edward L.; Chan, Andrew T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Div Network Med, Boston, MA 02115 USA. [Hayes, Richard B.] NYU, Sch Med, Dept Populat Hlth, Div Epidemiol, New York, NY USA. [Hopper, John L.; Jenkins, Mark A.] Univ Melbourne, Melbourne Sch Populat Hlth, Melbourne, Vic 3010, Australia. [Hudson, Thomas J.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [Hudson, Thomas J.; Lemire, Mathieu] Ontario Inst Canc Res, Toronto, ON, Canada. [Lindor, Noralane M.] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ USA. [Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. [Schoen, Robert E.] Univ Pittsburgh, Med Ctr, Dept Med & Epidemiol, Pittsburgh, PA USA. [Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Med Genet, Rochester, MN USA. [Thomas, Fridtjof] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Div Biostat & Epidemiol, Memphis, TN 38163 USA. [Zanke, Brent W.] Ottawa Hosp, Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada. [Hsu, Li] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. RP Hsu, L (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave North,M2-B500, Seattle, WA 98109 USA. EM lih@fredhutch.org; achan@mgh.harvard.edu RI Hoffmeister, Michael/B-5745-2012; Jenkins, Mark/P-7803-2015; Brenner, Hermann/B-4627-2017; OI Hoffmeister, Michael/0000-0002-8307-3197; Jenkins, Mark/0000-0002-8964-6160; Brenner, Hermann/0000-0002-6129-1572; Potter, John/0000-0001-5439-1500; Hayes, Richard/0000-0002-0918-661X FU National Cancer Institute (NCI), National Institutes of Health (NIH), US Department of Health and Human Services [U01 CA137088, RO1 CA059045]; NIH [RFA CA-95-011, R01 CA48998, P01 CA 055075, UM1 CA167552, R01137178, R01 CA137178, P01 CA 087969, RO1 CA151993, P50 CA 127003, U01 CA074783, R01 CA076366, K05 CA154337]; NCI, NIH [U01 CA122839]; NIH: Australasian Colorectal Cancer Family Registry [U01 CA097735]; Ontario Registry for Studies of Familial Colorectal Cancer [U01 CA074783]; Seattle Colorectal Cancer Family Registry [U01 CA074794]; German Research Council (Deutsche Forschungsgemeinschaft) [BR 1704/6-1, BR 1704163, BR 1704/6-4, CH 117/1-1]; German Federal Ministry of Education and Research [01KH0404, 01ER0814]; Ontario Research Fund [GL2]; Canadian Institutes of Health Research; Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute; Ontario Institute for Cancer Research through Ontario Ministry of Research and Innovation; Division of Cancer Epidemiology and Genetics; Division of Cancer Prevention, NCI, NIH, Department of Health and Human Services; National Heart, Lung, and Blood Institute, NIH, US Department of Health and Human Services [HHSN268201100046C, HH5N268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; [K24 DK098311] FX GECCO (Genetics and Epidemiology of Colorectal Cancer Consortium) was supported by the National Cancer Institute (NCI), National Institutes of Health (NIH), US Department of Health and Human Services (U01 CA137088; RO1 CA059045). CCFR (Colon Cancer Family Registry) was supported by the NIH (RFA CA-95-011) and through cooperative agreements with members of the Colon Cancer Family Registry and prinicipal investigators. This genome wide scan was supported by the NCI, NIH, by U01 CA122839. The following Colon CFR centers contributed data to this manuscript and were supported by NIH: Australasian Colorectal Cancer Family Registry (U01 CA097735), Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783), and Seattle Colorectal Cancer Family Registry (U01 CA074794). DACHS (Darmkrebs: Chancen der Verhutung durch Screening Study) is supported by the German Research Council (Deutsche Forschungsgemeinschaft, BR 1704/6-1, BR 1704163, BR 1704/6-4 and CH 117/1-1) and the German Federal Ministry of Education and Research (01KH0404 and 01ER0814). DALS (Diet, Activity and Lifestyle Study) is suported by the NIH (R01 CA48998 to Dr Slattery). HPFS (Health Professionals Follow-up Study) is supported by the NIH (P01 CA 055075, UM1 CA167552, R01137178, RO1 CA151993, and P50 CA 127003) and the NHS (Nurses Health Study) by the NIH (R01 CA137178, P01 CA 087969, RO1 CA151993, and P50 CA 127003). Dr Chan is also supported by K24 DK098311 and is a Damon Runyon Clinical Investigator. OFCCR (Ontario Familial Colorectal Cancer Registry) is supported by the NIH through funding allocated to the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783) (see CCFR section above). As subset of ARCTIC, OFCCR is supported by a GL2 grant from the Ontario Research Fund, the Canadian Institutes of Health Research, and the Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute. Dr Hudson and Dr Zanke are recipients of Senior Investigator Awards from the Ontario Institute for Cancer Research, through generous support from the Ontario Ministry of Research and Innovation. PLCO (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial) is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and by contracts from the Division of Cancer Prevention, NCI, NIH, Department of Health and Human Services. PMH-CCFR (Postmenopausal Hormone Study-Colon Cancer Family Registry) is suported by the NIH (R01 CA076366 to Dr Newcomb). VITAL (VITamins And Lifestyle) is supported by the NIH (K05 CA154337). WHI (Women's Health Initiative) is supported by the National Heart, Lung, and Blood Institute, NIH, US Department of Health and Human Services, through contracts HHSN268201100046C, HH5N268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. NR 40 TC 42 Z9 43 U1 8 U2 30 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 17 PY 2015 VL 313 IS 11 BP 1133 EP 1142 DI 10.1001/jama.2015.1815 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CD5BP UT WOS:000351102500015 PM 25781442 ER PT J AU Friedman, MJ AF Friedman, Matthew J. TI Risk Factors for Suicides Among Army Personnel SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID RESILIENCE; STARRS; PREVALENCE; SOLDIERS; CARE AB IMPORTANCE The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) is a multicomponent study designed to generate actionable recommendations to reduce Army suicides and increase knowledge of risk and resilience factors for suicidality. OBJECTIVES To present data on prevalence, trends, and basic sociodemographic and Army experience correlates of suicides and accident deaths among active duty Regular Army soldiers between January 1, 2004, and December 31, 2009, and thereby establish a foundation for future Army STARRS investigations. DESIGN, SETTING, AND PARTICIPANTS Analysis of trends and predictors of suicide and accident deaths using Army and Department of Defense administrative data systems. Participants were all members of the US Regular Army serving at any time between 2004 and 2009. MAIN OUTCOMES AND MEASURES Death by suicide or accident during active Army service. RESULTS The suicide rate rose between 2004 and 2009 among never deployed and currently and previously deployed Regular Army soldiers. Increased suicide risk was associated with being a man (or a woman during deployment), white race/ethnicity, junior enlisted rank, recent demotion, and current or previous deployment. Sociodemographic and Army experience predictors were generally similar for suicides and accident deaths. CONCLUSION Predictors of Army suicides were largely similar to those reported elsewhere for civilians, although some predictors distinct to Army service emerged that deserve more in-depth analysis. The existence of a time trend in suicide risk among never-deployed soldiers argues indirectly against the view that exposure to combat-related trauma is the exclusive cause of the increase in Army suicides. C1 [Friedman, Matthew J.] US Dept Vet Affairs, Natl Ctr PTSD, White River Jct, VT USA. [Friedman, Matthew J.] Geisel Sch Med Dartmouth, Dept Psychiat, Hanover, NH USA. [Friedman, Matthew J.] Geisel Sch Med Dartmouth, Dept Pharmacol & Toxicol, Hanover, NH USA. RP Friedman, MJ (reprint author), Natl Ctr PTSD, Dept Vet Affairs, 215 N Main St 116D, White River Jct, VT 05009 USA. EM matthew.friedman@dartmouth.edu NR 8 TC 3 Z9 3 U1 2 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 17 PY 2015 VL 313 IS 11 BP 1154 EP 1155 DI 10.1001/jamapsychiatry.2013.4417 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CD5BP UT WOS:000351102500017 PM 25781444 ER PT J AU Arora, P Wu, C Hamid, T Arora, G Hu, DJ Domain, IJ Buys, E Bloch, D Prabhu, S Bloch, KD Newton-Cheh, C Wang, T AF Arora, Pankaj Wu, Connie Hamid, Tariq Arora, Garima Hu, Dongjian Domain, Ibrahim J. Buys, Emmanuel Bloch, Donald Prabhu, Sumanth Bloch, Kenneth D. Newton-Cheh, Christopher Wang, Thomas TI ACUTE METABOLIC INFLUENCES ON THE NATRIURETIC PEPTIDE SYSTEM IN HUMANS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Alabama Birmingham, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 904-03 BP A2144 EP A2144 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328802466 ER PT J AU Balesh, ER Vadvala, H Kim, P Elmariah, S Olmos, C Mayrhofer, T Ghoshhajra, B AF Balesh, Elie Rashid Vadvala, Harshna Kim, Phillip Elmariah, Sammy Olmos, Carmen Mayrhofer, Thomas Ghoshhajra, Brian TI CONCOMITANT CORONARY CT ANGIOGRAPHY ON TRANSCATHETER AORTIC VALVE IMPLANTATION PLANNING CT SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Balesh, Elie Rashid; Vadvala, Harshna; Kim, Phillip; Elmariah, Sammy; Olmos, Carmen; Mayrhofer, Thomas; Ghoshhajra, Brian] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1207-036 BP A1273 EP A1273 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328801593 ER PT J AU Barnes, GD Stanislawski, M Baron, AE Armstrong, E Ho, PM Klein, A Maddox, T Nallamothu, B Rumsfeld, J Tsai, T Bradley, S AF Barnes, Geoffrey D. Stanislawski, Maggie Baron, Anna E. Armstrong, Ehrin Ho, P. Michael Klein, Andrew Maddox, Thomas Nallamothu, Brahmajee Rumsfeld, John Tsai, Thomas Bradley, Steven TI USE OF CONTRAINDICATED ANTITHROMBOTIC MEDICATIONS IN THE CARDIAC CATHETERIZATION LABORATORY: INSIGHTS FROM THE VETERANS AFFAIRS CLINICAL ASSESSMENT, REPORTING, AND TRACKING PROGRAM SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Univ Michigan, Frankel Cardiovasc Ctr, Ann Arbor, MI 48109 USA. Denver VA Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 915-04 BP A2159 EP A2159 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328802481 ER PT J AU Belcher, A Gandhi, P Januzzi, J Gaggin, H AF Belcher, Arianna Gandhi, Parul Januzzi, James Gaggin, Hanna TI SERIAL MEASUREMENT OF TUMOR NECROSIS FACTOR-A, INTERLEUKIN-6 AND VASCULAR ENDOTHELIAL GROWTH FACTOR AS A FUNCTION OF CACHEXIA IN PATIENTS WITH CHRONIC HEART FAILURE: RESULTS FROM THE PROBNP OUTPATIENT TAILORED CHRONIC HEART FAILURE (PROTECT) STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Belcher, Arianna; Gandhi, Parul; Januzzi, James; Gaggin, Hanna] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1217-213 BP A990 EP A990 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328801310 ER PT J AU Cheezum, M Ghoshhajra, B Bittencourt, M Hulten, E Mousavi, N Steigner, M Rybicki, F Shah, N MacGillivray, T Bhatt, A Valente, AM Abbara, S Hoffmann, U Di Carli, M Yeh, D Landzberg, M Liberthson, R Blankstein, R AF Cheezum, Michael Ghoshhajra, Brian Bittencourt, Marcio Hulten, Edward Mousavi, Negareh Steigner, Michael Rybicki, Frank Shah, Nishant MacGillivray, Thomas Bhatt, Ami Valente, Anne Marie Abbara, Suhny Hoffmann, Udo Di Carli, Marcelo Yeh, Doreen Landzberg, Michael Liberthson, Richard Blankstein, Ron TI ANOMALOUS ORIGIN OF THE CORONARY ARTERIES: INCIDENCE AND OUTCOMES AMONG PATIENTS UNDERGOING CORONARY CTA SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1271M-03 BP A499 EP A499 DI 10.1016/S0735-1097(15)60499-5 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328800500 ER PT J AU Le, DTE Wei, K Zhao, Y Nugent, M Belardinelli, L Kaul, S AF Dai-Trang Elizabeth Le Wei, Kevin Zhao, Yan Nugent, Matthew Belardinelli, Luiz Kaul, Sanjiv TI INTRAVENOUS RANOLAZINE RELIEVES ISCHEMIA BY INCREASING MYOCARDIAL ADENOSINE LEVELS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97201 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1133M-09 BP A1571 EP A1571 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328801891 ER PT J AU Donaldson, CW Waldo, S Li, DK Pomerantsev, E Garasic, J Rosenfield, K Yeh, R Drachman, D AF Donaldson, Cameron W. Waldo, Stephen Li, Darrick K. Pomerantsev, Eugene Garasic, Joseph Rosenfield, Kenneth Yeh, Robert Drachman, Douglas TI BLEEDING COMPLICATIONS AND PROCEDURAL TIMING IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY AND PERIPHERAL VASCULAR INTERVENTIONS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Donaldson, Cameron W.; Waldo, Stephen; Li, Darrick K.; Pomerantsev, Eugene; Garasic, Joseph; Rosenfield, Kenneth; Yeh, Robert; Drachman, Douglas] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 2101-297 BP A1784 EP A1784 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328802106 ER PT J AU Dudzinski, DM Isselbacher, E Bhatia, R Picard, M Weiner, R AF Dudzinski, David M. Isselbacher, Eric Bhatia, Rajan Picard, Michael Weiner, Rory TI EDUCATIONAL INTERVENTION REDUCED THE RATE OF "RARELY APPROPRIATE" OUTPATIENT TRANSTHORACIC ECHOCARDIOGRAMS ORDERED BY ATTENDING CARDIOLOGISTS: A RANDOMIZED CONTROLLED TRIAL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Dudzinski, David M.; Isselbacher, Eric; Bhatia, Rajan; Picard, Michael; Weiner, Rory] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1243-035 BP A1324 EP A1324 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328801644 ER PT J AU Ferencik, M Pencina, KM Liu, T Massaro, J D'Agostino, R O'Donnell, C Hoffmann, U AF Ferencik, Maros Pencina, Karol M. Liu, Ting Massaro, Joseph D'Agostino, Ralph O'Donnell, Christopher Hoffmann, Udo TI CORONARY ARTERY CALCIUM DISTRIBUTION IS AN INDEPENDENT PREDICTOR OF INCIDENT MAJOR CORONARY HEART DISEASE EVENTS: RESULTS FROM THE FRAMINGHAM HEART STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1136-021 BP A1156 EP A1156 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328801476 ER PT J AU Ferencik, M Puchner, SB Mayrhofer, T Lu, MT Liu, T Maurovich-Horvat, P Ghemigian, K Fleg, J Udelson, J Hoffmann, U AF Ferencik, Maros Puchner, Stefan B. Mayrhofer, Thomas Lu, Michael T. Liu, Ting Maurovich-Horvat, Pal Ghemigian, Khristine Fleg, Jerome Udelson, James Hoffmann, Udo TI CULPRIT LESIONS OF ACUTE CORONARY SYNDROME ARE CHARACTERIZED BY THE PRESENCE OF STENOSIS AND HIGH-RISK PLAQUE, BUT NOT HIGHER SEGMENTAL CORONARY ARTERY CALCIUM SCORE: RESULTS FROM THE ROMICAT II TRIAL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1244-065 BP A229 EP A229 DI 10.1016/S0735-1097(15)60229-7 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328800230 ER PT J AU Gandhi, PU Gaggin, H Belcher, AM Basile, A Falco, A Rosati, A Januzzi, J Turco, MC AF Gandhi, Parul U. Gaggin, Hanna Belcher, Arianna M. Basile, Anna Falco, Antonia Rosati, Alessandra Januzzi, James Turco, M. Caterina TI BCL-2-ASSOCIATED ATHANOGENE 3 CONCENTRATIONS ARE PROGNOSTIC IN PATIENTS WITH ACUTELY DECOMPENSATED HEART FAILURE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Salerno, Fisciano, SA, Italy. 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1217-230 BP A1007 EP A1007 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328801327 ER PT J AU Gandhi, PU Motiwala, S Belcher, A Gaggin, H Weiner, R Baggish, A Fiuzat, M Brunner-La Rocca, HP Januzzi, J AF Gandhi, Parul U. Motiwala, Shweta Belcher, Arianna Gaggin, Hanna Weiner, Rory Baggish, Aaron Fiuzat, Mona Brunner-La Rocca, Hans-Peter Januzzi, James TI ELEVATED GALECTIN-3 DOES NOT PREDICT BENEFIT FROM MINERALOCORTICOID RECEPTOR ANTAGONIST USE IN PATIENTS WITH CHRONIC HEART FAILURE DUE TO LEFT VENTRICULAR SYSTOLIC DYSFUNCTION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Gandhi, Parul U.; Motiwala, Shweta; Belcher, Arianna; Gaggin, Hanna; Weiner, Rory; Baggish, Aaron; Fiuzat, Mona; Brunner-La Rocca, Hans-Peter; Januzzi, James] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1216-193 BP A970 EP A970 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328801290 ER PT J AU Gao, L Itoh, T Choi, SY Park, SJ Jang, Y Lee, S Tian, JW Minami, Y Jia, HB Ong, D Soeda, T Vergallo, R Lee, H Yu, B Uemura, S Jang, IK AF Gao, Lei Itoh, Tomonori Choi, So-Yeon Park, Seung-Jung Jang, Yangsoo Lee, Stephen Tian, Jinwei Minami, Yoshiyasu Jia, Haibo Ong, Daniel Soeda, Tsunenari Vergallo, Rocco Lee, Hang Yu, Bo Uemura, Shiro Jang, Ik-Kyung TI COMPARISON OF NEOATHEROSCLEROSIS PATTERN BETWEEN PATIENTS WITH AND WITHOUT DIABETES: AN OPTICAL COHERENCE TOMOGRAPHY STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Gao, Lei; Itoh, Tomonori; Choi, So-Yeon; Park, Seung-Jung; Jang, Yangsoo; Lee, Stephen; Tian, Jinwei; Minami, Yoshiyasu; Jia, Haibo; Ong, Daniel; Soeda, Tsunenari; Vergallo, Rocco; Lee, Hang; Yu, Bo; Uemura, Shiro; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 2101-288 BP A1775 EP A1775 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328802097 ER PT J AU Gao, L Vergallo, R Minami, Y Jia, HB Ong, D Soeda, T Tian, JW Lee, H Yu, B Uemura, S Jang, IK AF Gao, Lei Vergallo, Rocco Minami, Yoshiyasu Jia, Haibo Ong, Daniel Soeda, Tsunenari Tian, Jinwei Lee, Hang Yu, Bo Uemura, Shiro Jang, Ik-Kyung TI COMPREHENSIVE PLAQUE DISTRIBUTION IN NATIVE CORONARY ARTERIES: A THREE-VESSEL OPTICAL COHERENCE TOMOGRAPHY ANALYSIS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Gao, Lei; Vergallo, Rocco; Minami, Yoshiyasu; Jia, Haibo; Ong, Daniel; Soeda, Tsunenari; Tian, Jinwei; Lee, Hang; Yu, Bo; Uemura, Shiro; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1244-068 BP A232 EP A232 DI 10.1016/S0735-1097(15)60232-7 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328800233 ER PT J AU Gilchrist, I Morrow, D Scirica, B Creager, M Bhatt, D He, P Murphy, S Braunwald, E Bonaca, M AF Gilchrist, Ian Morrow, David Scirica, Benjamin Creager, Mark Bhatt, Deepak He, Ping Murphy, Sabina Braunwald, Eugene Bonaca, Marc TI STATIN INTENSITY AND OUTCOME IN PATIENTS WITH PERIPHERAL ARTERY DISEASE: INSIGHTS FROM THE TRA2P-TIMI 50 TRIAL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, Boston, MA 02115 USA. Penn State Univ, Coll Med, Hershey, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1131M-03 BP A2043 EP A2043 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328802365 ER PT J AU Gutierrez, A Bonaca, M Scirica, B Creager, M Murphy, S Braunwald, E Morrow, D AF Gutierrez, Antonio Bonaca, Marc Scirica, Benjamin Creager, Mark Murphy, Sabina Braunwald, Eugene Morrow, David TI VORAPAXAR AND ACUTE LIMB ISCHEMIA: INSIGHTS FROM THE THROMBIN RECEPTOR ANTAGONIST IN SECONDARY PREVENTION OF ATHEROTHROMBOTIC ISCHEMIC EVENTS-TIMI 50 TRIAL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 TIMI Study Grp, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1131M-11 BP A2047 EP A2047 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328802369 ER PT J AU Hahn, VS Putt, M Sawaya, H Januzzi, J Sebag, IA Plana, J Picard, M Gerszten, R Halpern, E Kuter, I Martin, R Carver, J Scherrer-Crosbie, M Ky, B AF Hahn, Virginia Shalkey Putt, Mary Sawaya, Heloisa Januzzi, James Sebag, Igal A. Plana, Juan Picard, Michael Gerszten, Robed Halpern, Elkan Kuter, Irene Martin, Randolph Carver, Joseph Scherrer-Crosbie, Marielle Ky, Bonnie TI LONGITUDINAL CHANGES IN MULTIPLE BIOMARKERS ARE ASSOCIATED WITH CARDIOTOXICITY IN BREAST CANCER PATIENTS TREATED WITH DOXORUBICIN, TAXANES AND TRASTUZUMAB SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1217-224 BP A1001 EP A1001 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328801321 ER PT J AU Hu, SN Jia, HB Vergallo, R Tian, JW Soeda, T Minami, Y Gao, L Ong, D Lee, H Zhang, SS Yu, B Jang, IK AF Hu, Sining Jia, Haibo Vergallo, Rocco Tian, Jinwei Soeda, Tsunenari Minami, Yoshiyasu Gao, Lei Ong, Daniel Lee, Hang Zhang, Shaosong Yu, Bo Jang, Ik-Kyung TI DOES STATIN THERAPY PREVENT NEOATHEROSCLEROSIS? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. Harbin Med Univ, Key Laborator, Affiliated Hosp 2, Dept Cardiol, Harbin, Peoples R China. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1244-064 BP A228 EP A228 DI 10.1016/S0735-1097(15)60228-5 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328800229 ER PT J AU Hultein, EA Bittencourt, M Ghoshhajra, B Singh, A Abbara, S Nasir, K Blaha, M Hoffmann, U Di Carli, M Blankstein, R AF Hultein, Edward A. Bittencourt, Marcio Ghoshhajra, Brian Singh, Avinainder Abbara, Suhny Nasir, Khurram Blaha, Michael Hoffmann, Udo Di Carli, Marcelo Blankstein, Ron TI TRIGLYCERIDES AND HDL CHOLESTEROL ARE ASSOCIATED WITH CORONARY ARTERY DISEASE PROGNOSIS AMONG STATIN TREATED PATIENTS UNDERDOING CORONARY CT ANGIOGRAPHY: PARTNERS HEALTHCARE CT REGISTRY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1102-032 BP A1116 EP A1116 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328801436 ER PT J AU Jia, HB Hu, SN Kim, CJ Choi, SY Tian, JW Vergallo, R Ong, D Aguirre, AD Wang, Z Uemura, S Soeda, T Minami, Y Gao, L Lee, H Zhang, SS Hou, JB Hou, JB Yu, B Jang, IK AF Jia, Haibo Hu, Sining Kim, Chong-Jin Choi, So-Yeon Tian, Jinwei Vergallo, Rocco Ong, Daniel Aguirre, Aaron D. Wang, Zhao Uemura, Shiro Soeda, Tsunenari Minami, Yoshiyasu Gao, Lei Lee, Hang Zhang, Shaosong Hou, Jingbo Hou, Jingbo Yu, Bo Jang, Ik-Kyung TI PREVALENCE AND CHARACTERISTICS OF HEALED PLAQUES IN PATIENTS WITH SYMPTOMATIC CORONARY ARTERY DISEASE ASSESSED BY OPTICAL COHERENCE TOMOGRAPHY AND INTRAVASCULAR ULTRASOUND SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Harbin Med Univ, Key Lab Myocardial Ischemia, Chinese Minist Educ, Harbin, Peoples R China. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 2102-270 BP A1804 EP A1804 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328802126 ER PT J AU Jia, HB Hu, SN Lerman, A Toma, C Dauerman, H Ong, D Vergallo, R Tian, JW Soeda, T Minami, Y Gao, L Lee, H Zhang, SS Hou, JB Yu, B Jang, IK AF Jia, Haibo Hu, Sining Lerman, Amir Toma, Catalin Dauerman, Harold Ong, Daniel Vergallo, Rocco Tian, Jinwei Soeda, Tsunenari Minami, Yoshiyasu Gao, Lei Lee, Hang Zhang, Shaosong Hou, Jingbo Yu, Bo Jang, Ik-Kyung TI ACUTE CORONARY SYNDROME CAUSED BY NON-CRITICAL CORONARY STENOSIS: INSIGHT FROM AN IN VIVO OPTICAL COHERENCE TOMOGRAPHY STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin, Peoples R China. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1244-073 BP A237 EP A237 DI 10.1016/S0735-1097(15)60237-6 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328800238 ER PT J AU Lu, MT Park, J Mayrhofer, T Ghemigian, K Puchner, S Liu, T Fleg, J Udeson, J Ferencik, M Hoffmann, U AF Lu, Michael T. Park, Jakob Mayrhofer, Thomas Ghemigian, Khristine Puchner, Stefan Liu, Ting Fleg, Jerome Udeson, James Ferencik, Maros Hoffmann, Udo TI EXCESS EPICARDIAL ADIPOSE TISSUE IS ASSOCIATED WITH HIGH-RISK CORONARY PLAQUE ON CCTA INDEPENDENT OF RISK FACTORS, CORONARY CALCIUM SCORE AND STENOSIS: RESULTS FROM THE ROMICAT II TRIAL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Lu, Michael T.; Park, Jakob; Mayrhofer, Thomas; Ghemigian, Khristine; Puchner, Stefan; Liu, Ting; Fleg, Jerome; Udeson, James; Ferencik, Maros; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S BP A1175 EP A1175 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328801495 ER PT J AU Magnani, G O'Donoghue, M Braunwald, E Steen, D Jarolim, P Lukas, MA White, H Lewis, B de Winter, R Zhou, J Im, K Cannon, C Morrow, D AF Magnani, Giulia O'Donoghue, Michelle Braunwald, Eugene Steen, Dylan Jarolim, Petr Lukas, Mary Ann White, Harvey Lewis, Basil de Winter, Robbert Zhou, Jing Im, Kyungah Cannon, Christopher Morrow, David TI GALECTIN-3 FOR HEART FAILURE RISK STRATIFICATION IN PATIENTS AFTER ACUTE CORONARY SYNDROMES (ACS): INSIGHTS FROM THE SOLID-TIMI 52 TRIAL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Magnani, Giulia; O'Donoghue, Michelle; Braunwald, Eugene; Steen, Dylan; Jarolim, Petr; Lukas, Mary Ann; White, Harvey; Lewis, Basil; de Winter, Robbert; Zhou, Jing; Im, Kyungah; Cannon, Christopher; Morrow, David] TIMI Study Grp, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1128M-09 BP A773 EP A773 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328801093 ER PT J AU Mauer, AC Hwang, SJ Yao, J Smith, AV Thanassoulis, G Budoff, M Rotter, J Kathiresan, S Gudnason, V Post, W O'Donnell, C AF Mauer, Andreas C. Hwang, Shih-Jen Yao, Jie Smith, Albert V. Thanassoulis, George Budoff, Matthew Rotter, Jerome Kathiresan, Sekar Gudnason, Vilmundur Post, Wendy O'Donnell, Christopher CA CHARGE Investigators TI RARE VARIANT ASSOCIATION STUDY FINDS NO LARGE-EFFECT, LOW-FREQUENCY VARIANTS FOR AORTIC AND MITRAL VALVE CALCIFICATION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Univ, Baltimore, MD 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1121-358 BP A1980 EP A1980 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328802302 ER PT J AU May, EAB White, JA Blazing, M Giugliano, R Musliner, T Tershakovec, A McCagg, A Bhatt, D Cannon, C Califf, R Braunwald, E AF May, Erin Ann Bohula White, Jennifer A. Blazing, Michael Giugliano, Robert Musliner, Thomas Tershakovec, Andrew McCagg, Amy Bhatt, Deepak Cannon, Christopher Califf, Robert Braunwald, Eugene TI RISK STRATIFICATION FOR CARDIOVASCULAR EVENTS IN THE IMPROVE-IT TRIAL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Duke Clin Res Inst, Durham, NC USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1125M-07 BP A3 EP A3 DI 10.1016/50735-1097(15)60001-8 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328800004 ER PT J AU Minami, Y Phipps, J Hoyt, T Ong, DS Vergallo, R Feldman, MD Jang, IK AF Minami, Yoshiyasu Phipps, Jennifer Hoyt, Taylor Ong, Daniel S. Vergallo, Rocco Feldman, Marc D. Jang, Ik-Kyung TI INCREASED SUPERFICIAL BRIGHT SPOTS AT THE CULPRIT LESION IN PATIENTS WITH ACUTE CORONARY SYNDROME: AN OPTICAL COHERENCE TOMOGRAPHY STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Minami, Yoshiyasu; Phipps, Jennifer; Hoyt, Taylor; Ong, Daniel S.; Vergallo, Rocco; Feldman, Marc D.; Jang, Ik-Kyung] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 909-06 BP A2157 EP A2157 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328802479 ER PT J AU Minami, Y Hou, JB Jia, HB Hu, SN Vergallo, R Soeda, T Zhang, SS Yu, B Jang, IK AF Minami, Yoshiyasu Hou, Jingbo Jia, Haibo Hu, Sining Vergallo, Rocco Soeda, Tsunenari Zhang, Shaosong Yu, Bo Jang, Ik-Kyung TI PLAQUE CHARACTERISTICS AND VASCULAR RESPONSE TO LIPID-LOWERING THERAPY IN PATIENTS WITH HIGH VERSUS LOW HDL-CHOLESTEROL: SERIAL OPTICAL COHERENCE TOMOGRAPHY AND INTRAVASCULAR ULTRASOUND STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harbin Univ, Affiliated Hosp 2, Harbin, Peoples R China. 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1211-127 BP A1489 EP A1489 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328801809 ER PT J AU Minami, Y Hou, JB Jia, HB Hu, SN Vergallo, R Soeda, T Zhang, SS Yu, B Jang, IK AF Minami, Yoshiyasu Hou, Jingbo Jia, Haibo Hu, Sining Vergallo, Rocco Soeda, Tsunenari Zhang, Shaosong Yu, Bo Jang, Ik-Kyung TI VASCULAR RESPONSE TO LIPID-LOWERING THERAPY IN DIABETES VERSUS NON-DIABETES PATIENTS: SERIAL OPTICAL COHERENCE TOMOGRAPHY AND INTRAVASCULAR ULTRASOUND STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harbin Univ, Affiliated Hosp 2, Harbin, Peoples R China. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1140-112 BP A1410 EP A1410 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328801730 ER PT J AU Minami, Y Hou, JB Jia, HB Hu, SN Vergallo, R Soeda, T Zhang, SS Yu, B Jang, IK AF Minami, Yoshiyasu Hou, Jingbo Jia, Haibo Hu, Sining Vergallo, Rocco Soeda, Tsunenari Zhang, Shaosong Yu, Bo Jang, Ik-Kyung TI GENDER DIFFERENCE IN CHANGES OF PLAQUE CHARACTERISTICS IN RESPONSE TO INTENSIVE LIPID-LOWERING THERAPY: SERIAL OPTICAL COHERENCE TOMOGRAPHY AND INTRAVASCULAR ULTRASOUND ANALYSIS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harbin Univ, Affiliated Hosp 2, Harbin, Peoples R China. 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1210-093 BP A210 EP A210 DI 10.1016/S0735-1097(15)60210-8 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328800211 ER PT J AU Moazzami, K Kalantarian, S Retzepi, K Reynolds, NA Gollub, RL Ruskin, J AF Moazzami, Kasra Kalantarian, Shadi Retzepi, Kallirroi Reynolds, Nathaniel A. Gollub, Randy L. Ruskin, Jeremy TI INDEPENDENT CORRELATES OF COGNITIVE IMPAIRMENT IN PATIENTS WITH ATRIAL FIBRILLATION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1115-241 BP A306 EP A306 DI 10.1016/S0735-1097(15)60306-0 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328800307 ER PT J AU Naderi, S Weinberg, I Lindsay, M Wood, M AF Naderi, Sahar Weinberg, Ido Lindsay, Mark Wood, Malissa TI SPONTANEOUS CORONARY ARTERY DISSECTION PATIENTS SIGNIFICANTLY MORE FIT THAN THE AVERAGE PATIENT REFERRED FOR EXERCISE STRESS TESTING SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Naderi, Sahar; Weinberg, Ido; Lindsay, Mark; Wood, Malissa] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1242-014 BP A1303 EP A1303 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328801623 ER PT J AU Nakamura, K Zhang, M Dudzinski, D AF Nakamura, Kenta Zhang, Mary Dudzinski, David TI A YOUNG MALE WITH DEBILITATING POLYNEUROPATHY AND MONOCLONAL GAMMOPATHY PRESENTS WITH PERICARDIAL EFFUSION AND RIGHT HEART FAILURE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1109-143 BP A602 EP A602 DI 10.1016/S0735-1097(15)60602-7 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328800603 ER PT J AU Osborn, EA Ughi, GJ Mauskapf, A El Maghraby, A Oettgen, J Tearney, G Jaffer, F AF Osborn, Eric A. Ughi, Giovanni J. Mauskapf, Adam El Maghraby, Amr Oettgen, Joerg Tearney, Guillermo Jaffer, Farouc TI IN VIVO OPTICAL MOLECULAR - STRUCTURAL IMAGING OF CORONARY ARTERY STENT INFLAMMATION PREDICTS THE SITE-APECIFIC RESTENOSIS RISK SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 2101-307 BP A1793 EP A1793 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328802115 ER PT J AU Park, YH Handschumacher, M Zeng, X Tan, T Capoulade, R Hung, J AF Park, Yong Hyun Handschumacher, Mark Zeng, Xin Tan, Timothy Capoulade, Remain Hung, Judy TI CHARACTERIZATION OF REGIONAL DIFFERENCES IN PATHOLOGICAL LV REMODELING: INSIGHTS FROM 3D ECHOCARDIOGRAPHIC ANALYSIS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Park, Yong Hyun; Handschumacher, Mark; Zeng, Xin; Tan, Timothy; Capoulade, Remain; Hung, Judy] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1243-039 BP A1327 EP A1327 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328801647 ER PT J AU Pursnani, A Massaro, J D'Agostino, R O'Donnell, C Hoffmann, U AF Pursnani, Amit Massaro, Joseph D'Agostino, Ralph O'Donnell, Christopher Hoffmann, Udo TI GUIDELINE-BASED STATIN ALLOCATION TO DISTINGUISH BOTH CARDIOVASCULAR EVENTS AND CORONARY ARTERY CALCIFICATION IN THE COMMUNITY: A COMPARISON OF THE 2004 NCEP ATP III AND 2013 ACC/AHA CHOLESTEROL TREATMENT GUIDELINE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Pursnani, Amit; Massaro, Joseph; D'Agostino, Ralph; O'Donnell, Christopher; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1233M-03 BP A1355 EP A1355 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328801675 ER PT J AU Schopfer, DW Rush, KM Rohrbach, G Hasara, S Bettencourt, M Pabst, MS Whooley, M AF Schopfer, David W. Rush, Kimberly M. Rohrbach, Greg Hasara, Stephanie Bettencourt, Michael Pabst, Mark S. Whooley, Mary TI THE HEALTHY HEART CARDIAC REHABILITATION PROGRAM SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Schopfer, David W.; Rush, Kimberly M.; Rohrbach, Greg; Hasara, Stephanie; Bettencourt, Michael; Pabst, Mark S.; Whooley, Mary] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1212-131 BP A1493 EP A1493 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328801813 ER PT J AU Shimada, YJ Yamashita, T Koretsune, Y Kimura, T Abe, K Sasaki, S Mercuri, M Ruff, CT Giugliano, RP AF Shimada, Yuichi J. Yamashita, Takeshi Koretsune, Yukihiro Kimura, Tetsuya Abe, Kenji Sasaki, Shunichi Mercuri, Michele Ruff, Christian T. Giugliano, Robert P. TI EFFECTS OF REGIONAL DIFFERENCES IN ASIA ON EFFICACY AND SAFETY OF EDOXABAN COMPARED TO WARFARIN: INSIGHTS FROM THE ENGAGE AF-TIMI 48 TRIAL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Shimada, Yuichi J.; Yamashita, Takeshi; Koretsune, Yukihiro; Kimura, Tetsuya; Abe, Kenji; Sasaki, Shunichi; Mercuri, Michele; Ruff, Christian T.; Giugliano, Robert P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1148-256 BP A356 EP A356 DI 10.1016/S0735-1097(15)60356-4 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328800357 ER PT J AU Singer, D Ziegler, P Schmitt, S Chang, YC Fan, J Than, CT Turakhia, M AF Singer, Daniel Ziegler, Paul Schmitt, Susan Chang, Yuchiao Fan, Jun Than, Claire T. Turakhia, Mintu TI PAROXYSMAL ATRIAL FIBRILLATION POSES A LARGE BUT TRANSIENT INCREASE IN ISCHEMIC STROKE RISK: A CASE-CROSSOVER STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. NR 0 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1115-249 BP A314 EP A314 DI 10.1016/S0735-1097(15)60314-X PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328800315 ER PT J AU Soeda, T Park, SJ Jang, Y Lee, S Mizuno, K Ltoh, T Chieh, JTW Lee, H Jia, HB Yu, B Uemura, S Saito, Y Jang, LK AF Soeda, Tsunenari Park, Seung-Jung Jang, Yangsoo Lee, Stephen Mizuno, Kyoichi Ltoh, Tomonori Chieh, Jack Tan Wei Lee, Hang Jia, Haibo Yu, Bo Uemura, Shiro Saito, Yoshihiko Jang, Lk-Kyung TI INCIDENCE AND PREDICTORS OF STENT EDGE MEDIAL DISRUPTION: AN IN VIVO OPTICAL COHERENCE TOMOGRAPHY STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Soeda, Tsunenari; Park, Seung-Jung; Jang, Yangsoo; Lee, Stephen; Mizuno, Kyoichi; Ltoh, Tomonori; Chieh, Jack Tan Wei; Lee, Hang; Jia, Haibo; Yu, Bo; Uemura, Shiro; Saito, Yoshihiko; Jang, Lk-Kyung] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 2103-311 BP A1893 EP A1893 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328802215 ER PT J AU Soeda, T Hou, JB Jia, HB Hu, SN Minami, Y Vergallo, R Zhang, SS Yu, B Jang, IK AF Soeda, Tsunenari Hou, Jingbo Jia, Haibo Hu, Sining Minami, Yoshiyasu Vergallo, Rocco Zhang, Shaosong Yu, Bo Jang, Ik-Kyung TI DOES PLAQUE BURDEN PREDICT VASCULAR RESPONSE TO STATIN THERAPY? A COMBINED OCT AND IVUS STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Soeda, Tsunenari; Hou, Jingbo; Jia, Haibo; Hu, Sining; Minami, Yoshiyasu; Vergallo, Rocco; Zhang, Shaosong; Yu, Bo; Jang, Ik-Kyung] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1133M-15 BP A1574 EP A1574 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328801894 ER PT J AU Soeda, T Higuma, T Abe, N Yamada, M Yokoyama, H Shibutani, S Jia, HB Tian, JW Vergallo, R Minami, Y Lee, H Okumura, K Jang, IK AF Soeda, Tsunenari Higuma, Takumi Abe, Naoki Yamada, Masahiro Yokoyama, Hiroaki Shibutani, Shuji Jia, Haibo Tian, Jinwei Vergallo, Rocco Minami, Yoshiyasu Lee, Hang Okumura, Ken Jang, Ik-Kyung TI INTRAVASCULAR ULTRASOUND, BUT NOT OPTICAL COHERENCE TOMOGRAPHY, PREDICTS NO REFLOW PHENOMENON AFTER PRIMARY PERCUTANEOUS CORONARY INTERVENTION IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION CAUSED BY PLAQUE RUPTURE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Soeda, Tsunenari; Higuma, Takumi; Abe, Naoki; Yamada, Masahiro; Yokoyama, Hiroaki; Shibutani, Shuji; Jia, Haibo; Tian, Jinwei; Vergallo, Rocco; Minami, Yoshiyasu; Lee, Hang; Okumura, Ken; Jang, Ik-Kyung] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1244-071 BP A235 EP A235 DI 10.1016/S0735-1097(15)60235-2 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328800236 ER PT J AU Stefanescu, A AF Stefanescu, Ada TI MULTIORGAN INVOLVEMENT OF AMYLOID: HOW TO FLY UNDER THE RADAR SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Stefanescu, Ada] Massachusetts Gen Hosp, Boston, MA 02114 USA. OI Stefanescu Schmidt, Ada/0000-0002-5692-2616 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1109-158 BP A617 EP A617 DI 10.1016/S0735-1097(15)60617-9 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328800618 ER PT J AU Stefanescu, A AF Stefanescu, Ada TI ARRHYTHMIAS AND CARDIOGENIC SHOCK AS A PRESENTATION OF HYPERTHERMIA SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Stefanescu, Ada] Massachusetts Gen Hosp, Boston, MA 02114 USA. OI Stefanescu Schmidt, Ada/0000-0002-5692-2616 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1109-157 BP A616 EP A616 DI 10.1016/S0735-1097(15)60616-7 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328800617 ER PT J AU Stefanescu, A Bhatt, A Serfas, J Tabtabai, S Ruff, J Yeh, D AF Stefanescu, Ada Bhatt, Ami Serfas, John Tabtabai, Sara Ruff, Joshua Yeh, Doreen TI POOR RIGHT VENTRICULAR EXERCISE RESERVE PREDICTS HEART FAILURE AND ARRHYTHMIA IN ADULTS WITH CONGENITAL RIGHT HEART DISEASE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Stefanescu, Ada; Bhatt, Ami; Serfas, John; Tabtabai, Sara; Ruff, Joshua; Yeh, Doreen] Massachusetts Gen Hosp, Boston, MA 02114 USA. OI Stefanescu Schmidt, Ada/0000-0002-5692-2616 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1255-320 BP A563 EP A563 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328800564 ER PT J AU Tabtabai, S Vaduganathan, M Steiner, J Stone, J Estep, J Witteles, R Feltrin, G Zucker, M Baran, D Seldin, D Patel, J Hanna, M Cordero-Reyes, A Selby, V Semigran, M Maurer, M AF Tabtabai, Sara Vaduganathan, Muthiah Steiner, Johannes Stone, James Estep, Jerry Witteles, Ronald Feltrin, Giuseppe Zucker, Mark Baran, David Seldin, David Patel, Jignesh Hanna, Mazen Cordero-Reyes, Andrea Selby, Van Semigran, Marc Maurer, Mathew TI MODIFIED BMI DOES NOT PREDICT ADVERSE OUTCOMES IN PATIENTS WITH CARDIAC AMYLOID UNDERGOING HEART TRANSPLANTATION: A REPORT FROM ICCAT (INTERNATIONAL CONSORTIUM FOR CARDIAC AMYLOID TRANSPLANTATION) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Columbia Univ, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1184-219 BP A943 EP A943 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328801263 ER PT J AU Takx, R Leiner, T Hoffmann, U AF Takx, Richard Leiner, Tim Hoffmann, Udo TI ADDITIONAL VALUE OF FUNCTIONAL CT FOR THE ASSESSMENT OF HEMODYNAMICALLY SIGNIFICANT CORONARY ARTERY DISEASE: A META-ANALYSIS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Med Ctr Utrecht, Utrecht, Netherlands. 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1102-021 BP A1106 EP A1106 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328801426 ER PT J AU Tan, T Flynn, A Mehrotra, P Nunes, MC Shahian, D Picard, M Afilalo, J AF Tan, Timothy Flynn, Aidan Mehrotra, Praveen Nunes, Maria C. Shahian, David Picard, Michael Afilalo, Jonathan TI THE IMPACT OF NON-SEVERE TRICUSPID REGURGITATION ON LONG-TERM MORTALITY AFTER CARDIAC SURGERY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1158-353 BP A1989 EP A1989 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328802311 ER PT J AU Tan, T Chin, J Lu, HM Depauw, N Booy, H Taghian, A Bauer, R Scherrer-Crosbie, M Januzzi, J Passer, J Macdonald, SM AF Tan, Timothy Chin, Joanna Lu, Hsiao-Ming Depauw, Nicholas Booy, Hanne Taghian, Alphonse Bauer, Roger Scherrer-Crosbie, MarieIle Januzzi, James Passer, Jonathan Macdonald, Shannon M. TI ASSESSMENT OF CARDIAC FUNCTION FOLLOWING PROTON RADIATION IN A COHORT OF POST MASTECTOMY PATIENTS WITH LOCALLY ADVANCED BREAST CANCER SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Tan, Timothy; Chin, Joanna; Lu, Hsiao-Ming; Depauw, Nicholas; Booy, Hanne; Taghian, Alphonse; Bauer, Roger; Scherrer-Crosbie, MarieIle; Januzzi, James; Passer, Jonathan; Macdonald, Shannon M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1184-214 BP A938 EP A938 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328801258 ER PT J AU Tian, JW Jia, HB Soeda, T Vergallo, R Lee, H Yu, B Jang, IK AF Tian, Jinwei Jia, Haibo Soeda, Tsunenari Vergallo, Rocco Lee, Hang Yu, Bo Jang, Ik-Kyung TI CAN BASELINE PLAQUE CHARACTERISTICS PREDICT FUTURE VASCULAR REMODELING PROCESS? A COMBINED OPTICAL COHERENCE TOMOGRAPHY AND INTRAVASCULAR ULTRASOUND STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Harbin Med Univ, Affiliated Hosp 2, Harbin, Peoples R China. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 2101-316 BP A1802 EP A1802 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328802124 ER PT J AU Tian, JW Jia, HB Minami, Y Gao, L Lee, H Yu, B Jang, IK AF Tian, Jinwei Jia, Haibo Minami, Yoshiyasu Gao, Lei Lee, Hang Yu, Bo Jang, Ik-Kyung TI NATURAL HISTORY OF CORONARY ARTERIAL REMODELING IN PATIENTS WITH ACUTE CORONARY SYNDROME: A SERIAL INTRAVASCULAR ULTRASOUND STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Harbin Med Univ, Affiliated Hosp 2, Harbin, Peoples R China. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1244-070 BP A234 EP A234 DI 10.1016/S0735-1097(15)60234-0 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328800235 ER PT J AU Trieu, L Zamani, P Doulias, PT Rawat, D Kumar, PS Bhuva, R Vadde, N Dunde, A Soto-Calderon, H Tariq, A Javaheri, A Haines, P Ischiropoulos, H Akers, S Medina, JC AF Trieu, Lien Zamani, Payman Doulias, Paschalis-Thomas Rawat, Deepa Kumar, Prithvi Shiva Bhuva, Rushik Vadde, Neetha Dunde, Anjaneyulu Soto-Calderon, Haideliza Tariq, Ali Javaheri, Ali Haines, Philip Ischiropoulos, Harry Akers, Scott Medina, Julio Chirinos TI PLASMA LEVELS OF NITRIC OXIDE METABOLITES ARE LOWER IN HFPEF SUBJECTS COMPARED TO HFREF AND HYPERTENSIVES SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1113-208 BP A825 EP A825 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328801145 ER PT J AU Vaid, J Poh, MZ Saleh, A Kalantarian, S Poh, YKC Rafael, A Ruskin, J AF Vaid, Jeena Poh, Ming-Zher Saleh, Ahmed Kalantarian, Shadi Poh, Yuk Kee C. Rafael, Allon Ruskin, Jeremy TI DIAGNOSTIC ACCURACY OF A NOVEL MOBILE APPLICATION (CARDIIO RHYTHM) FOR DETECTING ATRIAL FIBRILLATION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Vaid, Jeena; Poh, Ming-Zher; Saleh, Ahmed; Kalantarian, Shadi; Poh, Yuk Kee C.; Rafael, Allon; Ruskin, Jeremy] Massachusetts Gen Hosp, Boston, MA 02114 USA. OI Poh, Ming-Zher/0000-0002-3510-1923 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1149-261 BP A361 EP A361 DI 10.1016/S0735-1097(15)60361-8 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328800362 ER PT J AU Vergallo, R Kuramitsu, S Choi, SY Uemura, S Yu, B Minami, Y Soeda, T Jia, H Jang, IK AF Vergallo, Rocco Kuramitsu, Shoichi Choi, So-Yeon Uemura, Shiro Yu, Bo Minami, Yoshiyasu Soeda, Tsunenari Jia, Haibo Jang, Ik-Kyung TI CORONARY PLAQUE CHARACTERISTICS IN PATIENTS WITH HYPERTENSION: A 3-VESSEL OPTICAL COHERENCE TOMOGRAPHY STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Vergallo, Rocco; Kuramitsu, Shoichi; Choi, So-Yeon; Uemura, Shiro; Yu, Bo; Minami, Yoshiyasu; Soeda, Tsunenari; Jia, Haibo; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1198M-05 BP A1353 EP A1353 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328801673 ER PT J AU Vergallo, R Itoh, T Tan, JW Kim, CJ Uemura, S Yu, B Minami, Y Soeda, T Jia, HB Jang, IK AF Vergallo, Rocco Itoh, Tomonori Tan, Jack W. Kim, Chong-Jin Uemura, Shiro Yu, Bo Minami, Yoshiyasu Soeda, Tsunenari Jia, Haibo Jang, Ik-Kyung TI INCIDENCE AND PREDICTORS OF MULTIPLE CORONARY PLAQUE RUPTURES: A 3-VESSEL OPTICAL COHERENCE TOMOGRAPHY STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Vergallo, Rocco; Itoh, Tomonori; Tan, Jack W.; Kim, Chong-Jin; Uemura, Shiro; Yu, Bo; Minami, Yoshiyasu; Soeda, Tsunenari; Jia, Haibo; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1244-072 BP A236 EP A236 DI 10.1016/S0735-1097(15)60236-4 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328800237 ER PT J AU Vergallo, R Hou, JB Jia, HB Minami, Y Soeda, T Hu, SN Zhang, SS Yu, B Jang, IK AF Vergallo, Rocco Hou, Jingbo Jia, Haibo Minami, Yoshiyasu Soeda, Tsunenari Hu, Sining Zhang, Shaosong Yu, Bo Jang, Ik-Kyung TI EFFECTS OF STATIN THERAPY ON CORONARY PLAQUE MORPHOLOGY IN PATIENTS WITH ACUTE CORONARY SYNDROME VERSUS STABLE ANGINA PECTORIS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 [Vergallo, Rocco; Hou, Jingbo; Jia, Haibo; Minami, Yoshiyasu; Soeda, Tsunenari; Hu, Sining; Zhang, Shaosong; Yu, Bo; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1210-091 BP A208 EP A208 DI 10.1016/S0735-1097(15)60208-X PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328800209 ER PT J AU Verrier, RL Carneiro, JS Bento, AA Bacic, D Nearing, B Rajamani, S Belardinelli, L AF Verrier, Richard L. Carneiro, Juliana S. Bento, Afonso Alves Bacic, Danilo Nearing, Bruce Rajamani, Sridharan Belardinelli, Luiz TI THE LATE SODIUM CURRENT INHIBITOR GS967 SUPPRESSES SPONTANEOUS ATRIAL FIBRILLATION IN AN INTACT PORCINE MODEL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Beth Israel Deacones Med Ctr, Boston, MA USA. Gilead Sci Inc, Foster City, CA 94404 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1187-255 BP A392 EP A392 DI 10.1016/S0735-1097(15)60392-8 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328800393 ER EF