FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Baselga, J de Azambuja, E Bradbury, I Gelber, R AF Baselga, Jose de Azambuja, Evandro Bradbury, Ian Gelber, Richard TI Neoadjuvant chemotherapy with HER2 inhibitors for breast cancer reply SO LANCET LA English DT Letter ID PATHOLOGICAL COMPLETE RESPONSE; TRASTUZUMAB; SURVIVAL; TRIAL; AMPLIFICATION C1 [Baselga, Jose] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA. [de Azambuja, Evandro] Inst Jules Bordet, Breast European Adjuvant Study Team, B-1000 Brussels, Belgium. [Bradbury, Ian] Frontier Sci Scotland, Kincraig, Scotland. [Bradbury, Ian] Queens Univ, Belfast, Antrim, North Ireland. [Gelber, Richard] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Gelber, Richard] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. RP Baselga, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA. EM jbaselga@partners.org NR 5 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 0140-6736 J9 LANCET JI Lancet PD JUN 16 PY 2012 VL 379 IS 9833 BP 2238 EP 2238 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 962AM UT WOS:000305511400020 ER PT J AU Zhong, WD Qin, GQ Dai, QS Han, ZD Chen, SM Ling, XH Fu, X Cai, C Chen, JH Chen, XB Lin, ZY Deng, YH Wu, SL He, HC Wu, CL AF Zhong, Wei-de Qin, Guo-qiang Dai, Qi-shan Han, Zhao-dong Chen, Shan-ming Ling, Xiao-hui Fu, Xin Cai, Chao Chen, Jia-hong Chen, Xi-bin Lin, Zhuo-yuan Deng, Ye-han Wu, Shu-lin He, Hui-chan Wu, Chin-lee TI SOXs in human prostate cancer: implication as progression and prognosis factors SO BMC CANCER LA English DT Article DE Prostate cancer; SOX; Clinicopathological feature; Biochemical recurrence-free survival ID EXPRESSION; CELLS; PROLIFERATION; DISEASE AB Background: SOX genes play an important role in a number of developmental processes. Potential roles of SOXs have been demonstrated in various neoplastic tissues as tumor suppressors or promoters depending on tumor status and types. The aim of this study was to investigate the involvement of SOXs in the progression and prognosis of human prostate cancer (PCa). Methods: The gene expression changes of SOXs in human PCa tissues compared with non-cancerous prostate tissues was detected using gene expression microarray, and confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohositochemistry. The roles of these genes in castration resistance were investigated in LNCaP xenograft model of PCa. Results: The microarray analysis identified three genes (SOX7, SOX9 and SOX10) of SOX family that were significantly dis-regulated in common among four PCa specimens. Consistent with the results of the microarray, differential mRNA and protein levels of three selected genes were found in PCa tissues by QRT-PCR analysis and immunohistochemistry. Additionally, we found that the immunohistochemical staining scores of SOX7 in PCa tissues with higher serum PSA level (P = 0.02) and metastasis (P = 0.03) were significantly lower than those with lower serum PSA level and without metastasis; the increased SOX9 protein expression was frequently found in PCa tissues with higher Gleason score (P = 0.02) and higher clinical stage (P < 0.0001); the down-regulation of SOX10 tend to be found in PCa tissues with higher serum PSA levels (P = 0.03) and advanced pathological stage (P = 0.01). Moreover, both univariate and multivariate analyses showed that the down-regulation of SOX7 and the up-regulation of SOX9 were independent predictors of shorter biochemical recurrence-free survival. Furthermore, we discovered that SOX7 was significantly down-regulated and SOX9 was significantly up-regulated during the progression to castration resistance. Conclusions: Our data offer the convince evidence that the dis-regulation of SOX7, SOX9 and SOX10 may be associated with the aggressive progression of PCa. SOX7 and SOX9 may be potential markers for prognosis in PCa patients. Interestingly, the down-regulation of SOX7 and the up-regulation of SOX9 may be important mechanisms for castration-resistant progression of PCa. C1 [Zhong, Wei-de; Qin, Guo-qiang; Dai, Qi-shan; Han, Zhao-dong; Chen, Shan-ming; Ling, Xiao-hui; Fu, Xin; Cai, Chao; Chen, Jia-hong; Chen, Xi-bin; Lin, Zhuo-yuan; Deng, Ye-han; He, Hui-chan] Guangzhou First Municipal Peoples Hosp, Affiliated Guangzhou Med Coll, Dept Urol, Guangdong Key Lab Clin Mol Med & Diagnost, Guangzhou 510180, Guangdong, Peoples R China. [Zhong, Wei-de] Guangzhou Med Univ, Urol Key Lab Guangdong Prov, Guangzhou 510230, Guangdong, Peoples R China. [Zhong, Wei-de; Qin, Guo-qiang; Dai, Qi-shan] So Med Univ, Guangdong Prov Inst Nephrol, Guangzhou 510515, Guangdong, Peoples R China. [Wu, Shu-lin; Wu, Chin-lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Wu, Shu-lin; Wu, Chin-lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Boston, MA USA. RP He, HC (reprint author), Guangzhou First Municipal Peoples Hosp, Affiliated Guangzhou Med Coll, Dept Urol, Guangdong Key Lab Clin Mol Med & Diagnost, Guangzhou 510180, Guangdong, Peoples R China. EM zhongwd2009@live.cn OI Zhong, Weide/0000-0002-0430-2845 FU National Natural Science Foundation of China [81170699]; Guangzhou Municipal Science and Technology Key Project [11C23150711]; Key Projects of Bureau of Health in Guangzhou Municipality [201102A212015]; Projects of Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics [2010A060801016]; Medical and Health Science and Technology Project in Guangzhou Municipality [20121A011004]; Projects of Guangdong Key Laboratory of Urology FX This work was supported by grants from National Natural Science Foundation of China (81170699), Guangzhou Municipal Science and Technology Key Project (11C23150711), Key Projects of Bureau of Health in Guangzhou Municipality (201102A212015), Projects of Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Projects of Guangdong Key Laboratory of Urology (2010A060801016), Medical and Health Science and Technology Project in Guangzhou Municipality (20121A011004). NR 28 TC 23 Z9 25 U1 0 U2 7 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 JUN 15 PY 2012 VL 12 AR 248 DI 10.1186/1471-2407-12-248 PG 11 WC Oncology SC Oncology GA 026XV UT WOS:000310317300001 PM 22703285 ER PT J AU Zhao, S Yu, ZY Zhao, G Xing, CH Hayakawa, K Whalen, MJ Lok, JM Lo, EH Wang, XY AF Zhao, Song Yu, Zhanyang Zhao, Gang Xing, Changhong Hayakawa, Kazuhide Whalen, Michael J. Lok, Josephine M. Lo, Eng H. Wang, Xiaoying TI Neuroglobin-overexpression reduces traumatic brain lesion size in mice SO BMC NEUROSCIENCE LA English DT Article DE Neuroglobin; Neuroprotection; Controlled cortical impact; Oxidative stress; Traumatic brain injury ID OXIDATIVE STRESS; IN-VIVO; INJURY; EXPRESSION; PROTECTS; OUTCOMES; NEUROPROTECTION; MECHANISMS; ISCHEMIA; PROTEINS AB Background: Accumulating evidence has demonstrated that over-expression of Neuroglobin (Ngb) is neuroprotective against hypoxic/ischemic brain injuries. In this study we tested the neuroprotective effects of Ngb over-expression against traumatic brain injury (TBI) in mice. Results: Both Ngb over-expression transgenic (Ngb-Tg) and wild-type (WT) control mice were subjected to TBI induced by a controlled cortical impact (CCI) device. TBI significantly increased Ngb expression in the brains of both WT and Ngb-Tg mice, but Ngb-Tg mice had significantly higher Ngb protein levels at the pre-injury baseline and post-TBI. Production of oxidative tissue damage biomarker 3NT in the brain was significantly reduced in Ngb-Tg mice compared to WT controls at 6 hours after TBI. The traumatic brain lesion volume was significantly reduced in Ngb Tg mice compared to WT mice at 3 weeks after TBI; however, there were no significant differences in the recovery of sensorimotor and spatial memory functional deficits between Ngb-Tg and WT control mice for up to 3 weeks after TBI. Conclusion: Ngb over-expression reduced traumatic lesion volume, which might partially be achieved by decreasing oxidative stress. C1 [Zhao, Song; Yu, Zhanyang; Xing, Changhong; Hayakawa, Kazuhide; Lok, Josephine M.; Lo, Eng H.; Wang, Xiaoying] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Neurol, Charlestown, MA 02129 USA. [Zhao, Song; Yu, Zhanyang; Xing, Changhong; Hayakawa, Kazuhide; Lok, Josephine M.; Lo, Eng H.; Wang, Xiaoying] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA 02129 USA. [Zhao, Song; Zhao, Gang] Jilin Univ, Bethune Hosp 1, Dept Orthoped, Changchun 130023, Jilin, Peoples R China. [Zhao, Song; Zhao, Gang] Jilin Univ, Bethune Hosp 1, Dept Neurosurg, Changchun 130023, Jilin, Peoples R China. [Whalen, Michael J.; Lok, Josephine M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA 02129 USA. RP Wang, XY (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Neurol, 149 13th St,Room 2401, Charlestown, MA 02129 USA. EM wangxi@helix.mgh.harvard.edu FU NIH [R01-NS049476] FX This work was supported in part by NIH grant R01-NS049476 (to X.W.). We appreciate Ms. Jessica L. Poppe for language editorial assistance. NR 31 TC 15 Z9 18 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2202 J9 BMC NEUROSCI JI BMC Neurosci. PD JUN 15 PY 2012 VL 13 AR 67 DI 10.1186/1471-2202-13-67 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 010PJ UT WOS:000309106300001 PM 22703519 ER PT J AU Richardson, AL Iglehart, JD AF Richardson, Andrea L. Iglehart, J. Dirk TI BEAMing Up Personalized Medicine: Mutation Detection in Blood SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID BREAST-CANCER; CLINICAL-TRIALS C1 [Richardson, Andrea L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Iglehart, J. Dirk] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Richardson, Andrea L.; Iglehart, J. Dirk] Harvard Univ, Sch Med, Boston, MA USA. [Richardson, Andrea L.; Iglehart, J. Dirk] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Richardson, AL (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM arichardson@partners.org FU NCI NIH HHS [P50 CA089393] NR 12 TC 12 Z9 13 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2012 VL 18 IS 12 BP 3209 EP 3211 DI 10.1158/1078-0432.CCR-12-0871 PG 3 WC Oncology SC Oncology GA 988PD UT WOS:000307502100001 PM 22550168 ER PT J AU Hong, DS Kurzrock, R Supko, JG He, XY Naing, A Wheler, J Lawrence, D Eder, JP Meyer, CJ Ferguson, DA Mier, J Konopleva, M Konoplev, S Andreeff, M Kufe, D Lazarus, H Shapiro, GI Dezube, BJ AF Hong, David S. Kurzrock, Razelle Supko, Jeffrey G. He, Xiaoying Naing, Aung Wheler, Jennifer Lawrence, Donald Eder, Joseph Paul Meyer, Colin J. Ferguson, Deborah A. Mier, James Konopleva, Marina Konoplev, Sergej Andreeff, Michael Kufe, Donald Lazarus, Hillard Shapiro, Geoffrey I. Dezube, Bruce J. TI A Phase I First-in-Human Trial of Bardoxolone Methyl in Patients with Advanced Solid Tumors and Lymphomas SO CLINICAL CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; TRITERPENOID CDDO-ME; LUNG-CANCER CELLS; INFLAMMATORY RESPONSE; APOPTOTIC ACTIVITY; DIRECT INHIBITION; OXIDATIVE STRESS; KIDNEY-FUNCTION; ESTER; EXPRESSION AB Purpose: Bardoxolone methyl, a novel synthetic triterpenoid and antioxidant inflammation modulator, potently induces Nrf2 and inhibits NF-kappa B and Janus-activated kinase/STAT signaling. This first-in-human phase I clinical trial aimed to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and appropriate dose for phase II studies; characterize pharmacokinetic and pharmacodynamic parameters; and assess antitumor activity. Experimental Design: Bardoxolone methyl was administered orally once daily for 21 days of a 28-day cycle. An accelerated titration design was employed until a grade 2-related adverse event occurred. A standard 3 + 3 dose escalation was then employed until the MTD was reached. Single dose and steady-state plasma pharmacokinetics of the drug were characterized. Assessment of Nrf2 activation was examined in peripheral blood mononuclear cells (PBMC) by measuring NAD(P) H: quinone oxidoreductase (NQO1) mRNA levels. Immunohistochemical assessment of markers of inflammation, cell cycle, and apoptosis was carried out on tumor biopsies. Results: The DLTs were grade 3 reversible liver transaminase elevations. The MTD was established as 900 mg/d. A complete tumor response occurred in a mantle cell lymphoma patient, and a partial response was observed in an anaplastic thyroid carcinoma patient. NQO1 mRNA levels increased in PBMCs, and NF-kappa B and cyclin D1 levels decreased in tumor biopsies. Estimated glomerular filtration rate (eGFR) was also increased. Conclusions: Bardoxolone methyl was well tolerated with an MTD of 900 mg/d. The increase in eGFR suggests that bardoxolone methyl might be beneficial in chronic kidney disease. Objective tumor responses and pharmacodynamic effects were observed, supporting continued development of other synthetic triterpenoids in cancer. Clin Cancer Res; 18(12); 3396-406. (C) 2012 AACR. C1 [Konopleva, Marina] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Leukemia, Houston, TX 77030 USA. [Konoplev, Sergej] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. [Andreeff, Michael] Univ Texas MD Anderson Canc Ctr, Dept Mol Hematol Therapy, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. [Meyer, Colin J.; Ferguson, Deborah A.] Reata Pharmaceut Inc, Irving, TX USA. [Mier, James] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dana Farber Harvard Canc Ctr, Boston, MA 02215 USA. [Eder, Joseph Paul; Shapiro, Geoffrey I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Early Drug Dev Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Lawrence, Donald] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA USA. [Lazarus, Hillard] Univ Hosp Case Med Ctr, Dept Med, Cleveland, OH USA. [Dezube, Bruce J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Hematol & Oncol, Boston, MA 02215 USA. [Hong, David S.; Kurzrock, Razelle; Naing, Aung; Wheler, Jennifer] Univ Texas MD Anderson Canc Ctr, Phase Clin Trials Program 1, Dept Invest Canc Therapeut, Houston, TX 77030 USA. RP Hong, DS (reprint author), Univ Texas MD Anderson Canc Ctr, Div Canc Med, Phase Clin Trials Program 1,Unit 455, Dept Invest Canc Therapeut, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM dshong@mdanderson.org FU REATA Pharmaceuticals, Inc. (Irving, TX); Leukemia and Lymphoma Society [R6149-07 01]; Haas Chair in Genetics; Reata Pharmaceuticals FX This work was supported by REATA Pharmaceuticals, Inc. (Irving, TX) and by the Leukemia and Lymphoma Society (R6149-07 01) to M. Konoplev, and the Haas Chair in Genetics (M. Andreeff).; D.S. Hong and J.G. Supko have a commercial research grant from Reata Pharmaceuticals. C.J. Meyer, D.A. Ferguson, M. Konopleva, M. Andreeff and D.W. Kufe have an ownership interest (including patents) in Reata Pharmaceuticals. M. Konopleva, M. Andreeff, and D.W. Kufe are consultants/advisory board members of Reata Pharmaceuticals. No potential conflicts of interest were disclosed by the other authors. NR 40 TC 64 Z9 69 U1 2 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2012 VL 18 IS 12 BP 3396 EP 3406 DI 10.1158/1078-0432.CCR-11-2703 PG 11 WC Oncology SC Oncology GA 988PD UT WOS:000307502100020 PM 22634319 ER PT J AU Higgins, MJ Jelovac, D Barnathan, E Blair, B Slater, S Powers, P Zorzi, J Jeter, SC Oliver, GR Fetting, J Emens, L Riley, C Stearns, V Diehl, F Angenendt, P Huang, P Cope, L Argani, P Murphy, KM Bachman, KE Greshock, J Wolff, AC Park, BH AF Higgins, Michaela J. Jelovac, Danijela Barnathan, Evan Blair, Brian Slater, Shannon Powers, Penny Zorzi, Jane Jeter, Stacie C. Oliver, George R. Fetting, John Emens, Leisha Riley, Carol Stearns, Vered Diehl, Frank Angenendt, Philipp Huang, Peng Cope, Leslie Argani, Pedram Murphy, Kathleen M. Bachman, Kurtis E. Greshock, Joel Wolff, Antonio C. Park, Ben H. TI Detection of Tumor PIK3CA Status in Metastatic Breast Cancer Using Peripheral Blood SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; COLORECTAL-CANCER; MUTATIONS; PTEN; DNA; QUANTIFICATION; CARCINOMAS; PHENOTYPE; EVOLUTION; GENE AB Purpose: We sought to evaluate the feasibility of detecting PIK3CA mutations in circulating tumor DNA (ctDNA) from plasma of patients with metastatic breast cancer using a novel technique called BEAMing. Experimental Design: In a retrospective analysis, 49 tumor and temporally matched plasma samples from patients with breast cancer were screened for PIK3CA mutations by BEAMing. We then prospectively screened the ctDNA of 60 patients with metastatic breast cancer for PIK3CA mutations by BEAMing and compared the findings with results obtained by screening corresponding archival tumor tissue DNA using both sequencing and BEAMing. Results: The overall frequency of PIK3CA mutations by BEAMing was similar in both patient cohorts (29% and 28.3%, respectively). In the retrospective cohort, the concordance of PIK3CA mutation status by BEAMing between formalin-fixed, paraffin-embedded (FFPE) samples and ctDNA from temporally matched plasma was 100% (34 of 34). In the prospective cohort, the concordance rate among 51 evaluable cases was 72.5% between BEAMing of ctDNA and sequencing of archival tumor tissue DNA. When the same archival tissue DNA was screened by both sequencing and BEAMing for PIK3CA mutations (n = 41 tissue samples), there was 100% concordance in the obtained results. Conclusions: Analysis of plasma-derived ctDNA for the detection of PIK3CA mutations in patients with metastatic breast cancer is feasible. Our results suggest that PIK3CA mutational status can change upon disease recurrence, emphasizing the importance of reassessing PIK3CA status on contemporary (not archival) biospecimens. These results have implications for the development of predictive biomarkers of response to targeted therapies. Clin Cancer Res; 18(12); 3462-9. (c) 2012 AACR. C1 [Jelovac, Danijela; Barnathan, Evan; Blair, Brian; Slater, Shannon; Powers, Penny; Zorzi, Jane; Jeter, Stacie C.; Fetting, John; Emens, Leisha; Riley, Carol; Stearns, Vered; Huang, Peng; Cope, Leslie; Argani, Pedram; Wolff, Antonio C.; Park, Ben H.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21287 USA. [Higgins, Michaela J.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Murphy, Kathleen M.] ProPath, Dallas, TX USA. [Diehl, Frank; Angenendt, Philipp] Inostics GmbH, Hamburg, Germany. [Bachman, Kurtis E.; Greshock, Joel] GlaxoSmithKline, Oncol R&D, Collegeville, PA USA. RP Park, BH (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, 1650 Orleans St,Rm 151, Baltimore, MD 21287 USA. EM awolff@jhmi.edu; bpark2@jhmi.edu OI Wolff, Antonio/0000-0003-3734-1063 FU Department of the Defense Breast Cancer Research Program [W81XWH-10-1-0244]; Susan G. Komen for the Cure [PDF0707944, SAC110053]; Avon Foundation; NIH/National Cancer Institute [CA009071, CA088843, CA121937, CA109274]; Breast Cancer Research Foundation FX This work was supported in part by the Department of the Defense Breast Cancer Research Program W81XWH-10-1-0244; Susan G. Komen for the Cure PDF0707944, SAC110053; The Avon Foundation; NIH/National Cancer Institute CA009071, CA088843 (Breast SPORE), CA121937, CA109274, and the Breast Cancer Research Foundation. NR 34 TC 115 Z9 124 U1 7 U2 29 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2012 VL 18 IS 12 BP 3462 EP 3469 DI 10.1158/1078-0432.CCR-11-2696 PG 8 WC Oncology SC Oncology GA 988PD UT WOS:000307502100026 PM 22421194 ER PT J AU Earley, S Vinegoni, C Dunham, J Gorbatov, R Feruglio, PF Weissleder, R AF Earley, Sarah Vinegoni, Claudio Dunham, Joshua Gorbatov, Rostic Feruglio, Paolo Fumene Weissleder, Ralph TI In Vivo Imaging of Drug-Induced Mitochondrial Outer Membrane Permeabilization at Single-Cell Resolution SO CANCER RESEARCH LA English DT Article ID BCL-2 FAMILY INHIBITOR; LIVING CELLS; APOPTOSIS; CANCER; MICROSCOPY; PROTEIN; ACTIVATION; DYNAMICS; ABT-263; BRIGHT AB Observing drug responses in the tumor microenvironment in vivo can be technically challenging. As a result, cellular responses to molecularly targeted cancer drugs are often studied in cell culture, which does not accurately represent the behavior of cancer cells growing in vivo. Using high-resolution microscopy and fluorescently labeled genetic reporters for apoptosis, we developed an approach to visualize drug-induced cell death at single-cell resolution in vivo. Stable expression of the mitochondrial intermembrane protein IMS-RP was established in human breast and pancreatic cancer cells. Image analysis was then used to quantify release of IMS-RP into the cytoplasm upon apoptosis and irreversible mitochondrial permeabilization. Both breast and pancreatic cancer cells showed higher basal apoptotic rates in vivo than in culture. To study drug-induced apoptosis, we exposed tumor cells to navitoclax (ABT-263), an inhibitor of Bcl-2, Bcl-xL, and Bcl-w, both in vitro and in vivo. Although the tumors responded to Bcl-2 inhibition in vivo, inducing apoptosis in around 20% of cancer cells, the observed response was much higher in cell culture. Together, our findings show an imaging technique that can be used to directly visualize cell death within the tumor microenvironment in response to drug treatment. Cancer Res; 72(12); 2949-56. (C)2012 AACR. C1 [Earley, Sarah; Vinegoni, Claudio; Dunham, Joshua; Gorbatov, Rostic; Feruglio, Paolo Fumene; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu FU NIH [2P50CA086355, 2R01EB006432, 1P01CA139980, 1R01CA164448, T32-CA79443] FX This work was supported in part by NIH grants: 2P50CA086355, 2R01EB006432, 1P01CA139980, 1R01CA164448, and T32-CA79443. NR 36 TC 6 Z9 6 U1 2 U2 14 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 2012 VL 72 IS 12 BP 2949 EP 2956 DI 10.1158/0008-5472.CAN-11-4096 PG 8 WC Oncology SC Oncology GA 986NO UT WOS:000307348500005 PM 22505651 ER PT J AU Lin, JH Morikawa, T Chan, AT Kuchiba, A Shima, K Nosho, K Kirkner, G Zhang, SMM Manson, JE Giovannucci, E Fuchs, CS Ogino, S AF Lin, Jennifer H. Morikawa, Teppei Chan, Andrew T. Kuchiba, Aya Shima, Kaori Nosho, Katsuhiko Kirkner, Gregory Zhang, Shumin M. Manson, JoAnn E. Giovannucci, Edward Fuchs, Charles S. Ogino, Shuji TI Postmenopausal Hormone Therapy Is Associated with a Reduced Risk of Colorectal Cancer Lacking CDKN1A Expression SO CANCER RESEARCH LA English DT Article ID ESTROGEN PLUS PROGESTIN; MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; ISLAND METHYLATOR PHENOTYPE; RANDOMIZED CONTROLLED-TRIAL; COLON-CANCER; MICROSATELLITE INSTABILITY; REPLACEMENT THERAPY; COMPETING RISKS; RECEPTOR-BETA; WOMEN AB Experimental studies have shown that estrogen-or progesterone-activated signaling leads to growth inhibition effects on colon cancer cells through the upregulation of several cell-cycle regulators. However, epidemiologic studies evaluating hormone therapy use and colorectal cancer risk by the status of cell-cycle regulators are lacking. In this study, we used data from the prospective Nurses' Health Study to evaluate whether the association between hormone therapy use and colorectal cancer risk differs by the molecular pathologic status of microsatellite instability (MSI) and expression of cell-cycle-related tumor biomarkers, including CDKN1A (p21, CIP1), CDKN1B (p27, KIP1), and TP53 (p53) by immunohistochemistry. Duplication Cox regression analysis was used to determine an association between hormone therapy use, cancer risk, and specific tumor biomarkers in 581 incident colon and rectal cancer cases that occurred during 26 years of follow-up among 105,520 postmenopausal women. We found a difference between hormone therapy use and colorectal cancer risk according to CDKN1A expression (P-heterogeneity = 0.01). Current hormone therapy use was associated with a reduced risk for CDKN1A-nonexpressed [multivariate relative risk (RR), 0.61; 95% confidence interval (CI), 0.46-0.82] but not for CDKN1A-expressed (RR, 1.32; 95% CI, 0.76-2.31) tumors. The lower risk for CDKN1A-nonexpressed but not for CDKN1A-expressed cancers was also present among current users of estrogen-alone therapy. We found no significant difference in the relations between hormone therapy use and cancer risk according to MSI, CDKN1B, or TP53 status. Together, our molecular pathological epidemiology findings suggest a preventive effect of hormone therapy against colorectal carcinogenesis that depends, in part, on loss of cyclin-dependent kinase inhibitor CDKN1A. Cancer Res; 72(12); 3020-8. (C)2012 AACR. C1 [Lin, Jennifer H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med,Dept Med, Boston, MA 02215 USA. [Chan, Andrew T.; Kirkner, Gregory; Manson, JoAnn E.; Giovannucci, Edward; Fuchs, Charles S.; Ogino, Shuji] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Morikawa, Teppei; Kuchiba, Aya; Shima, Kaori; Nosho, Katsuhiko; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Manson, JoAnn E.; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02215 USA. RP Lin, JH (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med,Dept Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM jhlin@rics.bwh.harvard.edu FU National Cancer Institute; National Institutes of Health [P01CA87969]; National Colorectal Cancer Research Alliance; [R01CA126846]; [R01CA151993]; [P50CA127003]; [R01CA137178]; [R01CA123089] FX The work was supported by grants R01CA126846 (J.H. Lin), R01CA151993 (S. Ogino), P50CA127003 (C. S. Fuchs), R01CA137178 (A. T. Chan), R01CA123089 (S. M. Zhang), and from the National Cancer Institute. The Nurses' Health Study is supported by grants P01CA87969 from the National Institutes of Health and from the National Colorectal Cancer Research Alliance. Dr. Chan is a Damon Runyon Clinical Investigator. NR 50 TC 12 Z9 12 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 2012 VL 72 IS 12 BP 3020 EP 3028 DI 10.1158/0008-5472.CAN-11-2619 PG 9 WC Oncology SC Oncology GA 986NO UT WOS:000307348500012 PM 22511578 ER PT J AU Abrol, R Edderkaoui, M Goddard, WA Pandol, SJ AF Abrol, Ravinder Edderkaoui, Mouad Goddard, William A., III Pandol, Stephen J. TI Molecular basis for the interplay of apoptosis and proliferation mediated by Bcl-xL:Bim interactions in pancreatic cancer cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Bcl-2 family; Mutagenesis; Apoptosis; Proliferation; Computational biochemistry ID INHIBITION; MODEL; EXPRESSION; BIOLOGY; BAX AB A major mechanism through which cancer cells avoid apoptosis is by promoting the association of antiapoptotic members of the pro-survival Bcl-2 protein family (like Bcl-2 and Bcl-xL) with BH3 domain-only proteins (like Bim and Bid). Apoptosis and cell proliferation have been shown to be linked for many cancers but the molecular basis for this link is far from understood. We have identified the Bcl-xL:Bim protein-protein interface as a direct regulator of proliferation and apoptosis in pancreatic cancer cells. We were able to predict and subsequently verify experimentally the effect of various Bcl-xL single-point mutants (at the position A142) on binding to Bim by structural analysis and computational modeling of the inter-residue interactions at the Bcl-xL:Bim protein-protein interface. The mutants A142N, A142Q and A142Y decreased binding of Bim to Bcl-xL and A142S increased this binding. The Bcl-xL mutants, with decreased affinity for Bim, caused an increase in apoptosis and a corresponding decrease in cell proliferation. However, we could prevent these effects by introducing a small interfering RNA (siRNA) targeted at Bim. These results show a novel role played by the Bcl-xL:Bim interaction in regulating proliferation of pancreatic cancer cells at the expense of apoptosis. This study presents a physiologically relevant model of the Bcl-xL:Bim interface that can be used for rational therapeutic design for the inhibition of proliferation and cancer cell resistance to apoptosis. (C) 2012 Elsevier Inc. All rights reserved. C1 [Abrol, Ravinder; Goddard, William A., III] CALTECH, Div Chem & Chem Engn, Mat & Proc Simulat Ctr, Pasadena, CA 91125 USA. [Edderkaoui, Mouad; Pandol, Stephen J.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Edderkaoui, Mouad; Pandol, Stephen J.] Univ Calif Los Angeles, Los Angeles, CA 90073 USA. RP Abrol, R (reprint author), CALTECH, Div Chem & Chem Engn, Mat & Proc Simulat Ctr, MC 139-74, Pasadena, CA 91125 USA. EM abrol@wag.caltech.edu; stephen.pandol@va.gov RI babakinejad, babak/G-2674-2012; Abrol, Ravinder/B-4980-2010 FU Department of Veterans Affairs; UCLA Center for Excellence in Pancreatic Diseases; National Center for Complementary and Alternative Medicine [1 P01 AT003960]; National Institute on Alcohol Abuse and Alcoholism [1K01AA019996] FX This work was supported by the Department of Veterans Affairs and the UCLA Center for Excellence in Pancreatic Diseases and National Center for Complementary and Alternative Medicine (1 P01 AT003960), National Institute on Alcohol Abuse and Alcoholism (1K01AA019996), and in part through gifts to the Materials and Process Simulation Center at Caltech. NR 27 TC 2 Z9 2 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 15 PY 2012 VL 422 IS 4 BP 596 EP 601 DI 10.1016/j.bbrc.2012.05.032 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 974NU UT WOS:000306443900012 PM 22609401 ER PT J AU Ahmad, R Alam, M Rajabi, H Kufe, D AF Ahmad, Rehan Alam, Maroof Rajabi, Hasan Kufe, Donald TI The MUC1-C Oncoprotein Binds to the BH3 Domain of the Pro-apoptotic BAX Protein and Blocks BAX Function SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CARCINOMA-ASSOCIATED ANTIGEN; BETA-CATENIN; SURVIVAL RESPONSE; MITOCHONDRIAL DYSFUNCTION; TRANSCRIPTION FACTOR; OXIDATIVE STRESS; PROAPOPTOTIC BAX; C-SRC; ACTIVATION; DIMERIZATION AB The pro-apoptotic BAX protein contains a BH3 domain that is necessary for its dimerization and for activation of the intrinsic apoptotic pathway. The MUC1(mucin 1) heterodimeric protein is overexpressed in diverse human carcinomas and blocks apoptosis in the response to stress. In this study, we demonstrate that the oncogenic MUC1-C subunit associates with BAX in human cancer cells. MUC1-C.BAX complexes are detectable in the cytoplasm and mitochondria and are induced by genotoxic and oxidative stress. The association between MUC1-C and BAX is supported by the demonstration that the MUC1-C cytoplasmic domain is sufficient for the interaction with BAX. The results further show that the MUC1-C cytoplasmic domain CQC motif binds directly to the BAX BH3 domain at Cys-62. Consistent with binding to the BAX BH3 domain, MUC1-C blocked BAX dimerization in response to (i) truncated BID in vitro and (ii) treatment of cancer cells with DNA-damaging agents. In concert with these results, MUC1-C attenuated localization of BAX to mitochondria and the release of cytochrome c. These findings indicate that the MUC1-C oncoprotein binds directly to the BAX BH3 domain and thereby blocks BAX function in activating the mitochondrial death pathway. C1 [Ahmad, Rehan; Alam, Maroof; Rajabi, Hasan; Kufe, Donald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM donald_kufe@dfci.havard.edu FU National Institutes of Health from NCI [CA97098, CA42802, CA100707] FX This work was supported, in whole or in part, by National Institutes of Health Grants CA97098, CA42802, and CA100707 from NCI. D. K. holds equity in Genus Oncology and is a consultant to the company. NR 41 TC 20 Z9 21 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 15 PY 2012 VL 287 IS 25 BP 20866 EP 20875 DI 10.1074/jbc.M112.357293 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 974FQ UT WOS:000306416800008 PM 22544745 ER PT J AU Ho, JE Waters, DD Kean, A Wilson, DJ DeMicco, DA Breazna, A Wun, CC Deedwania, PC Khush, KK AF Ho, Jennifer E. Waters, David D. Kean, Allison Wilson, Daniel J. DeMicco, David A. Breazna, Andrei Wun, Chuan-Chuan Deedwania, Prakash C. Khush, Kiran K. CA TNT Investigators TI Relation of Improvement in Estimated Glomerular Filtration Rate With Atorvastatin to Reductions in Hospitalizations for Heart Failure (from the Treating to New Targets [TNT] Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; HIGH-DOSE ATORVASTATIN; RENAL-FUNCTION; SUBGROUP ANALYSIS; CORONARY-DISEASE; ROSUVASTATIN; SIMVASTATIN; THERAPY; STATINS; PEOPLE AB Impaired kidney function often accompanies heart failure (HF) and is associated with a worse prognosis. This post hoc analysis of the Treating to New Targets (TNT) trial examined whether the observed decrease in HF hospitalizations with high- compared to low-dose atorvastatin could be related to improvements in kidney function. Of 10,001 TNT participants, 9,376 had estimated glomerular filtration rate (eGFR) measurements at baseline and 1 year and were included in this analysis. The association of change in year-1 eGFR and subsequent HF hospitalization was examined using Cox regression models. In total 218 participants developed subsequent HF hospitalization. Little change in eGFR occurred over 1 year in the atorvastatin 10-mg group, whereas eGFR improved in the 80-mg group by 1.48 ml/min/1.73 m(2) (95% confidence interval 1.29 to 1.67, p <0.0001). Subsequent HF was preceded by a decrease in eGFR over 1 year compared to modest improvement in those without subsequent HF (-0.09 +/- 7.89 vs 0.81 +/- 6.90 ml/min/1.73 m(2), p = 0.0015). After adjusting for baseline eGFR, each 5-ml/min/1.73 m(2) increase in eGFR at 1 year was associated with a lower risk of subsequent HF hospitalization (hazard ratio 0.85, 95% confidence interval 0.77 to 0.94, p = 0.002). This relation was independent of treatment effect or change in low-density lipoprotein cholesterol level at 1 year. In conclusion, treatment with high- compared to low-dose atorvastatin was associated with improvement in eGFR at 1 year, which was related to a decrease in subsequent HF hospitalization. This suggests that improvement in kidney function may be related to the beneficial effect of high-dose atorvastatin on HF hospitalization. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;109:1761-1766) C1 [Waters, David D.] San Francisco Gen Hosp, Div Cardiol, San Francisco, CA 94110 USA. [Waters, David D.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Ho, Jennifer E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Kean, Allison; Wilson, Daniel J.; DeMicco, David A.; Breazna, Andrei; Wun, Chuan-Chuan] Pfizer Pharmaceut Inc, New York, NY USA. [Deedwania, Prakash C.] VA Cent Calif Healthcare Syst, Fresno, CA USA. [Deedwania, Prakash C.] Univ Calif San Francisco, Sch Med, Fresno, CA USA. [Khush, Kiran K.] Stanford Univ, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA. RP Waters, DD (reprint author), San Francisco Gen Hosp, Div Cardiol, San Francisco, CA 94110 USA. EM dwaters@medsfgh.ucsf.edu OI Ho, Jennifer/0000-0002-7987-4768 FU Pfizer Pharmaceuticals, Inc., New York, New York FX The Treating to New Targets trial was funded by Pfizer Pharmaceuticals, Inc., New York, New York. Dr. Ho and Dr. Khush have served as consultants for Pfizer Pharmaceuticals. Dr. Waters has served as a consultant for Anthera, Hayward, California, Aegerion, Cambridge, Massachusetts, Biosante, Lincolnshire, Illinois, Cerenis, Ann Arbor. Missouri, CSL, Ltd., Parkville, Victoria, Australia, Genentech, South San Francisco, California, Merck-Schering Plough, Whitehouse Station, New Jersey, Pfizer Pharmaceuticals, Roche, Basel, Switzerland, Sanofi-Aventis, Paris, France, and Servier and has received honoraria for lectures from Pfizer Pharmaceuticals, and Bristol-Myers Squibb, New York, New York. Dr. Deedwania has received honoraria for lectures and has served as a consultant for Pfizer Pharmaceuticals and AstraZeneca, London, UK. NR 28 TC 9 Z9 9 U1 1 U2 6 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 15 PY 2012 VL 109 IS 12 BP 1761 EP 1766 DI 10.1016/j.amjcard.2012.02.019 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 964XE UT WOS:000305729200014 PM 22459310 ER PT J AU Chen, SZ Ma, J Wu, FZ Xiong, LJ Ma, HH Xu, WQ Lv, RT Li, XD Villen, J Gygi, SP Liu, XS Shi, Y AF Chen, Shuzhen Ma, Jian Wu, Feizhen Xiong, Li-jun Ma, Honghui Xu, Wenqi Lv, Ruitu Li, Xiaodong Villen, Judit Gygi, Steven P. Liu, Xiaole Shirley Shi, Yang TI The histone H3 Lys 27 demethylase JMJD3 regulates gene expression by impacting transcriptional elongation SO GENES & DEVELOPMENT LA English DT Article DE JMJD3; chromatin; transcriptional elongation ID RNA-POLYMERASE-II; EMBRYONIC STEM-CELLS; P-TEFB; PAF1 COMPLEX; HL-60 CELLS; METHYLATION; POLYCOMB; DIFFERENTIATION; CHROMATIN; LYSINE-27 AB The histone H3 Lys 27 (H3K27) demethylase JMJD3 has been shown to play important roles in transcriptional regulation and cell differentiation. However, the mechanism underlying JMJD3-mediated transcriptional regulation remains incompletely understood. Here we show that JMJD3 is associated with KIAA1718, whose substrates include dimethylated H3K27 (H3K27me2), and proteins involved in transcriptional elongation. JMJD3 and KIAA1718 directly bind to and regulate the expression of a plethora of common target genes in both a demethylase activity-dependent and -independent manner in the human promyelocytic leukemia cell line HL-60. We found that JMJD3 and KIAA1718 collaborate to demethylate trimethylated H3K27 (H3K27me3) on a subset of their target genes, some of which are bivalently marked by H3K4me3 and H3K27me3 and associated with promoter-proximal, paused RNA polymerase II (Pol II) before activation. Reduction of either JMJD3 or KIAA1718 diminishes Pol II traveling along the gene bodies of the affected genes while having no effect on the promoter-proximal Pol II. Furthermore, JMJD3 and KIAA1718 also play a role in localizing elongation factors SPT6 and SPT16 to the target genes. Our results support the model whereby JMJD3 activates bivalent gene transcription by demethylating H3K27me3 and promoting transcriptional elongation. Taken together, these findings provide new insight into the mechanisms by which JMJD3 regulates gene expression. C1 [Chen, Shuzhen; Li, Xiaodong; Shi, Yang] Harvard Univ, Childrens Hosp, Div Newborn Med, Dept Med,Med Sch, Boston, MA 02115 USA. [Chen, Shuzhen; Li, Xiaodong; Shi, Yang] Harvard Univ, Program Epigenet, Dept Med, Childrens Hosp,Med Sch, Boston, MA 02115 USA. [Ma, Jian; Liu, Xiaole Shirley] Harvard Univ, Dept Biostat & Computat Biol, Dana Farber Canc Inst, Sch Publ Hlth, Boston, MA 02115 USA. [Wu, Feizhen; Xiong, Li-jun; Ma, Honghui; Xu, Wenqi; Lv, Ruitu] Fudan Univ, Inst Biomed Sci, Dept Biochem, Shanghai 200032, Peoples R China. [Wu, Feizhen; Xiong, Li-jun; Ma, Honghui; Xu, Wenqi; Lv, Ruitu] Fudan Univ, Inst Biomed Sci, Epigenet Lab, Shanghai 200032, Peoples R China. [Villen, Judit; Gygi, Steven P.; Shi, Yang] Harvard Univ, Dept Cell Biol, Sch Med, Boston, MA 02115 USA. RP Shi, Y (reprint author), Harvard Univ, Childrens Hosp, Div Newborn Med, Dept Med,Med Sch, Boston, MA 02115 USA. EM yshi@hms.harvard.edu OI Villen, Judit/0000-0002-1005-1739 FU National Basic Research (973) Program of China [2010CB944904]; National Institutes of Health [GM099409, GM071004] FX We thank Karen Adelman and T. Keith Blackwell for critical reading of the manuscript. We are grateful to Hank Qi and Fei Lan for technical support, and members of the Shi laboratory for helpful discussions. We also thank Katherine A. Jones and William F. Simonds for the SPT6 and CDC73 antibodies, respectively. This work was supported by grants from the National Basic Research (973) Program of China (no. 2010CB944904 to J.M.), and the National Institutes of Health (GM099409 to X.S.L., and GM071004 to Y.S.). Y.S. is a cofounder of Constellation Pharmaceuticals and a member of its scientific advisory board. NR 56 TC 59 Z9 60 U1 0 U2 16 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUN 15 PY 2012 VL 26 IS 12 BP 1364 EP 1375 DI 10.1101/gad.186056.111 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 961RK UT WOS:000305485300010 PM 22713873 ER PT J AU Craig, JM Vena, N Ramkissoon, S Idbaih, A Fouse, SD Ozek, M Sav, A Hill, DA Margraf, LR Eberhart, CG Kieran, MW Norden, AD Wen, PY Loda, M Santagata, S Ligon, KL Ligon, AH AF Craig, Justin M. Vena, Natalie Ramkissoon, Shakti Idbaih, Ahmed Fouse, Shaun D. Ozek, Memet Sav, Aydin Hill, D. Ashley Margraf, Linda R. Eberhart, Charles G. Kieran, Mark W. Norden, Andrew D. Wen, Patrick Y. Loda, Massimo Santagata, Sandro Ligon, Keith L. Ligon, Azra H. TI DNA Fragmentation Simulation Method (FSM) and Fragment Size Matching Improve aCGH Performance of FFPE Tissues SO PLOS ONE LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; PARAFFIN-EMBEDDED TISSUES; HIGH-RESOLUTION ANALYSIS; COPY-NUMBER; ARRAY-CGH; NUCLEIC-ACID; SAMPLES; CANCER; TUMORS; MICROARRAYS AB Whole-genome copy number analysis platforms, such as array comparative genomic hybridization (aCGH) and single nucleotide polymorphism (SNP) arrays, are transformative research discovery tools. In cancer, the identification of genomic aberrations with these approaches has generated important diagnostic and prognostic markers, and critical therapeutic targets. While robust for basic research studies, reliable whole-genome copy number analysis has been unsuccessful in routine clinical practice due to a number of technical limitations. Most important, aCGH results have been suboptimal because of the poor integrity of DNA derived from formalin-fixed paraffin-embedded (FFPE) tissues. Using self-hybridizations of a single DNA sample we observed that aCGH performance is significantly improved by accurate DNA size determination and the matching of test and reference DNA samples so that both possess similar fragment sizes. Based on this observation, we developed a novel DNA fragmentation simulation method (FSM) that allows customized tailoring of the fragment sizes of test and reference samples, thereby lowering array failure rates. To validate our methods, we combined FSM with Universal Linkage System (ULS) labeling to study a cohort of 200 tumor samples using Agilent 1 M feature arrays. Results from FFPE samples were equivalent to results from fresh samples and those available through the glioblastoma Cancer Genome Atlas (TCGA). This study demonstrates that rigorous control of DNA fragment size improves aCGH performance. This methodological advance will permit the routine analysis of FFPE tumor samples for clinical trials and in daily clinical practice. C1 [Craig, Justin M.; Vena, Natalie; Ramkissoon, Shakti; Ligon, Keith L.; Ligon, Azra H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Craig, Justin M.; Vena, Natalie; Loda, Massimo; Ligon, Keith L.; Ligon, Azra H.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Ramkissoon, Shakti; Loda, Massimo; Santagata, Sandro; Ligon, Keith L.; Ligon, Azra H.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Idbaih, Ahmed] Hop La Pitie Salpetriere, Serv Neurol Mazarin, Paris, France. [Fouse, Shaun D.] Univ Calif San Francisco, Brain Tumor Res Ctr, Dept Neurosurg, San Francisco, CA 94143 USA. [Ozek, Memet] Acibadem Univ, Med Ctr, Div Pediat Neurosurg, Istanbul, Turkey. [Sav, Aydin] Acibadem Univ, Med Ctr, Dept Pathol, Istanbul, Turkey. [Hill, D. Ashley] Childrens Natl Med Ctr, Dept Pathol, Washington, DC 20010 USA. [Margraf, Linda R.] Univ Texas SW Med Ctr Dallas, Childrens Med Ctr, Dept Pathol, Dallas, TX 75390 USA. [Eberhart, Charles G.] Johns Hopkins Univ, Sch Med, Dept Pathol Oncol & Ophthalmol, Baltimore, MD USA. [Kieran, Mark W.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Kieran, Mark W.] Boston Childrens Hosp, Dept Pediat, Boston, MA USA. [Norden, Andrew D.; Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Norden, Andrew D.; Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neuro Oncol, Boston, MA 02115 USA. [Santagata, Sandro; Ligon, Keith L.] Boston Childrens Hosp, Dept Pathol, Boston, MA USA. [Kieran, Mark W.; Norden, Andrew D.; Wen, Patrick Y.; Loda, Massimo; Santagata, Sandro; Ligon, Keith L.; Ligon, Azra H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Craig, JM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM keith_ligon@dfci.harvard.edu; aligon@rics.bwh.harvard.edu OI Ligon, Keith/0000-0002-7733-600X; Kieran, Mark/0000-0003-2184-7692; sav, aydin/0000-0002-7326-7801 FU National Institutes of Health (NIH) [CA142536, CA095616, NS064168]; Eleanor and Miles Shore 50th Anniversary Fellowship Program for Scholars in Medicine; Goldhirsh Foundation; Sontag Foundation; American Brain Tumor Association; Friends of Dana-Farber Cancer Institute; DFCI Pediatric Low Grade Astrocytoma Foundation FX This work was supported by the National Institutes of Health (NIH) grant CA142536 (KLL), CA095616 (KLL), NS064168 (SS), the Eleanor and Miles Shore 50th Anniversary Fellowship Program for Scholars in Medicine (AHL), the Goldhirsh Foundation (KLL), the Sontag Foundation (KLL), the American Brain Tumor Association (AI), Friends of Dana-Farber Cancer Institute (ADN) and the DFCI Pediatric Low Grade Astrocytoma Foundation (MWK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 15 Z9 15 U1 2 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 JUN 15 PY 2012 VL 7 IS 6 AR e38881 DI 10.1371/journal.pone.0038881 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959WX UT WOS:000305350000025 PM 22719973 ER PT J AU Mikkelsen, ME Christie, JD Lanken, PN Biester, RC Thompson, BT Bellamy, SL Localio, AR Demissie, E Hopkins, RO Angus, DC AF Mikkelsen, Mark E. Christie, Jason D. Lanken, Paul N. Biester, Rosette C. Thompson, B. Taylor Bellamy, Scarlett L. Localio, A. Russell Demissie, Ejigayehu Hopkins, Ramona O. Angus, Derek C. TI The Adult Respiratory Distress Syndrome Cognitive Outcomes Study Long-Term Neuropsychological Function in Survivors of Acute Lung Injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory distress syndrome; acute lung injury; cognitive function; critical illness ID QUALITY-OF-LIFE; POSTTRAUMATIC-STRESS-DISORDER; CARE-UNIT SURVIVORS; CRITICALLY-ILL PATIENTS; CRITICAL ILLNESS; PULMONARY-ARTERY; DEPRESSIVE SYMPTOMS; TELEPHONE BATTERY; HEALTH-STATUS; IMPAIRMENT AB Rationale: Cognitive and psychiatric morbidity is common and potentially modifiable after acute lung injury (ALI). However, practical measures of neuropsychological function for use in multicenter trials are lacking. Objectives: To determine whether a validated telephone-based neuropsychological test battery is feasible in a multicenter trial. To determine the frequency and risk factors for long-term neuropsychological impairment. Methods: As an adjunct study to the Acute Respiratory Distress Syndrome Clinical Trials Network Fluid and Catheter Treatment Trial, we assessed neuropsychological function at 2 and 12 months post hospital discharge. Measurements and Main Results: Of 406 eligible survivors, we approached 261 to participate and 213 consented. We tested 122 subjects at least once, including 102 subjects at 12 months. Memory, verbal fluency, and executive function were impaired in 13% (12 of 92), 16% (15 of 96), and 49% (37 of 76) of long-term survivors. Long-term cognitive impairment was present in 41 of the 75 (55%) survivors who completed cognitive testing. Depression, post-traumatic stress disorder, or anxiety was present in 36% (37 of 102), 39% (40 of 102), and 62% (63 of 102) of long-term survivors. Enrollment in a conservative fluid-management strategy (P = 0.005) was associated with cognitive impairment and lower partial pressure of arterial oxygen during the trial was associated with cognitive (P = 0.02) and psychiatric impairment (P = 0.02). Conclusions: Neuropsychological function can be assessed by telephone in a multicenter trial. Long-term neuropsychological impairment is common in survivors of ALI. Hypoxemia is a risk factor for long-term neuropsychological impairment. Fluid management strategy is a potential risk factor for long-term cognitive impairment; however, given the select population studied and an unclear mechanism, this finding requires confirmation. C1 [Mikkelsen, Mark E.; Christie, Jason D.; Lanken, Paul N.; Demissie, Ejigayehu] Univ Penn, Perelman Sch Med, Pulm Allergy & Crit Care Div, Dept Med, Philadelphia, PA 19104 USA. [Mikkelsen, Mark E.; Christie, Jason D.; Bellamy, Scarlett L.; Localio, A. Russell; Demissie, Ejigayehu] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Biester, Rosette C.] Univ Penn, Perelman Sch Med, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA. [Biester, Rosette C.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Thompson, B. Taylor] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Hopkins, Ramona O.] Intermt Med Ctr, Div Pulm & Crit Care Med, Dept Med, Murray, UT USA. [Hopkins, Ramona O.] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. [Hopkins, Ramona O.] Brigham Young Univ, Ctr Neurosci, Provo, UT 84602 USA. [Angus, Derek C.] Univ Pittsburgh, CRISMA Ctr, Dept Crit Care Med, Pittsburgh, PA USA. [Angus, Derek C.] Univ Pittsburgh, Dept Hlth Policy & Management, Pittsburgh, PA USA. RP Mikkelsen, ME (reprint author), Univ Penn, Perelman Sch Med, Pulm Allergy & Crit Care Div, Dept Med, 836 W Gates Pavil,3400 Spruce St, Philadelphia, PA 19104 USA. EM mark.mikkelsen@uphs.upenn.edu RI Angus, Derek/E-9671-2012 FU National Heart, Lung and Blood Institute; National Institutes of Health; [N01-HR-46058]; [N01-HR-46046-64]; [N01-HR-16146-54]; [T32 HL07891] FX Supported in part by N01-HR-46058, N01-HR-46046-64, N01-HR-16146-54, and T32 HL07891 training grant, National Institutes of Health, and National Heart, Lung and Blood Institute. NR 70 TC 117 Z9 122 U1 2 U2 12 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUN 15 PY 2012 VL 185 IS 12 BP 1307 EP 1315 DI 10.1164/rccm.201111-2025OC PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 955VR UT WOS:000305049500013 PM 22492988 ER PT J AU Arvold, ND Ryan, DP Niemierko, A Blaszkowsky, LS Kwak, EL Wo, JY Allen, JN Clark, JW Wadlow, RC Zhu, AX Fernandez-del Castillo, C Hong, TS AF Arvold, Nils D. Ryan, David P. Niemierko, Andrzej Blaszkowsky, Lawrence S. Kwak, Eunice L. Wo, Jennifer Y. Allen, Jill N. Clark, Jeffrey W. Wadlow, Raymond C. Zhu, Andrew X. Fernandez-del Castillo, Carlos Hong, Theodore S. TI Long-term outcomes of neoadjuvant chemotherapy before chemoradiation for locally advanced pancreatic cancer SO CANCER LA English DT Article DE locally advanced pancreatic cancer; neoadjuvant chemotherapy; chemoradiation; gemcitabine; resection; survival ID PHASE-I TRIAL; MAINTENANCE GEMCITABINE; RADIATION-THERAPY; ONCOLOGY-GROUP; MITOMYCIN-C; III TRIAL; RADIOTHERAPY; CHEMORADIOTHERAPY; ADENOCARCINOMA; 5-FLUOROURACIL AB BACKGROUND: Neoadjuvant chemotherapy before chemoradiation therapy (CRT) may improve outcomes for patients with locally advanced pancreatic cancer, but optimal management remains controversial, and prior reports have limited follow-up. METHODS: Seventy consecutive patients with unresectable (n = 46) or borderline resectable (n = 24) locally advanced pancreatic cancer were treated with CRT from 2005 to 2009. Patients typically received 50.4 grays in 28 fractions (91%) with concurrent 5-fluorouracil (84%) or capecitabine (14%). Forty patients received CRT alone, and 30 patients received neoadjuvant chemotherapy before CRT for a median of 4 months, typically gemcitabine (93%). All patients without progression after neoadjuvant chemotherapy were offered CRT. RESULTS: Median follow-up was 14.2 months (range, 3-57 months). Fifty-three percent of patients in the CRT group versus 83% in the neoadjuvant chemotherapy before CRT group had unresectable tumors at diagnosis; after completion of CRT, 20% of patients in both groups underwent resection. Compared with CRT alone, the neoadjuvant chemotherapy before CRT group demonstrated improved median overall survival (OS; 18.7 vs 12.4 months; P = .02) and progression-free survival (11.4 vs 6.7 months; P = .02). On multivariate analysis, receipt of neoadjuvant chemotherapy (adjusted hazard ratio [HR], 0.49; 95% CI, 0.28-0.87; P = .02) and surgical resection (adjusted HR, 0.38; 95% CI, 0.17-0.85; P = .02) were associated with increased OS. CONCLUSIONS: Gemcitabine-based neoadjuvant chemotherapy confers a significant OS advantage by allowing the selection of patients who will derive greatest benefit from CRT. Median survival with this approach was similar to that seen with surgical resection. Cancer 2012;118: 302635. (C) 2011 American Cancer Society. C1 [Niemierko, Andrzej; Wo, Jennifer Y.; Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Arvold, Nils D.] Harvard Radiat Oncol Program, Boston, MA USA. [Ryan, David P.; Blaszkowsky, Lawrence S.; Kwak, Eunice L.; Allen, Jill N.; Clark, Jeffrey W.; Wadlow, Raymond C.; Zhu, Andrew X.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Hong, TS (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM Tshong1@partners.org NR 38 TC 22 Z9 23 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JUN 15 PY 2012 VL 118 IS 12 BP 3026 EP 3035 DI 10.1002/cncr.26633 PG 10 WC Oncology SC Oncology GA 952AB UT WOS:000304761000005 PM 22020923 ER PT J AU Bodurka, DC Deavers, MT Tian, CQ Sun, CC Malpica, A Coleman, RL Lu, KH Sood, AK Birrer, MJ Ozols, R Baergen, R Emerson, RE Steinhoff, M Behmaram, B Rasty, G Gershenson, DM AF Bodurka, Diane C. Deavers, Michael T. Tian, Chunqiao Sun, Charlotte C. Malpica, Anais Coleman, Robert L. Lu, Karen H. Sood, Anil K. Birrer, Michael J. Ozols, Robert Baergen, Rebecca Emerson, Robert E. Steinhoff, Margaret Behmaram, Behnaz Rasty, Golnar Gershenson, David M. TI Reclassification of serous ovarian carcinoma by a 2-tier system SO CANCER LA English DT Article DE ovarian cancer; serous histology; 2-tier grading system; FIGO grading ID GYNECOLOGIC-ONCOLOGY-GROUP; UNIVERSAL GRADING SYSTEM; MUTATIONAL ANALYSIS; CANCER; TUMORS; EXPRESSION; NEOPLASMS; KRAS; BRAF; P53 AB BACKGROUND: A study was undertaken to use the 2-tier system to reclassify the grade of serous ovarian tumors previously classified using the International Federation of Gynecology and Obstetrics (FIGO) 3-tier system and determine the progression-free survival (PFS) and overall survival (OS) of patients treated on Gynecologic Oncology Group (GOG) Protocol 158. METHODS: The authors retrospectively reviewed demographic, pathologic, and survival data of 290 patients with stage III serous ovarian carcinoma treated with surgery and chemotherapy on GOG Protocol 158, a cooperative multicenter group trial. A blinded pathology review was performed by a panel of 6 gynecologic pathologists to verify histology and regrade tumors using the 2-tier system. The association of tumor grade with PFS and OS was assessed. RESULTS: Of 241 cases, both systems demonstrated substantial agreement when combining FIGO grades 2 and 3 (overall agreement, 95%; kappa statistic, 0.68). By using the 2-tier system, patients with low-grade versus high-grade tumors had significantly longer PFS (45.0 vs 19.8 months, respectively; P = .01). By using FIGO criteria, median PFS for patients with grade 1, 2, and 3 tumors was 37.5, 19.8, and 20.1 months, respectively (P = .07). There was no difference in clinical outcome in patients with grade 2 or 3 tumors in multivariate analysis. Woman with high-grade versus low-grade tumors demonstrated significantly higher risk of death (hazard ratio, 2.43; 95% confidence interval, 1.17-5.04; P = .02). CONCLUSIONS: Women with high-grade versus low-grade serous carcinoma of the ovary are 2 distinct patient populations. Adoption of the 2-tier grading system provides a simple yet precise framework for predicting clinical outcomes. Cancer 2012;118: 308794. (C) 2011 American Cancer Society. C1 [Bodurka, Diane C.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. [Tian, Chunqiao] Roswell Pk Canc Inst, Gynecol Oncol Grp Stat & Data Ctr, Buffalo, NY 14263 USA. [Birrer, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ozols, Robert] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Baergen, Rebecca] New York Presbyterian Hosp, Weill Cornell Med Ctr, New York, NY USA. [Emerson, Robert E.] Indiana Univ Sch Med, Indianapolis, IN USA. [Steinhoff, Margaret] Brown Univ, Women & Infants Hosp, Providence, RI USA. [Behmaram, Behnaz] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Rasty, Golnar] Univ Hlth Network, Toronto, ON, Canada. RP Bodurka, DC (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, 1155 Herman Pressler,Unit 1362, Houston, TX 77030 USA. EM dcbodurka@mdanderson.org FU National Cancer Institute [CA 27469, CA 37517] FX This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office (CA 27469) and Gynecologic Oncology Group Statistical and Data Center (CA 37517). NR 24 TC 48 Z9 50 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JUN 15 PY 2012 VL 118 IS 12 BP 3087 EP 3094 DI 10.1002/cncr.26618 PG 8 WC Oncology SC Oncology GA 952AB UT WOS:000304761000012 PM 22072418 ER PT J AU Park, ER Japuntich, SJ Rigotti, NA Traeger, L He, YL Wallace, RB Malin, JL Zallen, JP Keating, NL AF Park, Elyse R. Japuntich, Sandra J. Rigotti, Nancy A. Traeger, Lara He, Yulei Wallace, Robert B. Malin, Jennifer L. Zallen, Jennifer P. Keating, Nancy L. TI A snapshot of smokers after lung and colorectal cancer diagnosis SO CANCER LA English DT Article DE cigarette smoking; lung cancer; colorectal cancer; tobacco; risk factors ID CARE OUTCOMES RESEARCH; 2ND PRIMARY CANCERS; QUALITY-OF-LIFE; SMOKING-CESSATION; CIGARETTE-SMOKING; UNITED-STATES; QUIT-SMOKING; COLON-CANCER; RISK-FACTOR; HEALTH AB BACKGROUND: Continued smoking after a cancer diagnosis may adversely affect treatment effectiveness, subsequent cancer risk, and survival. The prevalence of continued smoking after cancer diagnosis is understudied. METHODS: In the multi-regional Cancer Care Outcomes Research and Surveillance cohort (lung cancer [N = 2456], colorectal cancer [N = 3063]), the authors examined smoking rates at diagnosis and 5 months after diagnosis and also study factors associated with continued smoking. RESULTS: Overall, 90.2% of patients with lung cancer and 54.8% of patients with colorectal cancer reported ever smoking. At diagnosis, 38.7% of patients with lung cancer and 13.7% of patients with colorectal cancer were smoking; whereas, 5 months after diagnosis, 14.2% of patients with lung cancer and 9.0% of patients with colorectal cancer were smoking. Factors that were associated independently with continued smoking among patients with nonmetastatic lung cancer were coverage by Medicare, other public/unspecified insurance, not receiving chemotherapy, not undergoing surgery, prior cardiovascular disease, lower body mass index, lower emotional support, and higher daily ever-smoking rates (all P < .05). Factors that were associated independently with continued smoking among patients with nonmetastatic colorectal cancer were male sex, high school education, being uninsured, not undergoing surgery, and higher daily ever-smoking rates (all P < .05). CONCLUSIONS: After diagnosis, a substantial minority of patients with lung and colorectal cancers continued smoking. Patients with lung cancer had higher rates of smoking at diagnosis and after diagnosis; whereas patients with colorectal cancer were less likely to quit smoking after diagnosis. Factors that were associated with continued smoking differed between lung and colorectal cancer patients. Future smoking-cessation efforts should examine differences by cancer type, particularly when comparing cancers for which smoking is a well established risk factor versus cancers for which it is not. Cancer 2012;118: 315364. (C) 2012 American Cancer Society. C1 [Park, Elyse R.; Japuntich, Sandra J.; Rigotti, Nancy A.; Zallen, Jennifer P.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Park, Elyse R.; Japuntich, Sandra J.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Dept Med, Boston, MA 02114 USA. [Park, Elyse R.; Japuntich, Sandra J.; Traeger, Lara] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [He, Yulei; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Wallace, Robert B.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA. [Malin, Jennifer L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. RP Park, ER (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM epark@partners.org FU National Cancer Institute (NCI) [U01 CA093344, U01 CA093332, U01 CA093324, U01 CA093348, U01 CA093329, U01 CA093339, U01 CA093326, CRS 02-164]; American Cancer Society [MSRG 005-05-CPPB]; Pfizer; Nabi Biopharmaceuticals FX The work of the CanCORS Consortium was supported by grants from the National Cancer Institute (NCI) to the Statistical Coordinating Center (U01 CA093344) and the NCI-supported Primary Data Collection and Research Centers (U01 CA093332, U01 CA093324, U01 CA093348, U01 CA093329, U01 CA093339, U01 CA093326, CRS 02-164) and by the American Cancer Society (MSRG 005-05-CPPB to E. R. Park).; Dr. Rigotti has consulted for Pfizer, Free & Clear, and has served as site principal investigator for research grants from Pfizer and Nabi Biopharmaceuticals. NR 53 TC 39 Z9 39 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JUN 15 PY 2012 VL 118 IS 12 BP 3153 EP 3164 DI 10.1002/cncr.26545 PG 12 WC Oncology SC Oncology GA 952AB UT WOS:000304761000020 PM 22271645 ER PT J AU Ganis, JJ Hsia, N Trompouki, E de Jong, JLO DiBiase, A Lambert, JS Jia, ZY Sabo, PJ Weaver, M Sandstrom, R Stamatoyannopoulos, JA Zhou, Y Zon, LI AF Ganis, Jared J. Hsia, Nelson Trompouki, Eirini de Jong, Jill L. O. DiBiase, Anthony Lambert, Janelle S. Jia, Zhiying Sabo, Peter J. Weaver, Molly Sandstrom, Richard Stamatoyannopoulos, John A. Zhou, Yi Zon, Leonard I. TI Zebrafish globin switching occurs in two developmental stages and is controlled by the LCR SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Zebrafish; Erythropoiesis; Globin switching; Locus control region ID LONG-RANGE REGULATION; SICKLE-CELL-DISEASE; GENE-EXPRESSION; TRANSGENIC MICE; REGULATORY ELEMENTS; DANIO-RERIO; THALASSEMIA; HEMOGLOBIN; CLUSTER; GENOME AB Globin gene switching is a complex, highly regulated process allowing expression of distinct globin genes at specific developmental stages. Here, for the first time, we have characterized all of the zebrafish globins based on the completed genomic sequence. Two distinct chromosomal loci, termed major (chromosome 3) and minor (chromosome 12), harbor the globin genes containing alpha/beta pairs in a 5'-3' to 3'-5' orientation. Both these loci share synteny with the mammalian alpha-globin locus. Zebrafish globin expression was assayed during development and demonstrated two globin switches, similar to human development. A conserved regulatory element, the locus control region (LCR), was revealed by analyzing DNase I hypersensitive sites. H3K4 trimethylation marks and GATA1 binding sites. Surprisingly, the position of these sites with relation to the globin genes is evolutionarily conserved, despite a lack of overall sequence conservation. Motifs within the zebrafish LCR include CACCC, GATA, and NFE2 sites, suggesting functional interactions with known transcription factors but not the same LCR architecture. Functional homology to the mammalian alpha-LCR MCS-R2 region was confirmed by robust and specific reporter expression in erythrocytes of transgenic zebrafish. Our studies provide a comprehensive characterization of the zebrafish globin loci and clarify the regulation ofglobin switching. (C) 2012 Elsevier Inc. All rights reserved. C1 [Zon, Leonard I.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Ganis, Jared J.; Hsia, Nelson; Trompouki, Eirini; de Jong, Jill L. O.; DiBiase, Anthony; Jia, Zhiying; Zhou, Yi; Zon, Leonard I.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Ganis, Jared J.; Hsia, Nelson; Trompouki, Eirini; de Jong, Jill L. O.; DiBiase, Anthony; Jia, Zhiying; Zhou, Yi; Zon, Leonard I.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Ganis, Jared J.; Hsia, Nelson; Trompouki, Eirini; de Jong, Jill L. O.; DiBiase, Anthony; Jia, Zhiying; Zhou, Yi; Zon, Leonard I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ganis, Jared J.; Hsia, Nelson; Trompouki, Eirini; de Jong, Jill L. O.; Jia, Zhiying; Zhou, Yi; Zon, Leonard I.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Lambert, Janelle S.] Harvard Univ, Cambridge, MA 02138 USA. [Sabo, Peter J.; Weaver, Molly; Sandstrom, Richard; Stamatoyannopoulos, John A.] Univ Washington, Sch Med, Dept Genome Sci & Med, Seattle, WA 98195 USA. RP Zon, LI (reprint author), Childrens Hosp, Howard Hughes Med Inst, 300 Longwood Ave,Karp 7, Boston, MA 02115 USA. EM jganis@fas.harvard.edu; nelhsia@gmail.com; etrompouki@enders.tch.harvard.edu; jdejong@peds.bsd.uchicago.edu; adibiase@enders.tch.harvard.edu; adibiase@enders.tch.harvard.edu; zyjia2010@163.com; psabo@stamlab.org; mweaver@stamlab.org; sull@uw.edu; jstam@u.washington.edu; yzhou@enders.tch.harvard.edu; zon@enders.tch.harvard.edu OI Trompouki, Eirini/0000-0002-7242-8810 FU National Institutes Health (NIDDK) [5RO1 DK53298-14, 2P30 DK49216-17, 5R37 DK55381-11]; National Institutes Health (NHLBI) [5R01HL048801-18, R01GM71923, 5PO1HL32262-29]; Howard Hughes Medical Institute; UW FX We would like to thank Owen Tamplin for providing pME-MinPro-GFP. We would like to thank Hsuan-Ting Huang for reviewing the manuscript. The authors acknowledge the help of the UW High-Throughput Genomic Center staff. The authors would like to thank members of the Zon laboratory for suggestions on the manuscript. This work was supported by grants from the National Institutes Health (NIDDK 5RO1 DK53298-14 to L.I.Z.; NIDDK 2P30 DK49216-17, NIDDK 5R37 DK55381-11 and NHLBI 5R01HL048801-18 to Y.Z.; R01GM71923 to J.A.S.; NHLBI 5PO1HL32262-29 to E.T.) and the Howard Hughes Medical Institute (L.I.Z.). J.A.S. was also supported by UW internal sources. J.J.G. and N.H. designed and performed experiments, analyzed data and wrote the manuscript; E.T., J.L.O.d., P.J.S., M.W. and R.S. performed experiments and analyzed data; A.D. analyzed data; J.S.L. and Z.J. performed experiments; J.A.S. and Y.Z. designed experiments and analyzed data; L.I.Z. designed experiments, analyzed data and wrote the manuscript. NR 54 TC 34 Z9 35 U1 2 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 EI 1095-564X J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 2012 VL 366 IS 2 BP 185 EP 194 DI 10.1016/j.ydbio.2012.03.021 PG 10 WC Developmental Biology SC Developmental Biology GA 952JK UT WOS:000304788600008 PM 22537494 ER PT J AU Zhang, SC Martin, E Shimada, M Godfrey, SB Fricke, J Locastro, S Lai, NY Liebesny, P Carlson, JM Brumme, CJ Ogbechie, OA Chen, HB Walker, BD Brumme, ZL Kavanagh, DG Le Gall, S AF Zhang, Shao Chong Martin, Eric Shimada, Mariko Godfrey, Sasha Blue Fricke, Jennifer Locastro, Shirley Lai, Nicole Y. Liebesny, Paul Carlson, Jonathan M. Brumme, Chanson J. Ogbechie, Oluwatobi Awele Chen, Huabiao Walker, Bruce D. Brumme, Zabrina L. Kavanagh, Daniel G. Le Gall, Sylvie TI Aminopeptidase Substrate Preference Affects HIV Epitope Presentation and Predicts Immune Escape Patterns in HIV-Infected Individuals SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MHC CLASS-I; VIRUS TYPE-1 INFECTION; T-LYMPHOCYTE EPITOPES; ANTIGEN PRESENTATION; LEUCINE AMINOPEPTIDASE; ENDOPLASMIC-RETICULUM; DENDRITIC CELLS; EVOLUTION; MUTATION; RESPONSES AB Viruses evade immune detection partly through immune-associated mutations. Analyses of HIV sequences derived from infected individuals have identified numerous examples of HLA-associated mutations within or adjacent to T cell epitopes, but the potential impact of most mutations on epitope production and presentation remains unclear. The multistep breakdown of proteins into epitopes includes trimming of N-extended peptides into epitopes by aminopeptidases before loading onto MHC class I molecules. Definition of sequence signatures that modulate epitope production would lead to a better understanding of factors driving viral evolution and immune escape at the population level. In this study, we identified cytosolic aminopeptidases cleavage preferences in primary cells and its impact on HIV Ag degradation into epitopes in primary human cell extracts by mass spectrometry and on epitope presentation to CTL. We observed a hierarchy of preferred amino acid cleavage by cytosolic aminopeptidases. We demonstrated that flanking mutations producing more or less cleavable motifs can increase or decrease epitope production and presentation by up to 14-fold. We found that the efficiency of epitope production correlates with cleavability of flanking residues. These in vitro findings were supported by in vivo population-level analyses of clinically derived viral sequences from 1134 antiretroviral-naive HIV-infected individuals: HLA-associated mutations immune pressures drove the selection of residues that are less cleavable by aminopeptidases predominantly at N-flanking sites, leading to reduced epitope production and immune recognition. These results underscore an important and widespread role of Ag processing mutations in HIV immune escape and identify molecular mechanisms underlying impaired epitope presentation. The Journal of Immunology, 2012, 188: 5924-5934. C1 [Le Gall, Sylvie] Harvard Univ, Sch Med, Ragon Inst MGH MIT & Harvard, Boston, MA 02129 USA. [Zhang, Shao Chong; Shimada, Mariko; Godfrey, Sasha Blue; Fricke, Jennifer; Locastro, Shirley; Lai, Nicole Y.; Liebesny, Paul; Ogbechie, Oluwatobi Awele; Chen, Huabiao; Walker, Bruce D.; Kavanagh, Daniel G.; Le Gall, Sylvie] Massachusetts Gen Hosp, Ragon Inst MGH, MIT & Harvard, Boston, MA 02129 USA. [Martin, Eric; Brumme, Zabrina L.] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. [Carlson, Jonathan M.] Microsoft Res, eSci Res Grp, Los Angeles, CA 90024 USA. [Brumme, Chanson J.] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC V6Z 1Y6, Canada. RP Le Gall, S (reprint author), Harvard Univ, Sch Med, Ragon Inst MGH MIT & Harvard, CNY Bldg 149,13th St, Boston, MA 02129 USA. EM sylvie_legall@hms.harvard.edu OI Brumme, Chanson/0000-0003-2722-5288; Godfrey, Sasha Blue/0000-0001-9992-5975 FU Harvard Center for AIDS Research [P30 AI060354]; Bill and Melinda Gates Foundation; National Institute of Allergy and Infectious Diseases [PO1 AI074415-01A1, AI074415-02S1, R01 AI084753]; Canadian Institutes for Health Research; Canadian Association of HIV Research; Abbott Virology FX This work was supported by Development Award P30 AI060354 from the Harvard Center for AIDS Research (to S. L. G.) for initial studies; the Bill and Melinda Gates Foundation (Collaboration for AIDS Vaccine Discovery; to S. L. G. and B. D. W.) for the modulation of epitope production; and the National Institute of Allergy and Infectious Diseases (PO1 AI074415-01A1 and AI074415-02S1 American Recovery and Reinvestment Act supplement, Special Emphasis Panel Vaccine Design and Acute HIV Infection, to S. L. G. and B. D. W.; R01 AI084753 to S. L. G.). Z.L.B. is supported by a New Investigator Award from the Canadian Institutes for Health Research. E. M. is supported by a Master's Scholarship from the Canadian Association of HIV Research and Abbott Virology. C.J.B. is supported by a Vanier Canada Graduate Scholarship from the Canadian Institutes for Health Research. NR 57 TC 19 Z9 20 U1 0 U2 9 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2012 VL 188 IS 12 BP 5924 EP 5934 DI 10.4049/jimmunol.1200219 PG 11 WC Immunology SC Immunology GA 956GK UT WOS:000305077900017 PM 22586036 ER PT J AU Yamada, Y Aoyama, A Tocco, G Boskovic, S Nadazdin, O Alessandrini, A Madsen, JC Cosimi, AB Benichou, G Kawai, T AF Yamada, Yohei Aoyama, Akihiro Tocco, Georges Boskovic, Svjetlan Nadazdin, Ognjenka Alessandrini, Alessandro Madsen, Joren C. Cosimi, A. Benedict Benichou, Gilles Kawai, Tatsuo TI Differential Effects of Denileukin Diftitox IL-2 Immunotoxin on NK and Regulatory T Cells in Nonhuman Primates SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; FUSION PROTEIN; IN-VIVO; DENDRITIC CELLS; PHASE-II; TOXIN; RECEPTOR; DEPLETION; LYMPHOMA; CANCER AB Denileukin diftitox (DD), a fusion protein comprising IL-2 and diphtheria toxin, was initially expected to enhance antitumor immunity by selectively eliminating regulatory T cells (Tregs) displaying the high-affinity IL-2R (alpha-beta-gamma trimers). Although DD was shown to deplete some Tregs in primates, its effects on NK cells (CD16(+)CD8(+)NKG2A(+)CD3(-)), which constitutively express the intermediate-affinity IL-2R (beta-gamma dimers) and play a critical role in antitumor immunity, are still unknown. To address this question, cynomolgus monkeys were injected i.v. with two doses of DD (8 or 18 mu g/kg). This treatment resulted in a rapid, but short-term, reduction in detectable peripheral blood resting Tregs (CD4(+)CD45RA(+)Foxp3(+)) and a transient increase in the number of activated Tregs (CD4(+)CD45RA(-)Foxp3(high)), followed by their partial depletion (50-60%). In contrast, all NK cells were deleted immediately and durably after DD administration. This difference was not due to a higher binding or internalization of DD by NK cells compared with Tregs. Coadministration of DD with IL-15, which binds to IL-2R beta-gamma, abrogated DD-induced NK cell deletion in vitro and in vivo, whereas it did not affect Treg elimination. Taken together, these results show that DD exerts a potent cytotoxic effect on NK cells, a phenomenon that might impair its antitumoral properties. However, coadministration of IL-15 with DD could alleviate this problem by selectively protecting potentially oncolytic NK cells, while allowing the depletion of immunosuppressive Tregs in cancer patients. The Journal of Immunology, 2012, 188: 6063-6070. C1 [Kawai, Tatsuo] Massachusetts Gen Hosp, Dept Surg, Transplant Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kawai, T (reprint author), Massachusetts Gen Hosp, Dept Surg, Transplant Res Ctr, White 521,55 Fruit St, Boston, MA 02114 USA. EM tkawai@partners.org FU National Institute of Allergy and Infectious Diseases [U19 AI066705, NIH 19 DK080652, HL018446, NIH U191066705, PO1HL18646, U01AI094374] FX This work was supported by National Institute of Allergy and Infectious Diseases Grants U19 AI066705, NIH 19 DK080652, HL018446, NIH U191066705, PO1HL18646, and U01AI094374. NR 44 TC 14 Z9 15 U1 1 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2012 VL 188 IS 12 BP 6063 EP 6070 DI 10.4049/jimmunol.1200656 PG 8 WC Immunology SC Immunology GA 956GK UT WOS:000305077900032 PM 22586034 ER PT J AU Schepp-Berglind, J Atkinson, C Elvington, M Qiao, F Mannon, P Tomlinson, S AF Schepp-Berglind, Jennifer Atkinson, Carl Elvington, Michelle Qiao, Fei Mannon, Peter Tomlinson, Stephen TI Complement-Dependent Injury and Protection in a Murine Model of Acute Dextran Sulfate Sodium-Induced Colitis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; DECAY-ACCELERATING FACTOR; ULCERATIVE-COLITIS; CROHNS-DISEASE; ISCHEMIA/REPERFUSION INJURY; ALTERNATIVE PATHWAY; ACTIVATION; EXPRESSION; EPITHELIUM; RECEPTOR AB Complement plays a key role in the pathophysiology of many inflammatory diseases, and in this study, we investigated the role of complement in the pathogenesis of inflammatory bowel disease. Compared to wild-type mice, mice deficient in C3 or factor B were protected from acute dextran sulfate sodium (DSS)-induced colitis. C1q/mannose-binding lectin (MBL) double-deficient mice, however, exhibited more severe colitis than wild-type mice. When mice were allowed to recover after DSS treatment, all C1q/MBL-/- mice died by day 2 of recovery period, and, surprisingly, all C3(-/-) and factor B-/- mice died by day 5. Serum endotoxin levels were significantly increased in complement-deficient mice prior to death, particularly in C1q/MBL-/- mice, and antibiotic treatment prevented the lethal effect of DSS in all complement-deficient mice. In contrast to complement deficiency, targeted complement inhibition with either complement receptor 2 (CR2)-Crry (blocks all pathways at C3 activation) or CR2-factor H (blocks alternative pathway) was highly protective at treating established acute colitis. Endotoxin levels remained low in complement-inhibited mice, and complement inhibition also reduced inflammatory cytokines, leukocyte infiltration, and tissue injury while improving wound repair and mucosal healing. CR2-factor H provided more effective protection than CR2-Crry. Thus, complement has both pathogenic and protective roles in acute DSS-induced colitis, and whereas the alternative pathway appears to play a key role in tissue inflammation and injury, the classical/lectin pathway provides important protection in terms of host defense and wound repair. Targeted inhibition of the alternative pathway may represent a therapeutic modality for treating acute phases of inflammatory bowel disease. The Journal of Immunology, 2012, 188: 6309-6318. C1 [Schepp-Berglind, Jennifer; Atkinson, Carl; Elvington, Michelle; Qiao, Fei; Tomlinson, Stephen] Med Univ S Carolina, Dept Microbiol & Immunol, Childrens Res Inst, Charleston, SC 29425 USA. [Mannon, Peter] Univ Alabama Birmingham, Dept Gastroenterol & Hepatol, Birmingham, AL 35294 USA. [Tomlinson, Stephen] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Tomlinson, S (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, Childrens Res Inst, Charleston, SC 29425 USA. EM tomlinss@musc.edu FU Crohn's and Colitis Foundation of America; National Institutes of Health [T32 AR050958] FX This work was supported by a grant from the Crohn's and Colitis Foundation of America (to S.T.) and National Institutes of Health Training Grant T32 AR050958 (to J.S.-B.). NR 31 TC 19 Z9 20 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2012 VL 188 IS 12 BP 6309 EP 6318 DI 10.4049/jimmunol.1200553 PG 10 WC Immunology SC Immunology GA 956GK UT WOS:000305077900056 PM 22566568 ER PT J AU Lipsky, BA Berendt, AR Cornia, PB Pile, JC Peters, EJG Armstrong, DG Deery, HG Embil, JM Joseph, WS Karchmer, AW Pinzur, MS Senneville, E AF Lipsky, Benjamin A. Berendt, Anthony R. Cornia, Paul B. Pile, James C. Peters, Edgar J. G. Armstrong, David G. Deery, H. Gunner Embil, John M. Joseph, Warren S. Karchmer, Adolf W. Pinzur, Michael S. Senneville, Eric TI 2012 Infectious Diseases Society of America Clinical Practice Guideline for the Diagnosis and Treatment of Diabetic Foot Infections SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID GRADE; RECOMMENDATIONS; CONSENSUS AB Foot infections are a common and serious problem in persons with diabetes. Diabetic foot infections (DFIs) typically begin in a wound, most often a neuropathic ulceration. While all wounds are colonized with microorganisms, the presence of infection is defined by >= 2 classic findings of inflammation or purulence. Infections are then classified into mild (superficial and limited in size and depth), moderate (deeper or more extensive), or severe (accompanied by systemic signs or metabolic perturbations). This classification system, along with a vascular assessment, helps determine which patients should be hospitalized, which may require special imaging procedures or surgical interventions, and which will require amputation. Most DFIs are polymicrobial, with aerobic gram-positive cocci (GPC), and especially staphylococci, the most common causative organisms. Aerobic gram-negative bacilli are frequently copathogens in infections that are chronic or follow antibiotic treatment, and obligate anaerobes may be copathogens in ischemic or necrotic wounds. Wounds without evidence of soft tissue or bone infection do not require antibiotic therapy. For infected wounds, obtain a post-debridement specimen (preferably of tissue) for aerobic and anaerobic culture. Empiric antibiotic therapy can be narrowly targeted at GPC in many acutely infected patients, but those at risk for infection with antibiotic-resistant organisms or with chronic, previously treated, or severe infections usually require broader spectrum regimens. Imaging is helpful in most DFIs; plain radiographs may be sufficient, but magnetic resonance imaging is far more sensitive and specific. Osteomyelitis occurs in many diabetic patients with a foot wound and can be difficult to diagnose (optimally defined by bone culture and histology) and treat (often requiring surgical debridement or resection, and/or prolonged antibiotic therapy). Most DFIs require some surgical intervention, ranging from minor (debridement) to major (resection, amputation). Wounds must also be properly dressed and off-loaded of pressure, and patients need regular follow-up. An ischemic foot may require revascularization, and some nonresponding patients may benefit from selected adjunctive measures. Employing multidisciplinary foot teams improves outcomes. Clinicians and healthcare organizations should attempt to monitor, and thereby improve, their outcomes and processes in caring for DFIs. C1 [Lipsky, Benjamin A.; Cornia, Paul B.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. [Berendt, Anthony R.] Oxford Univ Hosp NHS Trust, Nuffield Orthopaed Ctr, Bone Infect Unit, Oxford, England. [Pile, James C.] Metrohlth Med Ctr, Div Hosp Med, Cleveland, OH USA. [Pile, James C.] Metrohlth Med Ctr, Div Infect Dis, Cleveland, OH USA. [Peters, Edgar J. G.] Vrije Univ Amsterdam, Med Ctr, Dept Internal Med, Amsterdam, Netherlands. [Armstrong, David G.] Univ Arizona, Dept Surg, So Arizona Limb Salvage Alliance, Tucson, AZ USA. [Deery, H. Gunner] No Michigan Infect Dis, Petoskey, MI USA. [Embil, John M.] Univ Manitoba, Dept Med, Winnipeg, MB, Canada. [Joseph, Warren S.] Roxborough Mem Hosp, Dept Surg, Div Podiatr Surg, Philadelphia, PA USA. [Karchmer, Adolf W.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Infect Dis,Dept Med, Boston, MA 02215 USA. [Pinzur, Michael S.] Loyola Univ, Med Ctr, Dept Orthopaed Surg & Rehabil, Maywood, IL 60153 USA. [Senneville, Eric] Dron Hosp, Dept Infect Dis, Tourcoing, France. RP Lipsky, BA (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, 1660 S Columbian Way, Seattle, WA 98108 USA. EM balipsky@uw.edu RI Peters, Edgar /B-7790-2014; OI Lipsky, Benjamin A./0000-0001-9886-5114 FU Infectious Diseases Society of America FX Support for these guidelines was provided by the Infectious Diseases Society of America. NR 6 TC 31 Z9 37 U1 0 U2 17 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 15 PY 2012 VL 54 IS 12 BP 1679 EP 1684 DI 10.1093/cid/cis460 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 948YT UT WOS:000304541000007 PM 22619239 ER PT J AU Lipsky, BA Berendt, AR Cornia, PB Pile, JC Peters, EJG Armstrong, DG Deery, HG Embil, JM Joseph, WS Karchmer, AW Pinzur, MS Senneville, E AF Lipsky, Benjamin A. Berendt, Anthony R. Cornia, Paul B. Pile, James C. Peters, Edgar J. G. Armstrong, David G. Deery, H. Gunner Embil, John M. Joseph, Warren S. Karchmer, Adolf W. Pinzur, Michael S. Senneville, Eric TI 2012 Infectious Diseases Society of America Clinical Practice Guideline for the Diagnosis and Treatment of Diabetic Foot Infections SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; COLONY-STIMULATING FACTOR; SKIN-STRUCTURE INFECTIONS; PERIPHERAL ARTERIAL-DISEASE; TO-BONE TEST; PRESSURE WOUND THERAPY; RANDOMIZED CONTROLLED-TRIAL; LOWER-EXTREMITY INFECTIONS; HYPERBARIC-OXYGEN THERAPY; COMPLICATED SKIN AB Foot infections are a common and serious problem in persons with diabetes. Diabetic foot infections (DFIs) typically begin in a wound, most often a neuropathic ulceration. While all wounds are colonized with microorganisms, the presence of infection is defined by >= 2 classic findings of inflammation or purulence. Infections are then classified into mild (superficial and limited in size and depth), moderate (deeper or more extensive), or severe (accompanied by systemic signs or metabolic perturbations). This classification system, along with a vascular assessment, helps determine which patients should be hospitalized, which may require special imaging procedures or surgical interventions, and which will require amputation. Most DFIs are polymicrobial, with aerobic gram-positive cocci (GPC), and especially staphylococci, the most common causative organisms. Aerobic gram-negative bacilli are frequently copathogens in infections that are chronic or follow antibiotic treatment, and obligate anaerobes may be copathogens in ischemic or necrotic wounds. Wounds without evidence of soft tissue or bone infection do not require antibiotic therapy. For infected wounds, obtain a post-debridement specimen (preferably of tissue) for aerobic and anaerobic culture. Empiric antibiotic therapy can be narrowly targeted at GPC in many acutely infected patients, but those at risk for infection with antibiotic-resistant organisms or with chronic, previously treated, or severe infections usually require broader spectrum regimens. Imaging is helpful in most DFIs; plain radiographs may be sufficient, but magnetic resonance imaging is far more sensitive and specific. Osteomyelitis occurs in many diabetic patients with a foot wound and can be difficult to diagnose (optimally defined by bone culture and histology) and treat (often requiring surgical debridement or resection, and/or prolonged antibiotic therapy). Most DFIs require some surgical intervention, ranging from minor (debridement) to major (resection, amputation). Wounds must also be properly dressed and off-loaded of pressure, and patients need regular follow-up. An ischemic foot may require revascularization, and some nonresponding patients may benefit from selected adjunctive measures. Employing multidisciplinary foot teams improves outcomes. Clinicians and healthcare organizations should attempt to monitor, and thereby improve, their outcomes and processes in caring for DFIs. C1 [Lipsky, Benjamin A.; Cornia, Paul B.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. [Berendt, Anthony R.] Oxford Univ Hosp NHS Trust, Nuffield Orthopaed Ctr, Bone Infect Unit, Oxford, England. [Pile, James C.] Metrohlth Med Ctr, Div Hosp Med, Cleveland, OH USA. [Pile, James C.] Metrohlth Med Ctr, Div Infect Dis, Cleveland, OH USA. [Peters, Edgar J. G.] Vrije Univ Amsterdam, Med Ctr, Dept Internal Med, Amsterdam, Netherlands. [Armstrong, David G.] Univ Arizona, Dept Surg, So Arizona Limb Salvage Alliance, Tucson, AZ USA. [Deery, H. Gunner] No Michigan Infect Dis, Petoskey, MI USA. [Embil, John M.] Univ Manitoba, Dept Med, Winnipeg, MB, Canada. [Joseph, Warren S.] Roxborough Mem Hosp, Dept Surg, Div Podiatr Surg, Philadelphia, PA USA. [Karchmer, Adolf W.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Infect Dis,Dept Med, Boston, MA 02215 USA. [Pinzur, Michael S.] Loyola Univ, Med Ctr, Dept Orthopaed Surg & Rehabil, Maywood, IL 60153 USA. [Senneville, Eric] Dron Hosp, Dept Infect Dis, Tourcoing, France. RP Lipsky, BA (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, 1660 S Columbian Way, Seattle, WA 98108 USA. EM balipsky@uw.edu RI Peters, Edgar /B-7790-2014; OI Lipsky, Benjamin A./0000-0001-9886-5114 FU Infectious Diseases Society of America FX Support for these guidelines was provided by the Infectious Diseases Society of America. NR 358 TC 210 Z9 229 U1 11 U2 50 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 15 PY 2012 VL 54 IS 12 BP E132 EP U232 DI 10.1093/cid/cis346 PG 42 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 948YT UT WOS:000304541000005 PM 22619242 ER PT J AU van der Windt, GJW Blok, DC Hoogerwerf, JJ Lammers, AJJ de Vos, AF van't Veer, C Florquin, S Kobayashi, KS Flavell, RA van der Poll, T AF van der Windt, Gerritje J. W. Blok, Dana C. Hoogerwerf, Jacobien J. Lammers, Adriana J. J. de Vos, Alex F. van't Veer, Cornelis Florquin, Sandrine Kobayashi, Koichi S. Flavell, Richard A. van der Poll, Tom TI Interleukin 1 Receptor-Associated Kinase M Impairs Host Defense During Pneumococcal Pneumonia SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; TOLL-LIKE RECEPTOR-4; IRAK-M EXPRESSION; INNATE IMMUNITY; STREPTOCOCCUS-PNEUMONIAE; ENDOTOXIN TOLERANCE; NEGATIVE REGULATOR; UP-REGULATION; IN-VIVO; SEPSIS AB Background. Streptococcus pneumoniae is the most common causative organism in community-acquired pneumonia. Pneumococci that try to invade the lower airways are recognized by innate immune cells through pattern recognition receptors, including Toll-like receptors 2, 4, and 9. Interleukin 1 (IL-1) receptor-associated kinase (IRAK)-M is a proximal inhibitor of Toll-like receptor signaling. Methods. To determine the role of IRAK-M in host defense during pneumococcal pneumonia, IRAK-M-deficient and wild-type mice were intranasally infected with S. pneumoniae. Results. IRAK-M-deficient mice demonstrated a reduced lethality after infection with S. pneumoniae via the airways. Whereas bacterial burdens were similar in IRAK-M-deficient and wild-type mice early (3 hours) after infection, from 24 hours onward the number of pneumococci recovered from lungs and distant body sites were 10-100-fold lower in the former mouse strain. The diminished bacterial growth and dissemination in IRAK-M-deficient mice were preceded by an increased early influx of neutrophils into lung tissue and elevated pulmonary levels of IL-1 beta and CXCL1. IRAK-M deficiency did not influence bacterial growth after intravenous administration of S. pneumoniae. Conclusions. These data suggest that IRAK-M impairs host defense during pneumococcal pneumonia at the primary site of infection at least in part by inhibiting the early immune response. C1 [van der Windt, Gerritje J. W.; Blok, Dana C.; Hoogerwerf, Jacobien J.; Lammers, Adriana J. J.; de Vos, Alex F.; van't Veer, Cornelis; van der Poll, Tom] Univ Amsterdam, Acad Med Ctr, Ctr Infect & Immun Amsterdam CINIMA, NL-1105 AZ Amsterdam, Netherlands. [van der Windt, Gerritje J. W.; Blok, Dana C.; Hoogerwerf, Jacobien J.; Lammers, Adriana J. J.; de Vos, Alex F.; van't Veer, Cornelis; van der Poll, Tom] Univ Amsterdam, Acad Med Ctr, Ctr Expt & Mol Med, NL-1105 AZ Amsterdam, Netherlands. [Florquin, Sandrine] Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1105 AZ Amsterdam, Netherlands. [Kobayashi, Koichi S.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Kobayashi, Koichi S.] Harvard Univ, Sch Med, Boston, MA USA. [Flavell, Richard A.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA. [Flavell, Richard A.] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. RP van der Poll, T (reprint author), Univ Amsterdam, Acad Med Ctr, Ctr Infect & Immun Amsterdam CINIMA, Meibergdreef 9,Rm G2-129, NL-1105 AZ Amsterdam, Netherlands. EM t.vanderpoll@amc.uva.nl FU Netherlands Organization of Scientific Research (NWO); Academic Medical Center, Amsterdam FX A. J. J. L. was supported by a research grant from the Netherlands Organization of Scientific Research (NWO). G. J. W. v. d. W., D. C. B., and J. J. H. were supported by institutional research grants from the Academic Medical Center, Amsterdam. R. A. F. is an investigator of the Howard Hughes Medical Institute. NR 46 TC 17 Z9 17 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 15 PY 2012 VL 205 IS 12 BP 1849 EP 1857 DI 10.1093/infdis/jis290 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 948YI UT WOS:000304539600013 PM 22492852 ER PT J AU Lyall, K Munger, K O'Reilly, EJ Santangelo, SL Ascherio, A AF Lyall, K. Munger, K. O'Reilly, E. J. Santangelo, S. L. Ascherio, A. TI MATERNAL DIETARY FAT AND FATTY ACID INTAKE IN ASSOCIATION WITH AUTISM SPECTRUM DISORDERS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the Society-for-Epidemiologic-Research (SER) CY JUN 27-30, 2012 CL Minneapolis, MN SP Soc Epidemiol Res (SER) C1 Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Univ Calif Davis, MIND Inst, Davis, CA USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 2012 VL 175 SU 11 BP S127 EP S127 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 197ED UT WOS:000322831400501 ER PT J AU Hall, DE Hanusa, BH Switzer, GE Fine, MJ Arnold, RM AF Hall, Daniel E. Hanusa, Barbara H. Switzer, Galen E. Fine, Michael J. Arnold, Robert M. TI The Impact of iMedConsent on Patient Decision-Making Regarding Cholecystectomy and Inguinal Herniorrhaphy SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE informed consent; decision-making; information preference; participation preference; ethics; trust; anxiety ID SURGICAL INFORMED-CONSENT; BONE-MARROW DONATION; SHORT-FORM; CLINICAL ANESTHESIA; SURGERY RESEARCH; PHYSICIAN SCALE; CANCER-PATIENTS; ANXIETY; INFORMATION; DONORS AB Background. The Veterans Affairs Healthcare System implemented a computer-based tool (iMedConsent) to improve the quality of informed consent in 2004. The impact of this tool on the process of informed consent remains unknown. Our aim was to determine the impact of iMedConsent on patient information preference, anxiety, trust in the surgeon, ambivalence about the surgical decision, and comprehension of procedure-specific risk, benefits, and alternatives. Materials and Methods. We prospectively enrolled a consecutive cohort of patients presenting to a general surgery clinic for possible cholecystectomy or inguinal herniorrhaphy from October 2009 to August 2010. We administered questionnaires before and after the clinic visit. Results. Seventy-five patients completed pre-visit questionnaires. After evaluation by the surgeon, 42 patients were offered surgery and documented their informed consent using iMedConsent, of whom 38 (90%) also completed a post-visit questionnaire. Among the participants who completed both pre- and post-visit questionnaires, participant comprehension of procedure-specific risks benefits and alternatives improved from 50% at baseline to 60% after the clinic visit (P < 0.001). No differences were noted in ambivalence, trust, or anxiety. After the clinic visit, significantly more patients expressed a preference for participating in decision making with their surgeon (98% versus 71%, P = 0.008). However, significantly fewer expressed a preference for knowing all possible details about their illness (25% to 83%, P <= 0.001). Conclusions. The informed consent process using iMedConsent improves patient comprehension of procedure-specific risks, benefits, and alternatives. It also increases patient preferences for participating more actively in the decision-making process. However, the process may provide more detail than patients want regarding their illness. Published by Elsevier Inc. C1 [Hall, Daniel E.; Hanusa, Barbara H.; Switzer, Galen E.; Fine, Michael J.] Healthcare Syst, VA Pittsburgh, VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Hall, Daniel E.] Univ Pittsburgh, Dept Gen Surg, Pittsburgh, PA USA. [Switzer, Galen E.; Fine, Michael J.; Arnold, Robert M.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. RP Hall, DE (reprint author), VA Pittsburgh Healthcare Syst, 7180 Highland Dr 151C-H, Pittsburgh, PA 15206 USA. EM hallde@upmc.edu RI Hall, Daniel/H-4843-2013; OI Hall, Daniel/0000-0001-6382-0522 FU VA HSRD [CDA 08-281]; VISN4 [XVA 72-057]; CHERP [LIP 72-043] FX The authors thank Drs. Aaron Fink and Alan Prochazka for their gracious advice regarding the design of this study. This research was funded by grants from VA HSR&D (CDA 08-281), VISN4 Competitive Pilot Project Fund (XVA 72-057), and the CHERP Pilot Project Program (LIP 72-043). NR 33 TC 3 Z9 3 U1 2 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 EI 1095-8673 J9 J SURG RES JI J. Surg. Res. PD JUN 15 PY 2012 VL 175 IS 2 BP 227 EP 233 DI 10.1016/j.jss.2011.04.056 PG 7 WC Surgery SC Surgery GA 939AB UT WOS:000303774400016 PM 21704336 ER PT J AU Bruinstroop, E Cano, G Vanderhorst, VGJM Cavalcante, JC Wirth, J Sena-Esteves, M Saper, CB AF Bruinstroop, Eveline Cano, Georgina Vanderhorst, Veronique G. J. M. Cavalcante, Judney C. Wirth, Jena Sena-Esteves, Miguel Saper, Clifford B. TI Spinal projections of the A5, A6 (locus coeruleus), and A7 noradrenergic cell groups in rats SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE pontine; spinal cord; adeno-associated viral vector; tracing ID SYMPATHETIC OUTFLOW; PARAVENTRICULAR NUCLEUS; PREGANGLIONIC NEURONS; EFFERENT PROJECTIONS; ANATOMICAL EVIDENCE; CERULEUS NEURONS; NERVOUS-SYSTEM; AXON TERMINALS; MOTOR-NEURONS; CORD AB The pontine noradrenergic cell groups, A5, A6 (locus coeruleus), and A7, provide the only noradrenergic innervation of the spinal cord, but the individual contribution of each of these populations to the regional innervation of the spinal cord remains controversial. We used an adeno-associated viral (AAV) vector encoding green fluorescent protein under an artificial dopamine beta-hydroxylase (PRSx8) promoter to trace the spinal projections from the A5, A6, and A7 groups. Projections from all three groups travel through the spinal cord in both the lateral and ventral funiculi and in the dorsal surface of the dorsal horn, but A6 axons take predominantly the dorsal and ventral routes, whereas A5 axons take mainly a lateral and A7 axons a ventral route. The A6 group provides the densest innervation at all levels, and includes all parts of the spinal gray matter, but it is particularly dense in the dorsal horn. The A7 group provides the next most dense innervation, again including all parts of the spinal cord, but is it denser in the ventral horn. The A5 group supplies only sparse innervation to the dorsal and ventral horns and to the cervical and lumbosacral levels, but provides the densest innervation to the thoracic intermediolateral cell column, and in particular to the sympathetic preganglionic neurons. Thus, the pontine noradrenergic cell groups project in a roughly topographic and complementary fashion onto the spinal cord. The pattern of spinal projections observed suggests that the locus coeruleus might have the greatest effect on somatosensory transmission, the A7 group on motor function, and the A5 group on sympathetic function. J. Comp. Neurol. 520:19852001, 2012. (c) 2011 Wiley Periodicals, Inc. C1 [Saper, Clifford B.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Bruinstroop, Eveline; Cano, Georgina; Vanderhorst, Veronique G. J. M.; Cavalcante, Judney C.; Saper, Clifford B.] Harvard Univ, Sch Med, Dept Neurol, Program Neurosci, Boston, MA 02115 USA. [Bruinstroop, Eveline; Cano, Georgina; Vanderhorst, Veronique G. J. M.; Cavalcante, Judney C.; Saper, Clifford B.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA 02115 USA. [Bruinstroop, Eveline] Univ Amsterdam, Acad Med Ctr, Dept Endocrinol & Metab, NL-1105 AZ Amsterdam, Netherlands. [Wirth, Jena; Sena-Esteves, Miguel] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Wirth, Jena; Sena-Esteves, Miguel] Massachusetts Gen Hosp, Program Neurosci, Charlestown, MA USA. [Wirth, Jena; Sena-Esteves, Miguel] Harvard Univ, Sch Med, Charlestown, MA USA. RP Saper, CB (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, 330 Brookline Ave, Boston, MA 02215 USA. EM csaper@bidmc.harvard.edu RI Cavalcante, Judney/C-3985-2011; OI Wirth, Jena/0000-0001-6094-8336; Bruinstroop, Eveline/0000-0001-6466-8497 FU United States Public Health Service (USPHS) [NS33987, NS072337, HL095491] FX Grant sponsor: United States Public Health Service (USPHS); Grant numbers: NS33987, NS072337 and HL095491. NR 46 TC 37 Z9 38 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUN 15 PY 2012 VL 520 IS 9 BP 1985 EP 2001 DI 10.1002/cne.23024 PG 17 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 922KB UT WOS:000302544700007 PM 22173709 ER PT J AU Caplan, LR Gonzalez, G Buonanno, FS AF Caplan, Louis R. Gonzalez, R. Gilberto Buonanno, Ferdinando S. TI Case 18-2012: A 35-Year-Old Man with Neck Pain, Hoarseness, and Dysphagia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CERVICAL ARTERY DISSECTION; TERM-FOLLOW-UP; OSTEOGENESIS-IMPERFECTA; HYPOPERFUSION; HEMORRHAGE; PATIENT; STROKE C1 [Caplan, Louis R.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Buonanno, Ferdinando S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Caplan, Louis R.; Buonanno, Ferdinando S.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Gonzalez, R. Gilberto] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Caplan, LR (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. NR 26 TC 2 Z9 2 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 14 PY 2012 VL 366 IS 24 BP 2306 EP 2314 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 957PD UT WOS:000305174100013 PM 22694002 ER PT J AU Mimura, N Fulciniti, M Gorgun, G Tai, T Cirstea, D Santo, L Hu, YG Fabre, C Ohguchi, JMH Kiziltepe, T Ikeda, H Kawano, Y French, M Blumenthal, M Tam, V Kertesz, NL Malyankar, UM Hokenson, M Pham, T Zeng, QP Patterson, JB Richardson, PG Munshi, NC Anderson, KC AF Mimura, Naoya Fulciniti, Mariateresa Gorgun, Gullu Tai, Tzu Cirstea, Diana Santo, Loredana Hu, Yiguo Fabre, Claire Ohguchi, Jiro Minami Hiroto Kiziltepe, Tanyel Ikeda, Hiroshi Kawano, Yutaka French, Maureen Blumenthal, Martina Tam, Victor Kertesz, Nathalie L. Malyankar, Uriel M. Hokenson, Mark Pham, Tuan Zeng, Qingping Patterson, John B. Richardson, Paul G. Munshi, Nikhil C. Anderson, Kenneth C. TI Blockade of XBP1 splicing by inhibition of IRE1 alpha is a promising therapeutic option in multiple myeloma SO BLOOD LA English DT Article ID UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM STRESS; TRANSCRIPTION FACTOR; BONE-MARROW; IN-VITRO; ER STRESS; CELLS; SURVIVAL; PATHWAY; IDENTIFICATION AB Multiple myeloma (MM) cells are characterized by high protein synthesis resulting in chronic endoplasmic reticulum (ER) stress, which is adaptively managed by the unfolded protein response. Inositol-requiring enzyme 1 alpha (IRE1 alpha) is activated to splice X-box binding protein 1 (XBP1) mRNA, thereby increasing XBP1s protein, which in turn regulates genes responsible for protein folding and degradation during the unfolded protein response. In this study, we examined whether IRE1 alpha-XBP1 pathway is a potential therapeutic target in MM using a small-molecule IRE1 alpha endoribonuclease domain inhibitor MKC-3946. MKC-3946 triggered modest growth inhibition in MM cell lines, without toxicity in normal mononuclear cells. Importantly, it significantly enhanced cytotoxicity induced by bortezomib or 17-AAG, even in the presence of bone marrow stromal cells or exogenous IL-6. Both bortezomib and 17-AAG induced ER stress, evidenced by induction of XBP1s, which was blocked by MKC-3946. Apoptosis induced by these agents was enhanced by MKC-3946, associated with increased CHOP. Finally, MKC-3946 inhibited XBP1 splicing in a model of ER stress in vivo, associated with significant growth inhibition of MM cells. Taken together, our results demonstrate that blockade of XBP1 splicing by inhibition of IRE1 alpha endoribonuclease domain is a potential therapeutic option in MM. (Blood. 2012; 119(24):5772-5781) C1 [Mimura, Naoya; Fulciniti, Mariateresa; Gorgun, Gullu; Tai, Tzu; Cirstea, Diana; Santo, Loredana; Hu, Yiguo; Fabre, Claire; Ohguchi, Jiro Minami Hiroto; Kiziltepe, Tanyel; Ikeda, Hiroshi; Kawano, Yutaka; French, Maureen; Richardson, Paul G.; Munshi, Nikhil C.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02215 USA. [Munshi, Nikhil C.] Boston Vet Adm Healthcare Syst, W Roxbury, MA USA. [Blumenthal, Martina; Tam, Victor; Kertesz, Nathalie L.; Malyankar, Uriel M.; Hokenson, Mark; Pham, Tuan; Zeng, Qingping; Patterson, John B.] MannKind Corp, Valencia, Spain. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Mayer 557,450 Brookline Ave, Boston, MA 02215 USA. EM kenneth_anderson@dfci.harvard.edu FU National Institutes of Health [SPORE-P50100707, PO1-CA078378, RO1CA050947]; Multiple Myeloma Research Foundation; International Myeloma Foundation FX This work was supported by the National Institutes of Health (grants SPORE-P50100707, PO1-CA078378, and RO1CA050947) and in part by the Multiple Myeloma Research Foundation (Biotech Investment Award). N.M. was a recipient of the International Myeloma Foundation Brian D. Novis Research Junior Grant Award. K. C. A. is an American Cancer Society Clinical Research Professor. NR 44 TC 109 Z9 111 U1 0 U2 18 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 14 PY 2012 VL 119 IS 24 BP 5772 EP 5781 DI 10.1182/blood-2011-07-366633 PG 10 WC Hematology SC Hematology GA 987DK UT WOS:000307396500030 PM 22538852 ER PT J AU Azab, AK Hu, JS Quang, P Azab, F Pitsillides, C Awwad, R Thompson, B Maiso, P Sun, JD Hart, CP Roccaro, AM Sacco, A Ngo, HT Lin, CP Kung, AL Carrasco, RD Vanderkerken, K Ghobrial, IM AF Azab, Abdel Kareem Hu, Jinsong Quang, Phong Azab, Feda Pitsillides, Costas Awwad, Rana Thompson, Brian Maiso, Patricia Sun, Jessica D. Hart, Charles P. Roccaro, Aldo M. Sacco, Antonio Ngo, Hai T. Lin, Charles P. Kung, Andrew L. Carrasco, Ruben D. Vanderkerken, Karin Ghobrial, Irene M. TI Hypoxia promotes dissemination of multiple myeloma through acquisition of epithelial to mesenchymal transition-like features SO BLOOD LA English DT Article ID BONE-MARROW MICROENVIRONMENT; SQUAMOUS-CELL CARCINOMA; TUMOR PROGRESSION; INCREASED EXPRESSION; C57BL/KALWRIJ MOUSE; INDUCIBLE FACTORS; FACTOR 1-ALPHA; LYSYL OXIDASE; PLASMA-CELLS; STEM-CELLS AB The spread of multiple myeloma (MM) involves (re) circulation into the peripheral blood and (re) entrance or homing of MM cells into new sites of the BM. Hypoxia in solid tumors was shown to promote metastasis through activation of proteins involved in the epithelialmesenchymal transition (EMT) process. We hypothesized that MM-associated hypoxic conditions activate EMT-related proteins and promote metastasis of MM cells. In the present study, we have shown that hypoxia activates EMT-related machinery in MM cells, decreases the expression of E-cadherin, and, consequently, decreases the adhesion of MM cells to the BM and enhances egress of MM cells to the circulation. In parallel, hypoxia increased the expression of CXCR4, consequently increasing the migration and homing of circulating MM cells to new BM niches. Further studies to manipulate hypoxia to regulate tumor dissemination as a therapeutic strategy are warranted. (Blood. 2012; 119(24):5782-5794) C1 [Azab, Abdel Kareem; Quang, Phong; Azab, Feda; Maiso, Patricia; Roccaro, Aldo M.; Sacco, Antonio; Ngo, Hai T.; Carrasco, Ruben D.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hu, Jinsong; Vanderkerken, Karin] Vrije Univ Brussel, Myeloma Ctr, Dept Hematol & Immunol, Brussels, Belgium. [Pitsillides, Costas; Thompson, Brian; Lin, Charles P.] Massachusetts Gen Hosp, Ctr Syst Biol, Adv Microscopy Program, Boston, MA 02114 USA. [Pitsillides, Costas; Thompson, Brian; Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Sun, Jessica D.; Hart, Charles P.] Threshold Pharmaceut, Redwood City, CA USA. [Awwad, Rana] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Kung, Andrew L.] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Ghobrial, IM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Mayer 548A, Boston, MA 02115 USA. EM irene_ghobrial@dfci.harvard.edu RI Hu, Jinsong/B-2508-2012; Vanderkerken, Karin/I-3513-2013; Sacco, Antonio/K-4681-2016; OI Hu, Jinsong/0000-0002-2414-707X; Sacco, Antonio/0000-0003-2945-9416; Maiso, Patricia/0000-0003-3745-1924; Roccaro, Aldo/0000-0002-1872-5128; Kung, Andrew/0000-0002-9091-488X; Hart, Charles/0000-0003-4440-726X FU National Institutes of Health [R01CA125690, R01CA152607]; American Association for Cancer Research-Amgen fellowship; Fonds voor Wetenschappelijk Onderzoek (National Fund for Scientific Research) FX This study was supported in part by the National Institutes of Health (R01CA125690 and R01CA152607), an American Association for Cancer Research-Amgen fellowship, and Fonds voor Wetenschappelijk Onderzoek (National Fund for Scientific Research). NR 50 TC 82 Z9 84 U1 1 U2 16 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 14 PY 2012 VL 119 IS 24 BP 5782 EP 5794 DI 10.1182/blood-2011-09-380410 PG 13 WC Hematology SC Hematology GA 987DK UT WOS:000307396500031 PM 22394600 ER PT J AU Bindels, EMJ Havermans, M Lugthart, S Erpelinck, C Wocjtowicz, E Krivtsov, AV Rombouts, E Armstrong, SA Taskesen, E Haanstra, JR Beverloo, HB Dohner, H Hudson, WA Kersey, JH Delwel, R Kumar, AR AF Bindels, Eric M. J. Havermans, Marije Lugthart, Sanne Erpelinck, Claudia Wocjtowicz, Elizabeth Krivtsov, Andrei V. Rombouts, Elwin Armstrong, Scott A. Taskesen, Erdogan Haanstra, Jurgen R. Beverloo, H. Berna Doehner, Hartmut Hudson, Wendy A. Kersey, John H. Delwel, Ruud Kumar, Ashish R. TI EVI1 is critical for the pathogenesis of a subset of MLL-AF9-rearranged AMLs SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; HIGH BRE EXPRESSION; TRANSCRIPTIONAL ELONGATION; H3K79 METHYLATION; BINDING PROTEIN; STEM-CELLS; MLL; GENE; INTERACTS; CHROMATIN AB The proto-oncogene EVI1 (ecotropic viral integration site-1), located on chromosome band 3q26, is aberrantly expressed in human acute myeloid leukemia (AML) with 3q26 rearrangements. In the current study, we showed, in a large AML cohort carrying 11q23 translocations, that similar to 43% of all mixed lineage leukemia (MLL)-rearranged leukemias are EVI1(pos). High EVI1 expression occurs in AMLs expressing the MLL-AF6, -AF9, -AF10, -ENL, or -ELL fusion genes. In addition, we present evidence that EVI1(pos) MLL-rearranged AMLs differ molecularly, morphologically, and immunophenotypically from EVI1(neg) MLL-rearranged leukemias. In mouse bone marrow cells transduced with MLL-AF9, we show that MLL-AF9 fusion protein maintains Evi1 expression on transformation of Evi1(pos) HSCs. MLL-AF9 does not activate Evi1 expression in MLL-AF9-transformed granulocyte macrophage progenitors (GMPs) that were initially Evi1(neg). Moreover, shRNA-mediated knockdown of Evi1 in an Evi1(pos) MLL-AF9 mouse model inhibits leukemia growth both in vitro and in vivo, suggesting that Evi1 provides a growth-promoting signal. Using the Evi1(pos) MLL-AF9 mouse leukemia model, we demonstrate increased sensitivity to chemotherapeutic agents on reduction of Evi1 expression. We conclude that EVI1 is a critical player in tumor growth in a subset of MLL-rearranged AMLs. (Blood. 2012; 119(24):5838-5849) C1 [Bindels, Eric M. J.; Havermans, Marije; Lugthart, Sanne; Erpelinck, Claudia; Rombouts, Elwin; Taskesen, Erdogan; Haanstra, Jurgen R.; Delwel, Ruud] Erasmus Univ, Med Ctr, Dept Hematol, NL-3015 GE Rotterdam, Netherlands. [Wocjtowicz, Elizabeth; Kumar, Ashish R.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Krivtsov, Andrei V.; Armstrong, Scott A.] Childrens Hosp, Dana Farber Canc Inst, Div Hematol Oncol, Dept Pediat Oncol, Boston, MA 02115 USA. [Krivtsov, Andrei V.; Armstrong, Scott A.] Harvard Univ, Sch Med, Boston, MA USA. [Beverloo, H. Berna] Erasmus Univ, Med Ctr, Dept Clin Genet, Rotterdam, Netherlands. [Doehner, Hartmut] Univ Ulm, Dept Internal Med 3, D-7900 Ulm, Germany. [Hudson, Wendy A.; Kersey, John H.; Kumar, Ashish R.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. RP Delwel, R (reprint author), Erasmus Univ, Med Ctr, Dept Hematol, Dr Molewaterpl 50, NL-3015 GE Rotterdam, Netherlands. EM h.delwel@erasmusmc.nl RI Taskesen, Erdogan/N-4983-2015; OI Taskesen, Erdogan/0000-0002-3430-9618; Haanstra, Jurgen/0000-0001-9652-0219 FU Dutch Cancer Society; Association for International Cancer Research (AICR) [118305-118297]; Leukemia & Lymphoma Society [116196-118309]; European Hematology Association (EHA); ZonMW; National Institutes of Health [R01-CA087053, K08-CA122191]; Leukemia Research Fund; Children's Cancer Research Fund FX This work was supported by grants from the Dutch Cancer Society (R. D., M. H., and S. L.), Association for International Cancer Research (AICR) grant 118305-118297 (E.M.J.B.), Leukemia & Lymphoma Society grant 116196-118309 (E.M.J.B.), a European Hematology Association (EHA) research fellowship (S. L.), a ZonMW fellowship (S. L.), the National Institutes of Health (R01-CA087053, J.H.K.; K08-CA122191, A. R. K.), the Leukemia Research Fund (A. R. K.), and the Children's Cancer Research Fund (J.H.K., A.R.K.). NR 49 TC 22 Z9 25 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 14 PY 2012 VL 119 IS 24 BP 5838 EP 5849 DI 10.1182/blood-2011-11-393827 PG 12 WC Hematology SC Hematology GA 987DK UT WOS:000307396500037 PM 22553314 ER PT J AU Scadden, DT AF Scadden, David T. TI Rethinking Stroma: Lessons from the Blood SO CELL STEM CELL LA English DT Editorial Material ID HEMATOPOIETIC STEM-CELLS; MORPHOGENESIS; REGENERATION AB Stroma is a largely understudied component of all organs that contributes to stem cell niches. Studies to define stromal components in the bone marrow have led to some unexpected findings that prompt further research. C1 [Scadden, David T.] Harvard Univ, Massachusetts Gen Hosp, Dept Stem Cell & Regenerat Biol, Ctr Regenerat Med,Harvard Stem Cell Inst, Boston, MA 02114 USA. [Scadden, David T.] Harvard Univ, Massachusetts Gen Hosp, Dept Stem Cell & Regenerat Biol, Canc Ctr,Harvard Stem Cell Inst, Boston, MA 02114 USA. RP Scadden, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Stem Cell & Regenerat Biol, Ctr Regenerat Med,Harvard Stem Cell Inst, 185 Cambridge St, Boston, MA 02114 USA. EM david_scadden@harvard.edu FU NHLBI NIH HHS [R01 HL044851, U01 HL100402] NR 10 TC 9 Z9 9 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD JUN 14 PY 2012 VL 10 IS 6 BP 648 EP 649 DI 10.1016/j.stem.2012.05.011 PG 2 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 965LD UT WOS:000305768400006 PM 22704500 ER PT J AU Daley, GQ AF Daley, George Q. TI The Promise and Perils of Stem Cell Therapeutics SO CELL STEM CELL LA English DT Review ID UMBILICAL-CORD BLOOD; PANCREATIC BETA-CELLS; PARKINSONS-DISEASE; SPINAL-CORD; BONE-MARROW; DOPAMINE NEURONS; IN-VIVO; ISLET TRANSPLANTATION; CLINICAL-TRIALS; HUMAN ES AB Stem cells are the seeds of tissue repair and regeneration and a promising source for novel therapies. However, apart from hematopoietic stem cell (HSC) transplantation, essentially all other stem cell treatments remain experimental. High hopes have inspired numerous clinical trials, but it has been difficult to obtain unequivocal evidence for robust clinical benefit. In recent years, unproven therapies have been widely practiced outside the standard clinical trial network, threatening the cause of legitimate clinical investigation. Numerous challenges and technical barriers must be overcome before novel stem cell therapies can achieve meaningful clinical impact. C1 [Daley, George Q.] Childrens Hosp Boston, Howard Hughes Med Inst, Stem Cell Transplantat Program, Div Pediat Hematol Oncol,Manton Ctr Orphan Dis Re, Boston, MA 02115 USA. [Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Daley, George Q.] Broad Inst, Cambridge, MA 02142 USA. [Daley, George Q.] Harvard Stem Cell Inst, Boston, MA 02138 USA. RP Daley, GQ (reprint author), Childrens Hosp Boston, Howard Hughes Med Inst, Stem Cell Transplantat Program, Div Pediat Hematol Oncol,Manton Ctr Orphan Dis Re, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu FU NIH [R24DK092760, UO1-HL100001, RC4-DK090913, P50HG005550]; ARRA [RC2-HL102815]; Roche Foundation for Anemia Research; Alex's Lemonade Stand; Ellison Medical Foundation; Doris Duke Medical Foundation; Harvard Stem Cell Institute FX G.Q.D. is supported by grants from the NIH (R24DK092760, UO1-HL100001, RC4-DK090913, P50HG005550, and special funds from the ARRA stimulus package- RC2-HL102815), the Roche Foundation for Anemia Research, Alex's Lemonade Stand, Ellison Medical Foundation, Doris Duke Medical Foundation, and the Harvard Stem Cell Institute. G.Q.D. is an affiliate member of the Broad Institute and an investigator of the Howard Hughes Medical Institute and the Manton Center for Orphan Disease Research. Disclosure: GOD is a member of the scientific advisory board and receives consulting fees and holds equity in the following companies that work with stem cells: Johnson & Johnson, Verastem, iPierian, and MPM Capital. NR 85 TC 82 Z9 82 U1 0 U2 36 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD JUN 14 PY 2012 VL 10 IS 6 BP 740 EP 749 DI 10.1016/j.stem.2012.05.010 PG 10 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 965LD UT WOS:000305768400020 PM 22704514 ER PT J AU Zeitler, P Hirst, K Pyle, L Linder, B Copeland, K Arslanian, S Cuttler, L Nathan, DM Tollefsen, S Wilfley, D Kaufman, F AF Zeitler, Phil Hirst, Kathryn Pyle, Laura Linder, Barbara Copeland, Kenneth Arslanian, Silva Cuttler, Leona Nathan, David M. Tollefsen, Sherida Wilfley, Denise Kaufman, Francine CA TODAY Study Grp TI A Clinical Trial to Maintain Glycemic Control in Youth with Type 2 Diabetes SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID WHITE ADOLESCENTS; OBESE BLACK; INSULIN; MELLITUS; METFORMIN; AMERICAN; CHILDREN; FAT AB BACKGROUND Despite the increasing prevalence of type 2 diabetes in youth, there are few data to guide treatment. We compared the efficacy of three treatment regimens to achieve durable glycemic control in children and adolescents with recent-onset type 2 diabetes. METHODS Eligible patients 10 to 17 years of age were treated with metformin (at a dose of 1000 mg twice daily) to attain a glycated hemoglobin level of less than 8% and were randomly assigned to continued treatment with metformin alone or to metformin combined with rosiglitazone (4 mg twice a day) or a lifestyle-intervention program focusing on weight loss through eating and activity behaviors. The primary outcome was loss of glycemic control, defined as a glycated hemoglobin level of at least 8% for 6 months or sustained metabolic decompensation requiring insulin. RESULTS Of the 699 randomly assigned participants (mean duration of diagnosed type 2 diabetes, 7.8 months), 319 (45.6%) reached the primary outcome over an average follow-up of 3.86 years. Rates of failure were 51.7% (120 of 232 participants), 38.6% (90 of 233), and 46.6% (109 of 234) for metformin alone, metformin plus rosiglitazone, and metformin plus lifestyle intervention, respectively. Metformin plus rosiglitazone was superior to metformin alone (P = 0.006); metformin plus lifestyle intervention was intermediate but not significantly different from metformin alone or metformin plus rosiglitazone. Prespecified analyses according to sex and race or ethnic group showed differences in sustained effectiveness, with metformin alone least effective in non-Hispanic black participants and metformin plus rosiglitazone most effective in girls. Serious adverse events were reported in 19.2% of participants. CONCLUSIONS Monotherapy with metformin was associated with durable glycemic control in approximately half of children and adolescents with type 2 diabetes. The addition of rosiglitazone, but not an intensive lifestyle intervention, was superior to metformin alone. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; TODAY ClinicalTrials.gov number, NCT00081328.) C1 [Zeitler, Phil] Univ Colorado, Denver, CO 80202 USA. [Hirst, Kathryn; Pyle, Laura] George Washington Univ, Washington, DC USA. [Linder, Barbara] NIDDK, Bethesda, MD USA. [Copeland, Kenneth] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Arslanian, Silva] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. [Cuttler, Leona] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Nathan, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tollefsen, Sherida] St Louis Univ, St Louis, MO 63103 USA. [Wilfley, Denise] Washington Univ, St Louis, MO 63130 USA. [Kaufman, Francine] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. RP Hirst, K (reprint author), George Washington Univ, Ctr Biostat, 6110 Execut Blvd,Suite 750, Rockville, MD 20850 USA. EM khirst@bsc.gwu.edu OI Zeitler, Philip/0000-0001-5756-7858 FU NIDDK [U01-DK61212, U01-DK61230, U01-DK61239, U01-DK61242, U01-DK61254]; National Center for Research Resources (NCRR) [M01-RR00036, M01-RR00043-45, M01-RR00069, M01-RR00084, M01-RR01066, M01-RR00125, M01-RR14467, UL1-RR024134, UL1-RR024139, UL1-RR024153, UL1-RR024989, UL1-RR024992, UL1-RR025758, UL1-RR025780]; Sanofi-Aventis; Novo Nordisk; Bristol-Myers Squibb; Daiichi Sankyo (Clinical Trial Steering Committee); DPS Health; UnitedHealth Group; Jenny Craig; Nestle; Shire on; Merck; National Institute of Diabetes and Digestive and Kidney Diseases [NCT00081328] FX Supported by grants from the NIDDK (U01-DK61212, U01-DK61230, U01-DK61239, U01-DK61242, and U01-DK61254) and the National Center for Research Resources (NCRR) (M01-RR00036, to the Washington University School of Medicine; M01-RR00043-45, to Children's Hospital Los Angeles; M01-RR00069, to the University of Colorado Denver; M01-RR00084, to Children's Hospital of Pittsburgh; M01-RR01066, to Massachusetts General Hospital; M01-RR00125, to Yale University; and M01-RR14467, to the University of Oklahoma Health Sciences Center); by NCRR Clinical and Translational Science Awards (UL1-RR024134, to Children's Hospital of Philadelphia; UL1-RR024139, to Yale University; UL1-RR024153, to Children's Hospital of Pittsburgh; UL1-RR024989, to Case Western Reserve University; UL1-RR024992, to Washington University in St. Louis; UL1-RR025758, to Massachusetts General Hospital; and UL1-RR025780, to the University of Colorado Denver); and by donations from Becton Dickinson, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, LifeScan, Pfizer, and Sanofi-Aventis.; Dr. Arslanian reports receiving consulting fees from Sanofi-Aventis, Novo Nordisk, and Bristol-Myers Squibb and serving on the data and safety monitoring board of Boehringer Ingelheim. Dr. Copeland reports receiving consulting fees from Novo Nordisk (advisory board membership) and from Daiichi Sankyo (Clinical Trial Steering Committee). Dr. Kaufman reports receiving consulting fees from DPS Health and being an employee of Medtronic. Dr. Wilfley reports receiving consulting fees from UnitedHealth Group, Jenny Craig, and Nestle and receiving grant support from Shire on behalf of her institution. Dr. Zeitler reports receiving consulting fees from Daiichi Sankyo, Merck, and Bristol-Myers Squibb on behalf of his institution. No other potential conflict of interest relevant to this article was reported.; Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; TODAY ClinicalTrials.gov number, NCT00081328. NR 20 TC 180 Z9 182 U1 3 U2 19 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 14 PY 2012 VL 366 IS 24 BP 2247 EP 2256 DI 10.1056/NEJMoa1109333 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 957PD UT WOS:000305174100005 ER PT J AU Susarla, SM Peacock, ZS AF Susarla, Srinivas M. Peacock, Zachary S. TI Obstructive Parotitis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Susarla, Srinivas M.; Peacock, Zachary S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Susarla, SM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 14 PY 2012 VL 366 IS 24 BP 2305 EP 2305 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 957PD UT WOS:000305174100011 PM 22694001 ER PT J AU Cruz-Gonzalez, I Inglessis-Azuaje, I Palacios, IF AF Cruz-Gonzalez, Ignacio Inglessis-Azuaje, Ignacio Palacios, Igor F. TI Device Closure for Stroke with Patent Foramen Ovale SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Cruz-Gonzalez, Ignacio] Univ Hosp Salamanca, Salamanca, Spain. [Inglessis-Azuaje, Ignacio; Palacios, Igor F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Cruz-Gonzalez, I (reprint author), Univ Hosp Salamanca, Salamanca, Spain. EM cruzgonzalez.ignacio@gmail.com 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 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 14 PY 2012 VL 366 IS 24 BP 2322 EP 2323 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 957PD UT WOS:000305174100020 PM 22694009 ER PT J AU David, WS Chad, DA AF David, William S. Chad, David A. TI Case 7-2012: A Man with Pain and Weakness in the Legs REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [David, William S.; Chad, David A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP David, WS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 14 PY 2012 VL 366 IS 24 BP 2326 EP 2326 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 957PD UT WOS:000305174100027 ER PT J AU Huttenhower, C Gevers, D Knight, R Abubucker, S Badger, JH Chinwalla, AT Creasy, HH Earl, AM FitzGerald, MG Fulton, RS Giglio, MG Hallsworth-Pepin, K Lobos, EA Madupu, R Magrini, V Martin, JC Mitreva, M Muzny, DM Sodergren, EJ Versalovic, J Wollam, AM Worley, KC Wortman, JR Young, SK Zeng, QD Aagaard, KM Abolude, OO Allen-Vercoe, E Alm, EJ Alvarado, L Andersen, GL Anderson, S Appelbaum, E Arachchi, HM Armitage, G Arze, CA Ayvaz, T Baker, CC Begg, L Belachew, T Bhonagiri, V Bihan, M Blaser, MJ Bloom, T Bonazzi, V Brooks, JP Buck, GA Buhay, CJ Busam, DA Campbell, JL Canon, SR Cantarel, BL Chain, PSG Chen, IMA Chen, L Chhibba, S Chu, K Ciulla, DM Clemente, JC Clifton, SW Conlan, S Crabtree, J Cutting, MA Davidovics, NJ Davis, CC DeSantis, TZ Deal, C Delehaunty, KD Dewhirst, FE Deych, E Ding, Y Dooling, DJ Dugan, SP Dunne, WM Durkin, AS Edgar, RC Erlich, RL Farmer, CN Farrell, RM Faust, K Feldgarden, M Felix, VM Fisher, S Fodor, AA Forney, LJ Foster, L Di Francesco, V Friedman, J Friedrich, DC Fronick, CC Fulton, LL Gao, HY Garcia, N Giannoukos, G Giblin, C Giovanni, MY Goldberg, JM Goll, J Gonzalez, A Griggs, A Gujja, S Haake, SK Haas, BJ Hamilton, HA Harris, EL Hepburn, TA Herter, B Hoffmann, DE Holder, ME Howarth, C Huang, KH Huse, SM Izard, J Jansson, JK Jiang, HY Jordan, C Joshi, V Katancik, JA Keitel, WA Kelley, ST Kells, C King, NB Knights, D Kong, HDH Koren, O Koren, S Kota, KC Kovar, CL Kyrpides, NC La Rosa, PS Lee, SL Lemon, KP Lennon, N Lewis, CM Lewis, L Ley, RE Li, K Liolios, K Liu, B Liu, Y Lo, CC Lozupone, CA Lunsford, RD Madden, T Mahurkar, AA Mannon, PJ Mardis, ER Markowitz, VM Mavromatis, K McCorrison, JM McDonald, D McEwen, J McGuire, AL McInnes, P Mehta, T Mihindukulasuriya, KA Miller, JR Minx, PJ Newsham, I Nusbaum, C O'Laughlin, M Orvis, J Pagani, I Palaniappan, K Patel, SM Pearson, M Peterson, J Podar, M Pohl, C Pollard, KS Pop, M Priest, ME Proctor, LM Qin, X Raes, J Ravel, J Reid, JG Rho, M Rhodes, R Riehle, KP Rivera, MC Rodriguez-Mueller, B Rogers, YH Ross, MC Russ, C Sanka, RK Sankar, P Sathirapongsasuti, JF Schloss, JA Schloss, PD Schmidt, TM Scholz, M Schriml, L Schubert, AM Segata, N Segre, JA Shannon, WD Sharp, RR Sharpton, TJ Shenoy, N Sheth, NU Simone, GA Singh, I Smillie, CS Sobel, JD Sommer, DD Spicer, P Sutton, GG Sykes, SM Tabbaa, DG Thiagarajan, M Tomlinson, CM Torralba, M Treangen, TJ Truty, RM Vishnivetskaya, TA Walker, J Wang, L Wang, ZY Ward, DV Warren, W Watson, MA Wellington, C Wetterstrand, KA White, JR Wilczek-Boney, K Wu, YQ Wylie, KM Wylie, T Yandava, C Ye, L Ye, YZ Yooseph, S Youmans, BP Zhang, L Zhou, YJ Zhu, YM Zoloth, L Zucker, JD Birren, BW Gibbs, RA Highlander, SK Methe, BA Nelson, KE Petrosino, JF Weinstock, GM Wilson, RK White, O AF Huttenhower, Curtis Gevers, Dirk Knight, Rob Abubucker, Sahar Badger, Jonathan H. Chinwalla, Asif T. Creasy, Heather H. Earl, Ashlee M. FitzGerald, Michael G. Fulton, Robert S. Giglio, Michelle G. Hallsworth-Pepin, Kymberlie Lobos, Elizabeth A. Madupu, Ramana Magrini, Vincent Martin, John C. Mitreva, Makedonka Muzny, Donna M. Sodergren, Erica J. Versalovic, James Wollam, Aye M. Worley, Kim C. Wortman, Jennifer R. Young, Sarah K. Zeng, Qiandong Aagaard, Kjersti M. Abolude, Olukemi O. Allen-Vercoe, Emma Alm, Eric J. Alvarado, Lucia Andersen, Gary L. Anderson, Scott Appelbaum, Elizabeth Arachchi, Harindra M. Armitage, Gary Arze, Cesar A. Ayvaz, Tulin Baker, Carl C. Begg, Lisa Belachew, Tsegahiwot Bhonagiri, Veena Bihan, Monika Blaser, Martin J. Bloom, Toby Bonazzi, Vivien Brooks, J. Paul Buck, Gregory A. Buhay, Christian J. Busam, Dana A. Campbell, Joseph L. Canon, Shane R. Cantarel, Brandi L. Chain, Patrick S. G. Chen, I-Min A. Chen, Lei Chhibba, Shaila Chu, Ken Ciulla, Dawn M. Clemente, Jose C. Clifton, Sandra W. Conlan, Sean Crabtree, Jonathan Cutting, Mary A. Davidovics, Noam J. Davis, Catherine C. DeSantis, Todd Z. Deal, Carolyn Delehaunty, Kimberley D. Dewhirst, Floyd E. Deych, Elena Ding, Yan Dooling, David J. Dugan, Shannon P. Dunne, Wm Michael Durkin, A. Scott Edgar, Robert C. Erlich, Rachel L. Farmer, Candace N. Farrell, Ruth M. Faust, Karoline Feldgarden, Michael Felix, Victor M. Fisher, Sheila Fodor, Anthony A. Forney, Larry J. Foster, Leslie Di Francesco, Valentina Friedman, Jonathan Friedrich, Dennis C. Fronick, Catrina C. Fulton, Lucinda L. Gao, Hongyu Garcia, Nathalia Giannoukos, Georgia Giblin, Christina Giovanni, Maria Y. Goldberg, Jonathan M. Goll, Johannes Gonzalez, Antonio Griggs, Allison Gujja, Sharvari Haake, Susan Kinder Haas, Brian J. Hamilton, Holli A. Harris, Emily L. Hepburn, Theresa A. Herter, Brandi Hoffmann, Diane E. Holder, Michael E. Howarth, Clinton Huang, Katherine H. Huse, Susan M. Izard, Jacques Jansson, Janet K. Jiang, Huaiyang Jordan, Catherine Joshi, Vandita Katancik, James A. Keitel, Wendy A. Kelley, Scott T. Kells, Cristyn King, Nicholas B. Knights, Dan Kong, Heidi H. Koren, Omry Koren, Sergey Kota, Karthik C. Kovar, Christie L. Kyrpides, Nikos C. La Rosa, Patricio S. Lee, Sandra L. Lemon, Katherine P. Lennon, Niall Lewis, Cecil M. Lewis, Lora Ley, Ruth E. Li, Kelvin Liolios, Konstantinos Liu, Bo Liu, Yue Lo, Chien-Chi Lozupone, Catherine A. Lunsford, R. Dwayne Madden, Tessa Mahurkar, Anup A. Mannon, Peter J. Mardis, Elaine R. Markowitz, Victor M. Mavromatis, Konstantinos McCorrison, Jamison M. McDonald, Daniel McEwen, Jean McGuire, Amy L. McInnes, Pamela Mehta, Teena Mihindukulasuriya, Kathie A. Miller, Jason R. Minx, Patrick J. Newsham, Irene Nusbaum, Chad O'Laughlin, Michelle Orvis, Joshua Pagani, Ioanna Palaniappan, Krishna Patel, Shital M. Pearson, Matthew Peterson, Jane Podar, Mircea Pohl, Craig Pollard, Katherine S. Pop, Mihai Priest, Margaret E. Proctor, Lita M. Qin, Xiang Raes, Jeroen Ravel, Jacques Reid, Jeffrey G. Rho, Mina Rhodes, Rosamond Riehle, Kevin P. Rivera, Maria C. Rodriguez-Mueller, Beltran Rogers, Yu-Hui Ross, Matthew C. Russ, Carsten Sanka, Ravi K. Sankar, Pamela Sathirapongsasuti, J. Fah Schloss, Jeffery A. Schloss, Patrick D. Schmidt, Thomas M. Scholz, Matthew Schriml, Lynn Schubert, Alyxandria M. Segata, Nicola Segre, Julia A. Shannon, William D. Sharp, Richard R. Sharpton, Thomas J. Shenoy, Narmada Sheth, Nihar U. Simone, Gina A. Singh, Indresh Smillie, Christopher S. Sobel, Jack D. Sommer, Daniel D. Spicer, Paul Sutton, Granger G. Sykes, Sean M. Tabbaa, Diana G. Thiagarajan, Mathangi Tomlinson, Chad M. Torralba, Manolito Treangen, Todd J. Truty, Rebecca M. Vishnivetskaya, Tatiana A. Walker, Jason Wang, Lu Wang, Zhengyuan Ward, Doyle V. Warren, Wesley Watson, Mark A. Wellington, Christopher Wetterstrand, Kris A. White, James R. Wilczek-Boney, Katarzyna Wu, YuanQing Wylie, Kristine M. Wylie, Todd Yandava, Chandri Ye, Liang Ye, Yuzhen Yooseph, Shibu Youmans, Bonnie P. Zhang, Lan Zhou, Yanjiao Zhu, Yiming Zoloth, Laurie Zucker, Jeremy D. Birren, Bruce W. Gibbs, Richard A. Highlander, Sarah K. Methe, Barbara A. Nelson, Karen E. Petrosino, Joseph F. Weinstock, George M. Wilson, Richard K. White, Owen CA Human Microbiome Project Consortiu TI Structure, function and diversity of the healthy human microbiome SO NATURE LA English DT Article ID IDENTIFICATION; BACTERIA AB Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat's signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81-99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome. C1 [Huttenhower, Curtis; Sathirapongsasuti, J. Fah; Segata, Nicola] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Huttenhower, Curtis; Gevers, Dirk; Earl, Ashlee M.; FitzGerald, Michael G.; Young, Sarah K.; Zeng, Qiandong; Alm, Eric J.; Alvarado, Lucia; Anderson, Scott; Arachchi, Harindra M.; Bloom, Toby; Ciulla, Dawn M.; Erlich, Rachel L.; Feldgarden, Michael; Fisher, Sheila; Friedrich, Dennis C.; Giannoukos, Georgia; Goldberg, Jonathan M.; Griggs, Allison; Gujja, Sharvari; Haas, Brian J.; Hepburn, Theresa A.; Howarth, Clinton; Huang, Katherine H.; Kells, Cristyn; Lennon, Niall; Mehta, Teena; Nusbaum, Chad; Pearson, Matthew; Priest, Margaret E.; Russ, Carsten; Shenoy, Narmada; Sykes, Sean M.; Tabbaa, Diana G.; Ward, Doyle V.; Yandava, Chandri; Zucker, Jeremy D.; Birren, Bruce W.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Knight, Rob; Clemente, Jose C.; Lozupone, Catherine A.; McDonald, Daniel] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA. [Knight, Rob] Howard Hughes Med Inst, Boulder, CO 80309 USA. [Abubucker, Sahar; Chinwalla, Asif T.; Fulton, Robert S.; Hallsworth-Pepin, Kymberlie; Lobos, Elizabeth A.; Magrini, Vincent; Martin, John C.; Mitreva, Makedonka; Sodergren, Erica J.; Wollam, Aye M.; Appelbaum, Elizabeth; Bhonagiri, Veena; Chen, Lei; Clifton, Sandra W.; Delehaunty, Kimberley D.; Dooling, David J.; Farmer, Candace N.; Fronick, Catrina C.; Fulton, Lucinda L.; Gao, Hongyu; Herter, Brandi; Kota, Karthik C.; Mardis, Elaine R.; Mihindukulasuriya, Kathie A.; Minx, Patrick J.; O'Laughlin, Michelle; Pohl, Craig; Tomlinson, Chad M.; Walker, Jason; Wang, Zhengyuan; Warren, Wesley; Wylie, Kristine M.; Wylie, Todd; Ye, Liang; Zhou, Yanjiao; Weinstock, George M.; Wilson, Richard K.] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63108 USA. [Badger, Jonathan H.; Madupu, Ramana; Bihan, Monika; Busam, Dana A.; Durkin, A. Scott; Foster, Leslie; Goll, Johannes; Li, Kelvin; McCorrison, Jamison M.; Miller, Jason R.; Rogers, Yu-Hui; Sanka, Ravi K.; Singh, Indresh; Sutton, Granger G.; Thiagarajan, Mathangi; Torralba, Manolito; Methe, Barbara A.; Nelson, Karen E.] J Craig Venter Inst, Rockville, MD 20850 USA. [Creasy, Heather H.; Giglio, Michelle G.; Wortman, Jennifer R.; Abolude, Olukemi O.; Arze, Cesar A.; Cantarel, Brandi L.; Crabtree, Jonathan; Davidovics, Noam J.; Felix, Victor M.; Jordan, Catherine; Mahurkar, Anup A.; Orvis, Joshua; Ravel, Jacques; Schriml, Lynn; White, James R.; White, Owen] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. [Muzny, Donna M.; Worley, Kim C.; Buhay, Christian J.; Ding, Yan; Dugan, Shannon P.; Holder, Michael E.; Jiang, Huaiyang; Joshi, Vandita; Kovar, Christie L.; Lee, Sandra L.; Lewis, Lora; Liu, Yue; Newsham, Irene; Qin, Xiang; Reid, Jeffrey G.; Wilczek-Boney, Katarzyna; Wu, YuanQing; Zhang, Lan; Zhu, Yiming; Gibbs, Richard A.; Highlander, Sarah K.; Petrosino, Joseph F.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Versalovic, James] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Versalovic, James] Texas Childrens Hosp, Dept Pathol, Houston, TX 77030 USA. [Aagaard, Kjersti M.] Baylor Coll Med, Dept Obstet & Gynecol, Div Maternal Fetal Med, Houston, TX 77030 USA. [Allen-Vercoe, Emma] Univ Guelph, Guelph, ON N1G 2W1, Canada. [Alm, Eric J.] MIT, Dept Civil & Environm Engn, Cambridge, MA 02139 USA. [Andersen, Gary L.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Ctr Environm Biotechnol, Berkeley, CA 94720 USA. [Armitage, Gary] Univ Calif San Francisco, Sch Dent, San Francisco, CA 94143 USA. [Baker, Carl C.] Natl Inst Arthrit & Musculoskeletal & Skin, NIH, Bethesda, MD 20892 USA. [Begg, Lisa] Off Res Womens Hlth, NIH, Bethesda, MD 20892 USA. [Belachew, Tsegahiwot; Campbell, Joseph L.; Deal, Carolyn; Di Francesco, Valentina; Giblin, Christina; Giovanni, Maria Y.] NIAID, NIH, Bethesda, MD 20892 USA. [Blaser, Martin J.] NYU, Langone Med Ctr, Dept Med, New York, NY 10016 USA. [Bonazzi, Vivien; Campbell, Joseph L.; Chhibba, Shaila; McEwen, Jean; Peterson, Jane; Proctor, Lita M.; Schloss, Jeffery A.; Wang, Lu; Wellington, Christopher; Wetterstrand, Kris A.] NHGRI, NIH, Bethesda, MD 20892 USA. [Brooks, J. Paul] Virginia Commonwealth Univ, Dept Stat Sci & Operat Res, Richmond, VA 23284 USA. [Brooks, J. Paul; Buck, Gregory A.; Rivera, Maria C.; Sheth, Nihar U.] Virginia Commonwealth Univ, Ctr Study Biol Complex, Richmond, VA 23284 USA. [Buck, Gregory A.; Rivera, Maria C.] Virginia Commonwealth Univ, Dept Biol, Richmond, VA 23284 USA. [Canon, Shane R.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Natl Energy Res Sci Comp Ctr, Technol Integrat Grp, Berkeley, CA 94720 USA. [Chain, Patrick S. G.; Lo, Chien-Chi; Scholz, Matthew] Los Alamos Natl Lab, Biosci Div, Genome Sci Grp, Los Alamos, NM 87545 USA. [Chain, Patrick S. G.; Kyrpides, Nikos C.; Liolios, Konstantinos; Markowitz, Victor M.; Mavromatis, Konstantinos; Pagani, Ioanna] Joint Genome Inst, Walnut Creek, CA 94598 USA. [Chen, I-Min A.; Chu, Ken; Markowitz, Victor M.; Palaniappan, Krishna] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Computat Res Div, Biol Data Management & Technol Ctr, Berkeley, CA 94720 USA. [Cutting, Mary A.; Hamilton, Holli A.; Harris, Emily L.; Lunsford, R. Dwayne; McInnes, Pamela] NIDCR, NIH, Bethesda, MD 20892 USA. [Davis, Catherine C.] Procter & Gamble Co, FemCare Prod Safety & Regulatory Affairs, Cincinnati, OH 45224 USA. [DeSantis, Todd Z.] Second Genome Inc, Bioinformat Dept, San Bruno, CA 94066 USA. [Dewhirst, Floyd E.; Izard, Jacques; Lemon, Katherine P.] Forsyth Inst, Dept Mol Genet, Cambridge, MA 02142 USA. [Dewhirst, Floyd E.; Izard, Jacques] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Deych, Elena; La Rosa, Patricio S.; Shannon, William D.] Washington Univ, Sch Med, Dept Med, Div Gen Med Sci, St Louis, MO 63110 USA. [Dunne, Wm Michael; Watson, Mark A.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Dunne, Wm Michael] bioMerieux Inc, Durham, SC 27712 USA. [Edgar, Robert C.] Drive5 Com, Tiburon, CA 94920 USA. [Farrell, Ruth M.; Sharp, Richard R.] Cleveland Clin, Ctr Eth Humanities & Spiritual Care, Cleveland, OH 44195 USA. [Faust, Karoline; Raes, Jeroen] VIB, Dept Biol Struct, B-1050 Ixelles, Belgium. [Faust, Karoline; Raes, Jeroen] Vrije Univ Brussel, Dept Appl Biol Sci DBIT, B-1050 Ixelles, Belgium. [Fodor, Anthony A.] Univ N Carolina, Dept Bioinformat & Genom, Charlotte, NC 28223 USA. [Forney, Larry J.] Univ Idaho, Dept Biol Sci, Moscow, ID 83844 USA. [Garcia, Nathalia] St Louis Univ, Ctr Adv Dent Educ, St Louis, MO 63104 USA. [Gonzalez, Antonio; Knights, Dan] Univ Colorado, Dept Comp Sci, Boulder, CO 80309 USA. [Haake, Susan Kinder] Univ Calif Los Angeles, Sch Dent, Div Associated Clin Specialties, Los Angeles, CA 90095 USA. [Haake, Susan Kinder] Univ Calif Los Angeles, Sch Dent, Dent Res Inst, Los Angeles, CA 90095 USA. [Hoffmann, Diane E.] Univ Maryland, Francis King Carey Sch Law, Baltimore, MD 21201 USA. [Huse, Susan M.] Marine Biol Lab, Josephine Bay Paul Ctr, Woods Hole, MA 02543 USA. [Jansson, Janet K.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Earth Sci, Dept Ecol, Berkeley, CA 94720 USA. [Katancik, James A.] Univ Texas Hlth Sci Ctr, Sch Dent, Dept Periodont, Houston, TX 77030 USA. [Kelley, Scott T.; Rodriguez-Mueller, Beltran] San Diego State Univ, Dept Biol, San Diego, CA 92182 USA. [King, Nicholas B.; Podar, Mircea] McGill Univ, Fac Med, Montreal, PQ H3A 1X1, Canada. [Kong, Heidi H.] NCI, Dermatol Branch, CCR, Bethesda, MD 20892 USA. [Koren, Omry; Ley, Ruth E.] Cornell Univ, Dept Microbiol, Ithaca, NY 14853 USA. [Koren, Sergey; Liu, Bo; Pop, Mihai; Sommer, Daniel D.] Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA. [Lemon, Katherine P.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Infect Dis, Boston, MA 02115 USA. [Lewis, Cecil M.; Spicer, Paul] Univ Oklahoma, Dept Anthropol, Norman, OK 73019 USA. [Madden, Tessa] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA. [Mannon, Peter J.] Univ Alabama Birmingham, Div Gastroenterol & Hepatol, Birmingham, AL 35294 USA. [McGuire, Amy L.] Baylor Coll Med, Ctr Med Eth & Hlth Policy, Houston, TX 77030 USA. [Vishnivetskaya, Tatiana A.] Oak Ridge Natl Lab, Biosci Div, Oak Ridge, TN 37831 USA. [Pollard, Katherine S.; Sharpton, Thomas J.; Truty, Rebecca M.] Univ Calif San Francisco, Gladstone Inst, San Francisco, CA 94158 USA. [Pollard, Katherine S.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94158 USA. [Pollard, Katherine S.] Univ Calif San Francisco, Div Biostat, San Francisco, CA 94158 USA. [Pop, Mihai] Univ Maryland, Dept Comp Sci, College Pk, MD 20742 USA. [Rho, Mina; Ye, Yuzhen] Indiana Univ, Sch Informat & Comp, Bloomington, IN 47405 USA. [Rhodes, Rosamond] Mt Sinai Sch Med, New York, NY 10029 USA. [Sankar, Pamela] Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. [Sankar, Pamela] Univ Penn, Dept Med Eth, Philadelphia, PA 19104 USA. [Schloss, Patrick D.; Schubert, Alyxandria M.] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. [Schmidt, Thomas M.] Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA. [Simone, Gina A.] EMMES Corp, Rockville, MD 20850 USA. [Sobel, Jack D.] Wayne State Univ, Sch Med, Harper Univ Hosp, Detroit, MI 48201 USA. [Treangen, Todd J.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. [Yooseph, Shibu] J Craig Venter Inst, San Diego, CA 92121 USA. [Zoloth, Laurie] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Petrosino, Joseph F.] Baylor Coll Med, Alkek Ctr Metagenom & Microbiome Res, Houston, TX 77030 USA. [Conlan, Sean; Segre, Julia A.] NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. RP Huttenhower, C (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM chuttenh@hsph.harvard.edu RI Conlan, Sean/B-4401-2008; Ley, Ruth/M-8542-2014; Vishnivetskaya, Tatiana/A-4488-2008; Andersen, Gary/G-2792-2015; Zucker, Jeremy/M-3643-2016; Knight, Rob/D-1299-2010; Pop, Mihai/A-7987-2013; Kyrpides, Nikos/A-6305-2014; Pagani, Ioanna/E-7390-2012; Walker, Jason/A-9702-2013; chain, patrick/B-9777-2013; Weinstock, George/C-6314-2013; Bihan, Monika/C-7469-2014; OI Conlan, Sean/0000-0001-6848-3465; Earl, Ashlee/0000-0001-7857-9145; King, Nicholas/0000-0002-2093-3380; Izard, Jacques/0000-0002-5904-5436; Podar, Mircea/0000-0003-2776-0205; Garcia, M. Nathalia/0000-0003-3685-027X; Schriml, Lynn/0000-0001-8910-9851; Mihindukulasuriya, Kathie/0000-0001-9372-3758; Ley, Ruth/0000-0002-9087-1672; Vishnivetskaya, Tatiana/0000-0002-0660-023X; Andersen, Gary/0000-0002-1618-9827; Zucker, Jeremy/0000-0002-7276-9009; Pop, Mihai/0000-0001-9617-5304; Kyrpides, Nikos/0000-0002-6131-0462; Wortman, Jennifer/0000-0002-8713-1227; Walker, Jason/0000-0001-7547-5789; Weinstock, George/0000-0002-2997-4592; Ravel, Jacques/0000-0002-0851-2233; Schloss, Patrick/0000-0002-6935-4275; Kong, Heidi/0000-0003-4424-064X; Faust, Karoline/0000-0001-7129-2803; Schmidt, Thomas/0000-0002-8209-6055; Koren, Omry/0000-0002-7738-1337; Huttenhower, Curtis/0000-0002-1110-0096; Segata, Nicola/0000-0002-1583-5794 FU National Institutes of Health [U54HG004969, U54HG003273, U54HG004973, U54HG003067, U54AI084844, N01AI30071, U54HG004968, U01HG004866, U54HG003079, R01HG005969, R01HG004872, R01HG004885, R01HG005975, R01HG004908, R01HG004900, R01HG005171, R01HG004853]; Army Research Office [W911NF-11-1-0473]; National Science Foundation [NSF DBI-1053486, NSF IIS-0812111]; Office of Science of the US Department of Energy [DE-AC02-05CH11231]; LANL Laboratory-Directed Research and Development [20100034DR]; US Defense Threat Reduction Agency [B104153I, B084531I]; Research Foundation - Flanders (FWO); Gordon & Betty Moore Foundation; J. David Gladstone Institutes; Rackham Graduate School; Colitis Foundation of Canada; IBM; [UH2AR057506]; [UH2AI083263]; [UH3AI083263]; [UH3DK083993]; [UH2DK083990]; [UH2AR057504]; [UH3AR057504]; [DP2OD001500]; [N01HG62088]; [U01DE016937]; [RC1DE0202098]; [R01DE021574]; [R21CA139193]; [P30DE020751] FX The Consortium would like to thank our external scientific advisory board: R. Blumberg, J. Davies, R. Holt, P. Ossorio, F. Ouellette, G. Schoolnik and A. Williamson. We would also like to thank our collaborators throughout the International Human Microbiome Consortium, particularly the investigators of the MetaHIT project, for advancing human microbiome research. Data repository management was provided by the National Center for Biotechnology Information and the Intramural Research Program of the NIH National Library of Medicine. We appreciate the participation of the individuals from the Saint Louis, Missouri, and Houston, Texas areas who made this study possible. This research was supported in part by National Institutes of Health grants U54HG004969 to B. W. B.; U54HG003273 to R. A. G.; U54HG004973 to R. A. G., S. K. H. and J.F.P.; U54HG003067 to E. S. Lander; U54AI084844 to K.E.N.; N01AI30071 to R. L. Strausberg; U54HG004968 to G. M. W.; U01HG004866 to O.R.W.; U54HG003079 to R. K. W.; R01HG005969 to C. H.; R01HG004872 to R. K.; R01HG004885 to M. P.; R01HG005975 to P. D. S.; R01HG004908 to Y.Y.; R01HG004900 to M.K.Cho and P. Sankar; R01HG005171 to D. E. H.; R01HG004853 to A. L. M.; R01HG004856 to R. R.; R01HG004877 to R. R. S. and R. F.; R01HG005172 to P. Spicer.; R01HG004857 to M. P.; R01HG004906 to T. M. S.; R21HG005811 to E. A. V.; M.J.B. was supported by UH2AR057506; G. A. B. was supported by UH2AI083263 and UH3AI083263 (G. A. B., C.N. Cornelissen, L. K. Eaves and J. F. Strauss); S. M. H. was supported by UH3DK083993 (V. B. Young, E. B. Chang, F. Meyer, T. M. S., M. L. Sogin, J. M. Tiedje); K. P. R. was supported by UH2DK083990 (J. V.); J. A. S. and H. H. K. were supported by UH2AR057504 and UH3AR057504 (J. A. S.); DP2OD001500 to K. M. A.; N01HG62088 to the Coriell Institute for Medical Research; U01DE016937 to F. E. D.; S. K. H. was supported by RC1DE0202098 and R01DE021574 (S. K. H. and H. Li); J. I. was supported by R21CA139193 (J. I. and D. S. Michaud); K. P. L. was supported by P30DE020751 (D. J. Smith); Army Research Office grant W911NF-11-1-0473 to C. H.; National Science Foundation grants NSF DBI-1053486 to C. H. and NSF IIS-0812111 to M. P.; The Office of Science of the US Department of Energy under Contract No. DE-AC02-05CH11231 for P. S. C.; LANL Laboratory-Directed Research and Development grant 20100034DR and the US Defense Threat Reduction Agency grants B104153I and B084531I to P. S. C.; Research Foundation - Flanders (FWO) grant to K. F. and J.Raes; R. K. is an HHMI Early Career Scientist; Gordon & Betty Moore Foundation funding and institutional funding from the J. David Gladstone Institutes to K. S. P.; A. M. S. was supported by fellowships provided by the Rackham Graduate School and the NIH Molecular Mechanisms in Microbial Pathogenesis Training Grant T32AI007528; a Crohn's and Colitis Foundation of Canada Grant in Aid of Research to E. A. V.; 2010 IBM Faculty Award to K. C. W.; analysis of the HMP data was performed using National Energy Research Scientific Computing resources, the BluBioU Computational Resource at Rice University. NR 26 TC 1904 Z9 1969 U1 201 U2 1216 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 JUN 14 PY 2012 VL 486 IS 7402 BP 207 EP 214 DI 10.1038/nature11234 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 957UH UT WOS:000305189000025 ER PT J AU Methe, BA Nelson, KE Pop, M Creasy, HH Giglio, MG Huttenhower, C Gevers, D Petrosino, JF Abubucker, S Badger, JH Chinwalla, AT Earl, AM FitzGerald, MG Fulton, RS Hallsworth-Pepin, K Lobos, EA Madupu, R Magrini, V Martin, JC Mitreva, M Muzny, DM Sodergren, EJ Versalovic, J Wollam, AM Worley, KC Wortman, JR Young, SK Zeng, Q Aagaard, KM Abolude, OO Allen-Vercoe, E Alm, EJ Alvarado, L Andersen, GL Anderson, S Appelbaum, E Arachchi, HM Armitage, G Arze, CA Ayvaz, T Baker, CC Begg, L Belachew, T Bhonagiri, V Bihan, M Blaser, MJ Bloom, T Bonazzi, VR Brooks, P Buck, G Buhay, CJ Busam, DA Campbell, JL Canon, SR Cantarel, BL Chain, PS Chen, IMA Chen, L Chhibba, S Chu, K Ciulla, DM Clemente, JC Clifton, SW Conlan, S Crabtree, J Cutting, MA Davidovics, NJ Davis, CC DeSantis, TZ Deal, C Delehaunty, KD Dewhisrst, FE Deych, E Ding, Y Dooling, DJ Dugan, SP Dunne, WM Durkin, AS Edgar, RC Erlich, RL Farmer, CN Farrell, RM Faust, K Feldgarden, M Felix, VM Fisher, S Fodor, AA Forney, L Foster, L Di Francesco, V Friedman, J Friedrich, DC Fronick, CC Fulton, LL Gao, H Garcia, N Giannoukos, G Giblin, C Giovanni, MY Goldberg, JM Goll, J Gonzalez, A Griggs, A Gujja, S Haas, BJ Hamilton, HA Harris, EL Hepburn, TA Herter, B Hoffmann, DE Holder, ME Howarth, C Huang, KH Huse, SM Izard, J Jansson, JK Jiang, HY Jordan, C Joshi, V Katancik, J Keitel, W Kelley, ST Kells, C Kinder-Haake, S King, NB Knight, R Knights, D Kong, HH Koren, O Koren, S Kota, KC Kovar, CL Kyrpides, NC La Rosa, PS Lee, SL Lemon, KP Lennon, N Lewis, CM Lewis, L Ley, RE Li, K Liolios, K Liu, B Liu, Y Lo, CC Lozupone, CA Lunsford, RD Madden, T Mahurkar, AA Mannon, PJ Mardis, ER Markowitz, VM Mavrommatis, K McCorrison, JM McDonald, D McEwen, J McGuire, AL McInnes, P Mehta, T Mihindukulasuriya, KA Miller, JR Minx, PJ Newsham, I Nusbaum, C O'Laughlin, M Orvis, J Pagani, I Palaniappan, K Patel, SM Pearson, M Peterson, J Podar, M Pohl, C Pollard, KS Priest, ME Proctor, LM Qin, X Raes, J Ravel, J Reid, JG Rho, M Rhodes, R Riehle, KP Rivera, MC Rodriguez-Mueller, B Rogers, YH Ross, MC Russ, C Sanka, RK Sankar, P Sathirapongsasuti, JF Schloss, JA Schloss, PD Schmidt, TM Scholz, M Schriml, L Schubert, AM Segata, N Segre, JA Shannon, WD Sharp, RR Sharpton, TJ Shenoy, N Sheth, NU Simone, GA Singh, I Smillie, CS Sobel, JD Sommer, DD Spicer, P Sutton, GG Sykes, SM Tabbaa, DG Thiagarajan, M Tomlinson, CM Torralba, M Treangen, TJ Truty, RM Vishnivetskaya, TA Walker, J Wang, L Wang, Z Ward, DV Warren, W Watson, MA Wellington, C Wetterstrand, KA White, JR Wilczek-Boney, K Wu, YQ Wylie, KM Wylie, T Yandava, C Ye, L Ye, Y Yooseph, S Youmans, BP Zhang, L Zhou, YJ Zhu, YM Zoloth, L Zucker, JD Birren, BW Gibbs, RA Highlander, SK Weinstock, GM Wilson, RK White, O AF Methe, Barbara A. Nelson, Karen E. Pop, Mihai Creasy, Heather H. Giglio, Michelle G. Huttenhower, Curtis Gevers, Dirk Petrosino, Joseph F. Abubucker, Sahar Badger, Jonathan H. Chinwalla, Asif T. Earl, Ashlee M. FitzGerald, Michael G. Fulton, Robert S. Hallsworth-Pepin, Kymberlie Lobos, Elizabeth A. Madupu, Ramana Magrini, Vincent Martin, John C. Mitreva, Makedonka Muzny, Donna M. Sodergren, Erica J. Versalovic, James Wollam, Aye M. Worley, Kim C. Wortman, Jennifer R. Young, Sarah K. Zeng, Qiandong Aagaard, Kjersti M. Abolude, Olukemi O. Allen-Vercoe, Emma Alm, Eric J. Alvarado, Lucia Andersen, Gary L. Anderson, Scott Appelbaum, Elizabeth Arachchi, Harindra M. Armitage, Gary Arze, Cesar A. Ayvaz, Tulin Baker, Carl C. Begg, Lisa Belachew, Tsegahiwot Bhonagiri, Veena Bihan, Monika Blaser, Martin J. Bloom, Toby Bonazzi, Vivien R. Brooks, Paul Buck, GregoryA. Buhay, Christian J. Busam, Dana A. Campbell, Joseph L. Canon, Shane R. Cantarel, Brandi L. Chain, Patrick S. Chen, I-Min A. Chen, Lei Chhibba, Shaila Chu, Ken Ciulla, Dawn M. Clemente, Jose C. Clifton, Sandra W. Conlan, Sean Crabtree, Jonathan Cutting, Mary A. Davidovics, Noam J. Davis, Catherine C. DeSantis, Todd Z. Deal, Carolyn Delehaunty, Kimberley D. Dewhisrst, Floyd E. Deych, Elena Ding, Yan Dooling, David J. Dugan, Shannon P. Dunne, W. Michael, Jr. Durkin, A. Scott Edgar, Robert C. Erlich, Rachel L. Farmer, Candace N. Farrell, Ruth M. Faust, Karoline Feldgarden, Michael Felix, Victor M. Fisher, Sheila Fodor, Anthony A. Forney, Larry Foster, Leslie Di Francesco, Valentina Friedman, Jonathan Friedrich, Dennis C. Fronick, Catrina C. Fulton, Lucinda L. Gao, Hongyu Garcia, Nathalia Giannoukos, Georgia Giblin, Christina Giovanni, Maria Y. Goldberg, Jonathan M. Goll, Johannes Gonzalez, Antonio Griggs, Allison Gujja, Sharvari Haas, Brian J. Hamilton, Holli A. Harris, Emily L. Hepburn, Theresa A. Herter, Brandi Hoffmann, Diane E. Holder, Michael E. Howarth, Clinton Huang, Katherine H. Huse, Susan M. Izard, Jacques Jansson, Janet K. Jiang, Huaiyang Jordan, Catherine Joshi, Vandita Katancik, JamesA. Keitel, WendyA. Kelley, Scott T. Kells, Cristyn Kinder-Haake, Susan King, Nicholas B. Knight, Rob Knights, Dan Kong, Heidi H. Koren, Omry Koren, Sergey Kota, Karthik C. Kovar, Christie L. Kyrpides, Nikos C. La Rosa, Patricio S. Lee, Sandra L. Lemon, Katherine P. Lennon, Niall Lewis, Cecil M. Lewis, Lora Ley, Ruth E. Li, Kelvin Liolios, Konstantinos Liu, Bo Liu, Yue Lo, Chien-Chi Lozupone, Catherine A. Lunsford, R. Dwayne Madden, Tessa Mahurkar, Anup A. Mannon, Peter J. Mardis, Elaine R. Markowitz, Victor M. Mavrommatis, Konstantinos McCorrison, Jamison M. McDonald, Daniel McEwen, Jean McGuire, Amy L. McInnes, Pamela Mehta, Teena Mihindukulasuriya, Kathie A. Miller, Jason R. Minx, Patrick J. Newsham, Irene Nusbaum, Chad O'Laughlin, Michelle Orvis, Joshua Pagani, Ioanna Palaniappan, Krishna Patel, Shital M. Pearson, Matthew Peterson, Jane Podar, Mircea Pohl, Craig Pollard, Katherine S. Priest, Margaret E. Proctor, Lita M. Qin, Xiang Raes, Jeroen Ravel, Jacques Reid, Jeffrey G. Rho, Mina Rhodes, Rosamond Riehle, Kevin P. Rivera, Maria C. Rodriguez-Mueller, Beltran Rogers, Yu-Hui Ross, Matthew C. Russ, Carsten Sanka, Ravi K. Sankar, Pamela Sathirapongsasuti, J. Fah Schloss, Jeffery A. Schloss, Patrick D. Schmidt, Thomas M. Scholz, Matthew Schriml, Lynn Schubert, Alyxandria M. Segata, Nicola Segre, Julia A. Shannon, William D. Sharp, Richard R. Sharpton, Thomas J. Shenoy, Narmada Sheth, Nihar U. Simone, Gina A. Singh, Indresh Smillie, Chris S. Sobel, Jack D. Sommer, Daniel D. Spicer, Paul Sutton, Granger G. Sykes, Sean M. Tabbaa, Diana G. Thiagarajan, Mathangi Tomlinson, Chad M. Torralba, Manolito Treangen, Todd J. Truty, Rebecca M. Vishnivetskaya, Tatiana A. Walker, Jason Wang, Lu Wang, Zhengyuan Ward, Doyle V. Warren, Wesley Watson, Mark A. Wellington, Christopher Wetterstrand, Kris A. White, James R. Wilczek-Boney, Katarzyna Wu, Yuan Qing Wylie, Kristine M. Wylie, Todd Yandava, Chandri Ye, Liang Ye, Yuzhen Yooseph, Shibu Youmans, Bonnie P. Zhang, Lan Zhou, Yanjiao Zhu, Yiming Zoloth, Laurie Zucker, Jeremy D. Birren, Bruce W. Gibbs, Richard A. Highlander, Sarah K. Weinstock, George M. Wilson, Richard K. White, Owen CA Human Microbiome Project Consortiu TI A framework for human microbiome research SO NATURE LA English DT Article ID CATALOG AB A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies. C1 [Methe, Barbara A.; Nelson, Karen E.; Madupu, Ramana; Bihan, Monika; Busam, Dana A.; Durkin, A. Scott; Foster, Leslie; Goll, Johannes; Li, Kelvin; McCorrison, Jamison M.; Miller, Jason R.; Orvis, Joshua; Rogers, Yu-Hui; Sanka, Ravi K.; Singh, Indresh; Sutton, Granger G.; Thiagarajan, Mathangi; Torralba, Manolito] J Craig Venter Inst, Rockville, MD 20850 USA. [Pop, Mihai; Koren, Sergey; Liu, Bo; Sommer, Daniel D.] Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA. [Pop, Mihai; Koren, Sergey; Liu, Bo; Sommer, Daniel D.] Univ Maryland, Dept Comp Sci, College Pk, MD 20742 USA. [Creasy, Heather H.; Giglio, Michelle G.; Abolude, Olukemi O.; Arze, Cesar A.; Cantarel, Brandi L.; Crabtree, Jonathan; Davidovics, Noam J.; Felix, Victor M.; Jordan, Catherine; Mahurkar, Anup A.; Ravel, Jacques; Schriml, Lynn; White, James R.; White, Owen] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. [Huttenhower, Curtis; Sathirapongsasuti, J. Fah; Segata, Nicola] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Huttenhower, Curtis; Gevers, Dirk; Earl, Ashlee M.; FitzGerald, Michael G.; Wortman, Jennifer R.; Young, Sarah K.; Zeng, Qiandong; Alm, Eric J.; Alvarado, Lucia; Anderson, Scott; Arachchi, Harindra M.; Bloom, Toby; Ciulla, Dawn M.; Erlich, Rachel L.; Feldgarden, Michael; Fisher, Sheila; Friedrich, Dennis C.; Giannoukos, Georgia; Goldberg, Jonathan M.; Griggs, Allison; Gujja, Sharvari; Haas, Brian J.; Hepburn, Theresa A.; Howarth, Clinton; Huang, Katherine H.; Jiang, Huaiyang; Kells, Cristyn; McDonald, Daniel; Mehta, Teena; Nusbaum, Chad; Pearson, Matthew; Priest, Margaret E.; Russ, Carsten; Shenoy, Narmada; Sykes, Sean M.; Tabbaa, Diana G.; Wang, Zhengyuan; Ward, Doyle V.; Wilczek-Boney, Katarzyna; Yandava, Chandri; Zucker, Jeremy D.; Birren, Bruce W.] Broad Inst & Harvard, Cambridge, MA 02142 USA. [Petrosino, Joseph F.; Muzny, Donna M.; Worley, Kim C.; Buhay, Christian J.; Ding, Yan; Dugan, Shannon P.; Holder, Michael E.; Joshi, Vandita; Kovar, Christie L.; Lee, Sandra L.; Lennon, Niall; Lewis, Lora; Liu, Yue; Newsham, Irene; Qin, Xiang; Reid, Jeffrey G.; Wu, Yuan Qing; Zhang, Lan; Zhu, Yiming; Gibbs, Richard A.; Highlander, Sarah K.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Abubucker, Sahar; Chinwalla, Asif T.; Fulton, Robert S.; Hallsworth-Pepin, Kymberlie; Lobos, Elizabeth A.; Magrini, Vincent; Martin, John C.; Mitreva, Makedonka; Sodergren, Erica J.; Wollam, Aye M.; Appelbaum, Elizabeth; Bhonagiri, Veena; Chen, Lei; Clifton, Sandra W.; Delehaunty, Kimberley D.; Deych, Elena; Dooling, David J.; Farmer, Candace N.; Fronick, Catrina C.; Fulton, Lucinda L.; Herter, Brandi; Kota, Karthik C.; Mardis, Elaine R.; Mihindukulasuriya, Kathie A.; Minx, Patrick J.; O'Laughlin, Michelle; Pagani, Ioanna; Pohl, Craig; Tomlinson, Chad M.; Walker, Jason; Warren, Wesley; Wylie, Kristine M.; Wylie, Todd; Ye, Liang; Zhou, Yanjiao; Weinstock, George M.; Wilson, Richard K.] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63108 USA. [Versalovic, James; Gao, Hongyu] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Versalovic, James] Texas Childrens Hosp, Dept Pathol, Houston, TX 77030 USA. [Aagaard, Kjersti M.] Baylor Coll Med, Dept Obstet & Gynecol, Div Maternal Fetal Med, Houston, TX 77030 USA. [Allen-Vercoe, Emma] Univ Guelph, Dept Mol & Cellular Biol, Guelph, ON N1G 2W1, Canada. [Alm, Eric J.] MIT, Dept Civil & Environm Engn, Parsons Lab, Cambridge, MA 02139 USA. [Andersen, Gary L.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Ctr Environm Biotechnol, Berkeley, CA 94720 USA. [Armitage, Gary] Univ Calif San Francisco, Sch Dent, San Francisco, CA 94143 USA. [Baker, Carl C.; Deal, Carolyn] Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, NIH, Bethesda, MD 20892 USA. [Begg, Lisa] NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA. [Belachew, Tsegahiwot; Campbell, Joseph L.; Di Francesco, Valentina; Giblin, Christina; Giovanni, Maria Y.] NIAID, NIH, Bethesda, MD 20892 USA. [Blaser, Martin J.] NYU, Langone Med Ctr, Dept Med, New York, NY 10016 USA. [Bonazzi, Vivien R.; Campbell, Joseph L.; Chhibba, Shaila; McEwen, Jean; Peterson, Jane; Proctor, Lita M.; Schloss, Jeffery A.; Wang, Lu; Wellington, Christopher; Wetterstrand, Kris A.] NHGRI, NIH, Bethesda, MD 20892 USA. [Brooks, Paul] Virginia Commonwealth Univ, Dept Stat Sci & Operat Res, Richmond, VA 23284 USA. [Brooks, Paul; Buck, GregoryA.; Rivera, Maria C.; Sheth, Nihar U.] Virginia Commonwealth Univ, Ctr Study Biol Complex, Richmond, VA 23284 USA. [Buck, GregoryA.; Rivera, Maria C.] Virginia Commonwealth Univ, Dept Biol, Richmond, VA 23284 USA. [Canon, Shane R.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Technol Integrat Grp, Natl Energy Res Sci Comp, Berkeley, CA 94720 USA. [Chain, Patrick S.; Lo, Chien-Chi; Scholz, Matthew] Los Alamos Natl Lab, Genome Sci Grp, Biosci Div, HRL, Los Alamos, NM 87545 USA. [Chain, Patrick S.; Kyrpides, Nikos C.; Liolios, Konstantinos; Markowitz, Victor M.; Mavrommatis, Konstantinos] Joint Genome Inst, Walnut Creek, CA 94598 USA. [Chen, I-Min A.; Chu, Ken; Markowitz, Victor M.; Palaniappan, Krishna] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Biol Data Management & Technol Ctr, Computat Res Div, Berkeley, CA 94720 USA. [Clemente, Jose C.; Knight, Rob; Lozupone, Catherine A.; McDonald, Daniel] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA. [Cutting, Mary A.; Hamilton, Holli A.; Harris, Emily L.; Lunsford, R. Dwayne; McInnes, Pamela] NIDCR, NIH, Bethesda, MD 20892 USA. [Davis, Catherine C.] Procter & Gamble Co, FemCare Prod Safety & Regulatory Affairs, Cincinnati, OH 45224 USA. [DeSantis, Todd Z.] Second Genome Inc, San Bruno, CA 94066 USA. [Dewhisrst, Floyd E.; Izard, Jacques; Lemon, Katherine P.] Forsyth Inst, Dept Mol Genet, Cambridge, MA 02142 USA. [Dewhisrst, Floyd E.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Dunne, W. Michael, Jr.; Watson, Mark A.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Dunne, W. Michael, Jr.] bioMerieux Inc, Durham, NC 27712 USA. [Edgar, Robert C.] Drive5 Com, Tiburon, CA 94920 USA. [Farrell, Ruth M.; Sharp, Richard R.] Cleveland Clin, Ctr Bioeth Human & Spiritual Care, Cleveland, OH 44195 USA. [Faust, Karoline; Raes, Jeroen] VIB, Dept Biol Struct, B-1050 Brussels, Belgium. [Faust, Karoline; Raes, Jeroen] Vrije Univ Brussel, Dept Appl Biol Sci DBIT, B-1050 Brussels, Belgium. [Fodor, Anthony A.] Univ N Carolina, Dept Bioinformat & Genom, Charlotte, NC 28223 USA. [Forney, Larry] Univ Idaho, Dept Biol Sci, Moscow, ID 83844 USA. [Friedman, Jonathan; Smillie, Chris S.] MIT, Parsons Lab, Cambridge, MA 02139 USA. [Garcia, Nathalia] St Louis Univ, Ctr Adv Dent Educ, St Louis, MO 63104 USA. [Gonzalez, Antonio; Knights, Dan] Univ Colorado, Dept Comp Sci, Boulder, CO 80309 USA. [Hoffmann, Diane E.] Univ Maryland, Francis King Carey Sch Law, Baltimore, MD 21201 USA. [Huse, Susan M.] Josephine Bay Paul Ctr, Marine Biol Lab, Woods Hole, MA 02543 USA. [Jansson, Janet K.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Dept Ecol, Div Earth Sci, Berkeley, CA 94720 USA. [Katancik, JamesA.] Univ Texas Hlth Sci Ctr Houston, Sch Dent, Dept Periodont, Houston, TX 77030 USA. [Kelley, Scott T.; Rodriguez-Mueller, Beltran] San Diego State Univ, Dept Biol, San Diego, CA 92182 USA. [Kinder-Haake, Susan] Univ Calif Los Angeles, Sch Dent, Div Associated Clin Specialties, Los Angeles, CA 90095 USA. [Kinder-Haake, Susan] Univ Calif Los Angeles, Dent Res Inst, Los Angeles, CA 90095 USA. [King, Nicholas B.] McGill Univ, Fac Med, Montreal, PQ H3A 1X1, Canada. [Knight, Rob] Howard Hughes Med Inst, Boulder, CO 80309 USA. [Kong, Heidi H.] NCI, NIH, Bethesda, MD 20892 USA. [Koren, Omry; Ley, Ruth E.] Cornell Univ, Dept Microbiol, Ithaca, NY USA. [La Rosa, Patricio S.; Shannon, William D.] Washington Univ, Sch Med, Dept Med, Div Gen Med Sci, St Louis, MO 63110 USA. [Lemon, Katherine P.; Ravel, Jacques] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Infect Dis, Boston, MA 02115 USA. [Lewis, Cecil M.; Rho, Mina; Spicer, Paul] Univ Oklahoma, Dept Anthropol, Norman, OK 73019 USA. [Madden, Tessa] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA. [Mannon, Peter J.] Univ Alabama Birmingham, Div Gastroenterol & Hepatol, Birmingham, AL 35294 USA. [Podar, Mircea; Vishnivetskaya, Tatiana A.] Oak Ridge Natl Lab, Biosci Div, Oak Ridge, TN 37831 USA. [Pollard, Katherine S.; Sharpton, Thomas J.; Truty, Rebecca M.] Univ Calif San Francisco, Gladstone Inst, San Francisco, CA 94158 USA. [Pollard, Katherine S.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94158 USA. [Pollard, Katherine S.] Univ Calif San Francisco, Div Biostat, San Francisco, CA 94158 USA. [Pollard, Katherine S.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. [Ye, Yuzhen] Indiana Univ, Sch Informat & Comp, Bloomington, IN 47405 USA. [Rhodes, Rosamond] Mt Sinai Sch Med, New York, NY 10029 USA. [Riehle, Kevin P.] Baylor Coll Med Mol & Human Genet, Houston, TX 77030 USA. [Sankar, Pamela] Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. [Sankar, Pamela] Univ Penn, Dept Med Eth, Philadelphia, PA 19104 USA. [Schloss, Patrick D.; Schubert, Alyxandria M.] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. [Schmidt, Thomas M.] Michigan State Univ, Dept Microbiol, E Lansing, MI 48824 USA. [Simone, Gina A.] EMMES Corp, Rockville, MD 20850 USA. [Sobel, Jack D.] Wayne State Univ, Sch Med, Harper Univ Hosp, Detroit, MI 48201 USA. [Treangen, Todd J.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Badger, Jonathan H.; Yooseph, Shibu] J Craig Venter Inst, San Diego, CA 92121 USA. [Zoloth, Laurie] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Petrosino, Joseph F.] Baylor Coll Med, Alkek Ctr Metagen & Microbiome Res, Houston, TX 77030 USA. [Conlan, Sean; Segre, Julia A.] NHGRI, NIH, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. RP Methe, BA (reprint author), J Craig Venter Inst, 9704 Med Ctr Dr, Rockville, MD 20850 USA. RI Conlan, Sean/B-4401-2008; Vishnivetskaya, Tatiana/A-4488-2008; Pagani, Ioanna/E-7390-2012; Pop, Mihai/A-7987-2013; Andersen, Gary/G-2792-2015; Walker, Jason/A-9702-2013; Zucker, Jeremy/M-3643-2016; Knight, Rob/D-1299-2010; chain, patrick/B-9777-2013; Weinstock, George/C-6314-2013; Bihan, Monika/C-7469-2014; Kyrpides, Nikos/A-6305-2014; Ley, Ruth/M-8542-2014 OI Ravel, Jacques/0000-0002-0851-2233; Schloss, Patrick/0000-0002-6935-4275; Kong, Heidi/0000-0003-4424-064X; Faust, Karoline/0000-0001-7129-2803; Schmidt, Thomas/0000-0002-8209-6055; Koren, Omry/0000-0002-7738-1337; Huttenhower, Curtis/0000-0002-1110-0096; Segata, Nicola/0000-0002-1583-5794; Conlan, Sean/0000-0001-6848-3465; Earl, Ashlee/0000-0001-7857-9145; King, Nicholas/0000-0002-2093-3380; Izard, Jacques/0000-0002-5904-5436; Podar, Mircea/0000-0003-2776-0205; Garcia, M. Nathalia/0000-0003-3685-027X; Schriml, Lynn/0000-0001-8910-9851; Mihindukulasuriya, Kathie/0000-0001-9372-3758; Vishnivetskaya, Tatiana/0000-0002-0660-023X; Pop, Mihai/0000-0001-9617-5304; Andersen, Gary/0000-0002-1618-9827; Walker, Jason/0000-0001-7547-5789; Zucker, Jeremy/0000-0002-7276-9009; Weinstock, George/0000-0002-2997-4592; Kyrpides, Nikos/0000-0002-6131-0462; Wortman, Jennifer/0000-0002-8713-1227; Ley, Ruth/0000-0002-9087-1672 FU NIH [U54HG004969, U54HG003273, U54HG004973, U54HG003067, U54AI084844, N01AI30071, U54HG004968, U01HG004866, U54HG003079, R01HG005969, R01HG004872, R01HG004885, R01HG005975, R01HG004908, R01HG004900, R01HG005171, R01HG004853, R01HG004856, R01HG004877, R01HG005172, R01HG004857, R01HG004906, R21HG005811, UH2AI083263, UH3AI083263, UH2AR057506, UH3DK083993, UH2DK083990, UH2AR057504, UH3AR057504, DP2OD001500, N01HG62088, U01DE016937, RC1DE020298, R01DE021574, R21CA139193, P30DE020751, T32AI007528]; Army Research Office [W911NF-11-1-0473]; National Science Foundation [NSF DBI-1053486, NSF IIS-0812111]; Office of Science of the US Department of Energy [DE-AC02-05CH11231]; LANL Laboratory [20100034DR]; US Defense Threat Reduction Agency [B104153I, B084531I]; Research Foundation - Flanders (FWO); Gordon & Betty Moore Foundation from the J. David Gladstone Institutes; Rackham Graduate School; Crohn's and Colitis Foundation of Canada; IBM FX The consortium would like to thank our external scientific advisory board: R. Blumberg, J. Davies, R. Holt, P. Ossorio, F. Ouellette, G. Schoolnik and A. Williamson. We would also like to thank our collaborators throughout the International Human Microbiome Consortium, particularly the investigators of the MetaHIT project, for advancing human microbiome research. Data repository management was provided by the NCBI and the Intramural Research Program of the NIH National Library of Medicine. We especially appreciate the generous participation of the individuals from the St Louis, Missouri, and Houston, Texas areas who made this study possible. This research was supported in part by NIH grants U54HG004969 to B. W. B.; U54HG003273 to R. A. G.; U54HG004973 to R. A. G., S. K. H. and J. F. P.; U54HG003067 to E. S. Lander.; U54AI084844 to K.E.N.; N01AI30071 to R. L. Strausberg; U54HG004968 to G. M. W.; U01HG004866 to O.W.; U54HG003079 to R. K. W.; R01HG005969 to C. H.; R01HG004872 to R. K.; R01HG004885 to M. P.; R01HG005975 to P. D. S.; R01HG004908 to Y.Y.; R01HG004900 to M. K. Cho and P. Sankar; R01HG005171 to D. E. H.; R01HG004853 to A. L. M.; R01HG004856 to R. R.; R01HG004877 to R. R. S. and R. M. F.; R01HG005172 to P. Spicer; R01HG004857 to M. P.; R01HG004906 to T. M. S.; R21HG005811 to E.A.-V.; G. A. B. was supported by UH2AI083263 and UH3AI083263 (G. A. B., C. N. Cornelissen, L. K. Eaves and J. F. Strauss); M. J. B. was supported by UH2AR057506, S. M. H. was supported by UH3DK083993 (V. B. Young, E. B. Chang, F. Meyer, T. M. S., M. L. Sogin, J. M. Tiedje); K. P. R. was supported by UH2DK083990 (J. V.); J. A. S. and H. H. K. were supported by UH2AR057504 and UH3AR057504 (J. A. S.); DP2OD001500 to K. M. A.; N01HG62088 to the Coriell Institute for Medical Research; U01DE016937 to F. E. D.; S.K.-H. was supported by RC1DE020298and R01DE021574 (S.K.-H. and H. Li); J. I. was supported by R21CA139193 (J. I. and D. S. Michaud); K. P. L. was supported by P30DE020751 (D. J. Smith); Army Research Office grant W911NF-11-1-0473 to C. H.; National Science Foundation grants NSF DBI-1053486 to C. H. and NSF IIS-0812111 to M. P.; The Office of Science of the US Department of Energy under contract no. DE-AC02-05CH11231 for P. S. C.; LANL Laboratory-Directed Research and Development grant 20100034DR and the US Defense Threat Reduction Agency grants B104153I and B084531I to P. S. C.; Research Foundation - Flanders (FWO) grant to K. F. and J. Raes; R. K. is a Howard Hughes Medical Institute (HHMI) Early Career Scientist; Gordon & Betty Moore Foundation funding and institutional funding from the J. David Gladstone Institutes to K. S. P.; A. M. S. was supported by fellowships provided by the Rackham Graduate School and the NIH Molecular Mechanisms in Microbial Pathogenesis Training Grant T32AI007528; a Crohn's and Colitis Foundation of Canada Grant in Aid of Research to E.A.-V.; 2010 IBM Faculty Award to K. C. W. Analysis of the HMP data was performed using National Energy Research Scientific Computing resources; the BluBioU Computational Resource at Rice University. NR 16 TC 475 Z9 488 U1 19 U2 262 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 JUN 14 PY 2012 VL 486 IS 7402 BP 215 EP 221 DI 10.1038/nature11209 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 957UH UT WOS:000305189000026 ER PT J AU Pena, JA Lewandrowski, KB Lewandrowski, EL Gregory, K Baron, JM Van Cott, EM AF Pena, J. A. Lewandrowski, K. B. Lewandrowski, E. L. Gregory, K. Baron, J. M. Van Cott, E. M. TI Evaluation of the i-STAT point-of-care capillary whole blood prothrombin time and international normalized ratio: Comparison to the Tcoag MDAII coagulation analyzer in the central laboratory SO CLINICA CHIMICA ACTA LA English DT Article DE Point-of-care testing; POCT; Prothrombin time; International normalized ratio; INR; Capillary blood ID ORAL ANTICOAGULANT-THERAPY; ACCURACY; MONITOR; DEVICES AB Background: Point-of-care devices for performing a prothrombin time/international normalized ratio (PT/INR) using capillary blood samples are being increasingly used to monitor patients receiving anticoagulation therapy. However, the performance of some devices has been shown to be suboptimal and there are only limited published data comparing specific devices to various central laboratory coagulation analyzers. We report an evaluation of the iSTAT PT/INR with a comparison to the Tcoag MDA II analyzer. Methods: We obtained simultaneous capillary/venous samples on 20 healthy volunteers for a normal range study and on 50 anticoagulated patients for a clinical evaluation. Testing was performed by phlebotomists. We also obtained 68 near simultaneous capillary/venous test results for assessment of performance by non-laboratory personnel. The criteria for determining clinical equivalence of the iSTAT to the MDA II were (1) same clinical category (subtherapeutic INR<2, therapeutic INR 2-3, and supratherapeutic INR>3) or (2) paired values within <= 0.4 INR. Results: Forty nine of 50 patient sample pairs collected by phlebotomists showed acceptable clinical agreement. Sixty one (61) of 68 patient sample pairs collected by nurses showed acceptable agreement. In all discordant cases the differences were minor and would have resulted in either no or minimal change in therapy. Conclusions: The iSTAT PT/INR compares well to the MDA II when performed by phlebotomists or nurses. (C) 2012 Elsevier B.V. All rights reserved. C1 [Pena, J. A.; Lewandrowski, K. B.; Lewandrowski, E. L.; Gregory, K.; Baron, J. M.; Van Cott, E. M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Van Cott, EM (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Gray 235, Boston, MA 02114 USA. NR 13 TC 6 Z9 7 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JUN 14 PY 2012 VL 413 IS 11-12 BP 955 EP 959 DI 10.1016/j.cca.2012.01.035 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 932FF UT WOS:000303275100001 PM 22330876 ER PT J AU Murata, Y Fujiwara, N Seo, JH Yan, F Liu, XR Terasaki, Y Luo, YM Arai, K Ji, XM Lo, EH AF Murata, Yoshihiro Fujiwara, Norio Seo, Ji Hae Yan, Feng Liu, Xiangrong Terasaki, Yasukazu Luo, Yumin Arai, Ken Ji, Xunming Lo, Eng H. TI Delayed Inhibition of c-Jun N-Terminal Kinase Worsens Outcomes after Focal Cerebral Ischemia SO JOURNAL OF NEUROSCIENCE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; SIGNALING PATHWAY; MATRIX METALLOPROTEINASES; STROKE; BRAIN; JNK; NEUROPROTECTION; DEGENERATION; INVOLVEMENT; APOPTOSIS AB The stress-activated protein kinase c-Jun N-terminal kinase (JNK) is a central regulator in neuronal death cascades. In animal models of cerebral ischemia, acute inhibition of JNK reduces infarction and improves outcomes. Recently however, emerging data suggest that many neuronal death mediators may have biphasic properties-deleterious in the acute stage but potentially beneficial in the delayed stage. Here, we hypothesized that JNK may also have biphasic actions, so some caution may be required in the development of JNK inhibitors for stroke. Sprague Dawley rats underwent 90 min transient occlusions of the middle cerebral artery. Acute treatment (10 min poststroke) with the JNK inhibitor SP600125 reduced infarction volumes. In contrast, delayed treatment (7 d poststroke) worsened infarction volumes and neurological outcomes. Immunostaining of peri-infarct cortex showed that JNK inhibition suppressed surrogate markers of neurovascular remodeling, including matrix metalloproteinase-9 in GFAP-positive astrocytes and microvascular density. Consistent with these in vivo data, SP600125 significantly suppressed in vitro angiogenesis in rat brain endothelial cultures. Our data provide initial proof-of-concept that the neuronal death target JNK may also participate in endogenous processes of neurovascular remodeling and recovery after cerebral ischemia. C1 [Murata, Yoshihiro; Fujiwara, Norio; Seo, Ji Hae; Terasaki, Yasukazu; Arai, Ken; Lo, Eng H.] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Boston, MA 02129 USA. [Murata, Yoshihiro; Fujiwara, Norio; Seo, Ji Hae; Terasaki, Yasukazu; Arai, Ken; Lo, Eng H.] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Boston, MA 02129 USA. [Murata, Yoshihiro; Fujiwara, Norio; Seo, Ji Hae; Terasaki, Yasukazu; Arai, Ken; Lo, Eng H.] Harvard Univ, Program Neurosci, Sch Med, Boston, MA 02129 USA. [Yan, Feng; Liu, Xiangrong; Luo, Yumin; Ji, Xunming] Capital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China. [Yan, Feng; Liu, Xiangrong; Luo, Yumin; Ji, Xunming] Capital Med Univ, Xuanwu Hosp, Dept Neurosurg, Beijing 100053, Peoples R China. [Yan, Feng; Liu, Xiangrong; Luo, Yumin; Ji, Xunming] Capital Med Univ, Xuanwu Hosp, Cerebrovasc Res Inst, Beijing 100053, Peoples R China. RP Lo, EH (reprint author), MGH E 149-2401, Boston, MA 02129 USA. EM Lo@helix.mgh.harvard.edu FU NIH [R37-NS37074, P01-NS55104]; National Basic Research Program of China 973 Program [2011CB707804]; Beijing Natural Science Foundation [7111003] FX This work was supported in part by NIH Grants R37-NS37074 and P01-NS55104, Grant 2011CB707804 from the National Basic Research Program of China 973 Program, and Grant 7111003 from the Beijing Natural Science Foundation. NR 21 TC 18 Z9 19 U1 1 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 13 PY 2012 VL 32 IS 24 BP 8112 EP 8115 DI 10.1523/JNEUROSCI.0219-12.2012 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 959EL UT WOS:000305295600003 PM 22699892 ER PT J AU Bilal, E Vassallo, K Toppmeyer, D Barnard, N Rye, IH Almendro, V Russnes, H Borresen-Dale, AL Levine, AJ Bhanot, G Ganesan, S AF Bilal, Erhan Vassallo, Kristen Toppmeyer, Deborah Barnard, Nicola Rye, Inga H. Almendro, Vanessa Russnes, Hege Borresen-Dale, Anne-Lise Levine, Arnold J. Bhanot, Gyan Ganesan, Shridar TI Amplified Loci on Chromosomes 8 and 17 Predict Early Relapse in ER-Positive Breast Cancers SO PLOS ONE LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; ENDOCRINE THERAPY RESISTANCE; ESTROGEN-RECEPTOR; CLINICAL-IMPLICATIONS; MOLECULAR SUBTYPES; RANDOMIZED-TRIALS; 8P11-12 AMPLICON; GROWTH-FACTOR; BONE-MARROW; CYCLIN D1 AB Adjuvant hormonal therapy is administered to all early stage ER+ breast cancers, and has led to significantly improved survival. Unfortunately, a subset of ER+ breast cancers suffer early relapse despite hormonal therapy. To identify molecular markers associated with early relapse in ER+ breast cancer, an outlier analysis method was applied to a published gene expression dataset of 268 ER+ early-stage breast cancers treated with tamoxifen alone. Increased expression of sets of genes that clustered in chromosomal locations consistent with the presence of amplicons at 8q24.3, 8p11.2, 17q12 (HER2 locus) and 17q21.33-q25.1 were each found to be independent markers for early disease recurrence. Distant metastasis free survival (DMFS) after 10 years for cases with any amplicon (DMFS = 56.1%, 95% CI = 48.3-63.9%) was significantly lower (P = 0.0016) than cases without any of the amplicons (DMFS = 87%, 95% CI = 76.3% -97.7%). The association between presence of chromosomal amplifications in these regions and poor outcome in ER+ breast cancers was independent of histologic grade and was confirmed in independent clinical datasets. A separate validation using a FISH-based assay to detect the amplicons at 8q24.3, 8p11.2, and 17q21.33-q25.1 in a set of 36 early stage ER+/HER2- breast cancers treated with tamoxifen suggests that the presence of these amplicons are indeed predictive of early recurrence. We conclude that these amplicons may serve as prognostic markers of early relapse in ER+ breast cancer, and may identify novel therapeutic targets for poor prognosis ER+ breast cancers. C1 [Bilal, Erhan; Bhanot, Gyan] State Univ New Jersey, Piscataway, NJ USA. [Toppmeyer, Deborah; Levine, Arnold J.; Bhanot, Gyan; Ganesan, Shridar] Canc Inst New Jersey, New Brunswick, NJ USA. [Vassallo, Kristen; Barnard, Nicola] Robert Wood Johnson Univ Hosp, New Brunswick, NJ USA. [Russnes, Hege; Borresen-Dale, Anne-Lise] Norwegian Radium Hosp, Inst Canc Res, Oslo, Norway. [Almendro, Vanessa; Russnes, Hege] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rye, Inga H.; Borresen-Dale, Anne-Lise] Univ Oslo, Inst Clin Med, Oslo, Norway. [Almendro, Vanessa] Hosp Clin Barcelona, Dept Med Oncol, Barcelona, Spain. [Levine, Arnold J.; Bhanot, Gyan] Inst Adv Study, Princeton, NJ 08540 USA. RP Bilal, E (reprint author), State Univ New Jersey, Piscataway, NJ USA. EM gyanbhanot@gmail.com; ganesash@umdnj.edu RI Russnes, Hege/N-6170-2015 OI Russnes, Hege/0000-0001-8724-1891 FU New Jersey Commission on Cancer Research; National Institutes of Health; Norwegian Cancer Association; The Norwegian Research Council; Raagholdt Foundation; Thorsteds Foundation; Radiumhospitalets legater; Cellex Foundation FX EB was supported in part by a grant from the New Jersey Commission on Cancer Research. SG has received support from the National Institutes of Health, and the New Jersey Commission on Cancer Research. HR is funded by the Norwegian Cancer Association, The Norwegian Research Council, Raagholdt Foundation, Thorsteds Foundation and Radiumhospitalets legater. VA is funded by Cellex Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 10 Z9 10 U1 0 U2 4 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 JUN 13 PY 2012 VL 7 IS 6 AR e38575 DI 10.1371/journal.pone.0038575 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959UV UT WOS:000305341900035 PM 22719901 ER PT J AU Jardine, MJ Kang, A Zoungas, S Navaneethan, SD Ninomiya, T Nigwekar, SU Gallagher, MP Cass, A Strippoli, G Perkovic, V AF Jardine, Meg J. Kang, Amy Zoungas, Sophia Navaneethan, Sankar D. Ninomiya, Toshiharu Nigwekar, Sagar U. Gallagher, Martin P. Cass, Alan Strippoli, Giovanni Perkovic, Vlado TI The effect of folic acid based homocysteine lowering on cardiovascular events in people with kidney disease: systematic review and meta-analysis SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Article ID STAGE RENAL-DISEASE; RANDOMIZED CONTROLLED-TRIAL; PLASMA TOTAL HOMOCYSTEINE; TRANSPLANT RECIPIENTS; B-VITAMINS; RISK-FACTOR; MYOCARDIAL-INFARCTION; ELEVATED HOMOCYSTEINE; HEMODIALYSIS-PATIENTS; REVERSE EPIDEMIOLOGY AB Objective To systematically review the effect of folic acid based homocysteine lowering on cardiovascular outcomes in people with kidney disease. Design Systematic review and meta-analysis. Data sources Medline, Embase, the Cochrane Library, and ClinicalTrials.gov to June 2011. Study selection Randomised trials in people with non-dialysis dependent chronic kidney disease or end stage kidney disease or with a functioning kidney transplant reporting at least 100 patient years of follow-up and assessing the effect of folic acid based homocysteine lowering therapy. No language restrictions were applied. Data extraction Two reviewers independently extracted data on study setting, design, and outcomes using a standardised form. The primary endpoint was cardiovascular events (myocardial infarction, stroke, and cardiovascular mortality, or as defined by study author). Secondary endpoints included the individual composite components, all cause mortality, access thrombosis, requirement for renal replacement therapy, and reported adverse events, including haematological and neurological events. The effect of folic acid based homocysteine lowering on outcomes was assessed with meta-analysis using random effects models. Results 11 trials were identified that reported on 4389 people with chronic kidney disease, 2452 with end stage kidney disease, and 4110 with functioning kidney transplants (10 951 participants in total). Folic acid based homocysteine therapy did not prevent cardiovascular events (relative risk 0.97, 95% confidence interval 0.92 to 1.03, P=0.326) or any of the secondary outcomes. There was no evidence of heterogeneity in subgroup analyses, including those of kidney disease category, background fortification, rates of pre-existing disease, or baseline homocysteine level. The definitions of chronic kidney disease varied widely between the studies. Non-cardiovascular events could not be analysed as few studies reported these outcomes. Conclusions Folic acid based homocysteine lowering does not reduce cardiovascular events in people with kidney disease. Folic acid based regimens should not be used for the prevention of cardiovascular events in people with kidney disease. C1 [Jardine, Meg J.; Kang, Amy; Zoungas, Sophia; Ninomiya, Toshiharu; Gallagher, Martin P.; Cass, Alan; Perkovic, Vlado] George Inst Global Hlth, Camperdown, NSW 2050, Australia. [Jardine, Meg J.; Gallagher, Martin P.] Concord Repatriat Gen Hosp, Sydney, NSW, Australia. [Kang, Amy] Royal N Shore Hosp, Sydney, NSW, Australia. [Zoungas, Sophia] Monash Univ, Sch Publ Hlth, Melbourne, Vic 3004, Australia. [Navaneethan, Sankar D.] Cleveland Clin, Dept Hypertens & Nephrol, Cleveland, OH 44106 USA. [Ninomiya, Toshiharu] Kyushu Univ, Grad Sch Med Sci, Dept Med & Clin Sci, Fukuoka 812, Japan. [Nigwekar, Sagar U.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Strippoli, Giovanni] Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia. [Strippoli, Giovanni] Mario Negri Sud Consortium, Santa Maria Imbaro, Italy. RP Jardine, MJ (reprint author), George Inst Global Hlth, POB M201, Camperdown, NSW 2050, Australia. EM mjardine@georgeinstitute.org.au OI Strippoli, Giovanni/0000-0002-6936-0616; Perkovic, Vlado/0000-0002-4257-7620 FU Royal Australasian College of Physicians Jacquot Research Establishment; Banyu Life Science Foundation International fellowship programme (Japan); Foundation of High Blood Pressure Research ISH visiting postdoctoral award (Australia); National Heart Foundation of Australia Career Development Award; NSW Cardiovascular Research Network Heart Foundation of Australia fellowship; MSD; Novo Nordisk; Astra Zeneca/BMS; Novartis; Sanofi Aventis; Servier International; KL2 grant from the National Institutes of Health; unrestricted grant from CSL; educational grant from Shire; Roche FX We thank SZ and K Polkinghorne for additional data from the ASFAST study; Gail Higgins, trials search coordinator of the Cochrane Renal Group, for assistance with the search strategy and implementation; MJJ and MPG were supported by grants from the Royal Australasian College of Physicians Jacquot Research Establishment; TN was supported by a Banyu Life Science Foundation International fellowship programme (Japan) and by a Foundation of High Blood Pressure Research ISH visiting postdoctoral award (Australia). SZ was supported by a National Heart Foundation of Australia Career Development Award. VP was supported by a NSW Cardiovascular Research Network Heart Foundation of Australia fellowship. The authors were independently responsible for the study design, analysis, interpretation, preparation of the manuscript, and the decision to submit for publication.; All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that : no support from any organisation for the submitted work; SZ is a member of the advisory boards for MSD, Novo Nordisk, and Boehringer Ingelheim, and has received consultancies from Novo Nordisk and Johnson and Johnson, speakers fees from MSD, Novo Nordisk, Astra Zeneca/BMS, Novartis, Sanofi Aventis, and Servier International, and payment for the development of educational presentations from Medi Mark; MG has received payment for lectures from Roche Pharmaceuticals; SDN has received a KL2 grant from the National Institutes of Health; AC has received payment for lectures from Roche, Servier, AMGEN, and MSD; MJ has received an unrestricted grant from CSL; Concord Hospital has received an educational grant from Shire; VP is a member of the Abbot advisory board, has grants or grants pending from Roche, Johnson and Johnson, Baxter, and Servier and has received payment for lectures from Roche, Servier, and Astra Zeneca; MJ, AK, SZ, TN, MG, AC, and VP are affiliated with the George Institute, which receives funding from various pharmaceutical companies to support parts of its research activities, which companies might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work. NR 51 TC 37 Z9 38 U1 1 U2 12 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 JUN 13 PY 2012 VL 344 AR e3533 DI 10.1136/bmj.e3533 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 961KT UT WOS:000305464000003 PM 22695899 ER PT J AU Gottumukkala, RVSRK Lv, H Cornivelli, L Wagers, AJ Kwong, RY Bronson, R Stewart, GC Schulze, PC Chutkow, W Wolpert, HA Lee, RT Lipes, MA AF Gottumukkala, Raju V. S. R. K. Lv, HuiJuan Cornivelli, Lizbeth Wagers, Amy J. Kwong, Raymond Y. Bronson, Roderick Stewart, Garrick C. Schulze, P. Christian Chutkow, William Wolpert, Howard A. Lee, Richard T. Lipes, Myra A. TI Myocardial Infarction Triggers Chronic Cardiac Autoimmunity in Type 1 Diabetes SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID IMMUNE-SYSTEM; TROPONIN-I; MAGNETIC-RESONANCE; SKELETAL-MUSCLE; DENDRITIC CELLS; HEART-FAILURE; T-CELLS; INFLAMMATION; DISEASE; ISCHEMIA AB Patients with type 1 diabetes (T1D) suffer excessive morbidity and mortality after myocardial infarction (MI) that is not fully explained by the metabolic effects of diabetes. Acute MI is known to trigger a profound innate inflammatory response with influx of mononuclear cells and production of proinflammatory cytokines that are crucial for cardiac repair. We hypothesized that these same pathways might exert "adjuvant effects" and induce pathological responses in autoimmune-prone T1D hosts. Here, we show that experimental MI in nonobese diabetic mice, but not in control C57BL/6 mice, results in a severe post-infarction autoimmune (PIA) syndrome characterized by destructive lymphocytic infiltrates in the myocardium, infarct expansion, sustained cardiac autoantibody production, and T helper type 1 effector cell responses against cardiac (alpha-)myosin. PIA was prevented by inducing tolerance to alpha-myosin, demonstrating that immune responses to cardiac myosin are essential for this disease process. Extending these findings to humans, we developed a panel of immunoassays for cardiac autoantibody detection and found autoantibody positivity in 83% post-MI T1D patients. We further identified shared cardiac myosin autoantibody signatures between post-MI T1D patients and nondiabetic patients with myocarditis, which were absent in post-MI type 2 diabetic patients, and confirmed the presence of myocarditis in T1D by cardiac magnetic resonance imaging techniques. These data provide experimental and clinical evidence for a distinct post-MI autoimmune syndrome in T1D. Our findings suggest that PIA may contribute to worsened post-MI outcomes in T1D and highlight a role for antigen-specific immunointervention to selectively block this pathway. C1 [Gottumukkala, Raju V. S. R. K.; Lv, HuiJuan; Cornivelli, Lizbeth; Wagers, Amy J.; Wolpert, Howard A.; Lipes, Myra A.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. [Wagers, Amy J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Wagers, Amy J.; Lee, Richard T.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Kwong, Raymond Y.; Stewart, Garrick C.; Schulze, P. Christian; Chutkow, William; Lee, Richard T.] Harvard Univ, Brigham & Womens Hosp, Cardiovasc Div, Sch Med, Boston, MA 02115 USA. [Bronson, Roderick] Harvard Univ, Dept Microbiol & Immunol, Sch Med, Boston, MA 02115 USA. [Schulze, P. Christian] Columbia Univ, Div Cardiol, Med Ctr, New York, NY 10032 USA. RP Lipes, MA (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. EM myra.lipes@joslin.harvard.edu FU NIH [R01 DK072090, HL077554]; Seaver Institute; Joslin Diabetes Center [P30 DK36836]; Burroughs Welcome Fund; Juvenile Diabetes Research Foundation FX This work was supported by NIH grants R01 DK072090 and HL077554 (to M.A.L.), the Seaver Institute (to M.A.L.) and P30 DK36836 to the Joslin Diabetes Center, Burroughs Welcome Fund (to A.J.W.), and Juvenile Diabetes Research Foundation Postdoctoral Fellowship Award (to H.L.). NR 49 TC 0 Z9 0 U1 1 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD JUN 13 PY 2012 VL 4 IS 138 PG 13 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 959RY UT WOS:000305331700011 ER PT J AU Kudva, IT Griffin, RW Krastins, B Sarracino, DA Calderwood, SB John, M AF Kudva, Indira T. Griffin, Robert W. Krastins, Bryan Sarracino, David A. Calderwood, Stephen B. John, Manohar TI Proteins other than the locus of enterocyte effacement-encoded proteins contribute to Escherichia coli O157:H7 adherence to bovine rectoanal junction stratified squamous epithelial cells SO BMC MICROBIOLOGY LA English DT Article DE O157; Rectoanal junction; LEE; Adherence; DMEM; GeLC-MS/MS ID III SECRETED PROTEINS; FEEDLOT CATTLE; MASS-SPECTROMETRY; TERMINAL RECTUM; O157-H7; O157H7; INFECTION; STRAINS; IDENTIFICATION; COLONIZATION AB Background: In this study, we present evidence that proteins encoded by the Locus of Enterocyte Effacement (LEE), considered critical for Escherichia coli O157 (O157) adherence to follicle-associated epithelial (FAE) cells at the bovine recto-anal junction (RAJ), do not appear to contribute to O157 adherence to squamous epithelial (RSE) cells also constituting this primary site of O157 colonization in cattle. Results: Antisera targeting intimin-gamma, the primary O157 adhesin, and other essential LEE proteins failed to block O157 adherence to RSE cells, when this pathogen was grown in DMEM, a culture medium that enhances expression of LEE proteins. In addition, RSE adherence of a DMEM grown O157 mutant lacking the intimin protein was comparable to that seen with its wild- type parent O157 strain grown in the same media. These adherence patterns were in complete contrast to that observed with HEp-2 cells (the adherence to which is mediated by intimin-gamma), assayed under same conditions. This suggested that proteins other than intimin-. that contribute to adherence to RSE cells are expressed by this pathogen during growth in DMEM. To identify such proteins, we defined the proteome of DMEM-grown- O157 (DMEM-proteome). GeLC-MS/MS revealed that the O157 DMEM-proteome comprised 684 proteins including several components of the cattle and human O157 immunome, orthologs of adhesins, hypothetical secreted and outer membrane proteins, in addition to the known virulence and LEE proteins. Bioinformatics-based analysis of the components of the O157 DMEM proteome revealed several new O157-specific proteins with adhesin potential. Conclusion: Proteins other than LEE and intimin-. proteins are involved in O157 adherence to RSE cells at the bovine RAJ. Such proteins, with adhesin potential, are expressed by this human pathogen during growth in DMEM. Ongoing experiments to evaluate their role in RSE adherence should provide both valuable insights into the O157-RSE interactions and new targets for more efficacious anti-adhesion O157 vaccines. C1 [Kudva, Indira T.] USDA ARS, Food Safety & Enter Pathogens Res Unit, Natl Anim Dis Ctr, Ames, IA 50010 USA. [Griffin, Robert W.; Calderwood, Stephen B.; John, Manohar] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Krastins, Bryan; Sarracino, David A.] Harvard Partners Ctr Genet & Genom, Cambridge, MA 02139 USA. [Calderwood, Stephen B.; John, Manohar] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02114 USA. RP Kudva, IT (reprint author), USDA ARS, Food Safety & Enter Pathogens Res Unit, Natl Anim Dis Ctr, Ames, IA 50010 USA. EM Indira.Kudva@ars.usda.gov FU US National Institutes of Health Grant [R21 AI055963] FX This work was supported by a US National Institutes of Health Grant R21 AI055963 to I.T.K. Intellectual property rights for the O157 proteome identified in this study are held by Massachusetts General Hospital, Boston, MA. NR 34 TC 11 Z9 11 U1 0 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2180 J9 BMC MICROBIOL JI BMC Microbiol. PD JUN 12 PY 2012 VL 12 AR 103 DI 10.1186/1471-2180-12-103 PG 11 WC Microbiology SC Microbiology GA 994WV UT WOS:000307966100001 PM 22691138 ER PT J AU Wexler, DJ Lee, TH AF Wexler, Deborah J. Lee, Thomas H. TI Taking AIM at a Moving Target The Challenge of Improving on High-Performance Care SO CIRCULATION LA English DT Editorial Material DE Editorials; diabetes mellitus; disease management; hypertension ID HEALTH-CARE C1 [Wexler, Deborah J.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Wexler, Deborah J.; Lee, Thomas H.] Harvard Univ, Sch Med, Boston, MA USA. [Lee, Thomas H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wexler, Deborah J.; Lee, Thomas H.] Partners Healthcare Syst, Boston, MA USA. RP Wexler, DJ (reprint author), Massachusetts Gen Hosp, Ctr Diabet, Bulfinch 408A,55 Fruit St, Boston, MA 02114 USA. EM dwexler@partners.org NR 10 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 12 PY 2012 VL 125 IS 23 BP 2812 EP 2814 DI 10.1161/CIRCULATIONAHA.112.110783 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 981NM UT WOS:000306975100017 PM 22570369 ER PT J AU Hattler, B Messenger, JC Shroyer, AL Collins, JF Haugen, SJ Garcia, JA Baltz, JH Cleveland, JC Novitzky, D Grover, FL AF Hattler, Brack Messenger, John C. Shroyer, A. Laurie Collins, Joseph F. Haugen, Scott J. Garcia, Joel A. Baltz, Janet H. Cleveland, Joseph C., Jr. Novitzky, Dimitri Grover, Frederick L. CA Vet Affairs Randomized On Off TI Off-Pump Coronary Artery Bypass Surgery Is Associated With Worse Arterial and Saphenous Vein Graft Patency and Less Effective Revascularization Results From the Veterans Affairs Randomized On/Off Bypass (ROOBY) Trial SO CIRCULATION LA English DT Article DE coronary artery bypass; coronary artery bypass; off-pump ID TERM-FOLLOW-UP; ON-PUMP; LIFE OUTCOMES; HEART; MORTALITY; SURVIVAL; PRAGUE-4; FATE AB Background-The Department of Veterans Affairs Randomized On/Off Bypass (ROOBY) trial compared clinical and angiographic outcomes in off-pump versus on-pump coronary artery bypass graft (CABG) surgery to ascertain the relative efficacy of the 2 techniques. Methods and Results-From February 2002 to May 2007, the ROOBY trial randomized 2203 patients to off-pump versus on-pump CABG. Follow-up angiography was obtained in 685 off-pump (62%) and 685 on-pump (62%) patients. Angiograms were analyzed (blinded to treatment) for FitzGibbon classification (A=widely patent, B=flow limited, O=occluded) and effective revascularization. Effective revascularization was defined as follows: All 3 major coronary territories with significant disease were revascularized by a FitzGibbon A-quality graft to the major diseased artery, and there were no new postanastomotic lesions. Off-pump CABG resulted in lower FitzGibbon A patency rates than on-pump CABG for arterial conduits (85.8% versus 91.4%; P=0.003) and saphenous vein grafts (72.7% versus 80.4%; P<0.001). Fewer off-pump patients were effectively revascularized (50.1% versus 63.9% on-pump; P<0.001). Within each major coronary territory, effective revascularization was worse off pump than on pump (all P<0.001). The 1-year adverse cardiac event rate was 16.4% in patients with ineffective revascularization versus 5.9% in patients with effective revascularization (P<0.001). Conclusions-Off-pump CABG resulted in significantly lower FitzGibbon A patency for arterial and saphenous vein graft conduits and less effective revascularization than on-pump CABG. At 1 year, patients with less effective revascularization had higher adverse event rates. C1 [Hattler, Brack; Shroyer, A. Laurie; Baltz, Janet H.; Cleveland, Joseph C., Jr.; Grover, Frederick L.] Eastern Colorado Hlth Care Syst, Dept Vet Affairs, Denver, CO USA. [Hattler, Brack; Messenger, John C.; Garcia, Joel A.] Univ Colorado Hosp Denver, Dept Med, Aurora, CO USA. [Hattler, Brack; Messenger, John C.; Garcia, Joel A.; Cleveland, Joseph C., Jr.; Grover, Frederick L.] Hlth Sci Ctr, Aurora, CO USA. [Shroyer, A. Laurie] Northport Vet Affairs Med Ctr, Northport, NY USA. [Collins, Joseph F.] Vet Affairs Med Ctr, Cooperat Studies Program Coordinating Ctr, Perry Point, MD USA. [Haugen, Scott J.] Bellevue Med Ctr, Grp Hlth Cooperat, Bellevue, WA USA. [Cleveland, Joseph C., Jr.; Grover, Frederick L.] Univ Colorado Hosp Denver, Dept Surg, Aurora, CO USA. [Novitzky, Dimitri] James A Haley Vet Hosp, Tampa, FL 33612 USA. RP Hattler, B (reprint author), Denver VAMC, 1055 Clermont St,111B, Denver, CO 80220 USA. EM brack.hattler@va.gov RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 FU VA Office of Research and Development; VA Central Office, Office of Patient Care Services; Office of Research and Development at the Eastern Colorado Health Care System; Office of Denver VA Medical Center; Office of Northport VA Medical Center FX This work was supported by the Cooperative Studies Program of the VA Office of Research and Development and the VA Central Office, Office of Patient Care Services, and in part by the Offices of Research and Development at the Eastern Colorado Health Care System, Denver VA Medical Center, and the Northport VA Medical Center. NR 25 TC 74 Z9 79 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 12 PY 2012 VL 125 IS 23 BP 2827 EP 2835 DI 10.1161/CIRCULATIONAHA.111.069260 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 981NM UT WOS:000306975100022 PM 22592900 ER PT J AU Bangalore, S Kumar, S Fusaro, M Amoroso, N Attubato, MJ Feit, F Bhatt, DL Slater, J AF Bangalore, Sripal Kumar, Sunil Fusaro, Mario Amoroso, Nicholas Attubato, Michael J. Feit, Frederick Bhatt, Deepak L. Slater, James TI Short- and Long-Term Outcomes With Drug-Eluting and Bare-Metal Coronary Stents A Mixed-Treatment Comparison Analysis of 117 762 Patient-Years of Follow-Up From Randomized Trials SO CIRCULATION LA English DT Article DE drug-eluting stents; paclitaxel; pannus formation; sirolimus; everolimus; zotarolimus; stents ID ELEVATION MYOCARDIAL-INFARCTION; GLYCOPROTEIN IIB/IIIA INHIBITOR; DE-NOVO LESIONS; ARTERY-DISEASE; CLINICAL-OUTCOMES; DIABETES-MELLITUS; UNCOATED STENTS; INTRAVASCULAR ULTRASOUND; ANGIOGRAPHIC OUTCOMES; MULTICENTER TRIAL AB Background-Drug-eluting stents (DES) have been in clinical use for nearly a decade; however, the relative short- and long-term efficacy and safety of DES compared with bare-metal stents (BMS) and among the DES types are less well defined. Methods and Results-PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized clinical trials, until March 2012, that compared any of the Food and Drug Administration-approved durable stent and polymer DES (sirolimus-eluting stent [SES], paclitaxel-eluting stent [PES], everolimus-eluting stent [EES], zotarolimus-eluting stent [ZES], and ZES-Resolute [ZES-R]) with each other or against BMS for de novo coronary lesions, enrolling at least 100 patients and with follow-up of at least 6 months. Short-term (<= 1 year) and long-term efficacy (target-vessel revascularization, target-lesion revascularization) and safety (death, myocardial infarction, stent thrombosis) outcomes were evaluated and trial-level data pooled by both mixed-treatment comparison and direct comparison analyses. From 76 randomized clinical trials with 117 762 patient-years of follow-up, compared with BMS, each DES reduced long-term target-vessel revascularization (39%-61%), but the magnitude varied by DES type (EES similar to SES similar to ZES-R similar to PES similar to ZES>BMS), with a >42% probability that EES had the lowest target-vessel revascularization rate. There was no increase in the risk of any long-term safety outcomes, including stent thrombosis, with any DES (versus BMS). In addition, there was reduction in myocardial infarction (all DES except PES versus BMS) and stent thrombosis (with EES versus BMS: Rate ratio, 0.51; 95% credibility interval, 0.35-0.73). The safest DES appeared to be EES (>86% probability), with reduction in myocardial infarction and stent thrombosis compared with BMS. Short-term outcomes were similar to long-term outcomes, with SES, ZES-R, and everolimus-eluting stent being the most efficacious and EES being the safest stent. Conclusions-DES are highly efficacious at reducing the risk of target-vessel revascularization without an increase in any safety outcomes, including stent thrombosis. However, among the DES types, there were considerable differences, such that EES, SES, and ZES-R were the most efficacious and EES was the safest stent. (Circulation. 2012;125:2873-2891.) C1 [Bangalore, Sripal] NYU, Sch Med, Cardiac Catheterizat Lab, Leon H Charney Div Cardiol, New York, NY 10016 USA. [Kumar, Sunil] Univ Nebraska, Omaha, NE 68182 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. RP Bangalore, S (reprint author), NYU, Sch Med, Cardiac Catheterizat Lab, Leon H Charney Div Cardiol, New York, NY 10016 USA. EM sripalbangalore@gmail.com RI Bangalore, Sripal/B-6246-2013; OI Slater, James/0000-0003-3888-0317; Bangalore, Sripal/0000-0001-9485-0652; Attubato, Michael/0000-0002-2772-9382 FU Amarin; AstraZeneca; Bristol-Myers Squibb; Eisai; Ethicon; Medtronic; Sanofi-aventis; The Medicines Company FX Dr Bhatt has served on an advisory board for Medscape Cardiology; on the board of directors for Boston VA Research Institute and the Society of Chest Pain Centers; and as the chair of the American Heart Association Get With The Guidelines Science Subcommittee; he also received honoraria from the American College of Cardiology (Editor, Clinical Trials, CardioSource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), WebMD (CME steering committees) and research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi-aventis, and The Medicines Company. He has conducted unfunded research for PLx Pharma and Takeda. Dr Feit is a shareholder of Boston Scientific, Johnson and Johnson, and Medtronic. The other authors report no conflicts. None of the authors received any compensation for their work on this manuscript. NR 141 TC 236 Z9 248 U1 3 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 12 PY 2012 VL 125 IS 23 BP 2873 EP + DI 10.1161/CIRCULATIONAHA.112.097014 PG 43 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 981NM UT WOS:000306975100027 PM 22586281 ER PT J AU Degousee, N Simpson, J Fazel, S Scholich, K Angoulvant, D Angioni, C Schmidt, H Korotkova, M Stefanski, E Wang, XH Lindsay, TF Ofek, E Pierre, S Butany, J Jakobsson, PJ Keating, A Li, RK Nahrendorf, M Geisslinger, G Backx, PH Rubin, BB AF Degousee, Norbert Simpson, Jeremy Fazel, Shafie Scholich, Klaus Angoulvant, Denis Angioni, Carlo Schmidt, Helmut Korotkova, Marina Stefanski, Eva Wang, Xing-Hua Lindsay, Thomas F. Ofek, Efrat Pierre, Sandra Butany, Jagdish Jakobsson, Per-Johan Keating, Armand Li, Ren-Ke Nahrendorf, Matthias Geisslinger, Gerd Backx, Peter H. Rubin, Barry B. TI Lack of Microsomal Prostaglandin E-2 Synthase-1 in Bone Marrow-Derived Myeloid Cells Impairs Left Ventricular Function and Increases Mortality After Acute Myocardial Infarction SO CIRCULATION LA English DT Article DE leukocytes; myocardial infarction; prostaglandins; remodeling; chimeric mice ID CARDIAC MYOCYTES; GASTROINTESTINAL TOXICITY; REPERFUSION INJURY; OXIDATIVE STRESS; BIOSYNTHESIS; MICE; EP4; CYCLOOXYGENASE-1; INHIBITION; EXPRESSION AB Background-Microsomal prostaglandin E-2 synthase-1 (mPGES-1), encoded by the Ptges gene, catalyzes prostaglandin E-2 biosynthesis and is expressed by leukocytes, cardiac myocytes, and cardiac fibroblasts. Ptges(-/-) mice develop more left ventricle (LV) dilation, worse LV contractile function, and higher LV end-diastolic pressure than Ptges(+/+) mice after myocardial infarction. In this study, we define the role of mPGES-1 in bone marrow-derived leukocytes in the recovery of LV function after coronary ligation. Methods and Results-Cardiac structure and function in Ptges(+/+) mice with Ptges(+/+) bone marrow (BM+/+) and Ptges(+/+) mice with Ptges(-/-) BM (BM-/-) were assessed by morphometric analysis, echocardiography, and invasive hemodynamics before and 7 and 28 days after myocardial infarction. Prostaglandin levels and prostaglandin biosynthetic enzyme gene expression were measured by liquid chromatography-tandem mass spectrometry and real-time polymerase chain reaction, immunoblotting, immunohistochemistry, and immunofluorescence microscopy, respectively. After myocardial infarction, BM-/- mice had more LV dilation, worse LV systolic and diastolic function, higher LV end-diastolic pressure, more cardiomyocyte hypertrophy, and higher mortality but similar infarct size and pulmonary edema compared with BM+/+ mice. BM-/- mice also had higher levels of COX-1 protein and more leukocytes in the infarct, but not the viable LV, than BM+/+ mice. Levels of prostaglandin E-2 were higher in the infarct and viable myocardium of BM-/- mice than in BM+/+ mice. Conclusions-Lack of mPGES-1 in bone marrow-derived leukocytes negatively regulates COX-1 expression, prostaglandin E-2 biosynthesis, and inflammation in the infarct and leads to impaired LV function, adverse LV remodeling, and decreased survival after acute myocardial infarction. (Circulation. 2012;125:2904-2913.) C1 [Degousee, Norbert; Stefanski, Eva; Lindsay, Thomas F.; Rubin, Barry B.] Univ Hlth Network, Div Vasc Surg, Peter Munk Cardiac Ctr, Toronto Gen Hosp, Toronto, ON M5G 2C4, Canada. [Fazel, Shafie; Li, Ren-Ke] Univ Hlth Network, Div Cardiac Surg, Peter Munk Cardiac Ctr, Toronto Gen Hosp, Toronto, ON M5G 2C4, Canada. [Backx, Peter H.] Univ Hlth Network, Div Cardiol, Peter Munk Cardiac Ctr, Toronto Gen Hosp, Toronto, ON M5G 2C4, Canada. [Ofek, Efrat; Butany, Jagdish] Univ Hlth Network, Div Pathol, Peter Munk Cardiac Ctr, Toronto Gen Hosp, Toronto, ON M5G 2C4, Canada. [Wang, Xing-Hua; Keating, Armand] Univ Hlth Network, Dept Med Oncol & Hematol, Toronto Gen Hosp, Toronto, ON M5G 2C4, Canada. [Simpson, Jeremy; Backx, Peter H.] Univ Toronto, Dept Physiol, Toronto, ON, Canada. [Simpson, Jeremy; Backx, Peter H.] Univ Toronto, Dept Med, Toronto, ON, Canada. [Scholich, Klaus; Angioni, Carlo; Schmidt, Helmut; Pierre, Sandra; Geisslinger, Gerd] Inst Klin Pharmakol, Frankfurt, Germany. [Angoulvant, Denis] Univ Tours, Ctr Hosp, Trousseau Hosp, Div Cardiol, Tours, France. [Angoulvant, Denis] Univ Tours, EA 4245, Tours, France. [Korotkova, Marina; Jakobsson, Per-Johan] Karolinska Univ Hosp, Rheumatol Unit, Dept Med, Stockholm, Sweden. [Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA USA. RP Rubin, BB (reprint author), Univ Hlth Network, Div Vasc Surg, Peter Munk Cardiac Ctr, Toronto Gen Hosp, 200 Elizabeth St,EN6-222, Toronto, ON M5G 2C4, Canada. EM barry.rubin@uhn.on.ca OI ANGOULVANT, Denis/0000-0003-0788-8092 FU Canadian Institutes of Health Research [53297, 14795]; Swedish Medical Research Council; Swedish Rheumatism Association; Marianne Foundation; Marcus Wallenberg's Foundation; Karolinska Institutet; Deutsche Forschungsgemeinschaft DFG [GE 695]; Excellence Cluster 147 Cardiopulmonary System (ECCPS) FX This study was supported by Canadian Institutes of Health Research grants (53297 to Dr Rubin, 14795 to Drs Li and Fazel), Swedish Medical Research Council, Swedish Rheumatism Association, King Gustaf V 80 Years and Marianne and Marcus Wallenberg's Foundation and Karolinska Institutet (Dr Jakobsson), and Deutsche Forschungsgemeinschaft DFG (GE 695) and Excellence Cluster 147 Cardiopulmonary System (ECCPS, Dr Geisslinger). Dr Keating is the Gloria and Seymour Epstein Chair in Cell Therapy and Transplantation at University Health Network. Dr Rubin is a Wylie Scholar in Academic Vascular Surgery, Foundation for Accelerated Vascular Research, San Francisco and the Peter Munk Cardiac Centre Medical Director Chair. NR 42 TC 8 Z9 10 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 12 PY 2012 VL 125 IS 23 BP 2904 EP + DI 10.1161/CIRCULATIONAHA.112.099754 PG 28 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 981NM UT WOS:000306975100029 PM 22589381 ER PT J AU Rienstra, M Lubitz, SA Mahida, S Magnani, JW Fontes, JD Sinner, MF Van Gelder, IC Ellinor, PT Benjamin, EJ AF Rienstra, Michiel Lubitz, Steven A. Mahida, Saagar Magnani, Jared W. Fontes, Joao D. Sinner, Moritz F. Van Gelder, Isabelle C. Ellinor, Patrick T. Benjamin, Emelia J. TI Symptoms and Functional Status of Patients With Atrial Fibrillation State of the Art and Future Research Opportunities SO CIRCULATION LA English DT Review DE arrhythmia; atrial fibrillation; review; signs and symptoms; exercise ID RHYTHM-MANAGEMENT AFFIRM; RADIOFREQUENCY CATHETER ABLATION; PAROXYSMAL SUPRAVENTRICULAR TACHYCARDIA; PATIENTS RECEIVING AZIMILIDE; PULMONARY-VEIN ABLATION; SINUS-RHYTHM; FOLLOW-UP; ANTIARRHYTHMIC-DRUGS; EXERCISE CAPACITY; HEART-FAILURE C1 [Rienstra, Michiel; Magnani, Jared W.; Fontes, Joao D.; Sinner, Moritz F.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA 01702 USA. [Rienstra, Michiel; Lubitz, Steven A.; Mahida, Saagar; Sinner, Moritz F.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Rienstra, Michiel; Van Gelder, Isabelle C.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Rienstra, Michiel; Magnani, Jared W.; Fontes, Joao D.; Sinner, Moritz F.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Magnani, Jared W.; Fontes, Joao D.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Prevent Med Sect, Dept Med, Boston, MA 02118 USA. [Sinner, Moritz F.] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany. [Van Gelder, Isabelle C.] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Benjamin, EJ (reprint author), Boston Univ, Framingham Heart Study, 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA. EM emelia@bu.edu OI Benjamin, Emelia/0000-0003-4076-2336; Rienstra, Michiel/0000-0002-2581-070X FU Netherlands Organization for Scientific Research [825.09.020]; National Institutes of Health [1RO1HL092577, RO1AG028321, RC1-HL01056, 1R01HL102214, R21, 5R21DA027021, 1RO1HL104156, 1K24HL105780, 6R01-NS 17950, N01-HC 25195]; American Heart Association [09FTF219028]; German Heart Foundation; Netherlands Heart Foundation; Interuniversity Cardiology Institute The Netherlands; AstraZeneca; Biotronik; Medtronic; Sanofi-aventis; Boehringer Ingelheim; St. Jude Medical; Boston Scientific FX Dr Rienstra is supported by a grant from the Netherlands Organization for Scientific Research (Rubicon grant 825.09.020). This work was supported by grants from the National Institutes of Health to Drs Benjamin and Ellinor (1RO1HL092577), Dr Benjamin (RO1AG028321, RC1-HL01056, 1R01HL102214), Drs Magnani (R21) and Benjamin (Evans Center for Interdisciplinary Biomedical Research ARC on Atrial Fibrillation at Boston University [http://www.bumc.bu.edu/evanscenteribr/]), Dr Ellinor (5R21DA027021, 1RO1HL104156, 1K24HL105780), 6R01-NS 17950, and N01-HC 25195. Dr Magnani is supported by American Heart Association Award 09FTF219028. Dr Sinner is supported by the German Heart Foundation. Dr Van Gelder is supported by the Netherlands Heart Foundation, Interuniversity Cardiology Institute The Netherlands, AstraZeneca, Biotronik, Medtronic, Sanofi-aventis, Boehringer Ingelheim, St. Jude Medical, and Boston Scientific. NR 109 TC 38 Z9 38 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 12 PY 2012 VL 125 IS 23 BP 2933 EP 2943 DI 10.1161/CIRCULATIONAHA.111.069450 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 981NM UT WOS:000306975100032 PM 22689930 ER PT J AU Menzaghi, C Salvemini, L Fini, G Thompson, R Mangiacotti, D Di Paola, R Morini, E Giorelli, M De Bonis, C De Cosmo, S Doria, A Trischitta, V AF Menzaghi, Claudia Salvemini, Lucia Fini, Grazia Thompson, Ryan Mangiacotti, Davide Di Paola, Rosa Morini, Eleonora Giorelli, Maddalena De Bonis, Concetta De Cosmo, Salvatore Doria, Alessandro Trischitta, Vincenzo TI Serum Resistin and Kidney Function: A Family-Based Study in Non-Diabetic, Untreated Individuals SO PLOS ONE LA English DT Article ID GLOMERULAR-FILTRATION-RATE; INSULIN-RESISTANCE; RENAL-FUNCTION; CARDIOVASCULAR-DISEASE; CIRCULATING RESISTIN; ADIPONECTIN; ASSOCIATION; CAUCASIANS; INFLAMMATION; LEPTIN AB Background: High serum resistin levels have been associated with kidney dysfunction. Most of these studies have been carried out in individuals with severe kidney impairment, diabetes, cardiovascular disease and related treatments. Thus, the observed association might have been influenced by these confounders. Our aim was to study the relationship between serum resistin, urinary albumin/creatinine ratio (ACR) and glomerular filtration rate (GFR) in a family-based sample, the Gargano Family Study (GFS) of 635 non diabetic, untreated Whites. Methods: A linear mixed effects model and bivariate analyses were used to evaluate the phenotypic and genetic relations between serum resistin and both ACR and eGFR. All analyses were adjusted for sex, age, age squared, BMI, systolic blood pressure, smoking habits and physical exercise. Results: After adjustments, resistin levels were slightly positively associated with ACR (beta +/- SE = 0.049 +/- 0.023, p = 0.035) and inversely related to eGFR (beta +/- SE = 21.43 +/- 0.61, p = 0.018) levels. These associations remained significant when either eGFR or ACR were, reciprocally, added as covariates. A genetic correlation (rho g = -0.31 +/- 0.12; adjusted p = 0.013) was observed between resistin and eGFR (but not ACR) levels. Conclusion: Serum resistin levels are independently associated with ACR and eGFR in untreated non-diabetic individuals. Serum resistin and eGFR share also some common genetic background. Our data strongly suggest that resistin plays a role in modulating kidney function. C1 [Menzaghi, Claudia; Salvemini, Lucia; Fini, Grazia; Mangiacotti, Davide; Di Paola, Rosa; Morini, Eleonora; Giorelli, Maddalena; De Bonis, Concetta; Trischitta, Vincenzo] IRCCS Casa Sollievo Sofferenza San Giovanni Roton, Res Unit Diabet & Endocrine Dis, San Giovanni Rotondo, Italy. [Thompson, Ryan; Doria, Alessandro] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [De Cosmo, Salvatore] IRCCS Casa Sollievo Sofferenza, Unit Endocrinol, San Giovanni Rotondo, Italy. [Doria, Alessandro] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Trischitta, Vincenzo] IRCSS Casa Sollievo Sofferenza,Rome, Mendel Lab, Rome, Italy. [Trischitta, Vincenzo] Univ Roma La Sapienza, Dept Expt Med, I-00185 Rome, Italy. RP Menzaghi, C (reprint author), IRCCS Casa Sollievo Sofferenza San Giovanni Roton, Res Unit Diabet & Endocrine Dis, San Giovanni Rotondo, Italy. EM c.menzaghi@operapadrepio.it; v.trischitta@operapadrepio.it RI Di Paola, Rosa/G-7813-2011; De Cosmo, Salvatore/J-7420-2016; Trischitta, Vincenzo/K-1487-2016; Salvemini, Lucia/K-2121-2016; OI Di Paola, Rosa/0000-0001-5837-9111; De Cosmo, Salvatore/0000-0001-8787-8286; Trischitta, Vincenzo/0000-0003-1174-127X; Salvemini, Lucia/0000-0001-8776-9477; Menzaghi, Claudia/0000-0002-7438-8955 FU Accordo Programma Quadro in Materia di Ricerca Scientifica nella Regione Puglia-PST; Italian Ministry of Health [RC2011]; EFSD/Pfizer; National Institutes of Health [HL073168] FX This study was supported by Accordo Programma Quadro in Materia di Ricerca Scientifica nella Regione Puglia-PST 2006, an Italian Ministry of Health grant (RC2011), a EFSD/Pfizer grant (C. M.) and National Institutes of Health grant HL073168 (A. D.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 10 Z9 10 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 JUN 12 PY 2012 VL 7 IS 6 AR e38414 DI 10.1371/journal.pone.0038414 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959UJ UT WOS:000305340000021 PM 22701635 ER PT J AU Meyerhardt, JA Ancukiewicz, M Abrams, TA Schrag, D Enzinger, PC Chan, JA Kulke, MH Wolpin, BM Goldstein, M Blaszkowsky, L Zhu, AX Elliott, M Regan, E Jain, RK Duda, DG AF Meyerhardt, Jeffrey A. Ancukiewicz, Marek Abrams, Thomas A. Schrag, Deborah Enzinger, Peter C. Chan, Jennifer A. Kulke, Matthew H. Wolpin, Brian M. Goldstein, Michael Blaszkowsky, Lawrence Zhu, Andrew X. Elliott, Meaghan Regan, Eileen Jain, Rakesh K. Duda, Dan G. TI Phase I Study of Cetuximab, Irinotecan, and Vandetanib (ZD6474) as Therapy for Patients with Previously Treated Metastastic Colorectal Cancer SO PLOS ONE LA English DT Article ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; CELL LUNG-CANCER; PLUS IRINOTECAN; ANTIANGIOGENIC THERAPY; ERLOTINIB OSI-774; PTK787/ZK 222584; GASTRIC-CANCER; BEVACIZUMAB; TRIAL AB Background: To determine the maximum tolerated dose (MTD) and safety, and explore efficacy and biomarkers of vandetanib with cetuximab and irinotecan in second-line metastatic colorectal cancer. Methods: Vandetanib (an orally bioavailable VEGFR-2 and EGFR tyrosine kinases inhibitor) was combined at 100 mg, 200 mg, or 300 mg daily with standard dosed cetuximab and irinotecan (3+3 dose-escalation design). Ten patients were treated at the MTD and plasma angiogenesis biomarkers (VEGF, PlGF, bFGF, sVEGFR1, sVEGFR2, IL-1 beta, IL-6, IL-8, TNF-alpha, SDF1 alpha) were measured before and after treatment. Results: Twenty-seven patients were enrolled at 4 dose levels and the MTD. Two dose-limiting toxicities (grade 3 QTc prolongation and diarrhea) were detected at 300 mg of vandetanib with cetuximab and irinotecan resulting in 200 mg being the MTD. Seven percent of patients had a partial response, 59% stable disease and 34% progressed. Median progression-free survival was 3.6 months (95% CI, 3.2-5.6) and median overall survival was 10.5 months (95% CI, 5.1-20.7). Toxicities were fairly manageable with grade 3 or 4 diarrhea being most prominent (30%). Vandetanib and cetuximab treatment induced a sustained increase in plasma PlGF and a transient decrease in plasma sVEGFR1, but no changes in plasma VEGF and sVEGFR2. Conclusions: Vandetanib can be safely combined with cetuximab and irinotecan for metastatic colorectal cancer. Exploratory biomarker analyses suggest differential effects on certain plasma biomarkers for VEGFR inhibition when combined with EGFR blockade and a potential correlation between baseline sVEGFR1 and response. However, while the primary endpoint was safety, the observed efficacy raises concern for moving forward with this combination. C1 [Meyerhardt, Jeffrey A.; Abrams, Thomas A.; Schrag, Deborah; Enzinger, Peter C.; Chan, Jennifer A.; Kulke, Matthew H.; Wolpin, Brian M.; Elliott, Meaghan; Regan, Eileen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ancukiewicz, Marek; Jain, Rakesh K.; Duda, Dan G.] Massachusetts Gen Hosp, Steele Lab Tumor Biol, Dept Radiat Oncol, Boston, MA 02114 USA. [Goldstein, Michael] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Blaszkowsky, Lawrence; Zhu, Andrew X.] Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. RP Meyerhardt, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM jmeyerhardt@partners.org FU Astra-Zeneca; Federal Share/National Cancer Institute Proton Beam Program Income Grants [P01-CA080124]; GI SPORE grant [P50CA127003]; National Foundation for Cancer Research (NFCR) FX This study was supported by Astra-Zeneca and in part by P01-CA080124 (to RKJ), Federal Share/National Cancer Institute Proton Beam Program Income Grants (to RKJ and DGD), and GI SPORE grant P50CA127003. RKJ is funded by the National Foundation for Cancer Research (NFCR) as a NFCR Project Director. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 53 TC 14 Z9 14 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 JUN 12 PY 2012 VL 7 IS 6 AR e38231 DI 10.1371/journal.pone.0038231 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959UJ UT WOS:000305340000015 PM 22701615 ER PT J AU Zamorano, S Rojas-Rivera, D Lisbona, F Parra, V Court, FA Villegas, R Cheng, EH Korsmeyer, SJ Lavandero, S Hetz, C AF Zamorano, Sebastian Rojas-Rivera, Diego Lisbona, Fernanda Parra, Valentina Court, Felipe A. Villegas, Rosario Cheng, Emily H. Korsmeyer, Stanley J. Lavandero, Sergio Hetz, Claudio TI A BAX/BAK and Cyclophilin D-Independent Intrinsic Apoptosis Pathway SO PLOS ONE LA English DT Article ID MITOCHONDRIAL PERMEABILITY TRANSITION; UNFOLDED PROTEIN RESPONSE; BCL-2-RELATED OVARIAN KILLER; ENDOPLASMIC-RETICULUM STRESS; BCL-2 FAMILY-MEMBERS; CELL-DEATH; ER STRESS; CYTOCHROME-C; MEMBRANE PERMEABILIZATION; TRIGGERS APOPTOSIS AB Most intrinsic death signals converge into the activation of pro-apoptotic BCL-2 family members BAX and BAK at the mitochondria, resulting in the release of cytochrome c and apoptosome activation. Chronic endoplasmic reticulum (ER) stress leads to apoptosis through the upregulation of a subset of pro-apoptotic BH3-only proteins, activating BAX and BAK at the mitochondria. Here we provide evidence indicating that the full resistance of BAX and BAK double deficient (DKO) cells to ER stress is reverted by stimulation in combination with mild serum withdrawal. Cell death under these conditions was characterized by the appearance of classical apoptosis markers, caspase-9 activation, release of cytochrome c, and was inhibited by knocking down caspase-9, but insensitive to BCL-XL overexpression. Similarly, the resistance of BIM and PUMA double deficient cells to ER stress was reverted by mild serum withdrawal. Surprisingly, BAX/BAK-independent cell death did not require Cyclophilin D (CypD) expression, an important regulator of the mitochondrial permeability transition pore. Our results suggest the existence of an alternative intrinsic apoptosis pathway emerging from a cross talk between the ER and the mitochondria. C1 [Zamorano, Sebastian; Rojas-Rivera, Diego; Lisbona, Fernanda; Hetz, Claudio] Univ Chile, Biomed Neurosci Inst, Fac Med, Santiago, Chile. [Zamorano, Sebastian; Rojas-Rivera, Diego; Lisbona, Fernanda; Parra, Valentina; Lavandero, Sergio; Hetz, Claudio] Univ Chile, Ctr Mol Studies Cell, Inst Biomed Sci, Santiago, Chile. [Parra, Valentina; Lavandero, Sergio] Univ Chile, Fac Chem & Pharmaceut Sci, Santiago, Chile. [Court, Felipe A.; Villegas, Rosario] P Catholic Univ Chile, Fac Biol, Santiago, Chile. [Cheng, Emily H.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Korsmeyer, Stanley J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Korsmeyer, Stanley J.] Harvard Univ, Sch Med, Boston, MA USA. [Lavandero, Sergio] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Cardiol, Dallas, TX 75390 USA. [Hetz, Claudio] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Hetz, Claudio] Neurounion Biomed Fdn, Santiago, Chile. RP Zamorano, S (reprint author), Univ Chile, Biomed Neurosci Inst, Fac Med, Santiago, Chile. EM chetz@med.uchile.cl RI Court, Felipe/C-5911-2015; Rojas Rivera, Diego/N-1870-2016; Hetz, Claudio/I-1900-2013 OI Rojas Rivera, Diego/0000-0002-8773-9830; Parra, Valentina/0000-0002-0080-6472; Lavandero, Sergio/0000-0003-4258-1483; Hetz, Claudio/0000-0001-7724-1767 FU FONDECYT [1100176, 1070377]; Millennium Institute [P09-015-F]; Michael J. Fox Foundation for Parkinson's Research; North American Spine Society; Muscular Dystrophy Association; ALS Therapy Allianze; FONDAP [15010006]; Millennium Nucleus [P-07-011-F]; National Institute of Health [R01CA125562]; American Cancer Society [RSG-10-030-01-CCG]; CONICYT; Alzheimer's Disease Foundation FX This work was supported by FONDECYT no. 1100176, Millennium Institute no. P09-015-F, Michael J. Fox Foundation for Parkinson's Research, Alzheimer's Disease Foundation, North American Spine Society, Muscular Dystrophy Association, ALS Therapy Allianze (to CH), FONDAP grant no. 15010006 (to CH and SL), Supported by grants from FONDECYT no. 1070377 and Millennium Nucleus no. P-07-011-F (to FC), National Institute of Health R01CA125562 and American Cancer Society RSG-10-030-01-CCG (to EC), and PhD fellowships from CONICYT (to DRR, FL, and VP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 61 TC 15 Z9 17 U1 1 U2 9 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 JUN 12 PY 2012 VL 7 IS 6 AR e37782 DI 10.1371/journal.pone.0037782 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959UJ UT WOS:000305340000005 PM 22719850 ER PT J AU Kleiner, S Mepani, RJ Laznik, D Ye, L Jurczak, MJ Jornayvaz, FR Estall, JL Bhowmick, DC Shulman, GI Spiegelman, BM AF Kleiner, Sandra Mepani, Rina J. Laznik, Dina Ye, Li Jurczak, Michael J. Jornayvaz, Francois R. Estall, Jennifer L. Bhowmick, Diti Chatterjee Shulman, Gerald I. Spiegelman, Bruce M. TI Development of insulin resistance in mice lacking PGC-1 alpha in adipose tissues SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE glucose metabolism; mitochondrial gene expression; thermogenesis; cold exposure; type 2 diabetes ID SKELETAL-MUSCLE; MITOCHONDRIAL BIOGENESIS; ADAPTIVE THERMOGENESIS; OXIDATIVE-PHOSPHORYLATION; GLUCOSE-METABOLISM; OBESE SUBJECTS; EXPRESSION; COACTIVATOR; PGC-1; GENE AB Reduced peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) expression and mitochondrial dysfunction in adipose tissue have been associated with obesity and insulin resistance. Whether this association is causally involved in the development of insulin resistance or is only a consequence of this condition has not been clearly determined. Here we studied the effects of adipose-specific deficiency of PGC-1 alpha on systemic glucose homeostasis. Loss of PGC-1 alpha in white fat resulted in reduced expression of the thermogenic and mitochondrial genes in mice housed at ambient temperature, whereas gene expression patterns in brown fat were not altered. When challenged with a high-fat diet, insulin resistance was observed in the mutant mice, characterized by reduced suppression of hepatic glucose output. Resistance to insulin was also associated with an increase in circulating lipids, along with a decrease in the expression of genes regulating lipid metabolism and fatty acid uptake in adipose tissues. Taken together, these data demonstrate a critical role for adipose PGC-1 alpha in the regulation of glucose homeostasis and a potentially causal involvement in the development of insulin resistance. C1 [Kleiner, Sandra; Mepani, Rina J.; Laznik, Dina; Ye, Li; Estall, Jennifer L.; Bhowmick, Diti Chatterjee; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kleiner, Sandra; Mepani, Rina J.; Laznik, Dina; Ye, Li; Estall, Jennifer L.; Bhowmick, Diti Chatterjee; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Jurczak, Michael J.; Jornayvaz, Francois R.; Shulman, Gerald I.] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. [Jurczak, Michael J.; Jornayvaz, Francois R.; Shulman, Gerald I.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Jurczak, Michael J.; Jornayvaz, Francois R.; Shulman, Gerald I.] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Bruce_Spiegelman@dfci.harvard.edu FU National Institutes of Health [DK54477, DK31405, DK40936, DK059635, DK45735] FX We thank the Harvard histology core facility for assistance with imbedding and processing fat tissue. We also gratefully acknowledge the Yale core metabolism center. This work was supported by National Institutes of Health Grants DK54477 and DK31405 (to B.M.S.) and DK40936, DK059635, and DK45735 (to G.I.S.). NR 51 TC 82 Z9 83 U1 2 U2 15 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 JUN 12 PY 2012 VL 109 IS 24 BP 9635 EP 9640 DI 10.1073/pnas.1207287109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 962AL UT WOS:000305511300084 PM 22645355 ER PT J AU Varetti, G Pellman, D AF Varetti, Gianluca Pellman, David TI "Two" Much of a Good Thing: Telomere Damage-Induced Genome Doubling Drives Tumorigenesis SO CANCER CELL LA English DT Editorial Material ID CONSEQUENCES; TETRAPLOIDY; POLYPLOIDY; MITOSIS; ERRORS C1 [Varetti, Gianluca; Pellman, David] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Varetti, Gianluca; Pellman, David] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Pellman, David] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Pellman, D (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM david_pellman@dfci.harvard.edu FU NIGMS NIH HHS [R01 GM083299] NR 11 TC 2 Z9 2 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUN 12 PY 2012 VL 21 IS 6 BP 712 EP 714 DI 10.1016/j.ccr.2012.05.033 PG 3 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 958TH UT WOS:000305263100002 PM 22698395 ER PT J AU Liu, WJ Monahan, KB Pfefferle, AD Shimamura, T Sorrentino, J Chan, KT Roadcap, DW Ollila, DW Thomas, NE Castrillon, DH Miller, CR Perou, CM Wong, KK Bear, JE Sharpless, NE AF Liu, Wenjin Monahan, Kimberly B. Pfefferle, Adam D. Shimamura, Takeshi Sorrentino, Jessica Chan, Keefe T. Roadcap, David W. Ollila, David W. Thomas, Nancy E. Castrillon, Diego H. Miller, C. Ryan Perou, Charles M. Wong, Kwok-Kin Bear, James E. Sharpless, Norman E. TI LKB1/STK11 Inactivation Leads to Expansion of a Prometastatic Tumor Subpopulation in Melanoma SO CANCER CELL LA English DT Article ID PEUTZ-JEGHERS-SYNDROME; BREAST-CANCER CELLS; KINASE C-YES; LUNG-CANCER; METASTATIC MELANOMA; MALIGNANT-MELANOMA; SOMATIC MUTATIONS; OVARIAN-CANCER; MOUSE MODEL; IN-VIVO AB Germ line mutations in LKB1 (STK11) are associated with the Peutz-Jeghers syndrome (PJS), which includes aberrant mucocutaneous pigmentation, and somatic LKB1 mutations occur in 10% of cutaneous melanoma. By somatically inactivating Lkb1 with K-Ras activation (+/- p53 loss) in murine melanocytes, we observed variably pigmented and highly metastatic melanoma with 100% penetrance. LKB1 deficiency resulted in increased phosphorylation of the SRC family kinase (SFK) YES, increased expression of WNT target genes, and expansion of a CD24(+) cell population, which showed increased metastatic behavior in vitro and in vivo relative to isogenic CD24(-) cells. These results suggest that LKB1 inactivation in the context of RAS activation facilitates metastasis by inducing an SFK-dependent expansion of a prometastatic, CD24(+) tumor subpopulation. C1 [Liu, Wenjin; Monahan, Kimberly B.; Sorrentino, Jessica; Perou, Charles M.; Sharpless, Norman E.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Genet, Sch Med, Chapel Hill, NC 27599 USA. [Pfefferle, Adam D.; Miller, C. Ryan] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Pathol & Lab Med, Sch Med, Chapel Hill, NC 27599 USA. [Chan, Keefe T.; Roadcap, David W.; Bear, James E.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Cell & Dev Biol, Sch Med, Chapel Hill, NC 27599 USA. [Chan, Keefe T.; Bear, James E.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Howard Hughes Med Inst, Sch Med, Chapel Hill, NC 27599 USA. [Sharpless, Norman E.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Med, Sch Med, Chapel Hill, NC 27599 USA. [Thomas, Nancy E.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Dermatol, Sch Med, Chapel Hill, NC 27599 USA. [Ollila, David W.] Univ N Carolina, Sch Med, Div Surg Oncol & Endocrine Surg, Chapel Hill, NC 27599 USA. [Perou, Charles M.] Univ N Carolina, Carolina Genome Sci Ctr, Chapel Hill, NC 27599 USA. [Shimamura, Takeshi] Loyola Univ, Chicago Stritch Sch Med, Dept Mol Pharmacol & Therapeut, Maywood, IL 60153 USA. [Castrillon, Diego H.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Wong, Kwok-Kin] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sharpless, NE (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Genet, Sch Med, Chapel Hill, NC 27599 USA. EM nes@med.unc.edu RI Miller, Ryan/B-9365-2008; OI Miller, Ryan/0000-0002-0096-8762; wong, kwok kin/0000-0001-6323-235X; Perou, Charles/0000-0001-9827-2247 FU UNC; NCI FX The authors wish to thank the UNC Lineberger Comprehensive Cancer Center Mouse Phase 1 Unit for assistance with animal handling and tumor assessment. We thank the UNC gastrointestinal histology and flow cytometry core facilities for assistance. This work was supported by the UNC University Cancer Research Fund, and grants from the NCI. NR 53 TC 53 Z9 53 U1 1 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUN 12 PY 2012 VL 21 IS 6 BP 751 EP 764 DI 10.1016/j.ccr.2012.03.048 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 958TH UT WOS:000305263100008 PM 22698401 ER PT J AU Armstrong, EJ Xing, L Zhang, JZ Zheng, YH Shunk, KA Yeh, RW Farzaneh-Far, R Yu, B Jang, IK AF Armstrong, Ehrin J. Xing, Lei Zhang, Jianzhong Zheng, Yanhua Shunk, Kendrick A. Yeh, Robert W. Farzaneh-Far, Ramin Yu, Bo Jang, Ik-Kyung TI Association Between Leukocyte Telomere Length and Drug-Eluting Stent Strut Coverage by Optical Coherence Tomography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Letter C1 [Yu, Bo] Harbin Med Univ, Affiliated Hosp 2, Harbin 150086, Peoples R China. [Jang, Ik-Kyung] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. EM ijang@partners.org NR 5 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN 12 PY 2012 VL 59 IS 24 BP 2218 EP 2219 DI 10.1016/j.jacc.2012.03.028 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 954FR UT WOS:000304932500014 PM 22676944 ER PT J AU McCabe, JM Armstrong, EJ Kulkarni, A Hoffmayer, KS Bhave, PD Garg, S Patel, A MacGregor, JS Hsue, P Stein, JC Kinlay, S Ganz, P AF McCabe, James M. Armstrong, Ehrin J. Kulkarni, Ameya Hoffmayer, Kurt S. Bhave, Prashant D. Garg, Sonia Patel, Ateet MacGregor, John S. Hsue, Priscilla Stein, John C. Kinlay, Scott Ganz, Peter TI Prevalence and Factors Associated With False-Positive ST-Segment Elevation Myocardial Infarction Diagnoses at Primary Percutaneous Coronary Intervention-Capable Centers A Report From the Activate-SF Registry SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID DOOR-TO-BALLOON; CATHETERIZATION LABORATORY ACTIVATION; EMERGENCY-DEPARTMENT; REDUCES DOOR; TIME; CARDIOLOGY; TEAM; IMPACT AB Background: Rapid activation of the cardiac catheterization laboratory for primary percutaneous coronary intervention (PCI) improves outcomes for ST-segment elevation myocardial infarction (STEMI), but selected emphasis on minimizing time to reperfusion may lead to a greater frequency of false-positive activations. Methods: We analyzed consecutive patients referred for primary PCI for a possible STEMI at 2 centers from October 2008 to April 2011. "False-positive STEMI activation" was defined as lack of a culprit lesion by angiography or by assessment of clinical, electrocardiographic, and biomarker data in the absence of angiography. Clinical and electrocardiographic factors associated with false-positive activations were evaluated in a backward stepwise selection bootstrapped logistic regression model. Results: Of 411 STEMI activations by emergency physicians, 146 (36%) were deemed to be false-positive activations. Structural heart disease and heart failure were the most common diagnoses among false-positive activations. Electrocardiographic left ventricular hypertrophy (adjusted odds ratio [AOR], 3.15; 95% CI, 1.556.40; P = .001), a history of coronary disease (AOR, 1.93; 95% CI, 1.04-3.59; P = .04), or prior illicit drug abuse (AOR, 2.67; 95% CI, 1.13-6.26; P = .02) independently increased the odds of false-positive STEMI activations. Increasing body mass index decreased the odds of a false-positive activation (AOR, 0.91; 95% CI, 0.86-0.97; P =. 004), as did angina at presentation (AOR, 0.28; 95% CI, 0.14-0.57; P < .001). Conclusions: More than a third of patients referred for primary PCI from the emergency department did not have a STEMI. Multiple patient-level characteristics were significantly associated with an increased odds of false-positive STEMI activation. C1 [McCabe, James M.; Kinlay, Scott] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. [McCabe, James M.; Kinlay, Scott] Harvard Univ, Sch Med, Boston, MA USA. [Armstrong, Ehrin J.] Univ Calif Davis, Div Cardiol, Davis, CA 95616 USA. [Kulkarni, Ameya; Hoffmayer, Kurt S.; MacGregor, John S.; Hsue, Priscilla; Ganz, Peter] Univ Calif San Francisco, Div Cardiol, San Francisco, CA USA. [Garg, Sonia; Patel, Ateet] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Stein, John C.] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA. [Bhave, Prashant D.] Northwestern Univ, Div Cardiol, Chicago, IL 60611 USA. [MacGregor, John S.; Hsue, Priscilla; Ganz, Peter] San Francisco Gen Hosp, Div Cardiol, San Francisco, CA 94110 USA. [Kinlay, Scott] VA Boston Healthcare Syst, Div Cardiovasc, W Roxbury, MA USA. RP McCabe, JM (reprint author), Brigham & Womens Hosp, Div Cardiol, Shapiro 5,75 Francis St, Boston, MA 02115 USA. EM mccabe@aya.yale.edu NR 30 TC 36 Z9 36 U1 3 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 11 PY 2012 VL 172 IS 11 BP 864 EP 871 DI 10.1001/archinternmed.2012.945 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 956KD UT WOS:000305087600009 PM 22566489 ER PT J AU Jena, AB Chandra, A Lakdawalla, D Seabury, S AF Jena, Anupam B. Chandra, Amitabh Lakdawalla, Darius Seabury, Seth TI Outcomes of Medical Malpractice Litigation Against US Physicians SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter C1 [Jena, Anupam B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wang Ambulatory Care Ctr,Dept Med, Boston, MA 02114 USA. [Chandra, Amitabh] Harvard Univ, John F Kennedy Sch Govt, Cambridge, MA 02138 USA. [Lakdawalla, Darius] Univ So Calif, Schaeffer Ctr Hlth Policy & Econ, Sol Price Sch Publ Policy, Los Angeles, CA USA. [Seabury, Seth] RAND Corp, Santa Monica, CA USA. RP Jena, AB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wang Ambulatory Care Ctr,Dept Med, 15 Parkman St, Boston, MA 02114 USA. EM jena.anupam@mgh.harvard.edu OI Lakdawalla, Darius/0000-0001-5934-8042 FU NIA NIH HHS [1RC4AG039036-01, 5P30AG024968, 7R01AG031544, P01 AG19783-02] NR 5 TC 29 Z9 29 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 11 PY 2012 VL 172 IS 11 BP 892 EP 894 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 956KD UT WOS:000305087600016 PM 22825616 ER PT J AU Ruan, GX Gamble, KL Risner, ML Young, LA McMahon, DG AF Ruan, Guo-Xiang Gamble, Karen L. Risner, Michael L. Young, Laurel A. McMahon, Douglas G. TI Divergent Roles of Clock Genes in Retinal and Suprachiasmatic Nucleus Circadian Oscillators SO PLOS ONE LA English DT Article ID SLEEP PHASE SYNDROME; MAMMALIAN RETINA; PHOTORECEPTOR DEGENERATION; MOUSE RETINA; DOPAMINE; RHYTHMS; POLYMORPHISM; MELATONIN; NEURONS; SYSTEM AB The retina is both a sensory organ and a self-sustained circadian clock. Gene targeting studies have revealed that mammalian circadian clocks generate molecular circadian rhythms through coupled transcription/translation feedback loops which involve 6 core clock genes, namely Period (Per) 1 and 2, Cryptochrome (Cry) 1 and 2, Clock, and Bmal1 and that the roles of individual clock genes in rhythms generation are tissue-specific. However, the mechanisms of molecular circadian rhythms in the mammalian retina are incompletely understood and the extent to which retinal neural clocks share mechanisms with the suprachiasmatic nucleus (SCN), the central neural clock, is unclear. In the present study, we examined the rhythmic amplitude and period of real-time bioluminescence rhythms in explants of retina from Per1-, Per2-, Per3-, Cry1-, Cry2-, and Clock-deficient mice that carried transgenic PERIOD2:: LUCIFERASE (PER2::LUC) or Period1::luciferase (Per1::luc) circadian reporters. Per1-, Cry1- and Clock-deficient retinal and SCN explants showed weakened or disrupted rhythms, with stronger effects in retina compared to SCN. Per2, Per3, and Cry2 were individually dispensable for sustained rhythms in both tissues. Retinal and SCN explants from double knockouts of Cry1 and Cry2 were arrhythmic. Gene effects on period were divergent with reduction in the number of Per1 alleles shortening circadian period in retina, but lengthening it in SCN, and knockout of Per3 substantially shortening retinal clock period, but leaving SCN unaffected. Thus, the retinal neural clock has a unique pattern of clock gene dependence at the tissue level that it is similar in pattern, but more severe in degree, than the SCN neural clock, with divergent clock gene regulation of rhythmic period. C1 [Ruan, Guo-Xiang; Gamble, Karen L.; Risner, Michael L.; Young, Laurel A.; McMahon, Douglas G.] Vanderbilt Univ, Dept Biol Sci, Nashville, TN USA. RP Ruan, GX (reprint author), Harvard Univ, Schepens Eye Res Inst, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. EM douglas.g.mcmahon@vanderbilt.edu OI Risner, Michael/0000-0002-8399-5036; Gamble, Karen/0000-0003-3813-8577 FU National Eye Institute [R01 EY15815] FX The work was funded by the National Eye Institute (R01 EY15815), www.nei.nih.gov/. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 20 Z9 20 U1 1 U2 14 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 JUN 11 PY 2012 VL 7 IS 6 AR e38985 DI 10.1371/journal.pone.0038985 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959TU UT WOS:000305337600063 PM 22701739 ER PT J AU Janne, PA Wang, XF Socinski, MA Crawford, J Stinchcombe, TE Gu, L Capelletti, M Edelman, MJ Villalona-Calero, MA Kratzke, R Vokes, EE Miller, VA AF Jaenne, Pasi A. Wang, Xiaofei Socinski, Mark A. Crawford, Jeffrey Stinchcombe, Thomas E. Gu, Lin Capelletti, Marzia Edelman, Martin J. Villalona-Calero, Miguel A. Kratzke, Robert Vokes, Everett E. Miller, Vincent A. TI Randomized Phase II Trial of Erlotinib Alone or With Carboplatin and Paclitaxel in Patients Who Were Never or Light Former Smokers With Advanced Lung Adenocarcinoma: CALGB 30406 Trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; METASTATIC BREAST-CANCER; 1ST-LINE TREATMENT; KINASE INHIBITORS; GENE-MUTATIONS; CHEMOTHERAPY; GEFITINIB; EGFR; BEVACIZUMAB; EFFICACY AB Purpose Erlotinib is clinically effective in patients with non-small-cell lung cancer (NSCLC) who have adenocarcinoma, are never or limited former smokers, or have EGFR mutant tumors. We investigated the efficacy of erlotinib alone or in combination with chemotherapy in patients with these characteristics. Patients and Methods Patients with advanced NSCLC (adenocarcinoma) who were epidermal growth factor receptor tyrosine kinase inhibitor and chemotherapy naive never or light former smokers (smokers of > 100 cigarettes and <= 10 pack years and quit >= 1 year ago) were randomly assigned to continuous erlotinib or in combination with carboplatin and paclitaxel (ECP) for six cycles followed by erlotinib alone. The primary end point was progression-free survival (PFS). Tissue collection was mandatory. Results PFS was similar (5.0 v 6.6 months; P = .1988) in patients randomly assigned to erlotinib alone (arm A; n = 81) or to ECP (arm B; n = 100). EGFR mutation analysis was possible in 91% (164 of 181) of patients, and EGFR mutations were detected in 40% (51 of 128) of never smokers and in 42% (15 of 36) of light former smokers. In arm A, response rate (70% v 9%), PFS (14.1 v 2.6 months), and overall survival (OS; 31.3 v 18.1 month) favored EGFR-mutant patients. In arm B, response rate (73% v 30%), PFS (17.2 v 4.8 months), and OS (38.1 v 14.4 months) favored EGFR-mutant patients. Incidence of grades 3 to 4 hematologic (2% v 49%; P < .001) and nonhematologic (24% v 52%; P < .001) toxicity was greater in patients treated with ECP. Conclusion Erlotinib and erlotinib plus chemotherapy have similar efficacy in clinically selected populations of patients with advanced NSCLC. EGFR mutations identify patients most likely to benefit. C1 [Jaenne, Pasi A.; Capelletti, Marzia] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Wang, Xiaofei; Crawford, Jeffrey; Gu, Lin] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Socinski, Mark A.; Stinchcombe, Thomas E.] Univ N Carolina, Chapel Hill, NC USA. [Edelman, Martin J.] Univ Maryland, Baltimore, MD 21201 USA. [Villalona-Calero, Miguel A.] Ohio State Univ, Columbus, OH 43210 USA. [Kratzke, Robert] Univ Minnesota, Minneapolis, MN USA. [Vokes, Everett E.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Miller, Vincent A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 450 Brookline Ave,M422, Boston, MA 02115 USA. EM pjanne@partners.org FU Genentech; Pfizer; GlaxoSmithKline; Synta Pharmaceuticals; Boehringer Ingelheim; ImClone Systems; Novartis FX Mark A. Socinski, Genentech; Thomas E. Stinchcombe, Genentech, Pfizer, GlaxoSmithKline, Synta Pharmaceuticals; Miguel A. Villalona-Calero, Genentech; Vincent A. Miller, Boehringer Ingelheim, Genentech, ImClone Systems, Novartis, Pfizer NR 29 TC 91 Z9 96 U1 0 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 10 PY 2012 VL 30 IS 17 BP 2063 EP 2069 DI 10.1200/JCO.2011.40.1315 PG 7 WC Oncology SC Oncology GA 957KB UT WOS:000305159200011 PM 22547605 ER PT J AU Kuhlthau, KA Pulsifer, MB Yeap, BY Morales, DR Delahaye, J Hill, KS Ebb, D Abrams, AN MacDonald, SM Tarbell, NJ Yock, TI AF Kuhlthau, Karen A. Pulsifer, Margaret B. Yeap, Beow Y. Morales, Dianali Rivera Delahaye, Jennifer Hill, Kristen S. Ebb, David Abrams, Annah N. MacDonald, Shannon M. Tarbell, Nancy J. Yock, Torunn I. TI Prospective Study of Health-Related Quality of Life for Children With Brain Tumors Treated With Proton Radiotherapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT Conference of the International-Society-for-Quality-of-Life-Research CY OCT 28-31, 2009 CL New Orleans, LA SP Int Soc Qual Life Res ID GENERIC CORE SCALES; PARENT PROXY-REPORTS; PEDIATRIC-PATIENTS; RADIATION-DOSIMETRY; RELIABILITY; VALIDITY; PEDSQL(TM)-4.0; THERAPY; CANCER; MEDULLOBLASTOMA AB Purpose We describe the health-related quality of life (HRQoL) of a cohort of children with brain tumors treated with proton radiotherapy. Patients and Methods We recruited 142 pediatric patients with brain tumors (age 2 to 18 years) and parents of such patients treated with proton radiation at Massachusetts General Hospital from 2004 to 2010. HRQoL was assessed using the PedsQL core, brain tumor, and cancer modules (range, 0 to 100). Assessments took place during radiation and annually thereafter. We examined correlations of HRQoL with disease, treatment, and cognitive and behavioral data. Results Overall reports of HRQoL during treatment were 74.8 and 78.1 for child self-report (CSR) and 67.0 and 74.8 for parent proxy report (PPR) for the core and brain tumor modules, respectively. PPR demonstrated lower HRQoL scores than CSR, but the two were highly correlated. Higher HRQoL scores were significantly associated with Wechsler Full Scale Intelligence Quotient scores (administered via the age-appropriate version) and better scores on two behavioral measures. Disease type also correlated with PPR core total HRQoL score at the beginning of treatment: medulloblastoma or primitive neuroectodermal tumors, 57.8; germ cell tumors, 63.5; ependymoma or high-grade glioma, 69.8; low-grade glioma, 71.5; and other low-grade neoplasms, 78.0 (P = .001). Craniospinal irradiation and chemotherapy were negatively correlated with HRQoL. Conclusion This is the first study to our knowledge of HRQoL in a cohort of children with brain tumors treated with proton radiation. This prospective study demonstrates the effect of disease type and intensity of treatment on HRQoL. It further suggests that where CSR is not possible, PPR is appropriate in most circumstances. C1 [Kuhlthau, Karen A.; Pulsifer, Margaret B.; Yeap, Beow Y.; Morales, Dianali Rivera; Delahaye, Jennifer; Hill, Kristen S.; Ebb, David; Abrams, Annah N.; MacDonald, Shannon M.; Tarbell, Nancy J.; Yock, Torunn I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kuhlthau, Karen A.; Pulsifer, Margaret B.; Yeap, Beow Y.; Ebb, David; Abrams, Annah N.; MacDonald, Shannon M.; Tarbell, Nancy J.; Yock, Torunn I.] Harvard Univ, Sch Med, Boston, MA USA. RP Kuhlthau, KA (reprint author), Massachusetts Gen Hosp, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM kkuhlthau@partners.org FU NCI NIH HHS [P01 CA021239, P01CA021239] NR 27 TC 29 Z9 30 U1 0 U2 7 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 10 PY 2012 VL 30 IS 17 BP 2079 EP 2086 DI 10.1200/JCO.2011.37.0577 PG 8 WC Oncology SC Oncology GA 957KB UT WOS:000305159200013 PM 22565004 ER PT J AU List, AF Baer, MR Steensma, DP Raza, A Esposito, J Martinez-Lopez, N Paley, C Feigert, J Besa, E AF List, Alan F. Baer, Maria R. Steensma, David P. Raza, Azra Esposito, Jason Martinez-Lopez, Noelia Paley, Carole Feigert, John Besa, Emmanuel TI Deferasirox Reduces Serum Ferritin and Labile Plasma Iron in RBC Transfusion-Dependent Patients With Myelodysplastic Syndrome SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CLINICAL EXPRESSION; OVERLOAD; HEMOCHROMATOSIS; POPULATION; REQUIREMENTS; SURVIVAL; CRITERIA; ANEMIA AB Purpose This 3-year, prospective, multicenter trial assessed the safety and efficacy of deferasirox in low-or intermediate-1-risk myelodysplastic syndrome (MDS). Patients and Methods Eligible patients had serum ferritin >= 1,000 mu g/L and had received >= 20 units of RBCs with ongoing transfusion requirements. The starting dose of deferasirox was 20 mg/kg/d, with dose escalation up to 40 mg/kg/d permitted. Results A total of 176 patients were enrolled, and 173 patients received therapy. Median serum ferritin decreased 23% in the 53% of patients who completed 12 months of treatment (n = 91), 36.7% in patients who completed 2 years (n = 49), and 36.5% in patients who completed 3 years (n = 33) despite continued transfusion requirement. Reduction in serum ferritin significantly correlated with ALT improvement (P < .001). Labile plasma iron (LPI) was measured quarterly during the first year of the study. Sixty-eight patients (39.3%) had elevated LPI at baseline. By week 13, LPI levels normalized in all patients with abnormal baseline level. Fifty-one (28%) of 173 patients experienced hematologic improvement by International Working Group 2006 criteria; of these, only seven patients received growth factors or MDS therapy. Over the 3-year study, 138 (79.8%) of 173 patients discontinued therapy, 43 patients (24.8%) because of adverse events or disease progression and 23 patients (13.2%) because of abnormal laboratory values. The most common drug-related adverse events were gastrointestinal disturbances and increased serum creatinine. There were 28 deaths, none of which were considered related to deferasirox. Conclusion Deferasirox reduces serum ferritin and LPI in transfusion-dependent patients with MDS. A subset of patients had an improvement in hematologic and hepatic parameters. C1 [List, Alan F.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Baer, Maria R.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Raza, Azra] Columbia Univ, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. [Esposito, Jason; Martinez-Lopez, Noelia; Paley, Carole] Nova Pharmaceut Corp, E Hanover, NJ USA. [Feigert, John] Fairfax No Virginia Hematol Oncol, Arlington, VA USA. [Besa, Emmanuel] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. RP List, AF (reprint author), H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM alan.list@moffitt.org OI Steensma, David/0000-0001-5130-9284 FU Novartis Pharmaceuticals; Novartis; Emmanuel Besa; Celgene FX Supported by Novartis Pharmaceuticals.; Alan F. List, Novartis; Emmanuel Besa, Celgene, Novartis NR 24 TC 65 Z9 67 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 JUN 10 PY 2012 VL 30 IS 17 BP 2134 EP 2139 DI 10.1200/JCO.2010.34.1222 PG 6 WC Oncology SC Oncology GA 957KB UT WOS:000305159200020 PM 22547607 ER PT J AU Greer, JA Muzikansky, A Pirl, WF Temel, JS AF Greer, Joseph A. Muzikansky, Alona Pirl, William F. Temel, Jennifer S. TI Exploring the Benefits of Early Access to Palliative Care in Advanced Lung Cancer: Living Better, Living Longer, or Both? Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 [Greer, Joseph A.; Pirl, William F.; Temel, Jennifer S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Greer, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 10 PY 2012 VL 30 IS 17 BP 2164 EP 2164 DI 10.1200/JCO.2012.42.1297 PG 1 WC Oncology SC Oncology GA 957KB UT WOS:000305159200026 ER PT J AU Sepucha, KR Belkora, JK Chang, YC Cosenza, C Levin, CA Moy, B Partridge, A Lee, CN AF Sepucha, Karen R. Belkora, Jeffrey K. Chang, Yuchiao Cosenza, Carol Levin, Carrie A. Moy, Beverly Partridge, Ann Lee, Clara N. TI Measuring decision quality: psychometric evaluation of a new instrument for breast cancer surgery SO BMC MEDICAL INFORMATICS AND DECISION MAKING LA English DT Article ID RANDOMIZED-TRIAL; OLDER WOMEN; INFORMED DECISION; MASTECTOMY; AID; PARTICIPATION; INVOLVEMENT; CHOICE; CARCINOMA; KNOWLEDGE AB Background: The purpose of this paper is to examine the acceptability, feasibility, reliability and validity of a new decision quality instrument that assesses the extent to which patients are informed and receive treatments that match their goals. Methods: Cross-sectional mail survey of recent breast cancer survivors, providers and healthy controls and a retest survey of survivors. The decision quality instrument includes knowledge questions and a set of goals, and results in two scores: a breast cancer surgery knowledge score and a concordance score, which reflects the percentage of patients who received treatments that match their goals. Hypotheses related to acceptability, feasibility, discriminant validity, content validity, predictive validity and retest reliability of the survey instrument were examined. Results: We had responses from 440 eligible patients, 88 providers and 35 healthy controls. The decision quality instrument was feasible to implement in this study, with low missing data. The knowledge score had good retest reliability (intraclass correlation coefficient = 0.70) and discriminated between providers and patients (mean difference 35%, p < 0.001). The majority of providers felt that the knowledge items covered content that was essential for the decision. Five of the 6 treatment goals met targets for content validity. The five goals had moderate to strong retest reliability (0.64 to 0.87). The concordance score was 89%, indicating that a majority had treatments concordant with that predicted by their goals. Patients who had concordant treatment had similar levels of confidence and regret as those who did not. Conclusions: The decision quality instrument met the criteria of feasibility, reliability, discriminant and content validity in this sample. Additional research to examine performance of the instrument in prospective studies and more diverse populations is needed. C1 [Sepucha, Karen R.; Chang, Yuchiao] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Sepucha, Karen R.; Chang, Yuchiao; Moy, Beverly; Partridge, Ann] Harvard Univ, Sch Med, Boston, MA USA. [Belkora, Jeffrey K.] Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA USA. [Cosenza, Carol] Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. [Levin, Carrie A.] Informed Med Decis Fdn, Boston, MA USA. [Moy, Beverly] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Partridge, Ann] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Lee, Clara N.] Univ N Carolina, Sheps Ctr Hlth Serv Res, Div Plast & Reconstruct Surg, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Sepucha, KR (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th floor, Boston, MA 02114 USA. EM ksepucha@partners.org FU Informed Medical Decision Foundation; NIH [1KL2RR025746] FX The study was funded by the Informed Medical Decision Foundation. Dr. Lee was also supported by the NIH 1KL2RR025746. The authors would like to acknowledge the contributions of the patients, providers and other respondents whose participation made this research possible. In addition, we would like to acknowledge the contributions of the project manager, Sandra Feibelmann and the research coordinators at each site including Nesochi Adimora, Sandra Kereakoglow, Ekeoma Uzogara, Shelley Volz, and Theresa Yang. NR 39 TC 18 Z9 18 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6947 J9 BMC MED INFORM DECIS JI BMC Med. Inform. Decis. Mak. PD JUN 8 PY 2012 VL 12 AR 51 DI 10.1186/1472-6947-12-51 PG 10 WC Medical Informatics SC Medical Informatics GA 984YB UT WOS:000307228500001 PM 22681763 ER PT J AU Lustgarten, MS Bhattacharya, A Muller, FL Jang, YC Shimizu, T Shirasawa, T Richardson, A Van Remmen, H AF Lustgarten, Michael S. Bhattacharya, Arunabh Muller, Florian L. Jang, Youngmok C. Shimizu, Takahiko Shirasawa, Takuji Richardson, Arlan Van Remmen, Holly TI Complex I generated, mitochondrial matrix-directed superoxide is released from the mitochondria through voltage dependent anion channels SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Mitochondria; Superoxide; Voltage dependent anion channels ID BENZODIAZEPINE-RECEPTOR; SKELETAL-MUSCLE; OXIDATIVE STRESS; CELL-DEATH; MEMBRANES; PERMEABILITY; DISMUTASE; DIPHENYLENEIODONIUM; PROTEIN; CYTOSOL AB Mitochondrial complex I has previously been shown to release superoxide exclusively towards the mitochondrial matrix, whereas complex III releases superoxide to both the matrix and the cytosol. Superoxide produced at complex III has been shown to exit the mitochondria through voltage dependent anion channels (VDAC). To test whether complex I-derived, mitochondrial matrix-directed superoxide can be released to the cytosol, we measured superoxide generation in mitochondria isolated from wild type and from mice genetically altered to be deficient in MnSOD activity (TnIFastCreSod2(fl/fl)). Under experimental conditions that produce superoxide primarily by complex I (glutamate/malate plus rotenone, GM + R), MnSOD-deficient mitochondria release similar to 4-fold more superoxide than mitochondria isolated from wild type mice. Exogenous CuZnSOD completely abolished the EPR-derived GM + R signal in mitochondria isolated from both genotypes, evidence that confirms mitochondrial superoxide release. Addition of the VDAC inhibitor DIDS significantly reduced mitochondrial superoxide release (similar to 75%) in mitochondria from either genotype respiring on GM + R. Conversely, inhibition of potential inner membrane sites of superoxide exit, including the matrix face of the mitochondrial permeability transition pore and the inner membrane anion channel did not reduce mitochondrial superoxide release in the presence of GM + R in mitochondria isolated from either genotype. These data support the concept that complex I-derived mitochondrial superoxide release does indeed occur and that the majority of this release occurs through VDACs. (C) 2012 Elsevier Inc. All rights reserved. C1 [Lustgarten, Michael S.; Bhattacharya, Arunabh; Muller, Florian L.; Jang, Youngmok C.; Richardson, Arlan; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Bhattacharya, Arunabh; Muller, Florian L.; Jang, Youngmok C.; Richardson, Arlan; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Richardson, Arlan; Van Remmen, Holly] S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX USA. [Shimizu, Takahiko] Chiba Univ, Grad Sch Med, Dept Adv Aging Med, Chiba, Japan. [Shirasawa, Takuji] Juntendo Univ, Grad Sch Med, Dept Aging Control Med, Tokyo, Japan. RP Van Remmen, H (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, 15355 Lambda Dr, San Antonio, TX 78229 USA. EM vanremmen@uthscsa.edu FU NIH [P01 AG020591]; NIA [5T3-AG021890-02] FX This work was funded by NIH Grant P01 AG020591 (to H.V.R.) and NIA Training Grant 5T3-AG021890-02. NR 30 TC 30 Z9 30 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 8 PY 2012 VL 422 IS 3 BP 515 EP 521 DI 10.1016/j.bbrc.2012.05.055 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 974NT UT WOS:000306443800027 PM 22613204 ER PT J AU Santa-Maria, I Varghese, M Ksiezak-Reding, H Dzhun, A Wang, J Pasinetti, GM AF Santa-Maria, Ismael Varghese, Merina Ksiezak-Reding, Hanna Dzhun, Anastasiya Wang, Jun Pasinetti, Giulio M. TI Paired Helical Filaments from Alzheimer Disease Brain Induce Intracellular Accumulation of Tau Protein in Aggresomes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROGRESSIVE SUPRANUCLEAR PALSY; SEED POLYPHENOLIC EXTRACT; NEURONAL CELLS; NEUROFIBRILLARY DEGENERATION; NEURODEGENERATIVE DISEASES; EXTRACELLULAR TAU; ALPHA-SYNUCLEIN; EXOSOMES; TAUOPATHY; MODEL AB Abnormal folding of tau protein leads to the generation of paired helical filaments (PHFs) and neurofibrillary tangles, a key neuropathological feature in Alzheimer disease and tauopathies. A specific anatomical pattern of pathological changes developing in the brain suggests that once tau pathology is initiated it propagates between neighboring neuronal cells, possibly spreading along the axonal network. We studied whether PHFs released from degenerating neurons could be taken up by surrounding cells and promote spreading of tau pathology. Neuronal and non-neuronal cells overexpressing green fluorescent protein-tagged tau (GFP-Tau) were treated with isolated fractions of human Alzheimer disease-derived PHFs for 24 h. We found that cells internalized PHFs through an endocytic mechanism and developed intracellular GFP-Tau aggregates with attributes of aggresomes. This was particularly evident by the perinuclear localization of aggregates and redistribution of the vimentin intermediate filament network and retrograde motor protein dynein. Furthermore, the content of Sarkosyl-insoluble tau, a measure of abnormal tau aggregation, increased 3-fold in PHF-treated cells. An exosome-related mechanism did not appear to be involved in the release of GFP-Tau from untreated cells. The evidence that cells can internalize PHFs, leading to formation of aggresome-like bodies, opens new therapeutic avenues to prevent propagation and spreading of tau pathology. C1 [Santa-Maria, Ismael; Varghese, Merina; Ksiezak-Reding, Hanna; Dzhun, Anastasiya; Wang, Jun; Pasinetti, Giulio M.] Mt Sinai Sch Med, Ctr Excellence Res Complementary & Alternat Med A, Ctr Excellence Novel Approaches Neurodiagnost & N, Brain Inst,Dept Neurol, New York, NY 10029 USA. [Varghese, Merina; Ksiezak-Reding, Hanna; Dzhun, Anastasiya; Pasinetti, Giulio M.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY 10468 USA. [Santa-Maria, Ismael] Queen Sofia Fdn, Ctr Invest Enfermedades Neurol Fdn, Alzheimer Dis Res Unit, Madrid 28031, Spain. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Ctr Excellence Res Complementary & Alternat Med A, Ctr Excellence Novel Approaches Neurodiagnost & N, Brain Inst,Dept Neurol, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu OI Varghese, Merina/0000-0002-1517-3903 FU NCI, National Institutes of Health [5R24 CA095823-04, PO1 AT004511]; National Institutes of Health Shared Instrumentation [1 S10 RR0 9145-01]; Society for Progressive Supranuclear Palsy; Veterans Affairs merit review grant; National Science Foundation Major Research Instrumentation [DBI-9724504] FX Confocal laser scanning microscopy was performed at the James J. Peters Veteran Affairs Medical Center and conventional fluorescence microscopy was performed at the Mount Sinai School of Medicine Microscopy Shared Resource Facility supported with funding from NCI, National Institutes of Health Shared Resource Grant 5R24 CA095823-04, National Science Foundation Major Research Instrumentation Grant DBI-9724504, and National Institutes of Health Shared Instrumentation Grant 1 S10 RR0 9145-01. We thank Jesus Avila (Universidad Auto noma de Madrid, Madrid, Spain) for help with preparing GFP and GFP-Tau plasmids. We also thank Miguel Gama-Sosa (Mount Sinai School of Medicine, New York, NY) for lending his expertise in confocal microscopy.; This work was supported, in whole or in part, by National Institutes of Health Grant PO1 AT004511 (to G. M. P.). This work was also supported by the Society for Progressive Supranuclear Palsy and in part by Veterans Affairs merit review grant (to G. M. P.). Dr. Pasinetti has filed a patent application (pending) through Mount Sinai School of Medicine related to grape seed polyphenolic extract. In the event that the pending patent is licensed, Dr. Pasinetti would be entitled to a share of any proceeds Mount Sinai School of Medicine receives from the license. NR 67 TC 43 Z9 45 U1 0 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 8 PY 2012 VL 287 IS 24 BP 20522 EP 20533 DI 10.1074/jbc.M111.323279 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 974FB UT WOS:000306414500073 PM 22496370 ER PT J AU Smith, KR Damiano, J Franceschetti, S Carpenter, S Canafoglia, L Morbin, M Rossi, G Pareyson, D Mole, SE Staropoli, JF Sims, KB Lewis, J Lin, WL Dickson, DW Dahl, HH Bahlo, M Berkovic, SF AF Smith, Katherine R. Damiano, John Franceschetti, Silvana Carpenter, Stirling Canafoglia, Laura Morbin, Michela Rossi, Giacomina Pareyson, Davide Mole, Sara E. Staropoli, John F. Sims, Katherine B. Lewis, Jada Lin, Wen-Lang Dickson, Dennis W. Dahl, Hans-Henrik Bahlo, Melanie Berkovic, Samuel F. TI Strikingly Different Clinicopathological Phenotypes Determined by Progranulin-Mutation Dosage SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID FRONTOTEMPORAL LOBAR DEGENERATION; NEURONAL CEROID-LIPOFUSCINOSIS; INBREEDING COEFFICIENT; SEQUENCING DATA; KUFS-DISEASE; GENE; HOMOZYGOSITY; VARIABILITY; DISORDERS; DEMENTIA AB We performed hypothesis-free linkage analysis and exome sequencing in a family with two siblings who had neuronal ceroid lipofuscinosis (NCL). Two linkage peaks with maximum LOD scores of 3.07 and 2.97 were found on chromosomes 7 and 17, respectively. Unexpectedly, we found these siblings to be homozygous for a c.813_816del (p.Thr272Serfs(star)10) mutation in the progranulin gene (GRN, granulin precursor) in the latter peak. Heterozygous mutations in GRN are a major cause of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP), the second most common early-onset dementia. Reexamination of progranulin-deficient mice revealed rectilinear profiles typical of NCL. The age-at-onset and neuropathology of FTLD-TDP and NCL are markedly different. Our findings reveal an unanticipated link between a rare and a common neurological disorder and illustrate pleiotropic effects of a mutation in the heterozygous or homozygous states. C1 [Smith, Katherine R.; Bahlo, Melanie] Walter & Eliza Hall Inst Med Res, Bioinformat Div, Parkville, Vic 3052, Australia. [Smith, Katherine R.] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia. [Damiano, John; Dahl, Hans-Henrik; Berkovic, Samuel F.] Univ Melbourne, Dept Med, Epilepsy Res Ctr, Austin Hlth, Heidelberg West, Vic 3081, Australia. [Franceschetti, Silvana; Canafoglia, Laura] IRCCS Fdn, Unit Neurophysiopathol, Carlo Besta Neurol Inst, I-20133 Milan, Italy. [Carpenter, Stirling] Hosp Sao Joao, Serv Anat Patol, P-4200319 Oporto, Portugal. [Morbin, Michela; Rossi, Giacomina] IRCCS Fdn, Div Neuropathol & Neurol 5, Carlo Besta Neurol Inst, I-20133 Milan, Italy. [Pareyson, Davide] IRCCS Fdn, Clin Cent, Carlo Besta Neurol Inst, I-20133 Milan, Italy. [Pareyson, Davide] IRCCS Fdn, Carlo Besta Neurol Inst, Dept Clin Neurosci, Peripheral Degenerat Neuropathies Unit, I-20133 Milan, Italy. [Mole, Sara E.] UCL, Med Res Council Lab Mol Cell Biol, Inst Child Hlth, Mol Med Unit, London WC1E 6BT, England. [Mole, Sara E.] UCL, Dept Genet Evolut & Environm, London WC1E 6BT, England. [Staropoli, John F.; Sims, Katherine B.] Massachusetts Gen Hosp, Neurogenet DNA Diagnost Lab, Ctr Human Genet Res, Boston, MA 02114 USA. [Lewis, Jada] Univ Florida, Ctr Translat Res Neurodegenerat Dis, Gainesville, FL 32610 USA. [Lewis, Jada] Univ Florida, Dept Neurosci, Gainesville, FL 32610 USA. [Lin, Wen-Lang; Dickson, Dennis W.] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. [Bahlo, Melanie] Univ Melbourne, Dept Math & Stat, Melbourne, Vic 3010, Australia. RP Bahlo, M (reprint author), Walter & Eliza Hall Inst Med Res, Bioinformat Div, 1G Royal Parade, Parkville, Vic 3052, Australia. EM bahlo@wehi.edu.au; s.berkovic@unimelb.edu.au RI Rossi, Giacomina/I-2783-2012; Canafoglia, Laura/K-4787-2016; OI Dickson, Dennis W/0000-0001-7189-7917; Berkovic, Samuel/0000-0003-4580-841X; Mole, Sara/0000-0003-4385-4957; Rossi, Giacomina/0000-0001-6680-2725; Canafoglia, Laura/0000-0002-5385-761X; Morbin, Michela/0000-0001-8034-3123 FU Pratt Foundation; National Health and Medical Research Council (NHMRC) Australia; NHMRC; Australian Research Council (ARC); Medical Research Council; Batten Disease Support and Research Association FX K.R.S. is supported by a PhD scholarship funded by the Pratt Foundation. S.F.B. is supported by a National Health and Medical Research Council (NHMRC) Australia Fellowship and an NHMRC Program Grant. M.B. is supported by an Australian Research Council (ARC) Future Fellowship and an NHMRC Program Grant. S.E.M. is supported by the Medical Research Council. The Batten Disease Support and Research Association supported S.E.M., J.S., and K.S. We thank Pawan Mann and Olivia Galante for technical assistance; Danya years, Robyn Ferguson, and Karen Oliver for technical support; the Rare NCL Gene Consortium for encouraging collaborative research on variant NCL cases; and the families and physicians for providing samples. NR 32 TC 109 Z9 113 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN 8 PY 2012 VL 90 IS 6 BP 1102 EP 1107 DI 10.1016/j.ajhg.2012.04.021 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 958TC UT WOS:000305262600015 PM 22608501 ER PT J AU Hu, B Castillo, E Harewood, L Ostano, P Reymond, A Dummer, R Raffoul, W Hoetzenecker, W Hofbauer, GFL Dotto, GP AF Hu, Bing Castillo, Einar Harewood, Louise Ostano, Paola Reymond, Alexandre Dummer, Reinhard Raffoul, Wassim Hoetzenecker, Wolfram Hofbauer, Guenther F. L. Dotto, G. Paolo TI Multifocal Epithelial Tumors and Field Cancerization from Loss of Mesenchymal CSL Signaling SO CELL LA English DT Article ID CELL FATE; NOTCH; CANCER; SKIN; EXPRESSION; GENE; DIFFERENTIATION; TUMORIGENESIS; ACTIVATION AB It is currently unclear whether tissue changes surrounding multifocal epithelial tumors are a cause or consequence of cancer. Here, we provide evidence that loss of mesenchymal Notch/CSL signaling causes tissue alterations, including stromal atrophy and inflammation, which precede and are potent triggers for epithelial tumors. Mice carrying a mesenchymal-specific deletion of CSL/RBP-J(k), a key Notch effector, exhibit spontaneous multifocal keratinocyte tumors that develop after dermal atrophy and inflammation. CSL-deficient dermal fibroblasts promote increased tumor cell proliferation through upregulation of c-Jun and c-Fos expression and consequently higher levels of diffusible growth factors, inflammatory cytokines, and matrix-remodeling enzymes. In human skin samples, stromal fields adjacent to multifocal premalignant actinic keratosis lesions exhibit decreased Notch/CSL signaling and associated molecular changes. Importantly, these changes in gene expression are also induced by UVA, a known environmental cause of cutaneous field cancerization and skin cancer. C1 [Hu, Bing; Castillo, Einar; Dotto, G. Paolo] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. [Harewood, Louise; Reymond, Alexandre] Univ Lausanne, CIG, CH-1015 Lausanne, Switzerland. [Ostano, Paola] Edo & Elvo Tempia Valenta Fdn, Canc Genom Lab, I-13900 Biella, Italy. [Dummer, Reinhard; Hofbauer, Guenther F. L.] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. [Raffoul, Wassim] Univ Lausanne Hosp, Dept Plast Reconstruct & Aesthet Surg, CH-1011 Lausanne, Switzerland. [Hoetzenecker, Wolfram] Univ Tubingen, Dept Dermatol, D-72076 Tubingen, Germany. [Hoetzenecker, Wolfram; Dotto, G. Paolo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Dotto, GP (reprint author), Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. EM paolo.dotto@unil.ch RI Hofbauer, Gunther/B-2671-2010; OI Hofbauer, Gunther/0000-0003-0542-7989; Harewood, Louise/0000-0002-6398-6714 FU Swiss National Science Foundation (SNSF) [3100A0-122281/1, CRSI33-130576/1]; Oncosuisse [02361-02-2009]; European Union [LSHB-CT-2005-019067]; National Institutes of Health [AR39190, AR054856]; Gottfried und Julia Bangerter Ryner Stiftung; European Commission [037627] FX We thank Drs. T. Honjo for RBP-J kappaloxP/loxP mice; P. Angel for Cre transgenics; D. Hohl for the TEWL measurement apparatus; N. Traber, I. Steiner, D. Singer, H. Janine, J.C. Stehle, and B.C. Nguyen for technical assistance; A. Balmain for advice; and C. Missero and C. Brisken for manuscript reading. This work was supported by grants from the Swiss National Science Foundation (SNSF; grant 3100A0-122281/1; CRSI33-130576/1) Oncosuisse (grant 02361-02-2009), the European Union (Epistem, Sixth Framework Program, LSHB-CT-2005-019067), and the National Institutes of Health (grants AR39190 and AR054856 to G.P.D.), the "Gottfried und Julia Bangerter Ryner Stiftung'' (to R.D.), and the European Commission (grant 037627) and the SNSF (to A.R.). NR 32 TC 67 Z9 68 U1 1 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JUN 8 PY 2012 VL 149 IS 6 BP 1207 EP 1220 DI 10.1016/j.cell.2012.03.048 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 956WF UT WOS:000305119600007 PM 22682244 ER PT J AU Jain, RK Carmeliet, P AF Jain, Rakesh K. Carmeliet, Peter TI SnapShot: Tumor Angiogenesis SO CELL LA English DT Editorial Material ID ANTIANGIOGENIC THERAPY; VASCULATURE; VESSELS C1 [Jain, Rakesh K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Carmeliet, Peter] VIB, Vesalius Res Ctr, B-3000 Louvain, Belgium. [Carmeliet, Peter] Katholieke Univ Leuven, B-3000 Louvain, Belgium. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 10 TC 41 Z9 44 U1 2 U2 36 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JUN 8 PY 2012 VL 149 IS 6 BP 1408 EP U257 AR 1408.e1 DI 10.1016/j.cell.2012.05.025 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 956WF UT WOS:000305119600022 PM 22682256 ER PT J AU Walensky, LD AF Walensky, Loren D. TI Stemming Danger with Golgified BAX SO MOLECULAR CELL LA English DT Editorial Material ID APOPTOSIS AB In this issue of Molecular Cell, Dumitru et al. (2012) report that hES cells localize a conformationally activated form of proapoptotic BAX to the trans Golgi network, a previously unanticipated launch pad for mitochondrial assault in response to DNA damage. C1 [Walensky, Loren D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Walensky, Loren D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02215 USA. RP Walensky, LD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. EM loren_walensky@dfci.harvard.edu FU NCI NIH HHS [R01 CA050239] NR 10 TC 0 Z9 0 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JUN 8 PY 2012 VL 46 IS 5 BP 554 EP 556 DI 10.1016/j.molcel.2012.05.034 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 956NC UT WOS:000305095400003 PM 22681883 ER PT J AU Centore, RC Yazinski, SA Tse, A Zou, L AF Centore, Richard C. Yazinski, Stephanie A. Tse, Alice Zou, Lee TI Spartan/C1orf124, a Reader of PCNA Ubiquitylation and a Regulator of UV-Induced DNA Damage Response SO MOLECULAR CELL LA English DT Article ID CELL NUCLEAR ANTIGEN; CROSS-LINK REPAIR; UBIQUITIN-BINDING DOMAINS; POLYMERASE-IOTA; TRANSLESION SYNTHESIS; STRUCTURAL BASIS; ETA; RAP80; MONOUBIQUITINATION; KIAA1018/FAN1 AB PCNA is a key component of DNA replication and repair machineries. DNA damage-induced PCNA ubiquitylation serves as a molecular mark to orchestrate postreplication repair. Here, we have identified and characterized Spartan, a protein that specifically recognizes ubiquitylated PCNA and plays an important role in cellular resistance to UV radiation. In vitro, Spartan engages ubiquitylated PCNA via both a PIP box and a UBZ domain. In cells, Spartan is recruited to sites of UV damage in a manner dependent upon the PIP box, the UBZ domain, and PCNA ubiquitylation. Furthermore, Spartan colocalizes and interacts with Rad18, the E3 ubiquitin ligase that modifies PCNA. Surprisingly, while Spartan is recruited by ubiquitylated PCNA, knockdown of Spartan compromised chromatin association of Rad18, monoubiquitylation of PCNA, and localization of Pol eta to UV damage. Thus, as a "reader" of ubiquitylated PCNA, Spartan promotes an unexpected feed-forward loop to enhance PCNA ubiquitylation and translesion DNA synthesis. C1 [Centore, Richard C.; Yazinski, Stephanie A.; Tse, Alice; Zou, Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. [Zou, Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. RP Zou, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. EM zou.lee@mgh.harvard.edu FU NIH [F32-GM089150, GM076388]; Federal Share of Proton Program Income FX We thank Lei Li for advice on the UV sensitivity assay, Junjie Chen for a plasmid containing the SFB tag, Satoshi Tateishi for Rad18 antibody, Alan Lehmann and Karlene Cimprich for the XP30RO cells expressing eGFP-Pol eta, and members of the Zou lab for helpful discussions. We also thank the reviewers for constructive suggestions. R.C.C. is supported by NIH fellowship F32-GM089150. L.Z. is supported by the NIH grant GM076388 and a grant funded by the Federal Share of Proton Program Income. L.Z. is a Jim and Ann Orr Massachusetts General Hospital Research Scholar and a Scholar of the Leukemia & Lymphoma Society. NR 43 TC 49 Z9 53 U1 0 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JUN 8 PY 2012 VL 46 IS 5 BP 625 EP 635 DI 10.1016/j.molcel.2012.05.020 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 956NC UT WOS:000305095400012 PM 22681887 ER PT J AU Sonnenberg, GF Monticelli, LA Alenghat, T Fung, TC Hutnick, NA Kunisawa, J Shibata, N Grunberg, S Sinha, R Zahm, AM Tardif, MR Sathaliyawala, T Kubota, M Farber, DL Collman, RG Shaked, A Fouser, LA Weiner, DB Tessier, PA Friedman, JR Kiyono, H Bushman, FD Chang, KM Artis, D AF Sonnenberg, Gregory F. Monticelli, Laurel A. Alenghat, Theresa Fung, Thomas C. Hutnick, Natalie A. Kunisawa, Jun Shibata, Naoko Grunberg, Stephanie Sinha, Rohini Zahm, Adam M. Tardif, Melanie R. Sathaliyawala, Taheri Kubota, Masaru Farber, Donna L. Collman, Ronald G. Shaked, Abraham Fouser, Lynette A. Weiner, David B. Tessier, Philippe A. Friedman, Joshua R. Kiyono, Hiroshi Bushman, Frederic D. Chang, Kyong-Mi Artis, David TI Innate Lymphoid Cells Promote Anatomical Containment of Lymphoid-Resident Commensal Bacteria SO SCIENCE LA English DT Article ID ALCALIGENES-XYLOSOXIDANS; INTESTINAL BACTERIA; HOST-DEFENSE; MICROBIOTA; ACHROMOBACTER; INFLAMMATION; HOMEOSTASIS; IDENTIFICATION; IMMUNITY; SYSTEM AB The mammalian intestinal tract is colonized by trillions of beneficial commensal bacteria that are anatomically restricted to specific niches. However, the mechanisms that regulate anatomical containment remain unclear. Here, we show that interleukin-22 (IL-22)-producing innate lymphoid cells (ILCs) are present in intestinal tissues of healthy mammals. Depletion of ILCs resulted in peripheral dissemination of commensal bacteria and systemic inflammation, which was prevented by administration of IL-22. Disseminating bacteria were identified as Alcaligenes species originating from host lymphoid tissues. Alcaligenes was sufficient to promote systemic inflammation after ILC depletion in mice, and Alcaligenes-specific systemic immune responses were associated with Crohn's disease and progressive hepatitis C virus infection in patients. Collectively, these data indicate that ILCs regulate selective containment of lymphoid-resident bacteria to prevent systemic inflammation associated with chronic diseases. C1 [Sonnenberg, Gregory F.; Monticelli, Laurel A.; Alenghat, Theresa; Fung, Thomas C.; Grunberg, Stephanie; Sinha, Rohini; Bushman, Frederic D.; Artis, David] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. [Sonnenberg, Gregory F.; Monticelli, Laurel A.; Alenghat, Theresa; Fung, Thomas C.; Grunberg, Stephanie; Sinha, Rohini; Bushman, Frederic D.; Artis, David] Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USA. [Hutnick, Natalie A.; Weiner, David B.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Kunisawa, Jun; Shibata, Naoko; Kiyono, Hiroshi] Univ Tokyo, Inst Med Sci, Div Mucosal Immunol, Tokyo 1088639, Japan. [Kunisawa, Jun; Shibata, Naoko; Kiyono, Hiroshi] Univ Tokyo, Grad Sch Frontier Sci, Dept Med Genome Sci, Chiba 2778562, Japan. [Zahm, Adam M.; Friedman, Joshua R.] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Dept Pediat,Div Gastroenterol Hepatol & Nutr, Philadelphia, PA 19104 USA. [Tardif, Melanie R.; Tessier, Philippe A.] Univ Laval, Fac Med, CHU Laval, Ctr Rech Infectiol, Quebec City, PQ G1K 7P4, Canada. [Sathaliyawala, Taheri; Kubota, Masaru; Farber, Donna L.] Columbia Univ, Med Ctr, Dept Surg, New York, NY 10032 USA. [Sathaliyawala, Taheri; Kubota, Masaru; Farber, Donna L.] Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, New York, NY 10032 USA. [Collman, Ronald G.; Chang, Kyong-Mi] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Shaked, Abraham] Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. [Fouser, Lynette A.] Pfizer Worldwide R&D, Inflammat & Immunol Res Unit, Biotherapeut Res & Dev, Cambridge, MA 02140 USA. [Kiyono, Hiroshi] Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol, Tokyo 1020075, Japan. [Chang, Kyong-Mi] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Artis, David] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA. RP Artis, D (reprint author), Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. EM dartis@mail.med.upenn.edu RI Weiner, David/H-8579-2014; OI Tessier, Philippe/0000-0001-7177-7763; Bushman, Frederic/0000-0003-4740-4056 FU NIH [AI061570, AI087990, AI074878, AI083480, AI095466, AI095608, T32-AI007532, T32-AI055428, T32-RR007063, K08-DK093784, AI47619, P30 AI 045008]; Burroughs Wellcome Fund Investigator in Pathogenesis of Infectious Disease Award; Philadelphia VA Medical Research and Merit Review; American Gastroenterological Association; Ministry of Education, Culture, Sports, Science and Technology of Japan; Program for Promotion of Basic and Applied Researches for Innovations in Bio-Oriented Industry; Matthew J. Ryan Veterinary Hospital Pathology Lab, the National Institute of Diabetes and Digestive and Kidney Disease Center for the Molecular Studies in Digestive and Liver Disease Molecular Pathology and Imaging Core [P30DK50306]; National Cancer Institute (NCI) Comprehensive Cancer Center [2-P30 CA016520] FX We thank members of the Artis laboratory for discussions and critical reading of the manuscript. We also thank S. Olland, R. Zollner, K. Lam, and A. Root at Pfizer for the preparation of IL-22 cytokine and antibodies. The research is supported by the NIH (grants AI061570, AI087990, AI074878, AI083480, AI095466, and AI095608 to D. A.; T32-AI007532 to G. F. S and L. A. M.; T32-AI055428 to G. F. S.; T32-RR007063 and K08-DK093784 to T. A.; and AI47619 to K.-M. C.); the NIH-funded Penn Center for AIDS Research (grant P30 AI 045008 to G. F. S. and D. A.); the Burroughs Wellcome Fund Investigator in Pathogenesis of Infectious Disease Award (to D. A.); the Philadelphia VA Medical Research and Merit Review and American Gastroenterological Association (to K.-M. C.); the Ministry of Education, Culture, Sports, Science and Technology of Japan (to J.K., N.S., and H. K); and the Program for Promotion of Basic and Applied Researches for Innovations in Bio-Oriented Industry (to J.K.). We also thank the Matthew J. Ryan Veterinary Hospital Pathology Lab, the National Institute of Diabetes and Digestive and Kidney Disease Center for the Molecular Studies in Digestive and Liver Disease Molecular Pathology and Imaging Core (grant P30DK50306), the Penn Microarray Facility, and the Abramson Cancer Center Flow Cytometry and Cell Sorting Resource Laboratory [partially supported by National Cancer Institute (NCI) Comprehensive Cancer Center Support grant # 2-P30 CA016520] for technical advice and support. Several human tissue samples were provided by the Cooperative Human Tissue Network, which is funded by the NCI. The data presented in the paper are tabulated in the main paper and in the supplementary materials. NR 29 TC 254 Z9 263 U1 2 U2 38 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 8 PY 2012 VL 336 IS 6086 BP 1321 EP 1325 DI 10.1126/science.1222551 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 953WV UT WOS:000304905300051 PM 22674331 ER PT J AU Brunstein, CG Eapen, M Ahn, KW Appelbaum, FR Ballen, KK Champlin, RE Cutler, C Kan, FY Laughlin, MJ Soiffer, RJ Weisdorf, DJ Woolfrey, A Wagner, JE AF Brunstein, Claudio G. Eapen, Mary Ahn, Kwang Woo Appelbaum, Frederick R. Ballen, Karen K. Champlin, Richard E. Cutler, Corey Kan, Fangyu Laughlin, Mary J. Soiffer, Robert J. Weisdorf, Daniel J. Woolfrey, Anne Wagner, John E. TI Reduced-intensity conditioning transplantation in acute leukemia: the effect of source of unrelated donor stem cells on outcomes SO BLOOD LA English DT Article ID UMBILICAL-CORD BLOOD; ACUTE MYELOID-LEUKEMIA; BONE-MARROW; HEMATOLOGIC MALIGNANCIES; ADULT PATIENTS; FLUDARABINE; ENGRAFTMENT; LYMPHOMA; DISEASE AB We report the relative efficacy of coinfusing 2 umbilical cord blood units (dUCB) compared with peripheral blood progenitor cells (PBPCs) from 8 of 8 or 7 of 8 HLA-matched unrelated donors. All patients received reduced-intensity conditioning (RIC) regimens. Four treatment groups were evaluated: 4-6 of 6 matched dUCB-TCF (n = 120; TCF = total body irradiation [TBI] 200 cGy + cyclophosphamide + fludarabine), 4-6 of 6 matched dUCB-other (n = 40; alkylating agent + fludarabine +/- TBI), and 8 of 8 (n = 313) and 7 of 8 HLA-matched PBPCs (n = 111). Compared with matched 8 of 8 PBPC transplantations, transplantation-related mortality (TRM), and overall mortality were similar after dUCB-TCF (relative risk [RR] 0.72, P = .72; RR 0.93, P = .60) but higher after dUCB-other RIC (hazard ratio [HR] 2.70, P = .0001; 1.79 P = .004). Compared with 7 of 8 PBPC transplantations, TRM (but not overall mortality) was lower after dUCB-TCF (RR 0.57, P = .04; RR 0.87 P = .41). The probabilities of survival after dUCB-TCF, dUCB-other RIC, and 8 of 8 PBPC and 7 of 8 PBPC transplantations were 38%, 19%, 44%, and 37%, respectively. With similar survival after 8 of 8, 7 of 8 matched PBPCs, and dUCB-TCF, these data support use of dUCB-TCF transplantation in adults with acute leukemia who may benefit from RIC transplantation urgently or lack a 7-8 of 8 unrelated donor. (Blood. 2012;119(23):5591-5598) C1 [Brunstein, Claudio G.] Univ Minnesota, Blood & Marrow Transplant Program, Minneapolis, MN 55455 USA. [Eapen, Mary; Ahn, Kwang Woo; Kan, Fangyu] Med Coll Wisconsin, Dept Med, Div Hematol Oncol, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Ahn, Kwang Woo] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA. [Appelbaum, Frederick R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Ballen, Karen K.; Woolfrey, Anne] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Champlin, Richard E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Cutler, Corey; Soiffer, Robert J.] Dana Farber Canc Ctr, Boston, MA USA. [Laughlin, Mary J.] Univ Virginia Hlth Syst, Charlottesville, VA USA. RP Brunstein, CG (reprint author), Univ Minnesota, Blood & Marrow Transplant Program, 420 Delaware St SE, Minneapolis, MN 55455 USA. EM bruns072@umn.edu FU Public Health Service from the National Cancer Institute [U24-CA76518]; National Institute of Allergy and Infectious Diseases, Health Resources and Services Administration [HHSH234200637015C]; Office of Naval Research, Department of Navy [N00014-10-01-0204]; National Heart, Lung, and Blood Institute FX This work was supported by a Public Health Service grant (U24-CA76518) from the National Cancer Institute, the National Heart, Lung, and Blood Institute, and the National Institute of Allergy and Infectious Diseases, Health Resources and Services Administration (HHSH234200637015C), and the Office of Naval Research, Department of Navy, to the National Marrow Donor Program (N00014-10-01-0204). NR 31 TC 72 Z9 73 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 7 PY 2012 VL 119 IS 23 BP 5591 EP 5598 DI 10.1182/blood-2011-12-400630 PG 8 WC Hematology SC Hematology GA 987BM UT WOS:000307391400033 PM 22496153 ER PT J AU Meyer, GS Demehin, AA Liu, X Neuhauser, D AF Meyer, Gregg S. Demehin, Akinluwa A. Liu, Xiu Neuhauser, Duncan TI Two Hundred Years of Hospital Costs and Mortality - MGH and Four Eras of Value in Medicine SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Meyer, Gregg S.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Demehin, Akinluwa A.] Natl Qual Forum, Washington, DC USA. [Liu, Xiu] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Neuhauser, Duncan] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. RP Meyer, GS (reprint author), Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. NR 6 TC 4 Z9 4 U1 1 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 7 PY 2012 VL 366 IS 23 BP 2147 EP 2149 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 953JO UT WOS:000304863400003 PM 22670900 ER PT J AU Sekulic, A Migden, MR Oro, AE Dirix, L Lewis, KD Hainsworth, JD Solomon, JA Yoo, S Arron, ST Friedlander, PA Marmur, E Rudin, CM Chang, ALS Low, JA Mackey, HM Yauch, RL Graham, RA Reddy, JC Hauschild, A AF Sekulic, Aleksandar Migden, Michael R. Oro, Anthony E. Dirix, Luc Lewis, Karl D. Hainsworth, John D. Solomon, James A. Yoo, Simon Arron, Sarah T. Friedlander, Philip A. Marmur, Ellen Rudin, Charles M. Chang, Anne Lynn S. Low, Jennifer A. Mackey, Howard M. Yauch, Robert L. Graham, Richard A. Reddy, Josina C. Hauschild, Axel TI Efficacy and Safety of Vismodegib in Advanced Basal-Cell Carcinoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SONIC-HEDGEHOG AB BACKGROUND Alterations in hedgehog signaling are implicated in the pathogenesis of basal-cell carcinoma. Although most basal-cell carcinomas are treated surgically, no effective therapy exists for locally advanced or metastatic basal-cell carcinoma. A phase 1 study of vismodegib (GDC-0449), a first-in-class, small-molecule inhibitor of the hedgehog pathway, showed a 58% response rate among patients with advanced basal-cell carcinoma. METHODS In this multicenter, international, two-cohort, nonrandomized study, we enrolled patients with metastatic basal-cell carcinoma and those with locally advanced basal-cell carcinoma who had inoperable disease or for whom surgery was inappropriate (because of multiple recurrences and a low likelihood of surgical cure, or substantial anticipated disfigurement). All patients received 150 mg of oral vismodegib daily. The primary end point was the independently assessed objective response rate; the primary hypotheses were that the response rate would be greater than 20% for patients with locally advanced basal-cell carcinoma and greater than 10% for those with metastatic basal-cell carcinoma. RESULTS In 33 patients with metastatic basal-cell carcinoma, the independently assessed response rate was 30% (95% confidence interval [CI], 16 to 48; P=0.001). In 63 patients with locally advanced basal-cell carcinoma, the independently assessed response rate was 43% (95% CI, 31 to 56; P<0.001), with complete responses in 13 patients (21%). The median duration of response was 7.6 months in both cohorts. Adverse events occurring in more than 30% of patients were muscle spasms, alopecia, dysgeusia (taste disturbance), weight loss, and fatigue. Serious adverse events were reported in 25% of patients; seven deaths due to adverse events were noted. CONCLUSIONS Vismodegib is associated with tumor responses in patients with locally advanced or metastatic basal-cell carcinoma. (Funded by Genentech; Erivance BCC ClinicalTrials.gov number, NCT00833417.) C1 [Sekulic, Aleksandar] Mayo Clin, Scottsdale, AZ 85259 USA. [Migden, Michael R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Oro, Anthony E.; Chang, Anne Lynn S.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Dirix, Luc] Sint Augustinus Hosp, Antwerp, Belgium. [Lewis, Karl D.] Univ Colorado, Ctr Canc, Denver, CO 80262 USA. [Hainsworth, John D.] Sarah Cannon Res Inst, Nashville, TN USA. [Solomon, James A.] Ameriderm Res, Ormond Beach, FL USA. [Yoo, Simon] Northwestern Univ, Chicago, IL 60611 USA. [Arron, Sarah T.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Friedlander, Philip A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Friedlander, Philip A.; Marmur, Ellen] Mt Sinai Med Ctr, New York, NY 10029 USA. [Rudin, Charles M.] Johns Hopkins Univ, Baltimore, MD USA. [Low, Jennifer A.; Mackey, Howard M.; Yauch, Robert L.; Graham, Richard A.; Reddy, Josina C.] Genentech Inc, San Francisco, CA 94080 USA. [Hauschild, Axel] Univ Klinikum Schleswig Holstein, Kiel, Germany. RP Sekulic, A (reprint author), Mayo Clin, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA. EM sekulic.aleksandar@mayo.edu FU Genentech FX Supported by Genentech. NR 14 TC 380 Z9 389 U1 7 U2 29 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 7 PY 2012 VL 366 IS 23 BP 2171 EP 2179 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 953JO UT WOS:000304863400006 PM 22670903 ER PT J AU Schumann, J Paganetti, H Shin, J Faddegon, B Perl, J AF Schuemann, J. Paganetti, H. Shin, J. Faddegon, B. Perl, J. TI Efficient voxel navigation for proton therapy dose calculation in TOPAS and Geant4 SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 4th International Workshop on Recent Advances in MonteCarlo Techniques for Radiation Therapy CY JUN 08-10, 2011 CL Montreal, CANADA ID MONTE-CARLO SIMULATIONS; TOOLKIT AB A key task within all Monte Carlo particle transport codes is 'navigation', the calculation to determine at each particle step what volume the particle may be leaving and what volume the particle may be entering. Navigation should be optimized to the specific geometry at hand. For patient dose calculation, this geometry generally involves voxelized computed tomography (CT) data. We investigated the efficiency of navigation algorithms on currently available voxel geometry parameterizations in the Monte Carlo simulation package Geant4: G4VPVParameterisation, G4VNestedParameterisation and G4PhantomParameterisation, the last with and without boundary skipping, a method where neighboring voxels with the same Hounsfield unit are combined into one larger voxel. A fourth parameterization approach (MGHParameterization), developed in-house before the latter two parameterizations became available in Geant4, was also included in this study. All simulations were performed using TOPAS, a tool for particle simulations layered on top of Geant4. Runtime comparisons were made on three distinct patient CT data sets: a head and neck, a liver and a prostate patient. We included an additional version of these three patients where all voxels, including the air voxels outside of the patient, were uniformly set to water in the runtime study. The G4VPVParameterisation offers two optimization options. One option has a 60-150 times slower simulation speed. The other is compatible in speed but requires 15-19 times more memory compared to the other parameterizations. We found the average CPU time used for the simulation relative to G4VNestedParameterisation to be 1.014 for G4PhantomParameterisation without boundary skipping and 1.015 for MGHParameterization. The average runtime ratio for G4PhantomParameterisation with and without boundary skipping for our heterogeneous data was equal to 0.97 : 1. The calculated dose distributions agreed with the reference distribution for all but the G4PhantomParameterisation with boundary skipping for the head and neck patient. The maximum memory usage ranged from 0.8 to 1.8 GB depending on the CT volume independent of parameterizations, except for the 15-19 times greater memory usage with the G4VPVParameterisation when using the option with a higher simulation speed. The G4VNestedParameterisation was selected as the preferred choice for the patient geometries and treatment plans studied. C1 [Schuemann, J.; Paganetti, H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Schuemann, J.; Paganetti, H.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Shin, J.; Faddegon, B.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Perl, J.] SLAC Natl Accelerator Lab, Menlo Pk, CA 94025 USA. RP Schumann, J (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM jschuemann@partners.org FU NIH/NCI [R01 CA 140735-01] FX This work was supported by NIH/NCI under R01 CA 140735-01. We would like to thank Makoto Asai for providing many helpful discussions as well as the illustration of G4Nested in figure 1, Nicolas Depauw for his help with the gamma index and Clemens Grassberger for helpful comments and discussions. NR 12 TC 21 Z9 21 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 JUN 7 PY 2012 VL 57 IS 11 BP 3281 EP 3293 DI 10.1088/0031-9155/57/11/3281 PG 13 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 944NJ UT WOS:000304210300007 PM 22572154 ER PT J AU Shin, J Perl, J Schumann, J Paganetti, H Faddegon, BA AF Shin, J. Perl, J. Schuemann, J. Paganetti, H. Faddegon, B. A. TI A modular method to handle multiple time-dependent quantities in Monte Carlo simulations SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 4th International Workshop on Recent Advances in MonteCarlo Techniques for Radiation Therapy CY JUN 08-10, 2011 CL Montreal, CANADA ID DOSE DISTRIBUTIONS; RADIATION-THERAPY; PROTON; FACILITY; WEDGE; IMRT AB A general method for handling time-dependent quantities in Monte Carlo simulations was developed to make such simulations more accessible to the medical community for a wide range of applications in radiotherapy, including fluence and dose calculation. To describe time-dependent changes in the most general way, we developed a grammar of functions that we call 'Time Features'. When a simulation quantity, such as the position of a geometrical object, an angle, a magnetic field, a current, etc, takes its value from a Time Feature, that quantity varies over time. The operation of time-dependent simulation was separated into distinct parts: the Sequence samples time values either sequentially at equal increments or randomly from a uniform distribution (allowing quantities to vary continuously in time), and then each time-dependent quantity is calculated according to its Time Feature. Due to this modular structure, time-dependent simulations, even in the presence of multiple time-dependent quantities, can be efficiently performed in a single simulation with any given time resolution. This approach has been implemented in TOPAS (TOol for PArticle Simulation), designed to make Monte Carlo simulations with Geant4 more accessible to both clinical and research physicists. To demonstrate the method, three clinical situations were simulated: a variable water column used to verify constancy of the Bragg peak of the Crocker Lab eye treatment facility of the University of California, the double-scattering treatment mode of the passive beam scattering system at Massachusetts General Hospital (MGH), where a spinning range modulator wheel accompanied by beam current modulation produces a spread-out Bragg peak, and the scanning mode at MGH, where time-dependent pulse shape, energy distribution and magnetic fields control Bragg peak positions. Results confirm the clinical applicability of the method. C1 [Shin, J.; Faddegon, B. A.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Perl, J.] SLAC Natl Accelerator Lab, Menlo Pk, CA 94025 USA. [Schuemann, J.; Paganetti, H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Shin, J (reprint author), UCSF Helen Diller Family Comprehens Canc Ctr, 1600 Divisadero St, San Francisco, CA 94143 USA. EM bfaddegon@radonc.ucsf.edu FU NIH/NCI [R01 CA 140735-01] FX This work was supported by NIH/NCI under R01 CA 140735-01. We would like to thank Inder Daftrari for providing us with data for UCSF/UCD, Takashi Sasaki and Tsukasa Aso for helping us to model the UCSF/UCD beamline, and Benjamin Clasie for providing information on the pencil beam scanning nozzle. NR 19 TC 12 Z9 12 U1 1 U2 6 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 JUN 7 PY 2012 VL 57 IS 11 BP 3295 EP 3308 DI 10.1088/0031-9155/57/11/3295 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 944NJ UT WOS:000304210300008 PM 22572201 ER PT J AU Mishra, P St James, S Segars, WP Berbeco, RI Lewis, JH AF Mishra, Pankaj St James, Sara Segars, W. Paul Berbeco, Ross I. Lewis, John H. TI Adaptation and applications of a realistic digital phantom based on patient lung tumor trajectories SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 4th International Workshop on Recent Advances in MonteCarlo Techniques for Radiation Therapy CY JUN 08-10, 2011 CL Montreal, CANADA ID COMPUTED-TOMOGRAPHY SIMULATION; 4D XCAT PHANTOM; HUMAN ANATOMY; CT; MOTION AB Digital phantoms continue to play a significant role in modeling and characterizing medical imaging. The currently available XCAT phantom incorporates both the flexibility of mathematical phantoms and the realistic nature of voxelized phantoms. This phantom generates images based on a regular breathing pattern and can include arbitrary lung tumor trajectories. In this work, we present an algorithm that modifies the current XCAT phantom to generate 4D imaging data based on irregular breathing. First, a parameter is added to the existing XCAT phantom to include any arbitrary tumor motion. This modification introduces the desired tumor motion but, comes at the cost of decoupled diaphragm, chest wall and lung motion. To remedy this problem diaphragm and chest wall motion is first modified based on initial tumor location and then input to the XCAT phantom. This generates a phantom with synchronized respiratory motion. Mapping of tumor motion trajectories to diaphragm and chest wall motion is done by adaptively calculating a scale factor based on tumor to lung contour distance. The distance is calculated by projecting the initial tumor location to lung edge contours characterized by quadratic polynomials. Data from ten patients were used to evaluate the accuracy between actual independent tumor location and the location obtained from the modified XCAT phantom. The RMSE and standard deviations for ten patients in x, y, and z directions are: (0.29 +/- 0.04, 0.54 +/- 0.17, and 0.39 +/- 0.06) mm. To demonstrate the utility of the phantom, we use the new phantom to simulate a 4DCT acquisition as well as a recently published method for phase sorting. The modified XCAT phantom can be used to generate more realistic imaging data for enhanced testing of algorithms for CT reconstruction, tumor tracking, and dose reconstruction. C1 [Mishra, Pankaj; St James, Sara; Berbeco, Ross I.; Lewis, John H.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Mishra, Pankaj; St James, Sara; Berbeco, Ross I.; Lewis, John H.] Harvard Univ, Sch Med, Boston, MA USA. [Segars, W. Paul] Duke Univ, Dept Radiol, Durham, NC 27710 USA. RP Mishra, P (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM pmishra@lroc.harvard.edu; jhlewis@lroc.harvard.edu FU National Cancer Institute [R21CA156068] FX The authors would like to express their gratitude to Drs Seiko Nishioka of the Department of Radiology, NTT Hospital, Sapporo, Japan and Hiroki Shirato of the Department of Radiation Medicine, Hokkaido University School of Medicine, Sapporo, Japan for sharing the Hokkaido dataset with us. We would also like to thank Dr Ruijiang Li for helpful discussion on the internal anatomical features based 4D CT sorting algorithm. The project described was supported, in part, by Award Number R21CA156068 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 22 TC 12 Z9 12 U1 1 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 JUN 7 PY 2012 VL 57 IS 11 BP 3597 EP 3608 DI 10.1088/0031-9155/57/11/3597 PG 12 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 944NJ UT WOS:000304210300026 PM 22595980 ER PT J AU Paganetti, H AF Paganetti, Harald TI Range uncertainties in proton therapy and the role of Monte Carlo simulations SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 4th International Workshop on Recent Advances in MonteCarlo Techniques for Radiation Therapy CY JUN 08-10, 2011 CL Montreal, CANADA ID RELATIVE BIOLOGICAL EFFECTIVENESS; CHARGED-PARTICLE RADIOTHERAPY; DOSE CALCULATION; RADIATION-THERAPY; BEAM THERAPY; PROMPT GAMMA; BRAGG PEAK; CT NUMBERS; COLLIMATOR SCATTER; QUALITY-ASSURANCE AB The main advantages of proton therapy are the reduced total energy deposited in the patient as compared to photon techniques and the finite range of the proton beam. The latter adds an additional degree of freedom to treatment planning. The range in tissue is associated with considerable uncertainties caused by imaging, patient setup, beam delivery and dose calculation. Reducing the uncertainties would allow a reduction of the treatment volume and thus allow a better utilization of the advantages of protons. This paper summarizes the role of Monte Carlo simulations when aiming at a reduction of range uncertainties in proton therapy. Differences in dose calculation when comparing Monte Carlo with analytical algorithms are analyzed as well as range uncertainties due to material constants and CT conversion. Range uncertainties due to biological effects and the role of Monte Carlo for in vivo range verification are discussed. Furthermore, the current range uncertainty recipes used at several proton therapy facilities are revisited. We conclude that a significant impact of Monte Carlo dose calculation can be expected in complex geometries where local range uncertainties due to multiple Coulomb scattering will reduce the accuracy of analytical algorithms. In these cases Monte Carlo techniques might reduce the range uncertainty by several mm. C1 [Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Paganetti, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM hpaganetti@partners.org FU NIH/NCI [PO1 CA21239] FX This work was funded in part by NIH/NCI PO1 CA21239. NR 87 TC 215 Z9 216 U1 7 U2 48 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 JUN 7 PY 2012 VL 57 IS 11 BP R99 EP R117 DI 10.1088/0031-9155/57/11/R99 PG 19 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 944NJ UT WOS:000304210300003 PM 22571913 ER PT J AU Muller, LUW Milsom, MD Harris, CE Vyas, R Brumme, KM Parmar, K Moreau, LA Schambach, A Park, IH London, WB Strait, K Schlaeger, T DeVine, AL Grassman, E D'Andrea, A Daley, GQ Williams, DA AF Mueller, Lars U. W. Milsom, Michael D. Harris, Chad E. Vyas, Rutesh Brumme, Kristina M. Parmar, Kalindi Moreau, Lisa A. Schambach, Axel Park, In-Hyun London, Wendy B. Strait, Kelly Schlaeger, Thorsten DeVine, Alexander L. Grassman, Elke D'Andrea, Alan Daley, George Q. Williams, David A. TI Overcoming reprogramming resistance of Fanconi anemia cells SO BLOOD LA English DT Article ID PLURIPOTENT STEM-CELLS; DNA-DAMAGE RESPONSE; HEMATOPOIETIC STEM; PROGENITOR CELLS; GENE-TRANSFER; GROUP-C; VECTOR; GENERATION; INACTIVATION; INSTABILITY AB Fanconi anemia (FA) is a recessive syndrome characterized by progressive fatal BM failure and chromosomal instability. FA cells have inactivating mutations in a signaling pathway that is critical for maintaining genomic integrity and protecting cells from the DNA damage caused by cross-linking agents. Transgenic expression of the implicated genes corrects the phenotype of hematopoietic cells, but previous attempts at gene therapy have failed largely because of inadequate numbers of hematopoietic stem cells available for gene correction. Induced pluripotent stem cells (iPSCs) constitute an alternate source of autologous cells that are amenable to ex vivo expansion, genetic correction, and molecular characterization. In the present study, we demonstrate that reprogramming leads to activation of the FApathway, increased DNA double-strand breaks, and senescence. We also demonstrate that defects in the FA DNA-repair pathway decrease the reprogramming efficiency of murine and human primary cells. FA pathway complementation reduces senescence and restores the reprogramming efficiency of somatic FA cells to normal levels. Disease-specific iPSCs derived in this fashion maintain a normal karyotype and are capable of hematopoietic differentiation. These data define the role of the FA pathway in reprogramming and provide a strategy for future translational applications of patient-specific FA iPSCs. (Blood. 2012;119(23):5449-5457) C1 [Mueller, Lars U. W.; Milsom, Michael D.; Harris, Chad E.; Vyas, Rutesh; Brumme, Kristina M.; Park, In-Hyun; London, Wendy B.; Strait, Kelly; Daley, George Q.; Williams, David A.] Childrens Hosp Boston, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Mueller, Lars U. W.; Milsom, Michael D.; Harris, Chad E.; Vyas, Rutesh; Brumme, Kristina M.; Park, In-Hyun; London, Wendy B.; Strait, Kelly; Daley, George Q.; Williams, David A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Parmar, Kalindi; Moreau, Lisa A.; D'Andrea, Alan] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Schambach, Axel] Hannover Med Sch, Dept Expt Hematol, D-3000 Hannover, Germany. [Schlaeger, Thorsten; DeVine, Alexander L.] Childrens Hosp Boston, Stem Cell Program, Boston, MA 02115 USA. [Grassman, Elke] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. RP Williams, DA (reprint author), Childrens Hosp Boston, Div Pediat Hematol Oncol, 300 Longwood Ave,Karp 08125-3, Boston, MA 02115 USA. EM dawilliams@childrens.harvard.edu FU NKDDK Hematology center [P30 DK049216-17]; St Baldrick's Foundation; Harvard Stem Cell Institute; Hood Foundation; National Institutes of Health [NIH R01 HL081499, DK074310, NIH 1RC4DK090913-01] FX The authors thank the Dana-Farber/Harvard Cancer Center Rodent Histopathology Core for assisting with teratoma histology and the Cytogenetics Core for carrying out the CGH analysis, and the Children's Hospital Boston Intellectual and Developmental Disabilities Research Center Imaging Core (P30HD 18655) for assisting with photomicrographs of the FAND2 foci. They would also like to thank Dr Yuko Fujiwara (Mouse Embryonic Stem Cells and Gene Targeting Core, Children's Hospital Boston; NKDDK Hematology center grant P30 DK049216-17) for assistance with the generation of chimeric mice.; This work was supported by a fellowship grant from the St Baldrick's Foundation (to L.M.), by the Harvard Stem Cell Institute (to L.M.), by the Hood Foundation (to L.M.), and by the National Institutes of Health (NIH R01 HL081499 and DK074310 to D.A.W. and NIH 1RC4DK090913-01 to D.A.W., A.D., and G.Q.D.). NR 50 TC 73 Z9 74 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 7 PY 2012 VL 119 IS 23 BP 5449 EP 5457 DI 10.1182/blood-2012-02-408674 PG 9 WC Hematology SC Hematology GA 987BM UT WOS:000307391400019 PM 22371882 ER PT J AU Bendlin, BB Carlsson, CM Johnson, SC Zetterberg, H Blennow, K Willette, AA Okonkwo, OC Sodhi, A Ries, ML Birdsill, AC Alexander, AL Rowley, HA Puglielli, L Asthana, S Sager, MA AF Bendlin, Barbara B. Carlsson, Cynthia M. Johnson, Sterling C. Zetterberg, Henrik Blennow, Kaj Willette, Auriel A. Okonkwo, Ozioma C. Sodhi, Aparna Ries, Michele L. Birdsill, Alex C. Alexander, Andrew L. Rowley, Howard A. Puglielli, Luigi Asthana, Sanjay Sager, Mark A. TI CSF T-Tau/A beta(42) Predicts White Matter Microstructure in Healthy Adults at Risk for Alzheimer's Disease SO PLOS ONE LA English DT Article ID MILD COGNITIVE IMPAIRMENT; CEREBROSPINAL-FLUID BIOMARKERS; VOXEL-BASED MORPHOMETRY; CORPUS-CALLOSUM ATROPHY; APOE EPSILON-4 ALLELE; BRAIN ATROPHY; IN-VIVO; NEUROFILAMENT PROTEIN; PHOSPHORYLATED-TAU; MYELIN BREAKDOWN AB Cerebrospinal fluid (CSF) biomarkers T-Tau and A beta(42) are linked with Alzheimer's disease (AD), yet little is known about the relationship between CSF biomarkers and structural brain alteration in healthy adults. In this study we examined the extent to which AD biomarkers measured in CSF predict brain microstructure indexed by diffusion tensor imaging (DTI) and volume indexed by T1-weighted imaging. Forty-three middle-aged adults with parental family history of AD received baseline lumbar puncture and MRI approximately 3.5 years later. Voxel-wise image analysis methods were used to test whether baseline CSF A beta(42), total tau (T-Tau), phosphorylated tau (P-Tau) and neurofilament light protein predicted brain microstructure as indexed by DTI and gray matter volume indexed by T1-weighted imaging. T-Tau and T-Tau/A beta(42) were widely correlated with indices of brain microstructure (mean, axial, and radial diffusivity), notably in white matter regions adjacent to gray matter structures affected in the earliest stages of AD. None of the CSF biomarkers were related to gray matter volume. Elevated P-Tau and P-Tau/A beta(42) levels were associated with lower recognition performance on the Rey Auditory Verbal Learning Test. Overall, the results suggest that CSF biomarkers are related to brain microstructure in healthy adults with elevated risk of developing AD. Furthermore, the results clearly suggest that early pathological changes in AD can be detected with DTI and occur not only in cortex, but also in white matter. C1 [Bendlin, Barbara B.; Carlsson, Cynthia M.; Johnson, Sterling C.; Willette, Auriel A.; Okonkwo, Ozioma C.; Sodhi, Aparna; Ries, Michele L.; Birdsill, Alex C.; Puglielli, Luigi; Asthana, Sanjay; Sager, Mark A.] William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI USA. [Bendlin, Barbara B.; Carlsson, Cynthia M.; Johnson, Sterling C.; Willette, Auriel A.; Okonkwo, Ozioma C.; Sodhi, Aparna; Ries, Michele L.; Birdsill, Alex C.; Puglielli, Luigi; Asthana, Sanjay; Sager, Mark A.] Univ Wisconsin, Dept Med, Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA. [Zetterberg, Henrik; Blennow, Kaj] Univ Gothenburg, Sahlgrenska Acad, Dept Psychiat & Neurochem, Inst Neurosci & Physiol, Gothenburg, Sweden. [Alexander, Andrew L.] Univ Wisconsin, Dept Med Phys, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Alexander, Andrew L.] Univ Wisconsin, Dept Psychiat, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Alexander, Andrew L.] Waisman Lab Brain Imaging & Behav, Madison, WI USA. [Rowley, Howard A.] Univ Wisconsin, Dept Radiol, Sch Med & Publ Hlth, Madison, WI 53706 USA. RP Bendlin, BB (reprint author), William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI USA. EM bbb@medicine.wisc.edu OI Bendlin, Barbara/0000-0002-0580-9875 FU National Institute on Aging [R01 AG027161, K23 AG026752, ADRC P50 AG033514]; University of Wisconsin Institute for Clinical and Translational Research; National Center for Research Resources/National Institutes of Health Clinical and Translational Science Award [1UL1RR025011]; program of the National Center for Research Resources, United States National Institutes of Health; Swedish Research Council; Pfizer Inc.; Innogenetics; Vastra Gotalandsregionen, Sweden; Swedish Brain Power Project; Swedish Council for Working Life and Social Research; Swedish Alzheimer Foundation; Stiftelsen for Gamla Tjanarinnor; King Gustaf V and Queen Victoria Foundation; Alzheimer's Association; Royal Swedish Academy of Sciences FX This project was supported in part by the National Institute on Aging (R01 AG027161 [MAS], K23 AG026752 [CMC]; ADRC P50 AG033514 [SA]), the University of Wisconsin Institute for Clinical and Translational Research, funded through a National Center for Research Resources/National Institutes of Health Clinical and Translational Science Award, 1UL1RR025011, a program of the National Center for Research Resources, United States National Institutes of Health, and the Swedish Research Council. The project was also facilitated by the facilities and resources at the Geriatric Research, Education, and Clinical Center (GRECC) of the William S. Middleton Memorial Veterans Hospital, Madison, WI. GRECC MS # 2011-19. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; Dr. Blennow has served on scientific advisory boards for Adlyfe Inc., Bayer Schering Pharma, Bristol-Myers Squibb, and Merz Pharmaceuticals GmbH; received a speaker honorarium from Pfizer Inc.; serves as a consultant for Wyeth, AstraZeneca, Bristol-Myers Squibb, and Eli Lilly and Company; and has received research support from Pfizer Inc., Innogenetics, the Swedish Research Council, Vastra Gotalandsregionen, Sweden, the Swedish Brain Power Project, the Swedish Council for Working Life and Social Research, the Swedish Alzheimer Foundation, Stiftelsen for Gamla Tjanarinnor, and the King Gustaf V and Queen Victoria Foundation. Dr. Zetterberg has served on a scientific advisory board for GlaxoSmithKline; serves as an Associate Editor for the Journal of Alzheimer's Disease; and receives research support from the Swedish Research Council, the Alzheimer's Association, and the Royal Swedish Academy of Sciences. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. NR 123 TC 23 Z9 23 U1 0 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 JUN 6 PY 2012 VL 7 IS 6 AR e37720 DI 10.1371/journal.pone.0037720 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959WK UT WOS:000305348400018 PM 22701578 ER PT J AU He, H Sui, J Yu, QB Turner, JA Ho, BC Sponheim, SR Manoach, DS Clark, VP Calhoun, VD AF He, Hao Sui, Jing Yu, Qingbao Turner, Jessica A. Ho, Beng-Choon Sponheim, Scott R. Manoach, Dara S. Clark, Vincent P. Calhoun, Vince D. TI Altered Small-World Brain Networks in Schizophrenia Patients during Working Memory Performance SO PLOS ONE LA English DT Article ID DORSOLATERAL PREFRONTAL CORTEX; INDEPENDENT COMPONENT ANALYSIS; FUNCTIONAL CONNECTIVITY MRI; COGNITIVE CONTROL; MOTION CORRECTION; DEFAULT NETWORK; SUBJECT MOTION; LOW-FREQUENCY; DYSFUNCTION; ACTIVATION AB Impairment of working memory (WM) performance in schizophrenia patients (SZ) is well-established. Compared to healthy controls (HC), SZ patients show aberrant blood oxygen level dependent (BOLD) activations and disrupted functional connectivity during WM performance. In this study, we examined the small-world network metrics computed from functional magnetic resonance imaging (fMRI) data collected as 35 HC and 35 SZ performed a Sternberg Item Recognition Paradigm (SIRP) at three WM load levels. Functional connectivity networks were built by calculating the partial correlation on preprocessed time courses of BOLD signal between task-related brain regions of interest (ROIs) defined by group independent component analysis (ICA). The networks were then thresholded within the small-world regime, resulting in undirected binarized small-world networks at different working memory loads. Our results showed: 1) at the medium WM load level, the networks in SZ showed a lower clustering coefficient and less local efficiency compared with HC; 2) in SZ, most network measures altered significantly as the WM load level increased from low to medium and from medium to high, while the network metrics were relatively stable in HC at different WM loads; and 3) the altered structure at medium WM load in SZ was related to their performance during the task, with longer reaction time related to lower clustering coefficient and lower local efficiency. These findings suggest brain connectivity in patients with SZ was more diffuse and less strongly linked locally in functional network at intermediate level of WM when compared to HC. SZ show distinctly inefficient and variable network structures in response to WM load increase, comparing to stable highly clustered network topologies in HC. C1 [He, Hao; Sui, Jing; Yu, Qingbao; Turner, Jessica A.; Clark, Vincent P.; Calhoun, Vince D.] Mind Res Network, Albuquerque, NM USA. [He, Hao; Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Ho, Beng-Choon] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Sponheim, Scott R.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Sponheim, Scott R.] Univ Minnesota, Minneapolis VA Hlth Care Syst, Minneapolis, MN USA. [Manoach, Dara S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Clark, Vincent P.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. [Calhoun, Vince D.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Calhoun, Vince D.] Yale Univ, Dept Neurobiol, New Haven, CT USA. [Calhoun, Vince D.] Olin Neuropsychiat Res Ctr, Hartford, CT USA. RP He, H (reprint author), Mind Res Network, Albuquerque, NM USA. EM vcalhoun@unm.edu RI Ho, Beng-Choon/D-6959-2011; Yu, Qingbao/I-2244-2013; He, Hao/H-9618-2014; Turner, Jessica/H-7282-2015; Clark, Vincent/B-3343-2010 OI Ho, Beng-Choon/0000-0003-3976-1555; Yu, Qingbao/0000-0003-4166-3102; Turner, Jessica/0000-0003-0076-8434; Clark, Vincent/0000-0002-9151-2102 FU Department of Energy [DE-FG02-99ER62764]; National Institutes of Health [R01 EB000840, 5P20RR021938] FX The data collection was funded by the Department of Energy, grant DE-FG02-99ER62764. This work was supported by the National Institutes of Health grants R01 EB000840 (PI: VDC) and 5P20RR021938 (PI: VDC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 89 TC 29 Z9 29 U1 4 U2 18 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 JUN 6 PY 2012 VL 7 IS 6 AR e38195 DI 10.1371/journal.pone.0038195 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959WK UT WOS:000305348400039 PM 22701611 ER PT J AU Staropoli, JF Haliw, L Biswas, S Garrett, L Holter, SM Becker, L Skosyrski, S Da Silva-Buttkus, P Calzada-Wack, J Neff, F Rathkolb, B Rozman, J Schrewe, A Adler, T Puk, O Sun, MX Favor, J Racz, I Bekeredjian, R Busch, DH Graw, J Klingenspor, M Klopstock, T Wolf, E Wurst, W Zimmer, A Lopez, E Harati, H Hill, E Krause, DS Guide, J Dragileva, E Gale, E Wheeler, VC Boustany, RM Brown, DE Breton, S Ruether, K Gailus-Durner, V Fuchs, H de Angelis, MH Cotman, SL AF Staropoli, John F. Haliw, Larissa Biswas, Sunita Garrett, Lillian Hoelter, Sabine M. Becker, Lore Skosyrski, Sergej Da Silva-Buttkus, Patricia Calzada-Wack, Julia Neff, Frauke Rathkolb, Birgit Rozman, Jan Schrewe, Anja Adler, Thure Puk, Oliver Sun, Minxuan Favor, Jack Racz, Ildiko Bekeredjian, Raffi Busch, Dirk H. Graw, Jochen Klingenspor, Martin Klopstock, Thomas Wolf, Eckhard Wurst, Wolfgang Zimmer, Andreas Lopez, Edith Harati, Hayat Hill, Eric Krause, Daniela S. Guide, Jolene Dragileva, Ella Gale, Evan Wheeler, Vanessa C. Boustany, Rose-Mary Brown, Diane E. Breton, Sylvie Ruether, Klaus Gailus-Durner, Valerie Fuchs, Helmut de Angelis, Martin Hrabe Cotman, Susan L. TI Large-Scale Phenotyping of an Accurate Genetic Mouse Model of JNCL Identifies Novel Early Pathology Outside the Central Nervous System SO PLOS ONE LA English DT Article ID NEURONAL CEROID-LIPOFUSCINOSIS; ATRIAL-NATRIURETIC-PEPTIDE; JUVENILE BATTEN-DISEASE; KNOCK-IN MICE; INDEPENDENT MECHANISMS; TRANSMEMBRANE PROTEIN; BETA-HEXOSAMINIDASE; INBRED MICE; V-ATPASE; CELLS AB Cln3(Delta ex7/8) mice harbor the most common genetic defect causing juvenile neuronal ceroid lipofuscinosis (JNCL), an autosomal recessive disease involving seizures, visual, motor and cognitive decline, and premature death. Here, to more thoroughly investigate the manifestations of the common JNCL mutation, we performed a broad phenotyping study of Cln3(Delta ex7/8) mice. Homozygous Cln3(Delta ex7/8) mice, congenic on a C57BL/6N background, displayed subtle deficits in sensory and motor tasks at 10-14 weeks of age. Homozygous Cln3(Delta ex7/8) mice also displayed electroretinographic changes reflecting cone function deficits past 5 months of age and a progressive decline of retinal post- receptoral function. Metabolic analysis revealed increases in rectal body temperature and minimum oxygen consumption in 12- 13 week old homozygous Cln3(Delta ex7/8) mice, which were also seen to a lesser extent in heterozygous Cln3(Delta ex7/8) mice. Heart weight was slightly increased at 20 weeks of age, but no significant differences were observed in cardiac function in young adults. In a comprehensive blood analysis at 15-16 weeks of age, serum ferritin concentrations, mean corpuscular volume of red blood cells (MCV), and reticulocyte counts were reproducibly increased in homozygous Cln3(Delta ex7/8) mice, and male homozygotes had a relative T- cell deficiency, suggesting alterations in hematopoiesis. Finally, consistent with findings in JNCL patients, vacuolated peripheral blood lymphocytes were observed in homozygous Cln3(Delta ex7/8) neonates, and to a greater extent in older animals. Early onset, severe vacuolation in clear cells of the epididymis of male homozygous Cln3(Delta ex7/8) mice was also observed. These data highlight additional organ systems in which to study CLN3 function, and early phenotypes have been established in homozygous Cln3(Delta ex7/8) mice that merit further study for JNCL biomarker development. C1 [Staropoli, John F.; Haliw, Larissa; Biswas, Sunita; Lopez, Edith; Harati, Hayat; Guide, Jolene; Dragileva, Ella; Gale, Evan; Wheeler, Vanessa C.; Cotman, Susan L.] Massachusetts Gen Hosp, Mol Neurogenet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Staropoli, John F.; Krause, Daniela S.; Brown, Diane E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Garrett, Lillian; Hoelter, Sabine M.; Puk, Oliver; Sun, Minxuan; Graw, Jochen; Wurst, Wolfgang] Helmholtz Zentrum Munchen, Inst Dev Genet, Neuherberg, Germany. [Becker, Lore; Klopstock, Thomas] Univ Munich, Dept Neurol, Friedrich Baur Inst, D-80804 Munich, Germany. [Becker, Lore; Rathkolb, Birgit; Rozman, Jan; Schrewe, Anja; Adler, Thure; Gailus-Durner, Valerie; Fuchs, Helmut; de Angelis, Martin Hrabe] Helmholtz Zentrum Munchen, German Mouse Clin, Inst Expt Genet, Neuherberg, Germany. [Skosyrski, Sergej] Campus Virchow Klinikum, Charite Eye Hosp, Berlin, Germany. [Da Silva-Buttkus, Patricia; Calzada-Wack, Julia; Neff, Frauke] Helmholtz Zentrum Munchen, Inst Pathol, Neuherberg, Germany. [Rathkolb, Birgit; Wolf, Eckhard] Univ Munich, Chair Mol Anim Breeding & Biotechnol, Gene Ctr, Munich, Germany. [Rozman, Jan; Klingenspor, Martin] TUM, Else Kroner Fresenius Ctr, Freising Weihenstephan, Germany. [Adler, Thure; Busch, Dirk H.] TUM, Inst Med Microbiol Immunol & Hyg, Munich, Germany. [Favor, Jack] Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany. [Racz, Ildiko; Zimmer, Andreas] Univ Bonn, Inst Mol Psychiat, Bonn, Germany. [Bekeredjian, Raffi] Univ Heidelberg, Dept Med 3, Div Cardiol, Otto Meyerhof Zentrum, Heidelberg, Germany. [Wurst, Wolfgang] TUM, Lehrstuhl Entwicklungsgenet, Freising Weihenstephan, Germany. [Wurst, Wolfgang] Max Planck Inst Psychiat, D-80804 Munich, Germany. [Wurst, Wolfgang] Deutsch Zentrum Neurodegenerat Erkrankungen eV Si, Munich, Germany. [Harati, Hayat; Boustany, Rose-Mary] Amer Univ Beirut, Neurogenet Program, Beirut, Lebanon. [Harati, Hayat; Boustany, Rose-Mary] Amer Univ Beirut, Div Pediat Neurol, Dept Pediat, Beirut, Lebanon. [Harati, Hayat; Boustany, Rose-Mary] Amer Univ Beirut, Div Pediat Neurol, Dept Biochem, Beirut, Lebanon. [Hill, Eric; Breton, Sylvie] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Div Nephrol, Boston, MA 02114 USA. [Brown, Diane E.] Massachusetts Gen Hosp, Ctr Comparat Med, Boston, MA 02114 USA. [Ruether, Klaus] Augenabt Sankt Gertrauden Krankenhaus, Berlin, Germany. [de Angelis, Martin Hrabe] TUM, Lehrstuhl Expt Genet, Freising Weihenstephan, Germany. RP Staropoli, JF (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. EM cotman@helix.mgh.harvard.edu RI Hrabe de Angelis, Martin/F-5531-2012; Zimmer, Andreas/B-8357-2009; Puk, Oliver/E-1443-2013; Graw, Jochen/D-9336-2013; Rathkolb, Birgit/F-7041-2013; Becker, Lore/E-3717-2010; Racz, Ildiko/C-3074-2009; Gailus-Durner, Valerie/M-7337-2014; Fuchs, Helmut/M-7347-2014; Holter, Sabine/N-5868-2014; Rozman, Jan/A-2540-2010; Klingenspor, Martin/D-6930-2011; OI Hrabe de Angelis, Martin/0000-0002-7898-2353; Racz, Ildiko/0000-0002-1549-3616; Fuchs, Helmut/0000-0002-5143-2677; Holter, Sabine/0000-0003-4878-5241; Rozman, Jan/0000-0002-8035-8904; Becker, Lore/0000-0002-6890-4984; Calzada, Julia/0000-0003-0816-9305; Wolf, Eckhard/0000-0002-0430-9510; Klingenspor, Martin/0000-0002-4502-6664; Graw, Jochen/0000-0003-0298-9660 FU Dubai-Harvard Foundation for Medical Research; NCL Stiftung; Batten Disease Support and Research Association; National Institutes of Health: National1380 Institute of Neurological Disorders Stroke [NS073813, NS049206]; German Federal Ministry of Education and Research [01GS0850, 01GS0851, 01GS0852, 01GS0853, 01GS0854, GS0868, 01GS0869]; EU [LSHG-2006-037188]; Initiative and Networking Fund of the Helmholtz Association [T(HA-215]; National Institute of Diabetes and Digestive and Kidney Diseases in the form of an Inflammatory Bowel Disease [DK43351]; Boston Area Diabetes and Endocrinology Research Center (BADERC) [DK57521] FX This work was supported by the Dubai-Harvard Foundation for Medical Research [to SLC and R-MB]; NCL Stiftung [to KR]; the Batten Disease Support and Research Association [to JFS]; the National Institutes of Health: National1380 Institute of Neurological Disorders & Stroke [NS073813 to SLC and NS049206 to VCW]; the German Federal Ministry of Education and Research [DZD E.V. to the German Center for Diabetes Research and NGFN-Plus grants 01GS0850, 01GS0851, 01GS0852, 01GS0853, 01GS0854, GS0868, 01GS0869 to the German Mouse Clinic]; EU grant [EUMODIC, LSHG-2006-037188 to the German Mouse Clinic]; and by the Initiative and Networking Fund of the Helmholtz Association in the framework of the Helmholtz Alliance for Mental Research in an Ageing Society [T(HA-215) to Systems Biology/Program in Membrane Biology is partially supported National Institute of Diabetes and Digestive and Kidney Diseases in the form of an Inflammatory Bowel Disease Grant [DK43351] and a Boston Area Diabetes and Endocrinology Research Center (BADERC) Award [DK57521]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 97 TC 18 Z9 18 U1 0 U2 9 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 JUN 6 PY 2012 VL 7 IS 6 AR e38310 DI 10.1371/journal.pone.0038310 PG 23 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959WK UT WOS:000305348400050 PM 22701626 ER PT J AU William, CM Andermann, ML Goldey, GJ Roumis, DK Reid, RC Shatz, CJ Albers, MW Frosch, MP Hyman, BT AF William, Christopher M. Andermann, Mark L. Goldey, Glenn J. Roumis, Demetris K. Reid, R. Clay Shatz, Carla J. Albers, Mark W. Frosch, Matthew P. Hyman, Bradley T. TI Synaptic Plasticity Defect Following Visual Deprivation in Alzheimer's Disease Model Transgenic Mice SO JOURNAL OF NEUROSCIENCE LA English DT Article ID OCULAR-DOMINANCE PLASTICITY; AMYLOID PRECURSOR PROTEIN; EXPERIENCE-DEPENDENT PLASTICITY; APPSWE/PS1DE9 MOUSE MODEL; LONG-TERM POTENTIATION; A-BETA; IN-VIVO; MONOCULAR DEPRIVATION; MEMORY DEFICITS; SPINE LOSS AB Amyloid-beta (A beta)-induced changes in synaptic function in experimental models of Alzheimer's disease ( AD) suggest that A beta generation and accumulation may affect fundamental mechanisms of synaptic plasticity. To test this hypothesis, we examined the effect of APP overexpression on a well characterized, in vivo, developmental model of systems-level plasticity, ocular dominance plasticity. Following monocular visual deprivation during the critical period, mice that express mutant alleles of amyloid precursor protein (APPswe) and Presenilin1 (PS1dE9), as well as mice that express APPswe alone, lack ocular dominance plasticity in visual cortex. Defects in the spatial extent and magnitude of the plastic response are evident using two complementary approaches, Arc induction and optical imaging of intrinsic signals in awake mice. This defect in a classic paradigm of systems level synaptic plasticity shows that A beta overexpression, even early in postnatal life, can perturb plasticity in cerebral cortex, and supports the idea that decreased synaptic plasticity due to elevated A beta exposure contributes to cognitive impairment in AD. C1 [William, Christopher M.; Albers, Mark W.; Frosch, Matthew P.; Hyman, Bradley T.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Boston, MA 02129 USA. [William, Christopher M.; Frosch, Matthew P.] Massachusetts Gen Hosp, Neuropathol Serv, Boston, MA 02129 USA. [Andermann, Mark L.; Goldey, Glenn J.; Roumis, Demetris K.; Reid, R. Clay] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Shatz, Carla J.] Stanford Univ, Stanford, CA 94305 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, 114 16th St, Boston, MA 02129 USA. EM bhyman@partners.org OI William, Christopher/0000-0001-8933-1639 FU NIH [K08 NS069811, R01 EY018742, DP2 OD006662]; Dr. and Mrs. E.P. Richardson Jr. Fund for Neuropathology; Ludcke Foundation; Pierce Charitable Trust; Mathers Charitable Foundation FX This work was supported by NIH (Grants K08 NS069811 to C.M.W., R01 EY018742 to R.C.R., DP2 OD006662 to M.W.A.), by the Dr. and Mrs. E.P. Richardson Jr. Fund for Neuropathology (C.M.W.), by a fellowship from the Ludcke Foundation and Pierce Charitable Trust (M.L.A.), and by the Mathers Charitable Foundation (C.J.S.). We thank Anthony Moffa for assistance with data collection and Sergey Yurgenson and Aleksandr Vagodny for technical contributions. We thank members of the Shatz, Hyman, and Reid laboratories for advice and discussion. NR 58 TC 17 Z9 18 U1 0 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 6 PY 2012 VL 32 IS 23 BP 8004 EP 8011 DI 10.1523/JNEUROSCI.5369-11.2012 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 956LT UT WOS:000305091800024 PM 22674275 ER PT J AU Lemon, KP Armitage, GC Relman, DA Fischbach, MA AF Lemon, Katherine P. Armitage, Gary C. Relman, David A. Fischbach, Michael A. TI Microbiota-Targeted Therapies: An Ecological Perspective SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Review ID INFLUENZAE TYPE-B; CLOSTRIDIUM-DIFFICILE INFECTION; ANTIBIOTIC-ASSOCIATED DIARRHEA; INVASIVE PNEUMOCOCCAL DISEASE; STAPHYLOCOCCUS-AUREUS; CONJUGATE VACCINE; NECROTIZING ENTEROCOLITIS; CHILDREN; CARRIAGE; COMMUNITIES AB The connection between disease and the disruption of homeostatic interactions between the host and its microbiota is now well established. Drug developers and clinicians are starting to rely more heavily on therapies that directly target the microbiota and on the ecology of the microbiota to understand the outcomes of these treatments. The effects of those microbiota-targeted therapies that alter community composition range in scale from eliminating individual strains of a single species (for example, with antibacterial conjugate vaccines) to replacing the entire community with a new intact microbiota (for example, by fecal transplantation). Secondary infections linked to antibiotic use provide a cautionary tale of the unintended consequences of perturbing a microbial species network and highlight the need for new narrow-spectrum antibiotics with rapid companion diagnostics. Insights into microbial ecology will also benefit the development of probiotics, whose therapeutic prospects will depend on rigorous clinical testing. Future probiotics may take the form of a consortium of long-term community residents: '' a fecal transplant in a capsule.'' The efficacy of microbiota-targeted therapies will need to be assessed using new diagnostic tools that measure community function rather than composition, including the temporal response of a microbial community to a defined perturbation such as an antibiotic or probiotic. C1 [Lemon, Katherine P.] Forsyth Inst, Dept Mol Genet, Cambridge, MA 02142 USA. [Lemon, Katherine P.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Infect Dis, Boston, MA 02115 USA. [Armitage, Gary C.] Univ Calif San Francisco, Sch Dent, Div Periodontol, San Francisco, CA 94143 USA. [Relman, David A.] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA. [Relman, David A.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Relman, David A.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA. [Fischbach, Michael A.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA. [Fischbach, Michael A.] Univ Calif San Francisco, Calif Inst Quantitat Biosci, San Francisco, CA 94158 USA. RP Lemon, KP (reprint author), Forsyth Inst, Dept Mol Genet, Cambridge, MA 02142 USA. EM klemon@forsyth.org; fischbach@fischbachgroup.org FU W.M. Keck Foundation; David and Lucile Packard Foundation; NIH [DP2 OD007290, DE020751, DP1OD000964]; Children's Hospital Boston, Office of Faculty Development Career Development Fellowship; Doris Duke Charitable Trust; Thomas C. and Joan M. Merigan Endowment at Stanford University FX Research in the authors' laboratories is supported by a Medical Research award from the W.M. Keck Foundation (M.A.F.), a Fellowship for Science and Engineering from the David and Lucile Packard Foundation (M.A.F.), NIH DP2 OD007290 (M.A.F.), NIH DE020751 (K.P.L.), a Children's Hospital Boston, Office of Faculty Development Career Development Fellowship (K.P.L.), a Distinguished Clinical Scientist Award from the Doris Duke Charitable Trust (D.A.R.), an NIH Pioneer Award DP1OD000964 (D.A.R.), and the Thomas C. and Joan M. Merigan Endowment at Stanford University (D.A.R.). NR 65 TC 46 Z9 48 U1 6 U2 74 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD JUN 6 PY 2012 VL 4 IS 137 AR 137rv5 DI 10.1126/scitranslmed.3004183 PG 8 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 956FO UT WOS:000305075700012 PM 22674555 ER PT J AU Thadhani, R Tamez, H Solomon, SD AF Thadhani, Ravi Tamez, Hector Solomon, Scott D. TI Vitamin D Therapy and Cardiac Function in Chronic Kidney Disease Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID LEFT-VENTRICULAR MASS; HYPERTENSION; HYPERTROPHY; LOSARTAN C1 [Thadhani, Ravi; Tamez, Hector] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Solomon, Scott D.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. RP Thadhani, R (reprint author), Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. EM thadhani.r@mgh.harvard.edu RI Solomon, Scott/I-5789-2013 NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 6 PY 2012 VL 307 IS 21 BP 2254 EP 2254 DI 10.1001/jama.2012.4176 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 952OL UT WOS:000304801700008 ER PT J AU Hughes, K Watkins, MT AF Hughes, Kakra Watkins, Michael T. TI Endovascular Repair of Juxtarenal Aneurysms Real-World Experience SO CIRCULATION LA English DT Editorial Material DE Editorials; abdominal aortic aneurysm; endovascular graft; endovascular repair ID AORTIC-ANEURYSM; MORTALITY; COMPLEX C1 [Watkins, Michael T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg,Dept Surg,Vasc Surg Res, Boston, MA 02114 USA. [Hughes, Kakra] Howard Univ, Dept Surg, Howard Univ Hosp, Coll Med, Washington, DC 20059 USA. RP Watkins, MT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg,Dept Surg,Vasc Surg Res, 15 Parkman St,Suite 440, Boston, MA 02114 USA. EM mtwatkins@partners.org NR 19 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 5 PY 2012 VL 125 IS 22 BP 2684 EP 2685 DI 10.1161/CIRCULATIONAHA.112.109298 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 981NB UT WOS:000306974000010 PM 22665883 ER PT J AU Ahveninen, J Jaaskelainen, IP Belliveau, JW Hamalainen, M Lin, FH Raij, T AF Ahveninen, Jyrki Jaaskelainen, Iiro P. Belliveau, John W. Hamalainen, Matti Lin, Fa-Hsuan Raij, Tommi TI Dissociable Influences of Auditory Object vs. Spatial Attention on Visual System Oscillatory Activity SO PLOS ONE LA English DT Article ID PARIETOOCCIPITAL ALPHA-RHYTHM; PARIETAL REACH REGION; HUMAN-BRAIN; OCCIPITAL CORTEX; SELECTIVE ATTENTION; BAND OSCILLATIONS; CORTICAL SURFACE; CONTROL MECHANISMS; NEURONAL-ACTIVITY; HEAD-DIRECTION AB Given that both auditory and visual systems have anatomically separate object identification ("what") and spatial ("where") pathways, it is of interest whether attention-driven cross-sensory modulations occur separately within these feature domains. Here, we investigated how auditory "what" vs. "where" attention tasks modulate activity in visual pathways using cortically constrained source estimates of magnetoencephalograpic (MEG) oscillatory activity. In the absence of visual stimuli or tasks, subjects were presented with a sequence of auditory-stimulus pairs and instructed to selectively attend to phonetic ("what") vs. spatial ("where") aspects of these sounds, or to listen passively. To investigate sustained modulatory effects, oscillatory power was estimated from time periods between sound-pair presentations. In comparison to attention to sound locations, phonetic auditory attention was associated with stronger alpha (7-13 Hz) power in several visual areas (primary visual cortex; lingual, fusiform, and inferior temporal gyri, lateral occipital cortex), as well as in higher-order visual/multisensory areas including lateral/medial parietal and retrosplenial cortices. Region-of-interest (ROI) analyses of dynamic changes, from which the sustained effects had been removed, suggested further power increases during Attend Phoneme vs. Location centered at the alpha range 400-600 ms after the onset of second sound of each stimulus pair. These results suggest distinct modulations of visual system oscillatory activity during auditory attention to sound object identity ("what") vs. sound location ("where"). The alpha modulations could be interpreted to reflect enhanced crossmodal inhibition of feature-specific visual pathways and adjacent audiovisual association areas during "what" vs. "where" auditory attention. C1 [Ahveninen, Jyrki; Belliveau, John W.; Hamalainen, Matti; Lin, Fa-Hsuan; Raij, Tommi] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Massachusetts Gen Hosp, Charlestown, MA USA. [Belliveau, John W.; Hamalainen, Matti] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Jaaskelainen, Iiro P.] Aalto Univ, Dept Biomed Engn & Computat Sci BECS, Espoo, Finland. [Lin, Fa-Hsuan] Natl Taiwan Univ, Inst Biomed Engn, Taipei 10764, Taiwan. RP Ahveninen, J (reprint author), Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Massachusetts Gen Hosp, Charlestown, MA USA. EM jyrki@nmr.mgh.harvard.edu RI Jaaskelainen, Iiro/C-7392-2012; Hamalainen, Matti/C-8507-2013; Lin, Fa-Hsuan/G-6988-2012 OI Jaaskelainen, Iiro/0000-0001-6001-6950; Lin, Fa-Hsuan/0000-0002-9539-1731 FU National Institutes of Health [R01MH083744, R21DC010060, R01HD040712, R01NS037462, R01NS057500, R01NS048279, 5R01EB009048, P41RR14075]; National Science Foundation [NSF 0351442]; Mental Illness and Neuroscience Discovery Institute; American Heart Association; Ella and Georg Ehrnrooth Foundation; Emil Aaltonen Foundation; Finnish Cultural Foundation; Sigrid Juselius Foundation; Academy of Finland; [S10RR14798]; [S10RR023401]; [S10RR019307]; [S10RR023043] FX This work was supported by National Institutes of Health Awards R01MH083744, R21DC010060, R01HD040712, R01NS037462, R01NS057500, R01NS048279, 5R01EB009048, and P41RR14075; Shared Instrumentation Grants S10RR14798, S10RR023401, S10RR019307, and S10RR023043; National Science Foundation Grant NSF 0351442; the Mental Illness and Neuroscience Discovery Institute, the American Heart Association, the Ella and Georg Ehrnrooth Foundation, the Emil Aaltonen Foundation, the Finnish Cultural Foundation, the Sigrid Juselius Foundation, and the Academy of Finland. The funding organizations had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 92 TC 7 Z9 7 U1 0 U2 10 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 JUN 5 PY 2012 VL 7 IS 6 AR e38511 DI 10.1371/journal.pone.0038511 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959VI UT WOS:000305343900052 PM 22693642 ER PT J AU Zhou, F Lu, Y Ficarro, SB Webber, JT Marto, JA AF Zhou, Feng Lu, Yu Ficarro, Scott B. Webber, James T. Marto, Jarrod A. TI Nanoflow Low Pressure High Peak Capacity Single Dimension LC-MS/MS Platform for High-Throughput, In-Depth Analysis of Mammalian Proteomes SO ANALYTICAL CHEMISTRY LA English DT Article ID CAPILLARY LIQUID-CHROMATOGRAPHY; IONIZATION-MASS-SPECTROMETRY; EMBRYONIC STEM-CELLS; INNER DIAMETERS; PERFORMANCE-CHARACTERISTICS; PEPTIDE SEPARATIONS; MONOLITHIC COLUMNS; PARTICLE-SIZE; FLOW-RATE; MU M AB The use of narrow bore LC capillaries operated at ultralow flow rates coupled with mass spectrometry provides a desirable convergence of figures of merit to support high-performance LC-MS/MS analysis. This configuration provides a viable means to achieve in-depth protein sequence coverage while maintaining a high rate of data production. Here we explore potential performance improvements afforded by use of 25 mu m X 100 cm columns fabricated with 5 mu m diameter reversed phase particles and integrated electrospray emitter tips. These columns achieve a separation peak capacity of approximate to 750 in a 600-min gradient, with average chromatographic peak widths of less than 1 min. At room temperature, a pressure drop of only approximate to 1500 psi is sufficient to maintain an effluent flow rate of <= 10 nL/min. Using mouse embryonic stem cells as a model for complex mammalian proteomes, we reproducibly identify over 4000 proteins across duplicate 600 min LC-MS/MS analyses. C1 [Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Ficarro, Scott B.; Webber, James T.; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02215 USA. [Zhou, Feng; Lu, Yu; Ficarro, Scott B.; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02215 USA. RP Marto, JA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave,Smith 1158A, Boston, MA 02215 USA. EM jarrod_marto@dfci.harvard.edu OI Webber, James/0000-0001-8594-9888 FU NHGRI NIH HHS [P50 HG004233, P50HG004233]; NINDS NIH HHS [P01 NS047572, P01NS047572] NR 65 TC 28 Z9 28 U1 4 U2 47 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 EI 1520-6882 J9 ANAL CHEM JI Anal. Chem. PD JUN 5 PY 2012 VL 84 IS 11 BP 5133 EP 5139 DI 10.1021/ac2031404 PG 7 WC Chemistry, Analytical SC Chemistry GA 952HK UT WOS:000304783100071 PM 22519751 ER PT J AU Henderson, TO Oeffinger, KC Whitton, J Leisenring, W Neglia, J Meadows, A Crotty, C Rubin, DT Diller, L Inskip, P Smith, SA Stovall, M Constine, LS Hammond, S Armstrong, GT Robison, LL Nathan, PC AF Henderson, Tara O. Oeffinger, Kevin C. Whitton, John Leisenring, Wendy Neglia, Joseph Meadows, Anna Crotty, Catherine Rubin, David T. Diller, Lisa Inskip, Peter Smith, Susan A. Stovall, Marilyn Constine, Louis S. Hammond, Sue Armstrong, Greg T. Robison, Leslie L. Nathan, Paul C. TI Secondary Gastrointestinal Cancer in Childhood Cancer Survivors A Cohort Study SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID 2ND MALIGNANT NEOPLASMS; LONG-TERM SURVIVORS; 5-YEAR SURVIVORS; HODGKINS-DISEASE; SUBSEQUENT NEOPLASMS; COLORECTAL-CANCER; FOLLOW-UP; RISK; SURVEILLANCE; CHEMOTHERAPY AB Background: Childhood cancer survivors develop gastrointestinal cancer more frequently and at a younger age than the general population, but the risk factors have not been well-characterized. Objective: To determine the risk and associated risk factors for gastrointestinal subsequent malignant neoplasms (SMNs) in childhood cancer survivors. Design: Retrospective cohort study. Setting: The Childhood Cancer Survivor Study, a multicenter study of childhood cancer survivors diagnosed between 1970 and 1986. Patients: 14 358 survivors of cancer diagnosed when they were younger than 21 years of age who survived for 5 or more years after the initial diagnosis. Measurements: Standardized incidence ratios (SIRs) for gastrointestinal SMNs were calculated by using age-specific population data. Multivariate Cox regression models identified associations between risk factors and gastrointestinal SMN development. Results: At median follow-up of 22.8 years (range, 5.5 to 30.2 years), 45 cases of gastrointestinal cancer were identified. The risk for gastrointestinal SMNs was 4.6-fold higher in childhood cancer survivors than in the general population (95% CI, 3.4 to 6.1). The SIR for colorectal cancer was 4.2 (CI, 2.8 to 6.3). The highest risk for gastrointestinal SMNs was associated with abdominal radiation (SIR, 11.2 [CI, 7.6 to 16.4]). However, survivors not exposed to radiation had a significantly increased risk (SIR, 2.4 [CI, 1.4 to 3.9]). In addition to abdominal radiation, high-dose procarbazine (relative risk, 3.2 [CI, 1.1 to 9.4]) and platinum drugs (relative risk, 7.6 [CI, 2.3 to 25.5]) independently increased the risk for gastrointestinal SMNs. Limitation: This cohort has not yet attained an age at which risk for gastrointestinal cancer is greatest. Conclusion: Childhood cancer survivors, particularly those exposed to abdominal radiation, are at increased risk for gastrointestinal SMNs. These findings suggest that surveillance of at-risk childhood cancer survivors should begin at a younger age than that recommended for the general population. C1 [Henderson, Tara O.] Univ Chicago, Dept Pediat, Sect Hematol Oncol & Stem Cell Transplantat, Chicago, IL 60637 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Minnesota, Minneapolis, MN USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Rochester, Rochester, NY USA. Nationwide Childrens Hosp, Columbus, OH USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. RP Henderson, TO (reprint author), Univ Chicago, Dept Pediat, Sect Hematol Oncol & Stem Cell Transplantat, 5841 S Maryland Ave,MC 4060, Chicago, IL 60637 USA. EM thenderson@peds.bsd.uchicago.edu FU National Cancer Institute [U24 CA55727, K07CA134935]; National Institutes of Health; American Lebanese-Syrian Associated Charities FX Primary Funding Source: National Cancer Institute.; By the NCI through grant U24 CA55727 awarded to Dr. Robison. Additional support was provided by the Intramural Research Program of the National Institutes of Health and NCI and by the American Lebanese-Syrian Associated Charities. Dr. Henderson received support from the NCI through grant K07CA134935. NR 29 TC 34 Z9 35 U1 0 U2 7 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 JUN 5 PY 2012 VL 156 IS 11 BP 757 EP + DI 10.7326/0003-4819-156-11-201206050-00002 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 954ZK UT WOS:000304986500001 PM 22665813 ER PT J AU Ritprajak, P Hayakawa, M Sano, Y Otsu, K Park, JM AF Ritprajak, Patcharee Hayakawa, Morisada Sano, Yasuyo Otsu, Kinya Park, Jin Mo TI Cell type-specific targeting dissociates the therapeutic from the adverse effects of protein kinase inhibition in allergic skin disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE allergic contact dermatitis; contact hypersensitivity; hapten ID CD8(+) T-CELLS; CUTANEOUS DENDRITIC CELLS; TOLL-LIKE RECEPTOR; CONTACT HYPERSENSITIVITY; RHEUMATOID-ARTHRITIS; DOUBLE-BLIND; CCL17; PHOSPHORYLATION; SENSITIZATION; SENSITIVITY AB The kinase p38 alpha, originally identified because of its endotoxin- and cytokine-inducible activity and affinity for antiinflammatory compounds, has been posited as a promising therapeutic target for various immune-mediated disorders. In clinical trials, however, p38 alpha inhibitors produced adverse skin reactions and other toxic effects that often outweighed their benefits. Such toxicity may arise from a perturbation of physiological functions unrelated to or even protective against the disease being treated. Here, we show that the effect of interfering with p38 alpha signaling can be therapeutic or adverse depending on the targeted cell type. Using a panel of mutant mice devoid of p38 alpha in distinct cell types and an experimental model of allergic skin disease, we find that dendritic cell (DC)-intrinsic p38 alpha function is crucial for both antigen-specific T-cell priming and T-cell-mediated skin inflammation, two independent processes essential for the immunopathogenesis. By contrast, p38 alpha in other cell types serves to prevent excessive inflammation or maintain naive T-cell pools in the peripheral lymphoid tissues. These findings highlight a dilemma in the clinical use of p38 alpha inhibitors, yet also suggest cell-selective targeting as a potential solution for improving their therapeutic index. C1 [Ritprajak, Patcharee; Hayakawa, Morisada; Sano, Yasuyo; Park, Jin Mo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Ritprajak, Patcharee; Hayakawa, Morisada; Sano, Yasuyo; Park, Jin Mo] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Ritprajak, Patcharee] Chulalongkorn Univ, Fac Dent, Dent Res Unit Oral Microbiol, Bangkok 10330, Thailand. [Ritprajak, Patcharee] Chulalongkorn Univ, Fac Dent, Dept Microbiol & Immunol, Bangkok 10330, Thailand. [Otsu, Kinya] Osaka Univ, Grad Sch Med, Dept Cardiovasc Med, Suita, Osaka 5650871, Japan. [Otsu, Kinya] Kings Coll London, Div Cardiovasc, London SE5 9NU, England. RP Park, JM (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM jmpark@cbrc2.mgh.harvard.edu OI Hayakawa, Morisada/0000-0002-1869-2450 FU National Institutes of Health [AI074957] FX This study was supported by National Institutes of Health Grant AI074957 (to J.M.P.). NR 29 TC 6 Z9 6 U1 1 U2 1 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 JUN 5 PY 2012 VL 109 IS 23 BP 9089 EP 9094 DI 10.1073/pnas.1202984109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 955BC UT WOS:000304991100064 PM 22615377 ER PT J AU Renquist, BJ Murphy, JG Larson, EA Olsen, D Klein, RF Ellacott, KLJ Cone, RD AF Renquist, Benjamin J. Murphy, Jonathan G. Larson, Emily A. Olsen, Dawn Klein, Robert F. Ellacott, Kate L. J. Cone, Roger D. TI Melanocortin-3 receptor regulates the normal fasting response SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE energy homeostasis; nonesterified fatty acid; corticotrophin-releasing hormone; hormone-sensitive lipase ID AGOUTI-RELATED PROTEIN; WHITE ADIPOSE-TISSUE; MONOCYTE CHEMOATTRACTANT PROTEIN-1; SYMPATHETIC NERVOUS-SYSTEM; PITUITARY-ADRENAL AXIS; INSULIN-RESISTANCE; BONE MASS; PROOPIOMELANOCORTIN PEPTIDES; FRAMESHIFT MUTATION; TRIGLYCERIDE LIPASE AB The melanocortin-3 receptor-deficient (MC3-R-/-) mouse exhibits mild obesity without hyperphagia or hypometabolism. MC3-R deletion is reported to increase adiposity, reduce lean mass and white adipose tissue inflammation, and increase sensitivity to salt-induced hypertension. We show here that the MC3-R-/- mouse exhibits defective fasting-induced white adipose tissue lipolysis, fasting-induced liver triglyceride accumulation, fasting-induced refeeding, and fasting-induced regulation of the adipostatic and hypothalamic-adrenal-pituitary axes. Close examination of the hypothalamic-pituitary-adrenal axis showed that MC3-R-/- mice exhibit elevated nadir corticosterone as well as a blunted fasting-induced activation of the axis. The previously described phenotypes of this animal and the reduced bone density reported here parallel those of Cushing syndrome. Thus, MC3-R is required for communicating nutritional status to both central and peripheral tissues involved in nutrient partitioning, and this defect explains much of the metabolic phenotype in the model. C1 [Renquist, Benjamin J.; Ellacott, Kate L. J.; Cone, Roger D.] Vanderbilt Univ Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Murphy, Jonathan G.] Univ Colorado Denver Sch Med, Dept Pharmacol, Aurora, CO 80045 USA. [Larson, Emily A.; Olsen, Dawn; Klein, Robert F.] Oregon Hlth & Sci Univ, Dept Med, Bone & Mineral Unit, Portland, OR 97201 USA. [Olsen, Dawn; Klein, Robert F.] Portland VA Med Ctr, Portland, OR 97201 USA. RP Cone, RD (reprint author), Vanderbilt Univ Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. EM roger.cone@vanderbilt.edu OI Ellacott, Kate/0000-0001-5261-7465 FU National Institutes of Health [DK078850]; VA Medical Research Service and National Institutes of Health [R01 AR44659] FX We thank Savannah Y. Williams and Katelijn Van Munster for technical assistance. This work was supported by National Institutes of Health Grant DK078850 (to R.D.C.), and by the VA Medical Research Service and National Institutes of Health Grant R01 AR44659 (to R.F.K.). NR 56 TC 27 Z9 27 U1 0 U2 5 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 JUN 5 PY 2012 VL 109 IS 23 BP E1489 EP E1498 DI 10.1073/pnas.1201994109 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 955BC UT WOS:000304991100008 PM 22573815 ER PT J AU Dey, N Das, F Ghosh-Choudhury, N Mandal, CC Parekh, DJ Block, K Kasinath, BS Abboud, HE Choudhury, GG AF Dey, Nirmalya Das, Falguni Ghosh-Choudhury, Nandini Mandal, Chandi Charan Parekh, Dipen J. Block, Karen Kasinath, Balakuntalam S. Abboud, Hanna E. Choudhury, Goutam Ghosh TI microRNA-21 Governs TORC1 Activation in Renal Cancer Cell Proliferation and Invasion SO PLOS ONE LA English DT Article ID TUMOR-SUPPRESSOR PTEN; GROWTH-FACTOR RECEPTOR; HIPPEL-LINDAU GENE; NF-KAPPA-B; KIDNEY CANCER; BREAST-CANCER; HIGH GLUCOSE; GLIOBLASTOMA CELLS; PROGNOSTIC-FACTORS; MAMMALIAN TARGET AB Metastatic renal cancer manifests multiple signatures of gene expression. Deviation in expression of mature miRNAs has been linked to human cancers. Importance of miR-21 in renal cell carcinomas is proposed from profiling studies using tumor tissue samples. However, the role of miR-21 function in causing renal cancer cell proliferation and invasion has not yet been shown. Using cultured renal carcinoma cells, we demonstrate enhanced expression of mature miR-21 along with pre-and pri-miR-21 by increased transcription compared to normal proximal tubular epithelial cells. Overexpression of miR-21 Sponge to quench endogenous miR-21 levels inhibited proliferation, migration and invasion of renal cancer cells. In the absence of mutation in the PTEN tumor suppressor gene, PTEN protein levels are frequently downregulated in renal cancer. We show that miR-21 targets PTEN mRNA 3'untranslated region to decrease PTEN protein expression and augments Akt phosphorylation in renal cancer cells. Downregulation of PTEN as well as overexpression of constitutively active Akt kinase prevented miR-21 Sponge-induced inhibition of renal cancer cell proliferation and migration. Moreover, we show that miR-21 Sponge inhibited the inactivating phosphorylation of the tumor suppressor protein tuberin and attenuated TORC1 activation. Finally, we demonstrate that expression of constitutively active TORC1 attenuated miR-21 Sponge-mediated suppression of proliferation and migration of renal cancer cells. Our results uncover a layer of post-transcriptional regulation of PTEN by transcriptional activation of miR-21 to force the canonical oncogenic Akt/TORC1 signaling conduit to drive renal cancer cell proliferation and invasion. C1 [Dey, Nirmalya; Das, Falguni; Block, Karen; Kasinath, Balakuntalam S.; Abboud, Hanna E.; Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Ghosh-Choudhury, Nandini; Block, Karen; Kasinath, Balakuntalam S.; Abboud, Hanna E.; Choudhury, Goutam Ghosh] S Texas Vet Hlth Care Syst, Vet Adm Res, San Antonio, TX USA. [Choudhury, Goutam Ghosh] S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. [Ghosh-Choudhury, Nandini; Mandal, Chandi Charan] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Parekh, Dipen J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. RP Dey, N (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. EM choudhuryg@uthscsa.edu FU United States National Institutes of Health (NIH) [RO1 DK50190]; VA Research Service Merit Review; Juvenile Diabetes Research Foundation [1-2008-185]; VA Senior Research Career Scientist Award; VA Merit Review, NIH [RO1 AR 52425]; Cancer Therapy and Research Center, San Antonio, Texas; VA Research Service Career Scientist Award; Merit Review Awards; [NIH RO1 CA 131272]; [NIH RO1 DK 077295]; [NIH RO1 DK078971]; [NIH RC2A 036613] FX A United States National Institutes of Health (NIH) RO1 DK50190 grant to GGC supported this work. Part of this work was also supported by VA Research Service Merit Review grant to GGC. GGC is also supported by Juvenile Diabetes Research Foundation 1-2008-185 grants and is recipient of VA Senior Research Career Scientist Award. NGC is supported by VA Merit Review, NIH RO1 AR 52425 grants and Ronald P. Williams Orthopedic Oncology Developmental Research Award from Cancer Therapy and Research Center, San Antonio, Texas. KB, BSK and HEA are supported by grants, NIH RO1 CA 131272 (KB), NIH RO1 DK 077295 (BSK), NIH RO1 DK078971 (HEA), NIH RC2A 036613 (BSK) and VA Research Service Career Scientist Award (KB) and Merit Review Awards (KB, BSK and HEA). NR 118 TC 35 Z9 35 U1 2 U2 9 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 JUN 4 PY 2012 VL 7 IS 6 AR e37366 DI 10.1371/journal.pone.0037366 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959UU UT WOS:000305341700013 PM 22685542 ER PT J AU Hacker, K Choi, YS Trebino, L Hicks, L Friedman, E Blanchfield, B Gazelle, GS AF Hacker, Karen Choi, Yoon Susan Trebino, Lisa Hicks, LeRoi Friedman, Elisa Blanchfield, Bonnie Gazelle, G. Scott TI Exploring the Impact of Language Services on Utilization and Clinical Outcomes for Diabetics SO PLOS ONE LA English DT Article ID LIMITED ENGLISH PROFICIENCY; HEALTH-CARE QUALITY; EMERGENCY-DEPARTMENT; MEDICAL INTERPRETATION; INTERPRETER SERVICES; SPEAKING PATIENTS; CONCORDANCE; SATISFACTION; DISPARITIES; MANAGEMENT AB Background: Significant health disparities exist between limited English proficient and English-proficient patients. Little is known about the impact of language services on chronic disease outcomes such as for diabetes. Methods/Principal Findings: To determine whether the amount and type of language services received during primary care visits had an impact on diabetes-related outcomes (hospitalization, emergency room utilization, glycemic control) in limited English proficient patients, a retrospective cohort design was utilized. Hospital and medical record data was examined for 1425 limited English proficient patients in the Cambridge Health Alliance diabetes registry. We categorized patients receiving usual care into 7 groups based on the amount and combination of language services (language concordant providers, formal interpretation and nothing) received at primary care visits during a 9 month period. Bivariate analyses and multiple logistic regression were used to determine relationships between language service categories and outcomes in the subsequent 6 months. Thirty-one percent of patients (445) had no documentation of interpreter use or seeing a language concordant provider in any visits. Patients who received 100% of their primary care visits with language concordant providers were least likely to have diabetes-related emergency department visits compared to other groups (p<0001) in the following 6 months. Patients with higher numbers of co-morbidities were more likely to receive formal interpretation. Conclusions/Significance: Language concordant providers may help reduce health care utilization for limited English proficient patients with diabetes. However, given the lack of such providers in sufficient numbers to meet patients' communication needs, strategies are needed to both increase their numbers and ensure that the highest risk patients receive the most appropriate language services. In addition, systems serving diverse populations must clarify why some limited English proficient patients do not receive language services at some or all of their visits and whether this has an impact on quality of care. C1 [Hacker, Karen; Choi, Yoon Susan; Trebino, Lisa; Friedman, Elisa] Cambridge Hlth Alliance, Inst Community Hlth, Cambridge, MA USA. [Hacker, Karen; Gazelle, G. Scott] Harvard Univ, Sch Med, Boston, MA USA. [Hicks, LeRoi] Univ Massachusetts, Sch Med, Umass Mem Hlth Care, Worcester, MA USA. [Blanchfield, Bonnie; Gazelle, G. Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Hacker, K (reprint author), Cambridge Hlth Alliance, Inst Community Hlth, Cambridge, MA USA. EM Khacker@challiance.org FU Robert Wood Johnson Foundation [55881] FX This work was funded in part by a grant from the Robert Wood Johnson Foundation Grant #55881 Cost Effectiveness of Language Services. No additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 6 Z9 6 U1 2 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 JUN 4 PY 2012 VL 7 IS 6 AR e38507 DI 10.1371/journal.pone.0038507 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959UU UT WOS:000305341700083 PM 22675571 ER PT J AU Nabuurs, RJA Rutgers, KS Welling, MM Metaxas, A de Backer, ME Rotman, M Bacskai, BJ van Buchem, MA van der Maarel, SM van der Weerd, L AF Nabuurs, Rob J. A. Rutgers, Kim S. Welling, Mick M. Metaxas, Athanasios de Backer, Maaike E. Rotman, Maarten Bacskai, Brian J. van Buchem, Mark A. van der Maarel, Silvere M. van der Weerd, Louise TI In Vivo Detection of Amyloid-beta Deposits Using Heavy Chain Antibody Fragments in a Transgenic Mouse Model for Alzheimer's Disease SO PLOS ONE LA English DT Article ID OCULOPHARYNGEAL MUSCULAR-DYSTROPHY; SINGLE-DOMAIN ANTIBODIES; BRAIN; MICE; ANGIOPATHY; PLAQUES; IMMUNOTHERAPY; PREVENTION; NANOBODIES; PEPTIDES AB This study investigated the in vivo properties of two heavy chain antibody fragments (VHH), ni3A and pa2H, to differentially detect vascular or parenchymal amyloid-beta deposits characteristic for Alzheimer's disease and cerebral amyloid angiopathy. Blood clearance and biodistribution including brain uptake were assessed by bolus injection of radiolabeled VHH in APP/PS1 mice or wildtype littermates. In addition, in vivo specificity for A beta was examined in more detail with fluorescently labeled VHH by circumventing the blood-brain barrier via direct application or intracarotid co-injection with mannitol. All VHH showed rapid renal clearance (10-20 min). Twenty-four hours post-injection Tc-99m-pa2H resulted in a small yet significant higher cerebral uptake in the APP/PS1 animals. No difference in brain uptake were observed for Tc-99m-ni3A or DTPA(In-111)-pa2H, which lacked additional peptide tags to investigate further clinical applicability. In vivo specificity for A beta was confirmed for both fluorescently labeled VHH, where pa2H remained readily detectable for 24 hours or more after injection. Furthermore, both VHH showed affinity for parenchymal and vascular deposits, this in contrast to human tissue, where ni3A specifically targeted only vascular A beta. Despite a brain uptake that is as yet too low for in vivo imaging, this study provides evidence that VHH detect A beta deposits in vivo, with high selectivity and favorable in vivo characteristics, making them promising tools for further development as diagnostic agents for the distinctive detection of different A beta deposits. C1 [Nabuurs, Rob J. A.; Welling, Mick M.; de Backer, Maaike E.; van Buchem, Mark A.; van der Weerd, Louise] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands. [Rutgers, Kim S.; Rotman, Maarten; van der Maarel, Silvere M.; van der Weerd, Louise] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands. [Metaxas, Athanasios] Free Univ Amsterdam, Med Ctr, Radionuclide Ctr, Amsterdam, Netherlands. [Bacskai, Brian J.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Bacskai, Brian J.] Harvard Univ, Sch Med, Charlestown, MA USA. [van der Weerd, Louise] Leiden Univ, Dept Anat & Embryol, Med Ctr, Leiden, Netherlands. RP Nabuurs, RJA (reprint author), Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands. EM R.J.A.Nabuurs@LUMC.nl RI van der Weerd, Louise/B-5421-2014; Metaxas, Athanasios/G-8198-2011; Welling, Mick/A-4582-2012 OI Metaxas, Athanasios/0000-0002-8747-7068; Welling, Mick/0000-0002-2249-5601 FU Center for Translational Molecular Medicine, LeARN; Innovatiegericht OnderzoeksProgramma (IOP)Genomics [IGE05005]; Center for Medical Systems Biology, CMSB2; Netherlands Organisation for Scientific Research (NWO) Athena [700.58.801] FX Research was supported by: (1) the Center for Translational Molecular Medicine, LeARN, http://www.ctmm.nl; (2) Innovatiegericht OnderzoeksProgramma (IOP)Genomics, IGE05005, http://www.agentschapnl.nl/nl/programmas-regelingen/iop-genomics; (3) the Center for Medical Systems Biology, CMSB2, http://www.cmsb.nl; and (4) The Netherlands Organisation for Scientific Research (NWO) Athena, 700.58.801, http://www.nwo.nl/nwohome.nsf/pages/NWOA_6ZXCX3. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 15 Z9 17 U1 3 U2 22 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 JUN 4 PY 2012 VL 7 IS 6 AR e38284 DI 10.1371/journal.pone.0038284 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959UU UT WOS:000305341700056 PM 22675537 ER PT J AU Saribasak, H Maul, RW Cao, Z Yang, WW Schenten, D Kracker, S Gearhart, PJ AF Saribasak, Huseyin Maul, Robert W. Cao, Zheng Yang, William W. Schenten, Dominik Kracker, Sven Gearhart, Patricia J. TI DNA polymerase zeta generates tandem mutations in immunoglobulin variable regions SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CLASS SWITCH RECOMBINATION; SOMATIC HYPERMUTATION; EMBRYONIC LETHALITY; ANTIBODY DIVERSIFICATION; B-CELLS; GENES; MICE; REPAIR; IG; DISRUPTION AB Low-fidelity DNA polymerases introduce nucleotide substitutions in immunoglobulin variable regions during somatic hypermutation. Although DNA polymerase (pol) eta is the major low-fidelity polymerase, other DNA polymerases may also contribute. Existing data are contradictory as to whether pol zeta is involved. We reasoned that the presence of pol eta may mask the contribution of pol zeta, and therefore we generated mice deficient for pol eta and heterozygous for pol zeta. The frequency and spectra of hypermutation was unaltered between Pol zeta(+/-) Pol eta(-/-) and Pol zeta(+/+) Pol eta(-/-) clones. However, there was a decrease in tandem double-base substitutions in Pol zeta(+/-) Pol eta(-/-). cells compared with Pol zeta(+/+) Pol eta(-/-) cells, suggesting that pol zeta generates tandem mutations. Contiguous mutations are consistent with the biochemical property of pol zeta to extend a mismatch with a second mutation. The presence of this unique signature implies that pol zeta contributes to mutational synthesis in vivo. Additionally, data on tandem mutations from wild type, Pol zeta(+/-), Pol zeta(-/-), Ung(-/-), Msh2(-/-), Msh6(-/-), and Ung(-/-) Msh2(-/-) clones suggest that pol zeta may function in the MSH2-MSH6 pathway. C1 [Saribasak, Huseyin; Maul, Robert W.; Cao, Zheng; Yang, William W.; Gearhart, Patricia J.] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. [Schenten, Dominik; Kracker, Sven] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. RP Gearhart, PJ (reprint author), NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. EM gearhartp@mail.nih.gov RI Saribasak, Huseyin/C-9331-2012 OI Saribasak, Huseyin/0000-0003-0055-062X FU National Institutes of Health, National Institute on Aging FX This research was supported entirely by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 36 TC 20 Z9 20 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 4 PY 2012 VL 209 IS 6 BP 1075 EP 1081 DI 10.1084/jem.20112234 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 953XT UT WOS:000304907800004 PM 22615128 ER PT J AU Wang, L Zhou, D Lee, J Niu, HT Faust, TW Frattini, S Kowal, C Huerta, PT Volpe, BT Diamond, B AF Wang, Li Zhou, Dun Lee, Ji Niu, Haitao Faust, Thomas W. Frattini, Stephen Kowal, Czeslawa Huerta, Patricio T. Volpe, Bruce T. Diamond, Betty TI Female mouse fetal loss mediated by maternal autoantibody SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; NMDA RECEPTORS; MISSING WOMEN; IN-VITRO; EXPRESSION; IMPAIRMENT; ANTIBODIES; DISORDERS; SUBUNITS; DEATH AB Systemic lupus erythematosus (SLE), a disease of women during childbearing years, is characterized by the production of double-stranded DNA antibodies. A subset of these antibodies, present in 40% of patients, cross-reacts with the NR2A and NR2B subunits of the N-methyl-D-aspartate receptor (NMDAR). In this study, we show that, in mouse models, these antibodies cause a loss of female fetus viability by inducing apoptosis of NR2A-expressing neurons within the brainstem late in fetal development; gender specificity derives from a time-dependent increased expression of NR2A in female brainstem or increased vulnerability of female fetal neurons to signaling through NR2A-containing NMDARs. This paradigm is consistent with available data on the sex ratio of live births of women with SLE. It represents a novel mechanism by which maternal autoantibodies can severely affect fetal health in a gender-specific fashion and raises the question of how many maternal antibodies affect brain development or exhibit gender-specific fetal effects. C1 [Wang, Li; Zhou, Dun; Niu, Haitao; Kowal, Czeslawa; Diamond, Betty] N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Ctr Autoimmune & Musculoskeletal Dis, Manhasset, NY 11030 USA. [Faust, Thomas W.; Frattini, Stephen; Huerta, Patricio T.] N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Ctr Biomed Sci, Lab Immune & Neural Networks, Manhasset, NY 11030 USA. [Volpe, Bruce T.] N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Lab Funct Neuropathol, Manhasset, NY 11030 USA. [Lee, Ji] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Diamond, B (reprint author), N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Ctr Autoimmune & Musculoskeletal Dis, Manhasset, NY 11030 USA. EM bdiamond@nshs.edu OI Huerta, Patricio/0000-0003-0270-2308; Volpe, Bruce/0000-0002-1098-1848 FU National Institutes of Health [5P01AI073693] FX This work was supported by National Institutes of Health Program Grant 5P01AI073693 (to B. Diamond, P.T. Huerta, and B.T. Volpe). NR 26 TC 19 Z9 19 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 4 PY 2012 VL 209 IS 6 BP 1083 EP 1089 DI 10.1084/jem.20111986 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 953XT UT WOS:000304907800005 PM 22565825 ER PT J AU Knaul, FM Shulman, LN Gralow, J Quick, J Bhadelia, A Frenk, J AF Knaul, Felicia M. Shulman, Lawrence N. Gralow, Julie Quick, Jonathan Bhadelia, Afsan Frenk, Julio TI Improving pathology for better cancer care and control in countries of low and middle income SO LANCET LA English DT Letter C1 [Knaul, Felicia M.; Bhadelia, Afsan] Harvard Global Equ Initiat, Boston, MA 02115 USA. [Shulman, Lawrence N.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gralow, Julie] Seattle Canc Care Alliance, Seattle, WA USA. [Quick, Jonathan] Management Sci Hlth, Cambridge, MA USA. [Frenk, Julio] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Knaul, FM (reprint author), Harvard Global Equ Initiat, Boston, MA 02115 USA. EM felicia_knaul@harvard.edu NR 4 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD JUN 2 PY 2012 VL 379 IS 9831 BP 2052 EP 2052 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 951ZI UT WOS:000304759100028 PM 22656884 ER PT J AU Gilman, SE Dupuy, JM Perlis, RH AF Gilman, Stephen E. Dupuy, Jamie M. Perlis, Roy H. TI Risks for the Transition From Major Depressive Disorder to Bipolar Disorder in the National Epidemiologic Survey on Alcohol and Related Conditions SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PSYCHIATRIC DIAGNOSTIC MODULES; GENERAL-POPULATION SAMPLE; IV AUDADIS-IV; ANXIETY DISORDERS; UNITED-STATES; SEXUAL-ABUSE; LIFE EVENTS; SUBTHRESHOLD BIPOLARITY; CANNABIS USE; FOLLOW-UP AB Objective: It is currently not possible to determine which individuals with unipolar depression are at highest risk for a manic episode. This study investigates clinical and psychosocial risk factors for mania among individuals with major depressive disorder (MDD), indicating diagnostic conversion from MDD to bipolar I disorder. Method: We fitted logistic regression models to predict the first onset of a manic episode among 6,214 cases of lifetime MDD according to DSM-IV criteria in the National Epidemiologic Survey on Alcohol and Related Conditions. Participants in this survey were interviewed twice over a period of 3 years, in 2000-2001 and in 2004-2005, and survey data were gathered using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV. Results: Approximately 1 in 25 individuals with MDD transitioned to bipolar disorder during the study's 3-year follow-up period. Demographic risk factors for the transition from MDD to bipolar disorder included younger age, black race/ethnicity, and less than high school education. Clinical characteristics of depression (eg, age at first onset, presence of atypical features) were not associated with diagnostic conversion. However, prior psychopathology was associated with the transition to bipolar disorder: history of social phobia (odds ratio [OR] = 2.20; 95% confidence interval [CI], 1.47-3.30) and generalized anxiety disorder (OR = 1.58; 95% CI, 1.06-2.35). Lastly, we identified environmental stressors over the life course that predicted the transition to bipolar disorder: these include a history of child abuse (OR = 1.26; 95% CI, 1.12-1.42) and past-year problems with one's social support group (OR = 1.79; 95% CI, 1.19-2.68). The overall predictive power of these risk factors based on a receiver operating curve analysis is modest. Conclusions: A wide range of demographic, clinical, and environmental risk factors were identified that indicate a heightened risk for the transition to bipolar disorder. Additional work is needed to further enhance the prediction of bipolar disorder among cases of MDD and to determine whether interventions targeting these factors could reduce the risk of bipolar disorder. J Clin Psychiatry 2012;73(6):829-836 (c) Copyright 2012 Physicians Postgraduate Press, Inc. C1 [Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Dupuy, Jamie M.; Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Dupuy, Jamie M.; Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Bipolar Clin & Res Program, Boston, MA 02114 USA. [Dupuy, Jamie M.; Perlis, Roy H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Gilman, SE (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM sgilman@hsph.harvard.edu RI Gilman, Stephen/E-7632-2010 OI Gilman, Stephen/0000-0002-8331-6419 FU National Institutes of Health [R01MH87544, R01MH086026] FX Supported by National Institutes of Health grants R01MH87544 (principal investigator: Dr Gilman) and R01MH086026 (principal investigator: Dr Perlis). NR 60 TC 16 Z9 17 U1 3 U2 10 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUN PY 2012 VL 73 IS 6 BP 829 EP 836 DI 10.4088/JCP.11m06912 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 090SK UT WOS:000315000100008 PM 22394428 ER PT J AU Mischoulon, D Alpert, JE Arning, E Bottiglieri, T Fava, M Papakostas, GI AF Mischoulon, David Alpert, Jonathan E. Arning, Erland Bottiglieri, Teodoro Fava, Maurizio Papakostas, George I. TI Bioavailability of S-Adenosyl Methionine and Impact on Response in a Randomized, Double-Blind, Placebo-Controlled Trial in Major Depressive Disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; TANDEM MASS-SPECTROMETRY; PLASMA; ADENOSYLMETHIONINE; HOMOCYSTEINE; DISEASE; ADENOSYLHOMOCYSTEINE; INFLAMMATION; BRAIN; MODEL AB Objective: To characterize the impact of S-adenosyl methionine (SAMe) on homocysteine and potential risk of adverse cardiovascular effects by examining plasma levels of SAMe, S-adenosyl homocysteine (SAH), total homocysteine (tHCY), methionine (MET), and 5-methyltetrahydrofolate (5-MTHF) in 35 of 73 patients from a 6-week randomized double-blind, placebo-controlled trial of SAMe augmentation in serotonin reuptake inhibitor partial responders with DSM-IV major depressive disorder (MDD), published in 2010. Method: Subjects were randomized from June 4, 2004, until August 8, 2008, to adjunctive placebo or SAMe 800-1600 mg/d for 6 weeks. Primary outcome measures included changes in one-carbon cycle intermediates within each treatment arm (by paired t test) and between treatment arms (by independent samples t test). Univariate analysis of variance and Fisher Protected Least Significant Difference were carried out to compare posttreatment levels of each one-carbon cycle intermediate. Secondary outcome measures included associations between clinical improvement and change in plasma intermediate levels, examined by linear regression (for change in Hamilton Depression Rating Scale scores) and logistic regression (for response or remission). Results: We found significant differences in pretreatment plasma levels of tHCY (P = .03) between the SAMe and placebo arms. Following 6 weeks of treatment, plasma SAMe (P = .002) and SAH (P < .0001) levels increased significantly in the SAMe arm; no intermediates in the placebo group changed significantly. Posttreatment plasma SAMe (P = .0035), SAH (P < .0001), and tHCY (P = .0016) levels differed significantly between the SAMe and placebo groups. No significant associations were found between plasma intermediate levels and clinical improvement, response, or remission. Conclusions: Despite concerns about the impact that SAMe therapy may have on homocysteine levels and risk of adverse cardiovascular effects, the lack of significant increase in tHCY levels after treatment suggests that no toxic effects from SAMe should be expected. Our findings, however, have some significant limitations and should be interpreted with caution. C1 [Mischoulon, David; Alpert, Jonathan E.; Fava, Maurizio; Papakostas, George I.] Massachusetts Gen Hosp, Clin & Res Program, Boston, MA 02114 USA. [Mischoulon, David; Alpert, Jonathan E.; Fava, Maurizio; Papakostas, George I.] Harvard Univ, Sch Med, Boston, MA USA. [Arning, Erland; Bottiglieri, Teodoro] Baylor Res Inst, Inst Metab Dis, Dallas, TX USA. RP Mischoulon, D (reprint author), Massachusetts Gen Hosp, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM dmischoulon@partners.org RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X FU Amarin (Laxdale); Bristol-Myers Squibb; Cederroth; Lichtwer Pharma GmbH; Nordic Naturals; Ganeden; Swiss Medica; Fisher-Wallace; Abbott; Alkermes; Lorex; Aspect Medical Systems; AstraZeneca; Cephalon; Cyberonics; Eli Lilly; Forest; GlaxoSmithKline; Johnson Johnson; Novartis; Organon Inc; Pamlab; Pfizer; Pharmavite; Roche; Sanofi/Synthelabo; Solvay; Wyeth-Ayerst; Belvoir Publishing; Bio Research; BrainCells; Clinical Trial Solutions; Ganeden Biotech; National Alliance for Research on Schizophrenia and Depression; National Center for Complementary and Alternative Medicine; National Institute on Drug and Alcohol Abuse; National Institute of Mental Health [5-K23 MH-069629]; Organon; Sanofi-Aventis; Shire; Synthelabo; Advanced Meeting Partners; American Psychiatric Association; Belvoir; Boehringer-Ingelheim; Imedex; PharmaStar; Massachusetts General Hospital Psychiatry Academy/Primedia; Massachusetts General Hospital Psychiatry Academy/Reed-Elsevier; UBC Pharma; Ridge Diagnostics; National Institutes of Health/National Center for Complementary and Alternative Medicine grant [AT002311-01] FX Dr Mischoulon has received research support for other clinical trials from Amarin (Laxdale), Bristol-Myers Squibb, Cederroth, Lichtwer Pharma GmbH, Nordic Naturals, Ganeden, Swiss Medica, and Fisher-Wallace; consulting and writing honoraria from Pamlab; speaking honoraria from Bristol-Myers Squibb, Nordic Naturals, Pfizer, Pamlab, Virbac, and Reed Medical Education (a company working as a logistics collaborator for the Massachusetts General Hospital Psychiatry Academy); and royalty income from Back Bay Scientific for PMS Escape, and from Lippincott Williams & Wilkins for Natural Medications for Psychiatric Disorders: Considering the Alternatives (editors: David Mischoulon and Jerrold F. Rosenbaum). Dr Alpert has received research support from Abbott, Alkermes, Lichtwer Pharma GmbH, Lorex. Aspect Medical Systems, AstraZeneca, Bristol-Myers Squibb, Cephalon, Cyberonics, Eli Lilly, Forest, GlaxoSmithKline, Johnson & Johnson, Novartis, Organon Inc, Pamlab, Pfizer, Pharmavite, Roche, Sanofi/Synthelabo, Solvay, and Wyeth-Ayerst; has participated on advisory boards for or consulted to Eli Lilly, Pamlab, and Pharmavite; has received speakers' honoraria from Eli Lilly, Xian-Janssen, Organon, MGH Psychiatry Academy/Reed Medical Education, MGH Psychiatry Academy/Primedia, and the American Psychiatric Association; and has received editorial fees from Belvoir Publishing. Dr Bottiglieri has been the Chairman of the Advisory Board for Methylation Sciences; holds stock options in Methylation Sciences; and has received grant/research funding from Pamlab.; Dr Fava has received research support from Abbott, Alkermes, Aspect Medical Systems, AstraZeneca, Bio Research, BrainCells, Bristol-Myers Squibb, Cephalon, Clinical Trial Solutions, Eli Lilly, Forest, Ganeden Biotech, GlaxoSmithKline, Johnson & Johnson, Lichtwer Pharma GmbH, Lorex, the National Alliance for Research on Schizophrenia and Depression, the National Center for Complementary and Alternative Medicine, the National Institute on Drug and Alcohol Abuse, the National Institute of Mental Health, Novartis, Organon, Pamlab, Pfizer, Pharmavite, Roche, Sanofi-Aventis, Shire, Solvay, Synthelabo, and Wyeth-Ayerst; has served on the advisory boards of or as a consultant to Abbott, Amarin, Aspect Medical Systems, AstraZeneca, Auspex, Bayer AG, Best Practice Project Management, BioMarin, Biovail, BrainCells, Bristol-Myers Squibb, Cephalon, Clinical Trials Solutions, CNS Response, Compellis, Cypress, Dov, Eli Lilly, EPIX, Euthymics Bioscience, Fabre-Kramer, Forest, GlaxoSmithKline, Grunenthal GmbH, Janssen, Jazz, Johnson & Johnson, Knoll, Labopharm, Lorex Pharmaceuticals, Lundbeck, MedAvante, Merck, Methylation Sciences, Neuronetics, Novartis, Nutrition 21, Organon, Pamlab, Pfizer, PharmaStar, Pharmavite, Precision Human Biolaboratory, PsychoGenics, Roche, Sanofi-Aventis, Sepracor, Schering-Plough, Solvay, Somaxon, Somerset, Synthelabo, Takeda, Tetragenex, TransForm, Transcept, Vanda, and Wyeth-Ayerst; has received speaker and publishing fees from Advanced Meeting Partners, the American Psychiatric Association, AstraZeneca, Belvoir, Boehringer-Ingelheim, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest, GlaxoSmithKline, Imedex, Novartis, Organon, Pfizer, PharmaStar, Massachusetts General Hospital Psychiatry Academy/Primedia, Massachusetts General Hospital Psychiatry Academy/Reed-Elsevier, UBC Pharma, and Wyeth-Ayerst; is a shareholder with Compellis; has patent applications for sequential parallel comparison of design and for a combination of azapirones and bupropion in major depressive disorder; and receives copyright royalties for the following Massachusetts General Hospital assessment tools: the Cognitive and Physical Functioning Questionnaire, the Sexual Functioning Inventory, the Antidepressant Treatment Response Questionnaire, the Discontinuation-Emergent Sign and Symptom scale, and SAFER. Dr Papakostas has served as a consultant for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Evotec AG, Inflabloc, Jazz, Otsuka, Pamlab, Pfizer, Pierre Fabre, Shire, and Wyeth; has received honoraria from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Evotec AG, GlaxoSmithKline, Inflabloc, Jazz, Lundbeck, Otsuka, Pam lab, Pfizer, Pierre Fabre, Shire, Titan, and Wyeth; has received research support from Bristol-Myers Squibb, Forest, the National Institute of Mental Health, Pamlab, Pfizer, and Ridge Diagnostics (formerly known as Precision Human Biolaboratories); and has served on the speakers bureau for Bristol-Myers Squibb and Pfizer. Dr Arian reports no relevant conflicts of interest.; The parent study was funded by a National Institute of Mental Health grant 5-K23 MH-069629 (Dr Papakostas) and National Institutes of Health/National Center for Complementary and Alternative Medicine grant AT002311-01 (Dr Bottiglieri). SAMe and matching placebo pills were provided free of cost by Pharmavite LLC (Mission Hills, California). NR 27 TC 13 Z9 14 U1 1 U2 9 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUN PY 2012 VL 73 IS 6 BP 843 EP 848 DI 10.4088/JCP.11m07139 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 090SK UT WOS:000315000100010 PM 22687580 ER PT J AU Houston, JP Lau, K Aris, V Liu, WL Fijal, BA Heinloth, AN Perlis, RH AF Houston, John P. Lau, Kit Aris, Virginie Liu, Wenlei Fijal, Bonnie A. Heinloth, Alexandra N. Perlis, Roy H. TI Association of Common Variations in the Norepinephrine Transporter Gene With Response to Olanzapine-Fluoxetine Combination Versus Continued-Fluoxetine Treatment in Patients With Treatment-Resistant Depression: A Candidate Gene Analysis SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID ANTIDEPRESSANT TREATMENT RESPONSE; MELANOCORTIN-3 RECEPTOR GENE; STAR-ASTERISK-D; CLINICAL-RESPONSE; MAJOR DEPRESSION; CHILDHOOD OBESITY; SYMPTOM RESPONSE; GENDEP PROJECT; POLYMORPHISMS; DISORDER AB Objective:To determine whether single-nucleotide polymorphisms (SNPs) in candidate genes are associated with response to olanzapine-fluoxetine combination. Method: A post hoc analysis of a priori-selected SNPs used data from a clinical trial (dates: April 2002-July 2005) of olanzapine-fluoxetine combination, fluoxetine, and olanzapine in patients with major depressive disorder (DSM-IV criteria) and with nonresponse to prestudy antidepressant treatment and nonresponse to fluoxetine treatment during the study. Patients received open-label treatment with fluoxetine for 8 weeks (2 weeks, 25 mg/d; then 6 weeks, 50 mg/d), at the end of which nonresponders (< 25% decline in the 17-item Hamilton Depression Rating Scale score) were randomized to receive double-blind, monotherapy treatment with olanzapine-fluoxetine combination (6/50-18/50 mg/d, n = 71), fluoxetine (50 mg/d, n = 78), or olanzapine (6-18 mg/d, n = 56) for 8 weeks. Statistical significance was assessed at P < .05. The primary efficacy measure for within-study treatment was improvement on the Montgomery-Asberg Depression Rating Scale (MADRS). Results: Rs36024, an intronic SNP in the norepinephrine transporter (SLC6A2), as well as 3 SNPs in melanocortin 3 receptor (MC3R) and 2 SNPs in tryptophan hydroxylase 2 (TPH2), were associated with MADRS-defined response to treatment with olanzapine-fluoxetine combination (adjusted Li-Nyholt P < .05). Except for 1 SNP in TPH2, identified SNPs were not significantly associated with response to continued-fluoxetine or olanzapine treatments. Conclusions: Our findings further support the hypothesis that the synergistic effect of olanzapine and fluoxetine on prefrontal cortical levels of norepinephrine and dopamine might be an underlying mechanism for the efficacy of olanzapine-fluoxetine combination in the treatment of treatment-resistant depression and, if replicated, may form a basis on which response to olanzapine-fluoxetine combination versus continued fluoxetine can be predicted based on variants in SLC6A2. C1 [Houston, John P.] Lilly USA LLC, Indianapolis, IN 46285 USA. [Houston, John P.] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN USA. [Liu, Wenlei; Fijal, Bonnie A.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Lau, Kit; Aris, Virginie; Heinloth, Alexandra N.] PharmaNet i3, Ann Arbor, MI USA. [Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Houston, JP (reprint author), Lilly USA LLC, Mail Code 4103, Indianapolis, IN 46285 USA. EM Houston_John_P@lilly.com FU Eli Lilly and Company; Proteus Biomedical; RIDventures; Genomind Equity; Lilly USA, LLC FX Dr Houston is a full-time employee of Lilly USA, LLC, and a minor stockholder of Eli Lilly and Company. Drs Lau, Aris, and Heinloth are full-time employees of PharmaNet/i3, an in Ventiv Health Company, which is a subsidiary of UnitedHealth Group. Dr Liu was a full-time employee and minor stockholder of Eli Lilly and Company at the time of manuscript completion and is now an employee of Pfizer. Dr Fijal is a full-time employee and minor stockholder of Eli Lilly and Company. Dr Perlis has received consulting fees from Eli Lilly and Company, Proteus Biomedical, RIDventures, and Genomind Equity; has received grant/research support from Proteus Biomedical; and holds patents with and receives royalties from Concordant Rater Systems.; This study was supported by Eli Lilly and Company and Lilly USA, LLC. NR 49 TC 6 Z9 6 U1 3 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUN PY 2012 VL 73 IS 6 BP 878 EP 885 DI 10.4088/JCP.10m06744 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 090SK UT WOS:000315000100015 PM 22480387 ER PT J AU Souza, P Hoover, E Gallun, F AF Souza, Pamela Hoover, Eric Gallun, Frederick TI Application of the Envelope Difference Index to Spectrally Sparse Speech SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE compression; consonant recognition; envelope; vocoding ID HEARING-IMPAIRED LISTENERS; PHONEME RECOGNITION; AMPLITUDE COMPRESSION; NOISE; INTELLIGIBILITY; INFORMATION; CHANNELS; QUALITY; CUES; MODULATION AB Purpose: Amplitude compression is a common hearing aid processing strategy that can improve speech audibility and loudness comfort but also has the potential to alter important cues carried by the speech envelope. In previous work, a measure of envelope change, the Envelope Difference Index (EDI; Fortune, Woodruff, & Preves, 1994), was moderately related to recognition of spectrally robust consonants. This follow-up study investigated the relationship between the EDI and recognition of spectrally sparse consonants. Method: Stimuli were vowel-consonant-vowel tokens processed to reduce spectral cues. Compression parameters were chosen to achieve a range of EDI values. Recognition was measured for 20 listeners with normal hearing. Results: Both overall recognition and perception of consonant features were reduced at higher EDI values. Similar effects were noted with noise-vocoded and sine-vocoded processing and regardless of whether periodicity cues were available. Conclusion: The data provide information about the acceptable limits of envelope distortion under constrained conditions. These limits can be used to consider the impact of envelope distortions in situations where other cues are available to varying extents. C1 [Souza, Pamela; Hoover, Eric] Northwestern Univ, Evanston, IL 60208 USA. [Gallun, Frederick] Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Portland, OR USA. RP Souza, P (reprint author), Northwestern Univ, Evanston, IL 60208 USA. EM p-souza@northwestern.edu OI Gallun, Frederick/0000-0002-4145-2199 FU National Institutes of Health [R01 DC0060014]; Department of Veterans Affairs Rehabilitation Research and Development Service [C4963W]; National Center for Rehabilitative Auditory Research FX This work was supported by National Institutes of Health Grant R01 DC0060014 to Pamela Souza, by Department of Veterans Affairs Rehabilitation Research and Development Service Grant C4963W to Frederick Gallun, and by the National Center for Rehabilitative Auditory Research. We thank Steve Armstrong and the Gennum Corporation for providing the hearing aid simulation software; Stuart Rosen for sharing the FIX program and vocoding algorithms; and Ashley Arrington, Alexandra Dykhouse, Louisa Ha, and Marcee Wickline for assistance in data collection. NR 56 TC 4 Z9 4 U1 2 U2 5 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD JUN 1 PY 2012 VL 55 IS 3 BP 824 EP 837 DI 10.1044/1092-4388(2011/10-0301) PG 14 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 084FO UT WOS:000314523500013 PM 22232401 ER PT J AU Carroll, RJ Thompson, WK Eyler, AE Mandelin, AM Cai, TX Zink, RM Pacheco, JA Boomershine, CS Lasko, TA Xu, H Karlson, EW Perez, RG Gainer, VS Murphy, SN Ruderman, EM Pope, RM Plenge, RM Kho, AN Liao, KP Denny, JC AF Carroll, Robert J. Thompson, Will K. Eyler, Anne E. Mandelin, Arthur M. Cai, Tianxi Zink, Raquel M. Pacheco, Jennifer A. Boomershine, Chad S. Lasko, Thomas A. Xu, Hua Karlson, Elizabeth W. Perez, Raul G. Gainer, Vivian S. Murphy, Shawn N. Ruderman, Eric M. Pope, Richard M. Plenge, Robert M. Kho, Abel Ngo Liao, Katherine P. Denny, Joshua C. TI Portability of an algorithm to identify rheumatoid arthritis in electronic health records SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID MEDICAL-SCHOOL CURRICULUM; GENOME-WIDE ASSOCIATION; EXTRACTION SYSTEM; ICD-9-CM CODES; DISEASE; RISK; IDENTIFICATION; INFORMATICS; ENTERPRISE; DISCOVERY AB Objectives Electronic health records (EHR) can allow for the generation of large cohorts of individuals with given diseases for clinical and genomic research. A rate-limiting step is the development of electronic phenotype selection algorithms to find such cohorts. This study evaluated the portability of a published phenotype algorithm to identify rheumatoid arthritis (RA) patients from EHR records at three institutions with different EHR systems. Materials and Methods Physicians reviewed charts from three institutions to identify patients with RA. Each institution compiled attributes from various sources in the EHR, including codified data and clinical narratives, which were searched using one of two natural language processing (NLP) systems. The performance of the published model was compared with locally retrained models. Results Applying the previously published model from Partners Healthcare to datasets from Northwestern and Vanderbilt Universities, the area under the receiver operating characteristic curve was found to be 92% for Northwestern and 95% for Vanderbilt, compared with 97% at Partners. Retraining the model improved the average sensitivity at a specificity of 97% to 72% from the original 65%. Both the original logistic regression models and locally retrained models were superior to simple billing code count thresholds. Discussion These results show that a previously published algorithm for RA is portable to two external hospitals using different EHR systems, different NLP systems, and different target NLP vocabularies. Retraining the algorithm primarily increased the sensitivity at each site. Conclusion Electronic phenotype algorithms allow rapid identification of case populations in multiple sites with little retraining. C1 [Carroll, Robert J.; Zink, Raquel M.; Lasko, Thomas A.; Xu, Hua; Denny, Joshua C.] Vanderbilt Univ, Sch Med, Dept Biomed Informat, Eskind Biomed Lib, Nashville, TN 37232 USA. [Thompson, Will K.; Pacheco, Jennifer A.] Northwestern Univ, Ctr Genet Med, Evanston, IL USA. [Eyler, Anne E.; Boomershine, Chad S.; Denny, Joshua C.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA. [Mandelin, Arthur M.; Ruderman, Eric M.; Pope, Richard M.] Northwestern Univ, Feinberg Sch Med, Div Rheumatol, Dept Med, Chicago, IL 60611 USA. [Cai, Tianxi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Karlson, Elizabeth W.; Plenge, Robert M.; Liao, Katherine P.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Perez, Raul G.; Gainer, Vivian S.; Murphy, Shawn N.] Partners HealthCare, Res Comp, Charlestown, MA USA. [Murphy, Shawn N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Plenge, Robert M.] Broad Inst, Cambridge, MA USA. [Plenge, Robert M.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Kho, Abel Ngo] Northwestern Univ, Feinberg Sch Med, Div Gen Internal Med, Dept Med, Chicago, IL 60611 USA. RP Denny, JC (reprint author), Vanderbilt Univ, Sch Med, Dept Biomed Informat, Eskind Biomed Lib, Room 448,2209 Garland Ave, Nashville, TN 37232 USA. EM josh.denny@vanderbilt.edu OI Pacheco, Jennifer/0000-0001-8021-5818 FU Pharmacogenomics Research Network (PGRN) [U01-GM092691]; National Library of Medicine (NLM) [U54-LM008748, R01-LM010685, 5T15LM007450-10]; NIH [U01-GM092691, R01-AR057108, R01-AR056768, R01-AR059648, K08-AR060257, R01-GM079330]; Burroughs Wellcome Fund; NSF [DMS-0854970]; National Center for Research Resources [UL1RR025741]; Vanderbilt CTSA grant from the National Center for Research Resources [1 UL1 RR024975] FX The project was supported by U01-GM092691 of the Pharmacogenomics Research Network (PGRN), as well as from award number U54-LM008748 from the National Library of Medicine (NLM). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NLM or the National Institutes of Health (NIH). RoMP was supported by grants from the NIH (U01-GM092691, R01-AR057108, R01-AR056768, R01-AR059648), and holds a career award for medical scientists from the Burroughs Wellcome Fund. KPL is supported by K08-AR060257 from the NIH. TC was supported by grants from the NIH (R01-GM079330) and NSF (DMS-0854970). JCD was also supported by R01-LM010685 from the NLM. RJC was supported by 5T15LM007450-10 from the NLM. The Partners Research Patient Data Repository is an integral part of the Partners i2b2 platform. The Northwestern EDW was funded in part by a grant from the National Center for Research Resources, UL1RR025741. BioVU and the Synthetic Derivative were supported in part by Vanderbilt CTSA grant 1 UL1 RR024975 from the National Center for Research Resources. NR 39 TC 67 Z9 68 U1 3 U2 26 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUN PY 2012 VL 19 IS E1 BP E162 EP E169 DI 10.1136/amiajnl-2011-000583 PG 8 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 079DV UT WOS:000314151400027 PM 22374935 ER PT J AU D'Avolio, L Ferguson, R Goryachev, S Woods, P Sabin, T O'Neil, J Conrad, C Gillon, J Escalera, J Brophy, M Lavori, P Fiore, L AF D'Avolio, Leonard Ferguson, Ryan Goryachev, Sergey Woods, Patricia Sabin, Thomas O'Neil, Joseph Conrad, Chester Gillon, Joseph Escalera, Jasmine Brophy, Mary Lavori, Phillip Fiore, Louis TI Implementation of the Department of Veterans Affairs' first point-of-care clinical trial SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article AB Objectives The Massachusetts Veterans Epidemiology Research and Information Center in collaboration with the Stanford Center for Innovative Study Design set out to test the feasibility of a new method of evidence generation. The first pilot of a point-of-care clinical trial (POCCT), adding randomization and other study processes to an electronic medical record (EMR) system, was launched to compare the effectiveness of two insulin regimens. Materials and Methods Existing functionalities of the Veterans Affairs (VA) computerized patient record system (CPRS)/veterans health information systems and technology architecture (VISTA) were modified to support the activities of a randomized controlled trial including enrolment, randomization, and longitudinal data collection. Results The VA's CPRS/VISTA was successfully adapted to support the processes of a clinical trial and longitudinal study data are being collected from the medical record automatically. As of 30 June 2011, 55 of the 67 eligible patients approached received a randomized intervention. Discussion The design of CPRS/VISTA made integration of study workflows and data collection possible. Institutions and investigators considering similar designs must carefully map clinical workflows and clinical trial workflows to EMR capabilities. POCCT study teams are necessarily interdisciplinary and interdepartmental. As a result, executive sponsorship is critical. Conclusion POCCT represent a promising new method for conducting clinical science. Much work is needed to understand better the optimal uses and designs for this new approach. Next steps include focus groups to measure patient and clinician perceptions, multisite deployment of the current pilot, and implementation of additional studies. C1 [D'Avolio, Leonard; Ferguson, Ryan; Goryachev, Sergey; Woods, Patricia; Sabin, Thomas; O'Neil, Joseph; Conrad, Chester; Gillon, Joseph; Escalera, Jasmine; Brophy, Mary; Fiore, Louis] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Cooperat Studies Coordinating Ctr, Jamaica Plain, MA 02130 USA. [D'Avolio, Leonard] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [D'Avolio, Leonard] Brigham & Womens Hosp, Dept Med, Div Ageing, Boston, MA 02115 USA. [D'Avolio, Leonard] Harvard Univ, Sch Med, Boston, MA USA. [Conrad, Chester] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Brophy, Mary; Fiore, Louis] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Lavori, Phillip] Stanford Univ, Stanford Ctr Innovat Study Design, Stanford, CA USA. RP D'Avolio, L (reprint author), VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, 150 S Huntington Ave,MAVERIC 151 MAV, Jamaica Plain, MA 02130 USA. EM leonard.davolio@va.gov FU VA Office of Research and Development; VA Cooperative Studies Program; [UL1 RR025744]; [R01 MH051481] FX This work was supported by the VA Office of Research and Development and the VA Cooperative Studies Program. PL was supported by grants UL1 RR025744 and R01 MH051481 to Stanford University. NR 11 TC 21 Z9 21 U1 2 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUN PY 2012 VL 19 IS E1 BP E170 EP E176 DI 10.1136/amiajnl-2011-000623 PG 7 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 079DV UT WOS:000314151400028 PM 22366293 ER PT J AU Al-Latayfeh, M Silva, PS Sun, JK Aiello, LP AF Al-Latayfeh, Motasem Silva, Paolo S. Sun, Jennifer K. Aiello, Lloyd Paul TI Antiangiogenic Therapy for Ischemic Retinopathies SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; RETINAL-VEIN-OCCLUSION; PROLIFERATIVE DIABETIC-RETINOPATHY; INTRAVITREAL BEVACIZUMAB AVASTIN; RANDOMIZED CLINICAL-TRIAL; MACULAR EDEMA SECONDARY; PROTEIN-KINASE-C; FACTOR TRAP-EYE; SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; VASCULAR-PERMEABILITY FACTOR AB Neovascularization is a common pathological process in various retinal vascular disorders including diabetic retinopathy (DR), age-related macular degeneration (AMD) and retinal vein occlusion (RVO). The development of neovascular vessels may lead to complications such as vitreous hemorrhage, fibrovascular tissue formation, and traction retinal detachments. Ultimately, irreversible vision loss may result. Various proangiogenic factors are involved in these complex processes. Different antiangiogenic drugs have been formulated in an attempt treat these vascular disorders. One factor that plays a major role in the development of retinal neovascularization is vascular endothelial growth factor (VEGF). Anti-VEGF agents are currently FDA approved for the treatment of AMD and RVO. They are also extensively used as an off-label treatment for diabetic macular edema (DME), proliferative DR, and neovascular glaucoma. However, at this time, the long-term safety of chronic VEGF inhibition has not been extensively evaluated. A large and rapidly expanding body of research on angiogenesis is being conducted at multiple centers across the globe to determine the exact contributions and interactions among a variety of angiogenic factors in an effort to determine the therapeutic potential of antiangiogenic agent in the treatment of a variety of retinal diseases. C1 [Aiello, Lloyd Paul] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02215 USA. RP Aiello, LP (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. EM lpaiello@joslin.harvard.edu NR 136 TC 15 Z9 16 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD JUN PY 2012 VL 2 IS 6 AR a006411 DI 10.1101/cshperspect.a006411 PG 20 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 080XW UT WOS:000314278600008 PM 22675660 ER PT J AU Thai, WE Wai, B Lin, K Cheng, T Heist, EK Hoffmann, U Singh, JP Truong, QA AF Thai, Wai-ee Wai, Bryan Lin, Kaity Cheng, Teresa Heist, E. Kevin Hoffmann, Udo Singh, Jagmeet P. Truong, Quynh A. TI Pulmonary Venous Anatomy Imaging With Low-Dose, Prospectively ECG-Triggered, High-Pitch 128-Slice Dual-Source Computed Tomography SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE arrhythmia (heart rhythm disorders); atrial fibrillation; computed tomography; imaging; pulmonary vein isolation ID RADIOFREQUENCY CATHETER ABLATION; ATRIAL-FIBRILLATION; CT ANGIOGRAPHY; VEIN ISOLATION; FOLLOW-UP; RADIATION AB Background-The efforts to reduce radiation from cardiac computed tomography (CT) are essential. Using a prospectively triggered, high-pitch dual-source CT protocol, we aim to determine the radiation dose and image quality in patients undergoing pulmonary vein (PV) imaging. Methods and Results-In 94 patients (61 +/- 9 years; 71% male) who underwent 128-slice dual-source CT (pitch 3.4), radiation dose and image quality were assessed and compared between 69 patients with sinus rhythm and 25 patients with atrial fibrillation. Radiation dose was compared in a subset of 19 patients with prior retrospective or prospectively triggered CT PV scans without high pitch. In a subset of 18 patients with prior magnetic resonance imaging for PV assessment, PV anatomy and scan duration were compared with high-pitch CT. Using the high-pitch protocol, total effective radiation dose was 1.4 (1.3, 1.9) mSv, with no difference between sinus rhythm and atrial fibrillation (1.4 versus 1.5 mSv; P=0.22). No high-pitch CT scans were nondiagnostic or had poor image quality. Radiation dose was reduced with high-pitch (1.6 mSv) compared with standard protocols (19.3 mSv; P<0.0001). This radiation dose reduction was seen with sinus rhythm (1.5 versus 16.7 mSv; P<0.0001) but was more profound with atrial fibrillation (1.9 versus 27.7 mSv; P=0.039). There was excellent agreement of PV anatomy (. 0.84; P<0.0001) and a shorter CT scan duration (6 minutes) compared with magnetic resonance imaging (41 minutes; P<0.0001). Conclusions-Using a high-pitch dual-source CT protocol, PV imaging can be performed with minimal radiation dose, short scan acquisition, and excellent image quality in patients with sinus rhythm or atrial fibrillation. This protocol highlights the success of new cardiac CT technology to minimize radiation exposure, giving clinicians a new low-dose imaging alternative to assess PV anatomy. (Circ Arrhythm Electrophysiol. 2012;5:521-530.) C1 [Thai, Wai-ee; Wai, Bryan; Cheng, Teresa; Hoffmann, Udo; Truong, Quynh A.] Harvard Univ, Div Cardiol, Cardiac MR PET CT Program, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. [Thai, Wai-ee; Wai, Bryan; Cheng, Teresa; Hoffmann, Udo; Truong, Quynh A.] Harvard Univ, Dept Radiol, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lin, Kaity; Heist, E. Kevin; Singh, Jagmeet P.] Harvard Univ, Cardiac Arrhythmia Serv, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Truong, QA (reprint author), Harvard Univ, Div Cardiol, Cardiac MR PET CT Program, Massachusetts Gen Hosp,Med Sch, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM qtruong@partners.org FU National Institutes of Health [K23HL098370, L30HL093896]; Ziosoft, Inc.; Biotronik; Boston Scientific Corp; Medtronic Inc; Sorin Group; St. Jude Medical; Boston Scientific FX Dr Truong was supported by National Institutes of Health grants K23HL098370 and L30HL093896.; Dr Truong receives research grant support from Ziosoft, Inc. Dr Heist receives research grant support and honoraria from Biotronik, Boston Scientific Corp, Medtronic Inc, Sorin Group, and St. Jude Medical and is a consultant to Boston Scientific, Sorin Group, and St. Jude Medical. Dr Singh receives research grant support and honoraria and is a consultant to St. Jude Medical, Medtronic Inc, Boston Scientific Corp, and Biotronik. He is a consultant to CardioInsight, Thoratec Inc, and Biosense Webster and receives honoraria from Guidant Corp and Sorin Group. The other authors have no conflicts to report. NR 23 TC 10 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD JUN PY 2012 VL 5 IS 3 BP 521 EP 530 DI 10.1161/CIRCEP.111.968313 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 071HU UT WOS:000313583100018 PM 22586259 ER PT J AU Rosenbloom, MH Schmahmann, JD Price, BH AF Rosenbloom, Michael H. Schmahmann, Jeremy D. Price, Bruce H. TI The Functional Neuroanatomy of Decision-Making SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID MEDIAL PREFRONTAL CORTEX; POSITRON-EMISSION-TOMOGRAPHY; COGNITIVE-AFFECTIVE SYNDROME; FRONTAL-LOBE; ORBITOFRONTAL CORTEX; MORAL JUDGMENT; RHESUS-MONKEY; ARCHITECTONIC SUBDIVISION; FRONTOTEMPORAL DEMENTIA; NEURONAL-ACTIVITY AB Decision-making is a complex executive function that draws on past experience, present goals, and anticipation of outcome, and which is influenced by prevailing and predicted emotional tone and cultural context. Functional imaging investigations and focal lesion studies identify the orbitofrontal, anterior cingulate, and dorsolateral prefrontal cortices as critical to decision-making. The authors review the connections of these prefrontal regions with the neocortex, limbic system, basal ganglia, and cerebellum, highlight current ideas regarding the cognitive processes of decision-making that these networks subserve, and present a novel integrated neuroanatomical model for decision-making. Finally, clinical relevance of this circuitry is illustrated through a discussion of frontotemporal dementia, traumatic brain injury, and sociopathy. (The Journal of Neuropsychiatry and Clinical Neurosciences 2012; 24:266-277) C1 [Rosenbloom, Michael H.] HealthPartners, Dept Neurol, Ctr Dementia & Alzheimers Care, St Paul, MN USA. [Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Dept Neurol, Cognit Behav Neurol Unit, Ataxia Unit, Boston, MA 02114 USA. [Schmahmann, Jeremy D.; Price, Bruce H.] Harvard Univ, Sch Med, Boston, MA USA. [Price, Bruce H.] McLean Hosp, Dept Neurol, Belmont, MA 02178 USA. [Price, Bruce H.] Massachusetts Gen Hosp, Ctr Law Brain & Behav, Boston, MA 02114 USA. RP Rosenbloom, MH (reprint author), HealthPartners, Dept Neurol, Ctr Dementia & Alzheimers Care, St Paul, MN USA. EM Michael.H.Rosenbloom@HealthPartners.com FU Birmingham Foundation; MINDlink Foundation; Sydney R. Baer Jr. Foundation FX This work was supported in part by the Birmingham, MINDlink, and Sydney R. Baer Jr. Foundations. We also acknowledge the Massachusetts General Hospital Center for Law, Brain, and Behavior. NR 101 TC 29 Z9 29 U1 6 U2 39 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SUM PY 2012 VL 24 IS 3 BP 266 EP 277 PG 12 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 057VS UT WOS:000312592800037 PM 23037641 ER PT J AU Welsh, RC Rao, SV Zeymer, U Thompson, VP Huber, K Kochman, J McClure, MW Gretler, DD Bhatt, DL Gibson, CM Angiolillo, DJ Gurbel, PA Berdan, LG Paynter, G Leonardi, S Madan, M French, WJ Harrington, RA AF Welsh, Robert C. Rao, Sunil V. Zeymer, Uwe Thompson, Vivian P. Huber, Kurt Kochman, Janusz McClure, Matthew W. Gretler, Daniel D. Bhatt, Deepak L. Gibson, C. Michael Angiolillo, Dominick J. Gurbel, Paul A. Berdan, Lisa G. Paynter, Gayle Leonardi, Sergio Madan, Mina French, William J. Harrington, Robert A. CA INNOVATE-PEI Investigators TI A Randomized, Double-Blind, Active-Controlled Phase 2 Trial to Evaluate a Novel Selective and Reversible Intravenous and Oral P2Y(12) Inhibitor Elinogrel Versus Clopidogrel in Patients Undergoing Nonurgent Percutaneous Coronary Intervention The INNOVATE-PCI Trial SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE chronic ischemic heart disease; catheter based coronary interventions; cardiovascular pharmacology; antiplatelets; platelet function inhibitors ID PLATELET INHIBITION; RESISTANCE; CANGRELOR AB Background-We evaluated the safety, efficacy, and tolerability of elinogrel, a competitive, reversible intravenous and oral P2Y(12) inhibitor that does not require metabolic activation, in patients undergoing nonurgent percutaneous coronary intervention. Methods and Results-In a randomized, double-blind, dose-ranging phase 2b trial, 652 patients received either 300 or 600 mg of clopidogrel pre-percutaneous coronary intervention followed by 75 mg daily or 80 or 120 mg of IV elinogrel followed by 50, 100, or 150 mg oral elinogrel twice daily. Numerous exploratory safety and efficacy end points were assessed and, as such, had no prespecified primary end point, and the study was not powered to conclusively evaluate its objectives. Thrombolysis in myocardial infarction combined bleeding was increased with elinogrel (hazard ratio, 1.98; 95% confidence interval, 1.10 to 3.57), related largely to increased bleeding requiring medical attention (elinogrel 47/408 [11.5%] versus clopidogrel 13/208 [6.3%]) and occurring primarily at the percutaneous coronary intervention access site. Efficacy end points and postprocedure cardiac enzyme were similar, but there was a nonsignificant higher frequency of periprocedural myocardial infarctions in the elinogrel arms (OR, 1.59; 95% confidence interval, 0.79 to 3.48). There was an increased incidence of dyspnea (elinogrel 50/408 [12.3%] versus clopidogrel 8/208 [3.8%]) and transaminase elevation (alanine transferase/aspartate transferase > 3X the upper limit of normal; elinogrel 18/408 [4.4%] versus clopidogrel 2/208 [1.0%]) in the elinogrel arms, but there were no cases of heart block, bradycardia, hypotension, or liver failure. Conclusions-In patients undergoing nonurgent percutaneous coronary intervention and in comparison with clopidogrel, intravenous and oral elinogrel therapy did not significantly increase thrombolysis in myocardial infarction major or minor bleeding, although bleeding requiring medical attention was more common. The significance of these findings will need to be more definitively determined in future Phase 3 studies. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00751231. (Circ Cardiovasc Interv. 2012;5:336-346.) C1 [Welsh, Robert C.] Univ Alberta, Edmonton, AB, Canada. [Welsh, Robert C.] Mazankowski Alberta Heart Inst, Edmonton, AB, Canada. [Rao, Sunil V.; Thompson, Vivian P.; Berdan, Lisa G.; Paynter, Gayle; Leonardi, Sergio; Harrington, Robert A.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Zeymer, Uwe] Inst Herzinfarktforsch, Ludwigshafen, Germany. [Huber, Kurt] Wilhelminenhosp, Dept Med 3, Vienna, Austria. [Kochman, Janusz] Med Univ Warsaw, Chair 1, Warsaw, Poland. [Kochman, Janusz] Med Univ Warsaw, Dept Cardiol, Warsaw, Poland. [McClure, Matthew W.; Gretler, Daniel D.] Portola Pharmaceut Inc, San Francisco, CA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Gibson, C. Michael] Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. [Angiolillo, Dominick J.] Univ Florida, Coll Med Jacksonville, Gainesville, FL 32611 USA. [Gurbel, Paul A.] Sinai Ctr Thrombosis Res, Baltimore, MD USA. [Leonardi, Sergio] Fdn IRCCS Policlin San Matteo, Pavia, Italy. [Madan, Mina] Univ Toronto, Toronto, ON, Canada. [Madan, Mina] Sunnybrook Hlth Sci Ctr, Schulich Heart Ctr, Toronto, ON M4N 3M5, Canada. [French, William J.] Methodist Hosp So Calif, Dept Cardiol, Arcadia, CA USA. RP Welsh, RC (reprint author), WMC, 8440 112 St NW, Edmonton, AB T6G 2B7, Canada. EM Robert.Welsh@albertahealthservices.ca OI Welsh, Robert/0000-0003-2613-9142 FU AstraZeneca; Boehringer Ingelheim; Bristol-Myers Squibb; Eli Lilly and Company; Portola Pharmaceuticals Inc; Sanofi-aventis; Amarin; Eisai Co Ltd; Ethicon; Medtronic; The Medicines Company; Bayer AG; Genentech; Johnson Johnson; Accumetrics; Boston Scientific; Daiichi Sankyo; GlaxoSmithKline; Otsuka; Schering-Plough; Bo3en; Haemonetics; Nanosphere; Novartis; Merck FX Dr Welsh has received research funding from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly and Company, Portola Pharmaceuticals Inc, and Sanofi-aventis; has received honoraria from AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, and Sanofi-aventis; and has served on consultant/advisory boards of AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, Roche, and Sanofi-aventis. Dr Rao has received research funding from Portola Pharmaceuticals Inc; honoraria: AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly and Company, Sanofi-aventis, and Terumo; has served on speakers bureaus for Bristol-Myers Squibb and Sanofi-aventis; and has served on the consultant/advisory boards of Bristol-Myers Squibb and The Medicines Company. Dr Zeymer has received research funding from Eli Lilly and Company and Portola Pharmaceuticals Inc; has received honoraria from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly and Company, Novartis, and Sanofi-aventis; and has served on the consultant/advisory boards of AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly and Company, Novartis, and Sanofi-aventis. V. Thompson has no conflicts to disclose. Dr Huber has no conflicts to disclose. Dr Kochman received research funding from Portola Pharmaceuticals Inc. Dr McClure is employed by Portola Pharmaceuticals Inc. Dr Gretler is employed by Portola Pharmaceuticals Inc. Dr Bhatt has served on the advisory board of Medscape Cardiology; has served on the board of directors of Boston VA Research Institute and the Society of Chest Pain Centers; has served as chair of the American Heart Association Get With The Guidelines Science Subcommittee; has received honoraria from the American College of Cardiology (Editor, Clinical Trials, CardioSource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), WebMD (CME steering committees); has received research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai Co Ltd, Ethicon, Medtronic, Sanofi-aventis, The Medicines Company; and has conducted unfunded research for PLx Pharma and Takeda. Dr Gibson has received research funding from AstraZeneca, Bayer AG, Genentech, Johnson & Johnson, and Sanofi-aventis; has served on speakers bureaus for Daiichi Sankyo, Eli Lilly and Company, Schering-Plough, and The Medicines Company; and has served on consultant/advisory boards of Bayer AG, Johnson & Johnson, Portola Pharmaceuticals Inc, Sanofi-aventis, Schering-Plough, and The Medicines Company. Dr Angiolillo has received research funding from Accumetrics, AstraZeneca, Bristol-Myers Squibb, Boston Scientific, Daiichi Sankyo, Eisai Co Ltd, Eli Lilly and Company, GlaxoSmithKline, Johnson & Johnson, Otsuka, Portola Pharmaceuticals Inc, Sanofi-aventis, and Schering-Plough; and has received honoraria from Accumetrics, Arena Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, Evolva, Novartis, Medicure, Portola Pharmaceuticals Inc, Roche, and The Medicines Company.; Dr Gurbel has received research funding from AstraZeneca, Bayer AG, Bo3en, Daiichi Sankyo, Eli Lilly and Company, Haemonetics, Nanosphere, Novartis, Portola Pharmaceuticals Inc, and Sanofi-aventis; has served on speakers bureaus for Accumetrics, AstraZeneca, Daiichi Sankyo, Eli Lilly and Company, Merck, Novartis, Portola Pharmaceuticals Inc, and Sanofi-aventis; has received honoraria from Accumetrics, AstraZeneca, Bayer AG, Daiichi Sankyo, Novartis, Portola Pharmaceuticals Inc, and The Medicines Company; and has served on consultant/advisory boards of AstraZeneca, Bayer AG, Bo3en, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly and Company, Merck, and Novartis. L. Berdan has no conflicts to disclose. G. Paynter has no conflicts to disclose. Dr Leonardi has no conflicts to disclose. Dr Madan MD has received research funding from AstraZeneca and Portola Pharmaceuticals Inc; has served on consultant/advisory boards of AstraZeneca and Eli Lilly and Company; and has received honoraria from AstraZeneca, Eli Lilly and Company, and Portola Pharmaceuticals Inc. Dr French has received research funding from Portola Pharmaceuticals Inc; has served on a speakers bureau for Eli Lilly and Company; and has fulfilled various speaking engagements. Dr Harrington has received research funding from AstraZeneca, Bristol-Myers Squibb, Novartis, Merck, Portola Pharmaceuticals Inc, Sanofi-aventis, and The Medicines Company; and has served on consultant/advisory boards of AstraZeneca, Bristol-Myers Squibb, Merck, Novartis, and Sanofi-aventis. NR 19 TC 53 Z9 62 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7640 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD JUN PY 2012 VL 5 IS 3 BP 336 EP 346 DI 10.1161/CIRCINTERVENTIONS.111.964197 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 045OT UT WOS:000311707000011 PM 22647518 ER PT J AU Izamis, ML Berendsen, TA Uygun, K Yarmush, ML AF Izamis, Maria-Louisa Berendsen, Tim A. Uygun, Korkut Yarmush, Martin L. TI Addressing the Donor Liver Shortage with EX VIVO Machine Perfusion SO JOURNAL OF HEALTHCARE ENGINEERING LA English DT Article DE machine perfusion; normothermic; hypothermic; subnormothermic; transplantation ID HEART-BEATING DONORS; TRYPTOPHAN-KETOGLUTARATE SOLUTION; ISCHEMIC RAT-LIVER; NORMOTHERMIC EXTRACORPOREAL PERFUSION; CONVENTIONAL COLD-STORAGE; HYDROPHILIC BILE-SALTS; OF-WISCONSIN SOLUTION; ORGAN-PRESERVATION; UW-SOLUTION; EXTENDED PRESERVATION AB Despite a critical shortage of viable donor livers for transplantation, only a fraction of the available organs are used. Donor organ defects, which in the majority of cases are caused by extensive exposure to ischemia, cannot be reversed by static cold storage, the current gold standard of organ preservation. In this review, the role of machine perfusion (MP) in the recovery of non-transplantable ischemic donor organs is discussed. Though still in the experimental phase, various models of MP have consistently demonstrated that ischemic donor organs can be recovered to a transplantable state through continuous perfusion. MP can also provide dynamic quantitative assessments of the extent of ischemia, in addition to predicting the likelihood of organ recovery. Continued endeavors to translate MP into clinical use and eventually incorporate it into routine donor organ care will have a significant impact on the quality and availability of transplantable donor organs. C1 [Izamis, Maria-Louisa; Berendsen, Tim A.; Uygun, Korkut; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med Surg Serv, Boston, MA USA. [Izamis, Maria-Louisa; Berendsen, Tim A.; Uygun, Korkut; Yarmush, Martin L.] Shriners Burns Hosp, Boston, MA USA. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. RP Uygun, K (reprint author), 51 Blossom St, Boston, MA 02114 USA. EM mizamis@partners.org; tberendsen@partners.org; uygun.korkut@mgh.harvard.edu; ireis@sbi.org FU National Institutes of Health [R00 DK080942, R01DK59766, R01 EB008678]; Shriners Hospitals for Children FX We gratefully acknowledge the National Institutes of Health (R00 DK080942, R01DK59766, R01 EB008678), and Shriners Hospitals for Children. NR 149 TC 4 Z9 4 U1 0 U2 7 PU MULTI-SCIENCE PUBL CO LTD PI BRENTWOOD PA 5 WATES WAY, BRENTWOOD CM15 9TB, ESSEX, ENGLAND SN 2040-2295 J9 J HEALTHC ENG JI J. Healthc. Eng. PD JUN PY 2012 VL 3 IS 2 BP 279 EP 297 DI 10.1260/2040-2295.3.2.279 PG 19 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 045DF UT WOS:000311674500006 ER PT J AU Boffa, DJ Gangadharan, S Kent, M Kerendi, F Onaitis, M Verrier, E Roselli, E AF Boffa, Daniel J. Gangadharan, Sidharta Kent, Michael Kerendi, Faraz Onaitis, Mark Verrier, Edward Roselli, Eric TI Self-perceived video-assisted thoracic surgery lobectomy proficiency by recent graduates of North American thoracic residencies SO INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY LA English DT Article DE VATS; Lobectomy; Proficiency ID THORACOSCOPIC LOBECTOMY; DATABASE AB Minimally invasive surgical techniques offer several advantages over traditional open procedures, yet the pathway to minimally invasive proficiency can be difficult to navigate. As a part of an effort of the Joint Council of Thoracic Surgical Education to increase access to this skill set in the general thoracic community, recent graduates of thoracic residencies were surveyed to determine the self-reported achievement of video-assisted thoracic surgery (VATS) lobectomy proficiency and the merits of various educational opportunities. The objective of this study was to estimate the comfort level of recent graduates with the minimally invasive approach, as this demographic not only reflects the current status of training, but represents the future of the specialty. Surgeons graduating North American thoracic residencies between 2006 and 2008 identifying themselves as practitioners of general thoracic surgery were surveyed. A total of 271 surgeons completed training between 2006 and 2008 and indicated general thoracic to be a part of their practice (84 dedicated thoracic and 187 mixed). One hundred and forty-six surgeons completed the survey (54%) including 74 of 84 (88%) dedicated thoracic surgeons. Overall, 58% of recent graduates who perform general thoracic procedures consider themselves proficient in VATS lobectomies (86% of dedicated thoracic surgeons and 28% of surgeons with a mixed practice, P < 0.0001). Of surgeons considering themselves to be proficient at VATS lobectomies, 66% felt thoracic residency was critical or very important to achieving proficiency. Fellowships after completing board residency, animal labs, and follow-up VATS courses put on by experts were much less consistently beneficial. The vast majority of the 25 dedicated general thoracic surgeons who graduate each year consider themselves proficient in VATS lobectomies, largely due to training in their thoracic residencies. On the other hand, the minority of surgeons performing general thoracic procedures as a part of a mixed practice consider themselves proficient in VATS lobectomies. Further study is warranted to enhance the VATS lobectomy experience of mixed practice surgeons particularly during their thoracic residencies. C1 [Boffa, Daniel J.] Yale Univ, Sch Med, Dept Thorac Surg, Smilow Canc Hosp, New Haven, CT USA. [Gangadharan, Sidharta; Kent, Michael] Beth Isreal Deaconess Med Ctr, Dept Thorac Surg, Boston, MA USA. [Kerendi, Faraz] Cardiovasc & Thorac Surg, Austin, TX USA. [Onaitis, Mark] Duke Univ, Sch Med, Dept Thorac Surg, Durham, NC USA. [Verrier, Edward] Univ Washington, Dept Cardiovasc Surg, Seattle, WA 98195 USA. [Roselli, Eric] Cleveland Clin, Dept Thorac & Cardiovasc Surg, Cleveland, OH 44106 USA. RP Boffa, DJ (reprint author), 330 Cedar St,BB205, New Haven, CT 06520 USA. EM daniel.boffa@yale.edu NR 8 TC 15 Z9 15 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1569-9293 J9 INTERACT CARDIOV TH JI Interact Cardiovasc. Thorac. Surg. PD JUN PY 2012 VL 14 IS 6 BP 797 EP 800 DI 10.1093/icvts/ivr098 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 025GK UT WOS:000310175300033 PM 22381653 ER PT J AU LeTonqueze, O Lee, JH Vasudevan, S AF LeTonqueze, Olivier Lee, Ju Huck Vasudevan, Shobha TI MicroRNA-mediated posttranscriptional mechanisms of gene expression in proliferating and quiescent cancer cells SO RNA BIOLOGY LA English DT Review DE microRNA; RNA-binding proteins; cancer; quiescence; regulation ID RNA-BINDING PROTEIN; TUMOR-ASSOCIATED MACROPHAGES; 3' UNTRANSLATED REGIONS; MESSENGER-RNA; STEM-CELL; TRANSLATIONAL REPRESSION; BREAST-CANCER; GW BODIES; ALTERNATIVE POLYADENYLATION; CAENORHABDITIS-ELEGANS AB MicroRNAs are small non-coding RNA regulators of gene expression that play important roles in critical biological processes, including cell division, self-renewal and cell state maintenance. Their deregulation leads to extensive clinical consequences in tumorigenesis. Cancers demonstrate heterogeneity in their cell states implicated in their resistance and resurgence. Apart from proliferating cells, cancers harbor a small proportion of assorted quiescent cells that resist conventional therapeutics and contribute to cancer recurrence. MicroRNA expression, targets, microRNPs (microRNA-protein complexes) and their functions have been demonstrated to be regulated in distinct tumor cell states and as an adaptive response to stress signals in tumor-unfavorable environments. In turn, altered microRNPs and their modified post-transcriptional mechanisms of gene expression may contribute to tumor resistance and influence tumor progression. An understanding of distinct microRNA mechanisms in cancer cells would provide extensive insights into the versatile roles of microRNAs in the perpetuation of tumors and indicate potential therapeutic avenues. C1 [LeTonqueze, Olivier; Lee, Ju Huck; Vasudevan, Shobha] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. RP Vasudevan, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. EM vasudevan.shobha@mgh.harvard.edu FU Cancer Research Investigator Award; D. and M-E Ryder Award; Smith Family Foundation Award FX The authors and this review were supported by a Cancer Research Investigator Award, the D. and M-E Ryder Award and a Smith Family Foundation Award to S.V. NR 149 TC 6 Z9 6 U1 1 U2 12 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1547-6286 EI 1555-8584 J9 RNA BIOL JI RNA Biol. PD JUN PY 2012 VL 9 IS 6 SI SI BP 871 EP 880 DI 10.4161/rna.20806 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 982XA UT WOS:000307077500017 PM 22699554 ER PT J AU Carroll, J Saxena, R Welt, CK AF Carroll, Jessica Saxena, Richa Welt, Corrine K. TI Environmental and genetic factors influence age at menarche in women with polycystic ovary syndrome SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article DE birth weight; body mass index (BMI); breastfeeding; puberty ID GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; YOUNGER WOMEN; ADMIXTURE MAP; BIRTH-WEIGHT; ADULTHOOD; GROWTH; LOCI; HISTORY; OBESITY AB Objective: We hypothesized that body mass index (BMI) and DNA variants would predict age at menarche in polycystic ovarian syndrome (PCOS). Subjects: Subjects aged 18-45 years with PCOS defined by the National Institutes of Health criteria (n=522) and controls with regular menstrual cycles and no hyperandrogenism (n=472) were studied. Methods: Age at menarche was compared between PCOS cases and controls and examined as a function of multiple parameters. Results: There was a strong inverse relationship between BMI and age at menarche in PCOS (r=-0.32, p=5x10(-11)). The chromosome 6 rs7759938-T variant was associated with earlier age at menarche in women with PCOS (12.60 +/- 0.09 vs. 13.41 +/- 0.23 years; genotype TT vs. CC; p=0.006). Age at menarche was predicted by PCOS status (beta=0.512, p<0.001), reported weight group at 10-14 years (beta=-0.432, p<0.001), current BMI (beta=-0.0202, p=0.01), and genotype (beta=0.169, p=0.02). Conclusions: Age at menarche in women with PCOS is influenced by BMI and genetic variants near LIN28B C1 [Carroll, Jessica; Welt, Corrine K.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. [Saxena, Richa] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. [Saxena, Richa] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Welt, CK (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX 511,55 Fruit St, Boston, MA 02114 USA. EM cwelt@partners.org OI Welt, Corrine/0000-0002-8219-5504 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [R01HD065029]; Harvard Clinical and Translational Science Center, from the National Center for Research Resources [1 UL1 RR025758]; American Diabetes Association [1-10-CT-57] FX The project described was supported by Award Number R01HD065029 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Award Number 1 UL1 RR025758, Harvard Clinical and Translational Science Center, from the National Center for Research Resources, and award 1-10-CT-57 from the American Diabetes Association. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Center For Research Resources, the National Institutes of Health, or the American Diabetes Association. NR 34 TC 8 Z9 8 U1 1 U2 5 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0334-018X EI 2191-0251 J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD JUN PY 2012 VL 25 IS 5-6 BP 459 EP 466 DI 10.1515/jpem-2012-0047 PG 8 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 019QQ UT WOS:000309754800010 PM 22876539 ER PT J AU Goldfarb, E Baer, L Fromson, JA Gorrindo, T Iodice, KE Birnbaum, RJ AF Goldfarb, Elizabeth Baer, Lee Fromson, John A. Gorrindo, Tristan Iodice, Kristin E. Birnbaum, Robert J. TI Attendees' perceptions of commercial influence in noncommercially funded CME programs SO JOURNAL OF CONTINUING EDUCATION IN THE HEALTH PROFESSIONS LA English DT Article DE commercial bias; continuing medical education; funding; attendee perception ID CONTINUING MEDICAL-EDUCATION; INDUSTRY SUPPORT; BIAS; ATTITUDES; QUALITY; EXPERTS AB Introduction: The controversy surrounding commercial support for continuing medical education (CME) programs has led to policy changes, but data show no significant difference in perceived bias between commercial and noncommercial CME. Indeed, what attendees perceive as commercial influence is not fully understood. We sought to clarify what sources contribute to attendees' perceptions of commercial influence in non-industry-supported CME programs, and how attendees perceive that this influence manifests itself on both speaker and program levels. Methods: Evaluation forms were received from 1 544 attendees at 14 live noncommercially supported CME programs in 2006, 2007, and 2010. Attendees rated perceived commercial influence for each lecture and the entire program. Using open-ended and check all that apply'' questions, participants specified perceived sources and manifestations of commercial influence. Results: Attendees rating individual lectures but not the entire program as commercially influenced accounted for 59.9% of those who identified bias. The most frequently endorsed source of commercial influence was individual speakers' funding, and the most listed manifestations were speakers' mentions of pharmaceuticals and expressions of personal opinions. Rating the entire program commercially influenced correlated with whether attendees considered the funding of referenced research a source of influence. Discussion: CME attendees consider a broad spectrum of factors when reporting commercial influence. Evaluation forms should include bias questions per lecture as well as items to clarify perceived sources and manifestations of commercial influence. C1 [Goldfarb, Elizabeth; Fromson, John A.; Gorrindo, Tristan; Iodice, Kristin E.] Massachusetts Gen Hosp, Div Postgrad Med Educ, Boston, MA 02114 USA. [Baer, Lee] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Baer, Lee; Fromson, John A.; Gorrindo, Tristan; Birnbaum, Robert J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Birnbaum, RJ (reprint author), 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM rjbirnbaum@partners.org FU Massachusetts General Hospital Psychiatry Academy FX This research was funded by academic institutional support from the Massachusetts General Hospital Psychiatry Academy. NR 24 TC 2 Z9 2 U1 0 U2 2 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 0894-1912 J9 J CONTIN EDUC HEALTH JI J. Contin. Educ. Health Prof. PD SUM PY 2012 VL 32 IS 3 BP 205 EP 211 DI 10.1002/chp.21146 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 010BW UT WOS:000309070400008 PM 23008083 ER PT J AU Rosca, F AF Rosca, Florin TI A hybrid electron and photon IMRT planning technique that lowers normal tissue integral patient dose using standard hardware SO MEDICAL PHYSICS LA English DT Article DE electrons; IMRT; brain; lung ID INTENSITY-MODULATED RADIOTHERAPY; RADIATION-THERAPY; MONTE-CARLO; HIGH-ENERGY; MULTILEAF COLLIMATOR; BREAST-CANCER; BEAM THERAPY; OPTIMIZATION; IRRADIATION; DOSIMETRY AB Purpose: To present a mixed electron and photon IMRT planning technique using electron beams with an energy range of 6-22 MeV and standard hardware that minimizes integral dose to patients for targets as deep as 7.5 cm. Methods: Ten brain cases, two lung, a thyroid, an abdominal, and a parotid case were planned using two planning techniques: a photon-only IMRT (IMRT) versus a mixed modality treatment (E + IMRT) that includes an enface electron beam and a photon IMRT portion that ensures a uniform target coverage. The electron beam is delivered using a regular cutout placed in an electron cone. The electron energy was chosen to provide a good trade-off between minimizing integral dose and generating a uniform, deliverable plan. The authors choose electron energies that cover the deepest part of PTV with the 65%-70% isodose line. The normal tissue integral dose, the dose for ring structures around the PTV, and the volumes of the 75%, 50%, and 25% isosurfaces were used to compare the dose distributions generated by the two planning techniques. Results: The normal tissue integral dose was lowered by about 20% by the E + IMRT plans compared to the photon-only IMRT ones for most studied cases. With the exception of lungs, the dose reduction associated to the E + IMRT plans was more pronounced further away from the target. The average dose ratio delivered to the 0-2 cm and the 2-4 cm ring structures for brain patients for the two planning techniques were 89.6% and 70.8%, respectively. The enhanced dose sparing away from the target for the brain patients can also be observed in the ratio of the 75%, 50%, and 25% isodose line volumes for the two techniques, which decreases from 85.5% to 72.6% and further to 65.1%, respectively. For lungs, the lateral electron beams used in the E + IMRT plans were perpendicular to the mostly anterior/posterior photon beams, generating much more conformal plans. Conclusions: The authors proved that even using the existing electron delivery hardware, a mixed electron/photon planning technique (E + IMRT) can decrease the normal tissue integral dose compared to a photon-only IMRT plan. Different planning approaches can be enabled by the use of an electron beam directed toward organs at risk distal to the target, which are still spared due the rapid dose fall-off of the electron beam. Examples of such cases are the lateral electron beams in the thoracic region that do not irradiate the heart and contralateral lung, electron beams pointed toward kidneys in the abdominal region, or beams treating brain lesions pointed toward the brainstem or optical apparatus. For brain, electron vertex beams can also be used without irradiating the whole body. Since radiation retreatments become more and more common, minimizing the normal tissue integral dose and the dose delivered to tissues surrounding the target, as enabled by E + IMRT type techniques, should receive more attention. (C) 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4709606] C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Danvers, MA 01923 USA. RP Rosca, F (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Danvers, MA 01923 USA. EM frosca@partners.org NR 34 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 2964 EP 2971 DI 10.1118/1.4709606 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905800003 PM 22755681 ER PT J AU Zhang, D Li, XH Liu, B AF Zhang, Da Li, Xinhua Liu, Bob TI X-ray spectral measurements for tungsten-anode from 20 to 49 kVp on a digital breast tomosynthesis system SO MEDICAL PHYSICS LA English DT Article DE x-ray spectrum; spectroscopy; digital breast tomosynthesis ID CONTRAST-ENHANCED TECHNIQUE; DUAL-ENERGY MAMMOGRAPHY; CDZNTE DETECTOR; CDTE DETECTOR; OPTIMIZATION; SPECTROSCOPY; SIMULATION; PROTOCOL; DENSITY AB Purpose: This paper presents new spectral measurements of a tungsten-target digital breast tomosynthesis (DBT) system, including spectra of 43-49 kVp. Methods: Raw x-ray spectra of 20-49 kVp were directly measured from the tube port of a Selenia Dimensions DBT system using a CdTe based spectrometer. Two configurations of collimation were employed: one with two tungsten pinholes of 25 mu m and 200 mu m diameters, and the other with a single pinhole of 25 mu m diameter, for acquiring spectra from the focal spot and from the focal spot as well as its vicinity. Stripping correction was applied to the measured spectra to compensate distortions due to escape events. The measured spectra were compared with the existing mammographic spectra of the TASMIP model in terms of photon fluence per exposure, spectral components, and half-value layer (HVL). HVLs were calculated from the spectra with a numerical filtration of 0.7 mm aluminum and were compared against actual measurements on the DBT system using W/Al (target-filter) combination, without paddle in the beam. Results: The spectra from the double-pinhole configuration, in which the acceptance aperture pointed right at the focal spot, were harder than the single-pinhole spectra which include both primary and off-focus radiation. HVL calculated from the single-pinhole setup agreed with the measured HVL within 0.04 mm aluminum, while the HVL values from the double-pinhole setup were larger than the single-pinhole HVL by at most 0.1 mm aluminum. The spectra from single-pinhole setup agreed well with the TASMIP mammographic spectra, and are more relevant for clinical purpose. Conclusions: The spectra data would be useful for future research on DBT system with tungsten targets. (C) 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4719958] C1 [Zhang, Da; Li, Xinhua; Liu, Bob] Massachusetts Gen Hosp, Dept Radiol, Div Diagnost Imaging Phys, Boston, MA 02114 USA. RP Liu, B (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Diagnost Imaging Phys, Boston, MA 02114 USA. EM bliu7@bics.bwh.harvard.edu NR 39 TC 8 Z9 8 U1 0 U2 9 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3493 EP 3500 DI 10.1118/1.4719958 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905803005 PM 22755729 ER PT J AU Saleh, Z Apte, A Sharp, G Rao, S Lee, N Deasy, J AF Saleh, Z. Apte, A. Sharp, G. Rao, S. Lee, N. Deasy, J. TI Exploring the Correlation Between 3D Spatial Dose Distribution and Toxicity in Normal Tissue SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Saleh, Z.; Apte, A.; Rao, S.; Lee, N.; Deasy, J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Sharp, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3601 EP 3601 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905804023 ER PT J AU Unkelbach, J Menze, B Konukoglu, E Motamedi, A Ayache, N Shih, H AF Unkelbach, J. Menze, B. Konukoglu, E. Motamedi, A. Ayache, N. Shih, H. TI Accounting for Anisotropic Growth of Glioma in Radiotherapy Planning SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Unkelbach, J.; Motamedi, A.; Shih, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Menze, B.] Swiss Fed Inst Technol, Zurich, Switzerland. [Konukoglu, E.] Microsoft Res, Cambridge, England. [Ayache, N.] INRIA Sophia Antipolis, Sophia Antipolis, France. RI Konukoglu, Ender/D-6719-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3602 EP 3602 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905804026 ER PT J AU Speier, C Sharp, G Wolfgang, J AF Speier, C. Sharp, G. Wolfgang, J. TI SPARK 4DCT-a Simulation, Post-Processing And Resorting Kit for 4DCTs SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Speier, C.; Sharp, G.; Wolfgang, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3603 EP 3603 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905804030 ER PT J AU Seco, J Oumano, M Depauw, N Dias, M Teixeira, R AF Seco, J. Oumano, M. Depauw, N. Dias, M. Teixeira, R. TI Characterizing the Modulation Transfer Function (MTF) of Proton Radiography SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Seco, J.] Mass Gen Hosp, Boston, MA USA. [Seco, J.] Harvard Med, Boston, MA USA. [Oumano, M.] Univ Massachusetts, Boston, MA 02125 USA. [Depauw, N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dias, M.; Teixeira, R.] Univ Lisbon, P-1699 Lisbon, Portugal. NR 0 TC 0 Z9 0 U1 1 U2 6 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3647 EP 3647 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905804213 ER PT J AU Raytchev, M Safai, S Seco, J AF Raytchev, M. Safai, S. Seco, J. TI Evaluation of the Analytical Scattering Models of 1) Lynch-Dahl 2) Highland and 3) Rossi for Proton Beams and Comparison with GEANT4 Monte Carlo Simulations as a Prerequisite for Proton Radiography Applications for Patients SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Raytchev, M.; Seco, J.] Harvard Med, Mass Gen Hosp, Boston, MA USA. [Safai, S.] Paul Scherrer Inst, Villigen, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3650 EP 3650 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905804227 ER PT J AU Winey, B Balter, J AF Winey, B. Balter, J. TI Multi-Criteria Optimization for IGRT Decision Processes SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Winey, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Winey, B.] Harvard Univ, Sch Med, Boston, MA USA. [Balter, J.] Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3666 EP 3666 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905804292 ER PT J AU Arbisser, A Sharp, G Golland, P Shusharina, N AF Arbisser, A. Sharp, G. Golland, P. Shusharina, N. TI Weighted Voting Method for Multi-Atlas Segmentation in CT Scans SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Arbisser, A.; Golland, P.] MIT, Cambridge, MA 02139 USA. [Sharp, G.; Shusharina, N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3675 EP 3676 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905804332 ER PT J AU Mishra, P Li, R St James, S Yue, Y Mak, R Berbeco, R Lewis, J AF Mishra, P. Li, R. St James, S. Yue, Y. Mak, R. Berbeco, R. Lewis, J. TI Generation of Fluoroscopic 3D Images Using Single X-Ray Projections On Realistic Modified XCAT Phantom Data SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Mishra, P.; St James, S.; Yue, Y.; Mak, R.; Berbeco, R.; Lewis, J.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. [Li, R.] Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3681 EP 3681 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905804356 ER PT J AU Wagar, M Mannarino, E Friesen, S Hacker, F Lewis, J AF Wagar, M. Mannarino, E. Friesen, S. Hacker, F. Lewis, J. TI Fabrication of An Anatomically Realistic Dynamic Respiratory Phantom SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3686 EP 3687 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905804378 ER PT J AU Riley, K Cascio, E AF Riley, K. Cascio, E. TI Neutron Damage of Power Electronics Used During Image Guidance in Proton Therapy SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Riley, K.; Cascio, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3739 EP 3739 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905804601 ER PT J AU Paganetti, H Moteabbed, M Athar, B Adams, J Schneider, U Yock, T AF Paganetti, H. Moteabbed, M. Athar, B. Adams, J. Schneider, U. Yock, T. TI Assessment of Radiation Induced Second Cancer Risks in Proton Therapy and IMRT for Organs Inside the Main Radiation Field SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Paganetti, H.; Moteabbed, M.; Athar, B.; Adams, J.; Yock, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Athar, B.] Hampton Univ, Hampton, VA 23668 USA. [Schneider, U.] Radioonkol Hirslanden, Aarau, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3762 EP 3763 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905804700 ER PT J AU Hacker, F Bondeson, J Lewis, J Mannarino, E Friesen, S Balboni, T Alexander, B Sher, D AF Hacker, F. Bondeson, J. Lewis, J. Mannarino, E. Friesen, S. Balboni, T. Alexander, B. Sher, D. TI Evaluation of Initial Setup Accuracy and Intra-Fraction Motion for Spine SBRT Using Stereotactic Body Frames SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Hacker, F.; Bondeson, J.; Lewis, J.; Mannarino, E.; Friesen, S.; Balboni, T.; Alexander, B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hacker, F.; Bondeson, J.; Lewis, J.; Mannarino, E.; Friesen, S.; Balboni, T.; Alexander, B.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hacker, F.; Bondeson, J.; Lewis, J.; Mannarino, E.; Friesen, S.; Balboni, T.; Alexander, B.] Harvard Univ, Sch Med, Boston, MA USA. [Sher, D.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3796 EP 3796 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905804843 ER PT J AU Ngwa, W Makrigiorgos, M Berbeco, R AF Ngwa, W. Makrigiorgos, M. Berbeco, R. TI Enhancing Stereotactic Radiosurgery for Neovascular Age-Related Macular Degeneration, Using Gold Nanoparticles SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Ngwa, W.; Makrigiorgos, M.; Berbeco, R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 5 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3798 EP 3798 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905804850 ER PT J AU Moteabbed, M Schuemann, J Paganetti, H AF Moteabbed, M. Schuemann, J. Paganetti, H. TI Comparison of Proton Treatment Planning and Monte Carlo Calculation Using TOPAS for Liver Cancer SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Moteabbed, M.; Schuemann, J.; Paganetti, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3813 EP 3813 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805023 ER PT J AU Perl, J Shin, J Schuemann, J Faddegon, B Paganetti, H AF Perl, J. Shin, J. Schuemann, J. Faddegon, B. Paganetti, H. TI Performance Assessment of the TOPAS Tool for Particle Simulation for Proton Therapy Applications SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Perl, J.] SLAC Natl Accelerator Lab, Menlo Pk, CA USA. [Shin, J.] UCSF, San Francisco, CA USA. [Schuemann, J.] MGH, Boston, MA USA. [Faddegon, B.] UC San Francisco, San Francisco, CA USA. [Paganetti, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3814 EP 3814 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805026 ER PT J AU Schuemann, J AF Schuemann, J. TI Nano-Dosimetric Track Structure Scoring Including Biological Modeling with TOPAS-NBio SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Schuemann, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3814 EP 3814 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805028 ER PT J AU Ramos-Mendez, J Perl, J Faddegon, B Paganetti, H AF Ramos-Mendez, J. Perl, J. Faddegon, B. Paganetti, H. TI Geometrical Splitting Technique to Improve the Computational Efficiency in Monte Carlo Calculations for Proton Therapy SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Ramos-Mendez, J.] Univ Utonoma Puebla, Puebla, Mexico. [Perl, J.] Stanford Linear Accelerator Ctr, Menlo Pk, CA USA. [Faddegon, B.] UC San Francisco, San Francisco, CA USA. [Paganetti, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3815 EP 3815 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805031 ER PT J AU Giantsoudi, D Paganetti, H AF Giantsoudi, D. Paganetti, H. TI Monte Carlo Dose Verification of Passive Scattering Proton Therapy for Prostate Cancer SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Giantsoudi, D.; Paganetti, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3819 EP 3819 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805048 ER PT J AU Schuemann, J Shin, J Perl, J Grassberger, C Verburg, J Faddegon, B Paganetti, H AF Schuemann, J. Shin, J. Perl, J. Grassberger, C. Verburg, J. Faddegon, B. Paganetti, H. TI Pencil-Beam Versus Monte Carlo Based Dose Calculation for Proton Therapy Patients with Complex Geometries. Clinical Use of the TOPAS Monte Carlo System SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Schuemann, J.; Grassberger, C.; Verburg, J.; Paganetti, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shin, J.; Faddegon, B.] UC San Francisco, San Francisco, CA USA. [Perl, J.] Stanford Linear Accelerator Ctr, Menlo Pk, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3820 EP 3820 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805053 ER PT J AU Zeng, C Giantsoudi, D Grassberger, C Goldberg, S Niemierko, A Paganetti, H Trofimov, A AF Zeng, C. Giantsoudi, D. Grassberger, C. Goldberg, S. Niemierko, A. Paganetti, H. Trofimov, A. TI Maximizing the Biological Effect of Proton Dose Delivered with Scanned Beam SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Zeng, C.; Giantsoudi, D.; Grassberger, C.; Goldberg, S.; Niemierko, A.; Paganetti, H.; Trofimov, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Zeng, Chuan/K-5694-2012 OI Zeng, Chuan/0000-0001-7069-2629 NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3832 EP 3832 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805105 ER PT J AU Ramakrishnan, J Craft, D Bortfeld, T Tsitsiklis, J AF Ramakrishnan, J. Craft, D. Bortfeld, T. Tsitsiklis, J. TI Quantifying the Benefit of Adaptive Fractionation SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Ramakrishnan, J.; Tsitsiklis, J.] MIT, Cambridge, MA 02139 USA. [Craft, D.; Bortfeld, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3847 EP 3847 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805168 ER PT J AU Salari, E Craft, D AF Salari, E. Craft, D. TI A Network-Flow Solution Approach to VMAT Treatment Plan Optimization SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3848 EP 3848 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805172 ER PT J AU Wala, J Chen, W Salari, E Craft, D AF Wala, J. Chen, W. Salari, E. Craft, D. TI Optimal Partial Arcs in VMAT Planning SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Wala, J.; Chen, W.; Salari, E.; Craft, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3850 EP 3850 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805180 ER PT J AU Chen, H Craft, D Gierga, D AF Chen, H. Craft, D. Gierga, D. TI MCO-Informed VMAT Planning for Prostate Cancer SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Chen, H.; Craft, D.; Gierga, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3851 EP 3851 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805182 ER PT J AU Halabi, T Craft, D AF Halabi, T. Craft, D. TI Convex Direct Aperture Optimization for Sliding Window IMRT SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Halabi, T.; Craft, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3851 EP 3852 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805186 ER PT J AU Min, C Zhu, X Grogg, K Winey, B Fakhri, G Bortfeld, T Shih, H Paganetti, H AF Min, C. Zhu, X. Grogg, K. Winey, B. Fakhri, G. Bortfeld, T. Shih, H. Paganetti, H. TI Evaluation of Distal Dose Surface with In-Room PET for Proton Therapy Monitoring SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3860 EP 3860 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805221 ER PT J AU Testa, M Bentefour, H Rose, M Paganetti, H Lu, H AF Testa, M. Bentefour, H. Rose, M. Paganetti, H. Lu, H. TI 2D Water Equivalent Path Length Imaging Technique For Pre-Treatment Range Verification In Proton Therapy SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Testa, M.; Paganetti, H.; Lu, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bentefour, H.] Ion Beam Applicat IBA, Louvain, Belgium. [Rose, M.] Sun Nucl Inc, Melbourne, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3860 EP 3860 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805222 ER PT J AU Verburg, J Shih, H Seco, J AF Verburg, J. Shih, H. Seco, J. TI Validation of Nuclear Reaction Models to Simulate Proton Therapy Range Verification Using Prompt Gamma-Rays SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3860 EP 3860 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805220 ER PT J AU Wang, Y Trofimov, A AF Wang, Yi Trofimov, Alexei TI Hypofractionated Proton Therapy of the Prostate: The Impact of the Uncertainties in Dose Delivery and Alpha/beta Ratio On Tumor Dose Escalation SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Wang, Yi; Trofimov, Alexei] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Francis H Burr Proton Therapy Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3860 EP 3861 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805223 ER PT J AU Winey, B Zhu, X Both, S Adams, J AF Winey, B. Zhu, X. Both, S. Adams, J. TI Proton Treatment Planning Issues SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Zhu, X.] UT MD Anderson Canc Ctr, Houston, TX USA. [Both, S.] Univ Penn, Philadelphia, PA 19104 USA. [Adams, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3871 EP 3871 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805264 ER PT J AU Dowdell, S Clasie, B Depauw, N Metcalfe, P Rosenfeld, A Kooy, H Flanz, J Paganetti, H AF Dowdell, S. Clasie, B. Depauw, N. Metcalfe, P. Rosenfeld, A. Kooy, H. Flanz, J. Paganetti, H. TI Potential Reduction in Out-Of-Field Dose in Pencil Beam Scanning Proton Therapy Through Use of a Patient-Specific Aperture SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Dowdell, S.; Clasie, B.; Depauw, N.; Kooy, H.; Flanz, J.; Paganetti, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dowdell, S.; Clasie, B.; Depauw, N.; Kooy, H.; Flanz, J.; Paganetti, H.] Harvard Univ, Sch Med, Boston, MA USA. [Dowdell, S.; Depauw, N.; Metcalfe, P.; Rosenfeld, A.] Univ Wollongong, Wollongong, NSW, Australia. RI Rosenfeld, Anatoly/D-1989-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3872 EP 3872 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805269 ER PT J AU Bueno, M Schuemann, J Duch, M Paganetti, H AF Bueno, M. Schuemann, J. Duch, M. Paganetti, H. TI A Method to Assess the Need for Clinical Monte Carlo Dose Calculations for Small Proton Therapy Fields SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Bueno, M.; Duch, M.] Univ Politecn Cataluna, Barcelona, Spain. [Schuemann, J.; Paganetti, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3874 EP 3874 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805277 ER PT J AU Ding, A Gao, Y Caracappa, P Liu, B Xu, X AF Ding, A. Gao, Y. Caracappa, P. Liu, B. Xu, X. TI Design and Testing of the VirtualDose Software Under the Software as a Service (SaaS) Platform for Tracking and Reporting CT Doses SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Ding, A.; Gao, Y.; Caracappa, P.; Xu, X.] Rensselaer Polytech Inst, Troy, NY USA. [Liu, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 2 U1 2 U2 9 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3876 EP 3877 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805289 ER PT J AU Rottmann, J Keall, P Yue, Y Berbeco, R AF Rottmann, J. Keall, P. Yue, Y. Berbeco, R. TI Real-Time Markerless Tumor Tracking with MV Imaging and a Dynamic Multi-Leaf Collimator (DMLC) SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Rottmann, J.; Yue, Y.; Berbeco, R.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rottmann, J.; Yue, Y.; Berbeco, R.] Harvard Univ, Sch Med, Boston, MA USA. [Rottmann, J.] German Canc Res Ctr, D-6900 Heidelberg, Germany. [Keall, P.] Univ Sydney, Sydney, NSW 2006, Australia. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3890 EP 3890 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805339 ER PT J AU Ngwa, W Tsiamas, P Zygmanski, P Makrigiorgos, M Berbeco, R AF Ngwa, W. Tsiamas, P. Zygmanski, P. Makrigiorgos, M. Berbeco, R. TI A Multipurpose Quality Assurance Phantom for the Small Animal Radiation Research Platform (SARRP) SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Ngwa, W.; Tsiamas, P.; Zygmanski, P.; Makrigiorgos, M.; Berbeco, R.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3899 EP 3899 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805379 ER PT J AU Berbeco, R Korideck, H Ngwa, W Kumar, R Patel, J Sridhar, S Johnson, S Price, B Kimmelman, A Makrigiorgos, M AF Berbeco, R. Korideck, H. Ngwa, W. Kumar, R. Patel, J. Sridhar, S. Johnson, S. Price, B. Kimmelman, A. Makrigiorgos, M. TI In Vitro Dose Enhancement From Gold Nanoparticles Under Different Clinical MV Photon Beam Configurations SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Berbeco, R.; Korideck, H.; Ngwa, W.; Kimmelman, A.; Makrigiorgos, M.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Div Med Phys & Biophys, Boston, MA 02115 USA. [Berbeco, R.; Korideck, H.; Ngwa, W.; Johnson, S.; Price, B.; Kimmelman, A.; Makrigiorgos, M.] Harvard Univ, Sch Med, Boston, MA USA. [Kumar, R.; Patel, J.; Sridhar, S.] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Johnson, S.; Price, B.] Dana Farber Canc Inst, Dept Radiat Oncol, Div Genom Instabil & DNA Repair, Boston, MA 02115 USA. RI Kumar, Rajiv/A-1457-2011 OI Kumar, Rajiv/0000-0003-2926-9866 NR 0 TC 2 Z9 2 U1 1 U2 3 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3900 EP 3901 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805384 ER PT J AU Mishra, P St James, S Segars, W Berbeco, R Lewis, J AF Mishra, P. St James, S. Segars, W. Berbeco, R. Lewis, J. TI Patient Lung Tumor Trajectory Based Modified-XCAT and Its Applications SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Mishra, P.; St James, S.; Berbeco, R.; Lewis, J.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Mishra, P.; St James, S.; Berbeco, R.; Lewis, J.] Harvard Univ, Sch Med, Boston, MA USA. [Segars, W.] Duke Univ, Durham, NC USA. NR 0 TC 0 Z9 0 U1 4 U2 4 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3903 EP 3903 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805394 ER PT J AU Paganetti, H AF Paganetti, H. TI Do Uncertainties in Proton Therapy Limit Its Clinical Potential? SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Paganetti, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3918 EP 3919 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805454 ER PT J AU Pursley, J Mauceri, T Sliski, A AF Pursley, J. Mauceri, T. Sliski, A. TI A Fiber Optic Dosimeter to Calibrate P-32 Conformal Brachytherapy Sources SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Pursley, J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Mauceri, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sliski, A.] Orbital Therapy LLC, Bedford, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3931 EP 3931 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805504 ER PT J AU Yue, Y Aristophanous, M Chen, A Killoran, J Yap, J Berbeco, R AF Yue, Y. Aristophanous, M. Chen, A. Killoran, J. Yap, J. Berbeco, R. TI Predicting Residual Disease for NSCLC Using Pre-Radiotherapy 4D PET/CT SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Yue, Y.; Chen, A.; Killoran, J.; Berbeco, R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Yue, Y.; Chen, A.; Killoran, J.; Yap, J.; Berbeco, R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Yue, Y.; Chen, A.; Killoran, J.; Yap, J.; Berbeco, R.] Harvard Univ, Sch Med, Boston, MA USA. [Aristophanous, M.] UT MD Anderson Canc Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3937 EP 3937 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805525 ER PT J AU Besemer, A Paganetti, H Bednarz, B AF Besemer, A. Paganetti, H. Bednarz, B. TI Clinical Impact of Uncertainties in the Mean Excitation Energy of Human Tissues During Proton Therapy SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Besemer, A.; Bednarz, B.] Univ Wisconsin, Dept Med Phys, Wisconsin Inst Med Res, Madison, WI 53706 USA. [Paganetti, H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Paganetti, H.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3944 EP 3944 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805558 ER PT J AU Jia, X Schuemann, J Paganetti, H Jiang, S AF Jia, X. Schuemann, J. Paganetti, H. Jiang, S. TI Development of a GPU-Based Monte Carlo Dose Calculation Package for Proton Radiotherapy SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Jia, X.; Jiang, S.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Schuemann, J.; Paganetti, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3945 EP 3945 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805561 ER PT J AU Testa, M Schuemann, J Paganetti, H AF Testa, M. Schuemann, J. Paganetti, H. TI Benchmarking of the TOPAS Monte Carlo System Against Phantom Dose Measurements in Proton Therapy SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Testa, M.; Schuemann, J.; Paganetti, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3945 EP 3945 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805559 ER PT J AU Peroni, M Sharp, GC Golland, P Baroni, G AF Peroni, M. Sharp, G. C. Golland, P. Baroni, G. TI Gaussian Weighted Multi-Atlas Based Segmentation for Head and Neck Radiotherapy Planning SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Peroni, M.; Baroni, G.] Politecn Milan, Dept Bioengn, I-20133 Milan, Italy. [Sharp, G. C.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Golland, P.] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Baroni, G.] Ctr Nazl Adroterapia Oncol, Bioengn Unit, Pavia, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3959 EP 3959 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805617 ER PT J AU Saleh, Z Apte, A Sharp, G Deasy, J AF Saleh, Z. Apte, A. Sharp, G. Deasy, J. TI A New Automatically Generated Metric for Evaluating the Spatial Precision of Deformable Image Registrations: The Distance Discordance Metric SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Saleh, Z.; Apte, A.; Deasy, J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Sharp, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3962 EP 3962 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805626 ER PT J AU Goulet, M Gingras, L Depauw, N Archambault, L Seco, J Beaulieu, L AF Goulet, M. Gingras, L. Depauw, N. Archambault, L. Seco, J. Beaulieu, L. TI Real-Time Radiation Field Tracking Using Long Scintillating Fibers SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Goulet, M.; Gingras, L.; Archambault, L.; Beaulieu, L.] Ctr Hosp Univ Quebec, Quebec City, PQ, Canada. [Depauw, N.; Seco, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Depauw, N.] Univ Wollongong, Ctr Med Radiat Phys, Wollongong, NSW, Australia. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3968 EP 3968 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805651 ER PT J AU Yue, Y Nguyen, P Rottmann, J Berbeco, R AF Yue, Y. Nguyen, P. Rottmann, J. Berbeco, R. TI Beam's-Eye-View Prostate Motion Detection During Arc Radiotherapy SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3971 EP 3971 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805665 ER PT J AU Chen, W Unkelbach, J Trofimov, A Madden, T Kooy, H Bortfeld, T Craft, D AF Chen, W. Unkelbach, J. Trofimov, A. Madden, T. Kooy, H. Bortfeld, T. Craft, D. TI Robust Multi-Criteria IMPT Optimization SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Chen, W.; Unkelbach, J.; Trofimov, A.; Madden, T.; Kooy, H.; Bortfeld, T.; Craft, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3981 EP 3981 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805700 ER PT J AU van de Water, S Kraan, A Breedveld, S Teguh, D Madden, T Kooy, H Heijmen, B Hoogeman, M AF van de Water, S. Kraan, A. Breedveld, S. Teguh, D. Madden, T. Kooy, H. Heijmen, B. Hoogeman, M. TI Improved Multi-Criteria Optimization for Intensity Modulated Proton Therapy Using Iterative Resampling of Randomly Placed Pencil-Beams SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [van de Water, S.; Kraan, A.; Breedveld, S.; Teguh, D.; Heijmen, B.; Hoogeman, M.] Daniel Denhoed Canc Ctr, Erasmus MC, Rotterdam, Netherlands. [Madden, T.; Kooy, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3981 EP 3982 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805702 ER PT J AU Kraan, A van de Water, S Teguh, D Al-Mamgani, A Madden, T Kooy, H Heijmen, B Hoogeman, M AF Kraan, A. van de Water, S. Teguh, D. Al-Mamgani, A. Madden, T. Kooy, H. Heijmen, B. Hoogeman, M. TI Dose Uncertainties in IMPT for Oropharyngeal Cancer in the Presence of Anatomical, Setup and Range Errors SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Kraan, A.; van de Water, S.; Teguh, D.; Al-Mamgani, A.; Heijmen, B.; Hoogeman, M.] Daniel Denhoed Canc Ctr, Erasmus MC, Rotterdam, Netherlands. [Madden, T.; Kooy, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3983 EP 3984 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805709 ER PT J AU Lin, C Winey, B AF Lin, C. Winey, B. TI Linear Regression Analysis of 2D Projection Image Data of 6 Degrees-Of-Freedom Transformed 3D Image Sets for Stereotactic Radiotherapy SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Lin, C.] MIT, Dept Nucl Sci & Engn, Cambridge, MA 02139 USA. [Winey, B.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3984 EP 3984 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805712 ER PT J AU Shusharina, N Chan, A Adams, J Chen, G Sharp, G AF Shusharina, N. Chan, A. Adams, J. Chen, G. Sharp, G. TI The Role of Treatment Plan Adaptation During the Course of Proton Radiotherapy for Patients with Head and Neck Cancer SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Shusharina, N.; Chan, A.; Adams, J.; Chen, G.; Sharp, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3985 EP 3986 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805717 ER PT J AU Depauw, N Seco, J AF Depauw, N. Seco, J. TI The Use of Scintillating Fibers for Proton Imaging Purposes SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Depauw, N.; Seco, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Depauw, N.] Univ Wollongong, CMRP, Wollongong, NSW, Australia. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3988 EP 3988 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805727 ER PT J AU Giantsoudi, D Grassberger, C Craft, D Niemierko, A Trofimov, A Paganetti, H AF Giantsoudi, D. Grassberger, C. Craft, D. Niemierko, A. Trofimov, A. Paganetti, H. TI LET-Guided Biological Optimization in IMPT SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Giantsoudi, D.; Grassberger, C.; Craft, D.; Niemierko, A.; Trofimov, A.; Paganetti, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3995 EP 3996 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805758 ER PT J AU Grassberger, C Shackleford, J Sharp, G Paganetti, H AF Grassberger, C. Shackleford, J. Sharp, G. Paganetti, H. TI Four-Dimensional Monte Carlo Simulations of Lung Cancer Patients Treated with Proton Beam Scanning to Assess Interplay Effects SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Grassberger, C.; Shackleford, J.; Sharp, G.; Paganetti, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Grassberger, C.] Paul Scherrer Inst, Ctr Proton Radiotherapy, Villigen, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 3998 EP 3998 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805768 ER PT J AU Warmerdam, G Steininger, P Neuner, M Sharp, G Winey, B AF Warmerdam, G. Steininger, P. Neuner, M. Sharp, G. Winey, B. TI An Open-Source 2D/3D-Image-Registration Algorithm: Cranial Image Guided Radiotherapy SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Warmerdam, G.] Eindhoven Univ Technol, NL-5600 MB Eindhoven, Netherlands. [Steininger, P.; Neuner, M.] Inst Res & Dev Adv Radiat Technol, Salzburg, Austria. [Steininger, P.; Neuner, M.] Paracelsus Med Univ, Salzburg, Austria. [Warmerdam, G.; Sharp, G.; Winey, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sharp, G.; Winey, B.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 4001 EP 4001 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805782 ER PT J AU Mohan, R Oelfke, U Paganetti, H Soukup, M AF Mohan, R. Oelfke, U. Paganetti, H. Soukup, M. TI Accuracy of Proton Dose Computation Algorithms and Need for Improvements SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Mohan, R.] UT MD Anderson Canc Ctr, Houston, TX USA. [Oelfke, U.] Deutsch Krebsforsch Zentrum, Heidelberg, Baden Wartthemb, Germany. [Paganetti, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Soukup, M.] Computerized Med Syst Elekta, Freiburg, Germany. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 4002 EP 4003 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805785 ER PT J AU Craft, D AF Craft, D. TI Automatic Treatment Planning - An MCO Perspective SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Craft, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 4007 EP 4007 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805803 ER PT J AU Moteabbed, M Schuemann, J Paganetti, H AF Moteabbed, M. Schuemann, J. Paganetti, H. TI Feasibility of Real Time MRI-Guidance in Proton Therapy SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Moteabbed, M.; Schuemann, J.; Paganetti, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 4012 EP 4013 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805823 ER PT J AU Spadea, M Fassi, A Depauw, N Riboldi, M Baroni, G Seco, J AF Spadea, M. Fassi, A. Depauw, N. Riboldi, M. Baroni, G. Seco, J. TI Improving the Contrast of Proton and Carbon Radiography by Using CT Prior Knowledge SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Fassi, A.; Riboldi, M.; Baroni, G.] Politecn Milano Univ, Milan, Italy. [Depauw, N.; Seco, J.] Harvard Med, Mass Gen Hosp, Boston, MA USA. Univ Wollongong UoW, Ctr Med Radiat Phys CMRP, Wollongong, NSW, Australia. NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 4012 EP 4012 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805822 ER PT J AU Richter, C Andronesi, OC Yuan, Y Bortfeld, T Guimaraes, AR Hong, TS Seco, J AF Richter, C. Andronesi, O. C. Yuan, Y. Bortfeld, T. Guimaraes, A. R. Hong, T. S. Seco, J. TI In-Vivo Dosimetric Verification of Hypo-Fractionated Proton Radiation Therapy of the Liver with Hepatocyte-Specific Functional MRI SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 29-AUG 02, 2012 CL Charlotte, NC SP Amer Assoc Physicists Med (AAPM) C1 [Richter, C.; Andronesi, O. C.; Yuan, Y.; Bortfeld, T.; Guimaraes, A. R.; Hong, T. S.; Seco, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Richter, C.] OncoRay Natl Ctr Radiat Res Oncol, Dresden, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2012 VL 39 IS 6 BP 4019 EP 4019 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007RM UT WOS:000308905805849 ER PT J AU Kieran, MW Roberts, CWM Biegel, JA MacConaill, LE Rich, BE Ligon, KL Chi, S AF Kieran, Mark W. Roberts, Charles W. M. Biegel, Jaclyn A. MacConaill, Laura E. Rich, Benjamin E. Ligon, Keith L. Chi, Susan TI ABSENCE OF ONCOGENE AND TUMOR SUPPRESSOR GENE MUTATIONS IN ATYPICAL TERATOID/RHABDOID TUMORS (AT/RT) SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 15th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 24-27, 2012 CL Toronto, CANADA C1 [Kieran, Mark W.; Roberts, Charles W. M.; Chi, Susan] Dana Farber Canc Inst, Boston, MA 02115 USA. [Biegel, Jaclyn A.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [MacConaill, Laura E.] Dana Farber Canc Inst Ctr Canc Genome Discovery, Boston, MA USA. [Rich, Benjamin E.; Ligon, Keith L.] Dana Farber Canc Inst Ctr Mol Oncol Pathol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2012 VL 14 SU 1 BP 2 EP 2 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 000NZ UT WOS:000308394400008 ER PT J AU Slavc, I Peyrl, A Chocholous, M Kieran, M Azizi, A Czech, T Dieckmann, K Haberler, C AF Slavc, Irene Peyrl, Andreas Chocholous, Monika Kieran, Mark Azizi, Amedeo Czech, Thomas Dieckmann, Karin Haberler, Christine TI ANTIANGIOGENIC COMBINATION THERAPY WITH AND WITHOUT METRONOMIC CHEMOTHERAPY FOR CHILDREN WITH RECURRENT BRAIN TUMORS OF VARIOUS HISTOLOGIES SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 15th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 24-27, 2012 CL Toronto, CANADA C1 [Slavc, Irene; Peyrl, Andreas; Chocholous, Monika; Azizi, Amedeo] Med Univ Vienna, Dept Pediat, Vienna, Austria. [Czech, Thomas] Med Univ Vienna, Dept Neurosurg, Vienna, Austria. [Dieckmann, Karin] Med Univ Vienna, Dept Radiotherapy, Vienna, Austria. [Haberler, Christine] Med Univ Vienna, Inst Neurol, Vienna, Austria. [Kieran, Mark] Dana Faber Canc Inst, Div Pediat Oncol, Boston, MA USA. [Kieran, Mark] Childrens Hosp Boston, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2012 VL 14 SU 1 BP 17 EP 18 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 000NZ UT WOS:000308394400067 ER PT J AU Macy, M Kieran, M Chi, S Cohen, K MacDonald, T Smith, A Etzl, M Naranderan, A Gore, L DiRenzo, J Trippett, T Foreman, N Dunkel, I AF Macy, Margaret Kieran, Mark Chi, Susan Cohen, Kenneth MacDonald, Tobey Smith, Amy Etzl, Michael Naranderan, Aru Gore, Lia DiRenzo, Jennifer Trippett, Tanya Foreman, Nicholas Dunkel, Ira TI A PHASE II TRIAL OF RADIATION AND CETUXIMAB FOLLOWED BY IRINOTECAN/CETUXIMAB FOR CHILDREN WITH NEWLY DIAGNOSED DIFFUSE PONTINE TUMORS AND HIGH GRADE ASTROCYTOMAS: A PRELIMINARY REPORT FROM POETIC SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 15th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 24-27, 2012 CL Toronto, CANADA C1 [Macy, Margaret; Gore, Lia; Foreman, Nicholas] Univ Colorado Denver, Childrens Hosp Colorado, Aurora, CO USA. [Kieran, Mark; Chi, Susan] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cohen, Kenneth] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [MacDonald, Tobey] Emory Univ, Sch Med, Childrens Healthcare Atlanta, Atlanta, GA USA. [Smith, Amy] Univ Florida, Gainesville, FL USA. [Etzl, Michael] Phoenix Childrens Hosp, Phoenix, AZ USA. [Naranderan, Aru] Alberta Childrens Prov Gen Hosp, Calgary, AB, Canada. [DiRenzo, Jennifer; Trippett, Tanya; Dunkel, Ira] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RI MacDonald, Tobey/D-4554-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2012 VL 14 SU 1 BP 18 EP 18 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 000NZ UT WOS:000308394400068 ER PT J AU Robison, N Campigotto, F Chi, S Manley, P Turner, C Zimmerman, MA Chordas, C Allen, J Goldman, S Rubin, J Isakoff, M Pan, W Khatib, Z Comito, M Bendel, A Pietrantonio, J Kondrat, L Hubbs, S Neuberg, D Kieran, M AF Robison, Nathan Campigotto, Federico Chi, Susan Manley, Peter Turner, Christopher Zimmerman, Mary Ann Chordas, Christine Allen, Jeffrey Goldman, Stewart Rubin, Joshua Isakoff, Michael Pan, Wilbur Khatib, Ziad Comito, Melanie Bendel, Anne Pietrantonio, Jay Kondrat, Laura Hubbs, Shannon Neuberg, Donna Kieran, Mark TI A PHASE II TRIAL OF THE FIVE-DRUG ORAL ANTIANGIOGENIC (METRONOMIC) REGIMEN IN CHILDREN WITH RECURRENT OR PROGRESSIVE CENTRAL NERVOUS SYSTEM TUMORS SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 15th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 24-27, 2012 CL Toronto, CANADA C1 [Robison, Nathan; Campigotto, Federico; Chi, Susan; Manley, Peter; Turner, Christopher; Zimmerman, Mary Ann; Chordas, Christine; Pietrantonio, Jay; Kondrat, Laura; Hubbs, Shannon; Neuberg, Donna; Kieran, Mark] Dana Farber Canc Inst, Boston, MA 02115 USA. [Allen, Jeffrey] NYU, Sch Med, New York, NY USA. [Goldman, Stewart] Childrens Mem Hosp, Chicago, IL 60614 USA. [Rubin, Joshua] Washington Univ, Sch Med, St Louis, MO USA. [Isakoff, Michael] Connecticut Childrens Med Ctr, Hartford, CT USA. [Pan, Wilbur] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. [Khatib, Ziad] Miami Childrens Hosp, Miami, FL USA. [Comito, Melanie] Penn State Hershey Childrens Hosp, Hershey, PA USA. [Bendel, Anne] Childrens Hosp & Clin Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2012 VL 14 SU 1 BP 20 EP 20 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 000NZ UT WOS:000308394400078 ER PT J AU MacDonald, S Ebb, D Lavally, B Yeap, B Marcus, K Tarbell, N Yock, T AF MacDonald, Shannon Ebb, David Lavally, Beverly Yeap, Beow Marcus, Karen Tarbell, Nancy Yock, Torunn TI PROTON RADIOTHERAPY FOR CHILDHOOD CNS EPENDYMOMA: CLINICAL OUTCOMES AND PATTERNS OF FAILURE FOR A COHORT OF 67 PATIENTS SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 15th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 24-27, 2012 CL Toronto, CANADA C1 [MacDonald, Shannon; Ebb, David; Lavally, Beverly; Yeap, Beow; Tarbell, Nancy; Yock, Torunn] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Marcus, Karen] Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2012 VL 14 SU 1 BP 40 EP 40 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 000NZ UT WOS:000308394400149 ER PT J AU Dagri, J Torkildson, J Cheng, J Wang, RX Yock, T Banerjee, A Dhall, G Finlay, J AF Dagri, Jennifer Torkildson, Joseph Cheng, Jerry Wang, Ricardo X. Yock, Torunn Banerjee, Anuradha Dhall, Girish Finlay, Jonathan TI CENTRAL NERVOUS SYSTEM (CNS) GERM CELL TUMORS (GCT) AND DOWN SYNDROME: TREATMENT STRATEGIES AND MORBIDITIES SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 15th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 24-27, 2012 CL Toronto, CANADA C1 [Dagri, Jennifer; Dhall, Girish; Finlay, Jonathan] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Torkildson, Joseph] Childrens Hosp & Res Ctr Oakland, Oakland, CA USA. [Cheng, Jerry; Wang, Ricardo X.] Kaiser Permanente Sunset, Los Angeles, CA USA. [Yock, Torunn] Massachussetts Gen Hosp, Boston, MA USA. [Banerjee, Anuradha] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2012 VL 14 SU 1 BP 50 EP 51 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 000NZ UT WOS:000308394400185 ER PT J AU Robison, N Prabhu, S Sun, PL Chi, SS Kieran, M Manley, P Cohen, L Goumnerova, L Smith, E Scott, M London, W Ullrich, NJ AF Robison, Nathan Prabhu, Sanjay Sun, Pengling Chi, Susan Kieran, Mark Manley, Peter Cohen, Laurie Goumnerova, Liliana Smith, Edward Scott, Michael London, Wendy Ullrich, Nicole J. TI EVALUATION OF PITUITARY STALK THICKENING IN CHILDREN AND ADOLESCENTS SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 15th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 24-27, 2012 CL Toronto, CANADA C1 [Robison, Nathan; Sun, Pengling; Chi, Susan; Kieran, Mark; Manley, Peter; London, Wendy] Dana Farber Canc Inst, Boston, MA 02115 USA. [Prabhu, Sanjay; Cohen, Laurie; Goumnerova, Liliana; Smith, Edward; Scott, Michael; Ullrich, Nicole J.] Childrens Hosp, Boston, MA 02115 USA. RI Prabhu, Sanjay/A-9947-2013 OI Prabhu, Sanjay/0000-0003-0871-115X NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2012 VL 14 SU 1 BP 55 EP 55 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 000NZ UT WOS:000308394400203 ER PT J AU Lee, C Fotovati, A Triscott, J Chen, J Venugopal, C Singhal, A Dunham, C Kerr, J Verreault, M Yip, S Wakimoto, H Jones, C Jayanthan, A Narendran, A Singh, S Dunn, S AF Lee, Cathy Fotovati, Abbas Triscott, Joanna Chen, James Venugopal, Chitra Singhal, Ash Dunham, Chris Kerr, John Verreault, Maite Yip, Stephen Wakimoto, Hiro Jones, Chris Jayanthan, Aarthi Narendran, Aru Singh, Sheila Dunn, Sandra TI POLO-LIKE KINASE 1 (PLK1) INHIBITION KILLS GLIOBLASTOMA MULTIFORME BRAIN TUMOUR CELLS IN PART THROUGH LOSS OF SOX2 AND DELAYS TUMOUR PROGRESSION IN MICE SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 15th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 24-27, 2012 CL Toronto, CANADA C1 [Lee, Cathy; Fotovati, Abbas; Triscott, Joanna; Chen, James; Singhal, Ash; Dunham, Chris; Kerr, John; Dunn, Sandra] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Venugopal, Chitra; Singh, Sheila] McMasters Univ, Hamilton, ON, Canada. [Verreault, Maite; Yip, Stephen] BC Canc Agcy, Vancouver, BC, Canada. [Wakimoto, Hiro] Mass Gen Hosp, Boston, MA USA. [Jones, Chris] Royal Marsden Hosp, Surrey, England. [Jayanthan, Aarthi; Narendran, Aru] Univ Calgary, Calgary, AB, Canada. NR 0 TC 0 Z9 0 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2012 VL 14 SU 1 BP 67 EP 67 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 000NZ UT WOS:000308394400251 ER PT J AU Arrington, D Manley, P Kieran, M Chi, S Robison, N Chordas, C Ullrich, N AF Arrington, Daniel Manley, Peter Kieran, Mark Chi, Susan Robison, Nathan Chordas, Christine Ullrich, Nicole TI PATIENTS WITH NEUROFIBROMATOSIS TYPE 1 ARE AT INCREASED RISK TO DEVELOP VINCRISTINE-INDUCED PERIPHERAL NEUROPATHY SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 15th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 24-27, 2012 CL Toronto, CANADA C1 [Arrington, Daniel; Ullrich, Nicole] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Manley, Peter; Kieran, Mark; Chi, Susan; Robison, Nathan; Chordas, Christine] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2012 VL 14 SU 1 BP 80 EP 81 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 000NZ UT WOS:000308394400304 ER PT J AU Hulleman, E Lagerweij, T Biesmans, D Crommentuijn, MHW Cloos, J Tannous, BA Vandertop, WP Noske, DP Kaspers, GJL Wurdinger, T AF Hulleman, Esther Lagerweij, Tonny Biesmans, Dennis Crommentuijn, Matheus H. W. Cloos, Jacqueline Tannous, Bakhos A. Vandertop, W. Peter Noske, David P. Kaspers, Gertjan J. L. Wurdinger, Tom TI A CHEMICAL SMALL MOLECULE SCREEN IDENTIFIES QUERCETIN AS A PUTATIVE RADIOSENSITIZER FOR THE TREATMENT OF MEDULLOBLASTOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 15th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 24-27, 2012 CL Toronto, CANADA C1 [Hulleman, Esther; Lagerweij, Tonny; Biesmans, Dennis; Cloos, Jacqueline; Kaspers, Gertjan J. L.] Vrije Univ Amsterdam Med Ctr, Dept Pediat Oncol Hematol, Amsterdam, Netherlands. [Hulleman, Esther; Lagerweij, Tonny; Biesmans, Dennis; Crommentuijn, Matheus H. W.; Vandertop, W. Peter; Noske, David P.; Wurdinger, Tom] Vrije Univ Amsterdam Med Ctr, Neurooncol Res Grp, Amsterdam, Netherlands. [Cloos, Jacqueline] Vrije Univ Amsterdam Med Ctr, Dept Hematol, Amsterdam, Netherlands. [Tannous, Bakhos A.; Wurdinger, Tom] Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. [Tannous, Bakhos A.] Harvard Univ, Sch Med, Boston, MA USA. [Vandertop, W. Peter; Noske, David P.; Wurdinger, Tom] Vrije Univ Amsterdam Med Ctr, Dept Neurosurg, Amsterdam, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2012 VL 14 SU 1 BP 90 EP 90 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 000NZ UT WOS:000308394400337 ER PT J AU Jones, DTW Jager, N Kool, M Zichner, T Hutter, B Sultan, M Cho, YJ Pugh, TJ Warnatz, HJ Reifenberger, G Northcott, PA Taylor, MD Meyerson, M Pomeroy, SL Yaspo, ML Korbel, JO Korshunov, A Eils, R Pfister, SM Lichter, P AF Jones, David T. W. Jaeger, Natalie Kool, Marcel Zichner, Thomas Hutter, Barbara Sultan, Marc Cho, Yoon-Jae Pugh, Trevor J. Warnatz, Hans-Joerg Reifenberger, Guido Northcott, Paul A. Taylor, Michael D. Meyerson, Matthew Pomeroy, Scott L. Yaspo, Marie-Laure Korbel, Jan O. Korshunov, Andrey Eils, Roland Pfister, Stefan M. Lichter, Peter TI ICGC PEDBRAIN TUMOR - DISSECTING THE GENOMIC COMPLEXITY UNDERLYING MEDULLOBLASTOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 15th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 24-27, 2012 CL Toronto, CANADA C1 [Jones, David T. W.; Jaeger, Natalie; Kool, Marcel; Hutter, Barbara; Eils, Roland; Pfister, Stefan M.; Lichter, Peter] German Canc Res Ctr, Heidelberg, Germany. [Zichner, Thomas; Korbel, Jan O.] European Mol Biol Lab, Heidelberg, Germany. [Sultan, Marc; Warnatz, Hans-Joerg; Yaspo, Marie-Laure] Max Planck Inst Mol Genet, D-14195 Berlin, Germany. [Cho, Yoon-Jae] Stanford Univ, Div Child Neurol, Palo Alto, CA 94304 USA. [Pugh, Trevor J.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Reifenberger, Guido] Univ Dusseldorf, Dept Neuropathol, D-40225 Dusseldorf, Germany. [Northcott, Paul A.; Taylor, Michael D.] Hosptial Sick Children, Arthur & Sonia Labbatt Brain Tumor Res Ctr, Toronto, ON, Canada. [Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pomeroy, Scott L.] Childrens Hosptial, Boston, MA USA. [Korshunov, Andrey] Univ Heidelberg, Dept Neuropathol, Heidelberg, Germany. RI Kool, Marcel/H-2541-2013; Pfister, Stefan/F-6860-2013 OI Pfister, Stefan/0000-0002-5447-5322 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2012 VL 14 SU 1 BP 92 EP 92 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 000NZ UT WOS:000308394400346 ER PT J AU Diver, T Manley, P Kieran, M Chordas, C Liptak, C Delaney, B Brand, S Rey-Casserly, C AF Diver, Tanya Manley, Peter Kieran, Mark Chordas, Christine Liptak, Cori Delaney, Brian Brand, Sarah Rey-Casserly, Celiane TI NEUROCOGNITIVE PREDICTORS OF ADAPTIVE FUNCTIONING IN CHILDREN/ADOLESCENTS TREATED FOR MEDULLOBLASTOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 15th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 24-27, 2012 CL Toronto, CANADA C1 [Diver, Tanya; Rey-Casserly, Celiane] Childrens Hosp, Boston, MA 02115 USA. [Manley, Peter; Kieran, Mark; Chordas, Christine; Liptak, Cori; Delaney, Brian; Brand, Sarah] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2012 VL 14 SU 1 BP 115 EP 115 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 000NZ UT WOS:000308394400434 ER PT J AU Sheehan, K Devorin, B AF Sheehan, Kathryn Devorin, Barbara TI A MULTIDISCIPLINARY APPROACH TO THE TREATMENT OF CEREBELLAR MUTISM SYNDROME SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 15th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 24-27, 2012 CL Toronto, CANADA C1 [Sheehan, Kathryn; Devorin, Barbara] Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2012 VL 14 SU 1 BP 121 EP 121 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 000NZ UT WOS:000308394400451 ER PT J AU Wells, EM Seidel, K Ullrich, NJ Leisenring, W Armstrong, G Diller, L King, A Krull, KR Neglia, J Robison, LL Stovall, M Whelan, K Sklar, C AF Wells, Elizabeth M. Seidel, Kristy Ullrich, Nicole J. Leisenring, Wendy Armstrong, Greg Diller, Lisa King, Allison Krull, Kevin R. Neglia, Joseph Robison, Leslie L. Stovall, Marilyn Whelan, Kimberly Sklar, Charles TI NEUROLOGIC SEQUELAE IN LONG-TERM SURVIVORS OF CHILDHOOD BRAIN TUMORS: A CHILDHOOD CANCER SURVIVOR STUDY (CCSS) UPDATE AND EXPANDED RISK FACTOR ANALYSIS SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 15th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 24-27, 2012 CL Toronto, CANADA C1 [Wells, Elizabeth M.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Seidel, Kristy; Leisenring, Wendy] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Ullrich, Nicole J.] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA. [Armstrong, Greg; Krull, Kevin R.; Robison, Leslie L.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Diller, Lisa] Dana Farber Canc Inst, Boston, MA 02115 USA. [King, Allison] Washington Univ, Sch Med, St Louis, MO USA. [Neglia, Joseph] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Stovall, Marilyn] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Whelan, Kimberly] Univ Alabama Birmingham, Birmingham, AL USA. [Sklar, Charles] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2012 VL 14 SU 1 BP 133 EP 133 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 000NZ UT WOS:000308394400502 ER PT J AU Warren, K Vezina, G Hargrave, D Poussaint, TY Goldman, S Packer, R Wen, P Pollack, I Zurakowski, D Kun, L Prados, M Kieran, M AF Warren, Katherine Vezina, Gilbert Hargrave, Darren Poussaint, Tina Young Goldman, Stewart Packer, Roger Wen, Patrick Pollack, Ian Zurakowski, David Kun, Larry Prados, Michael Kieran, Mark TI RESPONSE ASSESSMENT IN PEDIATRIC NEURO-ONCOLOGY (RAPNO): CURRENT PRACTICE AND ISSUES SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 15th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 24-27, 2012 CL Toronto, CANADA C1 [Warren, Katherine] NCI, Bethesda, MD 20892 USA. [Vezina, Gilbert; Packer, Roger] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Hargrave, Darren] Great Ormond St Hosp Sick Children, London WC1N 3JH, England. [Poussaint, Tina Young; Zurakowski, David; Kieran, Mark] Childrens Hosp, Boston, MA 02115 USA. [Goldman, Stewart] Childrens Mem Hosp, Chicago, IL 60614 USA. [Wen, Patrick] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pollack, Ian] Childrens Hosp, Pittsburgh, PA 15213 USA. [Kun, Larry] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Prados, Michael] UCSF Med Ctr, San Francisco, CA USA. OI Hargrave, Darren/0000-0001-8219-9807 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2012 VL 14 SU 1 BP 142 EP 142 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 000NZ UT WOS:000308394400539 ER PT J AU Robison, N Grant, F Treves, ST Bandopadhayay, P Manley, P Chi, S Zimmerman, MA Chordas, C Goumnerova, L Smith, E Scott, M Ullrich, NJ Poussaint, T Kieran, M AF Robison, Nathan Grant, Frederick Treves, S. Ted Bandopadhayay, Pratiti Manley, Peter Chi, Susan Zimmerman, Mary Ann Chordas, Christine Goumnerova, Liliana Smith, Edward Scott, Michael Ullrich, Nicole J. Poussaint, Tina Kieran, Mark TI 18F-FLT FOR PET IMAGING OF BRAIN TUMORS IN CHILDREN SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 15th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 24-27, 2012 CL Toronto, CANADA C1 [Robison, Nathan; Bandopadhayay, Pratiti; Manley, Peter; Chi, Susan; Zimmerman, Mary Ann; Chordas, Christine; Kieran, Mark] Dana Farber Canc Inst, Boston, MA 02115 USA. [Grant, Frederick; Treves, S. Ted; Goumnerova, Liliana; Smith, Edward; Scott, Michael; Ullrich, Nicole J.; Poussaint, Tina] Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2012 VL 14 SU 1 BP 144 EP 144 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 000NZ UT WOS:000308394400548 ER PT J AU Ford, JM Dierks, T Fisher, DJ Herrmann, CS Hubl, D Kindler, J Koenig, T Mathalon, DH Spencer, KM Strik, W van Lutterveld, R AF Ford, Judith M. Dierks, Thomas Fisher, Derek J. Herrmann, Christoph S. Hubl, Daniela Kindler, Jochen Koenig, Thomas Mathalon, Daniel H. Spencer, Kevin M. Strik, Werner van Lutterveld, Remko TI Neurophysiological Studies of Auditory Verbal Hallucinations SO SCHIZOPHRENIA BULLETIN LA English DT Article DE auditory hallucinations; EEG; MEG; ERPs ID MULTI-FEATURE PARADIGM; MISMATCH NEGATIVITY; SCHIZOPHRENIA; P300; ATTENTION; SYMPTOMS; CORTEX; SYNCHRONIZATION; METAANALYSIS; PERCEPTION AB We discuss 3 neurophysiological approaches to study auditory verbal hallucinations (AVH). First, we describe "state" (or symptom capture) studies where periods with and without hallucinations are compared "within" a patient. These studies take 2 forms: passive studies, where brain activity during these states is compared, and probe studies, where brain responses to sounds during these states are compared. EEG (electroencephalography) and MEG (magnetoencephalography) data point to frontal and temporal lobe activity, the latter resulting in competition with external sounds for auditory resources. Second, we discuss "trait" studies where EEG and MEG responses to sounds are recorded from patients who hallucinate and those who do not. They suggest a tendency to hallucinate is associated with competition for auditory processing resources. Third, we discuss studies addressing possible mechanisms of AVH, including spontaneous neural activity, abnormal self-monitoring, and dysfunctional interregional communication. While most studies show differences in EEG and MEG responses between patients and controls, far fewer show symptom relationships. We conclude that efforts to understand the pathophysiology of AVH using EEG and MEG have been hindered by poor anatomical resolution of the EEG and MEG measures, poor assessment of symptoms, poor understanding of the phenomenon, poor models of the phenomenon, decoupling of the symptoms from the neurophysiology due to medications and comorbidites, and the possibility that the schizophrenia diagnosis breeds truer than the symptoms it comprises. These problems are common to studies of other psychiatric symptoms and should be considered when attempting to understand the basic neural mechanisms responsible for them. C1 [Ford, Judith M.; Mathalon, Daniel H.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Psychiat Serv, Dept Psychiat, San Francisco, CA 94121 USA. [Dierks, Thomas; Hubl, Daniela; Kindler, Jochen; Koenig, Thomas; Strik, Werner] Univ Bern, Univ Hosp Psychiat, Bern, Switzerland. [Fisher, Derek J.] Mt St Vincent Univ, Dept Psychol, Halifax, NS B3M 2J6, Canada. [Fisher, Derek J.] Univ Ottawa, Neuroelectrophysiol Unit, Mental Hlth Res Inst, Ottawa, ON, Canada. [Herrmann, Christoph S.] Carl von Ossietzky Univ Oldenburg, Dept Expt Psychol, D-2900 Oldenburg, Germany. [Spencer, Kevin M.] Harvard Univ, Sch Med, Res Serv, Vet Affairs Boston Healthcare Syst, Boston, MA USA. [Spencer, Kevin M.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [van Lutterveld, Remko] Univ Med Ctr, Dept Psychiat, Utrecht, Netherlands. [van Lutterveld, Remko] Rudolf Magnus Inst Neurosci, Dept Psychiat, NL-3508 TA Utrecht, Netherlands. RP Ford, JM (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Psychiat Serv, Dept Psychiat, 116D,4150 Clement St, San Francisco, CA 94121 USA. EM judith.ford@ucsf.edu RI Dierks, Thomas/B-7092-2012; Koenig, Thomas/F-6454-2010; Fisher, Derek/H-2297-2013; Strik, Werner/N-7807-2013; OI Dierks, Thomas/0000-0002-4173-5308; Mathalon, Daniel/0000-0001-6090-4974; Koenig, Thomas/0000-0002-1472-4638; Fisher, Derek/0000-0003-2366-8225; Strik, Werner/0000-0001-7108-1993; Spencer, Kevin/0000-0002-5500-7627 FU National Institutes of Health [MH080187, MH076989, MH058262]; VA Merit Award; National Alliance for Research on Schizophrenia and Depression; Canadian Institutes of Health Research; Dutch Science Organization (Nederlandse Wetenschappelijke Organisatie) FX National Institutes of Health (MH080187 to K.M.S., MH076989 to D.H.M., and MH058262 to J.M.F.); VA Merit Award (K.M.S. and J.M.F.); National Alliance for Research on Schizophrenia and Depression (to D.H.M); Canadian Institutes of Health Research (to D.J.F.); Dutch Science Organization (Nederlandse Wetenschappelijke Organisatie) (to R.v.L.). NR 49 TC 25 Z9 26 U1 2 U2 22 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JUN PY 2012 VL 38 IS 4 BP 715 EP 723 DI 10.1093/schbul/sbs009 PG 9 WC Psychiatry SC Psychiatry GA 979ZX UT WOS:000306864500012 PM 22368236 ER PT J AU Green, MF Bearden, CE Cannon, TD Fiske, AP Hellemann, GS Horan, WP Kee, K Kern, RS Lee, J Sergi, MJ Subotnik, KL Sugar, CA Ventura, J Yee, CM Nuechterlein, KH AF Green, Michael F. Bearden, Carrie E. Cannon, Tyrone D. Fiske, Alan P. Hellemann, Gerhard S. Horan, William P. Kee, Kimmy Kern, Robert S. Lee, Junghee Sergi, Mark J. Subotnik, Kenneth L. Sugar, Catherine A. Ventura, Joseph Yee, Cindy M. Nuechterlein, Keith H. TI Social Cognition in Schizophrenia, Part 1: Performance Across Phase of Illness SO SCHIZOPHRENIA BULLETIN LA English DT Article DE social cognition; illness phase; schizophrenia ID FACIAL AFFECT RECOGNITION; NEUROCOGNITIVE ENDOPHENOTYPES; EMOTIONAL INTELLIGENCE; PERCEPTION DEFICITS; FUNCTIONAL STATUS; PSYCHOSIS; MIND; SCHIZOTYPY; METAANALYSIS; RISK AB Social cognitive impairments are consistently reported in schizophrenia and are associated with functional outcome. We currently know very little about whether these impairments are stable over the course of illness. In the current study, 3 different aspects of social cognition were assessed (emotion processing, Theory of Mind [ToM], and social relationship perception) at 3 distinct developmental phases of illness: prodromal, first episode, and chronic. In this cross-sectional study, participants included 50 individuals with the prodromal risk syndrome for psychosis and 34 demographically comparable controls, 81 first-episode schizophrenia patients and 46 demographically comparable controls, and 53 chronic schizophrenia patients and 47 demographically comparable controls. Outcome measures included total and subtest scores on 3 specialized measures of social cognition: (1) emotion processing assessed with the Mayer-Salovey-Caruso Emotional Intelligence Test, (2) ToM assessed with The Awareness of Social Inference Test, and (3) social relationship perception assessed the Relationships Across Domains Test. Social cognitive performance was impaired across all domains of social cognition and in all clinical samples. Group differences in performance were comparable across phase of illness, with no evidence of progression or improvement. Age had no significant effect on performance for either the clinical or the comparison groups. The findings suggest that social cognition in these 3 domains fits a stable pattern that has outcome and treatment implications. An accompanying article prospectively examines the longitudinal stability of social cognition and prediction of functional outcome in the first-episode sample. C1 [Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Green, Michael F.; Horan, William P.; Kee, Kimmy; Kern, Robert S.; Lee, Junghee; Sergi, Mark J.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Bearden, Carrie E.; Cannon, Tyrone D.; Yee, Cindy M.; Nuechterlein, Keith H.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Fiske, Alan P.] Univ Calif Los Angeles, Dept Anthropol, Los Angeles, CA 90095 USA. [Kee, Kimmy] Calif State Univ, Dept Psychol, Camarillo, CA USA. [Sergi, Mark J.] Calif State Univ Northridge, Dept Psychol, Northridge, CA 91330 USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90095 USA. RP Green, MF (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, 300 Med Plaza,Room 2263, Los Angeles, CA 90095 USA. EM mgreen@ucla.edu RI Lee, Junghee/C-5226-2014 OI Lee, Junghee/0000-0001-9567-8700 FU National Institute of Mental Health Center [P50 MH066286, MH037705, MH043292] FX National Institute of Mental Health Center grant (P50 MH066286 and MH037705 to K.H.N.; MH043292 to M.F.G.). NR 65 TC 132 Z9 137 U1 6 U2 43 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JUN PY 2012 VL 38 IS 4 BP 854 EP 864 DI 10.1093/schbul/sbq171 PG 11 WC Psychiatry SC Psychiatry GA 979ZX UT WOS:000306864500027 PM 21345917 ER PT J AU Horan, WP Green, MF DeGroot, M Fiske, A Hellemann, G Kee, K Kern, RS Lee, J Sergi, MJ Subotnik, KL Sugar, CA Ventura, J Nuechterlein, KH AF Horan, William P. Green, Michael F. DeGroot, Michael Fiske, Alan Hellemann, Gerhard Kee, Kimmy Kern, Robert S. Lee, Junghee Sergi, Mark J. Subotnik, Kenneth L. Sugar, Catherine A. Ventura, Joseph Nuechterlein, Keith H. TI Social Cognition in Schizophrenia, Part 2: 12-Month Stability and Prediction of Functional Outcome in First-Episode Patients SO SCHIZOPHRENIA BULLETIN LA English DT Article DE functional outcome; emotional processing; theory of mind; social perception; cross-lagged panel analyses; longitudinal prediction ID FACIAL AFFECT RECOGNITION; EMOTIONAL INTELLIGENCE; NEUROCOGNITIVE ENDOPHENOTYPES; PERCEPTION DEFICITS; 1ST EPISODE; MIND; SCHIZOTYPY; PSYCHOSIS; VULNERABILITY; REMISSION AB This study evaluated the longitudinal stability and functional correlates of social cognition during the early course of schizophrenia. Fifty-five first-episode schizophrenia patients completed baseline and 12-month follow-up assessments of 3 key domains of social cognition (emotional processing, theory of mind, and social/relationship perception), as well as clinical ratings of real-world functioning and symptoms. Scores on all 3 social cognitive tests demonstrated good longitudinal stability with test-retest correlations exceeding .70. Higher baseline and 12-month social cognition scores were both robustly associated with significantly better work functioning, independent living, and social functioning at the 12-month follow-up assessment. Furthermore, cross-lagged panel analyses were consistent with a causal model in which baseline social cognition drove later functional outcome in the domain of work, above and beyond the contribution of symptoms. Social cognitive impairments are relatively stable, functionally relevant features of early schizophrenia. These results extend findings from a companion study, which showed stable impairments across patients in prodromal, first-episode, and chronic phases of illness on the same measures. Social cognitive impairments may serve as useful vulnerability indicators and early clinical intervention targets. C1 [Horan, William P.] Univ Calif Los Angeles, Semel Inst, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Horan, William P.; Green, Michael F.; DeGroot, Michael; Kee, Kimmy; Kern, Robert S.; Lee, Junghee; Sergi, Mark J.; Subotnik, Kenneth L.; Sugar, Catherine A.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. [Fiske, Alan] Univ Calif Los Angeles, Dept Anthropol, Los Angeles, CA 90095 USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90095 USA. [Nuechterlein, Keith H.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Kee, Kimmy] Calif State Univ, Dept Psychol, Channel Islands, CA USA. [Sergi, Mark J.] Calif State Univ Northridge, Dept Psychol, Northridge, CA 91330 USA. RP Horan, WP (reprint author), Univ Calif Los Angeles, Semel Inst, Dept Psychiat & Biobehav Sci, 300 Med Plaza,Room 2263, Los Angeles, CA 90095 USA. EM horan@ucla.edu RI Lee, Junghee/C-5226-2014 OI Lee, Junghee/0000-0001-9567-8700 FU National Institute of Mental Health Center [MH066286, MH037705, MH043292] FX National Institute of Mental Health Center grant P50 (MH066286, MH037705 to K.H.N., MH043292 to M.F.G.). NR 55 TC 87 Z9 92 U1 3 U2 24 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JUN PY 2012 VL 38 IS 4 BP 865 EP 872 DI 10.1093/schbul/sbr001 PG 8 WC Psychiatry SC Psychiatry GA 979ZX UT WOS:000306864500028 PM 21382881 ER PT J AU Usenovic, M Krainc, D AF Usenovic, Marija Krainc, Dimitri TI Lysosomal dysfunction in neurodegeneration The role of ATP13A2/PARK9 SO AUTOPHAGY LA English DT Editorial Material DE ATP13A2; lysosomal dysfunction; alpha-synuclein; Parkinsonism; neurodegeneration AB Neuronal homeostasis and survival critically depend on an efficient autophagy-lysosomal degradation pathway, especially since neurons cannot reduce the concentration of misfolded proteins and damaged organelles by cell division. While increasing evidence implicates lysosomal dysfunction in the pathogenesis of neurodegenerative disorders, the molecular underpinnings of the role of lysosomes in neurodegeneration remain largely unknown. To this end, studies of neurodegenerative disorders caused by mutations in lysosomal proteins offer an opportunity to elucidate such mechanisms and potentially identify specific therapeutic targets. One of these disorders is Kufor-Rakeb syndrome, caused by mutations in the lysosomal protein ATP13A2/PARK9 and characterized by early-onset Parkinsonism, pyramidal degeneration and dementia. We found that loss of ATP13A2 function results in impaired lysosomal function and, consequently, accumulation of SNCA/alpha-synuclein and neurotoxicity. Our results suggest that targeting of ATP13A2 to lysosomes to enhance lysosomal function may result in neuroprotection in Kufor-Rakeb syndrome. From a broader perspective, these findings, together with other recent studies of lysosomal dysfunction in neurodegeneration, suggest that strategies to upregulate lysosomal function in neurons represent a promising therapeutic approach for neurodegenerative disorders. C1 [Usenovic, Marija; Krainc, Dimitri] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. RP Krainc, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. EM krainc@helix.mgh.harvard.edu NR 0 TC 10 Z9 10 U1 2 U2 6 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD JUN PY 2012 VL 8 IS 6 BP 987 EP 988 DI 10.4161/auto.20256 PG 2 WC Cell Biology SC Cell Biology GA 984MI UT WOS:000307193400017 PM 22561922 ER PT J AU Everitt, A Clare, S Pertel, T John, S Wash, R Smith, S Chin, C Feeley, E Simms, J Adams, D Wise, H Kane, L Goulding, D Digard, P Anttila, V Baillie, K Walsh, T Hume, D Palotie, A Xue, Y Colonna, V Tyler-Smith, C Dunning, J Gordon, S Smyth, RS Openshaw, P Dougan, G Brass, A Kellam, P AF Everitt, A. Clare, S. Pertel, T. John, S. Wash, R. Smith, S. Chin, C. Feeley, E. Simms, J. Adams, D. Wise, H. Kane, L. Goulding, D. Digard, P. Anttila, V. Baillie, K. Walsh, T. Hume, D. Palotie, A. Xue, Y. Colonna, V. Tyler-Smith, C. Dunning, J. Gordon, S. Smyth, R. S. Openshaw, P. Dougan, G. Brass, A. Kellam, P. TI IFITM3 restricts the morbidity and mortality associated with influenza SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 [Everitt, A.; Clare, S.; Wash, R.; Smith, S.; Adams, D.; Kane, L.; Goulding, D.; Anttila, V.; Palotie, A.; Xue, Y.; Colonna, V.; Tyler-Smith, C.; Dougan, G.; Kellam, P.] Wellcome Trust Sanger Inst, Cambridge, England. [Pertel, T.; John, S.; Chin, C.; Feeley, E.; Simms, J.; Brass, A.] Harvard Univ, Sch Med, Boston, MA USA. [Pertel, T.; John, S.; Chin, C.; Feeley, E.; Simms, J.; Brass, A.] Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA. [Wise, H.; Digard, P.] Div Virol, Cambridge, England. [Baillie, K.; Hume, D.] Roslin Inst, Edinburgh, Midlothian, Scotland. [Walsh, T.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Dunning, J.; Openshaw, P.] Univ London Imperial Coll Sci Technol & Med, London, England. [Gordon, S.] Liverpool Sch Hyg & Trop Med, Liverpool, Merseyside, England. [Smyth, R. S.] Univ Liverpool, Liverpool L69 3BX, Merseyside, England. RI Digard, Paul/B-7717-2008 OI Digard, Paul/0000-0002-0872-9440 NR 0 TC 1 Z9 1 U1 2 U2 15 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD JUN PY 2012 VL 16 SU 1 BP E79 EP E79 DI 10.1016/j.ijid.2012.05.191 PG 1 WC Infectious Diseases SC Infectious Diseases GA 999YX UT WOS:000308353100176 ER PT J AU Sundt, TM Agnihotri, AK AF Sundt, Thoralf M. Agnihotri, Arvind K. TI Percutaneous intervention for "ischaemic mitral regurgitation" SO EUROINTERVENTION LA English DT Editorial Material ID VALVE; REVASCULARIZATION; SURVIVAL; CARDIOMYOPATHY; ANNULOPLASTY; SURGERY C1 [Sundt, Thoralf M.; Agnihotri, Arvind K.] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP Sundt, TM (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, 55 Fruit St,Cox 652, Boston, MA 02114 USA. EM TSUNDT@PARTNERS.ORG NR 11 TC 0 Z9 0 U1 0 U2 0 PU EUROPA EDITION PI TOULOUSE CEDEX 6 PA 5, RUE SAINT-PANTALEON, BP 61508, TOULOUSE CEDEX 6, 31015, FRANCE SN 1774-024X J9 EUROINTERVENTION JI EuroIntervention PD JUN PY 2012 VL 8 IS 2 BP 185 EP 186 DI 10.4244/EIJV8I2A31 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 987QP UT WOS:000307432500005 PM 22717924 ER PT J AU Ustyugova, IV Zhi, L Abramowitz, J Birnbaumer, L Wu, MX AF Ustyugova, Irina V. Zhi, Liang Abramowitz, Joel Birnbaumer, Lutz Wu, Mei X. TI IEX-1 Deficiency Protects against Colonic Cancer SO MOLECULAR CANCER RESEARCH LA English DT Article ID DEXTRAN SULFATE SODIUM; INFLAMMATORY-BOWEL-DISEASE; ULCERATIVE-COLITIS; COLORECTAL NEOPLASIA; CELLS; MICE; APOPTOSIS; MODEL; GENE; GROWTH AB The immediate early response gene X-1 (IEX-1) is involved in regulation of various cellular processes including proliferation, apoptosis in part by controlling homeostasis of reactive oxygen species (ROS) at mitochondria. The present study shows reduced inflammatory responses and colorectal cancer in IEX-1 knockout (KO) mice treated with azoxymethane/dextran sulfate sodium (DSS). However, DSS induced worse colitis in RAG(-/-)IEX-1(-/-) double KO mice than in RAG and IEX-1 single KO mice, underscoring an importance of T cells in IEX-1 deficiency-induced protection against colon inflammation. Lack of IEX-1 promoted the differentiation of interleukin (IL)-17-producing T cells, concomitant with upregulation of G alpha i2 expression, a gene that is well-documented for its role in the control of inflammation in the colon. In accordance with this, T-helper 17 (T(H)17) cell differentiation was compromised in the absence of G alpha i2, and deletion of G alpha i2 in T cells alone aggravated colon inflammation and colorectal cancer development after azoxymethane/DSS treatment. Null mutation of IEX-1 also enhanced both proliferation and apoptosis of intestinal epithelial cells (IEC) after injury. A potential impact of this altered IEC turnover on colon inflammation and cancer development is discussed. These observations provide a linkage of IEX-1 and G alpha i2 expression in the regulation of T(H)17 cell differentiation and suggest a previously unappreciated role for IEX-1 in the control of colon epithelial homeostasis. Mol Cancer Res; 10(6); 760-7. (C) 2012 AACR. C1 [Ustyugova, Irina V.; Zhi, Liang; Wu, Mei X.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Dept Dermatol, Boston, MA 02114 USA. [Ustyugova, Irina V.; Zhi, Liang; Wu, Mei X.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Wu, Mei X.] Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. [Abramowitz, Joel; Birnbaumer, Lutz] NIEHS, Neurobiol Lab, Div Intramural Res, NIH,DHHS, Durham, NC USA. RP Wu, MX (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Dept Dermatol, Edwards 222,50 Blossom St, Boston, MA 02114 USA. EM mwu2@partners.org RI Abramowitz, Joel/A-2620-2015 FU NIH [AI050822, AI070785]; Senior Research Award from the Crohn's & Colitis Foundation of America; Intramural Research Program of the NIH [Z01-ES-101643] FX This work is supported in part by NIH grants AI050822 and AI070785 and a Senior Research Award from the Crohn's & Colitis Foundation of America (to M.X. Wu) and by the Intramural Research Program of the NIH (Z01-ES-101643 to L. Birnbaumer). NR 43 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 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD JUN PY 2012 VL 10 IS 6 BP 760 EP 767 DI 10.1158/1541-7786.MCR-11-0556 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 995QJ UT WOS:000308026400009 PM 22550081 ER PT J AU Carlson, RW O'Neill, A Vidaurre, T Gomez, HL Badve, SS Sledge, GW AF Carlson, Robert W. O'Neill, Anne Vidaurre, Tatiana Gomez, Henry L. Badve, Sunil S. Sledge, George W. TI A randomized trial of combination anastrozole plus gefitinib and of combination fulvestrant plus gefitinib in the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Metastatic breast cancer; Gefitinib; Anastrozole; Fulvestrant; Randomized phase II ID GROWTH-FACTOR RECEPTOR; NO CHANGE CATEGORY; ENDOCRINE THERAPY; PHASE-II; TAMOXIFEN RESISTANCE; STATIC DISEASE; EXPRESSION; CARCINOMA; PLACEBO; TUMORS AB EGFR signalling pathways appear involved in endocrine therapy resistance in breast cancer. This trial estimates the antitumor efficacy and toxicity of the EGFR tyrosine kinase inhibitor gefitinib in combination with anastrozole or fulvestrant in postmenopausal hormone receptor positive breast cancer. Subjects with estrogen receptor and/or PgR positive, metastatic breast cancer were randomized into this phase II study of gefitinib (initial dose was 500 mg orally daily, due to high rate of diarrhea, starting dose was reduced to 250 mg orally daily) with either anastrozole 1 mg daily or fulvestrant 250 mg every 4 weeks. The primary endpoint was clinical benefit (complete responses plus partial responses plus stable disease for 6 months or longer). 141 eligible subjects were enrolled, 72 in the anastrozole plus gefitinib arm, and 69 in the fulvestrant plus gefitinib arm. Anastrozole plus gefitinib had a clinical benefit rate of 44% [95% confidence interval (CI) 33-57%] and fulvestrant plus gefitinib 41% (95% CI 29-53%). Median progression-free survival was 5.3 months (95% CI 3.1-10.4) versus 5.2 months (95% CI 2.9-8.2) for anastrozole plus gefitinib versus fulvestrant plus gefitinib, respectively. Median survival was 30.3 months (95% CI 21.2-38.9+) versus 23.9 months (95% CI 15.4-33.5) for anastrozole plus gefitinib versus fulvestrant plus gefitinib, respectively. In general, the toxicity is greater than expected for single agent endocrine therapy alone. Anastrozole plus gefitinib and fulvestrant plus gefitinib have similar clinical benefit rates in the treatment of estrogen and/or PgR positive metastatic breast cancer, and the rates of response are not clearly superior to gefitinib or endocrine therapy alone. Further studies of EGFR inhibition plus endocrine therapy do not appear warranted, but if performed should include attempts to identify biomarkers predictive of antitumor activity. C1 [Carlson, Robert W.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Carlson, Robert W.; O'Neill, Anne; Vidaurre, Tatiana; Gomez, Henry L.; Badve, Sunil S.; Sledge, George W.] Eastern Cooperat Oncol Grp, Boston, MA USA. [O'Neill, Anne] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Vidaurre, Tatiana; Gomez, Henry L.] Inst Nacl Enfermedades Neoplas, Dept Med Oncol, Lima, Peru. [Badve, Sunil S.] Indiana Univ, Dept Pathol, Indianapolis, IN 46204 USA. [Sledge, George W.] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. RP Carlson, RW (reprint author), Stanford Univ, Dept Med, 875 Blake Wilbur Dr,CC 2236, Stanford, CA 94305 USA. EM rcarlson@stanford.edu OI Gomez, Henry/0000-0003-2660-1843 FU Public Health Service [CA23318, CA66636, CA21115, CA49883]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services FX This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, MD, Chair) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA49883 and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 26 TC 21 Z9 23 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2012 VL 133 IS 3 BP 1049 EP 1056 DI 10.1007/s10549-012-1997-5 PG 8 WC Oncology SC Oncology GA 967NM UT WOS:000305914900022 PM 22418699 ER PT J AU Lin, NU Winer, EP Wheatley, D Carey, LA Houston, S Mendelson, D Munster, P Frakes, L Kelly, S Garcia, AA Cleator, S Uttenreuther-Fischer, M Jones, H Wind, S Vinisko, R Hickish, T AF Lin, Nancy U. Winer, Eric P. Wheatley, Duncan Carey, Lisa A. Houston, Stephen Mendelson, David Munster, Pamela Frakes, Laurie Kelly, Steve Garcia, Agustin A. Cleator, Susan Uttenreuther-Fischer, Martina Jones, Hilary Wind, Sven Vinisko, Richard Hickish, Tamas TI A phase II study of afatinib (BIBW 2992), an irreversible ErbB family blocker, in patients with HER2-positive metastatic breast cancer progressing after trastuzumab SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; ErbB1; ErbB2; Human epidermal growth factor receptor; Second-generation small molecule kinase inhibitors; Trastuzumab ID GROWTH-FACTOR RECEPTOR; DUAL EGFR/HER2 INHIBITOR; TYROSINE KINASE; SOLID TUMORS; RESISTANCE; CELLS; EXPRESSION; LAPATINIB; EGFR AB Afatinib is an oral, ErbB family blocker, which covalently binds and irreversibly blocks all kinase-competent ErbB family members. This phase II, open-label, single-arm study explored afatinib activity in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients progressing after trastuzumab treatment. Patients had stage IIIB/IV HER2-positive metastatic breast cancer, with progression following trastuzumab or trastuzumab intolerance and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Patients received 50 mg afatinib once-daily until disease progression. Primary endpoint was objective response rate (Response Evaluation Criteria in Solid Tumors 1.0), with tumor assessments every 8 weeks. Forty-one patients were treated. Patients had received a median of three prior chemotherapy lines (range, 0-15) and 68.3% had received trastuzumab for > 1 year. Four patients (10% of 41 treated; 11% of evaluable patients) had partial response. Fifteen patients (37% of 41) had stable disease as best response and 19 (46% of 41) achieved clinical benefit. Median progression-free survival was 15.1 weeks (95% confidence interval [CI]: 8.1-16.7); median overall survival was 61.0 weeks (95% CI: 56.7-not evaluable). Most frequent common terminology criteria for adverse events grade 3 treatment-related adverse events were diarrhea (24.4%) and rash (9.8%). Afatinib monotherapy was associated with promising clinical activity in extensively pretreated HER2-positive breast cancer patients who had progressed following trastuzumab treatment. C1 [Lin, Nancy U.; Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Wheatley, Duncan] Royal Cornwall Hosp, Truro, England. [Carey, Lisa A.] Univ N Carolina, Chapel Hill, NC USA. [Houston, Stephen] Royal Surrey Cty Hosp, Guildford, Surrey, England. [Mendelson, David] Pinnacle Oncol Hematol, Scottsdale, AZ USA. [Munster, Pamela] UCSF, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Frakes, Laurie] San Diego Pacific Oncol & Hematol Associates Inc, Encinitas, CA USA. [Kelly, Steve] Derriford Hosp, Plymouth PL6 8DH, Devon, England. [Garcia, Agustin A.] USC Norris Comprehens Canc Ctr & Hosp, Los Angeles, CA USA. [Cleator, Susan] St Marys Hosp, London, England. [Uttenreuther-Fischer, Martina; Wind, Sven] Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany. [Jones, Hilary] Boehringer Ingelheim Ltd, Bracknell, Berks, England. [Vinisko, Richard] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. [Hickish, Tamas] Dorset Canc Ctr, Bournemouth, Dorset, England. [Hickish, Tamas] Bournemouth Hosp, Bournemouth, Dorset, England. RP Lin, NU (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Nancy_Lin@dfci.harvard.edu; Eric_Winer@dfci.harvard.edu; duncan.wheatley@rcht.cornwall.nhs.uk; lisa_carey@med.unc.edu; shouston@nhs.net; dmendelson@azpoh.com; pmunster@medicine.ucsf.edu; lfrakes@pacificoncology.com; stevekelly1@nhs.net; aagarcia@usc.edu; s.cleator@imperial.ac.uk; Martina.Uttenreuther-Fischer@boehringer-ingelheim.com; hilary.jones@boehringer-ingelheim.com; sven.wind@boehringer-ingelheim.com; richard.vinisko@boehringer-ingelheim.com; tamas.hickish@rbch.nhs.uk FU Boehringer Ingelheim; Genentech; GlaxoSmithKline FX This study was supported by Boehringer Ingelheim. The authors would like to acknowledge the editorial assistance of Ogilvy Healthworld Medical Education. Boehringer Ingelheim provided financial support for this assistance.; Nancy Lin: currently conducting research supported by Genentech, GlaxoSmithKline and has conducted research supported by Infinity; David Mendelson: research funding from Boehringer Ingelheim; Martina Uttenreuther-Fischer: employed by Boehringer Ingelheim GmBH & Co Germany, Senior Clinical Research Physician; Hilary Jones: employed by Boehringer Ingelheim, UK, Senior Clinical Scientist; Sven Wind: employed by Boehringer Ingelheim GmBH & Co, Germany, Project Pharmacokineticist; Richard Vinisko: employed by Boehringer Ingelheim, Principal Bio-statistician; Tamas Hickish: consultant/advisor for Boehringer Ingelheim, honoraria from Boehringer Ingelheim, research funding from Boehringer Ingelheim, other remuneration from Boehringer Ingelheim; Tamas Hickish: is the Principal Investigator of this study; Eric Winer, Duncan Wheatley, Lisa Carey, Stephen Houston, Pamela Munster, Laurie Frakes, Steve Kelly, Agustin Garcia, Susan Cleator: no disclosures. NR 30 TC 98 Z9 99 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2012 VL 133 IS 3 BP 1057 EP 1065 DI 10.1007/s10549-012-2003-y PG 9 WC Oncology SC Oncology GA 967NM UT WOS:000305914900023 PM 22418700 ER PT J AU Masciari, S Dillon, DA Rath, M Robson, M Weitzel, JN Balmana, J Gruber, SB Ford, JM Euhus, D Lebensohn, A Telli, M Pochebit, SM Lypas, G Garber, JE AF Masciari, Serena Dillon, Deborah A. Rath, Michelle Robson, Mark Weitzel, Jeffrey N. Balmana, Judith Gruber, Stephen B. Ford, James M. Euhus, David Lebensohn, Alexandra Telli, Melinda Pochebit, Stephen M. Lypas, Georgios Garber, Judy E. TI Breast cancer phenotype in women with TP53 germline mutations: a Li-Fraumeni syndrome consortium effort SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast Cancer; Li-Fraumeni syndrome; TP53 mutations; HER2; Hormone receptors ID FAMILIAL SYNDROME; P53 MUTATIONS; CARCINOMAS; BRCA1; NEOPLASMS; SARCOMAS; HER-2 AB Breast cancer is the most common tumor in women with Li-Fraumeni Syndrome (LFS), an inherited cancer syndrome associated with germline mutations in the TP53 tumor suppressor gene. Their lifetime breast cancer risk is 49% by age 60. Breast cancers in TP53 mutation carriers recently have more often been reported to be hormone receptor and HER-2 positive by immunohistochemistry and FISH in small series. We seek to complement the existing small literature with this report of a histopathologic analysis of breast cancers from women with documented LFS. Unstained slides and paraffin-embedded tumor blocks from breast cancers from 39 germline TP53 mutation carriers were assembled from investigators in the LFS consortium. Central histology review was performed on 93% of the specimens by a single breast pathologist from a major university hospital. Histology, grade, and hormone receptor status were assessed by immunohistochemistry; HER-2 status was defined by immunohistochemistry and/or FISH. The 43 tumors from 39 women comprise 32 invasive ductal carcinomas and 11 ductal carcinomas in situ (DCIS). No other histologies were observed. The median age at diagnosis was 32 years (range 22-46). Of the invasive cancers, 84% were positive for ER and/or PR; and 81% were high grade. Sixty three percent of invasive and 73% of in situ carcinomas were positive for Her2/neu (IHC 3+ or FISH amplified). Of the invasive tumors, 53% were positive for both ER and HER2+; other ER/PR/HER2 combinations were observed. The DCIS were positive for ER and HER2 in 27% of the cases. This report of the phenotype of breast cancers from women with LFS nearly doubles the literature on this topic. Most DCIS and invasive ductal carcinomas in LFS are hormone receptor positive and/or HER-2 positive. These findings suggest that modern treatments may result in improved outcomes for women with LFS-associated breast cancer. C1 [Masciari, Serena; Rath, Michelle; Lypas, Georgios; Garber, Judy E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Dillon, Deborah A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Robson, Mark] Mem Sloan Kettering Canc Ctr, Clin Genet & Breast Canc Med Serv, New York, NY 10021 USA. [Weitzel, Jeffrey N.] City Hope Natl Med Ctr, Div Clin Canc Genet, Duarte, CA 91010 USA. [Balmana, Judith] Hosp Valle De Hebron, Barcelona, Spain. [Gruber, Stephen B.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Ford, James M.; Lebensohn, Alexandra; Telli, Melinda] Stanford Univ, Dept Med, Div Oncol, Sch Med, Stanford, CA 94305 USA. [Euhus, David] Univ Texas SW Med Ctr Dallas, Dept Surg, Dallas, TX 75390 USA. [Pochebit, Stephen M.] Faulkner Hosp, Dept Pathol, Boston, MA USA. RP Garber, JE (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave D1123, Boston, MA 02215 USA. EM judy_garber@dfci.harvard.edu OI Robson, Mark/0000-0002-3109-1692 FU NCI Cancer Center Support Grant [NIH 5 P30 CA06516]; Dana-Farber/Harvard SPORE in Breast Cancer [CA 89393]; National Cancer Institute [RC4A153828, P30 CA014089-37]; Office of the Director, National Institutes of Health; Hellenic Society of Medical Oncology (HeSMO) scholarship FX The authors gratefully acknowledge the expert technical assistance of the Dana Farber Harvard Cancer Center Specialized Histopathology Core Laboratory, particularly Teri Bowman and Donna Skinner for assistance with slide preparation, as well as Chungdak Namgyal for construction of the tissue microarray, Mei Zheng for immunohistochemistry, and Krishan Taneja for fluorescence in situ hybridization. Dana-Farber/Harvard Cancer Center is supported in part by NCI Cancer Center Support Grant # NIH 5 P30 CA06516. This research is supported in part by the Dana-Farber/Harvard SPORE in Breast Cancer (CA 89393). The City of Hope Clinical Cancer Genetics Community Research Network is supported in part by Award Number RC4A153828 (PI: JN Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. Supported by NCI P30 CA014089-37 (S. Gruber). Partially funded by a Hellenic Society of Medical Oncology (HeSMO) scholarship (G. Lypas). NR 30 TC 46 Z9 47 U1 2 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2012 VL 133 IS 3 BP 1125 EP 1130 DI 10.1007/s10549-012-1993-9 PG 6 WC Oncology SC Oncology GA 967NM UT WOS:000305914900030 PM 22392042 ER PT J AU Xie, J Du, H Guan, GB Tong, YJ Kourkoumpetis, TK Zhang, LX Bai, FY Huang, GH AF Xie, Jing Du, Han Guan, Guobo Tong, Yaojun Kourkoumpetis, Themistoklis K. Zhang, Lixin Bai, Feng-yan Huang, Guanghua TI N-Acetylglucosamine Induces White-to-Opaque Switching and Mating in Candida tropicalis, Providing New Insights into Adaptation and Fungal Sexual Evolution SO EUKARYOTIC CELL LA English DT Article ID ACETYL-D-GLUCOSAMINE; MASTER REGULATOR; ALBICANS; TRANSITION; REPRODUCTION; EXPRESSION; CELLS AB Pathogenic fungi are capable of switching between different phenotypes, each of which has a different biological advantage. In the most prevalent human fungal pathogen, Candida albicans, phenotypic transitions not only improve its adaptation to a continuously changing host microenvironment but also regulate sexual mating. In this report, we show that Candida tropicalis, another important human opportunistic pathogen, undergoes reversible and heritable phenotypic switching, referred to as the "white-opaque" transition. Here we show that N-acetylglucosamine (GlcNAc), an inducer of white-to-opaque switching in C. albicans, promotes opaque-cell formation and mating and also inhibits filamentation in a number of natural C. tropicalis strains. Our results suggest that host chemical signals may facilitate this phenotypic switching and mating of C. tropicalis, which had been previously thought to reproduce asexually. Overexpression of the C. tropicalis WOR1 gene in C. albicans induces opaque-cell formation. Additionally, an intermediate phase between white and opaque was observed in C. tropicalis, indicating that the switching could be tristable. C1 [Xie, Jing; Du, Han; Guan, Guobo; Tong, Yaojun; Bai, Feng-yan; Huang, Guanghua] Chinese Acad Sci, Inst Microbiol, State Key Lab Mycol, Beijing, Peoples R China. [Xie, Jing; Tong, Yaojun] Chinese Acad Sci, Grad Univ, Beijing, Peoples R China. [Kourkoumpetis, Themistoklis K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zhang, Lixin] Chinese Acad Sci, Inst Microbiol, Chinese Acad Sci Key Lab Pathogen Microbiol & Imm, Beijing, Peoples R China. RP Huang, GH (reprint author), Chinese Acad Sci, Inst Microbiol, State Key Lab Mycol, Beijing, Peoples R China. EM Baify@im.ac.cn; huanggh@im.ac.cn OI Tong, Yaojun/0000-0003-4042-2462; huang, guang hua/0000-0002-4761-7548 FU Chinese Academy of Sciences; Chinese National Natural Science Foundation [31170086] FX This project is supported by a "100 Talent Program" grant from the Chinese Academy of Sciences and Chinese National Natural Science Foundation grant 31170086 to G.H. NR 44 TC 21 Z9 25 U1 1 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD JUN PY 2012 VL 11 IS 6 BP 773 EP 782 DI 10.1128/EC.00047-12 PG 10 WC Microbiology; Mycology SC Microbiology; Mycology GA 984LF UT WOS:000307190500008 PM 22544905 ER PT J AU Segev, D Levi, R Dunn, PF Sandberg, WS AF Segev, Danny Levi, Retsef Dunn, Peter F. Sandberg, Warren S. TI Modeling the impact of changing patient transportation systems on peri-operative process performance in a large hospital: insights from a computer simulation study SO HEALTH CARE MANAGEMENT SCIENCE LA English DT Article DE Hospital transportation; Logistics; Operating room; Elevators; First case on time starts; Perioperative systems design ID OPERATING-ROOM; RECOVERY ROOM; RESOURCES; CAPACITY; TIME AB Transportation of patients is a key hospital operational activity. During a large construction project, our patient admission and prep area will relocate from immediately adjacent to the operating room suite to another floor of a different building. Transportation will require extra distance and elevator trips to deliver patients and recycle transporters (specifically: personnel who transport patients). Management intuition suggested that starting all 52 first cases simultaneously would require many of the 18 available elevators. To test this, we developed a data-driven simulation tool to allow decision makers to simultaneously address planning and evaluation questions about patient transportation. We coded a stochastic simulation tool for a generalized model treating all factors contributing to the process as JAVA objects. The model includes elevator steps, explicitly accounting for transporter speed and distance to be covered. We used the model for sensitivity analyses of the number of dedicated elevators, dedicated transporters, transporter speed and the planned process start time on lateness of OR starts and the number of cases with serious delays (i.e., more than 15 min). Allocating two of the 18 elevators and 7 transporters reduced lateness and the number of cases with serious delays. Additional elevators and/or transporters yielded little additional benefit. If the admission process produced ready-for-transport patients 20 min earlier, almost all delays would be eliminated. Modeling results contradicted clinical managers' intuition that starting all first cases on time requires many dedicated elevators. This is explained by the principle of decreasing marginal returns for increasing capacity when there are other limiting constraints in the system. C1 [Sandberg, Warren S.] Vanderbilt Univ, Sch Med, Dept Anesthesiol Surg & Biomed Informat, Nashville, TN 37212 USA. [Segev, Danny] Univ Haifa, Dept Stat, IL-31905 Haifa, Israel. [Levi, Retsef] MIT, Sloan Sch Management, Cambridge, MA 02139 USA. [Dunn, Peter F.] Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Dunn, Peter F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sandberg, WS (reprint author), Vanderbilt Univ, Sch Med, Dept Anesthesiol Surg & Biomed Informat, 1211 21st Ave S,701 MAB, Nashville, TN 37212 USA. EM Warren.sandberg@vanderbilt.edu OI Sandberg, Warren/0000-0002-9246-777X NR 26 TC 5 Z9 5 U1 2 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1386-9620 J9 HEALTH CARE MANAG SC JI Health Care Manag. Sci. PD JUN PY 2012 VL 15 IS 2 BP 155 EP 169 DI 10.1007/s10729-012-9191-1 PG 15 WC Health Policy & Services SC Health Care Sciences & Services GA 985EO UT WOS:000307246400006 PM 22350687 ER PT J AU DuPriest, EA Kupfer, P Lin, B Sekiguchi, K Morgan, TK Saunders, KE Chatkupt, TT Denisenko, ON Purnell, JQ Bagby, SP AF DuPriest, E. A. Kupfer, P. Lin, B. Sekiguchi, K. Morgan, T. K. Saunders, K. E. Chatkupt, T. T. Denisenko, O. N. Purnell, J. Q. Bagby, S. P. TI Altered adipocyte structure and function in nutritionally programmed microswine offspring SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE LA English DT Article DE adipose tissue; catch-up growth; maternal protein restriction ID FOR-GESTATIONAL-AGE; PITUITARY-ADRENAL AXIS; LOW-BIRTH-WEIGHT; ADIPONECTIN GENE-EXPRESSION; PLASMA-CORTISOL CONCENTRATIONS; MATERNAL PROTEIN RESTRICTION; INSULIN-RESISTANCE SYNDROME; ADIPOSE-TISSUE; 11-BETA-HYDROXYSTEROID DEHYDROGENASE; VISCERAL ADIPOSITY AB Adipose tissue (AT) dysfunction links obesity of any cause with cardiometabolic disease, but whether early-life nutritional deficiency can program adipocyte dysfunction independently of obesity is untested. In 3-5-month-old juvenile microswine offspring exposed to isocaloric perinatal maternal protein restriction (MPR) and exhibiting accelerated prepubertal fat accrual without obesity, we assessed markers of acquired obesity: adiponectin and tumor necrosis factor (TNF)-alpha messenger ribonucleic acid (mRNA) levels and adipocyte size in intra-abdominal (ABD-AT) and subcutaneous (SC-AT) adipose tissues. Plasma cortisol, leptin and insulin levels were measured in fetal, neonatal and juvenile offspring. In juvenile low-protein offspring (LPO), adipocyte size in ABD-AT was reduced 22% (P = 0.011 v. controls), whereas adipocyte size in SC-AT was increased in female LPO (P = 0.05) and normal in male LPO; yet, adiponectin mRNA in LPO was low in both sexes and in both depots (P < 0.001). Plasma leptin (P = 0.004) and cortisol (P < 0.05) were reduced only in neonatal LPO during MPR. In juveniles, correlations between % body fat and adiponectin mRNA, TNF-alpha mRNA or plasma leptin were significant in normal-protein offspring (NPO) but absent in LPO. Plasma glucose in juvenile LPO was increased in males but decreased in females (interaction, P = 0.023); plasma insulin levels and insulin sensitivity were unaffected. Findings support nutritional programming of adipocyte size and gene expression and subtly altered glucose homeostasis. Reduced adiponectin mRNA and adipokine dysregulation in juvenile LPO following accelerated growth occurred independently of obesity, adipocyte hypertrophy or inflammatory markers; thus, perinatal MPR and/or growth acceleration can alter adipocyte structure and disturb adipokine homeostasis in metabolically adverse patterns predictive of enhanced disease risk. C1 [Bagby, S. P.] Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Dept Med, Portland, OR 97239 USA. [DuPriest, E. A.; Bagby, S. P.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. [DuPriest, E. A.; Kupfer, P.; Lin, B.; Sekiguchi, K.; Bagby, S. P.] Portland VA Med Ctr, Res Serv, Portland, OR USA. [DuPriest, E. A.] Warner Pacific Coll, Dept Nat Sci & Hlth, Portland, OR USA. [Morgan, T. K.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA. [Saunders, K. E.; Chatkupt, T. T.] Oregon Hlth & Sci Univ, Dept Comparat Med, Portland, OR 97239 USA. [Denisenko, O. N.] Univ Washington, Dept Med, Seattle, WA USA. RP Bagby, SP (reprint author), Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Dept Med, 3303 SW Bond Ave,CH12R, Portland, OR 97239 USA. EM bagbys@ohsu.edu FU NIH/NICHD [1P01 HD34430, R01 HD042570]; Medical Research Foundation of Oregon; Eagles Foundation of Spokane, WA; American Heart Association Pacific Mountain Affiliate Predoctoral Fellowship Award [0415530Z]; Oregon Health & Science University Tartar Trust Fellowship FX Work was supported by NIH/NICHD 1P01 HD34430, R01 HD042570, Medical Research Foundation of Oregon, and the Eagles Foundation of Spokane, WA. EA DuPriest was supported by American Heart Association Pacific Mountain Affiliate Predoctoral Fellowship Award no. 0415530Z and by the Oregon Health & Science University Tartar Trust Fellowship. NR 69 TC 0 Z9 0 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 2040-1744 J9 J DEV ORIG HLTH DIS JI J. Dev. Orig. Health Dis. PD JUN PY 2012 VL 3 IS 3 BP 198 EP 209 DI 10.1017/S2040174412000232 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 984IL UT WOS:000307183200009 PM 25102010 ER PT J AU Patel, SM Rahman, MA Mohasin, M Riyadh, MA Leung, DT Alam, MM Chowdhury, F Khan, AI Weil, AA Aktar, A Nazim, M LaRocque, RC Ryan, ET Calderwood, SB Qadri, F Harris, JB AF Patel, Sweta M. Rahman, Mohammad Arif Mohasin, M. Riyadh, M. Asrafuzzaman Leung, Daniel T. Alam, Mohammad Murshid Chowdhury, Fahima Khan, Ashraful I. Weil, Ana A. Aktar, Amena Nazim, Mohammad LaRocque, Regina C. Ryan, Edward T. Calderwood, Stephen B. Qadri, Firdausi Harris, Jason B. TI Memory B Cell Responses to Vibrio cholerae O1 Lipopolysaccharide Are Associated with Protection against Infection from Household Contacts of Patients with Cholera in Bangladesh SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID EL-TOR; ANTIBODY; TOXIN; SUSCEPTIBILITY; TRANSMISSION; IMMUNITY; CYCLASE; OGAWA; DHAKA AB Vibrio cholerae O1 causes cholera, a dehydrating diarrheal disease. We have previously shown that V. cholerae-specific memory B cell responses develop after cholera infection, and we hypothesize that these mediate long-term protective immunity against cholera. We prospectively followed household contacts of cholera patients to determine whether the presence of circulating V. cholerae O1 antigen-specific memory B cells on enrollment was associated with protection against V. cholerae infection over a 30-day period. Two hundred thirty-six household contacts of 122 index patients with cholera were enrolled. The presence of lipopolysaccharide (LPS)-specific IgG memory B cells in peripheral blood on study entry was associated with a 68% decrease in the risk of infection in household contacts (P = 0.032). No protection was associated with cholera toxin B subunit (CtxB)-specific memory B cells or IgA memory B cells specific to LPS. These results suggest that LPS-specific IgG memory B cells may be important in protection against infection with V. cholerae O1. C1 [Leung, Daniel T.; LaRocque, Regina C.; Ryan, Edward T.; Calderwood, Stephen B.; Harris, Jason B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Patel, Sweta M.; Rahman, Mohammad Arif; Mohasin, M.; Riyadh, M. Asrafuzzaman; Alam, Mohammad Murshid; Chowdhury, Fahima; Khan, Ashraful I.; Weil, Ana A.; Aktar, Amena; Nazim, Mohammad; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [Leung, Daniel T.; Weil, Ana A.; LaRocque, Regina C.; Ryan, Edward T.; Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Harris, Jason B.] Massachusetts Gen Hosp Children, Div Global Hlth, Boston, MA USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Harris, JB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM jbharris@partners.org OI leung, daniel/0000-0001-8401-0801 FU National Institutes of Health; National Institute of Allergy and Infectious Diseases [U01 AI058935, R03 AI063079, U01 AI077883]; Fogarty International Center [TW005572, TW007409, TW07144]; American Recovery and Reinvestment Act (ARRA) FIC [TW05572]; Harvard Initiative for Global Health; Howard Hughes Medical Institute; Vanderbilt University [R24 TW007988]; American Relief and Recovery Act FX This work was supported by the icddr,b and grants from the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases (U01 AI058935 [to S. B. C. and E. T. R.], R03 AI063079 [to F. Q.], and U01 AI077883 [to E. T. R.]), a Training Grant in Vaccine Development from the Fogarty International Center (TW005572 [to M. M. A. and F. Q.]), an American Recovery and Reinvestment Act (ARRA) FIC Post-doctoral Fellowship in Global Infectious Diseases (TW05572 [to D. T. L.]), Career Development Awards (K01) from the Fogarty International Center (TW007409 [to J.B.H.] and TW07144 [to R. C. L.]), the Harvard Initiative for Global Health Post-doctoral Fellowship in Global Infectious Diseases (to D. T. L), and a Physician Scientist Early Career Award from the Howard Hughes Medical Institute (to R. C. L.). S. M. P. is the recipient of a Fogarty International Clinical Research Scholars award from the Fogarty International Center and Vanderbilt University (R24 TW007988) and the American Relief and Recovery Act. NR 31 TC 24 Z9 24 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD JUN PY 2012 VL 19 IS 6 BP 842 EP 848 DI 10.1128/CVI.00037-12 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 983HN UT WOS:000307110500003 PM 22518009 ER PT J AU Abeijon, C Kashino, SS Silva, FO Costa, DL Fujiwara, RT Costa, CHN Campos-Neto, A AF Abeijon, Claudia Kashino, Suely S. Silva, Fernando O. Costa, Dorcas L. Fujiwara, Ricardo T. Costa, Carlos H. N. Campos-Neto, Antonio TI Identification and Diagnostic Utility of Leishmania infantum Proteins Found in Urine Samples from Patients with Visceral Leishmaniasis SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LATEX AGGLUTINATION-TEST; STREPTOCOCCUS-PNEUMONIAE ANTIGEN; ACTIVE PULMONARY TUBERCULOSIS; LINKED-IMMUNOSORBENT-ASSAY; POLYMERASE-CHAIN-REACTION; ALTERNATIVE APPROACH; INFECTED PATIENTS; RECOMBINANT K-39; IMMUNE-RESPONSE AB Despite the clear need to control visceral leishmaniasis (VL), the existing diagnostic tests have serious shortcomings. Here, we introduce an innovative approach to directly identify Leishmania infantum antigens produced in vivo in humans with VL. We combined reverse-phase high-performance liquid chromatography (RP-HPLC) with mass spectrometry and categorized three distinct L. infantum proteins presumably produced in bone marrow/spleen/liver and excreted in the urine of patients with VL. The genes coding for these proteins (L. infantum iron superoxide dismutase, NCBI accession number XP_001467866.1; L. infantum tryparedoxin, NCBI accession number XP_001466642.1; and L. infantum nuclear transport factor 2, NCBI accession number XP_001463738.1) were cloned, and the recombinant molecules were produced in Escherichia coli. Antibodies to these proteins were produced in rabbits and chickens and were used to develop a capture enzyme-linked immunosorbent assay (ELISA) designed to detect these L. infantum antigens in the urine of VL patients. Specificity of the antibodies was confirmed by a Western blot analysis using both recombinant proteins and whole parasite extract. Importantly, a urinary antigen detection assay assembled with pairs of antibodies specific for each of these antigens identified 17 of 19 patients with VL. These results indicate that an improved antigen detection assay based on L. infantum proteins present in the urine of patients with VL may represent an important new strategy for the development of a specific and accurate diagnostic test that has the potential to both distinguish active VL from asymptomatic infection and serve as an important tool to monitor therapy efficacy. C1 [Abeijon, Claudia; Campos-Neto, Antonio] DetectoGen Inc, Grafton, MA USA. [Kashino, Suely S.; Campos-Neto, Antonio] Forsyth Inst, Cambridge, MA USA. [Silva, Fernando O.; Costa, Dorcas L.; Costa, Carlos H. N.] Univ Fed Piaui, Natan Portella Inst Trop Med, Lab Leishmaniasis, Teresina, Piaui, Brazil. [Fujiwara, Ricardo T.] Univ Fed Minas Gerais, Dept Parasitol, Horizonte, MG, Brazil. RP Campos-Neto, A (reprint author), DetectoGen Inc, Grafton, MA USA. EM acampos@forsyth.org RI Fujiwara, Ricardo/J-7579-2012 OI Fujiwara, Ricardo/0000-0002-4713-575X FU NIH [R43AI084259-01] FX This work was supported by NIH grant R43AI084259-01, awarded to C.A. NR 53 TC 6 Z9 6 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD JUN PY 2012 VL 19 IS 6 BP 935 EP 943 DI 10.1128/CVI.00125-12 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 983HN UT WOS:000307110500017 PM 22518013 ER PT J AU Denny-Brown, S Stanley, TL Grinspoon, SK Makimura, H AF Denny-Brown, S. Stanley, T. L. Grinspoon, S. K. Makimura, H. TI The association of macro- and micronutrient intake with growth hormone secretion SO GROWTH HORMONE & IGF RESEARCH LA English DT Article DE Diet; Vitamin C; Ascorbic acid; Frequent sampling ID ALPHA-AMIDATING MONOOXYGENASE; PITUITARY-CELLS; VITAMIN-C; SOMATOTROPIC AXIS; ASCORBIC-ACID; ENERGY-INTAKE; FOOD RECORDS; IGF-I; PROTEIN; WOMEN AB Context: Growth hormone (GH) is known to be nutritionally regulated, but the effect of dietary composition on detailed GH secretion parameters has not previously been comprehensively evaluated. Objective: The objective of the study was to determine whether specific macro- and micronutrients are associated with discrete parameters of GH secretion among subjects with wide ranges of body mass index. Design: Detailed macro- and micronutrient intake was assessed by 4-day food records while GH secretion was assessed by standard stimulation testing in 108 men and women in one study (Study 1), and by overnight frequent blood sampling in 12 men in another study (Study 2). Results: Peak stimulated GH was positively associated with vitamin C (r = +0.29; P=0.003), dietary fiber (r = +0.27; P=0.004), arachidic acid (r= +0.25; P=0.008), and behenic acid (r = +0.30; P=0.002) intake in univariate analysis. Controlling for age, gender, race/ethnicity, visceral fat, HOMA-IR, total caloric intake and these four dietary factors in step-wise multivariate modeling, peak GH remained significantly associated with vitamin C and visceral fat (both P<0.05). In addition, vitamin C intake was associated with various parameters of endogenous GH secretion including basal GH secretion (r = +0.95; P<0.0001), GH half-life (r = +.75; P=0.005), total GH production (r = +0.76; P=0.004), GH area-under-the-curve (r = +0.89; P=0.0001), mean log(10) GH pulse area (r = +0.67; P=0.02), and overnight maximum (r = +0.62; P=0.03), nadir (r = +0.97; P<0.0001), and mean GH secretion (r = +0.89; P=0.0001). Conclusions: These results suggest that certain micronutrients such as vitamin C intake are strongly and uniquely associated with stimulated and endogenous spontaneous GH secretion. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Stanley, T. L.; Grinspoon, S. K.; Makimura, H.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Stanley, T. L.; Grinspoon, S. K.; Makimura, H.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Stanley, T. L.; Grinspoon, S. K.; Makimura, H.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Denny-Brown, S.] Eastern Virginia Med Sch, Norfolk, VA 23507 USA. [Stanley, T. L.] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. RP Makimura, H (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON 211, Boston, MA 02114 USA. EM hmakimura@partners.org FU National Institutes of Health [T32DK007028, K23DK089910, R01HL085268, R01DK63639, K24DK064545, K23DK087857, M01RR01066, UL1RR025758]; Harvard Clinical and Translational Science Center, from the National Center for Research Resources FX National Institutes of Health grant T32DK007028 to SDB, K23DK089910 to TLS, R01HL085268 to SKG, R01DK63639 to SKG, K24DK064545 to SKG, K23DK087857 to HM, and M01RR01066 and UL1RR025758, 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 40 TC 2 Z9 2 U1 0 U2 6 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1096-6374 EI 1532-2238 J9 GROWTH HORM IGF RES JI Growth Horm. IGF Res. PD JUN-AUG PY 2012 VL 22 IS 3-4 BP 102 EP 107 DI 10.1016/j.ghir.2012.03.001 PG 6 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 982FN UT WOS:000307028400002 PM 22465725 ER PT J AU Puppin, C Passon, N Hershman, JM Filetti, S Bulotta, S Celano, M Russo, D Damante, G AF Puppin, Cinzia Passon, Nadia Hershman, Jerome M. Filetti, Sebastiano Bulotta, Stefania Celano, Marilena Russo, Diego Damante, Giuseppe TI Cooperative effects of SAHA and VPA on NIS gene expression and proliferation of thyroid cancer cells SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Article ID HISTONE DEACETYLASE INHIBITORS; SODIUM-IODIDE SYMPORTER; SODIUM/IODIDE SYMPORTER; NA+/I-SYMPORTER; UPSTREAM ENHANCER; BREAST-CANCER; VALPROIC ACID; ACETYLATION; H3; IDENTIFICATION AB Histone deacetylase inhibitors (HDACi) have shown both anti-proliferative and redifferentiating effects in thyroid cancer cells. Also, they induce the expression of the sodium-iodide symporter gene (NIS (SLC5A5)), a crucial step for radioiodine treatment of thyroid malignancies. Here we investigated the effects of suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA) on BCPAP and FRO thyroid cancer cells, extending our analysis on the epigenetic mechanisms underlying the NIS gene expression stimulation. In both cell lines we found a cooperative effect of the two compounds on either cell viability and NIS gene expression, resulting in acquired/increased ability to uptake the radioiodine. Such effect was specific since it was not observed for expression of other genes or when SAHA was used in combination with trichostatin A. By using chromatin immunoprecipitation, we investigated epigenetic mechanisms underlying SAHA and VPA effects. Cooperation among the two HDACi occurred on H3 histone trimethylation at lysine 4 (H3K4me3) and not on histone acetylation. However, effects on H3K4me3 were detected only at the level of NIS Proximal Basal Promoter (NIS-PBP) in FRO cells and only at the level of NIS Upstream Enhancer (NIS-NUE) in BCPAP cells. Our data indicate that epigenetic changes are involved in the synergistic effects of VPA and SAHA on NIS gene expression and that the cellular context modifies effects of HDACi in terms of H3K4me3 target sequence. Investigation of cooperation among different HDACi may provide clues for better defining their mechanism of action in view of their use in thyroid cancer treatment. Journal of Molecular Endocrinology (2012) 48, 217-227 C1 [Puppin, Cinzia; Passon, Nadia; Damante, Giuseppe] Univ Udine, Dipartimento Sci Med & Biol, I-33100 Udine, Italy. [Hershman, Jerome M.] Vet Adm Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. [Filetti, Sebastiano] Univ Roma La Sapienza, Dipartimento Med Interna & Specialita Med, Rome, Italy. [Bulotta, Stefania; Celano, Marilena; Russo, Diego] Univ Catanzaro, Dipartimento Sci Farmacobiol, Catanzaro, Italy. [Damante, Giuseppe] Univ S Maria della Misericordia, Azienda Osped, Udine, Italy. RP Damante, G (reprint author), Univ Udine, Dipartimento Sci Med & Biol, Piazzale Kolbe 1, I-33100 Udine, Italy. EM giuseppe.damante@uniud.it FU Associazione Italiana per la Ricerca sul Cancro (AIRC) [IG 10296]; MIUR (PRIN) [20093WAPIK_003] FX This work was supported by grants to G D from Associazione Italiana per la Ricerca sul Cancro (AIRC) (grant number IG 10296) and MIUR (PRIN grant number 20093WAPIK_003). NR 51 TC 8 Z9 8 U1 0 U2 2 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD JUN PY 2012 VL 48 IS 3 BP 217 EP 227 DI 10.1530/JME-11-0063 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 985PI UT WOS:000307279100006 ER PT J AU Zhou, YL Zhang, X Klibanski, A AF Zhou, Yunli Zhang, Xun Klibanski, Anne TI MEG3 noncoding RNA: a tumor suppressor SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Review ID NONFUNCTIONING PITUITARY-ADENOMAS; DLK1-GTL2 IMPRINTED DOMAIN; GENE-EXPRESSION; PROMOTER REGION; GTL2 GENE; P53; ORIGIN; GROWTH; CANCER; LOCUS AB Maternally expressed gene 3 (MEG3) is an imprinted gene belonging to the imprinted DLK1-MEG3 locus located at chromosome 14q32.3 in humans. Its mouse ortholog, Meg3, also known as gene trap locus 2 (Gtl2), is located at distal chromosome 12. The MEG3 gene encodes a long noncoding RNA (lncRNA) and is expressed in many normal tissues. MEG3 gene expression is lost in an expanding list of primary human tumors and tumor cell lines. Multiple mechanisms contribute to the loss of MEG3 expression in tumors, including gene deletion, promoter hypermethylation, and hypermethylation of the intergenic differentially methylated region. Re-expression of MEG3 inhibits tumor cell proliferation in culture and colony formation in soft agar. This growth inhibition is partly the result of apoptosis induced by MEG3. MEG3 induces accumulation of p53 (TP53) protein, stimulates transcription from a p53-dependent promoter, and selectively regulates p53 target gene expression. Maternal deletion of the Meg3 gene in mice results in skeletal muscle defects and perinatal death. Inactivation of Meg3 leads to a significant increase in expression of angiogenesis-promoting genes and microvessel formation in the brain. These lines of evidence strongly suggest that MEG3 functions as a novel lncRNA tumor suppressor. Journal of Molecular Endocrinology (2012) 48, R45-R53 C1 [Zhou, Yunli] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Zhou, YL (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,Bulfinch 457, Boston, MA 02114 USA. EM yzhou2@partners.org FU National Institutes of Health [R01DK40947]; Guthart Family Foundation; Jarislowsky Foundation FX This work was supported by grants from the National Institutes of Health (A K, R01DK40947), the Guthart Family Foundation, and the Jarislowsky Foundation. NR 54 TC 194 Z9 224 U1 6 U2 50 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD JUN PY 2012 VL 48 IS 3 BP R45 EP R53 DI 10.1530/JME-12-0008 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 985PI UT WOS:000307279100003 PM 22393162 ER PT J AU Hosain, GMM Khan, MM Amiel, GE Lerner, SP Latini, DM Chen, GJ AF Hosain, G. M. Monawar Khan, Myrna M. Amiel, Gilad E. Lerner, Seth P. Latini, David M. Chen, G. John TI RACIAL/ETHNIC DIFFERENCES IN UPPER-TRACT UROTHELIAL CANCER SO ETHNICITY & DISEASE LA English DT Article DE Race/ethnicity; Urothelial Cancer; Difference; SEER Program ID UPPER URINARY-TRACT; BLADDER-CANCER; AFRICAN-AMERICAN; PROSTATE-CANCER; BREAST-CANCER; LYMPH-NODES; PELVIC LYMPHADENECTOMY; RACIAL DISPARITY; BLACK PATIENTS; WHITE PATIENTS AB Objectives: Information on clinical characteristics, pattern of initial treatment and survival in patient with upper-tract urothelial carcinomas (UTUC) is scarce. Our study examined the racial/ethnic differences in patients diagnosed with incident UTUC. Design: Observational study. The data analyses included: proportion and ANOVA for categorical and continuous variables, respectively; Kaplan-Meier method for calculating overall survival; and Cox-proportional hazards models for obtaining adjusted hazard-ratios. Setting: Regions of the Surveillance, Epidemiology and End Results (SEER). Patients or Participants: 16,702 incident UTUC patients identified from the SEER dataset 1988-2007 (14,192 White, 967 Hispanic, 718 African American and 825 Asian). Interventions: None. Main Outcome Measures: Race/ethnicity-specific distributions of demographics, tumor characteristics, patterns of initial treatment, and survival. Results: African American and Hispanic patients were diagnosed at a younger age than Whites and Asians (P=.001). Hispanics were more likely to be diagnosed with larger tumor size than Whites and Asians (P<.0001). Asians were more likely to be diagnosed with advanced stage and higher tumor grade. Cox-regression revealed that Whites and Asians were significantly less likely to die after UTUC diagnosis than African Americans (HR=.78, 95% CI=.67.91 and HR=.75, 95% C1.61.91, respectively; all P=<.01). Conclusions: Our study found that Asians had worse tumor characteristics at the initial presentation than the other groups in this study, but that their risk of dying was lower. Further research is needed to include a larger number of Asian patients to examine subgroup differences and to confirm the paradoxical finding of higher survival with poor clinical characteristics. (Ethn Dis. 2012;22[3]:295-301) C1 [Hosain, G. M. Monawar; Khan, Myrna M.; Chen, G. John] VA Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. [Khan, Myrna M.; Amiel, Gilad E.; Lerner, Seth P.; Latini, David M.; Chen, G. John] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. RP Hosain, GMM (reprint author), DeBakey Vet Affairs Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM monawarhosain@gmail.com OI Latini, David/0000-0002-6161-4861 FU Houston VA HSR&D Center of Excellence [HFP90-020] FX This work was supported in part by the Houston VA HSR&D Center of Excellence (HFP90-020). The views expressed reflect those of the authors and not necessarily those of the Department of Veterans Affairs (Baylor College of Medicine). NR 37 TC 1 Z9 2 U1 1 U2 2 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD SUM PY 2012 VL 22 IS 3 BP 295 EP 301 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 978EP UT WOS:000306723700007 PM 22870572 ER PT J AU Sawers, A Hahn, ME AF Sawers, Andrew Hahn, Michael E. TI Regulation of whole-body frontal plane balance varies within a step during unperturbed walking SO GAIT & POSTURE LA English DT Article DE Balance; Gait; Variability; Motor control; Rehabilitation ID LATERAL MOTION; STABILIZATION AB This study sought to determine whether the need to actively control lateral balance is consistent within a step. Variability of the frontal plane COM-Ankle angle was calculated over 50 strides at discrete gait events for twenty-one healthy young adults to quantify active control of lateral balance within a step. Frontal plane COM-Ankle angle variability was found to vary significantly between all gait events, decreasing progressively within a step. This suggests that active control of lateral balance varies significantly within a step and that the greatest degree of active control occurs at heel-strike. The increased active control of lateral balance during heel-strike indicates a degree of preparation to ensure sufficient lateral balance control prior to more challenging events. These results provide insight into the mechanisms of lateral balance control and how to assess and treat locomotor balance control impairments. Published by Elsevier B.V. C1 [Sawers, Andrew; Hahn, Michael E.] Rehabil Res & Dev Ctr Excellence Limb Loss Preven, Dept Vet Affairs VA, VA Puget Sound, Seattle, WA 98108 USA. [Sawers, Andrew] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Hahn, Michael E.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. RP Hahn, ME (reprint author), Rehabil Res & Dev Ctr Excellence Limb Loss Preven, Dept Vet Affairs VA, VA Puget Sound, 1660 S Columbian Way, Seattle, WA 98108 USA. EM mehahn@u.washington.edu FU Center of Excellence grant from the Department of Veterans Affairs, Rehabilitation Research and Development [A4843C] FX This research was supported by a Center of Excellence grant (A4843C) from the Department of Veterans Affairs, Rehabilitation Research and Development. NR 16 TC 7 Z9 7 U1 1 U2 13 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0966-6362 J9 GAIT POSTURE JI Gait Posture PD JUN PY 2012 VL 36 IS 2 BP 322 EP 324 DI 10.1016/j.gaitpost.2012.03.003 PG 3 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA 976YP UT WOS:000306623600030 PM 22465707 ER PT J AU Haining, WN Pulendran, B AF Haining, W. Nicholas Pulendran, Bali TI Identifying gnostic predictors of the vaccine response SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID SET ENRICHMENT ANALYSIS; SYSTEMS BIOLOGY; TUBERCULOSIS; MICROARRAYS; SIGNATURES; DISCOVERY; CIRCUITS; GENOMES; HUMANS; GENES AB Molecular predictors of the response to vaccination could transform vaccine development. They would allow larger numbers of vaccine candidates to be rapidly screened, shortening the development time for new vaccines. Gene-expression based predictors of vaccine response have shown early promise. However, a limitation of gene-expression based predictors is that they often fail to reveal the mechanistic basis of their ability to classify response. Linking predictive signatures to the function of their component genes would advance basic understanding of vaccine immunity and also improve the robustness of vaccine prediction. New analytic tools now allow more biological meaning to be extracted from predictive signatures. Functional genomic approaches to perturb gene expression in mammalian cells permit the function of predictive genes to be surveyed in highly parallel experiments. The challenge for vaccinologists is therefore to use these tools to embed mechanistic insights into predictors of vaccine response. C1 [Haining, W. Nicholas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp,Dept Pediat Oncol, Boston, MA 02115 USA. [Haining, W. Nicholas] Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Haining, W. Nicholas] Broad Inst Harvard & MIT, Cambridge, MA USA. [Pulendran, Bali] Yerkes Natl Primate Ctr, Emory Vaccine Ctr, Dept Pathol, Atlanta, GA 30329 USA. RP Haining, WN (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp,Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM nicholas_haining@dfci.harvard.edu FU NIAID NIH HHS [R01 AI091493-03, HHSN266200700006C, N01 AI050025, R01 AI091493, R01AI091493, R37 AI048638, R37 AI048638-09A1, R37AI48638, U19 AI057266, U19 AI082630, U19 AI090023, U19 AI090023-03, U19AI057266, U19AI082630, U19AI090023, U54 AI057157, U54AI057157]; NIDDK NIH HHS [R01 DK057665, R01DK057665, R37 DK057665]; PHS HHS [HHSN266200700006C] NR 34 TC 11 Z9 11 U1 0 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 2012 VL 24 IS 3 BP 332 EP 336 DI 10.1016/j.coi.2012.03.010 PG 5 WC Immunology SC Immunology GA 974QA UT WOS:000306450200014 PM 22633886 ER PT J AU Corbacioglu, S Kernan, N Lehmann, L Brochstein, J Revta, C Grupp, S Martin, P Richardson, PG AF Corbacioglu, Selim Kernan, Nancy Lehmann, Leslie Brochstein, Joel Revta, Carolyn Grupp, Stephan Martin, Paul Richardson, Paul G. TI Defibrotide for the treatment of hepatic veno-occlusive disease in children after hematopoietic stem cell transplantation SO EXPERT REVIEW OF HEMATOLOGY LA English DT Review DE defibrotide; sinusoidal obstruction syndrome; veno-occlusive disease ID BONE-MARROW-TRANSPLANTATION; SINUSOIDAL OBSTRUCTION SYNDROME; TISSUE-PLASMINOGEN ACTIVATOR; REGIMEN-RELATED TOXICITY; HIGH-RISK POPULATION; IN-VITRO; GEMTUZUMAB OZOGAMICIN; URSODEOXYCHOLIC ACID; INTRAVENOUS BUSULFAN; VENOCCLUSIVE DISEASE AB Hepatic veno-occlusive disease (VOD) is a serious complication of stem cell transplantation in children. VOD is characterized by rapid weight gain, hepatomegaly, hyperbilirubinemia and ascites. The pathogenesis of VOD is thought to involve chemotherapy and radiation-induced damage to the sinusoidal endothelium, resulting in endothelial injury, microthrombosis, subendothelial damage and cytokine activation. These processes lead to concomitant progressive hepatocellular dysfunction and subsequent fluid retention and renal impairment. Severe VOD is typically associated with multiorgan failure and high mortality. A number of possible strategies for the prevention and/or treatment of VOD in children have been investigated. The most promising agent to date is defibrotide, a novel polydeoxyribonucleotide with fibrinolytic properties but no major bleeding risk. Numerous studies, including Phase II/III trials, have shown clinical benefit in pediatric patients with the use of defibrotide treatment and prophylaxis. This review discusses VOD in children and focuses on therapeutic options, including defibrotide, in this patient population. C1 [Lehmann, Leslie; Revta, Carolyn; Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Corbacioglu, Selim] Univ Regensburg, Regensburg, Germany. [Kernan, Nancy] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Brochstein, Joel] Steven & Alexandra Cohen Childrens Med Ctr New Y, New Hyde Pk, NY USA. [Grupp, Stephan] Childrens Hosp, Philadelphia, PA 19104 USA. [Martin, Paul] Duke Univ, Med Ctr, Durham, NC USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu OI Kernan, Nancy/0000-0003-1417-1823 FU Gentium S.p.A.; Rick Corman Multiple Myeloma Research Fund FX P Martin has received research support for the defibrotide studies from Gentium S.p.A. S Corbacioglu and PG Richardson have served on the advisory board for Gentium S.p.A., in accordance with each investigators' institutional guidelines and specified limitations, and within each investigator's institutional de minimis. 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.; Writing assistance was utilized in the production of this manuscript. The authors acknowledge K Silverthorne and A Marmont for their assistance in writing this manuscript. Funding for writing and administrative assistance was provided by Gentium S.p.A and the Rick Corman Multiple Myeloma Research Fund, respectively. NR 79 TC 14 Z9 14 U1 0 U2 2 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1747-4086 J9 EXPERT REV HEMATOL JI Expert Rev. Hematol. PD JUN PY 2012 VL 5 IS 3 BP 291 EP 302 DI 10.1586/EHM.12.18 PG 12 WC Hematology SC Hematology GA 975WT UT WOS:000306543000010 PM 22780209 ER PT J AU Flint, LA Sudore, RL Widera, E AF Flint, Lynn A. Sudore, Rebecca L. Widera, Eric TI Assessing Financial Capacity Impairment in Older Adults SO GENERATIONS-JOURNAL OF THE AMERICAN SOCIETY ON AGING LA English DT Article ID COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; DEMENTIA; COMPETENCE; CAREGIVERS; ABILITIES C1 [Flint, Lynn A.; Sudore, Rebecca L.; Widera, Eric] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Flint, Lynn A.; Sudore, Rebecca L.; Widera, Eric] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. RP Flint, LA (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. EM lynn.flint@ucsf.edu; rebecca.sudore@ucsf.edu; eric.widera@ucsf.edu NR 17 TC 3 Z9 3 U1 0 U2 2 PU AMER SOC AGING PI SAN FRANCISCO PA 833 MARKET ST, STE 511, SAN FRANCISCO, CA 94103-1824 USA SN 0738-7806 J9 GENERATIONS JI Generations-J. Am. Soc. Aging PD SUM PY 2012 VL 36 IS 2 BP 59 EP 65 PG 7 WC Gerontology SC Geriatrics & Gerontology GA 970DL UT WOS:000306108200010 ER PT J AU Roush, RE Moye, JA Mills, WL Kunik, ME Wilson, NL Taffet, GE Naik, AD AF Roush, Robert E. Moye, Jennifer A. Mills, Whitney L. Kunik, Mark E. Wilson, Nancy L. Taffet, George E. Naik, Aanand D. TI Why Clinicians Need to Know About the Elder Investment Fraud and Financial Exploitation Program SO GENERATIONS-JOURNAL OF THE AMERICAN SOCIETY ON AGING LA English DT Article ID MILD COGNITIVE IMPAIRMENT; UNITED-STATES; PREVALENCE C1 [Roush, Robert E.; Taffet, George E.] Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA. [Moye, Jennifer A.] VA Boston Healthcare Syst, Boston, MA USA. [Moye, Jennifer A.] Harvard Univ, Sch Med, Boston, MA USA. [Mills, Whitney L.; Naik, Aanand D.] Michael E DeBakey VA Med Ctr, Houston Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. [Taffet, George E.] Baylor Coll Med, Dept Med, Sect Geriatr, Houston, TX 77030 USA. RP Roush, RE (reprint author), Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA. RI Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X NR 14 TC 4 Z9 4 U1 3 U2 7 PU AMER SOC AGING PI SAN FRANCISCO PA 833 MARKET ST, STE 511, SAN FRANCISCO, CA 94103-1824 USA SN 0738-7806 J9 GENERATIONS JI Generations-J. Am. Soc. Aging PD SUM PY 2012 VL 36 IS 2 BP 94 EP 97 PG 4 WC Gerontology SC Geriatrics & Gerontology GA 970DL UT WOS:000306108200015 ER PT J AU Taylor, E AF Taylor, Eugene TI The Immortalization Commission: Science and the Strange Quest to Cheat Death SO JOURNAL OF THE HISTORY OF THE BEHAVIORAL SCIENCES LA English DT Book Review C1 [Taylor, Eugene] Saybrook Univ, Coll Humanist Studies, San Francisco, CA 94111 USA. [Taylor, Eugene] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Taylor, Eugene] Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. RP Taylor, E (reprint author), Saybrook Univ, Coll Humanist Studies, San Francisco, CA 94111 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-5061 J9 J HIST BEHAV SCI JI J. Hist. Behav. Sci. PD SUM PY 2012 VL 48 IS 3 BP 293 EP 294 DI 10.1002/jhbs.21558 PG 2 WC History Of Social Sciences SC Social Sciences - Other Topics GA 975LO UT WOS:000306513000013 ER PT J AU Partridge, AH Hughes, ME Ottesen, RA Wong, YN Edge, SB Theriault, RL Blayney, DW Niland, JC Winer, EP Weeks, JC Tamimi, RM AF Partridge, Ann H. Hughes, Melissa E. Ottesen, Rebecca A. Wong, Yu-Ning Edge, Stephen B. Theriault, Richard L. Blayney, Douglas W. Niland, Joyce C. Winer, Eric P. Weeks, Jane C. Tamimi, Rulla M. TI The Effect of Age on Delay in Diagnosis and Stage of Breast Cancer SO ONCOLOGIST LA English DT Article DE Breast cancer; Young age; Delay in diagnosis; Breast cancer screening ID SURVIVAL; WOMEN; SYMPTOMS; SEEKING; IMPACT; HELP; NCCN AB Background. Young women with breast cancer are more likely to present with more advanced disease and are more likely to die as a result of breast cancer than their older counterparts. We sought to examine the relationship among young age (<= 40 years), the likelihood of a delay in diagnosis, and stage. Methods. We examined data from women with newly diagnosed stage I-IV breast cancer presenting to one of eight National Comprehensive Cancer Network centers in January 2000 to December 2007. Delay in diagnosis was defined as time from initial sign or symptom to breast cancer diagnosis >60 days. Results. Among 21,818 women with breast cancer eligible for analysis, 2,445 were aged <= 40 years at diagnosis. Young women were not more likely to have a delay in diagnosis >60 days (odds ratio [OR], 1.08; 95% confidence interval [CI], 0.98-1.19) after adjustment for type of initial sign or symptom. Young women were only modestly more likely to present with higher stage disease after a similar adjustment (OR, 1.18; 95% CI, 1.07-1.31). Women presenting with symptomatic disease, more common in younger women, were more likely to have a delay in diagnosis (OR, 3.31; 95% CI, 3.08-3.56) and higher stage (OR, 4.31; 95% CI 4.05-4.58). Conclusion. Young age is not an independent predictor of delay in diagnosis of breast cancer and only modestly is associated with higher stage disease. Presenting with symptoms of breast cancer predicts delay and higher stage at diagnosis. The Oncologist 2012;17:775-782 C1 [Partridge, Ann H.; Hughes, Melissa E.; Winer, Eric P.; Weeks, Jane C.; Tamimi, Rulla M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Partridge, Ann H.; Hughes, Melissa E.; Winer, Eric P.; Weeks, Jane C.; Tamimi, Rulla M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ottesen, Rebecca A.; Niland, Joyce C.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Wong, Yu-Ning] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Edge, Stephen B.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Theriault, Richard L.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Blayney, Douglas W.] Stanford Univ, Ctr Canc, Palo Alto, CA 94304 USA. RP Partridge, AH (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM ahpartridge@partners.org RI Inov Farmaceutica, Inct/K-2313-2013 FU Blue Cross Blue Shield of Michigan; NCCN FX Douglas W. Blayney: Bristol-Myers Squibb, Optum (C/A); Blue Cross Blue Shield of Michigan (RF); Abbot Labs, ADR Novartis, Bristol-Myers Squibb, Johnson & Johnson, McKesson, United Health Group (OI); Joyce C. Niland: NCCN (RF). The other authors indicated no financial relationships. NR 30 TC 30 Z9 30 U1 2 U2 8 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD JUN PY 2012 VL 17 IS 6 BP 775 EP 782 DI 10.1634/theoncologist.2011-0469 PG 8 WC Oncology SC Oncology GA 970QK UT WOS:000306147200009 PM 22554997 ER PT J AU Cardoso, F Costa, A Norton, L Cameron, D Cufer, T Fallowfield, L Francis, P Gligorov, J Kyriakides, S Lin, N Pagani, O Senkus, E Thomssen, C Aapro, M Bergh, J Di Leo, A El Saghir, N Ganz, PA Gelmon, K Goldhirsch, A Harbeck, N Houssami, N Hudis, C Kaufman, B Leadbeater, M Mayer, M Rodger, A Rugo, H Sacchini, V Sledge, G van't Veer, L Viale, G Krop, I Winer, E AF Cardoso, F. Costa, A. Norton, L. Cameron, D. Cufer, T. Fallowfield, L. Francis, P. Gligorov, J. Kyriakides, S. Lin, N. Pagani, O. Senkus, E. Thomssen, C. Aapro, M. Bergh, J. Di Leo, A. El Saghir, N. Ganz, P. A. Gelmon, K. Goldhirsch, A. Harbeck, N. Houssami, N. Hudis, C. Kaufman, B. Leadbeater, M. Mayer, M. Rodger, A. Rugo, H. Sacchini, V. Sledge, G. van't Veer, L. Viale, G. Krop, I. Winer, E. TI 1st International consensus guidelines for advanced breast cancer (ABC 1) SO BREAST LA English DT Article DE Advanced breast cancer; Metastatic breast cancer; Guidelines; Consensus; ABC 1 ID PROGRESSION-FREE SURVIVAL; BRAIN RADIATION-THERAPY; QUALITY-OF-LIFE; STEREOTACTIC RADIOSURGERY; AROMATASE INHIBITOR; 1ST-LINE TREATMENT; RANDOMIZED-TRIAL; PHASE-III; SINGLE METASTASES; SOLID TUMORS AB The 1st international Consensus Conference for Advanced Breast Cancer (ABC 1) took place on November 2011, in Lisbon. Consensus guidelines for the management of this disease were developed. This manuscript summarizes these international consensus guidelines. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Cardoso, F.] European Sch Oncol, Lisbon, Portugal. [Cardoso, F.] Champalimaud Canc Ctr, Breast Unit, Lisbon, Portugal. [Costa, A.] European Sch Oncol, IT & Bellinzona, Milan, Switzerland. [Norton, L.] Mem Sloan Kettering Canc Ctr, Breast Canc Program, New York, NY 10021 USA. [Cameron, D.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Cameron, D.] Western Gen Hosp, NHS Lothian, Edinburgh EH4 2XU, Midlothian, Scotland. [Fallowfield, L.] Univ Sussex, Brighton & Sussex Med Sch, Falmer, England. [Francis, P.] Peter MacCallum Canc Inst, Div Canc Med, Melbourne, Vic 3000, Australia. [Gligorov, J.] Univ Paris 05, Francilian Breast Intergrp Paris, CancerEst APHP Tenon, F-75270 Paris 06, France. [Kyriakides, S.] Europa Donna Cyprus, Nicosia, Cyprus. [Lin, N.] Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA. [Pagani, O.] Oncol Inst So Switzerland, Bellinzona, Switzerland. [Pagani, O.] Breast Unit So Switzerland, Bellinzona, Switzerland. [Senkus, E.] Med Univ Gdansk, Dep Oncol & Radiotherapy, Gdansk, Poland. [Thomssen, C.] Univ Halle Wittenberg, Klinikum Krollwitz, Clin Gynaecol, Halle, Saale, Germany. [Aapro, M.] Inst Multidisciplinaire Oncol, Div Oncol, Genolier, Switzerland. [Bergh, J.] Karolinska Inst, Dep Oncol Pathol, Stockholm, Sweden. [Di Leo, A.] Osped Misericordia & Dolce, Prato, Italy. [El Saghir, N.] Amer Univ Beirut, Med Ctr, NK Basile Canc Inst Breast Ctr Excellence, Beirut, Lebanon. [Ganz, P. A.] Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90034 USA. [Gelmon, K.] BC Canc Agcy, Vancouver, BC, Canada. [Goldhirsch, A.] European Inst Oncol, Dep Med, Milan, Italy. [Harbeck, N.] Univ Munich, Brustzentrum, Munich, Germany. [Houssami, N.] Univ Sydney, Screening & Test Evaluat Program, Sch Publ Hlth, Sydney Med Sch, Sydney, NSW 2006, Australia. [Hudis, C.] Mem Sloan Kettering Canc Ctr, Breast Canc Med Serv, New York, NY 10021 USA. [Kaufman, B.] Chaim Sheba Med Ctr, Tel Hashomer, Israel. [Leadbeater, M.] Breast Canc Care, London, England. [Mayer, M.] AdvancedBC Org, New York, NY USA. [Rugo, H.] UCSF Helen Diller Family Comprehens Canc Ctr, Dept Med, Breast Oncol Program, San Francisco, CA USA. [Sacchini, V.] Mem Sloan Kettering Canc Ctr, Breast Serv, New York, NY 10021 USA. [Sledge, G.] Indiana Univ, Med Ctr, Indianapolis, IN USA. [van't Veer, L.] UCSF Helen Diller Family Comprehens Canc Ctr, Breast Oncol Program, San Francisco, CA USA. [Viale, G.] Univ Milan, I-20122 Milan, Italy. [Krop, I.; Winer, E.] Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA. RP Cardoso, F (reprint author), Champalimaud Canc Ctr, Breast Canc Unit, ESO Breast Canc Program, Av Brasilia Doca Pedroucos, P-1400048 Lisbon, Portugal. EM fatimacardoso@fundacaochampalimaud.pt RI Francis, Prudence/J-4003-2012; OI Gligorov, Joseph/0000-0002-9900-6386; Cardoso, Fatima/0000-0002-6692-2249; Norton, Larry/0000-0003-3701-9250; Senkus, Elzbieta/0000-0001-6855-397X; Fallowfield, Lesley/0000-0003-0577-4518 FU Abraxis; Amgen; AstraZeneca; Bayer Schering; Bristol Myers; Celgene; Cephalon; GSK; Helsinn; Hospira; Johnson and Johnson; Ortho Biotech; Merck; MSD; Novartis; Pfizer; Pierre-Fabre; Roche; Sandoz; Schering; Sanofi-Aventis; Vifor; Breast Oncology Center; Dana-Farber Cancer Institute; Boston; U.S. Genentech; Boehringer Ingelheim; Bayer; Genentech/Roche; Merck, Novartis, BMS; Sanofi/Bipar; Lilly/Imclone FX Matti Aapro - Division of Oncology, Institut Multidisciplinaire d'Oncologie, Genolier, CH. Abraxis, Amgen, AstraZeneca, Bayer Schering, Bristol Myers, Celgene, Cephalon, GSK, Helsinn, Hospira, Johnson and Johnson, Ortho Biotech, Merck, MSD, Novartis, Pfizer, Pierre-Fabre, Roche, Sandoz, Schering, Sanofi-Aventis, Vifor: speakers bureau, consultant, research support.; Nancy U. Lin - Breast Oncology Center, Dana-Farber Cancer Institute, Boston, U.S. Genentech, GSK, Boehringer Ingelheim, Bayer: research support; Hope S. Rugo - Department of Medicine, Breast Oncology Program, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, US. Genomic: consultant. Genentech/Roche, Merck, Novartis, BMS, Celgene, Sanofi/Bipar, Lilly/Imclone: research support to UCSF. NR 112 TC 154 Z9 156 U1 2 U2 31 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 EI 1532-3080 J9 BREAST JI Breast PD JUN PY 2012 VL 21 IS 3 BP 242 EP 252 DI 10.1016/j.breast.2012.03.003 PG 11 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 973TA UT WOS:000306381500006 PM 22425534 ER PT J AU Martins, FC De, S Almendro, V Goenen, M Park, SY Blum, JL Herlihy, W Ethington, G Schnitt, SJ Tung, N Garber, JE Fetten, K Michor, F Polyak, K AF Martins, Filipe C. De, Subhajyoti Almendro, Vanessa Goenen, Mithat Park, So Yeon Blum, Joanne L. Herlihy, William Ethington, Gabrielle Schnitt, Stuart J. Tung, Nadine Garber, Judy E. Fetten, Katharina Michor, Franziska Polyak, Kornelia TI Evolutionary Pathways in BRCA1-Associated Breast Tumors SO CANCER DISCOVERY LA English DT Article ID PIK3CA MUTATIONS; MUTANT-CELLS; IN-SITU; BRCA1; CANCER; TUMORIGENESIS; PTEN; INSTABILITY; METASTASIS; CENTROSOME AB BRCA1-associated breast tumors display loss of BRCA1 and frequent somatic mutations of PTEN and TP53. Here we describe the analysis of BRCA1, PTEN, and p53 at the single cell level in 55 BRCA1-associated breast tumors and computational methods to predict the relative temporal order of somatic events, on the basis of the frequency of cells with single or combined alterations. Although there is no obligatory order of events, we found that loss of PTEN is the most common first event and is associated with basal-like subtype, whereas in the majority of luminal tumors, mutation of TP53 occurs first and mutant PIK3CA is rarely detected. We also observed intratumor heterogeneity for the loss of wild-type BRCA1 and increased cell proliferation and centrosome amplification in the normal breast epithelium of BRCA1 mutation carriers. Our results have important implications for the design of chemopreventive and therapeutic interventions in this high-risk patient population. SIGNIFICANCE: Defining the temporal order of tumor-driving somatic events is critical for early detection, risk stratification, and the design of chemopreventive therapies. Our combined experimental and computational approach reveal that the loss of wild-type BRCA1 may not be the first event in the majority of BRCA1-associated breast tumors and may not be present in all cancer cells within tumors. Cancer Discov; 2(6); 503-11. (C) 2012 AACR. C1 [Martins, Filipe C.; Almendro, Vanessa; Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [De, Subhajyoti; Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Garber, Judy E.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. [Martins, Filipe C.; Almendro, Vanessa; Garber, Judy E.; Polyak, Kornelia] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Martins, Filipe C.; Almendro, Vanessa; Tung, Nadine; Garber, Judy E.; Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Schnitt, Stuart J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [De, Subhajyoti; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Schnitt, Stuart J.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Tung, Nadine; Fetten, Katharina] Beth Israel Deaconess Med Ctr, Dept Hemat Oncol, Boston, MA 02215 USA. [Martins, Filipe C.] Hosp Univ Coimbra, Dept Obstet & Gynaecol, Coimbra, Portugal. [De, Subhajyoti] Univ Cambridge, Univ London Kings Coll, Cambridge, England. [Almendro, Vanessa] Hosp Clin Barcelona, Dept Med Oncol, Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain. [Goenen, Mithat] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Park, So Yeon] Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 151, South Korea. [Park, So Yeon] Seoul Natl Univ, Bundang Hosp, Dept Pathol, Songnam, Gyeonggi, South Korea. [Herlihy, William] Baylor Univ, Med Ctr, Dept Pathol, Dallas, TX USA. [Polyak, Kornelia] Harvard Stem Cell Inst, Cambridge, MA USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,D740C, Boston, MA 02215 USA. EM michor@jimmy.harvard.edu; Kornelia_polyak@dfci.harvard.edu FU National Cancer Institute [P50 CA89383, U54CA143798]; Cellex foundation; Human Frontier Science Program long-term fellowship; Susan G. Komen Foundation; Breast Cancer Research Foundation; Calouste Gulbenkian Foundation; Champalimaud Foundation; Ministerio da Saude; Fundacao para a Ciencia e Tecnologia, Portugal FX This work was supported by the National Cancer Institute P50 CA89383 (to K. Polyak) and U54CA143798 (to F. Michor and M. Gonen), the Cellex foundation (to V. Almendro), Human Frontier Science Program long-term fellowship (to S. De), the Susan G. Komen Foundation (to K. Polyak and J. Garber), and the Breast Cancer Research Foundation (to K. Polyak, J. Garber, N. Tung, and S. Schnitt). The Programme for Advanced Medical Education (to F. C. Martins) is sponsored by Calouste Gulbenkian Foundation, Champalimaud Foundation, Ministerio da Saude and Fundacao para a Ciencia e Tecnologia, Portugal. NR 38 TC 54 Z9 54 U1 2 U2 18 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD JUN PY 2012 VL 2 IS 6 BP 503 EP 511 DI 10.1158/2159-8290.CD-11-0325 PG 9 WC Oncology SC Oncology GA 973ME UT WOS:000306363400018 PM 22628410 ER PT J AU Leykum, L Kumar, P Parchman, M McDaniel, RR Lanham, H Agar, M AF Leykum, Luci Kumar, Pradeep Parchman, Michael McDaniel, Reuben R. Lanham, Holly Agar, Michael TI Use of an Agent-Based Model to Understand Clinical Systems SO JASSS-THE JOURNAL OF ARTIFICIAL SOCIETIES AND SOCIAL SIMULATION LA English DT Article DE Healthcare Delivery; Sensemaking; Clinical Systems ID RANDOMIZED-TRIAL; PRIMARY-CARE; INTERVENTION; REMINDERS AB Health care improvement efforts often focus on changing the behavior of individuals while the interdependencies among individuals are overlooked. The application of complex adaptive systems approach to studying healthcare delivery changes the focus of improvement efforts from the individual to the relationships and interdependencies among individuals in the system. Sensemaking and improvising are social activities that take place in the context of relationships between individuals. We explore the impact of sensemaking and improvising on patient outcomes in healthcare settings. We conducted an in-depth observational study of relationships in inpatient general medicine teams. Data collection focused on examining associations between team relationship behaviors of sensemaking and improvising and patient outcomes. Data analysis revealed that these activities were positively associated with patient outcomes. Based on these observational data and findings, we developed an agent-based model to further explore and clarify the relationships between sensemaking and improvising on physician teams and patient outcomes. Specifically, we used the agent-based model to simulate the impact of variation in physicians' sensemaking and improvisation abilities on patient length of stay, the likelihood of a patient worsening or developing complications, the need for transfer to a higher level of care, and mortality. Our in-depth study indicates that systematic differences in patient outcomes are associated with differences in the capacity of physician teams to effectively make sense and improvise in the dynamic conditions inherent in healthcare systems. The results of our simulation demonstrate that an agent-based modeling approach is feasible and useful for exploring the impact of physician team behaviors on patient outcomes. This finding suggests the need for new tools and approaches to improve sensemaking and improvisation in physician care teams as strategies to improve patient outcomes. C1 [Leykum, Luci; Lanham, Holly] UTHSCSA, South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Kumar, Pradeep] Univ Texas, Austin, TX USA. [Parchman, Michael] Univ Texas Hlth Sci Ctr, San Antonio, TX USA. [McDaniel, Reuben R.] McCombs Sch Business, Austin, TX USA. [Agar, Michael] Ethknoworks, Santa Fe, NM USA. RP Leykum, L (reprint author), Univ Texas Hlth Sci Ctr, Sch Med, Off Dean 373L,7703 Floyd Curl Dr, San Antonio, TX 78209 USA. EM leykum@uthscsa.edu; pradeepkumar23@ymail.com; parchman@uthscsa.edu; reuben.mcdaniel@mccombs.utexas.edu; lanham@uthscsa.edu; magar@anth.umd.edu NR 25 TC 4 Z9 4 U1 1 U2 13 PU J A S S S PI GUILDFORD PA UNIV SURREY, DEPT SOCIOLOGY, GUILDFORD GU2 7XH, SURREY, ENGLAND SN 1460-7425 J9 JASSS-J ARTIF SOC S JI JASSS PD JUN PY 2012 VL 15 IS 3 AR 2 PG 25 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA 976FY UT WOS:000306567500008 ER PT J AU Zhao, J Wei, JX Mialki, R Zou, CB Mallampalli, RK Zhao, YT AF Zhao, Jing Wei, Jianxin Mialki, Rachel Zou, Chunbin Mallampalli, Rama K. Zhao, Yutong TI Extracellular Signal-regulated Kinase (ERK) Regulates Cortactin Ubiquitination and Degradation in Lung Epithelial Cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIGHT-CHAIN KINASE; F-BOX PROTEINS; KAPPA-B-ALPHA; ARP2/3 COMPLEX; TYROSINE PHOSPHORYLATION; ACTIN POLYMERIZATION; BETA-TRCP; BARRIER ENHANCEMENT; PROTEASOME PATHWAY; MIGRATION AB Cortactin, an actin-binding protein, is essential for cell growth and motility. We have shown that cortactin is regulated by reversible phosphorylation, but little is known regarding cortactin protein stability. Here, we show that lipopolysaccharide (LPS)-induced cortactin degradation is mediated by extracellular regulated signal kinase (ERK). LPS induces cortactin serine phosphorylation, ubiquitination, and degradation in mouse lung epithelia, an effect abrogated by ERK inhibition. Serine phosphorylation sites mutant, cortactin(S405A/S418A), enhances its protein stability. Cortactin is polyubiquitinated and degraded within the proteasome, whereas a cortactin(K79R) mutant exhibited proteolytic stability during cyclohexamide (CHX) or LPS treatment. The E3 ligase subunit beta-Trcp interacts with cortactin, and its overexpression reduced cortactin protein levels, an effect attenuated by ERK inhibition. Overexpression of beta-Trcp was sufficient to reduce the protective effects of exogenous cortactin on epithelial cell barrier integrity, an effect not observed after expression of a cortactin(K79R) mutant. These results provide evidence that LPS modulation of cortactin stability is coordinately regulated by stress kinases and the ubiquitin-proteasomal network. C1 [Zhao, Jing; Wei, Jianxin; Mialki, Rachel; Zou, Chunbin; Mallampalli, Rama K.; Zhao, Yutong] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA 15240 USA. RP Zhao, J (reprint author), Univ Pittsburgh, Dept Med, 3459 5th Ave,MUH NW628, Pittsburgh, PA 15213 USA. EM zhaoj@upmc.edu RI Wei, Jianxin/P-5431-2016 FU National Institutes of Health [R01 HL091916, R01 HL096376, R01 HL097376, R01 HL098174]; United States Department of Veterans Affairs; American Heart Association Scientist Development [12SDG9050005]; United States Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development FX This work was supported, in whole or in part, by National Institutes of Health Grants R01 HL091916 (to Y. Z.), and R01 HL096376, R01 HL097376, and R01 HL098174 (to R. K. M.). This work was also supported by a Merit Review Award from the United States Department of Veterans Affairs and American Heart Association Scientist Development Grant 12SDG9050005 (to J. Z.). This material is based upon work supported, in part, by the United States Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. NR 52 TC 12 Z9 12 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 1 PY 2012 VL 287 IS 23 BP 19105 EP 19114 DI 10.1074/jbc.M112.339507 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 974EF UT WOS:000306411900021 PM 22514278 ER PT J AU Pauls, E Shpiro, N Peggie, M Young, ER Sorcek, RJ Tan, L Choi, HG Cohen, P AF Pauls, Eduardo Shpiro, Natalia Peggie, Mark Young, Erick R. Sorcek, Ronald J. Tan, Li Choi, Hwan Geun Cohen, Philip TI Essential Role for IKK beta in Production of Type 1 Interferons by Plasmacytoid Dendritic Cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID KAPPA-B KINASE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; TOLL-LIKE RECEPTORS; I INTERFERON; TRANSCRIPTION FACTORS; AUTOIMMUNE-DISEASES; IMMUNE-RESPONSES; ALPHA INDUCTION; GENE INDUCTION; NUCLEIC-ACIDS AB Plasmacytoid dendritic cells (pDCs) are characterized by their ability to produce high levels of type 1 interferons in response to ligands that activate TLR7 and TLR9, but the signaling pathways required for IFN production are incompletely understood. Here we exploit the human pDC cell line Gen2.2 and improved pharmacological inhibitors of protein kinases to address this issue. We demonstrate that ligands that activate TLR7 and TLR9 require the TAK1-IKK beta signaling pathway to induce the production of IFN beta via a pathway that is independent of the degradation of I kappa B alpha. We also show that IKK beta activity, as well as the subsequent IFN beta-stimulated activation of the JAK-STAT1/2 signaling pathway, are essential for the production of IFN alpha by TLR9 ligands. We further show that TLR7 ligands CL097 and R848 fail to produce significant amounts of IFN alpha because the activation of IKK beta is not sustained for a sufficient length of time. The TLR7/9-stimulated production of type 1 IFNs is inhibited by much lower concentrations of IKK beta inhibitors than those needed to suppress the production of NF kappa B-dependent proinflammatory cytokines, such as IL-6, suggesting that drugs that inhibit IKK beta may have a potential for the treatment of forms of lupus that are driven by self-RNA and self-DNA-induced activation of TLR7 and TLR9, respectively. C1 [Pauls, Eduardo; Shpiro, Natalia; Peggie, Mark; Cohen, Philip] Univ Dundee, Sir James Black Ctr, MRC Prot Phosphorylat Unit, Coll Life Sci, Dundee DD1 5EH, Scotland. [Young, Erick R.; Sorcek, Ronald J.] Boehringer Ingelheim Pharmaceut Inc, Dept Med Chem, Ridgefield, CT 06877 USA. [Tan, Li; Choi, Hwan Geun] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Tan, Li; Choi, Hwan Geun] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Cohen, P (reprint author), Univ Dundee, Sir James Black Ctr, MRC Prot Phosphorylat Unit, Coll Life Sci, Dow St, Dundee DD1 5EH, Scotland. EM p.cohen@dundee.ac.uk FU United Kingdom Medical Research Council FX This work was supported by the United Kingdom Medical Research Council. NR 39 TC 21 Z9 21 U1 2 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 1 PY 2012 VL 287 IS 23 BP 19216 EP 19228 DI 10.1074/jbc.M112.345405 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 974EF UT WOS:000306411900032 PM 22511786 ER PT J AU Kearney, DJ Milton, ML Malte, CA McDermott, KA Martinez, M Simpson, TL AF Kearney, David J. Milton, Meredith L. Malte, Carol A. McDermott, Kelly A. Martinez, Michelle Simpson, Tracy L. TI Participation in mindfulness-based stress reduction is not associated with reductions in emotional eating or uncontrolled eating SO NUTRITION RESEARCH LA English DT Article DE Food intake; Posttraumatic stress disorders; Eating behavior; Meditation; Longitudinal studies; Veterans ID DIALECTICAL BEHAVIOR-THERAPY; FOOD-FREQUENCY QUESTIONNAIRE; TERM WEIGHT-LOSS; BODY-MASS INDEX; QUALITY-OF-LIFE; COGNITIVE THERAPY; WOMEN; OBESITY; PROGRAM; DISINHIBITION AB The adverse health effects and increasing prevalence of obesity in the United States make interventions for obesity a priority in health research. Diet-focused interventions generally do not result in lasting reductions in weight. Behavioral interventions that increase awareness of eating cues and satiety have been postulated to result in healthier eating habits. We hypothesized that participation in a program called mindfulness-based stress reduction (MBSR) would positively influence the eating behaviors and nutritional intake of participants through changes in emotional eating (EE), uncontrolled eating (UE), and type and quantity of food consumed. Forty-eight veterans at a large urban Veterans Administration medical center were assessed before MBSR, after MBSR, and 4 months later. For all participants (N = 48), MBSR participation was not associated with significant changes in EE or UE. In addition, there were no significant differences in the intake of energy, fat, sugar, fruit, or vegetables at either follow-up time point as compared with baseline.. Enhanced mindfulness skills and reduced depressive symptoms were seen over time with medium to large effect sizes. Changes in mindfulness skills were significantly and negatively correlated with changes in EE and UE over time. Overall, there was no evidence that participation in MBSR was associated with beneficial changes in eating through reductions in disinhibited eating or significant changes in dietary intake. Randomized studies are needed to further define the relationship between mindfulness program participation and eating behaviors. Published by Elsevier Inc. C1 [Kearney, David J.] Univ Washington, Sch Med, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. [Milton, Meredith L.] Bastyr Univ, Sch Nutr & Exercise Sci, Kenmore, WA USA. [Malte, Carol A.; Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, CESATE, Seattle, WA USA. [Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, MIRECC, Seattle, WA USA. [Simpson, Tracy L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Kearney, DJ (reprint author), Seattle VAMC 111GI, Seattle, WA 98108 USA. EM david.kearney@va.gov NR 52 TC 16 Z9 17 U1 7 U2 69 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD JUN PY 2012 VL 32 IS 6 BP 413 EP 420 DI 10.1016/j.nutres.2012.05.008 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 973XE UT WOS:000306392800004 PM 22749177 ER PT J AU Gradl, G Jupiter, JB AF Gradl, G. Jupiter, J. B. TI Current Concepts Review - Fractures in the Region of the Elbow SO ACTA CHIRURGIAE ORTHOPAEDICAE ET TRAUMATOLOGIAE CECHOSLOVACA LA English DT Review ID DISTAL HUMERAL FRACTURES; RADIAL HEAD FRACTURES; POSTERIOR INTEROSSEOUS NERVE; INTERNAL-FIXATION; OPEN REDUCTION; OLECRANON FRACTURES; HETEROTOPIC OSSIFICATION; PLATE-FIXATION; COMMINUTED FRACTURES; OPERATIVE TREATMENT AB Elbow injuries continue to rise with increased athletic activity and life expectancy. Knowledge of anatomy and biomechanics of this sophisticated joint, various injury patterns, and the implication of injury to the static and dynamic stabilizers will result in improvement in specific diagnosis, and therapy. The surgical treatment of trauma to the adult elbow has evolved rapidly in recent years and many useful concepts and techniques have been established. This paper reviews the published scientific data and current opinion available to guide patient care. C1 [Gradl, G.] Massachussetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Yawkey Ctr, Boston, MA 02114 USA. [Gradl, G.] Univ Aachen, Dept Trauma Surg, Aachen, Germany. RP Gradl, G (reprint author), Massachussetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Yawkey Ctr, 55 Fruit St,Suite 2100, Boston, MA 02114 USA. EM ggradl@ukaachen.de NR 74 TC 3 Z9 3 U1 0 U2 4 PU GALEN SRO PI PRAGUE 5 PA NA BELIDLE 34, PRAGUE 5, 150 00, CZECH REPUBLIC SN 0001-5415 J9 ACTA CHIR ORTHOP TR JI Acta Chir. Orthop. Traumatol. Cechoslov. PD JUN PY 2012 VL 79 IS 3 BP 203 EP 212 PG 10 WC Orthopedics SC Orthopedics GA 972TP UT WOS:000306303700002 PM 22840951 ER PT J AU De Los Angeles, A Loh, YH Tesar, PJ Daley, GQ AF De Los Angeles, Alejandro Loh, Yuin-Han Tesar, Paul J. Daley, George Q. TI Accessing naive human pluripotency SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID EMBRYONIC STEM-CELLS; HUMAN SOMATIC-CELLS; X-CHROMOSOME INACTIVATION; GROUND-STATE PLURIPOTENCY; SELF-RENEWAL; MOUSE EMBRYOS; HOMOLOGOUS RECOMBINATION; RAT BLASTOCYSTS; EPIBLAST; FGF AB Pluripotency manifests during mammalian development through formation of the epiblast, founder tissue of the embryo proper. Rodent pluripotent stem cells can be considered as two distinct states: naive and primed. Naive pluripotent stem cell lines are distinguished from primed cells by self-renewal in response to LIF signaling and MEK/GSK3 inhibition (LIF/2i conditions) and two active X chromosomes in female cells. In rodent cells, the naive pluripotent state may be accessed through at least three routes: explantation of the inner cell mass, somatic cell reprogramming by ectopic Oct4, Sox2, Klf4, and C-myc, and direct reversion of primed post-implantation-associated epiblast stem cells (EpiSCs). In contrast to their rodent counterparts, human embryonic stem cells and induced pluripotent stem cells more closely resemble rodent primed EpiSCs. A critical question is whether naive human pluripotent stem cells with bona fide features of both a pluripotent state and naive-specific features can be obtained. In this review, we outline current understanding of the differences between these pluripotent states in mice, new perspectives on the origins of naive pluripotency in rodents, and recent attempts to apply the rodent paradigm to capture naive pluripotency in human cells. Unraveling how to stably induce naive pluripotency in human cells will influence the full realization of human pluripotent stem cell biology and medicine. C1 [De Los Angeles, Alejandro; Loh, Yuin-Han; Daley, George Q.] Harvard Univ, Sch Med, Stem Cell Transplantat Program, Div Pediat Hematol Oncol,Childrens Hosp Boston, Boston, MA 02115 USA. [De Los Angeles, Alejandro; Loh, Yuin-Han; Daley, George Q.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [De Los Angeles, Alejandro; Loh, Yuin-Han; Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA 02115 USA. [Tesar, Paul J.] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. [Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Harvard Univ, Sch Med, Stem Cell Transplantat Program, Div Pediat Hematol Oncol,Childrens Hosp Boston, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu RI Tesar, Paul/C-9848-2014; Loh, Yuin-Han/E-1096-2014 OI Tesar, Paul/0000-0003-1532-3155; Loh, Yuin-Han/0000-0002-4715-6454 FU Howard Hughes Medical Institute; NIMH NIH HHS [R33 MH087877] NR 52 TC 40 Z9 41 U1 2 U2 19 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD JUN PY 2012 VL 22 IS 3 BP 272 EP 282 DI 10.1016/j.gde.2012.03.001 PG 11 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 970VN UT WOS:000306160500012 PM 22463982 ER PT J AU Yu, ZY Liu, N Liu, JX Yang, K Wang, XY AF Yu, Zhanyang Liu, Ning Liu, Jianxiang Yang, Kevin Wang, Xiaoying TI Neuroglobin, a Novel Target for Endogenous Neuroprotection against Stroke and Neurodegenerative Disorders SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Review DE neuroglobin; neuroprotection; stroke; neurodegenerative diseases; hypoxia/ischemia; high-throughput screening ID NUCLEOTIDE DISSOCIATION INHIBITOR; OUTER MITOCHONDRIAL-MEMBRANE; CYTOCHROME BC(1) COMPLEX; FOCAL CEREBRAL-ISCHEMIA; INDUCED CELL-DEATH; OXIDATIVE STRESS; NITRIC-OXIDE; GLUCOSE DEPRIVATION; DRUG DISCOVERY; ESTRADIOL PROTECTS AB Brain neurons and tissues respond to sublethal injury by activating endogenous protective pathways. Recently, following the failure of a large number of clinical trials for protective strategies against stroke that aim to inhibit a specific ischemia response pathway, endogenous neuroprotection has emerged as a more promising and hopeful strategy for development of therapeutics against stroke and neurodegenerative disorders. Neuroglobin (Ngb) is an oxygen-binding globin protein that is highly and specifically expressed in brain neurons. Accumulating evidence have clearly demonstrated that Ngb is an endogenous neuroprotective molecule against hypoxic/ischemic and oxidative stress-related insults in cultured neurons and animals, as well as neurodegenerative disorders such as Alzheimer's disease, thus any pharmacological strategy that can up-regulate endogenous Ngb expression may lead to novel therapeutics against these brain disorders. In this review, we summarize recent studies about the biological function, regulation of gene expression, and neuroprotective mechanisms of Ngb. Furthermore, strategies for identification of chemical compounds that can up-regulate endogenous Ngb expression for neuroprotection against stroke and neurodegenerative disorders are discussed. C1 [Yu, Zhanyang; Liu, Ning; Yang, Kevin; Wang, Xiaoying] Harvard Univ, Sch Med, Neuroprotect Res Lab, Dept Neurol & Radiol,Massachusetts Gen Hosp,Neuro, Charlestown Boston, MA 02129 USA. [Liu, Jianxiang] China Ctr Dis Control & Prevent, Natl Inst Radiol Protect, Beijing 100088, Peoples R China. RP Yu, ZY (reprint author), Harvard Univ, Sch Med, Neuroprotect Res Lab, Dept Neurol & Radiol,Massachusetts Gen Hosp,Neuro, Room 2401-2411A,149 13th St, Charlestown Boston, MA 02129 USA. EM zyu@partners.org; liuning0731@yahoo.cn; jxlamy@gmail.com; kevin.yang95@gmail.com; wangxi@helix.mgh.harvard.edu FU NIH [R01-NS049476, RO1-NS065998]; American Heart Association [12POST9720007] FX This work was supported in part by NIH grants R01-NS049476 and RO1-NS065998 (to X. W.), and Postdoctoral Fellowship (12POST9720007) from the American Heart Association (to Z.Y.). We appreciate Eng H. Lo for his very helpful discussion. The authors declare no conflicts of interest. NR 114 TC 23 Z9 28 U1 1 U2 25 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD JUN PY 2012 VL 13 IS 6 BP 6995 EP 7014 DI 10.3390/ijms13066995 PG 20 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA 971FH UT WOS:000306188700029 PM 22837676 ER PT J AU Nakao, S Zandi, S Lara-Castillo, N Taher, M Ishibashi, T Hafezi-Moghadam, A AF Nakao, Shintaro Zandi, Souska Lara-Castillo, Nuria Taher, Mahdi Ishibashi, Tatsuro Hafezi-Moghadam, Ali TI Larger Therapeutic Window for Steroid versus VEGF-A Inhibitor in Inflammatory Angiogenesis: Surprisingly Similar Impact on Leukocyte Infiltration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID NF-KAPPA-B; LYMPHANGIOGENESIS; BEVACIZUMAB; CELLS; NEOVASCULARIZATION; MACROPHAGES; MOLECULES; MECHANISM; GROWTH; CANCER AB PURPOSE. The current treatments against inflammatory angiogenesis are steroids and anti-VEGF-A, such as dexamethasone and bevacizumab, respectively. However, the therapeutic windows for dexamethasone and bevacizumab against inflammatory angiogenesis are unknown. METHODS. To investigate the therapeutic windows for dexamethasone and bevacizumab, we used the corneal pocket assay. IL-1 beta pellets were implanted in corneas of BALB/c mice that were then treated with dexamethasone or bevacizumab at different time points. Angiogenesis (area, number of vessels, and sprouting) was quantitated at various time points after implantation. Nuclear Factor-kappa B (NF-kappa B) signaling and leukocyte accumulation in inflammatory angiogenesis were examined by Western blotting, by immunohistochemistry, and in the authors' novel leukocyte transmigration assay. RESULTS. Dexamethasone inhibited IL-1 beta-induced angiogenesis when treatment started 4 days after IL-1 beta implantation, while bevacizumab only inhibited angiogenesis by day 2 after implantation. Both bevacizumab and dexamethasone inhibited angiogenic sprouting. Interestingly, bevacizumab did not affect NF-kappa B activation, which is one of the main signaling targets for steroid action. The authors' new imaging approach revealed that bevacizumab and steroid treatment blocked leukocyte infiltration into implanted corneas. CONCLUSIONS. VEGF-A inhibition affected angiogenic sprouting, while it was not effective against matured vessels. Both dexamethasone and bevacizumab inhibited leukocyte transmigration from angiogenic vessels; however, dexamethasone had a larger therapeutic window. These insights improve the treatment strategy in angiogenic disorders. (Invest Ophthalmol Vis Sci. 2012;53:3296-3302) DOI:10.1167/iovs.11-8114 C1 [Nakao, Shintaro; Zandi, Souska; Lara-Castillo, Nuria; Taher, Mahdi; Hafezi-Moghadam, Ali] Brigham & Womens Hosp, Ctr Excellence Funct & Mol Imaging, Boston, MA 02115 USA. [Nakao, Shintaro; Zandi, Souska; Lara-Castillo, Nuria; Taher, Mahdi; Hafezi-Moghadam, Ali] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Nakao, Shintaro; Zandi, Souska; Lara-Castillo, Nuria; Taher, Mahdi; Hafezi-Moghadam, Ali] Harvard Univ, Sch Med, Dept Ophthalmol, Angiogenesis Lab,Massachusetts Eye & Ear Infirm, Boston, MA USA. [Nakao, Shintaro; Ishibashi, Tatsuro] Kyushu Univ, Dept Ophthalmol, Grad Sch Med Sci, Fukuoka 812, Japan. RP Hafezi-Moghadam, A (reprint author), Brigham Womens Hosp, 221 Longwood Ave, Boston, MA 02115 USA. EM ahm@bwh.harvard.edu OI Hafezi-Moghadam, Ali/0000-0002-5336-0697 FU National Institutes of Health [AI050775]; Bausch Lomb; Japan Eye Bank Association; Tear Film and Ocular Surface Society FX Supported by National Institutes of Health Grant AI050775 (AHM), an overseas Research Fellowship Award from Bausch & Lomb, a Fellowship Award from the Japan Eye Bank Association, and a Tear Film and Ocular Surface Society Young Investigator Fellowship (to SN under the mentorship of AH-M). NR 26 TC 18 Z9 19 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2012 VL 53 IS 7 BP 3296 EP 3302 DI 10.1167/iovs.11-8114 PG 7 WC Ophthalmology SC Ophthalmology GA 971CM UT WOS:000306181200005 PM 22427602 ER PT J AU Sadrai, Z Stevenson, W Okanobo, A Chen, YH Dohlamn, TH Hua, J Amparo, F Chauhan, SK Dana, R AF Sadrai, Zahra Stevenson, William Okanobo, Andre Chen, Yihe Dohlamn, Thomas H. Hua, Jing Amparo, Francisco Chauhan, Sunil K. Dana, Reza TI PDE4 Inhibition Suppresses IL-17-Associated Immunity in Dry Eye Disease SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID DESICCATING STRESS; PHOSPHODIESTERASE-4 INHIBITORS; RHEUMATOID-ARTHRITIS; SJOGRENS-SYNDROME; EPITHELIAL-CELLS; TH17 CELLS; TEAR FLUID; TNF-ALPHA; CYCLOSPORINE; KERATOCONJUNCTIVITIS AB PURPOSE. To determine the effect of phosphodiesterase type-4 (PDE4) inhibition on IL-17-associated immunity in experimental dry eye disease (DED). METHODS. Murine DED was induced, after which a PDE4 inhibitor (cilomilast), dexamethasone, cyclosporine, or a relevant vehicle was administered topically. Real-time PCR, immunohistochemical staining, and flow cytometry were employed to evaluate the immuno-inflammatory parameters of DED with a focus on IL-17-associated immunity. Corneal fluorescein staining (CFS) was performed to evaluate clinical disease progression. RESULTS. DED induction increased proinflammatory cytokine expression, pathogenic immune cell infiltration, and CFS scores. Cilomilast significantly decreased the expression of TNF-alpha in the cornea (P <= 0.05) and IL-1 alpha, IL-1 beta, and TNF-alpha in the conjunctiva (P <= 0.05) as compared with vehicle control. Cilomilast treatment markedly decreased the presence of CD11b(+) antigen-presenting cells in the central and peripheral cornea (P <= 0.05), and led to decreased conjunctival expression of cytokines IL-6, IL-23, and IL-17 (P <= 0.05). Moreover, cilomilast decreased the expression of IL-17 and IL-23 in the draining lymph nodes (P <= 0.05). Topical cilomilast was significantly more effective than vehicle at reducing CFS scores (P <= 0.05). The therapeutic efficacy of cilomilast was comparable or superior to that of dexamethasone and cyclosporine in all tested measures. CONCLUSIONS. Topical cilomilast suppresses the generation of IL-17-associated immunity in experimental DED. (Invest Ophthalmol Vis Sci. 2012;53:3584-3591) DOI:10.1167/iovs.11-9110 C1 [Dana, Reza] Harvard Univ, Schepens Eye Res Inst, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Dana, R (reprint author), Harvard Univ, Schepens Eye Res Inst, Sch Med, 20 Staniford St, Boston, MA 02114 USA. EM reza.dana@schepens.harvard.edu FU Alcon Inc.; National Eye Institute [R01 EY-20889] FX Supported in part by Alcon Inc. and National Eye Institute Grant R01 EY-20889. NR 36 TC 9 Z9 9 U1 1 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2012 VL 53 IS 7 BP 3584 EP 3591 DI 10.1167/iovs.11-9110 PG 8 WC Ophthalmology SC Ophthalmology GA 971CM UT WOS:000306181200038 PM 22577075 ER PT J AU Lan, YN Kodati, S Lee, HS Omoto, M Jin, YP Chauhan, SK AF Lan, Yinan Kodati, Shilpa Lee, Hyun Soo Omoto, Masahiro Jin, Yiping Chauhan, Sunil K. TI Kinetics and Function of Mesenchymal Stem Cells in Corneal Injury SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID BONE-MARROW; INFLAMMATORY DAMAGE; IN-VIVO; TRANSPLANTATION; RECONSTRUCTION; MOBILIZATION; ENGRAFTMENT; MIGRATION; DISEASE; HEALTH AB PURPOSE. Bone marrow-derived mesenchymal stem cells (MSCs) hold great promise for wound healing and tissue regeneration. In the present study, we investigated the impact of corneal injury on the homeostasis of endogenous MSCs, and the potential of MSCs to home to injured tissue and promote corneal repair. METHODS. Corneal injury in mice was induced by thermal cauterization. Circulating MSCs were quantified by flow cytometric analysis. Ex vivo expanded red Q-dot-labeled or GFP + bone marrow-derived MSCs were intravenously injected after injury and detected using epifluorescence microscopy. Corneal fluorescein staining was performed to evaluate epithelial regeneration. RESULTS. Following the induction of corneal injury in mice, a 2-fold increase in the frequency of circulating endogenous MSCs was observed within 48 hours of injury, which was accompanied by increased levels of the stem cell chemoattractants, substance P and SDF-1, in both the injured cornea and blood. Systemically administered MSCs homed to the injured cornea, but not to the normal cornea, and showed long-term survival. In addition, in the setting of corneal injury, MSC administration showed significant and rapid corneal epithelial regeneration. CONCLUSIONS. These findings provide novel evidence that corneal injury causes significant mobilization of endogenous MSCs into blood, and that MSCs home specifically to the injured cornea and promote regeneration, highlighting the therapeutic implications of MSC-mediated tissue repair in corneal injury. (Invest Ophthalmol Vis Sci. 2012;53:3638-3644) DOI:10.1167/iovs.11-9311 C1 [Chauhan, Sunil K.] Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Chauhan, SK (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM sunil.chauhan@schepens.harvard.edu FU Department of Defense; Harvard Medical School, Boston, Massachusetts FX Supported in part by grants from the Department of Defense and the Eleanor and Miles Shore Fellowship for Scholars in Medicine, Harvard Medical School, Boston, Massachusetts. NR 28 TC 20 Z9 21 U1 1 U2 5 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2012 VL 53 IS 7 BP 3638 EP 3644 DI 10.1167/iovs.11-9311 PG 7 WC Ophthalmology SC Ophthalmology GA 971CM UT WOS:000306181200044 PM 22562508 ER PT J AU Wang, RL Jiang, CH Ma, J Young, MJ AF Wang, Ruilin Jiang, Caihui Ma, Jie Young, Michael J. TI Monitoring Morphological Changes in the Retina of Rhodopsin(-/-) Mice with Spectral Domain Optical Coherence Tomography SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID KNOCKOUT MOUSE; DEGENERATION; CELLS; TRANSPLANTATION; REPAIR; MODEL AB PURPOSE. The rhodopsin(-/-) C57Bl/6 (rho(-/-)) mouse is a very important model for understanding retinal degenerative diseases. In this study, spectral domain optical coherence tomography (SD-OCT) was used to monitor the dynamic morphological changes in retina of rho(-/-) mice. METHODS. Rho(-/-) mice and wild type C57Bl/6 (B6) mice at the age of 3, 6, 9, and 12 weeks were investigated using SD-OCT to obtain cross-sectional images of the retina. The outer nuclear layer (ONL) thickness was measured. Histological sections were used to compare to the OCT data. Electroretinograms (ERG) were performed to evaluate the physiological change for establishing the relationship between retinal morphology and its functional changes. RESULTS. There was no apparent morphological or functional change in B6 mice at any time point. The SD-OCT measurement showed that the ONL thickness in rho(-/-) mice was significantly decreased from 40.6 mu m to 6.0 mu m from week 3 to week 12 postnatal. Histological examinations identified a similar trend, although the average thickness of ONL from histological sections at these time points was slightly larger (ranging from 55.4 mu m to 14.9 mu m). The ERG in rho(-/-) mice indicated functional changes that were in concordant with morphological changes; a significant linear positive association was identified between the amplitude of b-wave and the ONL thickness. CONCLUSIONS. Our findings confirmed that the functional changes in retina were concordant with morphological changes measured by SD-OCT in vivo, which indicates that SD-OCT can be used as a reliable noninvasive method to monitor the degenerative progression in retinal disease models. Invest Ophthalmol Vis Sci. 2012;53:3967-3972) DOI:10.1167/iovs.12-9716 C1 [Wang, Ruilin; Jiang, Caihui; Ma, Jie; Young, Michael J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA 02114 USA. [Wang, Ruilin] Huazhong Univ Sci & Technol, Tongji Med Sch, Tongji Hosp, Dept Ophthalmol, Wuhan 430074, Peoples R China. RP Young, MJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, 20 Staniford St, Boston, MA 02114 USA. EM michael.young@schepens.harvard.edu FU Reneuron Group plc; Charles de Gunzburg Foundation; Grousbeck Foundation FX Supported by grants from Reneuron Group plc, Charles de Gunzburg Foundation, and Grousbeck Foundation. NR 29 TC 10 Z9 10 U1 0 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2012 VL 53 IS 7 BP 3967 EP 3972 DI 10.1167/iovs.12-9716 PG 6 WC Ophthalmology SC Ophthalmology GA 971CM UT WOS:000306181200083 PM 22618589 ER PT J AU Suzuki, J Yoshimura, T Simeonova, M Takeuchi, K Murakami, Y Morizane, Y Miller, JW Sobrin, L Vavvas, DG AF Suzuki, Jun Yoshimura, Takeru Simeonova, Marina Takeuchi, Kimio Murakami, Yusuke Morizane, Yuki Miller, Joan W. Sobrin, Lucia Vavvas, Demetrios G. TI Aminoimidazole Carboxamide Ribonucleotide Ameliorates Experimental Autoimmune Uveitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ACTIVATED PROTEIN-KINASE; REGULATORY T-CELLS; ENDOTOXIN-INDUCED UVEITIS; 5-AMINOIMIDAZOLE-4-CARBOXAMIDE RIBOSIDE; LYMPHOCYTE-RESPONSES; SKELETAL-MUSCLE; VISUAL-LOSS; UVEORETINITIS; MICE; ENCEPHALOMYELITIS AB PURPOSE. To investigate the anti-inflammatory effect of an adenosine monophosphate (AMP) analog, aminoimidazole carboxamide ribonucleotide (AICAR), in experimental autoimmune uveoretinitis (EAU). METHODS. C57BL6 mice were injected daily with AICAR (200 mg/kg, intraperitoneally [IP]) from day 0, the day of interphotoreceptor retinoid-binding protein (IRBP) immunization, until day 21. The severity of uveitis was assessed clinically and histopathologically. T-cell proliferation and cytokine production of IFN-gamma, IL-17, and IL-10 in response to IRBP stimulation were determined. In addition, regulatory T-cell (Treg) populations were measured. Co-stimulatory molecule expression (CD40, 80, 86, and I-A(b)) on dendritic cells (DCs) in EAU and on bone marrow-derived dendritic cells (BMDCs) treated with AICAR was measured. RESULTS. AICAR treatment significantly reduced clinical and histologic severity of EAU as well as ocular cytokine production. An anti-inflammatory effect associated with the inhibition of T-cell proliferation and Th1 and Th17 cytokine production was observed. Increases in the Th2 response and Treg population were not observed with AICAR treatment. AICAR did significantly inhibit BMDC maturation by reducing co-stimulatory molecule expression. CONCLUSIONS. AICAR attenuates EAU by preventing generation of Ag-specific Th1 and Th17 cells. Impaired DC maturation may be an underlying mechanism for this anti-inflammatory effect observed with AICAR. (Invest Ophthalmol Vis Sci. 2012;53:4158-4169) DOI:10.1167/iovs.11-9323 C1 [Suzuki, Jun; Simeonova, Marina; Takeuchi, Kimio; Murakami, Yusuke; Morizane, Yuki; Miller, Joan W.; Sobrin, Lucia; Vavvas, Demetrios G.] Harvard Univ, Massachusetts Eye & Ear Infirm, Retina Serv, Angiogenesis Lab,Dept Ophthalmol,Med Sch, Boston, MA 02114 USA. [Yoshimura, Takeru] Childrens Hosp Boston, Dept Surg, Boston, MA USA. [Yoshimura, Takeru] Childrens Hosp Boston, Vasc Biol Program, Boston, MA USA. RP Vavvas, DG (reprint author), 243 Charles St, Boston, MA 02114 USA. EM vavvas@meei.harvard.edu OI Vavvas, Demetrios/0000-0002-8622-6478 FU National Eye Institute [EY014104] FX Supported in part by National Eye Institute Grant EY014104 (Massachusetts Eye and Ear Infirmary core grant). Submitted for publication December 14, 2011; revised March 23 and April 17, 2012; accepted April 19, 2012. NR 48 TC 11 Z9 12 U1 0 U2 5 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2012 VL 53 IS 7 BP 4158 EP 4169 DI 10.1167/iovs.11-9323 PG 12 WC Ophthalmology SC Ophthalmology GA 971CM UT WOS:000306181200105 PM 22562518 ER PT J AU Zhang, Y Nateras, OS Peng, Q Rosende, CA Duong, TQ AF Zhang, Yi Nateras, Oscar San Emeterio Peng, Qi Rosende, Carlos A. Duong, Timothy Q. TI Blood Flow MRI of the Human Retina/Choroid during Rest and Isometric Exercise SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID INTRAOCULAR-PRESSURE; OCULAR HEMODYNAMICS; PERFUSION; AUTOREGULATION; INVERSION; RELAXATION; EFFICIENCY; RETINA; RABBIT; WATER AB PURPOSE. To investigate blood flow (BF) in the human retina/choroid during rest and handgrip isometric exercise using magnetic resonance imaging (MRI). METHODS. Four healthy volunteers (25-36 years old) in multiple sessions (1-3) on different days. MRI studies were performed on a 3-Tesla scanner using a custom-made surface coil (7 x 5cm in diameter) at the spatial resolution of 0.5 x 0.8 x 6.0 mm. BF was measured using the pseudo-continuous arterial-spin-labeling technique with background suppression and turbo-spin-echo acquisition. During MRI, subjects rested for 1 minute followed by 1 minute of handgrip, repeating three times, while maintaining stable eye fixation on a target with cued eye blinks at the end of each data acquisition (every 4.6 seconds). RESULTS. Robust BF of the unanesthetized human retina/choroid was detected. Basal BF in the posterior retina/choroid was 149 +/- 48 mL/100 mL/min with a mean heart rate of 60 +/- 5 beats per minute, mean arterial pressure of 78 +/- 5 mm Hg, ocular perfusion pressure of 67 +/- 4 mm Hg at rest (mean +/- SD, n = 4 subjects). Handgrip significantly increased retina/choroid BF by 25% +/- 7%, heart rate by 19% +/- 8%, mean arterial pressure by 22% +/- 5% (measured at the middle of the handgrip task), and ocular perfusion pressure by 25% +/- 6% (averaged across the entire handgrip task) (P < 0.01), but did not change intraocular pressure, arterial oxygen saturation, end-tidal CO2, and respiration rate (P > 0.05). CONCLUSIONS. This study demonstrates a novel MRI application to image quantitative BF of the human retina/choroid during rest and isometric exercise. Retina/choroid BF increases during brief handgrip exercise, paralleling increases in mean arterial pressure. Handgrip exercise changes ocular perfusion pressure free of potential drug side effect and can be done in the MRI scanner. MRI offers quantitative BF with large field of view without depth limitation, potentially providing insights into retinal pathophysiology. (Invest Ophthalmol Vis Sci. 2012;53:4299-4305) DOI:10.1167/iovs.11-9384 C1 [Zhang, Yi; Nateras, Oscar San Emeterio; Peng, Qi; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Rosende, Carlos A.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Zhang, Yi; Peng, Qi; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008 FU Pilot grant via the Clinical Translational Science Award (CTSA) [UL1RR025767]; Translational Technology Resource grant via the Clinical Translational Science Award (CTSA) [UL1RR025767]; NIH/NEI [R01 EY014211, EY018855]; Department of Veterans Affairs FX Supported by a Pilot grant (TQD) and a Translational Technology Resource grant (QP) via the Clinical Translational Science Award (CTSA, Parent Grant UL1RR025767), NIH/NEI Grants R01 EY014211 and EY018855 (TQD), and a MERIT award from the Department of Veterans Affairs (TQD). NR 39 TC 15 Z9 15 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2012 VL 53 IS 7 BP 4299 EP 4305 DI 10.1167/iovs.11-9384 PG 7 WC Ophthalmology SC Ophthalmology GA 971CM UT WOS:000306181200121 PM 22661466 ER PT J AU Watts, NB Adler, RA Bilezikian, JP Drake, MT Eastell, R Orwoll, ES Finkelstein, JS AF Watts, Nelson B. Adler, Robert A. Bilezikian, John P. Drake, Matthew T. Eastell, Richard Orwoll, Eric S. Finkelstein, Joel S. TI Osteoporosis in Men: An Endocrine Society Clinical Practice Guideline SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BONE-MINERAL DENSITY; ANDROGEN-DEPRIVATION THERAPY; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; VERTEBRAL FRACTURE RISK; VITAMIN-D DEFICIENCY; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; ABSORPTIOMETRY TECHNICAL ISSUES; SERUM 25-HYDROXYVITAMIN D; ISCD OFFICIAL POSITIONS AB Objective: The aim was to formulate practice guidelines for management of osteoporosis in men. Evidence: We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and evidence quality. Consensus Process: Consensus was guided by systematic evidence reviews, one in-person meeting, and multiple conference calls and e-mails. Task Force drafts were reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee and Clinical Affairs Core Committee; representatives of ASBMR, ECTS, ESE, ISCD; and members at large. At each stage, the Task Force received written comments and incorporated needed changes. The reviewed document was approved by The Endocrine Society Council before submission for peer review. Conclusions: Osteoporosis in men causes significant morbidity and mortality. We recommend testing higher risk men [ aged >= 70 and men aged 50-69 who have risk factors ( e. g. low body weight, prior fracture as an adult, smoking, etc.)] using central dual-energy x-ray absorptiometry. Laboratory testing should be done to detect contributing causes. Adequate calcium and vitamin D and weight-bearing exercise should be encouraged; smoking and excessive alcohol should be avoided. Pharmacological treatment is recommended for men aged 50 or older who have had spine or hip fractures, those with T-scores of -2.5 or below, and men at high risk of fracture based on low bone mineral density and/or clinical risk factors. Treatment should be monitored with serial dual-energy x-ray absorptiometry testing. (J Clin Endocrinol Metab 97: 1802-1822, 2012) C1 [Watts, Nelson B.] Mercy Hlth Osteoporosis & Bone Hlth Serv, Cincinnati, OH 45236 USA. [Adler, Robert A.] McGuire Vet Affairs Med Ctr, Richmond, VA 23298 USA. [Adler, Robert A.] Virginia Commonwealth Univ, Sch Med, Richmond, VA 23298 USA. [Bilezikian, John P.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Drake, Matthew T.] Mayo Clin, Coll Med, Rochester, MN 55905 USA. [Eastell, Richard] Univ Sheffield, Sch Med, Sheffield S10 2RX, S Yorkshire, England. [Orwoll, Eric S.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Finkelstein, Joel S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Watts, NB (reprint author), Endocrine Soc, 8401 Connecticut Ave,Suite 900, Chevy Chase, MD 20815 USA. EM govt-prof@endo-society.org OI Orwoll, Eric/0000-0002-8520-7355 NR 202 TC 135 Z9 142 U1 1 U2 27 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2012 VL 97 IS 6 BP 1802 EP 1822 DI 10.1210/jc.2011-3045 PG 21 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 970AP UT WOS:000306100800029 PM 22675062 ER PT J AU Fleseriu, M Biller, BMK Findling, JW Molitch, ME Schteingart, DE Gross, C AF Fleseriu, Maria Biller, Beverly M. K. Findling, James W. Molitch, Mark E. Schteingart, David E. Gross, Coleman CA SEISMIC Study Investigators TI Mifepristone, a Glucocorticoid Receptor Antagonist, Produces Clinical and Metabolic Benefits in Patients with Cushing's Syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MEDICAL-TREATMENT; RU-486; MANAGEMENT; DISEASE; SECRETION; PSYCHOSIS; DIAGNOSIS; THERAPY; BINDING; SAFETY AB Context: Cushing's syndrome (CS) is a disorder associated with significant morbidity and mortality due to prolonged exposure to high cortisol concentrations. Objective: Our objective was to evaluate the safety and efficacy of mifepristone, a glucocorticoid receptor antagonist, in endogenous CS. Design and Setting: We conducted a 24-wk multicenter, open-label trial after failed multimodality therapy at 14 U. S. academic medical centers and three private research centers. Participants: Participants included 50 adults with endogenous CS associated with type 2 diabetes mellitus/impaired glucose tolerance (C-DM) or a diagnosis of hypertension alone (C-HT). Intervention: Mifepristone was administered at doses of 300-1200 mg daily. Main Outcome Measures: We evaluated change in area under the curve for glucose on 2-h oral glucose test for C-DM and change in diastolic blood pressure from baseline to wk 24 for C-HT. Results: In the C-DM cohort, an area under the curve for glucose(AUC(glucose)) response was seen in 60% of patients (P < 0.0001). Mean +/- SD glycated hemoglobin (HbA1c) decreased from 7.43 +/- 1.52% to 6.29 +/- 0.99% (P < 0.001); fasting plasma glucose decreased from 149.0 +/- 75.7 mg/dl (8.3 +/- 4.1 mmol/liter) to 104.7 +/- 37.5 mg/dl (5.8 +/- 2.1 mmol/liter, P < 0.03). In C-HT cohort, a diastolic blood pressure response was seen in 38% of patients (P < 0.05). Mean weight change was -5.7 +/- 7.4% (P < 0.001) with waist circumference decrease of -6.78 +/- 5.8 cm (P < 0.001) in women and -8.44 +/- 5.9 cm (P < 0.001) in men. Overall, 87% (P < 0.0001) had significant improvement in clinical status. Insulin resistance, depression, cognition, andquality of life also improved. Common adverse events were fatigue, nausea, headache, low potassium, arthralgia, vomiting, edema, and endometrial thickening in women. Conclusions: Mifepristone produced significant clinical and metabolic improvement in patients with CS with an acceptable risk-benefit profile during 6 months of treatment. (J Clin Endocrinol Metab 97: 2039-2049, 2012) C1 [Fleseriu, Maria] Oregon Hlth & Sci Univ, NW Pituitary Ctr, Dept Med, Portland, OR 97239 USA. [Biller, Beverly M. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Findling, James W.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Molitch, Mark E.] Northwestern Univ, Feinberg Med Sch, Chicago, IL 60611 USA. [Schteingart, David E.] Univ Michigan, Ann Arbor, MI 48109 USA. [Gross, Coleman] Corcept Therapeut, Menlo Pk, CA 94025 USA. RP Fleseriu, M (reprint author), Oregon Hlth & Sci Univ, NW Pituitary Ctr, Dept Med, 3181 SW Sam Jackson Pk Rd BTE 472, Portland, OR 97239 USA. EM fleseriu@ohsu.edu FU Corcept Therapeutics; Corcept Therapeutics, Inc.; Novartis FX This study was supported by Corcept Therapeutics.; Disclosure Summary: B.M.K.B., J.W.F., and M.E.M. are consultants to Corcept Therapeutics, Inc. B.M.K.B., J.W.F., M.E.M., M.F., and D.E.S. served as investigators on research grants to their institutions from Corcept Therapeutics, Inc. C.G. is an employee of Corcept Therapeutics, Inc. B.M.K.B., J.W.F., and M. . are consultants to and serve as investigators on research grants to their institutions from Novartis. NR 42 TC 128 Z9 133 U1 1 U2 12 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2012 VL 97 IS 6 BP 2039 EP 2049 DI 10.1210/jc.2011-3350 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 970AP UT WOS:000306100800057 PM 22466348 ER PT J AU Shores, MM Smith, NL Forsberg, CW Anawalt, BD Matsumoto, AM AF Shores, Molly M. Smith, Nicholas L. Forsberg, Christopher W. Anawalt, Bradley D. Matsumoto, Alvin M. TI Testosterone Treatment and Mortality in Men with Low Testosterone Levels SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LOW SERUM TESTOSTERONE; ANDROGEN DEFICIENCY SYNDROMES; CLINICAL-PRACTICE GUIDELINE; QUALITY-OF-LIFE; ELDERLY-MEN; VETERANS-AFFAIRS; HEART-FAILURE; DOUBLE-BLIND; OLDER MEN; RISK AB Context: Low testosterone levels in men have been associated with increased mortality. However, the influence of testosterone treatment on mortality in men with low testosterone levels is not known. Objective: The objective of the study was to examine the association between testosterone treatment and mortality in men with low testosterone levels. Design: This was an observational study of mortality in testosterone-treated compared with untreated men, assessed with time-varying, adjusted Cox proportional hazards regression models. Effect modification by age, diabetes, and coronary heart disease was tested a priori. Setting: The study was conducted with a clinical database that included seven Northwest Veterans Affairs medical centers. Patients: Patients included a cohort of 1031 male veterans, aged older than 40 yr, with low total testosterone [<= 250 ng/dl (8.7 nmol/liter)] and no history of prostate cancer, assessed between January 2001 and December 2002 and followed up through the end of 2005. Main Outcome Measure: Total mortality in testosterone-treated compared with untreated men was measured. Results: Testosterone treatment was initiated in 398 men (39%) during routine clinical care. The mortality in testosterone-treated men was 10.3% compared with 20.7% in untreated men (P<0.0001) with a mortality rate of 3.4 deaths per 100 person-years for testosterone-treated men and 5.7 deaths per 100 person-years in men not treated with testosterone. After multivariable adjustment including age, body mass index, testosterone level, medical morbidity, diabetes, and coronary heart disease, testosterone treatment was associated with decreased risk of death (hazard ratio 0.61; 95% confidence interval 0.42-0.88; P = 0.008). No significant effect modification was found by age, diabetes, or coronary heart disease. Conclusions: In an observational cohort of men with low testosterone levels, testosterone treatment was associated with decreased mortality compared with no testosterone treatment. These results should be interpreted cautiously because residual confounding may still be a source of bias. Large, randomized clinical trials are needed to better characterize the health effects of testosterone treatment in older men with low testosterone levels. (J Clin Endocrinol Metab 97: 2050-2058, 2012) C1 [Shores, Molly M.; Smith, Nicholas L.; Forsberg, Christopher W.; Matsumoto, Alvin M.] Vet Affairs VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Smith, Nicholas L.; Forsberg, Christopher W.] VA Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. [Matsumoto, Alvin M.] VA Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Shores, Molly M.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98105 USA. [Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98105 USA. [Anawalt, Bradley D.; Matsumoto, Alvin M.] Univ Washington, Dept Med, Seattle, WA 98105 USA. [Smith, Nicholas L.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA. RP Shores, MM (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-116PES, Seattle, WA 98108 USA. EM molly.shores@va.gov FU Abbott; GSK; BHR Pharmaceuticals; Department of Veterans Affairs, Office of Research and Development; Veterans Affairs Puget Sound Health Care System; Royalty Research Fund of the University of Washington FX This manuscript is based on work supported in part by the Department of Veterans Affairs, Office of Research and Development, and the Veterans Affairs Puget Sound Health Care System, and the Royalty Research Fund of the University of Washington. Analytic support was provided by the Cooperative Studies Seattle Epidemiologic Research and Information Center of the Veterans Affairs Office of Research and Development, Seattle, Washington. The content of this article does not necessarily represent the views of the Department of Veterans Affairs or the U. S. Government. We thank Daniel Kivlahan, Ph.D., who provided excellent consultation for the grant proposal for this study, and Margaret Moroz for technical support. M.M.S. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.; Disclosure Summary: A.M.M. received research support from Abbott, GSK, and BHR Pharmaceuticals and served on advisory boards for Abbott, Endo Pharmaceuticals, Ligand Pharmaceuticals, and Trimmel. All other authors have no disclosures to make. NR 35 TC 173 Z9 177 U1 0 U2 10 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2012 VL 97 IS 6 BP 2050 EP 2058 DI 10.1210/jc.2011-2591 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 970AP UT WOS:000306100800058 PM 22496507 ER PT J AU Hatoum, IJ Stylopoulos, N Vanhoose, AM Boyd, KL Yin, DP Ellacott, KLJ Ma, LL Blaszczyk, K Keogh, JM Cone, RD Farooqi, IS Kaplan, LM AF Hatoum, Ida J. Stylopoulos, Nicholas Vanhoose, Amanda M. Boyd, Kelli L. Yin, Deng Ping Ellacott, Kate L. J. Ma, Lian Li Blaszczyk, Kasia Keogh, Julia M. Cone, Roger D. Farooqi, I. Sadaf Kaplan, Lee M. TI Melanocortin-4 Receptor Signaling Is Required for Weight Loss after Gastric Bypass Surgery SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LIFE-STYLE INTERVENTION; CENTRAL-NERVOUS-SYSTEM; BARIATRIC SURGERY; MORBID-OBESITY; RISK-FACTORS; BODY-WEIGHT; DEFICIENCY; RATS; MICE; HYPOTHALAMUS AB Context: Roux-en-Y gastric bypass (RYGB) is one of the most effective long-term therapies for the treatment of severe obesity. Recent evidence indicates that RYGB effects weight loss through multiple physiological mechanisms, including changes in energy expenditure, food intake, food preference, and reward pathways. Objective: Because central melanocortin signaling plays an important role in the regulation of energy homeostasis, we investigated whether genetic disruption of the melanocortin-4 receptor (MC4R) in rodents and humans affects weight loss after RYGB. Methods and Results: Here we report that MC4R(-/-) mice lost substantially less weight after surgery than wild-type animals, indicating that MC4R signaling is necessary for the weight loss effects of RYGB in this model. Mice heterozygous for MC4R remain fully responsive to gastric bypass. To determine whether mutations affect surgically induced weight loss in humans, we sequenced the MC4R gene in 972 patients undergoing RYGB. Patients heterozygous for MC4R mutations exhibited the same magnitude and distribution of postoperative weight loss as patients without such mutations, suggesting that although two normal copies of the MC4R gene are necessary for normal weight regulation, a single normal copy of the MC4R gene is sufficient to mediate the weight loss effects of RYGB. Conclusions: MC4R is the first gene identified that is required for the sustained effects of bariatric surgery. The need for MC4R signaling for the weight loss effects of RYGB in mice underscores the physiological mechanisms of action of this procedure and demonstrates that RYGB both influences and is dependent on the normal pathways that regulate energy balance. (J Clin Endocrinol Metab 97: E1023-E1031, 2012) C1 [Hatoum, Ida J.; Stylopoulos, Nicholas; Kaplan, Lee M.] Massachusetts Gen Hosp, Obes Metab & Nutr Inst, Boston, MA 02129 USA. [Hatoum, Ida J.; Stylopoulos, Nicholas; Kaplan, Lee M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02129 USA. [Hatoum, Ida J.; Stylopoulos, Nicholas; Kaplan, Lee M.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Vanhoose, Amanda M.; Ellacott, Kate L. J.; Cone, Roger D.] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Blaszczyk, Kasia] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA. [Yin, Deng Ping] Vanderbilt Univ, Sch Med, Dept Surg, Nashville, TN 37232 USA. [Yin, Deng Ping; Ellacott, Kate L. J.; Ma, Lian Li] Vanderbilt Univ, Sch Med, Vanderbilt Mouse Metab Phenotyping Ctr, Nashville, TN 37232 USA. [Boyd, Kelli L.; Keogh, Julia M.; Farooqi, I. Sadaf] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Res Labs, Cambridge DB2 2QQ, England. RP Kaplan, LM (reprint author), Massachusetts Gen Hosp, 149 13th St,Room 8219, Charlestown, MA 02129 USA. EM LMKaplan@partners.org OI Ellacott, Kate/0000-0001-5261-7465; Farooqi, Sadaf/0000-0001-7609-3504 FU National Institute of Diabetes and Digestive and Kidney Diseases; Vanderbilt Mouse Metabolic Phenotyping Center (National Institute of Diabetes and Digestive and Kidney Diseases); Merck Research Laboratories; Ethicon Endo-Surgery; Wellcome Trust; Medical Research Council Centre for Obesity and Related Disorders; National Institute for Health Research Cambridge Biomedical Research Centre FX I.J.H., N.S., D.P.Y., K.L.J.E., R.D.C., and L.M.K. received research support from the National Institute of Diabetes and Digestive and Kidney Diseases. D.P.Y., K.L.J.E., and L.M. received support from the Vanderbilt Mouse Metabolic Phenotyping Center (National Institute of Diabetes and Digestive and Kidney Diseases). I.J.H., N.S., and L.M.K. received support from Merck Research Laboratories and Ethicon Endo-Surgery. I.S.F. received support from the Wellcome Trust, the Medical Research Council Centre for Obesity and Related Disorders and the National Institute for Health Research Cambridge Biomedical Research Centre. NR 39 TC 49 Z9 49 U1 1 U2 7 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2012 VL 97 IS 6 BP E1023 EP E1031 DI 10.1210/jc.2011-3432 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 970AP UT WOS:000306100800020 PM 22492873 ER PT J AU Jonklaas, J Nogueras-Gonzalez, G Munsell, M Litofsky, D Ain, KB Bigos, ST Brierley, JD Cooper, DS Haugen, BR Ladenson, PW Magner, J Robbins, J Ross, DS Skarulis, MC Steward, DL Maxon, HR Sherman, SI AF Jonklaas, J. Nogueras-Gonzalez, G. Munsell, M. Litofsky, D. Ain, K. B. Bigos, S. T. Brierley, J. D. Cooper, D. S. Haugen, B. R. Ladenson, P. W. Magner, J. Robbins, J. Ross, D. S. Skarulis, M. C. Steward, D. L. Maxon, H. R. Sherman, S. I. CA Natl Thyroid Canc Treatment Cooper TI The Impact of Age and Gender on Papillary Thyroid Cancer Survival SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID REPRODUCTIVE FACTORS; PROGNOSTIC-FACTORS; POOLED ANALYSIS; REPLACEMENT THERAPY; HORMONAL FACTORS; RISK-FACTORS; CARCINOMA; ESTROGEN; WOMEN; INSTITUTION AB Context: Thyroid cancer predominately affects women, carries a worse prognosis in older age, and may have higher mortality in men. Superimposed on these observations is the fact that most women have attained menopause by age 55 yr. Objective: The objective of the study was to determine whether men contribute disproportionately to papillary thyroid cancer (PTC) mortality or whether menopause affects PTC prognosis. Design: Gender-specific mortality was normalized using age-matched subjects from the U.S. population. Multivariate Cox proportional hazard regression models incorporating gender, age, and National Thyroid Cancer Treatment Cooperative Study Group stage were used to model disease-specific survival (DSS). Participants and Setting: Patients were followed in a prospective registry. Main Outcome Measure: The relationships between gender, age, and PTC outcomes were analyzed. Results: The unadjusted hazard ratio (HR) for DSS for women was 0.40 [confidence interval (CI) 0.24-0.65]. This female advantage diminished when DSS was adjusted for age at diagnosis and stage with a HR encompassing unity (HR 0.72, CI 0.44-1.19). Additional multivariate models of DSS considering gender, disease stage, and various age groupings showed that the DSS for women diagnosed at under 55 yr was improved over men (HR 0.33, CI 0.13-0.81). However, the HR for DSS increased to become similar to men for women diagnosed at 55-69 yr (HR 1.01, CI 0.42-2.37) and at 70 yr or greater (HR 1.17, CI 0.48-2.85). Conclusions: Although the overall outcome of women with PTC is similar to men, subgroup analysis showed that this composite outcome is composed of two periods with different outcomes. The first period is a period with better outcomes for women than men when the diagnosis occurs at younger than 55 yr; the second is a period with similar outcomes for both women and men diagnosed at ages greater than 55 yr. These data raise the question of whether an older age cut off would improve current staging systems. We hypothesize that older age modifies the effect of gender on outcomes due to menopause-associated hormonal alterations. (J Clin Endocrinol Metab 97: E878-E887, 2012) C1 [Jonklaas, J.] Georgetown Univ, Med Ctr, Dept Med, Div Endocrinol, Washington, DC 20007 USA. [Nogueras-Gonzalez, G.; Munsell, M.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77230 USA. [Litofsky, D.; Sherman, S. I.] Univ Texas MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, Houston, TX 77230 USA. [Ain, K. B.] Vet Affairs Med Ctr, Dept Internal Med, Lexington, KY 40536 USA. [Ain, K. B.] Univ Kentucky, Lexington, KY 40536 USA. [Bigos, S. T.] Maine Med Ctr, Div Endocrinol, Portland, ME 04102 USA. [Brierley, J. D.] Princess Margaret Hosp, Dept Radiat Oncol, Toronto, ON M5G 2M9, Canada. [Cooper, D. S.; Ladenson, P. W.] Johns Hopkins Univ, Sch Med, Div Endocrinol & Metab, Baltimore, MD 21287 USA. [Haugen, B. R.] Univ Colorado Denver, Div Endocrinol Metab & Diabet, Aurora, CO 80045 USA. [Haugen, B. R.] Hlth Sci Ctr, Aurora, CO 80045 USA. [Magner, J.] Genzyme Corp, Cambridge, MA 02142 USA. [Robbins, J.; Skarulis, M. C.] NIH, Clin Endocrinol Branch, Bethesda, MD 20892 USA. [Ross, D. S.] Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02114 USA. [Steward, D. L.] Univ Cincinnati, Med Ctr, Dept Head & Neck Surg, Cincinnati, OH 45267 USA. [Maxon, H. R.] Univ Cincinnati, Med Ctr, Dept Nucl Med, Cincinnati, OH 45267 USA. RP Jonklaas, J (reprint author), Georgetown Univ, Med Ctr, Div Endocrinol & Metab, Suite 230,Bldg D,4000 Reservoir Rd NW, Washington, DC 20007 USA. EM jonklaaj@georgetown.edu RI Jonklaas, Jacqueline/G-2807-2010; OI Jonklaas, Jacqueline/0000-0002-2238-2666; Sherman, Steven/0000-0002-3079-5153 FU Genzyme Corporation; Pfizer; University of Texas M.D. Anderson Cancer Center Support Grant (NCI) [P30 CA016672]; National Center for Research Resources, National Institutes of Health [1UL1RR031975] FX The NTCTCSG is supported in part by research grants from Genzyme Corporation and Pfizer, and by the University of Texas M.D. Anderson Cancer Center Support Grant (NCI Grant P30 CA016672). J.J. is supported by Grant 1UL1RR031975 from the National Center for Research Resources, National Institutes of Health. NR 63 TC 44 Z9 46 U1 2 U2 10 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2012 VL 97 IS 6 BP E878 EP E887 DI 10.1210/jc.2011-2864 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 970AP UT WOS:000306100800002 PM 22496497 ER PT J AU Perez-Nanclares, G Romanelli, V Mayo, S Garin, I Zazo, C Fernandez-Rebollo, E Martinez, F Lapunzina, P de Nanclares, GP AF Perez-Nanclares, Gustavo Romanelli, Valeria Mayo, Sonia Garin, Intza Zazo, Celia Fernandez-Rebollo, Eduardo Martinez, Francisco Lapunzina, Pablo Perez de Nanclares, Guiomar CA Spanish PHP Grp TI Detection of Hypomethylation Syndrome among Patients with Epigenetic Alterations at the GNAS Locus SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PSEUDOHYPOPARATHYROIDISM TYPE-IB; BECKWITH-WIEDEMANN-SYNDROME; NEONATAL DIABETES-MELLITUS; SILVER-RUSSELL-SYNDROME; HEREDITARY OSTEODYSTROPHY; AUTOSOMAL-DOMINANT; IMPRINTING DEFECT; FETAL OVERGROWTH; NO EVIDENCE; METHYLATION AB Context: Genomic imprinting is the modification of the genome so that genes from only one(rather than two) of the parental alleles are expressed. The mechanism underlying imprinting is epigenetic, occurring via changes in DNA methylation and histone modifications rather than through alterations in the DNA sequence. To date, nine different imprinting disorders have been clinically and genetically identified and a considerable research effort has been focused on determining the cause of the corresponding methylation defects. Objective: Our objective was to identify multilocus imprinting defects and characterize any mutations in trans-acting genes in patients with pseudohypoparathyroidism (PHP) caused by epigenetic alterations at GNAS locus. Design: We have investigated multilocus imprinting defects in 22 PHP patients with aberrant methylation at the GNAS locus not due to previously described deletions or to paternal uniparental disomy (UPD) of chromosome 20. Results: We found that, in contrast to what has been described in growth disorders, multilocus hypomethylation is an uncommon event in PHP patients. We were also unable to identify any genetic alteration causative of the epigenetic defects in the currently known methylation regulatory genes. Conclusion: Our work suggests that a trans-acting gene regulating the establishment or maintenance of imprinting at GNAS locus, if it exists, should be specific to PHP cases caused by epigenetic defects at GNAS. (J Clin Endocrinol Metab 97: E1060-E1067, 2012) C1 [Perez-Nanclares, Gustavo; Garin, Intza; Zazo, Celia; Perez de Nanclares, Guiomar] Hosp Txagorritxu, Mol Epi Genet Lab, Res Unit, E-01009 Vitoria, Alava, Spain. [Perez-Nanclares, Gustavo] Hosp Cruces, Endocrinol & Diabet Res Grp, E-48903 Baracaldo, Basque Country, Spain. [Romanelli, Valeria; Lapunzina, Pablo] Univ Autonoma Madrid, Inst Invest Hosp Univ La Paz, Inst Genet Med & Mol, E-28049 Madrid, Spain. [Romanelli, Valeria; Lapunzina, Pablo] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras U753, E-28029 Madrid, Spain. [Mayo, Sonia; Martinez, Francisco] Hosp Univ La Fe, Unidad Genet & Diagnost Prenatal, E-46009 Valencia, Spain. [Fernandez-Rebollo, Eduardo] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Fernandez-Rebollo, Eduardo] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Perez-Nanclares, G (reprint author), Hosp Txagorritxu, Mol Epi Genet Lab, Res Unit, E-01009 Vitoria, Alava, Spain. EM gnanclares@osakidetza.net RI Luque, Inmaculada/K-9464-2014; Martinez, Francisco/A-2543-2009; Audiparera, Laura/H-7291-2012; , Ivan/D-6804-2012; Menendez Torre, Edelmiro/G-1547-2013; Argente , Jesus /K-1167-2014; OI Mayo, Sonia/0000-0002-5465-7783; Luque, Inmaculada/0000-0003-1838-2636; FERNANDEZ-REBOLLO, EDUARDO/0000-0002-4378-7590; Martinez, Francisco/0000-0002-0589-2584; , Ivan/0000-0002-3108-058X; Perez de Nanclares, Guiomar/0000-0002-2424-5294; Menendez Torre, Edelmiro/0000-0002-9548-7821; Argente , Jesus /0000-0001-5826-0276; Sanchez Diaz, Aurora/0000-0003-1167-1451; Castano, Luis/0000-0003-0437-9401 FU I3SNS Program of the Spanish Ministry of Health [CP03/0064, SIVI 1395/09]; FIS programs [I3SNS-ECA07/036, I3SNS-CA10/01056]; Fundacion para la Investigacion del Hospital la Fe/Fundacion Bancaja fellowship; Basque Department of Health [GV2008/111035]; Fundacion Eugenio Rodriguez Pascual [BIO08/ER/001]; Instituto de Salud Carlos III [PI10/0148, PI08/1360] FX G.P.d.N. is cofunded by the I3SNS Program of the Spanish Ministry of Health (CP03/0064; SIVI 1395/09). G.P.-N. and I.G. are supported by FIS programs I3SNS-ECA07/036 and I3SNS-CA10/01056, respectively. S.M. is supported by Fundacion para la Investigacion del Hospital la Fe/Fundacion Bancaja fellowship. This work was partially supported by Grants GV2008/111035 from the Basque Department of Health, BIO08/ER/001, Fundacion Eugenio Rodriguez Pascual, and grants from the Instituto de Salud Carlos III to G.P.D.N. (PI10/0148) and to V.R. and P.L. (PI08/1360). NR 42 TC 22 Z9 22 U1 0 U2 7 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2012 VL 97 IS 6 BP E1060 EP E1067 DI 10.1210/jc.2012-1081 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 970AP UT WOS:000306100800024 PM 22492776 ER PT J AU Shampo, MA Kyle, RA Steensma, DP AF Shampo, Marc A. Kyle, Robert A. Steensma, David P. TI William Shockley and the Transistor SO MAYO CLINIC PROCEEDINGS LA English DT Biographical-Item C1 [Shampo, Marc A.; Kyle, Robert A.] Mayo Clin, Rochester, MN 55905 USA. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Shampo, MA (reprint author), Mayo Clin, Rochester, MN 55905 USA. OI Steensma, David/0000-0001-5130-9284 NR 1 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 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JUN PY 2012 VL 87 IS 6 BP E43 EP E43 DI 10.1016/j.mayocp.2012.01.019 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 969QT UT WOS:000306071600002 PM 22677083 ER PT J AU Casement, MD Harrington, KM Miller, MW Resick, PA AF Casement, Melynda D. Harrington, Kelly M. Miller, Mark W. Resick, Patricia A. TI Associations between Pittsburgh Sleep Quality Index factors and health outcomes in women with posttraumatic stress disorder SO SLEEP MEDICINE LA English DT Article DE Factor analysis; Pittsburgh Sleep Quality Index; Sleep; PTSD; Depression; Anger; Physical symptoms ID ADMINISTERED PTSD SCALE; COGNITIVE-PROCESSING THERAPY; RANDOMIZED CONTROLLED-TRIAL; BECK DEPRESSION INVENTORY; PSYCHOMETRIC EVALUATION; IMAGERY REHEARSAL; PERCEIVED HEALTH; DISTURBANCES; VALIDATION; NIGHTMARES AB Objective: The Pittsburgh Sleep Quality Index (PSQI) is a widely used measure of subjective sleep disturbance in clinical populations, including individuals with posttraumatic stress disorder (PTSD). Although the severity of sleep disturbance is generally represented by a global symptom score, recent factor analytic studies suggest that the PSQI is better characterized by a two- or three-factor model than a one-factor model. This study examined the replicability of two- and three-factor models of the PSQI, as well as the relationship between PSQI factors and health outcomes, in a female sample with PTSD. Methods: The PSQI was administered to 319 women with PTSD related to sexual or physical assault. Confirmatory factor analyses tested the relative fit of one-, two-, and three-factor solutions. Bivariate correlations were performed to examine the shared variance between PSQI sleep factors and measures of PTSD, depression, anger, and physical symptoms. Results: Confirmatory factor analyses supported a three-factor model with Sleep Efficiency, Perceived Sleep Quality, and Daily Disturbances as separate indices of sleep quality. The severity of symptoms represented by the PSQI factors was positively associated with the severity of PTSD, depression, and physical symptoms. However, these health outcomes correlated as much or more with the global PSQI score as with PSQI factor scores. Conclusions: These results support the multidimensional structure of the PSQI. Despite this, the global PSQI score has as much or more explanatory power as individual PSQI factors in predicting health outcomes. Published by Elsevier B.V. C1 [Casement, Melynda D.; Harrington, Kelly M.; Miller, Mark W.; Resick, Patricia A.] Natl Ctr PTSD, VA Boston Healthcare Syst, Boston, MA 02130 USA. [Casement, Melynda D.; Harrington, Kelly M.; Miller, Mark W.; Resick, Patricia A.] Boston Univ, Med Ctr, Boston, MA 02130 USA. RP Resick, PA (reprint author), Natl Ctr PTSD, VA Boston Healthcare Syst, 150 S Huntington Ave 116B-3, Boston, MA 02130 USA. EM Melynda.Casement@va.gov; Kelly.Harring-ton@va.gov; Mark.Miller5@va.gov; Patricia.Re-sick@va.gov RI Miller, Mark/G-7322-2011; OI Miller, Mark/0000-0001-6393-8563; Casement, Melynda/0000-0002-5906-0994 FU National Institute of Mental Health [R01-MH51509, T32-MH019836] FX This research was supported in part by National Institute of Mental Health Grant R01-MH51509, awarded to Patricia A. Resick at the University of Missouri, St. Louis. Support for the first and second authors was provided by National Institute of Mental Health Institutional Training Grant T32-MH019836, awarded to Terence M. Keane at the National Center for PTSD, Boston, MA. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health. We thank all of the contributors to this work, including the research participants, assessors, therapists, research assistants, fidelity raters, and data managers. NR 40 TC 11 Z9 12 U1 3 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-9457 J9 SLEEP MED JI Sleep Med. PD JUN PY 2012 VL 13 IS 6 BP 752 EP 758 DI 10.1016/j.sleep.2012.02.014 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 972TZ UT WOS:000306304700033 PM 22542787 ER PT J AU Eyler, LT Chen, CH Panizzon, MS Fennema-Notestine, C Neale, MC Jak, A Jernigan, TL Fischl, B Franz, CE Lyons, MJ Grant, M Prom-Wormley, E Seidman, LJ Tsuang, MT Fiecas, MJA Dale, AM Kremen, WS AF Eyler, Lisa T. Chen, Chi-Hua Panizzon, Matthew S. Fennema-Notestine, Christine Neale, Michael C. Jak, Amy Jernigan, Terry L. Fischl, Bruce Franz, Carol E. Lyons, Michael J. Grant, Michael Prom-Wormley, Elizabeth Seidman, Larry J. Tsuang, Ming T. Fiecas, Mark Joseph A. Dale, Anders M. Kremen, William S. TI A Comparison of Heritability Maps of Cortical Surface Area and Thickness and the Influence of Adjustment for Whole Brain Measures: A Magnetic Resonance Imaging Twin Study SO TWIN RESEARCH AND HUMAN GENETICS LA English DT Article DE surface area; cortical thickness; region of interest; heritability maps ID HUMAN CEREBRAL-CORTEX; VIETNAM ERA TWIN; GENETIC INFLUENCES; REGISTRY; SYSTEM AB Understanding the genetic and environmental contributions to measures of brain structure such as surface area and cortical thickness is important for a better understanding of the nature of brain-behavior relationships and changes due to development or disease. Continuous spatial maps of genetic influences on these structural features can contribute to our understanding of regional patterns of heritability, since it remains to be seen whether genetic contributions to brain structure respect the boundaries of any traditional parcellation approaches. Using data from magnetic resonance imaging scans collected on a large sample of monozygotic and dizygotic twins in the Vietnam Era Twin Study of Aging, we created maps of the heritability of areal expansion (a vertex-based area measure) and cortical thickness and examined the degree to which these maps were affected by adjustment for total surface area and mean cortical thickness. We also compared the approach of estimating regional heritability based on the average heritability of vertices within the region to the more traditional region-of-interest (ROI)-based approach. The results suggested high heritability across the cortex for areal expansion and, to a slightly lesser degree, for cortical thickness. There was a great deal of genetic overlap between global and regional measures for surface area, so maps of region-specific genetic influences on surface area revealed more modest heritabilities. There was greater inter-regional variability in heritabilities when calculated using the traditional ROI-based approach compared to summarizing vertex-by-vertex heritabilities within regions. Discrepancies between the approaches were greatest in small regions and tended to be larger for surface area than for cortical thickness measures. Implications regarding brain phenotypes for future genetic association studies are discussed. C1 [Eyler, Lisa T.; Chen, Chi-Hua; Panizzon, Matthew S.; Fennema-Notestine, Christine; Jak, Amy; Jernigan, Terry L.; Franz, Carol E.; Tsuang, Ming T.; Kremen, William S.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Eyler, Lisa T.] VA San Diego Healthcare Syst, Mental Illness Res Educ & Clin Ctr, San Diego, CA USA. [Chen, Chi-Hua; Panizzon, Matthew S.; Franz, Carol E.; Tsuang, Ming T.; Kremen, William S.] Univ Calif San Diego, Ctr Behav Genom, La Jolla, CA 92093 USA. [Fennema-Notestine, Christine; Fiecas, Mark Joseph A.; Dale, Anders M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Neale, Michael C.; Prom-Wormley, Elizabeth] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. [Neale, Michael C.; Prom-Wormley, Elizabeth] Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA USA. [Jak, Amy] VA San Diego Healthcare Syst, Psychol Serv, San Diego, CA USA. [Jernigan, Terry L.] Univ Calif San Diego, Dept Cognit Sci, San Diego, CA 92103 USA. [Fischl, Bruce] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Fischl, Bruce] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lyons, Michael J.; Grant, Michael] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Tsuang, Ming T.] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA. [Tsuang, Ming T.; Kremen, William S.] VA San Diego Healthcare Syst, Ctr Excellence Stress & Mental Hlth, San Diego, CA USA. [Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Eyler, LT (reprint author), 9500 Gilman Dr,Mail Code 9151B, La Jolla, CA 92093 USA. EM lteyler@ucsd.edu OI Prom-Wormley, Elizabeth/0000-0001-9230-9723; Lyons, Michael/0000-0001-6516-9219; Fennema-Notestine, Christine/0000-0002-6527-6361 FU National Institutes of Health (NIH) National Institute on Aging [U24 RR021382, R01 AG18386, R01 AG18384, R01 AG22381, R01 AG 22982]; National Institute for Mental Health [T32 MH20030]; National Institute for Drug Abuse [R01 DA18673]; VA Desert Pacific Mental Illness Research Education and Clinical Center; National Center for Research Resources [U24 RR021382, P41-RR14075, BIRN002]; National Institute for Biomedical Imaging and Bioengineering [R01 EB006758]; National Institute for Neurological Disorders and Stroke [R01 NS052585-01]; The Autism and Dyslexia Project; Ellison Medical Foundation FX This work was supported by grants from National Institutes of Health (NIH) National Institute on Aging (U24 RR021382, R01 AG18386, R01 AG18384, R01 AG22381, and R01 AG 22982); National Institute for Mental Health (T32 MH20030); National Institute for Drug Abuse (R01 DA18673); and VA Desert Pacific Mental Illness Research Education and Clinical Center. Additional support was provided in part by the National Center for Research Resources (P41-RR14075 and the NCRR BIRN Morphometric Project BIRN002, U24 RR021382), the National Institute for Biomedical Imaging and Bioengineering (R01 EB006758), the National Institute for Neurological Disorders and Stroke (R01 NS052585-01), and The Autism and Dyslexia Project funded by the Ellison Medical Foundation. The US Department of Veterans Affairs has provided support for the development and maintenance of the VET Registry. Numerous organizations have provided invaluable assistance in developing and maintaining the VET Registry, including VA Cooperative Studies Program; Department of Defense; National Personnel Records Center, National Archives and Records Administration; the Internal Revenue Service; NIH; National Opinion Research Center; National Research Council; National Academy of Sciences; and the Institute for Survey Research, Temple University; Schulman, Ronca, and Bucuvalas, Inc. Most importantly, we gratefully acknowledge the cooperation and participation of the members of the VET Registry and their families. Without their contribution this research would not have been possible. NR 27 TC 37 Z9 37 U1 0 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1832-4274 J9 TWIN RES HUM GENET JI Twin Res. Hum. Genet. PD JUN PY 2012 VL 15 IS 3 SI SI BP 304 EP 314 DI 10.1017/thg.2012.3 PG 11 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA 972CD UT WOS:000306253200005 PM 22856366 ER PT J AU Turner, JA Calhoun, VD Michael, A van Erp, TGM Ehrlich, S Segall, JM Gollub, RL Csernansky, J Potkin, SG Ho, BC Bustillo, J Schulz, SC Wang, L AF Turner, Jessica A. Calhoun, Vince D. Michael, Andrew van Erp, Theo G. M. Ehrlich, Stefan Segall, Judith M. Gollub, Randy L. Csernansky, John Potkin, Steven G. Ho, Beng-Choon Bustillo, Juan Schulz, S. Charles Wang, Lei CA FBIRN TI Heritability of Multivariate Gray Matter Measures in Schizophrenia SO TWIN RESEARCH AND HUMAN GENETICS LA English DT Article DE Schizophrenia; brain structure; heritability; Independent Components Analysis ID VOXEL-BASED MORPHOMETRY; BRAIN STRUCTURE; NONPSYCHOTIC SIBLINGS; SHAPE ABNORMALITIES; UNAFFECTED SIBLINGS; CORTICAL THICKNESS; GENETIC INFLUENCES; BIPOLAR DISORDER; VOLUME; METAANALYSIS AB Structural brain measures are employed as endophenotypes in the search for schizophrenia susceptibility genes. We analyzed two independent structural imaging datasets with voxel-based morphometry and with source-based morphometry, a multivariate, independent components analysis, to determine the stability and heritability of regional gray matter concentration abnormalities in schizophrenia. The samples comprised 209 and 102 patients with schizophrenia and 208 and 96 healthy volunteers, respectively. The second sample additionally included non-ill siblings of participants with and without schizophrenia. A standard voxel-based analysis showed reproducible regional gray matter deficits in the affected participants compared with unrelated, unaffected controls in both datasets: patients showed significant gray matter concentration deficits in cortical frontal, temporal, and insular lobes. Source-based morphometry (SBM) was applied to the gray matter images of the entire sample to determine the effects of diagnosis on networks of covarying structures. The SBM analysis extracted 24 significant sets of covarying regions (components). Four of these components showed significantly lower gray matter concentrations in patients (p < .05). We determined the familiality of the observed SBM components based on 66 sibling pairs (25 discordant for schizophrenia). Two components, one including the medial frontal, insular, inferior frontal, and temporal lobes, and the other including the posterior occipital lobe, showed significant familiality (p < .05). We conclude that structural brain deficits in schizophrenia are replicable, and that SBM can extract unique familial and likely heritable components. SBM provides a useful data reduction technique that can provide measures that may serve as endophenotypes for schizophrenia. C1 [Turner, Jessica A.; Calhoun, Vince D.; Michael, Andrew; Segall, Judith M.] Mind Res Network, Albuquerque, NM 87106 USA. [Turner, Jessica A.; Bustillo, Juan] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. [Turner, Jessica A.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. [Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [van Erp, Theo G. M.; Potkin, Steven G.; FBIRN] Univ Calif Irvine, Dept Psychiat, Irvine, CA 92717 USA. [Ehrlich, Stefan] Tech Univ Dresden, Dept Child & Adolescent Psychiat, Univ Hosp CG Carus, Dresden, Germany. [Ehrlich, Stefan; Gollub, Randy L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Csernansky, John; Wang, Lei] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Csernansky, John; Wang, Lei] Northwestern Univ, Feinberg Sch Med, Dept Radiol, Chicago, IL 60611 USA. [Ho, Beng-Choon] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Schulz, S. Charles] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. RP Turner, JA (reprint author), Mind Res Network, 1101 Yale Blvd NE, Albuquerque, NM 87106 USA. EM Jturner@mrn.org RI Ho, Beng-Choon/D-6959-2011; Potkin, Steven/A-2021-2013; Wang, Lei/I-7552-2013; bustillo, juan/J-7067-2013; Turner, Jessica/H-7282-2015; OI Ho, Beng-Choon/0000-0003-3976-1555; Wang, Lei/0000-0003-3870-3388; Turner, Jessica/0000-0003-0076-8434; Ehrlich, Stefan/0000-0003-2132-4445; Gollub, Randy L./0000-0002-9434-4044; Potkin, Steven/0000-0003-1028-1013 FU Biomedical Informatics Research Network [NIH 1 U24 RR025736-01]; MCIC, Dept of Energy [DE-FG02-99ER62764, 1R01 MH084803, P50 MH071616, R01 MH056584] FX This work was supported by: the Biomedical Informatics Research Network (NIH 1 U24 RR025736-01), MCIC, Dept of Energy DE-FG02-99ER62764, 1R01 MH084803, P50 MH071616, R01 MH056584. NR 52 TC 21 Z9 21 U1 0 U2 9 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1832-4274 J9 TWIN RES HUM GENET JI Twin Res. Hum. Genet. PD JUN PY 2012 VL 15 IS 3 SI SI BP 324 EP 335 DI 10.1017/thg.2012.1 PG 12 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA 972CD UT WOS:000306253200007 PM 22856368 ER PT J AU Ryan, D Reddy, S Bahary, N Uronis, H Sigal, DS Cohn, A Schelman, WR Chiorean, EG Rosen, PJ Ulrich, B Dragovich, T Del Prete, S Rarick, M Eng, C Kroll, S AF Ryan, D. Reddy, S. Bahary, N. Uronis, H. Sigal, D. S. Cohn, Allen Schelman, W. R. Chiorean, E. G. Rosen, P. J. Ulrich, B. Dragovich, T. Del Prete, S. Rarick, M. Eng, C. Kroll, S. TI PHASE II STUDY OF GEMCITABINE + TH-302 VS GEMCITABINE ALONE IN PATIENTS WITH LOCALLY ADVANCED AND METASTATIC PANCREATIC CANCER SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 14th World Congress on Gastrointestinal Cancer of the European-Society-for-Medical-Oncology (ESMO) CY JUN 27-30, 2012 CL Barcelona, SPAIN SP European Soc Med Oncol (ESMO) C1 [Ryan, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Reddy, S.] Louisiana State Univ, Hlth Sci Ctr, Shreveport, LA 71105 USA. [Bahary, N.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Uronis, H.] Duke Univ, Med Ctr, Durham, NC USA. [Sigal, D. S.] Scripps Clin Med Grp, La Jolla, CA USA. [Cohn, Allen] Rocky Mt Canc Ctr, Denver, CO USA. [Schelman, W. R.] Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. [Chiorean, E. G.] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. [Rosen, P. J.] Providence St Joseph Med Ctr, Burbank, CA USA. [Ulrich, B.] Texas Oncol, Wichita Falls, TX USA. [Dragovich, T.] Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. [Del Prete, S.] Hematol Oncol, Stamford, CT USA. [Rarick, M.] Kaiser Permanente NW Reg Oncol Hematol, Portland, OR USA. [Eng, C.; Kroll, S.] Threshold Pharmaceut, San Francisco, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2012 VL 23 SU 4 BP 8 EP 8 PG 1 WC Oncology SC Oncology GA 966GW UT WOS:000305826900009 ER PT J AU Quackenbush, J AF Quackenbush, J. TI MOVING BEYOND THE MEAN: THE ROLE OF VARIATION IN DETERMINING PHENOTYPE SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 4th WIN Symposium on Efficacy of Biomarkers and Personalized Cancer Therapeutics CY JUN 28-29, 2012 CL Paris, FRANCE C1 [Quackenbush, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2012 VL 23 SU 5 BP 11 EP 11 PG 1 WC Oncology SC Oncology GA 966GM UT WOS:000305825900025 ER PT J AU Tate, DF Shenton, ME Bigler, ED AF Tate, D. F. Shenton, M. E. Bigler, E. D. TI Introduction to the brain imaging and behavior special issue on neuroimaging findings in mild traumatic brain injury SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Mild traumatic brain injury; Neuroimaging; Neuropsychological testing; Heterogeneity ID POSTTRAUMATIC-STRESS-DISORDER; PERSISTENT SYMPTOMS; HEAD-INJURY; ENCEPHALOPATHY; LESIONS; IRAQ AB Contemporary neuroimaging methods and research findings in mild traumatic brain injury (mTBI) are reviewed in this special issue. Topics covered include structural and functional neuroimaging techniques with a particular emphasis on the most contemporary research involving magnetic resonance imaging (MRI). Future research directions as well as applied applications of using neuroimaging techniques to define biomarkers of brain injury are covered. C1 [Tate, D. F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, Res Imaging Inst, San Antonio, TX 78229 USA. [Tate, D. F.] Henry M Jackson Fdn Adv Mil Med, Def Ctr, San Antonio, TX USA. [Tate, D. F.] Henry M Jackson Fdn Adv Mil Med, Vet Brain Injury Ctr, San Antonio, TX USA. [Shenton, M. E.] Harvard Univ, Sch Med, Dept Psychiat & Radiol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Shenton, M. E.] Harvard Univ, VA Boston Healthcare Syst, Sch Med, Brockton, MA 02401 USA. [Bigler, E. D.] Brigham Young Univ, Dept Psychol Sci, Provo, UT 84602 USA. [Bigler, E. D.] Brigham Young Univ, Neurosci Ctr, Provo, UT 84602 USA. [Bigler, E. D.] Univ Utah, Dept Psychiat, Salt Lake City, UT USA. [Bigler, E. D.] Utah Brain Inst, Salt Lake City, UT USA. RP Tate, DF (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, Res Imaging Inst, San Antonio, TX 78229 USA. EM tatedf@uthscsa.edu FU NINDS NIH HHS [L30 NS063444] NR 29 TC 5 Z9 5 U1 2 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD JUN PY 2012 VL 6 IS 2 SI SI BP 103 EP 107 DI 10.1007/s11682-012-9185-0 PG 5 WC Neuroimaging SC Neurosciences & Neurology GA 967LI UT WOS:000305908900001 PM 22706729 ER PT J AU Shenton, ME Hamoda, HM Schneiderman, JS Bouix, S Pasternak, O Rathi, Y Vu, MA Purohit, MP Helmer, K Koerte, I Lin, AP Westin, CF Kikinis, R Kubicki, M Stern, RA Zafonte, R AF Shenton, M. E. Hamoda, H. M. Schneiderman, J. S. Bouix, S. Pasternak, O. Rathi, Y. Vu, M. -A. Purohit, M. P. Helmer, K. Koerte, I. Lin, A. P. Westin, C. -F. Kikinis, R. Kubicki, M. Stern, R. A. Zafonte, R. TI A review of magnetic resonance imaging and diffusion tensor imaging findings in mild traumatic brain injury SO BRAIN IMAGING AND BEHAVIOR LA English DT Review DE Mild traumatic brain injury; mTBI; TBI; Diffusion tensor imaging; DTI; Magnetic resonance imaging; MRI; Diffusion-weighted imaging; DWI; Susceptibility-weighted imaging; SWI; Signature injury of war; Concussion; Postconcussive syndrome; Postconcussive symptoms; Complicated mTBI; Uncomplicated mTBI; Physiogenesis; Psychogenesis; Miserable minority ID MINOR HEAD-INJURY; WHITE-MATTER INJURY; POST-CONCUSSIVE SYNDROME; PROTON MR SPECTROSCOPY; COMMON DATA ELEMENTS; LIVING HUMAN BRAIN; AXONAL INJURY; CORPUS-CALLOSUM; H-1 MRS; NEUROIMAGING TECHNIQUES AB Mild traumatic brain injury (mTBI), also referred to as concussion, remains a controversial diagnosis because the brain often appears quite normal on conventional computed tomography (CT) and magnetic resonance imaging (MRI) scans. Such conventional tools, however, do not adequately depict brain injury in mTBI because they are not sensitive to detecting diffuse axonal injuries (DAI), also described as traumatic axonal injuries (TAI), the major brain injuries in mTBI. Furthermore, for the 15 to 30 % of those diagnosed with mTBI on the basis of cognitive and clinical symptoms, i.e., the "miserable minority," the cognitive and physical symptoms do not resolve following the first 3 months post-injury. Instead, they persist, and in some cases lead to long-term disability. The explanation given for these chronic symptoms, i.e., postconcussive syndrome, particularly in cases where there is no discernible radiological evidence for brain injury, has led some to posit a psychogenic origin. Such attributions are made all the easier since both posttraumatic stress disorder (PTSD) and depression are frequently co-morbid with mTBI. The challenge is thus to use neuroimaging tools that are sensitive to DAI/TAI, such as diffusion tensor imaging (DTI), in order to detect brain injuries in mTBI. Of note here, recent advances in neuroimaging techniques, such as DTI, make it possible to characterize better extant brain abnormalities in mTBI. These advances may lead to the development of biomarkers of injury, as well as to staging of reorganization and reversal of white matter changes following injury, and to the ability to track and to characterize changes in brain injury over time. Such tools will likely be used in future research to evaluate treatment efficacy, given their enhanced sensitivity to alterations in the brain. In this article we review the incidence of mTBI and the importance of characterizing this patient population using objective radiological measures. Evidence is presented for detecting brain abnormalities in mTBI based on studies that use advanced neuroimaging techniques. Taken together, these findings suggest that more sensitive neuroimaging tools improve the detection of brain abnormalities (i.e., diagnosis) in mTBI. These tools will likely also provide important information relevant to outcome (prognosis), as well as play an important role in longitudinal studies that are needed to understand the dynamic nature of brain injury in mTBI. Additionally, summary tables of MRI and DTI findings are included. We believe that the enhanced sensitivity of newer and more advanced neuroimaging techniques for identifying areas of brain damage in mTBI will be important for documenting the biological basis of postconcussive symptoms, which are likely associated with subtle brain alterations, alterations that have heretofore gone undetected due to the lack of sensitivity of earlier neuroimaging techniques. Nonetheless, it is noteworthy to point out that detecting brain abnormalities in mTBI does not mean that other disorders of a more psychogenic origin are not co-morbid with mTBI and equally important to treat. They arguably are. The controversy of psychogenic versus physiogenic, however, is not productive because the psychogenic view does not carefully consider the limitations of conventional neuroimaging techniques in detecting subtle brain injuries in mTBI, and the physiogenic view does not carefully consider the fact that PTSD and depression, and other co-morbid conditions, may be present in those suffering from mTBI. Finally, we end with a discussion of future directions in research that will lead to the improved care of patients diagnosed with mTBI. C1 [Shenton, M. E.; Hamoda, H. M.; Schneiderman, J. S.; Bouix, S.; Pasternak, O.; Rathi, Y.; Vu, M. -A.; Purohit, M. P.; Koerte, I.; Kubicki, M.] Brigham & Womens Hosp, Psychiat Neuroimaging Lab, Dept Psychiat, Boston, MA 02215 USA. [Pasternak, O.; Westin, C. -F.] Brigham & Womens Hosp, Dept Radiol, Lab Math Imaging, Boston, MA 02215 USA. [Shenton, M. E.; Hamoda, H. M.; Schneiderman, J. S.; Bouix, S.; Pasternak, O.; Rathi, Y.; Vu, M. -A.; Purohit, M. P.; Koerte, I.; Lin, A. P.; Westin, C. -F.; Kikinis, R.; Kubicki, M.; Zafonte, R.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Shenton, M. E.] VA Boston Healthcare Syst, Clin Neurosci Lab, Lab Neurosci, Dept Psychiat, Brockton, MA USA. [Shenton, M. E.] Harvard Univ, Sch Med, Brockton, MA 02401 USA. [Hamoda, H. M.] Childrens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Purohit, M. P.; Zafonte, R.] Massachusetts Gen Hosp, Spaulding Rehabil Hosp, Boston, MA 02114 USA. [Purohit, M. P.] Beth Israel Deaconness Med Ctr, Div Med, Boston, MA USA. [Helmer, K.] Massachusetts Gen Hosp, Dept Radiol, Athinoula Martinos Ctr, Charlestown, MA USA. [Helmer, K.] Harvard Univ, Sch Med, Charlestown, MA USA. [Lin, A. P.] Brigham & Womens Hosp, Ctr Clin Spect, Dept Radiol, Boston, MA 02215 USA. [Kikinis, R.] Brigham & Womens Hosp, Surg Planning Lab, MRI Div, Dept Radiol, Boston, MA 02215 USA. [Stern, R. A.] Boston Univ, Sch Med, Ctr Study Traumat Encephalopathy, Dept Neurol, Boston, MA 02118 USA. [Stern, R. A.] Boston Univ, Sch Med, Dept Neurosurg, Boston, MA 02118 USA. RP Shenton, ME (reprint author), Brigham & Womens Hosp, Psychiat Neuroimaging Lab, Dept Psychiat, 1249 Boylston St, Boston, MA 02215 USA. EM Shenton@bwh.harvard.edu RI Schneiderman, Jason/E-1528-2013; OI Schneiderman, Jason/0000-0002-9313-0415; Stern, Robert/0000-0002-5008-077X FU INTRuST Posttraumatic Stress Disorder and Traumatic Brain Injury Clinical Consortium; Department of Defense Psychological Health/Traumatic Brain Injury Research Program [X81XWH-07-CC-CS-DoD]; NIH NINDS [R01 (R01 NS 078337)]; Center for Integration of Medicine (CIMIT) Soldier in Medicine Award; NIH NIMH [R01 (R01 MH082918)]; National Research Service Award from the National Center for Complementary and Alternative Medicine (NCCAM) at the National Institute of Health [T32AT000051]; Harvard Medical School Fellowship as part of the Eleanor and Miles Shore Fellowship Program; Deutsche Akademischer Austauschdienst (DAAD); NCRR; National Alliance for Medical Image Computing [NAMIC-U54 EBOO5149]; Neuroimaging Analysis Center (NAC) [P41RR13218] FX This work was supported in part by the INTRuST Posttraumatic Stress Disorder and Traumatic Brain Injury Clinical Consortium funded by the Department of Defense Psychological Health/Traumatic Brain Injury Research Program(X81XWH-07-CC-CS-DoD; MES, JSS, SB, OP, MK, YR, M-AV, C-FW, RZ), by an NIH NINDS funded R01 (R01 NS 078337; RS, MES, JSS), by a Center for Integration of Medicine (CIMIT) Soldier in Medicine Award (SB, MES), by an NIH NIMH funding R01 (R01 MH082918; SB), by funding from the National Research Service Award (T32AT000051; MPP) from the National Center for Complementary and Alternative Medicine (NCCAM) at the National Institute of Health, by the Harvard Medical School Fellowship as part of the Eleanor and Miles Shore Fellowship Program (HH), by the Deutsche Akademischer Austauschdienst (DAAD; IK), and by funding from NCRR, including the National Alliance for Medical Image Computing (NAMIC-U54 EBOO5149; RK, MK, MES), and the Neuroimaging Analysis Center (NAC; P41RR13218; RK and CF). NR 207 TC 217 Z9 223 U1 17 U2 128 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD JUN PY 2012 VL 6 IS 2 SI SI BP 137 EP 192 DI 10.1007/s11682-012-9156-5 PG 56 WC Neuroimaging SC Neurosciences & Neurology GA 967LI UT WOS:000305908900003 PM 22438191 ER PT J AU Rudin, CM Hann, CL Garon, EB de Oliveira, MR Bonomi, PD Camidge, DR Chu, Q Giaccone, G Khaira, D Ramalingam, SS Ranson, MR Dive, C McKeegan, EM Chyla, BJ Dowell, BL Chakravartty, A Nolan, CE Rudersdorf, N Busman, TA Mabry, MH Krivoshik, AP Humerickhouse, RA Shapiro, GI Gandhi, L AF Rudin, Charles M. Hann, Christine L. Garon, Edward B. de Oliveira, Moacyr Ribeiro Bonomi, Philip D. Camidge, D. Ross Chu, Quincy Giaccone, Giuseppe Khaira, Divis Ramalingam, Suresh S. Ranson, Malcolm R. Dive, Caroline McKeegan, Evelyn M. Chyla, Brenda J. Dowell, Barry L. Chakravartty, Arunava Nolan, Cathy E. Rudersdorf, Niki Busman, Todd A. Mabry, Mack H. Krivoshik, Andrew P. Humerickhouse, Rod A. Shapiro, Geoffrey I. Gandhi, Leena TI Phase II Study of Single-Agent Navitoclax (ABT-263) and Biomarker Correlates in Patients with Relapsed Small Cell Lung Cancer SO CLINICAL CANCER RESEARCH LA Serbian DT Article ID SMALL-MOLECULE INHIBITOR; CIRCULATING TUMOR-CELLS; BCL-2 FAMILY INHIBITOR; APOPTOSIS PROTEIN XIAP; X-LINKED INHIBITOR; CARCINOMA-CELLS; PROGNOSTIC-FACTORS; CLINICAL-EFFICACY; GENE-EXPRESSION; SOLID TUMORS AB Purpose: Bcl-2 is a critical regulator of apoptosis that is overexpressed in the majority of small cell lung cancers (SCLC). Nativoclax (ABT-263) is a potent and selective inhibitor of Bcl-2 and Bcl-x(L). The primary objectives of this phase IIa study included safety at the recommended phase II dose and preliminary, exploratory efficacy assessment in patients with recurrent and progressive SCLC after at least one prior therapy. Experimental Design: Thirty-nine patients received navitoclax 325 mg daily, following an initial lead-in of 150 mg daily for 7 days. Study endpoints included safety and toxicity assessment, response rate, progression-free and overall survival (PFS and OS), as well as exploratory pharmacodynamic correlates. Results: The most common toxicity associated with navitoclax was thrombocytopenia, which reached grade III-IV in 41% of patients. Partial response was observed in one (2.6%) patient and stable disease in 9 (23%) patients. Median PFS was 1.5 months and median OS was 3.2 months. A strong association between plasma pro-gastrin-releasing peptide (pro-GRP) level and tumor Bcl-2 copy number (R = 0.93) was confirmed. Exploratory analyses revealed baseline levels of cytokeratin 19 fragment antigen 21-1, neuron-specific enolase, pro-GRP, and circulating tumor cell number as correlates of clinical benefit. Conclusion: Bcl-2 targeting by navitoclax shows limited single-agent activity against advanced and recurrent SCLC. Correlative analyses suggest several putative biomarkers of clinical benefit. Preclinical models support that navitoclax may enhance sensitivity of SCLC and other solid tumors to standard cytotoxics. Future studies will focus on combination therapies. Clin Cancer Res; 18(11); 3163-9. (C) 2012 AACR. C1 [Rudin, Charles M.; Hann, Christine L.] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Giaccone, Giuseppe] NCI, Baltimore, MD USA. [Garon, Edward B.] Univ Calif Los Angeles, Los Angeles, CA USA. [de Oliveira, Moacyr Ribeiro] PLLC, Tacoma, WA USA. [Bonomi, Philip D.] Rush Univ, Med Ctr, Chicago, IL USA. [McKeegan, Evelyn M.; Chyla, Brenda J.; Dowell, Barry L.; Chakravartty, Arunava; Nolan, Cathy E.; Rudersdorf, Niki; Busman, Todd A.; Mabry, Mack H.; Krivoshik, Andrew P.; Humerickhouse, Rod A.] Abbott Labs, Chicago, IL USA. [Camidge, D. Ross] UC Davis Canc Ctr, Sacramento, CA USA. [Chu, Quincy] Univ Alberta, Cross Canc Inst, Alberta Hlth Serv, Edmonton, AB T6G 2M7, Canada. [Khaira, Divis] Sunterra Oncol Associates, Phoenix, AZ USA. [Ramalingam, Suresh S.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Ranson, Malcolm R.] Christie NHS Fdn Trust, Manchester, Lancs, England. [Dive, Caroline] Univ Manchester, Paterson Inst Canc Res, Manchester, Lancs, England. [Shapiro, Geoffrey I.; Gandhi, Leena] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Rudin, CM (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Canc Res Bldg 2,Room 544,1550 Orleans St, Baltimore, MD 21231 USA. EM rudin@jhmi.edu RI Giaccone, Giuseppe/E-8297-2017; OI Giaccone, Giuseppe/0000-0002-5023-7562; Dive, Caroline/0000-0002-1726-8850; Gandhi, Leena/0000-0002-2398-9179 FU NCI NIH HHS [P30 CA006973] NR 43 TC 156 Z9 160 U1 0 U2 20 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2012 VL 18 IS 11 BP 3163 EP 3169 DI 10.1158/1078-0432.CCR-11-3090 PG 7 WC Oncology SC Oncology GA 967IN UT WOS:000305900600019 PM 22496272 ER PT J AU Demetri, GD Garrett, CR Schoffski, P Shah, MH Verweij, J Leyvraz, S Hurwitz, HI Pousa, AL Le Cesne, A Goldstein, D Paz-Ares, L Blay, JY McArthur, GA Xu, Q Huang, X Harmon, CS Tassell, V Cohen, DP Casali, PG AF Demetri, George D. Garrett, Christopher R. Schoffski, Patrick Shah, Manisha H. Verweij, Jaap Leyvraz, Serge Hurwitz, Herbert I. Lopez Pousa, Antonio Le Cesne, Axel Goldstein, David Paz-Ares, Luis Blay, Jean-Yves McArthur, Grant A. Xu, Qiang (Casey) Huang, Xin Harmon, Charles S. Tassell, Vanessa Cohen, Darrel P. Casali, Paolo G. TI Complete Longitudinal Analyses of the Randomized, Placebo-Controlled, Phase III Trial of Sunitinib in Patients with Gastrointestinal Stromal Tumor following Imatinib Failure SO CLINICAL CANCER RESEARCH LA English DT Article ID TYROSINE KINASE INHIBITOR; GROWTH-FACTOR; IN-VIVO; SU11248; CANCER; BIOMARKERS; MUTATIONS; CARCINOMA; PROTEINS; MODELS AB Purpose: To analyze final long-term survival and clinical outcomes from the randomized phase III study of sunitinib in gastrointestinal stromal tumor patients after imatinib failure; to assess correlative angiogenesis biomarkers with patient outcomes. Experimental Design: Blinded sunitinib or placebo was given daily on a 4-week-on/2-week-off treatment schedule. Placebo-assigned patients could cross over to sunitinib at disease progression/study unblinding. Overall survival (OS) was analyzed using conventional statistical methods and the rank-preserving structural failure time (RPSFT) method to explore cross-over impact. Circulating levels of angiogenesis biomarkers were analyzed. Results: In total, 243 patients were randomized to receive sunitinib and 118 to placebo, 103 of whom crossed over to open-label sunitinib. Conventional statistical analysis showed that OS converged in the sunitinib and placebo arms (median 72.7 vs. 64.9 weeks; HR, 0.876; P = 0.306) as expected, given the crossover design. RPSFT analysis estimated median OS for placebo of 39.0 weeks (HR, 0.505, 95% CI, 0.262-1.134; P 0.306). No new safety concerns emerged with extended sunitinib treatment. No consistent associations were found between the pharmacodynamics of angiogenesis-related plasma proteins during sunitinib treatment and clinical outcome. Conclusions: The cross-over design provided evidence of sunitinib clinical benefit based on prolonged time to tumor progression during the double-blind phase of this trial. As expected, following cross-over, there was no statistical difference in OS. RPSFT analysis modeled the absence of cross-over, estimating a substantial sunitinib OS benefit relative to placebo. Long-term sunitinib treatment was tolerated without new adverse events. Clin Cancer Res; 18(11); 3170-9. (C) 2012 AACR. C1 [Demetri, George D.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Ludwig Ctr, Dana Farber Harvard Canc Ctr, Boston, MA 02215 USA. [Garrett, Christopher R.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Schoffski, Patrick] Catholic Univ Louvain, Univ Hosp Leuven, Leuven Canc Inst, B-3000 Louvain, Belgium. [Shah, Manisha H.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Verweij, Jaap] Erasmus Univ, Med Ctr, Rotterdam, Netherlands. [Leyvraz, Serge] CHU Vaudois, CH-1011 Lausanne, Switzerland. [Hurwitz, Herbert I.] Duke Univ, Med Ctr, Durham, NC USA. [Lopez Pousa, Antonio] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Le Cesne, Axel] Inst Gustave Roussy, Villejuif, France. [Goldstein, David] UNSW Prince Wales Clin Sch, Randwick, NSW, Australia. [Paz-Ares, Luis] Inst Biomed Sevilla IBIS, Seville, Spain. [Paz-Ares, Luis] Hosp Univ Doce Octubre, Madrid, Spain. [Blay, Jean-Yves] Univ Lyon 1, Ctr Leon Berard, F-69365 Lyon, France. [McArthur, Grant A.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Xu, Qiang (Casey)] Columbia Univ, New York, NY USA. [Huang, Xin; Harmon, Charles S.; Tassell, Vanessa; Cohen, Darrel P.] Pfizer Oncol, La Jolla, CA USA. [Casali, Paolo G.] Ist Nazl Tumori, I-20133 Milan, Italy. RP Demetri, GD (reprint author), Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Ludwig Ctr, Dana Farber Harvard Canc Ctr, 450 Brookline Ave,Dana 1212, Boston, MA 02215 USA. EM gdemetri@partners.org RI IBIS, NUEVAS TERAPIA/P-3415-2015; Blay, Jean-Yves/N-3966-2016; casali, Paolo Giovanni/D-1524-2017 OI Blay, Jean-Yves/0000-0001-7190-120X; casali, Paolo Giovanni/0000-0003-4056-8023 FU Pfizer; Novartis; Ariad; Johnson Johnson; Bristol-Myers Squibb; Infinity; Daiichi-Sankyo; Cellgene; Amgen; Pfizer Inc.; Pfizer Inc. (New York, NY); Virginia and Daniel K. Ludwig Trust for Cancer Research; Rubenstein Foundation; Katz Foundation; Quick Family Fund for Cancer Research; Ronald O. Perelman Fund for Cancer Research at Dana-Farber; Stutman GIST Cancer Research Fund; Paul's Posse; Leslie's Links; Spanish National Health Service [FIS PI 081156] FX G.D. Demetri has received commercial research support from Pfizer, Novartis, Ariad, Johnson & Johnson, Bristol-Myers Squibb, Infinity, and Daiichi-Sankyo, and has served as a consultant for Pfizer, Novartis, Ariad, Johnson & Johnson, Genentech, Infinity, Bayer, EMD-Serono, GlaxoSmithKline, Amgen, Daiichi-Sankyo, ArQule, Enzon, and Millenium/Takeda. He has also served as a member of an advisory board for ZioPharm. C.R. Garrett, L. Paz-Arez, and J. Verweij have served as consultants or members of advisory boards for Pfizer. P. Schoffski has received a commercial research grant, other commercial research support, and honoraria from speakers bureau from and has served as a consultant or member of an advisory board for Pfizer. M.H. Shah has received a commercial research grant from Pfizer. H.I. Hurwitz has received a commercial research grant and has served as a consultant or member of an advisory board for Pfizer. A. Le Cesne has received honoraria from speakers bureau from Pfizer, Novartis, and Pharmamar. D. Goldstein has received commercial research grants from Pfizer, Cellgene, and Amgen, and has received honoraria from and served as a member of advisory boards for Pfizer, Novartis, Bayer, GlaxoSmithKline, and Roche. J.-Y. Blay has received honoraria from speakers bureau from and has served as a consultant or member of advisory boards for Pfizer and Novartis. G.A. McArthur has received commercial research grants from Pfizer and Novartis. Q. Xu has served as a consultant for Pfizer. C.S. Harmon is a previous employee of and has had an ownership interest in Pfizer. X. Huang, V. Tassell, and D.P. Cohen are employees of and have ownership interests in Pfizer. P.G. Casali has received honoraria for lectures and/or for serving in an advisory role for Pfizer, Novartis, and Bayer.; The authors thank all the participating patients and their families, as well as the global network of investigators (listed in Supplementary Data), research nurses, study coordinators, and operations staff. C.S. Harmon was an employee of Atrium Staffing (New York, NY) and was a paid contractor of Pfizer in the development of this article and the analysis and interpretation of data involving circulating biomarkers of angiogenesis. Medical writing support was provided by Wendy Sacks at ACUMED (New York, NY) and was funded by Pfizer Inc.; This study was sponsored by Pfizer Inc. (New York, NY). Additional funding was provided by the Virginia and Daniel K. Ludwig Trust for Cancer Research, the Rubenstein Foundation, the Katz Foundation, the Quick Family Fund for Cancer Research, the Ronald O. Perelman Fund for Cancer Research at Dana-Farber, the Stutman GIST Cancer Research Fund, Paul's Posse, and Leslie's Links (G.D. Demetri); and grant no. FIS PI 081156 from the Spanish National Health Service (L. Paz-Ares). NR 23 TC 44 Z9 45 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2012 VL 18 IS 11 BP 3170 EP 3179 DI 10.1158/1078-0432.CCR-11-3005 PG 10 WC Oncology SC Oncology GA 967IN UT WOS:000305900600020 PM 22661587 ER PT J AU Gillet, JP Calcagno, AM Varma, S Davidson, B Elstrand, MB Ganapathi, R Kamat, AA Sood, AK Ambudkar, SV Seiden, MV Rueda, BR Gottesman, MM AF Gillet, Jean-Pierre Calcagno, Anna Maria Varma, Sudhir Davidson, Ben Elstrand, Mari Bunkholt Ganapathi, Ram Kamat, Aparna A. Sood, Anil K. Ambudkar, Suresh V. Seiden, Michael V. Rueda, Bo R. Gottesman, Michael M. TI Multidrug Resistance-Linked Gene Signature Predicts Overall Survival of Patients with Primary Ovarian Serous Carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID EXPRESSION PROFILES; CELL-DEATH; PROTEIN EXPRESSION; BREAST-CANCER; BCL-2 FAMILY; PHASE-II; BNIP3; MICROARRAY; CHEMOTHERAPY; MANAGEMENT AB Purpose: This study assesses the ability of multidrug resistance (MDR)-associated gene expression patterns to predict survival in patients with newly diagnosed carcinoma of the ovary. The scope of this research differs substantially from that of previous reports, as a very large set of genes was evaluated whose expression has been shown to affect response to chemotherapy. Experimental Design: We applied a customized TaqMan low density array, a highly sensitive and specific assay, to study the expression profiles of 380 MDR-linked genes in 80 tumor specimens collected at initial surgery to debulk primary serous carcinoma. The RNA expression profiles of these drug resistance genes were correlated with clinical outcomes. Results: Leave-one-out cross-validation was used to estimate the ability of MDR gene expression to predict survival. Although gene expression alone does not predict overall survival (OS; P = 0.06), four covariates (age, stage, CA125 level, and surgical debulking) do (P = 0.03). When gene expression was added to the covariates, we found an 11-gene signature that provides a major improvement in OS prediction (log-rank statistic P < 0.003). The predictive power of this 11-gene signature was confirmed by dividing high-and low-risk patient groups, as defined by their clinical covariates, into four specific risk groups on the basis of expression levels. Conclusion: This study reveals an 11-gene signature that allows a more precise prognosis for patients with serous cancer of the ovary treated with carboplatin-and paclitaxel-based therapy. These 11 new targets offer opportunities for new therapies to improve clinical outcome in ovarian cancer. Clin Cancer Res; 18(11); 3197-206. (C) 2012 AACR. C1 [Gillet, Jean-Pierre; Calcagno, Anna Maria; Ambudkar, Suresh V.; Gottesman, Michael M.] NCI, Cell Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Varma, Sudhir] NIAID, Bioinformat & Computat Biosci Branch, NIH, Bethesda, MD 20892 USA. [Davidson, Ben] Oslo Univ Hosp, Div Pathol, Norwegian Radium Hosp, Oslo, Norway. [Davidson, Ben] Univ Oslo, Fac Med, N-0316 Oslo, Norway. [Elstrand, Mari Bunkholt] Oslo Univ Hosp, Dept Gynecol Oncol, Norwegian Radium Hosp, Oslo, Norway. [Ganapathi, Ram] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Kamat, Aparna A.; Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. [Kamat, Aparna A.; Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. [Kamat, Aparna A.; Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Ctr RNA Interference & Noncoding RNA, Houston, TX 77030 USA. [Seiden, Michael V.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, 37 Convent Dr,Room 2108, Bethesda, MD 20892 USA. EM mgottesman@nih.gov RI gillet, jean-pierre/A-3714-2012; Varma, Sudhir/N-8763-2014; OI Varma, Sudhir/0000-0002-4096-4782; Calcagno, Anna Maria/0000-0002-0804-2753 FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; NIGMS Pharmacology Research Associate (PRAT) Program; Inger and Jon Fredriksen Ovarian Cancer Research Foundation; University of Texas M.D. Anderson Cancer Center Ovarian Cancer Specialized Program of Research Excellence [P50 CA083639]; Betty Ann Asche Murray Distinguished Professorship; Advanced Medical Research Foundation; Ovarian Cancer Research Fund; Ovarian Cancer Education and Awareness Network (O.C.E.A.N.); Vincent Memorial Research Funds; MGH Cancer Center; DFHCC Ovarian SPORE [5P50CA105009]; CCF Translational Research Core [P30CA043703]; FISH fund; CARES grant FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. A.M. Calcagno was supported by the NIGMS Pharmacology Research Associate (PRAT) Program. B. Davidson and M.B. Elstrand were supported by the Inger and Jon Fredriksen Ovarian Cancer Research Foundation. A.K. Sood and A.A. Kamat were supported by the University of Texas M.D. Anderson Cancer Center Ovarian Cancer Specialized Program of Research Excellence (P50 CA083639) and the Betty Ann Asche Murray Distinguished Professorship (A.K Sood). The sample collection and preparation from Massachusetts General Hospital was funded in part by the Advanced Medical Research Foundation, Ovarian Cancer Research Fund, Ovarian Cancer Education and Awareness Network (O.C.E.A.N.), Vincent Memorial Research Funds, MGH Cancer Center, and the DFHCC Ovarian SPORE (5P50CA105009). R. Ganapathi was supported by CCF Translational Research Core (P30CA043703), FISH fund, and CARES grant. NR 48 TC 20 Z9 21 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2012 VL 18 IS 11 BP 3197 EP 3206 DI 10.1158/1078-0432.CCR-12-0056 PG 10 WC Oncology SC Oncology GA 967IN UT WOS:000305900600023 PM 22492981 ER PT J AU Mischoulon, D Lamon-Fava, S Selhub, J Katz, J Papakostas, GI Iosifescu, DV Yeung, AS Dording, CM Farabaugh, AH Clain, AJ Baer, L Alpert, JE Nierenberg, AA Fava, M AF Mischoulon, David Lamon-Fava, Stefania Selhub, Jacob Katz, Judith Papakostas, George I. Iosifescu, Dan V. Yeung, Albert S. Dording, Christina M. Farabaugh, Amy H. Clain, Alisabet J. Baer, Lee Alpert, Jonathan E. Nierenberg, Andrew A. Fava, Maurizio TI Prevalence of MTHFR C677T and MS A2756G polymorphisms in major depressive disorder, and their impact on response to fluoxetine treatment SO CNS SPECTRUMS LA English DT Article DE Methylene Tetrahydrofolate Reductase; MTHFR; Methionine Synthase; MS; C677T; A2756G; depression; antidepressant; fluoxetine ID METHYLENETETRAHYDROFOLATE REDUCTASE VARIANT; CORONARY-ARTERY-DISEASE; METHIONINE SYNTHASE; FOLIC-ACID; HOMOCYSTEINE LEVELS; GENE POLYMORPHISM; SERUM FOLATE; INDIAN POPULATION; RISK-FACTORS; EARLY-ONSET AB Objective. To examine the prevalence of the C677T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene and the A2756G polymorphism of methionine synthase (MS), and their impact on antidepressant response. Methods. We screened 224 subjects (52% female, mean age 39 +/- 11 years) with SCID-diagnosed major depressive disorder (MDD), and obtained 194 genetic samples. 49 subjects (49% female, mean age 36 +/- 11 years) participated in a 12-week open clinical trial of fluoxetine 20-60 mg/day. Association between clinical response and C677T and A2756G polymorphisms, folate, B12, and homocysteine was examined. Results. Prevalence of the C677T and A2756G polymorphisms was consistent with previous reports (C/C = 41%, C/T = 47%, T/T = 11%, A/A = 66%, A/G = 29%, G/G = 4%). In the fluoxetine-treated subsample (n=49), intent-to-treat (ITT) response rates were 47% for C/C subjects and 46% for pooled C/T and T/T subjects (nonsignificant). ITT response rates were 38% for A/A subjects and 60% for A/G subjects (nonsignificant), with no subjects exhibiting the G/G homozygote. Mean baseline plasma B12 was significantly lower in A/G subjects compared to A/A, but folate and homocysteine levels were not affected by genetic status. Plasma folate was negatively associated with treatment response. Conclusion. The C677T and A2756G polymorphisms did not significantly affect antidepressant response. These preliminary findings require replication in larger samples. C1 [Mischoulon, David; Katz, Judith; Papakostas, George I.; Iosifescu, Dan V.; Yeung, Albert S.; Dording, Christina M.; Farabaugh, Amy H.; Clain, Alisabet J.; Baer, Lee; Alpert, Jonathan E.; Nierenberg, Andrew A.; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Mischoulon, David; Katz, Judith; Papakostas, George I.; Iosifescu, Dan V.; Yeung, Albert S.; Dording, Christina M.; Farabaugh, Amy H.; Clain, Alisabet J.; Baer, Lee; Alpert, Jonathan E.; Nierenberg, Andrew A.; Fava, Maurizio] Harvard Univ, Sch Med, Boston, MA USA. [Lamon-Fava, Stefania; Selhub, Jacob] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. RP Mischoulon, D (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM dmischoulon@partners.org RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X FU National Association for Research on Schizophrenia and Depression (NARSAD); NIMH [R10-MH56058]; State of New York; Nordic Naturals; Fisher Wallace; Bowman Family Foundation; Ganeden; Back Bay Scientific; AstraZeneca PLC; Bristol-Myers Squibb Company; Forest Pharmaceuticals; National Institute of Mental Health; PAMLAB LLC; Pfizer Inc.; Ridge Diagnostics; Aspect Medical Systems; Forest Laboratories; Janssen Pharmaceutica; Eli Lilly; Pamlab; Pfizer; American Society of Clinical Psychopharmacology; Australasian Society for Bipolar Disorder; Bayamon Region Psychiatric Society; San Juan; Belvoir Publishing; CRICO; Dartmouth; Dey Pharma; L. P./Mylan Inc.; Israel Society for Biological Psychiatry; John Hopkins University; National Association of Continuing Education; Physicians Postgraduate Press; Slack Publishing; University of Florida; Alkermes; Astra-Zeneca; BioResearch; BrainCells, Inc.; Cephalon; Clinical Trial Solutions, LLC; Eli Lilly Company; EnVivo Pharmaceuticals, Inc.; Forest Pharmaceuticals Inc.; GlaxoSmithKline; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; NARSAD; NCCAM; NIDA; Novartis; Organon Inc.; PamLab, LLC; Pfizer Inc; Pharmavite; Roche; Sanofi-Aventis; Shire; Solvay Pharmaceuticals, Inc.; Synthelabo; Wyeth-Ayerst Laboratories FX Dr. David Mischoulon was supported in this investigation by a Young Investigator Award from the National Association for Research on Schizophrenia and Depression (NARSAD).; The fluoxetine parent study was supported by NIMH grant R10-MH56058 to Dr. Patrick McGrath and by infrastructure and salary support from the State of New York. The authors thank Dr. McGrath and his colleagues at Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York.; Dr. David Mischoulon has received research support from Nordic Naturals, Fisher Wallace, the Bowman Family Foundation, and Ganeden. He has served as a consultant to Bristol-Meyers-Squibb Company. He has received writing honoraria from Pamlab and Nordic Naturals and speaking honoraria from Nordic Naturals. He has received royalties from Back Bay Scientific for PMS Escape, and royalties from Lippincott Williams & Wilkins, for textbook "Natural Medications for Psychiatric Disorders: Considering the Alternatives'' (David Mischoulon and Jerrold F Rosenbaum, Eds.).; Dr. George Papakostas has served as a consultant for Abbott Laboratories, AstraZeneca PLC, Brainsway Ltd, Bristol-Myers Squibb Company, Cephalon Inc., Dey Pharma, L. P., Eli Lilly Co., GlaxoSmithKline, Evotec AG, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, Otsuka Pharmaceuticals, PAMLAB LLC, Pfizer Inc., Pierre Fabre Laboratories, Ridge Diagnostics (formerly known as Precision Human Biolaboratories), Shire Pharmaceuticals, Takeda Pharmaceutical Company LTD, Theracos, Inc., and Wyeth, Inc. He has received honoraria from Abbott Laboratories, Astra Zeneca PLC, Bristol-Myers Squibb Company, Brainsway Ltd, Cephalon Inc., Dey Pharma, L. P., Eli Lilly Co., Evotec AG, GlaxoSmithKline, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, Lundbeck, Otsuka Pharmaceuticals, PAMLAB LLC, Pfizer, Pierre Fabre Laboratories, Ridge Diagnostics, Shire Pharmaceuticals, Takeda Pharmaceutical Company LTD, Theracos, Inc., Titan Pharmaceuticals, and Wyeth Inc. He has received research support from AstraZeneca PLC, Bristol-Myers Squibb Company, Forest Pharmaceuticals, the National Institute of Mental Health, PAMLAB LLC, Pfizer Inc., and Ridge Diagnostics (formerly known as Precision Human Biolaboratories). He has served (not currently) on the speaker's bureau for BristolMyersSquibb Co and Pfizer, Inc.; Dr. Daniel Iosifescu has received research support from Aspect Medical Systems, Forest Laboratories and Janssen Pharmaceutica; he has been a consultant for Forest Laboratories, Gerson Lehrman Group and Pfizer, Inc., and he has been a speaker for Cephalon, Inc., Eli Lilly & Co., Forest Laboratories, and Pfizer, Inc.; Dr. Jonathan Alpert has received research support from Aspect Medical Systems, Eli Lilly, Pamlab, and Pfizer; he has received speaker's honoraria from Reed Medical Education and Belvoir Publishing.; Dr. Andrew Nierenberg has received honoraria or travel expenses from: American Society of Clinical Psychopharmacology, Australasian Society for Bipolar Disorder, Bayamon Region Psychiatric Society, San Juan, Puerto Rico, Belvoir Publishing, CRICO, Dartmouth, Dey Pharma, L. P./Mylan Inc., Israel Society for Biological Psychiatry, John Hopkins University, National Association of Continuing Education, Physicians Postgraduate Press, Slack Publishing, University of Florida, University of Michigan, University of Miami, Wolters Klower Publishing. Dr. Nierenberg owns stock options in Appliance Computing, Inc. (MindSite.com) and Brain Cells, Inc. Additional income is possible from Infomedic.com depending on overall revenues of the company but no revenue has been received to date. Through MGH, Dr. Nierenberg is named for copyrights to: the Clinical Positive Affect Scale and the MGH Structured Clinical Interview for the Montgomery Asberg Depression Scale exclusively licensed to the MGH Clinical Trials Network and Institute (CTNI).; Dr. Maurizio Fava has received research support from Abbott Laboratories, Alkermes, Aspect Medical Systems, Astra-Zeneca, BioResearch, BrainCells, Inc., Bristol-Myers Squibb Company, Cephalon, Clinical Trial Solutions, LLC, Eli Lilly & Company, EnVivo Pharmaceuticals, Inc., Forest Pharmaceuticals Inc., Ganeden, GlaxoSmithKline, J & J Pharmaceuticals, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, NARSAD, NCCAM, NIDA, NIMH, Novartis, Organon Inc., PamLab, LLC, Pfizer Inc, Pharmavite, Roche, Sanofi-Aventis, Shire, Solvay Pharmaceuticals, Inc., Synthelabo, and Wyeth-Ayerst Laboratories. He has served as an advisor and consultant to Abbott Laboratories, Affectis Pharmaceuticals AG, Amarin, Aspect Medical Systems, Astra-Zeneca, Auspex Pharmaceuticals, Bayer AG, Best Practice Project Management, Inc, BioMarin Pharmaceuticals, Inc., Biovail Pharmaceuticals, Inc., BrainCells, Inc, Bristol-Myers Squibb Company, Cephalon, Clinical Trials Solutions, LLC, CNS Response, Compellis, Cypress Pharmaceuticals, Dov Pharmaceuticals, Eisai, Inc., Eli Lilly & Company, EPIX Pharmaceuticals, Euthymics Bioscience, Inc., Fabre-Kramer, Pharmaceuticals, Inc., Forest Pharmaceuticals Inc., GlaxoSmithKline, Grunenthal GmBH, Janssen Pharmaceutica, Jazz Pharmaceuticals, J & J Pharmaceuticals, Knoll Pharmaceutical Company, Labopharm, Lorex Pharmaceuticals, Lundbeck, MedAvante Inc., Merck, Methylation Sciences, Neuronetics, Novartis, Nutrition 21, Organon Inc., PamLab, LLC, Pfizer Inc, PharmaStar, Pharmavite, Precision Human Biolaboratory, Prexa Pharmaceuticals, Inc., PsychoGenics, Psylin Neurosciences, Inc., Ridge Diagnostics, Inc., Roche, Sanofi-Aventis, Sepracor, Schering-Plough, Solvay Pharmaceuticals, Inc., Somaxon, Somerset Pharmaceuticals, Synthelabo, Takeda, Tetragenex, TransForm Pharmaceuticals, Inc., Transcept Pharmaceuticals, Vanda Pharmaceuticals Inc, Wyeth-Ayerst Laboratories. He has received speaking and publishing honoraria from Adamed, Co., Advanced Meeting Partners, American Psychiatric Association, American Society of Clinical Psychopharmacology, Astra-Zeneca, Belvoir, Boehringer-Ingelheim, Bristol-Myers Squibb Company, Cephalon, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithKline, Imedex, Novartis, Organon Inc., Pfizer Inc, PharmaStar, MGH Psychiatry Academy/Primedia, MGH Psychiatry Academy/Reed-Elsevier, UBC, and Wyeth-Ayerst Laboratories. He holds equity in Compellis. He currently holds a patent for SPCD and a patent application for a combination of azapirones and bupropion in MDD, and has received copyright royalties for the MGH CPFQ, SFI, ATRQ, DESS, and SAFER diagnostic instruments. NR 59 TC 5 Z9 6 U1 1 U2 12 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD JUN PY 2012 VL 17 IS 2 BP 76 EP 86 DI 10.1017/S1092852912000430 PG 11 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 967LL UT WOS:000305909200003 PM 22789065 ER PT J AU Kristinsson, SY Tang, M Pfeiffer, RM Bjorkholm, M Goldin, LR Blimark, C Mellqvist, UH Wahlin, A Turesson, I Landgren, O AF Kristinsson, Sigurdur Y. Tang, Min Pfeiffer, Ruth M. Bjorkholm, Magnus Goldin, Lynn R. Blimark, Cecilie Mellqvist, Ulf-Henrik Wahlin, Anders Turesson, Ingemar Landgren, Ola TI Monoclonal gammopathy of undetermined significance and risk of infections: a population-based study SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE monoclonal gammopathy of undetermined significance; infections; multiple myeloma; bacteria; virus ID MULTIPLE-MYELOMA; SIGNIFICANCE MGUS; LYMPHOCYTES; THROMBOSIS AB No comprehensive evaluation has been made to assess the risk of viral and bacterial infections among patients with monoclonal gammopathy of undetermined significance. Using population-based data from Sweden, we estimated risk of infections among 5,326 monoclonal gammopathy of undetermined significance patients compared to 20,161 matched controls. Patients with monoclonal gammopathy of undetermined significance had a 2-fold increased risk (P < 0.05) of developing any infection at 5- and 10-year follow up. More specifically, patients with monoclonal gammopathy of undetermined significance had an increased risk (P < 0.05) of bacterial (pneumonia, osteomyelitis, septicemia, pyelonephritis, cellulitis, endocarditis, and meningitis), and viral (influenza and herpes zoster) infections. Patients with monoclonal gammopathy of undetermined significance with M-protein concentrations over 2.5 g/dL at diagnosis had highest risks of infections. However, the risk was also increased (P < 0.05) among those with concentrations below 0.5 g/dL. Patients with monoclonal gammopathy of undetermined significance who developed infections had no excess risk of developing multiple myeloma, Waldenstrom macroglobulinemia or related malignancy. Our findings provide novel insights into the mechanisms behind infections in patients with plasma cell dyscrasias, and may have clinical implications. C1 [Kristinsson, Sigurdur Y.; Bjorkholm, Magnus; Landgren, Ola] Karolinska Univ Hosp Solna, Div Hematol, Dept Med, SE-17176 Stockholm, Sweden. [Kristinsson, Sigurdur Y.; Bjorkholm, Magnus; Landgren, Ola] Karolinska Inst, Stockholm, Sweden. [Tang, Min] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Tang, Min] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Pfeiffer, Ruth M.; Goldin, Lynn R.; Landgren, Ola] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Blimark, Cecilie; Mellqvist, Ulf-Henrik] Sahlgrens Univ Hosp, Sect Hematol & Coagulat, Dept Med, Gothenburg, Sweden. [Wahlin, Anders] Umea Univ, Dept Radiat Sci, Umea, Sweden. [Turesson, Ingemar] Skane Univ Hosp, Dept Hematol, Malmo, Sweden. [Landgren, Ola] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kristinsson, SY (reprint author), Karolinska Univ Hosp Solna, Div Hematol, Dept Med, SE-17176 Stockholm, Sweden. EM sigurdur.kristinsson@karolinska.se RI Wahlin, Anders/F-6043-2013; Kristinsson, Sigurdur /M-2910-2015 OI Wahlin, Anders/0000-0001-6402-0463; Kristinsson, Sigurdur /0000-0002-4964-7476 FU Stockholm County Council; Karolinska Institutet; Cancer Society in Stockholm; NIH, NCI FX this research was supported by grants from the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, the Cancer Society in Stockholm, and the Intramural Research Program of the NIH, NCI. NR 24 TC 16 Z9 16 U1 1 U2 3 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2012 VL 97 IS 6 BP 854 EP 858 DI 10.3324/haematol.2011.054015 PG 5 WC Hematology SC Hematology GA 969PA UT WOS:000306066500014 PM 22180421 ER PT J AU Tan, TC Sindone, AP Denniss, AR AF Tan, Timothy C. Sindone, Andrew P. Denniss, A. Robert TI Cardiac Electronic Implantable Devices in the Treatment of Heart Failure SO HEART LUNG AND CIRCULATION LA English DT Article DE Heart failure; Device therapy; Implantable cardiac defibrillators; ICD; Cardiac resynchronisation therapy; CRT ID VENTRICULAR ASSIST DEVICE; BUNDLE-BRANCH-BLOCK; NONISCHEMIC DILATED CARDIOMYOPATHY; INTRAVENTRICULAR-CONDUCTION DELAY; PERCUTANEOUS CORONARY INTERVENTION; RANDOMIZED CONTROLLED-TRIALS; ANTIARRHYTHMIC-DRUG THERAPY; ACUTE MYOCARDIAL-INFARCTION; RESYNCHRONIZATION THERAPY; CARDIOVERTER-DEFIBRILLATOR AB Heart failure is a condition which has an increasing incidence as the population ages, leading to increasing prevalence globally and in Australia. This condition also carries very high morbidity and mortality rates, attributed in part to electrical conduction disturbances which lead to sudden cardiac death or pathophysiological cardiac changes due to delayed activation of the left free wall and mechanical dyssynchrony. Current pharmacologic therapy has made impressive advances in improving survival rates in this population, but morbidity and mortality rates still remain high. Additionally, there is also a population of heart failure patients on optimal medical therapy who still suffer from functionally debilitating symptoms of heart failure. Device therapy comprising of implantable cardioverter-defibrillator (ICD) and cardiac resynchronisation therapy (CRT) are used to treat heart rhythm disturbances in a broad range of patients with heart disease and have now become established therapies in patients with heart failure receiving standard medical therapy. This review examines current evidence for the use of implantable cardioverter-defibrillators in the reduction of sudden cardiac death in patients with advanced systolic dysfunction and the use of cardiac resynchronisation therapy in improving ventricular performance as well as mortality and morbidity rates. (Heart, Lung and Circulation 2012;21:338-351) Crown Copyright (C) 2012 Published by Elsevier Inc. on behalf of Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved. C1 [Tan, Timothy C.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Tan, Timothy C.; Denniss, A. Robert] Westmead Hosp, Dept Cardiol, Westmead, NSW 2145, Australia. [Sindone, Andrew P.] Concord Repatriat Gen Hosp, Heart Failure Unit, Concord, NSW 2139, Australia. [Sindone, Andrew P.] Concord Repatriat Gen Hosp, Dept Cardiac Rehabil, Concord, NSW 2139, Australia. [Denniss, A. Robert] Blacktown Hosp, Dept Cardiol, Blacktown, NSW 2148, Australia. RP Tan, TC (reprint author), Massachusetts Gen Hosp, Dept Cardiol, 55 Fruit St,Yawkey 5E, Boston, MA 02114 USA. EM tctan@partners.org NR 126 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1443-9506 J9 HEART LUNG CIRC JI Heart Lung Circ. PD JUN-JUL PY 2012 VL 21 IS 6-7 SI SI BP 338 EP 351 DI 10.1016/j.hlc.2012.03.124 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 967AB UT WOS:000305877400005 PM 22682103 ER PT J AU Heckman, CJ Darlow, S Cohen-Filipic, J Kloss, JD Manne, SL Munshi, T Perlis, CS AF Heckman, Carolyn J. Darlow, Susan Cohen-Filipic, Jessye Kloss, Jacqueline D. Manne, Sharon L. Munshi, Teja Perlis, Clifford S. TI Psychosocial Correlates of Sunburn among Young Adult Women SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Article DE sunburn; young adult women; psychosocial correlates; sunscreen; Health Beliefs Model; skin cancer prevention ID SUN PROTECTION PRACTICES; INDOOR TANNING BEHAVIORS; SKIN-CANCER; SUNSCREEN USE; MALIGNANT-MELANOMA; HEALTH BELIEFS; ATTITUDES; ADOLESCENTS; STUDENTS; NORMS AB Skin cancer is an increasingly common disease, particularly among young adult women. Sunburn early in life is a risk factor for skin cancer. Few studies have reported on psychosocial correlates of sunburn. The current study consisted of an online survey of undergraduate women from a university in the northeastern part of the USA. A logistic regression demonstrated that young women who reported a history of four or more sunburns were significantly more likely to report fair skin, higher perceived susceptibility to skin cancer, greater perceived benefits of tanning (e.g., appearance enhancement), lower perceived control over skin protection, and more frequent sunscreen use. Sunbathing was not associated with a greater number of sunburns. These results suggest that young women who sunburn more often possess other skin cancer risk factors, are aware of their susceptibility to skin cancer, and try to use sunscreen, but feel limited control over their skin protection behavior and are not less likely to sunbathe than others. Therefore, interventions are needed to assist high risk young women in asserting more control over their sun protection behavior and perhaps improve the effectiveness of the sunscreen or other skin protection methods they do employ. C1 [Heckman, Carolyn J.; Darlow, Susan; Munshi, Teja; Perlis, Clifford S.] Fox Chase Canc Ctr, Canc Prevent & Control Program, Philadelphia, PA 19111 USA. [Cohen-Filipic, Jessye] Portland VA Med Ctr, Portland, OR 97239 USA. [Kloss, Jacqueline D.] Drexel Univ, Dept Psychol, Philadelphia, PA 19104 USA. [Manne, Sharon L.] Canc Inst New Jersey, Canc Prevent & Control Program, New Brunswick, NJ 08901 USA. RP Heckman, CJ (reprint author), Fox Chase Canc Ctr, Canc Prevent & Control Program, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM Carolyn.Heckman@fccc.edu; susan.darlow@fccc.edu; jessyecohen@gmail.com; jdk29@drexel.edu; mannesl@umdnj.edu; teja.munshi@fccc.edu; clifford.perlis@fccc.edu FU Cancer Center Grant [R03CA1504202, P30CA006927] FX This work was funded by R03CA1504202 (CH) and P30CA006927 (Cancer Center Grant). The authors would like to thank Jeanne Pomenti, BS for her technical assistance in the preparation of this manuscript and Sara Filseth, BA for her assistance with data collection. NR 48 TC 8 Z9 8 U1 0 U2 11 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1660-4601 J9 INT J ENV RES PUB HE JI Int. J. Environ. Res. Public Health PD JUN PY 2012 VL 9 IS 6 BP 2241 EP 2251 DI 10.3390/ijerph9062241 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 966AM UT WOS:000305808900016 PM 22829801 ER PT J AU Kozin, SV Duda, DG Munn, LL Jain, RK AF Kozin, Sergey V. Duda, Dan G. Munn, Lance L. Jain, Rakesh K. TI Neovascularization After Irradiation: What is the Source of Newly Formed Vessels in Recurring Tumors? SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID ENDOTHELIAL-CELL APOPTOSIS; STEM-LIKE CELLS; X-IRRADIATION; IONIZING-RADIATION; BLOOD-FLOW; VASCULAR CHANGES; STROMAL SENSITIVITY; CANCER-CELLS; ANGIOGENESIS; RADIOTHERAPY AB Local relapse of tumors after radiation therapy remains a challenge in oncology. To devise rational approaches for preventing this relapse, we have to improve our understanding of how new vessels form in previously irradiated tumors. We propose that tumor regrowth after local irradiation is dependent on blood vessel formation by local endothelial cells without the need for recruitment of endothelial precursor cells from distant nonirradiated tissues or bone marrow. We also suggest that infiltrating myeloid bone marrow-derived cells promote survival of local endothelial cells during the early period after irradiation and angiogenesis during the later stage of tumor regrowth, both via paracrine mechanisms. J Natl Cancer Inst 2012;104:899-905 C1 [Kozin, Sergey V.; Duda, Dan G.; Munn, Lance L.; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab, Boston, MA 02114 USA. [Kozin, Sergey V.; Duda, Dan G.; Munn, Lance L.; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab, 100 Blossom St,Cox 734, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NCI NIH HHS [R01 CA085140, R01 CA115767, R01 CA126642, R01 CA159258, R01-CA085140, P01 CA080124, R01-CA115767, R01-CA126642, R01-CA159258, T32 CA073479, T32-CA073479, P01-CA080124]; NHLBI NIH HHS [R01 HL106584] NR 71 TC 27 Z9 29 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD JUN PY 2012 VL 104 IS 12 BP 899 EP 905 DI 10.1093/jnci/djs239 PG 7 WC Oncology SC Oncology GA 969PL UT WOS:000306067700007 PM 22572994 ER PT J AU Atassi, N Nakano, I Mora, JS Drory, V Cudkowicz, M Shefner, J Chio, A Mitsumoto, H Silani, V Zinman, L Weber, M van den Berg, LH Robberecht, W Ronnevi, LO Hardiman, O Bruijn, L Kerr, D Williams, JR AF Atassi, N. Nakano, I. Mora, J. S. Drory, V. Cudkowicz, M. Shefner, J. Chio, A. Mitsumoto, H. Silani, V. Zinman, L. Weber, M. van den Berg, L. H. Robberecht, W. Ronnevi, L-O Hardiman, O. Bruijn, L. Kerr, D. Williams, J. R. TI Development of a "red flags'' symptom list to assist with early recognition and diagnosis of amyotrophic lateral sclerosis SO JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 22nd Meeting of the European-Neurological-Society CY JUN 09-12, 2012 CL Prague, CZECH REPUBLIC SP European Neurol Soc C1 Massachussetts Gen Hosp, Charlestown, MA USA. Jichi Med Univ, Togichi, Japan. Hosp Carlos III, Madrid, Spain. Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel. Upstate Med Univ, Syracuse, NY USA. Univ Turin, Turin, Italy. Columbia Univ, Med Ctr, New York, NY USA. Univ Milan, Sch Med, Milan, Italy. Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. Kantonsspital St Gallen, St Gallen, Switzerland. Univ Med Ctr Utrecht, Utrecht, Netherlands. Katholieke Univ Leuven Hosp, Louvain, Belgium. Karolinska Inst, Stockholm, Sweden. Trinity Coll Dublin, Dublin, Ireland. Beaumont Hosp, Dublin 9, Ireland. Biogen Idec Inc, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD JUN PY 2012 VL 259 SU 1 BP S52 EP S52 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 969TY UT WOS:000306083200138 ER PT J AU Bonmassar, G Lee, SW Freeman, DK Polasek, M Fried, SI Gale, JT AF Bonmassar, Giorgio Lee, Seung Woo Freeman, Daniel K. Polasek, Miloslav Fried, Shelley I. Gale, John T. TI Microscopic magnetic stimulation of neural tissue SO NATURE COMMUNICATIONS LA English DT Article ID DEEP BRAIN-STIMULATION; PARKINSONS-DISEASE; ELECTRIC-STIMULATION; RETINAL PROSTHESIS; ABSORPTION RATE; MOTOR CORTEX; IMPLANTS; PATTERNS; ISSUES; CELLS AB Electrical stimulation is currently used to treat a wide range of cardiovascular, sensory and neurological diseases. Despite its success, there are significant limitations to its application, including incompatibility with magnetic resonance imaging, limited control of electric fields and decreased performance associated with tissue inflammation. Magnetic stimulation overcomes these limitations but existing devices (that is, transcranial magnetic stimulation) are large, reducing their translation to chronic applications. In addition, existing devices are not effective for deeper, sub-cortical targets. Here we demonstrate that sub-millimeter coils can activate neuronal tissue. Interestingly, the results of both modelling and physiological experiments suggest that different spatial orientations of the coils relative to the neuronal tissue can be used to generate specific neural responses. These results raise the possibility that micro-magnetic stimulation coils, small enough to be implanted within the brain parenchyma, may prove to be an effective alternative to existing stimulation devices. C1 [Lee, Seung Woo; Freeman, Daniel K.; Fried, Shelley I.] Boston VA Healthcare Syst, Ctr Innovat Visual Rehabil, Boston, MA 02130 USA. [Bonmassar, Giorgio; Polasek, Miloslav] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Lee, Seung Woo; Freeman, Daniel K.; Fried, Shelley I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Gale, John T.] Cleveland Clin, Dept Neurosci, Cleveland, OH 44195 USA. [Gale, John T.] Cleveland Clin, Ctr Neurol Restorat, Neurol Inst, Cleveland, OH 44195 USA. [Gale, John T.] Case Western Reserve Univ, Sch Med, Cleveland Clin Lerner Coll Med, Cleveland, OH 44195 USA. RP Fried, SI (reprint author), Boston VA Healthcare Syst, Ctr Innovat Visual Rehabil, Boston, MA 02130 USA. EM Fried.Shelley@mgh.harvard.edu RI Polasek, Miloslav/G-5949-2014 FU Boston VA Healthcare System [MR 1I01RX000350-01A1]; National Eye Institute [1R21EY020961-01, R01EY019967]; National Institute of Biomedical Imaging and Bioengineering [R01EB006385]; National Center for Research Resources (NCRR) [P41-RR14075]; MIND institute; Center for Integration of Medicine and Innovative Technology (CIMIT) FX This work was supported in part by the Boston VA Healthcare System (MR 1I01RX000350-01A1), the National Eye Institute (1R21EY020961-01 & R01EY019967), the National Institute of Biomedical Imaging and Bioengineering (R01EB006385), the National Center for Research Resources (NCRR) (P41-RR14075), and by the MIND institute. We also acknowledge the support of the Center for Integration of Medicine and Innovative Technology (CIMIT). NR 41 TC 26 Z9 26 U1 2 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JUN PY 2012 VL 3 AR 921 DI 10.1038/ncomms1914 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 970AG UT WOS:000306099900048 PM 22735449 ER PT J AU Boucher, J Mori, MA Lee, KY Smyth, G Liew, CW Macotela, Y Rourk, M Bluher, M Russell, SJ Kahn, CR AF Boucher, Jeremie Mori, Marcelo A. Lee, Kevin Y. Smyth, Graham Liew, Chong Wee Macotela, Yazmin Rourk, Michael Bluher, Matthias Russell, Steven J. Kahn, C. Ronald TI Impaired thermogenesis and adipose tissue development in mice with fat-specific disruption of insulin and IGF-1 signalling SO NATURE COMMUNICATIONS LA English DT Article ID ACTIVATED RECEPTOR-GAMMA; GROWTH-FACTOR-I; ADIPOCYTE DIFFERENTIATION; ADAPTIVE THERMOGENESIS; GENE-EXPRESSION; ADULT HUMANS; C/EBP-BETA; OBESITY; COLD; RESISTANCE AB Insulin and insulin-like growth factor 1 (IGF-1) have important roles in adipocyte differentiation, glucose tolerance and insulin sensitivity. Here to assess how these pathways can compensate for each other, we created mice with a double tissue-specific knockout of insulin and IGF-1 receptors to eliminate all insulin/IGF-1 signalling in fat. These FIGIRKO mice had markedly decreased white and brown fat mass and were completely resistant to high fat diet-induced obesity and age-and high fat diet-induced glucose intolerance. Energy expenditure was increased in FIGIRKO mice despite a >85% reduction in brown fat mass. However, FIGIRKO mice were unable to maintain body temperature when placed at 4 degrees C. Brown fat activity was markedly decreased in FIGIRKO mice but was responsive to beta 3-receptor stimulation. Thus, insulin/IGF-1 signalling has a crucial role in the control of brown and white fat development, and, when disrupted, leads to defective thermogenesis and a paradoxical increase in basal metabolic rate. C1 [Boucher, Jeremie; Mori, Marcelo A.; Lee, Kevin Y.; Smyth, Graham; Liew, Chong Wee; Macotela, Yazmin; Rourk, Michael; Russell, Steven J.; Kahn, C. Ronald] Brigham & Womens Hosp, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA. [Boucher, Jeremie; Mori, Marcelo A.; Lee, Kevin Y.; Smyth, Graham; Liew, Chong Wee; Macotela, Yazmin; Rourk, Michael; Russell, Steven J.; Kahn, C. Ronald] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. [Boucher, Jeremie; Mori, Marcelo A.; Lee, Kevin Y.; Smyth, Graham; Liew, Chong Wee; Macotela, Yazmin; Rourk, Michael; Russell, Steven J.; Kahn, C. Ronald] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Bluher, Matthias] Univ Leipzig, Dept Med, D-04103 Leipzig, Germany. RP Kahn, CR (reprint author), Brigham & Womens Hosp, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu RI Smyth, Gordon/B-5276-2008 OI Smyth, Gordon/0000-0001-9221-2892 FU NIH [DK59637, DK31036, DK82659]; DERC [DK34834]; American Diabetes Association FX We thank K.C. Hayes and the staff of the Foster Biomedical Research Laboratory at Brandeis University for excellent care of the animals used in this study. We thank the Joslin Diabetes and Endocrinology Research Center Specialized assay (5P30 DK 36836) and Physiology cores, and the Longwood Small Animal Imaging Facility. We also thank Kate Ellacott and the staff of the Vanderbilt Mouse Metabolic Phenotyping Center for the energy expenditure studies. The Vanderbilt MMPC is supported by NIH Grant DK59637. This work was supported by NIH grants (DK31036 and DK82659), DERC grants (DK34834) and an American Diabetes Association mentor-based award. NR 40 TC 45 Z9 45 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JUN PY 2012 VL 3 AR 902 DI 10.1038/ncomms1905 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 970AG UT WOS:000306099900029 PM 22692545 ER PT J AU Lundby, A Secher, A Lage, K Nordsborg, NB Dmytriyev, A Lundby, C Olsen, JV AF Lundby, Alicia Secher, Anna Lage, Kasper Nordsborg, Nikolai B. Dmytriyev, Anatoliy Lundby, Carsten Olsen, Jesper V. TI Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues SO NATURE COMMUNICATIONS LA English DT Article ID TYROSINE PHOSPHORYLATION; SIGNALING NETWORKS; MASS-SPECTROMETRY; IN-VIVO; PHOSPHOPROTEOMICS; PROTEOMICS; CANCER; QUANTIFICATION; ACTIVATION; ENRICHMENT AB Deregulated cellular signalling is a common hallmark of disease, and delineating tissue phosphoproteomes is key to unravelling the underlying mechanisms. Here we present the broadest tissue catalogue of phosphoproteins to date, covering 31,480 phosphorylation sites on 7,280 proteins quantified across 14 rat organs and tissues. We provide the data set as an easily accessible resource via a web-based database, the CPR PTM Resource. A major fraction of the presented phosphorylation sites are tissue-specific and modulate protein interaction networks that are essential for the function of individual organs. For skeletal muscle, we find that phosphotyrosines are over-represented, which is mainly due to proteins involved in glycogenolysis and muscle contraction, a finding we validate in human skeletal muscle biopsies. Tyrosine phosphorylation is involved in both skeletal and cardiac muscle contraction, whereas glycogenolytic enzymes are tyrosine phosphorylated in skeletal muscle but not in the liver. The presented phosphoproteomic method is simple and rapid, making it applicable for screening of diseased tissue samples. C1 [Lundby, Alicia; Secher, Anna; Lage, Kasper; Dmytriyev, Anatoliy; Olsen, Jesper V.] Univ Copenhagen, NNF Ctr Prot Res, Fac Hlth Sci, DK-2200 Copenhagen, Denmark. [Lundby, Alicia] Univ Copenhagen, Dept Biomed Sci, Danish Natl Res Fdn Ctr Cardiac Arrhythmia, DK-2100 Copenhagen, Denmark. [Secher, Anna] Novo Nordisk AS, DK-2760 Malov, Denmark. [Lage, Kasper] Massachusetts Gen Hosp, Pediat Surg Res Lab, Boston, MA 02114 USA. [Lage, Kasper] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Lage, Kasper] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Nordsborg, Nikolai B.] Univ Copenhagen, Dept Exercise & Sport Sci, DK-2100 Copenhagen, Denmark. [Lundby, Carsten] Univ Zurich, Dept Physiol, Zurich Ctr Integrat Human Physiol, CH-8057 Zurich, Switzerland. RP Olsen, JV (reprint author), Univ Copenhagen, NNF Ctr Prot Res, Fac Hlth Sci, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark. EM Jesper.Olsen@cpr.ku.dk RI Lundby, Alicia/H-3322-2013; OI Lundby, Alicia/0000-0002-1612-6041; Olsen, Jesper/0000-0002-4747-4938 FU Novo Nordisk Foundation; European Union [262067-PRIME-XS]; Danish Council for Independent Research for Medical Sciences FX We thank all members of the Department for Proteomics at the Center for Protein Research for fruitful discussions and inputs to the manuscript. We are especially grateful to Dr. Omid Hekmat for help with the method optimization, Professor Lars J. Jensen for input on the data analysis and Christian Kelstrup for help with data visualization. The Center for Protein Research is partly supported by a generous donation from the Novo Nordisk Foundation. This work was supported by the 7th framework programme of the European Union (Contract no. 262067-PRIME-XS) and the research career programme Sapere Aude from The Danish Council for Independent Research for Medical Sciences (A.L. and J.V.O.). NR 54 TC 102 Z9 1802 U1 11 U2 50 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JUN PY 2012 VL 3 AR 876 DI 10.1038/ncomms1871 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 970AG UT WOS:000306099900003 PM 22673903 ER PT J AU Kret, ME De Gelder, B AF Kret, M. E. De Gelder, B. TI A review on sex differences in processing emotional signals SO NEUROPSYCHOLOGIA LA English DT Review DE Emotion; Sex differences; Brain; Evolution; Social psychology ID CEREBRAL-BLOOD-FLOW; CENTRAL-NERVOUS-SYSTEM; THREATENING FACIAL EXPRESSIONS; GENDER-DIFFERENCES; TURNER-SYNDROME; HUMAN BRAIN; HEMISPHERIC LATERALIZATION; RECOGNITION DEFICITS; AMYGDALA ACTIVATION; VISUAL-STIMULATION AB Interest in sex-related differences in psychological functioning has again come to the foreground with new findings about their possible functional basis in the brain. Sex differences may be one way how evolution has capitalized on the capacity of homologous brain regions to process social information between men and women differently. This paper focuses specifically on the effects of emotional valence, sex of the observed and sex of the observer on regional brain activations. We also discuss the effects of and interactions between environment, hormones, genes and structural differences of the brain in the context of differential brain activity patterns between men and women following exposure to seen expressions of emotion and in this context we outline a number of methodological considerations for future research. Importantly, results show that although women are better at recognizing emotions and express themselves more easily, men show greater responses to threatening cues (dominant, violent or aggressive) and this may reflect different behavioral response tendencies between men and women as well as evolutionary effects. We conclude that sex differences must not be ignored in affective research and more specifically in affective neuroscience. (C) 2012 Published by Elsevier Ltd. C1 [Kret, M. E.; De Gelder, B.] Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. [De Gelder, B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP De Gelder, B (reprint author), Postbus 90153, NL-5000 LE Tilburg, Netherlands. EM degelder@nmr.mgh.harvard.edu RI Kret, Mariska/B-4798-2010 FU Human Frontiers Science Program [RGP54/2004]; NWO Nederlandse Organisatie voor Wetenschappelijk Onderzoek [400.04081]; EU [FP6-NEST-COBOL043403, FP7 TANGO] FX We thank the two anonymous reviewers for thoroughly reading the manuscript and providing thoughtful comments. We are grateful to Arik Cheshin for his comments and to Uludag Kamil for the interesting discussion on possibly confounding factors in the BOLD response. This study was supported by Human Frontiers Science Program RGP54/2004, NWO Nederlandse Organisatie voor Wetenschappelijk Onderzoek 400.04081 to BdG, and EU FP6-NEST-COBOL043403 and FP7 TANGO to BdG. NR 164 TC 87 Z9 90 U1 16 U2 131 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD JUN PY 2012 VL 50 IS 7 BP 1211 EP 1221 DI 10.1016/j.neuropsychologia.2011.12.022 PG 11 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 966RQ UT WOS:000305855500001 PM 22245006 ER PT J AU Munhall, AC Wu, YN Belknap, JK Meshul, CK Johnson, SW AF Munhall, Adam C. Wu, Yan-Na Belknap, John K. Meshul, Charles K. Johnson, Steven W. TI NMDA alters rotenone toxicity in rat substantia nigra zona compacta and ventral tegmental area dopamine neurons SO NEUROTOXICOLOGY LA English DT Article DE Dendrite; Histology; N-methyl-D-aspartate; Rotenone; Substantia nigra; Ventral tegmental area ID PARKINSONS-DISEASE; NEUROTROPHIC FACTOR; COMPLEX-I; RECEPTOR CHANNELS; BRAIN SLICES; CELL-DEATH; NEUROPROTECTION; CURRENTS; DEGENERATION; STIMULATION AB Previous patch-clamp studies by our laboratory showed that acute exposure to the pesticide rotenone augments inward currents evoked by N-methyl-D-aspartate (NMDA) in substantia nigra zona compacta (SNC) dopamine neurons in slices of rat brain. The present experiments were done to search for histological evidence of increased neurotoxicity produced by combined rotenone and NMDA treatments. In horizontal slices of rat midbrain, we found that a 30 min superfusion with 100 nM rotenone caused significant injury to tyrosine hydroxylase (TH)-positive proximal dendrites in dorsal and ventral regions of the SNC and ventral tegmental area (VTA). Moreover, treatment with 100 mu M NMDA potentiated rotenone toxicity. In contrast, treatment with 30 mu M NMDA protected against rotenone-induced injury to dendrites in the ventral SNC and ventral VTA. Interestingly, treatment with 30 mu M NMDA-alone produced an apparent increase in proximal dendrite scores in ventral SNC and dorsal VTA. We conclude that NMDA has concentration-dependent actions on rotenone toxicity that differ according to regional subtype of dopamine neuron. Published by Elsevier Inc. C1 [Johnson, Steven W.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Neurol, Portland, OR 97239 USA. [Belknap, John K.; Meshul, Charles K.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. [Belknap, John K.; Meshul, Charles K.; Johnson, Steven W.] Vet Affairs Med Ctr, Portland, OR 97207 USA. RP Johnson, SW (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Neurol, R&D-61,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM johnsost@ohsu.edu FU Department of Veterans Affairs; American Parkinson's Disease Association; Portland Veterans Affairs Parkinson's Disease Research, Education, and Clinical Center FX This research was supported by Department of Veterans Affairs Merit Review grants (SWJ and CKM), a grant from the American Parkinson's Disease Association (SWJ), and by the Portland Veterans Affairs Parkinson's Disease Research, Education, and Clinical Center (SWJ). NR 37 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD JUN PY 2012 VL 33 IS 3 BP 429 EP 435 DI 10.1016/j.neuro.2012.04.006 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 951OO UT WOS:000304730100019 PM 22521663 ER PT J AU Kawada, M Seno, H Kanda, K Nakanishi, Y Akitake, R Komekado, H Kawada, K Sakai, Y Mizoguchi, E Chiba, T AF Kawada, M. Seno, H. Kanda, K. Nakanishi, Y. Akitake, R. Komekado, H. Kawada, K. Sakai, Y. Mizoguchi, E. Chiba, T. TI Chitinase 3-like 1 promotes macrophage recruitment and angiogenesis in colorectal cancer SO ONCOGENE LA English DT Article DE chitinase; tumor; microenvironment; chemokine; MAPK ID COLONIC EPITHELIAL-CELLS; SMOOTH-MUSCLE-CELLS; TUMOR ANGIOGENESIS; BACTERIAL ADHESION; ENDOTHELIAL-CELLS; SERUM YKL-40; PROTEIN; CHEMOKINES; INFLAMMATION; CLASSIFICATION AB Chitinase 3-like 1 (CHI3L1), one of the mammalian members of the chitinase family, is expressed in several types of human cancer, and elevated serum level of CHI3L1 is suggested to be a biomarker of poor prognosis in advanced cancer patients. However, the overall biological function of CHI3L1 in human cancers still remains unknown. Studies were performed to characterize the role of CHI3L1 in cancer pathophysiology utilizing human colorectal cancer samples and human cell lines. Plasma protein and tissue mRNA expression levels of CHI3L1 in colorectal cancer were strongly upregulated. Immunohistochemical analysis showed that CHI3L1 was expressed in cancer cells, and CHI3L1 expression had a significant association with the number of infiltrated macrophages and microvessel density (MVD). By utilizing transwell migration and tube-formation assays, overexpression of CHI3L1 in SW480 cells (human colon cancer cells) enhanced the migration of THP-1 cells (human macrophage cells) and HUVECs (human endothelial cells), and the tube formation of HUVECs. The knockdown of CHI3L1 by RNA interference or the neutralization of CHI3L1 by anti-CHI3L1 antibody displayed strong suppression of CHI3L1-induced migration and tube formation. Cell proliferation assay showed that CHI3L1 overexpression significantly enhanced the proliferation of SW480 cells. Enzyme-linked immunosorbent assay (ELISA) analysis showed that CHI3L1 increased the secretion of inflammatory chemokines, IL-8 and monocyte chemoattractant protein-1 (MCP-1), from SW480 cells through mitogen-activated protein kinase (MAPK) signaling pathway. Both neutralization of IL-8 or MCP-1 and inhibition or knockdown of MAPK in SW480 cells significantly inhibited CHI3L1-induced migration and tube formation. In a xenograft mouse model, overexpression of CHI3L1 in HCT116 cells (human colon cancer cells) enhanced the tumor growth as well as macrophage infiltration and MVD. In conclusion, CHI3L1 expressed in colon cancer cells promotes cancer cell proliferation, macrophage recruitment and angiogenesis. Thus, the inhibition of CHI3L1 activity may be a novel therapeutic strategy for human colorectal cancer. Oncogene (2012) 31, 3111-3123; doi:10.1038/onc.2011.498; published online 7 November 2011 C1 [Kawada, M.; Seno, H.] Kyoto Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, Sakyo Ku, Shogoin, Kyoto 6068507, Japan. [Kawada, M.] Japan Soc Promot Sci JSPS, Tokyo, Japan. [Kawada, K.; Sakai, Y.] Kyoto Univ, Grad Sch Med, Dept Surg, Kyoto, Japan. [Mizoguchi, E.] Harvard Univ, Sch Med, Dept Med, Gastrointestinal Unit, Boston, MA USA. [Mizoguchi, E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. RP Kawada, M (reprint author), Kyoto Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, Sakyo Ku, 54 Kawahara Cho, Shogoin, Kyoto 6068507, Japan. EM kawadam@kuhp.kyoto-u.ac.jp; seno@kuhp.kyoto-u.ac.jp FU Japan Society for the Promotion of Science (JSPS) [20790493, 21-40033, 23590937, 21229009]; Ministry of Health, Labor and Welfare, Japan; National Institutes of Health in USA [R01DK80070]; Research Foundation of Translational Research Center, Kyoto University FX This work was supported by Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research (20790493, 21-40033, 23590937, 21229009), and Health and Labor Science Research Grants for Research on Intractable Diseases, and Research on Hepatitis from the Ministry of Health, Labor and Welfare, Japan, and Research Foundation of Translational Research Center, Kyoto University and by a research grant (R01DK80070) from the National Institutes of Health in USA. NR 34 TC 51 Z9 54 U1 1 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN PY 2012 VL 31 IS 26 BP 3111 EP 3123 DI 10.1038/onc.2011.498 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 967UX UT WOS:000305934400001 PM 22056877 ER PT J AU Abubucker, S Segata, N Goll, J Schubert, AM Izard, J Cantarel, BL Rodriguez-Mueller, B Zucker, J Thiagarajan, M Henrissat, B White, O Kelley, ST Methe, B Schloss, PD Gevers, D Mitreva, M Huttenhower, C AF Abubucker, Sahar Segata, Nicola Goll, Johannes Schubert, Alyxandria M. Izard, Jacques Cantarel, Brandi L. Rodriguez-Mueller, Beltran Zucker, Jeremy Thiagarajan, Mathangi Henrissat, Bernard White, Owen Kelley, Scott T. Methe, Barbara Schloss, Patrick D. Gevers, Dirk Mitreva, Makedonka Huttenhower, Curtis TI Metabolic Reconstruction for Metagenomic Data and Its Application to the Human Microbiome SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID ASSESSING FUNCTIONAL DIVERSITY; GUT MICROBIOME; BETA-GLUCURONIDASE; HUMAN INTESTINE; DISEASE; GENE; BACTERIA; GLYCOSAMINOGLYCANS; EXPRESSION; HEPARANASE AB Microbial communities carry out the majority of the biochemical activity on the planet, and they play integral roles in processes including metabolism and immune homeostasis in the human microbiome. Shotgun sequencing of such communities' metagenomes provides information complementary to organismal abundances from taxonomic markers, but the resulting data typically comprise short reads from hundreds of different organisms and are at best challenging to assemble comparably to single-organism genomes. Here, we describe an alternative approach to infer the functional and metabolic potential of a microbial community metagenome. We determined the gene families and pathways present or absent within a community, as well as their relative abundances, directly from short sequence reads. We validated this methodology using a collection of synthetic metagenomes, recovering the presence and abundance both of large pathways and of small functional modules with high accuracy. We subsequently applied this method, HUMAnN, to the microbial communities of 649 metagenomes drawn from seven primary body sites on 102 individuals as part of the Human Microbiome Project (HMP). This provided a means to compare functional diversity and organismal ecology in the human microbiome, and we determined a core of 24 ubiquitously present modules. Core pathways were often implemented by different enzyme families within different body sites, and 168 functional modules and 196 metabolic pathways varied in metagenomic abundance specifically to one or more niches within the microbiome. These included glycosaminoglycan degradation in the gut, as well as phosphate and amino acid transport linked to host phenotype (vaginal pH) in the posterior fornix. An implementation of our methodology is available at http://huttenhower.sph.harvard.edu/humann. This provides a means to accurately and efficiently characterize microbial metabolic pathways and functional modules directly from high-throughput sequencing reads, enabling the determination of community roles in the HMP cohort and in future metagenomic studies. C1 [Abubucker, Sahar; Mitreva, Makedonka] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63130 USA. [Segata, Nicola; Huttenhower, Curtis] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Goll, Johannes; Thiagarajan, Mathangi; Methe, Barbara] J Craig Venter Inst, Rockville, MD USA. [Schubert, Alyxandria M.; Schloss, Patrick D.] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. [Izard, Jacques] Forsyth Inst, Dept Mol Genet, Cambridge, MA USA. [Izard, Jacques; Rodriguez-Mueller, Beltran] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Cantarel, Brandi L.; White, Owen] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. [Zucker, Jeremy; Gevers, Dirk; Huttenhower, Curtis] Broad Inst MIT & Harvard, Cambridge, MA USA. [Henrissat, Bernard] Univ Aix Marseille 2, UMR CNRS 6098, Marseille, France. [Kelley, Scott T.] San Diego State Univ, Dept Biol, San Diego, CA 92182 USA. RP Abubucker, S (reprint author), Washington Univ, Sch Med, Genome Inst, St Louis, MO 63130 USA. EM chuttenh@hsph.harvard.edu RI Henrissat, Bernard/J-2475-2012; Zucker, Jeremy/M-3643-2016; OI Zucker, Jeremy/0000-0002-7276-9009; Izard, Jacques/0000-0002-5904-5436; Schloss, Patrick/0000-0002-6935-4275; Huttenhower, Curtis/0000-0002-1110-0096; Segata, Nicola/0000-0002-1583-5794 FU NIH [U54HG004968, CA139193, DE017106, 5R01HG005975, U54HG004969, 1R01HG005969]; University of Michigan FX This work was supported in part by grants NIH U54HG004968 (George Weinstock), University of Michigan Rackham Graduate Student Research Grant (AMS), NIH CA139193 and DE017106 (JI), NIH 5R01HG005975 (PDS), NIH U54HG004969 (DG), and NIH 1R01HG005969 (CH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 72 TC 222 Z9 224 U1 9 U2 56 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD JUN PY 2012 VL 8 IS 6 AR e1002358 DI 10.1371/journal.pcbi.1002358 PG 17 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 968GM UT WOS:000305965300001 PM 22719234 ER PT J AU Gulbahce, N Yan, H Dricot, A Padi, M Byrdsong, D Franchi, R Lee, DS Rozenblatt-Rosen, O Mar, JC Calderwood, MA Baldwin, A Zhao, B Santhanam, B Braun, P Simonis, N Huh, KW Hellner, K Grace, M Chen, A Rubio, R Marto, JA Christakis, NA Kieff, E Roth, FP Roecklein-Canfield, J DeCaprio, JA Cusick, ME Quackenbush, J Hill, DE Munger, K Vidal, M Barabasi, AL AF Gulbahce, Natali Yan, Han Dricot, Amelie Padi, Megha Byrdsong, Danielle Franchi, Rachel Lee, Deok-Sun Rozenblatt-Rosen, Orit Mar, Jessica C. Calderwood, Michael A. Baldwin, Amy Zhao, Bo Santhanam, Balaji Braun, Pascal Simonis, Nicolas Huh, Kyung-Won Hellner, Karin Grace, Miranda Chen, Alyce Rubio, Renee Marto, Jarrod A. Christakis, Nicholas A. Kieff, Elliott Roth, Frederick P. Roecklein-Canfield, Jennifer DeCaprio, James A. Cusick, Michael E. Quackenbush, John Hill, David E. Muenger, Karl Vidal, Marc Barabasi, Albert-Laszlo TI Viral Perturbations of Host Networks Reflect Disease Etiology SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; PROTEIN INTERACTION NETWORK; TYPE-16 E7 ONCOPROTEIN; HUMAN-PAPILLOMAVIRUS; INTERACTION DATABASE; BIOLOGY; GENE; RETINOBLASTOMA; PATHWAY; CELLS AB Many human diseases, arising from mutations of disease susceptibility genes (genetic diseases), are also associated with viral infections (virally implicated diseases), either in a directly causal manner or by indirect associations. Here we examine whether viral perturbations of host interactome may underlie such virally implicated disease relationships. Using as models two different human viruses, Epstein-Barr virus (EBV) and human papillomavirus (HPV), we find that host targets of viral proteins reside in network proximity to products of disease susceptibility genes. Expression changes in virally implicated disease tissues and comorbidity patterns cluster significantly in the network vicinity of viral targets. The topological proximity found between cellular targets of viral proteins and disease genes was exploited to uncover a novel pathway linking HPV to Fanconi anemia. C1 [Gulbahce, Natali; Lee, Deok-Sun; Barabasi, Albert-Laszlo] Northeastern Univ, CCNR, Boston, MA 02115 USA. [Gulbahce, Natali; Lee, Deok-Sun; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Gulbahce, Natali; Yan, Han; Dricot, Amelie; Byrdsong, Danielle; Franchi, Rachel; Calderwood, Michael A.; Santhanam, Balaji; Braun, Pascal; Simonis, Nicolas; Roth, Frederick P.; Roecklein-Canfield, Jennifer; Cusick, Michael E.; Hill, David E.; Vidal, Marc; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. [Gulbahce, Natali; Yan, Han; Dricot, Amelie; Padi, Megha; Byrdsong, Danielle; Franchi, Rachel; Mar, Jessica C.; Calderwood, Michael A.; Santhanam, Balaji; Braun, Pascal; Simonis, Nicolas; Rubio, Renee; Marto, Jarrod A.; Roth, Frederick P.; Roecklein-Canfield, Jennifer; Cusick, Michael E.; Quackenbush, John; Hill, David E.; Vidal, Marc; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Yan, Han; Dricot, Amelie; Byrdsong, Danielle; Franchi, Rachel; Santhanam, Balaji; Braun, Pascal; Simonis, Nicolas; Roecklein-Canfield, Jennifer; Cusick, Michael E.; Hill, David E.; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Padi, Megha; Mar, Jessica C.; Rubio, Renee; Quackenbush, John] Dana Farber Canc Inst, CCCB, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Padi, Megha; Mar, Jessica C.; Rubio, Renee; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Franchi, Rachel; Roecklein-Canfield, Jennifer] Simmons Coll, Dept Chem, Boston, MA 02115 USA. [Lee, Deok-Sun] Inha Univ, Dept Nat Med Sci, Inchon, South Korea. [Lee, Deok-Sun] Inha Univ, Dept Phys, Inchon, South Korea. [Rozenblatt-Rosen, Orit; DeCaprio, James A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Calderwood, Michael A.; Baldwin, Amy; Zhao, Bo; Huh, Kyung-Won; Hellner, Karin; Grace, Miranda; Chen, Alyce; Kieff, Elliott; Muenger, Karl] Brigham & Womens Hosp, Channing Lab, Div Infect Dis, Boston, MA 02115 USA. [Calderwood, Michael A.; Baldwin, Amy; Zhao, Bo; Huh, Kyung-Won; Hellner, Karin; Grace, Miranda; Chen, Alyce; Kieff, Elliott; Muenger, Karl] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. [Christakis, Nicholas A.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Cambridge, MA 02138 USA. [Christakis, Nicholas A.] Harvard Univ, Dept Sociol, Cambridge, MA 02138 USA. [Roth, Frederick P.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Rozenblatt-Rosen, Orit; DeCaprio, James A.; Barabasi, Albert-Laszlo] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA. RP Gulbahce, N (reprint author), Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA. EM marc_vidal@dfci.harvard.edu; alb@neu.edu RI Lee, Deok-Sun/D-1335-2011; Hill, David/B-6617-2011; Roth, Frederick/H-6308-2011; Calderwood, Mike/B-2475-2014; Braun, Pascal/B-9669-2013; OI Calderwood, Mike/0000-0001-6475-1418; Braun, Pascal/0000-0003-2012-6746; Roth, Frederick/0000-0002-6628-649X; Munger, Karl/0000-0003-3288-9935 FU National Institutes of Health (NIH) [P50-HG004233 CEGS, R01-HG001715]; National Human Genome Research Institute; National Institute of Environmental Health Sciences [R01-ES015728]; Ellison Foundation; National Research Foundation of Korea (NRF) [2009-0063911]; NIH from National Institute of Mental Health [MH087394]; Canadian Institute for Advanced Science Fellowship; Fonds de la Recherche Scientifique (FRS-FNRS, French Community of Belgium) FX This work was supported by National Institutes of Health (NIH) grants P50-HG004233 CEGS and R01-HG001715 awarded by the National Human Genome Research Institute and R01-ES015728 awarded by the National Institute of Environmental Health Sciences, and by a grant from the Ellison Foundation to M.V. D.S.L. was supported by a National Research Foundation of Korea (NRF) Grant (2009-0063911). F.P.R. was also supported by NIH grant MH087394 from the National Institute of Mental Health and a Canadian Institute for Advanced Science Fellowship. M.V. receives support as a Chercheur Qualifie Honoraire from the Fonds de la Recherche Scientifique (FRS-FNRS, French Community of Belgium). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 41 Z9 43 U1 0 U2 21 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD JUN PY 2012 VL 8 IS 6 AR e1002531 DI 10.1371/journal.pcbi.1002531 PG 10 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 968GM UT WOS:000305965300009 PM 22761553 ER PT J AU Pukkila-Worley, R Feinbaum, R Kirienko, NV Larkins-Ford, J Conery, AL Ausubel, FM AF Pukkila-Worley, Read Feinbaum, Rhonda Kirienko, Natalia V. Larkins-Ford, Jonah Conery, Annie L. Ausubel, Frederick M. TI Stimulation of Host Immune Defenses by a Small Molecule Protects C. elegans from Bacterial Infection SO PLOS GENETICS LA English DT Article ID OXIDATIVE STRESS-RESPONSE; CAENORHABDITIS-ELEGANS; TRANSLATIONAL INHIBITION; LONGEVITY ASSURANCE; MODEL; PATHOGEN; SKN-1; DETOXIFICATION; EXPRESSION; GENES AB The nematode Caenorhabditis elegans offers currently untapped potential for carrying out high-throughput, live-animal screens of low molecular weight compound libraries to identify molecules that target a variety of cellular processes. We previously used a bacterial infection assay in C. elegans to identify 119 compounds that affect host-microbe interactions among 37,214 tested. Here we show that one of these small molecules, RPW-24, protects C. elegans from bacterial infection by stimulating the host immune response of the nematode. Using transcriptome profiling, epistasis pathway analyses with C. elegans mutants, and an RNAi screen, we show that RPW-24 promotes resistance to Pseudomonas aeruginosa infection by inducing the transcription of a remarkably small number of C. elegans genes (similar to 1.3% of all genes) in a manner that partially depends on the evolutionarily-conserved p38 MAP kinase pathway and the transcription factor ATF-7. These data show that the immunostimulatory activity of RPW-24 is required for its efficacy and define a novel C. elegans-based strategy to identify compounds with activity against antibiotic-resistant bacterial pathogens. C1 [Pukkila-Worley, Read] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA. [Pukkila-Worley, Read; Feinbaum, Rhonda; Kirienko, Natalia V.; Larkins-Ford, Jonah; Conery, Annie L.; Ausubel, Frederick M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA USA. [Pukkila-Worley, Read; Feinbaum, Rhonda; Kirienko, Natalia V.; Larkins-Ford, Jonah; Conery, Annie L.; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Pukkila-Worley, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA. EM ausubel@molbio.mgh.harvard.edu FU Cancer Research Institute-Irvington Institute Fellowship Program; National Institutes of Health [K08 AI081747, R01 AI085581] FX This study was supported by the Cancer Research Institute-Irvington Institute Fellowship Program (to RP-W) and by National Institutes of Health awards K08 AI081747 (to RP-W) and R01 AI085581 (to FMA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 25 Z9 25 U1 4 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD JUN PY 2012 VL 8 IS 6 AR e1002733 DI 10.1371/journal.pgen.1002733 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 968EW UT WOS:000305961000010 PM 22719261 ER PT J AU Basu, S Andrews, J Kishore, S Panjabi, R Stuckler, D AF Basu, Sanjay Andrews, Jason Kishore, Sandeep Panjabi, Rajesh Stuckler, David TI Comparative Performance of Private and Public Healthcare Systems in Low- and Middle-Income Countries: A Systematic Review SO PLOS MEDICINE LA English DT Review ID SEXUALLY-TRANSMITTED-DISEASES; SOUTH-AFRICA; TUBERCULOSIS-CONTROL; PRESCRIPTION PRACTICES; PRESCRIBING PATTERNS; COMBINATION THERAPY; CHILDHOOD DIARRHEA; TREATMENT OUTCOMES; SECTOR PROVISION; SEEKING BEHAVIOR AB Introduction: Private sector healthcare delivery in low- and middle-income countries is sometimes argued to be more efficient, accountable, and sustainable than public sector delivery. Conversely, the public sector is often regarded as providing more equitable and evidence-based care. We performed a systematic review of research studies investigating the performance of private and public sector delivery in low- and middle-income countries. Methods and Findings: Peer-reviewed studies including case studies, meta-analyses, reviews, and case-control analyses, as well as reports published by non-governmental organizations and international agencies, were systematically collected through large database searches, filtered through methodological inclusion criteria, and organized into six World Health Organization health system themes: accessibility and responsiveness; quality; outcomes; accountability, transparency, and regulation; fairness and equity; and efficiency. Of 1,178 potentially relevant unique citations, data were obtained from 102 articles describing studies conducted in low- and middle-income countries. Comparative cohort and cross-sectional studies suggested that providers in the private sector more frequently violated medical standards of practice and had poorer patient outcomes, but had greater reported timeliness and hospitality to patients. Reported efficiency tended to be lower in the private than in the public sector, resulting in part from perverse incentives for unnecessary testing and treatment. Public sector services experienced more limited availability of equipment, medications, and trained healthcare workers. When the definition of "private sector'' included unlicensed and uncertified providers such as drug shop owners, most patients appeared to access care in the private sector; however, when unlicensed healthcare providers were excluded from the analysis, the majority of people accessed public sector care. "Competitive dynamics'' for funding appeared between the two sectors, such that public funds and personnel were redirected to private sector development, followed by reductions in public sector service budgets and staff. Conclusions: Studies evaluated in this systematic review do not support the claim that the private sector is usually more efficient, accountable, or medically effective than the public sector; however, the public sector appears frequently to lack timeliness and hospitality towards patients. C1 [Basu, Sanjay] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Basu, Sanjay] San Francisco Gen Hosp, Div Gen Internal Med, San Francisco, CA 94110 USA. [Basu, Sanjay; Stuckler, David] London Sch Hyg & Trop Med, Dept Publ Hlth & Policy, London WC1, England. [Andrews, Jason] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Kishore, Sandeep] Rockefeller Univ, Sloan Kettering Inst, Triinst MD PhD Program, Weill Cornell Med Coll, New York, NY 10021 USA. [Panjabi, Rajesh] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Global Hlth Equ, Boston, MA 02115 USA. [Stuckler, David] Univ Cambridge, Dept Sociol, Cambridge, England. RP Basu, S (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. EM sanjay.basu@ucsf.edu RI Stuckler, David/H-2261-2012; OI Stuckler, David/0000-0002-1288-8401; Andrews, Jason/0000-0002-5967-251X NR 115 TC 83 Z9 85 U1 6 U2 39 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD JUN PY 2012 VL 9 IS 6 AR e1001244 DI 10.1371/journal.pmed.1001244 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 967ZH UT WOS:000305946200015 PM 22723748 ER PT J AU Van Nieuwenhove, L Buscher, P Balharbi, F Humbert, M Dieltjens, T Guisez, Y Lejon, V AF Van Nieuwenhove, Liesbeth Buscher, Philippe Balharbi, Fatima Humbert, Michael Dieltjens, Tessa Guisez, Yves Lejon, Veerle TI Identification of Mimotopes with Diagnostic Potential for Trypanosoma brucei gambiense Variant Surface Glycoproteins Using Human Antibody Fractions SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID OPERATING CHARACTERISTIC CURVES; SLEEPING SICKNESS; AFRICAN TRYPANOSOMIASIS; SEROLOGICAL DIAGNOSIS; CEREBROSPINAL-FLUID; ANTIGENIC VARIATION; AGGLUTINATION-TEST; PEPTIDE LIBRARIES; SERUM; DISPLAY AB Background: At present, screening of the population at risk for gambiense human African trypanosomiasis (HAT) is based on detection of antibodies against native variant surface glycoproteins (VSGs) of Trypanosoma brucei (T.b.) gambiense. Drawbacks of these native VSGs include culture of infective T.b. gambiense trypanosomes in laboratory rodents, necessary for production, and the exposure of non-specific epitopes that may cause cross-reactions. We therefore aimed at identifying peptides that mimic epitopes, hence called "mimotopes," specific to T.b. gambiense VSGs and that may replace the native proteins in antibody detection tests. Methodology/Principal Findings: A Ph.D.-12 peptide phage display library was screened with polyclonal antibodies from patient sera, previously affinity purified on VSG LiTat 1.3 or LiTat 1.5. The peptide sequences were derived from the DNA sequence of the selected phages and synthesised as biotinylated peptides. Respectively, eighteen and twenty different mimotopes were identified for VSG LiTat 1.3 and LiTat 1.5, of which six and five were retained for assessment of their diagnostic performance. Based on alignment of the peptide sequences on the original protein sequence of VSG LiTat 1.3 and 1.5, three additional peptides were synthesised. We evaluated the diagnostic performance of the synthetic peptides in indirect ELISA with 102 sera from HAT patients and 102 endemic negative controls. All mimotopes had areas under the curve (AUCs) of >= 0.85, indicating their diagnostic potential. One peptide corresponding to the VSG LiTat 1.3 protein sequence also had an AUC of >= 0.85, while the peptide based on the sequence of VSG LiTat 1.5 had an AUC of only 0.79. Conclusions/Significance: We delivered the proof of principle that mimotopes for T.b. gambiense VSGs, with diagnostic potential, can be selected by phage display using polyclonal human antibodies. C1 [Van Nieuwenhove, Liesbeth; Buscher, Philippe; Balharbi, Fatima; Dieltjens, Tessa; Lejon, Veerle] Inst Trop Med, Dept Biomed Sci, B-2000 Antwerp, Belgium. [Humbert, Michael] Harvard Univ, Sch Med, Boston, MA USA. [Humbert, Michael] Dana Farber Canc Inst, Boston, MA 02115 USA. [Guisez, Yves] Univ Antwerp, Dept Biol, B-2020 Antwerp, Belgium. RP Van Nieuwenhove, L (reprint author), Inst Trop Med, Dept Biomed Sci, B-2000 Antwerp, Belgium. EM pbuscher@itg.be RI Buscher, Philippe/B-9956-2012; OI Buscher, Philippe/0000-0002-1926-7472; Lejon, Veerle/0000-0002-6795-0962 FU Belgian Directorate General for Development Cooperation (DGDC); Research Foundation of Flanders (FWO) [1.5.169.07N, 1.5.074.09.N]; FWO [1.1.270.07.N.00, 1.1.270.09.N.01] FX The project was funded by the Belgian Directorate General for Development Cooperation (DGDC) and the Research Foundation of Flanders (FWO, 1.5.169.07N and 1.5.074.09.N). Liesbeth Van Nieuwenhove is supported by a PhD scholarship of the FWO (1.1.270.07.N.00 and 1.1.270.09.N.01). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 9 Z9 9 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JUN PY 2012 VL 6 IS 6 AR e1682 DI 10.1371/journal.pntd.0001682 PG 11 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 967YY UT WOS:000305945300024 PM 22720103 ER PT J AU Young, BC Wylie, BJ AF Young, Brett C. Wylie, Blair J. TI Effects of Twin Gestation on Maternal Morbidity SO SEMINARS IN PERINATOLOGY LA English DT Review DE maternal morbidity; twin gestation; pregnancy complications; hypertensive disorders; cesarean delivery; nutritional deficiencies ID PREGNANCY WEIGHT-GAIN; CESAREAN DELIVERY; HYPERTENSIVE DISORDERS; MULTIPLE GESTATION; RISK-FACTORS; PELVIC PAIN; BLOOD-TRANSFUSION; PLACENTA PREVIA; UNITED-STATES; PREECLAMPSIA AB As the incidence of twin gestation increases, it is important to consider the maternal risks associated with carrying multiples. Compared with singleton gestation, there are increased risks to the mother during the antepartum, intrapartum, and postpartum periods. Certain pregnancy complications are more likely to occur during a twin gestation, including preeclampsia and other hypertensive disorders, antepartum hospitalization for preterm labor or abnormal bleeding, nutritional deficiencies, cesarean delivery, and postpartum hemorrhage. Women carrying twins may benefit from early education regarding these issues, close maternal monitoring as well as physical therapy sessions, and nutrition counseling during their pregnancies. Semin Perinatol 36:162-168 (c) 2012 Elsevier Inc. All rights reserved. C1 [Young, Brett C.; Wylie, Blair J.] Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02114 USA. RP Young, BC (reprint author), Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02114 USA. EM byoung1@partners.org NR 63 TC 16 Z9 18 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 0146-0005 J9 SEMIN PERINATOL JI Semin. Perinatol. PD JUN PY 2012 VL 36 IS 3 BP 162 EP 168 DI 10.1053/j.semperi.2012.02.007 PG 7 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 969BJ UT WOS:000306030400003 PM 22713496 ER PT J AU Takhar, SS Ting, SA Camargo, CA Pallin, DJ AF Takhar, Sukhjit S. Ting, Sarah A. Camargo, Carlos A., Jr. Pallin, Daniel J. TI U.S. Emergency Department Visits for Meningitis, 1993-2008 SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID BACTERIAL-MENINGITIS; UNITED-STATES; VIRAL MENINGITIS; MANAGEMENT; EPIDEMIOLOGY; INFECTIONS; CHILDREN AB Objectives: Large-scale epidemiologic studies of meningitis in the emergency department (ED) setting are lacking. Using a nationwide sample, the authors determined the frequency of meningitis visits and characterize management. Methods: Using National Hospital Ambulatory Medical Care Survey (NHAMCS) data, 1993 through 2008, meningitis diagnoses were studied and national rates were estimated via standard weighting procedures. Results: Meningitis was diagnosed at 1,048,000 visits (95% confidence interval [CI] = 893,000 to 1,203,000) during 1993 through 2008. This is 66,000 cases annually, or 62 per 100,000 visits, with no change over time (p = 0.20). ED diagnoses were unspecified (60%), viral (31%), bacterial (8%), and fungal (1%) meningitis. Median age was 24 years (interquartile range = 9 to 40 years). While 1.97 times as many adults were diagnosed with meningitis (95% CI = 1.83 to 2.13), meningitis accounted for a similar proportion of visits among children and adults (ratio = 1.33, 95% CI = 0.58 to 2.63). Per population, children were more likely to have a meningitis visit (31 vs. 21 per 100,000; ratio = 1.48, 95% CI = 1.003 to 2.10); children aged younger than 3 years had the highest rate (98 per 100,000, 95% CI = 63 to 133). Spring and summer visits were 1.25 times as numerous as fall and winter (95% CI = 1.15 to 1.36). Third-generation cephalosporins were administered in 42%, analgesics in 19%, and antiemetics in 15% of cases, and 66% were admitted to the hospital (95% CI = 58% to 73%). Conclusions: Meningitis is rare, diagnosed at 62 per 100,000 ED visits. Rates have been stable over time. Children are 1.48 times more likely to have a visit for meningitis, although adults make twice as many visits. Absence of consensus guidelines for patients suspected of having viral meningitis but being tested for bacterial meningitis may lead to variability in admission and prescribing decisions. ACADEMIC EMERGENCY MEDICINE 2012; 19: 632-639 (C) 2012 by the Society for Academic Emergency Medicine C1 [Takhar, Sukhjit S.; Pallin, Daniel J.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Ting, Sarah A.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Pallin, Daniel J.] Childrens Hosp, Div Emergency Med, Boston, MA 02115 USA. RP Takhar, SS (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. EM stakhar@partners.org RI Pallin, Daniel/H-6382-2013 OI Pallin, Daniel/0000-0002-8517-9702 NR 20 TC 6 Z9 8 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD JUN PY 2012 VL 19 IS 6 BP 632 EP 639 DI 10.1111/j.1553-2712.2012.01377.x PG 8 WC Emergency Medicine SC Emergency Medicine GA 965BJ UT WOS:000305740800003 PM 22687178 ER PT J AU Tsai, CL Delclos, GL Camargo, CA AF Tsai, Chu-Lin Delclos, George L. Camargo, Carlos A., Jr. TI Emergency Department Case Volume and Patient Outcomes in Acute Exacerbations of Chronic Obstructive Pulmonary Disease SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; QUALITY-OF-CARE; HOSPITAL VOLUME; LOGISTIC-REGRESSION; MORTALITY; ASSOCIATION; VARIABLES; FAILURE; TIME AB Objectives: The objective was to determine whether emergency department (ED) case volume of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is associated with patient outcomes in AECOPD. Methods: The authors analyzed the 2007 Nationwide Emergency Department Sample (NEDS), the largest publicly available all-payer ED database in the United States. ED visits for AECOPD were identified with a principal diagnosis of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 491.21. EDs were categorized into quartiles by ED case volume of AECOPD. The primary outcome measures were early inpatient mortality (within the first 3 days of admission) and hospital length of stay (LOS). Results: The 2007 NEDS sample contained 126,045 ED visits for AECOPD from 946 U. S. EDs; 58% were hospitalized. Of these, the overall inpatient mortality rate was 2.0%, the early inpatient mortality 0.6%, and the median hospital LOS 4 days. Early inpatient mortality was lower in the highest-volume EDs (0.47%), compared with the lowest-volume EDs (1.13%). In a multivariable analysis adjusting for 37 patient and hospital characteristics, early inpatient mortality remained lower in patients admitted through the highest-volume EDs (adjusted odds ratios [ORs] = 0.51; 95% confidence interval [CI] = 0.32 to 0.82), compared with the lowest-volume EDs; however, the hospital LOS in the highest-volume EDs was slightly longer (adjusted difference in LOS = 0.53 day; 95% CI = 0.29 to 0.77). The volume threshold for reduced early mortality was approximately 200 cases per year. Conclusions: ED patients who are hospitalized for AECOPD have an approximately 50% reduction in early inpatient mortality if they were admitted from an ED that handles a large volume of AECOPD cases. ACADEMIC EMERGENCY MEDICINE 2012; 19: 656-663 (C) 2012 by the Society for Academic Emergency Medicine C1 [Tsai, Chu-Lin; Delclos, George L.] Univ Texas Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Tsai, CL (reprint author), Univ Texas Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA. EM cltsai@post.harvard.edu OI TSAI, CHU-LIN/0000-0003-4639-1513 FU Agency for Healthcare Research and Quality (AHRQ) [R03HS020722] FX This project was supported by grant R03HS020722 from the Agency for Healthcare Research and Quality (AHRQ). The content is solely the responsibility of the authors and does not necessarily represent the official views of the AHRQ. The sponsor had no role in the design and conduct of the study; the analysis and interpretation of the data; or the preparation, review, and approval of the manuscript. The authors have no conflicts of interest or other financial disclosures to report. NR 37 TC 12 Z9 12 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD JUN PY 2012 VL 19 IS 6 BP 656 EP 663 DI 10.1111/j.1553-2712.2012.01363.x PG 8 WC Emergency Medicine SC Emergency Medicine GA 965BJ UT WOS:000305740800006 PM 22687180 ER PT J AU Beehler, S AF Beehler, Sarah TI REFINING (NOT NARROWING) NOTIONS OF PROGRAM SUSTAINABILITY SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter ID DARE C1 VA Boston Healthcare Syst, COLMR, Hlth Serv Res & Dev, Jamaica Plain, MA 02130 USA. RP Beehler, S (reprint author), VA Boston Healthcare Syst, COLMR, Hlth Serv Res & Dev, 150 S Huntington Ave 152-M, Jamaica Plain, MA 02130 USA. EM sarah.beehler@va.gov NR 7 TC 1 Z9 1 U1 2 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 2012 VL 102 IS 6 BP 1051 EP 1052 DI 10.2105/AJPH.2011.300604 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 951LX UT WOS:000304723200003 PM 22515875 ER PT J AU Marcus, SC Bridge, JA Olfson, M AF Marcus, Steven C. Bridge, Jeffrey A. Olfson, Mark TI Payment Source and Emergency Management of Deliberate Self-Harm SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID QUALITY-OF-CARE; SUICIDE ATTEMPTS; COMPLETED SUICIDE; MENTAL-HEALTH; FOLLOW-UP; COHORT; RISK; REPEAT; HOSPITALIZATION; PREVENTION AB Objectives. We investigated whether health insurance type (private vs Medicaid) influences the delivery of acute mental health care to patients with deliberate self-harm. Methods. Using National Medicaid Analytic Extract Files (2006) and Market-Scan Research Databases (2005-2007), we analyzed claims focusing on emergency episodes of deliberate self-harm of Medicaid- (n = 8228) and privately (n = 2352) insured adults. We analyzed emergency department mental health assessments and outpatient mental health visits in the 30 days following the emergency visit for discharged patients. Results. Medicaid-insured patients were more likely to be discharged (62.7%), and among discharged patients they were less likely to receive a mental health assessment in the emergency department (47.8%) and more likely to receive follow-up outpatient mental health care (52.9%) than were privately insured patients (46.9%, 57.3%, and 41.2%, respectively). Conclusions. Acute emergency management of deliberate self-harm is less intensive for Medicaid- than for privately insured patients, although discharged Medicaid-insured patients are more likely to receive follow-up care. Programmatic reforms are needed to improve access to emergency mental health services, especially in hospitals that serve substantial numbers of Medicaid-insured patients. (Am J Public Health. 2012;102:1145-1153. doi:10.2105/AJPH.2011.300598) C1 [Olfson, Mark] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Olfson, Mark] Columbia Univ, Dept Psychiat, New York, NY USA. [Marcus, Steven C.] Univ Penn, Ctr Hlth Equ Res & Promot, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. [Bridge, Jeffrey A.] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA. [Bridge, Jeffrey A.] Ohio State Univ, Res Inst, Nationwide Childrens Hosp, Ctr Innovat Pediat Practice, Columbus, OH 43210 USA. RP Olfson, M (reprint author), New York State Psychiat Inst & Hosp, 1051 Riverside Dr, New York, NY 10032 USA. EM mo49@columbia.edu FU American Foundation for Suicide Prevention of Columbia University [2DIG-00005-1207-1208] FX The American Foundation for Suicide Prevention of Columbia University supported this study (grant no. 2DIG-00005-1207-1208). NR 49 TC 6 Z9 6 U1 2 U2 5 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 2012 VL 102 IS 6 BP 1145 EP 1153 DI 10.2105/AJPH.2011.300598 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 951LX UT WOS:000304723200020 PM 22515853 ER PT J AU Metsch, LR Feaster, DJ Gooden, L Matheson, T Mandler, RN Haynes, L Tross, S Kyle, T Gallup, D Kosinski, AS Douaihy, A Schackman, BR Das, M Lindblad, R Erickson, S Korthuis, PT Martino, S Sorensen, JL Szapocznik, J Walensky, R Branson, B Colfax, GN AF Metsch, Lisa R. Feaster, Daniel J. Gooden, Lauren Matheson, Tim Mandler, Raul N. Haynes, Louise Tross, Susan Kyle, Tiffany Gallup, Dianne Kosinski, Andrzej S. Douaihy, Antoine Schackman, Bruce R. Das, Moupali Lindblad, Robert Erickson, Sarah Korthuis, P. Todd Martino, Steve Sorensen, James L. Szapocznik, Jose Walensky, Rochelle Branson, Bernard Colfax, Grant N. TI Implementing Rapid HIV Testing With or Without Risk-Reduction Counseling in Drug Treatment Centers: Results of a Randomized Trial SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID ABUSE TREATMENT PROGRAMS; SEXUALLY-TRANSMITTED INFECTIONS; HUMAN-IMMUNODEFICIENCY-VIRUS; HEALTH-CARE SETTINGS; UNITED-STATES; ADOLESCENTS; HIV/AIDS; EFFICACY; SERVICES; NETWORK AB Objectives. We examined the effectiveness of risk reduction counseling and the role of on-site HIV testing in drug treatment. Methods. Between January and May 2009, we randomized 1281 HIV-negative (or status unknown) adults who reported no past-year HIV testing to (1) referral for off-site HIV testing, (2) HIV risk-reduction counseling with on-site rapid HIV testing, or (3) verbal information about testing only with on-site rapid HIV testing. Results. We defined 2 primary self-reported outcomes a priori: receipt of HIV test results and unprotected anal or vaginal intercourse episodes at 6-month follow-up. The combined on-site rapid testing participants received more HIV test results than off-site testing referral participants (P<.001; Mantel-Haenszel risk ratio = 4.52; 97.5% confidence interval [CI]= 3.57, 5.72). At 6 months, there were no significant differences in unprotected intercourse episodes between the combined on-site testing arms and the referral arm (P=.39; incidence rate ratio [IRR] = 1.04; 97.5% CI = 0.95, 1.14) or the 2 on-site testing arms (P=.81; IRR = 1.03; 97.5% CI = 0.84, 1.26). Conclusions. This study demonstrated on-site rapid HIV testing's value in drug treatment centers and found no additional benefit from HIV sexual risk-reduction counseling. (Am J Public Health. 2012;102:1160-1167. doi:10.2105/AJPH.2011.300460) C1 [Metsch, Lisa R.] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. [Matheson, Tim; Das, Moupali; Colfax, Grant N.] San Francisco Dept Publ Hlth, San Francisco, CA USA. [Mandler, Raul N.] NIDA, Bethesda, MD 20892 USA. [Haynes, Louise] Med Univ S Carolina, Charleston, SC 29425 USA. [Tross, Susan] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Tross, Susan] Columbia Univ, New York, NY USA. [Kyle, Tiffany] Ctr Drug Free Living Inc, Orlando, FL USA. [Gallup, Dianne; Kosinski, Andrzej S.] Duke Clin Res Inst, Durham, NC USA. [Kosinski, Andrzej S.] Duke Univ, Med Ctr, Durham, NC USA. [Douaihy, Antoine] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Douaihy, Antoine] Western Psychiat Inst & Clin, Pittsburgh, PA USA. [Schackman, Bruce R.] Weill Cornell Med Coll, New York, NY USA. [Lindblad, Robert] EMMES Corp Inc, Rockville, MD USA. [Erickson, Sarah] Univ New Mexico, Albuquerque, NM 87131 USA. [Korthuis, P. Todd] Oregon Hlth & Sci Univ, Portland, OR USA. [Martino, Steve] Yale Univ, New Haven, CT USA. [Sorensen, James L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Walensky, Rochelle] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Walensky, Rochelle] Brigham & Womens Hosp, Boston, MA 02115 USA. [Walensky, Rochelle] Harvard Univ, Sch Med, Boston, MA USA. [Branson, Bernard] Ctr Dis Control & Prevent, Atlanta, GA USA. RP Metsch, LR (reprint author), Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, 1120 NW 14th St,Suite 1019, Miami, FL 33136 USA. EM Lmetsch@med.miami.edu RI Feaster, Daniel/I-6079-2013; OI Walensky, Rochelle P./0000-0002-8795-379X; Feaster, Daniel/0000-0002-6172-7460 FU National Drug Abuse Treatment Clinical Trials Network [U10DA013720, U10DA13720-09S, U10DA020036, U10DA15815, U10DA13034, U10DA013038, U10DA013732, U10DA13036, U10DA13727, U10DA015833, HHSN271200522081C, HHSN271200522071C] FX Funding for this study and analysis was provided by the National Drug Abuse Treatment Clinical Trials Network under the following cooperative agreements, awards, and contracts: U10DA013720, U10DA13720-09S, U10DA020036, U10DA15815, U10DA13034, U10DA013038, U10DA013732, U10DA13036, U10DA13727, U10DA015833, HHSN271200522081C, and HHSN271200522071C. NR 25 TC 42 Z9 42 U1 3 U2 12 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 2012 VL 102 IS 6 BP 1160 EP 1167 DI 10.2105/AJPH.2011.300460 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 951LX UT WOS:000304723200022 PM 22515871 ER PT J AU Nogueira, RD Sesso, MLT Borges, MCL Mattos-Graner, RO Smith, DJ Ferriani, VPL AF Nogueira, Ruchele Dias Talarico Sesso, Maria Lucia Loureiro Borges, Mariana Castro Mattos-Graner, Renata O. Smith, Daniel James Leme Ferriani, Virginia Paes TI Salivary IgA antibody responses to Streptococcus mitis and Streptococcus mutans in preterm and fullterm newborn children SO ARCHIVES OF ORAL BIOLOGY LA English DT Article DE Streptococcus mutans; Streptococcus mitis; IgA; Saliva; Prematurity ID IMMUNOGLOBULIN-A; IMMUNE-SYSTEM; INFANTS; INFECTION; HUMANS; AGE; BACTERIA; ANTIGEN AB Objectives: The intensities and specificities of salivary IgA antibody responses to antigens of Streptococcus mutans, the main pathogen of dental caries, may influence colonization by these organisms during the first 1.5 year of life. Thus, the ontogeny of salivary IgA responses to oral colonizers continues to warrant investigation, especially with regard to the influence of birth conditions, e.g. prematurity, on the ability of children to efficiently respond to oral microorganisms. In this study, we characterised the salivary antibody responses to two bacterial species which are prototypes of pioneer and pathogenic microorganisms of the oral cavity (Streptococcus mitis and Streptococcus mutans, respectively) in fullterm (FT) and preterm (PT) newborn children. Methods: Salivas from 123 infants (70 FT and 53 PT) were collected during the first 10 h after birth and levels of IgA and IgM antibodies and the presence of S. mutans and S. mitis were analysed respectively by ELISA and by chequerboard DNA-DNA hybridization. Two subgroups of 24 FT and 24 PT children were compared with respect to patterns of antibody specificities against S. mutans and S. mitis antigens, using Western blot assays. Cross-adsorption of 10 infant's saliva was tested to S. mitis, S. mutans and Enterococcus faecalis antigens. Results: Salivary levels of IgA at birth were 2.5-fold higher in FT than in PT children (Mann-Whitney; P < 0.05). Salivary IgA antibodies reactive with several antigens of S. mitis and S. mutans were detected at birth in children with undetectable levels of those bacteria. Adsorption of infant saliva with cells of S. mutans produced a reduction of antibodies recognizing S. mitis antigens in half of the neonates. The diversity and intensity of IgA responses were lower in PT compared to FT children, although those differences were not significant. Conclusion: These data provide evidence that children have salivary IgA antibodies shortly after birth, which might influence the establishment of the oral microbiota, and that the levels of salivary antibody might be related to prematurity. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Nogueira, Ruchele Dias] Univ Uberaba, Minas Gerais, Brazil. [Nogueira, Ruchele Dias; Talarico Sesso, Maria Lucia; Loureiro Borges, Mariana Castro; Leme Ferriani, Virginia Paes] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Pediat, Sao Paulo, Brazil. [Mattos-Graner, Renata O.] Univ Estadual Campinas, Piracicaba Sch Dent, Dept Microbiol & Immunol, Sao Paulo, Brazil. [Smith, Daniel James] Forsyth Inst, Dept Immunol, Cambridge, MA USA. RP Nogueira, RD (reprint author), Fac Med Ribeirao Preto, Dept Puericultura & Pediat, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil. EM ruchele_nogueira@yahoo.com.br RI Ferriani, Virginia/E-2209-2012; Mattos-Graner, Renata/C-9410-2012; Sesso, Maria Lucia/C-4681-2017 OI Nogueira, Ruchele Dias/0000-0002-7706-1376; Mattos-Graner, Renata/0000-0001-8309-8135; FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [07/57346-5, 07/50807-7]; Conselho Nacional de Pesquisa (CNPq) [472928/2007-4] FX This study was supported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), proc. 07/57346-5, and proc. 07/50807-7 and Conselho Nacional de Pesquisa (CNPq), proc. 472928/2007-4. NR 29 TC 10 Z9 12 U1 4 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0003-9969 J9 ARCH ORAL BIOL JI Arch. Oral Biol. PD JUN PY 2012 VL 57 IS 6 BP 647 EP 653 DI 10.1016/j.archoralbio.2011.11.011 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 963DS UT WOS:000305600900010 PM 22169809 ER PT J AU Thase, ME Kennedy, SH Larsen, KG AF Thase, Michael E. Kennedy, Sidney H. Larsen, Klaus G. TI Can a 'true' effect be built on a 'wrong' model? reply SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Letter C1 [Thase, Michael E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Kennedy, Sidney H.] H Lundbeck & Co AS, Copenhagen, Denmark. [Larsen, Klaus G.] Univ Toronto, Toronto, ON, Canada. RP Thase, ME (reprint author), Univ Penn, Sch Med, Suite 689,3535 Market St, Philadelphia, PA 19104 USA. EM thase@mail.med.upenn.edu NR 1 TC 0 Z9 0 U1 0 U2 1 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD JUN PY 2012 VL 200 IS 6 BP 512 EP 513 DI 10.1192/bjp.200.6.512a PG 2 WC Psychiatry SC Psychiatry GA 959GK UT WOS:000305300700017 ER PT J AU Merrick, DT AF Merrick, Daniel T. TI GRP78, Intronic Polymorphisms, and Pharmacogenomics in Non-small Cell Lung Cancer SO CHEST LA English DT Editorial Material ID ENDOPLASMIC-RETICULUM C1 Denver Vet Affairs Med Ctr, Dept Pathol, Denver, CO 80220 USA. RP Merrick, DT (reprint author), Denver Vet Affairs Med Ctr, Dept Pathol, 113,1055 Clermont St, Denver, CO 80220 USA. EM Daniel.Merrick@va.gov FU NCI NIH HHS [P50-CA058187] NR 8 TC 4 Z9 4 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUN PY 2012 VL 141 IS 6 BP 1377 EP 1378 DI 10.1378/chest.11-2662 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 955RT UT WOS:000305039300004 PM 22670016 ER PT J AU Villar, SR Casado, MS Prigerson, HG Garcia, SM Villar, M Martin, VAH Schulke, CMM Vega, RB Quintana, M AF Rodriguez Villar, Sancho Sanchez Casado, Marceline Prigerson, Holly G. Mesa Garcia, Silvia Rodriguez Villar, Maria Martin, Victoria A. Hortigueela Schulke, Carlos M. Marco Barrientos Vega, Rafael Quintana, Manolo TI Prolonged Grief Disorder in the Next of Kin of Adult Patients Who Die During or After Admission to Intensive Care SO CHEST LA English DT Letter ID SYMPTOMS; DEPRESSION; ANXIETY C1 [Rodriguez Villar, Sancho] Hosp Prov Misericordia, Toledo, Spain. [Sanchez Casado, Marceline; Mesa Garcia, Silvia; Rodriguez Villar, Maria; Martin, Victoria A. Hortigueela; Schulke, Carlos M. Marco; Barrientos Vega, Rafael] Virgen de la Salud Hosp, Toledo, Spain. [Quintana, Manolo] Univ Hosp La Paz, Madrid, Spain. [Prigerson, Holly G.] Dana Farber Canc Inst, Boston, MA USA. [Prigerson, Holly G.] Harvard Univ, Sch Med, Ctr Psychooncol & Palliat Care Res, Boston, MA USA. RP Villar, SR (reprint author), Hosp Ntra Sna Del Prado, Dept Intens Care, Madrid Km 116, Toledo 45600, Spain. EM sancho.rodvil@hotmail.com NR 6 TC 5 Z9 5 U1 0 U2 3 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUN PY 2012 VL 141 IS 6 BP 1635 EP 1636 DI 10.1378/chest.11-3099 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 955RT UT WOS:000305039300040 ER PT J AU Jensen, RJ AF Jensen, Ralph J. TI Activation of ganglion cells in wild-type and P23H rat retinas with a small subretinal electrode SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE retinal ganglion cell; P23H rat; electrical stimulation; retinal prosthesis; mGluR6 ID ELECTRICAL-STIMULATION; PERCEPTUAL THRESHOLDS; RESPONSE PROPERTIES; PROSTHESIS; DEGENERATION; PERFORMANCE; PATTERNS AB Electronic retinal prostheses are being developed for people who become blind due to loss of photoreceptors from the disease retinitis pigmentosa. Previously, we reported on the responses of RGCs in the P23H rat (a model of retinitis pigmentosa) and the Sprague-Dawley (SD) rat to stimulation with a 400-mu m diameter electrode (Jensen and Rizzo, 2011). With recent clinical trials now utilizing smaller (50-200 mu m) electrodes, I sought to investigate the electrically evoked responses of RGCs in P23H and SD rat retinas with a smaller (125-mu m diameter) electrode. Here, I report on the electrically evoked spike activity from RGCs that arose from stimulation of the retinal neural network. With biphasic current pulses of 1 ms per phase, the thresholds for activation of SD rat RGCs ranged from 0.52 to 2.8 mu A; thresholds of P23H rat RGCs ranged from 1.2 to 7.8 mu A. Median thresholds of RGCs were 1.4 mu A in SD rats and 2.5 mu A in P23H rats. These thresholds measurements were obtained with the recording electrode placed over the stimulating electrode. I also examined how thresholds of RGCs change as a function of distance (100-500 mu m) from the center of the stimulating electrode. The median threshold currents of RGCs were much higher in P23H rats for all distances. What was striking was that the thresholds for activation of RGCs in P23H rat retinas rose much more rapidly. When the recording electrode was only 100-200 mu m from the center of the stimulating electrode, the median threshold current of P23H rat RGCs rose by 460%. In contrast, the median threshold current of SD rat RGCs increased only 29%. I also investigated the contribution of photoreceptors to the electrically evoked responses of ON-center RGCs in SD rat retinas by examining the change in RGC thresholds when photoreceptor input to ON bipolar cells was blocked with the mGluR6 antagonist CPPG. At 500-600 mu m, CPPG suppressed the light-evoked responses of the RGCs and at the same time increased the amount of current needed to generate an electrically evoked response. Similar to what was observed with SD rat RGCs, CPPG suppressed the light-evoked responses of ON-center P23H rat RGCs. However, the stimulation thresholds were not significantly altered. In conclusion, the data show that the threshold currents for indirect stimulation of both SD and P23H rat RGCs with a 125-mu m diameter electrode are much lower than what we found previously with a 400-mu m diameter electrode. To achieve high resolution vision with a multielectrode array, the spread of activation of RGCs needs to be limited. Our findings indicate that the spread of activation of RGCs is more confined in the degenerate retina. Lastly, my findings indicate that photoreceptors contribute to the lower stimulation thresholds of RGCs in normal, healthy retinas. Published by Elsevier Ltd. C1 VA Boston Healthcare Syst, Boston, MA 02130 USA. RP Jensen, RJ (reprint author), VA Boston Healthcare Syst, Mail Stop 151E,150 S Huntington Ave, Boston, MA 02130 USA. EM Ralph.jensen@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service FX The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service. NR 33 TC 5 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD JUN PY 2012 VL 99 BP 71 EP 77 DI 10.1016/j.exer.2012.03.016 PG 7 WC Ophthalmology SC Ophthalmology GA 957YO UT WOS:000305203200009 PM 22542904 ER PT J AU Kim, KH Pierce, MC Maguluri, G Park, BH Yoon, SJ Lydon, M Sheridan, R de Boerh, JF AF Kim, Ki Hean Pierce, Mark C. Maguluri, Gopi Park, B. Hyle Yoon, Sang June Lydon, Martha Sheridan, Robert de Boerh, Johannes F. TI In vivo imaging of human burn injuries with polarization-sensitive optical coherence tomography SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE optical coherence tomography; polarization-sensitive optical coherence tomography; burn; in vivo imaging; non-invasive; medical imaging ID DEPTH ASSESSMENT; MICROCIRCULATION; DIAGNOSIS; PERFUSION; TRIAL; TIME; AID AB The accurate determination of burn depth is critical in the clinical management of burn wounds. Polarization-sensitive optical coherence tomography (PS-OCT) has been proposed as a potentially non-invasive method for determining burn depth by measuring thermally induced changes in the structure and birefringence of skin, and has been investigated in pre-clinical burn studies with animal models and ex vivo human skin. In this study, we applied PS-OCT to the in-vivo imaging of two pediatric burn patients. Deep and superficial burned skins along with contralateral controls were imaged in 3D. The imaging size was 8 mm x 6 mm x 2 mm in width, length, and depth in the air respectively, and the imaging time was approximately 6 s per volume. Superficially burned skins exhibited the same layered structure as the contralateral controls, but more visible vasculature and reduced birefringence compared to the contralateral controls. In contrast, a deeply burned skin showed loss of the layered structure, almost absent vasculature, and smaller birefringence compared to superficial burns. This study suggested the vasculature and birefringence as parameters for characterizing burn wounds. (C) 2012 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.JBO.17.6.066012] C1 [Kim, Ki Hean; Yoon, Sang June] Pohang Univ Sci & Technol, Dept Mech Engn, Pohang 790784, South Korea. [Kim, Ki Hean] Pohang Univ Sci & Technol, Div Integrat Biosci & Biotechnol, Pohang 790784, South Korea. [Pierce, Mark C.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. [Maguluri, Gopi] Thorlabs Inc, Newton, NJ 07860 USA. [Park, B. Hyle] UC Riverside, Dept Bioengn, Riverside, CA 92521 USA. [Lydon, Martha; Sheridan, Robert] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Sheridan, Robert] Shriners Hosp Children, Dept Surg, Boston, MA 02114 USA. [de Boerh, Johannes F.] Vrije Univ Amsterdam, Inst Lasers Life & Biophoton Amsterdam, Dept Phys & Astron, NL-1081 HV Amsterdam, Netherlands. RP Kim, KH (reprint author), Pohang Univ Sci & Technol, Dept Mech Engn, Pohang 790784, South Korea. EM kiheankim@postech.edu FU National Research Foundation of Korea [2010-0028014, 2010-0014874, 20110030780]; Bio & Medical Technology Development Program [2011-0019619, 2011-0019632]; Industrial Strategic Technology Development Program [10040121]; Ministry of Education, Science and Technology [R31-2008-000-10105-0]; MFEL program in the Department of Defense, US FX This research was supported in part by the National Research Foundation of Korea (2010-0028014, 2010-0014874, 20110030780), the Bio & Medical Technology Development Program (2011-0019619, 2011-0019632), Industrial Strategic Technology Development Program (10040121), World Class University Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (R31-2008-000-10105-0), and the MFEL program in the Department of Defense, US. NR 22 TC 29 Z9 30 U1 1 U2 21 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JUN PY 2012 VL 17 IS 6 AR 066012 DI 10.1117/1.JBO.17.6.066012 PG 5 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 962XI UT WOS:000305582500045 PM 22734768 ER PT J AU Tichauer, KM Samkoe, KS Sexton, KJ Gunn, JR Hasan, T Pogue, BW AF Tichauer, Kenneth M. Samkoe, Kimberley S. Sexton, Kristian J. Gunn, Jason R. Hasan, Tayyaba Pogue, Brian W. TI Improved tumor contrast achieved by single time point dual-reporter fluorescence imaging SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE binding potential; epidermal growth factor receptor; fluorescence; receptor; xenograft; molecular imaging; cancer ID EPIDERMAL-GROWTH-FACTOR; IN-VIVO; CARCINOEMBRYONIC ANTIGEN; GUIDED SURGERY; OVARIAN-CANCER; BREAST-CANCER; SOLID TUMORS; RECEPTOR; RADIOIMMUNODETECTION; EXPRESSION AB In this study, we demonstrate a method to quantify biomarker expression that uses an exogenous dual-reporter imaging approach to improve tumor signal detection. The uptake of two fluorophores, one nonspecific and one targeted to the epidermal growth factor receptor (EGFR), were imaged at 1 h in three types of xenograft tumors spanning a range of EGFR expression levels (n = 6 in each group). Using this dual-reporter imaging methodology, tumor contrast-to-noise ratio was amplified by >6 times at 1 h postinjection and >2 times at 24 h. Furthermore, by as early as 20 min postinjection, the dual-reporter imaging signal in the tumor correlated significantly with a validated marker of receptor density (P < 0.05, r = 0.93). Dual-reporter imaging can improve sensitivity and specificity over conventional fluorescence imaging in applications such as fluorescence-guided surgery and directly approximates the receptor status of the tumor, a measure that could be used to inform choices of biological therapies. (C) 2012 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.JBO.17.6.066001] C1 [Tichauer, Kenneth M.; Samkoe, Kimberley S.; Sexton, Kristian J.; Gunn, Jason R.; Pogue, Brian W.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Samkoe, Kimberley S.; Pogue, Brian W.] Dartmouth Med Sch, Dept Surg, Lebanon, NH 03756 USA. [Hasan, Tayyaba; Pogue, Brian W.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Tichauer, KM (reprint author), Dartmouth Coll, Thayer Sch Engn, 8000 Cummings Hall, Hanover, NH 03766 USA. EM kenneth.tichauer@dartmouth.edu OI Tichauer, Kenneth/0000-0003-1667-3026 FU NIH [P01CA84201, R01CA156177, U54CA151662]; Canadian Institutes of Health FX This research was funded by NIH grants P01CA84201, R01CA156177, and U54CA151662. K. M. Tichauer acknowledges funding from the Canadian Institutes of Health Research postdoctoral fellowship program. NR 41 TC 15 Z9 15 U1 1 U2 6 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JUN PY 2012 VL 17 IS 6 AR 066001 DI 10.1117/1.JBO.17.6.066001 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 962XI UT WOS:000305582500034 PM 22734757 ER PT J AU Maguen, S Cohen, B Cohen, G Madden, E Bertenthal, D Seal, K AF Maguen, Shira Cohen, Beth Cohen, Greg Madden, Erin Bertenthal, Daniel Seal, Karen TI Gender Differences in Health Service Utilization Among Iraq and Afghanistan Veterans with Posttraumatic Stress Disorder SO JOURNAL OF WOMENS HEALTH LA English DT Article ID MENTAL-HEALTH; FEMALE VETERANS; MILITARY SERVICE; CARE SERVICES; VA; DIAGNOSES; WOMEN; PREVALENCE; SYMPTOMS; EXPOSURE AB Background: Little is known about gender differences in healthcare use among newly returning veterans with posttraumatic stress disorder (PTSD). We investigated gender differences in Veterans Affairs (VA) medical center health service use among Iraq and Afghanistan veterans with PTSD with and without comorbid depression and alcohol use disorders (AUD). Methods: Using VA administrative data, bivariate and multivariate statistics were used to examine gender differences in health service use among 159,705 Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans with PTSD seeking VA healthcare from October 7, 2001, to December 31, 2010. Results: Female veterans with PTSD were more likely to be black and single and to have higher mental health, primary care, and emergency care use compared to men with PTSD. Men were more likely to have higher mental health inpatient use compared to women. Women and men with comorbid PTSD and depression or comorbid PTSD and AUD were more likely to have higher use in all domains compared to their counterparts with PTSD without these comorbid disorders. Women with comorbid PTSD and depression were 12.5 times more likely to have a mental health inpatient hospitalization compared to their female counterparts without depression and twice as likely to have a mental health hospitalization compared to men with comorbid PTSD and depression. Conclusions: Women with PTSD had higher use than men in almost all areas, as did all veterans with comorbid PTSD and depression and comorbid PTSD and AUD, regardless of gender. Better understanding these health service use differences will allow for targeted evaluation and integrated treatment interventions in veterans with PTSD. C1 [Maguen, Shira; Cohen, Beth; Cohen, Greg; Madden, Erin; Bertenthal, Daniel; Seal, Karen] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Maguen, Shira; Cohen, Beth; Seal, Karen] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Bertenthal, Daniel] Mental Illness Res Educ & Clin Ctr, San Francisco, CA USA. RP Maguen, S (reprint author), San Francisco VA Med Ctr, 4150 Clement St 116-P, San Francisco, CA 94121 USA. EM shira.maguen@va.gov FU Department of Defense Concept Award [W81XWH-08-2-0077]; VA Health Services Research and Development Career Development Award [RCD 06-042] FX This research was supported by Department of Defense Concept Award Grant W81XWH-08-2-0077 and VA Health Services Research and Development Career Development Award RCD 06-042. NR 33 TC 22 Z9 22 U1 1 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD JUN PY 2012 VL 21 IS 6 BP 666 EP 673 DI 10.1089/jwh.2011.3113 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 962VK UT WOS:000305575100010 PM 22313026 ER PT J AU Schuler, M Yang, JCH Yamamoto, N O'Byrne, K Hirsh, V Mok, T Massey, D Zazulina, V Shahidi, M Sequist, L AF Schuler, Martin Yang, James Chih-Hsin Yamamoto, Nobuyuki O'Byrne, Ken Hirsh, Vera Mok, Tony Massey, Dan Zazulina, Victoria Shahidi, Mehdi Sequist, Lecia TI LUX-lung 3: A randomized, open-label, phase III study of afatinib vs pemetrexed and cisplatin as first-line treatment for patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations SO LUNG CANCER LA English DT Meeting Abstract C1 [Schuler, Martin] Univ Duisburg Essen, W German Canc Ctr, Essen, Germany. [Yang, James Chih-Hsin] Natl Taiwan Univ Hosp, Taipei, Taiwan. [Yamamoto, Nobuyuki] Shizuoka Canc Ctr, Shizuoka, Japan. [O'Byrne, Ken] St James Hosp, Dublin 8, Ireland. [Hirsh, Vera] McGill Univ, Montreal, PQ, Canada. [Mok, Tony] Prince Wales Hosp, Shatin, Hong Kong, Peoples R China. [Massey, Dan; Zazulina, Victoria; Shahidi, Mehdi] Boehringer Ingelheim Ltd, Bracknell, Berks, England. [Sequist, Lecia] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD JUN PY 2012 VL 77 SU 1 BP S25 EP S26 DI 10.1016/j.lungcan.2012.05.043 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 966MP UT WOS:000305842300044 ER PT J AU Dodge, HH Mattek, NC Austin, D Hayes, TL Kaye, JA AF Dodge, H. H. Mattek, N. C. Austin, D. Hayes, T. L. Kaye, J. A. TI In-home walking speeds and variability trajectories associated with mild cognitive impairment SO NEUROLOGY LA English DT Article ID ALZHEIMER-DISEASE; OLDER-ADULTS; GAIT; MOBILITY; ABNORMALITY; DYSFUNCTION; ATTENTION; DEMENTIA; DECLINE; MRI AB Objective: To determine whether unobtrusive long-term in-home assessment of walking speed and its variability can distinguish those with mild cognitive impairment (MCI) from those with intact cognition. Methods: Walking speed was assessed using passive infrared sensors fixed in series on the ceiling of the homes of elderly individuals participating in the Intelligent Systems for Assessing Aging Change (ISAAC) cohort study. Latent trajectory models were used to analyze weekly mean speed and walking speed variability (coefficient of variation [COV]). Results: ISAAC participants living alone included 54 participants with intact cognition, 31 participants with nonamnestic MCI (naMCI), and 8 participants with amnestic MCI at baseline, with a mean follow-up of 2.6 +/- 1.0 years. Trajectory models identified 3 distinct trajectories (fast, moderate, and slow) of mean weekly walking speed. Participants with naMCI were more likely to be in the slow speed group than in the fast (p = 0.01) or moderate (p = 0.04) speed groups. For COV, 4 distinct trajectories were identified: group 1, the highest baseline and increasing COV followed by a sharply declining COV; groups 2 and 3, relatively stable COV; and group 4, the lowest baseline and decreasing COV. Participants with naMCI were more likely to be members of either highest or lowest baseline COV groups (groups 1 or 4), possibly representing the trajectory of walking speed variability for early-and late-stage MCI, respectively. Conclusion: Walking speed and its daily variability may be an early marker of the development of MCI. These and other real-time measures of function may offer novel ways of detecting transition phases leading to dementia. Neurology (R) 2012; 78: 1946-1952 C1 [Dodge, H. H.; Mattek, N. C.; Austin, D.; Hayes, T. L.; Kaye, J. A.] Oregon Hlth & Sci Univ, Oregon Ctr Aging & Technol, Portland, OR 97201 USA. [Dodge, H. H.; Mattek, N. C.; Kaye, J. A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Hayes, T. L.] Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR 97201 USA. [Kaye, J. A.] Portland VA Med Ctr, Neurol Serv, Portland, OR USA. RP Dodge, HH (reprint author), Oregon Hlth & Sci Univ, Oregon Ctr Aging & Technol, Portland, OR 97201 USA. EM dodgeh@ohsu.edu OI Kaye, Jeffrey/0000-0002-9971-3478 FU National Institutes of Health [P30-AG024978, R01-AG024059, P30-AG008017, R01-AG033581]; Intel Corporation FX Supported by grants from the National Institutes of Health (P30-AG024978, R01-AG024059, P30-AG008017, and R01-AG033581) and the Intel Corporation. NR 40 TC 34 Z9 35 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 2012 VL 78 IS 24 BP 1946 EP 1952 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 958ZG UT WOS:000305278900013 PM 22689734 ER PT J AU Kanno, T Kamba, T Yamasaki, T Shibasaki, N Saito, R Terada, N Toda, Y Mikami, Y Inoue, T Kanematsu, A Nishiyama, H Ogawa, O Nakamura, E AF Kanno, T. Kamba, T. Yamasaki, T. Shibasaki, N. Saito, R. Terada, N. Toda, Y. Mikami, Y. Inoue, T. Kanematsu, A. Nishiyama, H. Ogawa, O. Nakamura, E. TI JunB promotes cell invasion and angiogenesis in VHL-defective renal cell carcinoma SO ONCOGENE LA English DT Article DE renal-cell carcinoma; VHL gene; JunB invasion; angiogenesis ID VON-HIPPEL-LINDAU; TUMOR-SUPPRESSOR PROTEIN; NF-KAPPA-B; MATRIX METALLOPROTEINASES-2; TRANSCRIPTIONAL ACTIVATION; GENE-EXPRESSION; KIDNEY CANCER; IDENTIFICATION; PVHL; AP-1 AB Inactivation of the von Hippel-Lindau (VHL) tumor-suppressor gene causes both hereditary and sporadic clear-cell renal-cell carcinoma (ccRCC). Although the best-characterized function of the VHL protein (pVHL) is regulation of hypoxia-inducible factor-alpha (HIF alpha), pVHL also controls the development of pheochromocytoma through HIF-independent pathways by regulating JunB. However, it is largely unknown how these pathways contribute to the development and progression of ccRCC. In the present study, we confirmed that JunB was upregulated in VHL-defective ccRCC specimens by immunostaining. Short-hairpin RNA (shRNA)-mediated knockdown of JunB in 786-O and A498 VHL null ccRCC cells suppressed their invasiveness. In addition, JunB knockdown significantly repressed tumor growth and microvessel density in xenograft tumor assays. Conversely, forced expression of wild-type, but not dimerization-defective, JunB in a VHL-restored 786-O subclone promoted invasion in vitro and tumor growth and vessel formation in vivo. Quantitative PCR array analysis revealed that JunB regulated multiple genes relating to tumor invasion and angiogenesis such as matrix metalloproteinase-2 (MMP-2), MMP-9 and chemokine (C-C motif) ligand-2 (CCL2) in 786-O cells. JunB knockdown in these cells reduced the proteolytic activity of both MMPs in gelatin zymography and the amount of CCL2 in the culture supernatant. Moreover, shRNA-mediated knockdown of MMP-2 or inhibition of CCL2 activity with a neutralizing antibody repressed xenograft tumor growth and angiogenesis. Collectively, these results suggest that JunB promotes tumor invasiveness and enhances angiogenesis in VHL-defective ccRCCs. Oncogene (2012) 31, 3098-3110; doi: 10.1038/onc.2011.475; published online 24 October 2011 C1 [Nakamura, E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Nakamura, E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kanno, T.; Kamba, T.; Yamasaki, T.; Shibasaki, N.; Saito, R.; Terada, N.; Inoue, T.; Kanematsu, A.; Nishiyama, H.; Ogawa, O.] Kyoto Univ, Grad Sch Med, Dept Urol, Kyoto, Japan. [Toda, Y.] Kyoto Univ, Grad Sch Med, Anat Ctr, Kyoto, Japan. [Mikami, Y.] Kyoto Univ, Grad Sch Med, Anat Pathol Lab, Kyoto, Japan. RP Nakamura, E (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Mayer 457, Boston, MA 02115 USA. EM Nakamura_Eijiro@dfci.harvard.edu FU Ministry of Education, Culture, Sports, Science and Technology, Japan FX We thank Dr William G Kaelin, Jr, for critical comments and for providing us with the different RCC cell lines. We appreciate all members of Cancer Research Courses for Integrated Research Training at Kyoto University Graduate School of Medicine for helpful advice and discussion. We also thank Tomoko Matsushita, Megumi Kuraguchi and Yuko Fujieda for technical assistance. Grant support: Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan. NR 48 TC 19 Z9 21 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN PY 2012 VL 31 IS 25 BP 3098 EP 3110 DI 10.1038/onc.2011.475 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 964OP UT WOS:000305705900008 PM 22020339 ER PT J AU Restrepo, MI Anzueto, A AF Restrepo, Marcos I. Anzueto, Antonio TI Global Trends in Community-Acquired Pneumonia Preface SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material C1 [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Pulm & Crit Care Med, S Texas Vet Hlth Care Syst Audie L Murphy Div, San Antonio, TX 78229 USA. [Restrepo, Marcos I.; Anzueto, Antonio] S Texas Vet Hlth Care Syst Audie Murphy VA Hosp, Vet Evidence Res Disseminat & Implementat Ctr VER, San Antonio, TX USA. RP Restrepo, MI (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Pulm & Crit Care Med, S Texas Vet Hlth Care Syst Audie L Murphy Div, 7400 Merton Minter Blvd 11C6, San Antonio, TX 78229 USA. EM restrepom@uthscsa.edu RI Restrepo, Marcos/H-4442-2014 FU NHLBI NIH HHS [K23 HL096054] NR 0 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1069-3424 J9 SEMIN RESP CRIT CARE JI Semin. Respir. Crit. Care Med. PD JUN PY 2012 VL 33 IS 3 BP 211 EP 211 DI 10.1055/s-0032-1315646 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 963PK UT WOS:000305634500001 PM 22718206 ER PT J AU Elliott, SJ Shera, CA AF Elliott, Stephen J. Shera, Christopher A. TI The cochlea as a smart structure SO SMART MATERIALS AND STRUCTURES LA English DT Article; Proceedings Paper CT 14th International Adaptronic Congress CY SEP 07-08, 2011 CL Darmstadt, GERMANY ID OTOACOUSTIC EMISSIONS; COHERENT REFLECTION; TRAVELING-WAVE; MODEL; MECHANICS; AMPLIFICATION; CHINCHILLA; RESPONSES; STIMULI AB The cochlea is part of the inner ear and its mechanical response provides us with many aspects of our amazingly sensitive and selective hearing. The human cochlea is a coiled tube, with two main fluid chambers running along its length, separated by a 35 mm-long flexible partition that has its own internal dynamics. A dispersive wave can propagate along the cochlea due to the interaction between the inertia of the fluid and the dynamics of the partition. This partition includes about 12 000 outer hair cells, which have different structures, on a micrometre and a nanometre scale, and act both as motional sensors and as motional actuators. The local feedback action of all these cells amplifies the motion inside the inner ear by more than 40 dB at low sound pressure levels. The feedback loops become saturated at higher sound pressure levels, however, so that the feedback gain is reduced, leading to a compression of the dynamic range in the cochlear amplifier. This helps the sensory cells, with a dynamic range of only about 30 dB, to respond to sounds with a dynamic range of more than 120 dB. The active and nonlinear nature of the dynamics within the cochlea give rise to a number of other phenomena, such as otoacoustic emissions, which can be used as a diagnostic test for hearing problems in newborn children, for example. In this paper we view the mechanical action of the cochlea as a smart structure. In particular a simplified wave model of the cochlear dynamics is reviewed that represents its essential features. This can be used to predict the motion along the cochlea when the cochlea is passive, at high levels, and also the effect of the cochlear amplifier, at low levels. C1 [Elliott, Stephen J.] Univ Southampton, Inst Sound & Vibrat Res, Southampton SO17 1BJ, Hants, England. [Shera, Christopher A.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. [Shera, Christopher A.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Elliott, SJ (reprint author), Univ Southampton, Inst Sound & Vibrat Res, Tizard Bldg, Southampton SO17 1BJ, Hants, England. EM s.j.elliott@soton.ac.uk FU NIDCD NIH HHS [R01 DC003687] NR 42 TC 12 Z9 12 U1 0 U2 16 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0964-1726 EI 1361-665X J9 SMART MATER STRUCT JI Smart Mater. Struct. PD JUN PY 2012 VL 21 IS 6 AR 064001 DI 10.1088/0964-1726/21/6/064001 PG 11 WC Instruments & Instrumentation; Materials Science, Multidisciplinary SC Instruments & Instrumentation; Materials Science GA 959BZ UT WOS:000305286400002 PM 23148128 ER PT J AU Wu, JC Qi, L Wang, Y Kegel, KB Yoder, J Difiglia, M Qin, ZH Lin, F AF Wu, Jun-chao Qi, Lin Wang, Yan Kegel, Kimberly B. Yoder, Jennifer Difiglia, Marian Qin, Zheng-hong Lin, Fang TI The regulation of N-terminal Huntingtin (Htt552) accumulation by Beclin1 SO ACTA PHARMACOLOGICA SINICA LA English DT Article DE Huntingtin (Htt); Beclin1; protein degradation; autophagy; RNA interference; ubiquitin-proteasome system; autophagy/lysosome pathway ID DISEASE GENE HOMOLOG; MUTANT HUNTINGTIN; EMBRYONIC LETHALITY; WILD-TYPE; AUTOPHAGY; INHIBITION; FRAGMENTS; POLYGLUTAMINE; DEGRADATION; EXPANSIONS AB Aim: Huntingtin protein (Htt) was a neuropathological hallmark in human Huntington's Disease. The study aimed to investigate whether the macroautophagy regulator, Beclin1, was involved in the degradation of Htt. Methods: PC12 cells and primary cultured brain neurons of rats were examined. pDC316 adenovirus shuttle plasmid was used to mediate the expression of wild-type Htt-18Q-552 or mutant Htt-100Q-552 in PC12 cells. The expression of the autophagy-related proteins LC3 II and Beclin1, as well as the lysosome-associated enzymes Cathepsin B and L was evaluated using Western blotting. The locations of Beclin1 and Htt were observed with immunofluorescence and confocal microscope. Results: Htt552 expression increased the expression of LC3 II, Beclin1, cathepsin B and L in autophagy/lysosomal degradation pathway. Treatment with the autophagy inhibitor 3-MA or the proteasome inhibitors lactacystin and MG-132 increased Htt552 levels in PC12 cells infected with Ad-Htt-18Q-552 or Ad-Htt-100Q-552. The proteasome inhibitor caused a higher accumulation of Htt552-18Q than Htt552-100Q, and the autophagy inhibitor resulted in a higher accumulation of Htt552-100Q than Htt552-18Q. Similar results were observed in primary cultured neurons infected with adenovirus. In Htt552-expressing cells, Beclin1 was redistributed from the nucleus to the cytoplasm. Htt siRNA prevented Beclin1 redistribution in starvation conditions. Blockade of Beclin1 nuclear export by leptomycin B or Beclin1 deficiency caused by RNA interference induced the formation of mHtt552 aggregates. Conclusion: Beclin1 regulates the accumulation of Htt via macroautophagy. C1 [Wu, Jun-chao; Qi, Lin; Wang, Yan; Qin, Zheng-hong; Lin, Fang] Soochow Univ, Dept Pharmacol, Lab Aging & Nervous Dis, Sch Pharmaceut Sci, Suzhou 215123, Peoples R China. [Kegel, Kimberly B.; Yoder, Jennifer; Difiglia, Marian] Massachusetts Gen Hosp, Dept Neurol, Lab Cellular Neurobiol, Charlestown, MA 02129 USA. [Kegel, Kimberly B.; Yoder, Jennifer; Difiglia, Marian] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Lin, F (reprint author), Soochow Univ, Dept Pharmacol, Lab Aging & Nervous Dis, Sch Pharmaceut Sci, Suzhou 215123, Peoples R China. EM bluestonelin@hotmail.com FU National Natural Science Foundation of China [30600197]; Natural Science Foundation of Jiangsu Province for College [09KJB310014] FX This work was supported by grants from the National Natural Science Foundation of China (No 30600197) and the Natural Science Foundation of Jiangsu Province for College (No 09KJB310014). NR 33 TC 11 Z9 11 U1 1 U2 5 PU ACTA PHARMACOLOGICA SINICA PI SHANGHAI PA 294 TAI-YUAN RD, SHANGHAI, 200031, PEOPLES R CHINA SN 1671-4083 J9 ACTA PHARMACOL SIN JI Acta Pharmacol. Sin. PD JUN PY 2012 VL 33 IS 6 BP 743 EP 751 DI 10.1038/aps.2012.14 PG 9 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 955PX UT WOS:000305034500004 PM 22543707 ER PT J AU Truong, QA Bayley, J Hoffmann, U Bamberg, F Schlett, CL Nagurney, JT Koenig, W Januzzi, JL AF Truong, Quynh A. Bayley, James Hoffmann, Udo Bamberg, Fabian Schlett, Christopher L. Nagurney, John T. Koenig, Wolfgang Januzzi, James L. TI Multi-marker strategy of natriuretic peptide with either conventional or high-sensitivity troponin-T for acute coronary syndrome diagnosis in emergency department patients with chest pain: From the "Rule Out Myocardial Infarction Using Computer Assisted Tomography" (ROMICAT) trial SO AMERICAN HEART JOURNAL LA English DT Article ID HEART-FAILURE; INFORMATION; PREDICTION; ADMISSION; COPEPTIN; PLASMA; ASSAY AB Background Compared to troponin alone, a dual-marker strategy with natriuretic peptides may improve acute coronary syndrome (ACS) diagnosis with a single blood draw and provide physiologic information regarding underlying heart disease. We evaluate the value of adding natriuretic peptides (myocyte stress markers) to troponins (myocardial injury markers) for diagnosing ACS in emergency department patients with chest pain. Methods In 328 patients (53 +/- 12 years, 63% men) with an initially negative conventional troponin and nonischemic electrocardiogram who underwent 64-slice cardiac computed tomography (CT), we measured conventional troponin-T (cTnT), high-sensitivity troponin-T (hsTnT), N-terminal pro-B type natriuretic peptide, and mid-regional pro-atrial natriuretic peptide. ACS was defined as myocardial infarction or unstable angina. CT was evaluated for coronary plaque, stenosis, and regional wall motion abnormality. Results Patients with ACS (n = 29, 9%) had higher concentrations of each biomarker compared to those without (all P < .01). Adding natriuretic peptides, especially N-terminal pro-B type natriuretic peptide, to both cTnT or hsTnT improved the C-statistics and net reclassification index for ACS, largely driven by correctly reclassifying events. Dual-negative marker results improved sensitivity (cTnT 38% to 83%-86%, hsTnT 59% to 86%-90%; all P < .01) and negative predictive value (cTnT 94% to 97%-98%, hsTnT 96% to 97%-98%) for ACS. Patients with dual-negative markers had the lowest percentage of CT coronary plaque, stenosis, and regional wall motion abnormality (all P-trend < .001). Conclusion Among emergency department patients with low-intermediate likelihood of ACS, combining natriuretic peptides with either conventional or highly-sensitive troponin improved discriminatory capacity and allowed for better reclassification of ACS, findings supported by structural and functional CT results. (Am Heart J 2012;163:972-979.e1.) C1 [Truong, Quynh A.; Hoffmann, Udo; Januzzi, James L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Truong, Quynh A.; Bayley, James; Hoffmann, Udo; Bamberg, Fabian; Schlett, Christopher L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Nagurney, John T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Koenig, Wolfgang] Univ Ulm, Ulm, Germany. RP Truong, QA (reprint author), 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM qtruong@partners.org FU NHLBI NIH HHS [L30 HL093806, K23 HL098370, K24 HL113128, R01 HL080053, R01 HL080053-03, L30 HL093806-02, K23 HL098370-04] NR 22 TC 14 Z9 15 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 2012 VL 163 IS 6 BP 972 EP + AR 979.e1 DI 10.1016/j.ahj.2012.03.010 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 960YB UT WOS:000305428200008 PM 22709749 ER PT J AU Pascual-Figal, DA Casas, T Ordonez-LLanos, J Manzano-Fernandez, S Bonaque, JC Boronat, M Munoz-Esparza, C Valdes, M Januzzi, JL AF Pascual-Figal, Domingo A. Casas, Teresa Ordonez-LLanos, Jordi Manzano-Fernandez, Sergio Bonaque, Juan C. Boronat, Miguel Munoz-Esparza, Carmen Valdes, Mariano Januzzi, James L. TI Highly sensitive troponin T for risk stratification of acutely destabilized heart failure SO AMERICAN HEART JOURNAL LA English DT Article ID BRAIN NATRIURETIC PEPTIDE; CARDIAC TROPONIN; MYOCARDIAL-INFARCTION; PROGNOSTIC VALUE; OF-CARDIOLOGY; GUIDELINES; DIAGNOSIS AB Background A highly sensitive assay for troponin T (hsTnT) has been recently developed, which allows for the detection of even minor myocardial necrosis with high precision. It remains unexplored whether hsTnT provides incremental prognostic accuracy beyond conventional (c)TnT in patients with acutely decompensated heart failure (ADHF). Methods A total of 202 consecutive patients admitted with ADHF and without criteria for acute myocardial infarction were studied. Troponin T was measured using the highly sensitive assay and compared with the conventional method. Patients were clinically followed up at a median of 406 days, with a primary outcome measure of all-cause mortality. Results The high-sensitive assay detected measurable TnT in 98% of patients vs 56% for cTnT; 81% had an hsTnT above the 99th percentile for a healthy reference population, and it reclassified 60% of those with undetectable cTnT. Both TnT methods predicted the risk of death in adjusted multivariable Cox regression analyses, without a superiority of hsTnT over cTnT in the entire population (area under the curve 0.67 vs 0.71, P = .2). Among patients with a cTnT below 0.03 ng/mL (the lowest cut-point with <10% imprecision; n = 134), solely hsTnT improved the prediction of death over clinical risk factors (relative integrated discrimination improvement +36%, P = .01) and hsTnT above 20 pg/mL identified a significant higher risk of death (hazard ratio 4.7, 95% CI 1.6-13.8, P = .005). Conclusion Among patients with ADHF, myocardial necrosis (as detected with the hsTnT assay) was nearly ubiquitous. The highly sensitive assay for TnT provides comparable prognostic information to cTnT overall, but among those in whom the cTnT method was less precise or frankly negative, the hsTnT assay provided prognostic information. (Am Heart J 2012;163:1002-10.) C1 [Pascual-Figal, Domingo A.; Manzano-Fernandez, Sergio; Bonaque, Juan C.; Munoz-Esparza, Carmen; Valdes, Mariano] Univ Murcia, Virgen Arrixaca Hosp, Cardiol Dept, Murcia, Spain. [Pascual-Figal, Domingo A.; Manzano-Fernandez, Sergio; Bonaque, Juan C.; Munoz-Esparza, Carmen; Valdes, Mariano] Univ Murcia, Sch Med, Murcia, Spain. [Casas, Teresa; Boronat, Miguel] Virgen Arrixaca Hosp, Biochem Serv, Murcia, Spain. [Ordonez-LLanos, Jordi] St Pau Hosp, Biochem Serv, Barcelona, Spain. [Ordonez-LLanos, Jordi] Autonomous Univ Barcelona, Dept Biochem & Mol Biol, Barcelona, Spain. [Januzzi, James L.] Massachusetts Gen Hosp, Cardiol Div, Boston, MA 02114 USA. RP Pascual-Figal, DA (reprint author), Univ Hosp Virgen Arrixaca, Dept Cardiol, Ctra Madrid Cartagena S-N, Murcia 30120, Spain. EM dpascual@um.es RI Pascual Figal, Domingo /B-3794-2008; ordonez-llanos, jorge/B-4961-2011 OI Pascual Figal, Domingo /0000-0002-4993-9540; ordonez-llanos, jorge/0000-0003-4896-5832 FU Roche Diagnostics FX Dr Pascual-Figal, Dr Ordonez-Llanos, and Dr Januzzi report grant support from Roche Diagnostics. NR 18 TC 32 Z9 34 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 2012 VL 163 IS 6 BP 1002 EP 1010 DI 10.1016/j.ahj.2012.03.015 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 960YB UT WOS:000305428200012 PM 22709753 ER PT J AU Steinman, MA Sudore, RL Peterson, CA Harlow, JB Fried, TR AF Steinman, Michael A. Sudore, Rebecca L. Peterson, Carolyn A. Harlow, John B. Fried, Terri R. TI Influence of Patient Age and Comorbid Burden on Clinician Attitudes Toward Heart Failure Guidelines SO AMERICAN JOURNAL OF GERIATRIC PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Gen Internal Med DE aged; clinical practice guidelines; comorbidity; geriatrics; physician attitudes ID QUALITY-OF-CARE; ELDERLY-PATIENTS; EFFECTIVE MANAGEMENT; BARRIERS; TRIAL; THERAPY; RISK; LIFE AB Background: Clinical practice guidelines have been criticized for insufficient attention to the unique needs of patients of advanced age and with multiple comorbid conditions. However, little empiric research is available to inform this topic. Methods: We conducted telephone interviews with staff physicians and nurse practitioners in 4 VA health care systems. Respondents were asked to rate the usefulness of national heart failure guidelines for patients of different ages and levels of comorbid burden on a 5-point scale and to comment on the reasons for their ratings. Results: Of 139 clinicians contacted, 65 (47%) completed the interview. Almost half (49%) were women, and 48 (74%) were general internists or family practitioners. On a 5-point scale assessing the usefulness of clinical practice guidelines for heart failure, the mean (SD) response ranged from 4.4 (0.7) for patients younger than 65 years with few comorbid conditions to 3.5 (1.2) for patients older than 80 years with multiple comorbid conditions (P < 0.001). The difference in perceived usefulness varied more by patient age than by degree of comorbidity (P = 0.02). Four major concepts underlay the perceived usefulness of guidelines across different patient types: (1) harm of treatment and complexity of the patient's clinical condition and pharmacologic needs, (2) expected benefits of treatment, (3) patient preferences and abilities, and (4) confidence in the validity of guideline recommendations. Conclusion: Clinicians perceive heart failure guidelines to be substantially less useful in patients of older age and with greater comorbid burden. Concerns about the clinical and pharmacologic complexity of these patients and the expected benefits of drug therapy were commonly invoked as reasons for this skepticism. (Am J Geriatr Pharmacother. 2012;10:211-218) Published by Elsevier HS Journals, Inc. C1 [Steinman, Michael A.; Sudore, Rebecca L.; Peterson, Carolyn A.; Harlow, John B.] San Francisco VA Med Ctr, Hlth Serv Res & Dev Res Enhancement Award Program, San Francisco, CA 94121 USA. [Steinman, Michael A.; Sudore, Rebecca L.; Peterson, Carolyn A.; Harlow, John B.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Harlow, John B.] Med Univ S Carolina, Sch Med, Charleston, SC 29425 USA. [Fried, Terri R.] Yale Univ, Sch Med, Div Geriatr, New Haven, CT USA. RP Steinman, MA (reprint author), San Francisco VA Med Ctr, Hlth Serv Res & Dev Res Enhancement Award Program, 4150 Clement St,Box 181G, San Francisco, CA 94121 USA. EM mike.steinman@ucsf.edu FU NIA NIH HHS [K24 AG028443, K23 AG030999] NR 31 TC 4 Z9 4 U1 0 U2 5 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 1543-5946 J9 AM J GERIATR PHARMAC JI Am. J. Geriatr. Pharmacother. PD JUN PY 2012 VL 10 IS 3 BP 211 EP 218 DI 10.1016/j.amjopharm.2012.04.003 PG 8 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 962LE UT WOS:000305545800006 PM 22579695 ER PT J AU Reidelberger, R Haver, A Chelikani, PK Apenteng, B Perriotte-Olson, C Anders, K Steenson, S Blevins, JE AF Reidelberger, Roger Haver, Alvin Chelikani, Prasanth K. Apenteng, Bettye Perriotte-Olson, Curtis Anders, Krista Steenson, Sharalyn Blevins, James E. TI Effects of leptin replacement alone and with exendin-4 on food intake and weight regain in weight-reduced diet-induced obese rats SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE food restriction; hyperphagia; leptin sensitivity; glucagon-like peptide-1 receptor agonist ID INTERMITTENT INTRAPERITONEAL INFUSION; Y GASTRIC BYPASS; LOW-DOSE LEPTIN; BODY-WEIGHT; INTRAVENOUS-INFUSION; RODENT MODELS; GUT HORMONE; ADIPOSITY; AMYLIN; CHOLECYSTOKININ AB Weight loss in obese humans produces a relative leptin deficiency, which is postulated to activate potent orexigenic and energy conservation mechanisms to restrict weight loss and promote weight regain. Here we determined whether leptin replacement alone or with GLP-1 receptor agonist exendin-4 attenuates weight regain or promotes greater weight loss in weight-reduced diet-induced obese (DIO) rats. Forty percent restriction in daily intake of a high-fat diet in DIO rats for 4 wk reduced body weight by 12%, body fat by 29%, and plasma leptin by 67% and normalized leptin sensitivity. When food restriction ended, body weight, body fat, and plasma leptin increased rapidly. Daily administration of leptin [3-h intraperitoneal (ip) infusions (4 nmol.kg (-1).h (-1))] at onset and end of dark period for 3 wk did not attenuate hyperphagia and weight regain, nor did it affect mean daily meal sizes or meal numbers. Exendin-4 (50 pmol.kg (-1).h (-1)) infusions during the same intervals prevented postrestriction hyperphagia and weight regain by normalizing meal size. Coadministration of leptin and exendin-4 did not reduce body weight more than exendin-4 alone. Instead, leptin began to attenuate the inhibitory effects of exendin-4 on food intake, meal size, and weight regain by the end of the second week of administration. Plasma leptin in rats receiving leptin was sevenfold greater than in rats receiving vehicle and 17-fold greater than in rats receiving exendin-4. Together, these results do not support the hypothesis that leptin replacement alone or with exendin-4 attenuates weight regain or promotes greater weight loss in weight-reduced DIO rats. C1 [Reidelberger, Roger; Haver, Alvin; Perriotte-Olson, Curtis] Vet Affairs Nebraska Western Iowa Hlth Care Syst, Vet Affairs Res Serv, Omaha, NE USA. [Reidelberger, Roger; Haver, Alvin; Chelikani, Prasanth K.; Apenteng, Bettye; Anders, Krista; Steenson, Sharalyn] Creighton Univ, Dept Biomed Sci, Omaha, NE 68178 USA. [Blevins, James E.] Vet Affairs Puget Sound Hlth Care Syst, Vet Affairs Res Serv, Seattle, WA USA. [Blevins, James E.] Univ Washington, Sch Med, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Chelikani, Prasanth K.] Univ Calgary, Gastrointestinal Res Grp, Dept Prod Anim Hlth, Snyder Inst Chron Dis,Fac Vet Med, Calgary, AB, Canada. RP Reidelberger, R (reprint author), VA NWIHCS 151,4101 Woolworth Ave, Omaha, NE 68105 USA. EM rogerr@creighton.edu FU National Institutes of Health [R01-DK-70851, P20-RR-16469]; National Institutes of Health Diabetes Research Center [P30-DK-17047]; Department of Veterans Affairs; Veterans Health Administration; Office of Research and Development; Rehabilitation Research, and Development Service and Biomedical Laboratory Research and Development FX This work was performed at the Veterans Affairs Nebraska-Western Iowa Health Care System and Veterans Affairs Puget Sound Health Care System and was supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research, and Development Service and Biomedical Laboratory Research and Development. This research was also supported in part by the National Institutes of Health (R01-DK-70851 and P20-RR-16469) and the Cellular and Molecular Imaging Core of the National Institutes of Health Diabetes Research Center (P30-DK-17047). The contents of this article do not represent the views of the Department of Veterans Affairs or the US Government. NR 49 TC 9 Z9 9 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUN PY 2012 VL 302 IS 12 BP E1576 EP E1585 DI 10.1152/ajpendo.00058.2012 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 960XQ UT WOS:000305426900014 PM 22510712 ER PT J AU Velez, JCQ Ierardi, JL Bland, AM Morinelli, TA Arthur, JM Raymond, JR Janech, MG AF Velez, Juan Carlos Q. Ierardi, Jessalyn L. Bland, Alison M. Morinelli, Thomas A. Arthur, John M. Raymond, John R. Janech, Michael G. TI Enzymatic processing of angiotensin peptides by human glomerular endothelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE angiotensin-converting enzyme; prolylendopeptidase; endothelium ID CONVERTING-ENZYME; ASPARTYL AMINOPEPTIDASE; PERIPHERAL-TISSUES; ACE2 EXPRESSION; IGA NEPHROPATHY; CLEAVING ENZYME; HUMAN KIDNEY; SYSTEM; LOCALIZATION; METABOLISM AB Velez JC, Ierardi JL, Bland AM, Morinelli TA, Arthur JM, Raymond JR, Janech MG. Enzymatic processing of angiotensin peptides by human glomerular endothelial cells. Am J Physiol Renal Physiol 302: F1583-F1594, 2012. First published March 28, 2012; doi: 10.1152/ajprenal.00087.2012.-The intraglomerular renin-angiotensin system (RAS) is linked to the pathogenesis of progressive glomerular diseases. Glomerular podocytes and mesangial cells play distinct roles in the metabolism of angiotensin (ANG) peptides. However, our understanding of the RAS enzymatic capacity of glomerular endothelial cells (GEnCs) remains incomplete. We explored the mechanisms of endogenous cleavage of ANG substrates in cultured human GEnCs (hGEnCs) using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and isotope-labeled peptide quantification. Overall, hGEnCs metabolized ANG II at a significantly slower rate compared with podocytes, whereas the ANG I processing rate was comparable between glomerular cell types. ANG II was the most abundant fragment of ANG I, with lesser amount of ANG-(1-7) detected. Formation of ANG II from ANG I was largely abolished by an ANG-converting enzyme (ACE) inhibitor, whereas ANG-(1-7) formation was decreased by a prolylendopeptidase (PEP) inhibitor, but not by a neprilysin inhibitor. Cleavage of ANG II resulted in partial conversion to ANG-(1-7), a process that was attenuated by an ACE2 inhibitor, as well as by an inhibitor of PEP and prolylcarboxypeptidase. Further fragmentation of ANG-(1-7) to ANG-(1-5) was mediated by ACE. In addition, evidence of aminopeptidase N activity (APN) was demonstrated by detecting amelioration of conversion of ANG III to ANG IV by an APN inhibitor. While we failed to find expression or activity of aminopeptidase A, a modest activity attributable to aspartyl aminopeptidase was detected. Messenger RNA and gene expression of the implicated enzymes were confirmed. These results indicate that hGEnCs possess prominent ACE activity, but modest ANG II-metabolizing activity compared with that of podocytes. PEP, ACE2, prolylcarboxypeptidase, APN, and aspartyl aminopeptidase are also enzymes contained in hGEnCs that participate in membrane-bound ANG peptide cleavage. Injury to specific cell types within the glomeruli may alter the intrarenal RAS balance. C1 [Velez, Juan Carlos Q.; Ierardi, Jessalyn L.; Bland, Alison M.; Morinelli, Thomas A.; Arthur, John M.; Janech, Michael G.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Velez, Juan Carlos Q.; Arthur, John M.; Janech, Michael G.] Ralph H Johnson Vet Affairs Med Ctr, Med & Res Serv, Charleston, SC USA. [Raymond, John R.] Med Coll Wisconsin, Dept Med, Div Nephrol, Milwaukee, WI 53226 USA. RP Velez, JCQ (reprint author), 96 Jonathan Lucas St,Clinical Sci Bldg,Rm 826F, Charleston, SC 29425 USA. EM velezj@musc.edu RI Velez, Juan Carlos/N-3782-2016; OI Janech, Michael/0000-0002-3202-4811 FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [DK080944-04]; Dialysis Clinics, Inc.; Ralph H. Johnson Veterans Affairs Med. Ctr.; Veterans Affairs CDA-2 Career Development Award; Nephcure Foundation FX J.C.V. is supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, Grant DK080944-04, Dialysis Clinics, Inc., and the Ralph H. Johnson Veterans Affairs Med. Ctr. Research Enhancement Award Program. M.G.J. was supported by a Veterans Affairs CDA-2 Career Development Award and the Nephcure Foundation Young Investigator Award. NR 65 TC 18 Z9 19 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUN PY 2012 VL 302 IS 12 BP F1583 EP F1594 DI 10.1152/ajprenal.00087.2012 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 960XC UT WOS:000305425300009 PM 22461301 ER PT J AU Iglehart, JD Valero, MG AF Iglehart, J. Dirk Valero, Monica G. TI Commentary on "The role of the breast cancer surgeon in personalized cancer care: clinical utility of the 21-gene assay" SO AMERICAN JOURNAL OF SURGERY LA English DT Review ID GENE-EXPRESSION; RECURRENCE SCORE; TAMOXIFEN C1 [Iglehart, J. Dirk] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Iglehart, J. Dirk; Valero, Monica G.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Iglehart, JD (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM jiglehart@partners.org NR 10 TC 0 Z9 0 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD JUN PY 2012 VL 203 IS 6 BP 759 EP 760 DI 10.1016/j.amjsurg.2011.09.030 PG 2 WC Surgery SC Surgery GA 961NL UT WOS:000305471600014 PM 22494880 ER PT J AU Vickrey, BG Hirtz, D Waddy, S Cheng, EM Johnston, SC AF Vickrey, Barbara G. Hirtz, Deborah Waddy, Salina Cheng, Eric M. Johnston, S. Claiborne TI Comparative effectiveness and implementation research: Directions for Neurology SO ANNALS OF NEUROLOGY LA English DT Article ID HEALTH-SERVICES RESEARCH; MYOCARDIAL-INFARCTION; ETHNIC DISPARITIES; CONTROLLED-TRIAL; STROKE; OUTCOMES; WARFARIN; EPILEPSY; THERAPY; ASPIRIN AB There is an enormous unmet need for knowledge about how new insights from discovery and translational research can yield measurable, population-level improvements in health and reduction in mortality among those having or at risk for neurological disease. Once several, well-conducted randomized controlled trials establish the efficacy of a given therapy, implementation research can generate new knowledge about barriers to uptake of the therapy into widespread clinical care, and what strategies are effective in overcoming those barriers and in addressing health disparities. Comparative effectiveness research aims to elucidate the relative value (including clinical benefit, clinical harms, and/or costs) of alternative efficacious management approaches to a neurological disorder, generally through direct comparisons, and may include comparisons of methodologies for implementation. Congress has recently appropriated resources and established an institute to prioritize funding for such research. Neurologists and neuroscientists should understand the scope and objectives of comparative effectiveness and implementation research, their range of methodological approaches (formal literature syntheses, randomized trials, observational studies, modeling), and existing research resources (centers for literature synthesis, registries, practice networks) relevant to research for neurological conditions, to close the well-documented evidence-to-practice gap. Future directions include building this research resource capacity, producing scientists trained to conduct rigorous comparative effectiveness and implementation research, and embracing innovative strategies to set research priorities in these areas. Ann Neurol 2012;71:732742 C1 [Vickrey, Barbara G.; Cheng, Eric M.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. [Vickrey, Barbara G.; Cheng, Eric M.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Hirtz, Deborah; Waddy, Salina] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Johnston, S. Claiborne] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Vickrey, BG (reprint author), Univ Calif Los Angeles, Dept Neurol, Box 951769,C128 RNRC,710 Westwood Plaza, Los Angeles, CA 90095 USA. EM bvickrey@ucla.edu FU Genentech; Kansas City Area Life Sciences Institute; NINDS; Partners Neurology; University of Maryland FX B.G.V.: board membership, National Advisory Neurological Disorders and Stroke, National Multiple Sclerosis Society, Sports Concussion Institute; consultancy, EMD Serono, Research Triangle Institute, RAND, National Academy of Sciences; grants/grants pending, Genentech; speaking fees, Kansas City Area Life Sciences Institute, Partners Neurology, University of Maryland; travel expenses, French National Foundation on Alzheimer's Disease and Related Disorders. E.M.C.: grants/grants pending, NINDS. NR 59 TC 10 Z9 11 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 2012 VL 71 IS 6 BP 732 EP 742 DI 10.1002/ana.22672 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 961YU UT WOS:000305506300005 PM 22718542 ER PT J AU Lin, MT Cantuti-Castelvetri, I Zheng, KN Jackson, KE Tan, YB Arzberger, T Lees, AJ Betensky, RA Beal, MF Simon, DK AF Lin, Michael T. Cantuti-Castelvetri, Ippolita Zheng, Kangni Jackson, Katie E. Tan, Yong B. Arzberger, Thomas Lees, Andrew J. Betensky, Rebecca A. Beal, M. Flint Simon, David K. TI Somatic mitochondrial DNA mutations in early parkinson and incidental lewy body disease SO ANNALS OF NEUROLOGY LA English DT Article ID SUBSTANTIA-NIGRA; NEURONS; DAMAGE; BRAIN; CHAIN; MTDNA AB Somatic mutations in mitochondrial DNA (mtDNA) are hypothesized to play a role in Parkinson disease (PD), but large increases in mtDNA mutations have not previously been found in PD, potentially because neurons with high mutation levels degenerate and thus are absent in late stage tissue. To address this issue, we studied early stage PD cases and cases of incidental Lewy body disease (ILBD), which is thought to represent presymptomatic PD. We show for the first time that mtDNA mutation levels in substantia nigra neurons are significantly elevated in this group of early PD and ILBD cases. Ann Neurol 2012;71:850854 C1 [Zheng, Kangni; Jackson, Katie E.; Tan, Yong B.; Simon, David K.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Cantuti-Castelvetri, Ippolita; Zheng, Kangni; Jackson, Katie E.; Tan, Yong B.; Simon, David K.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Lin, Michael T.; Beal, M. Flint] Weill Cornell Med Coll, Dept Neurol & Neurosci, New York, NY USA. [Cantuti-Castelvetri, Ippolita] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Arzberger, Thomas] Univ Munich, Ctr Neuropathol & Prion Res, Munich, Germany. [Lees, Andrew J.] UCL, Reta Lila Weston Inst Neurol Studies, Inst Neurol, London, England. [Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. RP Simon, DK (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, 330 Brookline Ave,Room CLS 638, Boston, MA 02215 USA. EM dsimon1@bidmc.harvard.edu RI Lees, Andrew/A-6605-2009 FU NIH National Institute of Neurological Disorders and Stroke [K02NS043311, R03NS053840, R01NS058988]; Harvard University; NIH National Institute on Aging [R01AG20729]; United States Army Medical Research and Materiel Command [W81XWH-04-1-0802]; American Federation for Aging Research-Paul Beeson Physician Faculty Scholarship; Massachusetts General Hospital/Massachusetts Institute of Technology Morris Udall Center of Excellence in PD Research [NIH NS38372]; American Parkinson's Disease Association Advanced Center for Parkinson Research at Massachusetts General Hospital; Harvard Neurodiscovery Center; Harvard Catalyst; German Federal Ministry of Research and Technology; Public Health Service [R24MH068855, P50AG005134]; NIH [UL1 RR025758]; Harvard University and its affiliated academic health care centers; Columbia University; Harvard Medical School; MJFF; European Commission; PSP Association; Weston Trust-Reta Lila Howard Foundation; Novartis; Teva; Meda; Boehringer Ingelheim; GSK; Ipsen; Lundbeck; Allergan; Orion; BIAL; Noscira; Roche; NIH (NINDS) FX This work was supported by grants from the NIH National Institute of Neurological Disorders and Stroke (K02NS043311, R03NS053840, R01NS058988, D. K. S.), William F. Milton Fund of Harvard University (D. K. S.), NIH National Institute on Aging (R01AG20729, M. T. L.), United States Army Medical Research and Materiel Command (W81XWH-04-1-0802, M. F. B.), American Federation for Aging Research-Paul Beeson Physician Faculty Scholarship (M. T. L.), Massachusetts General Hospital/Massachusetts Institute of Technology Morris Udall Center of Excellence in PD Research (NIH NS38372), American Parkinson's Disease Association Advanced Center for Parkinson Research at Massachusetts General Hospital (I. C.-C.), Harvard Neurodiscovery Center (R. A. B.), Harvard Catalyst (R. A. B.), and German Federal Ministry of Research and Technology (T. A.).; Brain tissue was provided by the Harvard Brain Tissue Resource Center (McLean Hospital, Boston, MA, partly supported by Public Health Service grant R24MH068855); Neuropathology Core of the Massachusetts Alzheimer Disease Research Center (supported by Public Health Service grant P50AG005134) and Neuropathology Service of the Massachusetts General Hospital (Boston, MA); Brain-Net Germany, Neurobiobank Munich (Center for Neuropathology and Prion Research), and Ludwig Maximilians University, Munich, Germany; and the Queen Square Brain Bank for Neurological Disorders (University College London, Institute of Neurology, Queen Square, London, UK). This work was conducted with biostatistical support from Harvard Catalyst/Harvard Clinical and Translational Science Center (NIH award UL1 RR025758 and financial contributions from Harvard University and its affiliated academic health care centers).; M.T.L.: speaking fees, Columbia University, Harvard Medical School; site PI for trial of IVIG in Alzheimer disease for Baxter Bioscience. I. C.-C.: grants/grants pending, MJFF. T. A.: grants/grants pending, European Commission. A.J.L.:board membership, Novartis, Teva, Meda, Boehringer Ingelheim, GSK, Ipsen, Lundbeck, Allergan, Orion, BIAL, Noscira, Roche; consultancy, Genus; employment, UCL/UCLH; grants/grants pending, PSP Association, Weston Trust-Reta Lila Howard Foundation; speaking fees, Novartis, Teva, Meda, Boehringer Ingelheim, GSK, Ipsen, Lundbeck, Allergan, Orion, BIAL, Noscira, Roche. D. K. S.: grants/grants pending, NIH (NINDS). NR 20 TC 32 Z9 32 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 2012 VL 71 IS 6 BP 850 EP 854 DI 10.1002/ana.23568 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 961YU UT WOS:000305506300017 PM 22718549 ER PT J AU Girouard, SD Velez, NF Penson, RT Massarotti, EM Vleugels, RA AF Girouard, Sasha D. Velez, Nicole F. Penson, Richard T. Massarotti, Elena M. Vleugels, Ruth Ann TI Panniculitis Associated With Dermatomyositis and Recurrent Ovarian Cancer SO ARCHIVES OF DERMATOLOGY LA English DT Article ID JUVENILE DERMATOMYOSITIS; POLYMYOSITIS; LIPOATROPHY; DISEASE AB Background: Panniculitis is a rare cutaneous manifestation of dermatomyositis (DM), typically presenting as tender, erythematous subcutaneous nodules. Complications, such as pain, calcinosis, and lipoatrophy, are associated with high morbidity. While it has been suggested that panniculitis in DM may correlate with a better prognosis, our understanding of its true significance, prognostic implications, and management is limited by the paucity of reported cases. We describe the first reported case to our knowledge of DM-associated panniculitis in the setting of ovarian adenocarcinoma as well as in association with a recurrent malignancy. Observations: A 63-year-old woman with a history of DM and recurrent ovarian adenocarcinoma presented with multiple painful, erythematous subcutaneous nodules on the bilateral upper arms, thighs, and buttocks. Histologic examination showed lymphoplasmacytic panniculitis with associated dermal mucin deposition, consistent with lobular panniculitis in association with connective-tissue disease. Treatment with oral methotrexate resulted in sustained clinical improvement over a 10-month period. Conclusions: Although panniculitis in DM has previously been suggested to be a good prognostic indicator, our case report describes an association with ovarian adenocarcinoma and a recurrent malignancy. Methotrexate may be an effective treatment for panniculitis in DM. C1 [Girouard, Sasha D.; Velez, Nicole F.; Penson, Richard T.; Massarotti, Elena M.; Vleugels, Ruth Ann] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Massarotti, Elena M.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Penson, Richard T.] Massachusetts Gen Hosp, Dept Med, Div Med Gynecol Oncol, Boston, MA 02114 USA. [Vleugels, Ruth Ann] Childrens Hosp Boston, Div Allergy & Immunol, Boston, MA USA. [Velez, Nicole F.; Vleugels, Ruth Ann] Brigham & Womens Hosp, Dept Dermatol, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. RP Vleugels, RA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, 221 Longwood Ave, Boston, MA 02115 USA. EM rvleugels@partners.org NR 29 TC 2 Z9 5 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUN PY 2012 VL 148 IS 6 BP 740 EP 744 DI 10.1001/archdermatol.2012.288 PG 5 WC Dermatology SC Dermatology GA 960TI UT WOS:000305413100015 PM 22431715 ER PT J AU Merkow, RP Bilimoria, KY Chow, WB Merkow, JS Weyant, MJ Ko, CY Bentrem, DJ AF Merkow, Ryan P. Bilimoria, Karl Y. Chow, Warren B. Merkow, Justin S. Weyant, Michael J. Ko, Clifford Y. Bentrem, David J. TI Variation in Lymph Node Examination After Esophagectomy for Cancer in the United States SO ARCHIVES OF SURGERY LA English DT Article ID US-POPULATION DATABASE; LONG-TERM SURVIVAL; LYMPHADENECTOMY EXTENT; COLON-CANCER; PANCREATIC-CANCER; PREDICTS SURVIVAL; QUALITY MEASURE; GASTRIC-CANCER; STAGING SYSTEM; NUMBER AB Objectives: To evaluate the quality of lymph node examination after esophagectomy for cancer in the United States based on current treatment guidelines (>= 15 nodes) and to assess the association of patient, tumor, and hospital factors with the adequacy of lymph node examination. Design: Retrospective observational study from 1998 to 2007. Setting: National cancer database. Patients: Patients with stage I through III esophageal cancer undergoing esophagectomy and not treated with neoadjuvant chemoradiotherapy. Main Outcome Measure: Rate of adequate lymph node examination (>= 15 nodes). Results: A total of 13 995 patients were identified from 639 hospitals. Overall, 4014 patients (28.7%) had at least 15 lymph nodes examined, which increased from 23.5% to 34.4% during the study period. At the hospital level, only 45 centers (7.0%) examined a median of at least 15 lymph nodes. In the most recent period (2005-2007), at least 15 nodes were examined in 38.9% of patients at academic centers vs 28.0% at community hospitals and in 44.1% at high-volume centers vs 29.3% at low-volume centers. On multivariable analysis, hospital type, surgical volume status, and geographic location remained significant predictors of having at least 15 lymph nodes examined. Conclusions: Fewer than one-third of patients and fewer than 1 in 10 hospitals met the benchmark of examining at least 15 lymph nodes. Hospitals should perform internal process improvement activities to improve guideline adherence. C1 [Merkow, Ryan P.; Bilimoria, Karl Y.; Bentrem, David J.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. [Merkow, Ryan P.; Merkow, Justin S.; Weyant, Michael J.] Univ Colorado, Sch Med, Dept Surg, Aurora, CO USA. [Chow, Warren B.; Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Chow, Warren B.; Ko, Clifford Y.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Bentrem, DJ (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Surg, 676 St Clair St,Ste 650, Chicago, IL 60611 USA. EM dbentrem@nmff.org NR 36 TC 9 Z9 9 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD JUN PY 2012 VL 147 IS 6 BP 505 EP 511 DI 10.1001/archsurg.2011.2215 PG 7 WC Surgery SC Surgery GA 960YD UT WOS:000305428500003 PM 22351873 ER PT J AU Antiel, RM Van Arendonk, KJ Reed, DA Terhune, KP Tarpley, JL Porterfield, JR Hall, DE Joyce, DL Wightman, SC Horvath, KD Heller, SF Farley, DR AF Antiel, Ryan M. Van Arendonk, Kyle J. Reed, Darcy A. Terhune, Kyla P. Tarpley, John L. Porterfield, John R. Hall, Daniel E. Joyce, David L. Wightman, Sean C. Horvath, Karen D. Heller, Stephanie F. Farley, David R. TI Surgical Training, Duty-Hour Restrictions, and Implications for Meeting the Accreditation Council for Graduate Medical Education Core Competencies Views of Surgical Interns Compared With Program Directors SO ARCHIVES OF SURGERY LA English DT Article ID INSTITUTE-OF-MEDICINE; HOURS ENHANCING SLEEP; OPERATIVE EXPERIENCE; GENERAL-SURGERY; SUPERVISION; SAFETY; RECOMMENDATIONS; ASSOCIATION; RESIDENTS; TRAINEES AB Objective: To describe the perspectives of surgical interns regarding the implications of the new Accreditation Council for Graduate Medical Education (ACGME) duty-hour regulations for their training. Design: We compared responses of interns and surgery program directors on a survey about the proposed ACGME mandates. Setting: Eleven general surgery residency programs. Participants: Two hundred fifteen interns who were administered the survey during the summer of 2011 and a previously surveyed national sample of 134 surgery program directors. Main Outcome Measures: Perceptions of the implications of the new duty-hour restrictions on various aspects of surgical training, including the 6 ACGME core competencies of graduate medical education, measured using 3-point scales (increase, no change, or decrease). Results: Of 215 eligible surgical interns, 179 (83.3%) completed the survey. Most interns believed that the new duty-hour regulations will decrease continuity with patients (80.3%), time spent operating (67.4%), and coordination of patient care (57.6%), while approximately half believed that the changes will decrease their acquisition of medical knowledge (48.0%), development of surgical skills (52.8%), and overall educational experience (51.1%). Most believed that the changes will improve or will not alter other aspects of training, and 61.5% believed that the new standards will decrease resident fatigue. Surgical interns were significantly less pessimistic than surgery program directors regarding the implications of the new duty-hour restrictions on all aspects of surgical training (P <.05 for all comparisons). Conclusions: Although less pessimistic than program directors, interns beginning their training under the new paradigm of duty-hour restrictions have significant concerns about the effect of these regulations on the quality of their training. C1 [Antiel, Ryan M.; Heller, Stephanie F.; Farley, David R.] Mayo Clin, Dept Surg, Rochester, MN 55905 USA. [Reed, Darcy A.] Mayo Clin, Dept Primary Care Internal Med, Rochester, MN 55905 USA. [Van Arendonk, Kyle J.] Johns Hopkins Univ, Dept Surg, Baltimore, MD USA. [Terhune, Kyla P.; Tarpley, John L.] Vanderbilt Univ, Nashville, TN USA. [Porterfield, John R.] Univ Alabama Birmingham, Birmingham, AL USA. [Hall, Daniel E.] Univ Pittsburgh, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Joyce, David L.] Stanford Univ, Stanford, CA 94305 USA. [Wightman, Sean C.] Univ Chicago, Chicago, IL 60637 USA. [Horvath, Karen D.] Univ Washington, Seattle, WA 98195 USA. RP Farley, DR (reprint author), Mayo Clin, Dept Surg, 200 1st St SW, Rochester, MN 55905 USA. EM farley.david@mayo.edu RI Hall, Daniel/H-4843-2013; OI Hall, Daniel/0000-0001-6382-0522 NR 24 TC 23 Z9 23 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0004-0010 EI 1538-3644 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD JUN PY 2012 VL 147 IS 6 BP 536 EP 541 PG 6 WC Surgery SC Surgery GA 960YD UT WOS:000305428500010 PM 22786539 ER PT J AU Piccini, JP Singer, DE AF Piccini, Jonathan P. Singer, Daniel E. TI Putting risk prediction in atrial fibrillation into perspective SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID STRATIFICATION SCHEMES; STROKE RISK; THROMBOEMBOLISM; ANTICOAGULATION; COHORT C1 [Piccini, Jonathan P.] Duke Univ, Med Ctr, Duke Clin Res Inst, Electrophysiol Sect, Durham, NC 27710 USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Div Gen Med, Clin Epidemiol Unit, Boston, MA 02114 USA. RP Piccini, JP (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, Electrophysiol Sect, POB 17969, Durham, NC 27710 USA. EM jonathan.piccini@duke.edu NR 12 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD JUN PY 2012 VL 33 IS 12 BP 1431 EP 1433 DI 10.1093/eurheartj/ehs031 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 960WI UT WOS:000305423000009 PM 22378796 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Reliability measures in managing GI bleeding SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID EPIDEMIOLOGY; DIAGNOSIS AB Background: Multiple procedures and devices are used in a complex interplay to diagnose and treat GI bleeding. Objective: To model how a large variety of diagnostic and therapeutic components interact in the successful management of GI bleeding. Design: The analysis uses the concept of reliability block diagrams from probability theory to model management outcome. Separate components of the management process are arranged in a serial or parallel fashion. If the outcome depends on the function of each component individually, such components are modeled to be arranged in series. If components complement each other and can mutually compensate for each of their failures, such components are arranged in a parallel fashion. Setting: General endoscopy practice. Patients: Patients with GI bleeding of unknown etiology. Interventions: All available endoscopic and radiographic means to diagnose and treat GI bleeding. Main Outcome Measurements: Process reliability in achieving hemostasis. Results: Serial arrangements tend to reduce process reliability, whereas parallel arrangements increase it. Whenever possible, serial components should be bridged and complemented by additional alternative (parallel) routes of operation. Parallel components with low individual reliability can still contribute to overall process reliability as long as they function independently of other pre-existing alternatives. Limitations: Probability of success associated with individual components is partly unknown. Conclusions: Modeling management of GI bleeding by a reliability block diagram provides a useful tool in assessing the impact of individual endoscopic techniques and administrative structures on the overall outcome. (Gastrointest Endosc 2012;75:1184-9.) C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR 97239 USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. NR 9 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JUN PY 2012 VL 75 IS 6 BP 1184 EP 1189 DI 10.1016/j.gie.2012.01.047 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 961HA UT WOS:000305453700009 PM 22624809 ER PT J AU Huang, ES Karsan, S Makhani, M Kanwal, F Singh, I Spiegel, BM AF Huang, Edward S. Karsan, Sundip Makhani, Marc Kanwal, Fasiha Singh, Inder Spiegel, Brennan M. TI Sensitivity analysis, not a calculation of sensitivity, is essential in a propensity score analysis Response SO GASTROINTESTINAL ENDOSCOPY LA English DT Letter ID TRIALS; BIAS C1 [Huang, Edward S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02215 USA. [Karsan, Sundip; Makhani, Marc] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. [Karsan, Sundip; Makhani, Marc] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. [Kanwal, Fasiha] St Louis Univ, Div Gastroenterol & Hepatol, Sch Med, St Louis, MO USA. [Kanwal, Fasiha; Spiegel, Brennan M.] UCLA VA Ctr Outcomes Res & Educ, Los Angeles, CA USA. [Singh, Inder; Spiegel, Brennan M.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Spiegel, Brennan M.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Gastroenterol & Hepatol, Los Angeles, CA USA. RP Huang, ES (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02215 USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JUN PY 2012 VL 75 IS 6 BP 1290 EP 1291 DI 10.1016/j.gie.2012.01.030 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 961HA UT WOS:000305453700036 ER PT J AU Hara, T Bhayana, B Thompson, B Kessinger, CW Khatri, A McCarthy, JR Weissleder, R Lin, CP Tearney, GJ Jaffer, FA AF Hara, Tetsuya Bhayana, Brijesh Thompson, Brian Kessinger, Chase W. Khatri, Ashok McCarthy, Jason R. Weissleder, Ralph Lin, Charles P. Tearney, Guillermo J. Jaffer, Farouc A. TI Molecular Imaging of Fibrin Deposition in Deep Vein Thrombosis Using Fibrin-Targeted Near-Infrared Fluorescence SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE DVT; fibrin; fluorescence; molecular imaging; optical imaging ID CONTRAST AGENT; IN-VIVO; VENOUS THROMBOSIS; ATHEROSCLEROSIS; INFLAMMATION; EP-2104R; MECHANISMS; RESOLUTION; CATHETER; INJURY AB OBJECTIVES The goal of this study was to develop and validate a new fibrin-targeted imaging agent that enables high-resolution near-infrared fluorescence (NIRF) imaging of deep vein thrombosis (DVT). BACKGROUND NIRF imaging of fibrin could enable highly sensitive and noninvasive molecular imaging of thrombosis syndromes in vivo. METHODS A fibrin-targeted peptide was conjugated to a near-infrared fluorophore Cy7, termed FTP11-Cy7. The NIRF peptide is based on a fibrin-specific imaging agent that has completed Phase II clinical magnetic resonance imaging trials. In vitro binding of FTP11-Cy7 to human plasma clots was assessed by using fluorescence reflectance imaging. Next, FTP11-Cy7 was intravenously injected in mice with femoral DVT induced by topical 7.5% ferric chloride treatment. Intravital fluorescence microscopy and noninvasive fluorescence molecular tomography-computed tomography were performed in 32 mice with DVT, followed by histological analyses. RESULTS In vitro human clot-binding analyses showed a 6-fold higher NIRF clot target-to-background ratio (TBR) of FTP11-Cy7 than free Cy7 (6.3 +/- 0.34 vs. 1.2 +/- 0.03; p < 0.0001). The thrombus TBR of acute and subacute femoral DVT with FTP11-Cy7 obtained by using intravital fluorescence microscopy was >400% higher than control free Cy7. Binding of FTP11-Cy7 to thrombi was blocked by a 100-fold excess of unlabeled competitor peptide both in vitro and in vivo (p < 0.001 for each). Histological analyses confirmed that FTP11-Cy7 specifically accumulated in thrombi. Noninvasive fluorescence molecular tomography-computed tomography imaging of fibrin in jugular DVT demonstrated strong NIRF signal in thrombi compared with sham-operated jugular veins (mean TBR 3.5 +/- 0.7 vs. 1.5 +/- 0.3; p < 0.05). CONCLUSIONS The fibrin-targeted NIRF agent FTP11-Cy7 was shown to avidly and specifically bind human and murine thrombi, and enable sensitive, multimodal intravital and noninvasive NIRF molecular imaging detection of acute and subacute murine DVT in vivo. (J Am Coll Cardiol Img 2012; 5: 607-15) (C) 2012 by the American College of Cardiology Foundation C1 [Hara, Tetsuya; Thompson, Brian; Kessinger, Chase W.; Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Hara, Tetsuya; Thompson, Brian; Kessinger, Chase W.; Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. [Bhayana, Brijesh; Thompson, Brian; Lin, Charles P.; Tearney, Guillermo J.; Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Thompson, Brian; McCarthy, Jason R.; Weissleder, Ralph; Lin, Charles P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Khatri, Ashok] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. RP Jaffer, FA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Simches Res Bldg,Room 3206,185 Cambridge St, Boston, MA 02114 USA. EM fjaffer@mgh.harvard.edu OI Jaffer, Farouc/0000-0001-7980-384X FU National Institutes of Health [R01HL108229, R01HL076398, R01HL093717]; American Heart Association [0830352N]; Howard Hughes Medical Institute; Broadview Ventures; Society of Nuclear Medicine Wagner-Torizuka Fellowship FX This study was funded by the following sources: National Institutes of Health R01HL108229 (Dr. Jaffer) and R01HL076398 and R01HL093717 (Dr. Tearney); American Heart Association Scientist Development grant 0830352N (Dr. Jaffer); Howard Hughes Medical Institute Career Development Award (Dr. Jaffer); Broadview Ventures (Dr. Jaffer); and the Society of Nuclear Medicine Wagner-Torizuka Fellowship (Dr. Hara). Dr. Jaffer has received an honorarium from GE Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Tearney and Jaffer share senior authorship on this paper. NR 27 TC 25 Z9 28 U1 0 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD JUN PY 2012 VL 5 IS 6 BP 607 EP 615 DI 10.1016/j.jcmg.2012.01.017 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 961KC UT WOS:000305462300005 PM 22698530 ER PT J AU Adams, JM Osborne-McKenzie, T AF Adams, Jeffrey M. Osborne-McKenzie, Tanya TI Advancing the Evidence Base for a Standardized Provider Handover Structure: Using Staff Nurse Descriptions of Information Needed to Deliver Competent Care SO JOURNAL OF CONTINUING EDUCATION IN NURSING LA English DT Article ID HANDOFFS AB Using existing gold standard structures to manage "handover" was a conceptual communication challenge for nurses involved in critically important shift-to-shift transitions in this study, which was conducted at a Central Coast California District Hospital. An extensive body of literature identifies poor communication as jeopardizing patient safety, quality, and continuity of care. Researchers who used the prevailing structures, Situation-Background-Assessment-Recommendation (SBAR), used by the World Health Organization (WHO), and the Communication During Patient Handover (CDPH), sanctioned by The Joint Commission (TJC), had difficulty categorizing content described by nurses as necessary to the delivery of competent care. This article describes a study that resulted in an alternative structure for handover, D-BANQ, which aligns with prevailing WHO-SBAR and TJC-CDPH handover structures and provides an easy-to-follow chronological format for the content that nurses identified as necessary to communicate during this important nursing activity. J Contin Educ Nurs 2012; 43(6):261-266. C1 [Adams, Jeffrey M.] Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, Boston, MA 02114 USA. [Adams, Jeffrey M.] Massachusetts Gen Hosp, Ctr Innovat Patient Care, Boston, MA 02114 USA. [Osborne-McKenzie, Tanya] Salinas Valley Mem Healthcare Syst, Salinas, CA USA. RP Adams, JM (reprint author), Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, 275 Cambridge St, Boston, MA 02114 USA. EM jadams9@partners.org FU Sigma Theta Tau Rho Chapter Research Grant; Yvonne L. Munn Postdoctoral Fellowship Grant FX This research was supported in part by a Sigma Theta Tau Rho Chapter Research Grant and a Yvonne L. Munn Postdoctoral Fellowship Grant. NR 25 TC 4 Z9 5 U1 1 U2 33 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0022-0124 J9 J CONTIN EDUC NURS JI J. Contin. Educ. Nursing PD JUN PY 2012 VL 43 IS 6 BP 261 EP 266 DI 10.3928/00220124-20120215-88 PG 6 WC Nursing SC Nursing GA 962ON UT WOS:000305554700006 PM 22356245 ER PT J AU Gidwani, R Goetz, MB Kominski, G Asch, S Mattocks, K Samet, JH Justice, A Gandhi, N Needleman, J AF Gidwani, Risha Goetz, Matthew Bidwell Kominski, Gerald Asch, Steven Mattocks, Kristin Samet, Jeffrey H. Justice, Amy Gandhi, Neel Needleman, Jack TI A BUDGET IMPACT ANALYSIS OF RAPID HUMAN IMMUNODEFICIENCY VIRUS SCREENING IN VETERANS ADMINISTRATION EMERGENCY DEPARTMENTS SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE HIV; screening; budget impact; Rapid Testing; Emergency Department ID HEALTH-CARE SETTINGS; COST-EFFECTIVENESS; HIV-INFECTION; ANTIRETROVIRAL THERAPY; UNITED-STATES; OUTCOMES AB Background: Human immunodeficiency virus (HIV) screening is cost-effective and recommended in populations with low disease prevalence. However, because screening is not cost-saying, its financial feasibility must be understood. Study Objectives: We forecast the costs of two Emergency Department-based HIV testing programs in the Veterans Administration: 1) implementing a non-targeted screening program and providing treatment for all patients thusly identified (Rapid Testing); and 2) treating patients identified due to late-stage symptoms (Usual Care); to determine which program was the most financially feasible. Methods: Using a dynamic decision-analysis model, we estimated the financial impact of each program over a 7-year period. Costs were driven by patient disease-severity at diagnosis, measured by CD4+ category, and the proportion of patients in each disease-severity category. Cost per CD4+ category was modeled from chart review and database analysis of treatment-naive HIV-positive patients. Distributions of CD4+ counts differed in patients across the Rapid Testing and Usual Care arms. Results: A non-targeted Rapid Testing program was not significantly more costly than Usual Care. Although Rapid Testing had substantial screening costs, they were offset by lower inpatient expenses associated with earlier identification of disease. Assuming an HIV prevalence of 1% and 80% test acceptance, the cost of Rapid Testing was $1,418,088, vs. $1,320,338 for Usual Care (p = 0.5854). Results support implementation of non-targeted rapid HIV screening in integrated systems. Conclusions: This analysis adds a new component of support for HIV screening by demonstrating that rapid, non-targeted testing does not cost significantly more than a diagnostic testing approach. (C) 2012 Elsevier Inc. C1 [Gidwani, Risha; Goetz, Matthew Bidwell; Asch, Steven] VA Greater Los Angeles Healthcare Syst, QUERI HIV HEPATITIS C, Los Angeles, CA USA. [Gidwani, Risha; Kominski, Gerald; Needleman, Jack] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Goetz, Matthew Bidwell; Asch, Steven] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Mattocks, Kristin; Justice, Amy] W Haven VA Healthcare Syst, West Haven, CT USA. [Mattocks, Kristin; Justice, Amy] Yale Univ, Sch Med, New Haven, CT USA. [Samet, Jeffrey H.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Gandhi, Neel] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Gandhi, Neel] Montefiore Med Ctr, Bronx, NY 10467 USA. RP Gidwani, R (reprint author), VA Greater Los Angeles Healthcare Syst, QUERI HIV HEPATITIS C, Los Angeles, CA USA. EM rishagidwani@yahoo.com RI Needleman, Jack/I-5461-2013; OI Needleman, Jack/0000-0002-2875-0589; Samet, Jeffrey/0000-0002-0897-3400; Goetz, Matthew/0000-0003-4542-992X; Kominski, Gerald/0000-0001-5214-7133 FU VA Health Services Research & Development Service Rapid Response Project (RRP) [07-283] FX This work was funded by the VA Health Services Research & Development Service Rapid Response Project (RRP) 07-283. NR 18 TC 1 Z9 1 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD JUN PY 2012 VL 42 IS 6 BP 719 EP 726 DI 10.1016/j.jemermed.2010.11.038 PG 8 WC Emergency Medicine SC Emergency Medicine GA 962ZX UT WOS:000305591000019 PM 21277144 ER PT J AU Nedjat-Haiem, FR Lorenz, KA Ell, K Hamilton, A Palinkas, L AF Nedjat-Haiem, Frances R. Lorenz, Karl A. Ell, Kathleen Hamilton, Alison Palinkas, Lawrence TI Experiences With Advanced Cancer Among Latinas in a Public Health Care System SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Sociocultural; advanced cancer; low-income Latinas; pain; coping; religious beliefs ID QUALITY-OF-LIFE; HISPANIC PATIENTS; LOW-INCOME; EXPLANATORY MODELS; PATIENT NAVIGATION; BREAST; DEPRESSION; WOMEN; END; COMMUNICATION AB Context. Cultural dimensions related to illness are triggered at significant times in an illness trajectory, such as at illness onset or when death approaches. These factors influence views on how illness is understood and managed, which is likely more difficult for minority populations. Although Latinos experience barriers to high-quality health care, late-stage cancer diagnoses, and poor health outcomes, little is known about their experiences with advanced, life-threatening cancers. Objectives. We examined Latinas' experiences with advanced, metastatic cancers to identify sociocultural beliefs that influenced their care. Methods. We interviewed 24 Latinas taking part in a randomized controlled trial focused on improving quality-of-life outcomes for co-occurring cancer and depression and explored their beliefs about the cause, course, and cure of cancer. This study used a phenomenological analytical approach to explore women's lived experiences of having advanced cancer. Results. Themes revealed issues about experiencing advanced cancer that included the following: initial reactions to cancer, disbelief about the lack of pain, economic impact, beliefs about the cause, coping with cancer, beliefs about the cure, and confusion about cancer severity. Sociocultural factors influence misunderstanding and confusion about cancer care but also can be a source of strength. Conclusion. Providers need to become culturally sensitive to the needs of underserved Latinas. Denial or ignorance of these issues can create other problems, such as gaps in patient-centered decision making from diagnosis through the end of life. J Pain Symptom Manage 2012; 43: 1013-1024. Published by Elsevier Inc. on behalf of U.S. Cancer Pain Relief Committee. C1 [Nedjat-Haiem, Frances R.; Lorenz, Karl A.; Hamilton, Alison] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Ell, Kathleen; Palinkas, Lawrence] Univ So Calif, Sch Social Work, Los Angeles, CA 90089 USA. [Hamilton, Alison] Univ Calif Los Angeles, Los Angeles, CA USA. RP Nedjat-Haiem, FR (reprint author), VA Greater Los Angeles Healthcare Syst, HSR&D Ctr Excellence, Off Acad Affiliat, VA Associated Hlth Postdoctoral Fellowship Progra, 11301 Wilshire Blvd,Code 111-G, Los Angeles, CA 90073 USA. EM nedjatha@gmail.com FU Office of Academic Affiliations, VA Associated Health Postdoctoral Fellowship Program, VA Greater Los Angeles, Healthcare System, HSR&D Center of Excellence; American Cancer Society Doctoral Training Grants in Oncology Social Work [DSW-06-220-01-SW]; National Cancer Institute [R01CA105269] FX This research was supported by the Office of Academic Affiliations, VA Associated Health Postdoctoral Fellowship Program, VA Greater Los Angeles, Healthcare System, HSR&D Center of Excellence, the American Cancer Society Doctoral Training Grants in Oncology Social Work DSW-06-220-01-SW (F.R. Nedjat-Haiem, Principal Investigator) and the National Cancer Institute grant R01CA105269 (K. Ell, Principal Investigator). The authors declare no conflicts of interest. NR 35 TC 6 Z9 6 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JUN PY 2012 VL 43 IS 6 BP 1013 EP 1024 DI 10.1016/j.jpainsymman.2011.06.018 PG 12 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 961HY UT WOS:000305456500004 PM 22575719 ER PT J AU Weingart, SN Cleary, A Stuver, SO Lynch, M Brandoff, D Schaefer, KG Zhu, J Berry, DL Block, S Weeks, JC AF Weingart, Saul N. Cleary, Angela Stuver, Sherri O. Lynch, Maureen Brandoff, Douglas Schaefer, Kristen G. Zhu, Junya Berry, Donna L. Block, Susan Weeks, Jane C. TI Assessing the Quality of Pain Care in Ambulatory Patients With Advanced Stage Cancer SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Cancer pain; pain assessment; pain management; palliative care; quality of care ID NECK-CANCER; PREVALENCE; MANAGEMENT; EPIDEMIOLOGY; TRIAL; HEAD; SEVERITY; SYMPTOMS; DISEASE; PATTERN AB Context. Pain is common among patients with advanced cancer despite the dissemination of clinical pain care guidelines. Objectives. We sought to assess the quality of pain care among patients with advanced disease. Methods. We reviewed the records of 85 adult ambulatory patients with advanced breast, lung, and gastrointestinal cancer treated in 2004-2006. Patients' screening pain intensity scores were at least 7 of 10. Nurse reviewers completed medical record reviews of care rendered at the index visit and over the subsequent 30 days based on the 2004 National Comprehensive Cancer Network pain guideline. An expert panel then rated the quality of the evaluation, treatment, and overall pain care. We used a multivariable model to analyze guideline compliance and resolution of severe pain. Results. Among advanced cancer patients with severe pain, clinicians adjusted pain medications only half the time and made few timely referrals for pain-related consultations. By 30 days after the index visit, 34% of patients continued to report severe pain. The expert panel judged the overall quality of pain care as "fair'' or "poor'' in about two-thirds of cases because more timely and effective intervention could have reduced the severity and duration of pain. Resolution of severe pain was associated with adjustment of pain medications at the index visit (adjusted odds ratio 3.8, 95% CI 1.3-10.6). Conclusion. There is room for improvement in the pain care of patients with advanced cancer. Additional research is needed to understand the reasons for poor performance. J Pain Symptom Manage 2012; 43: 1072-1081. (C) 2012 U. S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Weingart, Saul N.; Cleary, Angela; Stuver, Sherri O.; Zhu, Junya] Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA 02115 USA. [Lynch, Maureen; Brandoff, Douglas; Schaefer, Kristen G.; Block, Susan] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Phyllis F Cantor Ctr Res Nursing, Boston, MA 02115 USA. [Berry, Donna L.] Dana Farber Canc Inst, Patient Care Serv, Boston, MA 02115 USA. [Weeks, Jane C.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. RP Weingart, SN (reprint author), Dana Farber Canc Inst, Ctr Patient Safety, 450 Brookline Ave, Boston, MA 02115 USA. EM saul_weingart@dfci.harvard.edu OI Stuver, Sherri/0000-0002-4027-2663 FU American Cancer Society Pilot and Exploratory Project Grant [PEP-08-273-01-PC1] FX This research was supported by an American Cancer Society Pilot and Exploratory Project Grant (PEP-08-273-01-PC1). The funders had no role in the study design or in the collection, analysis, interpretation, or presentation of the data or in the drafting of this manuscript. The authors declare no conflicts of interest. NR 47 TC 5 Z9 5 U1 0 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JUN PY 2012 VL 43 IS 6 BP 1072 EP 1081 DI 10.1016/j.jpainsymman.2011.06.022 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 961HY UT WOS:000305456500009 PM 22651950 ER PT J AU Karima, MM Van Dyke, TE AF Karima, Mamdouh M. Van Dyke, Thomas E. TI Enamel Matrix Derivative Promotes Superoxide Production and Chemotaxis but Reduces Matrix Metalloproteinase-8 Expression by Polymorphonuclear Leukocytes SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE Chemotaxis; enamel matrix proteins; inflammation; matrix metalloproteinases; neutrophils; superoxides ID GINGIVAL CREVICULAR FLUID; INTRABONY PERIODONTAL DEFECTS; IN-VITRO; PORPHYROMONAS-GINGIVALIS; HUMAN-NEUTROPHILS; TISSUE INHIBITOR; EMDOGAIN(R); PROTEINS; ACTIVATION; VIVO AB Background: Polymorphonuclear leukocyte (PMN) is the predominant innate immune cell type activated in acute inflammation. The aim of this study is to determine the impact of enamel matrix derivative (EMD) on superoxide (O-2(-)) generation, chemotaxis, and matrix metalloproteinase-8 (MMP-8) secretion by PMN in vitro to better understand the role of EMD in surgical wound healing. Methods: PMNs were isolated from healthy volunteers (n = 14). O-2(-) generation was measured using a cytochrome c reduction assay. Chemotaxis was measured in a modified Boyden chamber. MMP-8 secretion was analyzed by Western blotting. A relative density method was used to determine the percentage of MMP-8 released from the PMNs in relation to the total cellular MMP-8 content. Results: O-2(-) generation was significantly elevated when PMNs were stimulated with EMD (200 mu g/mL) (P<0.01). Secondary stimulation of PMNs with 1 mu M N-formyl-methionyl-leucyl-phenylalanine (fMLP) triggered earlier and more sustained O-2(-) generation with EMD.EMD significantly increased PMN chemotactic activity (P<0.05). Combined stimulation with EMD plus fMLP resulted in significantly higher chemotaxis compared to fMLP alone (P<0.05). Conversely, EMD did not induce MMP-8 secretion from PMNs. MMP-8 secretion by PMNs in response to fMLP or serum-opsonized zymosan stimulation was significantly inhibited by EMD (P<0.05). Conclusions: EMD has specific, differential actions on PMNs that suggest potential for enhancement of wound healing, bacterial and tissue debris clearance (O-2(-) generation and chemotaxis), and suppression of tissue damage and degradation (MMP-8). Together, the data suggest that EMD enhances wound healing and reduces inflammation. J Periodontol 2012;83:780-786. C1 [Karima, Mamdouh M.] King Abdulaziz Univ, Fac Dent, Dept Oral Basic & Clin Sci, Jeddah 21413, Saudi Arabia. [Van Dyke, Thomas E.] Forsyth Inst, Dept Periodontol, Cambridge, MA USA. RP Van Dyke, TE (reprint author), 245 1st St, Cambridge, MA 02142 USA. EM tvandyke@forsyth.org FU U.S. Public Health Service [DE 19938, DE 15566]; King Abdulaziz University in Saudi Arabia FX This work was supported in part by U.S. Public Health Service Grants DE 19938 and DE 15566 (TVD) and an educational grant from the King Abdulaziz University in Saudi Arabia (MK). The authors thank Biora/Straumann, Malmo, Sweden, for providing enamel matrix derivative and propylene glycol alginate and Martha Warbington (deceased), Boston University, Boston, Massachusetts, for her excellent technical assistance. The authors report no conflicts of interest related to this study. NR 42 TC 5 Z9 5 U1 0 U2 2 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD JUN PY 2012 VL 83 IS 6 BP 780 EP 786 DI 10.1902/jop.2011.110397 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 961TQ UT WOS:000305492800013 PM 22050547 ER PT J AU Weiner, RB Baggish, AL AF Weiner, Rory B. Baggish, Aaron L. TI Exercise-induced cardiac remodelling: the need for assessment of regional myocardial function SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Editorial Material ID MECHANICS; HUMANS; IMPACT; HEART C1 [Weiner, Rory B.; Baggish, Aaron L.] Massachusetts Gen Hosp, Cardiovasc Performance Program, Div Cardiol, Boston, MA 02114 USA. RP Weiner, RB (reprint author), Massachusetts Gen Hosp, Cardiovasc Performance Program, Div Cardiol, Boston, MA 02114 USA. EM rweiner@partners.org NR 7 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JUN PY 2012 VL 590 IS 12 BP 2829 EP 2830 DI 10.1113/jphysiol.2012.233585 PG 2 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 960PZ UT WOS:000305401700008 PM 22707589 ER PT J AU Perez-Rodriguez, MM Hazlett, EA Rich, EL Ripoll, LH Weiner, DM Spence, N Goodman, M Koenigsberg, HW Siever, LJ New, AS AF Perez-Rodriguez, M. Mercedes Hazlett, Erin A. Rich, Erin L. Ripoll, Luis H. Weiner, Daniel M. Spence, Nicole Goodman, Marianne Koenigsberg, Harold W. Siever, Larry J. New, Antonia S. TI Striatal activity in borderline personality disorder with comorbid intermittent explosive disorder: Sex differences SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Borderline personality disorder; Intermittent explosive disorder; Striatum; Aggression; Positron emission tomography ID POSITRON-EMISSION-TOMOGRAPHY; BRAIN GLUCOSE-METABOLISM; EVENT-RELATED FMRI; ACTIVATED FDG-PET; DSM-IV CRITERIA; BASAL GANGLIA; GENDER-DIFFERENCES; ORBITOFRONTAL CORTEX; IMPULSIVE-AGGRESSION; NEURONAL-ACTIVITY AB Borderline Personality Disorder (BPD) is associated with behavioral and emotional dysregulation, particularly in social contexts; however, the underlying pathophysiology at the level of brain function is not well understood. Previous studies found abnormalities in frontal cortical and limbic areas suggestive of poor frontal regulation of downstream brain regions. However, the striatum, which is closely connected with the medial frontal cortices and plays an important role in motivated behaviors and processing of rewarding stimuli, has been understudied in BPD. Here we hypothesized that, in addition to frontal dysfunction, BPD patients may show abnormal striatal function. In this study, 38 BPD patients with intermittent explosive disorder (BPD-IED) and 36 healthy controls (HC) participated in the Point Subtraction Aggression Paradigm (PSAP), a computer game played with a fictitious other player. (18)Fluoro-deoxyglucose positron emission tomography (FOG-PET) measured relative glucose metabolism (rGMR) within caudate and putamen in response to aggression-provoking and non-provoking versions of the PSAP. Male BPD-IED patients had significantly lower striatal rGMR than all other groups during both conditions, although male and female BPD-IED patients did not differ in clinical or behavioral measures. These sex differences suggest differential involvement of frontal-striatal circuits in BPD-IED, and are discussed in relation to striatal involvement in affective learning and social decision-making. Published by Elsevier Ltd. C1 [Perez-Rodriguez, M. Mercedes; Hazlett, Erin A.; Ripoll, Luis H.; Goodman, Marianne; Koenigsberg, Harold W.; Siever, Larry J.; New, Antonia S.] James J Peters Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY 10468 USA. [Perez-Rodriguez, M. Mercedes; Hazlett, Erin A.; Rich, Erin L.; Ripoll, Luis H.; Weiner, Daniel M.; Spence, Nicole; Goodman, Marianne; Koenigsberg, Harold W.; Siever, Larry J.; New, Antonia S.] Mt Sinai Sch Med, Dept Psychiat, MIRECC, Bronx, NY 10468 USA. [Rich, Erin L.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. RP New, AS (reprint author), James J Peters Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM antonia.new@mssm.edu RI Perez Rodriguez, Maria/B-9410-2013 OI Perez Rodriguez, Maria/0000-0001-5137-1993 FU James J. Peters Veterans Affairs Medical Center; National Institutes of Health (NIH) [1-R01-MH067918-01, 1-R01-MH07911]; Mount Sinai General Clinical Research Center from the National Center for Research Resources at the NIH [5-M01 RR00071] FX This work was supported by the James J. Peters Veterans Affairs Medical Center and by a grant to ASN from the National Institutes of Health (NIH) (1-R01-MH067918-01) and to EAH (1-R01-MH07911) and by 5-M01 RR00071 for the Mount Sinai General Clinical Research Center from the National Center for Research Resources at the NIH. NR 97 TC 12 Z9 12 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD JUN PY 2012 VL 46 IS 6 BP 797 EP 804 DI 10.1016/j.jpsychires.2012.02.014 PG 8 WC Psychiatry SC Psychiatry GA 961UD UT WOS:000305494100016 PM 22464337 ER PT J AU Brouwer, KM Lindenhovius, AL Dyer, GS Zurakowski, D Mudgal, CS Ring, D AF Brouwer, Kim M. Lindenhovius, Anneluuk L. Dyer, George S. Zurakowski, David Mudgal, Chaitanya S. Ring, David TI Diagnostic accuracy of 2- and 3-dimensional imaging and modeling of distal humerus fractures SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Computed tomography; fracture morphology; distal humerus fracture; 3-dimensional models; fracture type; interobserver reliability; accuracy ID PLANNING CORRECTIVE OSTEOTOMY; COMPUTED-TOMOGRAPHY; PROXIMAL HUMERUS; PLAIN RADIOGRAPHS; CLASSIFICATION; RADIUS; END; CT; RELIABILITY AB Purpose: This investigation used prospectively recorded intraoperative evaluation as the reference standard for distal humerus fracture type and characteristics, in order to measure the diagnostic performance characteristics of computed tomography (CT) and physical models. In secondary analyses, we assessed the reliability of classification. Methods: Thirty-five fractures were evaluated by the treating surgeon and first assistant on radiographs and 2-dimensional CT (2DCT) images first; a second time based on radiographs and 2- and 3-dimensional CT (3DCT) images; a third time based on 2- and 3DCT as well as 3D physical models; and a fourth time based on intraoperative visualization of the fracture characteristics. The intraoperative evaluation of the attending surgeon was used as the reference standard. Results: The addition of 3DCT and the 3D models to 2DCT and radiographs led to significant improvements in sensitivity, but not specificity, in the diagnosis and proposed treatment, and improved the inter-observer agreement with respect to specific fracture characteristics but not classification. Conclusion: Increasingly sophisticated imaging and modeling leads to slight but significant improvements in diagnostic performance characteristics and interobserver agreement on fracture characteristics. C1 [Brouwer, Kim M.; Lindenhovius, Anneluuk L.; Dyer, George S.; Zurakowski, David; Mudgal, Chaitanya S.; Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 27 TC 7 Z9 7 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD JUN PY 2012 VL 21 IS 6 BP 772 EP 776 DI 10.1016/j.jse.2012.01.009 PG 5 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 961IS UT WOS:000305458700016 PM 22516572 ER PT J AU Siegel, CL Andreotti, RF Cardenes, HR Brown, DL Gaffney, DK Horowitz, NS Javitt, MC Lee, SI Mitchell, DG Moore, DH Rao, GG Royal, HD Small, W Varia, MA Yashar, CM AF Siegel, Cary Lynn Andreotti, Rochelle F. Cardenes, Higinia Rosa Brown, Douglas L. Gaffney, David K. Horowitz, Neil S. Javitt, Marcia C. Lee, Susanna I. Mitchell, Donald G. Moore, David H. Rao, Gautam G. Royal, Henry D. Small, William, Jr. Varia, Mahesh A. Yashar, Catheryn M. TI ACR Appropriateness Criteria (R) Pretreatment Planning of Invasive Cancer of the Cervix SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Appropriateness Criteria; cervical cancer; imaging; invasive; pretreatment ID POSITRON-EMISSION-TOMOGRAPHY; LYMPH-NODE METASTASIS; SQUAMOUS-CELL CARCINOMA; CLINICAL STAGE-I; COMPUTED-TOMOGRAPHY; FDG-PET; INTEGRATED PET/CT; PREDICTIVE-VALUE; F-18-FDG PET; INTERGROUP AB The prognosis of cervical cancer is linked to lymph node involvement, and this is predicted clinically and pathologically by the stage of the disease, as well as the volume and grade of the tumor. Staging of cervical cancer based on International Federation of Gynecology and Obstetrics (FIGO) staging uses physical examination, cystoscopy, proctoscopy, intravenous urography, and barium enema. It does not include CT Of MRI. Evaluation of the parametrium is limited in FIGO staging, and lymph node metastasis, an important prognostic factor, is not included in FIGO staging. The most important role for imaging is to distinguish stages Ia, Ib, and ha disease treated with surgery from advanced disease treated with radiation therapy with or without chemotherapy. This article reviews the current role of imaging in pretreatment planning of invasive cervical cancer. The ACR Appropriateness Criteria (R) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinaty expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Siegel, Cary Lynn; Royal, Henry D.] Mallinckrodt Inst Radiol, St Louis, MO USA. [Andreotti, Rochelle F.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Cardenes, Higinia Rosa] Indiana Univ, Med Ctr, Indianapolis, IN USA. [Brown, Douglas L.] Mayo Clin, Rochester, MN USA. [Gaffney, David K.] Univ Utah, Med Ctr, Salt Lake City, UT USA. [Horowitz, Neil S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Horowitz, Neil S.] Soc Gynecol Oncologists, Chicago, IL USA. [Javitt, Marcia C.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Lee, Susanna I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mitchell, Donald G.] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Moore, David H.] Indiana Univ Sch Med, Indianapolis, IN USA. [Moore, David H.] Amer Coll Obstetricians & Gynecologists, Washington, DC 20024 USA. [Rao, Gautam G.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Rao, Gautam G.] Amer Soc Clin Oncol, Alexandria, VA USA. [Royal, Henry D.] Soc Nucl Med, Reston, VA USA. [Small, William, Jr.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Varia, Mahesh A.] Univ N Carolina Hosp, Chapel Hill, NC USA. [Yashar, Catheryn M.] Univ Calif San Diego, San Diego, CA 92103 USA. RP Siegel, CL (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA 20191 USA. EM siegelc@mir.wustl.edu NR 68 TC 15 Z9 16 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JUN PY 2012 VL 9 IS 6 BP 395 EP 402 DI 10.1016/j.jacr.2012.02.021 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 960BU UT WOS:000305363800009 PM 22632665 ER PT J AU Resick, PA Bovin, MJ Calloway, AL Dick, AM King, MW Mitchell, KS Suvak, MK Wells, SY Stirman, SW Wolf, EJ AF Resick, Patricia A. Bovin, Michelle J. Calloway, Amber L. Dick, Alexandra M. King, Matthew W. Mitchell, Karen S. Suvak, Michael K. Wells, Stephanie Y. Stirman, Shannon Wiltsey Wolf, Erika J. TI A critical evaluation of the complex PTSD literature: Implications for DSM-5 SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; BORDERLINE PERSONALITY-DISORDER; COGNITIVE-PROCESSING THERAPY; CHILDHOOD SEXUAL-ABUSE; EXTREME STRESS; STRUCTURED INTERVIEW; LATENT STRUCTURE; INTERPERSONAL PROBLEMS; SCALE DEVELOPMENT; CLINICAL-TRIAL AB Complex posttraumatic stress disorder (CPTSD) has been proposed as a diagnosis for capturing the diverse clusters of symptoms observed in survivors of prolonged trauma that are outside the current definition of PTSD. Introducing a new diagnosis requires a high standard of evidence, including a clear definition of the disorder, reliable and valid assessment measures, support for convergent and discriminant validity, and incremental validity with respect to implications for treatment planning and outcome. In this article, the extant literature on CPTSD is reviewed within the framework of construct validity to evaluate the proposed diagnosis on these criteria. Although the efforts in support of CPTSD have brought much needed attention to limitations in the trauma literature, we conclude that available evidence does not support a new diagnostic category at this time. Some directions for future research are suggested. C1 [Resick, Patricia A.; Bovin, Michelle J.; Calloway, Amber L.; Dick, Alexandra M.; King, Matthew W.; Mitchell, Karen S.; Suvak, Michael K.; Wells, Stephanie Y.; Stirman, Shannon Wiltsey; Wolf, Erika J.] VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA 02130 USA. [Resick, Patricia A.; Mitchell, Karen S.; Stirman, Shannon Wiltsey; Wolf, Erika J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Suvak, Michael K.] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. RP Resick, PA (reprint author), VA Boston Healthcare Syst, Womens Hlth Sci Div 116B3, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA. EM Patricia.Resick@va.gov OI Wolf, Erika/0000-0003-2666-2435 NR 96 TC 67 Z9 67 U1 14 U2 81 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUN PY 2012 VL 25 IS 3 BP 241 EP 251 DI 10.1002/jts.21699 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 962VV UT WOS:000305576500003 PM 22729974 ER PT J AU Goodman, M AF Goodman, Marianne TI Complex PTSD is on the trauma spectrum: Comment on Resick et al. (2012) SO JOURNAL OF TRAUMATIC STRESS LA English DT Article AB Conceptualizing posttraumatic stress disorder (PTSD) along a spectrum with complex and simple features is integrative and models an approach taken by disciplines in medicine outside of psychiatry. This perspective is offered in the Resick et al. (2012) review. To best delineate the nature and permeability of the border between Complex PTSD and PTSD, an emphasis on clarifying underlying biological processes is needed to move beyond our current reliance on symptomatic description. C1 [Goodman, Marianne] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Goodman, Marianne] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. RP Goodman, M (reprint author), Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. EM marianne.goodman@va.gov NR 8 TC 8 Z9 8 U1 3 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUN PY 2012 VL 25 IS 3 BP 254 EP 255 DI 10.1002/jts.21695 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 962VV UT WOS:000305576500005 PM 22729976 ER PT J AU Resick, PA Wolf, EJ Stirman, SW Wells, SY Suvak, MK Mitchell, KS King, MW Bovin, MJ AF Resick, Patricia A. Wolf, Erika J. Stirman, Shannon Wiltsey Wells, Stephanie Y. Suvak, Michael K. Mitchell, Karen S. King, Matthew W. Bovin, Michelle J. TI Advocacy through science: Reply to comments on Resick et al. (2012) SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; SEXUAL-ABUSE; THERAPY; EXPOSURE; TRIAL; PTSD AB The 4 comments on the review by Resick et al. (2012) of the complex posttraumatic stress disorder (CPTSD) literature highlight important theoretical and conceptual questions about the nature and utility of CPTSD and echo the very questions that motivated the review. We discuss the points raised in the comments, particularly with respect to the definition of CPTSD, its relationship to PTSD, and treatment implications. We suggest that setting high scientific standards for CPTSD research is an optimal way to advance the conceptualization of the construct and the treatment of this population. C1 [Resick, Patricia A.; Wolf, Erika J.; Stirman, Shannon Wiltsey; Wells, Stephanie Y.; Suvak, Michael K.; Mitchell, Karen S.; King, Matthew W.; Bovin, Michelle J.] VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA USA. [Resick, Patricia A.; Wolf, Erika J.; Stirman, Shannon Wiltsey; Mitchell, Karen S.; Bovin, Michelle J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Suvak, Michael K.] Suffolk Univ, Boston, MA 02114 USA. RP Resick, PA (reprint author), VA Boston Healthcare Syst, Womens Hlth Sci Div 116B3, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA. EM Patricia.Resick@va.gov OI Wolf, Erika/0000-0003-2666-2435 NR 15 TC 2 Z9 2 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUN PY 2012 VL 25 IS 3 BP 260 EP 263 DI 10.1002/jts.21702 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 962VV UT WOS:000305576500008 ER PT J AU Jeon, GS Kim, KY Hwang, YJ Jung, MK An, S Ouchi, M Ouchi, T Kowall, N Lee, J Ryu, H AF Jeon, Gye Sun Kim, Ki Yoon Hwang, Yu Jin Jung, Min-Kyung An, Sungkwan Ouchi, Mutsuko Ouchi, Toru Kowall, Neil Lee, Junghee Ryu, Hoon TI Deregulation of BRCA1 Leads to Impaired Spatiotemporal Dynamics of gamma-H2AX and DNA Damage Responses in Huntington's Disease SO MOLECULAR NEUROBIOLOGY LA English DT Article DE DNA damage; BRCA1; H2AX; Neurodegeneration; Huntington's disease ID CELL-CYCLE; DEPENDENT PHOSPHORYLATION; GENETIC INSTABILITY; EMBRYONIC LETHALITY; HISTONE H2AX; MICE LACKING; MUTATION; REPAIR; ATM; TRANSCRIPTION AB Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder of mid-life onset characterized by involuntary movements and progressive cognitive decline caused by a CAG repeat expansion in exon 1 of the Huntingtin (Htt) gene. Neuronal DNA damage is one of the major features of neurodegeneration in HD, but it is not known how it arises or relates to the triplet repeat expansion mutation in the Htt gene. Herein, we found that imbalanced levels of non-phosphorylated and phosphorylated BRCA1 contribute to the DNA damage response in HD. Notably, nuclear foci of gamma-H2AX, the molecular component that recruits various DNA damage repair factors to damage sites including BRCA1, were deregulated when DNA was damaged in HD cell lines. BRCA1 specifically interacted with gamma-H2AX via the BRCT domain, and this association was reduced in HD. BRCA1 overexpression restored gamma-H2AX level in the nucleus of HD cells, while BRCA1 knockdown reduced the spatiotemporal propagation of gamma-H2AX foci to the nucleoplasm. The deregulation of BRCA1 correlated with an abnormal nuclear distribution of gamma-H2AX in striatal neurons of HD transgenic (R6/2) mice and BRCA1(+/-) mice. Our data indicate that BRCA1 is required for the efficient focal recruitment of gamma-H2AX to the sites of neuronal DNA damage. Taken together, our results show that BRCA1 directly modulates the spatiotemporal dynamics of gamma-H2AX upon genotoxic stress and serves as a molecular maker for neuronal DNA damage response in HD. C1 [Kowall, Neil; Lee, Junghee; Ryu, Hoon] Boston Univ, Dept Neurol, Sch Med, Boston, MA 02118 USA. [Kowall, Neil; Lee, Junghee; Ryu, Hoon] Boston Univ, Sch Med, Rush Alzheimers Dis Ctr, Boston, MA 02118 USA. [Kowall, Neil; Lee, Junghee; Ryu, Hoon] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Ouchi, Mutsuko; Ouchi, Toru] Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA. [Ouchi, Mutsuko; Ouchi, Toru] Univ Chicago, Pritzker Sch Med, Syst Biol Program, NUHS, Evanston, IL USA. [An, Sungkwan] Konkuk Univ, Dept Microbial Engn, Funct Genoproteome Res Ctr, Seoul, South Korea. [Jeon, Gye Sun; Kim, Ki Yoon; Hwang, Yu Jin; Jung, Min-Kyung; Ryu, Hoon] Seoul Natl Univ, Coll Med, Dept Biomed Sci, WCU Neurocyt Grp, Seoul 110799, South Korea. RP Ryu, H (reprint author), Boston Univ, Dept Neurol, Sch Med, 150 S Huntington Ave, Boston, MA 02118 USA. EM hoonryu@bu.edu RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU KOSEF [2010-0029-403, 800-20080848]; NIH [NS 067283-01A1]; Susan G. Komen Breast Cancer Research Award; [R01CA79892]; [R01CA90631] FX We thank Dr. Marcy MacDonald (Harvard Medical School) for STHdhQ7/7 and STHdhQ111/111 cells. This study was supported by WCU Neurocytomics Program Grant (800-20080848) (H. R.) and SRC Grant (2010-0029-403) (H. R.) from KOSEF, NIH NS 067283-01A1 (H. R.), and R01CA79892 (TO), R01CA90631 (TO), and Susan G. Komen Breast Cancer Research Award (TO). NR 40 TC 12 Z9 12 U1 0 U2 8 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0893-7648 J9 MOL NEUROBIOL JI Mol. Neurobiol. PD JUN PY 2012 VL 45 IS 3 BP 550 EP 563 DI 10.1007/s12035-012-8274-9 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 962QF UT WOS:000305559300013 PM 22580959 ER PT J AU Lee, AH Weintraub, D AF Lee, Angela H. Weintraub, Daniel TI Psychosis in Parkinson's disease without dementia: Common and comorbid with other non-motor symptoms SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; psychosis; non-demented; cognitively intact ID DEPRESSIVE SYMPTOMATOLOGY IDS; SLEEP BEHAVIOR DISORDER; COGNITIVE IMPAIRMENT; DAYTIME SLEEPINESS; HALLUCINATIONS; INVENTORY; SCALE; INSTRUMENT; MORTALITY AB Psychosis in Parkinson's disease (PD) is common and associated with a range of negative outcomes. Dementia and psychosis are highly correlated in PD, but the frequency and correlates of psychosis in patients without cognitive impairment are not well understood. One hundred and ninety-one non-demented PD patients at two movement disorders centers participated in a study of neuropsychiatric complications in PD and completed a detailed neurological and neuropsychiatric assessment, including the rater-administered Parkinson Psychosis Rating Scale for hallucinations, delusions, and minor symptoms of psychosis (illusions and misidentification of persons). Psychotic symptoms were present in 21.5% of the sample. Visual hallucinations were most common (13.6%), followed by auditory hallucinations (6.8%), illusions or misidentification of people (7.3%), and paranoid ideation (4.7%). Visual hallucinations and illusions or misidentification of people were the most common comorbid symptoms (3.1%). Depression (P = 0.01) and rapid eye movement behavior disorder symptoms (P = 0.03) were associated with psychosis in a multivariable model. The odds of experiencing psychotic symptoms were approximately five times higher in patients with comorbid disorders of depression and sleep-wakefulness. Even in patients without global cognitive impairment, psychosis in PD is common and most highly correlated with other non-motor symptoms. Screening for psychosis should occur at all stages of PD as part of a broad non-motor assessment. In addition, these findings suggest a common neural substrate for disturbances of perception, mood, sleep-wakefulness, and incipient cognitive decline in PD. (c) 2012 Movement Disorder Society C1 [Weintraub, Daniel] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Perelman Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Parkinsons Dis Res Educ & Clin Ctr, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Weintraub, Daniel] Mental Illness Res Educ & Clin Ctr, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Weintraub, D (reprint author), 3615 Chestnut St,330, Philadelphia, PA 19104 USA. EM daniel.weintraub@uphs.upenn.edu FU National Institute of Mental Health [067894]; Mental Illness Research, Education, and Clinical Center at the Philadelphia Veterans Affairs Medical Center FX Funding agencies: This work was supported, in part, by grants from the National Institute of Mental Health (067894) and the Mental Illness Research, Education, and Clinical Center at the Philadelphia Veterans Affairs Medical Center. NR 42 TC 36 Z9 37 U1 4 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JUN PY 2012 VL 27 IS 7 BP 858 EP 863 DI 10.1002/mds.25003 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 962XE UT WOS:000305581900011 PM 22674352 ER PT J AU Chattergoon, NN Louey, S Stork, P Giraud, GD Thornburg, KL AF Chattergoon, Natasha N. Louey, Samantha Stork, Philip Giraud, George D. Thornburg, Kent L. TI Mid-Gestation Ovine Cardiomyocytes Are Vulnerable to Mitotic Suppression by Thyroid Hormone SO REPRODUCTIVE SCIENCES LA English DT Article DE fetal heart; cardiomyocyte proliferation; thyroid hormone; p21; cyclin D1 ID FETAL SHEEP CARDIOMYOCYTES; SIGNAL-REGULATED KINASE; CELL-CYCLE ACTIVITY; CARDIAC MYOCYTES; NEONATAL-RAT; FETUS; PLACENTA; GROWTH; PROLIFERATION; HYPERTROPHY AB Circulating fetal 3,3',5-tri-iodo-L-thyronine (T-3) is maintained at very low levels until a dramatic prepartum surge. 3,3',5-Tri-iodo-L-thyronine inhibits serum-stimulated proliferation in near-term ovine cardiomyocytes, but it is not known whether midgestation myocytes are also inhibited. Because early cessation of cardiomyocyte mitosis would result in an underendowed heart, we hypothesized that 0.67 gestation (100 of 145 days gestation) ovine cardiomyocytes would be insensitive to suppressive growth effects of T-3. These younger cardiomyocytes were grown with T-3 in 10% serum-enriched media for 24 hours. Physiological (0.37, 0.75, and 1.5 nmol/L) concentrations of T-3 dramatically suppressed mitotic activity in cardiomyocytes (P < .001). 3,30,5-Tri-iodo-L-thyronine stimulated phosphorylation of extracellular signal-regulated kinase and AKT (also known as Protein Kinase B [PKB]) signaling pathways. Nevertheless, the protein content of the cell cycle suppressor, p21, increased 2-fold (P < .05), and promoter, cyclin D1, decreased by 50%. Contrary to our hypothesis, elevated levels of T-3 powerfully inhibit proliferation of midgestation fetal cardiomyocytes. Thus, midgestation maternal hyperthyroidism might lead to an underendowed fetal myocardium. C1 [Chattergoon, Natasha N.; Louey, Samantha; Stork, Philip; Giraud, George D.; Thornburg, Kent L.] Oregon Hlth & Sci Univ, Heart Res Ctr, Portland, OR 97239 USA. [Louey, Samantha; Giraud, George D.; Thornburg, Kent L.] Oregon Hlth & Sci Univ, Dept Med Cardiovasc Med, Portland, OR 97201 USA. [Stork, Philip] Oregon Hlth & Sci Univ, Vollum Inst Adv Biomed Res, Portland, OR 97201 USA. [Giraud, George D.; Thornburg, Kent L.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. [Giraud, George D.] Portland VA Med Ctr, Portland, OR USA. RP Thornburg, KL (reprint author), Oregon Hlth & Sci Univ, Heart Res Ctr, 3303 SW Bond Ave,CH15H, Portland, OR 97239 USA. EM thornbur@ohsu.edu FU NIH [NICHD P01 HD 34430, NINDS R37, NS045737, NHLBI R21 HL093617, R01 HL102763]; NHLBI [T32HL094294]; M. Lowell Edwards Endowment FX The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: supported by NIH grants NICHD P01 HD 34430, NINDS R37, NS045737, NHLBI R21 HL093617, and R01 HL102763; NNC was supported by NHLBI training grant T32HL094294 and KLT was supported by the M. Lowell Edwards Endowment. NR 44 TC 6 Z9 6 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD JUN PY 2012 VL 19 IS 6 BP 642 EP 649 DI 10.1177/1933719111432860 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 963NH UT WOS:000305627200010 PM 22421446 ER PT J AU Adams, RB Franklin, RG Kveraga, K Ambady, N Kleck, RE Whalen, PJ Hadjikhani, N Nelson, AJ AF Adams, Reginald B., Jr. Franklin, Robert G., Jr. Kveraga, Kestutis Ambady, Nalini Kleck, Robert E. Whalen, Paul J. Hadjikhani, Nouchine Nelson, Anthony J. TI Amygdala responses to averted vs direct gaze fear vary as a function of presentation speed SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE threat perception; amygdala; fMRI; eye gaze; fear expression ID GENERALIZED SOCIAL PHOBIA; FACIAL EXPRESSIONS; EMOTIONAL EXPRESSION; PREFRONTAL CORTEX; ATTENTIONAL BIAS; FACE PERCEPTION; NEURAL SYSTEMS; EYE GAZE; ANXIETY; SIGNAL AB We examined whether amygdala responses to rapidly presented fear expressions are preferentially tuned to averted vs direct gaze fear and conversely whether responses to more sustained presentations are preferentially tuned to direct vs averted gaze fear. We conducted three functional magnetic resonance imaging (fMRI) studies to test these predictions including: Study 1: a block design employing sustained presentations (1 s) of averted vs direct gaze fear expressions taken from the Pictures of Facial Affect; Study 2: a block design employing rapid presentations (300 ms) of these same stimuli and Study 3: a direct replication of these studies in the context of a single experiment using stimuli selected from the NimStim Emotional Face Stimuli. Together, these studies provide evidence consistent with an early, reflexive amygdala response tuned to clear threat and a later reflective response tuned to ambiguous threat. C1 [Adams, Reginald B., Jr.; Franklin, Robert G., Jr.; Nelson, Anthony J.] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA. [Kveraga, Kestutis; Hadjikhani, Nouchine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Ambady, Nalini] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Kleck, Robert E.; Whalen, Paul J.] Dartmouth Coll, Dept Psychol & Brain Sci, Hanover, NH 03755 USA. [Hadjikhani, Nouchine] Ecole Polytech Fed Lausanne, Brain Mind Inst, CH-1015 Lausanne, Switzerland. RP Adams, RB (reprint author), Penn State Univ, Dept Psychol, University Pk, PA 16802 USA. EM radams@psu.edu RI Hadjikhani, Nouchine/C-2018-2008 OI Hadjikhani, Nouchine/0000-0003-4075-3106 FU Social Science Research Institute; Pennsylvania State University; National Science Foundation [0544533]; National Institute of Mental Health [K01MH84011] FX This work was partially supported by Social Science Research Institute research grant, the Pennsylvania State University, National Science Foundation research grant (0544533 to R.B.A. Jr.), National Institute of Mental Health grant (K01MH84011 to K.K.). NR 77 TC 21 Z9 21 U1 9 U2 33 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD JUN PY 2012 VL 7 IS 5 BP 568 EP 577 DI 10.1093/scan/nsr038 PG 10 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 960SK UT WOS:000305409900009 PM 21666261 ER PT J AU Boes, AD Mehta, S Rudrauf, D Van der Plas, E Grabowski, T Adolphs, R Nopoulos, P AF Boes, Aaron D. Mehta, Sonya Rudrauf, David Van der Plas, Ellen Grabowski, Thomas Adolphs, Ralph Nopoulos, Peg TI Changes in cortical morphology resulting from long-term amygdala damage SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE amygdala; lesions; morphometry; plasticity; prefrontal cortex; ventromedial ID HUMAN CEREBRAL-CORTEX; MACAQUE MONKEY AMYGDALA; SURFACE-BASED ANALYSIS; URBACH-WIETHE-DISEASE; LIPOID PROTEINOSIS; PREFRONTAL CORTEX; TOPOGRAPHIC ORGANIZATION; MACACA-FASCICULARIS; DECISION-MAKING; RHESUS-MONKEY AB The amygdala's contribution to emotion, cognition and behavior depends on its interactions with subcortical and cortical regions. Amygdala lesions result in altered functional activity in connected regions, but it is not known whether there might be long-term structural sequelae as well. We hypothesized that developmental bilateral amygdala lesions would be associated with specific gray matter morphometric abnormalities in the ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC) and the ventral visual stream. We conducted regions of interest and vertex-based analyses of structural MRI data acquired in two patients with long-standing focal bilateral amygdala lesions (S.M. and A.P.), compared to gender- and age-matched healthy comparison subjects. Both patients showed significant proportional increases in gray matter volume of the vmPFC. Cortical thickness was increased in the vmPFC and ACC and decreased in the ventral visual stream. There were no morphometric changes in dorsolateral prefrontal cortex or dorsal visual stream cortices. These findings support the hypothesis that cortical regions strongly connected with the amygdala undergo morphometric changes with long-standing amygdala damage. This is the first evidence in humans of the remote alteration of brain morphology in association with amygdala lesions, and will help in interpreting the structural and functional consequences of amygdala pathology in neuropsychiatric disorders. C1 [Adolphs, Ralph] CALTECH, Div Humanities & Social Sci, Pasadena, CA 91125 USA. [Boes, Aaron D.] Harvard Univ, Massachusetts Gen Hosp, Dept Pediat Neurol, Cambridge, MA 02138 USA. [Mehta, Sonya; Grabowski, Thomas] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Mehta, Sonya; Grabowski, Thomas] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Rudrauf, David] Univ Iowa, Dept Neurol, Carver Coll Med, Iowa City, IA 52242 USA. [Rudrauf, David] Univ Iowa, Dept Radiol, Carver Coll Med, Iowa City, IA 52242 USA. [Van der Plas, Ellen; Nopoulos, Peg] Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA. RP Adolphs, R (reprint author), CALTECH, Div Humanities & Social Sci, Pasadena, CA 91125 USA. EM radolphs@hss.caltech.edu FU NIH [NS 019632] FX This research was supported in part by the following grants: NIH NS 019632. The authors thank Douglas Langbehn for his guidance in the statistical analysis. The authors also thank Hans Johnson, Greg Harris and Nick Jones for technical support. *These authors contributed equally to this work. NR 52 TC 4 Z9 4 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD JUN PY 2012 VL 7 IS 5 BP 588 EP 595 DI 10.1093/scan/nsr047 PG 8 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 960SK UT WOS:000305409900011 PM 21896493 ER PT J AU Shahian, DM Nordberg, P Meyer, GS Blanchfield, BB Mort, EA Torchiana, DF Normand, SLT AF Shahian, David M. Nordberg, Paul Meyer, Gregg S. Blanchfield, Bonnie B. Mort, Elizabeth A. Torchiana, David F. Normand, Sharon-Lise T. TI Contemporary Performance of US Teaching and Nonteaching Hospitals SO ACADEMIC MEDICINE LA English DT Article ID QUALITY-OF-CARE; MEDICARE BENEFICIARIES; SURGICAL OUTCOMES; ADJUSTED MORTALITY; ADVERSE EVENTS; UNITED-STATES; HEALTH-CARE; PATIENT; RATES; SAFETY AB Purpose To compare the performance of U. S. teaching and nonteaching hospitals using a portfolio of contemporary, publicly reported metrics. Method The authors classified acute care general hospitals filing a Medicare Institutional Cost Report according to teaching intensity: nonteaching, teaching, or Council of Teaching Hospitals member. They compared aggregate results across categories for Hospital Compare process compliance, mortality, and readmission rates (acute myocardial infarction [AMI], heart failure, pneumonia); Surgical Care Improvement Project (SCIP) performance; compliance with Leapfrog standards; patient experience; patient services and key technologies; safety (computerized physician order entry, intensive care unit staffing, National Quality Forum safe practices, hospital-acquired conditions); and cost/resource utilization (Medicare-adjusted expense per case; Leapfrog efficiency and resource use standards). Results Availability of patient services and advanced technologies were associated with teaching intensity (P < .0001), as were most hospital safety metrics. Teaching intensity was favorably associated with SCIP performance, AMI and heart failure process scores, and mortality (P < .0001). It was unfavorably associated with higher AMI and pneumonia readmission rates (P < .0001) and lower scores for individual patient satisfaction measures. Costs per case were similar (P = .4194) across hospital categories after correction for federally allowed adjustments (case mix, wages, and low-income patient care). Conclusions Teaching hospitals offer advanced clinical capabilities, educate the next generation of providers, care for disadvantaged urban populations, and are leaders in health care research and innovation. However, many stakeholders may be unaware of an additional value-relatively higher quality and safety in many areas, with similar adjusted costs. C1 [Shahian, David M.; Nordberg, Paul; Meyer, Gregg S.; Mort, Elizabeth A.] Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA. [Shahian, David M.; Meyer, Gregg S.; Mort, Elizabeth A.; Torchiana, David F.; Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Blanchfield, Bonnie B.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Blanchfield, Bonnie B.; Torchiana, David F.] Massachusetts Gen Hosp, Massachusetts Gen Hosp Phys Org, Boston, MA 02114 USA. RP Shahian, DM (reprint author), Massachusetts Gen Hosp, Ctr Qual & Safety, 55 Fruit St, Boston, MA 02114 USA. EM dshahian@partners.org FU Massachusetts General Hospital Center for Quality and Safety FX Internal funding, Massachusetts General Hospital Center for Quality and Safety. NR 58 TC 29 Z9 29 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD JUN PY 2012 VL 87 IS 6 BP 701 EP 708 DI 10.1097/ACM.0b013e318253676a PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 956EY UT WOS:000305074100013 PM 22534588 ER PT J AU Liu, QS Ren, T Fresques, T Oppliger, W Niles, BJ Hur, W Sabatini, DM Hall, MN Powers, T Gray, NS AF Liu, Qingsong Ren, Tao Fresques, Tara Oppliger, Wolfgang Niles, Brad J. Hur, Wooyoung Sabatini, David M. Hall, Michael N. Powers, Ted Gray, Nathanael S. TI Selective ATP-Competitive Inhibitors of TOR Suppress Rapamycin-Insensitive Function of TORC2 in Saccharomyces cerevisiae SO ACS CHEMICAL BIOLOGY LA English DT Article ID MAMMALIAN TARGET; KINASE INHIBITOR; YEAST; DISCOVERY; GROWTH; POTENT; MTOR AB The target of rapamycin (TOR) is a critical regulator of growth, survival, and energy metabolism. The allosteric TORC1 inhibitor rapamycin has been used extensively to elucidate the TOR related signal pathway but is limited by its inability to inhibit TORC2. We used an unbiased cell proliferation assay of a kinase inhibitor library to discover QL-IX-55 as a potent inhibitor of S. cerevisiae growth. The functional target of QL-IX-55 is the ATP-binding site of TOR2 as evidenced by the discovery of resistant alleles of TOR2 through rational design and unbiased selection strategies. QL-IX-55 is capable of potently inhibiting both TOR complex 1 and 2 (TORC1 and TORC2) as demonstrated by biochemical IP kinase assays (IC50 < 50 nM) and cellular assays for inhibition of substrate YPK1 phosphorylation. In contrast to rapamycin, QL-IX-55 is capable of inhibiting TORC2-dependent transcription, which suggests that this compound will be a powerful probe to dissect the Tor2/TORC2-related signaling pathway in yeast. C1 [Liu, Qingsong; Hur, Wooyoung; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Liu, Qingsong; Hur, Wooyoung; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Fresques, Tara; Niles, Brad J.; Powers, Ted] Univ Calif Davis, Coll Biol Sci, Dept Mol & Cellular Biol, Davis, CA 95616 USA. [Oppliger, Wolfgang; Hall, Michael N.] Univ Basel, Biozentrum, CH-4056 Basel, Switzerland. [Sabatini, David M.] Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. [Sabatini, David M.] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. [Sabatini, David M.] MIT, Koch Ctr Integrat Canc Res, Cambridge, MA 02139 USA. RP Gray, NS (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM Nathanael_Gray@dfci.harvard.edu OI liu, qing song/0000-0002-7829-2547 FU NERCE [U54 A1057159]; NIH LINCS [HG006097]; NIH [R01GM86387] FX We thank K. Struhl (Harvard Medical School) for providing yeast plasmids and medium and H. H. Wong (Harvard Medical School) for productive discussion. We thank T. Kapoor for suggesting we perform an unbiased kinase library screen for antifungals. We are also acknowledge a NERCE Grant (U54 A1057159) for partial financial support to R.T., a NIH LINCS Grant (HG006097) for the support of Q.L., and a NIH Grant (R01GM86387) to T.P. NR 23 TC 4 Z9 4 U1 1 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD JUN PY 2012 VL 7 IS 6 BP 982 EP 987 DI 10.1021/cb300058v PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 958AE UT WOS:000305207400006 PM 22496512 ER PT J AU Kefala, K Kotsifaki, D Providaki, M Kapetaniou, EG Rahme, L Kokkinidis, M AF Kefala, Katerina Kotsifaki, Dina Providaki, Mary Kapetaniou, Evangelia G. Rahme, Lawrence Kokkinidis, Michael TI Purification, crystallization and preliminary X-ray diffraction analysis of the C-terminal fragment of the MvfR protein from Pseudomonas aeruginosa SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS LA English DT Article DE MvfR; LysR-type transcriptional regulators; Pseudomonas aeruginosa ID TO-CELL COMMUNICATION; GENE; REGULATOR AB The LysR-type transcriptional regulator MvfR plays a critical role in Pseudomonas aeruginosa pathogenicity via the transcriptional regulation of multiple quorum-sensing-regulated virulence factors. The protein also controls pathogenic type VI secretion loci. MvfRC87, a 242-residue C-terminal segment of MvfR, was produced in Escherichia coli, purified and crystallized. X-ray diffraction data were collected using synchrotron radiation and crystallographic parameters were determined. C1 [Kefala, Katerina; Kokkinidis, Michael] Univ Crete, Dept Biol, GR-71003 Iraklion, Crete, Greece. [Kotsifaki, Dina; Providaki, Mary; Kapetaniou, Evangelia G.; Kokkinidis, Michael] Inst Mol Biol & Biotechnol, GR-71110 Iraklion, Crete, Greece. [Rahme, Lawrence] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. [Rahme, Lawrence] Massachusetts Gen Hosp, Shriners Burns Inst, Boston, MA 02114 USA. RP Kokkinidis, M (reprint author), Univ Crete, Dept Biol, POB 2208, GR-71003 Iraklion, Crete, Greece. EM kokkinid@imbb.forth.gr FU European Molecular Biology Laboratory, Hamburg Outstation; European Union [RII3/CT/2004/5060008] FX We thank the European Molecular Biology Laboratory, Hamburg Outstation and the European Union for support through the EU-I3 access grant from the EU Research Infrastructure Action under the FP6 'Structuring the European Research Area Programme', contract No. RII3/CT/2004/5060008. NR 11 TC 5 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1744-3091 J9 ACTA CRYSTALLOGR F JI Acta Crystallogr. F-Struct. Biol. Cryst. Commun. PD JUN PY 2012 VL 68 BP 695 EP 697 DI 10.1107/S1744309112016661 PN 6 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 956EU UT WOS:000305073600020 PM 22684073 ER PT J AU Beidas, RS Birkett, M Newcomb, ME Mustanski, B AF Beidas, Rinad S. Birkett, Michelle Newcomb, Michael E. Mustanski, Brian TI Do Psychiatric Disorders Moderate the Relationship Between Psychological Distress and Sexual Risk-Taking Behaviors in Young Men Who Have Sex with Men? A Longitudinal Perspective SO AIDS PATIENT CARE AND STDS LA English DT Article ID HIV-RISK; SUBSTANCE USE; INFORMED CONSENT; HEALTH BEHAVIORS; DIVERSE SAMPLE; SELF-EFFICACY; BLACK-MEN; ADOLESCENTS; DEPRESSION; INFECTION AB Young men who have sex with men (YMSM) account for two-thirds of new HIV infections in young people in the United States. Identifying between-person and within-person correlates of sexual risk-taking provides critical information for developing behavioral prevention efforts for this group. Possible predictors of sexual-risk behavior in YMSM include major depressive disorder (MDD), post-traumatic stress disorder (PTSD), and variation in psychological distress over time. To date, research has been equivocal with regard to the relationship between psychiatric disorders, psychological distress, and sexual risk behaviors. Participants included 119 16-20-year-old YMSM. Ethnicity/race of the participants included: black/African-American (46.2%), white (19.3%), Latino/Hispanic (12.6%), multiracial (11.8%), Asian/Pacific Islander (2.5%), and other (5.9%). Sexual risk outcomes included total number of male partners and unprotected anal sex acts across four waves of data collection (24 months). The study found that the between-person correlates, including ethnicity and age, predicted total male partners. Between-person correlates, including ethnicity, MDD, and a moderating effect of PTSD on psychological distress emerged as determinants of unprotected anal sex acts. C1 [Birkett, Michelle; Mustanski, Brian] Northwestern Univ, Dept Med Social Sci, Chicago, IL 60611 USA. [Beidas, Rinad S.] Univ Pensylvania, Dept Psychiat, Philadelphia, PA USA. [Beidas, Rinad S.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Newcomb, Michael E.] Univ Illinois, Dept Psychol, Chicago, IL 60680 USA. [Newcomb, Michael E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Mustanski, B (reprint author), Northwestern Univ, Dept Med Social Sci, 625 N Michigan Ave,Suite 2700, Chicago, IL 60611 USA. EM brian@northwestern.edu FU American Foundation for Suicide Prevention; William T. Grant Foundation FX We thank the staff of the IMPACT program, the youth who participated in this study, and the staff at the Broadway Youth Center. This research was funded in part by a grant from the American Foundation for Suicide Prevention and a scholar's award to Dr. Brian S. Mustanski from the William T. Grant Foundation. NR 57 TC 14 Z9 14 U1 1 U2 12 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD JUN PY 2012 VL 26 IS 6 BP 366 EP 374 DI 10.1089/apc.2011.0418 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 957KK UT WOS:000305160100008 PM 22680282 ER PT J AU Axelrod, L AF Axelrod, Lloyd TI Strange Case of Dr Jekyll and Mr Hyde-and John Hunter SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Axelrod, Lloyd] Harvard Univ, Massachusetts Gen Hosp, Diabet Unit, Sch Med, Boston, MA 02114 USA. [Axelrod, Lloyd] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Axelrod, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Diabet Unit, Sch Med, Bulfinch 402,55 Fruit St, Boston, MA 02114 USA. EM laxelrod@partners.org NR 6 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 0002-9343 J9 AM J MED JI Am. J. Med. PD JUN PY 2012 VL 125 IS 6 BP 618 EP 620 DI 10.1016/j.amjmed.2012.01.011 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 958QZ UT WOS:000305256800030 PM 22502957 ER PT J AU Gupta, AC Schaefer, PW Chaudhry, ZA Leslie-Mazwi, TM Chandra, RV Gonzalez, RG Hirsch, JA Yoo, AJ AF Gupta, A. C. Schaefer, P. W. Chaudhry, Z. A. Leslie-Mazwi, T. M. Chandra, R. V. Gonzalez, R. G. Hirsch, J. A. Yoo, A. J. TI Interobserver Reliability of Baseline Noncontrast CT Alberta Stroke Program Early CT Score for Intra-Arterial Stroke Treatment Selection SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; THROMBOLYTIC THERAPY; COMPUTED-TOMOGRAPHY; PROUROKINASE; AGREEMENT; KAPPA AB BACKGROUND AND PURPOSE: Early ischemic changes on pretreatment NCCT quantified using ASPECTS have been demonstrated to predict outcomes after IAT. We sought to determine the interobserver reliability of ASPECTS for patients with AIS with PAO and to determine whether pretreatment ASPECTS dichotomized at 7 would demonstrate at least substantial kappa agreement. MATERIALS AND METHODS: From our prospective IAT data base, we identified consecutive patients with anterior circulation PAO who underwent IAT over a 6-year period. Only those with an evaluable pretreatment NCCT were included. ASPECTS was graded independently by 2 experienced readers. Interrater agreement was assessed for total ASPECTS, dichotomized ASPECTS (<= 7 versus >7), and each ASPECTS region. Statistical analysis included determination of Cohen kappa coefficients and concordance correlation coefficients. PABAK coefficients were also calculated. RESULTS: One hundred fifty-five patients met our study criteria. Median pretreatment ASPECTS was 8 (interquartile. range 7-91. Interrater agreement for total ASPECTS was substantial (concordance correlation coefficient = 0.77). The mean ASPECTS difference between readers was 0.2 (95% confidence interval, -2.8 to 2.4). For dichotomized ASPECTS, there was a 76.8% (119/155) observed rate of agreement, with a moderate kappa = 0.53 (PABAK = 0.54). By region, agreement was worst in the internal capsule and the cortical areas, ranging from fair to moderate. After adjusting for prevalence and bias, agreement improved to substantial or near perfect in most regions. CONCLUSIONS: Interobserver reliability is substantial for total ASPECTS but is only moderate for ASPECTS dichotomized at 7. This may limit the utility of dichotomized ASPECTS for IAT selection. C1 [Gupta, A. C.; Schaefer, P. W.; Chaudhry, Z. A.; Gonzalez, R. G.; Yoo, A. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Diagnost, Boston, MA USA. RP Yoo, AJ (reprint author), 55 Fruit St,GRB241, Boston, MA 02114 USA. EM ajyoo@partners.org FU CareFusion; Penumbra FX Disclosures: Joshua Hirsch-UNRELATED: Consultancy: Phillips, CareFusion, Comments: Participated in focus group of NI specialists for NI suites of the future (Phillips); participated on NextGen team for product development (CareFusion); Royalties: CareFusion, Comments: as above; Stock/Stock Options: IntraTech, Nevro, NFocus, Comments: Development stage companies that are working on NI products (IntraTech and N-Focus) and nerve imaging (Nevro). Albert Yoo UNRELATED: Grants/Grants Pending: Penumbra* *Money paid to institution NR 21 TC 25 Z9 26 U1 1 U2 1 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JUN-JUL PY 2012 VL 33 IS 6 BP 1046 EP 1049 DI 10.3174/ajnr.A2942 PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 957OH UT WOS:000305171800013 PM 22322602 ER PT J AU Phan, CM Yoo, AJ Hirsch, JA Nogueira, RG Gupta, R AF Phan, C. M. Yoo, A. J. Hirsch, J. A. Nogueira, R. G. Gupta, R. TI Differentiation of Hemorrhage from Iodinated Contrast in Different Intracranial Compartments Using Dual-Energy Head CT SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID INTRAARTERIAL THROMBOLYSIS; INTRACEREBRAL HEMORRHAGE; COMPUTED-TOMOGRAPHY; ISCHEMIC-STROKE; INITIAL-EXPERIENCE; EXTRAVASATION; THERAPY AB BACKGROUND AND PURPOSE: Identification of ICH, particularly after ischemic stroke therapy, is important for guiding subsequent antithrombotic management and is often confounded by contrast staining or extravasations within intracerebral or extra-axial compartments. This study evaluates the accuracy of DECT in distinguishing ICH from iodinated contrast in patients who received contrast via IA or IV delivery. MATERIALS AND METHODS: Forty patients who had received IA or IV contrast were evaluated using a DECT scanner at 80kV and 140kV to distinguish hyperdensities secondary to contrast staining or extravasation from those representing ICH. A 3-material decomposition algorithm was used to obtain virtual noncontrast images and iodine overlay images. Sensitivity, specificity, and accuracy of DECT in prospectively distinguishing intracranial contrast from hemorrhage within parenchymal, subarachnoid, extra-axial, intraventricular, and intra-arterial compartments were computed using routine clinical follow-up imaging as the standard of reference. RESULTS: A total of 148 foci of intracranial hyperattenuation were identified. Of these, 142 were correctly classified for the presence of hemorrhage by DECT. The sensitivity, specificity, and accuracy for identifying hemorrhage, depending on the compartment being considered, were 100%, 84.4%- 100%, and 87.2%-100%, respectively. The only instances where DECT failed to correctly identify the source of hyperattenuation was in the presence of diffuse parenchymal calcification (n = 5) and a metallic streak artifact (n = 1). CONCLUSION: After IA and/or IV contrast administration, DECT can accurately differentiate all types of ICH from iodinated contrast without employing any additional radiation. C1 [Phan, C. M.; Yoo, A. J.; Hirsch, J. A.; Nogueira, R. G.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Nogueira, R. G.] Emory Univ, Sch Med, Dept Neurol, Marcus Stroke & Neurosci Ctr,Grady Mem Hosp, Atlanta, GA 30322 USA. [Nogueira, R. G.] Emory Univ, Sch Med, Dept Neurosurg, Marcus Stroke & Neurosci Ctr,Grady Mem Hosp, Atlanta, GA USA. [Nogueira, R. G.] Emory Univ, Sch Med, Dept Radiol, Marcus Stroke & Neurosci Ctr,Grady Mem Hosp, Atlanta, GA 30322 USA. [Nogueira, R. G.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Wang Ambulatory Care Ctr, Boston, MA 02115 USA. RP Phan, CM (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM cmphan@partners.org FU Siemens Medical Solutions; CareFusion FX Disclosures: Joshua Hirsch-UNRELATED: Consultancy: Phillips, CareFusion, Comments: Phillips involvement not directly related. Phillips is a multinational company focused on imaging. I participated in a focus group regarding NI practice for which I was given an honorarium. I would imagine (though I am not certain) that Phillips makes some sort of Dual Energy Product. CareFusion manufactures products for vertebral augmentation; participated in NextGen team; Royalties: CareFusion; Stock/Stock Options: IntraTech, NFocus, Nevro, Comments: IntraTech is a development stage company for ischemic stroke. NFocus is a development stage company for hemorrhagic stroke. Nevro is a development stage company for nerve imaging. Raul Nogueira-UNRELATED: Board Membership: Concentric Medical, eV3 Neurovascular, Coaxia, Neurointervention. Rajiv Gupta-UNRELATED; Payment for Lectures (including service on speakers bureaus): Siemens Erlangen, Comments: Rajiv Gupta presented a talk titled "Neuro Applications of Dual Energy CT" at Somatom World Conference, sponsored by Siemens Medical Solutions. NR 21 TC 36 Z9 36 U1 0 U2 3 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JUN-JUL PY 2012 VL 33 IS 6 BP 1088 EP 1094 DI 10.3174/ajnr.A2909 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 957OH UT WOS:000305171800019 PM 22268092 ER PT J AU Lee, TC Selvarajan, SK Curtin, H Mukundan, S AF Lee, T. C. Selvarajan, S. K. Curtin, H. Mukundan, S. TI Zuckerkandl Tubercle of the Thyroid: A Common Imaging Finding That May Mimic Pathology SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID RECURRENT LARYNGEAL NERVE AB BACKGROUND AND PURPOSE: The posterior thyroid tubercle, also known as ZT, is an important surgical landmark due to its close proximity to the recurrent laryngeal nerve. A recent case of ZT with a nodular configuration caused clinical concern but was shown on biopsy to be normal thyroid tissue. The purpose of this study was to review a series of CT neck studies to identify how often ZT-specifically, a nodular subtype was present. MATERIALS AND METHODS: A total of 96 neck CTs from sequential patients were retrospectively identified from January 2010 to July 2010. ZT was defined on imaging as a thyroid lobe extending posterior to the tracheoesophageal groove. A nodular subtype was defined as having a narrowed neck at the level of the tracheoesophageal groove. RESULTS: There were 31 women and 45 men (mean age of 56.1 years, range 22-100 years) who met inclusion criteria. Sixty-seven patients had thyroid glands that extended posterior to the tracheoesophageal groove at CT imaging; this finding was bilateral in 43 patients, more commonly on the right 160 versus 49). Thirty-two of these patients (42.1%; 16 male, 16 female) had a nodular subtype. CONCLUSIONS: ZT is an important surgical landmark of the thyroid that has important radiologic variations. It has a nodular shape in over a third of CT neck studies in our series. Recognition of this feature of the thyroid gland at CT imaging can obviate the need for biopsy and avoid potential recurrent laryngeal nerve injury. C1 [Lee, T. C.; Selvarajan, S. K.; Curtin, H.; Mukundan, S.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Curtin, H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Lee, TC (reprint author), Brigham & Womens Hosp, Dept Radiol, PBB3,Room 339,75 Francis St, Boston, MA 02115 USA. EM tclee@post.harvard.edu FU Toshiba; Siemens FX Disclosures: Srini Mukundan-UNRELATED: Consultancy: Toshiba America Medical Systems,* Comments: Served on focus group; Grants/Grants Pending: Toshiba,* Siemens;* Payment for Lectures (including service on speakers bureaus): Toshiba, Comments: "Lunch and Learn" lecture at ASNR Annual Meeting in Vancouver (2009). (* Money paid to institution) NR 15 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JUN-JUL PY 2012 VL 33 IS 6 BP 1134 EP 1138 DI 10.3174/ajnr.A2914 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 957OH UT WOS:000305171800026 PM 22300934 ER PT J AU Vincent, DF Gout, J Chuvin, N Arfi, V Pommier, RM Bertolino, P Jonckheere, N Ripoche, D Kaniewski, B Martel, S Langlois, JB Goddard-Leon, S Colombe, A Janier, M Van Seuningen, I Losson, R Valcourt, U Treilleux, I Dubus, P Bardeesy, N Bartholin, L AF Vincent, David F. Gout, Johann Chuvin, Nicolas Arfi, Vanessa Pommier, Roxane M. Bertolino, Philippe Jonckheere, Nicolas Ripoche, Doriane Kaniewski, Bastien Martel, Sylvie Langlois, Jean-Baptiste Goddard-Leon, Sophie Colombe, Amelie Janier, Marc Van Seuningen, Isabelle Losson, Regine Valcourt, Ulrich Treilleux, Isabelle Dubus, Pierre Bardeesy, Nabeel Bartholin, Laurent TI Tif1 gamma Suppresses Murine Pancreatic Tumoral Transformation by a Smad4-Independent Pathway SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID DUCTAL ADENOCARCINOMA; UBIQUITIN LIGASE; SMAD4; TIF1-GAMMA; PROGRESSION; EXPRESSION; CHROMATIN; BRANCHES; DISTINCT; BIOLOGY AB Transcriptional intermediary factor 1 gamma (TIF1 gamma; alias, TRIM33/RFG7/PTC7/ectodermin) belongs to an evolutionarily conserved family of nuclear factors that have been implicated in stem cell pluripotency, embryonic development, and tumor suppression. TIF1 gamma expression is markedly down-regulated in human pancreatic tumors, and Pdx1-driven Tif1 gamma inactivation cooperates with the Kras(G12D) oncogene in the mouse pancreas to induce intraductal papillary mucinous neoplasms. In this study, we report that aged Pdx1-Cre; LSL-Kras(G12D); Tif1 gamma(lox/lox) mice develop pancreatic ductal adenocarcinomas (PDACs), an aggressive and always fatal neoplasm, demonstrating a Tif1 gamma tumor-suppressive function in the development of pancreatic carcinogenesis. Deletion of SMAD4/DPC4 (deleted in pancreatic carcinoma locus 4) occurs in approximately 50% of human cases of PDAC. We, therefore, assessed the genetic relationship between Tif1 gamma and Smad4 signaling in pancreatic tumors and found that Pdx1-Cre; LSL-Kras(G12D); Smad4(lox/lox); Tif1 gamma(lox/lox) (alias, KSSTT) mutant mice exhibit accelerated tumor progression. Consequently, Tif1 gamma tumor-suppressor effects during progression from a premalignant to a malignant state in our mouse model of pancreatic cancer are independent of Smad4. These findings establish, for the first time to our knowledge, that Tif1 gamma and Smad4 both regulate an intraductal papillary mucinous neoplasm-to-PDAC sequence through distinct tumor-suppressor programs. (Am J Pathol 2012, 180:2214-2221; http://dx.doi.org/10.1016/j.ajpath.2012.02.006) C1 [Vincent, David F.; Gout, Johann; Chuvin, Nicolas; Arfi, Vanessa; Pommier, Roxane M.; Bertolino, Philippe; Ripoche, Doriane; Kaniewski, Bastien; Martel, Sylvie; Goddard-Leon, Sophie; Colombe, Amelie; Valcourt, Ulrich; Treilleux, Isabelle; Bartholin, Laurent] Ctr Leon Berard, F-69373 Lyon, France. [Vincent, David F.; Gout, Johann; Chuvin, Nicolas; Arfi, Vanessa; Pommier, Roxane M.; Bertolino, Philippe; Ripoche, Doriane; Kaniewski, Bastien; Martel, Sylvie; Valcourt, Ulrich; Treilleux, Isabelle; Bartholin, Laurent] CRCL, INSERM, U1052, Lyon, France. [Vincent, David F.; Gout, Johann; Chuvin, Nicolas; Arfi, Vanessa; Pommier, Roxane M.; Bertolino, Philippe; Ripoche, Doriane; Kaniewski, Bastien; Martel, Sylvie; Valcourt, Ulrich; Treilleux, Isabelle; Bartholin, Laurent] CRCL, CNRS, UMR5286, Lyon, France. [Vincent, David F.; Gout, Johann; Chuvin, Nicolas; Arfi, Vanessa; Pommier, Roxane M.; Bertolino, Philippe; Ripoche, Doriane; Kaniewski, Bastien; Martel, Sylvie; Janier, Marc; Valcourt, Ulrich; Treilleux, Isabelle; Bartholin, Laurent] Univ Lyon 1, F-69365 Lyon, France. [Vincent, David F.; Gout, Johann; Chuvin, Nicolas; Arfi, Vanessa; Pommier, Roxane M.; Bertolino, Philippe; Ripoche, Doriane; Kaniewski, Bastien; Martel, Sylvie; Janier, Marc; Valcourt, Ulrich; Treilleux, Isabelle; Bartholin, Laurent] Univ Lyon, Lyon, France. [Chuvin, Nicolas] Ecole Normale Super Lyon, F-69364 Lyon, France. [Jonckheere, Nicolas; Van Seuningen, Isabelle] Jean Pierre Aubert Res Ctr, INSERM, UMR837, Lille, France. [Langlois, Jean-Baptiste] CERMEP, Bron, France. [Janier, Marc] Hosp Civils Lyon, Nucl Med Serv, Hop Edouard Herriot, Lyon, France. [Janier, Marc] Lab Phys Chem Luminescent Mat, Villeurbanne, France. [Losson, Regine] Inst Genet & Mol & Cellular Biol IGBMC, Illkirch Graffenstaden, France. [Dubus, Pierre] Univ Bordeaux, EA 2406, Bordeaux, France. [Bardeesy, Nabeel] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. RP Bartholin, L (reprint author), Ctr Leon Berard, 28 Rue Laennec, F-69373 Lyon, France. EM laurent.bartholin@lyon.unicancer.fr RI Jonckheere, Nicolas/J-6028-2013; OI Jonckheere, Nicolas/0000-0002-0496-0661; Vincent, David/0000-0001-6482-8040 FU INSERM; Centre National de la Recherche Scientifique (CNRS); Ministere de l'Enseignement Superieur et de la Recherche of France; Association pour la Recherche sur le Cancer; Ligue Nationale contra le Cancer; NIH [R01 CA133557-01] FX Supported by INSERM (Avenir program), the Centre National de la Recherche Scientifique (CNRS), fellowships from the Ministere de l'Enseignement Superieur et de la Recherche of France (D.F.V., R.M.P., and D.R.) and the Association pour la Recherche sur le Cancer (D.F.V.), fellowships from the Ligue Nationale contra le Cancer (J.G., V.A., and N.J.), and a grant from the NIH (R01 CA133557-01 to N.B.). NR 22 TC 14 Z9 14 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 2012 VL 180 IS 6 BP 2214 EP 2221 DI 10.1016/j.ajpath.2012.02.006 PG 8 WC Pathology SC Pathology GA 956PJ UT WOS:000305101300006 PM 22469842 ER PT J AU Shirley, SH Greene, VR Duncan, LM Cabala, CAT Grimm, EA Kusewitt, DF AF Shirley, Stephanie H. Greene, Victoria R. Duncan, Lyn M. Cabala, Carlos A. Torres Grimm, Elizabeth A. Kusewitt, Donna F. TI Slug Expression during Melanoma Progression SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID E-CADHERIN EXPRESSION; EPITHELIAL-MESENCHYMAL TRANSITION; TRANSCRIPTION FACTOR SLUG; RETINAL-PIGMENT EPITHELIUM; REPRESSES E-CADHERIN; MALIGNANT-MELANOMA; GENE-EXPRESSION; WAARDENBURG-SYNDROME; TUMOR PROGRESSION; GROWTH-FACTOR AB Slug (Snai2), a member of the Snail family of zinc finger transcription factors, plays a role in the epithelial-to-mesenchymal transformation (EMT) that occurs during melanocyte emigration from the neural crest. A role for Slug in the EMT-like loss of cell adhesion and increased cell motility exhibited during melanoma progression has also been proposed. Our immunohistochemical studies of melanoma arrays, however, revealed that Slug expression was actually higher in nevi than in primary or metastatic melanomas. Moreover, Slug expression in melanomas was not associated with decreased expression of E-cadherin, the canonical Slug target in EMT. Comparisons of endogenous Slug and E-cadherin expression in cultured normal human melanocytes and melanoma cell lines supported our immunohistochemical findings. Expression of exogenous Slug in melanocytes and melanoma cells in vitro, however, suppressed E-cadherin expression, enhanced N-cadherin expression, and stimulated cell migration and invasion. Interestingly, both in tumors and cultured cell lines, there was a clear relationship between expression of Slug and MITF, a transcription factor known to regulate Slug expression during development. Taken together, our findings suggest that Slug expression during melanomagenesis is highest early in the process and that persistent Slug expression is not required for melanoma progression. The precise role of Slug in melanomagenesis remains to be elucidated and may be related to its interactions with other drivers of EMT, such as Snail. (Am J Pathol 2012, 180:2479-2489; http://dx.doi.org/10.1016/j.ajpath.2012.02.014) C1 [Shirley, Stephanie H.; Kusewitt, Donna F.] Univ Texas MD Anderson Canc Ctr, Dept Mol Carcinogenesis, Smithville, TX 78957 USA. [Greene, Victoria R.; Grimm, Elizabeth A.] Melanoma Med Oncol, Houston, TX USA. [Cabala, Carlos A. Torres] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Duncan, Lyn M.] Massachusetts Gen Hosp, Dermatopathol Unit, Pathol Serv, Boston, MA 02114 USA. [Duncan, Lyn M.] Harvard Univ, Sch Med, Boston, MA USA. RP Kusewitt, DF (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Mol Carcinogenesis, Sci Pk,1808 Pk Rd 1C, Smithville, TX 78957 USA. EM dkusewitt@mdanderson.org FU University of Texas MD Anderson Cancer Center SPORE in Melanoma [P50 CA093459]; University of Texas MD Anderson Cancer Center [P30 CA016672]; Center for Research in Environmental Disease [P30 ES007784]; Research Training in Carcinogenesis and Mutagenesis [T32 CA09480]; Baker Foundation FX Supported by grants from the University of Texas MD Anderson Cancer Center SPORE in Melanoma (P50 CA093459), University of Texas MD Anderson Cancer Center Support Grant (P30 CA016672), the Center for Research in Environmental Disease (P30 ES007784), the Research Training in Carcinogenesis and Mutagenesis (T32 CA09480), and a Baker Foundation Fellowship (to S.H.S.). NR 71 TC 23 Z9 24 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 2012 VL 180 IS 6 BP 2479 EP 2489 DI 10.1016/j.ajpath.2012.02.014 PG 11 WC Pathology SC Pathology GA 956PJ UT WOS:000305101300030 PM 22503751 ER PT J AU Desikan, RS McEvoy, LK Thompson, WK Holland, D Brewer, JB Aisen, PS Sperling, RA Dale, AM AF Desikan, Rahul S. McEvoy, Linda K. Thompson, Wesley K. Holland, Dominic Brewer, James B. Aisen, Paul S. Sperling, Reisa A. Dale, Anders M. CA Alzheimer's Dis Neuroimaging Initi TI Amyloid-beta-Associated Clinical Decline Occurs Only in the Presence of Elevated P-tau SO ARCHIVES OF NEUROLOGY LA English DT Article ID PRECLINICAL ALZHEIMERS-DISEASE; COGNITIVE-DECLINE; FLUID BIOMARKER; VOLUME LOSS; FOLLOW-UP; PREDICTION; A-BETA(42); RATIO AB Objective: To elucidate the relationship between the 2 hallmark proteins of Alzheimer disease (AD), amyloid-beta (A beta) and tau, and clinical decline over time among cognitively normal older individuals. Design: A longitudinal cohort of clinically and cognitively normal older individuals assessed with baseline lumbar puncture and longitudinal clinical assessments. Setting: Research centers across the United States and Canada. Patients: Weexamined 107 participants with a Clinical Dementia Rating (CDR) of 0 at baseline examination. Main Outcome Measures: Using linear mixed effects models, we investigated the relationship between cerebrospinal fluid (CSF) phospho-tau 181 (p-tau(181p)), CSF A beta(1-42), and clinical decline as assessed using longitudinal change in global CDR, CDR-Sum of Boxes, and the Alzheimer Disease Assessment Scale-cognitive subscale. Results: We found a significant relationship between decreased CSFA beta(1-42) and longitudinal change in global CDR, CDR-Sum of Boxes, and Alzheimer Disease Assessment Scale-cognitive subscale in individuals with elevated CSF p-tau(181p). In the absence of CSF p-tau(181p), the effect of CSF A beta(1-42) on longitudinal clinical decline was not significantly different from 0. Conclusions: In cognitively normal older individuals, A beta-associated clinical decline during a mean of 3 years may occur only in the presence of ongoing downstream neurodegeneration. Arch Neurol. 2012; 69(6): 709-713. Published online April 23, 2012. doi:10.1001/archneurol.2011.3354 C1 [Desikan, Rahul S.; McEvoy, Linda K.; Brewer, James B.; Dale, Anders M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92037 USA. [Thompson, Wesley K.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92037 USA. [Holland, Dominic; Brewer, James B.; Aisen, Paul S.; Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92037 USA. [Sperling, Reisa A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Sperling, Reisa A.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Desikan, RS (reprint author), Univ Calif San Diego, Dept Radiol, 8950 Villa La Jolla Dr,Ste C101, La Jolla, CA 92037 USA. EM rdesikan@ucsd.edu RI Kowall, Neil/G-6364-2012; Preda, Adrian /K-8889-2013; Saykin, Andrew/A-1318-2007 OI Kowall, Neil/0000-0002-6624-0213; Preda, Adrian /0000-0003-3373-2438; Saykin, Andrew/0000-0002-1376-8532 FU Pfizer; Baxter International; National Institutes of Health from National Institute on Aging [01-AG10483, U01-AG024904, R01-AG030048, R01-AG16381]; National Institutes of Health [R01AG031224, K01AG029218, K02 NS067427, T32 EB005970, P01 AG036694, K24 AG035007, P30 AG010129, K01 AG030514]; Alzheimer's Association San Diego; Alzheimer's Disease Neuroimaging Initiative from National Institutes of Health [U01 AG024904]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Dana Foundation FX Dr McEvoy's spouse is the chief executive officer of CorTechs Labs. Dr Aisen serves on a scientific advisory board for NeuroPhage as well as serves as a consultant to Elan, Wyeth, Eisai, Bristol-Myers Squibb, Eli Lilly, NeuroPhage, Merck, Roche, Amgen, Abbott Laboratories, Pfizer, Novartis, Bayer, Astellas Pharma, Dainippon, Biomarin, Solvay, Otsuka, Daiichi Sankyo, AstraZeneca, Janssen Pharmaceuticals, Medivation, Theravance, Cardeus, and Anavex. He also receives research support from Pfizer, Baxter International, and the National Institutes of Health (grants 01-AG10483, U01-AG024904, R01-AG030048, and R01-AG16381 from the National Institute on Aging). He has also received stock options from Medivation. Dr Dale is a founder and holds equity in CorTechs Labs and also serves on the company's Scientific Advisory Board. The terms of this arrangement have been reviewed and approved by the University of California-San Diego in accordance with its conflict of interest policies.; This study was supported by grants R01AG031224, K01AG029218, K02 NS067427, T32 EB005970, P01 AG036694, and K24 AG035007 from the National Institutes of Health and a Young Scholar Award from the Alzheimer's Association San Diego/Imperial Chapter.. Data collection and sharing for this study was funded by the Alzheimer's Disease Neuroimaging Initiative (grant U01 AG024904 from the National Institutes of Health). The Alzheimer's Disease Neuroimaging Initiative (ADNI) is funded by the National Institute on Aging; the National Institute of Biomedical Imaging and Bioengineering; and contributions from Abbott Laboratories, AstraZeneca, Bayer Schering Pharma, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson&Johnson, Eli Lilly, Medpace, Merck, Novartis, Pfizer, F. Hoffman-La Roche, Schering-Plough, Synarc, and Wyeth, as well as non-profit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the US Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California-San Diego. Alzheimer's Disease Neuroimaging Initiative data are disseminated by the Laboratory for Neuro Imaging at the University of California-Los Angeles. This research was also supported by grants P30 AG010129 and K01 AG030514 from the National Institutes of Health and the Dana Foundation. NR 23 TC 60 Z9 62 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUN PY 2012 VL 69 IS 6 BP 709 EP 713 DI 10.1001/archneurol.2011.3354 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 957DW UT WOS:000305139900004 PM 22529247 ER PT J AU Berson, EL Rosner, B Sandberg, MA Weigel-DiFranco, C Willett, WC AF Berson, Eliot L. Rosner, Bernard Sandberg, Michael A. Weigel-DiFranco, Carol Willett, Walter C. TI omega-3 Intake and Visual Acuity in Patients With Retinitis Pigmentosa Receiving Vitamin A SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID DOCOSAHEXAENOIC ACID; CLINICAL-TRIAL; PREVALENCE; RATES; DIET AB Objective: To evaluate whether a diet high in long-chain omega-3 fatty acids can slow the rate of visual acuity loss among patients with retinitis pigmentosa receiving vitamin A palmitate. Methods: We calculated dietary intake from questionnaires completed annually by 357 adult patients from 3 randomized trials who were all receiving vitamin A, 15 000 IU/d, for 4 to 6 years. Rates of visual acuity decline were compared between those with high (>= 0.20 g/d) vs low (<0.20 g/d) omega-3 intake. Analyses took age into account. Results: Mean rates of decline of acuity were slower among those with high omega-3 intake: Early Treatment Diabetic Retinopathy Study distance acuity: high intake=0.59 letter per year, low intake=1.00 letter per year, P=.001; Snellen retinal acuity: high intake=1.5% per year, low intake=2.8% per year, P=.03. Conclusions: We conclude that mean annual rates of decline in distance and retinal visual acuities in adults with retinitis pigmentosa receiving vitamin A, 15 000 IU/d, are slower over 4 to 6 years among those consuming a diet rich in omega-3 fatty acids. To our knowledge, this is the first report that nutritional intake can modify the rate of decline of visual acuity in retinitis pigmentosa. C1 [Berson, Eliot L.; Rosner, Bernard; Sandberg, Michael A.; Weigel-DiFranco, Carol] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab,Study Retinal Degenerat, Boston, MA 02114 USA. [Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Berson, EL (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab,Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. EM linda_berard@meei.harvard.edu FU National Eye Institute [U10 EY02014, U10 EY011030, U10 EY013945]; Foundation Fighting Blindness, Columbia, Maryland FX This research was supported by National Eye Institute grants U10 EY02014, U10 EY011030, and U10 EY013945 and the Foundation Fighting Blindness, Columbia, Maryland. NR 33 TC 29 Z9 29 U1 0 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUN PY 2012 VL 130 IS 6 BP 707 EP 711 DI 10.1001/archophthalmol.2011.2580 PG 5 WC Ophthalmology SC Ophthalmology GA 957FS UT WOS:000305145600006 PM 22332205 ER PT J AU Veldman, PB Behlau, I Soriano, E Starling, JC Pineda, R AF Veldman, Peter B. Behlau, Irmgard Soriano, Eduardo Starling, Jay C. Pineda, Roberto TI Two Cases of Cosmetic Iris Implant Explantation Secondary to Uveitis, Glaucoma, and Corneal Decompensation SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material C1 [Veldman, Peter B.; Behlau, Irmgard; Pineda, Roberto] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Soriano, Eduardo] Escola Paulista Med, Sao Paulo, Brazil. [Starling, Jay C.] USN, Med Ctr, Portsmouth, VA USA. RP Veldman, PB (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM peter_veldman@meei.harvard.edu NR 3 TC 5 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUN PY 2012 VL 130 IS 6 BP 787 EP 789 PG 3 WC Ophthalmology SC Ophthalmology GA 957FS UT WOS:000305145600023 PM 22801843 ER PT J AU Nybo, K Joung, K AF Nybo, Kristie Joung, Keith TI Building with Biological LEGO SO BIOTECHNIQUES LA English DT Editorial Material C1 [Joung, Keith] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BIOTECHNIQUES OFFICE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JUN PY 2012 VL 52 IS 6 BP 351 EP 351 DI 10.2144/000113870 PG 1 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 959GF UT WOS:000305300200002 ER PT J AU Xu, WH Gao, H Seok, J Wilhelmy, J Mindrinos, MN Davis, RW Xiao, WZ AF Xu, Weihong Gao, Hong Seok, Junhee Wilhelmy, Julie Mindrinos, Michael N. Davis, Ronald W. Xiao, Wenzhong TI Coding SNPs as intrinsic markers for sample tracking in large-scale transcriptome studies SO BIOTECHNIQUES LA English DT Article DE microarray; transcriptome profiling; coding SNP; outlier detection; sample tracking ID OUTLIER DETECTION; GENE-EXPRESSION; MODEL AB Large-scale transcriptome profiling in clinical studies often involves assaying multiple samples of a patient to monitor disease progression, treatment effect, and host response in multiple tissues. Such profiling is prone to human error, which often results in mislabeled samples. Here, we present a method to detect mislabeled sample outliers using coding single nucleotide polymorphisms (cSNPs) specifically designed on the microarray and demonstrate that the mislabeled samples can be efficiently identified by either simple clustering of allele-specific expression scores or Mahalanobis distance-based outlier detection method. Based on our results, we recommend the incorporation of cSNPs into future transcriptome array designs as intrinsic markers for sample tracking. C1 [Xu, Weihong; Gao, Hong; Seok, Junhee; Wilhelmy, Julie; Mindrinos, Michael N.; Davis, Ronald W.; Xiao, Wenzhong] Stanford Univ, Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA. [Xiao, Wenzhong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Shriners Hosp Children, Boston, MA USA. RP Xiao, WZ (reprint author), Stanford Univ, Genome Technol Ctr, Palo Alto, CA 94304 USA. EM wxiaol@partners.org OI xiao, wenzhong/0000-0003-4944-6380 FU National Institutes of Health [PO1-HG00205, U54-GM62119] FX Data presented in this work were generated by the Inflammation and Host Response to Injury Large-Scale Collaborative Research Program. This study was supported by grants from National Institutes of Health (PO1-HG00205, U54-GM62119). NR 15 TC 2 Z9 2 U1 0 U2 5 PU BIOTECHNIQUES OFFICE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JUN PY 2012 VL 52 IS 6 BP 386 EP 388 DI 10.2144/0000113879 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 959GF UT WOS:000305300200007 PM 22668418 ER PT J AU Ringden, O Shrestha, S da Silva, GT Zhang, MJ Dispenzieri, A Remberger, M Kamble, R Freytes, CO Gale, RP Gibson, J Gupta, V Holmberg, L Lazarus, H McCarthy, P Meehan, K Schouten, H Milone, GA Lonial, S Hari, PN AF Ringden, O. Shrestha, S. da Silva, G. T. Zhang, M-J Dispenzieri, A. Remberger, M. Kamble, R. Freytes, C. O. Gale, R. P. Gibson, J. Gupta, V. Holmberg, L. Lazarus, H. McCarthy, P. Meehan, K. Schouten, H. Milone, G. A. Lonial, S. Hari, P. N. TI Effect of acute and chronic GVHD on relapse and survival after reduced-intensity conditioning allogeneic transplantation for myeloma SO BONE MARROW TRANSPLANTATION LA English DT Article DE graft-vs-host disease; reduced intensity; allogeneic; myeloma ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; DIAGNOSED MULTIPLE-MYELOMA; VERSUS-HOST DISEASE; CHRONIC GRAFT; CHRONIC LEUKEMIA; EUROPEAN GROUP; RECIPIENTS; TRIAL; CYCLOSPORINE AB We evaluated the effect of acute and chronic GVHD on relapse and survival after allogeneic hematopoietic SCT (HSCT) for multiple myeloma using non-myeloablative conditioning (NMA) and reduced-intensity conditioning (RIC). The outcomes of 177 HLA-identical sibling HSCT recipients between 1997 and 2005, following NMA (n = 98) or RIC (n = 79) were analyzed. In 105 patients, autografting was followed by planned NMA/RIC allogeneic transplantation. The impact of GVHD was assessed as a time-dependent covariate using Cox models. The incidence of acute GVHD (aGVHD; grades I-IV) was 42% (95% confidence interval (CI), 35-49%) and of chronic GVHD (cGVHD) at 5 years was 59% (95% CI, 49-69%), with 70% developing extensive cGVHD. In multivariate analysis, aGVHD (>= grade I) was associated with an increased risk of TRM (relative risk (RR) = 2.42, P = 0.016), whereas limited cGVHD significantly decreased the risk of myeloma relapse (RR = 0.35, P = 0.035) and was associated with superior EFS (RR = 0.40, P = 0.027). aGVHD had a detrimental effect on survival, especially in those receiving autologous followed by allogeneic HSCT (RR = 3.52, P = 0.001). The reduction in relapse risk associated with cGVHD is consistent with a beneficial graft-vs-myeloma effect, but this did not translate into a survival advantage. Bone Marrow Transplantation (2012) 47, 831-837; doi:10.1038/bmt.2011.192; published online 26 September 2011 C1 [Shrestha, S.; Zhang, M-J; Hari, P. N.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Ringden, O.; Remberger, M.] Karolinska Univ Hosp, Dept Clin Immunol, Stockholm, Sweden. [da Silva, G. T.] Univ Sao Paulo, Dept Stat, Sao Paulo, Brazil. [Dispenzieri, A.] Mayo Clin, Rochester, MN USA. [Kamble, R.] Baylor Coll Med, Dept Hematol & Oncol, Houston, TX 77030 USA. [Freytes, C. O.] S Texas Vet Hlth Care Syst, Dept Hematol, San Antonio, TX USA. [Gale, R. P.] Celgene Corp, Dept Hematol & Oncol, Summit, NJ USA. [Gibson, J.] Royal Prince Alfred Hosp, Dept Haematol, Inst Haematol, Camperdown, NSW 2050, Australia. [Gupta, V.] Princess Margaret Hosp, Dept Med, Toronto, ON M4X 1K9, Canada. [Holmberg, L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Lazarus, H.] Univ Hosp Case Med Ctr, Dept Med, Cleveland, OH USA. [McCarthy, P.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Meehan, K.] Dartmouth Hitchcock Med Ctr, Dept Med, Lebanon, NH 03766 USA. [Schouten, H.] Univ Hosp Maastricht, Dept Internal Med, Maastricht, Netherlands. [Milone, G. A.] Angelica Ocampo Fundaleu, Buenos Aires, DF, Argentina. [Lonial, S.] Emory Univ Hosp, Dept Med, Atlanta, GA 30322 USA. RP Hari, PN (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, 9200 W Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA. EM phari@mcw.edu OI Hari, Parameswaran/0000-0002-8800-297X; Dispenzieri, Angela/0000-0001-8780-9512 FU Public Health Service from the National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases; NHLBI [5U01HL069294]; NCI; Health Resources and Services Administration (HRSA/DHHS) [HHSH 234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; AABB; Aetna; American Society for Blood and Marrow Transplantation; Amgen, Inc.; Swedish Cancer Society; Children's Cancer Foundation; Swedish Research Council; Cancer Society in Stockholm; Karolinska Institutet FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases; a Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; a contract HHSH 234200637015C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from AABB; Aetna; American Society for Blood and Marrow Transplantation, Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US, Inc.; Baxter International, Inc.; Bayer HealthCare Pharmaceuticals; Be the Match Foundation; Biogen IDEC; BioMarin Pharmaceutical, Inc.; Biovitrum AB; BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Buchanan Family Foundation; Canadian Blood and Marrow Transplant Group; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Centers for Disease Control and Prevention; Children's Leukemia Research Association; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Cubist Pharmaceuticals; Cylex, Inc.; CytoTherm; DOR BioPharma, Inc.; Dynal Biotech (an Invitrogen Company); Eisai, Inc.; Enzon Pharmaceuticals, Inc.; European Group for Blood and Marrow Transplantation; Gamida Cell, Ltd.; GE Healthcare; Genentech, Inc.; Genzyme Corporation; Histogenetics, Inc.; HKS Medical Information Systems; Hospira, Inc.; Infectious Diseases Society of America; Kiadis Pharma; Kirin Brewery Co., Ltd.; The Leukemia and Lymphoma Society; Merck and Company; The Medical College of Wisconsin; MGI Pharma, Inc.; Michigan Community Blood Centers; Millennium Pharmaceuticals, Inc.; Miller Pharmacal Group; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Nature Publishing Group; New York Blood Center; Novartis Oncology; Oncology Nursing Society; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Pall Life Sciences; Pfizer, Inc.; Saladax Biomedical, Inc.; Schering Corporation; Society for Healthcare Epidemiology of America; Soligenix, Inc.; StemCyte, Inc.; StemSoft Software, Inc.; Sysmex America, Inc.; THERAKOS, Inc.; Thermogenesis Corporation; Vidacare Corporation; Vion Pharmaceuticals, Inc.; ViraCor Laboratories; ViroPharma, Inc.; and Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense or any other agency of the US Government. Olle Ringden is supported by grants from the Swedish Cancer Society, the Children's Cancer Foundation, the Swedish Research Council, the Cancer Society in Stockholm, and Karolinska Institutet. NR 28 TC 14 Z9 14 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JUN PY 2012 VL 47 IS 6 BP 831 EP 837 DI 10.1038/bmt.2011.192 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 958YF UT WOS:000305276200010 PM 21946381 ER PT J AU Murphy, SN Dubey, A Embi, PJ Harris, PA Richter, BG Turisco, F Weber, GM Tcheng, JE Keogh, D AF Murphy, Shawn N. Dubey, Anil Embi, Peter J. Harris, Paul A. Richter, Brent G. Turisco, Fran Weber, Griffin M. Tcheng, James E. Keogh, Diane TI Current State of Information Technologies for the Clinical Research Enterprise across Academic Medical Centers SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Article DE clinical research informatics; clinical Research Forum; health informatics ID CHALLENGES AB Information technology (IT) to support clinical research has steadily grown over the past 10 years. Many new applications at the enterprise level are available to assist with the numerous tasks necessary in performing clinical research. However, it is not clear how rapidly this technology is being adopted or whether it is making an impact upon how clinical research is being performed. The Clinical Research Forum's IT Roundtable performed a survey of 17 representative academic medical centers (AMCs) to understand the adoption rate and implementation strategies within this field. The results were compared with similar surveys from 4 and 6 years ago. We found the adoption rate for four prominent areas of IT-supported clinical research had increased remarkably, specifically regulatory compliance, electronic data capture for clinical trials, data repositories for secondary use of clinical data, and infrastructure for supporting collaboration. Adoption of other areas of clinical research IT was more irregular with wider differences between AMCs. These differences appeared to be partially due to a set of openly available applications that have emerged to occupy an important place in the landscape of clinical research enterprise-level support at AMC's. Clin Trans Sci 2012; Volume 5: 281-284 C1 [Murphy, Shawn N.; Dubey, Anil; Keogh, Diane] Partners HealthCare Syst Inc, Res Comp, Charlestown, MA USA. [Murphy, Shawn N.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Murphy, Shawn N.; Dubey, Anil] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. [Dubey, Anil] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Embi, Peter J.] Ohio State Univ, Dept Biomed Informat, Columbus, OH 43210 USA. [Embi, Peter J.] Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA. [Embi, Peter J.] Ohio State Univ, Ctr Clin & Translat Sci, Columbus, OH 43210 USA. [Harris, Paul A.] Vanderbilt Univ, Dept Biomed Informat, Nashville, TN USA. [Richter, Brent G.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02114 USA. [Turisco, Fran] Aspen Advisors LLC, Morrison, CO USA. [Weber, Griffin M.] Beth Israel Deaconess Med Ctr, Dept Med, IMBIO, Boston, MA 02215 USA. [Tcheng, James E.] Duke Univ, Duke Translat Med Inst, Durham, NC USA. [Tcheng, James E.] Duke Univ, Dept Med, Durham, NC USA. RP Murphy, SN (reprint author), Partners HealthCare Syst Inc, Res Comp, Charlestown, MA USA. EM snmurphy@partners.org RI Embi, Peter/E-3030-2011; OI Weber, Griffin/0000-0002-2597-881X FU NCATS NIH HHS [UL1 TR000090]; PHS HHS [UL1 TR000090] NR 14 TC 8 Z9 8 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1752-8054 J9 CTS-CLIN TRANSL SCI JI CTS-Clin. Transl. Sci. PD JUN PY 2012 VL 5 IS 3 BP 281 EP 284 DI 10.1111/j.1752-8062.2011.00387.x PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 956GC UT WOS:000305077100001 PM 22686207 ER PT J AU Deng, XM Gray, NS AF Deng, Xianming Gray, Nathanael S. TI Pyrazolopyridines as inhibitors of the kinase LRRK2: a patent evaluation (WO2011141756) SO EXPERT OPINION ON THERAPEUTIC PATENTS LA English DT Article DE LRRK2 kinase inhibitor; Parkinson's disease; patent evaluation; pyrazolopyridine ID PARKINSONS-DISEASE; MODELS AB Scientific evaluation of a patent aiming for the development of pyrazolopyridine derivatives as LRRK2 kinase inhibitors, a potential therapeutic target for combating Parkinson's disease. C1 [Deng, Xianming; Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Deng, Xianming; Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Deng, Xianming] Xiamen Univ, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen 361005, Fujian, Peoples R China. RP Gray, NS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, 250 Longwood Ave,SGM 628, Boston, MA 02115 USA. EM xmdeng@xmu.edu.cn; nathanael_gray@dfci.harvard.edu FU NIH [P41 GM079575-03]; Michael J Fox foundation for Parkinson's disease research; Fundamental Research Funds for the Central Universities of China [2011121030] FX This work was supported by NIH grant P41 GM079575-03 (N. Gray), the Michael J Fox foundation for Parkinson's disease research (N. Gray), and the Fundamental Research Funds for the Central Universities of China, project number 2011121030 (X. Deng). The authors state no conflict of interest. NR 18 TC 2 Z9 2 U1 0 U2 8 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3776 J9 EXPERT OPIN THER PAT JI Expert Opin. Ther. Patents PD JUN PY 2012 VL 22 IS 6 BP 709 EP 713 DI 10.1517/13543776.2012.691968 PG 5 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 958NG UT WOS:000305245000008 PM 22607035 ER PT J AU Bressler, NM Miller, KM Beck, RW Bressler, SB Glassman, AR Kitchens, JW Melia, M Schlossman, DK AF Bressler, N. M. Miller, K. M. Beck, R. W. Bressler, S. B. Glassman, A. R. Kitchens, J. W. Melia, M. Schlossman, D. K. CA Diabetic Retinopathy Clinical Res TI Observational study of subclinical diabetic macular edema SO EYE LA English DT Article DE diabetic macular edema; optical coherence tomography; subclinical diabetic macular edema ID OPTICAL COHERENCE TOMOGRAPHY; RETINOPATHY AB Purpose To determine the rate of progression of eyes with subclinical diabetic macular edema (DME) to clinically apparent DME or DME necessitating treatment during a 2-year period. Methods In all, 43 eyes from 39 study participants with subclinical DME, defined as absence of foveal center edema as determined with slit lamp biomicroscopy but a center point thickness (CPT) between 225 and 299 mu m on time domain (Stratus, Carl Zeiss Meditec) optical coherence tomography (OCT) scan, were enrolled from 891 eyes of 582 subjects screened. Eyes were evaluated annually for up to 2 years for the primary outcome, which was an increase in OCT CPT of at least 50 mu m from baseline and a CPT of at least 300 mu m, or treatment for DME (performed at the discretion of the investigator). Results The cumulative probability of meeting an increase in OCT CPT of at least 50 mu m from baseline and a CPT of at least 300 mu m, or treatment for DME was 27% (95% confidence interval (CI): 14%, 38%) by 1 year and 38% (95% CI: 23%, 50%) by 2 years. Conclusions Although subclinical DME may be uncommon, this study suggests that between approximately one-quarter and one-half of eyes with subclinical DME will progress to more definite thickening or be judged to need treatment for DME within 2 years after its identification. Eye (2012) 26, 833-840; doi:10.1038/eye.2012.53; published online 23 March 2012 C1 [Miller, K. M.; Beck, R. W.; Glassman, A. R.; Melia, M.] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA. [Bressler, N. M.; Bressler, S. B.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. [Kitchens, J. W.] Retina & Vitreous Associates Kentucky, Lexington, KY USA. [Schlossman, D. K.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02115 USA. RP Glassman, AR (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA. EM drcrstat3@jaeb.org NR 7 TC 17 Z9 17 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X J9 EYE JI Eye PD JUN PY 2012 VL 26 IS 6 BP 833 EP 840 DI 10.1038/eye.2012.53 PG 8 WC Ophthalmology SC Ophthalmology GA 960LL UT WOS:000305389400012 ER PT J AU Barnes, DE Palmer, RM Kresevic, DM Fortinsky, RH Kowal, J Chren, MM Landefeld, CS AF Barnes, Deborah E. Palmer, Robert M. Kresevic, Denise M. Fortinsky, Richard H. Kowal, Jerome Chren, Mary-Margaret Landefeld, C. Seth TI Acute Care For Elders Units Produced Shorter Hospital Stays At Lower Cost While Maintaining Patients' Functional Status SO HEALTH AFFAIRS LA English DT Article ID COMPREHENSIVE GERIATRIC ASSESSMENT; RANDOMIZED CONTROLLED-TRIAL; OLDER PATIENTS; MEDICAL UNIT; METAANALYSIS; OUTCOMES; ADULTS; HOME; ACE; INTERVENTION AB Acute Care for Elders Units offer enhanced care for older adults in specially designed hospital units. The care is delivered by interdisciplinary teams, which can include geriatricians, advanced practice nurses, social workers, pharmacists, and physical therapists. In a randomized controlled trial of 1,632 elderly patients, length-of-stay was significantly shorter-6.7 days per patient versus 7.3 days per patient-among those receiving care in the Acute Care for Elders Unit compared to usual care. This difference produced lower total inpatient costs-$9,477 per patient versus $10,451 per patient-while maintaining patients' functional abilities and not increasing hospital readmission rates. The practices of Acute Care for Elders Units, and the principles they embody, can provide hospitals with effective strategies for lowering costs while preserving quality of care for hospitalized elders. C1 [Barnes, Deborah E.; Landefeld, C. Seth] Univ Calif San Francisco, Mt Zion Ctr Aging, San Francisco, CA 94143 USA. [Barnes, Deborah E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Palmer, Robert M.] Eastern Virginia Med Sch, Glennan Ctr Geriatr & Gerontol, Norfolk, VA 23501 USA. [Kresevic, Denise M.] Louis Stokes Vet Affairs Med Ctr, Cleveland, OH USA. [Fortinsky, Richard H.] Univ Connecticut, Sch Med, Farmington, CT USA. [Kowal, Jerome] Case Western Reserve Sch Med, Cleveland, OH USA. [Landefeld, C. Seth] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Barnes, DE (reprint author), Univ Calif San Francisco, Mt Zion Ctr Aging, San Francisco, CA 94143 USA. EM deborah.barnes@ucsf.edu FU National Institutes of Health [R01 AG029233, AG10418, K24 AR052667]; S.D. Bechtel Jr. Foundation FX Some results from this paper were presented to the Society of General Internal Medicine, Chicago, Illinois, April 23-25, 1998. Support for this study was provided by the National Institutes of Health (R01 AG029233 and AG10418, principal investigator C. Seth Landefeld; K24 AR052667, principal investigator Mary-Margaret Chren) and the S.D. Bechtel Jr. Foundation. The authors thank Laura Sands and Katharine Kirby for performing statistical analyses, Ken Covinsky for providing comments on the manuscript, and the clinical Acute Care for Elders teams that have provided care to the authors' patients. NR 32 TC 19 Z9 19 U1 1 U2 13 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JUN PY 2012 VL 31 IS 6 BP 1227 EP 1236 DI 10.1377/hlthaff.2012.0142 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 957AM UT WOS:000305130900010 PM 22665834 ER PT J AU Adler, LA Shaw, DM Spencer, TJ Newcorn, JH Hammerness, P Sitt, DJ Minerly, C Davidow, JV Faraone, SV AF Adler, Lenard A. Shaw, David M. Spencer, Thomas J. Newcorn, Jeffrey H. Hammerness, Paul Sitt, David J. Minerly, Christina Davidow, Jennifer V. Faraone, Stephen V. TI Preliminary Examination of the Reliability and Concurrent Validity of the Attention-Deficit/Hyperactivity Disorder Self-Report Scale v1.1 Symptom Checklist to Rate Symptoms of Attention-Deficit/Hyperactivity Disorder in Adolescents SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; ONCE-DAILY ATOMOXETINE; LISDEXAMFETAMINE DIMESYLATE; DOUBLE-BLIND; ADULT ADHD; CHILDREN; COMORBIDITY; TRIAL; TOLERABILITY; DIAGNOSIS AB Objective: To validate the attention-deficit/hyperactivity disorder (ADHD) Self-Report Scale (ASRS) v1.1 Symptom Checklist versus the clinician-administered ADHD Rating Scale (ADHD-RS) in adolescents with ADHD. Method: A total of 88 adolescents with ADHD aged 13-17 years participated in the study. The study was completed in one or two visits, 1-9 weeks apart. At each visit, participants completed the ASRS v1.1 Symptom Checklist, after which raters administered the ADHD-RS. Internal consistency of the ASRS v1.1 Symptom Checklist was assessed by Cronbach's alpha (Cronbach's a). Concurrent validity between the scales was assessed using Pearson's correlation coefficients. Item-by-item reliability between the scales was assessed by the Kappa coefficient of agreement. Results: The mean age of participants was 14.9 +/- 1.5 SD years. 76.1% (n = 67) were male. 73.9% (n = 65) were currently receiving medication for ADHD. Internal consistency of ASRS v1.1 Symptom Checklist items was high, with Cronbach's a coefficients of 0.93 at Visit 1 and 0.94 at Visit 2. Pearson's correlation coefficients between the ASRS v1.1 Symptom Checklist and ADHD-RS were highly significant at Visit 1 (r = 0.72, p < 0.0001) and Visit 2 (r = 0.73, p < 0.0001). There was moderate item-by-item agreement between individual items on the scales (% agreement: 35.2%-63.4%) with statistically significant kappa coefficients for 17 of the 18 items. Conclusion: The ASRS v1.1 Symptoms Checklist showed high internal consistency and high concurrent validity with the clinician-administered ADHD-RS in adolescents with ADHD. Results of this study suggest that the ASRS v1.1 Symptom Checklist is an internally consistent self-report scale for the assessment of adolescent ADHD and is moderately associated with a concurrently administered clinician measure of ADHD symptoms. C1 [Adler, Lenard A.; Shaw, David M.] NYU, Sch Med, Dept Psychiat, New York, NY 10016 USA. [Adler, Lenard A.] NYU, Sch Med, Dept Child & Adolescent Psychiat, New York, NY 10016 USA. [Adler, Lenard A.] VA New York Harbor Healthcare Syst, Psychiat Serv, New York, NY USA. [Spencer, Thomas J.] Harvard Univ, Sch Med, Dept Psychiat, New York, NY USA. [Spencer, Thomas J.; Hammerness, Paul] Massachusetts Gen Hosp, Pediat Psychopharmacol Res Program, Boston, MA 02114 USA. [Newcorn, Jeffrey H.; Davidow, Jennifer V.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Sitt, David J.] CUNY, Baruch Coll, Dept Psychol, New York, NY 10021 USA. [Minerly, Christina] CUNY Hunter Coll, Dept Psychol, New York, NY 10021 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA. RP Adler, LA (reprint author), NYU, Sch Med, Dept Psychiat, 650 1st Ave,7th Floor, New York, NY 10016 USA. EM lenard.adler@nyumc.org OI Newcorn, Jeffrey /0000-0001-8993-9337; Adler, Len/0000-0002-9812-8234; Faraone, Stephen/0000-0002-9217-3982 FU Eli Lilly and Company, Indianapolis, IN; Bristol-Myers Squibb; Shire; Chelsea Therapeutics; Eli Lilly and Company; National Institute of Drug Abuse; NYU School of Medicine; Shire Laboratories, Inc.; Cephalon; Glaxo-Smith Kline; Janssen; McNeil Pharmaceutical; Novartis Pharmaceuticals; Pfizer; NIMH; Ortho-McNeil-Janssen; Abbott; Forest; McNeil; Elminda Ltd; Bristol Myers Squibb; Eli Lilly; Glaxo-SmithKline; Johnson and Johnson; Merck; New River; Organon; Takeda; National Institutes of Health FX Findings of this study were presented in part at the Annual Meeting of the American Academy of Child and Adolescent Psychiatry, New York, NY, October 2010. This study was funded in part by an investigator-initiated research grant from Eli Lilly and Company, Indianapolis, IN. In compliance with the Uniform Requirements for Manuscripts, established by the International Committee of Medical Journal Editors, Eli Lilly and Company did not impose any impediment, directly or indirectly, on the publication of the study's results. Employees of Eli Lilly and Company were not involved in the study design, in the collection, analysis, and interpretation of data, in the writing of the article, and in the decision to submit the article for publication.; Dr. Lenard Adler has received grant/research support from the following sources: Bristol-Myers Squibb, Shire, Chelsea Therapeutics, Eli Lilly and Company, and the National Institute of Drug Abuse. Dr. Adler has served on the advisory board for AstraZeneca Pharmaceuticals, Eli Lilly and Company, Major League Baseball, Mindsite, Shire, and i3 Research. Dr. Adler has consulted with Abbott Laboratories, AstraZeneca Pharmaceuticals, Cortex Pharmaceuticals, Cephalon, Eli Lilly and Company, Epi-Q, i3 Research, INC Research, Major League Baseball, Merck and Company, Mindsite, Novartis Pharmaceuticals, Organon, Ortho McNeil/Jannsen/Johnson and Johnson, Otsuka Pharmaceuticals, Psychogenics, Sanofi-Aventis Pharmaceuticals, Shire, and United Biosource. Dr. Adler has received royalty payments (as inventor) from the NYU School of Medicine for license of adult ADHD scales and training materials since 2004.; Dr. Thomas Spencer has received research support from the following sources: Shire Laboratories, Inc., Cephalon, Eli Lilly and Company, Glaxo-Smith Kline, Janssen, McNeil Pharmaceutical, Novartis Pharmaceuticals, Pfizer, and NIMH. Dr. Thomas Spencer has been a speaker or on a speaker's bureau for the following pharmaceutical companies: Shire Laboratories, Inc., Eli Lilly and Company, Glaxo-Smith Kline, Janssen, McNeil Pharmaceutical, and Novartis Pharmaceuticals. Dr. Thomas Spencer has been an advisor or on an advisory board for the following pharmaceutical companies: Shire Laboratories, Inc., Cephalon, Eli Lilly and Company, Glaxo-Smith Kline, Janssen, McNeil Pharmaceutical, Novartis Pharmaceuticals, and Pfizer.; Dr. Jeffrey Newcorn has received research support from the following sources: Eli Lilly and Company, Ortho-McNeil-Janssen, and Shire Laboratories, Inc. Dr. Newcorn has consulted with Eli Lilly and Company, Ortho-McNeil-Janssen, and Shire Laboratories, Inc. Dr. Newcorn has served on the advisory board for Eli Lilly and Company, Ortho-McNeil-Janssen, Schering-Plough, and Shire Laboratories, Inc.; Dr. Paul Hammerness has received research funds or participated in CME activities/professional talks supported by the following pharmaceutical companies: Abbott, Eli Lilly and Company, Forest, McNeil, and Shire. Dr. Hammerness has also received research funds from Elminda Ltd and has participated in speaker training and served on the advisory board for Shire. Dr. Hammerness has participated, as an investigator, in research studies funded by the following pharmaceutical companies: Abbott, Bristol Myers Squibb, Cephalon, Eli Lilly, Glaxo-SmithKline, Johnson and Johnson, McNeil, Merck, New River, Organon, Pfizer, Shire, and Takeda. Dr. Hammerness has also received honoraria from Reed Medical Education (a logistics collaborator for the MGH Psychiatry Academy). Commercial entities supporting the MGH Psychiatry Academy are listed on the Academy's website, www.mghcme.org.; Dr. Stephen Faraone has consulted with, has served the advisory board, or has been a speaker for the following sources: Shire, McNeil, Janssen, Novartis, Pfizer, Ortho-McNeil, and Eli Lilly and Company. Dr. Faraone has received research support from Eli Lilly and Company, Shire, Pfizer, and the National Institutes of Health. NR 38 TC 27 Z9 27 U1 3 U2 10 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD JUN PY 2012 VL 22 IS 3 BP 238 EP 244 DI 10.1089/cap.2011.0062 PG 7 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 959TS UT WOS:000305337300008 PM 22537184 ER PT J AU Pena, JA Ferraro, MJ Hoffman, CG Branda, JA AF Pena, Jeremy A. Ferraro, Mary Jane Hoffman, Colleen G. Branda, John A. TI Growth Detection Failures by the Nonradiometric Bactec MGIT 960 Mycobacterial Culture System SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CLINICAL SPECIMENS; RECOVERY; IDENTIFICATION; MULTICENTER AB Mycobacterial growth in liquid culture can go undetected by automated, nonradiometric growth detection systems. In our laboratory, instrument-negative tubes from the Bactec MGIT 960 system are inspected visually for clumps suggestive of mycobacterial growth, which (if present) are examined by acid-fast smear analysis. A 3-year review demonstrated that similar to 1% of instrument-negative MGIT cultures contained mycobacterial growth and that 10% of all cultures yielding mycobacteria were instrument negative. Isolates from instrument-negative MGIT cultures included both tuberculous and nontuberculous mycobacteria. C1 [Branda, John A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Branda, JA (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM jbranda@partners.org NR 17 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 2012 VL 50 IS 6 BP 2092 EP 2095 DI 10.1128/JCM.00108-12 PG 4 WC Microbiology SC Microbiology GA 956VZ UT WOS:000305119000048 PM 22493332 ER PT J AU Mian, MK Nahed, BV Walcott, BP Ogilvy, CS Curry, WT AF Mian, Matthew K. Nahed, Brian V. Walcott, Brian P. Ogilvy, Christopher S. Curry, William T. TI Glioblastoma multiforme and cerebral cavernous malformations: intersection of pathophysiologic pathways SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Cavernoma; Glioblastoma; Brain tumor; Cavernous malformation; Glioma ID ANGIOMA; OLIGODENDROGLIOMA; HEMANGIOMAS; ASTROCYTOMA; EXPRESSION; ETIOLOGY; BRAIN AB Cerebral cavernous malformations (CCM) are known to occur in both sporadic and familial forms. To date. there has been no identified association of CCM with glioblastoma multiforme. We present a 69-year-old woman with a 14 year history of multiple CCM who developed progressive aphasia. She had no radiation exposure and had only undergone a single computed tomography scan in her entire life. MRI demonstrated irregular gadolinium enhancement in the area of a prior stable CCM, suspicious for a high grade tumor. Stereotactic biopsy revealed a glioblastoma multiforme. This is a unique case of glioblastoma multiforme arising from the "site" of a known CCM. We review the literature on the genetics of cavernous malformations and propose a mechanism for the tumorigenic potential of these vascular malformations. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Walcott, Brian P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu NR 26 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD JUN PY 2012 VL 19 IS 6 BP 884 EP 886 DI 10.1016/j.jocn.2011.07.017 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 955SH UT WOS:000305040700023 PM 22099074 ER PT J AU Fachin, F Nikles, SA Wardle, BL AF Fachin, Fabio Nikles, Stefan A. Wardle, Brian L. TI Mechanics of Out-of-Plane MEMS via Postbuckling: Model-Experiment Demonstration Using CMOS SO JOURNAL OF MICROELECTROMECHANICAL SYSTEMS LA English DT Article DE Analytical design; boundary flexibility; nonlinear structural mechanics; out-of-plane microelectromechanical systems (MEMS); postbuckling; residual stresses; thermal accelerometer ID 3-DIMENSIONAL NANOSTRUCTURES; LITHOGRAPHY; MICROFABRICATION; STRESSES AB A novel approach to out-of-plane microelectromechanical systems (MEMS) is demonstrated where elements are designed in the postbuckling regime, exploiting buckling phenomena and residual-stress control to create functional elements that extend significantly out of the wafer plane. An analytical tool for out-of-plane MEMS design is presented, based on nonlinear postbuckling of layered structures, including boundary nonideality. The analytical design tool is applied to several MEMS designs where low-order elements (e. g., beams) are controllably formed into out-of-plane shapes. Various architectures are experimentally demonstrated using CMOS processes, including one that could find application in three-axis single-heater thermal accelerometers. The on chip approach is compatible with several MEMS fabrication techniques (e. g., CMOS and micromachining), thus providing a new extension of state-of-the-art microfabrication techniques to out-of-plane elements. [2011-0337] C1 [Fachin, Fabio; Wardle, Brian L.] MIT, Dept Aeronaut & Astronaut, Cambridge, MA 02139 USA. [Nikles, Stefan A.] ePack Inc, Ann Arbor, MI 48103 USA. RP Fachin, F (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. EM ffachin@mit.edu; stefan.nikles@yahoo.com; stefan.nikles@yahoo.com FU MEMSIC, Inc.; U.S. Department of State's Fulbright Science and Technology FX This work was supported in part by MEMSIC, Inc., and in part by the U.S. Department of State's Fulbright Science and Technology Award. Subject Editor L. Lin. NR 40 TC 2 Z9 2 U1 3 U2 9 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1057-7157 J9 J MICROELECTROMECH S JI J. Microelectromech. Syst. PD JUN PY 2012 VL 21 IS 3 BP 621 EP 634 DI 10.1109/JMEMS.2012.2189365 PG 14 WC Engineering, Electrical & Electronic; Nanoscience & Nanotechnology; Instruments & Instrumentation; Physics, Applied SC Engineering; Science & Technology - Other Topics; Instruments & Instrumentation; Physics GA 953WN UT WOS:000304904400015 ER PT J AU Quigley, KS McAndrew, LM Almeida, L D'Andrea, EA Engel, CC Hamtil, H Ackerman, AJ AF Quigley, Karen S. McAndrew, Lisa M. Almeida, Liliana D'Andrea, Elizabeth A. Engel, Charles C. Hamtil, Heather Ackerman, Adam J. TI Prevalence of Environmental and Other Military Exposure Concerns in Operation Enduring Freedom and Operation Iraqi Freedom Veterans SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID GULF-WAR VETERANS; TRAUMATIC BRAIN-INJURY; UNEXPLAINED PHYSICAL SYMPTOMS; PRIMARY-CARE; HEALTH; SEEKING; STRESS; ASSOCIATION; POPULATION; COMMUNITY AB Objective: This study examined the prevalence of self-reported exposures in returning Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) veterans and the relationship of exposure reports to current physical symptoms. Methods: Using self-reports obtained immediately after return from deployment in a cohort of 760 enlisted Army reserve component military personnel, we assessed prevalence rates of environmental and other exposures and the association of these exposures to severity of physical symptoms. Results: Reporting of environmental exposures was relatively low in veterans of OEF/OIF, but reporting more environmental and other exposures, in particular screening positive for a traumatic brain injury, was related to greater physical symptom severity immediately after deployment. Conclusions: Non-treatment-seeking, enlisted Army reserve component personnel reported relatively few exposures immediately after return from deployment; however, more exposures was modestly associated with greater severity of physical symptoms when controlling for predeployment symptoms, gender, and other deployment-related exposures. C1 [Quigley, Karen S.] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Quigley, Karen S.] Edith Nourse Rogers Mem Vet Adm Hosp, Bedford, MA 01730 USA. [Quigley, Karen S.; McAndrew, Lisa M.; Almeida, Liliana; Hamtil, Heather; Ackerman, Adam J.] NJ WRIISC, Dept Vet Affairs New Jersey Healthcare Syst, E Orange, NJ USA. [Quigley, Karen S.; McAndrew, Lisa M.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Psychiat, Newark, NJ 07103 USA. [D'Andrea, Elizabeth A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Engel, Charles C.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [Engel, Charles C.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Psychiat, Bethesda, MD 20814 USA. [Almeida, Liliana] Alliant Int Univ, CSPP, Los Angeles, CA USA. [Hamtil, Heather] Rutgers State Univ, Ctr Behav Hlth Serv & Criminal Justice Res, New Brunswick, NJ 08903 USA. RP Quigley, KS (reprint author), Northeastern Univ, Dept Psychol, 125 Nightingale Hall, Boston, MA 02115 USA. EM k.quigley@neu.edu RI Quigley, Karen/B-9003-2013 OI Quigley, Karen/0000-0001-8844-990X FU Department of Veterans Affairs [IIR 02-296]; NJ WRIISC; Jersey Healthcare System at Department of Veterans Affairs; Deployment Health Clinical Center, Walter Reed Army Medical Center FX This work was supported by a Department of Veterans Affairs, Health Services Research and Development grant (IIR 02-296) to Dr Quigley while she was employed. at the NJ WRIISC. Additional funds were provided by the NJ WRIISC and the Center for Healthcare Knowledge Management (NJ REAP; VA Health Services Research and Development) at the Department of Veterans Affairs Now Jersey Healthcare System, and by the Deployment Health Clinical Center, Walter Reed Army Medical Center. NR 40 TC 10 Z9 10 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD JUN PY 2012 VL 54 IS 6 SI SI BP 659 EP 664 DI 10.1097/JOM.0b013e3182570506 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 957MA UT WOS:000305165900002 PM 22588478 ER PT J AU Kasotakis, G Michailidou, M Bramos, A Chang, YC Velmahos, G Alam, H King, D de Moya, MA AF Kasotakis, George Michailidou, Maria Bramos, Athanosios Chang, Yuchiao Velmahos, George Alam, Hasan King, David de Moya, Marc A. TI Intraparenchymal vs Extracranial Ventricular Drain Intracranial Pressure Monitors in Traumatic Brain Injury: Less Is More? SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID SEVERE HEAD-INJURY; INTRA-CRANICAL PRESSURE; INTENSIVE-CARE; COMPLICATIONS; MANAGEMENT; INTUBATION; EXPERIENCE; MANNITOL; PROPHYLAXIS; PLACEMENT AB BACKGROUND: Management of severe traumatic brain injury has centered on continuous intracranial pressure (ICP) monitoring with intraparenchymal ICP monitors (IPM) or extracranial ventricular drains (EVD). Our hypothesis was that neurologic outcomes are unaffected by the type of ICP monitoring device. STUDY DESIGN: We reviewed 377 adult patients with traumatic brain injury requiring ICP monitoring. Primary outcome was Glasgow Outcome Score (GOS) 1 month after injury. Secondary outcomes included mortality, monitoring-related complications, and length of ICU and hospital stay. RESULTS: There were 253 patients managed with an IPM and 124 with an EVD. There was no difference in GlasgowOutcome Score (2.7 +/- 1.3 vs 2.5 +/- 1.3, p = 0.45), mortality (30.9% vs 32.2%, p = 0.82), and hospital length of stay (LOS) (15.6 +/- 12.4 days vs 16.4 +/- 10.7 days, p = 0.57). Device-related complications (11.9% vs 31.1%, p < 0.001), duration of ICP monitoring (3.8 +/- 2.6 days vs 7.3 +/- 5.6 days, p < 0.001), and ICU LOS (7.6 +/- 5.6 days vs 9.5 +/- 6.2 days, p = 0.004) were longer in the EVD group. Age, opening ICP, and size of midline shift were independent predictors for neurologic outcomes and mortality, when type and severity of brain injury, as well as overall injury severity were controlled for. Duration of ICP monitoring and opening ICP were independent predictors for hospital LOS and the former predicted prolonged ICU stay. Device-related complications were affected by type of device. CONCLUSIONS: Use of EVDs in adult traumatic brain injury patients is associated with prolonged ICP monitoring, ICU LOS, and more frequent device-related complications. (J Am Coll Surg 2012;214:950-957. (C) 2012 by the American College of Surgeons) C1 [Kasotakis, George; Michailidou, Maria; Bramos, Athanosios; Chang, Yuchiao; Velmahos, George; Alam, Hasan; King, David; de Moya, Marc A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Trauma Emergency Surg & Surg Crit C, Boston, MA 02114 USA. RP de Moya, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Trauma Emergency Surg & Surg Crit C, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. OI King, David/0000-0003-1028-1478; Kasotakis, George/0000-0002-7630-0742 NR 54 TC 12 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2012 VL 214 IS 6 BP 950 EP 957 DI 10.1016/j.jamcollsurg.2012.03.004 PG 8 WC Surgery SC Surgery GA 958NM UT WOS:000305245800012 PM 22541986 ER PT J AU Friedlander, AH AF Friedlander, Arthur H. TI PROSTHETIC JOINT INFECTIONS SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Letter ID DENTAL PROCEDURES C1 Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Friedlander, AH (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JUN PY 2012 VL 143 IS 6 BP 552 EP + PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 957LF UT WOS:000305163800003 PM 22653926 ER PT J AU Spira, AP Covinsky, K Rebok, GW Punjabi, NM Stone, KL Hillier, TA Ensrud, KE Yaffe, K AF Spira, Adam P. Covinsky, Kenneth Rebok, George W. Punjabi, Naresh M. Stone, Katie L. Hillier, Teresa A. Ensrud, Kristine E. Yaffe, Kristine TI Poor Sleep Quality and Functional Decline in Older Women SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE sleep; actigraphy; function; IADLs; women ID OSTEOPOROTIC FRACTURES; CARDIOVASCULAR HEALTH; ELDERLY PERSONS; PERSISTENCE; ACTIVATION; ACTIGRAPHY; COMPLAINTS; COMMUNITY; ADULTS; MEN AB Objectives To determine whether objectively measured sleep quality predicts 5-year incident instrumental activity of daily living (IADL) impairment and decline in grip strength and gait speed in older women. Design Prospective cohort. Setting Participants' homes, Study of Osteoporotic Fractures sites. Participants Eight hundred seventeen women with a mean age of 82.4 at baseline. Measurements Participants completed 4.1 +/- 0.7 nights of wrist actigraphy at baseline and measures of IADL impairment, grip strength, and gait speed at baseline and 5-year follow-up. Results After 5years of follow-up, approximately 41% of participants had incident impairment in one or more IADLs. The quartile of women with the shortest total sleep time (TST) had 93% greater odds of incident IADL impairment than the longest sleepers (adjusted odds ratio (AOR)=1.93, 95% confidence interval (CI)=1.252.97). Similarly, the quartile of women with the lowest sleep efficiency (SE) had 65% greater odds of impairment than those with the highest (AOR=1.65, 95% CI=1.062.57). Women in the shortest TST quartile had twice the odds of declining grip strength as those with the longest TST (AOR=1.97, 95% CI=1.173.32). Finally, women in the quartiles with the most wake after sleep onset (WASO) and the lowest SE had approximately 90% greater odds of grip strength decline than those with the least WASO (AOR=1.90, 95% CI=1.113.24) and SE (AOR=1.92, 95% CI=1.123.29). Conclusion Findings indicate that shorter sleep duration, greater WASO, and lower SE are risk factors for functional or physical decline in older women. C1 [Spira, Adam P.; Rebok, George W.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Covinsky, Kenneth] Univ Calif San Francisco, Div Geriatr, Dept Med, San Francisco, CA USA. [Covinsky, Kenneth] San Francisco VA Med Ctr, San Francisco, CA USA. [Punjabi, Naresh M.] Johns Hopkins Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD USA. [Punjabi, Naresh M.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Stone, Katie L.] Calif Pacific Med Ctr Res Inst, San Francisco, CA USA. [Hillier, Teresa A.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. [Ensrud, Kristine E.] Minneapolis Vet Affairs Med Ctr, Dept Med, Minneapolis, MN USA. [Ensrud, Kristine E.] Univ Minnesota, Dept Med, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. RP Spira, AP (reprint author), 624 N Broadway,Hampton House,Rm 794, Baltimore, MD 21205 USA. EM aspira@jhsph.edu FU National Institutes of Health (NIH) [R01 AR35582, R01 AR35583, R01 AR35584, R01 AG026720, R01 AG005407, R01 AG027574, R01 AG027576, R01 AG005394, 2R01-HL075078, 5R01-HL089467]; Alzheimer's Association [IIRG-08-88872]; National Institute on Aging [1K01AG033195, K24AG031155]; National Institute of Mental Health; National Institute of Diabetes and Digestive and Kidney Diseases; Department of Defense; Department of Veterans Affairs FX Supported by National Institutes of Health (NIH) Grants R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG026720, R01 AG005407, R01 AG027574, R01 AG027576, and R01 AG005394, and by and Alzheimer's Association award IIRG-08-88872. Dr. Spira is supported by a Mentored Research Scientist Development Award (1K01AG033195) from the National Institute on Aging. Dr. Yaffe is partially supported by a Midcareer Investigator Award in Patient-Oriented Research (K24AG031155) from the National Institute on Aging. Dr. Punjabi was supported by NIH grants 2R01-HL075078 and 5R01-HL089467. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Aging, or the National Institutes of Health.; Adam Spira is supported by a grant from the National Institute on Aging (NIA); he received honoraria while serving as a clinical editor for the International Journal of Sleep and Wakefulnessu Primary Care, which receives pharmaceutical company support. Kenneth Covinsky is supported by grants from the NIA. Naresh Punjabi is supported by National Institutes of Health (NIH) grants 2R01-HL075078 and 5R01-HL089467, and has received grant support from Resmed for a multicenter clinical trial on the effects of positive airway pressure therapy for sleep apnea in type 2 diabetes mellitus. Katie Stone reports that NIH funding has been obtained for this work. Teresa Hillier received support from the NIA for this work. Kristine Ensrud received grant support from the NIH (and supporting agencies) as listed under Funding Sources. Kristine Yaffe has received grants from the NIA, National Institute of Mental Health, National Institute of Diabetes and Digestive and Kidney Diseases, Department of Defense, Department of Veterans Affairs, the Alzheimer's Association, and an anonymous donor. She has served on data safety monitoring boards for Pfizer and Medivation, and received honoraria from Novartis as an advisory board member. She is a member of the boards of the Beeson Program, the National Institute of Mental Health, and the National Heart, Lung, and Blood Institute. NR 25 TC 18 Z9 19 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUN PY 2012 VL 60 IS 6 BP 1092 EP 1098 DI 10.1111/j.1532-5415.2012.03968.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 957AW UT WOS:000305131900013 PM 22690985 ER PT J AU Williams, BA Goodwin, JS Baillargeon, J Ahalt, C Walter, LC AF Williams, Brie A. Goodwin, James S. Baillargeon, Jacques Ahalt, Cyrus Walter, Louise C. TI Addressing the Aging Crisis in US Criminal Justice Health Care SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE aging; health disparities; prisoner ID PRISON; INMATES; SYSTEM AB The U.S. criminal justice population is aging at a significantly more rapid rate than the overall U.S. population, with the population of older adults in prison having more than tripled since 1990. This increase is at the root of a prison healthcare crisis that is spilling into communities and public healthcare systems because nearly 95% of prisoners are eventually released. The graying prison population is also straining state and local budgets. In prison, older prisoners cost approximately three times as much as younger prisoners to incarcerate, largely because of healthcare costs. In the community, older former prisoners present the least risk of recidivism yet are vulnerable to serious and costly social and medical challenges such as housing instability, poor employability, multiple chronic health conditions, and health-related mortality; however older current and former prisoners are largely ignored in the current geriatrics evidence base. Knowledge about the health, functional, and cognitive status of older prisoners is limited, with even less known about risk factors for long-term poor health outcomes during and after incarceration. This article provides an overview of aging in the criminal justice system. It then describes how geriatric models of care could be adapted to address the mounting older prisoner healthcare crisis and identifies areas where additional research is needed to explore prison-specific models of care for older adults. C1 [Williams, Brie A.; Ahalt, Cyrus; Walter, Louise C.] Univ Calif San Francisco, Div Geriatr, Dept Med, San Francisco, CA 94118 USA. [Williams, Brie A.; Walter, Louise C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Goodwin, James S.] Univ Texas Med Branch, Dept Internal Med, Div Geriatr Med, Galveston, TX USA. [Baillargeon, Jacques] Univ Texas Med Branch, Dept Prevent Med & Community Hlth, Galveston, TX USA. RP Williams, BA (reprint author), Univ Calif San Francisco, Div Geriatr, Dept Med, 3333 Calif St,Suite 380, San Francisco, CA 94118 USA. EM brie.williams@ucsf.edu FU National Institute of Aging [K23AG033102]; Jacob & Valeria Langeloth Foundation; University of California at San Francisco; National Cancer Institute [R01 CA134425] FX Dr. Williams is supported by the National Institute of Aging (K23AG033102), The Jacob & Valeria Langeloth Foundation, and the University of California at San Francisco Program for the Aging Century. Dr. Walter is supported by National Cancer Institute Contract R01 CA134425. Drs. Williams and Walter are employees of the Department of Veterans Affairs (VA). The opinions expressed in this manuscript may not represent those of the VA. NR 30 TC 27 Z9 27 U1 2 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUN PY 2012 VL 60 IS 6 BP 1150 EP 1156 DI 10.1111/j.1532-5415.2012.03962.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 957AW UT WOS:000305131900023 PM 22642489 ER PT J AU Saboo, SS Brodsky, GL Di Salvo, D AF Saboo, Sachin S. Brodsky, Gilbert L. Di Salvo, Donald TI Sonographic-Pathologic Correlation of Epididymal Changes in a Suspected Case of Postvasectomy Pain Syndrome SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Letter ID VASECTOMY C1 [Saboo, Sachin S.; Di Salvo, Donald] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [Saboo, Sachin S.; Brodsky, Gilbert L.; Di Salvo, Donald] Harvard Univ, Sch Med, Boston, MA USA. [Brodsky, Gilbert L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Saboo, SS (reprint author), Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. NR 6 TC 0 Z9 0 U1 0 U2 3 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD JUN PY 2012 VL 31 IS 6 BP 973 EP 974 PG 2 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 953TA UT WOS:000304894900021 PM 22644697 ER PT J AU Tsibris, AMN Hu, ZX Paredes, R Leopold, KE Putcharoen, O Schure, AL Mazur, N Coakley, E Su, ZH Gulick, RM Kuritzkes, DR AF Tsibris, Athe M. N. Hu, Zixin Paredes, Roger Leopold, Kay E. Putcharoen, Opass Schure, Allison L. Mazur, Natalie Coakley, Eoin Su, Zhaohui Gulick, Roy M. Kuritzkes, Daniel R. TI Vicriviroc Resistance Decay and Relative Replicative Fitness in HIV-1 Clinical Isolates under Sequential Drug Selection Pressures SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CCR5 ANTAGONIST; IN-VIVO; ENFUVIRTIDE RESISTANCE; SUSCEPTIBILITY SCORES; MUTATIONS; INHIBITOR; MARAVIROC; THERAPY; GP41 AB We previously described an HIV-1-infected individual who developed resistance to vicriviroc (VCV), an investigational CCR5 antagonist, during 28 weeks of therapy (Tsibris AM et al., J. Virol. 82:8210-8214, 2008). To investigate the decay of VCV resistance mutations, a standard clonal analysis of full-length env (gp160) was performed on plasma HIV-1 samples obtained at week 28 (the time of VCV discontinuation) and at three subsequent time points (weeks 30, 42, and 48). During 132 days, VCV-resistant HIV-1 was replaced by VCV-sensitive viruses whose V3 loop sequences differed from the dominant pretreatment forms. A deep-sequencing analysis showed that the week 48 VCV-sensitive V3 loop form emerged from a preexisting viral variant. Enfuvirtide was added to the antiretroviral regimen at week 30; by week 48, enfuvirtide treatment selected for either the G36D or N43D HR-1 mutation. Growth competition experiments demonstrated that viruses incorporating the dominant week 28 VCV-resistant env were less fit than week 0 viruses in the absence of VCV but more fit than week 48 viruses. This week 48 fitness deficit persisted when G36D was corrected by either site-directed mutagenesis or week 48 gp41 domain swapping. The correction of N43D, in contrast, restored fitness relative to that of week 28, but not week 0, viruses. Virus entry kinetics correlated with observed fitness differences; the slower entry of enfuvirtide-resistant viruses corrected to wild-type rates in the presence of enfuvirtide. These findings suggest that while VCV and enfuvirtide select for resistance mutations in only one env subunit, gp120 and gp41 coevolve to maximize viral fitness under sequential drug selection pressures. C1 [Tsibris, Athe M. N.; Putcharoen, Opass; Kuritzkes, Daniel R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Tsibris, Athe M. N.; Hu, Zixin; Kuritzkes, Daniel R.] Harvard Univ, Sch Med, Boston, MA USA. [Hu, Zixin; Schure, Allison L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Paredes, Roger] Univ Autonoma Barcelona, Fdn IrsiCaixa & Lluita SIDA, Hosp Univ Germans Trias & Pujol, Badalona, Catalonia, Spain. [Leopold, Kay E.; Mazur, Natalie] Harvard Univ, Cambridge, MA 02138 USA. [Putcharoen, Opass; Su, Zhaohui] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Putcharoen, Opass] Chulalongkorn Univ, Div Infect Dis, Dept Med, King Chulalongkorn Mem Hosp, Bangkok, Thailand. [Coakley, Eoin] Monogram Biosci, San Francisco, CA USA. [Gulick, Roy M.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. RP Tsibris, AMN (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM atsibris@partners.org FU CHAIN; European Community [22313]; AIDS Clinical Trials Group; National Institute of Allergy and Infectious Diseases, National Institutes of Health [AI068636, AI069419, AI051966, AI055357]; National Center for Research Resources [RR024996, RR016482]; Schering-Plough Research Institute; [K08 AI081547] FX A.M.N.T. was supported by K08 AI081547. R.P. was supported in part by CHAIN, funded through the European Community's Seventh Framework Programme FP7/2007-2013 under grant agreement no. 22313. This work was also supported in part by the AIDS Clinical Trials Group, which is funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (AI068636 [AIDS Clinical Trials Group], AI069419 [Cornell CTU], AI051966 [to R.M.G.], and AI055357 (to D.R.K.]) and the National Center for Research Resources (RR024996 [Cornell CTSC] and RR016482 [to D.R.K.]). The Schering-Plough Research Institute provided the study drug, funds to support patient screening, and specialized laboratory assays. NR 63 TC 8 Z9 8 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2012 VL 86 IS 12 BP 6416 EP 6426 DI 10.1128/JVI.00286-12 PG 11 WC Virology SC Virology GA 953SS UT WOS:000304894100004 PM 22491471 ER PT J AU Kwon, DS Angin, M Hongo, T Law, KM Johnson, J Porichis, F Hart, MG Pavlik, DF Tighe, DP Kavanagh, DG Streeck, H Addo, MM Kaufmann, DE AF Kwon, Douglas S. Angin, Mathieu Hongo, Tomoyuki Law, Kenneth M. Johnson, Jessica Porichis, Filippos Hart, Meghan G. Pavlik, David F. Tighe, Daniel P. Kavanagh, Daniel G. Streeck, Hendrik Addo, Marylyn M. Kaufmann, Daniel E. TI CD4(+) CD25(+) Regulatory T Cells Impair HIV-1-Specific CD4 T Cell Responses by Upregulating Interleukin-10 Production in Monocytes SO JOURNAL OF VIROLOGY LA English DT Article ID CHRONIC VIRAL-INFECTION; HIV-INFECTION; DISEASE PROGRESSION; PROMOTER POLYMORPHISMS; IL-10 PRODUCTION; MESSENGER-RNA; CUTTING EDGE; VIRUS; PATHOGENESIS; MACROPHAGES AB T cell dysfunction in the presence of ongoing antigen exposure is a cardinal feature of chronic viral infections with persistent high viremia, including HIV-1. Although interleukin-10 (IL-10) has been implicated as an important mediator of this T cell dysfunction, the regulation of IL-10 production in chronic HIV-1 infection remains poorly understood. We demonstrated that IL-10 is elevated in the plasma of individuals with chronic HIV-1 infection and that blockade of IL-10 signaling results in a restoration of HIV-1-specific CD4 T cell proliferation, gamma interferon (IFN-gamma) secretion, and, to a lesser extent, IL-2 production. Whereas IL-10 blockade leads to restoration of IFN-gamma secretion by HIV-1-specific CD4 T cells in all categories of subjects investigated, significant enhancement of IL-2 production and improved proliferation of CD4 T helper cells are restricted to viremic individuals. In peripheral blood mononuclear cells (PBMCs), this IL-10 is produced primarily by CD14(+) monocytes, but its production is tightly controlled by regulatory T cells (Tregs), which produce little IL-10 directly. When Tregs are depleted from PBMCs of viremic individuals, the effect of the IL-10 signaling blockade is abolished and IL-10 production by monocytes decreases, while the production of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), increases. The regulation of IL-10 by Tregs appears to be mediated primarily by contact or paracrine-dependent mechanisms which involve IL-27. This work describes a novel mechanism by which regulatory T cells control IL-10 production and contribute to dysfunctional HIV-1-specific CD4 T cell help in chronic HIV-1 infection and provides a unique mechanistic insight into the role of regulatory T cells in immune exhaustion. C1 [Kwon, Douglas S.; Angin, Mathieu; Hongo, Tomoyuki; Law, Kenneth M.; Johnson, Jessica; Porichis, Filippos; Hart, Meghan G.; Pavlik, David F.; Tighe, Daniel P.; Kavanagh, Daniel G.; Streeck, Hendrik; Addo, Marylyn M.; Kaufmann, Daniel E.] Ragon Inst MGH MIT & Harvard, Charlestown, MA USA. [Kwon, Douglas S.; Addo, Marylyn M.; Kaufmann, Daniel E.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Kaufmann, DE (reprint author), Ragon Inst MGH MIT & Harvard, Charlestown, MA USA. EM dkaufmann@partners.org OI Angin, Mathieu/0000-0002-6867-4680 FU National Institutes of Health [1K08 AI084546-01, RO1 HL092565, P01 AI-080192]; Harvard University Center for AIDS Research [NIH P30 AI060354] FX This work was supported by the National Institutes of Health (grant 1K08 AI084546-01 to D. Kwon, RO1 HL092565 to D. Kaufmann, and P01 AI-080192 to D. Kaufmann and D. Kavanagh) and the Harvard University Center for AIDS Research (NIH P30 AI060354). The authors have no conflicting financial interests. NR 46 TC 15 Z9 15 U1 3 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2012 VL 86 IS 12 BP 6586 EP 6594 DI 10.1128/JVI.06251-11 PG 9 WC Virology SC Virology GA 953SS UT WOS:000304894100020 PM 22496237 ER PT J AU Ng, AKL Lam, MKH Zhang, HM Liu, JH Au, SWN Chan, PKS Wang, JH Shaw, PC AF Ng, Andy Ka-Leung Lam, Mandy Ka-Han Zhang, Hongmin Liu, Jinhuan Au, Shannon Wing-Ngor Chan, Paul Kay-Sheung Wang, Jiahuai Shaw, Pang-Chui TI Structural Basis for RNA Binding and Homo-Oligomer Formation by Influenza B Virus Nucleoprotein SO JOURNAL OF VIROLOGY LA English DT Article ID NUCLEAR-LOCALIZATION SIGNAL; CRYSTAL-STRUCTURE; H5N1 NUCLEOPROTEIN; AMINO-ACIDS; COMPLEX; REPLICATION; POLYMERASE; MOLECULES; REVEALS; PROTEIN AB Influenza virus nucleoprotein (NP) is the major component of the viral ribonucleoprotein complex, which is crucial for the transcription and replication of the viral genome. We have determined the crystal structure of influenza B virus NP to a resolution of 3.2 angstrom. Influenza B NP contains a head, a body domain, and a tail loop. The electropositive groove between the head and body domains of influenza B NP is crucial for RNA binding. This groove also contains an extended flexible charged loop (amino acids [aa] 125 to 149), and two lysine clusters at the first half of this loop were shown to be crucial for binding RNA. Influenza B virus NP forms a crystallographic homotetramer by inserting the tail loop into the body domain of the neighboring NP molecule. A deeply buried salt bridge between R472 and E395 and a hydrophobic cluster at F468 are the major driving forces for the insertion. The analysis of the influenza B virus NP structure and function and comparisons with influenza A virus NP provide insights into the mechanisms of action and underpin efforts to design inhibitors for this class of proteins. C1 [Ng, Andy Ka-Leung; Lam, Mandy Ka-Han; Au, Shannon Wing-Ngor; Shaw, Pang-Chui] Chinese Univ Hong Kong, Sch Life Sci, Ctr Prot Sci & Crystallog, Shatin, Hong Kong, Peoples R China. [Zhang, Hongmin; Liu, Jinhuan; Wang, Jiahuai] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Dept Pediat, Boston, MA 02115 USA. [Zhang, Hongmin; Liu, Jinhuan; Wang, Jiahuai] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Chan, Paul Kay-Sheung] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Microbiol, Shatin, Hong Kong, Peoples R China. RP Shaw, PC (reprint author), Chinese Univ Hong Kong, Sch Life Sci, Ctr Prot Sci & Crystallog, Shatin, Hong Kong, Peoples R China. EM jwang@red.dfci.harvard.edu; pcshaw@cuhk.edu.hk RI Chan, Paul/J-9360-2013 FU Research Grants Council of Hong Kong [CUHK473810]; Claudia Adams Barr Program in Cancer Research; University Grants Council of Hong Kong [SEG CUHK08] FX This research was supported by a General Research Fund grant (CUHK473810) from the Research Grants Council of Hong Kong (P.-C.S.) and the Claudia Adams Barr Program in Cancer Research (J.W.). Equipment used was obtained through a Special Equipment Grant (SEG CUHK08) from the University Grants Council of Hong Kong. The diffraction data were collected at the Shanghai Synchrotron Radiation Facility (Shanghai, China). NR 35 TC 33 Z9 34 U1 1 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2012 VL 86 IS 12 BP 6758 EP 6767 DI 10.1128/JVI.00073-12 PG 10 WC Virology SC Virology GA 953SS UT WOS:000304894100035 PM 22496219 ER PT J AU Brockman, MA Chopera, DR Olvera, A Brumme, CJ Sela, J Markle, TJ Martin, E Carlson, JM Le, AQ McGovern, R Cheung, PK Kelleher, AD Jessen, H Markowitz, M Rosenberg, E Frahm, N Sanchez, J Mallal, S John, M Harrigan, PR Heckerman, D Brander, C Walker, BD Brumme, ZL AF Brockman, Mark A. Chopera, Denis R. Olvera, Alex Brumme, Chanson J. Sela, Jennifer Markle, Tristan J. Martin, Eric Carlson, Jonathan M. Le, Anh Q. McGovern, Rachel Cheung, Peter K. Kelleher, Anthony D. Jessen, Heiko Markowitz, Martin Rosenberg, Eric Frahm, Nicole Sanchez, Jorge Mallal, Simon John, Mina Harrigan, P. Richard Heckerman, David Brander, Christian Walker, Bruce D. Brumme, Zabrina L. TI Uncommon Pathways of Immune Escape Attenuate HIV-1 Integrase Replication Capacity SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; VIRAL LOAD; LYMPHOCYTE EPITOPES; ELITE CONTROLLERS; PRIMARY INFECTION; GAG-PROTEASE; CTL EPITOPES; AMINO-ACID; TYPE-1 AB An attenuation of the HIV-1 replication capacity (RC) has been observed for immune-mediated escape mutations in Gag restricted by protective HLA alleles. However, the extent to which escape mutations affect other viral proteins during natural infection is not well understood. We generated recombinant viruses encoding plasma HIV-1 RNA integrase sequences from antiretroviral-naive individuals with early (n = 88) and chronic (n = 304) infections and measured the in vitro RC of each. In contrast to data from previous studies of Gag, we observed little evidence that host HLA allele expression was associated with integrase RC. A modest negative correlation was observed between the number of HLA-B-associated integrase polymorphisms and RC in chronic infection (R = -0.2; P = 0.003); however, this effect was not driven by mutations restricted by protective HLA alleles. Notably, the integrase variants S119R, G163E, and I220L, which represent uncommon polymorphisms associated with HLA-C*05, -A*33, and -B*52, respectively, correlated with lower RC (all q < 0.2). We identified a novel C*05-restricted epitope (HTDNGSNF(114-121)) that likely contributes to the selection of the S119R variant, the polymorphism most significantly associated with lower RC in patient sequences. An NL4-3 mutant encoding the S119R polymorphism displayed a similar to 35%-reduced function that was rescued by a single compensatory mutation of A91E. Together, these data indicate that substantial HLA-driven attenuation of integrase is not a general phenomenon during HIV-1 adaptation to host immunity. However, uncommon polymorphisms selected by HLA alleles that are not conventionally regarded to be protective may be associated with impaired protein function. Vulnerable epitopes in integrase might therefore be considered for future vaccine strategies. C1 [Brockman, Mark A.; Chopera, Denis R.; Markle, Tristan J.; Martin, Eric; Le, Anh Q.; Brumme, Zabrina L.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. [Brockman, Mark A.; Brumme, Chanson J.; McGovern, Rachel; Cheung, Peter K.; Harrigan, P. Richard; Brumme, Zabrina L.] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Olvera, Alex; Brander, Christian] AIDS Res Inst IrsiCaixa, Badalona, Spain. [Brumme, Chanson J.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Sela, Jennifer; Walker, Bruce D.] Ragon Inst MGH MIT & Harvard, Boston, MA USA. [Carlson, Jonathan M.; Heckerman, David] Microsoft Res, Los Angeles, CA USA. [Kelleher, Anthony D.] Univ New S Wales, Kirby Inst, Sydney, NSW, Australia. [Jessen, Heiko] Jessen Praxis, Berlin, Germany. [Markowitz, Martin] Aaron Diamond AIDS Res Ctr, New York, NY USA. [Rosenberg, Eric] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Frahm, Nicole] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Sanchez, Jorge] Asociac Civil IMPACTA Salud & Educ, Lima, Peru. [Mallal, Simon; John, Mina] Murdoch Univ, Perth, WA, Australia. [Brander, Christian] ICREA, Barcelona, Spain. RP Brockman, MA (reprint author), Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. EM mark_brockman@sfu.ca OI Brander, Christian/0000-0002-0548-5778; Brumme, Chanson/0000-0003-2722-5288; Brockman, Mark/0000-0001-6432-1426 FU Canadian Institutes for Health Research (CIHR) [MOP-93536]; Microsoft Research; National Institutes of Health (NIH) [RO1AI030914]; National Institute on Drug Abuse, NIH [RO1DA011591, RO1DA021525]; CIHR; Sanofi-Aventis; Canadian Association of HIV Research; Abbott Virology FX This work was supported by an operating grant from the Canadian Institutes for Health Research (CIHR) (MOP-93536), by a Jim Gray Seed grant from Microsoft Research (to M.A.B. and Z.L.B.), and by the National Institutes of Health (NIH) (grant RO1AI030914 to B.D.W.). The VIDUS and ACCESS projects were funded by the National Institute on Drug Abuse, NIH (grants RO1DA011591 and RO1DA021525). D.R.C. is a recipient of the Canada-HOPE fellowship from CIHR and Sanofi-Aventis. C.J.B. is supported by a Vanier Canada graduate scholarship from the CIHR. E.M. is supported by a master's scholarship from the Canadian Association of HIV Research and Abbott Virology. P.R.H. is the CIHR-GSK research chair in HIV/AIDS. M.A.B. holds a Canada research chair, tier 2, in viral pathogenesis and immunity. Z.L.B. is the recipient of a CIHR new investigator award. NR 67 TC 17 Z9 17 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2012 VL 86 IS 12 BP 6913 EP 6923 DI 10.1128/JVI.07133-11 PG 11 WC Virology SC Virology GA 953SS UT WOS:000304894100049 PM 22496233 ER PT J AU Ndhlovu, ZM Proudfoot, J Cesa, K Alvino, DM McMullen, A Vine, S Stampouloglou, E Piechocka-Trocha, A Walker, BD Pereyra, F AF Ndhlovu, Zaza M. Proudfoot, Jacqueline Cesa, Kevin Alvino, Donna Marie McMullen, Ashley Vine, Seanna Stampouloglou, Eleni Piechocka-Trocha, Alicja Walker, Bruce D. Pereyra, Florencia TI Elite Controllers with Low to Absent Effector CD8(+) T Cell Responses Maintain Highly Functional, Broadly Directed Central Memory Responses SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; LONG-TERM NONPROGRESSORS; DISEASE PROGRESSION; HIV CONTROLLERS; AIDS VACCINE; EX-VIVO; REPLICATION; LYMPHOCYTES; VIREMIA; EXPRESSION AB Analyses of the breadth and specificity of virus-specific CD8(+) T cell responses associated with control of HIV have largely relied on measurement of cytokine secretion by effector T cells. These have resulted in the identification of HIV elite controllers with low or absent responses in which non-T-cell mechanisms of control have been suggested. However, successful control of HIV infection may be associated with central memory T cells, which have not been consistently examined in these individuals. Gag-specific T cells were characterized using a peptide-based cultured enzyme-linked immunosorbent spot assay (ELISpot). Peripheral blood mononuclear cells from HIV elite controllers (n = 10), progressors (n = 12), and antiretroviral-treated individuals (n = 9) were cultured with overlapping peptides for 12 days. Specificity was assessed by tetramer staining, functional features of expanded cells were assessed by cytokine secretion, and virus inhibition and phenotypic characteristics were assessed by cell sorting and coculture assays. After peptide stimulation, elite controllers showed a greater number of previously undetectable (new) responses compared to progressors (P = 0.0008). These responses were highly polyfunctional, with 64.5% of responses having 3 to 5 functions. Expandable epitope-specific CD8(+) T cells from elite controllers had strong virus inhibitory capacity and predominantly displayed a central memory phenotype. These data indicate that elite controllers with minimal T cell responses harbor a highly functional, broadly directed central memory T cell population that is capable of suppressing HIV in vitro. Comprehensive examination of this cell population could provide insight into the immune responses associated with successful containment of viremia. C1 [Ndhlovu, Zaza M.; Proudfoot, Jacqueline; Cesa, Kevin; Alvino, Donna Marie; McMullen, Ashley; Vine, Seanna; Stampouloglou, Eleni; Piechocka-Trocha, Alicja; Walker, Bruce D.; Pereyra, Florencia] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Pereyra, Florencia] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. RP Pereyra, F (reprint author), Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA USA. EM fpereyra@partners.org FU Collaboration for AIDS Vaccine Discovery of the Bill and Melinda Gates Foundation; Howard Hughes Medical Institute; Mark and Lisa Schwartz Foundation; Bill and Melinda Gates Foundation; Harvard University Center for AIDS Research FX This work was supported by the Collaboration for AIDS Vaccine Discovery of the Bill and Melinda Gates Foundation (F.P. and B.D.W.) and the Howard Hughes Medical Institute (B.D.W. and Z.M.N.).; Patient recruitment was conducted by the International HIV Controllers Study (www.hivcontrollers.org) and supported by the Mark and Lisa Schwartz Foundation, the Bill and Melinda Gates Foundation, and the Harvard University Center for AIDS Research. NR 49 TC 47 Z9 49 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2012 VL 86 IS 12 BP 6959 EP 6969 DI 10.1128/JVI.00531-12 PG 11 WC Virology SC Virology GA 953SS UT WOS:000304894100053 PM 22514340 ER PT J AU Bar-Natan, M Nelson, EA Walker, SR Kuang, Y Distel, RJ Frank, DA AF Bar-Natan, M. Nelson, E. A. Walker, S. R. Kuang, Y. Distel, R. J. Frank, D. A. TI Dual inhibition of Jak2 and STAT5 enhances killing of myeloproliferative neoplasia cells SO LEUKEMIA LA English DT Letter ID MYELOFIBROSIS; EXPRESSION; DISORDERS; JAK2V617F C1 [Bar-Natan, M.; Nelson, E. A.; Walker, S. R.; Frank, D. A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bar-Natan, M.; Frank, D. A.] Harvard Univ, Sch Med, Boston, MA USA. [Bar-Natan, M.; Frank, D. A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Kuang, Y.; Distel, R. J.] Dana Farber Canc Inst, Ctr Clin & Translat Res, Translat Res Lab, Boston, MA 02115 USA. RP Bar-Natan, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM david_frank@dfci.harvard.edu NR 14 TC 12 Z9 12 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUN PY 2012 VL 26 IS 6 BP 1407 EP 1410 DI 10.1038/leu.2011.338 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 956HP UT WOS:000305081000031 PM 22134716 ER PT J AU Tam, JM Mansour, MK Vyas, JM AF Tam, J. M. Mansour, M. K. Vyas, J. M. TI Dectin-1 signaling recruits elements of autophagic machinery to Candida albicans-containing phagosomes SO MYCOSES LA English DT Meeting Abstract C1 [Tam, J. M.; Mansour, M. K.; Vyas, J. M.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Vyas, J. M.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0933-7407 J9 MYCOSES JI Mycoses PD JUN PY 2012 VL 55 SU 4 SI SI BP 24 EP 24 PG 1 WC Dermatology; Mycology SC Dermatology; Mycology GA 956DK UT WOS:000305069800080 ER PT J AU Quintin, J Saeed, S Martens, JHA Giamarellos-Bourboulis, EJ Ifrim, DC Logie, C Kullberg, BJ Joosten, LAB Xavier, RJ Stunnenberg, HG van der Meer, JWM Netea, MG AF Quintin, J. Saeed, S. Martens, J. H. A. Giamarellos-Bourboulis, E. J. Ifrim, D. C. Logie, C. Kullberg, B-J. Joosten, L. A. B. Xavier, R. J. Stunnenberg, H. G. van der Meer, J. W. M. Netea, M. G. TI Candida albicans induces monocyte training via epigenetic reprogramming through a dectin-1-dependent pathway SO MYCOSES LA English DT Meeting Abstract C1 [Quintin, J.; Ifrim, D. C.; Kullberg, B-J.; Joosten, L. A. B.; van der Meer, J. W. M.; Netea, M. G.] Radboud Univ Nijmegen, Med Ctr, Dept Expt Internal Med, NL-6525 ED Nijmegen, Netherlands. [Quintin, J.; Ifrim, D. C.; Kullberg, B-J.; Joosten, L. A. B.; van der Meer, J. W. M.; Netea, M. G.] Radboud Univ Nijmegen, Med Ctr, Nijmegen Inst Infect Inflammat & Immun, NL-6525 ED Nijmegen, Netherlands. [Saeed, S.; Martens, J. H. A.; Logie, C.; Stunnenberg, H. G.] Nijmegen Ctr Mol Life Sci, Dept Mol Biol, Nijmegen, Netherlands. [Giamarellos-Bourboulis, E. J.] Univ Athens, Dept Internal Med 44, Athens, Greece. [Xavier, R. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Xavier, R. J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Xavier, R. J.] Broad Inst MIT, Cambridge, MA USA. [Xavier, R. J.] Harvard Univ, Cambridge, MA 02138 USA. RI Martens, Joost/D-4966-2012; Kullberg, Bart Jan/C-8520-2013; Stunnenberg, Hendrik/D-6875-2012; Joosten, Leo/H-3138-2015; Netea, Mihai/N-5155-2014; van der Meer, Jos/C-8521-2013 OI van der Meer, Jos/0000-0001-5120-3690 NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0933-7407 J9 MYCOSES JI Mycoses PD JUN PY 2012 VL 55 SU 4 SI SI BP 58 EP 58 PG 1 WC Dermatology; Mycology SC Dermatology; Mycology GA 956DK UT WOS:000305069800185 ER PT J AU Mansour, M Tam, J Khan, N Puranam, S Vyas, J AF Mansour, M. Tam, J. Khan, N. Puranam, S. Vyas, J. TI Dectin-1 controls maturation of fungal phagosomes SO MYCOSES LA English DT Meeting Abstract C1 [Mansour, M.; Tam, J.; Khan, N.; Puranam, S.; Vyas, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 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 0933-7407 J9 MYCOSES JI Mycoses PD JUN PY 2012 VL 55 SU 4 SI SI BP 61 EP 61 PG 1 WC Dermatology; Mycology SC Dermatology; Mycology GA 956DK UT WOS:000305069800195 ER PT J AU Kirkpatrick, WR Wiederhold, NP Najvar, LK Bocanegra, RA Patterson, TF AF Kirkpatrick, W. R. Wiederhold, N. P. Najvar, L. K. Bocanegra, R. A. Patterson, T. F. TI Comparison of disseminated and pulmonary models of invasive Aspergillosis for the detection of surrogate markers of infection SO MYCOSES LA English DT Meeting Abstract C1 [Kirkpatrick, W. R.; Wiederhold, N. P.; Najvar, L. K.; Bocanegra, R. A.; Patterson, T. F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Kirkpatrick, W. R.; Najvar, L. K.; Bocanegra, R. A.; Patterson, T. F.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Wiederhold, N. P.] Univ Texas Austin, Austin, TX 78712 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0933-7407 J9 MYCOSES JI Mycoses PD JUN PY 2012 VL 55 SU 4 SI SI BP 283 EP 283 PG 1 WC Dermatology; Mycology SC Dermatology; Mycology GA 956DK UT WOS:000305069801228 ER PT J AU Romero, JM AF Romero, Javier M. TI STROKE Is spot sign the answer for intracerebral haemorrhage? SO NATURE REVIEWS NEUROLOGY LA English DT Editorial Material ID PREDICTS HEMATOMA EXPANSION; CONTRAST EXTRAVASATION; IDENTIFIES PATIENTS; HIGHEST RISK; SCORE AB Intracerebral haemorrhage continues to carry a poor prognosis despite several recent therapeutic clinical trials. A study has demonstrated that CT angiography of the brain on admission can predict haematoma expansion and clinical outcome. This CT 'spot sign' could, therefore, help physicians to select patients who are likely to benefit from treatment. Romero, J. M. Nat. Rev. Neurol. 8, 300-301 (2012); published online 22 May 2012; doi:10.1038/nrneurol.2012.93 C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Romero, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,Off Gray 279, Boston, MA 02114 USA. EM jmromero@partners.org NR 10 TC 3 Z9 5 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4758 J9 NAT REV NEUROL JI Nat. Rev. Neurol. PD JUN PY 2012 VL 8 IS 6 BP 300 EP 301 DI 10.1038/nrneurol.2012.93 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 956JI UT WOS:000305085500002 PM 22614854 ER PT J AU Johansen, KL Finkelstein, FO Revicki, DA Evans, C Wan, SW Gitlin, M Agodoa, IL AF Johansen, Kirsten L. Finkelstein, Fredric O. Revicki, Dennis A. Evans, Christopher Wan, Shaowei Gitlin, Matthew Agodoa, Irene L. TI Systematic review of the impact of erythropoiesis-stimulating agents on fatigue in dialysis patients SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Review DE anemia; dialysis; ESA; fatigue; hemoglobin ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; QUALITY-OF-LIFE; CHRONIC KIDNEY-DISEASE; HEMODIALYSIS-PATIENTS; EPOETIN-ALPHA; RECEIVING HEMODIALYSIS; DARBEPOETIN ALPHA; HEALTH-STATUS; ANEMIA; TRIAL AB Background. One of the cardinal symptoms of anemia in chronic kidney disease (CKD) patients is fatigue. Recently, results from Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT) raised questions about the role of erythropoiesis-stimulating agents (ESAs) in improving fatigue and the appropriate hemoglobin (Hb) target in anemic patients with CKD. These discussions should be considered with all available evidence to determine the level of benefits and risks associated with ESA therapy on fatigue among both early-stage CKD patients and end-stage renal disease patients on dialysis. Methods. The study was a systematic review of the literature on fatigue in adults on maintenance dialysis therapy. The requirement for inclusion in the review was the measurement of fatigue before and after ESA treatment. Outcomes that were assessed were fatigue as measured by the Kidney Disease Questionnaire, the 36-item Short-Form general health survey, the Nottingham Health Profile, the Profile of Mood States or the Functional Assessment of Chronic Illness Therapy-Fatigue scale. Several different measures of fatigue were used in the studies. Results. Fifteen articles met the criteria for inclusion, including 10 distinct studies and one extension study. There was one placebo-controlled randomized clinical trial (RCT) and one extension, five single-arm, three high versus low, one intravenous versus subcutaneous and one switch from epoetin alfa to darbepoetin alfa. The only placebo-controlled RCT found a 22-26% improvement in fatigue. Single-arm cohort studies demonstrated a reduction in fatigue after a substantial increase in Hb. Studies with a baseline Hb <10 g/dL and partial correction to a minimum Hb >= 10 g/dL showed an average improvement in fatigue of 34.6%. Studies with a baseline Hb >= 11 g/dL and full correction to a minimum Hb >= 12 g/dL showed an average improvement in fatigue of 5.5%, while studies with no change in Hb (either placebo or control group) showed a decline of 0.7% in fatigue outcomes. Conclusion. Partial correction of anemia with ESA results in improvement of fatigue among patients on dialysis, most strikingly in those patients with baseline Hb levels <10 g/dL. C1 [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA USA. [Finkelstein, Fredric O.] Yale Univ, Hosp St Raphael, New Haven, CT USA. [Revicki, Dennis A.] United BioSource Corp, Bethesda, MD USA. [Evans, Christopher] Mapi Values, Boston, MA USA. [Wan, Shaowei; Gitlin, Matthew; Agodoa, Irene L.] Amgen Inc, Thousand Oaks, CA 91320 USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA USA. EM Kirsten.Johansen@ucsf.edu FU Amgen FX K.L.J. and F.O.F. have received research support from Amgen; D.A.R. and C.E. have received consulting fees and research support from Amgen; S.W., M.G. and I.L.A. are employees of Amgen. This study was funded by Amgen and conceived by employees of Amgen. NR 34 TC 16 Z9 16 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 EI 1460-2385 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD JUN PY 2012 VL 27 IS 6 BP 2418 EP 2425 DI 10.1093/ndt/gfr697 PG 8 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 952YK UT WOS:000304832100045 PM 22187314 ER PT J AU Race, E Verfaellie, M AF Race, Elizabeth Verfaellie, Mieke TI Remote Memory Function and Dysfunction in Korsakoff's Syndrome SO NEUROPSYCHOLOGY REVIEW LA English DT Review DE Korsakoff's syndrome; Retrograde amnesia; Remote memory; Autobiographical; Semantic ID POSITRON-EMISSION-TOMOGRAPHY; AUTOBIOGRAPHICAL MEMORY; RETROGRADE-AMNESIA; SEMANTIC MEMORY; ANTEROGRADE AMNESIA; FALSE MEMORIES; ALZHEIMER-TYPE; CONFABULATION; IMPAIRMENT; RETRIEVAL AB Korsakoff's syndrome (KS) is a pervasive disorder of memory characterized by both anterograde and retrograde amnesia. Although retrograde memory impairment in KS has been less frequently studied, the status of remote memory in KS has been tested across a number of different tasks that measure knowledge of public information (e.g., famous faces/news events), general semantic information (e.g., vocabulary words), personal semantic information (e.g., facts about oneself), and autobiographical events (e.g., events from one's personal past). In each of these domains, Korsakoff patients demonstrate remote memory impairments that can extend back many years or decades. In addition, a majority of studies report that the extensive remote memory impairment in KS is temporally graded, with relative preservation of memories from childhood and early adulthood. The current paper reviews published experimental studies of remote memory in KS, with particular attention paid to (a) the selectivity of the deficit with respect to the age of the memory and (b) the relationship of memory impairment to underlying neuropathology. We discuss the significance of the reported pattern and extent of remote memory impairment with respect to theories about the nature of the underlying cognitive deficits in KS. C1 [Race, Elizabeth; Verfaellie, Mieke] Boston VA Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02130 USA. [Race, Elizabeth; Verfaellie, Mieke] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Verfaellie, M (reprint author), Boston VA Healthcare Syst, Memory Disorders Res Ctr, 150 S Huntington Ave,151-A, Boston, MA 02130 USA. EM verf@bu.edu OI Verfaellie, Mieke/0000-0001-5535-4584 FU VA Clinical Science Research and Development Service; NIH-NINDS National Research Service [F32NS073212] FX This work was supported by VA Clinical Science Research and Development Service and NIH-NINDS National Research Service award F32NS073212. NR 54 TC 6 Z9 6 U1 0 U2 25 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1040-7308 J9 NEUROPSYCHOL REV JI Neuropsychol. Rev. PD JUN PY 2012 VL 22 IS 2 BP 105 EP 116 DI 10.1007/s11065-012-9197-y PG 12 WC Psychology, Clinical; Neurosciences SC Psychology; Neurosciences & Neurology GA 958OI UT WOS:000305248800005 PM 22528863 ER PT J AU Hayes, SM Fortier, CB Levine, A Milberg, WP McGlinchey, R AF Hayes, Scott M. Fortier, Catherine B. Levine, Andrea Milberg, William P. McGlinchey, Regina TI Implicit Memory in Korsakoff's Syndrome: A Review of Procedural Learning and Priming Studies SO NEUROPSYCHOLOGY REVIEW LA English DT Review DE Procedural memory; Implicit memory; Priming; Amnesia; Korsakoff's syndrome; Wernicke's encephalopathy ID AMNESIC PATIENTS; UNCONSCIOUS INFLUENCES; ABSTINENT ALCOHOLICS; LONGITUDINAL CHANGES; HUNTINGTONS-DISEASE; VERBAL RECOGNITION; CORPUS-CALLOSUM; SKILL; DISSOCIATION; PERFORMANCE AB Korsakoff's syndrome (KS) is characterized by dense anterograde amnesia resulting from damage to the diencephalon region, typically resulting from chronic alcohol abuse and thiamine deficiency. This review assesses the integrity of the implicit memory system in KS, focusing on studies of procedural learning and priming. KS patients are impaired on several measures of procedural memory, most likely due to impairment in cognitive functions associated with alcohol-related neural damage outside of the diencephalon. The pattern of performance on tasks of implicit priming suggests reliance on a residual, non-flexible memory operating more or less in an automatic fashion. Our review concludes that whether measures of implicit memory reveal intact or impaired performance in individuals with KS depends heavily on specific task parameters and demands, including timing between stimuli, the specific nature of the stimuli used in a task, and the integrity of supportive cognitive functions necessary for performance. C1 [Hayes, Scott M.] VA Boston Healthcare Syst, Memory Disorders Res Ctr 151A, Boston, MA 02130 USA. [Hayes, Scott M.] VA Boston Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02130 USA. [Hayes, Scott M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Hayes, Scott M.] Neuroimaging Vet Res Ctr, Boston, MA USA. [Fortier, Catherine B.; Levine, Andrea; Milberg, William P.; McGlinchey, Regina] VA Boston Healthcare Syst, Geriatr Res & Educ Clin Ctr, Boston, MA 02130 USA. [Fortier, Catherine B.; Milberg, William P.; McGlinchey, Regina] VA Boston Healthcare Syst, Translat Res Ctr Traumat Brain Injury & Stress Di, Boston, MA 02130 USA. [Fortier, Catherine B.; Milberg, William P.; McGlinchey, Regina] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Hayes, SM (reprint author), VA Boston Healthcare Syst, Memory Disorders Res Ctr 151A, 150 S Huntington Ave, Boston, MA 02130 USA. EM smhayes@bu.edu FU Department of Veterans Affairs Rehabilitation Research & Development Service; VA Clinical Science Research & Development Service; VA RR&D TBI Center of Excellence: Translational Research Center for TBI and Stress Disorders (TRACTS) [B6796-C]; NIH NIA [K01AG024898] FX We would like to thank Kathleen Moriarty for assistance with preparation of the Tables. We would also like to acknowledge Laird S. Cermak, whose scope of work reviewed in the current paper served as a reminder of his impressive contributions to memory research. This work was supported by the Department of Veterans Affairs Rehabilitation Research & Development Service Career Development Award to Scott Hayes; VA Clinical Science Research & Development Service Merit Review award to Regina McGlinchey; VA RR&D TBI Center of Excellence: Translational Research Center for TBI and Stress Disorders (TRACTS) (B6796-C) to Regina McGlinchey and William Milberg; and NIH NIA K01AG024898 to Catherine Fortier. NR 83 TC 9 Z9 9 U1 1 U2 38 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1040-7308 J9 NEUROPSYCHOL REV JI Neuropsychol. Rev. PD JUN PY 2012 VL 22 IS 2 BP 132 EP 153 DI 10.1007/s11065-012-9204-3 PG 22 WC Psychology, Clinical; Neurosciences SC Psychology; Neurosciences & Neurology GA 958OI UT WOS:000305248800007 PM 22592661 ER PT J AU Castro, B Walcott, BP Redjal, N Coumans, JV Nahed, BV AF Castro, Brandyn Walcott, Brian P. Redjal, Navid Coumans, Jean-Valery Nahed, Brian V. TI Cerebrospinal fluid fistula prevention and treatment following frontal sinus fractures: a review of initial management and outcomes SO NEUROSURGICAL FOCUS LA English DT Review DE trauma; cranialization; frontal sinus; cerebrospinal fluid; endoscopic; obliteration; outflow ID DUAL-ENERGY CT; SURGICAL-MANAGEMENT; BASE FRACTURES; EXPERIENCE; OBLITERATION; RHINORRHEA; BONE; RECONSTRUCTION; COMPLICATIONS; ANGIOGRAPHY AB Frontal sinus fractures are heterogeneous, and management of these fractures is often modified based on injury pattern and institutional experience. The optimal initial treatment of frontal sinus fractures is controversial. Treatment strategies are aimed at correcting cosmetic deformity, as well as at preventing delayed complications, including CSF fistulas, mucocele formation, and infection. Existing treatment options include observation, reconstruction, obliteration, cranialization, or a combination thereof. Modalities for treatment encompass both open surgical approaches and endoscopic techniques. In the absence of Class I data, the authors review the existing literature related to treatment strategies of frontal sinus fractures, particularly as they relate to CSF fistulas, to provide recommendations based on the best available evidence. (http://thejns.org/doi/abs/10.3171/2012.3.FOCUS1266) C1 [Castro, Brandyn; Walcott, Brian P.; Redjal, Navid; Coumans, Jean-Valery; Nahed, Brian V.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Castro, Brandyn; Walcott, Brian P.; Redjal, Navid; Coumans, Jean-Valery; Nahed, Brian V.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Walcott, Brian P.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Castro, Brandyn] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White Bldg,Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu NR 32 TC 4 Z9 4 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1092-0684 J9 NEUROSURG FOCUS JI Neurosurg. Focus PD JUN PY 2012 VL 32 IS 6 AR E1 DI 10.3171/2012.3.FOCUS1266 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 954DQ UT WOS:000304927100003 PM 22655690 ER PT J AU Papadimitriou, E Vasilaki, E Vorvis, C Iliopoulos, D Moustakas, A Kardassis, D Stournaras, C AF Papadimitriou, E. Vasilaki, E. Vorvis, C. Iliopoulos, D. Moustakas, A. Kardassis, D. Stournaras, C. TI Differential regulation of the two RhoA-specific GEF isoforms Net1/Net1A by TGF-beta and miR-24: role in epithelial-to-mesenchymal transition SO ONCOGENE LA English DT Article DE TGF-beta; Net1A; RhoA; EMT; miR-24 ID GROWTH-FACTOR-BETA; EXCHANGE FACTOR NET1; SMAD PROTEINS; MEDIATED DEGRADATION; SIGNAL-TRANSDUCTION; ADHERENS JUNCTIONS; TUMOR-SUPPRESSOR; TARGETING RHOA; FAMILY; CANCER AB In the present study we analyzed the regulation of the two isoforms of the RhoA-specific guanine nucleotide exchange factor Net1 by transforming growth factor-beta (TGF-beta) in keratinocytes. We report that short-term TGF-beta treatment selectively induced Net1 isoform2 (Net1A) but not Net1 isoform1. This led to upregulation of cytoplasmic Net1A protein levels that were necessary for TGF-beta-mediated RhoA activation. Smad signaling and the MAPK/ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway were involved in Net1A upregulation by TGF-beta. Interestingly, long-term TGF-beta treatment resulted in Net1 mRNA downregulation and Net1A protein degradation by the proteasome. Furthermore, we identified the microRNA miR-24 as a novel post-transcriptional regulator of Net1A expression. Silencing of Net1A resulted in disruption of E-cadherin-and zonula occludens-1 (ZO-1)-mediated junctions, as well as expression of the transcriptional repressor of E-cadherin, Slug and the mesenchymal markers N-cadherin, plasminogen activator inhibitor-1 (PAI-1) and fibronectin, indicating that late TGF-beta-induced downregulation of Net1A is involved in epithelial-to-mesenchymal transition (EMT). Finally, miR-24 was found to be implicated in the regulation of the EMT program in response to TGF-beta and was shown to be directly involved in the TGF-beta-induced breast cancer cell invasiveness through Net1A regulation. Our results emphasize the importance of Net1 isoform2 in the short-and long-term TGF-beta-mediated regulation of EMT. Oncogene (2012) 31, 2862-2875; doi:10.1038/onc.2011.457; published online 10 October 2011 C1 [Papadimitriou, E.; Vasilaki, E.; Kardassis, D.; Stournaras, C.] Univ Crete, Dept Biochem, Sch Med, Iraklion 71003, Crete, Greece. [Vorvis, C.; Iliopoulos, D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Vorvis, C.; Iliopoulos, D.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Vasilaki, E.; Moustakas, A.] Uppsala Univ, Ludwig Inst Canc Res, Uppsala, Sweden. [Moustakas, A.] Uppsala Univ, Dept Med Biochem & Microbiol, Sci Life Lab, Uppsala, Sweden. RP Stournaras, C (reprint author), Univ Crete, Dept Biochem, Sch Med, POB 2208, Iraklion 71003, Crete, Greece. EM cstourn@med.uoc.gr FU PENED program of the Greek Secretariat for Research and Technology [PENED03-688] FX This work was supported by the PENED program of the Greek Secretariat for Research and Technology (Grant no. PENED03-688). We thank Dr EA Papakonstanti for valuable comments. NR 44 TC 37 Z9 37 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN PY 2012 VL 31 IS 23 BP 2862 EP 2875 DI 10.1038/onc.2011.457 PG 14 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 958YW UT WOS:000305277900006 PM 21986943 ER PT J AU Napadow, V Edwards, RR Cahalan, CM Mensing, G Greenbaum, S Valovska, A Li, A Kim, J Maeda, Y Park, K Wasan, AD AF Napadow, Vitaly Edwards, Robert R. Cahalan, Christine M. Mensing, George Greenbaum, Seth Valovska, Assia Li, Ang Kim, Jieun Maeda, Yumi Park, Kyungmo Wasan, Ajay D. TI Evoked Pain Analgesia in Chronic Pelvic Pain Patients Using Respiratory-Gated Auricular Vagal Afferent Nerve Stimulation SO PAIN MEDICINE LA English DT Article DE Chronic Pain; TENS; Transcutaneous Electrical Nerve Stimulation (TENS); Acupuncture ID VULVAR VESTIBULITIS SYNDROME; HEART-RATE VARIABILITY; EAR-COUGH REFLEX; VAGUS NERVE; CARDIOVASCULAR CONTROL; SEX-DIFFERENCES; THERMAL PAIN; BRAIN-STEM; BACK-PAIN; ACUPUNCTURE AB Objective. Previous vagus nerve stimulation (VNS) studies have demonstrated antinociceptive effects, and recent noninvasive approaches, termed transcutaneous-vagus nerve stimulation (t-VNS), have utilized stimulation of the auricular branch of the vagus nerve in the ear. The dorsal medullary vagal system operates in tune with respiration, and we propose that supplying vagal afferent stimulation gated to the exhalation phase of respiration can optimize t-VNS. Design. Counterbalanced, crossover study. Patients. Patients with chronic pelvic pain (CPP) due to endometriosis in a specialty pain clinic. Interventions/Outcomes. We evaluated evoked pain analgesia for respiratory-gated auricular vagal afferent nerve stimulation (RAVANS) compared with nonvagal auricular stimulation (NVAS). RAVANS and NVAS were evaluated in separate sessions spaced at least 1 week apart. Outcome measures included deep-tissue pain intensity, temporal summation of pain, and anxiety ratings, which were assessed at baseline, during active stimulation, immediately following stimulation, and 15 minutes after stimulus cessation. Results. RAVANS demonstrated a trend for reduced evoked pain intensity and temporal summation of mechanical pain, and significantly reduced anxiety in N = 15 CPP patients, compared with NVAS, with moderate to large effect sizes (?2 > 0.2). Conclusion. Chronic pain disorders such as CPP are in great need of effective, nonpharmacological options for treatment. RAVANS produced promising antinociceptive effects for quantitative sensory testing (QST) outcomes reflective of the noted hyperalgesia and central sensitization in this patient population. Future studies should evaluate longer-term application of RAVANS to examine its effects on both QST outcomes and clinical pain. C1 [Napadow, Vitaly; Li, Ang; Kim, Jieun; Maeda, Yumi] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Napadow, Vitaly; Edwards, Robert R.; Cahalan, Christine M.; Mensing, George; Greenbaum, Seth; Valovska, Assia; Wasan, Ajay D.] Brigham & Womens Hosp, Dept Anesthesiol, Boston, MA 02115 USA. [Wasan, Ajay D.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Park, Kyungmo] Kyung Hee Univ, Dept Biomed Engn, Yongin, South Korea. RP Napadow, V (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Dept Radiol, 149 13th St 2301, Charlestown, MA 02129 USA. EM vitaly@nmr.mgh.harvard.edu FU National Institutes of Health [R01-AT004714, P01-AT002048, R01-AG034982, R21-AR057920, F05-AT003770, K23-DA020681]; Institute of Information Technology Advancement, Korea [IITA-2008-[C1090-0801-0002]] FX We would like to thank the National Institutes of Health for funding support (VN: R01-AT004714, P01-AT002048; RRE: R01-AG034982, R21-AR057920; KP: F05-AT003770; ADW: K23-DA020681). Dr. Park was also supported by the Institute of Information Technology Advancement, Korea (IITA-2008-[C1090-0801-0002]). The content is solely the responsibility of the authors and does not necessarily represent the official views of our sponsors. NR 82 TC 20 Z9 21 U1 4 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD JUN PY 2012 VL 13 IS 6 BP 777 EP 789 DI 10.1111/j.1526-4637.2012.01385.x PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 958KO UT WOS:000305235600006 PM 22568773 ER PT J AU Saedi, N Jalian, HR Petelin, A Zachary, C AF Saedi, Nazanin Jalian, H. Ray Petelin, Anthony Zachary, Christopher TI Fractionation: Past, Present, Future SO SEMINARS IN CUTANEOUS MEDICINE AND SURGERY LA English DT Article DE fractional; Fraxel; fractionation; laser; resurfacing; photothermolysis ID RANDOMIZED CONTROLLED-TRIAL; LASER PHOTOTHERMOLYSIS; TATTOO REMOVAL; DRUG-DELIVERY; SCARS; COMPLICATIONS; HYPERPIGMENTATION; EFFICACY; DEVICE; RISK AB The development of fractional photothermolysis is a milestone in the history of laser technology and cutaneous resurfacing. Based on the concept that skin is treated in a fractional manner, where narrow cylinders of tissue are thermally heated and normal adjacent skin is left unaffected, the fractional devices have shown effectiveness in treating a variety of conditions. Since its development, we are becoming more adept at using optimal parameters to induce near carbon dioxide laser benefits with a much more comfortable postoperative period and fewer complications. The future remains bright for fractionated laser devices and with new devices and wavelengths, the applications of this technology continue to grow. Semin Cutan Med Surg 31:105-109 (C) 2012 Elsevier Inc. All rights reserved. C1 [Saedi, Nazanin] SkinCare Phys, Chestnut Hill, MA 02467 USA. [Jalian, H. Ray] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Petelin, Anthony; Zachary, Christopher] Univ Calif Irvine, Dept Dermatol, Irvine, CA 92717 USA. RP Saedi, N (reprint author), SkinCare Phys, 1244 Boylston St,Suite 103, Chestnut Hill, MA 02467 USA. EM nsaedi@skincarephysicians.net NR 40 TC 10 Z9 10 U1 1 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1085-5629 J9 SEMIN CUTAN MED SURG JI Semin. Cutan. Med. Surg. PD JUN PY 2012 VL 31 IS 2 BP 105 EP 109 DI 10.1016/j.sder.2012.02.003 PG 5 WC Dermatology; Surgery SC Dermatology; Surgery GA 959JS UT WOS:000305309300007 PM 22640430 ER PT J AU Jalian, HR Avram, MM AF Jalian, H. Ray Avram, Mathew M. TI Body Contouring: The Skinny on Noninvasive Fat Removal SO SEMINARS IN CUTANEOUS MEDICINE AND SURGERY LA English DT Article DE fat; cryolipolysis; high-intensity focused ultrasound; low-level laser therapy ID INTENSITY FOCUSED ULTRASOUND; ADIPOSE-TISSUE; LASER; CRYOLIPOLYSIS(TM); PANNICULITIS; DESTRUCTION; REDUCTION; EFFICACY; DEVICE; SAFETY AB Historically, the approach to body contouring has largely involved invasive procedures, such as liposuction. Recently, several new devices for noninvasive fat removal have received clearance by the Food and Drug Administration for the treatment of focal adiposity. Modalities are aimed primarily at targeting the physical properties of fat that differentiate it from the overlying epidermis and dermis, thus selectively resulting in removal. This review will focus on 3 novel approaches to noninvasive selective destruction of fat. Semin Cutan Med Surg 31:121-125 (C) 2012 Published by Elsevier Inc. C1 [Jalian, H. Ray; Avram, Mathew M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Jalian, H. Ray; Avram, Mathew M.] Massachusetts Gen Hosp, Laser & Cosmet Ctr, Boston, MA 02114 USA. [Jalian, H. Ray; Avram, Mathew M.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Avram, MM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, BHX 630, Boston, MA 02114 USA. EM MAvram@partners.org NR 27 TC 13 Z9 13 U1 3 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1085-5629 J9 SEMIN CUTAN MED SURG JI Semin. Cutan. Med. Surg. PD JUN PY 2012 VL 31 IS 2 BP 121 EP 125 DI 10.1016/j.sder.2012.02.004 PG 5 WC Dermatology; Surgery SC Dermatology; Surgery GA 959JS UT WOS:000305309300009 PM 22640432 ER PT J AU Minehart, RD Pian-Smith, MCM Walzer, TB Gardner, R Rudolph, JW Simon, R Raemer, DB AF Minehart, Rebecca D. Pian-Smith, May C. M. Walzer, Toni B. Gardner, Roxane Rudolph, Jenny W. Simon, Robert Raemer, Daniel B. TI Speaking Across the Drapes Communication Strategies of Anesthesiologists and Obstetricians During a Simulated Maternal Crisis SO SIMULATION IN HEALTHCARE LA English DT Article DE Communication; Teamwork; Simulation; Medical education; Obstetrics; Anesthesiology; Maternal code ID PERIMORTEM CESAREAN DELIVERY; HIGH-RELIABILITY; OPERATING-ROOM; FEEDBACK; ERROR; EMERGENCY; EDUCATION; TEAMWORK; MEDICINE; SAFETY AB Introduction: Organizational behavior and management fields have long realized the importance of teamwork and team-building skills, but only recently has health care training focused on these critical elements. Communication styles and strategies are a common focus of team training but have not yet been consistently applied to medicine. We sought to determine whether such communication strategies, specifically "advocacy'' and "inquiry,'' were used de novo by medical professionals in a simulation-based teamwork and crisis resource management course. Explicit expression of a jointly managed clinical plan between providers, a strategy shown to improve patient safety, was also evaluated. Methods: Forty-four of 54 videotaped performances of an ongoing team-building skills course were viewed and analyzed for presence of advocacy and/or inquiry that related to information or a plan; inclusion criteria were participation of a nonconfederate obstetrician and an anesthesiologist. Verbal statement of a jointly managed clinical plan was also recorded. Results: Anesthesiologists advocated information in 100% of cases and advocated their plans in 93% of cases but inquired information in 30% of cases and inquired about the obstetricians' plans in 11% of cases. Obstetricians advocated information in 73% of cases, advocated their plans in 73% of cases, inquired information in 75% of cases, and inquired about the anesthesiologists' plans in 59% of cases. An explicitly stated joint team plan was formed in 45% of cases. Conclusions: Anesthesiologists advocated more frequently than obstetricians, while obstetricians inquired and advocated in more balanced proportions. However, fewer than half of the teams explicitly agreed on a joint plan. Increasing awareness of communication styles, and possibly incorporating these skills into medical training, may help teams arrive more efficiently at jointly managed clinical plans in crisis situations. (Sim Healthcare 7:166-170, 2012) C1 [Minehart, Rebecca D.; Pian-Smith, May C. M.; Rudolph, Jenny W.; Simon, Robert; Raemer, Daniel B.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Walzer, Toni B.; Gardner, Roxane] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Minehart, Rebecca D.; Pian-Smith, May C. M.; Walzer, Toni B.; Gardner, Roxane; Rudolph, Jenny W.; Raemer, Daniel B.] Ctr Med Simulat, Cambridge, MA USA. RP Minehart, RD (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM rminehart@partners.org OI Minehart, Rebecca/0000-0001-8504-8967 FU Foundation for Anesthesia Education and Research; Anesthesia Patient Safety Foundation; National Patient Safety Foundation FX Three of the authors (R.D.M., D.B.R., M.C.M.P.-S.) were recipients of grants (from the Foundation for Anesthesia Education and Research, the Anesthesia Patient Safety Foundation, and the National Patient Safety Foundation) for other projects during the time that this article was in preparation. Two of the authors (R.S., J.W.R.) received honoraria for presenting educational sessions at academic conferences. NR 44 TC 6 Z9 6 U1 1 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-2332 J9 SIMUL HEALTHC JI Simul. Healthc. PD JUN PY 2012 VL 7 IS 3 BP 166 EP 170 DI 10.1097/SIH.0b013e31824e73fb PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 956HQ UT WOS:000305081100005 PM 22569284 ER PT J AU Schmitz, WM Allen, MH Feldman, BN Gutin, NJ Jahn, DR Kleespies, PM Quinnett, P Simpson, S AF Schmitz, William M., Jr. Allen, Michael H. Feldman, Barry N. Gutin, Nina J. Jahn, Danielle R. Kleespies, Phillip M. Quinnett, Paul Simpson, Skip TI Preventing Suicide through Improved Training in Suicide Risk Assessment and Care: An American Association of Suicidology Task Force Report Addressing Serious Gaps in US Mental Health Training SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID CONTINUING MEDICAL-EDUCATION; PATIENT SUICIDE; NATIONAL-SURVEY; IMPACT; BEHAVIOR; PSYCHIATRISTS; PSYCHOLOGISTS; INTERVENTION; THERAPISTS; FREQUENCY AB There are twice as many suicides as homicides in the United States, and the suicide rate is rising. Suicides increased 12% between 1999 and 2009. Mental health professionals often treat suicidal patients, and suicide occurs even among patients who are seeking treatment or are currently in treatment. Despite these facts, training of most mental health professionals in the assessment and management of suicidal patients is surprisingly limited. The extant literature regarding the frequency with which mental health professionals encounter suicidal patients is reviewed, as is the prevalence of training in suicide risk assessment and management. Most importantly, six recommendations are made to address the longstanding insufficient training within the mental health professions regarding the assessment and management of suicidal patients. C1 [Schmitz, William M., Jr.] SE Louisiana Vet Healthcare Syst, Baton Rouge, LA USA. [Allen, Michael H.] Univ Colorado, Dept Psychiat, Depress Ctr, Denver, CO 80202 USA. [Allen, Michael H.] VISN 19 Suicide MIRECC, Denver, CO USA. [Feldman, Barry N.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Gutin, Nina J.] Didi Hirsch Mental Hlth Serv, Pasadena, CA USA. [Jahn, Danielle R.] Texas Tech Univ, Dept Psychol, Lubbock, TX 79409 USA. [Kleespies, Phillip M.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA. [Kleespies, Phillip M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Quinnett, Paul] Univ Washington, Dept Psychiat, Sch Med, Seattle, WA 98195 USA. [Simpson, Skip] Law Off Skip Simpson, San Antonio, TX USA. [Simpson, Skip] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Schmitz, WM (reprint author), 7850 Anselmo Lane, Baton Rouge, LA 70810 USA. EM william.schmitzjr@va.gov RI Allen, Michael/A-8776-2011; OI Jahn, Danielle/0000-0003-0156-9680 NR 54 TC 37 Z9 38 U1 2 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0363-0234 J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD JUN PY 2012 VL 42 IS 3 BP 292 EP 304 DI 10.1111/j.1943-278X.2012.00090.x PG 13 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 956FU UT WOS:000305076300006 PM 22494118 ER PT J AU Kearns, JW Bowerman, D Kemmis, K Izquierdo, RE Wade, M Weinstock, RS AF Kearns, JoAnn W. Bowerman, Deborah Kemmis, Karen Izquierdo, Roberto E. Wade, Michael Weinstock, Ruth S. TI Group Diabetes Education Administered Through Telemedicine: Tools Used and Lessons Learned SO TELEMEDICINE AND E-HEALTH LA English DT Article DE distance learning; telemedicine; telehealth; diabetes ID SELF-MANAGEMENT EDUCATION AB Objective: To describe the use of telemedicine for teaching group diabetes education classes to individuals with diabetes mellitus in a rural medically underserved area. Subjects and Methods: Adults with diabetes from a rural area served by Oswego Hospital in upstate New York were asked to participate in this study. Volunteers received diabetes education through real-time teleconferencing (n=27) by joining age and sex-matched patients from the Joslin Diabetes Center, Syracuse, NY, in our "Living with Diabetes Class" (n=39). The two 3-h sessions offered comprehensive diabetes education by a diabetes nurse educator, dietitian, and exercise physiologist. These sessions were followed in 3 months by a 3-h follow-up class. Each group receiving tele-education consisted of two or three patients with diabetes. Results: The hemoglobin Ale test (a blood test that estimates the overall average glucose levels over the past 3 months) improved in the face-to-face and the telemedicine groups. There was no significant change in weight between groups. Each group had significant improvements in scores on the Problem Areas In Diabetes survey, which is a measure of emotional functioning in diabetes. Diabetes treatment satisfaction as measured in the Diabetes Treatment Satisfaction Questionnaire improved in the face-to-face group but not in the telemedicine group. Although the face-to-face group had significantly higher scores in the Diabetes Treatment Satisfaction Questionnaire, the telemedicine group was highly satisfied with the services provided. Conclusions: Telemedicine offers an effective alternative approach for providing group diabetes education to individuals with poor access to diabetes education programs. C1 [Kearns, JoAnn W.] SUNY Upstate Med Univ, Joslin Diabet Ctr, Syracuse, NY 13214 USA. [Wade, Michael] Dept Vet Affairs Med Ctr, Syracuse, NY USA. RP Kearns, JW (reprint author), SUNY Upstate Med Univ, Joslin Diabet Ctr, 3229 E Genesee St, Syracuse, NY 13214 USA. EM Kearnsj@upstate.edu FU New York State Department of Health FX The authors thank Dr. Dennis Norfolk and Mary Hitchcock, R.N., at Oswego County Opportunities for their assistance. This work was supported, in part, by the New York State Department of Health. NR 7 TC 9 Z9 9 U1 3 U2 13 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED E-HEALTH JI Telemed. e-Health PD JUN PY 2012 VL 18 IS 5 BP 347 EP 353 DI 10.1089/tmj.2011.0165 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 956OA UT WOS:000305097800005 PM 22468984 ER PT J AU Hsueh, MT Eastman, K McFarland, LV Raugi, GJ Reiber, GE AF Hsueh, Martha T. Eastman, Kristin McFarland, Lynne V. Raugi, Gregory J. Reiber, Gayle E. TI Teledermatology Patient Satisfaction in the Pacific Northwest SO TELEMEDICINE AND E-HEALTH LA English DT Article DE teledermatology; patient satisfaction; store-and-forward; Veterans Affairs ID RANDOMIZED CONTROLLED-TRIAL; FORWARD TELEDERMATOLOGY; CONSULT SYSTEM; TELEMEDICINE; DERMATOLOGY AB Background: The aim of this quality improvement project is to assess patient satisfaction with a store-and-forward teledermatology project and to identify factors associated with patient satisfaction and dissatisfaction. Subjects and Methods: Veterans receiving care in rural clinics in the Pacific Northwest were surveyed using a 5-point Likert scale about satisfaction with face-to-face care for a skin complaint prior to any teledermatology exposure. One year later, veterans in the same rural clinics were surveyed about satisfaction with teledermatology care using a more comprehensive survey. Ninety-six patients completed the face-to-face satisfaction survey questions, and 501 completed the teledermatology satisfaction survey. Results: Most (78%) of surveyed patients were highly satisfied or satisfied with face-to-face dermatology care. After 1 year of teledermatology, 77% of patients were highly satisfied or satisfied with teledermatology care. The mean patient satisfaction score for teledermatology was equivalent to face-to-face care (4.1 +/- 1.2 and 4.3 +/- 1.0, p= 0.4). Factors associated with teledermatology patient satisfaction included short wait times for initial consultation, a perception that the initial wait time was not too long, a perception that the skin condition was properly treated, and the belief that adequate follow-up was received. Factors associated with teledermatology patient dissatisfaction included perceptions that the skin condition was not properly treated and that inadequate follow-up was received. Conclusions: Teledermatology was widely accepted by the majority of patients receiving care at rural clinics. Patient satisfaction with care received through teledermatology was equivalent to that with face-to-face dermatology. C1 [Eastman, Kristin; McFarland, Lynne V.; Raugi, Gregory J.; Reiber, Gayle E.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Res & Dev, Seattle, WA 98101 USA. [Hsueh, Martha T.; Eastman, Kristin] Univ Washington, Sch Med, Seattle, WA USA. [Eastman, Kristin; Reiber, Gayle E.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Rehabil Res & Dev, Seattle, WA 98101 USA. [Raugi, Gregory J.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Primary Med Serv, Dermatol Sect, Seattle, WA 98101 USA. [Raugi, Gregory J.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Specialty Med Serv, Dermatol Sect, Seattle, WA 98101 USA. RP McFarland, LV (reprint author), VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Res & Dev, Metropolitan Pk W,1100 Olive Way,1400, Seattle, WA 98101 USA. EM lynne.mcfarland@va.gov FU Veterans Health Administration Office of Rural Health, U.S. Department of Veterans Affairs; Veterans Health Administration Health Services Research & Development, U.S. Department of Veterans Affairs FX We are indebted to Jeff Rodenbaugh for database programming. G.E.R. is the recipient of a Veterans Affairs Senior Career Scientist award. Funding for the VISN 20 Rural Teledermatology Project came from the Veterans Health Administration Office of Rural Health, U.S. Department of Veterans Affairs. This project was supported by the Veterans Health Administration Health Services Research & Development, U.S. Department of Veterans Affairs. NR 12 TC 18 Z9 18 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED E-HEALTH JI Telemed. e-Health PD JUN PY 2012 VL 18 IS 5 BP 377 EP 381 DI 10.1089/tmj.2011.0181 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 956OA UT WOS:000305097800009 PM 22489931 ER PT J AU Vaillant, GE AF Vaillant, George E. TI Positive mental health: is there a cross-cultural definition? SO WORLD PSYCHIATRY LA English DT Article DE Positive mental health; maturity; resilience; coping mechanisms; subjective well-being; emotional intelligence; positive emotions ID PSYCHOLOGICAL HEALTH; ADOLESCENCE; ADULTHOOD; NEURONS; SCALE AB Seven models for conceptualizing positive mental health are reviewed: mental health as above normal, epitomized by a DSM-IV's Global Assessment of Functioning (GAF) score of over 80; mental health as the presence of multiple human strengths rather than the absence of weaknesses; mental health conceptualized as maturity; mental health as the dominance of positive emotions; mental health as high socio-emotional intelligence; mental health as subjective well-being; mental health as resilience. Safeguards for the study of mental health are suggested, including the need to define mental health in terms that are culturally sensitive and inclusive, and the need to empirically and longitudinally validate criteria for mental health. C1 Harvard Univ, Dept Psychiat, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Vaillant, GE (reprint author), Harvard Univ, Dept Psychiat, Sch Med, Massachusetts Gen Hosp, 151 Merrimac St, Boston, MA 02114 USA. FU National Institute of Mental Health [MH42248] FX This work was supported by research grant MH42248 from the National Institute of Mental Health. NR 56 TC 24 Z9 27 U1 3 U2 24 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 1723-8617 J9 WORLD PSYCHIATRY JI World Psychiatry PD JUN PY 2012 VL 11 IS 2 BP 93 EP 99 PG 7 WC Psychiatry SC Psychiatry GA 959OC UT WOS:000305321200006 PM 22654934 ER PT J AU Shah, K AF Shah, Khalid TI Mesenchymal stem cells engineered for cancer therapy SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE Mesenchymal stem cells; Cancer therapy; Migration; Delivery vehicles; Targeting; Molecular imaging ID UMBILICAL-CORD BLOOD; MARROW STROMAL CELLS; MULTIPLE LUNG-TUMORS; HUMAN BONE-MARROW; APOPTOSIS-INDUCING LIGAND; RAT GLIOMA MODEL; GROWTH IN-VIVO; PROGENITOR CELLS; TARGETED-DELIVERY; INTERFERON-BETA AB Recent pre-clinical and clinical studies have shown that stem cell-based therapies hold tremendous promise for the treatment of human disease. Mesenchymal stem cells (MSC) are emerging as promising anti-cancer agents which have an enormous potential to be utilized to treat a number of different cancer types. MSC have inherent tumor-trophic migratory properties, which allows them to serve as vehicles for delivering effective, targeted therapy to isolated tumors and metastatic disease. MSC have been readily engineered to express anti-proliferative, pro-apoptotic, anti-angiogenic agents that specifically target different cancer types. Many of these strategies have been validated in a wide range of studies evaluating treatment feasibility or efficacy, as well as establishing methods for real-time monitoring of stem cell migration in vivo for optimal therapy surveillance and accelerated development. This review aims to provide an in depth status of current MSC-based cancer therapies, as well as the prospects for their clinical translation. (C) 2011 Elsevier B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Shah, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. EM kshah@helix.mgh.harvard.edu FU National Institutes of Health [CA138922-01A2]; American Cancer Society; James McDonnel Foundation FX This work was supported in part by National Institutes of Health (CA138922-01A2; KS), American Cancer Society (KS) and James McDonnel Foundation (KS). NR 132 TC 88 Z9 95 U1 4 U2 63 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD JUN 1 PY 2012 VL 64 IS 8 BP 739 EP 748 DI 10.1016/j.addr.2011.06.010 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 951SB UT WOS:000304739200005 PM 21740940 ER PT J AU Gubner, NR McKinnon, CS Cunningham, CL Phillips, TJ AF Gubner, N. R. McKinnon, C. S. Cunningham, C. L. Phillips, T. J. TI VARENICLINE DOES NOT ATTENUATE THE EXPRESSION OF ETHANOL-INDUCED CPP OR THE DEVELOPMENT OF ETHANOL-INDUCED SENSITIZATION IN DBA/2J MICE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 [Gubner, N. R.; McKinnon, C. S.; Cunningham, C. L.; Phillips, T. J.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland Alcohol Res Ctr, Portland VA Med Ctr, Portland, OR 97239 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 19A EP 19A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806000034 ER PT J AU Kincaid, CL Rasmussen, DD AF Kincaid, C. L. Rasmussen, D. D. TI PRAZOSIN, AN alpha 1-ADRENERGIC RECEPTOR ANTAGONIST, DECREASES VOLUNTARY ALCOHOL INTAKE BY WISTAR RATS IN THE INTERMITTENT ACCESS TO ALCOHOL (IAA) MODEL SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 Univ Washington, VISN Mental Illness Res 20, Educ & Clin Ctr MIRECC, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat, Seattle, WA 98108 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 22A EP 22A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806000046 ER PT J AU Fryer, SL Shanbhag, H Watson, TD Krystal, JH Mathalon, DH AF Fryer, S. L. Shanbhag, H. Watson, T. D. Krystal, J. H. Mathalon, D. H. TI FMRI REVEALS DIFFERENTIAL LIMBIC RESPONSE TO ALCOHOL CUE DISTRACTORS ACROSS STAGES OF ALCOHOL DEPENDENCE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94122 USA. San Francisco VA Med Ctr, San Francisco, CA 92121 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 46A EP 46A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806000141 ER PT J AU Rubin, A Lachowicz, M Brief, D Roy, M Enggasser, J Hermos, J Rosenbloom, D Helmuth, E Benitez, D Keane, T AF Rubin, A. Lachowicz, M. Brief, D. Roy, M. Enggasser, J. Hermos, J. Rosenbloom, D. Helmuth, E. Benitez, D. Keane, T. TI EFFICACY OF WEB INTERVENTION FOR MALE AND FEMALE DRINKERS WITH AND WITHOUT A RECENT IN-PERSON TREATMENT HISTORY SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 VA Boston Healthcare Syst, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02118 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 69A EP 69A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806000234 ER PT J AU Hristova, V Kelly, JF AF Hristova, V. Kelly, J. F. TI CHARACTERISTICS AND TREATMENT RESPONSE IN ADOLESCENTS WITH AND WITHOUT FAMILY HISTORY OF ALCOHOL AND DRUG USE DISORDER SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 [Hristova, V.; Kelly, J. F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 74A EP 74A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806000254 ER PT J AU Hoeppner, BH Paskausky, A Jackson, KM Barnett, NP AF Hoeppner, B. H. Paskausky, A. Jackson, K. M. Barnett, N. P. TI GENDER DIFFERENCES IN COLLEGE STUDENT ADHERENCE TO NIAAA DAILY AND WEEKLY DRINKING GUIDELINES SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 [Hoeppner, B. H.; Paskausky, A.; Jackson, K. M.; Barnett, N. P.] Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 76A EP 76A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806000259 ER PT J AU Kincaid, CL Rasmussen, DD AF Kincaid, C. L. Rasmussen, D. D. TI SOURCE (VENDOR) OF WISTAR RATS IS AN IMPORTANT VARIABLE IN THE INTERMITTENT ACCESS TO ALCOHOL (IAA) MODEL OF INCREASED VOLUNTARY ALCOHOL DRINKING SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 Univ Washington, VISN Mental Illness Res Educ & Clin Ctr MIRECC 20, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat, Seattle, WA 98108 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 108A EP 108A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806000390 ER PT J AU Rasmussen, DD Kincaid, CL AF Rasmussen, D. D. Kincaid, C. L. TI ACOUSTIC STARTLE AMPLITUDE PREDICTS VOLUNTARY ALCOHOL INTAKE DURING SUBSEQUENT INTERMITTENT ACCESS TO ALCOHOL (IAA) SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 Univ Washington, VA Puget Sound Hlth Care Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 20, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat, Seattle, WA 98108 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 111A EP 111A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806000401 ER PT J AU Rasmussen, DD Kincaid, CL Froehlich, JC AF Rasmussen, D. D. Kincaid, C. L. Froehlich, J. C. TI PRAZOSIN, AN alpha 1-ADRENERGIC RECEPTOR ANTAGONIST, BLOCKS THE EFFECT OF STRESS ON ANXIETY BEHAVIOR DURING SUBSEQUENT ALCOHOL WITHDRAWAL SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 Univ Washington, VA Puget Sound Hlth Care Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 20, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat, Seattle, WA 98108 USA. 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 112A EP 112A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806001004 ER PT J AU Lapham, GT Rubinsky, AD Williams, EC Maynard, C Heagerty, P Kivlahan, DR Au, DH Bradley, KA AF Lapham, G. T. Rubinsky, A. D. Williams, E. C. Maynard, C. Heagerty, P. Kivlahan, D. R. Au, D. H. Bradley, K. A. TI FACTORS ASSOCIATED WITH REPEATED NEGATIVE ALCOHOL SCREENS: IS ANNUAL ALCOHOL SCREENING UNNECESSARY FOR SOME VA PATIENTS? SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 US Dept Vet Affairs, Seattle, WA 98101 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98104 USA. Grp Hlth Res Inst, Seattle, WA 98101 USA. RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 155A EP 155A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806001169 ER PT J AU Dow, SJ Kelly, JF AF Dow, S. J. Kelly, J. F. TI LISTENING TO YOUTH: ADOLESCENTS' SELF-REPORTED REASONS FOR ALCOHOL AND DRUG USE AS A UNIQUE PREDICTOR OF TREATMENT RESPONSE AND OUTCOME SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 [Dow, S. J.; Kelly, J. F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 158A EP 158A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806001184 ER PT J AU Kelly, JF Yeterian, JD Kim, JJ AF Kelly, John F. Yeterian, Julie D. Kim, Jessica Jin TI HOW DO JUSTICE-SYSTEM INVOLVED ADOLESCENTS FARE IN OUTPATIENT ALCOHOL AND DRUG TREATMENT? SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 [Kelly, John F.; Yeterian, Julie D.; Kim, Jessica Jin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 159A EP 159A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806001185 ER PT J AU Grossbard, JR Hawkins, EJ Lapham, GT Williams, EC Rubinsky, AD Chavez, LJ Bradley, KA AF Grossbard, J. R. Hawkins, E. J. Lapham, G. T. Williams, E. C. Rubinsky, A. D. Chavez, L. J. Bradley, K. A. TI RATES OF ALCOHOL MISUSE AND FOLLOW-UP CARE AMONG OEF/OIF VETERANS IN VA: ASSOCIATIONS WITH SUBSTANCE USE DISORDERS AND PTSD SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 VA Puget Sound, Dept Vet Affairs, Hlth Serv Res & Dev, Seattle, WA 98101 USA. SUD QuERI, Seattle, WA 98101 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 160A EP 160A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806001191 ER PT J AU Batki, SL Lasher, BA Heinz, AJ Herbst, E Metzler, T Prathikanti, S Waldrop, A Neylan, TC Tarasovsky, G AF Batki, S. L. Lasher, B. A. Heinz, A. J. Herbst, E. Metzler, T. Prathikanti, S. Waldrop, A. Neylan, T. C. Tarasovsky, G. TI RISK-TAKING, IMPULSIVITY, MEMORY & EXECUTIVE FUNCTIONING AS OUTCOME PREDICTORS IN A TRIAL OF TOPIRAMATE FOR ALCOHOL DEPENDENCE IN VETERANS WITH PTSD SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 UCSF, Dept Psychiat, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA 94121 USA. NR 0 TC 1 Z9 1 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 226A EP 226A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806002055 ER PT J AU Heinz, AJ Waldrop, A Lasher, BA Herbst, E Prathikanti, S Neylan, TC Metzler, T Petrakis, I Tarasovsky, G Batki, SL AF Heinz, A. J. Waldrop, A. Lasher, B. A. Herbst, E. Prathikanti, S. Neylan, T. C. Metzler, T. Petrakis, I. Tarasovsky, G. Batki, S. L. TI COGNITIVE FUNCTIONING, IMPULSIVITY AND RISK-TAKING: RELATIONSHIPS WITH MEASURES OF CLINICAL SYMPTOMOLOGY IN VETERANS WITH PTSD AND AUD SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 UCSF, Dept Psychiat, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA 94121 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 226A EP 226A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806002054 ER PT J AU Raskind, MA Simpson, T AF Raskind, M. A. Simpson, T. TI EFFECTS OF PRAZOSIN ON DRINKING PARAMETERS IN ALCOHOL DEPENDENCE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 [Raskind, M. A.; Simpson, T.] VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Tacoma, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 247A EP 247A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806002140 ER PT J AU Marinkovic, K Rosen, BQ Cox, B Kovacevic, S AF Marinkovic, K. Rosen, B. Q. Cox, B. Kovacevic, S. TI EFFECTS OF ALCOHOL INTOXICATION ON EVENT-RELATED THETA OSCILLATIONS DURING LANGUAGE PROCESSING: ANATOMICALLY-CONSTRAINED MEG SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 Univ Calif San Diego, Boston, MA USA. Massachusetts Gen Hosp, Martinos Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 269A EP 269A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806002227 ER PT J AU Dou, X Menkari, CE Charness, ME AF Dou, X. Menkari, C. E. Charness, M. E. TI EFFECT OF LIPID RAFT DISRUPTION ON ETHANOL INHIBITION OF L1 ADHESION SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 VA Boston Healthcare Syst, W Roxbury, MA 02132 USA. Harvard Univ, Sch Med, W Roxbury, MA 02132 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 280A EP 280A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806002269 ER PT J AU Kelly, JF Stout, RL Slaymaker, V AF Kelly, John F. Stout, Robert L. Slaymaker, Valerie TI EMERGING ADULTS AND ALCOHOLICS ANONYMOUS: ATTENDANCE, INVOLVEMENT, AND RECOVERY-RELATED BENEFITS IN THE YEAR FOLLOWING RESIDENTIAL TREATMENT SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 [Kelly, John F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Stout, Robert L.] Decis Sci Inst, Atlanta, GA USA. [Slaymaker, Valerie] Hazelden Fdn, Center City, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 293A EP 293A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806002321 ER PT J AU Chen, S Charness, ME AF Chen, S. Charness, M. E. TI ALCOHOL DISRUPTION OF CEREBELLAR NEURAL CIRCUIT DEVELOPMENT SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 VA Boston Healthcare Syst, W Roxbury, MA 02132 USA. Harvard Univ, Sch Med, Dept Neurol, W Roxbury, MA 02132 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 312A EP 312A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806002398 ER PT J AU Hahn, JA Santos, GM Emenyonu, NI Bwana, MB Muzoora, C Martin, JN Bangsberg, DR AF Hahn, J. A. Santos, G. M. Emenyonu, N. I. Bwana, M. B. Muzoora, C. Martin, J. N. Bangsberg, D. R. TI PREDICTORS OF REPORTED ABSTINENCE FROM ALCOHOL AMONG HIV-INFECTED PERSONS PRIOR TO ANTIRETROVIRAL THERAPY IN RURAL UGANDA SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mbarara Univ Sci & Technol, Mbarara, Uganda. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 315A EP 315A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806002410 ER PT J AU Raskind, M Simpson, T AF Raskind, M. Simpson, T. TI EFFECTS OF PRAZOSIN ON DRINKING PARAMETERS IN ALCOHOL DEPENDENCE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98108 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 318A EP 318A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806002424 ER PT J AU Rasmussen, DD Froehlich, JC AF Rasmussen, D. D. Froehlich, J. C. TI PRECLINICAL PRAZOSIN STUDIES: DEPENDENCE OF APPROPRIATE DOSE ON DRINKING HISTORY, AND BENEFIT OF COMBINING PRAZOSIN plus PROPRANOLOL TO DECREASE RELAPSE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98108 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 318A EP 318A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806002422 ER PT J AU Brief, D Rubin, A Enggasser, J Roy, M Lachowicz, M Helmuth, E Rosenbloom, D Benitez, D Hermos, J Keane, T AF Brief, D. Rubin, A. Enggasser, J. Roy, M. Lachowicz, M. Helmuth, E. Rosenbloom, D. Benitez, D. Hermos, J. Keane, T. TI WEB-BASED INTERVENTION FOR RETURNING VETERANS WITH RISKY ALCOHOL USE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 VA Boston Healthcare Syst, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02130 USA. NR 0 TC 2 Z9 2 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 347A EP 347A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806002537 ER PT J AU Durazzo, TC Mon, A Pennington, D Abe, C Meyerhoff, DJ AF Durazzo, T. C. Mon, A. Pennington, D. Abe, C. Meyerhoff, D. J. TI CHRONIC CIGARETTE SMOKING IN ALCOHOL USE DISORDERS: ASSOCIATIONS WITH NEUROBIOLOGICAL ABNORMALITIES IN THE BRAIN REWARD/EXECUTIVE OVERSIGHT SYSTEM SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 349A EP 349A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806002546 ER PT J AU Miller, KW AF Miller, K. W. TI WHERE ARE THE BINDING SITES FOR ALCOHOLS AND ANESTHETICS ON CYS-LOOP LIGAND-GATED ION CHANNELS? SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 [Miller, K. W.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. [Miller, K. W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 362A EP 362A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806002598 ER PT J AU Schacht, JP Anton, RF Randall, PK Li, X Henderson, S Myrick, H AF Schacht, J. P. Anton, R. F. Randall, P. K. Li, X. Henderson, S. Myrick, H. TI INTERACTING EFFECTS OF NALTREXONE AND OPRM1 AND DAT VARIATION ON THE NEURAL RESPONSE TO ALCOHOL CUES SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 23-27, 2012 CL San Francisco, CA SP Res Soc Alcoholism (RSA) C1 [Schacht, J. P.; Anton, R. F.; Randall, P. K.; Li, X.; Henderson, S.; Myrick, H.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Myrick, H.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2012 VL 36 SU 1 SI SI BP 366A EP 366A PG 1 WC Substance Abuse SC Substance Abuse GA 952QA UT WOS:000304806002616 ER PT J AU Maron, BJ Braunwald, E AF Maron, Barry J. Braunwald, Eugene TI Eugene Braunwald, MD and the Early Years of Hypertrophic Cardiomyopathy: A Conversation With Dr. Barry J. Maron SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material ID LEFT-VENTRICULAR OUTFLOW; VALVULAR AORTIC STENOSIS; BETA-ADRENERGIC BLOCKADE; SUBAORTIC STENOSIS; OBSTRUCTIVE CARDIOMYOPATHY; OPERATIVE TREATMENT; YOUNG-ADULTS; HEART; PREVALENCE; MECHANISM C1 [Maron, Barry J.] Minneapolis Heart Inst Fdn, Hypertroph Cardiomyopathy Ctr, Minneapolis, MN USA. [Braunwald, Eugene] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. RP Maron, BJ (reprint author), Minneapolis Heart Inst Fdn, Hypertroph Cardiomyopathy Ctr, Minneapolis, MN USA. NR 50 TC 7 Z9 7 U1 0 U2 4 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 1 PY 2012 VL 109 IS 11 BP 1539 EP 1547 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 951RN UT WOS:000304737800001 PM 22425332 ER PT J AU Hua, P Feng, WG Rezonzew, G Chumley, P Jaimes, EA AF Hua, Ping Feng, Wenguang Rezonzew, Gabriel Chumley, Phillip Jaimes, Edgar A. TI The transcription factor ETS-1 regulates angiotensin II-stimulated fibronectin production in mesangial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE chronic kidney disease; renin-angiotensin system ID NF-KAPPA-B; RECEPTOR TRANSACTIVATION; EXTRACELLULAR-MATRIX; PROTEIN-SYNTHESIS; POINTED DOMAIN; EXPRESSION; BINDING; GROWTH; GENE; PHOSPHORYLATION AB Hua P, Feng W, Rezonzew G, Chumley P, Jaimes EA. The transcription factor ETS-1 regulates angiotensin II-stimulated fibronectin production in mesangial cells. Am J Physiol Renal Physiol 302: F1418-F1429, 2012. First published February 22, 2012; doi:10.1152/ajprenal.00477.2011.-Angiotensin II (ANG II) produced as result of activation of the renin-angiotensin system (RAS) plays a critical role in the pathogenesis of chronic kidney disease via its hemodynamic effects on the renal microcirculation as well as by its nonhemodynamic actions including the production of extracellular matrix proteins such as fibronectin, a multifunctional extracellular matrix protein that plays a major role in cell adhesion and migration as well as in the development of glomerulosclerosis. ETS-1 is an important transcription factor essential for normal kidney development and glomerular integrity. We previously showed that ANG II increases ETS-1 expression and is required for fibronectin production in mesangial cells. In these studies, we determined that ANG II induces phosphorylation of ETS-1 via activation of the type 1 ANG II receptor and that Erk1/2 and Akt/PKB phosphorylation are required for these effects. In addition, we characterized the role of ETS-1 on the transcriptional activation of fibronectin production in mesangial cells. We determined that ETS-1 directly activates the fibronectin promoter and by utilizing gel shift assays and chromatin immunoprecipitation assays identified two different ETS-1 binding sites that promote the transcriptional activation of fibronectin in response to ANG II. In addition, we identified the essential role of CREB and its coactivator p300 on the transcriptional activation of fibronectin by ETS-1. These studies unveil novel mechanisms involved in RAS-induced production of the extracellular matrix protein fibronectin in mesangial cells and establish the role of the transcription factor ETS-1 as a direct mediator of these effects. C1 [Hua, Ping; Feng, Wenguang; Rezonzew, Gabriel; Chumley, Phillip; Jaimes, Edgar A.] Univ Alabama Birmingham, Div Nephrol, Birmingham, AL 35294 USA. [Jaimes, Edgar A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Jaimes, EA (reprint author), Univ Alabama Birmingham, Div Nephrol, 1530 3rd Ave S,ZRB 637, Birmingham, AL 35294 USA. EM ejaimes@uab.edu FU Veterans Affairs Administration; O'Brien Kidney Center at the University of Alabama at Birmingham FX These studies were funded by a Merit Review Award of the Veterans Affairs Administration (to E. A. Jaimes). We also thank the support of the O'Brien Kidney Center at the University of Alabama at Birmingham. NR 49 TC 12 Z9 12 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUN PY 2012 VL 302 IS 11 BP F1418 EP F1429 DI 10.1152/ajprenal.00477.2011 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 952SN UT WOS:000304812700008 PM 22357921 ER PT J AU Masia, R Pratt, DS Misdraji, J AF Masia, Ricard Pratt, Daniel S. Misdraji, Joseph TI A Histopathologic Pattern of Centrilobular Hepatocyte Injury Suggests 6-Mercaptopurine-Induced Hepatotoxicity in Patients With Inflammatory Bowel Disease SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID NODULAR REGENERATIVE HYPERPLASIA; MITOCHONDRIAL INJURY; AZATHIOPRINE; THERAPY; ROLES AB Context.-Hepatotoxicity is an important side effect of thiopurine analog treatment for inflammatory bowel disease. A variety of histopathologic findings have been observed in patients with inflammatory bowel disease with thiopurine-induced hepatotoxicity, including nodular regenerative hyperplasia, vascular injury, and cholestasis. Objective.-To describe the histologic features shared by 3 cases of thiopurine-induced hepatotoxicity in patients with inflammatory bowel disease. Design.-We identified 3 patients with inflammatory bowel disease who developed hepatotoxicity due to 6-mercaptopurine from the educational files of the Department of Pathology at Massachusetts General Hospital (Boston). Histology slides (stained with hematoxylin-eosin, trichrome, periodic-acid Schiff with diastase digestion, and iron stains) and patients' medical records were reviewed retrospectively. Results.-All 3 patients were receiving 6-mercaptopurine monotherapy at therapeutic doses, had normal thiopurine metabolite levels, and presented with elevated aminotransferase levels. Biopsies from all 3 cases exhibited a pattern of centrilobular hepatocyte injury characterized by ceroid-laden macrophages, hepatocyte anisonucleosis, and increased lipofuscin pigment, as well as centrilobular steatosis. Aminotransferase levels trended downward and either normalized or remained at borderline elevated levels after 6-mercaptopurine dose was reduced (in 1 patient) or discontinued (in 2 patients). Conclusions.-Recognition of a pattern of centrilobular injury enables pathologists to suggest thiopurine-induced liver injury as the cause of elevated aminotransferases in patients with inflammatory bowel disease. (Arch Pathol Lab Med. 2012;136:618-622; doi: 10.5858/arpa.2011-0214-OA) C1 [Masia, Ricard; Misdraji, Joseph] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Pratt, Daniel S.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Misdraji, J (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 219, Boston, MA 02114 USA. EM jmisdraji@partners.org NR 13 TC 2 Z9 2 U1 0 U2 2 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JUN PY 2012 VL 136 IS 6 BP 618 EP 622 DI 10.5858/arpa.2011-0214-OA PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 954YW UT WOS:000304985100007 PM 22646267 ER PT J AU Starr, JR Collett, BR Gaither, R Kapp-Simon, KA Cradock, MM Cunningham, ML Speltz, ML AF Starr, Jacqueline R. Collett, Brent R. Gaither, Rebecca Kapp-Simon, Kathleen A. Cradock, Mary Michaeleen Cunningham, Michael L. Speltz, Matthew L. TI Multicenter Study of Neurodevelopment in 3-Year-Old Children With and Without Single-Suture Craniosynostosis SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID NONSYNDROMIC CRANIOSYNOSTOSIS; ANESTHESIA; INFANTS; BRAIN; ASSOCIATION; EXPOSURE; OUTCOMES; COHORT; TIME; AGE AB Objective: To evaluate the hypothesis that 3-year-old children with single-suture craniosynostosis would receive lower neurodevelopmental scores than a comparable group of children born with patent sutures. Design: Longitudinal comparison study. Setting: Five tertiary care craniofacial centers. Participants: Patients with craniosynostosis (cases) and a comparison group of children without craniosynostosis (controls). Patients diagnosed with single-suture craniosynostosis from 2002 to 2006 were eligible as cases. Controls were frequency-matched to cases on age, sex, race, socioeconomic status, and study site. Main Exposure: Craniosynostosis. Main Outcome Measures: We administered the Bayley Scales of Infant Development, Second Edition, mental and motor development indices and the Preschool Language Scales, Third Edition, receptive and expressive communication scales. Children were evaluated at baseline (before surgery in cases and at a similar age in controls) and at 18 and 36 months of age. We compared the groups' performances at 36 months by fitting adjusted linear and logistic regression models. We also estimated adjusted associations between age at surgery and neurodevelopmental scores. Results: Adjusted mean case deficits ranged from 3 to 6 points (P <=.008 for all comparisons). Compared with controls, the odds of cases being delayed ranged from 1.5 to 2.0, depending on the neurodevelopmental scale (P values ranged from .03 to .09). Cases' ages at craniosynostosis repair were not strongly related to neurodevelopmental performance. Conclusions: In this large, carefully controlled, multicenter study, we observed consistently lower mean neurodevelopmental scores in children with single-suture craniosynostosis compared with controls. These results provide further support for neurodevelopmental screening in young children with single-suture craniosynostosis. C1 [Collett, Brent R.; Speltz, Matthew L.] Seattle Childrens Hosp, Dept Psychiat & Behav Med, Seattle, WA 98105 USA. [Starr, Jacqueline R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Collett, Brent R.; Speltz, Matthew L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Cunningham, Michael L.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Cunningham, Michael L.; Speltz, Matthew L.] Childrens Craniofacial Ctr, Seattle, WA USA. [Starr, Jacqueline R.] Forsyth Inst, Cambridge, MA USA. [Gaither, Rebecca; Kapp-Simon, Kathleen A.] Northwestern Univ, Dept Surg, Chicago, IL 60611 USA. [Gaither, Rebecca; Kapp-Simon, Kathleen A.] Shriners Hosp Children, Chicago, IL USA. [Cradock, Mary Michaeleen] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [Cradock, Mary Michaeleen] Washington Univ, St Louis Childrens Hosp, Sch Med, Dept Psychol, St Louis, MO 63110 USA. RP Speltz, ML (reprint author), Seattle Childrens Hosp, Dept Psychiat & Behav Med, 4800 Sand Point Way NE,Mailstop CL-08, Seattle, WA 98105 USA. EM mspeltz@uw.edu OI Starr, Jacqueline/0000-0002-3039-2311 FU National Institute of Dental and Craniofacial Research [R01 DE 13813] FX This work was supported by grant R01 DE 13813 from the National Institute of Dental and Craniofacial Research (awarded to Dr Speltz). NR 40 TC 24 Z9 26 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1072-4710 EI 1538-3628 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD JUN PY 2012 VL 166 IS 6 BP 536 EP 542 DI 10.1001/archpediatrics.2011.1800 PG 7 WC Pediatrics SC Pediatrics GA 952GM UT WOS:000304779600008 PM 22312170 ER PT J AU Keough, ME Porter, E Kredlow, MA Worthington, JJ Hoge, EA Pollack, MH Shear, MK Simon, NM AF Keough, Meghan E. Porter, Eliora Kredlow, M. Alexandra Worthington, John J. Hoge, Elizabeth A. Pollack, Mark H. Shear, M. Katherine Simon, Naomi M. TI Anchoring the Panic Disorder Severity Scale SO ASSESSMENT LA English DT Article DE Panic Disorder Severity Scale; panic disorder; Clinical Global Impression-Severity Scale; quality of life ID REPLICATION AB The Panic Disorder Severity Scale (PDSS) is a clinician-administered measure of panic disorder symptom severity widely used in clinical research. This investigation sought to provide clinically meaningful anchor points for the PDSS both in terms of clinical severity as measured by the Clinical Global Impression-Severity Scale (CGI-S) and to extend its clinical meaningfulness by examining its association with quality of life. A total of 63 individuals with a primary diagnosis of panic disorder were assessed on completion of a 6- or 8-week psychotherapy or pharmacotherapy trial for the treatment of panic disorder. As expected, the PDSS was correlated with both the CGI-S and quality of life. These results provide further support for the validity and clinical utility of the PDSS and provide simple anchors to help guide the potential use of the PDSS scale to measure treatment progress in clinical practice. C1 [Keough, Meghan E.; Porter, Eliora; Kredlow, M. Alexandra; Worthington, John J.; Hoge, Elizabeth A.; Pollack, Mark H.; Simon, Naomi M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Keough, Meghan E.; Worthington, John J.; Hoge, Elizabeth A.; Pollack, Mark H.; Simon, Naomi M.] Harvard Univ, Sch Med, Boston, MA USA. [Shear, M. Katherine] Columbia Univ, New York, NY USA. RP Keough, ME (reprint author), Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Box 359911,325 9th Ave, Seattle, WA 98104 USA. EM mkeough@uw.edu RI Hoge, Elizabeth/H-5879-2012 OI Hoge, Elizabeth/0000-0002-5513-2292 FU NIMH NIH HHS [5K23MH01831, T32 MH082709, K23 MH001831] NR 12 TC 4 Z9 4 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-1911 J9 ASSESSMENT JI Assessment PD JUN PY 2012 VL 19 IS 2 BP 257 EP 259 DI 10.1177/1073191112436668 PG 3 WC Psychology, Clinical SC Psychology GA 951CZ UT WOS:000304699700011 PM 22327206 ER PT J AU Majhail, NS Brazauskas, R Hassebroek, A Bredeson, CN Hahn, T Hale, GA Horowitz, MM Lazarus, HM Maziarz, RT Wood, WA Parsons, SK Joffe, S Rizzo, JD Lee, SJ Hayes-Lattin, BM AF Majhail, Navneet S. Brazauskas, Ruta Hassebroek, Anna Bredeson, Christopher N. Hahn, Theresa Hale, Gregory A. Horowitz, Mary M. Lazarus, Hillard M. Maziarz, Richard T. Wood, William A. Parsons, Susan K. Joffe, Steven Rizzo, J. Douglas Lee, Stephanie J. Hayes-Lattin, Brandon M. TI Outcomes of Allogeneic Hematopoietic Cell Transplantation for Adolescent and Young Adults Compared with Children and Older Adults with Acute Myeloid Leukemia SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Hematopoietic cell transplantation; Allogeneic; Acute myeloid leukemia; Adolescent and young adults; Survival ID UNRELATED DONOR TRANSPLANTATION; INTERNATIONAL BLOOD; CANCER; SURVIVAL AB Adolescents and young adults (AYAs) with cancer have not experienced improvements in survival to the same extent as children and older adults. We compared outcomes among children (<15 years), AYAs (15-40 years) and older adults (>40 years) receiving allogeneic hematopoietic cell transplant (HCT) for acute myeloid leukemia (AML). Our cohort consisted of 900 children, 2,708 AYA, and 2,728 older adult recipients of HLA-identical sibling or unrelated donor (URD) transplantation using myeloablative or reduced-intensity/nonmyeloablative conditioning. Outcomes were assessed over three time periods (1980-1988, 1989-1997, 1998-2005) for siblings and two time periods (1989-1997, 1998-2005) for URD HCT. Analyses were stratified by donor type. Results showed overall survival for AYAs using either siblings or URD improved over time. Although children had better and older adults had worse survival compared with AYAs, improvements in survival for AYAs did not lag behind those for children and older adults. After sibling donor HCT, 5-year adjusted survival for the three time periods was 40%, 48%, and 53% for children, 35%, 41%, and 42% for AYAs, and 22%, 30%, and 34% for older adults. Among URD HCT recipients, 5-year adjusted survival for the two time periods was 38% and 37% for children, 24% and 28% for AYAs, and 19% and 23% for older adults. Improvements in survival occurred because of a reduction in risk of treatment-related mortality. The risk of relapse did not change over time. Improvements in survival among AYAs undergoing allogeneic HCT for AML have paralleled those among children and older adults. Biol Blood Marrow Transplant 18: 861-873 (2012) (C) 2012 American Society for Blood and Marrow Transplantation C1 [Majhail, Navneet S.; Hassebroek, Anna] Natl Marrow Donor Program, Minneapolis, MN 55413 USA. [Majhail, Navneet S.; Hassebroek, Anna] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. [Horowitz, Mary M.; Rizzo, J. Douglas] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Bredeson, Christopher N.] Ottawa Hosp, Blood & Marrow Transplant Program, Ottawa, ON, Canada. [Hahn, Theresa] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [Hale, Gregory A.] Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Maziarz, Richard T.; Hayes-Lattin, Brandon M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Wood, William A.] Univ N Carolina, Chapel Hill, NC USA. [Parsons, Susan K.] Tufts Med Ctr, Boston, MA USA. [Joffe, Steven] Dana Farber Canc Inst, Boston, MA 02115 USA. [Joffe, Steven] Childrens Hosp, Boston, MA 02115 USA. [Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Majhail, NS (reprint author), Natl Marrow Donor Program, 3001 Broadway St NE,Suite 100, Minneapolis, MN 55413 USA. EM nmajhail@nmdp.org OI Wood, William/0000-0001-7439-2543; Joffe, Steven/0000-0002-0667-7384 FU Public Health Service from National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung and Blood institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID) from NHLBI [5U01HL069294]; NCI [HHSH234200637015C]; Health Resources and Services Administration (HRSA/DHHS); Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; AABB; Allos, Inc.; Amgen, Inc.; Medical College of Wisconsin; Astellas Pharma US, Inc.; Be the Match Foundation; Biogen IDEC; BioMarin Pharmaceutical, Inc.; Biovitrum AB; Blood Center of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Eisai, Inc.; Genentech, Inc.; Genzyme Corporation; Histogenetics, Inc.; HKS Medical Information Systems; Hospira, Inc.; Kirin Brewery Co. Ltd.; Leukemia Sz: Lymphoma Society; Merck Company; Millennium Pharmaceuticals, Inc.; Miller Pharmacal Group; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Nature Publishing Group; Novartis Oncology; Oncology Nursing Society; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Pall Life Sciences; Pfizer Inc; Schering Corporation; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, Inc.; Stem Soft Software, Inc.; Sysmex America, Inc.; THERAKOS, Inc.; Vidacare Corporation; ViraCor Laboratories; ViroPharma, Inc.; Wellpoint, Inc FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 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 5U01HL069294 from NHLBI and NCI; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); two grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from AABB; Allos, Inc.; Amgen, Inc.; anonymous donation to the Medical College of Wisconsin; Astellas Pharma US, Inc.; Be the Match Foundation; Biogen IDEC; BioMarin Pharmaceutical, Inc.; Biovitrum AB; Blood Center of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Eisai, Inc.; Genentech, Inc.; Genzyme Corporation; Histogenetics, Inc.; HKS Medical Information Systems; Hospira, Inc.; Kirin Brewery Co., Ltd.; The Leukemia Sz: Lymphoma Society; Merck & Company; The Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Miller Pharmacal Group; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Nature Publishing Group; Novartis Oncology; Oncology Nursing Society; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Pall Life Sciences; Pfizer Inc; Schering Corporation; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, Inc.; Stem Soft Software, Inc.; Sysmex America, Inc.; THERAKOS, Inc.; Vidacare Corporation; ViraCor Laboratories; ViroPharma, Inc.; and Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, or any other agency of the US Government. NR 18 TC 13 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUN PY 2012 VL 18 IS 6 BP 861 EP 873 DI 10.1016/j.bbmt.2011.10.031 PG 13 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 950IM UT WOS:000304642800006 PM 22040843 ER PT J AU Ballen, KK Klein, JP Pedersen, TL Bhatla, D Duerst, R Kurtzberg, J Lazarus, HM LeMaistre, CF McCarthy, P Mehta, P Palmer, J Setterholm, M Wingard, JR Joffe, S Parsons, SK Switzer, GE Lee, SJ Rizzo, JD Majhail, NS AF Ballen, Karen K. Klein, John P. Pedersen, Tanya L. Bhatla, Deepika Duerst, Reggie Kurtzberg, Joanne Lazarus, Hillard M. LeMaistre, Charles F. McCarthy, Phillip Mehta, Paulette Palmer, Jeanne Setterholm, Michelle Wingard, John R. Joffe, Steven Parsons, Susan K. Switzer, Galen E. Lee, Stephanie J. Rizzo, J. Douglas Majhail, Navneet S. TI Relationship of Race/Ethnicity and Survival after Single Umbilical Cord Blood Transplantation for Adults and Children with Leukemia and Myelodysplastic Syndromes SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Umbilical cord blood; Leukemia; Myelodysplastic syndrome; Race; Ethnicity; Transplantation ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; INTERNATIONAL BLOOD; ETHNIC-MINORITIES; UNRELATED DONORS; OUTCOMES; POPULATIONS; REGISTRY AB The relationship of race/ethnicity with outcomes of umbilical cord blood transplantation (UCBT) is not well known. We analyzed the association between race/ethnicity and outcomes of unrelated single UCBT for leukemia and myelodysplastic syndromes. Our retrospective cohort study consisted of 885 adults and children (6 I 2 whites, 145 blacks, and 128 Hispanics) who received unrelated single UCBT for leukemia and myelodysplastic syndromes between 1995 and 2006 and were reported to the Center for International Blood and Marrow Transplant Research. A 5-6/6 FILA-matched unit with a total nucleated cell count infused of >= 2.5 x 10(7)/kg was given to 40% white and 42% Hispanic, but only 21% black patients. Overall survival at 2 years was 44%. for whites, 34% for blacks, and 46% for Hispanics (P = .008). In multivariate analysis adjusting for patient, disease, and treatment factors (including HLA match and cell dose), blacks had inferior overall survival (relative risk of death, 1.31; P = .02), whereas overall survival of Hispanics was similar (relative risk, 1.03; P = .81) to that of whites. For all patients, younger age, early-stage disease, use of units with higher cell dose, and performance status >= 80 were independent predictors of improved survival. Black patients and white patients infused with well-matched cords had comparable survival; similarly, black and white patients receiving units with adequate cell dose had similar survival. These results suggest that blacks have inferior survival to whites after single UCBT, but outcomes are improved when units with a higher cell dose are used. Biol Blood Marrow Transplant 18: 903-912 (2012) (C) 2012 American Society for Blood and Marrow Transplantation C1 [Ballen, Karen K.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Klein, John P.; Rizzo, J. Douglas] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Pedersen, Tanya L.; Majhail, Navneet S.] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. [Bhatla, Deepika] St Louis Univ, St Louis, MO 63103 USA. [Duerst, Reggie] Childrens Mem Hosp, Chicago, IL 60614 USA. [Kurtzberg, Joanne] Duke Univ, Med Ctr, Durham, NC USA. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [LeMaistre, Charles F.] Texas Transplant Inst, San Antonio, TX USA. [McCarthy, Phillip] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Mehta, Paulette] Univ Arkansas, Little Rock, AR 72204 USA. [Palmer, Jeanne] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Setterholm, Michelle] Natl Marrow Donor Program, Minneapolis, MN USA. [Wingard, John R.] Univ Florida, Shands Canc Ctr, Gainesville, FL USA. [Joffe, Steven] Dana Farber Canc Inst, Boston, MA 02115 USA. [Parsons, Susan K.] Tufts Med Ctr, Boston, MA USA. [Switzer, Galen E.] UPMC Hillman Canc Ctr, Pittsburgh, PA USA. [Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Majhail, Navneet S.] Univ Minnesota, Minneapolis, MN USA. RP Ballen, KK (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Suite 118, Boston, MA 02114 USA. EM kballen@partners.org OI Joffe, Steven/0000-0002-0667-7384 FU Public Health Service from National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID); NHLBI [5U01HL069294]; Health Resources and Services Administration (HRSA/DHHS) [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; AABB; Allos, Inc.; Amgen, Inc.; College of Wisconsin; Astellas Pharma US, Inc.; Be the Match Foundation; Biogen IDEC; BioMarin Pharmaceutical, Inc.; Biovitrum AB; Blood Center of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Eisai, Inc.; Genentech, Inc; Genzyme Corporation; Histogenetics, Inc.; HKS Medical Information Systems; Hospira, Inc.; Kirin Brewery Co., Ltd.; Leukemia & Lymphoma Society; Merck Company; Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Miller Pharmacal Group; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Nature Publishing Group; Novartis Oncology; Oncology Nursing Society; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Pall Life Sciences; Pfizer Inc; Schering Corporation; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, Inc.; Stem Soft Software, Inc.; Sysmex America, Inc.; THERAKOS, Inc.; Vidacare Corporation; ViraCor Laboratories; ViroPharma, Inc.; Wellpoint, Inc. FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 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 5U01HL069294 from NHLBI and NCI; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from AABB; Allos, Inc.; Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US, Inc.; Be the Match Foundation; Biogen IDEC; BioMarin Pharmaceutical, Inc.; Biovitrum AB; Blood Center of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Eisai, Inc.; Genentech, Inc.; Genzyme Corporation; Histogenetics, Inc.; HKS Medical Information Systems; Hospira, Inc.; Kirin Brewery Co., Ltd.; The Leukemia & Lymphoma Society; Merck & Company; The Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Miller Pharmacal Group; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Nature Publishing Group; Novartis Oncology; Oncology Nursing Society; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Pall Life Sciences; Pfizer Inc; Schering Corporation; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, Inc.; Stem Soft Software, Inc.; Sysmex America, Inc.; THERAKOS, Inc.; Vidacare Corporation; ViraCor Laboratories; ViroPharma, Inc.; and Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, or any other agency of the US Government. NR 31 TC 17 Z9 17 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUN PY 2012 VL 18 IS 6 BP 903 EP 912 DI 10.1016/j.bbmt.2011.10.040 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 950IM UT WOS:000304642800011 PM 22062801 ER PT J AU Chen, CC Lin, WC Kong, MS Shi, HN Walker, WA Lin, CY Huang, CT Lin, YC Jung, SM Lin, TY AF Chen, Chien-Chang Lin, Wei-Chuan Kong, Man-Shan Shi, Hai Ning Walker, W. Allan Lin, Chun-Yen Huang, Ching-Tai Lin, Yung-Chang Jung, Shih-Ming Lin, Tzou-Yien TI Oral inoculation of probiotics Lactobacillus acidophilus NCFM suppresses tumour growth both in segmental orthotopic colon cancer and extra-intestinal tissue SO BRITISH JOURNAL OF NUTRITION LA English DT Article DE Probiotics; Lactobacillus acidophilus NCFM; CT-26 cells; Colon carcinogenesis; Apoptosis ID CLASS-I MOLECULE; COLORECTAL-CANCER; KNOCKOUT MICE; BIFIDOBACTERIUM-LACTIS; CHEMOKINE RECEPTORS; IMMUNE-RESPONSE; MOUSE MODEL; CELLS; APOPTOSIS; BACTERIA AB Modulation of the cellular response by the administration of probiotic bacteria may be an effective strategy for preventing or inhibiting tumour growth. We orally pre-inoculated mice with probiotics Lactobacillus acidophilus NCFM (La) for 14 d. Subcutaneous dorsal-flank tumours and segmental orthotopic colon cancers were implanted into mice using CT-26 murine colon adenocarcinoma cells. On day 28 after tumour initiation, the lamina propria of the colon, mesenteric lymph nodes (MLN) and spleen were harvested and purified for flow cytometry and mRNA analyses. We demonstrated that La pre-inoculation reduced tumour volume growth by 50.3%, compared with untreated mice at 28 d after tumour implants (2465.5 (SEM 1290.4) v. 4950.9 (SEM 1689.3) mm(3), P<0.001). Inoculation with La reduced the severity of colonic carcinogenesis caused by CT-26 cells, such as level of colonic involvement and structural abnormality of epithelial/crypt damage. Moreover, La enhanced apoptosis of CT-26 cells both in dorsal-flank tumour and segmental orthotopic colon cancer, and the mean counts of apoptotic body were higher in mice pre-inoculated with La (P<0.05) compared with untreated mice. La pre-inoculation down-regulated the CXCR4 mRNA expressions in the colon, MLN and extra-intestinal tissue, compared with untreated mice (P<0.05). In addition, La pre-inoculation reduced the mean fluorescence index of MHC class I (H-2Dd, -Kd and -Ld) in flow cytometry analysis. Taken together, these findings suggest that probiotics La may play a role in attenuating tumour growth during CT-26 cell carcinogenesis. The down-regulated expression of CXCR4 mRNA and MHC class I, as well as increasing apoptosis in tumour tissue, indicated that La may be associated with modulating the cellular response triggered by colon carcinogenesis. C1 [Chen, Chien-Chang; Lin, Wei-Chuan; Kong, Man-Shan; Lin, Tzou-Yien] Chang Gung Univ, Chang Gung Mem Hosp, Chang Gung Childrens Hosp, Dept Pediat,Coll Med, Tao Yuan 333, Taiwan. [Shi, Hai Ning; Walker, W. Allan] Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA USA. [Shi, Hai Ning; Walker, W. Allan] Harvard Univ, Sch Med, Charlestown, MA USA. [Lin, Chun-Yen; Huang, Ching-Tai] Chang Gung Univ, Chang Gung Mem Hosp, Dept Internal Med, Coll Med, Tao Yuan 333, Taiwan. [Lin, Yung-Chang] Chang Gung Univ, Chang Gung Mem Hosp, Dept Hematol Oncol, Coll Med, Tao Yuan 333, Taiwan. [Jung, Shih-Ming] Chang Gung Univ, Chang Gung Mem Hosp, Dept Pathol, Coll Med, Tao Yuan 333, Taiwan. RP Lin, TY (reprint author), Chang Gung Univ, Chang Gung Mem Hosp, Chang Gung Childrens Hosp, Dept Pediat,Coll Med, 12L,5 Fu Hsing St, Tao Yuan 333, Taiwan. EM pedcgl1969@gmail.com OI Lin, Chun-Yen/0000-0003-3007-3190 FU National Science Council, Taiwan [NMRP 94-2314-B-182A-104]; Chang Gung Memorial Hospital [CMRPG 460091, 460092] FX This study was supported by NMRP 94-2314-B-182A-104 from the National Science Council, Taiwan, and by CMRPG 460091, 460092 from the Chang Gung Memorial Hospital Medical Research Project Fund. C.-C. C., W. A. W. and T.-Y. L. designed the research; C.-C. C., W.-C. L., H. N. S. and T.-Y. L. conducted the research; C.-C. C., W.-C. L., M.-S. K., C.-Y. L., C.-T. H., Y.-C. L. and S.-M. J. analysed the data; C.-C. C., H. N. S., W.-C. L. and T.-Y. L. wrote the manuscript. C.-C. C. and T.-Y. L. had primary responsibility for the final content. All authors read and approved the final manuscript. There are no conflicts of interest. NR 49 TC 17 Z9 19 U1 3 U2 16 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0007-1145 J9 BRIT J NUTR JI Br. J. Nutr. PD JUN PY 2012 VL 107 IS 11 BP 1623 EP 1634 DI 10.1017/S0007114511004934 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 953QR UT WOS:000304887300008 PM 21992995 ER PT J AU Ojha, RP Hanzis, CA Hunter, ZR Greenland, S Offutt-Powell, TN Manning, RJ Lewicki, M Brodsky, PS Ioakimidis, L Tripsas, CK Patterson, CJ Sheehy, P Singh, KP Treon, SP AF Ojha, Rohit P. Hanzis, Christina A. Hunter, Zachary R. Greenland, Sander Offutt-Powell, Tabatha N. Manning, Robert J. Lewicki, Megan Brodsky, Philip S. Ioakimidis, Leukothea Tripsas, Christina K. Patterson, Christopher J. Sheehy, Patricia Singh, Karan P. Treon, Steven P. TI Family history of non-hematologic cancers among Waldenstrom macroglobulinemia patients: A preliminary study SO CANCER EPIDEMIOLOGY LA English DT Article DE Waldenstrom Macroglobulinemia; Epidemiology; Family history; Risk factor; Breast cancer; Colorectal cancer; Lung cancer; Ovarian cancer; Prostate cancer ID AGGREGATION; MUTATIONS; LYMPHOMA AB Background: Little is known about the epidemiology and etiology of Waldenstrom macroglobulinemia (WM). Despite several studies of the relation between family history and B-cell disorders and WM, family history of non-hematologic cancers has not been systematically investigated. We thus examined associations of family history of breast, colorectal, lung, ovarian, and prostate cancers with WM. Methods: All probands aged 20-79 years with bone marrow biopsy-confirmed diagnosis of WM between May 1, 1999 and January 1, 2010 at the Bing Center for Waldenstrom Macroglobulinemia were eligible for inclusion in our analysis. We reviewed medical records for eligible probands to determine family history of cancer (defined as a cancer diagnosis for >1 first-degree relative(s) of the proband). Using expected values constructed from the United States National Health Interview Survey, we estimated age- and race-standardized rate ratios (RRs) for family history of breast, colorectal, lung, ovarian, and prostate cancers by WM subtype. Results: Family history of prostate cancer had the largest overall rate ratio (RR = 1.4, 95% confidence limits [CL]: 1.1, 1.7), and among sporadic cases, family history of prostate and breast cancer had the largest rate ratios (prostate: RR = 1.3, 95% CL: 1.1, 1.7; breast: RR = 1.3, 95% CL: 1.2, 1.6). Conclusion: Our study suggests that it may be worthwhile to pursue these associations in a case-control study with uniform selection and data collection for cases and controls, and at least some record-based information on family history. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Ojha, Rohit P.] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Hanzis, Christina A.; Hunter, Zachary R.; Manning, Robert J.; Lewicki, Megan; Brodsky, Philip S.; Ioakimidis, Leukothea; Tripsas, Christina K.; Patterson, Christopher J.; Sheehy, Patricia; Treon, Steven P.] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. [Greenland, Sander] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. [Greenland, Sander] Univ Calif Los Angeles, Coll Letters & Sci, Dept Stat, Los Angeles, CA USA. [Offutt-Powell, Tabatha N.] Univ N Texas, Hlth Sci Ctr, Dept Epidemiol, Sch Publ Hlth, Ft Worth, TX USA. [Singh, Karan P.] Univ N Texas, Hlth Sci Ctr, Dept Biostat, Sch Publ Hlth, Ft Worth, TX USA. [Treon, Steven P.] Harvard Univ, Sch Med, Boston, MA USA. RP Ojha, RP (reprint author), Dana Farber Canc Inst, Div Populat Sci, 450 Brookline Ave,SM 271, Boston, MA 02115 USA. EM rohit_ojha@dfci.harvard.edu; christina_hanzis@dfci.harvard.edu; zachary_hunter@dfci.harvard.edu; lesdomes@ucla.edu; topowell@email.unc.edu; robert_manning@dfci.harvard.edu; megan_lewicki@dfci.harvard.edu; philips_brodsky@dfci.harvard.edu; leukothea_ioakimidis@dfci.harvard.edu; christinaK_tripsas@dfci.harvard.edu; christopher_patterson@dfci.harvard.edu; patricia_sheehy@dfci.harvard.edu; karan.singh@unthsc.edu; steven_treon@dfci.harvard.edu RI Hunter, Zachary/H-3018-2013; OI Hunter, Zachary/0000-0002-1689-1691; Ojha, Rohit/0000-0003-0595-8990 FU Bing Fund for Waldenstrom's Macroglobulinemia FX This study was supported by an award from the Bing Fund for Waldenstrom's Macroglobulinemia. NR 18 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1877-7821 J9 CANCER EPIDEMIOL JI Cancer Epidemiol. PD JUN PY 2012 VL 36 IS 3 BP 294 EP 297 DI 10.1016/j.canep.2011.10.010 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 954ZU UT WOS:000304987700016 PM 22099500 ER PT J AU Palacios, IF AF Palacios, Igor F. TI Left ventricular assistant device impella 2.5 usage for patients undergoing high-risk PCI SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material ID PERCUTANEOUS CORONARY INTERVENTION; TRIAL C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Palacios, IF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. EM ipalacios@partners.org NR 8 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JUN 1 PY 2012 VL 79 IS 7 BP 1135 EP 1137 DI 10.1002/ccd.24461 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 951XN UT WOS:000304753500013 PM 22570078 ER PT J AU Ruan, GX Kazlauskas, A AF Ruan, Guo-Xiang Kazlauskas, Andrius TI VEGF-A engages at least three tyrosine kinases to activate PI3K/Akt SO CELL CYCLE LA English DT Editorial Material ID ANGIOGENESIS; MECHANISMS; CANCER; AXL C1 [Ruan, Guo-Xiang; Kazlauskas, Andrius] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA 02215 USA. RP Kazlauskas, A (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA 02215 USA. EM andrius_kazlauskas@meei.harvard.edu NR 10 TC 6 Z9 7 U1 1 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUN 1 PY 2012 VL 11 IS 11 BP 2047 EP 2048 DI 10.4161/cc.20535 PG 2 WC Cell Biology SC Cell Biology GA 952DK UT WOS:000304770100005 PM 22647379 ER PT J AU Genovese, G Ghosh, P Li, HY Rettino, A Sioletic, S Cittadini, A Sgambato, A AF Genovese, Giannicola Ghosh, Papia Li, Haiyang Rettino, Alessando Sioletic, Stefano Cittadini, Achille Sgambato, Alessandro TI The tumor suppressor HINT1 regulates MITF and beta-catenin transcriptional activity in melanoma cells SO CELL CYCLE LA English DT Article DE melanoma; tumor suppressor gene; tumorigenesis; HIT protein superfamily ID MAST-CELLS; HEPATOCELLULAR-CARCINOMA; MALIGNANT-MELANOMA; LINEAGE SURVIVAL; CANCER CELLS; FHIT GENE; EXPRESSION; GROWTH; NUCLEOTIDE; DYSTROGLYCAN AB Histidine triad nucleotide-binding protein 1 (HINT1) is a haploinsufficient tumor suppressor gene that inhibits the Wnt/beta-catenin pathway in colon cancer cells and Microphthalmia-associated transcription factor (MITF) activity in human mast cells. MITF and beta-catenin play a central role in melanocyte and melanoma cell survival, and this study aimed to investigate the effects of HINT1 on the MITF and beta-catenin pathways in malignant melanoma cells. We found that HINT1 inhibits MITF and beta-catenin transcriptional activity, and both proteins can be co-immunoprecipitated with an anti-HINT1-specific antibody in melanoma cell lines. Stable, constitutive overexpression of the HINT1 protein in human melanoma cells significantly impaired cell proliferation in vitro and tumorigenesis in vivo. These effects were associated with a decreased expression of cyclin D1 and BCL2, well known MITF and beta-catenin transcription targets, respectively. We also demonstrated that BCL2 and cyclin D1 can partially rescue the HINT1-driven phenotype. Moreover, we found in ChIP assays that HINT1 binds the chromatin at MITF and beta-catenin sites in BCL2 and cyclin D1 promoters, respectively, and that mSIN3a and HDAC1, well known transcriptional repressors, can be co-immunoprecipitated with an anti-HINT1-specific antibody. These findings support the tumor suppressor activity of HINT1 gene in melanoma cells by promoting the formation of non-functional complexes with oncogenic transcription factors like MITF and beta-catenin. C1 [Genovese, Giannicola; Rettino, Alessando; Sioletic, Stefano; Cittadini, Achille; Sgambato, Alessandro] Univ Cattolica Sacro Cuore, Ctr Ric Oncol Giovanni XXIII, Rome, Italy. [Genovese, Giannicola; Li, Haiyang] Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Ctr, New York, NY USA. [Genovese, Giannicola; Ghosh, Papia] Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Sgambato, A (reprint author), Univ Cattolica Sacro Cuore, Ctr Ric Oncol Giovanni XXIII, Rome, Italy. EM asgambato@rm.unicatt.it RI Sgambato, Alessandro/K-7266-2016 OI Sgambato, Alessandro/0000-0002-9487-4563 NR 34 TC 11 Z9 14 U1 1 U2 5 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUN 1 PY 2012 VL 11 IS 11 BP 2206 EP 2215 DI 10.4161/cc.20765 PG 10 WC Cell Biology SC Cell Biology GA 952DK UT WOS:000304770100029 PM 22647378 ER PT J AU Underhill, ML Boucher, J Roper, K Berry, DL AF Underhill, Meghan L. Boucher, Jean Roper, Kristin Berry, Donna L. TI Symptom Management Excellence Initiative: Promoting Evidence-Based Oncology Nursing Practice SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article ID FRAMEWORK AB Accessing and using the best evidence for cancer symptom interventions are prerequisites for nursing excellence. To incorporate evidence into direct care practice, staff at the Dana-Farber Cancer Institute implemented the Symptom Management Excellence initiative to compare patients' and nurses' reports of their most frequent and highest priority cancer symptoms. Interdisciplinary teams then convened to design and test the feasibility of bringing symptom management evidence into clinical practice. This article describes how the initiative has successfully used patient-reported data, direct-care nurse input, research evidence, and expert opinion to systematically improve cancer symptom management. C1 [Underhill, Meghan L.; Boucher, Jean; Roper, Kristin; Berry, Donna L.] Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA. [Boucher, Jean] Univ Massachusetts Worcester, Grad Sch Nursing, Dept Nursing & Med, Worcester, MA USA. [Boucher, Jean] Univ Massachusetts Mem Hlth Care, Worcester, MA USA. [Roper, Kristin] Univ Massachusetts Boston, Sch Nursing, Boston, MA USA. [Berry, Donna L.] Harvard Univ, Sch Med, Boston, MA USA. RP Underhill, ML (reprint author), Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA. EM meghanl_underhill@dfci.harvard.edu NR 22 TC 5 Z9 6 U1 0 U2 3 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD JUN PY 2012 VL 16 IS 3 BP 247 EP 250 DI 10.1188/12.CJON.247-250 PG 4 WC Oncology; Nursing SC Oncology; Nursing GA 953BI UT WOS:000304841500005 PM 22641315 ER PT J AU Mannix, CM Bartholomay, MM Doherty, CS Lewis, M Bilodeau, MLC AF Mannix, Catherine Marie Bartholomay, Marian Mahin Doherty, Carol S. Lewis, Maryellen Bilodeau, Mary-Liz Connors TI A Feasibility Study of Low-Cost, Self-Administered Skin Care Interventions in Patients With Head and Neck Cancer Receiving Chemoradiation SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article ID RADIATION-THERAPY; MANAGEMENT; DERMATITIS; PREVENTION; SOAP AB Current evidence for the management of radiation skin toxicities demonstrates equivocal outcomes using a variety of interventions, leaving substantial gaps in knowledge. Skin toxicities can lead to treatment delays, infection, pain, and increased costs for the patient. Patients with head and neck cancers receiving chemoradiation (N = 100), a population particularly vulnerable to disruptions in skin integrity, were enrolled into a prospective, descriptive study. Data collection was conducted and photographs were taken at baseline and weekly throughout treatment. Patients received skin care kits, instructions, and a diary to record adherence. Skin toxicity was measured and validated by at least three observers using serial photographs with 100% interrater agreement. Data were analyzed using descriptive statistics, graphs, and bivariate analysis. Adherence to both washing and moisturizing was consistently high. Although a correlation existed between the radiation dose and skin toxicity at week 6, no correlation existed between skin toxicity and adherence. Given the rate of grade 3 toxicities at week 6 and product costs, this proved to be an affordable regimen to which patients could easily adhere. Positive patient outcomes can be promoted through teaching and reinforcement of self-care measures to reduce skin toxicity. C1 [Mannix, Catherine Marie] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Bartholomay, Marian Mahin] Massachusetts Gen Hosp, Dept Patient Care Serv Nursing, Boston, MA 02114 USA. [Bilodeau, Mary-Liz Connors] Massachusetts Gen Hosp, Div Burns, Boston, MA 02114 USA. RP Mannix, CM (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM mbartholomay1@partners.org NR 21 TC 4 Z9 4 U1 0 U2 0 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD JUN PY 2012 VL 16 IS 3 BP 278 EP 285 DI 10.1188/12.CJON.278-285 PG 8 WC Oncology; Nursing SC Oncology; Nursing GA 953BI UT WOS:000304841500010 PM 22641320 ER PT J AU Weisbord, SD AF Weisbord, Steven D. TI Female Sexual Dysfunction in ESRD: An Underappreciated Epidemic? SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID QUALITY-OF-LIFE; CHRONIC KIDNEY-DISEASE; HEMODIALYSIS-PATIENTS; ERECTILE DYSFUNCTION; DIALYSIS; WOMEN; PREVALENCE; SYMPTOMS; INDEX; MEN C1 [Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Renal Sect, Med Specialty Serv Line, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Med Specialty Serv Line, 7E Room 120,111F U, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu NR 17 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JUN PY 2012 VL 7 IS 6 BP 881 EP 883 DI 10.2215/CJN.03870412 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 954VE UT WOS:000304975100003 PM 22580787 ER PT J AU Kang, EW Pike, F Ramer, S Abdel-Kader, K Myaskovsky, L Dew, MA Unruh, M AF Kang, Ea Wha Pike, Francis Ramer, Sarah Abdel-Kader, Khaled Myaskovsky, Larissa Dew, Mary Anianda Unruh, Mark TI The Association of Mental Health over Time with Cardiac Outcomes in HEMO Study Patients SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID QUALITY-OF-LIFE; STAGE RENAL-DISEASE; HEMODIALYSIS-PATIENTS; DIALYSIS PATIENTS; MAINTENANCE HEMODIALYSIS; PRACTICE PATTERNS; UNITED-STATES; MORTALITY; DEPRESSION; SF-36 AB Background and objectives Poor mental health over time is significantly associated with cardiovascular morbidity and mortality in the general population, which is the leading cause of death in dialysis patients. Most studies of dialysis patients, however, have investigated the relationship between baseline mental health measurements and all-cause mortality and not mental health measured longitudinally throughout a study and cause-specific mortality. Design, setting, participants, & measurements This study examined the association of changes in mental health over time with all-cause and cause-specific deaths and cardiac hospitalizations in the Hemodialysis study patients. Mental health was assessed at baseline and annually during the study with short form 36 mental health index scores. Poorer mental health was defined by a mental health index score <= 60. Results Patients with poorer mental health at baseline were more likely to have less than a high school education and be unmarried, have significantly higher index of coexistent disease scores, and report taking beta-blockers and sleep medications. Low mental health scores over time were independently associated with a decrease in survival time from all-cause mortality by -0.06 (-0.10, -0.03; P<0.001), and they also significantly hastened time to first cardiac hospitalization by -0.08 (-0.13, -0.02; P=0.01) and composite of first cardiac hospitalization or cardiac death by -0.04 (-0.07, -0.02; P<0.001). Conclusions This study found an independent association between poor mental health over time and all-cause mortality, cardiac hospitalization, and the composite of cardiac death or cardiac hospitalization in hemodialysis patients. The results underscore the importance of attention to mental health related to cardiac complications and even death in dialysis patients. Clin J Am Soc Nephrol 7: 957-964, 2012. doi: 10.2215/CJN.06730711 C1 [Unruh, Mark] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Med Ctr, Pittsburgh, PA 15213 USA. [Kang, Ea Wha] Natl Hlth Insurance Corp, Dept Med, Ilsan Hosp, Goyangshi, Gyeonggi Do, South Korea. [Myaskovsky, Larissa] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Myaskovsky, Larissa] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Dew, Mary Anianda] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15213 USA. RP Unruh, M (reprint author), Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Med Ctr, 200 Lothrop St,PUH C-1111, Pittsburgh, PA 15213 USA. EM unruh@pitt.edu OI Abdel-Kader, Khaled/0000-0002-6412-8498 FU NIDDK NIH HHS [K23 DK090304] NR 46 TC 8 Z9 9 U1 0 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JUN PY 2012 VL 7 IS 6 BP 957 EP 964 DI 10.2215/CJN.06730711 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 954VE UT WOS:000304975100013 PM 22490873 ER PT J AU Motiwala, SR Wang, TJ AF Motiwala, Shweta R. Wang, Thomas J. TI Vitamin D and Cardiovascular Risk SO CURRENT HYPERTENSION REPORTS LA English DT Article DE Vitamin D; Cardiovascular disease; Blood pressure; Hypertension; Diabetes mellitus; Coronary artery disease; Cardiovascular risk ID 25-HYDROXYVITAMIN D LEVELS; BETA-CELL FUNCTION; NUTRITION EXAMINATION SURVEY; RENIN-ANGIOTENSIN SYSTEM; 3RD NATIONAL-HEALTH; RANDOMIZED CONTROLLED-TRIAL; CALCIUM/VITAMIN-D SUPPLEMENTATION; CORONARY-ARTERY CALCIFICATION; TYPE-2 DIABETES-MELLITUS; INSULIN-RECEPTOR GENE AB Vitamin D deficiency is a common condition that has well-documented effects on musculoskeletal health. A growing body of literature has related vitamin D deficiency to other chronic disorders, including cardiovascular disease. Several plausible biological mechanisms have been postulated to explain this association, including the effect of poor vitamin D status on intermediate risk factors (eg, hypertension and diabetes), neurohormonal activation, inflammation, and cardiac remodeling. These mechanisms have been explored in experimental and animal studies, as well as several small interventional studies. The results of the controlled trials have not been conclusive to date. In this review, we summarize the existing studies investigating the effects of vitamin D on cardiovascular health, and propose that additional well-designed, prospective, randomized controlled trials are necessary to delineate the appropriate role of vitamin D supplementation in reducing the burden of cardiovascular disease. C1 [Motiwala, Shweta R.; Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Wang, TJ (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB 800,55 Fruit St, Boston, MA 02114 USA. EM tjwang@partners.org FU National Institutes of Health; American Heart Association; Diasorin FX Dr. Wang has received research support from the National Institutes of Health and the American Heart Association.; Dr. Wang has participated on the scientific advisory board for, served as a consultant for, been paid for the development of educational presentations by, and received research support from Diasorin. NR 113 TC 16 Z9 17 U1 2 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1522-6417 J9 CURR HYPERTENS REP JI Curr. Hypertens. Rep. PD JUN PY 2012 VL 14 IS 3 BP 209 EP 218 DI 10.1007/s11906-012-0262-y PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 953GM UT WOS:000304855000004 PM 22457243 ER PT J AU Maker, MP Noble, J Silva, PS Cavallerano, JD Murtha, TJ Sun, JK Aiello, LM Bursell, SE Aiello, LP AF Maker, Manvi P. Noble, Jason Silva, Paolo S. Cavallerano, Jerry D. Murtha, Timothy J. Sun, Jennifer K. Aiello, Lloyd M. Bursell, Sven-Erik Aiello, Lloyd Paul TI Automated Retinal Imaging System (ARIS) Compared with ETDRS Protocol Color Stereoscopic Retinal Photography to Assess Level of Diabetic Retinopathy SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID SLIDE FILM; TELEOPHTHALMOLOGY; IDENTIFICATION; TELEMEDICINE; AGREEMENT; CAMERA AB Background: Early Treatment Diabetic Retinopathy Study (ETDRS) seven-standard-field color stereoscopic retinal photography (ETDRS photos) has been a gold standard for determining diabetic retinopathy (DR) severity. The Automated Retinal Imaging System (ARIS (TM), model 110, Visual Pathways, Inc., Prescott, AZ) acquires seven-sequential color stereoscopic digital images (ARTS images) by a semiautomated technician-run process generally corresponding to ETDRS photos. We assessed the correlation between a single semiautomated ARIS imaging session without any re-imaging and ETDRS photos performed by a certified photographer for the determination of DR severity. Methods: Two independent masked readers graded mydriatic ARTS images and ETDRS photos. A third masked retinal specialist adjudicated discrepancies. Correlation between the two modalities was compared using weighted-kappa statistics. Results: We evaluated 211 eyes of 106 patients with varying levels of DR. Partially ungradable images were present in 3.4% of ETDRS photos versus 31.8% of ARIS images. Exact agreement and agreement within one level between ETDRS photos and ARIS images using only completely gradable image sets occurred in 69% (kappa=0.81) and 90% of cases, respectively. Exact agreement for clinically significant macular edema was 92.1% (kappa=0.59). There was 100% agreement for eyes with high-risk proliferative DR. Within one level of DR severity, 100% agreement occurred for the following: questionable nonproliferative DR (NPDR), moderate NPDR, and severe NPDR. Conclusions: Results suggest that semiautomated ARIS images compare favorably with ETDRS photos when full image sets can be obtained; however, partially ungradable image sets occurred almost 10 times more frequently with ARTS images than with ETDRS photos. In the two-thirds of cases where ARTS images can be utilized, ARTS can obtain retinal images comparable to ETDRS photos while requiring less highly trained personnel than generally needed for standard ETDRS photos. C1 [Maker, Manvi P.; Noble, Jason; Silva, Paolo S.; Cavallerano, Jerry D.; Murtha, Timothy J.; Sun, Jennifer K.; Aiello, Lloyd M.; Aiello, Lloyd Paul] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [Bursell, Sven-Erik] Univ Hawaii, Telehlth Res Inst, Honolulu, HI 96822 USA. RP Silva, PS (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM paoloantonio.silva@joslin.harvard.edu NR 20 TC 7 Z9 7 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD JUN PY 2012 VL 14 IS 6 BP 515 EP 522 DI 10.1089/dia.2011.0270 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 952JI UT WOS:000304788400012 PM 22385213 ER PT J AU Markowitz, JT Pratt, K Aggarwal, J Volkening, LK Laffel, LMB AF Markowitz, Jessica T. Pratt, Katherine Aggarwal, Jyoti Volkening, Lisa K. Laffel, Lori M. B. TI Psychosocial Correlates of Continuous Glucose Monitoring Use in Youth and Adults with Type 1 Diabetes and Parents of Youth SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article AB Background: Continuous glucose monitoring (CGM) has been shown to improve glycemic control and reduce hypoglycemia with consistent use. Youth, however, are unlikely to use CGM consistently. We compared psychological characteristics of youth with type 1 diabetes, their parents, and adults with type 1 diabetes randomized to CGM or standard blood glucose monitoring (BGM). This study was an ancillary study, and participants completed the questionnaires at the 6-month visit of the main study. Subjects and Methods: Participants enrolled at a single site of the Juvenile Diabetes Research Foundation CGM trial completed questionnaires and provided diabetes management data. Participants were randomized to the CGM or BGM group for 6 months. Results: Parents in both groups reported more fear of hypoglycemia than youth in the corresponding groups. CGM youth and parents reported more negative affect around BGM than those in the BGM group. CGM youth reported more trait anxiety than BGM youth, whereas CGM adults reported less state and trait anxiety than BGM adults. CGM parent-proxy report of depression was significantly higher than that reported by BGM parents. Conclusions: Youth, their parents, and adults report different psychological impacts of CGM use. In some groups and with some variables, CGM use was associated with a positive psychosocial impact, whereas in others CGM use was associated with a negative psychosocial impact. Future research should explore the psychological consequences of CGM use. C1 [Laffel, Lori M. B.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. RP Laffel, LMB (reprint author), Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu FU National Institutes of Health [T32 DK007260]; Juvenile Diabetes Research Foundation International; Katherine Adler Astrove Youth Education Fund; Maria Griffin Drury Pediatric Fund FX This work was supported in part by National Institutes of Health Training Grant T32 DK007260, the Juvenile Diabetes Research Foundation International, the Katherine Adler Astrove Youth Education Fund, and the Maria Griffin Drury Pediatric Fund. J.T.M. wrote the manuscript, K.P. researched data, J.A. researched and analyzed data, L.K.V. researched data and reviewed/edited the manuscript, and L.M.B.L. researched data and reviewed/edited the manuscript. NR 15 TC 15 Z9 17 U1 2 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD JUN PY 2012 VL 14 IS 6 BP 523 EP 526 DI 10.1089/dia.2011.0201 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 952JI UT WOS:000304788400013 PM 22524590 ER PT J AU Bangi, E Pitsouli, C Rahme, LG Cagan, R Apidianakis, Y AF Bangi, Erdem Pitsouli, Chrysoula Rahme, Laurence G. Cagan, Ross Apidianakis, Yiorgos TI Immune response to bacteria induces dissemination of Ras-activated Drosophila hindgut cells SO EMBO REPORTS LA English DT Article DE Drosophila; cancer; innate immunity ID GENE-EXPRESSION; HOST-DEFENSE; MELANOGASTER; INFECTION; CANCER; ULTRASTRUCTURE; INVASION; GROWTH AB Although pathogenic bacteria are suspected contributors to colorectal cancer progression, cancer-promoting bacteria and their mode of action remain largely unknown. Here we report that sustained infection with the human intestinal colonizer Pseudomonas aeruginosa synergizes with the Ras1(V12) oncogene to induce basal invasion and dissemination of hindgut cells to distant sites. Cross-talk between infection and dissemination requires sustained activation by the bacteria of the Imd-dTab2-dTak1 innate immune pathway, which converges with Ras1(V12) signalling on JNK pathway activation, culminating in extracellular matrix degradation. Hindgut, but not midgut, cells are amenable to this cooperative dissemination, which is progressive and genetically and pharmacologically inhibitable. Thus, Drosophila hindgut provides a valuable system for the study of intestinal malignancies. C1 [Pitsouli, Chrysoula; Apidianakis, Yiorgos] Univ Cyprus, Dept Biol Sci, CY-1678 Nicosia, Cyprus. [Bangi, Erdem; Cagan, Ross] Mt Sinai Sch Med, Dept Dev & Regenerat Biol, New York, NY 10029 USA. [Rahme, Laurence G.; Apidianakis, Yiorgos] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. [Rahme, Laurence G.; Apidianakis, Yiorgos] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rahme, Laurence G.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA. [Rahme, Laurence G.; Apidianakis, Yiorgos] Shriners Burn Inst, Boston, MA 02114 USA. RP Apidianakis, Y (reprint author), Univ Cyprus, Dept Biol Sci, CY-1678 Nicosia, Cyprus. EM apidiana@ucy.ac.cy OI Apidianakis, Yiorgos/0000-0002-7465-3560 FU National Cancer Institute [R01-CA109730] FX We thank Bernard Mathey-Prevot for critical comments on the manuscript. E. B. and R. C. were supported by National Cancer Institute grant R01-CA109730. NR 27 TC 21 Z9 21 U1 3 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-221X EI 1469-3178 J9 EMBO REP JI EMBO Rep. PD JUN PY 2012 VL 13 IS 6 BP 569 EP 576 DI 10.1038/embor.2012.44 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 956DG UT WOS:000305069400020 PM 22498775 ER PT J AU Vandenberg, LN Colborn, T Hayes, TB Heindel, JJ Jacobs, DR Lee, DH Shioda, T Soto, AM vom Saal, FS Welshons, WV Zoeller, RT Myers, JP AF Vandenberg, Laura N. Colborn, Theo Hayes, Tyrone B. Heindel, Jerrold J. Jacobs, David R., Jr. Lee, Duk-Hee Shioda, Toshi Soto, Ana M. vom Saal, Frederick S. Welshons, Wade V. Zoeller, R. Thomas Myers, John Peterson TI Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses SO ENDOCRINE REVIEWS LA English DT Review ID ESTROGEN-RECEPTOR-ALPHA; BISPHENOL-A EXPOSURE; MAMMARY-GLAND DEVELOPMENT; BREAST-CANCER-CELLS; MESSENGER-RNA EXPRESSION; IN-UTERO EXPOSURE; LONG-EVANS RATS; PERSISTENT ORGANIC POLLUTANTS; NUTRITION EXAMINATION SURVEY; SERUM DIOXIN CONCENTRATIONS AB For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of "the dose makes the poison," because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from the cell culture, animal, and epidemiology literature. We illustrate that nonmonotonic responses and low-dose effects are remarkably common in studies of natural hormones and EDCs. Whether low doses of EDCs influence certain human disorders is no longer conjecture, because epidemiological studies show that environmental exposures to EDCs are associated with human diseases and disabilities. We conclude that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health. (Endocrine Reviews 33: 378-455, 2012) C1 [Vandenberg, Laura N.] Tufts Univ, Ctr Regenerat & Dev Biol, Medford, MA 02155 USA. [Vandenberg, Laura N.] Tufts Univ, Dept Biol, Medford, MA 02155 USA. [Colborn, Theo] Endocrine Disrupt Exchange, Paonia, CO 81428 USA. [Hayes, Tyrone B.] Univ Calif Berkeley, Lab Integrat Studies Amphibian Biol, Grp Endocrinol, Energy & Resources Grp,Museum Vertebrate Zool, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA. [Heindel, Jerrold J.] NIEHS, Div Extramural Res & Training, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. [Jacobs, David R., Jr.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA. [Lee, Duk-Hee] Kyungpook Natl Univ, Sch Med, Dept Prevent Med, Taegu 702701, South Korea. [Shioda, Toshi] Massachusetts Gen Hosp, Ctr Canc Res, Mol Profiling Lab, Charlestown, MA 02129 USA. [Soto, Ana M.] Tufts Univ, Sch Med, Dept Anat & Cellular Biol, Boston, MA 02111 USA. [vom Saal, Frederick S.] Univ Missouri, Div Biol Sci, Columbia, MO 65211 USA. [Welshons, Wade V.] Univ Missouri, Dept Biomed Sci, Columbia, MO 65211 USA. [Zoeller, R. Thomas] Univ Massachusetts, Dept Biol, Amherst, MA 01003 USA. [Myers, John Peterson] Environm Hlth Sci, Charlottesville, VA 22902 USA. RP Vandenberg, LN (reprint author), Tufts Univ, Ctr Regenerat & Dev Biol, 200 Boston Ave,Suite 4600, Medford, MA 02155 USA. EM laura.vandenberg@tufts.edu; jpmyers@ehsciences.org FU National Institutes of Health (NIH) [GM 087107, ES 08314, ES 010026, ES018764, HL 53560]; Susan G. Komen for Cure [FAS0703860]; Mitchell Kapor Foundation; Cornell-Douglas Foundation; Wallace Global Fund; Kendeda Foundation; UMC [MO-VMFC0018] FX This work was supported by National Institutes of Health (NIH) Grants GM 087107 (to L.N.V.), ES 08314 (to A.M.S.), ES 010026 (to R.T.Z.), ES018764 (to F.S.v.S.), HL 53560 (to D.R.J.), UMC MO-VMFC0018 (to W.V.W.), a Susan G. Komen for Cure Grant FAS0703860 (to T.S.), grants from the Mitchell Kapor Foundation, the Cornell-Douglas Foundation, and the Wallace Global Fund (to T.B.H.) and a grant from the Kendeda Foundation ( to J.P.M.). This article may be the work product of an employee or group of employees of the National Institute of Environmental Health Sciences (NIEHS), NIH; however, the statements, opinions or conclusions contained therein do not necessarily represent the statements, opinions or conclusions of NIEHS, NIH, or the U.S. government. NR 843 TC 738 Z9 767 U1 77 U2 491 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2012 VL 33 IS 3 BP 378 EP 455 DI 10.1210/er.2011-1050 PG 78 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 956KR UT WOS:000305089000004 PM 22419778 ER PT J AU Rosen, CJ Adams, JS Bikle, DD Black, DM Demay, MB Manson, JE Murad, MH Kovacs, CS AF Rosen, Clifford J. Adams, John S. Bikle, Daniel D. Black, Dennis M. Demay, Marie B. Manson, Joann E. Murad, M. Hassan Kovacs, Christopher S. TI The Nonskeletal Effects of Vitamin D: An Endocrine Society Scientific Statement SO ENDOCRINE REVIEWS LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; SERUM 25-HYDROXYVITAMIN D; RECEPTOR-KNOCKOUT MICE; HUMAN SYNCYTIOTROPHOBLAST CELLS; NUTRITION EXAMINATION SURVEY; PLACEBO-CONTROLLED TRIAL; D-DEFICIENCY RICKETS; D-BINDING PROTEIN; THYROID-HORMONE RECEPTOR; BLOOD MONONUCLEAR-CELLS AB Significant controversy has emerged over the last decade concerning the effects of vitamin D on skeletal and nonskeletal tissues. The demonstration that the vitamin D receptor is expressed in virtually all cells of the body and the growing body of observational data supporting a relationship of serum 25-hydroxyvitamin D to chronic metabolic, cardiovascular, and neoplastic diseases have led to widespread utilization of vitamin D supplementation for the prevention and treatment of numerous disorders. In this paper, we review both the basic and clinical aspects of vitamin D in relation to nonskeletal organ systems. We begin by focusing on the molecular aspects of vitamin D, primarily by examining the structure and function of the vitamin D receptor. This is followed by a systematic review according to tissue type of the inherent biological plausibility, the strength of the observational data, and the levels of evidence that support or refute an association between vitamin D levels or supplementation and maternal/child health as well as various disease states. Although observational studies support a strong case for an association between vitamin D and musculoskeletal, cardiovascular, neoplastic, and metabolic disorders, there remains a paucity of large-scale and long-term randomized clinical trials. Thus, at this time, more studies are needed to definitively conclude that vitamin D can offer preventive and therapeutic benefits across a wide range of physiological states and chronic nonskeletal disorders. (Endocrine Reviews 33: 456-492, 2012) C1 [Rosen, Clifford J.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Adams, John S.] Univ Calif Los Angeles, Orthopaed Hosp, Dept Orthoped Surg, Los Angeles, CA 90095 USA. [Bikle, Daniel D.] Univ Calif San Francisco, San Francisco, CA 94121 USA. [Black, Dennis M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Demay, Marie B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. [Manson, Joann E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02215 USA. [Murad, M. Hassan] Mayo Clin, Coll Med, Rochester, MN 55905 USA. [Kovacs, Christopher S.] Mem Univ Newfoundland, St John, NF A1B 3V6, Canada. RP Rosen, CJ (reprint author), Maine Med Ctr, Res Inst, 81 Res Dr, Scarborough, ME 04074 USA. EM crofen@gmail.com RI Adams, John/I-3365-2013; OI Adams, John/0000-0001-9607-5020; Kovacs, Christopher/0000-0002-5219-9993; Murad, Mohammad Hassan/0000-0001-5502-5975 FU National Institutes of Health [DK092759, UL1RR033176, UL1TR000124, R21AR056885, RO1AI073539, T32AR059033, RO1 AR050023]; Veterans Administration [DK46974]; Canadian Institutes of Health Research [MOP-84253, CA13896] FX This work was supported by funding from the National Institutes of Health [Grants DK092759 (to CJR); UL1RR033176, UL1TR000124, R21AR056885, RO1AI073539, T32AR059033 (to JSA); and RO1 AR050023 (to DDB)], the Veterans Administration [Grant DK46974(to MBD)] and the Canadian Institutes of Health Research [Grants MOP-84253 (to CSK) and CA13896 (to JEM)]. NR 336 TC 222 Z9 229 U1 10 U2 42 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2012 VL 33 IS 3 BP 456 EP 492 DI 10.1210/er.2012-1000 PG 37 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 956KR UT WOS:000305089000005 PM 22596255 ER PT J AU Motazacker, MM Pirruccello, J Huijgen, R Do, R Gabriel, S Peter, J Kuivenhoven, JA Defesche, JC Kastelein, JJP Hovingh, GK Zelcer, N Kathiresan, S Fouchier, SW AF Motazacker, Mohammad Mahdi Pirruccello, James Huijgen, Roeland Do, Ron Gabriel, Stacey Peter, Jorge Kuivenhoven, Jan Albert Defesche, Joep C. Kastelein, John J. P. Hovingh, G. Kees Zelcer, Noam Kathiresan, Sekar Fouchier, Sigrid W. TI Advances in genetics show the need for extending screening strategies for autosomal dominant hypercholesterolaemia SO EUROPEAN HEART JOURNAL LA English DT Article DE Autosomal dominant hypercholesterolaemia; Familial defective apolipoproteinaemia B; APOB; LDL; Exome sequencing; Linkage analysis ID DEFECTIVE APOLIPOPROTEIN B-100; CELL-SURFACE RECEPTORS; APO-B GENE; DENSITY-LIPOPROTEIN CHOLESTEROL; FAMILIAL HYPERCHOLESTEROLEMIA; LDL RECEPTOR; PLASMA-LIPOPROTEINS; CLINICAL-DIAGNOSIS; LINKAGE ANALYSIS; MOLECULAR-BASIS AB Autosomal dominant hypercholesterolaemia (ADH) is a major risk factor for coronary artery disease. This disorder is caused by mutations in the genes coding for the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9). However, in 41 of the cases, we cannot find mutations in these genes. In this study, new genetic approaches were used for the identification and validation of new variants that cause ADH. Using exome sequencing, we unexpectedly identified a novel APOB mutation, p.R3059C, in a small-sized ADH family. Since this mutation was located outside the regularly screened APOB region, we extended our routine sequencing strategy and identified another novel APOB mutation (p.K3394N) in a second family. In vitro analyses show that both mutations attenuate binding to the LDLR significantly. Despite this, both mutations were not always associated with ADH in both families, which prompted us to validate causality through using a novel genetic approach. This study shows that advances in genetics help increasing our understanding of the causes of ADH. We identified two novel functional APOB mutations located outside the routinely analysed APOB region, suggesting that screening for mutations causing ADH should encompass the entire APOB coding sequence involved in LDL binding to help identifying and treating patients at increased cardiovascular risk. C1 [Motazacker, Mohammad Mahdi; Peter, Jorge; Kuivenhoven, Jan Albert; Defesche, Joep C.; Fouchier, Sigrid W.] Univ Amsterdam, Acad Med Ctr, Dept Expt Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Motazacker, Mohammad Mahdi; Huijgen, Roeland; Kastelein, John J. P.; Hovingh, G. Kees; Fouchier, Sigrid W.] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Pirruccello, James; Do, Ron; Gabriel, Stacey; Kathiresan, Sekar] Broad Inst, Cambridge, MA 02142 USA. [Pirruccello, James; Do, Ron; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Pirruccello, James; Do, Ron; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Pirruccello, James] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. [Do, Ron; Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Zelcer, Noam; Fouchier, Sigrid W.] Univ Amsterdam, Acad Med Ctr, Dept Med Biochem, NL-1105 AZ Amsterdam, Netherlands. RP Fouchier, SW (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Expt Vasc Med, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. EM s.w.fouchier@amc.uva.nl RI Fouchier, Sigrid/A-8310-2011 FU European Union (EU) [FP6-2005-LIFESCIHEALTH-6, 037631]; Fondation LeDucq (Transatlantic Network); Human Frontier Science Program Organization; VIDI from the Netherlands Organization for Scientific Research (NWO); Dutch Heart Foundation [2010T082] FX This work was supported by the European Union (EU FP6-2005-LIFESCIHEALTH-6; STREP contract number 037631; J.A.K. and M.M.M.) and has been partially funded by Fondation LeDucq (Transatlantic Network, 2009-2014, M.M.M.); N.Z. is supported by a Career Development Award from the Human Frontier Science Program Organization and by a VIDI grant from the Netherlands Organization for Scientific Research (NWO).; Dr J.J.P.K. is a recipient of the Lifetime Achievement Award of the Dutch Heart Foundation (2010T082). NR 65 TC 31 Z9 31 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD JUN PY 2012 VL 33 IS 11 BP 1360 EP 1366 DI 10.1093/eurheartj/ehs010 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 952ZA UT WOS:000304833800019 PM 22408029 ER PT J AU Lutz, HH Sackett, SD Kroy, DC Gassler, N Trautwein, C AF Lutz, H. H. Sackett, S. D. Kroy, D. C. Gassler, N. Trautwein, C. TI Deletion of gp130 in myeloid cells modulates IL-6-release and is associated with more severe liver injury of Con A hepatitis SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Article DE gp130; LysMCre; Concanavalin A; Hepatitis; IL-6; Macrophages ID CONCANAVALIN-A; MACROPHAGES; MICE; HEPATOCYTES; ACTIVATION; STAT3; PATHWAYS; SOCS3; IL-6; LPS AB IL-6/gp130 dependent signaling plays an important role in modulating inflammation in acute and chronic diseases. The course of Concanavalin A- (Con A) induced hepatitis can be modulated by different immune-mediated mechanisms. IL-6/gp130-dependent signaling has been shown to be protective in hepatocytes. However, the role of this pathway in myeloid cells has not yet been studied. In our present study we used macrophage/neutrophil-specific gp130 knockout (gp130(Delta Lys), KO) animals and analyzed its relevance in modulating Con A-induced hepatitis. Additionally, we performed in vitro studies with gp130(Delta Lys)-macrophages. We demonstrate that gp130(Delta Lys), animals are more susceptible to Con A-induced hepatitis. This is reflected by higher transaminases, higher lethality and more severe liver injury as shown by histological staining. Using flow cytometry analysis we further could show that increased liver injury of gp130(Delta Lys) animals is associated with a stronger infiltration of CD11b/F4/80 double-positive cells compared to wild-type (gp130(flox/flox), WT) controls. To further characterize our observations we studied thioglycolate-elicited peritoneal macrophages from gp130(Delta Lys) animals. Interestingly, the LPS-dependent IL-6 release in gp130(Delta Lys) macrophages is significantly reduced (p < 0.05) compared to WT macrophages. Additionally, IL-6 blood levels in vivo after Con A injection were significantly lower in gp130(Delta Lys) animals compared to WT animals (p < 0.05). In summary, our results suggest that gp130-deletion in macrophages and granulocytes leads to diminished IL-6 release from these cells, which is associated with more severe Con A-induced hepatitis. (C) 2011 Elsevier GmbH. All rights reserved. C1 [Lutz, H. H.; Sackett, S. D.; Kroy, D. C.; Trautwein, C.] Univ Aachen RWTH, RWTH Univ Hosp Aachen, Dept Gastroenterol & Metab Disorders, D-52074 Aachen, Germany. [Gassler, N.] RWTH Univ Hosp Aachen, Inst Pathol, Aachen, Germany. [Kroy, D. C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Trautwein, C (reprint author), Univ Aachen RWTH, RWTH Univ Hosp Aachen, Dept Gastroenterol & Metab Disorders, Pauwelsstr 30, D-52074 Aachen, Germany. EM ctrautwein@ukaachen.de FU Deutsche Forschungsgemeinschaft [DFG/SFB542-C14] FX The authors wish to express their gratitude to Leif E. Sander for high-quality technical assistance and invaluable advice throughout the project. This project was funded by the Deutsche Forschungsgemeinschaft (DFG/SFB542-C14). This work is dedicated to Professor Micheal P. Manns on the occasion of his 60th birthday. NR 18 TC 5 Z9 6 U1 1 U2 3 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD JUN-JUL PY 2012 VL 91 IS 6-7 BP 576 EP 581 DI 10.1016/j.ejcb.2011.09.006 PG 6 WC Cell Biology SC Cell Biology GA 956QB UT WOS:000305103100016 PM 22018663 ER PT J AU O'Connor, CM Mentz, RJ Cotter, G Metra, M Cleland, JG Davison, BA Givertz, MM Mansoor, GA Ponikowski, P Teerlink, JR Voors, AA Fiuzat, M Wojdyla, D Chiswell, K Massie, BM AF O'Connor, Christopher M. Mentz, Robert J. Cotter, Gad Metra, Marco Cleland, John G. Davison, Beth A. Givertz, Michael M. Mansoor, George A. Ponikowski, Piotr Teerlink, John R. Voors, Adriaan A. Fiuzat, Mona Wojdyla, Daniel Chiswell, Karen Massie, Barry M. TI The PROTECT in-hospital risk model: 7-day outcome in patients hospitalized with acute heart failure and renal dysfunction SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Heart failure; Risk model; Risk score; Worsening heart failure ID INITIATE LIFESAVING TREATMENT; NATIONAL REGISTRY ADHERE; ORGANIZED PROGRAM; OPTIMIZE-HF; MORTALITY; SURVIVAL; PREDICTORS; IMPACT; SCORE; ASSOCIATION AB In patients with acute heart failure (AHF), early worsening heart failure (WHF) predicts a significant proportion of post-discharge readmissions and mortality. We aimed to identify the predictors of 7-day heart failure events or death in patients hospitalized with AHF. A predictive model and risk score for the short-term primary composite endpoint of 7-day death, HF rehospitalization, or WHF was created using variables collected within 24 h of admission from patients with complete data (n 2015) enrolled in the PROTECT trial of AHF patients. The 7-day composite was experienced by 294 patients (14.6), with a mortality rate of 1.8 (n 37), HF rehospitalization rate of 0.5 (n 9), and WHF rate of 13.1 (n 264). In multivariable analyses, the strongest predictor of short-term morbidity and mortality was higher blood urea nitrogen (BUN) concentration. Additional independent predictors of a worse outcome were lower serum albumin, cholesterol, and systolic blood pressure, as well as higher heart rate and respiratory rate. Model coefficients were converted to an additive risk score for predicting the 7-day composite endpoint with a total point range of 0100. The risk score allowed discrimination of a wide spectrum of risk (4.8 risk with score 35, to 28.7 risk with score 55). Using the PROTECT 7-day risk model and score, the main determinants of an adverse outcome for AHF patients included impaired metabolic status, neurohormonal activation, and reduced cardiac performance, gauged by BUN, serum albumin and cholesterol levels, systolic blood pressure, heart rate, and respiratory rate. C1 [O'Connor, Christopher M.] Duke Univ, Med Ctr, Div Cardiol, Duke Clin Res Inst, Durham, NC 27710 USA. [Cotter, Gad; Davison, Beth A.] Momentum Res Inc, Durham, NC USA. [Metra, Marco] Univ Brescia, Pzza Spedali Civili, Brescia, Italy. [Cleland, John G.] Univ Hull, Kingston Upon Hull, Yorks, England. [Givertz, Michael M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Mansoor, George A.] Merck Res Labs, Rahway, NJ USA. [Ponikowski, Piotr] Kardiol Klin, Wroclaw, Poland. [Teerlink, John R.; Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Teerlink, John R.; Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. RP O'Connor, CM (reprint author), Duke Univ, Med Ctr, Div Cardiol, Duke Clin Res Inst, Box 3356, Durham, NC 27710 USA. EM christophe.oconnor@dm.duke.edu RI Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Davison, Beth/0000-0003-2374-6449; Cleland, John/0000-0002-1471-7016; Metra, Marco/0000-0001-6691-8568 FU NovaCardia, a subsidiary of Merck; Merck; Abbott; Amgen; Biogen Idec; Corthera; Cytokinetics; Johnson and Johnson; Scios; Novartis; Relypsa; Solvay; NovaCardia FX The PROTECT trial was supported by NovaCardia, a subsidiary of Merck.; C.M.O. is a consultant to Merck which purchased the rights to rolofylline from NovaCardia, sponsors of the PROTECT study, after completion of the PROTECT pilot study. G. C. and B. A. D are employees of Momentum Research Inc., which was contracted to perform work on the project by Merck & Co, Inc. M. M. has received honoraria and reimbursements from NovaCardia and from Merck. J.G.C. was on the Steering Committee for the study, served on the Advisory Board for MSD, and received payments for both. M. M. G. has received institutional research support and served on a scientific Advisory Board for Merck. G. A. M. is an employee of Merck. P. P. has received honoraria from Merck. J.R.T. has received research funds and consulting fees from Merck for the conduct of this study and has also received research funds and consulting fees from Abbott, Amgen, Biogen Idec, Corthera, Cytokinetics, Johnson and Johnson, Scios, Novartis, Relypsa, and Solvay for research in related areas. A. A. V. has received speakers and consultancy fees from Merck. B. M. M. has received consulting fees from NovaCardia and from Merck. The remaining authors report no relevant conflicts of interest. NR 34 TC 44 Z9 44 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD JUN PY 2012 VL 14 IS 6 BP 605 EP 612 DI 10.1093/eurjhf/hfs029 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 948VH UT WOS:000304530400008 PM 22535795 ER PT J AU Chatterjee, NA Upadhyay, GA Ellenbogen, KA Hayes, DL Singh, JP AF Chatterjee, Neal A. Upadhyay, Gaurav A. Ellenbogen, Kenneth A. Hayes, David L. Singh, Jagmeet P. TI Atrioventricular nodal ablation in atrial fibrillation: a meta-analysis of biventricular vs. right ventricular pacing mode SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Atrioventricular node; Biventricular pacing; Heart failure; Ablation; Fibrillation; Meta-analysis ID QUALITY-OF-LIFE; CARDIAC-RESYNCHRONIZATION THERAPY; PERMANENT PACEMAKER IMPLANTATION; HEART-FAILURE PATIENTS; CATHETER ABLATION; JUNCTION ABLATION; HEMODYNAMIC DETERIORATION; INTRAINDIVIDUAL CHANGES; CONDUCTION SYSTEM; RHYTHM CONTROL AB For patients with refractory atrial fibrillation (AF) undergoing atrioventricular nodal ablation (AVNA), initial single-chamber right ventricular (RV)-only pacing is standard. Given the deleterious effects of chronic RV-only pacing, the impact of an initial biventricular (BiV) pacing strategy post-ablation is of interest. We conducted a meta-analysis to determine the effect of BiV vs. RV-only pacing in patients undergoing AVNA for refractory atrial fibrillation. A search of multiple electronic databases identified 921 reports, which included four randomized controlled trials (n 534). Mean New York Heart Association (NYHA) class was 2.3 and mean left ventricular ejection fraction (LVEF) was 44. When compared with RV-only pacing, BiV pacing was not associated with reduced mortality [risk ratio 0.85, 95 confidence interval (CI) 0.401.82, P 0.68]. In three studies comprised of patients with left ventricular systolic dysfunction (mean EF 41 3), BiV pacing demonstrated a non-significant reduction in cardiac mortality (risk ratio 0.59, 95 CI 0.251.39; P 0.23). Compared with RV-only pacing, BiV pacing was associated with significant improvement in symptoms [Minnesota Living with Heart Failure Questionnaire (MLWHFQ) 2.72 points fewer, 95 CI 1.453.99] and increased LVEF (2.6, 95 CI 1.693.44), but no significant change in 6 min walk distance (6MWD) (5.02 ms more, 95 CI 1.56 to 11.59; P 0.13). In patients with refractory AF undergoing AVNA, BiV pacing was not associated with significantly improved survival when compared with RV-only pacing. A modest, but significant improvement in structural and functional response to BiV pacing was observed. C1 [Chatterjee, Neal A.; Upadhyay, Gaurav A.; Singh, Jagmeet P.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02411 USA. [Ellenbogen, Kenneth A.] Virginia Commonwealth Univ, Div Cardiol, Sch Med, Richmond, VA USA. [Hayes, David L.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. [Chatterjee, Neal A.; Upadhyay, Gaurav A.; Singh, Jagmeet P.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02411 USA. RP Singh, JP (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02411 USA. EM jsingh@partners.org FU Medtronic; Boston Science; St. Jude; Biotronik; Boston Scientific; Sorin Group; St. Jude Medical FX N.A.C. and G.A.U report no conflicts of interest. K.A.E. is a consultant for Biotronik, Boston Scientific, Medtronic, Sorin Group, and St. Jude Medical, receives research grants from Medtronic, Boston Science, and St. Jude, and fellowship support form Medtronic, Boston Science, and Biotronik. D. L. H receives lecture fees from Biotronik, Boston Scientific, Medtronic, Sorin Group, and St. Jude Medical, and is on advisory boards for Boston Scientific and Medtronic, and steering committees for Medtronic and St. Jude Medical. J.P.S. is a consultant for and receives lecture fees from Biotronik, Boston Scientific, Medtronic, Sorin Group, and St. Jude Medical, and is also a consultant for CardioInsight Inc., Thoratec Inc., and Biosense Webster. NR 43 TC 21 Z9 21 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD JUN PY 2012 VL 14 IS 6 BP 661 EP 667 DI 10.1093/eurjhf/hfs036 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 948VH UT WOS:000304530400015 PM 22436544 ER PT J AU Mejaddam, AY Velmahos, GC AF Mejaddam, A. Y. Velmahos, G. C. TI Randomized controlled trials affecting polytrauma care SO EUROPEAN JOURNAL OF TRAUMA AND EMERGENCY SURGERY LA English DT Review DE Polytrauma; Trauma management; Randomized controlled trials ID SPINAL-CORD-INJURY; TRAUMATIC BRAIN-INJURY; 7.5-PERCENT SODIUM-CHLORIDE; CRITICALLY ILL PATIENTS; SEVERE HEAD-INJURY; HYPERTONIC SALINE RESUSCITATION; ELEVATED INTRACRANIAL-PRESSURE; PREPERITONAL PELVIC PACKING; DECREASES MISSED INJURIES; PLACEBO-CONTROLLED TRIAL AB Trauma remains the leading cause of death in the world in patients under 45 years of age. The evaluation, resuscitation, and appropriate management of polytraumatized patients are paramount to successful outcomes. The advance of evidence-based medicine has had a powerful and positive impact on trauma care, even though the nature of many traumatic injuries lends itself poorly to study in a randomized fashion. During the initial management of bleeding patients, hypotensive resuscitation prior to surgical control has found strong support in the literature, and its use has been adopted by many surgeons. Head injury is the most common cause of traumatic death, and while high-level evidence is limited, adherence to management guidelines is associated with improved outcomes. For abdominal trauma, the concept of damage control surgery, while popular, has never been put to the test in a randomized controlled trial. Numerous randomized trials in the field of critical care have affected the management of severely injured patients, including intensive insulin therapy and low tidal volume ventilation in patients with compromised respiratory function. Finally, a multidisciplinary approach to trauma care in designated trauma centers allows for improved outcomes in polytraumatized patients. C1 [Mejaddam, A. Y.; Velmahos, G. C.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Mejaddam, A. Y.; Velmahos, G. C.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM gvelmahos@partners.org NR 108 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-9933 EI 1863-9941 J9 EUR J TRAUMA EMERG S JI Eur. J. Trauma Emerg. Surg. PD JUN PY 2012 VL 38 IS 3 BP 211 EP 221 DI 10.1007/s00068-011-0141-2 PG 11 WC Emergency Medicine SC Emergency Medicine GA 953GP UT WOS:000304855300002 PM 26815952 ER PT J AU Yeh, DD Kutcher, ME Lunghi, K AF Yeh, D. D. Kutcher, M. E. Lunghi, K. TI Traditional weight-based vancomycin dosing is inadequate in critically ill trauma patients SO EUROPEAN JOURNAL OF TRAUMA AND EMERGENCY SURGERY LA English DT Article DE Trauma; ICU; Vancomycin; Pneumonia; Antibiotics ID VENTILATOR-ASSOCIATED PNEUMONIA; INTERMITTENT INFUSION; STAPHYLOCOCCAL INFECTIONS; ANTIBIOTICS; REAPPRAISAL; PENETRATION; FLUID AB Our aim was to evaluate our institution's compliance with weight-based vancomycin dosing recommendations for pneumonia in critically ill injured patients and to assess the success rate in achieving therapeutic serum vancomycin levels. Additionally, we sought to assess the incidence of vancomycin-induced nephrotoxicity. All injured intensive care unit (ICU) patients receiving intravenous vancomycin between May 1, 2004 and July 31, 2010 were identified through our trauma database and pharmacy records. The initial weight-based dose was calculated and compared with vancomycin trough levels. Thirty patients were identified who satisfied the inclusion/exclusion criteria. Only 12 patients (40%) received adequate weight-based dosing (weight-based, 30 mg/kg/day). Weight-based patients weighed significantly less than non-weight-based patients (62.7 vs. 84.2 kg, p = 0.0008). Weight-based patients were more likely to achieve therapeutic trough levels than non-weight-based patients (58 vs. 33%, p = 0.176). Of patients who achieved therapeutic trough levels, more weight-based patients achieved it at first trough than non-weight-based patients (33 vs. 5.6%, p = 0.046). When prescribing commonly used dosing regimens, appropriate weight-based administration of vancomycin occurred in only approximately one-third of patients. Those patients who did receive weight-based vancomycin dosing were more likely to achieve therapeutic levels, both initially (33 vs. 5.6%) and overall (58 vs. 33%). C1 [Yeh, D. D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Div Trauma, Dept Surg Emergency Gen Surg & Surg Crit Care, Boston, MA 02114 USA. [Kutcher, M. E.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Lunghi, K.] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Clin Pharm, San Francisco, CA 94143 USA. RP Yeh, DD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Div Trauma, Dept Surg Emergency Gen Surg & Surg Crit Care, 165 Cambridge St 810, Boston, MA 02114 USA. EM daniel.dante.yeh@gmail.com; Matthew.kutcher@ucsfmedctr.org; kristin.lunghi@sfdph.org NR 31 TC 1 Z9 2 U1 0 U2 2 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-9933 J9 EUR J TRAUMA EMERG S JI Eur. J. Trauma Emerg. Surg. PD JUN PY 2012 VL 38 IS 3 BP 301 EP 306 DI 10.1007/s00068-011-0164-8 PG 6 WC Emergency Medicine SC Emergency Medicine GA 953GP UT WOS:000304855300012 PM 26815962 ER PT J AU Antolin, MF Jenkins, KP Bergstrom, CT Crespi, BJ De, S Hancock, A Hanley, KA Meagher, TR Moreno-Estrada, A Nesse, RM Omenn, GS Stearns, SC AF Antolin, Michael F. Jenkins, Kristin P. Bergstrom, Carl T. Crespi, Bernard J. De, Subhajyoti Hancock, Angela Hanley, Kathryn A. Meagher, Thomas R. Moreno-Estrada, Andres Nesse, Randolph M. Omenn, Gilbert S. Stearns, Stephen C. TI EVOLUTION AND MEDICINE IN UNDERGRADUATE EDUCATION: A PRESCRIPTION FOR ALL BIOLOGY STUDENTS SO EVOLUTION LA English DT Review DE Biomedical research; evolution of disease; host-pathogen interactions; human genetics; medical practice; mismatch hypothesis; premedical curriculum; public health; science education ID ANTIBIOTIC-RESISTANCE; POSITIVE SELECTION; PUBLIC-HEALTH; DEGENERATIVE DISEASES; POPULATION-GENETICS; GLOBAL DISTRIBUTION; SCHOOL CURRICULUM; VACCINE; CANCER; ASSOCIATION AB The interface between evolutionary biology and the biomedical sciences promises to advance understanding of the origins of genetic and infectious diseases in humans, potentially leading to improved medical diagnostics, therapies, and public health practices. The biomedical sciences also provide unparalleled examples for evolutionary biologists to explore. However, gaps persist between evolution and medicine, for historical reasons and because they are often perceived as having disparate goals. Evolutionary biologists have a role in building a bridge between the disciplines by presenting evolutionary biology in the context of human health and medical practice to undergraduates, including premedical and preprofessional students. We suggest that students will find medical examples of evolution engaging. By making the connections between evolution and medicine clear at the undergraduate level, the stage is set for future health providers and biomedical scientists to work productively in this synthetic area. Here, we frame key evolutionary concepts in terms of human health, so that biomedical examples may be more easily incorporated into evolution courses or more specialized courses on evolutionary medicine. Our goal is to aid in building the scientific foundation in evolutionary biology for all students, and to encourage evolutionary biologists to join in the integration of evolution and medicine. C1 [Antolin, Michael F.] Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA. [Bergstrom, Carl T.] Univ Washington, Dept Biol, Seattle, WA 98195 USA. [Crespi, Bernard J.] Simon Fraser Univ, Dept Biol Sci, Burnaby, BC V5A 1S6, Canada. [De, Subhajyoti] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Hancock, Angela] Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA. [Hanley, Kathryn A.] New Mexico State Univ, Dept Biol, Las Cruces, NM 88003 USA. [Meagher, Thomas R.] Univ St Andrews, Sch Biol, St Andrews KY15 4RP, Fife, Scotland. [Moreno-Estrada, Andres] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. [Nesse, Randolph M.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Omenn, Gilbert S.] Univ Michigan, Sch Publ Hlth, Dept Internal Med, Ctr Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. [Stearns, Stephen C.] Yale Univ, Dept Ecol & Evolutionary Biol, New Haven, CT 06520 USA. [Omenn, Gilbert S.] Univ Michigan, Sch Publ Hlth, Ctr Computat Med & Bioinformat, Dept Human Genet, Ann Arbor, MI 48109 USA. [Jenkins, Kristin P.] Natl Evolutionary Synth Ctr, Durham, NC 27705 USA. RP Antolin, MF (reprint author), Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA. EM michael.antolin@colostate.edu RI Stearns, Stephen/F-4099-2012; Evolutionary Ecology, Ecologia Evolutiva/M-3553-2014; OI Omenn, Gilbert S./0000-0002-8976-6074; Nesse, Randolph/0000-0003-1768-0949; Stearns, Stephen/0000-0002-6621-4373; Bergstrom, Carl/0000-0002-2070-385X FU Education and Outreach Committee of the Society for the Study of Evolution; National Evolutionary Synthesis Center FX Financial support for this symposium was provided by the Education and Outreach Committee of the Society for the Study of Evolution, by the National Evolutionary Synthesis Center, and by the co-authors home institutions. We thank the local organizers of the 2011 Evolution meetings, particularly R. Broughton, I. Schlupp, and L. Weider (special thanks for the use of the bicycle!). NR 146 TC 7 Z9 7 U1 10 U2 101 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-3820 EI 1558-5646 J9 EVOLUTION JI Evolution PD JUN PY 2012 VL 66 IS 6 BP 1991 EP 2006 DI 10.1111/j.1558-5646.2011.01552.x PG 16 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA 951YR UT WOS:000304757200026 PM 22671563 ER PT J AU Smits, M Wurdinger, T van het Hof, B Drexhage, JAR Geerts, D Wesseling, P Noske, DP Vandertop, WP de Vries, HE Reijerkerk, A AF Smits, Michiel Wurdinger, Thomas van het Hof, Bert Drexhage, Joost A. R. Geerts, Dirk Wesseling, Pieter Noske, David P. Vandertop, W. Peter de Vries, Helga E. Reijerkerk, Arie TI Myc-associated zinc finger protein (MAZ) is regulated by miR-125b and mediates VEGF-induced angiogenesis in glioblastoma SO FASEB JOURNAL LA English DT Article DE brain cancer; brain endothelial cell ID ENDOTHELIAL GROWTH-FACTOR; BREAST-CANCER CELLS; SAF-1 TRANSCRIPTION FACTOR; GENE-EXPRESSION; FUNCTIONAL COOPERATION; SIGNALING PATHWAY; SYNOVIOCYTE CELLS; BRAIN-TUMORS; FACTOR-I; INDUCTION AB In patients with glioblastomas, vascular endothelial growth factor (VEGF) is a key mediator of tumor-associated angiogenesis. Glioblastomas are notorious for their capacity to induce neovascularization, driving continued tumor growth. Here we report that miR-125b is down-regulated in glioblastoma-associated endothelial cells, resulting in increased expression of its target, myc-associated zinc finger protein (MAZ), a transcription factor that regulates VEGF. The down-regulation of miR-125b was also observed on exposure of endothelial cells to glioblastoma-conditioned medium or VEGF, resulting in increased MAZ expression. Further analysis revealed that inhibition of MAZ accumulation by miR-125b, or by MAZ-specific shRNAs, attenuated primary human brain endothelial cell migration and tubule formation in vitro, phenomena considered to mimick angiogenic processes in vitro. Moreover, MAZ expression was elevated in brain blood vessels of glioblastoma patients. Altogether these results demonstrate a functional feed-forward loop in glioblastoma-related angiogenesis, in which VEGF inhibits the expression of miR-125b, resulting in increased expression of MAZ, which in its turn causes transcriptional activation of VEGF. This loop is functionally impeded by the VEGF receptor inhibitor vandetanib, and our results may contribute to the further development of inhibitors of tumor-angiogenesis.-Smits, M., Wurdinger, T., van het Hof, B., Drexhage, J. A. R., Geerts, D., Wesseling, P., Noske, D. P., Vandertop, W. P., de Vries, H. E., Reijerkerk, A. Myc-associated zinc finger protein (MAZ) is regulated by miR-125b and mediates VEGF-induced angiogenesis in glioblastoma. FASEB J. 26, 2639-2647 (2012). www.fasebj.org C1 [van het Hof, Bert; Drexhage, Joost A. R.; de Vries, Helga E.; Reijerkerk, Arie] Vrije Univ Med Ctr, Blood Brain Barrier Res Grp, Dept Mol Cell Biol & Immunol, NL-1007 MB Amsterdam, Netherlands. [Smits, Michiel; Wurdinger, Thomas; Noske, David P.; Vandertop, W. Peter] Vrije Univ Med Ctr, Neurooncol Res Grp, Dept Neurosurg, Canc Ctr Amsterdam, NL-1007 MB Amsterdam, Netherlands. [Wesseling, Pieter] Vrije Univ Med Ctr, Neurooncol Res Grp, Dept Pathol, NL-1007 MB Amsterdam, Netherlands. [Wurdinger, Thomas] Harvard Univ, Sch Med, Dept Neurol, Mol Neurogenet Unit,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wurdinger, Thomas] Harvard Univ, Sch Med, Dept Radiol, Mol Neurogenet Unit,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wurdinger, Thomas] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. [Geerts, Dirk] Erasmus Univ, Dept Pediat Oncol & Hematol, Sophia Childrens Hosp, Med Ctr, Rotterdam, Netherlands. [Wesseling, Pieter] Radboud Univ Nijmegen, Dept Pathol, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Vandertop, W. Peter] Univ Amsterdam, Acad Med Ctr, Neurosurg Ctr Amsterdam, NL-1105 AZ Amsterdam, Netherlands. RP Reijerkerk, A (reprint author), Vrije Univ Med Ctr, Blood Brain Barrier Res Grp, Dept Mol Cell Biol & Immunol, NL-1007 MB Amsterdam, Netherlands. EM t.wurdinger@vumc.nl; a.reijerkerk@vumc.nl RI Wesseling, P./H-8114-2014; OI Wesseling, P./0000-0001-5453-5201; Geerts, Dirk/0000-0002-6386-8187 FU Stichting Translational Research Cancer Center Amsterdam/Vrije Universiteit Medical Center; Nederlandse Organisatie voor Wetenschappelijk Onderzoek-VIDI; Netherlands Genomics Initiative FX This work was supported by Stichting Translational Research Cancer Center Amsterdam/Vrije Universiteit Medical Center and Nederlandse Organisatie voor Wetenschappelijk Onderzoek-VIDI (T. W.) and Netherlands Genomics Initiative (A. R. and J. A. R. D.). M. S., T. W., and A. R. performed the expression analysis, target analysis, endothelial migration, and Matrigel experiments, wrote the manuscript, and designed the experiments; D. G. provided the shRNA constructs; P. W., D. P. N., W. P. V., and H. E. V. assisted in concept design and writing. NR 50 TC 34 Z9 34 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUN PY 2012 VL 26 IS 6 BP 2639 EP 2647 DI 10.1096/fj.11-202820 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 955KI UT WOS:000305017200039 PM 22415301 ER PT J AU Imudia, AN Awonuga, AO Doyle, JO Kaimal, AJ Wright, DL Toth, TL Styer, AK AF Imudia, Anthony N. Awonuga, Awoniyi O. Doyle, Joseph O. Kaimal, Anjali J. Wright, Diane L. Toth, Thomas L. Styer, Aaron K. TI Peak serum estradiol level during controlled ovarian hyperstimulation is associated with increased risk of small for gestational age and preeclampsia in singleton pregnancies after in vitro fertilization SO FERTILITY AND STERILITY LA English DT Article DE Estradiol; controlled ovarian hyperstimulation; IVF; small for gestational age; preterm delivery; preeclampsia; abnormal placentation ID ASSISTED REPRODUCTIVE TECHNOLOGY; INTRACYTOPLASMIC SPERM INJECTION; MATERNAL VASCULAR-RESPONSE; EARLY BABOON PREGNANCY; GROWTH-FACTOR; EXTRAVILLOUS TROPHOBLAST; PRIMATE PREGNANCY; HUMAN ENDOMETRIUM; ELECTIVE SINGLE; SPIRAL ARTERIES AB Objective: To assess the impact of elevated peak serum E-2 levels (EPE2; defined as levels >90th percentile) on the day of hCG administration during controlled ovarian hyperstimulation (COH) for IVF on the likelihood for small for gestational age (SGA), preeclampsia (PreE), and preterm delivery (PTD) in singleton pregnancies. Design: Retrospective cohort study. Setting: Tertiary-care academic medical center. Patient(s): Singleton live-birth pregnancies conceived after fresh IVF-ET. Intervention(s): None. Main Outcome Measure(s): The delivery rate of SGA infants and the development of PreE and PTD in patients with and without EPE2. Result(s): Patients with EPE2 during COH were more likely to deliver SGA infants (7 [26.9%] vs. 10 [3.8%]; odds ratio [OR], 95% confidence interval [CI] {9.40, 3.22-27.46}) and develop PreE (5 [18.5%] vs. 12 [4.5%]; adjusted OR, 95% CI {4.79, 1.55-14.84}). No association was found between EPE2 and the likelihood for delivery before 37 weeks, 35 weeks, or 32 weeks of gestation. Receiver operating characteristic analysis revealed that EPE2 level predicted adverse obstetrical outcome (SGA + PreE) with 38.5% and 91.7% sensitivity and specificity, respectively. Using a serum peak E-2 cutoff value of 3,450 pg/mL (>90th percentile level), the positive predictive value was 37%, while the negative predictive value was 92%. Conclusion(s): EPE2 level (>3,450 pg/mL) on the day of hCG administration during COH is associated with greater odds of developing PreE and delivery of an SGA infant in singleton pregnancies resulting from IVF cycles. (Fertil Steril (R) 2012;97:1374-9. (C) 2012 by American Society for Reproductive Medicine.) C1 [Imudia, Anthony N.; Doyle, Joseph O.; Wright, Diane L.; Toth, Thomas L.; Styer, Aaron K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Fertil Ctr,Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. [Awonuga, Awoniyi O.] Wayne State Univ, Sch Med, Div Reprod Endocrinol & Infertil, Detroit, MI USA. [Kaimal, Anjali J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Maternal Fetal Med,Vincent Dept Obstet & Gyne, Boston, MA 02114 USA. RP Imudia, AN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Fertil Ctr,Vincent Dept Obstet & Gynecol, 55 Fruit St,Yawkey 10A, Boston, MA 02114 USA. EM aimudia@partners.org NR 52 TC 40 Z9 42 U1 2 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JUN PY 2012 VL 97 IS 6 BP 1374 EP 1379 DI 10.1016/j.fertnstert.2012.03.028 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 952DR UT WOS:000304770900029 PM 22494926 ER PT J AU Carpenter, JS Guthrie, KA Larson, JC Freeman, EW Joffe, H Reed, SD Ensrud, KE LaCroix, AZ AF Carpenter, Janet S. Guthrie, Katherine A. Larson, Joseph C. Freeman, Ellen W. Joffe, Hadine Reed, Susan D. Ensrud, Kristine E. LaCroix, Andrea Z. TI Effect of escitalopram on hot flash interference: a randomized, controlled trial SO FERTILITY AND STERILITY LA English DT Article DE Menopause; hot flashes; night sweats; selective serotonin reuptake inhibitor ID PLACEBO-CONTROLLED TRIAL; SLEEP QUALITY INDEX; BREAST-CANCER; DOUBLE-BLIND; DEPRESSION; CITALOPRAM; SYMPTOMS; WOMEN; EFFICACY; IMPACT AB Objective: To estimate the effect of escitalopram (10-20 mg/d) versus placebo for reducing hot flash interference in daily life and understand correlates and predictors of reductions in hot flash interference, a key measure of quality of life. Design: Multisite, randomized, double-blind, placebo-controlled clinical trial. Setting: MsFLASH clinical sites in Boston, Indianapolis, Oakland, and Philadelphia. Patient(s): A total of 205 midlife women (46% African-American) who met criteria participated. Intervention(s): After baseline, women were randomized to one pill of escitalopram 10 mg/d (n = 104) or placebo (n = 101) with follow-up at 4 and 8 weeks. At week 4, those not achieving 50% fewer hot flashes were increased to two pills daily (20 mg/d or 2 placebo pills). Main Outcome Measure(s): The Hot Flash Related Daily Interference Scale; correlates were variables from hot flash diaries; predictors were baseline demographics, clinical variables, depression, anxiety, sleep quality, and hot flashes. Result(s): Compared to placebo, escitalopram significantly reduced hot flash interference by 6.0 points at week 4 and 3.4 points at week 8 more than placebo. Reductions in hot flash interference correlated with changes in hot flash diary variables. However, baseline variables did not significantly predict reductions in hot flash interference. Conclusion(s): Escitalopram (10-20 mg/d) for 8 weeks improves women's quality of life and this benefit did not vary by demographic, clinical, mood, sleep, or hot flash variables. Clinical Trial Registration Number: NCT00894543. (Fertil Steril (R) 2012;97:1399-404. (C) 2012 by American Society for Reproductive Medicine.) C1 [Carpenter, Janet S.] Indiana Univ, Indianapolis, IN 46202 USA. [Guthrie, Katherine A.; Larson, Joseph C.; LaCroix, Andrea Z.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Freeman, Ellen W.] Univ Penn, Philadelphia, PA 19104 USA. [Joffe, Hadine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Reed, Susan D.] Univ Washington, Sch Med, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Ensrud, Kristine E.] Univ Minnesota, Vet Adm Med Ctr, Minneapolis, MN USA. RP Carpenter, JS (reprint author), Indiana Univ, 1111 Middle Dr, Indianapolis, IN 46202 USA. EM carpentj@iupui.edu FU Bayer HealthCare Pharmaceuticals; Forest Laboratories; GlaxoSmithKline; National Institute of Aging; Eunice Kennedy Shriver National Institute of Child Health and Development; National Center for Complementary and Alternative Medicine; Office of Research and Women's Health; Indiana Clinical and Translational Sciences Institute from the National Center for Research Resources [UL1 RR025761]; [U01AG032656]; [U01AG032659]; [U01AG032669]; [U01AG032682]; [U01AG032699]; [U01AG032700] FX J.S.C. has nothing to disclose. K.A.G. has nothing to disclose. J.C.L. has nothing to disclose. E.W.F. has nothing to disclose. H.J. receives research support (to the Center for Women's Mental Health at Massachusetts General Hospital where she participates in protocols as a co-investigator) from Bayer HealthCare Pharmaceuticals, Forest Laboratories, and GlaxoSmithKline and has consulted for Sanofi-Aventis/Sunovion. S.D.R. has nothing to disclose. K.E.E. has nothing to disclose. A.Z.L. has nothing to disclose.; Supported by the National Institute of Aging, in collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Development, the National Center for Complementary and Alternative Medicine, the Office of Research and Women's Health, and grants U01AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, and U01AG032700. At Indiana, the project was supported by the Indiana Clinical and Translational Sciences Institute (UL1 RR025761) from the National Center for Research Resources, Clinical and Translational Sciences Award. NR 23 TC 18 Z9 19 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JUN PY 2012 VL 97 IS 6 BP 1399 EP + DI 10.1016/j.fertnstert.2012.03.001 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 952DR UT WOS:000304770900033 PM 22480818 ER PT J AU Mounzer, R Langmead, CJ Wu, BU Evans, AC Bishehsari, F Muddana, V Singh, VK Slivka, A Whitcomb, DC Yadav, D Banks, PA Papachristou, GI AF Mounzer, Rawad Langmead, Christopher J. Wu, Bechien U. Evans, Anna C. Bishehsari, Faraz Muddana, Venkata Singh, Vikesh K. Slivka, Adam Whitcomb, David C. Yadav, Dhiraj Banks, Peter A. Papachristou, Georgios I. TI Comparison of Existing Clinical Scoring Systems to Predict Persistent Organ Failure in Patients With Acute Pancreatitis SO GASTROENTEROLOGY LA English DT Article DE Marker; Organ Failure; Predictors; Pancreas ID INFLAMMATORY RESPONSE; CLASSIFICATION-SYSTEM; APACHE-II; SEVERITY; MORTALITY; MARKER; DYSFUNCTION; NECROSIS; INDEX; RISK AB BACKGROUND & AIMS: It is important to identify patients with acute pancreatitis who are at risk for developing persistent organ failure early in the course of disease. Several scoring systems have been developed to predict which patients are most likely to develop persistent organ failure. We head-to-head compared the accuracy of these systems in predicting persistent organ failure, developed rules that combined these scores to optimize predictive accuracy, and validated our findings in an independent cohort. METHODS: Clinical data from 2 prospective cohorts were used for training (n = 256) and validation (n = 397). Persistent organ failure was defined as cardiovascular, pulmonary, and/or renal failure that lasted for 48 hours or more. Nine clinical scores were calculated when patients were admitted and 48 hours later. We developed 12 predictive rules that combined these scores, in order of increasing complexity. RESULTS: Existing scoring systems showed modest accuracy (areas under the curve at admission of 0.62-0.84 in the training cohort and 0.57-0.74 in the validation cohort). The Glasgow score was the best classifier at admission in both cohorts. Serum levels of creatinine and blood urea nitrogen provided similar levels of discrimination in each set of patients. Our 12 predictive rules increased accuracy to 0.92 in the training cohort and 0.84 in the validation cohort. CONCLUSIONS: The existing scoring systems seem to have reached their maximal efficacy in predicting persistent organ failure in acute pancreatitis. Sophisticated combinations of predictive rules are more accurate but cumbersome to use, and therefore of limited clinical use. Our ability to predict the severity of acute pancreatitis cannot be expected to improve unless we develop new approaches. C1 [Mounzer, Rawad; Evans, Anna C.; Bishehsari, Faraz; Muddana, Venkata; Slivka, Adam; Whitcomb, David C.; Yadav, Dhiraj; Papachristou, Georgios I.] Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. [Langmead, Christopher J.] Carnegie Mellon Univ, Dept Comp Sci, Pittsburgh, PA 15213 USA. [Wu, Bechien U.; Singh, Vikesh K.; Banks, Peter A.] Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA. [Papachristou, Georgios I.] Vet Affairs Pittsburgh Hlth Syst, Div Gastroenterol & Hepatol, Pittsburgh, PA USA. RP Papachristou, GI (reprint author), Presbyterian Univ Hosp, Div Gastroenterol Hepatol & Nutr, M2,C Wing,200 Lothrop St, Pittsburgh, PA 15213 USA. EM papachri@pitt.edu FU Doris Duke Clinical Research Fellowship FX Anna Evans was supported by a Doris Duke Clinical Research Fellowship. NR 40 TC 80 Z9 88 U1 1 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2012 VL 142 IS 7 BP 1476 EP 1482 DI 10.1053/j.gastro.2012.03.005 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 952GF UT WOS:000304778700026 PM 22425589 ER PT J AU Lieberman, D AF Lieberman, David TI Presentation of the Julius M. Friedenwald Medal to Emmet B. Keeffe, MD SO GASTROENTEROLOGY LA English DT Biographical-Item C1 [Lieberman, David] Oregon Hlth & Sci Univ, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. [Lieberman, David] Portland VA Med Ctr, Portland, OR USA. RP Lieberman, D (reprint author), Oregon Hlth & Sci Univ, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2012 VL 142 IS 7 BP 1610 EP 1612 DI 10.1053/j.gastro.2012.04.041 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 952GF UT WOS:000304778700038 PM 22542834 ER PT J AU Hirschfield, GM Xie, G Lu, E Sun, Y Juran, BD Chellappa, V Coltescu, C Mason, AL Milkiewicz, P Myers, RP Odin, JA Luketic, VA Bacon, B Bodenheimer, H Liakina, V Vincent, C Levy, C Pillai, S Lazaridis, KN Amos, CI Siminovitch, KA AF Hirschfield, G. M. Xie, G. Lu, E. Sun, Y. Juran, B. D. Chellappa, V. Coltescu, C. Mason, A. L. Milkiewicz, P. Myers, R. P. Odin, J. A. Luketic, V. A. Bacon, B. Bodenheimer, H. Liakina, V. Vincent, C. Levy, C. Pillai, S. Lazaridis, K. N. Amos, C. I. Siminovitch, K. A. TI Association of primary biliary cirrhosis with variants in the CLEC16A, SOCS1, SPIB and SIAE immunomodulatory genes SO GENES AND IMMUNITY LA English DT Article DE autoimmunity; fine mapping; sequence analysis; primary biliary cirrhosis ID RISK ALLELES; T-CELLS; CYTOKINE; DIFFERENTIATION; AUTOIMMUNITY; DEFICIENCY; SUPPRESSOR; DISEASE; GAMMA AB We fine mapped two primary biliary cirrhosis (PBC) risk loci, CLEC16A (C-type lectin domain family 16 member A)-suppressor of cytokine signaling 1 (50051) and Spi-B protein (SPIB) and sequenced a locus, sialic acid acetylesterase (SIAE), proposed to harbor autoimmunity-associated mutations. In all, 1450 PBC cases and 2957 healthy controls were genotyped for 84 single-nucleotide polymorphisms (SNPs) across the CLEC16A-SOCS1 and SPIB loci. All 10 exons of the SIAE gene were resequenced in 381 cases and point substitutions of unknown significance assayed for activity and secretion. Fine mapping identified 26 SNPs across the CLEC16A-SOCS1 and 11 SNPs across the SPIB locus with significant association to PBC, the strongest signals at the CLEC16A-SOCS1 locus emanating from a SOCS1 intergenic SNP (rs243325; P=9.91 x 10(-9)) and at the SPIB locus from a SPIB intronic SNP (rs34944112; P=3.65 x 10(-9)). Among the associated SNPs at the CLEC16A-SOCS1 locus, two within the CLEC16A gene as well as one SOCS1 SNP (rs243325) remained significant after conditional logistic regression and contributed independently to risk. Sequencing of the SIAE gene and functional assays of newly identified variants revealed six patients with functional non-synonymous SIAE mutations (Fisher's P=9 x 10(-4) vs controls) We demonstrate independent effects on risk of PBC for CLEC16A, SOCS1 and SPIB variants, while identifying functionally defective SIAE variants as potential factors in risk for PBC. C1 [Xie, G.; Sun, Y.; Siminovitch, K. A.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Xie, G.; Sun, Y.; Siminovitch, K. A.] Toronto Gen Res Inst, Toronto, ON M5G 1X5, Canada. [Hirschfield, G. M.; Coltescu, C.] Toronto Western Hosp, Ctr Liver, Toronto, ON M5T 2S8, Canada. [Hirschfield, G. M.; Siminovitch, K. A.] Univ Toronto, Dept Med, Toronto, ON, Canada. [Lu, E.; Amos, C. I.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Juran, B. D.; Lazaridis, K. N.] Mayo Clin, Coll Med, Div Gastroenterol & Hepatol, Ctr Basic Res Digest Dis, Rochester, MN USA. [Chellappa, V.; Pillai, S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. [Mason, A. L.] Univ Alberta, Dept Med, Edmonton, AB, Canada. [Milkiewicz, P.] Pomeranian Med Sch, Liver Unit, Szczecin, Poland. [Myers, R. P.] Univ Calgary, Liver Unit, Calgary, AB, Canada. [Odin, J. A.] Mt Sinai Sch Med, Div Liver Dis, New York, NY USA. [Luketic, V. A.] Virginia Commonwealth Univ, Dept Gastroenterol, Richmond, VA USA. [Bacon, B.] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA. [Bodenheimer, H.] Albert Einstein Coll Med, Dept Med, New York, NY USA. [Liakina, V.] Vilnius State Univ, Ctr Gastroenterol & Dietet, Vilnius, Lithuania. [Vincent, C.] Univ Montreal, Ctr Hosp, St Luc Hosp, Montreal, PQ, Canada. [Levy, C.] Univ Miami, Sch Med, Ctr Liver Dis, Div Hepatol, Miami, FL USA. [Siminovitch, K. A.] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A1, Canada. [Siminovitch, K. A.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada. RP Siminovitch, KA (reprint author), Mt Sinai Hosp, Samuel Lunenfeld Res Inst, 600 Univ Ave,Room 778D, Toronto, ON M5G 1X5, Canada. EM ksimin@mshri.on.ca RI Siminovitch, Katherine/K-1475-2013; Hirschfield, Gideon/M-2143-2015; Sun, Ye/B-9814-2017; OI Hirschfield, Gideon/0000-0002-6736-2255; Mason, Andrew/0000-0002-0470-9522 FU Canadian Institutes for Health Research [MOP74621]; Ontario Research Fund [RE01-061]; Canadian Primary Biliary Cirrhosis Society; US National Institutes of Health [RO1 DK80670]; American Gastroenterological Association; AJ and Sigismunda Palumbo Charitable Trust; Alliance for Lupus Research; Center for the Study of Inflammatory Bowel Disease at MGH; NIH [AI 064930, AI 076505, AR 058481]; Sherman Family Chair in Genomic Medicine; Canada Research Chair award; Lung GO Sequencing Project [HL-102923]; WHI [HL-102924]; Broad GO Sequencing Project [HL-102925]; Seattle GO Sequencing Project [HL-102926]; Heart GO Sequencing Project [HL-103010] FX This work was supported by grants from the Canadian Institutes for Health Research (MOP74621), the Ontario Research Fund (RE01-061) and the Canadian Primary Biliary Cirrhosis Society (GMH and KAS), the US National Institutes of Health (RO1 DK80670), the American Gastroenterological Association and the AJ and Sigismunda Palumbo Charitable Trust (KNL) and Alliance for Lupus Research, the Center for the Study of Inflammatory Bowel Disease at MGH and the NIH (AI 064930, AI 076505 and AR 058481) to SP KAS holds the Sherman Family Chair in Genomic Medicine and a Canada Research Chair award. We thank the NHLBI GO Exome Sequencing Project and its ongoing studies, which produced and provided exome variant calls for comparison: the Lung GO Sequencing Project (HL-102923), the WHI Sequencing Project (HL-102924), the Broad GO Sequencing Project (HL-102925), the Seattle GO Sequencing Project (HL-102926) and the Heart GO Sequencing Project (HL-103010). NR 25 TC 31 Z9 31 U1 2 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD JUN PY 2012 VL 13 IS 4 BP 328 EP 335 DI 10.1038/gene.2011.89 PG 8 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 953EE UT WOS:000304848900005 PM 22257840 ER PT J AU Heilmann, AMF Dyson, NJ AF Heilmann, Andreas M. F. Dyson, Nicholas J. TI Phosphorylation puts the pRb tumor suppressor into shape SO GENES & DEVELOPMENT LA English DT Article DE Retinoblastoma protein; cell cycle regulation; multisite phosphorylation; cyclin-dependent kinase; X-ray crystal structure; small-angle X-ray scattering (SAXS) ID RETINOBLASTOMA PROTEIN; CELL-CYCLE; CRYSTAL-STRUCTURE; E2F; DOMAIN; GENE; PRODUCT AB In this issue of Genes & Development, Burke and colleagues (pp. 1156-1166) describe how the structure of retinoblastoma protein (pRb) is altered by phosphorylation at T373 or S608. These modifications cause specific conformational changes and alter pRb's interaction with E2F via two distinct mechanisms. The structures suggest that the panel of phosphorylation sites represents a versatile set of tools that are used to sculpt pRb in precise, but very different, ways. C1 [Heilmann, Andreas M. F.; Dyson, Nicholas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. RP Dyson, NJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. EM dyson@helix.mgh.harvard.edu FU NIH [CA64402] FX We thank Michael Korenjak for helpful discussions on the manuscript. We also apologize to our colleagues whose work was not cited due to space limitations. A.H. and N.D. are supported by NIH grant CA64402 (to N.D.). NR 21 TC 6 Z9 6 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUN 1 PY 2012 VL 26 IS 11 BP 1128 EP 1130 DI 10.1101/gad.195552.112 PG 3 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 952CJ UT WOS:000304767000002 PM 22661226 ER PT J AU Tsao, H Chin, L Garraway, LA Fisher, DE AF Tsao, Hensin Chin, Lynda Garraway, Levi A. Fisher, David E. TI Melanoma: from mutations to medicine SO GENES & DEVELOPMENT LA English DT Review DE BRAF; MITF pathway; melanoma ID GROWTH-FACTOR-RECEPTOR; MICROPHTHALMIA TRANSCRIPTION FACTOR; BCL-2 ANTISENSE OLIGONUCLEOTIDE; MALIGNANT MELANOCYTIC LESIONS; PRIMARY CUTANEOUS MELANOMAS; RADIATION-INDUCED APOPTOSIS; FREQUENT SOMATIC MUTATIONS; RAF INHIBITOR RESISTANCE; KIT PROTEIN EXPRESSION; CLEAR-CELL SARCOMA AB Melanoma is often considered one of the most aggressive and treatment-resistant human cancers. It is a disease that, due to the presence of melanin pigment, was accurately diagnosed earlier than most other malignancies and that has been subjected to countless therapeutic strategies. Aside from early surgical resection, no therapeutic modality has been found to afford a high likelihood of curative outcome. However, discoveries reported in recent years have revealed a near avalanche of breakthroughs in the melanoma field-breakthroughs that span fundamental understanding of the molecular basis of the disease all the way to new therapeutic strategies that produce unquestionable clinical benefit. These discoveries have been born from the successful fruits of numerous researchers working in many-sometimes-related, although also distinct-biomedical disciplines. Discoveries of frequent mutations involving BRAF(V600E), developmental and oncogenic roles for the microphthalmia-associated transcription factor (MITF) pathway, clinical efficacy of BRAF-targeted small molecules, and emerging mechanisms underlying resistance to targeted therapeutics represent just a sample of the findings that have created a striking inflection in the quest for clinically meaningful progress in the melanoma field. C1 [Tsao, Hensin; Fisher, David E.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Tsao, Hensin] Wellman Ctr Photomed, Boston, MA 02114 USA. [Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA. [Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. EM dfisher3@partners.org FU NIH [K24 CA149202, R01 AR043369, RO1 CA093947]; Starr Cancer Consortium; Melanoma Research Alliance; American Skin Association; Sheldon and Dr. Miriam Adelson Medical Research Foundation FX We extend our sincere apology to those colleagues whose studies were not cited in this review due to space constraints. Funding for this scholarly effort was supported in part by the NIH (K24 CA149202 to H.T., R01 AR043369 to D.F., and RO1 CA093947 to L.C.), the NIH Director's New Innovator Award to L.G., the Starr Cancer Consortium to L.G., the Melanoma Research Alliance (to all authors), the American Skin Association/Abby S. and Howard P. Milstein Award to H.T. and L.C., and the Sheldon and Dr. Miriam Adelson Medical Research Foundation to L.G. and D.F. NR 305 TC 176 Z9 179 U1 4 U2 60 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 EI 1549-5477 J9 GENE DEV JI Genes Dev. PD JUN 1 PY 2012 VL 26 IS 11 BP 1131 EP 1155 DI 10.1101/gad.191999.112 PG 25 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 952CJ UT WOS:000304767000003 PM 22661227 ER PT J AU Bernhardt, BA Zayac, C Trerotola, SO Asch, DA Pyeritz, RE AF Bernhardt, Barbara A. Zayac, Cara Trerotola, Scott O. Asch, David A. Pyeritz, Reed E. TI Cost savings through molecular diagnosis for hereditary hemorrhagic telangiectasia SO GENETICS IN MEDICINE LA English DT Article DE cost-effectiveness; economic analysis; genetic screening; genetic testing; hereditary hemorrhagic telangiectasia ID PULMONARY ARTERIOVENOUS-MALFORMATIONS; COLORECTAL-CANCER; LYNCH SYNDROME; HEALTH-CARE; STRATEGIES; MUTATIONS; MEDICINE; OUTCOMES; IMPACT; TESTS AB Purpose: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder of vascular development resulting in direct connections between the arterial and venous systems, bypassing capillaries. Symptoms and signs can appear throughout life and marked intrafamilial variability confounds diagnosis based purely on clinical criteria. We set out to determine the impact of genetic testing on the cost of screening for HHT in at-risk relatives. Methods: We performed economic modeling of idealized pedigrees following two scenarios: repeated clinical screening until an HHT diagnosis could be either affirmed or excluded, and mutation testing in the proband, followed by genetic testing of at-risk relatives and clinical monitoring of only those relatives who test positive for the familial mutation. Results: Based on actual reimbursement data from our region's largest health insurer, the molecular diagnostic model saved over $22,000 for a family with four relatives at risk for the initial diagnostic work-up. For a cohort of 100 probands, the total savings for the molecular diagnostic model over a reasonable period of follow-up was greater than $9 million. Conclusion: In this idealized setting in which all probands and at-risk relatives accepted molecular testing, the economic advantages of genetic screening over repeated clinical screening are substantial. C1 [Bernhardt, Barbara A.; Zayac, Cara; Pyeritz, Reed E.] Univ Penn, Div Translat Med & Human Genet, Philadelphia, PA 19104 USA. [Bernhardt, Barbara A.; Zayac, Cara; Asch, David A.; Pyeritz, Reed E.] Univ Penn, Raymond & Ruth Perelman Sch Med, Ctr Integrat Genet Healthcare Technol, Philadelphia, PA 19104 USA. [Bernhardt, Barbara A.; Asch, David A.; Pyeritz, Reed E.] Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. [Trerotola, Scott O.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Asch, David A.; Pyeritz, Reed E.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Pyeritz, Reed E.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Pyeritz, Reed E.] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. RP Pyeritz, RE (reprint author), Univ Penn, Div Translat Med & Human Genet, Philadelphia, PA 19104 USA. EM reed.pyeritz@uphs.upenn.edu OI Asch, David/0000-0002-7970-286X FU National Human Genome Research Institute [P50HG004487] FX We thank Joseph Monkoski for helpful information. This work was supported by National Human Genome Research Institute grant P50HG004487. The preparation of this manuscript occurred while R. E. P. was in residence at the Brocher Foundation, Hermance, Switzerland. NR 34 TC 5 Z9 5 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD JUN PY 2012 VL 14 IS 6 BP 604 EP 610 DI 10.1038/gim.2011.56 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 955GL UT WOS:000305005000005 PM 22281938 ER PT J AU He, HSHS Meyer, CA Chen, MW Jordan, VC Brown, M Liu, XS AF He, Housheng Hansen Meyer, Clifford A. Chen, Mei Wei Jordan, V. Craig Brown, Myles Liu, X. Shirley TI Differential DNase I hypersensitivity reveals factor-dependent chromatin dynamics SO GENOME RESEARCH LA English DT Article ID ANDROGEN RECEPTOR; PROSTATE-CANCER; CHIP-SEQ; TRANSCRIPTION; SWI/SNF; GENES; NORMALIZATION; NUCLEOSOMES; RECRUITMENT; PROMOTERS AB Transcription factor cistromes are highly cell-type specific. Chromatin accessibility, histone modifications, and nucleosome occupancy have all been found to play a role in defining these binding locations. Here, we show that hormone-induced DNase I hypersensitivity changes (Delta DHS) are highly predictive of androgen receptor (AR) and estrogen receptor 1 (ESR1) binding in prostate cancer and breast cancer cells, respectively. While chromatin structure prior to receptor binding and nucleosome occupancy after binding are strikingly different for ESR1 and AR, Delta DHS is highly predictive for both. AR binding is associated with changes in both local nucleosome occupancy and DNase I hypersensitivity. In contrast, while global ESR1 binding is unrelated to changes in nucleosome occupancy, DNase I hypersensitivity dynamics are also predictive of the ESR1 cistrome. These findings suggest that AR and ESR1 have distinct modes of interaction with chromatin and that DNase I hypersensitivity dynamics provides a general approach for predicting cell-type specific cistromes. C1 [He, Housheng Hansen; Chen, Mei Wei; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [He, Housheng Hansen; Chen, Mei Wei; Brown, Myles] Harvard Univ, Sch Med, Boston, MA 02115 USA. [He, Housheng Hansen; Meyer, Clifford A.; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [He, Housheng Hansen; Meyer, Clifford A.; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Chen, Mei Wei; Brown, Myles; Liu, X. Shirley] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. [Jordan, V. Craig] Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Dept Oncol, Washington, DC 20057 USA. RP Brown, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM myles_brown@dfcl.harvard.edu; xsliu@jimmy.harvard.edu RI Jordan, V. Craig/H-4491-2011; OI Brown, Myles/0000-0002-8213-1658 FU National Institutes of Health [1R01 GM099409, 2P50 CA090381-06, 2R01 DK074967-06, P30 CA051008]; Mazzon Award [GM099409]; Department of Defense [W81XWH-10-1-0557]; Prostate Cancer Foundation FX We thank Dr. David J. Waxman and Dr. Guoyu Ling for help with the DNase-seq protocol. We thank Dr. Jason D. Lieb and Dr. Piotr Mieczkowski for help with the high-throughput sequencing. This work was supported by grants from the National Institutes of Health (1R01 GM099409 to X.S.L.; 2P50 CA090381-06 to C.A.M. and M.B.; 2R01 DK074967-06 to M.B. and X.S.L.; P30 CA051008 to V.C.J), the Mazzon Award (GM099409 to X.S.L.), the Department of Defense (W81XWH-10-1-0557 to H.H.H.), and the Prostate Cancer Foundation (to M.B.). NR 39 TC 77 Z9 79 U1 2 U2 10 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JUN PY 2012 VL 22 IS 6 BP 1015 EP 1025 DI 10.1101/gr.133280.111 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 951NU UT WOS:000304728100003 PM 22508765 ER PT J AU Bloch, DB Nobre, R Steinbicker, AU Al-Herz, W Notarangelo, LD Recher, M AF Bloch, Donald B. Nobre, Rita Steinbicker, Andrea U. Al-Herz, Waleed Notarangelo, Luigi D. Recher, Mike TI Decreased IL-10 production by EBV-transformed B cells from patients with VODI: Implications for the pathogenesis of Crohn disease SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID INTERLEUKIN-10; MUTATIONS C1 [Bloch, Donald B.; Nobre, Rita] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Bloch, Donald B.; Nobre, Rita] Massachusetts Gen Hosp, Dept Med, Rheumatol Allergy & Immunol Div, Boston, MA 02114 USA. [Steinbicker, Andrea U.] Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Steinbicker, Andrea U.; Notarangelo, Luigi D.; Recher, Mike] Harvard Univ, Sch Med, Boston, MA USA. [Steinbicker, Andrea U.] Univ Munster, Dept Anesthesiol & Intens Care Med, Munster, Germany. [Al-Herz, Waleed] Al Sabah Hosp, Dept Pediat, Allergy & Clin Immunol Unit, Kuwait, Kuwait. [Notarangelo, Luigi D.; Recher, Mike] Childrens Hosp Boston, Div Immunol, Boston, MA USA. [Notarangelo, Luigi D.; Recher, Mike] Childrens Hosp Boston, Manton Ctr Orphan Dis Res, Boston, MA USA. RP Bloch, DB (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. EM bloch@helix.mgh.harvard.edu RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 8 TC 6 Z9 6 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 2012 VL 129 IS 6 BP 1678 EP 1680 DI 10.1016/j.jaci.2012.01.046 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 952BL UT WOS:000304764600034 PM 22341038 ER PT J AU Miller, MW Wolf, EJ Reardon, A Greene, A Ofrat, S McInerney, S AF Miller, Mark W. Wolf, Erika J. Reardon, Annemarie Greene, Ashley Ofrat, Shani McInerney, Scott TI Personality and the latent structure of PTSD comorbidity SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE PTSD; Comorbidity; Personality; Internalizing; Externalizing ID POSTTRAUMATIC-STRESS-DISORDER; COMMON MENTAL-DISORDERS; PSYCHOMETRIC PROPERTIES; INTERNALIZING SUBTYPES; NEGATIVE EMOTIONALITY; ANXIETY DISORDERS; MOOD DISORDERS; DSM-IV; MODEL; VETERANS AB This study examined the structure of PTSD comorbidity and its relationship to personality in a sample of 214 veterans using data from diagnostic interviews and the Multidimensional Personality Questionnaire-Brief Form (MPQ-BF; Patrick, Curtin, & Tellegen, 2002). Confirmatory factor analyses supported a three factor model composed of Externalizing. Fear and Distress factors. Analyses that examined the location of borderline personality disorder revealed significant cross-loadings for this disorder on both Externalizing and Distress. Structural equation models showed trait negative emotionality to be significantly related to all three comorbidity factors whereas positive emotionality and constraint evidenced specific associations with Distress and Externalizing, respectively. These results shed new light on the location of borderline personality disorder within the internalizing/externalizing model and clarify the relative influence of broad dimensions of personality on patterns of comorbidity. Published by Elsevier Ltd. C1 [Miller, Mark W.; Wolf, Erika J.] Boston Univ, Sch Med, Dept Psychiat, Natl Ctr PTSD,VA Boston Healthcare Syst, Boston, MA 02215 USA. RP Miller, MW (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B2, 150 S Huntington Ave, Boston, MA 02130 USA. EM mark.miller5@va.gov RI Miller, Mark/G-7322-2011; OI Miller, Mark/0000-0001-6393-8563; Wolf, Erika/0000-0003-2666-2435 FU CSRD VA [I01 CX000431]; Intramural VA [CDA-2-067-10S]; NIMH NIH HHS [R01 MH079806] NR 84 TC 15 Z9 15 U1 5 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD JUN PY 2012 VL 26 IS 5 BP 599 EP 607 DI 10.1016/j.janxdis.2012.02.016 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 955SN UT WOS:000305041300005 PM 22480716 ER PT J AU Bates, ML Fulmer, BR Farrell, ET Drezdon, A Pegelow, DF Conhaim, RL Eldridge, MW AF Bates, Melissa L. Fulmer, Brendan R. Farrell, Emily T. Drezdon, Alyssa Pegelow, David F. Conhaim, Robert L. Eldridge, Marlowe W. TI Hypoxia recruits intrapulmonary arteriovenous pathways in intact rats but not isolated rat lungs SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE arteriovenous anastamoses; hypoxia; intrapulmonary shunts; lung; microspheres ID PULMONARY GAS-EXCHANGE; HEALTHY HUMANS; VASCULAR PRESSURES; BLOOD VOLUME; EXERCISE; EPINEPHRINE; STROKE; TRANSPULMONARY; DISTENSIBILITY; PERFUSION AB Bates ML, Fulmer BR, Farrell ET, Drezdon A, Pegelow DF, Conhaim RL, Eldridge MW. Hypoxia recruits intrapulmonary arteriovenous pathways in intact rats but not isolated rat lungs. J Appl Physiol 112: 1915-1920, 2012. First published March 15, 2012; doi:10.1152/japplphysiol.00985.2011.-Intrapulmonary arteriovenous anastomoses (IPAVS) directly connect the arterial and venous circulations in the lung, bypassing the capillary network. Here, we used solid, latex microspheres and isolated rat lung and intact, spontaneously breathing rat models to test the hypothesis that IPAVS are recruited by alveolar hypoxia. We found that hypoxia recruits IPAVS in the intact rat, but not the isolated lung. IPAVS are at least 70 mu m in the rat and, interestingly, appear to be recruited when the mixed venous PO2 falls below 22 mmHg. These data provide evidence that large-diameter, direct arteriovenous connections exist in the lung and are recruitable by hypoxia in the intact animal. C1 [Bates, Melissa L.] Univ Wisconsin, Clin Sci Ctr H6 551, Sch Med & Publ Hlth, Dept Pediat, Madison, WI 53792 USA. [Bates, Melissa L.; Fulmer, Brendan R.; Farrell, Emily T.; Drezdon, Alyssa; Pegelow, David F.; Eldridge, Marlowe W.] Univ Wisconsin, Sch Med & Publ Hlth, John Rankin Lab Pulm Med, Madison, WI 53792 USA. [Eldridge, Marlowe W.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biomed Engn, Madison, WI 53792 USA. [Eldridge, Marlowe W.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Kinesiol, Madison, WI 53792 USA. [Conhaim, Robert L.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Madison, WI 53792 USA. [Conhaim, Robert L.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Bates, ML (reprint author), Univ Wisconsin, Clin Sci Ctr H6 551, Sch Med & Publ Hlth, Dept Pediat, 600 Highland Ave, Madison, WI 53792 USA. EM mlbates@pediatrics.wisc.edu FU National Institutes of Health [5R01-HL-086897, 5T32-HL-007654]; American Heart Association FX This work was supported by grants from the National Institutes of Health (5R01-HL-086897 and 5T32-HL-007654) and a postdoctoral fellowship from the American Heart Association. NR 32 TC 16 Z9 16 U1 0 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUN PY 2012 VL 112 IS 11 BP 1915 EP 1920 DI 10.1152/japplphysiol.00985.2011 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 952RS UT WOS:000304810500014 PM 22422800 ER PT J AU Rahko, JS Paakki, JJ Starck, TH Nikkinen, J Pauls, DL Katsyri, JV Jansson-Verkasalo, EM Carter, AS Hurtig, TM Mattila, ML Jussila, KK Remes, JJ Kuusikko-Gauffin, SA Sams, ME Bolte, S Ebeling, HE Moilanen, IK Tervonen, O Kiviniemi, V AF Rahko, Jukka S. Paakki, Jyri-Johan Starck, Tuomo H. Nikkinen, Juha Pauls, David L. Katsyri, Jari V. Jansson-Verkasalo, Eira M. Carter, Alice S. Hurtig, Tuula M. Mattila, Marja-Leena Jussila, Katja K. Remes, Jukka J. Kuusikko-Gauffin, Sanna A. Sams, Mikko E. Bolte, Sven Ebeling, Hanna E. Moilanen, Irma K. Tervonen, Osmo Kiviniemi, Vesa TI Valence Scaling of Dynamic Facial Expressions is Altered in High-Functioning Subjects with Autism Spectrum Disorders: an fMRI Study SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Emotional facial expressions; Face processing; Functional MRI; Mirror neuron system; Valence ID SCHOOL-AGE-CHILDREN; ASPERGER-SYNDROME; NEGATIVE EMOTION; BRAIN IMAGES; SOCIAL BRAIN; NEURAL BASIS; PERCEPTION; AMYGDALA; ADOLESCENTS; MECHANISMS AB FMRI was performed with the dynamic facial expressions fear and happiness. This was done to detect differences in valence processing between 25 subjects with autism spectrum disorders (ASDs) and 27 typically developing controls. Valence scaling was abnormal in ASDs. Positive valence induces lower deactivation and abnormally strong activity in ASD in multiple regions. Negative valence increased deactivation in visual areas in subjects with ASDs. The most marked differences between valences focus on fronto-insular and temporal regions. This supports the idea that subjects with ASDs may have difficulty in passive processing of the salience and mirroring of expressions. When the valence scaling of brain activity fails, in contrast to controls, these areas activate and/or deactivate inappropriately during facial stimuli presented dynamically. C1 [Rahko, Jukka S.; Hurtig, Tuula M.; Mattila, Marja-Leena; Jussila, Katja K.; Kuusikko-Gauffin, Sanna A.; Ebeling, Hanna E.; Moilanen, Irma K.] Univ OYS Oulu, Dept Child Psychiat, Inst Clin Med, Oulu 90029, Finland. [Rahko, Jukka S.; Paakki, Jyri-Johan; Starck, Tuomo H.; Nikkinen, Juha; Hurtig, Tuula M.; Mattila, Marja-Leena; Jussila, Katja K.; Remes, Jukka J.; Kuusikko-Gauffin, Sanna A.; Ebeling, Hanna E.; Moilanen, Irma K.; Tervonen, Osmo; Kiviniemi, Vesa] Univ Hosp Oulu, Oulu 90029, Finland. [Paakki, Jyri-Johan; Starck, Tuomo H.; Nikkinen, Juha; Remes, Jukka J.; Tervonen, Osmo; Kiviniemi, Vesa] Univ OYS Oulu, Dept Diagnost Radiol, Oulu 90029, Finland. [Pauls, David L.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Pauls, David L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Katsyri, Jari V.; Sams, Mikko E.] Univ Aalto, Aalto Univ Sch Sci & Technol, Dept Biomed Engn & Computat Sci BECS, Mind & Brain Lab, Espoo 00076, Finland. [Jansson-Verkasalo, Eira M.] Univ Turku, CCN, Dept Behav Sci & Philosophy, Oulu 20017, Finland. [Carter, Alice S.] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. [Bolte, Sven] Karolinska Inst, Karolinska Inst Ctr Neurodev Disorders KIND, S-17177 Stockholm, Sweden. RP Rahko, JS (reprint author), Univ OYS Oulu, Dept Child Psychiat, Inst Clin Med, POB 26, Oulu 90029, Finland. EM jrahko@me.com; jyri-johan.paakki@ppshp.fi; tuomo.starck@ppshp.fi; Juha.Nikkinen@ppshp.fi; dpauls@pngu.mgh.harvard.edu; jari.katsyri@hse.fi; eira.jansson-verkasalo@utu.fi; alice.carter@umb.edu; tuula.hurtig@oulu.fi; marja-leena.mattila@fimnet.fi; katja.jussila@nuorten-yst.fi; jukka.remes@oulu.fi; sanna.kuusikkogauffin@gmail.com; mikkosams@mac.com; sven.bolte@ki.se; hanna.ebeling@ppshp.fi; irma.moilanen@ppshp.fi; osmo.tervonen@ppshp.fi; vesa.kiviniemi@oulu.fi RI Sams, Mikko/G-7060-2012; Remes, Jukka/E-4217-2015 OI Remes, Jukka/0000-0003-1685-8346 NR 72 TC 5 Z9 6 U1 3 U2 18 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD JUN PY 2012 VL 42 IS 6 BP 1011 EP 1024 DI 10.1007/s10803-011-1332-8 PG 14 WC Psychology, Developmental SC Psychology GA 949YA UT WOS:000304613000013 PM 21822763 ER PT J AU Bent, S Bertoglio, K Ashwood, P Nemeth, E Hendren, RL AF Bent, Stephen Bertoglio, Kiah Ashwood, Paul Nemeth, Edward Hendren, Robert L. TI Brief Report: Hyperbaric Oxygen Therapy (HBOT) in Children with Autism Spectrum Disorder: A Clinical Trial SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Clinical trial; Alternative therapy ID OXIDATIVE STRESS; MULTICENTER; BRAIN AB We sought to determine whether HBOT leads to parental reported behavioral changes and alterations in cytokines in children with ASD. Ten children completed 80 sessions of HBOT and all improved by 2 points on the clinician-rated CGI-I scale (much improved) as well as several parent-completed measures of behavior. The lack of a control group limits the ability to determine if improvements were related to HBOT. Enrolled children did not exhibit abnormal cytokine levels at baseline and no significant changes in mean cytokine levels were observed. Although this study was limited by the small sample size and by the variable nature of cytokines, we found no evidence that HBOT affects cytokine levels or that cytokine levels were associated with behavioral changes. C1 [Bent, Stephen] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Bent, Stephen; Hendren, Robert L.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Bent, Stephen] Univ Calif San Francisco, Dept Med, Osher Ctr Integrat Med, San Francisco, CA USA. [Bent, Stephen] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Bertoglio, Kiah] Univ Calif Irvine, Sch Med, Irvine, CA 92717 USA. [Ashwood, Paul] Univ Calif Davis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. [Nemeth, Edward] CHERISH Fdn, Sacramento, CA USA. RP Bent, S (reprint author), San Francisco VA Med Ctr, 111-A1,4150 Clement St, San Francisco, CA 94121 USA. EM Stephen.Bent@ucsf.edu FU Autism Speaks [AS2311]; NCRR NIH HHS [UL1 RR024131] NR 17 TC 9 Z9 11 U1 1 U2 13 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD JUN PY 2012 VL 42 IS 6 BP 1127 EP 1132 DI 10.1007/s10803-011-1337-3 PG 6 WC Psychology, Developmental SC Psychology GA 949YA UT WOS:000304613000025 PM 21818676 ER PT J AU Goodlin, SJ AF Goodlin, Sarah J. TI Hospice Care Following Heart Failure Admission: What Next? SO JOURNAL OF CARDIAC FAILURE LA English DT Editorial Material ID PALLIATIVE CARE; COMMUNICATION C1 [Goodlin, Sarah J.] Portland VA Med Ctr, Portland, OR USA. [Goodlin, Sarah J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Goodlin, Sarah J.] Patient Ctr Educ & Res, Salt Lake City, UT USA. RP Goodlin, SJ (reprint author), P3 Med Portland VAMC, POB 1034, Portland, OR 97207 USA. EM sgoodlin@patient-centered.org NR 13 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD JUN PY 2012 VL 18 IS 6 BP 478 EP 479 DI 10.1016/j.cardfail.2012.03.004 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 957MF UT WOS:000305166400006 PM 22633305 ER PT J AU Verrier, RL Josephson, ME AF Verrier, Richard L. Josephson, Mark E. TI The Stress of Sleep in Patients Prone to Atrial Tachyarrhythmias SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Editorial Material ID FIBRILLATION; APNEA; OBESITY; ONSET; RISK C1 [Verrier, Richard L.; Josephson, Mark E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiovasc Med, Boston, MA 02215 USA. RP Verrier, RL (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiovasc Med, 99 Brookline Ave,RN-301, Boston, MA 02215 USA. EM rverrier@bidmc.harvard.edu NR 11 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD JUN PY 2012 VL 23 IS 6 BP 612 EP 613 DI 10.1111/j.1540-8167.2012.02294.x PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 955ZV UT WOS:000305060300008 PM 22494659 ER PT J AU Yamaleyeva, LM Lindsey, SH Varagic, J Zhang, LL Gallagher, PE Chen, AF Chappell, MC AF Yamaleyeva, Liliya M. Lindsey, Sarah H. Varagic, Jasmina Zhang, Li Li Gallagher, Patricia E. Chen, Alex F. Chappell, Mark C. TI Amelioration of Renal Injury and Oxidative Stress by the nNOS Inhibitor L-VNIO in the Salt-sensitive mRen2. Lewis Congenic Rat SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE albuminuria; renal inflammation; renal cortex; tetrahy-drobiopterin; 8-hydroxy-deoxyguanosine ID NITRIC-OXIDE SYNTHASE; BLOOD-PRESSURE; SEX-DIFFERENCES; ANGIOTENSIN-II; HYPERTENSION; KIDNEY; EXPRESSION; MECHANISM; DYSFUNCTION; ESTROGEN AB Salt sensitivity is a key risk factor for cardiovascular disease and renal injury. Alterations in renal nitric oxide may contribute to salt-dependent increases in blood pressure and tissue damage. Therefore, we assessed the expression of nitric oxide synthase (NOS) isoforms in the kidney and the effects of nNOS inhibition on renal injury, inflammation, and oxidative stress in the female mRen2.Lewis rat (mRen), a model of salt-sensitive hypertension. We find that a high-salt diet (4% sodium) significantly reduced endothelial NOS mRNA (2.6-fold) and protein (1.5-fold) but increased nNOS mRNA (2.4-fold) and protein (1.9-fold) in the renal cortex of these animals. Immunostaining for nNOS also seemed higher in macula densa and cortical tubules of the rats fed a high-salt diet. Circulating nitrate and nitrite levels were reduced, including the tissue levels of the NOS cofactor tetrahydrobiopterin. Cortical markers of oxidative stress (4HNE, 8-OH-deoxyguanosine) and fibrosis were increased; however, mRNA levels of the NAD(P) H oxidase components NOX4, p22phox, and p47phox were reduced. Chronic treatment with the nNOS inhibitor N-5-(1-Imino-3-butenyl)-L-ornithine did not influence systolic blood pressure after 4 weeks but significantly attenuated albuminuria, renal fibrosis, inflammation, and indices of oxidative stress. We conclude that an increase in nNOS expression in conjunction with reduced levels of cortical tetrahydrobiopterin may stimulate oxidative stress and renal injury in the salt-sensitive female mRen2.Lewis rat. C1 [Yamaleyeva, Liliya M.; Lindsey, Sarah H.; Varagic, Jasmina; Gallagher, Patricia E.; Chappell, Mark C.] Wake Forest Univ, Bowman Gray Sch Med, Hypertens & Vasc Res Ctr, Winston Salem, NC USA. [Zhang, Li Li; Chen, Alex F.] Univ Pittsburgh, Sch Med, Dept Surg, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Yamaleyeva, LM (reprint author), Wake Forest Sch Med, Hypertens & Vasc Res Ctr, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM lyamaley@wake-health.edu FU National Heart Lung and Blood Institute, NIH [HL-56973, HL-51952]; NIH [HL-103974]; American Heart Association Mid-Atlantic Affiliate [AHA-151521, AHA-2300114, AHA-525586U]; National Institute of General Medical Science, NIH [R01GM077352]; American Diabetes Association [7-08-RA-23] FX Supported by grants from the National Heart Lung and Blood Institute, NIH, to M.C. Chappell (HL-56973, HL-51952); NIH to S.H. Lindsey (HL-103974); the American Heart Association Mid-Atlantic Affiliate to M.C. Chappell (AHA-151521), J. Varagic (AHA-2300114), and to L.M. Yamaleyeva (AHA-525586U); the National Institute of General Medical Science, NIH (R01GM077352), and the American Diabetes Association (7-08-RA-23) to A.F. Chen. NR 39 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD JUN PY 2012 VL 59 IS 6 BP 529 EP 538 DI 10.1097/FJC.0b013e31824dd15b PG 10 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 956IF UT WOS:000305082600006 PM 22370956 ER PT J AU Xing, CH Leychenko, T Guo, SZ Stins, M Torchilin, VP Lo, EH AF Xing, Changhong Leychenko, Tatyana Guo, Shuzhen Stins, Monique Torchilin, Vladimir P. Lo, Eng H. TI Delivering minocycline into brain endothelial cells with liposome-based technology SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE brain endothelial cell; calpain; caspase; cell death; liposome; minocycline ID ISCHEMIC-STROKE; INJURY; TRIAL AB Minocycline has been proposed as a way to blunt neurovascular injury from matrix metalloproteinases (MMPs) during stroke. However, recent clinical trials suggest that high levels of minocycline may have deleterious side-effects. Here, we showed that very high minocycline concentrations damage endothelial cells via calpain/caspase pathways. To alleviate this potential cytotoxicity, we encapsulated minocycline in liposomes. Low concentrations of minocycline could not reduce tumor necrosis factor alpha (TNF alpha)-induced MMP-9 release from endothelial cells. But low concentrations of minocycline-loaded liposomes significantly reduced TNF alpha-induced MMP-9 release. This study provides proof-of-concept that liposomes may be used to deliver lower levels of minocycline for targeting MMPs in cerebral endothelium. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 983-988; doi:10.1038/jcbfm.2012.48; published online 11 April 2012 C1 [Xing, Changhong; Guo, Shuzhen; Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA USA. [Leychenko, Tatyana; Torchilin, Vladimir P.] Northeastern Univ, Dept Pharmaceut Sci, Boston, MA 02115 USA. [Stins, Monique] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Xing, Changhong; Guo, Shuzhen; Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Neurol, Charlestown, MA USA. RP Lo, EH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Radiol, MGH E 149-2401, Charlestown, MA USA. EM Lo@helix.mgh.harvard.edu FU NIH [R01-NS56458, R37-NS37074, P01-NS55104] FX This study was supported in part by NIH Grants R01-NS56458, R37-NS37074, and P01-NS55104. NR 15 TC 9 Z9 9 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2012 VL 32 IS 6 BP 983 EP 988 DI 10.1038/jcbfm.2012.48 PG 6 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 951RS UT WOS:000304738300008 PM 22491155 ER PT J AU Ingelfinger, JR Nuyt, AM AF Ingelfinger, Julie R. Nuyt, Anne-Monique TI Impact of Fetal Programming, Birth Weight, and Infant Feeding on Later Hypertension SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Review ID ISCHEMIC-HEART-DISEASE; CHRONIC LUNG-DISEASE; BLOOD-PRESSURE; ENDOTHELIAL FUNCTION; GESTATIONAL-AGE; ADULT LIFE; OXIDATIVE STRESS; YOUNG-ADULTS; IN-UTERO; BRONCHOPULMONARY DYSPLASIA AB J Clin Hypertens (Greenwich). 2012; 14:365371. (C) 2012 Wiley Periodicals, Inc. The concept of developmental origins of adult disease derives from both epidemiologic and basic sciences. This brief review considers the impact of the intrauterine milieu, intrauterine growth retardation, premature birth, and infant feeding on later hypertension and kidney disease. C1 [Ingelfinger, Julie R.] Massachusetts Gen Hosp, MassGen Hosp Children, Pediat Nephrol Unit, Dept Pediat,Div Nephrol, Boston, MA 02114 USA. [Nuyt, Anne-Monique] Ste Justine Univ Hosp & Res Ctr, Div Neonatol, Dept Pediat, Montreal, PQ, Canada. RP Ingelfinger, JR (reprint author), Massachusetts Gen Hosp, MassGen Hosp Children, Pediat Nephrol Unit, Dept Pediat,Div Nephrol, Yawkey 6C,55 Fruit St, Boston, MA 02114 USA. EM jingelfinger@partners.org FU Fonds de la Recherche en Sante du Quebec Senior Scholar Award; Canadian Institutes of Health Research FX Dr Nuyt is supported by a Fonds de la Recherche en Sante du Quebec Senior Scholar Award, and is an investigator on two grants from the Canadian Institutes of Health Research. Dr Ingelfinger and Dr Nuyt have stated that they have no competing interests to disclose. NR 78 TC 19 Z9 20 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1524-6175 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD JUN PY 2012 VL 14 IS 6 BP 365 EP 371 DI 10.1111/j.1751-7176.2012.00660.x PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 952OY UT WOS:000304803000005 PM 22672090 ER PT J AU Rothenberg, SM Ellisen, LW AF Rothenberg, S. Michael Ellisen, Leif W. TI The molecular pathogenesis of head and neck squamous cell carcinoma SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID RECEPTOR TYROSINE KINASE; HUMAN-PAPILLOMAVIRUS TYPE-16; COPY NUMBER ALTERATIONS; RAS ONCOGENE MUTATION; TUMOR-SUPPRESSOR GENE; CERVICAL-CANCER CELLS; LI-FRAUMENI-SYNDROME; SIGNALING PATHWAYS; HIGH-FREQUENCY; GROWTH ARREST AB Squamous cell carcinoma of the head and neck (HNSCC) is a relatively common human cancer characterized by high morbidity, high mortality, and few therapeutic options outside of surgery, standard cytotoxic chemotherapy, and radiation. Although the most important risk factors are tobacco use and alcohol consumption, the disease is also linked to infection with high-risk types of human papilloma viruses (HPVs). Recent genetic analyses have yielded new insights into the molecular pathogenesis of this disease. Overall, while somatic activating mutations within classical oncogenes including PIK3CA and RAS occur in HNSCC, they are relatively uncommon. Instead genetic data point to a contribution of multiple tumor suppressor pathways, including p53, Rb/INK4/ARF, and Notch, in tumor initiation, progression, and maintenance. The increasingly refined knowledge of HNSCC genetics, combined with ever-more-sophisticated animal models and newer drug targeting strategies, should promote novel therapeutic approaches and improved disease outcomes. C1 [Ellisen, Leif W.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ellisen, LW (reprint author), Massachusetts Gen Hosp, Ctr Canc, GRJ-904,55 Fruit St, Boston, MA 02114 USA. EM ellisen@helix.mgh.harvard.edu FU NIH [R01 DE-015945, K08 DE-020139] FX The authors wish to thank Lori Wirth and members of the Ellisen laboratory for helpful discussions and review of the manuscript. This work was supported by NIH R01 DE-015945 (to L.W. Ellisen) and by NIH K08 DE-020139 (to S.M. Rothenberg). NR 120 TC 121 Z9 124 U1 0 U2 24 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2012 VL 122 IS 6 BP 1951 EP 1957 DI 10.1172/JCI59889 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 951QY UT WOS:000304736300002 PM 22833868 ER PT J AU LaBelle, JL Katz, SG Bird, GH Gavathiotis, E Stewart, ML Lawrence, C Fisher, JK Godes, M Pitter, K Kung, AL Walensky, LD AF LaBelle, James L. Katz, Samuel G. Bird, Gregory H. Gavathiotis, Evripidis Stewart, Michelle L. Lawrence, Chelsea Fisher, Jill K. Godes, Marina Pitter, Kenneth Kung, Andrew L. Walensky, Loren D. TI A stapled BIM peptide overcomes apoptotic resistance in hematologic cancers SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID STABILIZED ALPHA-HELICES; ACUTE MYELOID-LEUKEMIA; BCL-2 FAMILY-MEMBERS; BH3 MIMETIC ABT-737; MEMBRANE PERMEABILIZATION; CELL-DEATH; IN-VIVO; CHEMOTHERAPEUTIC-AGENTS; HOMOZYGOUS DELETIONS; ANTIAPOPTOTIC BCL-2 AB Cancer cells subvert the natural balance between cellular life and death, achieving immortality through pathologic enforcement of survival pathways and blockade of cell death mechanisms. Pro-apoptotic BCL-2 family proteins are frequently disarmed in relapsed and refractory cancer through genetic deletion or interaction-based neutralization by overexpressed antiapoptotic proteins, resulting in resistance to chemotherapy and radiation treatments. New pharmacologic strategies are urgently needed to overcome these formidable apoptotic blockades. We harnessed the natural killing activity of BCL-2-interacting mediator of cell death (BIM), which contains one of the most potent BH3 death domains of the BCL-2 protein family, to restore BH3-dependent cell death in resistant hematologic cancers. A hydrocarbon-stapled peptide modeled after the BIM BH3 helix broadly targeted BCL-2 family proteins with high affinity, blocked inhibitory antiapoptotic interactions, directly triggered proapoptotic activity, and induced dose-responsive and BH3 sequence-specific cell death of hematologic cancer cells. The therapeutic potential of stapled BIM BH3 was highlighted by the selective activation of cell death in the aberrant lymphoid infiltrates of mice reconstituted with BIM-deficient bone marrow and in a human AML xenograft model. Thus, we found that broad and multimodal targeting of the BCL-2 family pathway can overcome pathologic barriers to cell death. C1 [LaBelle, James L.; Katz, Samuel G.; Bird, Gregory H.; Gavathiotis, Evripidis; Stewart, Michelle L.; Lawrence, Chelsea; Fisher, Jill K.; Godes, Marina; Pitter, Kenneth; Kung, Andrew L.; Walensky, Loren D.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [LaBelle, James L.; Katz, Samuel G.; Bird, Gregory H.; Gavathiotis, Evripidis; Stewart, Michelle L.; Lawrence, Chelsea; Fisher, Jill K.; Godes, Marina; Pitter, Kenneth; Kung, Andrew L.; Walensky, Loren D.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02215 USA. [LaBelle, James L.; Kung, Andrew L.; Walensky, Loren D.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [LaBelle, James L.; Bird, Gregory H.; Gavathiotis, Evripidis; Kung, Andrew L.; Walensky, Loren D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Katz, Samuel G.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Katz, Samuel G.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Walensky, LD (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 450 Brookline Ave,Mayer 664, Boston, MA 02215 USA. EM loren_walensky@dfci.harvard.edu OI Kung, Andrew/0000-0002-9091-488X FU Lauri Strauss Leukemia Foundation; Leukemia and Lymphoma Society; NIH [1K08CA151450, 5P01CA92625, 5R01CA050239]; Leukemia and Lymphoma Society SCOR; Todd J. Schwartz Pediatric Oncology Fund; Wolpoff Family Foundation; Burroughs Wellcome Fund Career Award FX We thank E.D. Smith, A.L. Christie, and L. Cameron for assistance with graphics, animal treatment and imaging, and confocal microscopy, respectively. This work was supported by a Lauri Strauss Leukemia Foundation Discovery Grant, a Leukemia and Lymphoma Society Special Fellow Award, and NIH grant 1K08CA151450 to J.L. LaBelle and NIH grants 5P01CA92625 and 5R01CA050239, a Leukemia and Lymphoma Society SCOR grant, the Todd J. Schwartz Pediatric Oncology Fund, a grant from the Wolpoff Family Foundation, and a Burroughs Wellcome Fund Career Award to L.D. Walensky. We thank the LaTorre family for their generous support of C. Lawrence. NR 50 TC 72 Z9 77 U1 1 U2 32 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2012 VL 122 IS 6 BP 2018 EP 2031 DI 10.1172/JCI46231 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 951QY UT WOS:000304736300012 PM 22622039 ER PT J AU Liu, T Berta, T Xu, ZZ Park, CK Zhang, L Lu, N Liu, Q Liu, Y Gao, YJ Liu, YC Ma, QF Dong, XZ Ji, RR AF Liu, Tong Berta, Temugin Xu, Zhen-Zhong Park, Chul-Kyu Zhang, Ling Lu, Ning Liu, Qin Liu, Yang Gao, Yong-Jing Liu, Yen-Chin Ma, Qiufu Dong, Xinzhong Ji, Ru-Rong TI TLR3 deficiency impairs spinal cord synaptic transmission, central sensitization, and pruritus in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TOLL-LIKE RECEPTOR-3; DOUBLE-STRANDED-RNA; DORSAL-HORN NEURONS; INNATE IMMUNITY; PAR-2 AGONIST; NERVE INJURY; DRY SKIN; ITCH; ACTIVATION; PAIN AB Itch, also known as pruritus, is a common, intractable symptom of several skin diseases, such as atopic dermatitis and xerosis. TLRs mediate innate immunity and regulate neuropathic pain, but their roles in pruritus are elusive. Here, we report that scratching behaviors induced by histamine-dependent and -independent pruritogens are markedly reduced in mice lacking the Tlr3 gene. TLR3 is expressed mainly by small-sized primary sensory neurons in dorsal root ganglions (DRGs) that coexpress the itch signaling pathway components transient receptor potential subtype V1 and gastrin-releasing peptide. Notably, we found that treatment with a TLR3 agonist induces inward currents and action potentials in DRG neurons and elicited scratching in WT mice but not Tlr3(-/-) mice. Furthermore, excitatory synaptic transmission in spinal cord slices and long-term potentiation in the intact spinal cord were impaired in Tlr3(-/-) mice but not Tlr7(-/-) mice. Consequently, central sensitization-driven pain hypersensitivity, but not acute pain, was impaired in Tlr3(-/-) mice. In addition, TLR3 knockdown in DRGs also attenuated pruritus in WT mice. Finally, chronic itch in a dry skin condition was substantially reduced in Tlr3(-/-) mice. Our findings demonstrate a critical role of TLR3 in regulating sensory neuronal excitability, spinal cord synaptic transmission, and central sensitization. TLR3 may serve as a new target for developing anti-itch treatment. C1 [Liu, Tong; Berta, Temugin; Xu, Zhen-Zhong; Park, Chul-Kyu; Zhang, Ling; Lu, Ning; Liu, Qin; Gao, Yong-Jing; Liu, Yen-Chin; Ji, Ru-Rong] Brigham & Womens Hosp, Sensory Plast Lab, Pain Res Ctr, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Dong, Xinzhong] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Ctr Sensory Biol, Baltimore, MD USA. [Liu, Yang; Ma, Qiufu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Liu, Yang; Ma, Qiufu] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Ji, RR (reprint author), Duke Univ, Med Ctr, Dept Anesthesiol, Pain Res Div, DUMC Box 3094,GSRB 1,Room 1027A,595 LaSalle St, Durham, NC 27710 USA. EM ru-rong.ji@duke.edu RI Liu, Tong/C-7810-2012; GAO, YONG-JING/E-6939-2015; Berta, Temugin/A-6908-2016; OI GAO, YONG-JING/0000-0002-7432-7458; Berta, Temugin/0000-0002-4486-8288; Liu, Yen-Chin/0000-0002-5247-1678; Ji, Ru-Rong/0000-0002-9355-3688 FU US NIH [R01-DE17794, R01-NS54362, R01-NS67686] FX This work was supported by US NIH grants R01-DE17794, R01-NS54362, and R01-NS67686 to R.-R. Ji. NR 47 TC 50 Z9 52 U1 1 U2 16 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2012 VL 122 IS 6 BP 2195 EP 2207 DI 10.1172/JCI45414 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 951QY UT WOS:000304736300026 PM 22565312 ER PT J AU Buys, ES Raher, MJ Kirby, A Mohd, S Baron, DM Hayton, SR Tainsh, LT Sips, PY Rauwerdink, KM Yan, QS Tainsh, RET Shakartzi, HR Stevens, C Decaluwe, K Rodrigues-Machado, MD Malhotra, R Van de Voorde, J Wang, T Brouckaert, P Daly, MJ Bloch, KD AF Buys, Emmanuel S. Raher, Michael J. Kirby, Andrew Mohd, Shahid Baron, David M. Hayton, Sarah R. Tainsh, Laurel T. Sips, Patrick Y. Rauwerdink, Kristen M. Yan, Qingshang Tainsh, Robert E. T. Shakartzi, Hannah R. Stevens, Christine Decaluwe, Kelly Rodrigues-Machado, Maria da Gloria Malhotra, Rajeev Van de Voorde, Johan Wang, Tong Brouckaert, Peter Daly, Mark J. Bloch, Kenneth D. TI Genetic modifiers of hypertension in soluble guanylate cyclase alpha 1-deficient mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID RENIN-ANGIOTENSIN SYSTEM; NITRIC-OXIDE SYNTHASE; BLOOD-PRESSURE REGULATION; GENOME-WIDE ASSOCIATION; QUANTITATIVE TRAIT LOCI; SMOOTH-MUSCLE-CELLS; TGR(MREN2) 27 RATS; KNOCKOUT MICE; CONVERTING ENZYME; KIDNEY-DISEASE AB Nitric oxide (NO) plays an essential role in regulating hypertension and blood flow by inducing relaxation of vascular smooth muscle. Male mice deficient in a NO receptor component, the alpha 1 subunit of soluble guanylate cyclase (sGC alpha(1)), are prone to hypertension in some, but not all, mouse strains, suggesting that additional genetic factors contribute to the onset of hypertension. Using linkage analyses, we discovered a quantitative trait locus (QTL) on chromosome 1 that was linked to mean arterial pressure (MAP) in the context of sGC alpha(1) deficiency. This region is syntenic with previously identified blood pressure-related QTLs in the human and rat genome and contains the genes coding for renin. Hypertension was associated with increased activity of the renin-angiotensin-aldosterone system (RAAS). Further, we found that RAAS inhibition normalized MAP and improved endothelium-dependent vasorelaxation in sGC alpha(1)-deficient mice. These data identify the RAAS as a blood pressure-modifying mechanism in a setting of impaired NO/cGMP signaling. C1 [Buys, Emmanuel S.; Raher, Michael J.; Mohd, Shahid; Baron, David M.; Hayton, Sarah R.; Tainsh, Laurel T.; Sips, Patrick Y.; Rauwerdink, Kristen M.; Tainsh, Robert E. T.; Shakartzi, Hannah R.; Rodrigues-Machado, Maria da Gloria; Bloch, Kenneth D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Anesthesia Ctr Crit Care Res,Dept Anesthesia Crit, Boston, MA 02114 USA. [Kirby, Andrew; Stevens, Christine; Daly, Mark J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Ctr Human Genet Res, Boston, MA 02114 USA. [Yan, Qingshang; Wang, Tong] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. [Decaluwe, Kelly; Van de Voorde, Johan] Univ Ghent, Dept Pharmacol, B-9000 Ghent, Belgium. [Malhotra, Rajeev] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA 02114 USA. [Brouckaert, Peter] Univ Ghent, Dept Biomed Mol Biol, B-9000 Ghent, Belgium. [Brouckaert, Peter] VIB, Dept Mol Biomed Res, Ghent, Belgium. RP Buys, ES (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Anesthesia Ctr Crit Care Res,Dept Anesthesia Crit, 55 Fruit St,Thier 511B, Boston, MA 02114 USA. EM Ebuys@partners.org OI Sips, Patrick/0000-0001-9241-5980 FU American Heart Association [10SDG2610313, 11FTF7290032]; Harvard Medical School; CAPES/National Institute of Science and Technology in Nanobiopharmaceutics-UFMG; George M. O'Brien Kidney Center at Yale; FWO-Vlaanderen; UGent-GOA; NHLBI [R01 HL74352]; Fondation Leducq FX This work was supported by Scientist Development Grant 10SDG2610313 from the American Heart Association (to E.S. Buys), an Eleanor and Miles Shore 50th Anniversary Fellowship program for Scholars in Medicine from Harvard Medical School (to E.S. Buys), the Resuscitation Fellowship Award from the American Heart Association and Philips (to P.Y. Sips), a postdoctoral fellowship from CAPES/National Institute of Science and Technology in Nanobiopharmaceutics-UFMG (to M.D.G. Rodrigues-Machado), Fellow-to-Faculty Transition Award 11FTF7290032 from the American Heart Association (to R. Malhotra), the George M. O'Brien Kidney Center at Yale, Core B (to T. Wang), grants from the FWO-Vlaanderen and the UGent-GOA programs (to K. Decaluwe, J. Van de Voorde, and P. Brouckaert), and NHLBI grant R01 HL74352 (to K.D. Bloch) and a grant from the Fondation Leducq (to K.D. Bloch). NR 85 TC 19 Z9 19 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2012 VL 122 IS 6 BP 2316 EP 2325 DI 10.1172/JCI60119 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 951QY UT WOS:000304736300038 PM 22565307 ER PT J AU Papp, K Kimball, A Wasfi, Y Chan, D Bissonnette, R Sofen, H Yeilding, N Li, S Szapary, P Gordon, K AF Papp, K. Kimball, A. Wasfi, Y. Chan, D. Bissonnette, R. Sofen, H. Yeilding, N. Li, S. Szapary, P. Gordon, K. TI Long term efficacy and safety of ustekinumab in patients with moderate to severe psoriasis through 5 years of follow-up: results from the PHOENIX 1 long-term extension SO JOURNAL OF DERMATOLOGY LA English DT Meeting Abstract C1 [Papp, K.; Yeilding, N.] Prob Med Res, Waterloo, ON, Canada. [Kimball, A.] Harvard Univ, Sch Med, Boston, MA USA. [Kimball, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wasfi, Y.; Li, S.; Szapary, P.] Janssen Res & Dev LLC, Spring House, PA USA. [Bissonnette, R.] Innovaderm Res Inc, Montreal, PQ, Canada. [Sofen, H.] Dermatol Res Associates, Los Angeles, CA USA. [Gordon, K.] N Shore Univ Hlth Syst, Chicago, IL USA. [Gordon, K.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0385-2407 J9 J DERMATOL JI J. Dermatol. PD JUN PY 2012 VL 39 SU 1 SI SI BP 239 EP 240 PG 2 WC Dermatology SC Dermatology GA 956AL UT WOS:000305061900615 ER PT J AU Fujimoto, WY Boyko, EJ Hayashi, T Kahn, SE Leonetti, DL McNeely, MJ Shuman, WP AF Fujimoto, Wilfred Y. Boyko, Edward J. Hayashi, Tomoshige Kahn, Steven E. Leonetti, Donna L. McNeely, Marguerite J. Shuman, William P. TI Risk factors for type 2 diabetes: Lessons learned from Japanese Americans in Seattle SO JOURNAL OF DIABETES INVESTIGATION LA English DT Review DE Japanese Americans; Lifestyle; Obesity ID IMPAIRED GLUCOSE-TOLERANCE; BETA-CELL FUNCTION; CORONARY-HEART-DISEASE; BODY-FAT DISTRIBUTION; FASTING PLASMA-GLUCOSE; EARLY INSULIN-RESPONSE; 5-YEAR FOLLOW-UP; VISCERAL ADIPOSITY; ORAL GLUCOSE; COMPUTED-TOMOGRAPHY AB Migrant Japanese populations in both the USA and Brazil have for a long time shown a higher prevalence of type 2 diabetes than native Japanese, suggesting an interaction of lifestyle and genetic predisposition in the etiology of type 2 diabetes. The overall objective of the Seattle Japanese American Community Diabetes Study was to learn more about the etiology and pathogenesis of type 2 diabetes in Japanese Americans. This metabolically based epidemiological study included extensive assessments of insulin sensitivity, insulin response, and adiposity with the latter including measurements of body fat distribution by both anthropometry and computed tomography. Because of this, the importance of visceral adiposity as a risk factor for abnormal glucose tolerance, hypertension, coronary heart disease and the metabolic syndrome was shown. In conjunction with an examination of diet and physical activity patterns, the result was a clearer understanding of the etiology and pathogenesis of type 2 diabetes in Japanese Americans. We propose that a lifestyle that fosters increased weight gain, especially in the visceral adipose depot, promotes the development of insulin resistance, which in turn exposes an underlying reduced beta-cell reserve in susceptible individuals, resulting in glucose intolerance and, eventually in many, the development of diabetes. We have shown that it might be possible to delay or prevent the development of diabetes through dietary and exercise interventions in individuals identified as having impaired glucose tolerance. The lessons learned from studying migrant Japanese in Seattle might in many ways be applicable to other populations of Asian origin. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00195.x, 2012) C1 [Fujimoto, Wilfred Y.; Boyko, Edward J.; Kahn, Steven E.; McNeely, Marguerite J.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Leonetti, Donna L.] Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. [Shuman, William P.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Boyko, Edward J.; Hayashi, Tomoshige] Epidemiol Res & Informat Ctr, Seattle, WA USA. [Boyko, Edward J.; Kahn, Steven E.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Hayashi, Tomoshige] Osaka City Univ, Dept Prevent Med & Environm Hlth, Grad Sch Med, Osaka 558, Japan. RP Fujimoto, WY (reprint author), Univ Washington, Dept Med, Seattle, WA 98195 USA. EM wilfuji@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 FU Kroc Foundation; American Diabetes Association; National Institutes of Health [DK-02654, DK-02860, DK-31170, DK-48152, DK-50703, DK-55460, HL-07028, HL-49293]; United States Department of Veterans Affairs; Japan Society for the Promotion of Science; Uehara Memorial Foundation; Nakatomi Foundation; Japanese Ministry of Education, Science, Sports, and Culture FX This work was supported by grants from the Kroc Foundation and American Diabetes Association; National Institutes of Health Grants DK-02654, DK-02860, DK-31170, DK-48152, DK-50703, DK-55460, HL-07028 and HL-49293; and facilities and services provided by the Diabetes and Endocrinology Research Center (DK-17047), Clinical Nutrition Research Unit (DK-35816), and the General Clinical Research Center (RR-00037) at the University of Washington. EJB and SEK were also supported by the United States Department of Veterans Affairs. WYF was also supported by a grant from the Japan Society for the Promotion of Science as a Visiting Researcher at the University of Tokyo, and gratefully acknowledges the support and assistance provided by Dr Kinori Kosaka, Dr Yasuo Akanuma and Dr Yasunori Kanazawa at the University of Tokyo and Dr Nobusada Kuzuya at the Asahi Institute in Tokyo. TH was supported by grants from the Uehara Memorial Foundation, the Nakatomi Foundation, and the Japanese Ministry of Education, Science, Sports, and Culture as a Visiting Scholar at the University of Washington. All of the authors have contributed significantly to the collection and analysis of data, have reviewed and edited the manuscript, and have agreed to its content and submission for publication, and none have any financial relationships or support that might pose a conflict of interest. We thank the many skilled staff members at the University of Washington, especially Pamela Asberry, Jane Shofer, Christine Tsunehara, Pamela Yang and the staff of the General Clinical Research Center for their assistance, and also acknowledge the collaboration of many colleagues whose contributions are documented by their co-authorship of the many papers that have resulted from this research. Last but not least, we are particularly grateful for the unswerving support and cooperation of the King County Japanese American community and our Community Advisory Board, without which we would not have been able to carry out this study. NR 91 TC 18 Z9 18 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2040-1116 J9 J DIABETES INVEST JI J. Diabetes Investig. PD JUN PY 2012 VL 3 IS 3 BP 212 EP 224 DI 10.1111/j.2040-1124.2012.00195.x PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 953KG UT WOS:000304865500003 PM 22798980 ER PT J AU Yoon, JW Kang, SM Vassy, JL Shin, H Lee, YH Ahn, HY Choi, SH Park, KS Jang, HC Lim, S AF Yoon, Ji Won Kang, Seon Mee Vassy, Jason L. Shin, Hayley Lee, Yun Hee Ahn, Hwa Young Choi, Sung Hee Park, Kyong Soo Jang, Hak Chul Lim, Soo TI Efficacy and safety of ginsam, a vinegar extract from Panax ginseng, in type 2 diabetic patients: Results of a double-blind, placebo-controlled study SO JOURNAL OF DIABETES INVESTIGATION LA English DT Article DE Ginsam; Oral antidiabetic therapy; Panax ginseng ID HIGH-FAT DIET; METABOLIC SYNDROME; GLUCOSE-HOMEOSTASIS; PLASMA-GLUCOSE; BERRY EXTRACT; BODY-WEIGHT; ICR MICE; INSULIN; MODEL; RG3 AB Aims/Introduction: The efficacy, doseresponse relationship and safety of ginsam, a vinegar extract from Panax ginseng, were evaluated in an 8-week, double-blind, randomized, placebo-controlled study in drug-naive patients with type 2 diabetes. Materials and Methods: A total of 72 diabetic patients were randomized to receive 1500, 2000 or 3000 mg of ginsam, or placebo daily for 8 weeks (n = 18 in each group). The primary end-point was the changes from the baseline HbA1c level. The secondary end-points were the changes of fasting and postprandial 2-h glucose concentration, and the proportion of patients achieving a reduction in HbA1c >0.5%. Results: In the intention-to-treat analysis, ginsam treatment reduced HbA1c level significantly: -0.56 +/- 0.25% in the 1500 mg group, -0.31 +/- 0.12% in the 2000 mg group, and -0.29 +/- 0.11% in the 3000 mg group (all P < 0.05), with a significant difference between the 1500 mg ginsam and the placebo group (-0.02 +/- 0.12%, P = 0.021). The changes in fasting glucose concentration followed the same pattern: -21.40, -14.27 and -6.76 mg/dL for 1500, 2000, and 3000 mg, respectively, vs -2.25 mg/dL for the placebo. The percentage of patients whose HbA1c level decreased by >0.5% differed significantly between the placebo group (11.1%) and the 1500 mg (27.8%) and 2000 mg (27.8%) groups. No severe adverse events were observed in any group. Conclusions: An 8-week treatment with ginsam, a vinegar extract from P. ginseng, moderately improved HbA1c level and was well tolerated in type 2 diabetic patients with inadequate glycemic control. This trial was registered with ClinicalTrial.Gov (no. NCT01008163). (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00185. , 2011) C1 [Yoon, Ji Won; Kang, Seon Mee; Ahn, Hwa Young; Choi, Sung Hee; Park, Kyong Soo; Jang, Hak Chul; Lim, Soo] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Yoon, Ji Won] Seoul Natl Univ Hosp, Healthcare Syst Gangnam Ctr, Inst Healthcare Res, Seoul 110744, South Korea. [Kang, Seon Mee; Lee, Yun Hee; Ahn, Hwa Young; Choi, Sung Hee; Jang, Hak Chul; Lim, Soo] Seoul Natl Univ, Bundang Hosp, Songnam, South Korea. [Vassy, Jason L.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Vassy, Jason L.] Harvard Univ, Sch Med, Boston, MA USA. [Shin, Hayley] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Lim, S (reprint author), Seoul Natl Univ, Coll Med, Seoul, South Korea. EM limsoo@snu.ac.kr RI Park, Kyong Soo/C-2265-2008; OI Park, Kyong Soo/0000-0003-3597-342X; CHOI, SUNG HEE/0000-0003-0740-8116 FU Gyeonggi Biocenter; Yuyu pharmaceutical company FX This work was supported by a research grant from the Gyeonggi Biocenter and Yuyu pharmaceutical company. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Yuyu. All authors had no potential conflicts of interest. The funding agency had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The sole responsibility for the content of this manuscript lies with the authors. NR 33 TC 5 Z9 6 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2040-1116 J9 J DIABETES INVEST JI J. Diabetes Investig. PD JUN PY 2012 VL 3 IS 3 BP 309 EP 317 DI 10.1111/j.2040-1124.2011.00185.x PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 953KG UT WOS:000304865500018 PM 24843582 ER PT J AU Carnes, M Devine, PG Isaac, C Manwell, LB Ford, CE Byars-Winston, A Fine, E Sheridan, J AF Carnes, Molly Devine, Patricia G. Isaac, Carol Manwell, Linda Baier Ford, Cecelia E. Byars-Winston, Angela Fine, Eve Sheridan, Jennifer TI Promoting Institutional Change Through Bias Literacy SO JOURNAL OF DIVERSITY IN HIGHER EDUCATION LA English DT Article DE gender bias; faculty; STEM; intervention studies; prejudice; academic medical centers ID SELF-REGULATION; TRANSTHEORETICAL MODEL; PREJUDICE-REDUCTION; INTERGROUP CONTACT; PERSPECTIVE-TAKING; QUEEN BEE; WOMEN; DISCRIMINATION; STEREOTYPES; COMMITMENT AB The National Science Foundation and others conclude that institutional transformation is required to ensure equal opportunities for the participation and advancement of men and women in academic science, technology, engineering, mathematics, and medicine (STEMM). Such transformation requires changing the habitual attitudes and behaviors of faculty. Approaching implicit bias as a remediable habit, we present the theoretical basis and conceptual model underpinning an educational intervention to promote bias literacy among university faculty as a step toward institutional transformation regarding gender equity. We describe the development and implementation of a Bias Literacy Workshop in detail so others can replicate or adapt it to their setting. Of the 220 (167 faculty and 53 nonfaculty) attendees from the initial 17 departments/divisions offered this workshop, all 180 who completed a written evaluation found the workshop at least "somewhat useful" and 74% found it "very useful." Over 68% indicated increased knowledge of the workshop material. Of the 186 participants who wrote a commitment to engage in new activities to promote gender equity, 87% incorporated specific workshop content. Twenty-four participants were interviewed 4-6 months after attending the workshop; 75% of these not only demonstrated increased bias awareness, but described plans to change-or had actually changed-behaviors because of the workshop. Based on our sample of faculty from a Midwestern university, we conclude that at least one third of STEMM faculty who are invited will attend a 2.5-hr Bias Literacy Workshop, that nearly all will find it useful, and that most will complete a written commitment to promoting gender equity. These findings suggest that this educational intervention May effectively promote institutional change regarding gender equity. C1 [Carnes, Molly; Isaac, Carol; Manwell, Linda Baier; Byars-Winston, Angela] Univ Wisconsin, Ctr Womens Hlth Res, Madison, WI 53715 USA. [Byars-Winston, Angela] Univ Wisconsin, Dept Med, Div Gen Internal Med, Madison, WI 53715 USA. [Carnes, Molly] Univ Wisconsin, Dept Psychiat, Madison, WI 53715 USA. [Carnes, Molly] Univ Wisconsin, Dept Ind & Syst Engn, Madison, WI 53715 USA. [Carnes, Molly; Manwell, Linda Baier; Fine, Eve; Sheridan, Jennifer] Univ Wisconsin, WISELI, Madison, WI 53715 USA. [Carnes, Molly] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Devine, Patricia G.] Univ Wisconsin, Dept Psychol, Madison, WI 53715 USA. [Ford, Cecelia E.] Univ Wisconsin, Dept English, Madison, WI 53715 USA. RP Carnes, M (reprint author), Univ Wisconsin, Ctr Womens Hlth Res, 700 Regent St,Suite 301, Madison, WI 53715 USA. EM mlcarnes@wisc.edu FU NIGMS NIH HHS [R01 GM088477] NR 76 TC 21 Z9 21 U1 4 U2 37 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1938-8926 J9 J DIVERS HIGH EDUC JI J. Divers. High. Educ. PD JUN PY 2012 VL 5 IS 2 BP 63 EP 77 DI 10.1037/a0028128 PG 15 WC Education & Educational Research; Psychology, Educational; Psychology, Social SC Education & Educational Research; Psychology GA 950ZM UT WOS:000304690400001 PM 22822416 ER PT J AU Wiggers, JK Brouwer, KM Helmerhorst, GTT Ring, D AF Wiggers, Jimme K. Brouwer, Kim M. Helmerhorst, Gijs T. T. Ring, David TI Predictors of Diagnosis of Ulnar Neuropathy After Surgically Treated Distal Humerus Fractures SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Distal humerus fracture; ulnar neuropathy ID REDUCTION-INTERNAL-FIXATION; INTERCONDYLAR FRACTURES; OPERATIVE APPROACH; ELDERLY-PATIENTS; NERVE; ELBOW; TRANSPOSITION; ADULTS AB Purpose Ulnar nerve dysfunction is a common sequela of surgical treatment of distal humerus fractures. This study addresses the null hypothesis that different types of distal humerus injuries have comparable rates of diagnosis of ulnar neuropathy. Methods We assessed diagnosis of ulnar neuropathy in 107 consecutive adults who had a surgically treated fracture of the distal humerus followed up at least 6 months after injury. Diagnosis of ulnar neuropathy was defined as documentation of sensory and motor dysfunction of the ulnar nerve in the medical record. Fractures were categorized as either columnar fractures or fractures of the capitellum and trochlea. The explanatory (independent) variables included age, sex, fracture type, AO type, associated wound, associated elbow dislocation, mechanism of trauma, ipsilateral skeletal injury, olecranon osteotomy, implant over or below the medial epicondyle, infection, time from injury to surgery, the number of surgeries within 4 weeks and 6 months of injury, the total number of surgeries, and whether the nerve was transposed. Results Postoperative ulnar neuropathy was diagnosed in 17 of 107 patients (16%), including 16 of 59 columnar fractures (21%). The only risk factor for ulnar neuropathy was columnar fracture. Conclusions Patients with columnar fractures might be at higher risk for the development of postoperative ulnar neuropathy than patients with capitellum and trochlea fractures, regardless of whether the ulnar nerve was transposed. (J Hand Surg 2012;37A:1168-1172. Copyright (C) 2012 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Ring, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 19 TC 2 Z9 3 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JUN PY 2012 VL 37A IS 6 BP 1168 EP 1172 DI 10.1016/j.jhsa.2012.02.045 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 954WB UT WOS:000304977600009 PM 22522105 ER PT J AU Huffaker, SJ Christoforou, DC Jupiter, JB AF Huffaker, Stephen J. Christoforou, Dimitrios C. Jupiter, Jesse B. TI Spontaneous Rupture of the Extensor Carpi Radialis Brevis in a 51-Year-Old Man: Case Report SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Carpal boss; tendon attrition; tendon rupture ID TENDON RUPTURES; RHEUMATOID-ARTHRITIS; BOSS AB Dorsal hand osteophytes are common findings in the general population, frequently presenting with dorsal pain and treated with surgical excision. We report the spontaneous rupture of the extensor carpi radialis brevis in association with a previously asymptomatic dorsal scaphoid spur. Following conservative management, surgical excision of dorsal hand osteophytes should be considered for both resolution of pain and prevention of attritional tendon rupture. (J Hand Surg 2012;37A:1221-1224. Copyright (C) 2012 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Huffaker, Stephen J.; Christoforou, Dimitrios C.; Jupiter, Jesse B.] Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Hand & Upper Extrem Serv, 55 Fruit St,Yawkey 2C, Boston, MA 02114 USA. EM jjupiter1@partners.org NR 16 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JUN PY 2012 VL 37A IS 6 BP 1221 EP 1224 DI 10.1016/j.jhsa.2012.03.017 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 954WB UT WOS:000304977600019 PM 22542060 ER PT J AU Choi, JW Lee, JW Kim, JK Jeon, HK Choi, JJ Kim, DG Kim, BG Nam, DH Kim, HJ Yun, SH Kim, S AF Choi, Jin Woo Lee, Jeong-Won Kim, Jun Ki Jeon, Hye-Kyung Choi, Jung-Joo Kim, Dae Gyu Kim, Byoung-Gie Nam, Do-Hyun Kim, Hong Joong Yun, Seok Hyun Kim, Sunghoon TI Splicing variant of AIMP2 as an effective target against chemoresistant ovarian cancer SO JOURNAL OF MOLECULAR CELL BIOLOGY LA English DT Article DE multi-tRNA synthetase complex; AIMP2; splicing variant; ovarian cancer; chemoresistant cancer; NF-B ID NF-KAPPA-B; RNA SYNTHETASE COMPLEX; NECROSIS-FACTOR-ALPHA; SIGNALING PATHWAY; TNF-ALPHA; ACTIVATION; APOPTOSIS; TRAF2; PROGRESSION; INHIBITION AB Chemoresistance is a main cause for the failure of cancer management and intensive investigation is on-going to control chemoresistant (CR) cancers. Although NF-B has been suggested as one of the potential targets to alleviate chemoresistance of epithelial ovarian cancer (EOC), direct targeting of NF-B may result in an unexpected effect due to the complex regulatory network via NF-B. Here we show that AIMP2-DX2, a splicing variant of tumor suppressor AIMP2, can be a therapeutic target to control CR EOC. AIMP2-DX2 was often highly expressed in CR EOC both in vitro and in vivo. AIMP2-DX2 compromised the tumor necrosis factor alpha-dependent pro-apoptotic activity of AIMP2 via the competitive inhibition of AIMP2 binding to TRAF2 that plays a pivotal role in the regulation of NF-B. The direct delivery of siRNA against AIMP2-DX2 into abdominal metastatic tumors of ovarian cancer using a microneedle converged on microendoscopy significantly suppressed the growth rate of tumors. The treated cancer tissues showed an enhanced apoptosis and the decreased TRAF2 level. Thus, we suggest that the downregulation of AIMP2-DX2 can be a potent adjuvant therapeutic approach for CR EOC that resulted from an aberrant activity of NF-B. C1 [Choi, Jin Woo; Kim, Dae Gyu; Kim, Sunghoon] Adv Inst Convergence Technol, Med Bioconvergence Res Ctr, Suwon 443759, Gyeonggi, South Korea. [Choi, Jin Woo; Kim, Jun Ki; Yun, Seok Hyun] Harvard Univ, Wellman Ctr Photomed, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Lee, Jeong-Won; Jeon, Hye-Kyung; Choi, Jung-Joo; Kim, Byoung-Gie] Sungkyunkwan Univ, Dept Obstet & Gynecol, Samsung Med Ctr, Sch Med, Seoul 135710, South Korea. [Lee, Jeong-Won; Jeon, Hye-Kyung; Choi, Jung-Joo; Kim, Byoung-Gie; Nam, Do-Hyun] Sungkyunkwan Univ, Samsung Biomed Res Inst, Sch Med, Seoul 135710, South Korea. [Nam, Do-Hyun] Sungkyunkwan Univ, Dept Neurosurg, Samsung Med Ctr, Sch Med, Seoul 135710, South Korea. [Kim, Hong Joong] Neomics Co Ltd, Suwon 443759, Gyeonggi, South Korea. [Kim, Sunghoon] Seoul Natl Univ, WCU Dept Mol Med & Biopharmaceut Sci, Seoul 151742, South Korea. RP Kim, S (reprint author), Adv Inst Convergence Technol, Med Bioconvergence Res Ctr, Suwon 443759, Gyeonggi, South Korea. EM sungkim@snu.ac.kr RI lee, jw/O-6237-2014 FU National Research Foundation (the Ministry of Education, Science, and Technology of Korea) [NRF-M1AXA002-2010-0029785]; Ministry for Health & Welfare Affairs, Korea [A092255] FX This work was supported in part by the Global Frontier grant (NRF-M1AXA002-2010-0029785) of National Research Foundation (the Ministry of Education, Science, and Technology of Korea) and by the Korea Healthcare technology R&D project grant (A092255, the Ministry for Health & Welfare Affairs, Korea). NR 32 TC 15 Z9 15 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1674-2788 J9 J MOL CELL BIOL JI J. Mol. Cell Biol. PD JUN PY 2012 VL 4 IS 3 SI SI BP 164 EP 173 DI 10.1093/jmcb/mjs018 PG 10 WC Cell Biology SC Cell Biology GA 952XV UT WOS:000304830400006 PM 22532625 ER PT J AU Peacock, ZS Kademani, D Le, AD Lee, JS Hale, RG Cunningham, LL AF Peacock, Zachary S. Kademani, Deepak Le, Anh D. Lee, Janice S. Hale, Robert G. Cunningham, Larry L., Jr. TI Proceedings From the 2011 American Association of Oral and Maxillofacial Surgeons Research Summit SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Editorial Material ID OBSTRUCTIVE SLEEP-APNEA; SQUAMOUS-CELL CARCINOMA; QUALITY-OF-LIFE; POSITIVE AIRWAY PRESSURE; LYMPH-NODE BIOPSY; HUMAN-PAPILLOMAVIRUS; HEART HEALTH; NECK-CANCER; RISK-FACTOR; CARDIOVASCULAR-DISEASE C1 [Cunningham, Larry L., Jr.] Univ Kentucky, Coll Dent, Div Oral & Maxillofacial Surg, Lexington, KY 40536 USA. [Peacock, Zachary S.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Peacock, Zachary S.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Kademani, Deepak] Univ Minnesota, Sch Dent, Dept Oral & Maxillofacial Surg, Minneapolis, MN 55455 USA. [Le, Anh D.] Univ So Calif, Los Angeles, CA USA. [Lee, Janice S.] Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, San Francisco, CA USA. [Hale, Robert G.] Brooke Army Med Ctr, Ft Sam Houston, TX 78234 USA. RP Cunningham, LL (reprint author), Univ Kentucky, Coll Dent, Div Oral & Maxillofacial Surg, 800 Rose St,D-508, Lexington, KY 40536 USA. EM llcunn2@email.uky.edu FU NIDCR NIH HHS [R13DE019744] NR 85 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUN PY 2012 VL 70 IS 6 BP 1271 EP 1279 DI 10.1016/j.joms.2012.01.029 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 950TS UT WOS:000304672700008 PM 22608814 ER PT J AU Demiris, G Oliver, DP Wittenberg-Lyles, E Washington, K Doorenbos, A Rue, T Berry, D AF Demiris, George Oliver, Debra Parker Wittenberg-Lyles, Elaine Washington, Karla Doorenbos, Ardith Rue, Tessa Berry, Donna TI A Noninferiority Trial of a Problem-Solving Intervention for Hospice Caregivers: In Person versus Videophone SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID FAMILY CAREGIVERS; ELDERLY-PATIENTS; CANCER; HEALTH; METAANALYSIS; CARE AB Purpose of the study: Problem-solving therapy (PST) has been found effective when delivered to informal caregivers of patients with various conditions. In hospice, however, its translation to practice is impeded by the increased resources needed for its delivery. The study purpose was to compare the effectiveness of a PST intervention delivered face-to-face with one delivered via videophone to hospice primary caregivers. Design and methods: The study design was a randomized noninferiority trial with two groups, Group 1 in which caregivers received PST face-to-face, and Group 2 in which caregivers received PST via videophone. Family hospice caregivers were recruited from two urban hospice agencies and received the PST intervention (in three visits for Group 1 or three video-calls in Group 2) in an approximate period of 20 days after hospice admission. Standard caregiver demographic data were collected. Psychometric instruments administered to caregivers at baseline and at study completion included the CQLI-R (Caregiver Quality of Life Index-Revised), the STAI (State-Trait Anxiety Inventory), and the PSI (Problem-Solving Inventory). Results: One hundred twenty-six caregivers were recruited in the study; 77 were randomly assigned to Group 1 and 49 to Group 2. PST delivered via video was not inferior to face-to-face delivery. The observed changes in scores were similar for each group. Caregiver quality of life improved and state anxiety decreased under both conditions. Conclusions: The delivery of PST via videophone was not inferior to face-to-face. Audiovisual feedback captured by technology may be sufficient, providing a solution to the geographic barriers that often inhibit the delivery of these types of interventions to older adults in hospice. C1 [Demiris, George; Doorenbos, Ardith; Rue, Tessa] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Oliver, Debra Parker] Univ Missouri, Sch Med, Columbia, MO USA. [Wittenberg-Lyles, Elaine] Univ N Texas, Dept Commun Studies, Denton, TX 76203 USA. [Washington, Karla] Univ Louisville, Raymond A Kent Sch Social Work, Louisville, KY 40292 USA. [Berry, Donna] Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA. RP Demiris, G (reprint author), Univ Washington, Sch Nursing, BNHS Box 357266, Seattle, WA 98195 USA. EM gdemiris@u.washington.edu OI Washington, Karla T./0000-0002-1100-9524; Demiris, George/0000-0002-6318-5829 FU National Institutes of Health (NIH) National Institute of Nursing Research [R21 NR010744-01] FX This project was funded in part by the National Institutes of Health (NIH) National Institute of Nursing Research Grant Nr. R21 NR010744-01 (A Technology Enhanced Nursing Intervention for Hospice Caregivers, Demiris PI). NR 28 TC 17 Z9 17 U1 2 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD JUN PY 2012 VL 15 IS 6 BP 653 EP 660 DI 10.1089/jpm.2011.0488 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 952GA UT WOS:000304778200007 PM 22536989 ER PT J AU Billings, JA Churchill, LR AF Billings, J. Andrew Churchill, Larry R. TI Monolithic Moral Frameworks: How Are the Ethics of Palliative Sedation Discussed in the Clinical Literature? SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Review ID CARE; RULE AB A variety of moral frameworks can assist clinicians in making ethical decisions. In examining articles on palliative sedation and terminal extubation, we were struck that bioethical discussions uniformly appealed to principlism and especially to the rule of double effect. Other moral frameworks were rarely invoked, an observation consistent with Daniel Callahan's assertion that principlism has a "blocking effect'' on broader ethical deliberation. We review here the principle of double effect as it applies to clinical acts that may hasten death, and present one radically different ethical formulation developed by Dan Brock. We then offer brief examples of how clinicians might use other moral frameworks to assess the ethics of preemptive sedation for terminal extubation. We argue for greater moral pluralism in approaching end-of-life decisions. C1 [Billings, J. Andrew] Cambridge Hlth Alliance, Cambridge, MA USA. [Billings, J. Andrew] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Billings, J. Andrew] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. [Churchill, Larry R.] Vanderbilt Univ, Med Ctr, Ctr Biomed Eth & Soc, Nashville, TN USA. RP Billings, JA (reprint author), 11 1-2 Hilliard St, Cambridge, MA 02138 USA. EM Jbillings@partners.org NR 34 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 J9 J PALLIAT MED JI J. Palliat. Med. PD JUN PY 2012 VL 15 IS 6 BP 709 EP 713 DI 10.1089/jpm.2011.0157 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 952GA UT WOS:000304778200015 PM 22545794 ER PT J AU Panda, B Panda, A Ueda, I Abrahams, VM Norwitz, ER Stanic, AK Young, BC Ecker, JL Altfeld, M Shaw, AC Rueda, BR AF Panda, Britta Panda, Alexander Ueda, Ikuyo Abrahams, Vikki M. Norwitz, Errol R. Stanic, Aleksandar K. Young, Brett C. Ecker, Jeffrey L. Altfeld, Marcus Shaw, Albert C. Rueda, Bo R. TI Dendritic cells in the circulation of women with preeclampsia demonstrate a pro-inflammatory bias secondary to dysregulation of TLR receptors SO JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE Preeclampsia; Toll-like receptors ID TOLL-LIKE RECEPTORS; NECROSIS-FACTOR-ALPHA; PREGNANCY; HYPERTENSION; RECOGNITION; MIGRATION; OBESITY; DANGER; SYSTEM AB Toll-like receptors (TLRs) are central components of the innate immune system that recognize both microbial ligands and host products released during tissue damage. Data from epidemiologic studies and animal models suggest that inappropriate activation of the immune system plays a critical role in the development of preeclampsia. This study evaluates in a systematic fashion the expression and function of TLRs in the circulation of patients with preeclampsia compared to healthy pregnant controls. We evaluated TLR expression and function in primary dendritic cells (DCs) of 30 patients with preeclampsia and 30 gestational age-matched healthy pregnant controls. DCs were stimulated with the different TLR ligands engaging TLR1/2,TLR2/6, TLR3, TLR4, TLR5, TLR7, TLR8 and TLR9. The expression of TLR-induced production of TNF-alpha, IFN-alpha, IL-6, and IL-12 were measured by multicolor flow cytometry. Basal expression of TLR3, TLR4 and TLR9 was significantly increased in DCs isolated from women with preeclampsia. Preeclamptic DCs also expressed significantly higher basal levels of cytokines. In contrast, preeclamptic DCs demonstrated a less robust response to stimulation with various TLR ligands as compared with healthy pregnant controls. Under basal conditions, DCs from preeclamptic individuals express higher levels of select TLRs and produce more pro-inflammatory cytokines as compared with healthy controls. As such, the ability of these cells to mount an inflammatory reaction in response to a TLR ligand is limited. These data demonstrate a dysregulated pattern of TLR expression and cytokine production in DCs from PE patients that may limit further activation by TLR engagement. (c) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Panda, Britta; Young, Brett C.; Ecker, Jeffrey L.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02114 USA. [Panda, Alexander; Ueda, Ikuyo; Shaw, Albert C.] Yale Univ, Dept Med, Div Infect Dis, New Haven, CT 06520 USA. [Abrahams, Vikki M.] Yale Univ, Dept Obstet & Gynecol, New Haven, CT 06520 USA. [Norwitz, Errol R.] Tufts Univ, Dept Obstet & Gynecol, Medford, MA 02155 USA. [Altfeld, Marcus] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. RP Panda, B (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, 55 Fruit St, Boston, MA 02114 USA. EM bpanda@partners.org OI Stanic-Kostic, Aleksandar/0000-0003-1946-6436 FU Preeclampsia Foundation; Vincent Memorial Research Funds FX The research was funded by The Preeclampsia Foundation and the Vincent Memorial Research Funds. NR 32 TC 10 Z9 14 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-0378 J9 J REPROD IMMUNOL JI J. Reprod. Immunol. PD JUN PY 2012 VL 94 IS 2 BP 210 EP 215 DI 10.1016/j.jri.2012.01.008 PG 6 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA 953SO UT WOS:000304893700012 PM 22440523 ER PT J AU Masri, KR Shaver, TS Shahouri, SH Wang, S Anderson, JD Busch, RE Michaud, K Mikuls, TR Caplan, L Wolfe, F AF Masri, Karim R. Shaver, Timothy S. Shahouri, Shadi H. Wang, Shirley Anderson, James D. Busch, Ruth E. Michaud, Kaleb Mikuls, Ted R. Caplan, Liron Wolfe, Frederick TI Validity and Reliability Problems with Patient Global as a Component of the ACR/EULAR Remission Criteria as Used in Clinical Practice SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE RHEUMATOID ARTHRITIS; REMISSION; RELIABILITY ID ARTHRITIS DISEASE-ACTIVITY; HEALTH-ASSESSMENT QUESTIONNAIRE; RHEUMATOID-ARTHRITIS; AMERICAN-COLLEGE; ACTIVITY INDEX; IMPORTANT DIFFERENCE; OSTEOARTHRITIS; FIBROMYALGIA; DETERMINANTS; FATIGUE AB Objective. To investigate what factors influence patient global health assessment (PtGlobal), and how those factors and the reliability of PtGlobal affect the rate, reliability, and validity of recently published American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) rheumatoid arthritis (RA) remission criteria when used in clinical practice. Methods. We examined consecutive patients with RA in clinical practice and identified 77 who met ACR/EULAR joint criteria for remission (<= 1 swollen joint and <= 1 tender joint). We evaluated factors associated with a PtGlobal > 1, because a PtGlobal <= 1 defined ACR/EULAR remission in this group of patients who had already met ACR/EULAR joint criteria. Results. Of the 77 patients examined, only 17 (22.1%) had PtGlobal <= 1 and thus fully satisfied ACR/EULAR criteria. A large proportion of patients not in remission by ACR/EULAR criteria had high PtGlobal related to noninflammatory issues, including low back pain, fatigue, and functional limitations, and a number of patients clustered in the range of PtGlobal > 1 and <= 2. However, the minimal detectable difference for PtGlobal was 2.3. In addition, compared with a PtGlobal severity score, a PtGlobal activity score was 3.3% less likely to be abnormal (> 1). Conclusion. Noninflammatory factors contribute to the level of PtGlobal and result in the exclusion of many patients who would otherwise be in "true" remission according to the ACR/EULAR definition. Reliability problems associated with PtGlobal can also result in misclassification, and may explain the observation of low longterm remission rates in RA. As currently constituted, the use of the ACR/EULAR remission criteria in clinical practice appears to be problematic. (First Release May 15 2012; J Rheumatol 2012;39:1139-45; doi:10.3899/jrheum.111543) C1 [Wolfe, Frederick] Univ Kansas, Natl Data Bank Rheumat Dis, Sch Med, Wichita, KS 67214 USA. [Shaver, Timothy S.; Shahouri, Shadi H.; Wang, Shirley; Anderson, James D.] Univ Kansas, Arthrit & Rheumatol Clin Kansas, Sch Med, Wichita, KS 67214 USA. [Busch, Ruth E.] Wichita State Univ, Arthrit & Rheumatol Clin Kansas, Wichita, KS 67260 USA. [Michaud, Kaleb] Univ Nebraska Med Ctr, Natl Data Bank Rheumat Dis, Omaha, NE USA. [Mikuls, Ted R.] Omaha VA Med Ctr, Omaha, NE USA. [Mikuls, Ted R.] Univ Nebraska, Omaha, NE 68182 USA. [Caplan, Liron] Denver VA Med Ctr, Denver, CO USA. [Caplan, Liron] Univ Colorado, Denver, CO 80202 USA. US Natl Data Bank Rheumat Dis, Wichita, KS USA. RP Wolfe, F (reprint author), Univ Kansas, Natl Data Bank Rheumat Dis, Sch Med, 1035 N Emporia,Suite 288, Wichita, KS 67214 USA. EM fwolfe@arthritis-research.org FU VA HSRD CDA [07-221] FX Dr. Caplan is supported by VA HSR&D CDA 07-221. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the US Department of Veterans Affairs or the US government. NR 33 TC 28 Z9 28 U1 0 U2 4 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUN PY 2012 VL 39 IS 6 BP 1139 EP 1145 DI 10.3899/jrheum.111543 PG 7 WC Rheumatology SC Rheumatology GA 953SP UT WOS:000304893800008 PM 22589262 ER PT J AU Cohen, JFW Smit, LA Parker, E Austin, SB Frazier, AL Economos, CD Rimm, EB AF Cohen, Juliana F. W. Smit, Liesbeth A. Parker, Ellen Austin, S. Bryn Frazier, A. Lindsay Economos, Christina D. Rimm, Eric B. TI Long-Term Impact of a Chef on School Lunch Consumption: Findings from a 2-Year Pilot Study in Boston Middle Schools SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS LA English DT Article DE Middle schools; Cafeteria; Adolescent; Plate-waste ID VEGETABLE CONSUMPTION; DIETARY PATTERNS; GLYCEMIC INDEX; PLATE WASTE; CHILDREN; INTERVENTION; FRUIT; OBESITY; HEALTH; WOMEN AB School cafeterias can play an important role in providing healthy meals. Although schools participating in the National School Lunch Program are required to meet minimum program standards, advocates recommend that innovations be sought to enhance menu dietary quality. This study evaluated the Chef Initiative, a 2-year pilot study in two Boston middle schools, designed to increase the availability and consumption of healthier school foods. Between 2007 and 2009, a professional chef trained cafeteria staff to prepare healthier school lunches (ie, more whole grains, fresh/frozen fruits and vegetables, and less sugar, salt, saturated fats, and trans fats). Meal nutrient compositions were monitored from 2007 to 2009, and a plate waste study conducted in the spring of 2009 compared food selection and consumption patterns among students at Chef Initiative schools, with students receiving standard school lunches at two matched control schools. Paired t tests and descriptive statistics were used to examine differences in menus and mixed-model analysis of variance was used to analyze differences in students' food selection and consumption between Chef Initiative and control schools. Overall, the Chef Initiative schools provided healthier lunches and the percent of foods consumed at Chef Initiative and control schools were similar (61.6% vs 57.3%; P=0.63). Of the areas targeted, there was greater whole-grain selection and vegetable consumption; 51% more students selected whole grains (P=0.02) and students consumed 0.36 more vegetable servings/day (P=0.01) at Chef Initiative schools. The potential of chefs collaborating with cafeteria staff to improve the availability, selection, and consumption of healthier meals is promising. J Acad Nutr Diet. 2012;112:927-933. C1 [Cohen, Juliana F. W.; Smit, Liesbeth A.] Harvard Univ, Dept Nutr, Sch Publ Hlth, Boston, MA 02115 USA. [Parker, Ellen] Project Bread, E Boston, MA USA. [Austin, S. Bryn] Harvard Univ, Dept Soc Human Dev & Hlth, Div Adolescent & Young Adult Med, Sch Publ Hlth,Childrens Hosp Boston, Boston, MA 02115 USA. [Austin, S. Bryn] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Frazier, A. Lindsay] Dana Farber Canc Inst, Boston, MA 02115 USA. [Economos, Christina D.] Tufts Univ, John Hancock Res Ctr Phys Act Nutr & Obes Prevent, Gerald J & Dorothy R Friedman Sch Nutr Sci & Poli, Boston, MA 02111 USA. [Rimm, Eric B.] Harvard Univ, Dept Nutr, Sch Publ Hlth,Brigham & Womens Hosp, Dept Epidemiol,Channing Lab,Dept Med, Boston, MA 02115 USA. RP Cohen, JFW (reprint author), Harvard Univ, Dept Nutr, Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02115 USA. EM Jcohen@hsph.harvard.edu FU Project Bread, Boston MA FX This study was supported by Project Bread, Boston MA (http://www.projectbread.org/). Additional research funding was provided in memory of O. Milton Gossett. NR 36 TC 31 Z9 33 U1 3 U2 28 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-2672 J9 J ACAD NUTR DIET JI J. Acad. Nutr. Diet. PD JUN PY 2012 VL 112 IS 6 BP 927 EP 933 DI 10.1016/j.jand.2012.01.015 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 951QU UT WOS:000304735900018 PM 22504283 ER PT J AU Stewart, SE AF Stewart, S. Evelyn TI Rage Takes Center Stage: Focus on an Underappreciated Aspect of Pediatric Obsessive-Compulsive Disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material ID TOURETTE-SYNDROME; CHILDREN; ANXIETY; SCALE; OCD C1 [Stewart, S. Evelyn] Univ British Columbia, BC Childrens Hosp, Vancouver, BC V5Z 1M9, Canada. [Stewart, S. Evelyn] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Stewart, S. Evelyn] McLean Hosp, Belmont, MA USA. RP Stewart, SE (reprint author), OCD Clin, A3-118,W 28th Ave, Vancouver, BC V5Z 4H4, Canada. EM sevelynstewart@gmail.com RI Stewart, Evelyn/K-6961-2014; OI Stewart, S. Evelyn/0000-0002-0994-6383 NR 11 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 2012 VL 51 IS 6 BP 569 EP 571 DI 10.1016/j.jaac.2012.04.002 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 951NK UT WOS:000304727100003 PM 22632616 ER PT J AU Maurasse, S AF Maurasse, Sophia TI Silver Sparrow. SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Maurasse, Sophia] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Maurasse, S (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM smaurasse@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 2012 VL 51 IS 6 BP 655 EP 656 DI 10.1016/j.jaac.2012.04.007 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 951NK UT WOS:000304727100014 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI The Top Five in Oncology: Where Do We Go From Here? SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material ID LIST; CARE C1 [Burstein, Harold J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA USA. [Burstein, Harold J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Burstein, Harold J.] St Gallen Breast Canc Panel, St Gallen, Switzerland. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. EM burstein@nccn.org NR 3 TC 0 Z9 0 U1 0 U2 3 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JUN PY 2012 VL 10 IS 6 BP 681 EP 682 PG 2 WC Oncology SC Oncology GA 953RF UT WOS:000304889700001 PM 22679112 ER PT J AU Tempero, MA Arnoletti, JP Behrman, SW Ben-Josef, E Benson, AB Casper, ES Cohen, SJ Czito, B Ellenhorn, JDI Hawkins, WG Herman, J Hoffman, JP Ko, A Komanduri, S Koong, A Ma, WW Malafa, MP Merchant, NB Mulvihill, SJ Muscarella, P Nakakura, EK Obando, J Pitman, MB Sasson, AR Tally, A Thayer, SR Whiting, S Wolff, RA Wolpin, BM Freedman-Cass, DA Shead, DA AF Tempero, Margaret A. Arnoletti, J. Pablo Behrman, Stephen W. Ben-Josef, Edgar Benson, Al B., III Casper, Ephraim S. Cohen, Steven J. Czito, Brian Ellenhorn, Joshua D. I. Hawkins, William G. Herman, Joseph Hoffman, John P. Ko, Andrew Komanduri, Srinadh Koong, Albert Ma, Wen Wee Malafa, Mokenge P. Merchant, Nipun B. Mulvihill, Sean J. Muscarella, Peter, II Nakakura, Eric K. Obando, Jorge Pitman, Martha B. Sasson, Aaron R. Tally, Anitra Thayer, Sarah R. Whiting, Samuel Wolff, Robert A. Wolpin, Brian M. Freedman-Cass, Deborah A. Shead, Dorothy A. TI Pancreatic Adenocarcinoma, Version 2.2012 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID COMPUTED-TOMOGRAPHY; CANCER STATISTICS; 2ND-LINE THERAPY; MARGIN STATUS; HELICAL CT; PHASE-II; RESECTION; PANCREATICODUODENECTOMY; CARCINOMA; SURVIVAL AB The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pancreatic Adenocarcinoma discuss the workup and management of tumors of the exocrine pancreas. These NCCN Guidelines Insights provide a summary and explanation of major changes to the 2012 NCCN Guidelines for Pancreatic Adenocarcinoma. The panel made 3 significant updates to the guidelines: 1) more detail was added regarding multiphase CT techniques for diagnosis and staging of pancreatic cancer, and pancreas protocol MRI was added as an emerging alternative to CT; 2) the use of a fluoropyrimidine plus oxaliplatin (e.g., 5-FU/leucovorin/oxaliplatin or capecitabine/oxaliplatin) was added as an acceptable chemotherapy combination for patients with advanced or metastatic disease and good performance status as a category 2B recommendation; and 3) the panel developed new recommendations concerning surgical technique and pathologic analysis and reporting. (JNCCN 2012;10:703-713) C1 [Arnoletti, J. Pablo] Univ Alabama Birmingham, Birmingham Comprehens Canc Ctr, Birmingham, AL USA. [Behrman, Stephen W.] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Ben-Josef, Edgar] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Benson, Al B., III; Komanduri, Srinadh] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Casper, Ephraim S.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Cohen, Steven J.; Hoffman, John P.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Ellenhorn, Joshua D. I.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Hawkins, William G.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Hawkins, William G.] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63130 USA. [Herman, Joseph] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Koong, Albert] Stanford Canc Inst, Stanford, CA USA. [Ma, Wen Wee] Roswell Pk Canc Inst, Buffalo, NY USA. [Malafa, Mokenge P.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Merchant, Nipun B.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Mulvihill, Sean J.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Muscarella, Peter, II] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Pitman, Martha B.; Thayer, Sarah R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Sasson, Aaron R.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Whiting, Samuel] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA. [Wolff, Robert A.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Wolpin, Brian M.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. RI Muscarella, Peter/J-4165-2013 OI Muscarella, Peter/0000-0003-1448-5507 FU NCI NIH HHS [K07 CA140790, P01 CA117969, P50 CA127003] NR 48 TC 125 Z9 136 U1 0 U2 9 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JUN PY 2012 VL 10 IS 6 BP 703 EP 713 PG 11 WC Oncology SC Oncology GA 953RF UT WOS:000304889700004 PM 22679115 ER PT J AU Kulke, MH Benson, AB Bergsland, E Berlin, JD Blaszkowsky, LS Choti, MA Clark, OH Doherty, GM Eason, J Emerson, L Engstrom, PF Goldner, WS Heslin, MJ Kandeel, F Kunz, PL Kuvshinoff, BW Moley, JF Pillarisetty, VG Saltz, L Schteingart, DE Shah, MH Shibata, S Strosberg, JR Vauthey, JN White, R Yao, JC Freedman-Cass, DA Dwyer, MA AF Kulke, Matthew H. Benson, Al B., III Bergsland, Emily Berlin, Jordan D. Blaszkowsky, Lawrence S. Choti, Michael A. Clark, Orlo H. Doherty, Gerard M. Eason, James Emerson, Lyska Engstrom, Paul F. Goldner, Whitney S. Heslin, Martin J. Kandeel, Fouad Kunz, Pamela L. Kuvshinoff, Boris W., II Moley, Jeffrey F. Pillarisetty, Venu G. Saltz, Leonard Schteingart, David E. Shah, Manisha H. Shibata, Stephen Strosberg, Jonathan R. Vauthey, Jean-Nicolas White, Rebekah Yao, James C. Freedman-Cass, Deborah A. Dwyer, Mary A. TI Neuroendocrine Tumors Clinical Practice Guidelines in Oncology SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID PROPOSED STAGING SYSTEM; RADIOLABELED SOMATOSTATIN ANALOG; PANCREATIC ENDOCRINE CARCINOMAS; SPORADIC ADRENOCORTICAL TUMORS; ADRENAL-CORTICAL CARCINOMA; HEPATIC ARTERIAL CHEMOEMBOLIZATION; ISLET-CELL CARCINOMA; LONG-TERM SURVIVAL; LIVER-TRANSPLANTATION; PROGNOSTIC-FACTORS AB Neuroendocrine tumors comprise a broad family of tumors, the most common of which are carcinoid and pancreatic neuroendocrine tumors. The NCCN Neuroendocrine Tumors Guidelines discuss the diagnosis and management of both sporadic and hereditary neuroendocrine tumors. Most of the recommendations pertain to well-differentiated, low- to intermediate-grade tumors. This updated version of the NCCN Guidelines includes a new section on pathology for diagnosis and reporting and revised recommendations for the surgical management of neuroendocrine tumors of the pancreas. (JNCCN 2012;10:724-764) C1 [Kulke, Matthew H.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Benson, Al B., III] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Berlin, Jordan D.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Blaszkowsky, Lawrence S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Choti, Michael A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Doherty, Gerard M.; Schteingart, David E.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Eason, James] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Emerson, Lyska] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Engstrom, Paul F.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Goldner, Whitney S.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Heslin, Martin J.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Kandeel, Fouad; Shibata, Stephen] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Kunz, Pamela L.] Stanford Canc Inst, Stanford, CA USA. [Kuvshinoff, Boris W., II] Roswell Pk Canc Inst, Buffalo, NY USA. [Moley, Jeffrey F.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Moley, Jeffrey F.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Pillarisetty, Venu G.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Saltz, Leonard] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Shah, Manisha H.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Strosberg, Jonathan R.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Vauthey, Jean-Nicolas; Yao, James C.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. RP Kulke, MH (reprint author), Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. OI Saltz, Leonard/0000-0001-8353-4670 NR 157 TC 69 Z9 71 U1 1 U2 12 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JUN PY 2012 VL 10 IS 6 BP 724 EP 764 PG 41 WC Oncology SC Oncology GA 953RF UT WOS:000304889700006 PM 22679117 ER PT J AU Antic, V Boyer, M Janne, P Mok, T O'Byrne, K Paz-Ares, L Ramalingam, SS Liang, J Taylor, I Letrent, S AF Antic, V. Boyer, M. Janne, P. Mok, T. O'Byrne, K. Paz-Ares, L. Ramalingam, S. S. Liang, J. Taylor, I. Letrent, S. TI ARCHER: A RANDOMIZED DOUBLE-BLINDED PHASE III STUDY OF DACOMITINIB (PF-00299804) VERSUS ERLOTINIB FOR ADVANCED (ADV) NON-SMALL CELL LUNG CANCER (NSCLC) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract CT 3rd European Lung Cancer Conference (ELCC) CY APR 18-21, 2012 CL Geneva, SWITZERLAND SP Lilly Oncol, AstraZeneca, Daiichi Sankyo, Pfizer Oncol, Roche, Abbott Oncol, Lets Work, Boehringer Ingelheim, Merck Serono, Merck C1 [Antic, V.] Pfizer AG, Med Oncol, Zurich, Switzerland. [Boyer, M.] Sydney Canc Ctr, Camperdown, NSW, Australia. [Janne, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mok, T.] Chinese Univ Hong Kong, Dept Clin Oncol, Hong Kong, Hong Kong, Peoples R China. [O'Byrne, K.] St James Hosp, Dublin 8, Ireland. [Paz-Ares, L.] Univ Hosp, Seville, Spain. [Ramalingam, S. S.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Liang, J.; Taylor, I.] Pfizer Oncol, Med Oncol, New London, CT USA. [Letrent, S.] Pfizer Oncol, Med Oncol, La Jolla, CA USA. RI IBIS, NUEVAS TERAPIA/P-3415-2015 NR 0 TC 0 Z9 0 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2012 VL 7 IS 6 SU S BP S67 EP S67 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 951NM UT WOS:000304727300185 ER PT J AU Wolf, J Nogova, L Heukamp, LC Bos, M Schuler, M Sequist, L Tian, GG Ringeisen, F Buettner, R Thomas, R AF Wolf, J. Nogova, L. Heukamp, L. C. Bos, M. Schuler, M. Sequist, L. Tian, G. G. Ringeisen, F. Buettner, R. Thomas, R. TI DEVELOPMENTS IN TARGETED THERAPY: FGFR1 INHIBITION IN LUNG CANCER SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract CT 3rd European Lung Cancer Conference (ELCC) CY APR 18-21, 2012 CL Geneva, SWITZERLAND SP Lilly Oncol, AstraZeneca, Daiichi Sankyo, Pfizer Oncol, Roche, Abbott Oncol, Lets Work, Boehringer Ingelheim, Merck Serono, Merck C1 [Wolf, J.; Nogova, L.; Bos, M.] Univ Hosp Koln, Ctr Integrated Oncol, Dept Internal Med 1, Cologne, Germany. [Heukamp, L. C.; Buettner, R.] Univ Hosp Koln, Dept Pathol, Cologne, Germany. [Schuler, M.] Univ Hosp Essen, Dept Internal Med, Essen, Germany. [Sequist, L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Tian, G. G.] W Clin, Memphis, TN USA. [Ringeisen, F.] Novartis, Oncol Translat Med, Basel, Switzerland. [Thomas, R.] Max Planck Inst Neurol Res, D-50931 Cologne, Germany. RI Heukamp, Lukas/A-8338-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2012 VL 7 IS 6 SU S BP S23 EP S23 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 951NM UT WOS:000304727300060 ER PT J AU Patel, IJ Davidson, JC Nikolic, B Salazar, GM Schwartzberg, MS Walker, TG Saad, WA AF Patel, Indravadan J. Davidson, Jon C. Nikolic, Boris Salazar, Gloria M. Schwartzberg, Marc S. Walker, T. Gregory Saad, Wael A. CA Stand Practice Comm CIRSE Endorsement TI Consensus Guidelines for Periprocedural Management of Coagulation Status and Hemostasis Risk in Percutaneous Image-guided Interventions SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID INTERNATIONAL NORMALIZED RATIO; CENTRAL VENOUS CATHETERS; FRESH-FROZEN PLASMA; THROMBOCYTOPENIC PATIENTS; PLATELET TRANSFUSION; LUMBAR PUNCTURE; LIVER-BIOPSY; SUBCUTANEOUS PHYTONADIONE; DESMOPRESSIN DDAVP; BLEEDING DISORDERS C1 [Patel, Indravadan J.; Davidson, Jon C.] Univ Hosp Case Med Ctr, Dept Radiol, Cleveland, OH USA. [Nikolic, Boris] Albert Einstein Med Ctr, Dept Radiol, Philadelphia, PA 19141 USA. [Salazar, Gloria M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Walker, T. Gregory] Massachusetts Gen Hosp, Sect Cardiovasc Imaging & Intervent, Boston, MA 02114 USA. [Schwartzberg, Marc S.] Radiol Associates Cent Florida, Leesburg, FL USA. [Saad, Wael A.] Univ Virginia Hlth Syst, Dept Radiol, Charlottesville, VA USA. RP Davidson, JC (reprint author), SIR, 3975 Fair Ridge Dr,Suite 400 N, Fairfax, VA 22033 USA. EM jon.davidson@uhhospitals.org NR 89 TC 104 Z9 104 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JUN PY 2012 VL 23 IS 6 BP 727 EP 736 DI 10.1016/j.jvir.2012.02.012 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 950ZW UT WOS:000304691400001 PM 22513394 ER PT J AU Yeh, CK Harris, SE Mohan, S Horn, D Fajardo, R Chun, YHP Jorgensen, J MacDougall, M Abboud-Werner, S AF Yeh, Chih-Ko Harris, Stephen E. Mohan, Sumathy Horn, Diane Fajardo, Roberto Chun, Yong-Hee Patricia Jorgensen, James MacDougall, Mary Abboud-Werner, Sherry TI Hyperglycemia and xerostomia are key determinants of tooth decay in type 1 diabetic mice SO LABORATORY INVESTIGATION LA English DT Article DE diabetes; enamel; hyperglycemia; pulpitis; saliva ID RAT PAROTID-GLAND; SALIVARY-GLAND; SECRETORY AMELOBLASTS; PROTEIN EXPRESSION; DENTINAL TUBULES; ORAL-HEALTH; MOUSE MODEL; IN-VITRO; STREPTOZOTOCIN; MELLITUS AB Insulin-dependent type 1 diabetes mellitus (DM) and oral diseases are closely interrelated. Poor metabolic control in diabetics is associated with a high risk of gingivitis, periodontitis and tooth loss. Salivary flow declines in diabetics and patients suffer from xerostomia. Reduced saliva predisposes to enamel hypomineralization and caries formation; however, the mechanisms that initiate and lead to progression of tooth decay and periodontitis in type 1 DM have not been explored. To address this issue, we analyzed tooth morphology in Akita -/- mice that harbor a point mutation in the Ins2 insulin gene, which leads to progressive hyperglycemia. Mandibles from Akita -/- and wild-type littermates were analyzed by microCT, scanning EM and histology; teeth were examined for amelogenin (Amel) and ameloblastin (Ambn) expression. Mice were injected with pilocarpine to assess saliva production. As hyperglycemia may alter pulp repair, the effect of high glucose levels on the proliferation/differentiation of cultured MD10-F2 pulp cells was also analyzed. Results showed that Akita -/- mice at 6 weeks of age showed chalky white incisors that correlated with marked hyperglycemia and impaired saliva production. MicroCT of Akita -/- teeth revealed excessive enamel wearing and hypomineralization; immunostaining for Amel and Ambn was decreased. A striking feature was invasion of dentinal tubules with Streptococcus mitis and microabcesses that originated in the coronal pulp and progressed to pulp necrosis and periapical periodontitis. High levels of glucose also inhibited MD10-F2 cell proliferation and differentiation. Our findings provide the first evidence that hyperglycemia in combination with reduced saliva in a model of type1 DM leads to decreased enamel mineralization/matrix proteins and predisposes to excessive wearing and decay. Importantly, hyperglycemia adversely affects enamel matrix proteins and pulp repair. Early detection and treatment of hyperglycemia and hyposalivation may provide a useful strategy for preventing the dental complications of diabetes and promoting oral health in this population. Laboratory Investigation (2012) 92, 868-882; doi:10.1038/labinvest.2012.60; published online 26 March 2012 C1 [Yeh, Chih-Ko] Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, San Antonio, TX 78229 USA. [Yeh, Chih-Ko; Abboud-Werner, Sherry] S Texas Vet Healthcare Syst, Geriatr Res Educ & Clin Ctr GRECC & Pathol, San Antonio, TX 78229 USA. [Harris, Stephen E.; Chun, Yong-Hee Patricia] Univ Texas Hlth Sci Ctr San Antonio, Dept Periodont, San Antonio, TX 78229 USA. [Mohan, Sumathy; Horn, Diane; Jorgensen, James; Abboud-Werner, Sherry] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Fajardo, Roberto] Univ Texas Hlth Sci Ctr San Antonio, Dept Orthoped, San Antonio, TX 78229 USA. [MacDougall, Mary] Univ Alabama Birmingham, Inst Oral Hlth Res, Birmingham, AL USA. RP Abboud-Werner, S (reprint author), S Texas Vet Healthcare Syst, GRECC, Dept Pathol, San Antonio, TX 78229 USA. EM abboudwerner@uthscsa.edu FU National Institutes of Health, NIDCR [DE015857, DE0211084] FX We thank the micro-CT Core Facility at UTHSCSA for their assistance in analyzing dental tissues and Drs Alan Lin and Yi Zhou (Comprehensive Dentistry, UTHSCSA) for assisting with saliva/salivary gland collection. We also thank Chris Edwards and the Microscopy and Image-analysis Laboratory at the University of Michigan School of Medicine for scanning electron microscopic studies. This work has been supported, in part, by funding from the National Institutes of Health, NIDCR (DE015857, SAW) and (DE0211084, C-KY). NR 59 TC 11 Z9 12 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JUN PY 2012 VL 92 IS 6 BP 868 EP 882 DI 10.1038/labinvest.2012.60 PG 15 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 951OT UT WOS:000304730600006 PM 22449801 ER PT J AU Kakarala, K Kieff, DA AF Kakarala, Kiran Kieff, David A. TI Bolsterless management for recurrent auricular hematomata SO LARYNGOSCOPE LA English DT Article DE Auricular hematoma; bolsterless; facial plastics; trauma AB Objectives/Hypothesis: The objectives were to describe our experience with a bolsterless technique for the management of auricular hematomata and discuss the management options for auricular hematomata and the comparative benefits of the bolsterless technique. Study Design: Retrospective case series. Methods: Patients presented with recurrent auricular hematomata following traditional treatment with incision and drainage and bolster placement. Revision incision and drainage were performed, and then auricular skin was stabilized using through-and-through absorbable horizontal mattress sutures. Patients were seen in follow-up to evaluate for recurrence and assess cosmetic results. Results: Twenty-eight patients were treated for recurrent auricular hematomata using the bolsterless technique. There were no recurrences in follow-up, and cosmetic results were judged to be excellent by both patient and surgeon. Conclusions: Bolsterless management for auricular hematomata using absorbable mattress sutures has been described intermittently in the otolaryngology literature since 1991 but is not widely utilized. In this series, patients presenting with recurrent auricular hematomata following failure of traditional bolster management were effectively managed with the bolsterless technique. This technique is well tolerated by patients and allows for early return to athletic activity. C1 [Kakarala, Kiran; Kieff, David A.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Kakarala, Kiran; Kieff, David A.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Kieff, DA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Emergency Room Otolaryngol,243 Charles St, Boston, MA 02114 USA. EM david_kieff@meei.harvard.edu OI Kakarala, Kiran/0000-0002-1003-8024 NR 6 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUN PY 2012 VL 122 IS 6 BP 1235 EP 1237 DI 10.1002/lary.23288 PG 3 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 951HH UT WOS:000304711000010 PM 22447489 ER PT J AU Gridelli, C de Marinis, F Di Maio, M Ardizzoni, A Belani, CP Cappuzzo, F Ciardiello, F Fidias, P Paz-Ares, L Perrone, F Pirker, R De Petris, L Stahel, R AF Gridelli, Cesare de Marinis, Filippo Di Maio, Massimo Ardizzoni, Andrea Belani, Chandra P. Cappuzzo, Federico Ciardiello, Fortunato Fidias, Panagiotis Paz-Ares, Luis Perrone, Francesco Pirker, Robert De Petris, Luigi Stahel, Rolf TI Maintenance treatment of advanced non-small-cell lung cancer: Results of an International Expert Panel Meeting of the Italian Association of Thoracic Oncology SO LUNG CANCER LA English DT Review DE Non-small cell lung cancer; Maintenance; Pemetrexed; Erlotinib; Gemcitabine; Docetaxel; Gefitinib; Bevacizumab; Cetuximab ID PHASE-III TRIAL; 1ST-LINE CHEMOTHERAPY; THERAPY; PLACEBO; GEMCITABINE; METAANALYSIS; MULTICENTER; BEVACIZUMAB; CARBOPLATIN; CISPLATIN AB Several randomized trials have recently investigated the role of maintenance treatment for patients with advanced non-small-cell lung cancer (NSCLC) with responding or stable disease after completion of first-line chemotherapy. Maintenance strategy has relevant implications in terms of potential toxicity, logistics and costs, and all of these aspects should be taken into account, together with the magnitude of benefit for the patient. In order to assess the strengths and limitations of available evidence, to help clinical practice, and to suggest priorities for future clinical research, the Italian Association of Thoracic Oncology (AIOT) organized an International Experts Panel Meeting on maintenance treatment of advanced NSCLC, which took place in Sperlonga (Italy) in May 2011. Based on the available evidence, panelists agreed that maintenance therapy represents a treatment option in advanced NSCLC. Maintenance should be discussed with patients not progressed after 4-6 cycles of first-line chemotherapy, who are fit (performance status 0-1) and without persistent chemotherapy-induced toxicity. Patients need to be well informed about potential advantages and disadvantages of accepting additional therapy without a "treatment-free period". Two different strategies, switch or continuation maintenance, are supported by available evidence. At the moment, there is no direct comparison between switch maintenance and continuation maintenance. For future trials, the panel recommends the use of overall survival as the primary endpoint, with pre-defined second-line treatment. Translational research is essential to identify predictive factors, and should be performed, whenever feasible, in order to achieve treatment optimization with proper patient selection. (c) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Gridelli, Cesare] SG Moscati Hosp, Div Med Oncol, I-83100 Avellino, Italy. [de Marinis, Filippo] San Camillo Hosp, Oncol Pulm Unit 1, Rome, Italy. [Di Maio, Massimo; Perrone, Francesco] Natl Canc Inst, Clin Trials Unit, Naples, Italy. [Ardizzoni, Andrea] Univ Hosp, Parma, Italy. [Belani, Chandra P.] Penn State Hershey Canc Inst, Hershey, PA USA. [Cappuzzo, Federico] Civil Hosp, Med Oncol Unit, Livorno, Italy. [Ciardiello, Fortunato] Univ Naples 2, Naples, Italy. [Fidias, Panagiotis] Massachusetts Gen Hosp, Ctr Thorac Canc, Boston, MA USA. [Paz-Ares, Luis] Hosp Univ Virgen Rocio, Seville, Spain. [Paz-Ares, Luis] IBIS, Dept Med Oncol, Seville, Spain. [Pirker, Robert] Med Univ, Vienna, Austria. [De Petris, Luigi] Karolinska Univ Hosp, Stockholm, Sweden. [Stahel, Rolf] Univ Hosp, Clin Oncol, Zurich, Switzerland. RP Gridelli, C (reprint author), SG Moscati Hosp, Div Med Oncol, I-83100 Avellino, Italy. EM cgridelli@libero.it RI IBIS, NUEVAS TERAPIA/P-3415-2015; Gridelli, Cesare/K-7909-2016; Di Maio, Massimo/K-9990-2016; OI Di Maio, Massimo/0000-0001-8906-3785; Belani, Chandra/0000-0001-5049-5329; Ciardiello, Fortunato/0000-0002-3369-4841; Cappuzzo, Federico/0000-0002-6295-6767 FU Boehringer Ingelheim; Eli Lilly; Merck Serono; Roche; Astra-Zeneca; Pfizer; Sanofi-Aventis; Glaxo; Associazione Italiana per la Ricerca sul Cancro FX Andrea Ardizzoni has received research grants or honoraria for Advisory Boards and/or invited lectures from Boehringer Ingelheim, Eli Lilly, Merck Serono, Roche, Astra-Zeneca, Pfizer, Sanofi-Aventis and Glaxo. NR 34 TC 10 Z9 10 U1 0 U2 5 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 JUN PY 2012 VL 76 IS 3 BP 269 EP 279 DI 10.1016/j.lungcan.2011.12.011 PG 11 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 950YR UT WOS:000304688300002 PM 22266040 ER PT J AU Wakelee, HA Dahlberg, SE Brahmer, JR Schiller, JH Perry, MC Langer, CJ Sandler, AB Belani, CP Johnson, DH AF Wakelee, H. A. Dahlberg, S. E. Brahmer, J. R. Schiller, J. H. Perry, M. C. Langer, C. J. Sandler, A. B. Belani, C. P. Johnson, D. H. CA Eastern Cooperative Oncology Grp TI Differential effect of age on survival in advanced NSCLC in women versus men: Analysis of recent Eastern Cooperative Oncology Group (ECOG) studies, with and without bevacizumab SO LUNG CANCER LA English DT Article DE Age/sex interactions; Bevacizumab; Chemotherapy; Sex/gender differences; NSCLC; Prognostic factors ID ENDOTHELIAL-GROWTH-FACTOR; CELL-LUNG-CANCER; HORMONE REPLACEMENT THERAPY; ESTROGEN-RECEPTOR-ALPHA; POSTMENOPAUSAL WOMEN; SEX-DIFFERENCES; FACTOR VEGF; DNA-DAMAGE; IN-VIVO; BETA AB Background: The impact of age on prognosis in advanced stage non-small cell lung cancer (NSCLC) may differ by sex. Patients and methods: Eligible patients (N = 1590) from E1594, a 4-arm platinum-based chemotherapy trial, and E4599 (carboplatin/paclitaxel +/- bevacizumab) chemotherapy arm were divided into male and female cohorts and separated into age groups of <60 or >= 60 years old. Eligible E4599 patients (N=850) were similarly separated by age and sex and by treatment (+/- bevacizumab). Survival was calculated separately for each cohort. Results: The median survival time (MST) for women >= 60 years old treated with chemotherapy alone on El 594 and E4599 was 11.6 months versus 9.0 months for women <60 (p = 0.03). MST was 7.4 and 83 months for men >= 60 and <60 years old respectively (NS). In E4599 the age <60 by bevacizumab treatment interaction was statistically significant (p = 0.03) for women (younger had greater benefit), with no age effect in men. Conclusions: In this unplanned, exploratory subgroup analysis of advanced stage NSCLC ECOG trials, women >= 60 years old treated with chemotherapy live longer than men and younger women. In contrast, bevacizumab survival benefit was more pronounced in men of any age and in younger women on E4599. (c) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Wakelee, H. A.] Stanford Univ, Sch Med, Dept Med, Div Oncol, Stanford, CA 94305 USA. [Dahlberg, S. E.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Brahmer, J. R.] Johns Hopkins Univ, Dept Oncol, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Schiller, J. H.; Johnson, D. H.] Univ Texas SW Med Ctr Dallas, Dept Med, Div Oncol, Dallas, TX 75390 USA. [Perry, M. C.] Univ Missouri, Ellis Fischel Canc Ctr, Columbia, MO USA. [Langer, C. J.] Univ Penn, Dept Med, Div Oncol, Philadelphia, PA 19104 USA. [Sandler, A. B.] Oregon Hlth & Sci Univ, Dept Med, Div Hematol Oncol, Portland, OR 97201 USA. [Sandler, A. B.] Knight Canc Inst, Portland, OR USA. [Belani, C. P.] Penn State Hershey Canc Inst, Dept Med, Div Oncol, Hershey, PA USA. RP Wakelee, HA (reprint author), Stanford Univ, Sch Med, Dept Med, Div Oncol, 875 Blake Wilbur Dr,Room 2233, Stanford, CA 94305 USA. EM hwakelee@stanford.edu OI Belani, Chandra/0000-0001-5049-5329 FU Public Health Service [CA23318, CA66636, CA21115, CA16116, CA21076, CA15488, CA27252, CA49957]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services FX This study was coordinated by the Eastern Cooperative Oncology Group (Robert L. Comis, M.D., Chair) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA16116, CA21076, CA15488, CA27252, CA49957, and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 35 TC 12 Z9 13 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD JUN PY 2012 VL 76 IS 3 BP 410 EP 415 DI 10.1016/j.lungcan.2011.12.006 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 950YR UT WOS:000304688300023 PM 22266041 ER PT J AU Seldin, EB AF Seldin, Edward B. TI Is there any reason to suspect that the determinants of mandibular bone mineral density might differ from those of systemic skeletal bone mineral density? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID HEALTH C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Seldin, EB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 8 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JUN PY 2012 VL 19 IS 6 BP 608 EP 609 DI 10.1097/gme.0b013e31824990a2 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 952BV UT WOS:000304765600006 PM 22453201 ER PT J AU Carpenter, JS Newton, KM Sternfeld, B Joffe, H Reed, SD Ensrud, KE Milata, JL AF Carpenter, Janet S. Newton, Katherine M. Sternfeld, Barbara Joffe, Hadine Reed, Susan D. Ensrud, Kristine E. Milata, Jennifer L. TI Laboratory and ambulatory evaluation of vasomotor symptom monitors from the Menopause Strategies Finding Lasting Answers for Symptoms and Health network SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Menopause; Vasomotor symptoms; Sternal skin conductance; Hygrometer; Hot flashes; Symptom assessment ID STERNAL SKIN-CONDUCTANCE; HOT FLASHES; BREAST-CANCER; DOUBLE-BLIND; CONCORDANCE; VENLAFAXINE; LIFE AB Objective: The aim of this study was to evaluate monitors for assessing vasomotor symptoms (VMS) in laboratory and ambulatory settings before use in the Menopause Strategies Finding Lasting Answers for Symptoms and Health network clinical trials testing VMS therapies. Methods: This was a three-phase study. Phase 1 included laboratory testing of the Freedman and prototype Bahr Monitor, phase 2 included laboratory testing of the commercial Bahr Monitor and Biolog, and phase 3 included ambulatory testing of the commercial Bahr Monitor and Biolog. All phases enrolled midlife women with VMS, midlife women without VMS, and young women without VMS. The participants self-reported VMS by pressing event marker buttons. Questionnaires assessed demographics (all phases) and monitor acceptability (phases 2 and 3). Results: Phase I testing was stopped because of sensitivity of the Freedman device to ambient humidity changes and lack of analytic software for the prototype Bahr Monitor. In phases 2 and 3, agreement between event-marked and commercial Bahr Monitor or Biolog-recorded VMS was higher in the laboratory than in the ambulatory setting; however, agreement between monitors was poor in two of three laboratory groups (midlife no VMS and young no VMS) and in all ambulatory groups. During ambulatory monitoring, the mean number of Bahr Monitor VMS was 16.33 in midlife women with VMS, 9.61 in midlife women without VMS, and 14.63 in young women without VMS (software version, March 2011). The Bahr Monitor was more acceptable than the larger Biolog, but feedback reflected annoyance at having to wear a device that itched and was visible under clothing. Conclusions: The Bahr Monitor and Biolog seem suitable for use in controlled laboratory conditions during short periods of time. However, the current versions of these monitors may not be suitable for ambulatory clinical trials at this time. C1 [Carpenter, Janet S.] Indiana Univ, Sch Nursing, Dept Adult Hlth, Indianapolis, IN 46202 USA. [Newton, Katherine M.] Grp Hlth Res Inst, Seattle, WA USA. [Sternfeld, Barbara] Kaiser Permanente, Div Res, Oakland, CA USA. [Joffe, Hadine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Reed, Susan D.] Univ Washington, Sch Med, Seattle, WA USA. [Ensrud, Kristine E.] Univ Minnesota, VA Med Ctr, Minneapolis, MN USA. [Milata, Jennifer L.] Indiana Univ, Sch Nursing, Ctr Nursing Res & Scholarship, Indianapolis, IN 46202 USA. RP Carpenter, JS (reprint author), Indiana Univ, Sch Nursing, Dept Adult Hlth, 1111 Middle Dr, Indianapolis, IN 46202 USA. EM carpentj@iupui.edu FU National Institute on Aging (NIA) [U01AG032659, U01AG032669, U01AG032682, U01AG032699, U01AG032700]; Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD); National Center for Complementary and Alternative Medicine (NCCAM); Office of Research and Women's Health (ORWH); Indiana Clinical and Translational Sciences Institute; National Institutes of Health, National Center for Research Resources, Clinical and Translational Sciences [UL1 RR025761]; Center for Women's Mental Health at Massachusetts General Hospital FX This study was supported by a cooperative agreement issued by the National Institute on Aging (NIA), in collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD), the National Center for Complementary and Alternative Medicine (NCCAM), and the Office of Research and Women's Health (ORWH) and NIA grants U01AG032659, U01AG032669, U01AG032682, U01AG032699, and U01AG032700. In Indiana, the project was supported by the Indiana Clinical and Translational Sciences Institute and funded, in part, by grant UL1 RR025761 from the National Institutes of Health, National Center for Research Resources, Clinical and Translational Sciences Award.; Hadine Joffe provides research support (to the Center for Women's Mental Health at Massachusetts General Hospital where she participates in protocols as a co-investigator) to Bayer HealthCare Pharmaceuticals, Forest Laboratories, and GlaxoSmithKline. She also provides advisory/consulting services to SanofiAventis/Sunovion. NR 16 TC 21 Z9 22 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JUN PY 2012 VL 19 IS 6 BP 664 EP 671 DI 10.1097/gme.0b013e31823dbbe3 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 952BV UT WOS:000304765600015 PM 22228321 ER PT J AU McLay, RN Graap, K Spira, J Perlman, K Johnston, S Rothbaum, BO Difede, J Deal, W Oliver, D Baird, A Bordnick, PS Spitalnick, J Pyne, JM Rizzo, A AF McLay, Robert N. Graap, Kenneth Spira, James Perlman, Karen Johnston, Scott Rothbaum, Barbara O. Difede, JoAnn Deal, William Oliver, David Baird, Alicia Bordnick, Patrick S. Spitalnick, Josh Pyne, Jeffrey M. Rizzo, Albert TI Development and Testing of Virtual Reality Exposure Therapy for Post-Traumatic Stress Disorder in Active Duty Service Members Who Served in Iraq and Afghanistan SO MILITARY MEDICINE LA English DT Article ID PSYCHOMETRIC PROPERTIES; ANXIETY DISORDERS; PTSD; TRIAL; FEAR; METAANALYSIS; VALIDATION; CLINICIAN; SYMPTOMS AB This study was an open-label, single-group, treatment-development project aimed at developing and testing a method for applying virtual reality exposure therapy (VRET) to active duty service members diagnosed with combat post-traumatic stress disorder (PTSD). Forty-two service members with PTSD were enrolled, and 20 participants completed treatment. The PTSD Checklist-Military version, Patient Health Questionnaire-9 for depression, and the Beck Anxiety Inventory were used as outcome measures. Of those who completed post-treatment assessment, 75% had experienced at least a 50% reduction in PTSD symptoms and no longer met DSM-IV criteria for PTSD at post treatment. Average PSTD scores decreased by 50.4%, depression scores by 46.6%, and anxiety scores by 36%. Intention-to-treat analyses showed that statistically significant improvements in PTSD, depression, and anxiety occurred over the course of treatment and were maintained at follow up. There were no adverse events associated with VRET treatment. This study provides preliminary support for the use of VRET in combat-related PTSD. Further study will be needed to determine the wider utility of the method and to determine if it offers advantages over other established PTSD treatment modalities. C1 [McLay, Robert N.; Deal, William; Oliver, David; Baird, Alicia] USN, San Diego Med Ctr, San Diego, CA 92134 USA. [Graap, Kenneth] CNS Response Inc, Aliso Viejo, CA 92656 USA. [Spira, James] US Dept Vet Affairs, Natl Ctr PTSD, Pacific Isl Div Vet Hlth Adm, Honolulu, HI 96819 USA. [Johnston, Scott] USN, Ctr Combat & Operat Stress Control, San Diego, CA 92134 USA. [Rothbaum, Barbara O.] Emory Univ, Trauma & Anxiety Recovery Program, Dept Psychiat, Sch Med, Atlanta, GA 30306 USA. [Difede, JoAnn] Weill Cornell Med Coll, Dept Psychiat, New York, NY 10021 USA. [Bordnick, Patrick S.] Univ Houston, Grad Coll Social Work, Child & Family Ctr Innovat Res, Houston, TX 77204 USA. [Spitalnick, Josh] Virtually Better Corp, Decatur, GA USA. [Pyne, Jeffrey M.] Centra, Arkansas Vet Healthcare Syst, Ctr Mental Hlth Outcomes Res, Little Rock, AR 72205 USA. [Rizzo, Albert] Univ So Calif, Inst Creat Technol, Marina Del Rey, CA 90292 USA. RP McLay, RN (reprint author), USN, San Diego Med Ctr, 34800 Bob Wilson Dr, San Diego, CA 92134 USA. FU Office of Naval Research [DOD-N0384] FX This study was funded by a grant from the Office of Naval Research, grant number DOD-N0384. NR 29 TC 11 Z9 12 U1 9 U2 34 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD JUN PY 2012 VL 177 IS 6 BP 635 EP 642 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 955QP UT WOS:000305036300004 PM 22730837 ER PT J AU Antao, JM Mason, JM Dejardin, J Kingston, RE AF Antao, Jose M. Mason, James M. Dejardin, Jerome Kingston, Robert E. TI Protein Landscape at Drosophila melanogaster Telomere-Associated Sequence Repeats SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID POSITION-EFFECT VARIEGATION; DISTINCT CHROMATIN DOMAINS; GENE-EXPRESSION; GAGA FACTOR; IN-VIVO; ENCODES; COMPLEX; WOC; HP1; LOCALIZATION AB The specific set of proteins bound at each genomic locus contributes decisively to regulatory processes and to the identity of a cell. Understanding of the function of a particular locus requires the knowledge of what factors interact with that locus and how the protein composition changes in different cell types or during the response to internal and external signals. Proteomic analysis of isolated chromatin segments (PICh) was developed as a tool to target, purify, and identify proteins associated with a defined locus and was shown to allow the purification of human telomeric chromatin. Here we have developed this method to identify proteins that interact with the Drosophila telomere-associated sequence (TAS) repeats. Several of the purified factors were validated as novel TAS-bound proteins by chromatin immunoprecipitation, and the Brahma complex was confirmed as a dominant modifier of telomeric position effect through the use of a genetic test. These results offer information on the efficacy of applying the PICh protocol to loci with sequence more complex than that found at human telomeres and identify proteins that bind to the TAS repeats, which might contribute to TAS biology and chromatin silencing. C1 [Antao, Jose M.; Kingston, Robert E.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Antao, Jose M.; Kingston, Robert E.] Harvard Univ, Harvard Med Sch, Dept Genet, Cambridge, MA 02138 USA. [Antao, Jose M.] Inst Gulbenkian Ciencias, Gulbenkian PhD Program Biomed, Oeiras, Portugal. [Mason, James M.] Natl Inst Environm Hlth Sci, Mol Genet Lab, Res Triangle Pk, NC USA. [Dejardin, Jerome] CNRS UPR 1142, Inst Human Genet, INSERM AVENIR Team, Montpellier, France. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM masonj@niehs.nih.gov; kingston@molbio.mgh.harvard.edu FU National Institutes of Health [GM43901]; National Institute of Environmental Health Sciences, National Institutes of Health; Fundacao para a Ciencia e Tecnologia [SFRH/BD/11800/2003] FX Funding for this work was provided by the National Institutes of Health (GM43901) and by the Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health. J.M.A. was supported in part by a fellowship from the Fundacao para a Ciencia e Tecnologia (SFRH/BD/11800/2003). NR 57 TC 19 Z9 19 U1 0 U2 17 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 JUN PY 2012 VL 32 IS 12 BP 2170 EP 2182 DI 10.1128/MCB.00010-12 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 953SV UT WOS:000304894400001 PM 22493064 ER PT J AU Sarruf, DA Bonner-Weir, S Schwartz, MW AF Sarruf, David A. Bonner-Weir, Susan Schwartz, Michael W. TI New clues to bariatric surgery's benefits SO NATURE MEDICINE LA English DT Editorial Material ID MEDICAL THERAPY AB Bariatric surgery to treat obesity can also be effective against type 2 diabetes, but it is unclear how such surgical procedures improve glucose metabolism. A new study in rats suggests that nutrient sensing in the jejunum contributes to the antidiabetic effects of duodenal-jejeunal bypass (pages 950-955). C1 [Sarruf, David A.] Novo Nordisk AS, Diabet Res Unit, Malov, Denmark. [Bonner-Weir, Susan] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Schwartz, Michael W.] Univ Washington, Dept Med, Diabet & Obes Ctr Excellence, Seattle, WA USA. [Schwartz, Michael W.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. RP Sarruf, DA (reprint author), Novo Nordisk AS, Diabet Res Unit, Malov, Denmark. EM mschwart@u.washington.edu RI Schwartz, Michael/H-9950-2012; OI Bonner-Weir, Susan/0000-0003-4682-0656 FU NIDDK NIH HHS [R01 DK052989, R01 DK083042, R01 DK090320] NR 9 TC 4 Z9 4 U1 0 U2 5 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 JUN PY 2012 VL 18 IS 6 BP 860 EP 861 DI 10.1038/nm.2801 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 956VD UT WOS:000305116600020 PM 22673995 ER PT J AU Yusuf, RZ Wang, YH Scadden, DT AF Yusuf, Rushdia Z. Wang, Ying-Hua Scadden, David T. TI Metabolic priming for AML SO NATURE MEDICINE LA English DT Editorial Material ID ACUTE MYELOID-LEUKEMIA; MUTATIONS; THERAPY; CELL; CANCER C1 [Yusuf, Rushdia Z.; Wang, Ying-Hua; Scadden, David T.] Harvard Univ, Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02115 USA. [Yusuf, Rushdia Z.; Wang, Ying-Hua; Scadden, David T.] Harvard Univ, Ctr Canc, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Boston, MA 02115 USA. RP Yusuf, RZ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02115 USA. EM dscadden@mgh.harvard.edu FU NHLBI NIH HHS [U01 HL100402, R01 HL044851] NR 18 TC 7 Z9 8 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUN PY 2012 VL 18 IS 6 BP 865 EP 867 DI 10.1038/nm.2831 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 956VD UT WOS:000305116600023 PM 22673998 ER PT J AU Tenbaum, SP Ordonez-Moran, P Puig, I Chicote, I Arques, O Landolfi, S Fernandez, Y Herance, JR Gispert, JD Mendizabal, L Aguilar, S Cajal, SRY Schwartz, S Vivancos, A Espin, E Rojas, S Baselga, J Tabernero, J Munoz, A Palmer, HG AF Tenbaum, Stephan P. Ordonez-Moran, Paloma Puig, Isabel Chicote, Irene Arques, Oriol Landolfi, Stefania Fernandez, Yolanda Raul Herance, Jose Gispert, Juan D. Mendizabal, Leire Aguilar, Susana Ramon y Cajal, Santiago Schwartz, Simo, Jr. Vivancos, Ana Espin, Eloy Rojas, Santiago Baselga, Jose Tabernero, Josep Munoz, Alberto Palmer, Hector G. TI beta-catenin confers resistance to PI3K and AKT inhibitors and subverts FOXO3a to promote metastasis in colon cancer SO NATURE MEDICINE LA English DT Article ID FORKHEAD TRANSCRIPTION FACTOR; STEM-CELLS; COLORECTAL-CANCER; BREAST-CANCER; TUMOR PROGRESSION; OXIDATIVE STRESS; GENE-EXPRESSION; E-CADHERIN; KINASE-B; PHASE-I AB The Wnt-beta-catenin and PI3K-AKT-FOXO3a pathways have a central role in cancer. AKT phosporylates FOXO3a, relocating it from the cell nucleus to the cytoplasm, an effect that is reversed by PI3K and AKT inhibitors. Simultaneous hyperactivation of the Wnt-beta-catenin pathway and inhibition of PI3K-AKT signaling promote nuclear accumulation of beta-catenin and FOXO3a, respectively, promoting cell scattering and metastasis by regulating a defined set of target genes. Indeed, the anti-tumoral AKT inhibitor API-2 promotes nuclear FOXO3a accumulation and metastasis of cells with high nuclear beta-catenin content. Nuclear beta-catenin confers resistance to the FOXO3a-mediated apoptosis induced by PI3K and AKT inhibitors in patient-derived primary cultures and in corresponding xenograft tumors in mice. This resistance is reversed by XAV-939, an inhibitor of Wnt-beta-catenin signaling. In the presence of high nuclear beta-catenin content, activation of FOXO3a by PI3K or AKT inhibitors makes it behave as a metastasis inductor rather than a proapoptotic tumor suppressor. We show that it is possible to evaluate the beta-catenin status of patients' carcinomas and the response of patient-derived cells to target-directed drugs that accumulate FOXO3a in the nucleus before deciding on a course of treatment. We propose that this evaluation could be essential to the provision of a safer and more effective personalized treatment. C1 [Tenbaum, Stephan P.; Puig, Isabel; Chicote, Irene; Arques, Oriol; Palmer, Hector G.] VHIO, Stem Cell & Canc Lab, Barcelona, Spain. [Ordonez-Moran, Paloma; Munoz, Alberto] Univ Autonoma Madrid, CSIC, Inst Invest Biomed Alberto Sols, Madrid, Spain. [Landolfi, Stefania; Ramon y Cajal, Santiago] Univ Autonoma Barcelona, Hosp Univ Vall Hebron, Dept Pathol, E-08193 Barcelona, Spain. [Fernandez, Yolanda; Schwartz, Simo, Jr.] Univ Autonoma Barcelona, Hosp Univ Vall Hebron,Inst Recerca Vall Hebron, Nanomed & Networking Biomed Res Ctr Bioengn Bioma, Ctr Invest Bioquim & Biol Mol CIBBIM,Grp Drug Del, E-08193 Barcelona, Spain. [Raul Herance, Jose; Gispert, Juan D.; Rojas, Santiago] Ctr Imatge Mol CRC Corp Sanitaria, Barcelona, Spain. [Mendizabal, Leire; Vivancos, Ana] VHIO, Genom Canc Grp, Barcelona, Spain. [Aguilar, Susana] UCL, Rayne Inst, Ctr Resp Res, London, England. [Aguilar, Susana] Canc Res UK, London Res Inst, Hematopoiet Stem Cell Lab, London, England. [Espin, Eloy] Hosp Univ Vall Hebron, Gen Surg Serv, Barcelona, Spain. [Baselga, Jose] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. [Baselga, Jose] Howard Hughes Med Inst, Chevy Chase, MD USA. [Tabernero, Josep] Hosp Univ Vall Hebron, Dept Med Oncol, Barcelona, Spain. RP Palmer, HG (reprint author), VHIO, Stem Cell & Canc Lab, Barcelona, Spain. EM hgpalmer@vhio.net RI Schwartz, Simo/H-7776-2012; Munoz, Alberto/O-6393-2014; Ramon y Cajal, Santiago/H-4955-2016 OI Munoz, Alberto/0000-0003-3890-4251; Ramon y Cajal, Santiago/0000-0002-3867-1390 FU VHIO; Instituto de Salud Carlos III (ISCIII) [FIS-PI081356, RETICC-RD06/0020/0075, RETICC-RD06/0020/0009]; Ministerio de Ciencia e Innovacion [SAF-18302]; Fundacio Olga Torres Fellowship; Fundacion Cientifica de la Asociacion Espanola Contra el Cancer (AECC) FX We thank W. Shao (Novartis Institutes for BioMedical Research, Inc.) for providing the experimental drug, XAV-939, and its inactive analog, LDW-643, and we thank K. F. Becker (Technische Universitat Munchen, Germany) for providing the antibody to Snail1. We also thank P.J. Coffer (Utrecht, Netherlands) for providing the pcDNA3-FOXO3a(A3):ER (TM) expression plasmid, as well as H. Clevers (Utrecht, Netherlands) for providing L8 colon cancer cells. J. Seoane and G. Folch (VHIO, Barcelona, Spain) provided technical advice and reagents. We thank R. Luthra (Molecular Diagnostics Laboratory, MD Anderson Cancer Center, Houston, Texas, USA) for providing the CLIA panel of somatic mutations. We thank M.J. Larriba (Instituto de Investigaciones Biomedicas 'Alberto Sols', Consejo Superior de Investigaciones Cientificas-Universidad Autonoma de Madrid, Madrid, Spain) for providing the reagents necessary for the analysis of Zeb1 and Slug expression and M. Scaltriti (Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts, USA) for supplying the lentiviruses used to knock down IQGAP2 expression. We acknowledge R. Rycroft and A. Wren for their valuable assistance in the preparation of the English version of the manuscript. Experiments were supported by a VHIO starting grant and grants from Fondo de Investigaciones Sanitarias-Instituto de Salud Carlos III (ISCIII) (FIS-PI081356, RETICC-RD06/0020/0075 and RETICC-RD06/0020/0009), and Plan Nacional de Biomedicina, Ministerio de Ciencia e Innovacion (SAF-18302). S. P. T. was supported by a Fundacio Olga Torres Fellowship, I. P. was funded by the Fundacion Cientifica de la Asociacion Espanola Contra el Cancer (AECC), and H. G. P. was supported by the Miguel Servet Program, ISCIII. NR 61 TC 119 Z9 124 U1 3 U2 55 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 JUN PY 2012 VL 18 IS 6 BP 892 EP + DI 10.1038/nm.2772 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 956VD UT WOS:000305116600026 PM 22610277 ER PT J AU Kiefer, FW Vernochet, C O'Brien, P Spoerl, S Brown, JD Nallamshetty, S Zeyda, M Stulnig, TM Cohen, DE Kahn, CR Plutzky, J AF Kiefer, Florian W. Vernochet, Cecile O'Brien, Patrick Spoerl, Steffen Brown, Jonathan D. Nallamshetty, Shriram Zeyda, Maximilian Stulnig, Thomas M. Cohen, David E. Kahn, C. Ronald Plutzky, Jorge TI Retinaldehyde dehydrogenase 1 regulates a thermogenic program in white adipose tissue SO NATURE MEDICINE LA English DT Article ID UNCOUPLING PROTEIN GENE; RETINOIC ACID; BROWN ADIPOCYTES; METABOLIC SYNDROME; NUCLEAR RECEPTORS; STEM-CELLS; OBESITY; MICE; FAT; ADIPOGENESIS AB Promoting brown adipose tissue (BAT) formation and function may reduce obesity. Recent data link retinoids to energy balance, but a specific role for retinoid metabolism in white versus brown fat is unknown. Retinaldehyde dehydrogenases (Aldhs), also known as aldehyde dehydrogenases, are rate-limiting enzymes that convert retinaldehyde (Rald) to retinoic acid. Here we show that Aldh1a1 is expressed predominately in white adipose tissue (WAT), including visceral depots in mice and humans. Deficiency of the Aldh1a1 gene induced a BAT-like transcriptional program in WAT that drove uncoupled respiration and adaptive thermogenesis. WAT-selective Aldh1a1 knockdown conferred this BAT program in obese mice, limiting weight gain and improving glucose homeostasis. Rald induced uncoupling protein-1 (Ucp1) mRNA and protein levels in white adipocytes by selectively activating the retinoic acid receptor (RAR), recruiting the coactivator PGC-1 alpha and inducing Ucp1 promoter activity. These data establish Aldh1a1 and its substrate Rald as previously unrecognized determinants of adipocyte plasticity and adaptive thermogenesis, which may have potential therapeutic implications. C1 [Kiefer, Florian W.; O'Brien, Patrick; Spoerl, Steffen; Brown, Jonathan D.; Nallamshetty, Shriram; Plutzky, Jorge] Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiovasc Div,Dept Med, Boston, MA 02115 USA. [Vernochet, Cecile; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Zeyda, Maximilian; Stulnig, Thomas M.] Christian Doppler Lab Cardiometab Immunotherapy, Vienna, Austria. [Zeyda, Maximilian; Stulnig, Thomas M.] Med Univ Vienna, Dept Med, Clin Div Endocrinol & Metab, Vienna, Austria. [Cohen, David E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gastroenterol,Dept Med, Boston, MA 02115 USA. RP Plutzky, J (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiovasc Div,Dept Med, Boston, MA 02115 USA. EM jplutzky@rics.bwh.harvard.edu OI Stulnig, Thomas/0000-0003-3300-6161; Zeyda, Maximilian/0000-0001-5000-1974 FU US National Institutes of Health [HL048743, AR054604-03S1, 5P30DK057521-12]; Mary K. Iacocca Professorship [DK082659]; National Institute of Diabetes and Digestive and Kidney Diseases [DK056626, DK048873, DK048873-14S2]; Austrian Science Fund (FWF) [J3107-B19] FX We thank H. Wang, G. Sukhova, E. Shvartz, T. A. Dang and V. Demchev for excellent technical support, R. Koza (Pennington Biomedical Research Center) for providing the Ucp1 promoter luciferase construct, H. Kagechika (University of Tokyo) for providing HX531 and G. Duester (Burnham Medical Research Institute) for the Aldh1a1-/- mice and helpful discussions. This work was supported by the US National Institutes of Health grants HL048743, AR054604-03S1, 5P30DK057521-12 (J.P.); Mary K. Iacocca Professorship DK082659 and the National Institute of Diabetes and Digestive and Kidney Diseases DK056626 (C. R. K.); DK048873 and DK048873-14S2 (D. E. C.); the Austrian Science Fund (FWF); J3107-B19 (F.W.K.). NR 48 TC 64 Z9 64 U1 1 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUN PY 2012 VL 18 IS 6 BP 918 EP + DI 10.1038/nm.2757 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 956VD UT WOS:000305116600029 PM 22561685 ER PT J AU Chen, YW Negre, N Li, QH Mieczkowska, JO Slattery, M Liu, T Zhang, Y Kim, TK He, HH Zieba, J Ruan, YJ Bickel, PJ Myers, RM Wold, BJ White, KP Lieb, JD Liuas, XS AF Chen, Yiwen Negre, Nicolas Li, Qunhua Mieczkowska, Joanna O. Slattery, Matthew Liu, Tao Zhang, Yong Kim, Tae-Kyung He, Housheng Hansen Zieba, Jennifer Ruan, Yijun Bickel, Peter J. Myers, Richard M. Wold, Barbara J. White, Kevin P. Lieb, Jason D. Liuas, X. Shirley TI Systematic evaluation of factors influencing ChIP-seq fidelity SO NATURE METHODS LA English DT Article ID FACTOR-BINDING SITES; MODEL-BASED ANALYSIS; RNA-SEQ; GENOME AB We evaluated how variations in sequencing depth and other parameters influence interpretation of chromatin immunoprecipitation-sequencing (ChIP-seq) experiments. Using Drosophila melanogaster S2 cells, we generated ChIP-seq data sets for a site-specific transcription factor (Suppressor of Hairy-wing) and a histone modification (H3K36me3). We detected a chromatin-state bias: open chromatin regions yielded higher coverage, which led to false positives if not corrected. This bias had a greater effect on detection specificity than any base-composition bias. Paired-end sequencing revealed that single-end data underestimated ChIP-library complexity at high coverage. Removal of reads originating at the same base reduced false-positives but had little effect on detection sensitivity. Even at mappable-genome coverage depth of similar to 1 read per base pair, similar to 1% of the narrow peaks detected on a tiling array were missed by ChIP-seq. Evaluation of widely used ChIP-seq analysis tools suggests that adjustments or algorithm improvements are required to handle data sets with deep coverage. C1 [Chen, Yiwen; Liu, Tao; He, Housheng Hansen; Liuas, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Chen, Yiwen; Liu, Tao; He, Housheng Hansen; Liuas, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Negre, Nicolas; Slattery, Matthew; Zieba, Jennifer; White, Kevin P.] Univ Chicago, Dept Human Genet, Inst Genom & Syst Biol, Chicago, IL 60637 USA. [Li, Qunhua] Penn State Univ, Dept Stat, University Pk, PA 16802 USA. [Mieczkowska, Joanna O.; Lieb, Jason D.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Carolina Ctr Genome Sci, Dept Biol, Chapel Hill, NC 27599 USA. [Zhang, Yong] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. [Kim, Tae-Kyung] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Ruan, Yijun] Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore. [Bickel, Peter J.] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA. [Myers, Richard M.] HudsonAlpha Inst Biotechnol, Huntsville, AL USA. [Wold, Barbara J.] CALTECH, Div Biol, Pasadena, CA 91125 USA. RP Liuas, XS (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM kpwhite@uchicago.edu; jlieb@bio.unc.edu; xsliu@jimmy.harvard.edu RI Liu, Tao/G-3585-2010; Zhang, Yong/B-4838-2011; OI Liu, Tao/0000-0002-8818-8313; Zhang, Yong/0000-0001-6316-2734; Liu, Tao/0000-0003-0446-9001; Negre, Nicolas/0000-0001-9727-3416 FU US National Institutes of Health [HG4069, 3U01 HG004270-03S1, U01HG004264] FX We thank the authors of all of the algorithms that we evaluated in this study: H. Ji, R. Jothi, P. Kharchenko, W. Li, D. Nix, J. Rozowsky and A. Valouev. We thank N. Bild, D. Roqueiro and M. Sabala for help in performing PeakSeq on the Bionimbus Cloud, D. Schmidt and D. Odom for sharing their sequencing data of the ENCODE spike-in sample, A. Kundaje for sharing his unpublished results on IDR analysis of H3K36me3 in humans, N. Rashid for sharing the mappability data of Drosophila genome, M. Greenberg for support in the early stage of this project, and E. Birney, M. Snyder, J. Ahringer, M. Gerstein, M. Kellis, P. Park and other members of modENCODE consortium for helpful discussions. This work was partially funded by US National Institutes of Health (HG4069 to X. S. L., 3U01 HG004270-03S1 to X. S. L. and J. D. L., and U01HG004264 to K.P.W.). NR 36 TC 68 Z9 71 U1 0 U2 24 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD JUN PY 2012 VL 9 IS 6 BP 609 EP + DI 10.1038/NMETH.1985 PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 952GD UT WOS:000304778500029 PM 22522655 ER PT J AU Chauhan, VP Stylianopoulos, T Martin, JD Popovic, Z Chen, O Kamoun, WS Bawendi, MG Fukumura, D Jain, RK AF Chauhan, Vikash P. Stylianopoulos, Triantafyllos Martin, John D. Popovic, Zoran Chen, Ou Kamoun, Walid S. Bawendi, Moungi G. Fukumura, Dai Jain, Rakesh K. TI Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner SO NATURE NANOTECHNOLOGY LA English DT Article ID VASCULAR NORMALIZATION; ANTIANGIOGENIC THERAPY; GLIOBLASTOMA PATIENTS; SOLID TUMORS; FLUID-FLOW; CANCER; PENETRATION; TRANSPORT; GROWTH; ANGIOGENESIS AB The blood vessels of cancerous tumours are leaky(1-3) and poorly organized(4-7). This can increase the interstitial fluid pressure inside tumours and reduce blood supply to them, which impairs drug delivery(8,9). Anti-angiogenic therapies-which 'normalize' the abnormal blood vessels in tumours by making them less leaky-have been shown to improve the delivery and effectiveness of chemotherapeutics with low molecular weights(10), but it remains unclear whether normalizing tumour vessels can improve the delivery of nanomedicines. Here, we show that repairing the abnormal vessels in mammary tumours, by blocking vascular endothelial growth factor receptor-2, improves the delivery of smaller nanoparticles (diameter, 12 nm) while hindering the delivery of larger nanoparticles (diameter, 125 nm). Using a mathematical model, we show that reducing the sizes of pores in the walls of vessels through normalization decreases the interstitial fluid pressure in tumours, thus allowing small nanoparticles to enter them more rapidly. However, increased steric and hydrodynamic hindrances, also associated with smaller pores, make it more difficult for large nanoparticles to enter tumours. Our results further suggest that smaller (similar to 12 nm) nanomedicines are ideal for cancer therapy due to their superior tumour penetration. C1 [Chauhan, Vikash P.; Stylianopoulos, Triantafyllos; Martin, John D.; Kamoun, Walid S.; Fukumura, Dai; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. [Chauhan, Vikash P.; Stylianopoulos, Triantafyllos; Martin, John D.; Kamoun, Walid S.; Fukumura, Dai; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chauhan, Vikash P.] Harvard Univ, Harvard Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Stylianopoulos, Triantafyllos] Univ Cyprus, Dept Mech & Mfg Engn, CY-1678 Nicosia, Cyprus. [Martin, John D.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Popovic, Zoran; Chen, Ou; Bawendi, Moungi G.] MIT, Dept Chem, Cambridge, MA 02139 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu RI Chauhan, Vikash/H-8172-2013; Martin, John/L-6892-2016; OI Chauhan, Vikash/0000-0001-9126-2302; Martin, John/0000-0002-9828-8203; Stylianopoulos, Triantafyllos/0000-0002-3093-1696 FU DoD [W81XWH-10-1-0016]; FP7 Marie-Curie IRG grant [PIRG08-GA-2010-276894] FX The authors thank J. Kahn and S. Roberge for technical assistance, J. Baish for assistance with the mathematical model and M. Ancukiewicz for assistance with statistical analysis. The authors acknowledge ImClone Systems for generously providing DC101, the National Institutes of Health (P01-CA080124, R01-CA126642, R01-CA115767, R01-CA096915, R01-CA085140, R01-CA098706, T32-CA073479), a DoD Breast Cancer Research Innovator award (W81XWH-10-1-0016) and an FP7 Marie-Curie IRG grant (PIRG08-GA-2010-276894). NR 30 TC 278 Z9 283 U1 18 U2 188 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1748-3387 EI 1748-3395 J9 NAT NANOTECHNOL JI Nat. Nanotechnol. PD JUN PY 2012 VL 7 IS 6 BP 383 EP 388 DI 10.1038/NNANO.2012.45 PG 6 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Science & Technology - Other Topics; Materials Science GA 955HO UT WOS:000305008200012 PM 22484912 ER PT J AU Lee, H Lytton-Jean, AKR Chen, Y Love, KT Park, AI Karagiannis, ED Sehgal, A Querbes, W Zurenko, CS Jayaraman, M Peng, CG Charisse, K Borodovsky, A Manoharan, M Donahoe, JS Truelove, J Nahrendorf, M Langer, R Anderson, DG AF Lee, Hyukjin Lytton-Jean, Abigail K. R. Chen, Yi Love, Kevin T. Park, Angela I. Karagiannis, Emmanouil D. Sehgal, Alfica Querbes, William Zurenko, Christopher S. Jayaraman, Muthusamy Peng, Chang G. Charisse, Klaus Borodovsky, Anna Manoharan, Muthiah Donahoe, Jessica S. Truelove, Jessica Nahrendorf, Matthias Langer, Robert Anderson, Daniel G. TI Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery SO NATURE NANOTECHNOLOGY LA English DT Article ID RNAI THERAPEUTICS; MAMMALIAN-CELLS; DRUG-DELIVERY; GENE DELIVERY; CANCER; DESIGN AB Nanoparticles are used for delivering therapeutics into cells(1,2). However, size, shape, surface chemistry and the presentation of targeting ligands on the surface of nanoparticles can affect circulation half-life and biodistribution, cell-specific internalization, excretion, toxicity and efficacy(3-7). A variety of materials have been explored for delivering small interfering RNAs (siRNAs)-a therapeutic agent that suppresses the expression of targeted genes(8,9). However, conventional delivery nanoparticles such as liposomes and polymeric systems are heterogeneous in size, composition and surface chemistry, and this can lead to suboptimal performance, a lack of tissue specificity and potential toxicity(10-12). Here, we show that self-assembled DNA tetrahedral nanoparticles with a well-defined size can deliver siRNAs into cells and silence target genes in tumours. Monodisperse nanoparticles are prepared through the self-assembly of complementary DNA strands. Because the DNA strands are easily programmable, the size of the nanoparticles and the spatial orientation and density of cancer-targeting ligands (such as peptides and folate) on the nanoparticle surface can be controlled precisely. We show that at least three folate molecules per nanoparticle are required for optimal delivery of the siRNAs into cells and, gene silencing occurs only when the ligands are in the appropriate spatial orientation. In vivo, these nanoparticles showed a longer blood circulation time (t(1/2) approximate to 24.2 min) than the parent siRNA (t(1/2) approximate to 6 min). C1 [Lee, Hyukjin; Lytton-Jean, Abigail K. R.; Chen, Yi; Love, Kevin T.; Park, Angela I.; Karagiannis, Emmanouil D.; Langer, Robert; Anderson, Daniel G.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Langer, Robert; Anderson, Daniel G.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Langer, Robert; Anderson, Daniel G.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Lee, Hyukjin] Ewha Womans Univ, Coll Pharm, Seoul, South Korea. [Sehgal, Alfica; Querbes, William; Zurenko, Christopher S.; Jayaraman, Muthusamy; Peng, Chang G.; Charisse, Klaus; Borodovsky, Anna; Manoharan, Muthiah] Alnylam Pharmaceut, Cambridge, MA 02142 USA. [Donahoe, Jessica S.; Truelove, Jessica; Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Donahoe, Jessica S.; Truelove, Jessica; Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Anderson, DG (reprint author), MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM dgander@mit.edu RI Chen, Yi/D-7943-2013; OI Lee, Hyukjin/0000-0001-9478-8473; Karagiannis, Emmanouil/0000-0003-0131-6552 FU National Institutes of Health [EB000244]; Center for Cancer Nanotechnology Excellence [U54 CA151884]; Alnylam Pharmaceuticals; National Research Foundation of Korea [NRF-2011-357-D00063] FX This work was supported by the National Institutes of Health (EB000244), the Center for Cancer Nanotechnology Excellence (U54 CA151884), Alnylam Pharmaceuticals and the National Research Foundation of Korea (NRF-2011-357-D00063). The authors thank J. Hong and C. Hong for figure drawing, and J. B. Lee and A. Schroeder for helpful discussions. NR 26 TC 312 Z9 319 U1 44 U2 368 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1748-3387 J9 NAT NANOTECHNOL JI Nat. Nanotechnol. PD JUN PY 2012 VL 7 IS 6 BP 389 EP 393 DI 10.1038/NNANO.2012.73 PG 5 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Science & Technology - Other Topics; Materials Science GA 955HO UT WOS:000305008200013 PM 22659608 ER PT J AU Leung, FW AF Leung, Felix W. TI COLONOSCOPY Reducing faecal incontinence following colonoscopy SO NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY LA English DT Editorial Material AB Faecal incontinence can occur in patients who have undergone a colonoscopy. The incidence of postexamination faecal incontinence in a large Norwegian cohort has now been reported, and the risk of faecal incontinence found to be reduced if CO2 is used instead of air to insufflate the colon. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Gastroenterol Sect, Sepulveda Ambulatory Care Ctr, N Hill, CA 91343 USA. RP Leung, FW (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Gastroenterol Sect, Sepulveda Ambulatory Care Ctr, 111G,16111 Plummer St, N Hill, CA 91343 USA. EM felix.leung@va.gov NR 10 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5045 J9 NAT REV GASTRO HEPAT JI Nat. Rev. Gastroenterol. Hepatol. PD JUN PY 2012 VL 9 IS 6 BP 308 EP 309 DI 10.1038/nrgastro.2012.93 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 955JZ UT WOS:000305016200003 PM 22585133 ER PT J AU Lassman, AB Iwamoto, FM Cloughesy, TF Aldape, KD Rivera, AL Eichler, AF Louis, DN Paleologos, NA Fisher, BJ Ashby, LS Cairncross, JG Urgoiti, GBR Wen, PY Ligon, KL Schiff, D Robins, HI Rocque, BG Chamberlain, MC Mason, WP Weaver, SA Green, RM Kamar, FG Abrey, LE DeAngelis, LM Jhanwar, SC Rosenblum, MK Panageas, KS AF Lassman, Andrew B. Iwamoto, Fabio M. Cloughesy, Timothy F. Aldape, Kenneth D. Rivera, Andreana L. Eichler, April F. Louis, David N. Paleologos, Nina A. Fisher, Barbara J. Ashby, Lynn S. Cairncross, J. Gregory Urgoiti, Gloria B. Roldan Wen, Patrick Y. Ligon, Keith L. Schiff, David Robins, H. Ian Rocque, Brandon G. Chamberlain, Marc C. Mason, Warren P. Weaver, Susan A. Green, Richard M. Kamar, Francois G. Abrey, Lauren E. DeAngelis, Lisa M. Jhanwar, Suresh C. Rosenblum, Marc K. Panageas, Katherine S. TI Response to Weltman and Fleury Malheiros, re Lassman et al. SO NEURO-ONCOLOGY LA English DT Letter C1 [Lassman, Andrew B.; Iwamoto, Fabio M.; Abrey, Lauren E.; DeAngelis, Lisa M.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. [Jhanwar, Suresh C.; Rosenblum, Marc K.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Panageas, Katherine S.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Brain Tumor Ctr, New York, NY 10021 USA. [Cloughesy, Timothy F.] Univ Calif Los Angeles, Los Angeles, CA USA. [Aldape, Kenneth D.; Rivera, Andreana L.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Eichler, April F.; Louis, David N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Paleologos, Nina A.] Univ Chicago, NorthShore Univ Hlth Syst, Evanston Hosp, Pritzker Sch Med,Kellogg Canc Ctr, Evanston, IL USA. [Fisher, Barbara J.] London Reg Canc Program, London, ON, Canada. [Ashby, Lynn S.] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Cairncross, J. Gregory; Urgoiti, Gloria B. Roldan] Univ Calgary, Calgary, AB, Canada. [Ligon, Keith L.] Brigham & Womens Hosp, Childrens Hosp Boston, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Robins, H. Ian; Rocque, Brandon G.] Univ Wisconsin, Madison, WI USA. [Schiff, David] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Chamberlain, Marc C.] Univ Washington, Seattle, WA 98195 USA. [Chamberlain, Marc C.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Mason, Warren P.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Weaver, Susan A.] Albany Med Ctr, Albany, NY USA. [Green, Richard M.] Kaiser Permanente Los Angeles, Med Ctr, Los Angeles, CA USA. [Kamar, Francois G.] Clemenceau Med Ctr, Beirut, Lebanon. [Kamar, Francois G.] Univ St Esprit Kaslik, Byblos, Lebanon. RP Lassman, AB (reprint author), Columbia Univ, Dept Neurol, Med Ctr, 710 W 168th St, New York, NY 10027 USA. EM abl7@columbia.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2012 VL 14 IS 6 BP 677 EP 678 DI 10.1093/neuonc/nos136 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 955PB UT WOS:000305031900003 ER PT J AU Zhang, W Zhang, J Hoadley, K Kushwaha, D Ramakrishnan, V Li, SW Kang, CS You, YP Jiang, CL Song, SW Jiang, T Chen, CC AF Zhang, Wei Zhang, Jing Hoadley, Katherine Kushwaha, Deepa Ramakrishnan, Valya Li, Shouwei Kang, Chunsheng You, Yongping Jiang, Chuanlu Song, Sonya Wei Jiang, Tao Chen, Clark C. TI miR-181d: a predictive glioblastoma biomarker that downregulates MGMT expression SO NEURO-ONCOLOGY LA English DT Article DE biomarker; glioblastoma; MGMT; miR-181d; temozolomide ID O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; ADJUVANT TEMOZOLOMIDE; PROMOTER METHYLATION; RADIOTHERAPY; CONCOMITANT AB Genome-wide microRNA (miRNA) profiling of 82 glioblastomas demonstrated that miR-181d was inversely associated with patient overall survival after correcting for age, Karnofsky performance status, extent of resection, and temozolomide (TMZ) treatment. This association was validated using the Cancer Genome Atlas (TCGA) dataset (n = 424) and an independent cohort (n = 35). In these independent cohorts, an association of miR-181d with survival was evident in patients who underwent TMZ treatment but was not observed in patients without TMZ therapy. Bioinformatic analysis of potential genes regulated by miR-181d revealed methyl-guanine-methyl-transferase (MGMT) as a downstream target. Indeed, transfection of miR-181d downregulated MGMT mRNA and protein expression. Furthermore, luciferase reporter assays and coprecipitation studies showed a direct interaction between miR-181d and MGMT 3'UTR. The suppressive effect of miR-181d on MGMT expression was rescued by the introduction of an MGMT cDNA. Finally, MGMT expression inversely correlated with miR-181d expression in independent glioblastoma cohorts. Together, these results suggest that miR-181d is a predictive biomarker for TMZ response and that its role is mediated, in part, by posttranscriptional regulation of MGMT. C1 [Song, Sonya Wei] Peking Univ, Canc Hosp & Inst, Minist Educ, Key Lab Carcinogenesis & Translat Res, Beijing 100871, Peoples R China. [Chen, Clark C.] Beth Israel Deaconess Med Ctr, Div Neurosurg, Boston, MA 02215 USA. [Zhang, Wei; Li, Shouwei; Jiang, Tao] Capital Med Univ, Tiantan Hosp, Dept Neurosurg, Beijing, Peoples R China. [Zhang, Jing] Chinese Acad Sci, Beijing Inst Genom, Ctr Computat Biol, Lab Dis Genom & Personalized Med, Beijing, Peoples R China. [Hoadley, Katherine] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Kushwaha, Deepa; Chen, Clark C.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Ramakrishnan, Valya; Chen, Clark C.] Univ Calif San Diego, Div Neurosurg, Moores Canc Ctr, Ctr Theoret & Appl Neurooncol, San Diego, CA 92103 USA. [Kang, Chunsheng] Tianjin Med Univ, Gen Hosp, Neurooncol Lab, Tianjin, Peoples R China. [You, Yongping] Jiangsu Prov Peoples Hosp, Dept Neurosurg, Nanjing, Jiangsu, Peoples R China. [Jiang, Chuanlu] Harbin Med Univ, Hosp 2, Dept Neurosurg, Harbin, Peoples R China. RP Song, SW (reprint author), Peking Univ, Canc Hosp & Inst, Minist Educ, Key Lab Carcinogenesis & Translat Res, Beijing 100871, Peoples R China. EM weisonyasong@gmail.com; taojiang1964@yahoo.com.cn; clarkchen@ucsd.edu RI Chen, Clark/C-8714-2013; Jiang, Tao/N-8142-2014; Zhang, Jing/F-4707-2015; RAMAKRISHNAN, VALYA/L-6415-2016 OI Chen, Clark/0000-0001-6258-9277; Zhang, Jing/0000-0001-5903-6487; FU National Key Project of Science and Technology Supporting Programs [2007BAI05B08]; National Natural Science Foundation [30772238, 30730035]; National Basic Research Program of China [2010CB529406]; National High Technology Research and Development Program of China [2012AA02A508]; Doris Duke Charitable Foundation; Sontag Foundation; Burroughs Wellcome Fund; Forbeck Foundation; Kimmel Foundation FX This work was supported by National Key Project of Science and Technology Supporting Programs (grant 2007BAI05B08), National Natural Science Foundation (grant 30772238 and 30730035), National Basic Research Program of China (grant 2010CB529406), and National High Technology Research and Development Program of China (grant 2012AA02A508) (to T.J.) and the Doris Duke Charitable Foundation, Sontag Foundation, Burroughs Wellcome Fund, Forbeck Foundation, and Kimmel Foundation (to C.C.C.). NR 20 TC 61 Z9 71 U1 6 U2 18 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2012 VL 14 IS 6 BP 712 EP 719 DI 10.1093/neuonc/nos089 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 955PB UT WOS:000305031900007 PM 22570426 ER PT J AU Panageas, KS Iwamoto, FM Cloughesy, TF Aldape, KD Rivera, AL Eichler, AF Louis, DN Paleologos, NA Fisher, BJ Ashby, LS Cairncross, JG Urgoiti, GBR Wen, PY Ligon, KL Schiff, D Robins, HI Rocque, BG Chamberlain, MC Mason, WP Weaver, SA Green, RM Kamar, FG Abrey, LE DeAngelis, LM Jhanwar, SC Rosenblum, MK Lassman, AB AF Panageas, Katherine S. Iwamoto, Fabio M. Cloughesy, Timothy F. Aldape, Kenneth D. Rivera, Andreana L. Eichler, April F. Louis, David N. Paleologos, Nina A. Fisher, Barbara J. Ashby, Lynn S. Cairncross, J. Gregory Urgoiti, Gloria B. Roldan Wen, Patrick Y. Ligon, Keith L. Schiff, David Robins, H. Ian Rocque, Brandon G. Chamberlain, Marc C. Mason, Warren P. Weaver, Susan A. Green, Richard M. Kamar, Francois G. Abrey, Lauren E. DeAngelis, Lisa M. Jhanwar, Suresh C. Rosenblum, Marc K. Lassman, Andrew B. TI Initial treatment patterns over time for anaplastic oligodendroglial tumors SO NEURO-ONCOLOGY LA English DT Article DE oligoastrocytoma; oligodendroglioma; PCV; temozolomide; 1p19q ID PHASE-III TRIAL; EUROPEAN ORGANIZATION; FOLLOW-UP; RADIOTHERAPY; CHEMOTHERAPY; TEMOZOLOMIDE; OLIGOASTROCYTOMAS; GLIOMA AB Anaplastic oligodendroglial tumors are rare neoplasms with no standard approach to treatment. We sought to determine patterns of treatment delivered over time and identify clinical correlates of specific strategies using an international retrospective cohort of 1013 patients diagnosed from 1981-2007. Prior to 1990, most patients received radiotherapy (RI) alone as initial postoperative treatment. After 1990, approximately 50% of patients received both RI and chemotherapy (CT) sequentially and/or concurrently. Treatment with RI alone became significantly less common (67% in 1980-1984 vs 5% in 2005-2007, P < .0001). CT alone was more frequently administered in later years (0% in 1980-1984 vs 38% in 2005-2007; P < .0001), especially in patients with 1p19q codeleted tumors (57% of codeleted vs 4% with no deletion in 2005-2007; P < .0001). Temozolomide replaced the combination of procarbazine, lomustine, and vincristine (PCV) among patients who received CT alone or with RI (87% vs 2% in 2005-2007). In the most recent time period, patients with 1p19q codeleted tumors were significantly more likely to receive CT alone (with temozolomide), whereas RI with temozolomide was a significantly more common treatment strategy than either CT or RI alone in cases with no deletion (P < .0001). In a multivariate polytomous logistic regression model, the following were significantly associated with type of treatment delivered: date (5-year interval) of diagnosis (P < .0001), 1p19q codeletion (P < .0001), pure anaplastic oligodendroglioma histology (P < .01), and frontal lobe predominance (P < .05). Limited level 1 evidence is currently available to guide treatment decisions, and ongoing phase III trials will be critical to understanding the optimal therapy. C1 [Panageas, Katherine S.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Iwamoto, Fabio M.; Abrey, Lauren E.; DeAngelis, Lisa M.; Lassman, Andrew B.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. [Jhanwar, Suresh C.; Rosenblum, Marc K.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Brain Tumor Ctr, New York, NY 10021 USA. [Cloughesy, Timothy F.] Univ Calif Los Angeles, Los Angeles, CA USA. [Aldape, Kenneth D.; Rivera, Andreana L.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Eichler, April F.; Louis, David N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Paleologos, Nina A.] Univ Chicago, NorthShore Univ Hlth Syst, Evanston Hosp, Pritzker Sch Med,Kellogg Canc Ctr, Evanston, IL USA. [Fisher, Barbara J.] London Reg Canc Program, London, ON, Canada. [Ashby, Lynn S.] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Cairncross, J. Gregory; Urgoiti, Gloria B. Roldan] Univ Calgary, Calgary, AB, Canada. [Ligon, Keith L.] Brigham & Womens Hosp, Childrens Hosp Boston, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Schiff, David] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Robins, H. Ian; Rocque, Brandon G.] Univ Wisconsin, Madison, WI USA. [Chamberlain, Marc C.] Univ Washington, Seattle, WA 98195 USA. [Chamberlain, Marc C.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Mason, Warren P.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Weaver, Susan A.] Albany Med Ctr, Albany, NY USA. [Green, Richard M.] Kaiser Permanente Los Angeles, Med Ctr, Los Angeles, CA USA. [Kamar, Francois G.] Clemenceau Med Ctr, Beirut, Lebanon. [Kamar, Francois G.] Univ St Esprit Kaslik, Byblos, Lebanon. RP Panageas, KS (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 307 E 63rd St,3rd Floor, New York, NY 10021 USA. EM panageak@mskcc.org FU Merck Co.; Sigma Tau Pharmaceuticals; Keryx Biopharmaceuticals; Astra Zeneca; Genentech/Roche; Roche; National Brain Tumor Society; Susan Smith Klein Brain Tumor Fund; Daniel E. Rich Fund FX A.B.L., T.F.C., N.A.P., J.G.C., P.Y.W., F.G.K., and W.P.M. consulted for and/or received honoraria from Schering Corp. and/or Merck & Co.; T.F.C., N.A.P., K.D.A., H.I.R., S.A.W., L.E.A., and A.B.L. consulted for Genentech/Roche; A.B.L. and K.D.A. consulted for Bristol-Myers Squibb; A.B.L. consulted for Abbott, Campus Bio, Cephalon, Eisai, GlaxoSmithKline, and Imclone; A.B.L. formerly served and N.A.P. and S.A.W. currently serve on a Speaker's Bureau for Merck & Co. (formerly Schering Corp.); N.A.P. serves on a Speaker's Bureau for Genentech; A.B.L. and L.E.A. received research funding from Merck & Co. (formerly Schering Corp.) and Sigma Tau Pharmaceuticals; A.B.L. received research funding from Keryx Biopharmaceuticals, Astra Zeneca, and Genentech/Roche; P.Y.W. received research funding from Merck & Co.; B.J.F. received research funding from Roche; L.E.A. became an employee of Roche Pharmaceuticals after this work was conducted. M.C.C. served as a consultant, advisor, or on a Speaker's Bureau for Merck, Serano, Sigma Tau, and Roche. T.F.C. consulted for Merck Serano, and Novartis.; Funding was provided by the National Brain Tumor Society, the Susan Smith Klein Brain Tumor Fund, and the Daniel E. Rich Fund. Funding sources had no access to patient data and no role in conceiving or designing the study, in data collection or analysis, or in interpretation of results. NR 17 TC 29 Z9 30 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2012 VL 14 IS 6 BP 761 EP 767 DI 10.1093/neuanc/nos065 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 955PB UT WOS:000305031900011 PM 22661585 ER PT J AU Terry, AR Barker, FG Leffert, L Bateman, BT Souter, I Plotkin, SR AF Terry, Anna R. Barker, Fred G. Leffert, Lisa Bateman, Brian T. Souter, Irene Plotkin, Scott R. TI Outcomes of hospitalization in pregnant women with CNS neoplasms: a population-based study SO NEURO-ONCOLOGY LA English DT Article DE brain tumors; epidemiology; outcome research; pregnancy; spine tumors ID INTRACRANIAL NEOPLASMS; UNITED-STATES; BRAIN; TUMOR; METAANALYSIS; MANAGEMENT; BIRTHS; RISK AB Managing a CNS neoplasm during pregnancy presents complex challenges, and population-based studies are lacking. We designed a retrospective cohort study using the Nationwide Inpatient Sample (NIS) to investigate pregnancy outcomes in women with CNS neoplasms. We constructed a logistic regression model for maternal mortality, preterm labor, intrauterine growth restriction (IUGR), and Caesarean delivery, controlling for age, comorbidities, and demographic characteristics. We identified 379 malignant brain tumors, 437 benign brain tumors, and 44 spine tumors among 19 million pregnancy-related admissions from 1988 through 2009. Malignant brain tumors were associated with maternal mortality (odds ratio [OR], 143), preterm labor (OR, 3.4), and IUGR (OR, 2.9). Benign brain tumors were associated with preterm labor (OR, 2.3). A diagnosis of hyperemesis gravidarum was more common in malignant (OR, 2.2) and benign (OR, 2.8) brain tumors. Compared with the general population, Caesarean delivery was more frequent for malignant (OR, 6.4) and benign (OR, 2.8) brain tumors and spine tumors (OR, 3.9). Admission without delivery was more common for malignant (OR, 8.6) and benign (OR, 4.3) brain tumors and spine tumors (OR, 3.8; P < .05 for all outcomes). Thirty-three percent of all hospitalizations involved neurosurgical procedures, but pregnancy complications were not significantly more likely to occur in surgical patients. In conclusion, malignant brain tumors were associated with adverse pregnancy outcomes, and CNS neoplasms were associated with higher rates of Caesarean delivery. Additional research is needed to improve understanding of obstetric risk in these patients and to assist with treatment, counseling, and monitoring during delivery. C1 [Terry, Anna R.; Barker, Fred G.] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. [Leffert, Lisa; Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Souter, Irene] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Terry, AR (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, White 502, Boston, MA 02114 USA. EM arterry1977@gmail.com FU MGH Neurosurgical Service; John and Cyndy Leahy Fellowship Fund FX We thank Dr. Robert Martuza and the MGH Neurosurgical Service for generous financial support of relevant coursework at the Harvard School of Public Health. A preliminary version of this work was presented as a poster at the annual Society for Neuro-Oncology meeting in Orange County, CA, November 2011.; This work was supported by the John and Cyndy Leahy Fellowship Fund. The authors were independent of the funders in all aspects of study design, data analysis, and writing of the manuscript. NR 35 TC 9 Z9 9 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2012 VL 14 IS 6 BP 768 EP 776 DI 10.1093/neuonc/nos078 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 955PB UT WOS:000305031900012 PM 22513749 ER PT J AU Harel, NY Tseng, BY AF Harel, Noam Y. Tseng, Benjamin Y. TI Cerebral perfusion in acute stroke prognostication Go with the flow, or know with the quo? SO NEUROLOGY LA English DT Editorial Material ID PREDICTION C1 [Harel, Noam Y.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Harel, Noam Y.] James J Peters VA Med Ctr, Natl Ctr Excellence Med Consequences Spinal Cord, New York, NY USA. [Tseng, Benjamin Y.] Univ Texas SW Med Ctr Dallas, Dept Internal Med Cardiol, Dallas, TX 75390 USA. [Tseng, Benjamin Y.] Texas Hlth Presbyterian Hosp, Inst Exercise & Environm Med, Dallas, TX USA. RP Harel, NY (reprint author), Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. EM noam.harel@mssm.edu NR 10 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 2012 VL 78 IS 23 BP 1811 EP 1812 DI 10.1212/WNL.0b013e318258f867 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 953XC UT WOS:000304906100005 PM 22573632 ER PT J AU Payabvash, S Souza, LCS Kamalian, S Wang, Y Passanese, J Kamalian, S Fung, SH Halpern, EF Schaefer, PW Gonzalez, RG Furie, KL Lev, MH AF Payabvash, S. Souza, L. C. S. Kamalian, S. Wang, Y. Passanese, J. Kamalian, S. Fung, S. H. Halpern, E. F. Schaefer, P. W. Gonzalez, R. G. Furie, K. L. Lev, M. H. TI Location-weighted CTP analysis predicts early motor improvement in stroke A preliminary study SO NEUROLOGY LA English DT Article ID ISCHEMIC-STROKE; RECOVERY; LESION; SCALE; SITE AB Objective: To develop multivariate models for prediction of early motor deficit improvement in acute stroke patients with focal extremity paresis, using admission clinical and imaging data. Methods: Eighty consecutive patients with motor deficit due to first-ever unilateral stroke underwent CT perfusion (CTP) within 9 hours of symptom onset. Limb paresis was prospectively assessed using admission and discharge NIH Stroke Scale (NIHSS) scoring. CTP scans were coregistered to the MNI-152 brain space and subsegmented to 146 pairs of cortical/subcortical regions based on preset atlases. Stepwise multivariate binary logistic regressions were performed to determine independent clinical and imaging predictors of paresis improvement. Results: The rates of early motor deficit improvement were 18/49 (37%), 15/42 (36%), 8/25 (32%), and 7/23 (30%) for the right arm, right leg, left arm, and left leg, respectively. Admission NIHSS was the only independent clinical predictor of early limb motor deficit improvement. Relative CTP values of the inferior frontal lobe white matter, lower insular cortex, superior temporal gyrus, retrolenticular portion of internal capsule, postcentral gyrus, precuneus parietal gyri, putamen, and caudate nuclei were also independent predictors of motor improvement of different limbs. The multivariate predictive models of motor function improvement for each limb had 84%-92% accuracy, 79%-100% positive predictive value, 75%-94% negative predictive value, 83%-88% sensitivity, and 80%-100% specificity. Conclusions: We developed pilot multivariate models to predict early motor functional improvement in acute stroke patients using admission NIHSS and atlas-based location-weighted CTP data. These models serve as a "proof-of-concept" for prospective location-weighted imaging prediction of clinical outcome in acute stroke. Neurology (R) 2012;78:1853-1859 C1 [Payabvash, S.; Souza, L. C. S.; Kamalian, S.; Passanese, J.; Kamalian, S.; Fung, S. H.; Halpern, E. F.; Schaefer, P. W.; Gonzalez, R. G.; Lev, M. H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Furie, K. L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Payabvash, S.] Univ Minnesota, Dept Radiol, Minneapolis, MN 55455 USA. [Wang, Y.] Univ Western Ontario, Schulich Sch Med & Dent, London, ON, Canada. [Fung, S. H.] Methodist Hosp, Dept Radiol, Houston, TX 77030 USA. [Fung, S. H.] Weill Cornell Med Coll, New York, NY USA. RP Payabvash, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM spayab@gmail.com RI Kamalian, Shervin/D-7667-2013; OI Kamalian, Shervin/0000-0001-8962-4773; Kamalian, Shahmir/0000-0002-9640-8144; Fung, Steve/0000-0002-1177-682X FU Specialized Programs of Translational Research in Acute Stroke (SPOTRIAS) Network; NIH [P50 NS051343]; Agency for Healthcare Research and Quality [AHRQ R01 HS11392]; Massachusetts General Hospital Clinical Research Center [1 UL1 RR025758-01]; GE Healthcare; Millennium Pharmaceuticals FX Supported by the Specialized Programs of Translational Research in Acute Stroke (SPOTRIAS) Network grant funded by the NIH (P50 NS051343), the Agency for Healthcare Research and Quality grant AHRQ R01 HS11392, and the Massachusetts General Hospital Clinical Research Center (No. 1 UL1 RR025758-01).; Dr. Payabvash, Dr. Souza, Dr. Kamalian, Dr. Wang, Dr. Passanese, Dr. Kamalian, Dr. Fung, Dr. Halpern, Dr. Schaefer, Dr. Gonzalez, and Dr. Furie report no disclosures. Dr. Lev receives research support and/or is consultant to GE Healthcare, and Millennium Pharmaceuticals. Go to Neurology.org for full disclosures. NR 24 TC 11 Z9 11 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 2012 VL 78 IS 23 BP 1853 EP 1859 DI 10.1212/WNL.0b013e318258f799 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 953XC UT WOS:000304906100013 PM 22573641 ER PT J AU Vakharia, KT Henstrom, D Plotkin, SR Cheney, M Hadlock, TA AF Vakharia, Kalpesh T. Henstrom, Doug Plotkin, Scott R. Cheney, Mack Hadlock, Tessa A. TI Facial Reanimation of Patients With Neurofibromatosis Type 2 SO NEUROSURGERY LA English DT Article DE Acoustic neuroma; Facial paralysis; Facial reanimation; Gracilis free flap; Neurofibromatosis type 2 ID FREE-MUSCLE TRANSFER; MOTOR-NERVE; PARALYSIS; VALIDATION; MANAGEMENT; EXCURSION; PALSY AB BACKGROUND: Neurofibromatosis type 2 (NF2) is a tumor suppressor syndrome defined by bilateral vestibular schwannomas. Facial paralysis, from either tumor growth or surgical intervention, is a devastating complication of this disorder and can contribute to disfigurement and corneal keratopathy. Historically, physicians have not attempted to treat facial paralysis in these patients. OBJECTIVE: To review our clinical experience with free gracilis muscle transfer for the purpose of facial reanimation in patients with NF2. METHODS: Five patients with NF2 and complete unilateral facial paralysis were referred to the facial nerve center at our institution. Charts and operative reports were reviewed; treatment details and functional outcomes are reported. RESULTS: Patients were treated between 2006 and 2009. Three patients were men and 2 were women. The age of presentation of debilitating facial paralysis ranged from 12 to 50 years. All patients were treated with a single-stage free gracilis muscle transfer for smile reanimation. Each obturator nerve of the gracilis was coapted to the masseteric branch of the trigeminal nerve. Measurement of oral commissure excursions at rest and with smile preoperatively and postoperatively revealed an improved and nearly symmetric smile in all cases. CONCLUSION: Management of facial paralysis is oftentimes overlooked when defining a care plan for NF2 patients who typically have multiple brain and spine tumors. The paralyzed smile may be treated successfully with single-stage free gracilis muscle transfer in the motivated patient. C1 [Hadlock, Tessa A.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Facial Nerve Ctr, Div Facial Plast & Reconstruct Surg, Boston, MA 02114 USA. [Vakharia, Kalpesh T.; Henstrom, Doug; Plotkin, Scott R.; Cheney, Mack; Hadlock, Tessa A.] Harvard Univ, Sch Med, Boston, MA USA. [Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Hadlock, TA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Facial Nerve Ctr, Div Facial Plast & Reconstruct Surg, 243 Charles St, Boston, MA 02114 USA. EM tessa_hadlock@meei.harvard.edu NR 24 TC 6 Z9 6 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUN PY 2012 VL 70 IS 6 SU 2 BP 237 EP 243 AR ons237 DI 10.1227/NEU.0b013e31823a819f PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 955QZ UT WOS:000305037300018 PM 21968382 ER PT J AU Brunner, AM Henn, CM Drewniak, EI Lesieur-Brooks, A Machan, J Crisco, JJ Ehrlich, MG AF Brunner, A. M. Henn, C. M. Drewniak, E. I. Lesieur-Brooks, A. Machan, J. Crisco, J. J. Ehrlich, M. G. TI High dietary fat and the development of osteoarthritis in a rabbit model SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE Dietary fat; Proteoglycan; Metalloproteinases; Cartilage; Bowing; Varus malalignment ID RETRACTED ARTICLE. SEE; KNEE OSTEOARTHRITIS; AGGRECAN DEGRADATION; ARTICULAR-CARTILAGE; METABOLIC FACTORS; RISK-FACTORS; BODY-WEIGHT; OBESITY; HAND; ASSOCIATION AB Objective: Osteoarthritis (OA) is associated with obesity, although this relationship remains unclear. Proposed etiologies of OA in obesity include mechanical loading of malaligned joints and possible toxicity of dietary fat. The hypothesis tested in the present study was that increased dietary fat worsens OA in both malaligned and normal joints, detected by biochemical and histological cartilage markers. Method: 83 New Zealand white rabbits were divided among two conditions related to OA: bowing of the knee and a 14% kcal vs 47.8% kcal fat diet. Rabbit weights and knee angles were compared throughout the experiment. At 28 and 38 weeks, intra-articular forces were measured, animals sacrificed, and knee cartilage examined for histological changes, glycosaminoglycan content, 35S uptake, and aggrecanase-1 expression. Results: There were no differences in animal weights or intra-articular forces between the two diets. Despite increased fat content in their diet, animals on the 47.8% kcal fat diet did not gain excess weight. Representative histology showed atypical shearing of articular cartilage among animals on the high fat diet. Animals on the 47.8% kcal fat diet had suppression of protein synthesis compared to the 14% kcal fat diet: lower glycosaminoglycan content and aggrecanase-1 expression in all knee compartments at both times, and lower 35S uptake at 38 weeks. Conclusion: These results suggest dietary fat, independent of animal weight, results in altered chondrocyte function. Increased dietary fat was associated with changes in rabbit cartilage in vivo and appears to be a risk factor for the development of OA. (C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 Rhode Isl Hosp, Dept Orthopaed, Providence, RI USA. Brown Univ, Providence, RI 02912 USA. RP Brunner, AM (reprint author), Massachusetts Gen Hosp, Dept Med, 15 Parkman St,WAC 635, Boston, MA 02114 USA. EM abrunner@partners.org RI Machan, Jason/D-3897-2013 OI Machan, Jason/0000-0003-2048-4914 FU Rhode Island Hospital Orthopaedic Foundation FX Funding for this project was provided by the Rhode Island Hospital Orthopaedic Foundation. The study sponsors had no role in the design, data collection, analysis, writing, or submission of the study. NR 49 TC 13 Z9 14 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 EI 1522-9653 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD JUN PY 2012 VL 20 IS 6 BP 584 EP 592 DI 10.1016/j.joca.2012.02.007 PG 9 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 951QA UT WOS:000304733900017 PM 22353745 ER EF