FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Jones, SB Thomas, GA Hesselsweet, SD Alvarez-Reeves, M Yu, H Irwin, ML AF Jones, Sara B. Thomas, Gwendolyn A. Hesselsweet, Sara D. Alvarez-Reeves, Marty Yu, Herbert Irwin, Melinda L. TI Effect of Exercise on Markers of Inflammation in Breast Cancer Survivors: The Yale Exercise and Survivorship Study SO CANCER PREVENTION RESEARCH LA English DT Article ID C-REACTIVE PROTEIN; RANDOMIZED CONTROLLED-TRIAL; TYPE-2 DIABETES-MELLITUS; CORONARY-HEART-DISEASE; INDUCED WEIGHT-LOSS; POSTMENOPAUSAL WOMEN; PHYSICAL-ACTIVITY; ADIPOSE-TISSUE; CIRCULATING INTERLEUKIN-6; AEROBIC EXERCISE AB Physical activity is associated with improved breast cancer survival, but the underlying mechanisms, possibly including modification of the inflammatory state, are not well understood. We analyzed changes in interleukin (IL)-6, C-reactive protein (CRP), and TNF-alpha in a randomized controlled trial of exercise in postmenopausal breast cancer survivors. Seventy-five women, recruited through the Yale-New Haven Hospital Tumor Registry, were randomized to either a six-month aerobic exercise intervention or usual care. Correlations were calculated between baseline cytokines, adiposity, and physical activity measures. Generalized linear models were used to assess the effect of exercise on IL-6, CRP, and TNF-alpha. At baseline, IL-6 and CRP were positively correlated with body fat and body mass index (BMI) and were inversely correlated with daily pedometer steps (P < 0.001). We found no significant effect of exercise on changes in inflammatory marker concentrations between women randomized to exercise versus usual care, though secondary analyses revealed a significant reduction in IL-6 among exercisers who reached 80% of the intervention goal compared with those who did not. Future studies should examine the effect of different types and doses of exercise and weight loss on inflammatory markers in large-scale trials of women diagnosed with breast cancer. Cancer Prev Res; 6(2); 109-18. (C)2012 AACR. C1 [Jones, Sara B.; Thomas, Gwendolyn A.; Hesselsweet, Sara D.; Yu, Herbert; Irwin, Melinda L.] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA. [Alvarez-Reeves, Marty] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Irwin, ML (reprint author), Yale Univ, Sch Publ Hlth, POB 208034, New Haven, CT 06520 USA. EM melinda.irwin@yale.edu FU American Cancer Society [MRSG 04 006 01 CPPB]; Susan G. Komen Breast Cancer Foundation [BCTR0201916]; General Clinical Research Center grant from the National Center of Research Resources, NIH [M01-RR00125]; National Institute of Nursing Research [T32 NR008346] FX This study was supported by American Cancer Society (MRSG 04 006 01 CPPB) and the Susan G. Komen Breast Cancer Foundation (BCTR0201916). Supported in part by a General Clinical Research Center grant from the National Center of Research Resources, NIH (grant # M01-RR00125) awarded to Yale University School of Medicine and the National Institute of Nursing Research (Research Training: Self and Family Management Research T32 NR008346). NR 64 TC 20 Z9 21 U1 3 U2 13 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD FEB PY 2013 VL 6 IS 2 BP 109 EP 118 DI 10.1158/1940-6207.CAPR-12-0278 PG 10 WC Oncology SC Oncology GA 086IF UT WOS:000314676600006 PM 23213072 ER PT J AU Adam, M Huang, HD Shahzad, SA Kar, B Virani, SS Rogers, PA Paniagua, D Bozkurt, B Palacios, I Kleiman, NS Jneid, H AF Adam, Mahboob Huang, Henry D. Shahzad, Saima A. Kar, Biswajit Virani, Salim S. Rogers, Paul A. Paniagua, David Bozkurt, Biykem Palacios, Igor Kleiman, Neal S. Jneid, Hani TI Percutaneous Coronary Intervention vs. Coronary Artery Bypass Graft Surgery for Unprotected Left Main Coronary Artery Disease in the Drug-Eluting Stents Era - An Aggregate Data Meta-Analysis of 11,148 Patients SO CIRCULATION JOURNAL LA English DT Article DE Coronary artery bypass grafting; Meta-analysis; Percutaneous coronary intervention; Unprotected left main coronary artery ID LONG-TERM OUTCOMES; AGED GREATER-THAN-OR-EQUAL-TO-75 YEARS; BARE-METAL STENTS; SURGICAL REVASCULARIZATION; SYNTAX TRIAL; TASK-FORCE; FOLLOW-UP; STENOSIS; REGISTRY; IMPLANTATION AB Background: Patients with unprotected left main coronary artery (LMCA) disease are increasingly treated with percutaneous coronary intervention (PCI) using drug-eluting stents (DES), but its benefits compared with coronary artery bypass grafting (CABG) remain controversial. We hypothesized that PCI with DES for unprotected LMCA disease is safe and effective compared with CABG. Methods and Results: We performed aggregate data meta-analyses of clinical outcomes [death; non-fatal myocardial infarction (MI); stroke; repeat revascularization; and major adverse cardiac and cerebrovascular events (MACCE)] in studies comparing PCI with DES vs. CABG in patients with LMCA disease. A comprehensive literature search (01/01/2003 to 12/01/2011) identified 27 studies comparing PCI and CABG (11,148 patients). Summary odds ratios (OR) were calculated using a random-effects model. At 30 days, PCI for unprotected LMCA disease was associated with lower MACCE [odds ratio (OR) 0.57, 95% confidence interval (CI) 0.36-0.89) and stroke rates (OR 0.22, 95% CI 0.11-0.44) compared with CABG. At 12 months, the PCI group experienced higher rates of repeat revascularization (OR 3.72, 95% CI 2.75-5.03), but lower rates of stroke (OR 0.25, 95% CI 0.14-0.44) and all-cause death (OR 0.69, 95% CI 0.49-0.97). At the longest follow-up of 60 months, PCI was associated with equivalent mortality, lower rates of stroke (OR 0.42, 95% CI 0.28-0.62) and higher rates of MACCE (OR 1.30, 95% CI 1.10-1.55) and repeat revascularization (OR 3.54, 95% CI 2.75-4.54). Conclusions: In the DES era, PCI for unprotected LMCA disease is associated with equivalent mortality and MI, lower stroke rates and higher rates of repeat revascularization compared with CABG. (Circ J 2013; 77: 372-382) C1 [Adam, Mahboob; Huang, Henry D.; Shahzad, Saima A.; Rogers, Paul A.; Paniagua, David; Bozkurt, Biykem; Jneid, Hani] Baylor Coll Med, Houston, TX 77030 USA. [Shahzad, Saima A.] Al Noor Specialist Hosp, Mecca, Saudi Arabia. [Kar, Biswajit; Virani, Salim S.; Paniagua, David; Bozkurt, Biykem; Jneid, Hani] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Palacios, Igor] Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. [Palacios, Igor] Harvard Univ, Sch Med, Boston, MA USA. [Kleiman, Neal S.] Methodist DeBakey Heart & Vasc Ctr, Houston, TX USA. [Kleiman, Neal S.] Weill Cornell Med Coll, New York, NY USA. RP Jneid, H (reprint author), Baylor Coll Med, Michael E DeBakey VA Med Ctr, 2002 Holcombe Blvd 3C-300A, Houston, TX 77030 USA. EM jneid@bcm.edu OI Virani, Salim/0000-0001-9541-6954 FU Department of Veterans Affairs Health Services Research and Development Service (HSR&D) Career Development Award [CDA-09-028] FX Dr Virani is supported by a Department of Veterans Affairs Health Services Research and Development Service (HSR&D) Career Development Award (CDA-09-028). NR 49 TC 0 Z9 0 U1 0 U2 8 PU JAPANESE CIRCULATION SOC PI KYOTO PA KINKI INVENTION CENTER, 14 YOSHIDA KAWAHARACHO, SAKYO-KU, KYOTO, 606-8305, JAPAN SN 1346-9843 J9 CIRC J JI Circ. J. PD FEB PY 2013 VL 77 IS 2 BP 372 EP 382 DI 10.1253/circj.CJ-12-0747 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 080SG UT WOS:000314263000019 ER PT J AU Lochhead, P Chan, AT AF Lochhead, Paul Chan, Andrew T. TI Statins and Colorectal Cancer SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Statin; Colon; Rectum; Adenoma; Chemoprevention ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MORPHOGENETIC PROTEIN PATHWAY; RANDOMIZED CONTROLLED-TRIAL; AVERAGE CHOLESTEROL LEVELS; LOWERING LDL CHOLESTEROL; A REDUCTASE INHIBITORS; LONG-TERM USE; COLON-CANCER; FOLLOW-UP; CARDIOVASCULAR-DISEASE AB The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, more commonly referred to as statins, comprise a family of lipid-lowering drugs that are prescribed on a global scale on account of their proven safety and efficacy in reducing mortality from cardiovascular disease. Beyond their potent pharmacologic inhibition of cholesterol biosynthesis, statins appear to have pleiotropic effects, including modulation of cell growth, apoptosis, and inflammation. Through modulation of these pathways, statins have the potential to influence a wide range of disease processes, including cancer. Much attention has focused on the association between statins and colorectal cancer, raising the prospect that these well-tolerated compounds could form the basis of future chemopreventive strategies. Herein, we review the epidemiologic, clinical, and preclinical data relevant to statins and colorectal neoplasia, and discuss the current status and future potential of statins as chemopreventive agents. C1 [Lochhead, Paul] Univ Aberdeen, Inst Med Sci, Gastrointestinal Res Grp, Div Appl Med, Aberdeen, Scotland. [Lochhead, Paul] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Chan, Andrew T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 722,55 Fruit St, Boston, MA 02114 USA. EM achan@partners.org FU Clinical Academic Fellowship from the Chief Scientist Office of the Scottish Government; Damon Runyon Clinical Investigator award FX Supported by a Clinical Academic Fellowship from the Chief Scientist Office of the Scottish Government (P.L.), and a Damon Runyon Clinical Investigator award (A.C.). NR 101 TC 23 Z9 23 U1 1 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD FEB PY 2013 VL 11 IS 2 BP 109 EP 118 DI 10.1016/j.cgh.2012.08.037 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 086RU UT WOS:000314705400006 PM 22982096 ER PT J AU Kentsis, A Shulman, A Ahmed, S Brennan, E Monuteaux, MC Lee, YH Lipsett, S Paulo, JA Dedeoglu, F Fuhlbrigge, R Bachur, R Bradwin, G Arditi, M Sundel, RP Newburger, JW Steen, H Kim, S AF Kentsis, Alex Shulman, Andrew Ahmed, Saima Brennan, Eileen Monuteaux, Michael C. Lee, Young-Ho Lipsett, Susan Paulo, Joao A. Dedeoglu, Fatma Fuhlbrigge, Robert Bachur, Richard Bradwin, Gary Arditi, Moshe Sundel, Robert P. Newburger, Jane W. Steen, Hanno Kim, Susan TI Urine proteomics for discovery of improved diagnostic markers of Kawasaki disease SO EMBO MOLECULAR MEDICINE LA English DT Article DE biomarker; Kawasaki disease; mass spectrometry; vasculitis; urinary proteome ID CORONARY-ARTERY INVOLVEMENT; AMERICAN-HEART-ASSOCIATION; MASS-SPECTROMETRY; SERUM INTERLEUKIN-6; NATIONWIDE SURVEY; RHEUMATIC-FEVER; CHILDREN; BIOMARKERS; EXPRESSION; ANEURYSMS AB Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. Absence of definitive diagnostic markers limits the accuracy of clinical evaluations of suspected KD with significant increases in morbidity. In turn, incomplete understanding of its molecular pathogenesis hinders the identification of rational targets needed to improve therapy. We used high-accuracy mass spectrometry proteomics to analyse over 2000 unique proteins in clinical urine specimens of patients with KD. We discovered that urine proteomes of patients with KD, but not those with mimicking conditions, were enriched for markers of cellular injury such as filamin and talin, immune regulators such as complement regulator CSMD3, immune pattern recognition receptor muclin, and immune cytokine protease meprin A. Significant elevations of filamin C and meprin A were detected in both the serum and urine in two independent cohorts of patients with KD, comprised of a total of 236 patients. Meprin A and filamin C exhibited superior diagnostic performance as compared to currently used markers of disease in a blinded case-control study of 107 patients with suspected KD, with receiver operating characteristic areas under the curve of 0.98 (95% confidence intervals [CI] of 0.971 and 0.951, respectively). Notably, meprin A was enriched in the coronary artery lesions of a mouse model of KD. In all, urine proteome profiles revealed novel candidate molecular markers of KD, including filamin C and meprin A that exhibit excellent diagnostic performance. These disease markers may improve the diagnostic accuracy of clinical evaluations of children with suspected KD, lead to the identification of novel therapeutic targets, and allow the development of a biological classification of Kawasaki disease. C1 [Kentsis, Alex] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Oncol,Dept Pediat Oncol,Boston Childr, Boston, MA 02115 USA. [Shulman, Andrew; Dedeoglu, Fatma; Fuhlbrigge, Robert; Sundel, Robert P.; Kim, Susan] Harvard Univ, Sch Med, Div Immunol, Rheumatol Program,Boston Childrens Hosp, Boston, MA USA. [Ahmed, Saima; Paulo, Joao A.; Steen, Hanno] Harvard Univ, Sch Med, Dept Pathol, Prote Ctr,Boston Childrens Hosp, Boston, MA 02115 USA. [Brennan, Eileen; Bradwin, Gary] Harvard Univ, Sch Med, Dept Lab Med, Boston Childrens Hosp, Boston, MA USA. [Monuteaux, Michael C.; Lipsett, Susan; Bachur, Richard] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Emergency Med, Boston, MA USA. [Arditi, Moshe] Cedars Sinai Med Ctr, Dept Pediat, Infect & Immunol Dis Res Ctr, Los Angeles, CA 90048 USA. [Newburger, Jane W.] Harvard Univ, Sch Med, Dept Cardiol, Boston Childrens Hosp, Boston, MA USA. RP Steen, H (reprint author), Harvard Univ, Sch Med, Dept Pathol, Prote Ctr,Boston Childrens Hosp, Boston, MA 02115 USA. EM hanno.steen@childrens.harvard.edu; susan.kim@childrens.harvard.edu OI Kentsis, Alex/0000-0002-8063-9191; Sundel, Robert/0000-0002-0083-5695; Bachur, Richard/0000-0001-8831-014X FU Boston Children's Hospital Division of Immunology Pilot Grant; Translational Research Program Pilot Grant; Boston Children's Hospital Clinical Research Program; Harvard Catalyst; Harvard Clinical and Translational Science Center [UL1 RR 025758]; National Institutes of Health [U01 HL068285, RR 02172, U01 HL068270, U01 HL068269, U01 HL068292, U01 HL068290, U01 HL068288, U01 HL068281, U01 HL068279]; [NIH-K08CA160660] FX We thank the staff of the Boston Children's Hospital Rheumatology and Cardiology Programs for help with patient recruitment. This research was funded by the Boston Children's Hospital Division of Immunology Pilot Grant, Translational Research Program Pilot Grant and supported by the Boston Children's Hospital Clinical Research Program and Harvard Catalyst. The Harvard Clinical and Translational Science Center (UL1 RR 025758). Collection of sera by the Pediatric Heart Network centres was supported by U01 HL068285, RR 02172, U01 HL068270, U01 HL068269, U01 HL068292, U01 HL068290, U01 HL068288, U01 HL068281 and U01 HL068279 from the National Institutes of Health. AK is supported by the NIH-K08CA160660. NR 45 TC 29 Z9 31 U1 0 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1757-4676 J9 EMBO MOL MED JI EMBO Mol. Med. PD FEB PY 2013 VL 5 IS 2 BP 210 EP 220 DI 10.1002/emmm.201201494 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 086CW UT WOS:000314661800008 PM 23281308 ER PT J AU Desai, A Bekelis, K Thadani, VM Roberts, DW Jobst, BC Duhaime, AC Gilbert, K Darcey, TM Studholme, C Siegel, A AF Desai, Atman Bekelis, Kimon Thadani, Vijay M. Roberts, David W. Jobst, Barbara C. Duhaime, Ann-Christine Gilbert, Karen Darcey, Terrance M. Studholme, Colin Siegel, Alan TI Interictal PET and ictal subtraction SPECT: Sensitivity in the detection of seizure foci in patients with medically intractable epilepsy SO EPILEPSIA LA English DT Article DE Epilepsy surgery; Seizure localization; Epilepsy imaging ID TEMPORAL-LOBE EPILEPSY; POSITRON-EMISSION-TOMOGRAPHY; COMPUTED-TOMOGRAPHY; FDG-PET; MRI; SURGERY; ABNORMALITIES; EEG; LATERALIZATION; PATHOLOGY AB Purpose: Interictal positron emission tomography (PET) and ictal subtraction single photon emission computed tomography (SPECT) of the brain have been shown to be valuable tests in the presurgical evaluation of epilepsy. To determine the relative utility of these methods in the localization of seizure foci, we compared interictal PET and ictal subtraction SPECT to subdural and depth electrode recordings in patients with medically intractable epilepsy. Methods: Between 2003 and 2009, clinical information on all patients at our institution undergoing intracranial electroencephalography (EEG) monitoring was charted in a prospectively recorded database. Patients who underwent preoperative interictal PET and ictal subtraction SPECT were selected from this database. Patient characteristics and the findings on preoperative interictal PET and ictal subtraction SPECT were analyzed. Sensitivity of detection of seizure foci for each modality, as compared to intracranial EEG monitoring, was calculated. Key Findings: Fifty-three patients underwent intracranial EEG monitoring with preoperative interictal PET and ictal subtraction SPECT scans. The average patient age was 32.7years (median 32years, range 160years). Twenty-seven patients had findings of reduced metabolism on interictal PET scan, whereas all 53 patients studied demonstrated a region of relative hyperperfusion on ictal subtraction SPECT suggestive of an epileptogenic zone. Intracranial EEG monitoring identified a single seizure focus in 45 patients, with 39 eventually undergoing resective surgery. Of the 45 patients in whom a seizure focus was localized, PET scan identified the same region in 25 cases (56% sensitivity) and SPECT in 39 cases (87% sensitivity). Intracranial EEG was concordant with at least one study in 41 cases (91%) and both studies in 23 cases (51%). In 16 (80%) of 20 cases where PET did not correlate with intracranial EEG, the SPECT study was concordant. Conversely, PET and intracranial EEG were concordant in two (33%) of the six cases where the SPECT did not demonstrate the seizure focus outlined by intracranial EEG. Thirty-three patients had surgical resection and >2years of follow-up, and 21 of these (64%) had Engel class 1 outcome. No significant effect of imaging concordance on seizure outcome was seen. Significance: Interictal PET and ictal subtraction SPECT studies can provide important information in the preoperative evaluation of medically intractable epilepsy. Of the two studies, ictal subtraction SPECT appears to be the more sensitive. When both studies are used together, however, they can provide complementary information. C1 [Desai, Atman; Bekelis, Kimon; Roberts, David W.] Dartmouth Hitchcock Med Ctr, Neurosurg Sect, Lebanon, NH 03756 USA. [Thadani, Vijay M.; Jobst, Barbara C.; Gilbert, Karen; Darcey, Terrance M.] Dartmouth Hitchcock Med Ctr, Dept Neurol, Lebanon, NH 03756 USA. [Duhaime, Ann-Christine] Massachusetts Gen Hosp, Sect Pediat Neurosurg, Boston, MA 02114 USA. [Studholme, Colin] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. [Siegel, Alan] Dartmouth Hitchcock Med Ctr, Dept Radiol, Lebanon, NH 03756 USA. RP Desai, A (reprint author), Dartmouth Hitchcock Med Ctr, Neurosurg Sect, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM atman.desai@hitchcock.org NR 31 TC 24 Z9 27 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD FEB PY 2013 VL 54 IS 2 BP 341 EP 350 DI 10.1111/j.1528-1167.2012.03686.x PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 087GT UT WOS:000314750200018 PM 23030361 ER PT J AU Heinz, AJ Peters, EN Boden, MT Bonn-Miller, MO AF Heinz, Adrienne J. Peters, Erica N. Boden, Matthew T. Bonn-Miller, Marcel O. TI A Comprehensive Examination of Delay Discounting in a Clinical Sample of Cannabis-Dependent Military Veterans Making a Self-Guided Quit Attempt SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE marijuana; Cannabis; cessation; delay discounting; impulsivity; relapse ID ADULTS SEEKING TREATMENT; SUBSTANCE-USE DISORDERS; ALCOHOL-USE DISORDERS; TIMELINE FOLLOW-BACK; MARIJUANA USE; BEHAVIORAL ECONOMICS; TREATMENT SEEKERS; MONEY MANAGEMENT; DRUG-DEPENDENCE; REPORTED USE AB Delay discounting (DD), an index of impulsivity, reflects individuals' preference for smaller immediate rewards to larger delayed rewards. The current study examined (a) relations between DD and quantity, frequency, and severity of Cannabis use, as well as several other measures of co-occurring substance use and clinical severity, and (b) whether DD predicted Cannabis-cessation outcomes. Cannabis-dependent United States (U. S.) veterans (N = 72; 95% male) who were interested in making serious self-quit attempts were evaluated prior to their cessation attempts, during which they completed a computerized DD task, and were followed throughout six months postattempt. Results indicated that higher DD was significantly correlated with higher compulsive craving for Cannabis (rho = .29, p < .05), younger age of first Cannabis use (r = -.32, p < .01), earlier commencement of regular Cannabis smoking (r = -.25, p < .05), and seeking professional help for a previous Cannabis quit attempt (rho = -.27, p < .05). DD did not significantly predict any Cannabis-cessation outcomes in the first week postattempt or during the 6-month follow-up. These results add to the literature on DD, which has focused on users of tobacco, alcohol, opioids, and cocaine, by demonstrating that DD is sensitive to developmental trajectories of Cannabis dependence, but does not reliably predict cessation outcomes. Results also suggest that DD may carry less relevance for Cannabis than for other substances of abuse. C1 [Heinz, Adrienne J.; Boden, Matthew T.; Bonn-Miller, Marcel O.] Vet Affairs Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Palo Alto, CA USA. [Heinz, Adrienne J.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Peters, Erica N.] Friends Res Inst, Baltimore, MD USA. [Peters, Erica N.] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Bonn-Miller, Marcel O.] Vet Affairs Palo Alto Hlth Care Syst, Natl Ctr Posttraumat Stress Disorder, Palo Alto, CA USA. [Bonn-Miller, Marcel O.] Philadelphia Vet Affairs Med Ctr, Ctr Excellence Subst Abuse Treatment & Educ, Philadelphia, PA USA. RP Heinz, AJ (reprint author), 795 Willow Rd,MPD 152, Menlo Pk, CA 94025 USA. EM aheinz@stanford.edu FU United States Department Veterans Affairs (VA); VA Health Services Research and Development Service funds FX Support for this research was provided by a United States Department Veterans Affairs (VA) Clinical Science Research and Development Career Development Award, Level 2, granted to Dr. Bonn-Miller, and VA Health Services Research and Development Service funds were provided to Dr. Heinz. These funding sources played no roles other than financial support. The expressed views do not necessarily represent those of the VA. The authors thank Neha Mitragotri, Johnna Medina, Meggan Bucossi, Nicole Short, and Jessica Galang for their assistance with data collection and management. All authors contributed in a significant way to the manuscript and all authors have read and approved the final manuscript. NR 91 TC 13 Z9 13 U1 6 U2 27 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 EI 1936-2293 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD FEB PY 2013 VL 21 IS 1 BP 55 EP 65 DI 10.1037/a0031192 PG 11 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 084KG UT WOS:000314537400007 PM 23379614 ER PT J AU Pekcec, A Yigitkanli, K Jung, JE Pallast, S Xing, CH Antipenko, A Minchenko, M Nikolov, DB Holman, TR Lo, EH van Leyen, K AF Pekcec, Anton Yigitkanli, Kazim Jung, Joo Eun Pallast, Stefanie Xing, Changhong Antipenko, Alexander Minchenko, Maria Nikolov, Dimitar B. Holman, Theodore R. Lo, Eng H. van Leyen, Klaus TI Following experimental stroke, the recovering brain is vulnerable to lipoxygenase-dependent semaphorin signaling SO FASEB JOURNAL LA English DT Article DE eicosanoid; 12-HPETE; cortex; axon growth; second messenger ID ENDOTHELIAL GROWTH-FACTOR; TRANSIENT FOCAL ISCHEMIA; CEREBRAL-BLOOD-FLOW; UP-REGULATION; TUMOR ANGIOGENESIS; PERIINFARCT CORTEX; NEUROVASCULAR UNIT; ARACHIDONIC-ACID; GENE-EXPRESSION; CONE COLLAPSE AB Recovery from stroke is limited, in part, by an inhibitory environment in the postischemic brain, but factors preventing successful remodeling are not well known. Using cultured cortical neurons from mice, brain endothelial cells, and a mouse model of ischemic stroke, we show that signaling from the axon guidance molecule Sema3A via eicosanoid second messengers can contribute to this inhibitory environment. Either 90 nM recombinant Sema3A, or the 12/15-lipoxygenase (12/15-LOX) metabolites 12-HETE and 12-HPETE at 300 nM, block axon extension in neurons compared to solvent controls, and decrease tube formation in endothelial cells. The Sema3A effect is reversed by inhibiting 12/15-LOX, and neurons derived from 12/15-LOX-knockout mice are insensitive to Sema3A. Following middle cerebral artery occlusion to induce stroke in mice, immunohistochemistry shows both Sema3A and 12/15-LOX are increased in the cortex up to 2 wk. To determine whether a Sema3A-dependent damage pathway is activated following ischemia, we injected recombinant Sema3A into the striatum. Sema3A alone did not cause injury in normal brains. But when injected into postischemic brains, Sema3A increased cortical damage by 79%, and again, this effect was reversed by 12/15-LOX inhibition. Our findings suggest that blocking the semaphorin pathway should be investigated as a therapeutic strategy to improve stroke recovery.-Pekcec, A., Yigitkanli, K., Jung, J. E., Pallast, S., Xing, C., Antipenko, A., Minchenko, M., Nikolov, D. B., Holman, T. R., Lo, E. H., van Leyen, K. Following experimental stroke, the recovering brain is vulnerable to lipoxygenase-dependent semaphorin signaling. FASEB J. 27, 437-445 (2013). www.fasebj.org C1 [Pekcec, Anton; Yigitkanli, Kazim; Jung, Joo Eun; Pallast, Stefanie; Xing, Changhong; Lo, Eng H.; van Leyen, Klaus] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA USA. [Antipenko, Alexander; Minchenko, Maria; Nikolov, Dimitar B.] Sloan Kettering Inst, Dept Biol Struct, New York, NY USA. [Holman, Theodore R.] Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA. RP van Leyen, K (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, 149 13th St,R 2401, Charlestown, MA 02129 USA. EM klaus_vanleyen@hms.harvard.edu RI van Leyen, Klaus/C-9126-2013 FU U.S. National Institutes of Health [NS049430, NS069939, NS048372, GM056062] FX The authors thank Dr. Emiri Mandeville for help with the injection experiments. This work was supported by U.S. National Institutes of Health grants NS049430 and NS069939 to K. V. L., NS048372 to D.B.N., and GM056062 to T.R.H. NR 66 TC 16 Z9 18 U1 0 U2 9 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 FEB PY 2013 VL 27 IS 2 BP 437 EP 445 DI 10.1096/fj.12-206896 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 081YG UT WOS:000314358000005 PM 23070608 ER PT J AU Zhang, JP Valianou, M Simmons, H Robinson, MK Lee, HO Mullins, SR Marasco, WA Adams, GP Weiner, LM Cheng, JD AF Zhang, Jiping Valianou, Matthildi Simmons, Heidi Robinson, Matthew K. Lee, Hyung-Ok Mullins, Stefanie R. Marasco, Wayne A. Adams, Gregory P. Weiner, Louis M. Cheng, Jonathan D. TI Identification of inhibitory scFv antibodies targeting fibroblast activation protein utilizing phage display functional screens SO FASEB JOURNAL LA English DT Article DE serine protease; single-chain variable fragment ID TUMOR STROMAL FIBROBLASTS; SERINE-PROTEASE; EXTRACELLULAR-MATRIX; EPITHELIAL CANCERS; MOLECULAR-CLONING; DIFFERENTIAL EXPRESSION; OVARIAN-CANCER; COLON-CANCER; PHASE-I; CELLS AB Fibroblast activation protein (FAP) is a serine protease selectively expressed on tumor stromal fibroblasts in epithelial carcinomas and is important in cancer growth, adhesion, and metastases. As FAP enzymatic activity is a potent therapeutic target, we aimed to identify inhibitory antibodies. Using a competitive inhibition strategy, we used phage display techniques to identify 53 single-chain variable fragments (scFvs) after three rounds of panning against FAP. These scFvs were expressed and characterized for binding to FAP by surface plasmon resonance and flow cytometry. Functional assessment of these antibodies yielded an inhibitory scFv antibody, named E3, which could attenuate 35% of FAP cleavage of the fluorescent substrate Ala-Pro-7-amido-4-trifluoromethylcoumarin compared with nonfunctional scFv control. Furthermore, a mutant E3 scFv was identified by yeast affinity maturation. It had higher affinity (4-fold) and enhanced inhibitory effect on FAP enzyme activity (3-fold) than E3. The application of both inhibitory anti-FAP scFvs significantly affected the formation of 3-dimensional FAP-positive cell matrix, as demonstrated by reducing the fibronectin fiber orientation from 41.18% (negative antibody control) to 34.06% (E3) and 36.15% (mutant E3), respectively. Thus, we have identified and affinity-maturated the first scFv antibody capable of inhibiting FAP function. This scFv antibody has the potential to disrupt the role of FAP in tumor invasion and metastasis.-Zhang, J., Valianou, M., Simmons, H., Robinson, M. K., Lee, H.-O., Mullins, S. R., Marasco, W. A., Adams, G. P., Weiner, L. M., Cheng, J. D. Identification of inhibitory ScFv antibodies targeting fibroblast activation protein utilizing phage display functional screens. FASEB J. 27, 581-589 (2013). www.fasebj.org C1 [Valianou, Matthildi; Lee, Hyung-Ok; Mullins, Stefanie R.; Cheng, Jonathan D.] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Zhang, Jiping; Simmons, Heidi; Robinson, Matthew K.; Adams, Gregory P.] Fox Chase Canc Ctr, Dev Therapeut Program, Philadelphia, PA 19111 USA. [Marasco, Wayne A.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Weiner, Louis M.] Georgetown Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC USA. RP Cheng, JD (reprint author), Fox Chase Canc Ctr, Dept Med Oncol, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM j_cheng@fccc.edu FU U.S. National Institutes of Health [CA090468, CA103991-01, CA09035-28]; Frank Strick Foundation; Bernard A. and Rebecca S. Bernard Foundation FX This study was supported by U.S. National Institutes of Health grants CA090468, CA103991-01, and CA09035-28; the Frank Strick Foundation; the Bernard A. and Rebecca S. Bernard Foundation; and an appropriation from the Commonwealth of Pennsylvania and the American Cancer Society. NR 38 TC 7 Z9 7 U1 0 U2 19 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 FEB PY 2013 VL 27 IS 2 BP 581 EP 589 DI 10.1096/fj.12-210377 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 081YG UT WOS:000314358000017 PM 23104982 ER PT J AU Furuya, H Wada, M Shimizu, Y Yamada, PM Hannun, YA Obeid, LM Kawamori, T AF Furuya, Hideki Wada, Masayuki Shimizu, Yoshiko Yamada, Paulette M. Hannun, Yusuf A. Obeid, Lina M. Kawamori, Toshihiko TI Effect of sphingosine kinase 1 inhibition on blood pressure SO FASEB JOURNAL LA English DT Article DE sphingolipids; cardiovascular functions; chemoprevention; prostacyclin; COX-2; mPGES-1 ID PROSTAGLANDIN-E SYNTHASE-1; II-INDUCED HYPERTENSION; ANGIOTENSIN-II; CYCLOOXYGENASE-2 INHIBITOR; COLON CARCINOGENESIS; OXIDATIVE STRESS; ENDOTHELIAL-CELLS; E-2 PROTECTS; TNF-ALPHA; 1-PHOSPHATE AB Accumulating evidence suggests that sphingosine kinase 1 (SphK1) plays a key role in carcinogenesis by regulating cyclooxygenase-2 (COX-2) expression. Recent clinical studies have revealed that COX-2 inhibitors cause adverse cardiovascular side effects, likely due to inhibition of prostacyclin (PGI(2)). In this work, we investigated the roles of SphK1 inhibition on blood pressure (BP). The results show that lack of SphK1 expression did not exacerbate angiotensin II (Ang II)-induced acute hypertension, whereas celecoxib, a COX-2 inhibitor, augmented and sustained higher BP in mice. Interestingly, SphK1-knockout mice inhibited prostaglandin E-2 (PGE(2)) but not PGI(2) production in response to Ang II, whereas celecoxib blocked both PGE(2) and PGI(2) production. Mechanistically, SphK1 down-regulation by siRNA in human umbilical vein endothelial cells decreased cytokine-induced PGE(2) production primarily through inhibition of microsomal PGE synthase-1 (mPGES-1), not COX-2. SphK1 downregulation also decreased MKK6 expression, which phosphorylates and activates P38 MAPK, which, in turn, regulates early growth response-1 (Egr-1), a transcription factor of mPGES-1. Together, these data indicate that SphK1 regulates PGE(2) production by mPGES-1 expression via the p38 MAPK pathway, independent of COX-2 signaling, in endothelial cells, suggesting that SphK1 inhibition may be a promising strategy for cancer chemoprevention with lack of the adverse cardiovascular side effects associated with coxibs.-Furuya, H., Wada, M., Shimizu, Y., Yamada, P. M., Hannun, Y. A., Obeid, L. M., Kawamori, T. Effect of sphingosine kinase 1 inhibition on blood pressure. FASEB J. 27, 656-664 (2013). www.fasebj.org C1 [Furuya, Hideki; Shimizu, Yoshiko; Yamada, Paulette M.; Kawamori, Toshihiko] Univ Hawaii, Ctr Canc, Honolulu, HI 96813 USA. [Furuya, Hideki; Wada, Masayuki; Kawamori, Toshihiko] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Hannun, Yusuf A.; Obeid, Lina M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Obeid, Lina M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Shimizu, Yoshiko; Kawamori, Toshihiko] Univ Hawaii Manoa, Dept Mol Biosci & Bioengn, Honolulu, HI 96822 USA. [Obeid, Lina M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Kawamori, T (reprint author), Univ Hawaii, Ctr Canc, 651 Ilalo St,BSB 222H, Honolulu, HI 96813 USA. EM kawamori@cc.hawaii.edu OI obeid, lina/0000-0002-0734-0847 FU U.S. National Institutes of Health (NIH) [R01CA124687, P20RR17677, P01CA97132]; Hollings Cancer Center, MUSC; NIH Extramural Research Facilities Program of the National Center for Research Resources [C06RR015455] FX The authors thank the Lipidomics Core Facility and Animal Carcinogenesis Core, Hollings Cancer Center, Medical University of South Carolina (MUSC), and Animal Carcinogenesis Shared Resource, University of Hawaii Cancer Center. This work was supported by U.S. National Institutes of Health (NIH) grants (R01CA124687 and P20RR17677 to T. K., P01CA97132 to T. K., Y.A.H., and L.M.O.) and a seed grant to T. K. from the Hollings Cancer Center, MUSC. This work was conducted in a facility constructed with support from the NIH Extramural Research Facilities Program of the National Center for Research Resources (C06RR015455). NR 52 TC 9 Z9 9 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD FEB PY 2013 VL 27 IS 2 BP 656 EP 664 DI 10.1096/fj.12-219014 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 081YG UT WOS:000314358000024 PM 23109673 ER PT J AU Liu, CH Yang, JS Ren, JQ Liu, CM You, ZR Liu, PK AF Liu, Christina H. Yang, Jinsheng Ren, Jia Q. Liu, Charng-Ming You, Zerong Liu, Philip K. TI MRI reveals differential effects of amphetamine exposure on neuroglia in vivo SO FASEB JOURNAL LA English DT Article DE drug delivery; molecular MR imaging; nanomedicine; gliogenesis ID BLOOD-BRAIN-BARRIER; METHAMPHETAMINE-INDUCED NEUROTOXICITY; FIBRILLARY ACIDIC PROTEIN; IRON-OXIDE PARTICLES; GENE-EXPRESSION; STEM-CELLS; MESSENGER-RNA; SEROTONIN NEUROTOXICITY; TRANSGENIC MICE; LIVING BRAINS AB How amphetamine affects the neuroglia in living brains is not well understood. In an effort to elucidate this effect, we investigated neuroglia in response to amphetamine exposure using antisense (AS) or sense (S) phosphorothioate-modified oligodeoxynucleotide (sODN) sequences that correspond to glial fibrillary acidic protein (GFAP) mRNA (AS-gfap or S-gfap, respectively) expression. The control is a random-sequence sODN (Ran). Using cyanine 5.5-super-paramagnetic iron oxide nanoparticle (Cy5.5-SPION) labeling and fluorescent microscopy, we demonstrated that living neural progenitor cells (PC-12.1), as well as the cells in fresh brain slices and intact brains of male C57BL6 mice, exhibited universal uptake of all of the sODNs but rapidly excluded all sODN-Ran and most S-gfap. Moreover, transmission electron microscopy revealed electron-dense nanoparticles only in the neuroglia of normal or transgenic mice [B6;DBA-Tg(Fos-tTA, Fos-EGFP*)1MmayTg(tetO-lacZ,tTA*)1Mmay/J] that had been administered AS-gfap or Cy5.5-SPION-gfap. Subtraction R2* maps from mice with acute and chronic amphetamine exposure demonstrated, validated by postmortem immunohistochemistry, a reduction in striatal neuroglia, with gliogenesis in the subventricular zone and the somatosensory cortex in vivo. The sensitivity of our unique gene transcript targeted MRI was illustrated by a positive linear correlation (r(2) = 1.0) between in vivo MRI signal changes and GFAP mRNA copy numbers determined by ex vivo quantitative RTPCR. The study provides direct evidence for targeting neuroglia by antisense DNA-based SPION-gfap that enables in vivo MRI of inaccessible tissue with PCR sensitivity. The results enable us to conclude that amphetamine induces toxicity to neuroglia in vivo, which may cause remodeling or reconnectivity of neuroglia.-Liu, C. H., Yang, J., Ren, J. Q., Liu, C.-M., You, Z., Liu, P. K. MRI reveals differential effects of amphetamine exposure on neuroglia in vivo. FASEB J. 27, 712-724 (2013). www.fasebj.org C1 [Liu, Christina H.; Yang, Jinsheng; Ren, Jia Q.; Liu, Charng-Ming; Liu, Philip K.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [You, Zerong] Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA USA. RP Liu, PK (reprint author), CNY149 2301 13th St, Charlestown, MA 02129 USA. EM philipl@nmr.mgh.harvard.edu OI Liu, Christina/0000-0002-5723-177X FU American Heart Association [2060416]; U.S. National Institutes of Health (NIH) [AT004974, DA026108, DA029889, EB013768, NS045776]; NIH [DK43351, DK57521] FX The authors thank Ms. N. Eusemann for help with editing. This project was supported by grants from the American Heart Association (09Grant2060416) and the U.S. National Institutes of Health (NIH; AT004974 to J.Q.R.; DA026108, DA029889, and EB013768 to P. K. L.; and NS045776 to the Massachusetts General Hospital Neuroscience Center). The 9.4-T MR system used for this work was funded in part by an NIH Shared Instrumentation grant awarded to the Athinoula A. Martinos Center for Biomedical Imaging. The authors appreciate the help of M. McKee with TEM, and the availability of the Microscopy Core (which is supported by NIH DK43351 and DK57521). Author contributions: C. H. L. contributed to MRI acquisition and data analysis and wrote the initial draft of the manuscript; J.Y. contributed to qRT-PCR and TaqMan analysis; J.Q.R. established brain slice cultures, delivered SPION-gfap, and contributed to histology and TEM; C.-M. L. synthesized and modified sODN and carried out PC-12.1 culture studies; Z.Y. contributed to immunohistology; P. K. L. coordinated and provided overall oversight for the project, designed and prepared SPION-sODN, carried out time-lapse microscopy, and supervised the various phases of revision of the manuscript. NR 61 TC 6 Z9 6 U1 2 U2 15 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 FEB PY 2013 VL 27 IS 2 BP 712 EP 724 DI 10.1096/fj.12-220061 PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 081YG UT WOS:000314358000030 PM 23150521 ER PT J AU Ho, L Ferruzzi, MG Janle, EM Wang, J Gong, B Chen, TY Lobo, J Cooper, B Wu, QL Talcott, ST Percival, SS Simon, JE Pasinetti, GM AF Ho, Lap Ferruzzi, Mario G. Janle, Elsa M. Wang, Jun Gong, Bing Chen, Tzu-Ying Lobo, Jessica Cooper, Bruce Wu, Qing Li Talcott, Stephen T. Percival, Susan S. Simon, James E. Pasinetti, Giulio Maria TI Identification of brain-targeted bioactive dietary quercetin-3-O-glucuronide as a novel intervention for Alzheimer's disease SO FASEB JOURNAL LA English DT Article DE polyphenol bioavailability; cognitive deterioration; neuroplasticity ID LONG-TERM POTENTIATION; RED WINE; TRANSGENIC MICE; MOUSE MODEL; IN-VIVO; LIQUID-CHROMATOGRAPHY; VARIETAL DIFFERENCES; SYNAPTIC PLASTICITY; OXIDATIVE STRESS; VITIS-VINIFERA AB Epidemiological and preclinical studies indicate that polyphenol intake from moderate consumption of red wines may lower the relative risk for developing Alzheimer's disease (AD) dementia. There is limited information regarding the specific biological activities and cellular and molecular mechanisms by which wine polyphenolic components might modulate AD. We assessed accumulations of polyphenols in the rat brain following oral dosage with a Cabernet Sauvignon red wine and tested brain-targeted polyphenols for potential beneficial AD disease-modifying activities. We identified accumulations of select polyphenolic metabolites in the brain. We demonstrated that, in comparison to vehicle-control treatment, one of the brain-targeted polyphenol metabolites, quercetin-3-O-glucuronide, significantly reduced the generation of beta-amyloid (A beta\) peptides by primary neuron cultures generated from the Tg2576 AD mouse model. Another brain-targeted metabolite, malvidin-3-O-glucoside, had no detectable effect on A beta generation. Moreover, in an in vitro analysis using the photo-induced cross-linking of unmodified proteins (PICUP) technique, we found that quercetin-3-O-glucuronide is also capable of interfering with the initial protein-protein interaction of A beta(1-40) and A beta(1-42) that is necessary for the formation of neurotoxic oligomeric A beta species. Lastly, we found that quercetin-3-O-glucuronide treatment, compared to vehicle-control treatment, significantly improved AD-type deficits in hippocampal formation basal synaptic transmission and long-term potentiation, possibly through mechanisms involving the activation of the c-Jun N-terminal kinases and the mitogen-activated protein kinase signaling pathways. Brain-targeted quercetin-3-O-glucuronide may simultaneously modulate multiple independent AD disease-modifying mechanisms and, as such, may contribute to the benefits of dietary supplementation with red wines as an effective intervention for AD.-Ho, L., Ferruzzi, M. G., Janle, E. M., Wang, J., Gong, B., Chen, T.-Y., Lobo, J., Cooper, B., Wu, Q. L., Talcott, S. T., Percival, S. S., Simon, J. E., Pasinetti, G. M. Identification of brain-targeted bioactive dietary quercetin-3-O-glucuronide as a novel intervention for Alzheimer's disease. FASEB J. 27, 769-781 (2013). www.fasebj.org C1 [Ho, Lap; Wang, Jun; Gong, Bing; Pasinetti, Giulio Maria] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Pasinetti, Giulio Maria] James J Peters Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. [Ferruzzi, Mario G.; Lobo, Jessica] Purdue Univ, Dept Food Sci, W Lafayette, IN 47907 USA. [Ferruzzi, Mario G.; Janle, Elsa M.; Chen, Tzu-Ying] Purdue Univ, Dept Nutr Sci, W Lafayette, IN 47907 USA. [Cooper, Bruce] Purdue Univ, Bindley Biosci Ctr, W Lafayette, IN 47907 USA. [Wu, Qing Li; Simon, James E.] Rutgers State Univ, Dept Plant Biol & Plant Pathol, New Brunswick, NJ 08903 USA. [Talcott, Stephen T.] Texas A&M Univ, Dept Nutr & Food Sci, College Stn, TX USA. [Percival, Susan S.] Univ Florida, Dept Food Sci & Human Nutr, Gainesville, FL USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Dept Neurol, 1468 Madison Ave,Annenberg Bldg,Rm 20-02, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu FU U.S. National Institutes of Health [National Center for Complementary and Alternative Medicine (NCCAM)] [PO1 AT004511] FX These studies were supported by the U.S. National Institutes of Health [grant PO1 AT004511; National Center for Complementary and Alternative Medicine (NCCAM) Project 1 to L. H. and Project 3 to G. M. P.]. The authors thank Dr. Kenjiro Ono (Kanazawa University Graduate School of Medical Science, Takara-Machi, Kanazawa, Japan), for valuable assistance and support with the PICUP analysis. NR 80 TC 52 Z9 55 U1 1 U2 50 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 FEB PY 2013 VL 27 IS 2 BP 769 EP 781 DI 10.1096/fj.12-212118 PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 081YG UT WOS:000314358000035 PM 23097297 ER PT J AU Manabe, Y Gollisch, KSC Holton, L Kim, YB Brandauer, J Fujii, NL Hirshman, MF Goodyear, LJ AF Manabe, Yasuko Gollisch, Katja S. C. Holton, Laura Kim, Young-Bum Brandauer, Josef Fujii, Nobuharu L. Hirshman, Michael F. Goodyear, Laurie J. TI Exercise training-induced adaptations associated with increases in skeletal muscle glycogen content SO FEBS JOURNAL LA English DT Article DE exercise; glycogen synthase; glycogen synthase kinase 3 (GSK-3); rat; skeletal muscle ID PROTEIN PHOSPHATASE 1; GLUCOSE-TRANSPORT; SYNTHASE KINASE-3; INSULIN SENSITIVITY; TARGETING SUBUNIT; PHOSPHORYLASE; METABOLISM; ACTIVATION; ACCUMULATION; EXPRESSION AB Chronic exercise training results in numerous skeletal muscle adaptations, including increases in insulin sensitivity and glycogen content. To understand the mechanism leading to increased muscle glycogen, we studied the effects of exercise training on glycogen regulatory proteins in rat skeletal muscle. Female Sprague Dawley rats performed voluntary wheel running for 1, 4 or 7 weeks. After 7 weeks of training, insulin-stimulated glucose uptake was increased in epitrochlearis muscle. As compared with sedentary control rats, muscle glycogen did not change after 1 week of training, but increased significantly after 4 and 7 weeks. The increases in muscle glycogen were accompanied by elevated glycogen synthase activity and protein expression. To assess the regulation of glycogen synthase, we examined its major activator, protein phosphatase 1 (PP1), and its major deactivator, glycogen synthase kinase (GSK)-3. Consistent with glycogen synthase activity, PP1 activity was unchanged after 1 week of training but significantly increased after 4 and 7 weeks of training. Protein expression of RGL(GM), another regulatory PP1 subunit, significantly decreased after 4 and 7 weeks of training. Unlike PP1 activity, GSK-3 phosphorylation did not follow the pattern of glycogen synthase activity. The 40% decrease in GSK-3a phosphorylation after 1 week of exercise training persisted until 7 weeks, and may function as a negative feedback mechanism in response to elevated glycogen. Our findings suggest that exercise training-induced increases in muscle glycogen content could be regulated by multiple mechanisms, including enhanced insulin sensitivity, glycogen synthase expression, allosteric activation of glycogen synthase, and PP1 activity. C1 [Manabe, Yasuko; Gollisch, Katja S. C.; Holton, Laura; Brandauer, Josef; Fujii, Nobuharu L.; Hirshman, Michael F.; Goodyear, Laurie J.] Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA. [Kim, Young-Bum] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab,Dept Med, Boston, MA 02215 USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Sect Integrat Physiol & Metab, 1 Joslin Pl, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 FU National Institutes of Health [AR45670, AR42338, T32DK07260-29]; Japan Society for the Promotion of Science [KAKENHI 24700700, KAKENHI 21240063]; Cabinet Office, Government of Japan [LS102]; German Academic Exchange Service DAAD FX This work was supported by the National Institutes of Health (Grants AR45670 and AR42338 to L. J. Goodyear and Training Grant T32DK07260-29 to J. Brandauer), by the Japan Society for the Promotion of Science (KAKENHI 24700700 to Y. Manabe and KAKENHI 21240063 to N. L. Fujii), by the Cabinet Office, Government of Japan (Funding Program for Next Generation World-Leading Researchers, LS102 to N. L. Fujii), and by a fellowship within the Postdoc Program of the German Academic Exchange Service DAAD (to K. S. C. Gollisch.). We thank Drs A. Saltiel (University of Michigan) and M. Brady (University of Chicago) for providing the RGL(GM) and PTG/R5 antibodies. NR 44 TC 8 Z9 9 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1742-464X J9 FEBS J JI FEBS J. PD FEB PY 2013 VL 280 IS 3 BP 916 EP 926 DI 10.1111/febs.12085 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 079JT UT WOS:000314167100011 PM 23206309 ER PT J AU Zou, L AF Zou, Lee TI Four pillars of the S-phase checkpoint SO GENES & DEVELOPMENT LA English DT Article DE DNA replication; cell cycle checkpoint; 9-1-1; ATR; ATM ID REPLICATION-PROTEIN-A; DNA-DAMAGE CHECKPOINT; CELL-CYCLE CHECKPOINT; ESSENTIAL IN-VIVO; C-TERMINAL TAIL; SACCHAROMYCES-CEREVISIAE; END-RESECTION; GENOME STABILITY; BUDDING YEAST; HOMOLOG MEC1 AB The yeast Mec1 kinase is a key regulator of the DNA damage response (DDR). In this issue of Genes & Development, Kumar and Burgers (pp. 313-321) report that Ddc1, Dpb11, and Dna2 function in concert to activate Mec1 during S phase of the cell cycle. Furthermore, the Tel1 kinase also contributes to the DDR in S phase when Mec1 activation is compromised. C1 [Zou, Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. [Zou, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 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 [GM076388]; MGH/NCI Proton Program FX I apologize to the colleagues whose work is not cited due to space constraints. Work in my laboratory is supported by grants from NIH (GM076388) and the MGH/NCI Proton Program. I am a Jim and Ann Orr MGH Research Scholar and a Scholar of the Ellison Medical Foundation. NR 55 TC 11 Z9 11 U1 0 U2 8 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD FEB 1 PY 2013 VL 27 IS 3 BP 227 EP 233 DI 10.1101/gad.213306.113 PG 7 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 088BS UT WOS:000314809400001 PM 23388823 ER PT J AU Wu, J Cohen, P Spiegelman, BM AF Wu, Jun Cohen, Paul Spiegelman, Bruce M. TI Adaptive thermogenesis in adipocytes: Is beige the new brown? SO GENES & DEVELOPMENT LA English DT Review DE brown fat; beige fat; obesity; adaptive thermogenesis; UCP1 ID WHITE ADIPOSE-TISSUE; DIET-INDUCED OBESITY; ACTIVATED RECEPTOR-GAMMA; MITOCHONDRIAL UNCOUPLING-PROTEIN; GROWTH-FACTOR-BETA; ENERGY-EXPENDITURE; SKELETAL-MUSCLE; INSULIN-RESISTANCE; PPAR-GAMMA; GENE-EXPRESSION AB One of the most promising areas in the therapeutics for metabolic diseases centers around activation of the pathways of energy expenditure. Brown adipose tissue is a particularly appealing target for increasing energy expenditure, given its amazing capacity to transform chemical energy into heat. In addition to classical brown adipose tissue, the last few years have seen great advances in our understanding of inducible thermogenic adipose tissue, also referred to as beige fat. A deeper understanding of the molecular processes involved in the development and function of these cell types may lead to new therapeutics for obesity, diabetes, and other metabolic diseases. C1 [Wu, Jun; Cohen, Paul; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Wu, Jun; Cohen, Paul; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Cohen, Paul] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc,Dept Med, Boston, MA 02115 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 NIH [1K01DK094824, DK31405, DK90861]; American Heart Association [11FTF7510004]; JPB Foundation FX We thank M. Khandekar for helpful discussions. We apologize to those whom we were unable to reference due to space limitations. J.W. is supported by an NIH grant (1K01DK094824). P. C. is supported by a grant from the American Heart Association (11FTF7510004). This work is funded by the JPB Foundation and NIH grants (DK31405 and DK90861) to B.M.S. NR 203 TC 239 Z9 242 U1 9 U2 88 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 FEB 1 PY 2013 VL 27 IS 3 BP 234 EP 250 DI 10.1101/gad.211649.112 PG 17 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 088BS UT WOS:000314809400002 PM 23388824 ER PT J AU Dai, N Christiansen, J Nielsen, FC Avruch, J AF Dai, Ning Christiansen, Jan Nielsen, Finn C. Avruch, Joseph TI mTOR complex 2 phosphorylates IMP1 cotranslationally to promote IGF2 production and the proliferation of mouse embryonic fibroblasts SO GENES & DEVELOPMENT LA English DT Article DE mTOR complex 2; IMP1; cotranslational phosphorylation; mRNA translation; IGF2; embryonic growth ID II MESSENGER-RNA; PROTEIN-KINASE INHIBITORS; BINDING PROTEINS; GROWTH; TRANSLATION; EXPRESSION; EMBRYOGENESIS; RIBOSOME; FAMILY; TARGET AB Lack of IGF2 in mice results in diminished embryonic growth due to diminished cell proliferation. Here we show that mouse embryonic fibroblasts lacking the RNA-binding protein IMP1 (IGF2 mRNA-binding protein 1) have defective splicing and translation of IGF2 mRNAs, markedly reduced IGF2 polypeptide production, and diminished proliferation. The proliferation of the IMP1-null fibroblasts can be restored to wild-type levels by IGF2 in vitro or by re-expression of IMP1, which corrects the defects in IGF2 RNA splicing and translation. The ability of IMP1 to correct these defects is dependent on IMP1 phosphorylation at Ser181, which is catalyzed cotranslationally by mTOR complex 2 (mTORC2). Phosphorylation strongly enhances IMP1 binding to the IGF2-leader 3 5' untranslated region, which is absolutely required to enable IGF2-leader 3 mRNA translational initiation by internal ribosomal entry. These findings uncover a new mechanism by which mTOR regulates organismal growth by promoting IGF2 production in the mouse embryo through mTORC2-catalyzed cotranslational IMP1/IMP3 phosphorylation. Inasmuch as TORC2 is activated by association with ribosomes, the present results indicate that mTORC2-catalyzed cotranslational protein phosphorylation is a core function of this complex. C1 [Dai, Ning; Avruch, Joseph] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Dai, Ning; Avruch, Joseph] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Dai, Ning; Avruch, Joseph] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Christiansen, Jan] Univ Copenhagen, Rigshosp, Dept Biol, DK-2100 Copenhagen, Denmark. [Nielsen, Finn C.] Univ Copenhagen, Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM avruch@molbio.mgh.harvard.edu RI Christiansen, Jan/L-3312-2014 OI Christiansen, Jan/0000-0001-8624-4601 FU NIH [DK17776, CA73818, DK057521] FX We thank E. Jacinto and colleagues for advice regarding the analysis of cotranslational phosphorylation. The work was supported by NIH grants DK17776, CA73818, and DK057521 (to J.A.) and by institutional funds. NR 29 TC 20 Z9 22 U1 0 U2 5 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 FEB 1 PY 2013 VL 27 IS 3 BP 301 EP 312 DI 10.1101/gad.209130.112 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 088BS UT WOS:000314809400007 PM 23388827 ER PT J AU Campos, SM Penson, RT Matulonis, U Horowitz, NS Whalen, C Pereira, L Tyburski, K Roche, M Szymonifka, J Berlin, S AF Campos, Susana M. Penson, Richard T. Matulonis, Ursula Horowitz, Neil S. Whalen, Christin Pereira, Lauren Tyburski, Karin Roche, Maria Szymonifka, Jackie Berlin, Suzanne TI A phase II trial of Sunitinib malate in recurrent and refractory ovarian, fallopian tube and peritoneal carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian cancer; Tyrosine kinase inhibitors; Angiogenic biomarkers; Targeted therapy ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; RENAL-CELL CARCINOMA; EPITHELIAL OVARIAN; BREAST-CANCER; BEVACIZUMAB; THERAPY; CYCLOPHOSPHAMIDE; POLYMORPHISMS; EXPRESSION AB Objective. Ovarian cancer is a highly angiogenic tumor and a model for antiangiogenic research. The tyrosine kinase receptor inhibitors target several receptors allowing for the pharmacological disruption of several independent pathways. Sunitinib malate (R) is a multitargeted tyrosine kinase inhibitor. A phase II study utilizing a modified dosing schedule was conducted to assess the efficacy and safety of Sunitinib in recurrent ovarian, fallopian tube and peritoneal carcinoma. Methods. A nonrandomized-phase II study was modeled as a two-stage Simon design initially enrolling 17 evaluable participants in stage one and 18 patients in stage two. Patients received the study drug at 37.5 mg every day over a 28 day treatment cycle until clinical or radiological evidence of progressive disease. Disease was evaluated radiographically and best overall response was defined using the RECIST 1.0 criteria. The primary objective of this study was to define the response rate (defined a complete response and partial response) while the secondary objectives included both the progression free rate as well as the safety of this agent in this patient population. Results. The response rate (PR+CR) was 8.3% (95% confidence interval: 1.8%, 22.5%). The 16-week and 24 week progression-free survival estimate was 36% (95% confidence interval and 19.2%), respectively. The median progression-free survival estimate was 9.9 weeks. Hypertension and gastrointestional events were the most common toxicities noted. Conclusions. A modest response rate of 8.3% was achieved with Sunitinib malate (R). This phase II study adds to the body of literature of VEGFR inhibitors and further underscores the need of defining a genetic angiogenic signature. (C) 2012 Published by Elsevier Inc. C1 [Campos, Susana M.; Matulonis, Ursula; Berlin, Suzanne] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. [Penson, Richard T.; Roche, Maria] Massachusetts Gen Hosp, Dept Med, Div Gynecol Oncol, Boston, MA 02114 USA. [Horowitz, Neil S.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02115 USA. [Campos, Susana M.; Whalen, Christin; Pereira, Lauren; Tyburski, Karin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Szymonifka, Jackie] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Campos, SM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM scampos@partners.org; rtpenson@partners.org; umatulonis@partners.org; nhorowitz@partners.org; cwhalen@partners.org; lpereira@partners.org; ktyburski@partners.org; maria.roche@kadman.com; jszymonifka@partners.org; sberlin@partners.org FU Genentech FX Susana Campos: Genentech: research funding; consultant to Pfizer (breast cancer). Richard Penson: Genentech: research funding. Otherwise there are no additional financial conflicts of interest. NR 40 TC 18 Z9 21 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 2013 VL 128 IS 2 BP 215 EP 220 DI 10.1016/j.ygyno.2012.07.126 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 083EK UT WOS:000314445300013 PM 22885865 ER PT J AU Winer, I Mahdi, H Bandyopadhyay, S Semaan, A Van de Vijver, KK Nucci, MR Abdul-Karim, F Hussein, Y Qureshi, F Hayek, K Alosh, B Schulz, D Cote, M Munkarah, A Morris, R Oliva, E Ali-Fehmi, R AF Winer, I. Mahdi, H. Bandyopadhyay, S. Semaan, A. Van de Vijver, K. K. Nucci, M. R. Abdul-Karim, F. Hussein, Y. Qureshi, F. Hayek, K. Alosh, B. Schulz, D. Cote, M. Munkarah, A. Morris, R. Oliva, E. Ali-Fehmi, R. TI Correlation of tumor size with other prognostic factors in uterine serous carcinoma: A large multi-institutional study SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Uterine serous carcinoma (USC); Staging; Tumor size; Prognostic factors ID LYMPH-NODE METASTASIS; ENDOMETRIAL CANCER; STAGE-I; FOLLOW-UP; SURVIVAL; ADENOCARCINOMA; RECURRENCE; PREDICTORS; DISEASE; SPREAD AB Objective. Uterine serous carcinoma (USC) constitutes 10% of uterine cancers but similar to 40% of deaths. Tumor size is a known prognostic factor in other solid tumors. In endometriod cancers it is one element used to identify the need for complete staging, while its significance in USC is debated. Therefore tumor size was examined as an independent prognostic factor. Methods. Clinical and pathologic variables were recorded for 236 institutional patients, and those patients in the SEER database with USC. Chi-square and Fisher exact t-tests were utilized and survival data generated via Kaplan-Meier method; multivariate analysis was performed via cox-regression. Results. The patients' mean age was 67.2 years (range 40-91). Survival ranged from 0 to 184 months (mean 42.8). We used a tumor size cut-off of 1 cm and noted significant associations with myometrial invasion (p < 0.0001), angiolymphatic invasion (p < 0.0001), peritoneal washings (p = 0.03), stage (p = 0.015) and positive lymph nodes (p = 0.05). Furthermore, recurrence was associated with larger tumors (p = 0.03). In multivariate analysis, extra-uterine disease was the only factor associated with both recurrence and survival. Review of the SEER database noted association of larger tumors with lymph node involvement and a significant survival advantage with tumors <1 cm in both univariate and multivariate analysis. Conclusions. Treatment options for USC are often predicated on the surgical stage and therefore components of the staging are vitally important. The I cm tumor-size cut-off should be studied prospectively as a prognostic indicator of survival and recurrence in USC and considered for inclusion in USC staging. (c) 2012 Published by Elsevier Inc. C1 [Winer, I.; Semaan, A.; Morris, R.] Wayne State Univ, Div Gynecol Oncol, Dept OB GYN, Detroit, MI USA. [Winer, I.; Semaan, A.; Morris, R.] Karmanos Canc Inst, Detroit, MI USA. [Mahdi, H.] Univ Washington, Med Ctr, Dept OB GYN, Seattle, WA 98195 USA. [Bandyopadhyay, S.; Hussein, Y.; Qureshi, F.; Hayek, K.; Alosh, B.; Ali-Fehmi, R.] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. [Van de Vijver, K. K.; Nucci, M. R.] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA. [Abdul-Karim, F.] Cleveland Clin Fdn, Dept Anat Pathol, Cleveland, OH 44195 USA. [Schulz, D.] Henry Ford Hlth Syst, Dept Pathol, Detroit, MI USA. [Cote, M.] Karmanos Canc Inst, Dept Epidemiol, Detroit, MI USA. [Munkarah, A.] Henry Ford Hlth Syst, Div Gynecol Oncol, Dept OB GYN, Detroit, MI USA. [Oliva, E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Ali-Fehmi, R (reprint author), Harper Univ Hosp, Dept Pathol, 3990 John R, Detroit, MI 48201 USA. EM rali@med.wayne.edu NR 41 TC 4 Z9 4 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 2013 VL 128 IS 2 BP 316 EP 321 DI 10.1016/j.ygyno.2012.10.027 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 083EK UT WOS:000314445300029 PM 23138135 ER PT J AU Lim, D Wang, WL Lee, CH Dodge, T Gilks, B Oliva, E AF Lim, D. Wang, W. L. Lee, C. H. Dodge, T. Gilks, B. Oliva, E. TI Old versus new FIGO staging systems in predicting overall survival in patients with uterine leiomyosarcoma: A study of 86 cases SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Leiomyosarcoma; FIGO; Staging; Uterus; Survival ID GYNECOLOGIC-ONCOLOGY-GROUP; SMOOTH-MUSCLE TUMORS; PROGNOSTIC-FACTORS; TREATMENT MODALITIES; ADJUVANT THERAPY; LYMPH-NODE; SARCOMA; UTERUS; CANCER; EXPERIENCE AB Objectives. Uterine leiomyosarcoma (uLMS) was staged using the FIGO system for endometrial cancers. The new FIGO system takes into consideration tumor size disregarding myometrial and cervical involvement. We aimed to compare the two systems and gee Which more accurately predicts overall survival (OS). Methods. 86 patients with uLMS (1984-2010) Were retrospectively staged using both FIGO systems. Mean OS rates were estimated using the Kaplan-Meier method. Results. More patients had stage-I disease by the new FIGO system (42 versus 33). Five versus 18 and 27 versus 5 had old and new stage-II and III diseases respectively. Five and 4 patients with old stage II and III uLMS respectively were downstaged to stage I while 18 with old stage III were downstaged to stage II. Median follow-up was 23.5 months with a median OS of 114 (95% CI, 61-166) months. Although patients with stage I tumors had a higher mean OS rate compared to those with higher stage disease by either system, patients with old stage II-IV disease showed similar mean OS rates, with stage III-IV patients having a slightly better mean OS and a similar trend was observed with the new system. Patients with new FIGO stage III had a higher mean OS rate than those with stage II or IV disease (37.6 versus 28.1 and 34.3 months). Nonetheless, no statistical significant differences were seen in OS according to stage using either system (p = 0.786 and p = 0.400 respectively). Conclusion. Neither FIGO staging system is ideal in classifying patients into four clinically significant stages. (c) 2012 Elsevier Inc. All rights reserved. C1 [Lim, D.] Natl Univ Hlth Syst, Dept Pathol, Singapore, Singapore. [Wang, W. L.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Lee, C. H.; Dodge, T.; Gilks, B.] Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. [Oliva, E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Oliva, E (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,55 Fruit St, Boston, MA 02114 USA. EM eoliva@partners.org NR 56 TC 5 Z9 5 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 2013 VL 128 IS 2 BP 322 EP 326 DI 10.1016/j.ygyno.2012.11.009 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 083EK UT WOS:000314445300030 PM 23153591 ER PT J AU Safren, SA O'Cleirigh, CM Skeer, M Elsesser, SA Mayer, KH AF Safren, Steven A. O'Cleirigh, Conall M. Skeer, Margie Elsesser, Steven A. Mayer, Kenneth H. TI Project Enhance: A Randomized Controlled Trial of an Individualized HIV Prevention Intervention for HIV-Infected Men Who Have Sex With Men Conducted in a Primary Care Setting SO HEALTH PSYCHOLOGY LA English DT Article DE MSM; HIV prevention; AIDS/HIV; high-risk sexual behavior; depression ID BEHAVIORAL INTERVENTION; ANTIRETROVIRAL THERAPY; TRANSMISSION RISK; UNITED-STATES; POSITIVE MEN; MSM; CHALLENGES; DEPRESSION; ADHERENCE; COMMUNITY AB Objective: Men who have sex with men (MSM) are the largest group of individuals in the U. S. living with HIV and have the greatest number of new infections. This study was designed to test a brief, culturally relevant prevention intervention for HIV-infected MSM, which could be integrated into HIV care. Method: HIV-infected MSM who received HIV care in a community health center (N = 201), and who reported HIV sexual transmission-risk behavior (TRB) in the prior 6 months, were randomized to receive the intervention or treatment as usual. The intervention, provided by a medical social worker, included proactive case management for psychosocial problems, counseling about living with HIV, and HIV TRB risk reduction. Participants were followed every 3 months for one year. Results: Participants, regardless of study condition, reported reductions in HIV TRB, with no significant differential effect by condition in primary intent-to-treat analyses. When examining moderators, the intervention was differentially effective in reducing HIV TRB for those who screened in for baseline depression, but this was not the case for those who did not screen in for depression. Conclusions: The similar level of reduction in HIV TRB in the intervention and control groups, consistent with other recent secondary prevention interventions, speaks to the need for new, creative designs, or more potent interventions in secondary HIV prevention trials, as the control group seemed to benefit from risk assessment, study contact, and referrals provided by study staff. The differential finding for those with depression may suggest that those without depression could reap benefits from limited interventions, but those with a comorbid psychiatric diagnosis may require additional interventions to modify their sexual risk behaviors. C1 [Safren, Steven A.; O'Cleirigh, Conall M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Safren, Steven A.; O'Cleirigh, Conall M.] Fenway Hlth, Boston, MA USA. [Skeer, Margie; Elsesser, Steven A.; Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Mayer, Kenneth H.] Brown Univ, Miriam Hosp, Providence, RI 02912 USA. RP Safren, SA (reprint author), 1 Bowdoin Sq, Boston, MA 02114 USA. EM ssafren@partners.org FU NIMH [5R01MH068746-05] FX This study was supported by NIMH grant 5R01MH068746-05 awarded to Kenneth H. Mayer and Steven A. Safren. The authors would like to thank the following individuals for their hard work that made the study possible: Daniel Aguilar, Jeremy Hobsen, Robert Knauz, Rodney VanDerwarker, Benjamin Capistrant, Jessica Ripton, Danielle Dang, Liz Salomon, Bonnie Kissler, Alex Weissman, Adam Sussman, Dhana Perry, Christopher Sterling, William O'Brien, Brett Goshe, the medical providers at Fenway Community Health, and the Fenway Community Advisory Board. We also thank Drs. Margaret Chesney and Ronald Stall for their consultation about the project. Finally, and most importantly, we thank the study participants. NR 34 TC 19 Z9 19 U1 0 U2 10 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD FEB PY 2013 VL 32 IS 2 BP 171 EP 179 DI 10.1037/a0028581 PG 9 WC Psychology, Clinical; Psychology SC Psychology GA 084JT UT WOS:000314535900007 PM 22746262 ER PT J AU Hoogeveen-Westerveld, M Ekong, R Povey, S Mayer, K Lannoy, N Elmslie, F Bebin, M Dies, K Thompson, C Sparagana, SP Davies, P van Eeghen, AM Thiele, EA van den Ouweland, A Halley, D Nellist, M AF Hoogeveen-Westerveld, Marianne Ekong, Rosemary Povey, Sue Mayer, Karin Lannoy, Nathalie Elmslie, Frances Bebin, Martina Dies, Kira Thompson, Catherine Sparagana, Steven P. Davies, Peter van Eeghen, Agnies M. Thiele, Elizabeth A. van den Ouweland, Ans Halley, Dicky Nellist, Mark TI Functional Assessment of TSC2 Variants Identified in Individuals with Tuberous Sclerosis Complex (vol 34, pg 167, 2013) SO HUMAN MUTATION LA English DT Correction C1 [Hoogeveen-Westerveld, Marianne; van den Ouweland, Ans; Halley, Dicky; Nellist, Mark] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. [Ekong, Rosemary; Povey, Sue] UCL, Res Dept Genet Evolut & Environm, London, England. [Mayer, Karin] Ctr Human Genet & Lab Med, Martinsried, Germany. [Lannoy, Nathalie] Ctr Human Genet, Brussels, Belgium. [Elmslie, Frances] St George Hosp, Dept Med Genet, London, England. [Bebin, Martina] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Dies, Kira] Childrens Hosp Boston, Dept Neurol, Boston, MA USA. [Thompson, Catherine; Sparagana, Steven P.] Texas Scottish Rite Hosp Children, Dept Neurol, Dallas, TX 75219 USA. [Sparagana, Steven P.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Davies, Peter] Cardiff Univ, Inst Med Genet, Cardiff CF10 3AX, S Glam, Wales. [Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Herscot Ctr Tuberous Sclerosis Complex, Boston, MA 02114 USA. RP Hoogeveen-Westerveld, M (reprint author), Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. NR 1 TC 0 Z9 0 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD FEB PY 2013 VL 34 IS 2 BP 409 EP 410 DI 10.1002/humu.22256 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 083PP UT WOS:000314477700021 ER PT J AU Aganj, I Yeo, BTT Sabuncu, MR Fischl, B AF Aganj, Iman Yeo, Boon Thye Thomas Sabuncu, Mert R. Fischl, Bruce TI On Removing Interpolation and Resampling Artifacts in Rigid Image Registration SO IEEE TRANSACTIONS ON IMAGE PROCESSING LA English DT Article DE Aliasing; image registration; image resampling; interpolation artifacts ID MUTUAL-INFORMATION; SUBPIXEL REGISTRATION; MRI DATA; MAXIMIZATION; DESIGN; RECONSTRUCTION; CONVOLUTION; ROTATIONS; SERIES; SIGNAL AB We show that image registration using conventional interpolation and summation approximations of continuous integrals can generally fail because of resampling artifacts. These artifacts negatively affect the accuracy of registration by producing local optima, altering the gradient, shifting the global optimum, and making rigid registration asymmetric. In this paper, after an extensive literature review, we demonstrate the causes of the artifacts by comparing inclusion and avoidance of resampling analytically. We show the sum-of-squared-differences cost function formulated as an integral to be more accurate compared with its traditional sum form in a simple case of image registration. We then discuss aliasing that occurs in rotation, which is due to the fact that an image represented in the Cartesian grid is sampled with different rates in different directions, and propose the use of oscillatory isotropic interpolation kernels, which allow better recovery of true global optima by overcoming this type of aliasing. Through our experiments on brain, fingerprint, and white noise images, we illustrate the superior performance of the integral registration cost function in both the Cartesian and spherical coordinates, and also validate the introduced radial interpolation kernel by demonstrating the improvement in registration. C1 [Aganj, Iman; Yeo, Boon Thye Thomas; Sabuncu, Mert R.; Fischl, Bruce] Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. [Aganj, Iman] MIT, Lab Informat & Decis Syst, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Yeo, Boon Thye Thomas] Duke NUS Grad Med Sch, Dept Neurosci & Behav Disorders, Singapore, Singapore. [Sabuncu, Mert R.; Fischl, Bruce] MIT, Comp Sci & Artificial Intelligence Lab, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Fischl, Bruce] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Aganj, I (reprint author), Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. EM iman@nmr.mgh.harvard.edu; ythomas@csail.mit.edu; msabuncu@csail.mit.edu; fischl@nmr.mgh.harvard.edu OI Yeo, B.T. Thomas/0000-0002-0119-3276 FU National Center for Research Resources [P41-RR14075]; NCRR BIRN Morphometric Project [BIRN002, U24RR021382]; National Institute for Biomedical Imaging and Bioengineering [R01EB006758]; National Institute on Aging [AG022381]; National Center for Alternative Medicine [RC1 AT005728-01]; National Institute for Neurological Disorders and Stroke [R01NS052585-01, 1R21NS072652-01, 1R01NS070963]; Shared Instrumentation Grant [1S10RR023401, 1S10RR019307, 1S10RR023043]; Ellison Medical Foundation; NIH Blueprint for Neuroscience Research [5U01-MH093765]; multi-institutional Human Connectome Project; Harvard Catalyst; Harvard Clinical and Translational Science Center under NIH [1KL2RR025757-01]; Harvard University; NIH [NIBIB 1K25EB013649-01] FX This work was supported in part by the National Center for Research Resources (P41-RR14075 and the NCRR BIRN Morphometric Project BIRN002, U24RR021382), the National Institute for Biomedical Imaging and Bioengineering (R01EB006758), the National Institute on Aging (AG022381), the National Center for Alternative Medicine (RC1 AT005728-01), the National Institute for Neurological Disorders and Stroke (R01NS052585-01, 1R21NS072652-01, 1R01NS070963), the Shared Instrumentation Grant 1S10RR023401, Grant 1S10RR019307, and Grant 1S10RR023043, the Autism and Dyslexia Project funded by the Ellison Medical Foundation, and the NIH Blueprint for Neuroscience Research (5U01-MH093765), part of the multi-institutional Human Connectome Project. The work of M. R. Sabuncu was supported in part by Harvard Catalyst, under the KL2 Medical Research Investigator Training (MeRIT) Grant, the Harvard Clinical and Translational Science Center under NIH Grant 1KL2RR025757-01 and financial contributions from Harvard University and its affiliated academic health care centers, and the NIH K25 Grant NIBIB 1K25EB013649-01. The associate editor coordinating the review of this manuscript and approving it for publication was Prof. Marios S. Pattichis. NR 71 TC 6 Z9 6 U1 0 U2 30 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1057-7149 J9 IEEE T IMAGE PROCESS JI IEEE Trans. Image Process. PD FEB PY 2013 VL 22 IS 2 BP 816 EP 827 DI 10.1109/TIP.2012.2224356 PG 12 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA 086VW UT WOS:000314717800033 PM 23076044 ER PT J AU Singh, KK Wang, Y Gray, KP Farhad, M Brummel, S Fenton, T Trout, R Spector, SA AF Singh, Kumud K. Wang, Yan Gray, Kathryn P. Farhad, Mona Brummel, Sean Fenton, Terence Trout, Rodney Spector, Stephen A. TI Genetic Variants in the Host Restriction Factor APOBEC3G are Associated With HIV-1-Related Disease Progression and Central Nervous System Impairment in Children SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE APOBEC3G; polymorphisms; HIV-1; children; disease progression; CNS impairment ID RNA-EDITING ENZYME; HIV-1 VIF; ANTIVIRAL ACTIVITY; POLYMORPHISMS; DEGRADATION; INFECTION; AIDS; PROTEASOME; DIDANOSINE; ZIDOVUDINE AB Background: Apolipoprotein B mRNA editing catalytic polypeptide 3G (APOBEC3G) protein is incorporated into nascent virus particles and mediates cytidine deamination (C-to-U) of first-strand reverse transcripts of HIV-1 in target cells resulting in G-to-A hypermutation of the coding strand and premature degradation. We investigated the effects of APOBEC3G genetic variants on HIV-1-related disease in children. Methods: APOBEC3G variants were detected using real-time polymerase chain reaction in HIV-1-infected children from Pediatric AIDS Clinical Trials Group (PACTG) protocols P152 and P300 that evaluated the effectiveness of 3 mono-or dual-nucleoside reverse transcriptase inhibitor treatments. Results: Of the 1049 children evaluated, 60% were non-Hispanic black, 26% Hispanic, 13% non-Hispanicwhite, and1% other or unknown race/ethnicity. Age ranged from 42 days to 18 years; 45% were males. APOBEC3G-H186R homozygous G/G genotype was associated with more rapid HIV-1 disease progression [hazard ratio (HR): 1.69; P = 0.01] and central nervous system (CNS) impairment (HR: 2.00; P = 0.02) compared with the wild-type A/A or heterozygous A/G genotype in a recessive model. In both additive and dominant models, APOBEC3G-F119F-C allele was associated with protection against disease progression (HR [additive]: 0.69; P = 0.002 and HR [dominant]: 0.60; P = 0.001, respectively) and CNS impairment (HR [additive]: 0.65; P = 0.02 and HR [dominant]: 0.54; P = 0.007, respectively). These associations remained significant in multivariate analyses controlling for baseline characteristics or previously identified genetic variants known to alter HIV-1-related disease in this cohort of children. Conclusions: APOBEC3G-H186R and F119F variants are associated with altered HIV-1-related disease progression and CNS impairment in children. C1 [Singh, Kumud K.; Trout, Rodney; Spector, Stephen A.] Univ Calif San Diego, Dept Pediat, Div Infect Dis, La Jolla, CA 92093 USA. [Wang, Yan; Gray, Kathryn P.; Farhad, Mona; Brummel, Sean; Fenton, Terence] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Gray, Kathryn P.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Spector, Stephen A.] Rady Childrens Hosp San Diego, San Diego, CA USA. RP Spector, SA (reprint author), Univ Calif San Diego, Dept Pediat, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM kusingh@ucsd.edu; saspector@ucsd.edu FU International Maternal Perinatal Adolescent AIDS Clinical Trials (IMPAACT) Network; National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632]; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health (NIMH) [AI068632]; Statistical and Data Analysis Center at Harvard School of Public Health under the National Institute of Allergy and Infectious Diseases [5 U01 AI41110]; Pediatric AIDS Clinical Trials Group (PACTG); IMPAACT Group [U01 AI068616]; National Institute of Allergy and Infectious Diseases (NIAID); NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network; NICHD [N01-DK-9-001/HHSN267200800001C]; National Institute of Health [1R01NS077874, 5R01MH085608] FX This research was supported in part by the International Maternal Perinatal Adolescent AIDS Clinical Trials (IMPAACT) Network. Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632], the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health (NIMH) [AI068632]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This work was supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases cooperative agreement #5 U01 AI41110 with the Pediatric AIDS Clinical Trials Group (PACTG) and U01 AI068616 with the IMPAACT Group. Support of the sites was provided by the National Institute of Allergy and Infectious Diseases (NIAID) and the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by NICHD (contract number N01-DK-9-001/HHSN267200800001C), and supported by National Institute of Health. 1R01NS077874 (S. A. S.) and 5R01MH085608 (K.K.S.). NR 33 TC 18 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD FEB 1 PY 2013 VL 62 IS 2 BP 197 EP 203 DI 10.1097/QAI.0b013e31827ab612 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 083JM UT WOS:000314459500016 PM 23138837 ER PT J AU Barbeau, EB Soulieres, I Dawson, M Zeffiro, TA Mottron, L AF Barbeau, Elise B. Soulieres, Isabelle Dawson, Michelle Zeffiro, Thomas A. Mottron, Laurent TI The Level and Nature of Autistic Intelligence III: Inspection Time SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE autism; Asperger syndrome; perception; processing speed; Raven Progressive Matrices ID CHILDREN; SPEED; DISORDER; SPECTRUM; INDIVIDUALS; PERFORMANCE; ABILITIES; SAVANT; FMRI; IQ AB Across the autism spectrum, level of intelligence is highly dependent on the psychometric instrument used for assessment, and there are conflicting views concerning which measures best estimate autistic cognitive abilities. Inspection time is a processing speed measure associated with general intelligence in typical individuals. We therefore investigated autism spectrum performance on inspection time in relation to two different general intelligence tests. Autism spectrum individuals were divided into autistic and Asperger subgroups according to speech development history. Compared to a typical control group, mean inspection time for the autistic subgroup but not the Asperger subgroup was significantly shorter (by 31%). However, the shorter mean autistic inspection time was evident only when groups were matched on Wechsler IQ and disappeared when they were matched using Raven's Progressive Matrices. When autism spectrum abilities are compared to typical abilities, results may be influenced by speech development history as well as by the instrument used for intelligence matching. C1 [Barbeau, Elise B.; Soulieres, Isabelle; Mottron, Laurent] Univ Montreal, Fernand Seguin Res Ctr, CET EDUM, Montreal, PQ, Canada. [Barbeau, Elise B.; Mottron, Laurent] Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada. [Soulieres, Isabelle] Univ Montreal, Dept Psychol, Montreal, PQ H3C 3J7, Canada. [Zeffiro, Thomas A.] Massachusetts Gen Hosp, Neural Syst Grp, Boston, MA 02114 USA. RP Mottron, L (reprint author), Hop Riviere Des Prairies, 7070 Blvd Perras, Montreal, PQ H1E 1A4, Canada. EM mottronl@uniserve.com FU Canadian Institutes of Health Research NR 44 TC 21 Z9 21 U1 7 U2 44 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD FEB PY 2013 VL 122 IS 1 BP 295 EP 301 DI 10.1037/a0029984 PG 7 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 085VD UT WOS:000314641500032 PM 23088375 ER PT J AU Goldvasser, D Marchie, A Bragdon, LK Bragdon, CR Weidenhielm, L Malchau, H AF Goldvasser, Dov Marchie, Anthony Bragdon, Louisa K. Bragdon, Charles R. Weidenhielm, Lars Malchau, Henrik TI Incidence of Osteolysis in Total Knee Arthroplasty Comparison Between Radiographic and Retrieval Analysis SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total knee arthroplasty; polyethylene; wear; radiograph; Computed tomography ID POLYETHYLENE TIBIAL INSERTS; TOTAL HIP-ARTHROPLASTY; WEAR; PROSTHESES; COMPONENT; REPLACEMENT; THICKNESS; FAILURE; JOINT AB Detection of polyethylene wear and osteolysis in total knee arthroplasty using radiographs is imprecise. To correlate radiographic findings with retrieved tibial component analysis, we reviewed knee revision cases. A joint registry was used to identify all knee revisions. Radiographic scoring systems were developed. Radiographs were analyzed for osteolysis and implant alignment. Polyethylene liner retrievals were visually and optically graded for surface damage. Statistical analyses that included correlation analysis and Mann-Whitney U test were used. When osteolysis was found, radiographic scores and delamination score were significantly higher (P = .047 and P = .014, respectively). Delamination is a good indicator for polyethylene wear and osteolysis. There is a need to develop in vivo methods to identify polyethylene changes and thereby prevent severe clinical outcomes. C1 [Goldvasser, Dov; Marchie, Anthony; Bragdon, Louisa K.; Bragdon, Charles R.; Malchau, Henrik] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goldvasser, Dov; Weidenhielm, Lars] Karolinska Inst, Sect Orthopaed & Sport Med, Dept Mol Med & Surg, Stockholm, Sweden. RP Goldvasser, D (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Labs, 55 Fruit St, Boston, MA 02114 USA. OI Malchau, Henrik/0000-0002-4291-2441 NR 22 TC 5 Z9 5 U1 0 U2 12 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD FEB PY 2013 VL 28 IS 2 BP 201 EP 206 DI 10.1016/j.arth.2012.06.008 PG 6 WC Orthopedics SC Orthopedics GA 083CP UT WOS:000314440600001 PM 22868074 ER PT J AU Saunders, JE Beeson, CC Schnellmann, RG AF Saunders, Janet E. Beeson, Craig C. Schnellmann, Rick G. TI Characterization of functionally distinct mitochondrial subpopulations SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Article DE Mitochondria; Heterogeneity; Flow cytometry; Kidney; Subpopulations ID SKELETAL-MUSCLE MITOCHONDRIA; FLOW-CYTOMETRIC ANALYSIS; RAT CARDIAC-MUSCLE; INTERMYOFIBRILLAR MITOCHONDRIA; OXIDATIVE-PHOSPHORYLATION; PERMEABILITY TRANSITION; LIVER-MITOCHONDRIA; LIGHT SCATTER; INTERFIBRILLAR MITOCHONDRIA; HEART-MITOCHONDRIA AB Mitochondrial stress results in changes in mitochondrial function, morphology and homeostasis (biogenesis, fission/fusion, mitophagy) and may lead to changes in mitochondrial subpopulations. While flow cytometric techniques have been developed to quantify features of individual mitochondria related to volume, Ca2+ concentration, mtDNA content, respiratory capacity and oxidative damage, less information is available concerning the identification and characterization of mitochondrial subpopulations, particularly in epithelial cells. Mitochondria from rabbit kidneys were stained with molecular probes for cardiolipin content (nonyl acridine orange, NAO) and membrane potential (tetramethylrhodamine, TMRM) and analyzed using flow cytometry. We validated that side scatter was a better indicator of volume and that as side scatter (SSC) decreased mitochondrial volume increased. Furthermore, those mitochondria with the highest NAO content had greater side scattering and were most highly charged. Mitochondria with average NAO content were of average side scattering and maintained an intermediate charge. Those mitochondria with low NAO content had minimal side scattering and exhibited minimal charge. Upon titration with the uncoupler carbonylcyanide-4-(trifluoromethoxy)-phenylhydrazone (FCCP), it was found that the high NAO content subpopulations were more resistant to uncoupling than lower NAO content populations. Ca2+-induced swelling of mitochondria was evaluated using probability binning (PB) analyses of SSC. Interestingly, only 30 % of the mitochondria showed changes in response to Ca2+, which was blocked by cyclosporine A. In addition, the small, high NAO content mitochondria swelled differentially in response to Ca2+ over time. Our results demonstrate that flow cytometry can be used to identify mitochondrial subpopulations based on high, mid and low NAO content and/or volume/complexity. These subpopulations showed differences in membrane potential, volume, and responses to uncoupling and Ca2+-induced swelling. C1 [Saunders, Janet E.; Beeson, Craig C.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Ctr Cell Death Injury & Regenerat, Charleston, SC 29425 USA. [Beeson, Craig C.] Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Beeson, CC (reprint author), Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, 280 Calhoun St,MSC140, Charleston, SC 29425 USA. EM beesonc@musc.edu FU NIH [GM 084147, C06 RR-015455]; NIM/NIEHS [T32ES012878-05]; NIH/NHLBI [T32HL007260-34]; Department of Veterans Affairs FX This study was supported by NIH Grant GM 084147, the NIM/NIEHS Training Program in Environmental Stress Signaling T32ES012878-05 and NIH/NHLBI Training to Improve Cardiovascular Therapies T32HL007260-34, and by the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs. Animal facilities were funded by NIH grant C06 RR-015455 NR 43 TC 6 Z9 6 U1 0 U2 22 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0145-479X J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD FEB PY 2013 VL 45 IS 1-2 BP 87 EP 99 DI 10.1007/s10863-012-9478-4 PG 13 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA 089GR UT WOS:000314899500008 PM 23080405 ER PT J AU Perron, NR Beeson, C Rohrer, B AF Perron, Nathan R. Beeson, Craig Rohrer, Barbel TI Early alterations in mitochondrial reserve capacity; a means to predict subsequent photoreceptor cell death SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Article DE Mitochondrial respiration; Cell death; Photoreceptors; Retinitis pigmentosa ID RETINAL MULLER CELLS; ACID PROTEIN ASSAY; OXIDATIVE STRESS; BICINCHONINIC ACID; ENERGY-METABOLISM; ROD PHOTORECEPTORS; DEGENERATION; CALCIUM; SUPEROXIDE; MECHANISMS AB Although genetic and environmental factors contribute to neurodegenerative disease, the underlying etiology common to many diseases might be based on metabolic demand. Mitochondria are the main producer of ATP, but are also the major source of reactive oxygen species. Under normal conditions, these oxidants are neutralized; however, under environmental insult or genetic susceptibility conditions, oxidative stress may exceed cellular antioxidant capacities, leading to degeneration. We tested the hypothesis that loss in mitochondrial reserve capacity plays a causative role in neuronal degeneration and chose a cone photoreceptor cell line as our model. 661W cells were exposed to agents that mimic oxidant stress or calcium overload. Real-time changes in cellular metabolism were assessed using the multi-well Seahorse Biosciences XF24 analyzer that measures oxygen consumption (OCR) and extracellular acidification rates (ECAR). Cellular stress resulted in an early loss of mitochondrial reserve capacity, without affecting basal respiration; and ECAR was increased, representing a compensatory shift of ATP productions toward glycolysis. The degree of change in energy metabolism was correlated with the amount of subsequent cell death 24-hours post-treatment, the concentration-dependent loss in mitochondrial reserve capacity correlated with the number of live cells. Our data suggested first, that loss in mitochondrial reserve capacity is a major contributor in disease pathogenesis; and second, that the XF24 assay might represent a useful surrogate assay amenable to the screening of agents that protect against loss of mitochondrial reserve capacity. In future experiments, we will explore these concepts for the development of neuroprotective agents. C1 [Rohrer, Barbel] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. [Perron, Nathan R.; Beeson, Craig] Med Univ S Carolina, Dept Pharmaceut Sci, Charleston, SC 29425 USA. [Rohrer, Barbel] Ralph H Johnson VA Med Ctr, Dept Res Serv, Charleston, SC 29425 USA. [Beeson, Craig] Med Univ S Carolina, Coll Pharm Pharmaceut & Biomed Sci, Charleston, SC 29425 USA. RP Rohrer, B (reprint author), Med Univ S Carolina, Dept Ophthalmol, 167 Ashley Ave,SEI 511, Charleston, SC 29425 USA. EM beesonc@musc.edu; rohrer@musc.edu FU National Institutes of Health [EY013520, EY019320]; Department for Veterans Affairs [RX000444]; Foundation Fighting Blindness; Research to Prevent Blindness (RPB), New York, NY FX This work was supported in part by National Institutes of Health grant EY013520, EY019320 (B.R.), a Department for Veterans Affairs merit award RX000444 (B.R.), the WG-TRAP award by Foundation Fighting Blindness (B.R. and C.B.), and an unrestricted grant to MUSC from Research to Prevent Blindness (RPB), New York, NY. B.R. is a RPB Olga Keith Wiess Scholar. NR 56 TC 11 Z9 11 U1 0 U2 16 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0145-479X J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD FEB PY 2013 VL 45 IS 1-2 BP 101 EP 109 DI 10.1007/s10863-012-9477-5 PG 9 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA 089GR UT WOS:000314899500009 PM 23090843 ER PT J AU Hoffmann, U Sukhotinsky, I Eikermann-Haerter, K Ayata, C AF Hoffmann, Ulrike Sukhotinsky, Irma Eikermann-Haerter, Katharina Ayata, Cenk TI Glucose modulation of spreading depression susceptibility SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE animal models; electrophysiology; glucose; migraine; spreading depression ID CORTICAL DEPRESSION; BRAIN GLUCOSE; RAT-BRAIN; PERIINFARCT DEPOLARIZATIONS; ONLINE MICRODIALYSIS; MIGRAINE PROPHYLAXIS; CEREBRAL-ISCHEMIA; REGIONAL CHANGES; BLOOD-FLOW; CORTEX AB Spreading depression of Leao is an intense spreading depolarization (SD) wave associated with massive transmembrane ionic, water, and neurotransmitter shifts. Spreading depolarization underlies migraine aura, and occurs in brain injury, making it a potential therapeutic target. While susceptibility to SD can be modulated pharmacologically, much less is known about modulation by systemic physiological factors, such as the glycemic state. In this study, we systematically examined modulation of SD susceptibility by blood glucose in anesthetized rats under full physiological monitoring. Hyperglycemia and hypoglycemia were induced by insulin or dextrose infusion (blood glucose similar to 40 and 400 mg/dL, respectively). Spreading depolarizations were evoked by direct cortical electrical stimulation to determine the intensity threshold, or by continuous topical KCI application to determine SD frequency. Hyperglycemia elevated the electrical SD threshold and reduced the frequency of KCI-induced SDs, without significantly affecting other SD properties. In contrast, hypoglycemia significantly prolonged individual and cumulative SD durations, but did not alter the electrical SD threshold, or SD frequency, amplitude or propagation speed. These data show that increased cerebral glucose availability makes the tissue resistant to SD. Journal of Cerebral Blood Flow & Metabolism (2013) 33, 191-195; doi:10.1038/jcbfm.2012.132; published online 12 September 2012 C1 [Hoffmann, Ulrike; Sukhotinsky, Irma; Eikermann-Haerter, Katharina; Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurovasc Res Lab,Dept Radiol, Charlestown, MA USA. [Hoffmann, Ulrike] Tech Univ Munich, Klinikum Rechts Isar, Klin Anaesthesiol, D-80290 Munich, Germany. [Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke Serv, Charlestown, MA USA. [Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Intens Care Unit,Dept Neurol, Charlestown, MA USA. RP Ayata, C (reprint author), Neurovasc Res Lab, 149 13th St,Room 6408, Charlestown, MA 02129 USA. EM cayata@partners.org FU National Institutes of Health [NS055104, NS061505] FX This study was supported by the National Institutes of Health (NS055104; NS061505). NR 32 TC 10 Z9 12 U1 0 U2 14 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 FEB PY 2013 VL 33 IS 2 BP 191 EP 195 DI 10.1038/jcbfm.2012.132 PG 5 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 087CT UT WOS:000314739600006 PM 22968322 ER PT J AU Zhang, R Huynh, A Whitcher, G Chang, J Maltzman, JS Turka, LA AF Zhang, Ruan Huynh, Alexandria Whitcher, Gregory Chang, JiHoon Maltzman, Jonathan S. Turka, Laurence A. TI An obligate cell-intrinsic function for CD28 in Tregs SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID REGULATORY T-CELLS; TRANSPLANTATION TOLERANCE; CUTTING EDGE; CD4(+)CD25(+); FOXP3; HOMEOSTASIS; CTLA-4; COMPARTMENTALIZATION; DIFFERENTIATION; COSTIMULATION AB Tregs expressing the transcription factor FOXP3 are critical for immune homeostasis. The costimulatory molecule CD28 is required for optimal activation and function of naive T cells; however, its role in Treg function has been difficult to dissect, as CD28 is required for thymic Treg development, and blockade of CD28-ligand. interactions has confounding effects in trans on nonregulatory cells. To address this question, we created Treg-specific Cd28 conditional knockout mice. Despite the presence of normal numbers of FOXP3(+) cells, these animals accumulated large numbers of activated T cells, developed severe autoimmunity that primarily affected the skin and lungs, and failed to appropriately resolve induced experimental allergic encephalomyelitis. This in vivo functional impairment was accompanied by dampened expression of CTLA-4, PD-1, and CCR6. Disease occurrence was not due to subversion of Cd28-deficient Tregs into pathogenic cells, as complementation with normal Tregs prevented disease occurrence. Interestingly, in these "competitive" environments, Cd28-deficient Tregs exhibited a pronounced proliferative/survival disadvantage. These data demonstrate clear postmaturational roles for CD28 in FOXP3(+) Tregs and provide mechanisms which we believe to be novel to explain how interruption of CD28-ligand interactions may enhance immune responses independent of effects on thymic development or on other cell types. C1 [Zhang, Ruan; Huynh, Alexandria; Whitcher, Gregory; Chang, JiHoon; Turka, Laurence A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Transplant Inst,Dept Med, Boston, MA 02215 USA. [Maltzman, Jonathan S.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Turka, LA (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. EM lturka@partners.org FU NIH [AI-037691, AI-085160] FX We thank Terry Strom, Arlene Sharpe, Christophe Benoist, and members of the Turka, Strom, and Maltzman laboratories for many helpful discussions and Eva Csizmadia and Weihua Gong for technical assistance. This work was funded by NIH grants AI-037691 and AI-085160. NR 39 TC 77 Z9 77 U1 0 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 2013 VL 123 IS 2 BP 580 EP 593 DI 10.1172/JCI65013 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 084QG UT WOS:000314553600015 PM 23281398 ER PT J AU Lotinun, S Kiviranta, R Matsubara, T Alzate, JA Neff, L Luth, A Koskivirta, I Kleuser, B Vacher, J Vuorio, E Horne, WC Baron, R AF Lotinun, Sutada Kiviranta, Riku Matsubara, Takuma Alzate, Jorge A. Neff, Lynn Lueth, Anja Koskivirta, Ilpo Kleuser, Burkhard Vacher, Jean Vuorio, Eero Horne, William C. Baron, Roland TI Osteoclast-specific cathepsin K deletion stimulates S1P-dependent bone formation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID DEFICIENT MICE; SPHINGOSINE 1-PHOSPHATE; PARATHYROID-HORMONE; TRANSGENIC MICE; HOMEOSTASIS; RESORPTION; EXPRESSION; MASS; PYCNODYSOSTOSIS; OSTEOPETROSIS AB Cathepsin K (CTSK) is secreted by osteoclasts to degrade collagen and other matrix proteins during bone resorption. Global deletion of Ctsk in mice decreases bone resorption, leading to osteopetrosis, but also increases the bone formation rate (BFR). To understand how Ctsk deletion increases the BFR, we generated osteoclast- and osteoblast-targeted Ctsk knockout mice using floxed Ctsk alleles. Targeted ablation of Ctsk in hematopoietic cells, or specifically in osteoclasts and cells of the monocyte-osteoclast lineage, resulted in increased bone volume and BFR as well as osteoclast and osteoblast numbers. In contrast, targeted deletion of Ctsk in osteoblasts had no effect on bone resorption or BFR, demonstrating that the increased BFR is osteoclast dependent. Deletion of Ctsk in osteoclasts increased their sphingosine kinase 1 (Sphk1) expression. Conditioned media from Ctsk-deficient osteoclasts, which contained elevated levels of sphingosine-l-phosphate (S1P), increased alkaline phosphatase and mineralized nodules in osteoblast cultures. An S1P(1,3) receptor antagonist inhibited these responses. Osteoblasts derived from mice with Ctsk-deficient osteoclasts had an increased RANKL/OPG ratio, providing a positive feedback loop that increased the number of osteoclasts. Our data provide genetic evidence that deletion of CTSK in osteoclasts enhances bone formation in vivo by increasing the generation of osteoclast-derived S1P. C1 [Lotinun, Sutada; Kiviranta, Riku; Matsubara, Takuma; Alzate, Jorge A.; Neff, Lynn; Horne, William C.; Baron, Roland] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Kiviranta, Riku; Koskivirta, Ilpo] Univ Turku, Dept Med Biochem, Turku, Finland. [Kiviranta, Riku; Koskivirta, Ilpo; Vuorio, Eero] Univ Turku, Dept Genet & Med, Turku, Finland. [Lueth, Anja; Kleuser, Burkhard] Univ Potsdam, Inst Nutr Sci, Dept Nutr Toxicol, Bergholz Rehbrucke, Germany. [Vacher, Jean] Univ Montreal, Fac Med, Clin Res Inst Montreal, Montreal, PQ H3C 3J7, Canada. [Baron, Roland] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02115 USA. RP Baron, R (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave,REB 310, Boston, MA 02115 USA. EM roland_baron@hsdm.harvard.edu FU Procter Gamble FX We thank Kei Yamana for providing PCR primer sequences. We also thank Nicholas Brady, Chantel Lester, and Antonios Aliprands for mu CT analysis. Confocal analysis was performed at the Harvard NeuroDiscovery Center (Boston, Massachusetts, USA). This work was supported in part by Procter & Gamble. NR 54 TC 99 Z9 104 U1 0 U2 29 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 FEB PY 2013 VL 123 IS 2 BP 666 EP 681 DI 10.1172/JCI64840 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 084QG UT WOS:000314553600023 PM 23321671 ER PT J AU Tzatsos, A Paskaleva, P Ferrari, F Deshpande, V Stoykova, S Contino, G Wong, KK Lan, F Trojer, P Park, PJ Bardeesy, N AF Tzatsos, Alexandros Paskaleva, Polina Ferrari, Francesco Deshpande, Vikram Stoykova, Svetlana Contino, Gianmarco Wong, Kwok-Kin Lan, Fei Trojer, Patrick Park, Peter J. Bardeesy, Nabeel TI KDM2B promotes pancreatic cancer via Polycomb-dependent and -independent transcriptional programs SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID REGULATES CELL-PROLIFERATION; GENE-EXPRESSION SIGNATURE; ZESTE HOMOLOG 2; DUCTAL ADENOCARCINOMA; HISTONE DEMETHYLASE; EMBRYONIC FIBROBLASTS; PATHWAY; MOUSE; TRANSFORMATION; TUMORIGENESIS AB Epigenetic mechanisms mediate heritable control of cell identity in normal cells and cancer. We sought to identify epigenetic regulators driving the pathogenesis of pancreatic ductal adenocarcinoma (PDAC), one of the most lethal human cancers. We found that KDM2B (also known as Ndy1, FBXL10, and JHDM1B), an H3K36 histone demethylase implicated in bypass of cellular senescence and somatic cell reprogramming, is markedly overexpressed in human PDAC, with levels increasing with disease grade and stage, and highest expression in metastases. KDM2B silencing abrogated tumorigenicity of PDAC cell lines exhibiting loss of epithelial differentiation, whereas KDM2B overexpression cooperated with Kras(G12D) to promote PDAC formation in mouse models. Gain- and loss-of-function experiments coupled to genome-wide gene expression and ChIP studies revealed that KDM2B drives tumorigenicity through 2 different transcriptional mechanisms. KDM2B repressed developmental genes through cobinding with Polycomb group (PcG) proteins at transcriptional start sites, whereas it activated a module of metabolic genes, including mediators of protein synthesis and mitochondrial function, cobound by the MYC oncogene and the histone demethylase KDM5A. These results defined epigenetic programs through which KDM2B subverts cellular differentiation and drives the pathogenesis of an aggressive subset of PDAC. C1 [Tzatsos, Alexandros; Paskaleva, Polina; Stoykova, Svetlana; Contino, Gianmarco; Bardeesy, Nabeel] Massachusetts Gen Hosp Canc Ctr, Boston, MA USA. [Tzatsos, Alexandros; Wong, Kwok-Kin; Bardeesy, Nabeel] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Ferrari, Francesco; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA USA. [Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Deshpande, Vikram] Harvard Univ, Sch Med, Boston, MA USA. [Wong, Kwok-Kin] Dana Farber Harvard Canc Ctr, Dept Med Oncol, Boston, MA USA. [Lan, Fei; Trojer, Patrick] Constellat Pharmaceut, Cambridge, MA USA. RP Tzatsos, A (reprint author), 185 Cambridge St, Boston, MA 02114 USA. EM Tzatsos.Alexandros@mgh.harvard.edu; Bardeesy.Nabeel@mgh.harvard.edu RI Ferrari, Francesco/H-5007-2012; OI Ferrari, Francesco/0000-0002-9811-3753; Contino, Gianmarco/0000-0001-5874-0405; wong, kwok kin/0000-0001-6323-235X FU Waxman Foundation; NCI [P01 CA117969-06, P50 CA127003, 1 R01 CA133557-01]; Andrew Warshaw Institute; Lynda J. Verville Foundation; Nestora fund; NIH [K99 CA158582]; Massachusetts Biomedical Research Corporation Tosteson Fellowship Award FX We are grateful to Nick Dyson, Mo Motamedi, Leif Ellisen, and Rushika Perera for critical reading of the manuscript and to members of the Bardeesy lab for helpful discussions throughout the course of these studies. This work was supported by grants from the Waxman Foundation, the NCI (P01 CA117969-06, P50 CA127003, and 1 R01 CA133557-01), the Andrew Warshaw Institute, and the Lynda J. Verville Foundation to N. Bardeesy. A. Tzatsos is supported by the Nestora fund, NIH grant K99 CA158582, and the Massachusetts Biomedical Research Corporation Tosteson Fellowship Award. NR 48 TC 51 Z9 52 U1 0 U2 25 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 FEB PY 2013 VL 123 IS 2 BP 727 EP 739 DI 10.1172/JCI64535 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 084QG UT WOS:000314553600027 PM 23321669 ER PT J AU Seo, JH Miyamoto, N Hayakawa, K Pham, LDD Maki, T Ayata, C Kim, KW Lo, EH Arai, K AF Seo, Ji Hae Miyamoto, Nobukazu Hayakawa, Kazuhide Pham, Loc-Duyen D. Maki, Takakuni Ayata, Cenk Kim, Kyu-Won Lo, Eng H. Arai, Ken TI Oligodendrocyte precursors induce early blood-brain barrier opening after white matter injury SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID RAT-BRAIN; STROKE; CELLS; ACTIVATION; PROLIFERATION; REGENERATION; REPERFUSION; ASTROCYTES; PLASTICITY; ISCHEMIA AB Oligodendrocyte precursor cells (OPCs) are thought to maintain homeostasis and contribute to long-term repair in adult white matter; however, their roles in the acute phase after brain injury remain unclear. Mice that were subjected to prolonged cerebral hypoperfusion stress developed white matter demyelination over time. Prior to demyelination, we detected increased MMP9 expression, blood-brain barrier (BBB) leakage, and neutrophil infiltration in damaged white matter. Notably, at this early stage, OPCs made up the majority of MMP9-expressing cells. The standard MMP inhibitor GM6001 reduced the early BBB leakage and neutrophil infiltration, indicating that OPC-derived MMP9 induced early BBB disruption after white matter injury. Cell-culture experiments confirmed that OPCs secreted MMP9 under pathological conditions, and conditioned medium prepared from the stressed OPCs weakened endothelial barrier tightness in vitro. Our study reveals that OPCs can rapidly respond to white matter injury and produce MMP9 that disrupts the BBB, indicating that OPCs may mediate injury in white matter under disease conditions. C1 [Seo, Ji Hae; Miyamoto, Nobukazu; Hayakawa, Kazuhide; Pham, Loc-Duyen D.; Maki, Takakuni; Lo, Eng H.; Arai, Ken] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Boston, MA 02114 USA. [Seo, Ji Hae; Miyamoto, Nobukazu; Hayakawa, Kazuhide; Pham, Loc-Duyen D.; Maki, Takakuni; Lo, Eng H.; Arai, Ken] Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Boston, MA 02114 USA. [Seo, Ji Hae; Miyamoto, Nobukazu; Hayakawa, Kazuhide; Pham, Loc-Duyen D.; Maki, Takakuni; Ayata, Cenk; Lo, Eng H.; Arai, Ken] Harvard Univ, Sch Med, Boston, MA USA. [Seo, Ji Hae; Kim, Kyu-Won] Seoul Natl Univ, Coll Pharm, NeuroVasc Coordinat Res Ctr, Seoul, South Korea. [Ayata, Cenk] Massachusetts Gen Hosp, Dept Radiol, Neurovasc Res Lab, Boston, MA 02114 USA. [Kim, Kyu-Won] Seoul Natl Univ, Grad Sch Convergence Sci & Technol, Dept Mol Med & Biopharmaceut Sci, Seoul, South Korea. [Kim, Kyu-Won] Seoul Natl Univ, Dept Internal Med, Seoul, South Korea. [Kim, Kyu-Won] Seoul Natl Univ, Innovat Res Inst Cell Therapy, Seoul, South Korea. RP Arai, K (reprint author), Neuroprotect Res Lab, MGH E 149-2401, Charlestown, MA 02129 USA. EM lo@helix.mgh.harvard.edu; karai@partners.org FU Deane Foundation; American Heart Association; NIH; National Research Foundation of Korea; World Class University Program; Global Research Laboratory Program FX This work was supported in part by the Deane Foundation, the American Heart Association, the NIH, the National Research Foundation of Korea, the World Class University Program, and the Global Research Laboratory Program. NR 25 TC 34 Z9 35 U1 0 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 FEB PY 2013 VL 123 IS 2 BP 782 EP 786 DI 10.1172/JCI65863 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 084QG UT WOS:000314553600031 PM 23281396 ER PT J AU Hassan, S Karpova, Y Baiz, D Yancey, D Pullikuth, A Flores, A Register, T Cline, JM D'Agostino, R Danial, N Datta, SR Kulik, G AF Hassan, Sazzad Karpova, Yelena Baiz, Daniele Yancey, Dana Pullikuth, Ashok Flores, Anabel Register, Thomas Cline, J. Mark D'Agostino, Ralph, Jr. Danial, Nika Datta, Sandeep Robert Kulik, George TI Behavioral stress accelerates prostate cancer development in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PROTEIN-KINASE-A; ANDROGEN RECEPTOR; GROWTH-FACTOR; PHOSPHATIDYLINOSITOL 3-KINASE; BETA(2)-ADRENERGIC RECEPTOR; BAD PHOSPHORYLATION; DISEASE PROGRESSION; GENE-EXPRESSION; CELLS; SURVIVAL AB Prostate cancer patients have increased levels of stress and anxiety. Conversely, men who take beta blockers, which interfere with signaling from the stress hormones adrenaline and noradrenaline, have a lower incidence of prostate cancer; however, the mechanisms underlying stress-prostate cancer interactions are unknown. Here, we report that stress promotes prostate carcinogenesis in mice in an adrenaline-dependent manner. Behavioral stress inhibited apoptosis and delayed prostate tumor involution both in phosphatase and tensin homolog-deficient (PTEN-deficient) prostate cancer xenografts treated with PI3K inhibitor and in prostate tumors of mice with prostate-restricted expression of c-MYC (Hi-Myc mice) subjected to androgen ablation therapy with bicalutamide. Additionally, stress accelerated prostate cancer development in Hi-Myc mice. The effects of stress were prevented by treatment with the selective beta(2)-adrenergic receptor (ADRB2) antagonist ICI118,551 or by inducible expression of PKA inhibitor (PKI) or of BCL2-associated death promoter (BAD) with a mutated PKA phosphorylation site (BAD(S112A)) in xenograft tumors. Effects of stress were also blocked in Hi-Myc mice expressing phosphorylation-deficient BAD (BAD(3SA)). These results demonstrate interactions between prostate tumors and the psychosocial environment mediated by activation of an adrenaline/ADRB2/PKA/BAD antiapoptotic signaling pathway. Our findings could be used to identify prostate cancer patients who could benefit from stress reduction or from pharmacological inhibition of stress-induced signaling. C1 [Hassan, Sazzad; Karpova, Yelena; Baiz, Daniele; Yancey, Dana; Pullikuth, Ashok; Flores, Anabel; Kulik, George] Wake Forest Univ, Bowman Gray Sch Med, Dept Canc Biol, Winston Salem, NC 27157 USA. [Register, Thomas; Cline, J. Mark] Wake Forest Univ, Bowman Gray Sch Med, Dept Pathol, Winston Salem, NC 27157 USA. [Register, Thomas; Cline, J. Mark; D'Agostino, Ralph, Jr.; Kulik, George] Wake Forest Univ, Bowman Gray Sch Med, Ctr Comprehens Canc, Winston Salem, NC 27157 USA. [Danial, Nika] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Datta, Sandeep Robert] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Kulik, G (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Canc Biol, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM gkulik@wakehealth.edu RI Dagostino Jr, Ralph/C-4060-2017; OI Dagostino Jr, Ralph/0000-0002-3550-8395; Pullikuth, Ashok/0000-0002-0041-3310 FU Department of Defense [PC073548]; National Cancer Institute [R01CA118329]; Wake Forest University Health Sciences; Research Supplement to Promote Diversity in Health-Related Research FX The authors are grateful to Anil Sood and Karen Klein for critical reading and helpful suggestions; to Dina Yamaleeva, Michael Mangiapani, and Michael Conlin for assistance with image analysis; to John Olson for MRI imaging; and to Michael Thomas for mass spectrometry detection of noradrenaline. This work was supported by federal grants PC073548 from the Department of Defense and R01CA118329 from the National Cancer Institute and by institutional grants from Wake Forest University Health Sciences to G. Kulik. D. Yancey was supported in part by Research Supplement to Promote Diversity in Health-Related Research. NR 61 TC 57 Z9 59 U1 1 U2 21 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 FEB PY 2013 VL 123 IS 2 BP 874 EP 886 DI 10.1172/JCI63324 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 084QG UT WOS:000314553600040 PM 23348742 ER PT J AU Broder, JS Hamedani, AG Liu, SW Emerman, CL AF Broder, Joshua S. Hamedani, Azita G. Liu, Shan W. Emerman, Charles L. TI EMERGENCY DEPARTMENT CONTRAST PRACTICES FOR ABDOMINAL/PELVIC COMPUTED TOMOGRAPHY-A NATIONAL SURVEY AND COMPARISON WITH THE AMERICAN COLLEGE OF RADIOLOGY APPROPRIATENESS CRITERIA (R) SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE emergency department; abdominal/pelvic CT(computed tomography); contrast; guidelines AB Background: Controversy exists regarding the need for contrast agents for emergency abdominal computed tomography (CT). Objectives: We surveyed United States (US) academic Emergency Departments (EDs) to document national practice. We hypothesized variable contrast use for abdominal/pelvic CT, including variance from the American College of Radiology's (ACR) Appropriateness Criteria (R), an evidence-based guideline. Methods: A survey was sent to physician leaders of US academic EDs, defined as primary site of an Emergency Medicine residency program. Respondents were asked about their institutions' use of oral, intravenous (i.v.), and rectal contrast for various abdominal/ pelvic CT indications. Responses were compared with the approach given the highest appropriateness rating by the American College of Radiology. Results: One hundred and six of 152 (70%) surveys were completed. Intravenous contrast was the most frequently cited contrast. At least 90% of respondents reported using i.v. contrast in 12 of 18 indications. Oral contrast use was more variable. In no indication did >= 90% of respondents indicate use of oral contrast, and in only two indications did >= 90% avoid its use. Rectal contrast was rarely used. The most common indications for which no contrast agent was used were suspected renal colic (79%), viscus perforation (19%), penetrating abdominal trauma (18%), and blunt abdominal trauma (15%). Conclusions: Contrast practices for abdominal/pelvic CT vary nationally, according to a survey of US academic EDs. For multiple indications, the contrast practices of a substantial number of respondents deviated from those recommendations given the highest clinical appropriateness rating by the American College of Radiology. (c) 2013 Elsevier Inc. C1 [Broder, Joshua S.] Duke Univ, Med Ctr, Dept Surg, Div Emergency Med, Durham, NC 27710 USA. [Hamedani, Azita G.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Emergency Med, Madison, WI USA. [Liu, Shan W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Emerman, Charles L.] Case Western Reserve Univ, Dept Emergency Med, Cleveland, OH 44106 USA. RP Broder, JS (reprint author), Duke Univ, Med Ctr, Dept Surg, Div Emergency Med, Box 3096, Durham, NC 27710 USA. OI Broder, Joshua/0000-0001-8030-2831 NR 20 TC 8 Z9 8 U1 0 U2 3 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 FEB PY 2013 VL 44 IS 2 BP 423 EP 433 DI 10.1016/j.jemermed.2012.08.027 PG 11 WC Emergency Medicine SC Emergency Medicine GA 086EC UT WOS:000314665400063 PM 23164558 ER PT J AU Gonen, L Binder, WD Nadel, ES Brown, DFM AF Gonen, Liza Binder, William D. Nadel, Eric S. Brown, David F. M. TI EOSINOPHILIA AND RASH SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID CHURG-STRAUSS-SYNDROME; ADRENAL INSUFFICIENCY; INFECTIONS C1 [Gonen, Liza; Binder, William D.; Nadel, Eric S.; Brown, David F. M.] Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. [Binder, William D.; Nadel, Eric S.; Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Nadel, Eric S.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St,Founders 114, Boston, MA 02114 USA. NR 11 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 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD FEB PY 2013 VL 44 IS 2 BP 469 EP 471 PG 3 WC Emergency Medicine SC Emergency Medicine GA 086EC UT WOS:000314665400071 PM 23103066 ER PT J AU Neuhaus, V Badri, O Ferree, S Bot, AGJ Ring, DC Mudgal, CS AF Neuhaus, Valentin Badri, Omar Ferree, Steven Bot, Arjan G. J. Ring, David C. Mudgal, Chaitanya S. TI Radiographic Alignment of Unstable Distal Radius Fractures Fixed With 1 or 2 Rows of Screws in Volar Locking Plates SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Distal radius fracture; DVR plate; secondary displacement; volar tilt ID FIXATION; OSTEOSYNTHESIS; MODEL AB Purpose We tested the null hypothesis that there is no difference in the change in volar tilt of the articular surface of the distal radius on lateral radiographs obtained before suture removal and 3 months or more after surgical fracture fixation when 1 or 2 rows of screws are used in the distal part of a volar locked plate. Methods We retrospectively identified 364 consecutive patients with a distal radius fracture treated by 2 surgeons with open reduction and volar locked plate fixation between 2007 and 2011 at our institution. A manually case-matched design with one-to-one matching of 2 different strategies for screws in the distal part of the plate (1 row versus 2 rows) on the basis of sex, AO type, presence of dorsal comminution, ulna fracture, mechanism of injury, and age (+/- 8 y) resulted in a group of 34 pairs, 68 total fractures. Radiographic alignment was measured before suture removal and 3 months or more after surgery. Results The change in volar tilt of the articular surface was -1.2 degrees in the. 1-row group and -0.9 degrees in the 2-row group, which was not significantly different. The secondary displacement of radial inclination and ulnar variance were likewise small and not statistically significant. Conclusions We found no advantage of 2 rows of distal screws over a single row of screws with respect to maintenance of achieved restoration of volar angulation after volar locked plate fixation of AO type A and C fractures of the distal radius. (J Hand Surg 2013;38A:297-301. Copyright (C) 2013 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Neuhaus, Valentin; Badri, Omar; Ferree, Steven; Bot, Arjan G. J.; Ring, David C.; Mudgal, Chaitanya S.] Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. RP Ring, DC (reprint author), Massachusetts Gen Hosp, Orthopaed Hand Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Neuhaus, Valentin/0000-0003-4012-5628 NR 19 TC 3 Z9 3 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD FEB PY 2013 VL 38A IS 2 BP 297 EP 301 DI 10.1016/j.jhsa.2012.10.040 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 087CR UT WOS:000314739400010 PM 23267755 ER PT J AU ten Berg, PWL Mudgal, CS Leibman, MI Belsky, MR Ruchelsman, DE AF ten Berg, Paul W. L. Mudgal, Chaitanya S. Leibman, Matthew I. Belsky, Mark R. Ruchelsman, David E. TI Quantitative 3-Dimensional CT Analyses of Intramedullary Headless Screw Fixation for Metacarpal Neck Fractures SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Hand fracture; headless screw; intramedullary fixation; metacarpal neck ID DISTAL RADIUS FRACTURES; K-WIRE FIXATION; CAPITELLAR FRACTURES; INTERNAL-FIXATION; PLATE FIXATION; OPEN REDUCTION; COMPLICATIONS; WRIST; HAND AB Purpose Fixation countersunk beneath the articular surface is well accepted for periarticular fractures. Limited open intramedullary headless compression screw (HCS) fixation offers clinical advantages over Kirschner wire and open techniques. We used quantitative 3-dimensional computed tomography to assess the articular starting point, surface area, and subchondral volumes used during HCS fixation of metacarpal neck fractures. Methods We simulated retrograde intramedullary insertion of 2.4- and 3.0-mm HCS and 1.1-mm Kirschner wires for metacarpal neck fracture fixation in 3-dimensional models from 16 adults. We used metacarpal head articular surface area (mm(2)) and subchondral volumes (mm(3)) and coronal and sagittal plane arcs of motion, during which we analyzed the center and rim of the articular base of the proximal phalanx engaging the countersunk entry site. Results Mean metacarpal head surface area mated to the proximal phalangeal base in neutral position was 93 mm(2); through the coronal plane arc (45 degrees) was 129 mm(2), and through the sagittal plane arc (120 degrees) was 265 mm(2) The mean articular surface area used by countersunk HCS threads was 12%, 8%, and 4%, respectively, in each of these arcs. The 1.1-mm Kirschner wire occupied 1.2%, 0.9%, and 0.4%, respectively. Mean metacarpal head volume was 927 mm(3). Mean subchondral volume occupied by the countersunk portion was 4%. The phalangeal base did not overlap the dorsally located countersunk entry site through most of the sagittal plane arc. During coronal plane motion in neutral extension, the center of the base never engaged the dorsally located countersunk entry site. Conclusions Metacarpal head surface area and subchondral head volume occupied by HCS were minimal. Articular surface area violation was least during the more clinically relevant sagittal plane arc of motion. Clinical relevance The dorsal articular starting point was in line with the medullary canal and avoided engaging the center of the articular base through most of the sagittal plane arc. Three-dimensional computed tomography data support the use of an articular starting point for these extra-articular fractures. (J Hand Surg 2013;38A:322-330. Copyright (C) 2013 by the American Society for Surgery of the Hand. All rights reserved.) C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hand & Upper Extrem Surg Serv, Boston, MA USA. Tufts Univ, Sch Med, Newton Wellesley Hosp, PC, Newton, MA USA. Acad Med Ctr, Amsterdam, Netherlands. RP Ruchelsman, DE (reprint author), Newton Wellesley Hosp, PC, 2000 Washington St,Blue Bldg,Suite 201, Newton, MA 02462 USA. EM druchelsman@partners.org NR 30 TC 8 Z9 8 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD FEB PY 2013 VL 38A IS 2 BP 322 EP 330 DI 10.1016/j.jhsa.2012.09.029 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 087CR UT WOS:000314739400014 PM 23200214 ER PT J AU Peters, F Vranceanu, AM Elbon, M Ring, D AF Peters, F. Vranceanu, A. -M. Elbon, M. Ring, D. TI Ganglions of the hand and wrist: determinants of treatment choice SO JOURNAL OF HAND SURGERY-EUROPEAN VOLUME LA English DT Article DE Depression; ganglions; pain catastrophizing; patient satisfaction; surgery ID PAIN CATASTROPHIZING SCALE; IDIOPATHIC ARM PAIN; VALIDATION; SYMPTOMS AB The aim of this study was to determine whether psychological factors (depression, catastrophic thinking, and pain anxiety) and pain intensity are associated with choice of operative treatment. Ninety new patients with a ganglion cyst on their hand or wrist completed psychological questionnaires (Pain Catastrophizing Scale, Pain Anxiety Symptoms Scale, and Center for the Epidemiological Study of Depression instrument) and an ordinal measure of pain intensity. After a minimum of 4 months, patients were contacted to determine if they chose operative treatment, to rate their pain intensity, and to complete the Disabilities of the Arm, Shoulder, and Hand questionnaire. Younger patients were more likely to choose operative treatment. Psychological factors were associated with pain intensity at enrolment, but not with treatment choice. Operative treatment did not result in less pain intensity or disability, or higher satisfaction compared with non-operative treatment. C1 [Peters, F.; Elbon, M.; Ring, D.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Vranceanu, A. -M.] Massachusetts Gen Hosp, Dept Behav Med, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org FU Wright; Biomet; Skeletal Dynamics FX David Ring MD PhD is a consultant for and has contracted royalties with Wright, Biomet, and Skeletal Dynamics. NR 18 TC 0 Z9 0 U1 0 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1753-1934 J9 J HAND SURG-EUR VOL JI J. Hand Surg.-Eur. Vol. PD FEB PY 2013 VL 38E IS 2 BP 151 EP 157 DI 10.1177/1753193412442468 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 085BX UT WOS:000314586800007 PM 22508801 ER PT J AU Hu, J Wen, PY Abrey, LE Fadul, CE Drappatz, J Salem, N Supko, JG Hochberg, F AF Hu, Jethro Wen, Patrick Y. Abrey, Lauren E. Fadul, Camilo E. Drappatz, Jan Salem, Nadia Supko, Jeffrey G. Hochberg, Fred TI A phase II trial of oral gimatecan for recurrent glioblastoma SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Gimatecan; Glioblastoma; Clinical trial; Camptothecin; Brain tumor; Glioma ID ADVANCED SOLID TUMORS; MALIGNANT GLIOMA; CAMPTOTHECIN GIMATECAN; EPITHELIAL OVARIAN; CLINICAL-TRIALS; STRAND BREAKS; IRINOTECAN; CANCER; ADULTS; ST1481 AB Gimatecan is a lipophilic oral camptothecin analogue with preclinical activity in glioma models. We conducted a multicenter phase II trial to evaluate the efficacy of gimatecan in adults with recurrent glioblastoma. Eligibility criteria included a parts per thousand currency sign1 prior treatment for recurrent disease, age a parts per thousand yen18, Eastern Cooperative Oncology Group performance status 0-1, and normal organ function. Patients taking enzyme-inducing anti-seizure medications were excluded. Gimatecan 1.22 mg/m(2) was given orally once daily for 5 consecutive days during each 28-day cycle. The primary endpoint was progression-free survival at 6 months. A Simon 2-stage optimal design was used in which 19 patients were evaluated in the 1st stage, with an additional 36 patients accrued if > 4 patients in stage 1 achieved PFS at 6 months. 29 patients were enrolled in the study, with median age of 58 years (range, 25-77 years); 58.6 % female. All patients received prior surgery, radiation therapy, and at least one chemotherapy regimen. The daily dose was reduced to 1.0 mg/m(2) after four of the first 10 patients experienced grade 4 hematologic toxicity. Treatment-related grade 3/4 toxicities included thrombocytopenia (17.2 %), leukopenia (17.2 %) and neutropenia (10.3 %). None of the 19 patients treated at 1.0 mg/m(2)/day experienced grade 4 hematologic toxicity. One patient had a partial radiographic response by modified Macdonald criteria. Only 3 patients (12 %) were progression-free at 6 months. Median time to progression was 12.0 weeks (7.0, 17.0).Treatment with gimatecan 1.0 mg/m(2)/day for 5 days, repeated every 28-days showed minimal efficacy. C1 [Hu, Jethro] Johnnie L Cochran Jr Brain Tumor Ctr, Los Angeles, CA 90048 USA. [Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02215 USA. [Abrey, Lauren E.] Univ Zurich, Dept Neurol, Zurich, Switzerland. [Fadul, Camilo E.] Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. [Drappatz, Jan] UPMC Canc Pavil, Pittsburgh, PA 15232 USA. [Salem, Nadia] Sigma Tau Pharmaceut Inc, Gaithersburg, MD 20878 USA. [Supko, Jeffrey G.] Massachusetts Gen Hosp, Clin Pharmacol Lab, Boston, MA 02114 USA. [Hochberg, Fred] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stephen E & Catherine Pappas Ctr Neurooncol,Canc, Boston, MA 02114 USA. RP Hu, J (reprint author), Johnnie L Cochran Jr Brain Tumor Ctr, 8631 W 3rd St,Suite 410E, Los Angeles, CA 90048 USA. EM jethro.hu@gmail.com FU Sigma-Tau Research FX Grant support from Sigma-Tau Research. NR 30 TC 8 Z9 8 U1 2 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD FEB PY 2013 VL 111 IS 3 BP 347 EP 353 DI 10.1007/s11060-012-1023-0 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 086VC UT WOS:000314715100015 PM 23232808 ER PT J AU Ransom, CB Tao, WC Wu, YM Spain, WJ Richerson, GB AF Ransom, Christopher B. Tao, Wucheng Wu, Yuanming Spain, William J. Richerson, George B. TI Rapid regulation of tonic GABA currents in cultured rat hippocampal neurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE tonic inhibition; gamma-aminobutyric acid receptor type A; gamma-aminobutyric acid transporter type 1; seizure ID CEREBELLAR GRANULE CELLS; ACTIVITY-DEPENDENT DISINHIBITION; CHLORIDE ACCUMULATION; DENTATE GYRUS; DELTA-SUBUNIT; MOUSE MODEL; IONIC BASIS; RECEPTORS; INHIBITION; TRANSPORTER AB Ransom CB, Tao W, Wu Y, Spain WJ, Richerson GB. Rapid regulation of tonic GABA currents in cultured rat hippocampal neurons. J Neurophysiol 109: 803-812, 2013. First published October 31, 2012; doi:10.1152/jn.00460.2012.-Subacute and chronic changes in tonic GABAergic inhibition occur in human and experimental epilepsy. Less is known about how tonic inhibition is modulated over shorter time frames (seconds). We measured endogenous tonic GABA currents from cultured rat hippocampal neurons to evaluate how they are affected by 1) transient increases in extracellular GABA concentration ([GABA]), 2) transient postsynaptic depolarization, and 3) depolarization of presynaptic cells. Transient increases in [GABA] (1 mu M) reduced tonic currents; this reduction resulted from GABA-induced shifts in the reversal potential for GABA currents (E-GABA). Transient depolarization of postsynaptic neurons reversed the effects of exogenous GABA and potentiated tonic currents. The voltage-dependent potentiation of tonic GABA currents was independent of E-GABA shifts and represented postdepolarization potentiation (PDP), an intrinsic GABA(A) receptor property (Ransom CB, Wu Y, Richerson GB. J Neurosci 30: 7672-7684, 2010). Inhibition of vesicular GABA release with concanamycin A (ConA) did not affect tonic currents. In ConA-treated cells, transient application of 12 mM K+ to depolarize presynaptic neurons and glia produced a persistent increase in tonic current amplitude. The K+-induced increase in tonic current was reversibly inhibited by SKF89976a (40 mu M), indicating that this was caused by nonvesicular GABA release from GABA transporter type 1 (GAT1). Nonvesicular GABA release due to GAT1 reversal also occurred in acute hippocampal brain slices. Our results indicate that tonic GABA currents are rapidly regulated by GABA-induced changes in intracellular Cl- concentration, PDP of extrasynaptic GABA(A) receptors, and nonvesicular GABA release. These mechanisms may influence tonic inhibition during seizures when neurons are robustly depolarized and extracellular GABA and K+ concentrations are elevated. C1 [Ransom, Christopher B.; Spain, William J.] Vet Affairs Puget Sound Hlth Care Syst, Epilepsy Ctr Excellence, Seattle, WA USA. [Ransom, Christopher B.; Spain, William J.] Univ Washington, Dept Neurol, Seattle, WA 98105 USA. [Tao, Wucheng; Spain, William J.] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98105 USA. [Wu, Yuanming; Richerson, George B.] Univ Iowa, Dept Neurol, Iowa City, IA 52242 USA. [Richerson, George B.] Univ Iowa, Dept Mol Physiol & Biophys, Iowa City, IA USA. RP Ransom, CB (reprint author), Univ Washington, Epilepsy Ctr Excellence, VA Puget Sound Hlth Care Syst, Dept Neurol, Seattle, WA 98105 USA. EM cbr5@u.washington.edu FU Department of Veterans Affairs Health Administration; National Institutes of Health; National Epifellows Foundation FX This work was supported by the Department of Veterans Affairs Health Administration (C. B. Ransom, W. J. Spain), the National Institutes of Health (G. B. Richerson), and the National Epifellows Foundation (C. B. Ransom). NR 60 TC 9 Z9 10 U1 2 U2 13 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB PY 2013 VL 109 IS 3 BP 803 EP 812 DI 10.1152/jn.00460.2012 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 085TI UT WOS:000314636800019 PM 23114210 ER PT J AU Gharagouzloo, CA Madi, S Seethamraju, RT Harisinghani, M Sridhar, S AF Gharagouzloo, C. A. Madi, S. Seethamraju, R. T. Harisinghani, M. Sridhar, S. TI Ultrashort TE imaging with SPIONs: bright prospects for in vivo applications SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT AACR/SNMMI Conference on State-of-the-Art Molecular Imaging in Cancer Biology and Therapy CY FEB 27-MAR 02, 2013 CL San Diego, CA SP Amer Assoc Canc Res (AACR), Soc Nucl Med & Mol Imaging (SNMMI) C1 [Gharagouzloo, C. A.; Sridhar, S.] Northeastern Univ, Boston, MA 02115 USA. [Madi, S.] Bruker BioSpin Corp, Billerica, MA USA. [Seethamraju, R. T.] Siemens Med Solut USA Inc, Boston, MA USA. [Harisinghani, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD FEB 1 PY 2013 VL 54 SU 1 BP 9 EP 9 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 086NK UT WOS:000314691400029 ER PT J AU Moore, A AF Moore, A. TI Image-guided siRNA and miRNA therapies SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT AACR/SNMMI Conference on State-of-the-Art Molecular Imaging in Cancer Biology and Therapy CY FEB 27-MAR 02, 2013 CL San Diego, CA SP Amer Assoc Canc Res (AACR), Soc Nucl Med & Mol Imaging (SNMMI) C1 [Moore, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD FEB 1 PY 2013 VL 54 SU 1 BP 33 EP 33 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 086NK UT WOS:000314691400103 ER PT J AU Choi, JG Kim, SY Perez-Atayde, AR Padwa, BL AF Choi, James G. Kim, Sang Yoon Perez-Atayde, Antonio R. Padwa, Bonnie L. TI Bilateral Coronoid Process Hyperplasia With Pseudocartilaginous Joint Formation: Jacob Disease SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID 3-DIMENSIONAL COMPUTED-TOMOGRAPHY; OSTEOCHONDROMA; MANAGEMENT C1 [Choi, James G.] Univ Penn, Sch Dent Med, Philadelphia, PA 19104 USA. [Kim, Sang Yoon] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Perez-Atayde, Antonio R.] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA. [Padwa, Bonnie L.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Padwa, Bonnie L.] Childrens Hosp Boston, Sect Oral & Maxillofacial Surg, Boston, MA USA. RP Padwa, BL (reprint author), Childrens Hosp Boston, Dept Plast & Oral Surg, 300 Longwood Ave, Boston, MA 02115 USA. EM bonnie.padwa@childrens.harvard.edu OI kim, sang/0000-0002-5860-3491 NR 13 TC 2 Z9 2 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD FEB PY 2013 VL 71 IS 2 BP 316 EP 321 DI 10.1016/j.joms.2012.05.029 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 086TN UT WOS:000314710200029 PM 22871308 ER PT J AU Kumar, N Garg, N Bailey, A AF Kumar, Nilay Garg, Neetika Bailey, Amos TI Opiate Receptor Antagonists for Treatment of Severe Pruritus Associated with Advanced Cholestatic Liver Disease SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Letter ID DOUBLE-BLIND C1 [Kumar, Nilay] Univ Alabama Birmingham, Dept Internal Med, Birmingham, AL 35294 USA. [Garg, Neetika] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Bailey, Amos] Birmingham VA Med Ctr, Div Palliat Care & Hosp Med, Birmingham, AL USA. RP Kumar, N (reprint author), Univ Alabama Birmingham, Dept Internal Med, BDB 327,1530 3rd Ave S, Birmingham, AL 35294 USA. EM nkumar@uab.edu OI Garg, Neetika/0000-0002-7001-2168 NR 6 TC 3 Z9 3 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 FEB PY 2013 VL 16 IS 2 BP 122 EP 123 DI 10.1089/jpm.2012.0452 PG 2 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 088FB UT WOS:000314818100003 PM 23391399 ER PT J AU Goldstein, R Rimer, KP AF Goldstein, Richard Rimer, Kathleen P. TI Parents' Views of Their Child's End-of-Life Care: Subanalysis of Primary Care Involvement SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID PEDIATRIC PALLIATIVE CARE; GENERAL-PRACTITIONERS; LAST YEAR; EDUCATION; PLACE; DEATH; NEEDS; HOME AB Background: The medical literature encourages primary care pediatricians (PCPs) to play a role in the care of patients who are dying. Actual involvement has not been investigated. Objective: Our objective was to explore current involvement of PCPs when their patients face the end of life and bereaved parents' attitudes toward it. Design: Individual, in-depth, semi-structured interviews were conducted using a focused ethnographic technique. Qualitative analysis was performed on the interviews. Setting/Subjects: Most (14/16) interviews were conducted in the family's home, involving parents of Massachusetts children who died aged 1 month to 11 years during 2005. Measurements: Themes identified through thematic analysis of interview transcripts were utilized. Results: Interviews were thematically analyzed, revealing four categories of themes: 1) the role of individual PCP in decision making and care at end of life; 2) general attitudes about the care provided by the PCP; 3) the impact of practice infrastructure on the PCP's care; and 4) bereavement involvement. From the interviews we hypothesize that PCPs play a supportive and appreciated role while having limited involvement in decision making and care; an involved PCP acting with knowledge of a family may in some cases provide profound guidance, but that kind of involvement is not typical; and although there is an articulated role for the PCP with the parents' and siblings' bereavement, it is not routinely exercised. Conclusions: The interviews suggest limited involvement by PCPs in care at the end of life and subsequent bereavement. Parents overall seem to accept this role. Further research is needed to examine these observations from the perspective of PCPs. C1 [Goldstein, Richard] Childrens Hosp, Dana Farber Canc Inst, Pediat Adv Care Team, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Rimer, Kathleen P.] Beth Israel Deaconess Med Ctr, Dept Pastoral Care & Educ, Boston, MA 02215 USA. RP Goldstein, R (reprint author), Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, 450 Brookline Ave,SW411, Boston, MA 02215 USA. EM richard_goldstein@dfci.harvard.edu FU Cameron and Hayden Lord Foundation FX This research was supported by a grant from the Cameron and Hayden Lord Foundation. We also thank Barry Zuckerman, M. D., Susan Block, M. D., and Joanne Wolfe, M. D., M. P. H., for their invaluable support for this project. NR 26 TC 3 Z9 3 U1 0 U2 18 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 FEB PY 2013 VL 16 IS 2 BP 198 EP 202 DI 10.1089/jpm.2012.0269 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 088FB UT WOS:000314818100017 PM 23098631 ER PT J AU Cheng, JT Hamade, M Merchant, SN Rosowski, JJ Harrington, E Furlong, C AF Cheng, Jeffrey Tao Hamade, Mohamad Merchant, Saumil N. Rosowski, John J. Harrington, Ellery Furlong, Cosme TI Wave motion on the surface of the human tympanic membrane: Holographic measurement and modeling analysis SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID TIME-AVERAGED HOLOGRAPHY; MIDDLE-EAR TRANSMISSION; DOPPLER VIBROMETER LDV; HUMAN TEMPORAL BONES; REFLECTION COEFFICIENT; ENERGY REFLECTANCE; INPUT IMMITTANCE; SOUND PRESSURE; EARDRUM; IMPEDANCE AB Sound-induced motions of the surface of the tympanic membrane (TM) were measured using stroboscopic holography in cadaveric human temporal bones at frequencies between 0.2 and 18 kHz. The results are consistent with the combination of standing-wave-like modal motions and traveling-wave-like motions on the TM surface. The holographic techniques also quantified sound-induced displacements of the umbo of the malleus, as well as volume velocity of the TM. These measurements were combined with sound-pressure measurements near the TM to compute middle-ear input impedance and power reflectance at the TM. The results are generally consistent with other published data. A phenomenological model that behaved qualitatively like the data was used to quantify the relative magnitude and spatial frequencies of the modal and traveling-wave-like displacement components on the TM surface. This model suggests the modal magnitudes are generally larger than those of the putative traveling waves, and the computed wave speeds are much slower than wave speeds predicted by estimates of middle-ear delay. While the data are inconsistent with simple modal displacements of the TM, an alternate model based on the combination of modal motions in a lossy membrane can also explain these measurements without invoking traveling waves. (C) 2013 Acoustical Society of America. [http://dx.doi.org/10.1121/1.4773263] C1 [Cheng, Jeffrey Tao; Hamade, Mohamad; Merchant, Saumil N.; Rosowski, John J.; Furlong, Cosme] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Harrington, Ellery; Furlong, Cosme] Worcester Polytech Inst, Dept Mech Engn, Ctr Holog Studies & Laser MicromechaTron, Worcester, MA 01609 USA. [Cheng, Jeffrey Tao; Hamade, Mohamad; Merchant, Saumil N.; Rosowski, John J.; Furlong, Cosme] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Rosowski, John J.] MIT Harvard Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. RP Cheng, JT (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM Tao_Cheng@meei.harvard.edu FU NIDCD [NRSA 1F32DC009949-01, 1R03DC011617-01, R01-DC008642] FX The authors thank Diane Jones at the Eaton-Peabody Laboratory of the Massachusetts Eye and Ear Infirmary (MEEI) for help in acquiring TB specimens. Dr. Maria del Socorro Hernandez-Montes, Ivo Dobrev, Dr. Mauricio Flores-Moreno, and Christopher Scarpino from the Center for Holographic Studies and Laser Mico-mechaTronics at the Worcester Polytechnic Institute have provided technical assistances in the use of the holographic interferometry system. We value discussions with Michael Ravicz, Dr. Heidi Nakajima, Melissa Woods, and Rachelle Horwitz at MEEI and Jef Aernouts of the University of Antwerp regarding our results. We also acknowledge the help of the four reviewers, all of whom helped improve the paper. This work was supported by NRSA 1F32DC009949-01, 1R03DC011617-01, and R01-DC008642 from NIDCD and a donation from L. Mittal. NR 54 TC 32 Z9 33 U1 0 U2 8 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD FEB PY 2013 VL 133 IS 2 BP 918 EP 937 DI 10.1121/1.4773263 PG 20 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 080TW UT WOS:000314267200040 PM 23363110 ER PT J AU Nigwekar, SU Thadhani, RI AF Nigwekar, Sagar U. Thadhani, Ravi I. TI Shining light on vitamin D trials in chronic kidney disease SO KIDNEY INTERNATIONAL LA English DT Editorial Material ID D THERAPY; INSULIN; CALCITRIOL AB Vitamin D compounds may have extraskeletal functions. Chronic kidney disease (CKD) offers an opportunity to investigate these actions, as vitamin D deficiency is prevalent in this population and actions of vitamin D such as those on the heart and glucose metabolism are highly relevant. However, recent randomized controlled trials have tempered enthusiasm. We appraise a trial by de Boer et al. that addresses effects of paricalcitol on glucose metabolism in CKD, and offer perspectives on future trials. Kidney International (2013) 83, 198-200. doi:10.1038/ki.2012.415 C1 [Nigwekar, Sagar U.; Thadhani, Ravi I.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Nigwekar, Sagar U.] Harvard Univ, Sch Med, Scholars Clin Sci Program, Boston, MA USA. RP Thadhani, RI (reprint author), Massachusetts Gen Hosp, Bulfinch 127,55 Fruit St, Boston, MA 02114 USA. EM rthadhani@partners.org FU NIDDK NIH HHS [K24 DK094872] NR 12 TC 4 Z9 4 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 2013 VL 83 IS 2 BP 198 EP 200 DI 10.1038/ki.2012.415 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 085NM UT WOS:000314621500006 PM 23364588 ER PT J AU de Boer, IH Sachs, M Hoofnagle, AN Utzschneider, KM Kahn, SE Kestenbaum, B Himmelfarb, J AF de Boer, Ian H. Sachs, Michael Hoofnagle, Andrew N. Utzschneider, Kristina M. Kahn, Steven E. Kestenbaum, Bryan Himmelfarb, Jonathan TI Paricalcitol does not improve glucose metabolism in patients with stage 3-4 chronic kidney disease SO KIDNEY INTERNATIONAL LA English DT Article DE chronic kidney disease; clinical trial; insulin resistance; metabolism; vitamin D ID FIBROBLAST GROWTH FACTOR-23; RANDOMIZED CONTROLLED-TRIAL; GLOMERULAR-FILTRATION-RATE; FGF23 GENE-EXPRESSION; VITAMIN-D THERAPY; INSULIN-RESISTANCE; SECONDARY HYPERPARATHYROIDISM; HEMODIALYSIS-PATIENTS; 1,25-DIHYDROXYVITAMIN D-3; INTRAVENOUS CALCITRIOL AB Patients with chronic kidney disease are often insulin resistant and glucose intolerant abnormalities that promote cardiovascular disease. Administration of 1,25-dihydroxyvitamin D (calcitriol) has improved glucose metabolism in patients with end-stage renal disease. We conducted a randomized, placebo-controlled clinical trial to test whether paricalcitol, a 1,25-dihydroxyvitamin D analog, changes glucose tolerance in earlier stages of chronic kidney disease. In a crossover design, 22 nondiabetic patients with estimated glomerular filtration rates of stage 3-4 chronic kidney disease and fasting plasma glucose of 100-125 mg/dl were given daily oral paricalcitol for 8 weeks and matching placebo for 8 weeks, separated by an 8-week washout period. The order of interventions was random and blinded to both participants and investigators. Paricalcitol significantly reduced serum concentrations of parathyroid hormone, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D while significantly increasing serum concentrations of fibroblast growth factor-23 and 24,25-dihydroxyvitamin D. Paricalcitol, however, had no significant effect on glucose tolerance (the primary outcome measure), insulin sensitivity, beta-cell insulin response, plasma free fatty acid suppression, or urinary F2-isoprostane excretion. Thus, despite substantial effects on vitamin D metabolism, paricalcitol did not improve glucose metabolism in nondiabetic patients with stage 3-4 chronic kidney disease. Kidney International (2013) 83, 323-330; doi:10.1038/ki.2012.311; published online 22 August 2012 C1 [de Boer, Ian H.; Sachs, Michael; Kestenbaum, Bryan; Himmelfarb, Jonathan] Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98104 USA. [de Boer, Ian H.; Sachs, Michael; Kestenbaum, Bryan; Himmelfarb, Jonathan] Univ Washington, Dept Med, Kidney Res Inst, Seattle, WA 98104 USA. [de Boer, Ian H.; Kestenbaum, Bryan] Univ Washington, Dept Epidemiol, Seattle, WA 98104 USA. [Hoofnagle, Andrew N.] Univ Washington, Dept Lab Med, Seattle, WA 98104 USA. [Utzschneider, Kristina M.; Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Utzschneider, Kristina M.; Kahn, Steven E.] Univ Washington, Seattle, WA 98104 USA. RP de Boer, IH (reprint author), Univ Washington, Dept Med, Div Nephrol, Box 359606,325 9th Ave, Seattle, WA 98104 USA. EM deboer@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 FU Abbott Laboratories; National Institutes of Health [1R01DK087726, 1R01HL096875, 5R01HL070938, 5KL2RR025015, P30DK035816, 5P30DK017047, UL1RR025014]; Veterans Affairs Puget Sound Health Care System, Seattle, WA FX This work was supported by an investigator-initiated grant from Abbott Laboratories and by grants 1R01DK087726, 1R01HL096875, 5R01HL070938, 5KL2RR025015, P30DK035816, 5P30DK017047, and UL1RR025014 from the National Institutes of Health. This material is the result of work supported in part by resources from the Veterans Affairs Puget Sound Health Care System, Seattle, WA. We thank the study participants for their generous dedication and Laura Curtin, BS, Alexandra Flynn, MD, Aparna Lakshman, BA, and the staff of the University of Washington Investigational Drug Services and Clinical Research Center for their hard work. NR 52 TC 14 Z9 14 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 2013 VL 83 IS 2 BP 323 EP 330 DI 10.1038/ki.2012.311 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 085NM UT WOS:000314621500022 PM 22913981 ER PT J AU Hardin, C Fredberg, JJ Krishnan, R AF Hardin, Corey Fredberg, Jeffrey J. Krishnan, Ramaswamy TI Real estate of monolayer permeability: location location location SO LABORATORY INVESTIGATION LA English DT Editorial Material ID COLLECTIVE CELL-MIGRATION; PHYSICAL FORCES C1 [Hardin, Corey] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Fredberg, Jeffrey J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Krishnan, Ramaswamy] Beth Israel Deaconess Med Ctr, Ctr Vasc Biol, Boston, MA 02215 USA. RP Fredberg, JJ (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM jjf@harvard.edu FU NHLBI NIH HHS [R01 HL107561] NR 14 TC 0 Z9 0 U1 0 U2 13 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 FEB PY 2013 VL 93 IS 2 BP 148 EP 150 DI 10.1038/labinvest.2012.168 PG 3 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 084SF UT WOS:000314558700001 PM 23361599 ER PT J AU Royall, DR AF Royall, Donald R. TI Fortress Brain SO MEDICAL HYPOTHESES LA English DT Article ID SIMPLEX-VIRUS TYPE-1; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; NEUROFIBRILLARY TANGLES; PARKINSONS-DISEASE; PERINEURONAL NETS; FOLLOW-UP; EXPRESSION; TAU; DISORDERS AB Neurodegenerative diseases are associated with neuronal inclusions, comprised of protein aggregates. In Alzheimer's Disease (AD) and Lewy Body Disease (LBD) such lesions are distributed in a hierarchical retrograde transynaptic spatial pattern. This implies a retrograde transynaptic temporal propagation as well. There can be few explanations for this other than infectious agents (prions and viruses). This suggests that AD and LBD (at least) may have infectious origins. Transynaptic infiltration of the CNS along cranial nerve or other major projections, by one or more infectious agents has important implications. The clinical syndrome and natural history of each neurodegenerative disorder will reflect its portal of entry. There may be a different neurodegenerative syndrome for each cranial nerve or other portal of entry, and not all may manifest as "dementia". Each syndrome may be associated with more than one pathological lesion. Each pathology may be associated with several clinical syndromes. Host-parasite interactions are species specific. This may explain the rarity of AD-like pathology in most other older mammals. Over evolutionary timescales, the human brain should be adapted to predation by neurotropic agents. Viewed from this perspective, the prion-like pro-inflammatory and pro-apoptotic properties of beta-amyloid and other proteins may be adaptive, and anti-microbial. Reductions in synaptic density may slow the progress of invading pathogens, while perineuronal nets and other structures may guard the gates. This suggests a defense in depth of a structure, the brain, that is inherently vulnerable to invasion along its neural networks. (c) 2012 Elsevier Ltd. All rights reserved. C1 [Royall, Donald R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Royall, Donald R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Royall, Donald R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA. [Royall, Donald R.] S Texas Vet Hlth Syst, Audie L Murphy Div, GRECC, San Antonio, TX USA. RP Royall, DR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. EM royall@uthscsa.edu NR 48 TC 1 Z9 1 U1 0 U2 9 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD FEB PY 2013 VL 80 IS 2 BP 118 EP 121 DI 10.1016/j.mehy.2012.11.005 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 083SO UT WOS:000314485700004 PM 23265350 ER PT J AU Cipriani, NA McLaughlin, PJ Borger, DR Nielsen, GP AF Cipriani, N. A. McLaughlin, P. J. Borger, D. R. Nielsen, G. P. TI BRAF Mutation in "Sarcomas": A Possible Method To Detect Melanomas SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Cipriani, N. A.; McLaughlin, P. J.; Borger, D. R.; Nielsen, G. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 30 BP 10A EP 10A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444400031 ER PT J AU Cipriani, NA Kurzawa, P Mullen, J Deshpande, V Ahmad, R Nielsen, GP AF Cipriani, N. A. Kurzawa, P. Mullen, J. Deshpande, V. Ahmad, R. Nielsen, G. P. TI Prognostic Value of Subclassification of Pleomorphic Soft Tissue Sarcoma (STS): Myogenic Versus Non-Myogenic Differentiation SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Greater Poland Canc Ctr, Poznan, Poland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 31 BP 10A EP 11A PG 2 WC Pathology SC Pathology GA 083EB UT WOS:000314444400032 ER PT J AU Kerr, DA Deshpande, V Kurzawa, P Nielsen, GP AF Kerr, D. A. Deshpande, V. Kurzawa, P. Nielsen, G. P. TI Chondroid Chordoma: A Chordoma Subtype with Worse Prognosis SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Greater Poland Canc Ctr, Poznan, Poland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 47 BP 14A EP 14A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444400048 ER PT J AU Lee, YD Nardi, V Le, LP Deshpande, V Hornicek, FJ Iafrate, AJ Nielsen, GP AF Lee, Y. D. Nardi, V. Le, L. P. Deshpande, V. Hornicek, F. J. Iafrate, A. J. Nielsen, G. P. TI Array Comparative Genomic Hybridization Analysis of a Conventional Chordoma and an Adjacent Benign Notochordal Tumor Shows No Direct Lineage Relationship SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Lee, Y. D.; Nardi, V.; Le, L. P.; Deshpande, V.; Hornicek, F. J.; Iafrate, A. J.; Nielsen, G. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 56 BP 16A EP 17A PG 2 WC Pathology SC Pathology GA 083EB UT WOS:000314444400057 ER PT J AU Shah, K Zhang, Y Nielsen, GP Rosenberg, AE AF Shah, K. Zhang, Y. Nielsen, G. P. Rosenberg, A. E. TI Primary Myoepithelioma of the Orbit SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Univ Miami, Miller Sch Med, Jackson Mem Hosp, Miami, FL 33136 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 71 BP 20A EP 20A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444400072 ER PT J AU Zhang, Y Nielsen, GP Raskin, K Cipriani, N Rosenberg, AE AF Zhang, Y. Nielsen, G. P. Raskin, K. Cipriani, N. Rosenberg, A. E. TI Primary Malignant Myoepithelial Tumor of Bone SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Univ Miami, Miller Sch Med, Jackson Mem Hosp, Miami, FL 33136 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 94 BP 25A EP 25A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444400095 ER PT J AU Brachtel, EF Kerr, SE Anderson, J Zhang, Y Singh, V Erlander, MG Carey, B Highsmith, WE Schnabel, CA Dry, SM Sullivan, PS AF Brachtel, E. F. Kerr, S. E. Anderson, J. Zhang, Y. Singh, V. Erlander, M. G. Carey, B. Highsmith, W. E. Schnabel, C. A. Dry, S. M. Sullivan, P. S. TI Diagnostic Utility of a 92-Gene Classifier in Triple-Negative Breast Carcinomas SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Mayo Clin, Rochester, MN USA. BioTheranostics Inc, San Diego, CA USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 121 BP 31A EP 31A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444400123 ER PT J AU Marques, RC Lerwill, MF AF Canas Marques, R. Lerwill, M. F. TI Incidence of Carcinoma and Atypia in Breast Reduction Mammoplasty Specimens SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 EPE, Inst Portugues Oncol Lisboa Francisco Gentil, Lisbon, Portugal. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 126 BP 32A EP 32A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444400128 ER PT J AU Auger, M Nayar, R Khalbuss, WE Barkan, GA Benedict, C Tambouret, R Schwartz, MR Howell, L Souers, R Hartley, A Thomas, N Moriarty, AT AF Auger, M. Nayar, R. Khalbuss, W. E. Barkan, G. A. Benedict, C. Tambouret, R. Schwartz, M. R. Howell, L. Souers, R. Hartley, A. Thomas, N. Moriarty, A. T. TI Implementation of the Bethesda System for Reporting Thyroid Cytopathology: Observations from the 2011 Thyroid Supplemental Questionnaire of the College of American Pathologists SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 McGill Univ, Montreal, PQ, Canada. McGill Unvers Hlth Ctr, Montreal, PQ, Canada. Northwestern Univ, Chicago, IL 60611 USA. NW Mem Hosp, Chicago, IL 60611 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Loyola Univ, Maywood, IL 60153 USA. Loyola Univ, Med Ctr Bedside Test, Maywood, IL 60153 USA. DCL Pathol LLC, Indianapolis, IN USA. Harvard Univ, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Methodist Hosp, Phys Org, Houston, TX 77030 USA. Univ Calif Davis, Sacramento, CA 95817 USA. Univ Calif Davis, Sch Med, Sacramento, CA 95817 USA. Coll Amer Pathologists, Northfield, MN USA. AmeriPath Indiana, Indianapolis, IN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 338 BP 83A EP 83A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444400341 ER PT J AU Balassanian, R Ono, JC Wool, GD Olejnik-Nave, J Mah, MM Sweeney, BJ Ljung, BM Pitman, MB AF Balassanian, R. Ono, J. C. Wool, G. D. Olejnik-Nave, J. Mah, M. M. Sweeney, B. J. Ljung, B-M Pitman, M. B. TI A SuperiorTechnique for Cell Block Preparation for Fine Needle Aspiration SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Lab Med Consultants, Las Vegas, NV USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 340 BP 83A EP 83A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444400343 ER PT J AU Linskey, K Kay, J Duncan, LM Nazarian, RM AF Linskey, K. Kay, J. Duncan, L. M. Nazarian, R. M. TI Wnt and Hedgehog Signaling Pathway Activation in Cutaneous Fibrosing Disorders: A Tissue Microarray Study SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. UMass Mem Med Ctr, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 479 BP 116A EP 117A PG 2 WC Pathology SC Pathology GA 083EB UT WOS:000314444400482 ER PT J AU Mochel, M Arakaki, R Wang, G Kroshinsky, D Hoang, M AF Mochel, M. Arakaki, R. Wang, G. Kroshinsky, D. Hoang, M. TI A Retrospective Histologic and Histochemical Evaluation of Cutaneous Calciphylaxis SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Mochel, M.; Arakaki, R.; Wang, G.; Kroshinsky, D.; Hoang, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 482 BP 117A EP 117A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444400485 ER PT J AU Prieto-Granada, CN Lezcano, C Piris, A Scoyler, R Mihm, M AF Prieto-Granada, C. N. Lezcano, C. Piris, A. Scoyler, R. Mihm, M. TI Lethal Childhood Melanoma: A Clinicopathological Study of 12 Cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Baystate Med Ctr, Springfield, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Sydney Med Sch, Sydney, NSW, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 489 BP 119A EP 119A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444400492 ER PT J AU Cipriani, NA Faquin, WC Sadow, PM AF Cipriani, N. A. Faquin, W. C. Sadow, P. M. TI Clear Cell Variant of Thyroid Carcinoma: A Clinicopathologic Study SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Cipriani, N. A.; Faquin, W. C.; Sadow, P. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 542 BP 131A EP 131A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444400545 ER PT J AU Agoston, AT Zheng, Y Bueno, R Lauwers, GY Odze, RD Srivastava, A AF Agoston, A. T. Zheng, Y. Bueno, R. Lauwers, G. Y. Odze, R. D. Srivastava, A. TI Clinicopathologic Predictors of Long Term and Disease-Free Survival in Esophageal Adenocarcinomas with Complete Pathologic Response to Neoadjuvant Chemoradiation SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 592 BP 142A EP 142A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444400595 ER PT J AU Arnason, T Pino, MS Chung, DC Sapp, HL Rayson, D Deshpande, V Zukerberg, LR AF Arnason, T. Pino, M. S. Chung, D. C. Sapp, H. L. Rayson, D. Deshpande, V. Zukerberg, L. R. TI Loss of Cables Expression in Neuroendocrine Tumors (NETS) of the Gastrointestinal Tract, Pancreas, and Lung SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Queen Elizabeth II HSC, Halifax, NS, Canada. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 600 BP 143A EP 144A PG 2 WC Pathology SC Pathology GA 083EB UT WOS:000314444401005 ER PT J AU Arnason, T Brown, I O'Brien, B Wilson, C Winter, H Lauwers, GY AF Arnason, T. Brown, I. O'Brien, B. Wilson, C. Winter, H. Lauwers, G. Y. TI Collagenous Gastritis: A Morphologic and Immunohistochemical Study of 27 Cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia. Sullivan Nicolaides Pathol, Brisbane, Qld, Australia. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 601 BP 144A EP 144A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401006 ER PT J AU Bandla, S Peters, JH Ruff, D Chen, SM Li, CY Song, K Thoms, K Litle, VR Watson, T Chapurin, N Pennathur, A Luketich, JD Peterson, D Dulak, A Lin, L Bass, A Beer, DG Godfrey, TE Zhou, Z AF Bandla, S. Peters, J. H. Ruff, D. Chen, S-M Li, C-Y Song, K. Thoms, K. Litle, V. R. Watson, T. Chapurin, N. Pennathur, A. Luketich, J. D. Peterson, D. Dulak, A. Lin, L. Bass, A. Beer, D. G. Godfrey, T. E. Zhou, Z. TI Analysis of Columnar Lined Esophagus Reveals Less Frequent Mutations in Non-Goblet Cell Metaplasia Than Intestinal Metaplasia SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 URMC, Rochester, NY USA. Univ Pittsburgh, Pittsburgh, PA USA. Life Technol, Foster City, CA USA. Dana Farber Canc Ctr, Boston, MA USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 604 BP 145A EP 145A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401009 ER PT J AU Bledsoe, JR Kamionek, M Shvetz, DE Mino-Kenudson, M AF Bledsoe, J. R. Kamionek, M. Shvetz, D. E. Mino-Kenudson, M. TI Loss of Expression of ARID1A and BRG1 in Colorectal Cancer Occurs Infrequently and Is Associated with BRAF Mutation and Microsatellite Instability SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Bledsoe, J. R.; Kamionek, M.; Shvetz, D. E.; Mino-Kenudson, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 608 BP 145A EP 146A PG 2 WC Pathology SC Pathology GA 083EB UT WOS:000314444401013 ER PT J AU Bledsoe, JR Shvetz, DE Mino-Kenudson, M AF Bledsoe, J. R. Shvetz, D. E. Mino-Kenudson, M. TI Phosphorylation of EGFR in Colorectal Cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Bledsoe, J. R.; Shvetz, D. E.; Mino-Kenudson, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 607 BP 145A EP 145A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401012 ER PT J AU Deshpande, A Deshpande, V O'Brien, MJ AF Deshpande, A. Deshpande, V. O'Brien, M. J. TI Interstitial Cells of Cajal in Gastrointestinal Leiomyoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Boston Med Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 621 BP 149A EP 149A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401026 ER PT J AU Huang, Q Shi, J Sun, Q Yu, H Chen, J Wu, H Gold, JK Mashimo, H Yu, C Lauwers, GY AF Huang, Q. Shi, J. Sun, Q. Yu, H. Chen, J. Wu, H. Gold, J. K. Mashimo, H. Yu, C. Lauwers, G. Y. TI Small (<= 2 cm) Carcinomas in the Proximal Stomach Demonstrate Distinct Clinicopathologic Features from Those in the Distal and Corpus: A Proposal for Classification of Gastric Cancer by Location SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Nanjing Drum Tower Hosp, Nanjing, Peoples R China. VA Boston Healthcare Syst, W Roxbury, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 648 BP 155A EP 155A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401053 ER PT J AU Imamura, Y Fuchs, C Ogino, S AF Imamura, Y. Fuchs, C. Ogino, S. TI KRAS c.35G > T (p.G12V) and c.34G > C (p.G12R) Mutations Predict Shorter Survival in 1925 Colorectal Cancers SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 651 BP 156A EP 157A PG 2 WC Pathology SC Pathology GA 083EB UT WOS:000314444401056 ER PT J AU Kuchiba, A Lochhead, P Ogino, S AF Kuchiba, A. Lochhead, P. Ogino, S. TI Colon Cancer Nodal Staging Score: A Tool To Assess Adequacy of Nodal Harvesting in Pathology Practice SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 672 BP 161A EP 162A PG 2 WC Pathology SC Pathology GA 083EB UT WOS:000314444401077 ER PT J AU Liang, WY Hsu, CY Arnason, T Hawkins, AT Sylla, P Lauwers, GY AF Liang, W. Y. Hsu, C. Y. Arnason, T. Hawkins, A. T. Sylla, P. Lauwers, G. Y. TI Retrospective Evaluation of Elastic Stain in the Assessment of Serosal Invasion of pT3N0Mx Colorectal Cancers SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Vet Gen Hosp, Taipei, Taiwan. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 683 BP 164A EP 165A PG 2 WC Pathology SC Pathology GA 083EB UT WOS:000314444401088 ER PT J AU Liang, WY Arnason, T Kelly, P Genevay, M Odze, RD Lauwers, GY AF Liang, W. Y. Arnason, T. Kelly, P. Genevay, M. Odze, R. D. Lauwers, G. Y. TI Morphology and Natural History of Familial Adenomatous Polyposis (FAP)-Associated Dysplastic Fundic Gland Polyps (FGPs) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 684 BP 165A EP 165A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401089 ER PT J AU Liao, X Imamura, Y Ogino, S AF Liao, X. Imamura, Y. Ogino, S. TI KRAS Codon 12, 13, 61 and 146 Mutations in 1267 Colorectal Cancers: Clinicopathological, Molecular, and Survival Analyses SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 685 BP 165A EP 165A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401090 ER PT J AU Lochhead, P Fuchs, C Ogino, S AF Lochhead, P. Fuchs, C. Ogino, S. TI Microsatellite Instability (MSI) and BRAF Mutation Tests Jointly Provide Useful Prognostic Information in 1861 Colorectal Cancers SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 688 BP 166A EP 166A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401093 ER PT J AU Masia, R Peyton, S Lauwers, GY Brown, I AF Masia, R. Peyton, S. Lauwers, G. Y. Brown, I. TI Gastrointestinal Biopsy Findings of Autoimmune Enteropathy - A Review of 20 Cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Pathol Queensland, Herston, Qld, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 690 BP 167A EP 167A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401095 ER PT J AU Nishihara, R Fuchs, C Ogino, S AF Nishihara, R. Fuchs, C. Ogino, S. TI Hereditary Predisposition to LINE-1 Hypomethylated Colorectal Cancer: Potential Clinical Utility of Tumor LINE-1 Methylation Test for Familial Cancer Risk Assessment SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 698 BP 169A EP 169A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401103 ER PT J AU Ogino, S Imamura, Y Fuchs, C AF Ogino, S. Imamura, Y. Fuchs, C. TI LINE-1 Hypomethylation and Patient Prognosis in 1253 Colorectal Cancers SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 702 BP 170A EP 170A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401107 ER PT J AU Primiani, A Shahid, M Yilmaz, O Ferrone, CR Borger, DR Iafrate, AJ Zhu, AX Deshpande, V AF Primiani, A. Shahid, M. Yilmaz, O. Ferrone, C. R. Borger, D. R. Iafrate, A. J. Zhu, A. X. Deshpande, V. TI Microsatellite Instability in Gallbladder Carcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Primiani, A.; Shahid, M.; Yilmaz, O.; Ferrone, C. R.; Borger, D. R.; Iafrate, A. J.; Zhu, A. X.; Deshpande, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 713 BP 172A EP 173A PG 2 WC Pathology SC Pathology GA 083EB UT WOS:000314444401118 ER PT J AU Primiani, A Shahid, M Yilmaz, O Ferrone, CR Borger, DR Iafrate, AJ Zhu, AX Deshpande, V AF Primiani, A. Shahid, M. Yilmaz, O. Ferrone, C. R. Borger, D. R. Iafrate, A. J. Zhu, A. X. Deshpande, V. TI The PI3K/mTOR Pathway in Gallbladder Carcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Primiani, A.; Shahid, M.; Yilmaz, O.; Ferrone, C. R.; Borger, D. R.; Iafrate, A. J.; Zhu, A. X.; Deshpande, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 715 BP 173A EP 173A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401120 ER PT J AU Primiani, A Nazarian, RM Linskey, K Doyle, LA Duncan, LM Odze, R Zukerberg, LR AF Primiani, A. Nazarian, R. M. Linskey, K. Doyle, L. A. Duncan, L. M. Odze, R. Zukerberg, L. R. TI CK17: An Adjunctive Marker of Invasion in Squamous Neoplastic Lesions of the Anus SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womans Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 714 BP 173A EP 173A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401119 ER PT J AU Shen, J Najarian, RM Dessauvagie, B Deshpande, V Kumarasinghe, MP Hamilton, M Shahid, M Lauwers, G Odze, RD Srivastava, A AF Shen, J. Najarian, R. M. Dessauvagie, B. Deshpande, V. Kumarasinghe, M. P. Hamilton, M. Shahid, M. Lauwers, G. Odze, R. D. Srivastava, A. TI Isolated Ileitis May Be a Manifestation of Crohn's Disease, but Only in Symptomatic Patients: A Multi-Institution Study of 131 Cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. PathW & UWA, Perth, WA, Australia. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 738 BP 179A EP 179A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401143 ER PT J AU Tse, JY Riggi, N Ting, DT Stone, JH Rivera, M Deshpande, V AF Tse, J. Y. Riggi, N. Ting, D. T. Stone, J. H. Rivera, M. Deshpande, V. TI Diagnosis of IgG4-Related Disease: No Longer an IS(H)-Sue? SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Tse, J. Y.; Riggi, N.; Ting, D. T.; Stone, J. H.; Rivera, M.; Deshpande, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 758 BP 184A EP 184A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401163 ER PT J AU Ushiku, T Moran, CJ Lauwers, GY AF Ushiku, T. Moran, C. J. Lauwers, G. Y. TI Focally Enhanced Gastritis in Pediatric Inflammatory Bowel Disease: Patterns, Associations and Significance SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Ushiku, T.; Moran, C. J.; Lauwers, G. Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 760 BP 184A EP 184A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401165 ER PT J AU Ushiku, T Ban, S Arnason, T Hishima, T Fukayama, M Lauwers, GY AF Ushiku, T. Ban, S. Arnason, T. Hishima, T. Fukayama, M. Lauwers, G. Y. TI Very Well Differentiated Gastric Cancer of Intestinal Metaplasia-Type: A Systemic Analysis SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Tokyo, Tokyo, Japan. Saiseikai Kawaguchi Gen Hosp, Saitama, Japan. Tokyo Metropolitan Komagome Hosp, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 761 BP 185A EP 185A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401166 ER PT J AU Ananthanarayanan, V Pan, Y Kocherginsky, M Tretiakova, M Amin, MB Cheng, L Epstein, JI Grignon, DJ Hansel, DE Jimenez, RE McKenney, JK Montironi, R Oliva, E Osunkoya, AO Rao, P Reuter, VE Ro, JY Shen, SS Srigley, JR Tsuzuki, T Yao, JL Antic, T Haber, M Taxy, JB Paner, GP AF Ananthanarayanan, V. Pan, Y. Kocherginsky, M. Tretiakova, M. Amin, M. B. Cheng, L. Epstein, J. I. Grignon, D. J. Hansel, D. E. Jimenez, R. E. McKenney, J. K. Montironi, R. Oliva, E. Osunkoya, A. O. Rao, P. Reuter, V. E. Ro, J. Y. Shen, S. S. Srigley, J. R. Tsuzuki, T. Yao, J. L. Antic, T. Haber, M. Taxy, J. B. Paner, G. P. TI Influence of Histologic Criteria and Confounding Factors (CFs) in Staging Equivocal Cases for Microscopic Perivesical Tissue Invasion (MPVI or pT3a): An Interobserver Study among Expert GU Pathologists SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Univ Chicago, Chicago, IL 60637 USA. Emory Univ, Atlanta, GA 30322 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Indiana Univ, Indianapolis, IN 46204 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Cleveland Clin, Cleveland, OH 44106 USA. Mayo Clin, Rochester, MN USA. Polytech Univ Marche Reg, Ancona, Italy. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Methodist Hosp, Houston, TX 77030 USA. McMaster Univ, Hamilton, ON, Canada. Nagoya Daini Red Cross Hosp, Nagoya, Aichi, Japan. Univ Rochester, Rochester, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 802 BP 194A EP 195A PG 2 WC Pathology SC Pathology GA 083EB UT WOS:000314444401206 ER PT J AU Dong, F Ping, Y Wang, C Wu, S Xiao, Y McDougal, WS Young, RH Wu, CL AF Dong, F. Ping, Y. Wang, C. Wu, S. Xiao, Y. McDougal, W. S. Young, R. H. Wu, C-L TI Architectural Heterogeneity and Cribriform Pattern Predict Adverse Clinical Outcome for Gleason Grade 4 Prostatic Adenocarcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Dong, F.; Ping, Y.; Wang, C.; Wu, S.; Xiao, Y.; McDougal, W. S.; Young, R. H.; Wu, C-L] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 852 BP 206A EP 206A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401256 ER PT J AU Flynn, L Sheils, O O'Leary, JJ Finn, SP Watson, W Loda, M Mucci, L AF Flynn, L. Sheils, O. O'Leary, J. J. Finn, S. P. Watson, W. Loda, M. Mucci, L. TI miRNA Signatures of Indolent and Aggressive Prostate Cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Dublin City Univ, Trinity Coll, Dublin 9, Ireland. Univ Coll Dublin, Dublin 2, Ireland. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 875 BP 211A EP 211A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401279 ER PT J AU Mason, EF Sadow, PM Wagner, AJ Remillard, SP Flood, TA Belanger, EC Hornick, JL Barletta, JA AF Mason, E. F. Sadow, P. M. Wagner, A. J. Remillard, S. P. Flood, T. A. Belanger, E. C. Hornick, J. L. Barletta, J. A. TI Identification of Succinate Dehydrogenase-Deficient Bladder Paragangliomas SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Ottawa Hosp, Ottawa, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 966 BP 233A EP 233A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401370 ER PT J AU Ali, RH Kurihara, S Endo, M Rouzbahman, M Hoang, LN Melnyk, N Marino-Enriquez, A Dal Cin, P Fletcher, JA Oliva, E Huntsman, DG Oda, Y Nucci, MR Lee, CH AF Ali, R. H. Kurihara, S. Endo, M. Rouzbahman, M. Hoang, L. N. Melnyk, N. Marino-Enriquez, A. Dal Cin, P. Fletcher, J. A. Oliva, E. Huntsman, D. G. Oda, Y. Nucci, M. R. Lee, C-H TI Genetic Reclassification of Undifferentiated Endometrial Sarcoma: Clinical Relevance SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Kyushu Univ, Fukuoka 812, Japan. Univ Toronto, Toronto, ON, Canada. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. NR 0 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1096 BP 263A EP 263A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401501 ER PT J AU Bandyopadhyay, S Winer, I Mert, I Oliva, E Nucci, M Al-Wahab, Z Guan, H Arabi, H Alosh, B Van de Vijver, KK Ali-Fehmi, R AF Bandyopadhyay, S. Winer, I. Mert, I. Oliva, E. Nucci, M. Al-Wahab, Z. Guan, H. Arabi, H. Alosh, B. Van de Vijver, K. K. Ali-Fehmi, R. TI Clinical Significance of Lymphovascular Space Invasion in Uterine Serous Carcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Wayne State Univ, Detroit, MI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. King Abdul Aziz Med City, Jeddah, Saudi Arabia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1106 BP 266A EP 266A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401511 ER PT J AU Hoang, LN McConechy, MK Koebel, M Han, G Rouzbahman, M Davidson, B Irving, J Ali, R Leung, S Oliva, E Nucci, MR Soslow, RA Huntsman, DG Gilks, CB Lee, CH AF Hoang, L. N. McConechy, M. K. Koebel, M. Han, G. Rouzbahman, M. Davidson, B. Irving, J. Ali, R. Leung, S. Oliva, E. Nucci, M. R. Soslow, R. A. Huntsman, D. G. Gilks, C. B. Lee, C-H TI Histotype-Genotype Correlation in 36 High-Grade Endometrial Carcinomas SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Univ Calgary, Calgary, AB, Canada. Univ Toronto, Toronto, ON, Canada. Norwegian Radium Hosp, Oslo, Norway. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1160 BP 278A EP 278A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401565 ER PT J AU Lee, CH Hoang, LN Reyes, C Saslow, RA Nucci, MR Oliva, E AF Lee, C-H Hoang, L. N. Reyes, C. Saslow, R. A. Nucci, M. R. Oliva, E. TI Frequent Immunohistochemical Expression of KIT in YWHAE-FAM22 Endometrial Stromal Sarcoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1192 BP 285A EP 285A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401597 ER PT J AU Wagner, AJ Remillard, SP Zhang, YX Doyle, LA George, S Hornick, JL AF Wagner, Andrew J. Remillard, Stephen P. Zhang, Yi-Xiang Doyle, Leona A. George, Suzanne Hornick, Jason L. TI Loss of expression of SDHA predicts SDHA mutations in gastrointestinal stromal tumors SO MODERN PATHOLOGY LA English DT Article DE gastrointestinal stromal tumor; succinate dehydrogenase; SDHA; SDHB; soft tissue sarcoma; immunohistochemistry ID V600E BRAF MUTATIONS; GERM-LINE MUTATIONS; SUCCINATE-DEHYDROGENASE; GENE-MUTATIONS; CARNEY-STRATAKIS; RENAL TUMORS; PHEOCHROMOCYTOMA; PARAGANGLIOMAS; IMMUNOHISTOCHEMISTRY; ADULTS AB Gastrointestinal stromal tumors (GISTs) are usually driven by mutations in KIT or PDGFRA, although 15% of GISTs in adults and >90% in children lack such mutations. The majority of gastric KIT/PDGFRA wild-type GISTs show distinctive morphological and clinical features and loss of expression of succinate dehydrogenase (SDH) B. Only a small subset of SDHB-deficient GISTs carries loss-of-function mutations in SDHB, SDHC, or SDHD. Because of the complexity of its locus (15 exons) and the presence of three pseudogenes, SDHA is rarely analyzed. Recently, mutations in SDHA were shown to lead to loss of expression of SDHA in a small group of paragangliomas. We sought to determine whether immunohistochemistry for SDHA could identify GISTs with SDHA mutations. Tumors (n = 33) with pathological features of SDH-deficient GIST were analyzed for expression of SDHA and SDHB by immunohistochemistry, and SDHA exons were sequenced from tumors lacking SDHA expression. Exons harboring somatic mutations were examined in DNA from corresponding normal tissue. All 33 tumors showed loss of SDHB expression. A total of 9 out of 33 (27%) tumors also lacked expression of SDHA. SDHA-deficient GISTs affected five men and four women (median age 38 years). SDHA expression was intact in the 24 remaining tumors, including those with known SDHB (n = 3) or SDHC (n = 2) mutations. Nonsense (n = 8) or missense (n = 1) mutations in SDHA were identified in all SDHA-deficient tumors. Heterozygous mutations were also found in DNA from normal tissues from six patients with available material. Somatic loss of the second allele has been found in seven tumors, five by loss of heterozygosity, one by a 13-bp deletion, and one by a missense mutation. Loss of SDHA expression in GIST reliably predicts the presence of SDHA mutations, which represent a relatively common cause of SDH-deficient GIST in adults. Immunohistochemistry for SDHA can be used to select patients for SDHA-specific genetic testing. Modern Pathology (2013) 26, 289-294; doi:10.1038/modpathol.2012.153; published online 7 September 2012 C1 [Wagner, Andrew J.; Remillard, Stephen P.; Zhang, Yi-Xiang; George, Suzanne] Harvard Univ, Sch Med, Ctr Sarcoma & Bone Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Doyle, Leona A.; Hornick, Jason L.] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Hornick, JL (reprint author), Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM jhornick@partners.org FU DK Ludwig Fund for Cancer Research FX We are grateful to Dr Esther Korpershoek (University Medical Center, Rotterdam) for providing SDHA primer sequences, and to the DK Ludwig Fund for Cancer Research for support of the Ludwig Center at Dana-Farber/Harvard. NR 35 TC 45 Z9 49 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 IS 2 BP 289 EP 294 DI 10.1038/modpathol.2012.153 PG 6 WC Pathology SC Pathology GA 083DX UT WOS:000314444000016 PM 22955521 ER PT J AU Zane, NA Kraft, S Faquin, W Stone, JH Deshpande, V AF Zane, N. A. Kraft, S. Faquin, W. Stone, J. H. Deshpande, V. TI IgG4-Related Disease Is a Rare Cause of Recurrent Mastoiditis and Can Be Mimicked by Severe Otitis Media SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Zane, N. A.; Kraft, S.; Faquin, W.; Stone, J. H.; Deshpande, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1317 BP 315A EP 315A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401722 ER PT J AU Boyer, DF Lindeman, NI Harris, NL Ferry, JA AF Boyer, D. F. Lindeman, N. I. Harris, N. L. Ferry, J. A. TI Peripheral T-Cell Lymphomas with Cytotoxic Phenotype in Patients with Nodal SLL/CLL SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1341 BP 321A EP 321A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401746 ER PT J AU Chen, BJ Ouyang, J Xu, ML Yu, H Fletcher, CDM Sun, H Shipp, MA Rodig, SJ AF Chen, B. J. Ouyang, J. Xu, M. L. Yu, H. Fletcher, C. D. M. Sun, H. Shipp, M. A. Rodig, S. J. TI Expression of the Immunosuppressive Molecules PD-L1 and Galectin-1 by EBV+ Lymphoproliferative Disorders: Novel Candidates for Targeted Immunotherapy SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. DFCI, Boston, MA USA. Yale Univ, Sch Med, New Haven, CT USA. UMass Mem Hosp, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1351 BP 323A EP 323A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444401756 ER PT J AU Huck, A Fathi, A Hasserjian, R AF Huck, A. Fathi, A. Hasserjian, R. TI Cytopenia Prior to AML Diagnosis Predicts Aggressive Behavior Even in the Absence of Antecedent MDS: Another Diagnostic Criterion for AML with Myelodysplasia-Related Changes? SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Huck, A.; Fathi, A.; Hasserjian, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1395 BP 333A EP 333A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402022 ER PT J AU Hwang, DG Dorfman, DM Briggs, DA Silverio, R Pozdnyakova, O AF Hwang, D. G. Dorfman, D. M. Briggs, D. A. Silverio, R. Pozdnyakova, O. TI Detecting Myelodysplastic Syndromes on Peripheral Blood Using a Machine Learning Approach To Analyze Multiparameter Hematology Analyzer Data SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Virginia Mason Med Ctr, Seattle, WA 98101 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1399 BP 334A EP 334A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402026 ER PT J AU Klepeis, V Hasserjian, RP AF Klepeis, V. Hasserjian, R. P. TI Refractory Anemia with Excess Blasts in Transformation Exhibits Clinicopathologic Features and Clinical Behavior Similar to AML with >= 30% Blasts SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Klepeis, V.; Hasserjian, R. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1410 BP 336A EP 336A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402037 ER PT J AU Klepeis, VE Zukerberg, LR Hasserjian, RP AF Klepeis, V. E. Zukerberg, L. R. Hasserjian, R. P. TI Genetic Subtypes of Acute Myeloid Leukemia Are Associated with Distinctive Features of the Bone Marrow Microenvironment SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Klepeis, V. E.; Zukerberg, L. R.; Hasserjian, R. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1411 BP 336A EP 337A PG 2 WC Pathology SC Pathology GA 083EB UT WOS:000314444402038 ER PT J AU Nicolae, A Huppmann, AR Slack, GW Ferry, JA Harris, NL Pittaluga, S Jaffe, ES Hasserjian, RP AF Nicolae, A. Huppmann, A. R. Slack, G. W. Ferry, J. A. Harris, N. L. Pittaluga, S. Jaffe, E. S. Hasserjian, R. P. TI EBV Is Infrequently Expressed in the LP Cells of Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) in Both Children and Adults SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 NCI, Bethesda, MD 20892 USA. BC Canc Agcy, Vancouver, BC, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1473 BP 352A EP 352A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402100 ER PT J AU O'Malley, DP Kim, YS Sohani, A Weiss, L Perkins, S Burke, JS Fisher, C Orazi, A AF O'Malley, D. P. Kim, Y. S. Sohani, A. Weiss, L. Perkins, S. Burke, J. S. Fisher, C. Orazi, A. TI Immunohistochemical Characterization of Vascular and Stromal Proliferations of Spleen SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Clarient Inc GE Healthcare, Aliso Viejo, CA USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Utah, Salt Lake City, UT USA. Alta Bates Med Ctr, Berkeley, CA USA. Royal Marsden Hosp, London SW3 6JJ, England. Weill Cornell Med Coll, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1475 BP 352A EP 352A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402102 ER PT J AU O'Malley, DP Zuckerberg, L Smith, L Barry, TS Gunn, S Tam, W Orazi, A Kim, YS Weiss, L AF O'Malley, D. P. Zuckerberg, L. Smith, L. Barry, T. S. Gunn, S. Tam, W. Orazi, A. Kim, Y. S. Weiss, L. TI The Genetics of Interdigitating Dendritic Cell Tumors Shares Some Changes with Langerhans Cell Histiocytosis in Select Cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Clarient Inc GE Healthcare, Aliso Viejo, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Spectrum Pathol, Mission Viejo, CA USA. PathCentral, Irvine, CA USA. Weill Cornell Med Ctr, New York, NY USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1476 BP 353A EP 353A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402103 ER PT J AU Pozdnyakova, O Shahsafaei, A Freeman, G Dorfman, D AF Pozdnyakova, O. Shahsafaei, A. Freeman, G. Dorfman, D. TI A Panel of Follicular Helper T-Cell (T-FH) Immunophenotypic Markers Identifies and Differentiates T-FH-Derived Neoplasms from Other T-Cell Neoplasms SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1486 BP 355A EP 355A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402113 ER PT J AU Rogers, HJ Vardiman, JW Anastasi, J Raca, G Savage, NM Cherry, AM Arber, D Moore, E Morrissette, JJD Bagg, A Liu, YC Mathew, S Orazi, A Lin, P Wang, SA Bueso-Ramos, CE Foucar, K Hasserjian, RP Hsi, ED AF Rogers, H. J. Vardiman, J. W. Anastasi, J. Raca, G. Savage, N. M. Cherry, A. M. Arber, D. Moore, E. Morrissette, J. J. D. Bagg, A. Liu, Y-C Mathew, S. Orazi, A. Lin, P. Wang, S. A. Bueso-Ramos, C. E. Foucar, K. Hasserjian, R. P. Hsi, E. D. TI Complex Karyotype but Not Blast Percentage Is Associated with Poor Survival in Acute Myeloid Leukemia and Myelodysplastic Syndrome with Inv(3)(q21q26.2)/t(3;3)(q21;q26.2); a Bone Marrow Pathology Group Study SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Cleveland Clin, Cleveland, OH 44106 USA. Univ Chicago, Chicago, IL 60637 USA. Stanford Univ, Stanford, CA 94305 USA. Univ Penn, Philadelphia, PA 19104 USA. Cornell Univ, Weill Med Coll, New York, NY 10021 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ New Mexico, Albuquerque, NM 87131 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1498 BP 358A EP 358A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402125 ER PT J AU Ryan, RJH Akin, C Castells, M Selig, MK Nielsen, GP Ferry, JA Hornick, JL AF Ryan, R. J. H. Akin, C. Castells, M. Selig, M. K. Nielsen, G. P. Ferry, J. A. Hornick, J. L. TI Mast Cell Sarcoma: An Aggressive and Potentially Under-Diagnosed Neoplasm That May Be Responsive to Targeted Therapy SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1501 BP 359A EP 359A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402128 ER PT J AU Tandon, B Swerdlow, SH Hasserjian, RP Gibson, SE AF Tandon, B. Swerdlow, S. H. Hasserjian, R. P. Gibson, S. E. TI Is Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) a Lymphoma of Mantle Zone B-Cells? SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1522 BP 364A EP 364A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402149 ER PT J AU Yagi, Y Qureshi, I Malik, AZ Wilbur, DC AF Yagi, Y. Qureshi, I. Malik, A. Z. Wilbur, D. C. TI Challenges in Establishing the WSI Based Digital Pathology Facility and Telepathology Network between Pakistna and USA SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Holy Family Hosp, Rawalpindi, Pakistan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1598 BP 382A EP 383A PG 2 WC Pathology SC Pathology GA 083EB UT WOS:000314444402224 ER PT J AU Fazlollahi, L Dias-Santagata, D Sahora, K Morales-Oyarvide, V Bernardo, LA Iafrate, AJ Pitman, MB Fernandez-del Castillo, C Mino-Kenudson, M AF Fazlollahi, L. Dias-Santagata, D. Sahora, K. Morales-Oyarvide, V. Bernardo, L. A. Iafrate, A. J. Pitman, M. B. Fernandez-del Castillo, C. Mino-Kenudson, M. TI GNAS Mutations in Concomitant Pancreatic Ductal Adenocarcinoma: A Pilot Study SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Fazlollahi, L.; Dias-Santagata, D.; Sahora, K.; Morales-Oyarvide, V.; Bernardo, L. A.; Iafrate, A. J.; Pitman, M. B.; Fernandez-del Castillo, C.; Mino-Kenudson, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1765 BP 424A EP 424A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402391 ER PT J AU Shahid, M Zukerberg, LR Deshpande, V AF Shahid, M. Zukerberg, L. R. Deshpande, V. TI Is Investing Additional Time on Mitotic Counts in Neuroendocrine Neoplasm Clinically Relevant? SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Shahid, M.; Zukerberg, L. R.; Deshpande, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1791 BP 430A EP 430A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402417 ER PT J AU Solus, JF Sahora, K Shvetz, D Fernandez-del-Castillo, C Pitman, MB Mino-Kenudson, M AF Solus, J. F. Sahora, K. Shvetz, D. Fernandez-del-Castillo, C. Pitman, M. B. Mino-Kenudson, M. TI Protein Expression of the SWI/SNF Chromatin Remolding Subunits in Intraductal Papillary Mucinous Neoplasm (IPMN) and Pancreatic Ductal Adenocarcinoma (PDAC) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Solus, J. F.; Sahora, K.; Shvetz, D.; Fernandez-del-Castillo, C.; Pitman, M. B.; Mino-Kenudson, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1796 BP 431A EP 431A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402422 ER PT J AU Wang, JL Shvetz, D Sahora, K Fernandez-del Castillo, C Pitman, M Mino-Kenudson, M AF Wang, J. L. Shvetz, D. Sahora, K. Fernandez-del Castillo, C. Pitman, M. Mino-Kenudson, M. TI Activation of Src and STAT3 in Intraductal Papillary Mucinous Neoplasm of the Pancreas (IPMN) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura 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 NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1800 BP 432A EP 432A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402426 ER PT J AU Lindeman, NI MacConaill, LE Garcia, E Kuo, FC Longtine, JA Hahn, WC Kantoff, PW Rollins, BJ AF Lindeman, N. I. MacConaill, L. E. Garcia, E. Kuo, F. C. Longtine, J. A. Hahn, W. C. Kantoff, P. W. Rollins, B. J. TI Profile: Results from Multiplexed Mass Spectrometric Genotyping of 2178 Cancer Patients SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Mt Sinai Hosp, New York, NY 10029 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1816 BP 436A EP 436A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402441 ER PT J AU Waldron, L Parmigiani, G Fuchs, C Huttenhower, C Ogino, S AF Waldron, L. Parmigiani, G. Fuchs, C. Huttenhower, C. Ogino, S. TI Expression Profiling and Molecular Classification of Colorectal Cancer: Meta-Analysis of 8 Independent mRNA Expression Datasets across the Globe SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1830 BP 439A EP 439A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402455 ER PT J AU Pessarakli, MM Phan, RT AF Pessarakli, M. M. Phan, R. T. TI Association between Methylenetetrahydrofolate Reductase (MTHFR) Gene Variants and Hyperhomocysteinemia in United States Veterans SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 USC, Keck Sch Med, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1853 BP 444A EP 445A PG 2 WC Pathology SC Pathology GA 083EB UT WOS:000314444402478 ER PT J AU Kovach, AE Cheng, GZ Channick, CL Channick, R Gaissert, HA Muniappan, A Kradin, RL AF Kovach, A. E. Cheng, G. Z. Channick, C. L. Channick, R. Gaissert, H. A. Muniappan, A. Kradin, R. L. TI The Pathology of Pulmonary Vein Radiofrequency Ablation SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Kovach, A. E.; Cheng, G. Z.; Channick, C. L.; Channick, R.; Gaissert, H. A.; Muniappan, A.; Kradin, R. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1901 BP 457A EP 457A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402526 ER PT J AU Kovach, AE Morales-Oyarvide, V Shvetz, DE Tammireddy, S Klepeis, V Mark, EJ Santagata, DD Iafrate, AJ Mino-Kenudson, M AF Kovach, A. E. Morales-Oyarvide, V. Shvetz, D. E. Tammireddy, S. Klepeis, V. Mark, E. J. Santagata, D. Dias Iafrate, A. J. Mino-Kenudson, M. TI Pathway Interplay: Activation of EGFR, ERK, and AKT in Early-Stage Lung Adenocarcinomas SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Kovach, A. E.; Morales-Oyarvide, V.; Shvetz, D. E.; Tammireddy, S.; Klepeis, V.; Mark, E. J.; Santagata, D. Dias; Iafrate, A. J.; Mino-Kenudson, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1900 BP 457A EP 457A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402525 ER PT J AU Matsubara, O Miyai, K Ishikawa, Y Nakatani, Y Mark, EJ AF Matsubara, O. Miyai, K. Ishikawa, Y. Nakatani, Y. Mark, E. J. TI Epithelial-Mesenchymal Transition (EMT) in Active Fibroblastic Foci in IPF/UIP SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Natl Def Med Coll, Tokorozawa, Saitama 359, Japan. Japanese Fdn Canc Res, Inst Canc, Koto Ku, Tokyo 170, Japan. Chiba Univ, Chiba, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1911 BP 459A EP 459A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402535 ER PT J AU Miyamoto, A Sharma, A Nishino, M Mino-Kenudson, M Mark, EJ AF Miyamoto, A. Sharma, A. Nishino, M. Mino-Kenudson, M. Mark, E. J. TI Acute Exacerbation of Non-Specific Interstitial Pneumonia Compared to That of Usual Interstitial Pneumonia SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Toranomon Gen Hosp, Tokyo, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1915 BP 460A EP 460A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402540 ER PT J AU Nishino, M Mathai, SK O'Donnell, WJ Kradin, RL AF Nishino, M. Mathai, S. K. O'Donnell, W. J. Kradin, R. L. TI Intraalveolar Fibrin Is Associated with Poor Outcomes in Cryptogenic Organizing Pneumonia SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 [Nishino, M.; Mathai, S. K.; O'Donnell, W. J.; Kradin, R. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1921 BP 462A EP 462A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402546 ER PT J AU Setia, N Janne, PA Sholl, LM AF Setia, N. Janne, P. A. Sholl, L. M. TI Long Term Effects of EGFR Tyrosine Kinase Inhibitor Therapy on the Non-Neoplastic Lung SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1939 BP 466A EP 466A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402564 ER PT J AU Sholl, L Sun, H Ligon, A Butaney, M Janne, PA Rodig, S AF Sholl, L. Sun, H. Ligon, A. Butaney, M. Janne, P. A. Rodig, S. TI MET Copy Number by Dual Color Brightfield In Situ Hybridization and Fluorescence In Situ Hybridization Correlates with Met Protein Expression in Lung Adenocarcinomas SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1942 BP 467A EP 467A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402567 ER PT J AU Sholl, L Sun, H Butaney, M Lee, C Janne, PA Rodig, S AF Sholl, L. Sun, H. Butaney, M. Lee, C. Janne, P. A. Rodig, S. TI ROS Immunohistochemistry Is a Sensitive and Specific Tool for Detection of ROS Rearrangements in Lung Adenocarcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 02-08, 2013 CL Baltimore, MD SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2013 VL 26 SU 2 MA 1943 BP 467A EP 467A PG 1 WC Pathology SC Pathology GA 083EB UT WOS:000314444402568 ER PT J AU Caretti, V Hiddingh, L Lagerweij, T Schellen, P Koken, PW Hulleman, E van Vuurden, DG Vandertop, WP Kaspers, GJL Noske, DP Wurdinger, T AF Caretti, Viola Hiddingh, Lotte Lagerweij, Tonny Schellen, Pepijn Koken, Phil W. Hulleman, Esther van Vuurden, Dannis G. Vandertop, W. Peter Kaspers, Gertjan J. L. Noske, David P. Wurdinger, Thomas TI WEE1 Kinase Inhibition Enhances the Radiation Response of Diffuse Intrinsic Pontine Gliomas SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID DNA-DAMAGING AGENTS; BRAIN-STEM GLIOMAS; GENE-EXPRESSION; MITOTIC CATASTROPHE; TYROSINE KINASE; CHECKPOINT KINASE; CLINICAL-TRIALS; TUMOR-CELLS; MK-1775; IDENTIFICATION AB Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric disease. Thus far, no therapeutic agent has proven beneficial in the treatment of this malignancy. Therefore, conventional DNA-damaging radiotherapy remains the standard treatment, providing transient neurologic improvement without improving the probability of overall survival. During radiotherapy, WEE1 kinase controls the G(2) cell-cycle checkpoint, allowing for repair of irradiation (IR)-induced DNA damage. Here, we show that WEE1 kinase is one of the highest overexpressed kinases in primary DIPG tissues compared with matching non-neoplastic brain tissues. Inhibition of WEE1 by MK-1775 treatment of DIPG cells inhibited the IR-induced WEE1-mediated phosphorylation of CDC2, resulting in reduced G(2)-M arrest and decreased cell viability. Finally, we show that MK-1775 enhances the radiation response of E98-Fluc-mCherry DIPG mouse xenografts. Altogether, these results show that inhibition of WEE1 kinase in conjunction with radiotherapy holds potential as a therapeutic approach for the treatment of DIPG. Mol Cancer Ther; 12(2); 141-50. (C)2012 AACR. C1 [Caretti, Viola; Hiddingh, Lotte; Lagerweij, Tonny; Schellen, Pepijn; Hulleman, Esther; van Vuurden, Dannis G.; Kaspers, Gertjan J. L.] Vrije Univ Amsterdam, Med Ctr, Dept Pediat Oncol, NL-1081 HV Amsterdam, Netherlands. [Caretti, Viola; Hiddingh, Lotte; Lagerweij, Tonny; Schellen, Pepijn; Hulleman, Esther; Vandertop, W. Peter; Noske, David P.; Wurdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, Dept Neurosurg, NL-1081 HV Amsterdam, Netherlands. [Koken, Phil W.] Vrije Univ Amsterdam, Med Ctr, Dept Radiat Oncol, NL-1081 HV Amsterdam, Netherlands. [Caretti, Viola; Hiddingh, Lotte; Lagerweij, Tonny; Schellen, Pepijn; Hulleman, Esther; van Vuurden, Dannis G.; Noske, David P.; Wurdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, Neurooncol Res Grp, NL-1081 HV Amsterdam, Netherlands. [Wurdinger, Thomas] Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. [Wurdinger, Thomas] Harvard Univ, Sch Med, Boston, MA USA. RP Wurdinger, T (reprint author), Vrije Univ Amsterdam, Med Ctr, CCA Room 3-36,De Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands. EM t.wurdinger@vumc.nl OI Lagerweij, Tonny/0000-0003-1043-7452; Van Vuurden, Dannis/0000-0002-1364-9007 FU Semmy foundation FX This research was financially supported by the Semmy foundation (G.J.L. Kaspers). NR 41 TC 15 Z9 15 U1 0 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD FEB PY 2013 VL 12 IS 2 BP 141 EP 150 DI 10.1158/1535-7163.MCT-12-0735 PG 10 WC Oncology SC Oncology GA 088NV UT WOS:000314842700003 PM 23270927 ER PT J AU Hart, S Novotny-Diermayr, V Goh, KC Williams, M Tan, YC Ong, LC Cheong, A Ng, BK Amalini, C Madan, B Nagaraj, H Jayaraman, R Pasha, KM Ethirajulu, K Chng, WJ Mustafa, N Goh, BC Benes, C McDermott, U Garnett, M Dymock, B Wood, JM AF Hart, Stefan Novotny-Diermayr, Veronica Goh, Kee Chuan Williams, Meredith Tan, Yong Cheng Ong, Lai Chun Cheong, Albert Ng, Bee Kheng Amalini, Chithra Madan, Babita Nagaraj, Harish Jayaraman, Ramesh Pasha, Khalid M. Ethirajulu, Kantharaj Chng, Wee Joo Mustafa, Nurulhuda Goh, Boon Cher Benes, Cyril McDermott, Ultan Garnett, Mathew Dymock, Brian Wood, Jeanette M. TI VS-5584, a Novel and Highly Selective PI3K/mTOR Kinase Inhibitor for the Treatment of Cancer SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID BREAST-CANCER; PI3K PATHWAY; MTOR; RAPAMYCIN; MODELS; TUMORS; SENSITIVITY; LIMITATIONS; STRATEGIES; GDC-0941 AB Dysregulation of the PI3K/mTOR pathway, either through amplifications, deletions, or as a direct result of mutations, has been closely linked to the development and progression of a wide range of cancers. Moreover, this pathway activation is a poor prognostic marker for many tumor types and confers resistance to various cancer therapies. Here, we describe VS-5584, a novel, low-molecular weight compound with equivalent potent activity against mTOR(IC50 = 37 nmol/L) and all class I phosphoinositide 3-kinase (PI3K) isoforms IC50: PI3K alpha = 16 nmol/L; PI3K beta = 68 nmol/L; PI3K gamma 25 nmol/L; PI3K delta 42 nmol/L, without relevant activity on 400 lipid and protein kinases. VS-5584 shows robust modulation of cellular PI3K/mTOR pathways, inhibiting phosphorylation of substrates downstream of PI3K and mTORC1/2. A large human cancer cell line panel screen (436 lines) revealed broad antiproliferative sensitivity and that cells harboring mutations in PI3KCA are generally more sensitive toward VS-5584 treatment. VS-5584 exhibits favorable pharmacokinetic properties after oral dosing in mice and is well tolerated. VS-5584 induces long-lasting and dose-dependent inhibition of PI3K/mTOR signaling in tumor tissue, leading to tumor growth inhibition in various rapalog-sensitive and -resistant human xenograft models. Furthermore, VS-5584 is synergistic with an EGF receptor inhibitor in a gastric tumor model. The unique selectivity profile and favorable pharmacologic and pharmaceutical properties of VS-5584 and its efficacy in a wide range of human tumor models supports further investigations of VS-5584 in clinical trials. Mol Cancer Ther; 12(2); 151-61. (C)2012 AACR. C1 [Hart, Stefan; Novotny-Diermayr, Veronica; Goh, Kee Chuan; Williams, Meredith; Tan, Yong Cheng; Ong, Lai Chun; Cheong, Albert; Ng, Bee Kheng; Amalini, Chithra; Madan, Babita; Nagaraj, Harish; Jayaraman, Ramesh; Pasha, Khalid M.; Ethirajulu, Kantharaj; Dymock, Brian; Wood, Jeanette M.] S BIO Pte Ltd, Singapore 117528, Singapore. [Chng, Wee Joo; Mustafa, Nurulhuda; Goh, Boon Cher] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117548, Singapore. [Chng, Wee Joo] Natl Univ Hlth Syst, Natl Univ Canc Inst Singapore, Dept Haematol Oncol, Singapore, Singapore. [Benes, Cyril] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. [McDermott, Ultan; Garnett, Mathew] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton, England. RP Hart, S (reprint author), S BIO Pte Ltd, 1 Sci Pk Rd,05-09 Capricorn, Singapore 117528, Singapore. EM stefan.sbio@gmail.com OI Madan, Babita/0000-0003-1065-8589; McDermott, Ultan/0000-0001-9032-4700 FU Astrazeneca FX C. Benes has a commercial research grant from Astrazeneca and has honoraria from Speakers Bureau of EMD serono. No potential conflicts of interest were disclosed by the other authors. NR 35 TC 14 Z9 16 U1 2 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD FEB PY 2013 VL 12 IS 2 BP 151 EP 161 DI 10.1158/1535-7163.MCT-12-0466 PG 11 WC Oncology SC Oncology GA 088NV UT WOS:000314842700004 PM 23270925 ER PT J AU Goss, K Wells, C Kao, D Bahia, A Salcedo, E Long, C Massoudi, F Fearing, M Sims, K Taylor, M AF Goss, Kendrick Wells, Cara Kao, David Bahia, Amit Salcedo, Ernesto Long, Carlin Massoudi, Fred Fearing, Marsha Sims, Katherine Taylor, Matthew TI Implementation of direct-to-patient (DPI) dried-blood-spot (DBS) screening for Fabry disease in adults with unexplained left-ventricular hypertrophy (LVH) SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 9th Annual World Symposium of the Lysosomal-Disease-Network (LDN) CY FEB 12-15, 2013 CL Orlando, FL SP Lysosomal Dis Network (LDN) C1 [Goss, Kendrick; Sims, Katherine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurogenet Diagnost Lab,Ctr Human Genet Res, Boston, MA USA. [Goss, Kendrick; Sims, Katherine] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wells, Cara; Kao, David; Bahia, Amit; Salcedo, Ernesto; Long, Carlin; Massoudi, Fred; Taylor, Matthew] Univ Colorado, Adult Med Genet Program, Aurora, CO USA. [Fearing, Marsha] Massachusetts Gen Hosp, Genet Unit, Dept Pediat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2013 VL 108 IS 2 MA 87 BP S45 EP S45 DI 10.1016/j.ymgme.2012.11.101 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 086FW UT WOS:000314670500089 ER PT J AU Hopkin, R Mauer, M Lemay, R Ortiz, J Sims, K Waldek, S AF Hopkin, Robert Mauer, Michael Lemay, Roberta Ortiz, Jose Sims, Kathy Waldek, Stephen TI Early initiation of agalsidase beta treatment is associated with fewer clinical events in women with Fabry disease: Data from the Fabry Registry SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 9th Annual World Symposium of the Lysosomal-Disease-Network (LDN) CY FEB 12-15, 2013 CL Orlando, FL SP Lysosomal Dis Network (LDN) C1 [Hopkin, Robert] Cincinnati Childrens Hosp Med Ctr, Cincninnati, OH USA. [Mauer, Michael] Univ Minnesota, Div Pediat Nephrol, Minneapolis, MN USA. [Lemay, Roberta] Genzyme, Biomed Data Sci & Informat, Cambridge, MA USA. [Ortiz, Jose] Fdn Jimenez Diaz, E-28040 Madrid, Spain. [Sims, Kathy] Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Boston, MA 02114 USA. [Sims, Kathy] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Waldek, Stephen] Salford Royal NHS Fdn Trust, Manchester, Lancs, England. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2013 VL 108 IS 2 MA 99 BP S49 EP S49 DI 10.1016/j.ymgme.2012.11.113 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 086FW UT WOS:000314670500101 ER PT J AU Pan, J Caruso, P Loes, D Kubilus, K Hayden, D Eichler, F AF Pan, Jessica Caruso, Paul Loes, Daniel Kubilus, Kim Hayden, Douglas Eichler, Florian TI Brain MRI abnormalities in GM2-gangliosidosis SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 9th Annual World Symposium of the Lysosomal-Disease-Network (LDN) CY FEB 12-15, 2013 CL Orlando, FL SP Lysosomal Dis Network (LDN) C1 [Pan, Jessica; Caruso, Paul; Eichler, Florian] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Loes, Daniel] Suburban Radiol Consultants, Minneapolis, MN USA. [Kubilus, Kim] Natl Tay Sachs & Allied Dis Assoc, Boston, MA USA. [Hayden, Douglas] MGH Biostat Ctr, Boston, MA USA. [Eichler, Florian] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2013 VL 108 IS 2 MA 173 BP S71 EP S72 DI 10.1016/j.ymgme.2012.11.187 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 086FW UT WOS:000314670500175 ER PT J AU Rost, N Metterville, DR Cloonan, LK Fitzpatrick, KM Germain, D Politei, JM Sims, KB AF Rost, Natalia Metterville, Danielle R. Cloonan, Lisa K. Fitzpatrick, Kaitlin M. Germain, Dominique Politei, Juan M. Sims, Katherine B. TI White matter hyperintensity volume assessment in patients with Fabry disease SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 9th Annual World Symposium of the Lysosomal-Disease-Network (LDN) CY FEB 12-15, 2013 CL Orlando, FL SP Lysosomal Dis Network (LDN) C1 [Rost, Natalia; Metterville, Danielle R.; Cloonan, Lisa K.; Fitzpatrick, Kaitlin M.; Sims, Katherine B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Germain, Dominique] Hop Raymond Poincare, Garches, France. [Politei, Juan M.] Juan Fernandez Hosp, Buenos Aires, DF, Argentina. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2013 VL 108 IS 2 MA 198 BP S80 EP S80 DI 10.1016/j.ymgme.2012.11.212 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 086FW UT WOS:000314670500200 ER PT J AU Schiffmann, R Forni, S Swift, C Wu, XY Lockhart, D Chee, M Kitaoka, T Chudin, E Pond, S McNeill, N Sims, K Benjamin, E Sweetman, L AF Schiffmann, Raphael Forni, Sabrina Swift, Caren Wu, Xiaoyang Lockhart, David Chee, Mark Kitaoka, Traci Chudin, Eugene Pond, Stephanie McNeill, Nathan Sims, Katherine Benjamin, Elfrida Sweetman, Lawrence TI High incidence of GLA variants in a non-selected heart disease patient population suggests that the Fabry trait is a common cardiovascular genetic risk factor SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 9th Annual World Symposium of the Lysosomal-Disease-Network (LDN) CY FEB 12-15, 2013 CL Orlando, FL SP Lysosomal Dis Network (LDN) C1 [Schiffmann, Raphael; Forni, Sabrina; Swift, Caren; McNeill, Nathan; Sweetman, Lawrence] Baylor Res Inst, Dallas, TX USA. [Wu, Xiaoyang; Lockhart, David; Benjamin, Elfrida] Amicus Therapeut, Cranbury, NJ USA. [Chee, Mark; Kitaoka, Traci; Chudin, Eugene; Pond, Stephanie] Prognosys Biosci Inc, La Jolla, CA USA. [Sims, Katherine] Massachusetts Gen Hosp, Neurogenet DNA Diagnost Lab, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2013 VL 108 IS 2 MA 204 BP S82 EP S82 DI 10.1016/j.ymgme.2012.11.218 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 086FW UT WOS:000314670500206 ER PT J AU Andres, PL English, R Mendoza, M Florence, J Malkus, E Schierbecker, J Siener, C Malspeis, S Schoenfeld, DA Munsat, TL Cudkowicz, ME AF Andres, Patricia L. English, Robert Mendoza, Michelle Florence, Julaine Malkus, Elizabeth Schierbecker, Jeanine Siener, Catherine Malspeis, Susan Schoenfeld, David A. Munsat, Theodore L. Cudkowicz, Merit E. TI Developing normalized strength scores for neuromuscular research SO MUSCLE & NERVE LA English DT Article DE ALS; neuromuscular; outcomes measures; strength testing; summary scores ID AMYOTROPHIC-LATERAL-SCLEROSIS; VOLUNTARY ISOMETRIC CONTRACTION; CLINICAL-TRIALS; ALS; MUSCLE AB Introduction: The Accurate Test of Limb Isometric Strength (ATLIS) device can reliably measure the strength of 12 muscle groups using a fixed load cell. The purpose of this study was to analyze ATLIS data from healthy adults to calculate an individual's predicted strength scores. Methods: ATLIS data were collected from 432 healthy adults. Linear regression models were developed to predict each muscle group's strength. The R-squared statistic assessed variability accounted for by the models. Results: Simple main effects models stratified by gender were used to establish regression equations for each muscle using factors of age, weight, and height. Conclusions: Normalizing raw strength scores controls for biometric factors, thus enabling meaningful comparisons between subjects and allowing each muscle to contribute equally to a summary score. Normalized scores are easily interpreted for broad clinical uses, and derived summary scores establish individuals' disease progression rates using a common scale, allowing for more efficient clinical trials. Muscle Nerve 47: 177-182, 2013 C1 [Andres, Patricia L.; Cudkowicz, Merit E.] Massachusetts Gen Hosp, Neurol Clin Trials Unit, Charlestown, MA 02129 USA. [English, Robert] Univ Kentucky, Dept Phys Therapy, Lexington, KY USA. [Mendoza, Michelle] Calif Pacific Med Ctr, Forbes Norris MDA ALS Res Ctr, San Francisco, CA USA. [Florence, Julaine; Malkus, Elizabeth; Schierbecker, Jeanine; Siener, Catherine] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Malspeis, Susan; Schoenfeld, David A.] Massachusetts Gen Hosp, Biostat Ctr, Charlestown, MA 02129 USA. [Munsat, Theodore L.] Tufts Med Ctr, Dept Neurol, Boston, MA USA. RP Andres, PL (reprint author), Massachusetts Gen Hosp, Neurol Clin Trials Unit, 149 13th St,Room 2274, Charlestown, MA 02129 USA. EM pandres1@partners.org FU ALS Association; Muscular Dystrophy Association; ALS Therapy Alliance; Northeast ALS Consortium FX The authors gratefully acknowledge support by the ALS Association, Muscular Dystrophy Association, the ALS Therapy Alliance, and the Northeast ALS Consortium. NR 33 TC 5 Z9 5 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD FEB PY 2013 VL 47 IS 2 BP 177 EP 182 DI 10.1002/mus.23516 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 078VS UT WOS:000314128700004 PM 23168880 ER PT J AU Khan, LA Zhang, HJ Abraham, N Sun, L Fleming, JT Buechner, M Hall, DH Gobel, V AF Khan, Liakot A. Zhang, Hongjie Abraham, Nessy Sun, Lei Fleming, John T. Buechner, Matthew Hall, David H. Gobel, Verena TI Intracellular lumen extension requires ERM-1-dependent apical membrane expansion and AQP-8-mediated flux SO NATURE CELL BIOLOGY LA English DT Article ID CAENORHABDITIS-ELEGANS; EXCRETORY CELL; WATER CHANNEL; ERM PROTEINS; C. ELEGANS; IN-VIVO; EZRIN; AQUAPORINS; MORPHOGENESIS; GENE AB Many unicellular tubes such as capillaries form lumens intracellularly, a process that is not well understood. Here we show that the cortical membrane organizer ERM-1 is required to expand the intracellular apical/lumenal membrane and its actin undercoat during single-cell Caenorhabditis elegans excretory canal morphogenesis. We characterize AQP-8, identified in an ERM-1-overexpression (ERM-1[++]) suppressor screen, as a canalicular aquaporin that interacts with ERM-1 in lumen extension in a mercury-sensitive manner, implicating water-channel activity. AQP-8 is transiently recruited to the lumen by ERM-1, co-localizing in peri-lumenal cuffs interspaced along expanding canals. An ERM-1[++]-mediated increase in the number of lumen-associated canaliculi is reversed by AQP-8 depletion. We propose that the ERM-1/AQP-8 interaction propels lumen extension by translumenal flux, suggesting a direct morphogenetic effect of water-channel-regulated fluid pressure. C1 [Khan, Liakot A.; Zhang, Hongjie; Abraham, Nessy; Fleming, John T.; Gobel, Verena] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Khan, Liakot A.; Zhang, Hongjie; Abraham, Nessy; Fleming, John T.; Gobel, Verena] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Buechner, Matthew] Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA. [Sun, Lei; Hall, David H.] Albert Einstein Coll Med, Ctr C Elegans Anat, Dept Neurosci, Bronx, NY 10461 USA. RP Gobel, V (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. EM gobel@helix.mgh.harvard.edu FU NIH [GM078653]; Mattina R. Proctor Award FX We thank D. Bailie (Simon Fraser University, Burnaby, British Columbia, Canada), M. Futai (Osaka University, Osaka, Japan), M. Labouesse (IGBMC, France), K. Nehrke (University of Rochester Medical Center, Rochester New York, USA) and J. Simske (Case Western Reserve University School of Medicine, Cleveland, Ohio, USA), and the following C. elegans resource centres: J. Kohara (National Institute of Genetics, Mishima, Japan), S. Mitani (National Bioresource Project, Tokyo Women's Medical University, Tokyo, Japan), the International C. elegans Gene Knockout Consortium and the Caenorhabditis elegans genetic centre (NIH Center for Research Resources) for providing plasmids and strains. We thank E. Membreno and D. Fernandez for technical support, A. Sengupta for three-dimensional graphics, A. Kim for image editing, F. Solomon for critical reading of the manuscript, and H. Weinstein and A. Walker for ongoing support. This work was supported by NIH grant GM078653 and a Mattina R. Proctor Award to V.G. NR 65 TC 30 Z9 32 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD FEB PY 2013 VL 15 IS 2 BP 143 EP 156 DI 10.1038/ncb2656 PG 14 WC Cell Biology SC Cell Biology GA 088SF UT WOS:000314856700006 PM 23334498 ER PT J AU Liew, CW Boucher, J Cheong, JK Vernochet, C Koh, HJ Mallol, C Townsend, K Langin, D Kawamori, D Hu, J Tseng, YH Hellerstein, MK Farmer, SR Goodyear, L Doria, A Bluher, M Hsu, SIH Kulkarni, RN AF Liew, Chong Wee Boucher, Jeremie Cheong, Jit Kong Vernochet, Cecile Koh, Ho-Jin Mallol, Cristina Townsend, Kristy Langin, Dominique Kawamori, Dan Hu, Jiang Tseng, Yu-Hua Hellerstein, Marc K. Farmer, Stephen R. Goodyear, Laurie Doria, Alessandro Blueher, Matthias Hsu, Stephen I-Hong Kulkarni, Rohit N. TI Ablation of TRIP-Br2, a regulator of fat lipolysis, thermogenesis and oxidative metabolism, prevents diet-induced obesity and insulin resistance SO NATURE MEDICINE LA English DT Article ID HORMONE-SENSITIVE LIPASE; WHITE ADIPOSE-TISSUE; ADIPOCYTE DIFFERENTIATION; BR FAMILY; MICE; OVEREXPRESSION; TRANSCRIPTION; INFLAMMATION; COREGULATORS; HOMEOSTASIS AB Obesity develops as a result of altered energy homeostasis favoring fat storage. Here we describe a new transcription co-regulator for adiposity and energy metabolism, SERTA domain containing 2 (TRIP-Br2, also called SERTAD2). TRIP-Br2 null mice are resistant to obesity and obesity-related insulin resistance. Adipocytes of these knockout mice showed greater stimulated lipolysis secondary to enhanced expression of hormone sensitive lipase (HSL) and beta 3-adrenergic (Adrb3) receptors. The knockout mice also have higher energy expenditure because of increased adipocyte thermogenesis and oxidative metabolism caused by upregulating key enzymes in their respective processes. Our data show that a cell-cycle transcriptional co-regulator, TRIP-Br2, modulates fat storage through simultaneous regulation of lipolysis, thermogenesis and oxidative metabolism. These data, together with the observation that TRIP-Br2 expression is selectively elevated in visceral fat in obese humans, suggests that this transcriptional co-regulator is a new therapeutic target for counteracting the development of obesity, insulin resistance and hyperlipidemia. C1 [Liew, Chong Wee; Boucher, Jeremie; Vernochet, Cecile; Koh, Ho-Jin; Townsend, Kristy; Kawamori, Dan; Hu, Jiang; Tseng, Yu-Hua; Goodyear, Laurie; Doria, Alessandro; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. [Cheong, Jit Kong] Duke Natl Univ Singapore, Grad Sch Med, Canc & Stem Cell Biol Program, Singapore, Singapore. [Vernochet, Cecile; Farmer, Stephen R.] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. [Mallol, Cristina] Univ Autonoma Barcelona, Ctr Anim Biotechnol & Gene Therapy, E-08193 Barcelona, Spain. [Langin, Dominique] Inst Metab & Cardiovasc Dis, Obes Res Lab, INSERM, U1048, Toulouse, France. [Hellerstein, Marc K.] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA. [Blueher, Matthias] Univ Leipzig, Dept Med, D-04109 Leipzig, Germany. [Hsu, Stephen I-Hong] Univ Florida, Coll Med, Dept Med, Gainesville, FL USA. [Hsu, Stephen I-Hong] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL USA. [Liew, Chong Wee] Univ Illinois, Dept Physiol & Biophys, Chicago, IL 60680 USA. RP Kulkarni, RN (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. EM clipcap2148@gmail.com; rohit.kulkarni@joslin.harvard.edu OI Langin, Dominique/0000-0002-2669-7825 FU US National Institutes of Health (NIH) [RO1 DK 67536]; Joslin Graetz Bridge Funds; Joslin Diabetes and Endocrinology Research Center Specialized Assay and Advanced Microscopy Cores [NIH P30 DK36836]; Deutsche Forschungsgemeinschaft Clinical Research group 'Atherobesity' [KFO152, BL 833/1-1]; US National Institutes of Health Interdisciplinary training grant [1RL9EB008539-01]; Manpei Suzuki Diabetes Foundation, Japan; Juvenile Diabetes Research Foundation; Dialysis Center, Inc.; University of Florida, Division of Nephrology Gatorade Fund; NIH [K99 DK090210, R01 HL073168, DK51586, DK58825]; Clinical Translational Science Institute at the University of Florida; [R00 DK090210] FX The authors thank C.R. Kahn (Joslin Diabetes Center) for providing reagents and discussions, E. Rosen for discussions, E. Morgan and K. Parlee for excellent assistance in the preparation of this manuscript, H. Li for assistance with hormone assays, O.P. McGuinness for mouse metabolic phenotyping, L. Fajas (INSERM) for providing reagents, M. Mori (Joslin Diabetes Center) for providing samples and R. Zechner for providing the protocol for triglyceride hydrolase activities. Funds to generate some reagents used in this research were supported by US National Institutes of Health (NIH) grant RO1 DK 67536 (R.N.K.) and the Joslin Graetz Bridge Funds (R.N.K.), NIH grants R01 HL073168 (A.D.), K99 DK090210 (C.W.L.), DK51586 and DK58825 (S.R.F.) and the Joslin Diabetes and Endocrinology Research Center Specialized Assay and Advanced Microscopy Cores (NIH P30 DK36836). The human studies were supported by a grant of the Deutsche Forschungsgemeinschaft Clinical Research group 'Atherobesity' (KFO152; BL 833/1-1). C.W.L. was supported by a US National Institutes of Health Interdisciplinary training grant (1RL9EB008539-01) (SysCODE), K99 DK090210 and R00 DK090210. D.K. is the recipient of a research fellowship (Manpei Suzuki Diabetes Foundation, Japan) and a Juvenile Diabetes Research Foundation postdoctoral Fellowship. S.I.-H.H. and J.K.C. were supported by the R. Glenn Davis (Dialysis Center, Inc.) Endowed Professorship in Clinical and Translational Medicine and by the University of Florida, Division of Nephrology Gatorade Fund. S.I.-H.H. was supported as a Scholar of the Clinical Translational Science Institute at the University of Florida. NR 49 TC 23 Z9 26 U1 4 U2 23 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 FEB PY 2013 VL 19 IS 2 BP 217 EP 226 DI 10.1038/nm.3056 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 086HY UT WOS:000314675900030 PM 23291629 ER PT J AU Gora, MJ Sauk, JS Carruth, RW Gallagher, KA Suter, MJ Nishioka, NS Kava, LE Rosenberg, M Bouma, BE Tearney, GJ AF Gora, Michalina J. Sauk, Jenny S. Carruth, Robert W. Gallagher, Kevin A. Suter, Melissa J. Nishioka, Norman S. Kava, Lauren E. Rosenberg, Mireille Bouma, Brett E. Tearney, Guillermo J. TI Tethered capsule endomicroscopy enables less invasive imaging of gastrointestinal tract microstructure SO NATURE MEDICINE LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; BARRETTS-ESOPHAGUS; INTESTINAL METAPLASIA; FEASIBILITY; ENDOSCOPY; DIAGNOSIS AB Here we introduce tethered capsule endomicroscopy, which involves swallowing an optomechanically engineered pill that captures cross-sectional microscopic images of the gut wall at 30 mu m (lateral) x 7 mu m (axial) resolution as it travels through the digestive tract. Results in human subjects show that this technique rapidly provides three-dimensional, microstructural images of the upper gastrointestinal tract in a simple and painless procedure, opening up new opportunities for screening for internal diseases. C1 [Gora, Michalina J.; Carruth, Robert W.; Gallagher, Kevin A.; Nishioka, Norman S.; Kava, Lauren E.; Rosenberg, Mireille; Bouma, Brett E.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Gora, Michalina J.; Sauk, Jenny S.; Carruth, Robert W.; Gallagher, Kevin A.; Nishioka, Norman S.; Kava, Lauren E.; Rosenberg, Mireille; Bouma, Brett E.; Tearney, Guillermo J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Sauk, Jenny S.; Nishioka, Norman S.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [Suter, Melissa J.] Massachusetts Gen Hosp, Dept Pulmonol, Boston, MA 02114 USA. [Tearney, Guillermo J.] Harvard MIT Hlth Sci & Technol, Cambridge, MA USA. [Tearney, Guillermo J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Tearney, GJ (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM gtearney@partners.org FU US National Institutes of Health [NIH R01DK091923, NIH R01CA103769] FX We thank B. Puricelli for his valuable assistance in the conduct of the clinical studies and M. Shishkov for useful discussions pertaining to device design. This work was supported in part by US National Institutes of Health grants NIH R01DK091923 (G.J.T.) and NIH R01CA103769 (G.J.T.). NR 14 TC 63 Z9 63 U1 1 U2 34 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 FEB PY 2013 VL 19 IS 2 BP 238 EP 240 DI 10.1038/nm.3052 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 086HY UT WOS:000314675900033 PM 23314056 ER PT J AU Vaduganathan, M Greene, SJ Ambrosy, AP Gheorghiade, M Butler, J AF Vaduganathan, Muthiah Greene, Stephen J. Ambrosy, Andrew P. Gheorghiade, Mihai Butler, Javed TI The disconnect between phase II and phase III trials of drugs for heart failure SO NATURE REVIEWS CARDIOLOGY LA English DT Review ID RANDOMIZED INTRAVENOUS TEZOSENTAN; BRAIN NATRIURETIC PEPTIDE; A(1) RECEPTOR ANTAGONIST; WORSENING RENAL-FUNCTION; COLLEGE-OF-CARDIOLOGY; DOUBLE-BLIND; CLINICAL-TRIALS; VASOPRESSIN ANTAGONIST; SYSTOLIC DYSFUNCTION; ORAL TOLVAPTAN AB Hospitalization for heart failure (HF) is a clinical entity associated with high postdischarge morbidity and mortality, yet few therapies are available to improve outcomes in patients with this condition. In the past debacle, large phase III studies of HF treatments have failed to demonstrate drug efficacy, safety, or both, despite encouraging results from preceding phase II trials. This Review is focused on this disconnect between the results of phase II and phase III trials of drugs for HF and discusses findings from five drug-development programs (for levosimendan, tezosentan, tolvaptan, rolofylline, and nesiritide) to shed light on common themes in clinical trials conducted in patients hospitalized for HF. In particular, the importance of selecting the 'right' patient population, drug, and clinical end points to optimize the trial design is discussed. Areas that require further investigation are highlighted and we suggest possible directions that will help to guide future clinical trials in these patients. Large, expensive phase III trials should not be initiated without adequate phase II evidence or on the basis of overly optimistic interpretation of phase II data. Additionally, drug development programs should be targeted not only to change short-term symptoms, but also to improve the postdischarge event rate. Vaduganathan, M. et al. Nat. Rev. Cardiol. 10, 85-97 (2013); published online 8 January 2013; doi:10.1038/nrcardio.2012.181 C1 [Vaduganathan, Muthiah] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Greene, Stephen J.; Gheorghiade, Mihai] NW Univ Feinberg, Ctr Cardiovasc Innovat, Sch Med, Chicago, IL 60611 USA. [Ambrosy, Andrew P.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Butler, Javed] Emory Univ, Div Cardiol, Atlanta, GA 30322 USA. RP Gheorghiade, M (reprint author), NW Univ Feinberg, Ctr Cardiovasc Innovat, Sch Med, 645 N Michigan Ave,Suite 1006, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu NR 78 TC 34 Z9 34 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5002 J9 NAT REV CARDIOL JI Nat. Rev. Cardiol. PD FEB PY 2013 VL 10 IS 2 BP 85 EP 97 DI 10.1038/nrcardio.2012.181 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 085OD UT WOS:000314623200007 PM 23296069 ER PT J AU Wang, CI Alekseyenko, AA LeRoy, G Elia, AEH Gorchakov, AA Britton, LMP Elledge, SJ Kharchenko, PV Garcia, BA Kuroda, MI AF Wang, Charlotte I. Alekseyenko, Artyom A. LeRoy, Gary Elia, Andrew E. H. Gorchakov, Andrey A. Britton, Laura-Mae P. Elledge, Stephen J. Kharchenko, Peter V. Garcia, Benjamin A. Kuroda, Mitzi I. TI Chromatin proteins captured by ChIP-mass spectrometry are linked to dosage compensation in Drosophila SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID X-CHROMOSOMAL GENES; VIVO CROSS-LINKING; RNA-POLYMERASE-II; MSL COMPLEX; PWWP DOMAIN; HISTONE H4; ANALYSIS REVEALS; METHYLATION; TRANSCRIPTION; GENOME AB X-chromosome dosage compensation by the MSL (male-specific lethal) complex is required in Drosophila melanogaster to increase gene expression from the single male X to equal that of both female X chromosomes. Instead of focusing solely on protein complexes released from DNA, here we used chromatin-interacting protein MS (ChIP-MS) to identify MSL interactions on cross-linked chromatin. We identified MSL-enriched histone modifications, including histone H4 Lys16 acetylation and histone H3 Lys36 methylation, and CG4747, a putative Lys36-trimethylated histone H3 (H3K36me3)-binding protein. CG4747 is associated with the bodies of active genes, coincident with H3K36me3, and is mislocalized in the Set2 mutant lacking H3K36me3. CG4747 loss of function in vivo results in partial mislocalization of the MSL complex to autosomes, and RNA interference experiments confirm that CG4747 and Set2 function together to facilitate targeting of the MSL complex to active genes, validating the ChIP-MS approach. C1 [Wang, Charlotte I.; Alekseyenko, Artyom A.; Elia, Andrew E. H.; Gorchakov, Andrey A.; Elledge, Stephen J.; Kuroda, Mitzi I.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Wang, Charlotte I.; Alekseyenko, Artyom A.; Elia, Andrew E. H.; Gorchakov, Andrey A.; Elledge, Stephen J.; Kuroda, Mitzi I.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [LeRoy, Gary; Britton, Laura-Mae P.; Garcia, Benjamin A.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. [Elia, Andrew E. H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Elia, Andrew E. H.; Elledge, Stephen J.] Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Gorchakov, Andrey A.] Inst Mol & Cell Biol, Novosibirsk, Russia. [Kharchenko, Peter V.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA USA. [Garcia, Benjamin A.] Univ Penn, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. RP Kuroda, MI (reprint author), Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA. EM mkuroda@genetics.med.harvard.edu RI Gorchakov, Andrey/N-5840-2015 OI Gorchakov, Andrey/0000-0003-2830-4236 FU Bloomington Stock Center and TRIP at Harvard Medical School [NIH/NIGMS R01-GM084947]; US National Institutes of Health (NIH) [GM45744, GM101958), K25AG037596, GM44664]; Jane Coffin Childs Foundation; American Society for Radiation Oncology; US National Science Foundation Early Faculty CAREER award and NIH award, Office of the Director [DP20D007447] FX We thank P. Kaiser (University of California, Irvine, Irvine, California, USA) for the HTB tag and insightful discussions. We thank G. Schotta (Ludwig-Maxirnilians Universitat, Munich, Germany) for the pGS-mw[+] vector. The anti-Z4 antibody was a generous gift from H. Saumweber (Humboldt University, Berlin, Germany). We thank E. Gerace from the Moazed lab (Harvard Medical School, Boston, Massachusetts, USA) for providing the protocol for coupling IgG to magnetic beads. We thank the Bloomington Stock Center and TRIP at Harvard Medical School (NIH/NIGMS R01-GM084947) for providing fly stocks used in this study. We are grateful to M. Gelbart for support and expertise, E. Smith for technical assistance and A. Ciccia, B. Adamson and A. Plachetka for critical reading of the manuscript. This work was supported by grants from the US National Institutes of Health (NIH) to M.I.K. (GM45744 and GM101958), P.V.K. (K25AG037596) and S.J.E. (GM44664). A.E.H.E. is supported by fellowships from The Jane Coffin Childs Foundation and The American Society for Radiation Oncology. B.A.G. is supported by a US National Science Foundation Early Faculty CAREER award and NIH award number DP20D007447 from the Office of the Director. NR 55 TC 43 Z9 44 U1 0 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD FEB PY 2013 VL 20 IS 2 BP 202 EP 209 DI 10.1038/nsmb.2477 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 085OF UT WOS:000314623400012 PM 23295261 ER PT J AU Mendez, MF Joshi, A Tassniyom, K Teng, E Shapira, JS AF Mendez, Mario F. Joshi, Aditi Tassniyom, Kanida Teng, Edmond Shapira, Jill S. TI Clinicopathologic differences among patients with behavioral variant frontotemporal dementia SO NEUROLOGY LA English DT Article ID CENTER NACC DATABASE; UNIFORM DATA SET; LOBAR DEGENERATION; ALZHEIMER-DISEASE; DIAGNOSTIC-CRITERIA; CONSORTIUM; CONSENSUS; FEATURES AB Objective: To characterize the presenting symptoms and signs of patients clinically diagnosed with behavioral variant frontotemporal dementia (bvFTD) and who had different neuropathologic findings on autopsy. Methods: This study reviewed all patients entered as clinical bvFTD in the National Alzheimer's Coordinating Center's database and who had both clinical and neuropathologic data from 2005 to 2011. Among the 107 patients identified, 95 had unambiguous pathologic findings, including 74 with frontotemporal lobar degeneration (bvFTD-FTLD) and 21 with Alzheimer disease (bvFTD-AD). The patients with bvFTD-FTLD were further subdivided into tau-positive (n = 23) or tau-negative (n = 51) histopathology subgroups. Presenting clinical signs and symptoms were compared between these neuropathologic groups. Results: The patients with bvFTD-FTLD were significantly more likely than patients with bvFTD-AD to have initially predominant personality changes and poor judgment/decision-making. In contrast, patients with bvFTD-AD were more likely than patients with bvFTD-FTLD to have memory difficulty and delusions/hallucinations and agitation. Within the bvFTD-FTLD group, the tau-positive subgroup had more patients with initial behavioral problems and personality change than the tau-negative subgroup, who, in turn, had more patients with initial cognitive impairment and speech problems. Conclusion: During life, patients with AD pathology may be misdiagnosed with bvFTD if they have an early age at onset and prominent neuropsychiatric features despite having greater memory difficulties and more intact personality and executive functions than patients with bvFTD-FTLD. Among those with FTLD pathology, patients with tau-positive bvFTD were likely to present with behavior/personality changes. These findings offer clues for antemortem recognition of neuropathologic subtypes of bvFTD. Neurology (R) 2013;80:561-568 C1 [Mendez, Mario F.; Joshi, Aditi; Teng, Edmond; Shapira, Jill S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Mendez, Mario F.; Teng, Edmond] VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. [Tassniyom, Kanida] Khon Kaen Univ, Dept Psychiat, Khon Kaen, Thailand. RP Mendez, MF (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. EM mmendez@ucla.edu FU NIA [R01AG034499-03]; VA Merit Review; Alzheimer's Disease Research Center Grant [NIA P50 AG-16570]; NACC [UO1 AG016976] FX Supported by NIA grant #R01AG034499-03 (M.F. Mendez), a VA Merit Review (A. Joshi, M.F. Mendez), Alzheimer's Disease Research Center Grant NIA P50 AG-16570 (M.F. Mendez), and the NACC grant (UO1 AG016976). NR 27 TC 29 Z9 32 U1 0 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 2013 VL 80 IS 6 BP 561 EP 568 DI 10.1212/WNL.0b013e3182815547 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 086OD UT WOS:000314693800014 PM 23325909 ER PT J AU Dunn, GP Andronesi, OC Cahill, DP AF Dunn, Gavin P. Andronesi, Ovidiu C. Cahill, Daniel P. TI From genomics to the clinic: biological and translational insights of mutant IDH1/2 in glioma SO NEUROSURGICAL FOCUS LA English DT Article DE isocitrate dehydrogenase 1; isocitrate dehydrogenase 2; glioblastoma; low-grade glioma; magnetic resonance spectroscopy ID ISOCITRATE DEHYDROGENASE 1; ACUTE MYELOID-LEUKEMIA; MAGNETIC-RESONANCE-SPECTROSCOPY; CODON 132 MUTATION; CELL LUNG-CANCER; IDH2 MUTATIONS; ONCOMETABOLITE 2-HYDROXYGLUTARATE; INDUCED APOPTOSIS; MAFFUCCI SYNDROME; OLLIER DISEASE AB The characterization of the genomic alterations across all human cancers is changing the way that malignant disease is defined and treated. This paradigm is extending to glioma, where the discovery of recurrent mutations in the isocitrate dehydrogenase 1 (IDH1) gene has shed new light on the molecular landscape in glioma and other IDH-mutant cancers. The IDH1 mutations are present in the vast majority of low-grade gliomas and secondary glioblastomas. Rapidly emerging work on the consequences of mutant IDH1 protein expression suggests that its neomorphic enzymatic activity catalyzing the production of the oncometabolite 2-hydroxyglutarate influences a range of cellular programs that affect the epigenome, transcriptional programs, hypoxia-inducible factor biology, and development. In the brief time since its discovery, knowledge of the IDH mutation status has had significant translational implications, and diagnostic tools are being used to monitor its expression and function. The concept of IDH1-mutant versus IDH1-wild type will become a critical early distinction in diagnostic and treatment algorithms. (http://thejns.org/doi/abs/10.3171/2012.12.FOCUS12355) C1 [Dunn, Gavin P.; Cahill, Daniel P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. [Andronesi, Ovidiu C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Cahill, DP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. EM dcahill@partners.org OI Cahill, Daniel/0000-0003-2552-6546 FU Buroughs-Wellcome Fund Career Award; American Brain Tumor Association; NIH NINDS [R25]; KL2 Medical Research Investigator Training (MeRIT) award from the Harvard Catalyst-The Harvard Clinical and Translational Science Center (National Center for Research Resources); National Center for Advancing Translational Sciences, NIH Award [8KL2TR000168-05]; National Institute of Biomedical Imaging and Bioengineering (NIBIB) of the NIH; NIH Shared Instrumentation Grant Program [S10RR021110]; NIH High-End Instrumentation Grant Program [S10RR021110] FX This work was supported by the Buroughs-Wellcome Fund Career Award (Dr. Cahill); the American Brain Tumor Association and the NIH NINDS R25 award (Dr. Dunn); and the KL2 Medical Research Investigator Training (MeRIT) award from the Harvard Catalyst-The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH Award 8KL2TR000168-05) (Dr. Andronesi). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, or the NIH.; Imaging research (Dr. Andronesi) was carried out in part at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41EB015896, a P41 Regional Resource supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) of the NIH. This work also involved the use of instrumentation supported by the NIH Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program, specifically Grant No. S10RR021110. NR 102 TC 15 Z9 17 U1 2 U2 19 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 FEB PY 2013 VL 34 IS 2 AR E2 DI 10.3171/2012.12.FOCUS12355 PG 15 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 084FD UT WOS:000314522200003 PM 23373447 ER PT J AU Jones, PS Dunn, GP Barker, FG Curry, WT Hochberg, FH Cahill, DP AF Jones, Pamela S. Dunn, Gavin P. Barker, Fred G., II Curry, William T. Hochberg, Fred H. Cahill, Daniel P. TI Molecular genetics of low-grade gliomas: genomic alterations guiding diagnosis and therapeutic intervention. 11th Annual Frye-Halloran Brain Tumor Symposium Meeting Report SO NEUROSURGICAL FOCUS LA English DT Article DE glioma; meeting report; IDH ID CENTRAL-NERVOUS-SYSTEM; ACUTE MYELOID-LEUKEMIA; IDH2 MUTATIONS; GLIOBLASTOMA-MULTIFORME; DIFFERENTIATION; CLASSIFICATION; SURVIVAL; OLIGODENDROGLIOMAS; HYPERMETHYLATION; IDENTIFICATION AB Object. The authors' goal was to review the current understanding of the underlying molecular and genetic mechanisms involved in low-grade glioma development and how these mechanisms can be targets for detection and treatment of the disease and its recurrence. Methods. On October 4, 2012, the authors convened a meeting of researchers and clinicians across a variety of pertinent medical specialties to review the state of current knowledge on molecular genetic mechanisms of low-grade gliomas and to identify areas for further research and drug development. Results. The meeting consisted of 3 scientific sessions ranging from neuropathology of IDH1 mutations; CIC, ATRX, and FUBP1 mutations in oligodendrogliomas and astrocytomas; and IDH1 mutations as therapeutic targets. Sessions consisted of a total of 10 talks by international leaders in low-grade glioma research, mutant IDH1 biology and its application in glioma research, and treatment. Conclusions. The recent discovery of recurrent gene mutations in low-grade glioma has increased the understanding of the molecular mechanisms involved in a host of biological activities related to low-grade gliomas. Understanding the role these genetic alterations play in brain cancer initiation and progression will help lead to the development of novel treatment modalities than can be personalized to each patient, thereby helping transform this now often-fatal malignancy into a chronic or even curable disease. (http://thejns.org/doi/abs/10.3171/2012.12.FOCUS12349) C1 [Jones, Pamela S.; Dunn, Gavin P.; Barker, Fred G., II; Curry, William T.; Hochberg, Fred H.; Cahill, Daniel P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Cahill, DP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,YAW 9E-9026, Boston, MA 02114 USA. EM dcahill@partners.org FU The Carolyn Frye-Halloran Brain Tumor Therapy Program FX The Carolyn Frye-Halloran Brain Tumor Therapy Program sponsored the symposium. NR 26 TC 5 Z9 7 U1 0 U2 17 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 FEB PY 2013 VL 34 IS 2 AR E9 DI 10.3171/2012.12.FOCUS12349 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 084FD UT WOS:000314522200010 PM 23373454 ER PT J AU Park, JW Piknova, B Huang, PL Noguchi, CT Schechter, AN AF Park, Ji Won Piknova, Barbora Huang, Paul L. Noguchi, Constance T. Schechter, Alan N. TI Effect of Blood Nitrite and Nitrate Levels on Murine Platelet Function SO PLOS ONE LA English DT Article ID OXIDE SYNTHASE; XANTHINE OXIDOREDUCTASE; DIETARY NITRATE; HYPOXIC CONDITIONS; RELAXING FACTOR; REDUCTION; ENDOTHELIUM; AGGREGATION; HUMANS; MICE AB Nitric oxide (NO) appears to play an important role in the regulation of thrombosis and hemostasis by inhibiting platelet function. The discovery of NO generation by reduction of nitrite (NO2-) and nitrate (NO3-) in mammals has led to increased attention to these anions with respect to potential beneficial effects in cardiovascular diseases. We have previously shown that nitrite anions at 0.1 mu M inhibit aggregation and activation of human platelet preparations in vitro in the presence of red blood cells and this effect was enhanced by deoxygenation, an effect likely due to NO generation. In the present study, we hypothesized that nitrite and nitrate derived from the diet could also alter platelet function upon their conversion to NO in vivo. To manipulate the levels of nitrite and nitrate in mouse blood, we used antibiotics, NOS inhibitors, low nitrite/nitrate (NOx) diets, endothelial NOS knock-out mice and also supplementation with high levels of nitrite or nitrate in the drinking water. We found that all of these perturbations affected nitrite and nitrate levels but that the lowest whole blood values were obtained by dietary restriction. Platelet aggregation and ATP release were measured in whole blood and the results show an inverse correlation between nitrite/nitrate levels and platelet activity in aggregation and ATP release. Furthermore, we demonstrated that nitrite-supplemented group has a prolonged bleeding time compared with control or low NOx diet group. These results show that diet restriction contributes greatly to blood nitrite and nitrate levels and that platelet reactivity can be significantly affected by these manipulations. Our study suggests that endogenous levels of nitrite and nitrate may be used as a biomarker for predicting platelet function and that dietary manipulation may affect thrombotic processes. C1 [Park, Ji Won; Piknova, Barbora; Noguchi, Constance T.; Schechter, Alan N.] NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA. [Huang, Paul L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Schechter, AN (reprint author), NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA. EM alans@intra.niddk.nih.gov OI Schechter, Alan N/0000-0002-5235-9408 FU National Institue of Diabetes and Digestive and Kidney Diseases FX This research was supported by grants from the intramural program of the National Institue of Diabetes and Digestive and Kidney Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 25 Z9 26 U1 0 U2 11 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 FEB 1 PY 2013 VL 8 IS 2 AR e55699 DI 10.1371/journal.pone.0055699 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 085EU UT WOS:000314597900051 PM 23383344 ER PT J AU Traeger, L Penedo, FJ Benedict, C Dahn, JR Lechner, SC Schneiderman, N Antoni, MH AF Traeger, Lara Penedo, Frank J. Benedict, Catherine Dahn, Jason R. Lechner, Suzanne C. Schneiderman, Neil Antoni, Michael H. TI Identifying how and for whom cognitive-behavioral stress management improves emotional well-being among recent prostate cancer survivors SO PSYCHO-ONCOLOGY LA English DT Article DE cancer; oncology; prostate carcinoma; psychosocial intervention; illness perceptions ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; RADICAL PROSTATECTOMY; FUNCTIONAL ASSESSMENT; BREAST-CANCER; MEN; THERAPY; OUTCOMES; ILLNESS; VALIDATION AB Objective The outcomes of a 10-week cognitive-behavioral stress management (CBSM) group intervention were evaluated in prostate cancer survivors. A model was tested in which CBSM-related improvements in emotional well-being were attained through changes in men's perceptions of their condition, as conceptualized by information processing explanations of self-regulation theory. The model also tested whether life stress and treatment-related side effects moderated intervention effects. Methods Men treated for localized prostate cancer (n=257) within the past 18months were randomized to CBSM or a half-day psycho-educational seminar. At pre-intervention and 12-week follow-up, emotional well-being, illness perceptions, life stress, and sexual and urinary function were assessed using validated questionnaires. Results After controlling for covariates, CBSM participants showed greater improvements in emotional well-being relative to control participants (=0.13, p<0.05). For men reporting higher stress upon study entry, CBSM-related improvements were partially explained by changes in some, but not all, illness perceptions. Sexual and urinary dysfunction did not influence CBSM-related gains. Conclusions Prostate cancer perceptions may be an important target for enhancing emotional well-being, particularly for men experiencing general life stress. However, interventions that explicitly target mental representations of cancer may be needed to modify perceptions of the disease. Copyright (c) 2011 John Wiley & Sons, Ltd. C1 [Traeger, Lara] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Penedo, Frank J.; Benedict, Catherine; Lechner, Suzanne C.; Schneiderman, Neil; Antoni, Michael H.] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. [Dahn, Jason R.] Miami VA Med Ctr, Psychol Serv, Miami, FL USA. RP Traeger, L (reprint author), Massachusetts Gen Hosp, Behav Med Serv, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ltraeger@partners.org FU NCI NIH HHS [1P50CA84944, U01CA861] NR 44 TC 12 Z9 12 U1 3 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2013 VL 22 IS 2 BP 250 EP 259 DI 10.1002/pon.2074 PG 10 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 083VQ UT WOS:000314493700003 PM 21932396 ER PT J AU Herndon, JE Kornblith, AB Holland, JC Paskett, ED AF Herndon, James E., II Kornblith, Alice B. Holland, Jimmie C. Paskett, Electra D. TI Effect of socioeconomic status as measured by education level on survival in breast cancer clinical trials SO PSYCHO-ONCOLOGY LA English DT Article DE breast cancer; oncology; education; survival; SES ID LEUKEMIA GROUP-B; AFRICAN-AMERICAN PATIENTS; INTERMEDIATE-DOSE CHEMOTHERAPY; CELL LUNG-CARCINOMA; QUALITY-OF-LIFE; ADJUVANT CHEMOTHERAPY; PHASE-III; SOCIAL INEQUALITIES; RACIAL-DIFFERENCES; PROGNOSTIC-FACTORS AB Objectives This paper aims to investigate the effect of socioeconomic status, as measured by education, on the survival of breast cancer patients treated on 10 studies conducted by the Cancer and Leukemia Group B. Methods Sociodemographic data, including education, were reported by the patient at trial enrollment. Cox proportional hazards model stratified by treatment arm/study was used to examine the effect of education on survival among patients with early stage and metastatic breast cancer, after adjustment for known prognostic factors. Results The patient population included 1020 patients with metastatic disease and 5146 patients with early stage disease. Among metastatic patients, factors associated with poorer survival in the final multivariable model included African American race, never married, negative estrogen receptor status, prior hormonal therapy, visceral involvement, and bone involvement. Among early stage patients, significant factors associated with poorer survival included African American race, separated/widowed, post/perimenopausal, negative/unknown estrogen receptor status, negative progesterone receptor status, >4 positive nodes, tumor diameter >2cm, and education. Having not completed high school was associated with poorer survival among early stage patients. Among metastatic patients, non-African American women who lacked a high school degree had poorer survival than other non-African American women, and African American women who lacked a high school education had better survival than educated African American women. Conclusions Having less than a high school education is a risk factor for death among patients with early stage breast cancer who participated in a clinical trial, with its impact among metastatic patients being less clear. Post-trial survivorship plans need to focus on women with low social status, as measured by education. Copyright (c) 2011 John Wiley & Sons, Ltd. C1 [Herndon, James E., II] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA. [Kornblith, Alice B.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Holland, Jimmie C.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Paskett, Electra D.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA. [Paskett, Electra D.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. RP Herndon, JE (reprint author), Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Hock Plaza,Suite 802,Box 2717, Durham, NC 27710 USA. EM james.herndon@duke.edu FU National Cancer Institute [CA31946, CA33601]; [CA32291]; [CA77651]; [CA77658] FX The research was supported, in part, by grants from the National Cancer Institute (CA31946) to the Cancer and Leukemia Group B (Richard L. Schilsky, MD, Chairman) and to the CALGB Statistical Center (Stephen George, PhD, CA33601). The authors were also supported by grants (Alice B. Kornblith, PhD, CA32291; Jimmie C. Holland, MD, CA77651; Electra D. Paskett, PhD, CA77658). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. NR 62 TC 6 Z9 6 U1 0 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2013 VL 22 IS 2 BP 315 EP 323 DI 10.1002/pon.2094 PG 9 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 083VQ UT WOS:000314493700010 PM 22021121 ER PT J AU Varela, VS Ng, A Mauch, P Recklitis, CJ AF Varela, Veronica Sanchez Ng, Andrea Mauch, Peter Recklitis, Christopher J. TI Posttraumatic stress disorder (PTSD) in survivors of Hodgkin's lymphoma: prevalence of PTSD and partial PTSD compared with sibling controls SO PSYCHO-ONCOLOGY LA English DT Article DE Hodgkin's lymphoma; long-term survivors; posttraumatic stress; survey; cancer; oncology ID BONE-MARROW-TRANSPLANTATION; BREAST-CANCER PATIENTS; LONG-TERM SURVIVORS; CHILDHOOD-CANCER; SYMPTOMS; DIAGNOSIS; SYMPTOMATOLOGY; CHILDREN; PARENTS; DISEASE AB Objectives Studies of posttraumatic stress disorder (PTSD) document a significant proportion of cancer survivors reporting severe posttraumatic stress symptoms, even when they do not meet full diagnostic criteria. However, few studies have directly examined the clinical significance of these partial PTSD' symptoms in survivors. This study aimed to investigate the prevalence of PTSD symptoms in a cohort of long-term survivors of Hodgkin's lymphoma (HL) and to explore the clinical relevance of the partial PTSD phenomenon by assessing impairment of function secondary to sub-threshold symptomatology. Methods The Posttraumatic Diagnostic Scale was completed by 105 HL survivors and 101 sibling controls. Survivors' age at time of participation ranged from 24 to 71 years, age at time of diagnosis ranged from 6 to 61 years, and the median time since diagnosis was 16 years (range=734). Results Posttraumatic stress disorder prevalence was not significantly higher in HL survivors (13%) compared with sibling controls (6.9%, p=0.098). However, a significantly larger proportion of survivors (35.2%) met criteria for partial PTSD compared with siblings (17.8%, p=0.004). Moreover, the majority of the survivors with partial PTSD (86.5%) reported experiencing some functional impairment related to these posttraumatic stress symptoms. Conclusions A significant number of HL survivors experience posttraumatic stress symptoms severe enough to result in functional impairment. This finding underscores the importance of future research detailing the psychological and functional outcomes in survivors with partial PTSD and of careful clinical practice that assesses for functional impairment secondary to partial PTSD symptomatology, in male and female survivors, even years after completion of therapy. Copyright (c) 2011 John Wiley & Sons, Ltd. C1 [Varela, Veronica Sanchez; Recklitis, Christopher J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ng, Andrea; Mauch, Peter] Brigham & Womens Hosp, Boston, MA 02115 USA. [Varela, Veronica Sanchez; Ng, Andrea; Mauch, Peter; Recklitis, Christopher J.] Harvard Univ, Sch Med, Boston, MA USA. RP Recklitis, CJ (reprint author), Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02115 USA. EM Christopher_Recklitis@dfci.harvard.edu FU National Cancer Institute [5R03CA134159-02] FX This research was supported by Grant Number 5R03CA134159-02 to Dr. Recklitis from the National Cancer Institute. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute or NIH. NR 33 TC 8 Z9 8 U1 7 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2013 VL 22 IS 2 BP 434 EP 440 DI 10.1002/pon.2109 PG 7 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 083VQ UT WOS:000314493700025 PM 22162210 ER PT J AU Fisher, DF Kondili, D Williams, J Hess, DR Bittner, EA Schmidt, UH AF Fisher, Daniel F. Kondili, Dhimiter Williams, June Hess, Dean R. Bittner, Edward A. Schmidt, Ulrich H. TI Tracheostomy Tube Change Before Day 7 Is Associated With Earlier Use of Speaking Valve and Earlier Oral Intake SO RESPIRATORY CARE LA English DT Article DE tracheostomy; mechanical ventilation; respiratory failure; outcomes; safety ID VENTILATION AB BACKGROUND: Presence of a tracheostomy tube often decreases the patient's ability to communicate and to tolerate oral intake. The initial tracheostomy tube change is often recommended between day 7 and 14 post insertion. Local guidelines permit tracheostomy tube change 5 days after insertion. OBJECTIVE: We hypothesized that changing tracheostomy tubes before day 7 is associated with earlier use of a speaking valve as well as earlier oral intake, compared to changing tracheostomy tubes after 7 days. METHODS: We prospectively enrolled 130 admitted subjects, after tracheostomy placement to a respiratory care unit between July 2008 and May 2010. Subject data were recorded from the electronic medical record. The primary end point was the time from tracheostomy tube placement to tolerating speaking valve. The secondary end point was the time from tracheostomy tube placement to tolerating oral intake. Complications of tracheostomy tube change were recorded. RESULTS: Thirty-eight subjects had the first tracheostomy tube change before 7 days (early group), and 92 subjects had the first tracheostomy tube change after 7 days (late group). The early group tolerated a speaking valve significantly sooner than the late group (7 d vs 12 d, P = .001). The early group also tolerated oral intake significantly sooner (10 d vs 20 d, P = .04). After change of the tracheostomy tube, the time to tolerating oral feeding was 5.5 days in both groups. There was no significant difference in time to decannulation between the groups. The early group had a shorter respiratory care unit stay (11 d vs 17 d, P = .001) and a shorter hospital stay (P = .05) than the late group. There was no difference in survival. There were no complications associated with tracheostomy tube change. CONCLUSIONS: Tracheostomy tube change before day 7 is associated with earlier ability to tolerate speaking valve and oral intake. In this series, early tracheostomy tube change was not associated with an increased rate of complications. C1 [Fisher, Daniel F.; Hess, Dean R.; Schmidt, Ulrich H.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Williams, June] Massachusetts Gen Hosp, Dept Speech Language & Swallowing Disorders, Boston, MA 02114 USA. [Kondili, Dhimiter; Hess, Dean R.; Bittner, Edward A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Hess, Dean R.; Bittner, Edward A.; Schmidt, Ulrich H.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [Schmidt, Ulrich H.] Massachusetts Gen Hosp, Surg Intens Care Unit, Boston, MA 02114 USA. RP Schmidt, UH (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Surg Intens Care Unit, 55 Fruit St,Gray 4, Boston, MA 02114 USA. EM uschmidt@partners.org NR 15 TC 4 Z9 5 U1 0 U2 7 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD FEB PY 2013 VL 58 IS 2 BP 257 EP 263 DI 10.4187/respcare.01714 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 084PY UT WOS:000314552800005 PM 22782273 ER PT J AU Wilcox, SR Richards, JB AF Wilcox, Susan R. Richards, Jeremy B. TI Noninvasive Carbon Monoxide Detection: Insufficient Evidence for Broad Clinical Use SO RESPIRATORY CARE LA English DT Editorial Material ID LABORATORY CARBOXYHEMOGLOBIN MEASUREMENT; PULSE COOXIMETER; EMERGENCY-DEPARTMENT; ICE STORM; OXIMETRY; METHEMOGLOBIN; DIAGNOSIS; PERFORMANCE; MANAGEMENT C1 [Wilcox, Susan R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Wilcox, Susan R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Richards, Jeremy B.] Beth Israel Deaconess Med Ctr, Dept Med, Div Pulm Crit Care & Sleep Med, Boston, MA 02215 USA. [Richards, Jeremy B.] Harvard Univ, Sch Med, Boston, MA USA. RP Wilcox, SR (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM swilcox1@partners.org OI Wilcox, Susan/0000-0001-7477-7531 NR 25 TC 1 Z9 1 U1 0 U2 5 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD FEB PY 2013 VL 58 IS 2 BP 376 EP 379 DI 10.4187/respcare.02288 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 084PY UT WOS:000314552800020 PM 23359727 ER PT J AU Gazourian, L Coronata, AMF Rogers, AJ Weinhouse, GL Soiffer, RJ Antin, JH Ritz, J Ho, VT Baron, RM Washko, GR AF Gazourian, Lee Coronata, Anna Maria F. Rogers, Angela J. Weinhouse, Gerald L. Soiffer, Robert J. Antin, Joseph H. Ritz, Jerome Ho, Vincent T. Baron, Rebecca M. Washko, George R. TI Airway dilation in bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation SO RESPIRATORY MEDICINE LA English DT Article DE Computed tomography; Bone marrowtransplantation; Bronchiolitis obliterans syndrome; Airway disease ID BONE-MARROW-TRANSPLANTATION; HIGH-RESOLUTION CT; THIN-SECTION CT; OBSTRUCTIVE PULMONARY-DISEASE; VERSUS-HOST-DISEASE; LUNG TRANSPLANTATION; COMPUTED-TOMOGRAPHY; FLOW OBSTRUCTION; FUNCTION TESTS; RISK-FACTORS AB Rationale: Bronchiolitis obliterans syndrome (BOS) is a late, non-infectious pulmonary complication following hematopoietic stem cell transplantation (HSCT). There is minimal data published on quantitative radiologic characterization of airway remodeling in these subjects. Objectives: To examine quantitative measurements of airway morphology and their correlation with lung function in a cohort of patients who underwent HSCT and developed BOS. Methods: All adult patients who underwent allogeneic HSCT at the Dana-Farber Cancer Institute/Brigham and Women's Hospital (n = 1854) between January 1st 2000 and June 30th 2010 were screened for the development of BOS. Clinically acquired high resolution CT (HRCT) scans of the chest were collected. For each subjects discrete measures of airway wall area were performed and the square root of wall area of a 10-mm luminal perimeter (Pi 10) was calculated. Measurements and main results: We identified 88 cases of BOS, and 37 of these patients had available HRCT. On CT scans obtained after BOS diagnosis, the Pi10 decreased (consistent with airway dilation) as compared with pre-BOS values (p < 0.001). After HSCT the Pi10 correlated with FEV1% predicted (r = 0.636, p < 0.0001), and RV/TLC% predicted (r = -0.736, p < 0.0001), even after adjusting for age, sex and total lung capacity (p < 0.0001 for both). Conclusions: On HRCT scan BOS is characterized by central airway dilation, the degree of which is correlated to decrements in lung function. This is opposite of what has been previously demonstrated in COPD and asthma that quantitative measure of proximal airway wall thickening directly correlate with pulmonary function. Our data suggests that the pathologic process affecting the central airways is different from the pathology observed in the distal airways. Further work is needed to determine if such change can be used as a sensitive and specific tool for the future diagnosis and staging of BOS. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Gazourian, Lee; Coronata, Anna Maria F.; Rogers, Angela J.; Weinhouse, Gerald L.; Baron, Rebecca M.; Washko, George R.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Rogers, Angela J.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Soiffer, Robert J.; Antin, Joseph H.; Ritz, Jerome; Ho, Vincent T.] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02115 USA. RP Gazourian, L (reprint author), Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA. EM lgazourian@partners.org OI Ritz, Jerome/0000-0001-5526-4669 FU National Institutes of Health [5T32HL007118-35, 5T32HL007680-20, K23HL089353-04, CA142106, PO1HL070149-02]; Ted and Eileen Pasquarello Research Fund; Jock and Bunny Adams Education and Research Fund; Parker B. Francis Foundation FX This work was supported by the following National Institutes of Health grants; Dr. Gazourian 5T32HL007118-35, 5T32HL007680-20, Dr. Washko, K23HL089353-04. The DFCI BMT data repository is supported, in part, by the Ted and Eileen Pasquarello Research Fund; NIH grants; CA142106, and PO1HL070149-02; and the Jock and Bunny Adams Education and Research Fund. Dr. Rogers and Dr. Washko were also supported by an award from the Parker B. Francis Foundation. NR 36 TC 6 Z9 6 U1 0 U2 5 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD FEB PY 2013 VL 107 IS 2 BP 276 EP 283 DI 10.1016/j.rmed.2012.11.002 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 084RE UT WOS:000314556000015 PM 23195332 ER PT J AU Sibila, O Restrepo, MI AF Sibila, Oriol Restrepo, Marcos I. TI Corticosteroids for pneumonia: Are we there yet? SO RESPIROLOGY LA English DT Editorial Material DE community-acquired pneumonia; corticosteroid; length of stay; pneumonia ID COMMUNITY-ACQUIRED PNEUMONIA; CONTROLLED-TRIAL; CLINICAL-COURSE; GLUCOCORTICOIDS C1 [Sibila, Oriol] Hosp Santa Creu & Sant Pau, Serv Pneumol, Barcelona, Spain. [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Restrepo, Marcos I.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Restrepo, Marcos I.] Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. RP Sibila, O (reprint author), Hosp Santa Creu & Sant Pau, Serv Pneumol, Barcelona, Spain. RI Restrepo, Marcos/H-4442-2014 FU NHLBI NIH HHS [K23HL096054, K23 HL096054] NR 12 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1323-7799 J9 RESPIROLOGY JI Respirology PD FEB PY 2013 VL 18 IS 2 BP 199 EP 200 DI 10.1111/resp.12012 PG 2 WC Respiratory System SC Respiratory System GA 078RH UT WOS:000314116500001 PM 23134329 ER PT J AU Bui, E Rodgers, R Simon, NM Jehel, L Metcalf, CA Birmes, P Schmitt, L AF Bui, Eric Rodgers, Rachel Simon, Naomi M. Jehel, Louis Metcalf, Christina A. Birmes, Philippe Schmitt, Laurent TI Body Piercings and Posttraumatic Stress Disorder Symptoms in Young Adults SO STRESS AND HEALTH LA English DT Article DE traumatic stress/disaster relief operations; group norms; psychological well-being ID SENSATION SEEKING; COLLEGE-STUDENTS; ADOLESCENTS; MOTIVATIONS; POPULATION; PERCEPTION; BEHAVIOR; TATTOOS; ART AB Body piercing, which is prevalent in young adults, has been suggested to be associated with features usually related to posttraumatic stress disorder (PTSD) such as high-risk behaviours and psychopathological symptoms and might be motivated by a wish to deal with prior traumatic experiences. However, to date, no research has investigated the relationship between this practice and PTSD symptoms. The present research aims to investigate the possible relationship between body piercing and PTSD symptoms in French-speaking young adults. According to our results, having two or more body piercings was associated with a twofold increased risk for scoring above the cut-off score for PTSD on the PTSD checklist. Our findings suggest that two or more body piercings might serve as an identifiable marker for PTSD symptoms and may have important implications for clinical screening. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 [Bui, Eric; Birmes, Philippe; Schmitt, Laurent] CHU Toulouse, Lab Stress Traumat EA4560, Toulouse, France. [Bui, Eric; Birmes, Philippe; Schmitt, Laurent] Univ Toulouse, Toulouse, France. [Bui, Eric; Simon, Naomi M.; Metcalf, Christina A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rodgers, Rachel] Univ Toulouse Le Mirail, Toulouse, France. [Rodgers, Rachel] Northeastern Univ, Boston, MA 02115 USA. [Jehel, Louis] Univ Antilles Guyane, CHU Ft de France, Fort De France, France. [Jehel, Louis] INSERM, U669, Fort De France, France. RP Bui, E (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. EM tebui@partners.org RI Bui, Eric/J-8347-2015 OI Bui, Eric/0000-0002-1413-6473 FU Traumapsy Association; Centre Hospitalier Universitaire de Toulouse FX This research was supported by a grant from the Traumapsy Association and the Centre Hospitalier Universitaire de Toulouse awarded to Eric Bui. NR 23 TC 0 Z9 0 U1 4 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1532-3005 J9 STRESS HEALTH JI Stress Health PD FEB PY 2013 VL 29 IS 1 BP 70 EP 74 DI 10.1002/smi.2427 PG 5 WC Psychology, Applied; Psychiatry; Psychology SC Psychology; Psychiatry GA 083NY UT WOS:000314472500011 PM 22499241 ER PT J AU Kelley, JM Onderdonk, AB Kao, G AF Kelley, James M. Onderdonk, Andrew B. Kao, Grace TI Bacillus cereus septicemia attributed to a matched unrelated bone marrow transplant SO TRANSFUSION LA English DT Article ID BACTERIAL-CONTAMINATION; DETECTION SYSTEM; CELL PRODUCTS; COMPONENTS; PLATELETS; OXYGEN AB BACKGROUND: Hematopoietic cell transplantation (HCT) is performed in more than 25,000 patients annually. Clinically significant bacterial transmission from HCT products is rare. CASE REPORT: A 36-year-old male of Asian descent with chronic myelogenous leukemia developed sepsis leading to acute renal failure and disseminated intravascular coagulation during infusion of matched unrelated donor bone marrow. This product later tested positive for Bacillus cereus. DISCUSSION: This HCT product traveled 31 hours at room temperature before arriving at the transplant center. Reducing transport times, transporting at 4 degrees C, and enhancing bacterial surveillance of HCT products may increase the ability to detect bacterial proliferation from transport. CONCLUSION: To prevent a similar case in the future, we will begin Gram staining all HCT products in transit more than 24 hours to alert physicians of the need for prophylactic antibiotic therapy. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Cell Manipulat Core Facil, Boston, MA 02215 USA. RP Kao, G (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,JFB313, Boston, MA 02215 USA. EM gkao@partners.org NR 21 TC 2 Z9 2 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD FEB PY 2013 VL 53 IS 2 BP 394 EP 397 DI 10.1111/j.1537-2995.2012.03723.x PG 4 WC Hematology SC Hematology GA 087ST UT WOS:000314783700022 PM 22624657 ER PT J AU Soskin, DP AF Soskin, David P. TI Artist's Statement: Puzzled Commentary SO ACADEMIC MEDICINE LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Treatment Resistant Depress,Depress Clin & Re, Boston, MA 02115 USA. RP Soskin, DP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Treatment Resistant Depress,Depress Clin & Re, Boston, MA 02115 USA. EM dsoskin@partners.org NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD FEB PY 2013 VL 88 IS 2 BP 215 EP 215 DI 10.1097/01.ACM.0000426356.35520.8c PG 1 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 081WA UT WOS:000314351900024 ER PT J AU Matthews, LT Crankshaw, T Giddy, J Kaida, A Smit, JA Ware, NC Bangsberg, DR AF Matthews, Lynn T. Crankshaw, Tamaryn Giddy, Janet Kaida, Angela Smit, Jennifer A. Ware, Norma C. Bangsberg, David R. TI Reproductive Decision-Making and Periconception Practices Among HIV-Positive Men and Women Attending HIV Services in Durban, South Africa SO AIDS AND BEHAVIOR LA English DT Article DE HIV-serodiscordant couples; HIV prevention; Safer conception; Family planning; South Africa ID SUB-SAHARAN AFRICA; SERO-DISCORDANT COUPLES; ANTIRETROVIRAL THERAPY; INFECTED WOMEN; FERTILITY INTENTIONS; MALE CIRCUMCISION; INVOLUNTARY CHILDLESSNESS; HIV-1-DISCORDANT COUPLES; PROSPECTIVE COHORT; COMMUNITY TRIAL AB Understanding reproductive decisions and periconception behavior among HIV-discordant couples is important for designing risk reduction interventions for couples who choose to conceive. In-depth interviews were conducted to explore reproductive decision-making and periconception practices among HIV-positive women with recent pregnancy (n = 30), and HIV-positive men (n = 20), all reporting partners of negative or unknown HIV-status, and attending HIV services in Durban, South Africa. Transcripts were coded for categories and emergent themes. Participants expressed strong reasons for having children, but rarely knew how to reduce periconception HIV transmission. Pregnancy planning occurred on a spectrum ranging from explicitly intended to explicitly unintended, with many falling in between the two extremes. Male fertility desire and misunderstanding serodiscordance contributed to HIV risk behavior. Participants expressed openness to healthcare worker advice for safer conception and modified risk behavior post-conception, suggesting the feasibility of safer conception interventions which may target both men and women and include serodiscordance counseling and promotion of contraception. C1 [Matthews, Lynn T.; Bangsberg, David R.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Matthews, Lynn T.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Matthews, Lynn T.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Crankshaw, Tamaryn; Giddy, Janet] PMTCT, McCord Hosp, Durban, South Africa. Simon Fraser Univ, Fac Hlth Sci, Vancouver, BC, Canada. [Smit, Jennifer A.] Univ Witwatersrand, Dept Obstet & Gynaecol, Maternal Adolescent & Child Hlth Div MatCH, Durban, South Africa. [Ware, Norma C.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02115 USA. [Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. RP Matthews, LT (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM ltmatthews@partners.org FU NIMH NIH HHS [K23 MH095655, K24 MH087227, K24 MH090894]; Wellcome Trust NR 80 TC 32 Z9 33 U1 1 U2 14 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD FEB PY 2013 VL 17 IS 2 BP 461 EP 470 DI 10.1007/s10461-011-0068-y PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 081FL UT WOS:000314302800002 PM 22038045 ER PT J AU Donnell, DJ Baeten, JM Hong, T Lingappa, JR Mujugira, A Nakku-Joloba, E Bangsberg, D Celum, C AF Donnell, Deborah J. Baeten, Jared M. Hong, Ting Lingappa, Jairam R. Mujugira, Andrew Nakku-Joloba, Edith Bangsberg, David Celum, Connie TI Correlation Between Pill Counts and Biologic Effects in an HIV-1 Prevention Clinical Trial: Implications for Measuring Adherence SO AIDS AND BEHAVIOR LA English DT Article; Proceedings Paper CT 6th International-AIDS-Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention CY JUL 17-20, 2011 CL Rome, ITALY SP Int AIDS Soc (IAS) DE Medication adherence; HIV prevention; Pill count ID HERPES-SIMPLEX-VIRUS; RECURRENT GENITAL HERPES; PLACEBO-CONTROLLED TRIAL; ANTIRETROVIRAL ADHERENCE; PROTEASE INHIBITORS; DOUBLE-BLIND; SUPPRESSION; ACYCLOVIR; THERAPY; WOMEN AB Clinic-based pill counts of unused study medication are frequently used to measure adherence in HIV-1 prevention trials. Monthly pill count adherence data from the Partners in Prevention HSV/HIV Transmission Study, a double-blind, placebo controlled trial of twice-daily acyclovir suppression of herpes simplex virus type 2 (HSV-2) in HIV-1 infected persons was used to compare changes between 3,381 placebo and active arm participants in two objective biologic measures of acyclovir's drug activity: reduction in plasma HIV-1 RNA and HSV-2 genital ulcer disease (GUD). Higher acyclovir pill count adherence was associated with greater reductions in plasma HIV-1 RNA and GUD, indicating pill count data is strongly correlated with biological effects of adherence. However, when calculated adherence exceeded 102 % (i.e., fewer pills returned than expected) and when pill counts were missing because bottles were not returned, plasma HIV-1 RNA and GUD effects were diminished, likely indicating periods of non-adherence. C1 [Donnell, Deborah J.; Baeten, Jared M.; Hong, Ting; Lingappa, Jairam R.; Mujugira, Andrew; Nakku-Joloba, Edith; Celum, Connie] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA. [Donnell, Deborah J.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA. [Baeten, Jared M.; Lingappa, Jairam R.; Celum, Connie] Univ Washington, Dept Med, Seattle, WA USA. [Baeten, Jared M.; Celum, Connie] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Lingappa, Jairam R.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Bangsberg, David] Harvard Univ, Sch Med, Boston, MA USA. [Bangsberg, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Donnell, DJ (reprint author), Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1100 Fairview Ave N,M2-200, Seattle, WA 98109 USA. EM deborah@scharp.org OI Donnell, Deborah/0000-0002-0587-7480 FU NIMH NIH HHS [R01-MH095507, R01 MH095507] NR 30 TC 5 Z9 5 U1 1 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS Behav. PD FEB PY 2013 VL 17 IS 2 BP 632 EP 639 DI 10.1007/s10461-012-0268-0 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 081FL UT WOS:000314302800020 PM 22869103 ER PT J AU Ananthakrishnan, AN Gainer, VS Perez, RG Cai, T Cheng, SC Savova, G Chen, P Szolovits, P Xia, Z De Jager, PL Shaw, SY Churchill, S Karlson, EW Kohane, I Perlis, RH Plenge, RM Murphy, SN Liao, KP AF Ananthakrishnan, A. N. Gainer, V. S. Perez, R. G. Cai, T. Cheng, S-C. Savova, G. Chen, P. Szolovits, P. Xia, Z. De Jager, P. L. Shaw, S. Y. Churchill, S. Karlson, E. W. Kohane, I. Perlis, R. H. Plenge, R. M. Murphy, S. N. Liao, K. P. TI Psychiatric co-morbidity is associated with increased risk of surgery in Crohn's disease SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; QUALITY-OF-LIFE; FUNCTIONAL GASTROINTESTINAL DISORDERS; OBSTRUCTIVE PULMONARY-DISEASE; IONIZING-RADIATION EXPOSURE; POPULATION-BASED SAMPLE; ULCERATIVE-COLITIS; HEALTH-CARE; PSYCHOLOGICAL STRESS; DEPRESSIVE SYMPTOMS AB Background Psychiatric co-morbidity, in particular major depression and anxiety, is common in patients with Crohn's disease (CD) and ulcerative colitis (UC). Prior studies examining this may be confounded by the co-existence of functional bowel symptoms. Limited data exist examining an association between depression or anxiety and disease-specific endpoints such as bowel surgery. Aims To examine the frequency of depression and anxiety (prior to surgery or hospitalisation) in a large multi-institution electronic medical record (EMR)-based cohort of CD and UC patients; to define the independent effect of psychiatric co-morbidity on risk of subsequent surgery or hospitalisation in CD and UC, and to identify the effects of depression and anxiety on healthcare utilisation in our cohort. Methods Using a multi-institution cohort of patients with CD and UC, we identified those who also had co-existing psychiatric co-morbidity (major depressive disorder or generalised anxiety). After excluding those diagnosed with such co-morbidity for the first time following surgery, we used multivariate logistic regression to examine the independent effect of psychiatric co-morbidity on IBD-related surgery and hospitalisation. To account for confounding by disease severity, we adjusted for a propensity score estimating likelihood of psychiatric co-morbidity influenced by severity of disease in our models. Results A total of 5405 CD and 5429 UC patients were included in this study; one-fifth had either major depressive disorder or generalised anxiety. In multivariate analysis, adjusting for potential confounders and the propensity score, presence of mood or anxiety co-morbidity was associated with a 28% increase in risk of surgery in CD (OR: 1.28, 95% CI: 1.031.57), but not UC (OR: 1.01, 95% CI: 0.801.28). Psychiatric co-morbidity was associated with increased healthcare utilisation. Conclusions Depressive disorder or generalised anxiety is associated with a modestly increased risk of surgery in patients with Crohn's disease. Interventions addressing this may improve patient outcomes. C1 [Ananthakrishnan, A. N.] Massachusetts Gen Hosp, Crohns & Colitis Ctr, Div Gastroenterol, Boston, MA 02114 USA. [Ananthakrishnan, A. N.; Xia, Z.; De Jager, P. L.; Shaw, S. Y.; Karlson, E. W.; Kohane, I.; Perlis, R. H.; Plenge, R. M.; Murphy, S. N.; Liao, K. P.] Harvard Univ, Sch Med, Boston, MA USA. [Gainer, V. S.; Perez, R. G.; Murphy, S. N.] Partners HealthCare, Res Comp, Charlestown, MA USA. [Cai, T.; Cheng, S-C.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Savova, G.; Chen, P.; Kohane, I.] Childrens Hosp, Boston, MA 02115 USA. [Szolovits, P.] MIT, Cambridge, MA 02139 USA. [Xia, Z.; De Jager, P. L.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Shaw, S. Y.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Churchill, S.; Kohane, I.] Brigham & Womens Hosp, Natl Ctr Biomed Comp i2b2, Boston, MA 02115 USA. [Karlson, E. W.; Plenge, R. M.; Liao, K. P.] Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA. [Perlis, R. H.] Massachusetts Gen Hosp, Psychiat Ctr Expt Drugs & Diagnost, Boston, MA 02114 USA. [Murphy, S. N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, Div Gastroenterol, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@partners.org OI Szolovits, Peter/0000-0001-8411-6403 FU NIH [U54-LM008748, K08 AR060257, K24 AR052403, P60 AR047782, R01 AR049880]; American Gastroenterological Association; US National Institutes of Health [K23 DK097142]; Katherine Swan Ginsburg Fund; US National Institutes of Health (NIH) [R01-AR056768, U01-GM092691, R01-AR059648]; Burroughs Wellcome Fund FX The study was supported by NIH U54-LM008748. A.N.A is supported by funding from the American Gastroenterological Association and from the US National Institutes of Health (K23 DK097142). K.P.L. is supported by NIH K08 AR060257 and the Katherine Swan Ginsburg Fund. R.M.P. is supported by grants from the US National Institutes of Health (NIH) (R01-AR056768, U01-GM092691 and R01-AR059648) and holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund. E.W.K is supported by grants from the NIH (K24 AR052403, P60 AR047782, R01 AR049880). NR 50 TC 20 Z9 21 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD FEB PY 2013 VL 37 IS 4 BP 445 EP 454 DI 10.1111/apt.12195 PG 10 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 075MW UT WOS:000313891900009 PM 23289600 ER PT J AU Busarla, SVP Sadruddin, FA Sohani, AR AF Busarla, Satya Vara Prasad Sadruddin, Feroz Allibhoy Sohani, Aliyah R. TI Pseudo-Gaucher cells in disseminated mycobacterial infection SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Editorial Material C1 [Busarla, Satya Vara Prasad] Aga Khan Hosp, Dept Pathol, Kisumu, Kenya. [Sadruddin, Feroz Allibhoy] Aga Khan Hosp, Dept Med, Kisumu, Kenya. [Sohani, Aliyah R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sohani, Aliyah R.] Harvard Univ, Sch Med, Boston, MA USA. RP Sohani, AR (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,WRN 219, Boston, MA 02114 USA. EM arsohani@partners.org NR 3 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD FEB PY 2013 VL 88 IS 2 BP 155 EP 155 DI 10.1002/ajh.22269 PG 1 WC Hematology SC Hematology GA 079DF UT WOS:000314149700014 PM 22307983 ER PT J AU Kring, AM Gur, RE Blanchard, JJ Horan, WP Reise, SP AF Kring, Ann M. Gur, Raquel E. Blanchard, Jack J. Horan, William P. Reise, Steven P. TI The Clinical Assessment Interview for Negative Symptoms (CAINS): Final Development and Validation SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PSYCHIATRIC RATING-SCALE; RESEARCH DOMAIN CRITERIA; ITEM RESPONSE THEORY; SCHIZOPHRENIA; ANHEDONIA; PERSPECTIVE; DEFICITS; EMOTION; RELIABILITY; REWARD AB Objective: A major barrier to developing treatments for negative symptoms has been measurement concerns with existing assessment tools. Fulfilling the top recommendation of the National Institute of Mental Health's Consensus Development Conference on Negative Symptoms, the Clinical Assessment Interview for Negative Symptoms (CAINS) was developed-using an iterative, empirical approach, and includes items assessing motivation, pleasure, and emotion expression. The authors employed multiple analytic techniques to develop the CAINS and here provide final development and validation results. Method: The CAINS structure, interrater agreement, test-retest reliability, and convergent and discriminant validity were assessed in a large and diverse sample of 162 outpatients with schizophrenia or schizo-affective disorder recruited from four sites. Results: Three items with poor psychometric properties were removed, resulting in a 13-item CAINS. The CAMS factor structure was replicated, demonstrating two modestly correlated scales: expression (four items) and motivation/pleasure (nine items). The scales demonstrated good internal consistency, test-retest stability, and interrater agreement. Strong convergent validity was demonstrated by linkages with other negative symptom measures, self-report scales of sociality, pleasure, and motivation, and coded facial expressions. Discriminant validity was shown by independence from depression, medication side effects, and cognition. Notably, the CAINS scales were related to real-world vocational, independent living, and social/familial functioning. Conclusions: The CAINS is an empirically developed and evaluated measure of negative symptoms. Findings indicate that the CAINS is brief yet comprehensive and employable across a wide range of research and clinical contexts. (Am J Psychiatry 2013; 170:165-172) C1 [Kring, Ann M.] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Kring, AM (reprint author), Univ Calif Berkeley, Dept Psychol, 3210 Tolman Hall, Berkeley, CA 94720 USA. EM akring@berkeley.edu FU Pfizer; AstraZeneca; NIH [1R01MH082890, 1R01MH082783, 1R01MH082839, 1R01MH082782] FX Dr. Gur has received investigator-initiated grants from Pfizer and AstraZeneca. Dr. Blanchard has received honoraria and travel support from Merck and Genentech for consulting. The other authors report no competing interests.; Supported in part by NIH grant 1R01MH082890 to Dr. Kring, grant 1R01MH082783 to Dr. Gur, grant 1R01MH082839 to Dr. Blanchard, and grant 1R01MH082782 to Dr. Horan. NR 44 TC 131 Z9 132 U1 4 U2 25 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2013 VL 170 IS 2 BP 165 EP 172 DI 10.1176/appi.ajp.2012.12010109 PG 8 WC Psychiatry SC Psychiatry GA 079VY UT WOS:000314201500008 PM 23377637 ER PT J AU Fishman, JA AF Fishman, J. A. TI Overview: Cytomegalovirus and the Herpesviruses in Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Epidemiology; herpesvirus; immunosuppression; latency; opportunistic infection; trans-plantation ID SARCOMA-ASSOCIATED HERPESVIRUS; KAPOSIS-SARCOMA; INFECTIOUS-MONONUCLEOSIS; HETEROLOGOUS IMMUNITY; LATENT INFECTION; GENITAL HERPES; VIRUS; RECIPIENTS; VACCINE; MEMORY AB Herpesviruses infect most animal species. Infections due to the eight human herpesviruses (HHV) are exacerbated by immunosuppression in organ transplantation. The special features of the herpesvirus life cycle include the ability to establish latent, nonproductive infection and the life-long capacity for reactivation to productive, lytic infection. Interactions between latent virus and the immune system determine the frequency and severity of symptomatic infections. The immunologic and cellular effects of herpesvirus infections contribute to risk for opportunistic infections and graft rejection. Among the most important advances in transplantation are laboratory assays for the diagnosis and monitoring of herpesvirus infections and antiviral agents with improved efficacy in prophylaxis and therapy. For herpes simplex virus, varicella zoster virus and cytomegalovirus, these advances have significantly reduced the morbidity of infection. The syndromes of EBV-associated posttransplant lymphoproliferative disorders (PTLD) and Kaposi's sarcoma remain important complications of immunosuppression. The epidemiology and essential biology of human herpesvirus is reviewed. C1 [Fishman, J. A.] Massachusetts Gen Hosp, MGH Transplant Ctr, Transplant Infect Dis & Compromised Host Ctr, Boston, MA 02114 USA. [Fishman, J. A.] Harvard Univ, Sch Med, Boston, MA USA. [Fishman, J. A.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, MGH Transplant Ctr, Transplant Infect Dis & Compromised Host Ctr, Boston, MA 02114 USA. EM jfishman@partners.org NR 34 TC 29 Z9 31 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD FEB PY 2013 VL 13 SU 3 SI SI BP 1 EP 8 DI 10.1111/ajt.12002 PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 079DX UT WOS:000314151600001 PM 23347210 ER PT J AU Kotton, CN AF Kotton, C. N. TI CMV: Prevention, Diagnosis and Therapy SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Cytomegalovirus; diagnostics; infection; prevention; transplant ID ORGAN TRANSPLANT RECIPIENTS; GANCICLOVIR-RESISTANT CYTOMEGALOVIRUS; EXTENDED VALGANCICLOVIR PROPHYLAXIS; BRONCHIOLITIS OBLITERANS SYNDROME; ORTHOTOPIC LIVER-TRANSPLANTATION; CELL IMMUNE RECONSTITUTION; HEPATIC-ARTERY THROMBOSIS; PREEMPTIVE THERAPY; LUNG TRANSPLANTATION; DRUG-RESISTANCE AB Cytomegalovirus (CMV) is the most common infection after organ transplantation and has a major impact on morbidity, mortality and graft survival. Optimal prevention, diagnosis and treatment of active CMV infection enhance transplant outcomes, and are the focus of this section. Methods to prevent CMV include universal prophylaxis and preemptive therapy; each has its merits, and will be compared and contrasted. Diagnostics have improved substantially in recent years, both in type and quality, allowing for more accurate and savvy treatment; advances in diagnostics include the development of an international standard, which should allow comparison of results across different methodologies, and assays for cellular immune function against CMV. Therapy primarily involves ganciclovir, now rendered more versatile by data suggesting oral therapy with valganciclovir is not inferior to intravenous therapy with ganciclovir. Treatment of resistant virus remains problematic, but is enhanced by the availability of multiple novel therapeutic agents. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Kotton, CN (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM ckotton@partners.org FU Genentech FX The author has served as a continuing medical education speaker on the topic of CMV for Genentech and Viropharma. She led The Transplantation Society International CMV Consensus Group with an investigator-initiated independent grant from Roche, now Genentech. She has been a scientific consultant for Genentech, Roche and CSL Behring. NR 151 TC 59 Z9 61 U1 1 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD FEB PY 2013 VL 13 SU 3 SI SI BP 24 EP 40 DI 10.1111/ajt.12006 PG 17 WC Surgery; Transplantation SC Surgery; Transplantation GA 079DX UT WOS:000314151600003 PM 23347212 ER PT J AU Fishman, JA AF Fishman, J. A. TI What's New and What's Hot? Basic Science at the American Transplant Congress 2012 SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Costimulation; heterologous immunity; infection; immune tolerance; microbiome; NK cells; Th17 cells ID NK CELL TRANSCRIPTS; T-CELLS; REJECTION; BIOPSIES; INJURY AB Application of advanced molecular techniques and novel animal models has provided new insights into basic mechanisms underlying clinical transplantation. Investigations in diverse areas, including graft rejection and tolerance, autoimmunity and infectious diseases, have revealed increasing complexity of the mechanisms controlling immune function, notably at the interface of the innate and adaptive immune systems and within secondary lymphoid organs. New roles have been identified for NK and dendritic cells, B-lymphocytes and for Th17 and regulatory T cells, notably in novel animal models of costimulatory blockade and tolerance. Confirmation of these observations will be needed in normal animals and in humans undergoing organ and cell transplantation. The impact of the microbiome, of vaccines, and of antimicrobial therapies on immune memory and reconstitution after lymphocyte depletion is beginning to be defined. C1 [Fishman, J. A.] Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, MGH Transplant Ctr, Boston, MA 02114 USA. [Fishman, J. A.] Harvard Univ, Sch Med, Boston, MA USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, MGH Transplant Ctr, Boston, MA 02114 USA. EM jfishman@partners.org NR 34 TC 1 Z9 1 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD FEB PY 2013 VL 13 IS 2 BP 275 EP 280 DI 10.1111/ajt.12015 PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 079LE UT WOS:000314171100008 PM 23279436 ER PT J AU Bagchi, A Eikermann, M AF Bagchi, Aranya Eikermann, Matthias TI Mashed Potatoes and Maize Are the Starches Safe? SO ANESTHESIOLOGY LA English DT Editorial Material ID HYDROXYETHYL STARCH; INTENSIVE-CARE; SEVERE SEPSIS; FLUID RESUSCITATION; RENAL-FUNCTION; SALINE C1 [Bagchi, Aranya; Eikermann, Matthias] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02115 USA. [Eikermann, Matthias] Dusiburg Essen Univ, Klin Anaesthesiol & Intens Med, Univ Klinikum Essen, Essen, Germany. RP Bagchi, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02115 USA. EM meikermann@partners.org NR 20 TC 6 Z9 6 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD FEB PY 2013 VL 118 IS 2 BP 244 EP 247 DI 10.1097/ALN.0b013e31827e5582 PG 4 WC Anesthesiology SC Anesthesiology GA 076SH UT WOS:000313977700003 PM 23340348 ER PT J AU Vaz-Luis, I Winer, EP Lin, NU AF Vaz-Luis, I. Winer, E. P. Lin, N. U. TI Human epidermal growth factor receptor-2-positive breast cancer: does estrogen receptor status define two distinct subtypes? SO ANNALS OF ONCOLOGY LA English DT Review DE breast cancer; estrogen receptor; human epidermal growth factor receptor-2; outcomes; subtypes ID PATHOLOGICAL COMPLETE RESPONSE; POLYMERASE CHAIN-REACTION; PLUS ADJUVANT CHEMOTHERAPY; STEROID-HORMONE RECEPTORS; GENE-EXPRESSION PATTERNS; PHASE-II TRIAL; ANDROGEN RECEPTOR; GUIDELINE RECOMMENDATIONS; NEOADJUVANT CHEMOTHERAPY; PROGESTERONE-RECEPTOR AB Human epidermal growth factor receptor-2 (HER2) overexpression occurs in similar to 20% of breast cancers and has historically been associated with decreased survival. Despite substantial improvements in clinical outcomes, particularly with the emergence of HER2-targeted therapy, a substantial minority of patients still relapses, and progression is inevitable in metastatic disease. Accumulating data indicate that HER2-positive disease is itself a heterogeneous entity. In this article, we qualitatively review the data supporting the classification of HER2-positive disease as at least two separate entities, distinguished by estrogen receptor (ER) status. We summarize differences in clinical outcomes, including response to neoadjuvant therapy, timing and patterns of dissemination, efficacy of therapy in the metastatic setting and survival outcomes. The collective data are sufficiently strong at this point to propose that ER status defines two distinct subtypes within HER2-positive breast cancer, and we highlight the implications of this knowledge in future research, including understanding of the basic biology of HER2-positive breast cancer and the design of future clinical trials. C1 [Vaz-Luis, I.; Winer, E. P.; Lin, N. U.] Dana Farber Canc Inst, Breast Oncol Ctr, Dept Med Oncol, Boston, MA 02215 USA. [Vaz-Luis, I.] Inst Mol Med, Clin & Translat Oncol Res Unit, Lisbon, Portugal. RP Lin, NU (reprint author), Dana Farber Canc Inst, Breast Oncol Ctr, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM nancy_lin@dfci.harvard.edu FU Breast Cancer Research Foundation; Fundacao da Ciencia e Tecnologia [HMSP-ICS/0004/2011]; The Harvard Clinical and Translational Science Center [UL1 RR025758] FX Additional support for this work has been provided by the Breast Cancer Research Foundation (no grant number assigned). IV-L is supported by Fundacao da Ciencia e Tecnologia (HMSP-ICS/0004/2011) and by the Scholars in Clinical Science Program of Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (Award No. UL1 RR025758 and contributions from Harvard University and its affiliated academic health-care centers). The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health-care centers, or the National Institutes of Health. NR 91 TC 17 Z9 19 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD FEB PY 2013 VL 24 IS 2 BP 283 EP 291 DI 10.1093/annonc/mds286 PG 9 WC Oncology SC Oncology GA 077VM UT WOS:000314057100004 PM 23022997 ER PT J AU Goss, PE Ingle, JN Martino, S Robert, NJ Muss, HB Livingston, RB Davidson, NE Perez, EA Chavarri-Guerra, Y Cameron, DA Pritchard, KI Whelan, T Shepherd, LE Tu, D AF Goss, P. E. Ingle, J. N. Martino, S. Robert, N. J. Muss, H. B. Livingston, R. B. Davidson, N. E. Perez, E. A. Chavarri-Guerra, Y. Cameron, D. A. Pritchard, K. I. Whelan, T. Shepherd, L. E. Tu, D. TI Impact of premenopausal status at breast cancer diagnosis in women entered on the placebo-controlled NCIC CTG MA17 trial of extended adjuvant letrozole SO ANNALS OF ONCOLOGY LA English DT Article DE adjuvant therapy; aromatase inhibitors; breast cancer; extended therapy; letrozole; menopausal status ID ENDOCRINE THERAPY; RANDOMIZED-TRIAL; POSTMENOPAUSAL WOMEN; AROMATASE INHIBITORS; ESTROGEN-RECEPTOR; TAMOXIFEN THERAPY; UPDATED FINDINGS; MA.17; SURVIVAL AB MA17 showed improved outcomes in postmenopausal women given extended letrozole (LET) after completing 5 years of adjuvant tamoxifen. Exploratory subgroup analyses of disease-free survival (DFS), distant DFS (DDFS), overall survival (OS), toxic effects and quality of life (QOL) in MA17 were performed based on menopausal status at breast cancer diagnosis. At diagnosis, 877 women were premenopausal and 4289 were postmenopausal. Extended LET was significantly better than placebo (PLAC) in DFS for premenopausal [hazard ratio (HR) = 0.26, 95% confidence interval (CI) 0.13-0.55; P = 0.0003] and postmenopausal women (HR = 0.67; 95% CI 0.51-0.89; P = 0.006), with greater DFS benefit in those premenopausal (interaction P = 0.03). In adjusted post-unblinding analysis, those who switched from PLAC to LET improved DDFS in premenopausal (HR = 0.15; 95% CI 0.03-0.79; P = 0.02) and postmenopausal women (HR = 0.45; 95% CI 0.22-0.94; P = 0.03). Extended LET after 5 years of tamoxifen was effective in pre- and postmenopausal women at diagnosis, and significantly better in those premenopausal. Women premenopausal at diagnosis should be considered for extended adjuvant therapy with LET if menopausal after completing tamoxifen. C1 [Goss, P. E.; Chavarri-Guerra, Y.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Ingle, J. N.] Mayo Clin, Dept Oncol, Div Med Oncol, Rochester, MN USA. [Martino, S.] Los Angeles Clin & Res Inst, Breast Canc Div, Santa Monica, CA USA. [Robert, N. J.] Inova Fairfax Hosp, Virgina Canc Specialists, Fairfax, VA USA. [Muss, H. B.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Muss, H. B.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Livingston, R. B.] Univ Washington, Seattle, WA 98195 USA. [Davidson, N. E.] Univ Pittsburgh, Sch Med, Inst Canc, Pittsburgh, PA USA. [Davidson, N. E.] Univ Pittsburgh, Sch Med, UPMC Canc Ctr, Pittsburgh, PA USA. [Perez, E. A.] Mayo Clin, Ctr Canc, Jacksonville, FL USA. [Cameron, D. A.] Western Gen Hosp, Edinburgh Breast Unit, Edinburgh EH4 2XU, Midlothian, Scotland. [Cameron, D. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Pritchard, K. I.] Univ Toronto, Sunnybrook Odette Reg Canc Ctr, Toronto, ON, Canada. [Whelan, T.] McMaster Univ, Dept Oncol, Hamilton, ON, Canada. [Shepherd, L. E.; Tu, D.] Natl Canc Inst Canada, Clin Trials Grp, Kingston, ON, Canada. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Lawrence House,LRH-302, Boston, MA 02114 USA. EM pgoss@partners.org RI Whelan, Timothy/D-3185-2017 FU Novartis Pharmaceuticals; Canadian Cancer Society through National Cancer Institute of Canada [10362]; National Cancer Institute in the United States [CA31946, CA21115, CA25224, CA38926, CA32102]; Avon Foundation in New York; Genentech; Sanofi; Novartis; Astra-Zeneca; Pfizer; Expert Testimony FX The authors are very grateful to the 5187 extraordinary women who agreed to participate in this study. The authors also acknowledge the trial committee; the many hundreds of investigators, pharmacists, and clinical research associates from the National Cancer Institute of Canada Clinical Trials Group, the Southwest Oncology Group, the Eastern Cooperative Oncology Group, the Cancer and Leukemia Group B, the North Central Cancer Treatment Group, the European Organization for Research and Treatment of Cancer, the International Breast Cancer Study Group, and Centers in England, including the Royal Marsden, St. George's, and Withington Hospitals; the members of the Data Safety Monitoring Committee: the central office staff of the NCIC Clinical Trials Group who contributed to the conduct of the trial; and to Novartis Pharmaceuticals for their support and provision of LET and PLAC. The authors thank Pedro Liedke for his review of the manuscript.; This work was supported by the Canadian Cancer Society through National Cancer Institute of Canada grant (10362) and grants from the National Cancer Institute in the United States (CA31946, CA21115, CA25224, CA38926, and CA32102). PEG and YC-G are supported by the Avon Foundation in New York.; EAP: Research funding: Genentech and Sanofi.; DAC: Consultant or advisory role: Novartis, Astra-Zeneca and Pfizer; Honoraria: Novartis, Astra-Zeneca and Pfizer; Research Funding: Novartis, Astra-Zeneca and Pfizer.; KIP: Consultant or advisory role: Novartis; Honoraria: Novartis; Research Funding: Novartis: Expert Testimony: Novartis. NR 20 TC 30 Z9 35 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD FEB PY 2013 VL 24 IS 2 BP 355 EP 361 DI 10.1093/annonc/mds330 PG 8 WC Oncology SC Oncology GA 077VM UT WOS:000314057100014 PM 23028039 ER PT J AU Bernhard, J Aldridge, J Butow, PN Zoller, P Brown, R Smith, A Juraskova, I AF Bernhard, J. Aldridge, J. Butow, P. N. Zoller, P. Brown, R. Smith, A. Juraskova, I. TI Patient-doctor agreement on recall of clinical trial discussion across cultures SO ANNALS OF ONCOLOGY LA English DT Article DE breast cancer; communication skills training; cross-cultural differences; patient-doctor agreement; shared decision-making ID SEEKING INFORMED-CONSENT; DECISION-MAKING; CANCER-PATIENTS; BREAST-CANCER; COMMUNICATION; SATISFACTION; PARTICIPATION; ONCOLOGISTS; INFORMATION; SCALE AB The purpose was to investigate patient-doctor agreement on clinical trial discussion cross-culturally. In the International Breast Cancer Study Group Trial 33-03 on shared decision-making for early breast cancer in Australian/New Zealand (ANZ) and Swiss/German/Austrian (SGA) centers, doctor and patient characteristics plus doctor stress and burnout were assessed. Within 2 weeks post-consultation about treatment options, the doctor and patient reported independently, whether a trial was discussed. Odds ratios of agreement for covariables were estimated by generalized estimating equations for each language cohort, with doctor as a random effect. In ANZ, 21 doctors and 339 patients were eligible; in SGA, 41 doctors and 427 patients. In cases where the doctor indicated 'no trial discussed', 82% of both ANZ and SGA patients agreed; if the doctor indicated 'trial discussed', 50% of ANZ and 38% of SGA patients agreed, respectively. Factors associated with higher agreement were: low tumor grade and fewer patients recruited into clinical trials in SGA; public institution, patient born in ANZ (versus other), higher doctor depersonalization and personal accomplishment in ANZ. There is discordance between oncologists and their patients regarding clinical trial discussion, particularly when the doctor indicates that a trial was discussed. Factors contributing to this agreement vary by culture. C1 [Bernhard, J.; Zoller, P.] Int Breast Canc Study Grp Coordinating Ctr, CH-3008 Bern, Switzerland. [Bernhard, J.] Univ Hosp Bern, Inselspital, Dept Med Oncol, CH-3010 Bern, Switzerland. [Aldridge, J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, IBCSG Stat Ctr, Boston, MA 02115 USA. [Butow, P. N.; Juraskova, I.] Univ Sydney, Sch Psychol, Ctr Med Psychol & Evidence Based Decis Making CeM, Sydney, NSW 2006, Australia. [Butow, P. N.; Smith, A.] Univ Sydney, Psychooncol Cooperat Res Grp PoCoG, Sydney, NSW 2006, Australia. [Brown, R.] Virginia Commonwealth Univ, Sch Med, Dept Social & Behav Hlth, Richmond, VA 23284 USA. RP Bernhard, J (reprint author), Int Breast Canc Study Grp Coordinating Ctr, Effingerstr 40, CH-3008 Bern, Switzerland. EM juerg.bernhard@ibcsg.org OI Smith, Allan 'Ben'/0000-0002-2496-7369 FU National Breast Cancer Foundation of Australia; Oncosuisse/Swiss Cancer League [OCS-01165-09-2001/KLS-01648-02-2005]; Deutsche Krebshilfe [106668]; IBCSG; US National Cancer Institute [CA-75362] FX We thank the National Breast Cancer Foundation of Australia (no grant number), Oncosuisse/Swiss Cancer League (OCS-01165-09-2001/KLS-01648-02-2005), Deutsche Krebshilfe (106668), and IBCSG for funding this trial. The IBCSG Statistical Center (JA) is partially funded through a grant from the US National Cancer Institute (CA-75362). NR 29 TC 1 Z9 1 U1 4 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD FEB PY 2013 VL 24 IS 2 BP 391 EP 397 DI 10.1093/annonc/mds288 PG 7 WC Oncology SC Oncology GA 077VM UT WOS:000314057100019 PM 23019277 ER PT J AU Mattei, PL Alora-Palli, MB Kraft, S Lawrence, DP Flaherty, KT Kimball, AB AF Mattei, P. L. Alora-Palli, M. B. Kraft, S. Lawrence, D. P. Flaherty, K. T. Kimball, A. B. TI Cutaneous effects of BRAF inhibitor therapy: a case series SO ANNALS OF ONCOLOGY LA English DT Article DE BRAF inhibitor; cutaneous squamous cell carcinoma; MEK inhibitor; photosensitivity; side effects ID RENAL-TRANSPLANT RECIPIENTS; HUMAN-PAPILLOMAVIRUS TYPES; NONMELANOMA SKIN CANCERS; SQUAMOUS-CELL CARCINOMA; IMMUNOCOMPETENT INDIVIDUALS; SORAFENIB; MUTATIONS; MELANOMA; PATHWAY; SURAMIN AB The cutaneous effects of rapidly accelerated fibrosarcoma kinase B (BRAF) inhibitors are not well understood. Squamous cell carcinoma (SCC), keratoacanthoma, and photosensitivity have been described in patients taking BRAF inhibitors. To characterize the timing and frequency of skin lesions in patients receiving BRAF inhibitor therapy, we utilized a retrospective case review of 53 patients undergoing treatment with BRAF inhibitors for 4-92 weeks of therapy. Patients were evaluated at baseline, and then followed at 4- to 12-week intervals. Charts were retrospectively reviewed, and the morphology and timing of cutaneous events were recorded. Thirty-three of the 53 charts met exclusion/inclusion criteria, 15 were treated with vemurafenib, and 18 were treated with GSK 2118436/GSK 1120212. Of 33 patients treated with BRAF inhibitor, 13 developed photosensitivity (39.4%), 10 developed actinic keratoses (30.3%), 10 developed warts (30.3%), and 6 developed SCC (18.2%). Multiple cutaneous findings were observed in the 33 patients taking BRAF inhibitors. The previously described association with SCC and photosensitivity was observed in these patients as well. Over half of the observed SCCs were invasive in nature. Photosensitivity continues to be frequent with BRAF inhibitors. Patients taking BRAF inhibitors should have regular full body skin exams. Further studies are necessary to better elucidate the rates of these adverse cutaneous effects. C1 [Mattei, P. L.; Alora-Palli, M. B.; Kimball, A. B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Kraft, S.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lawrence, D. P.; Flaherty, K. T.] Massachusetts Gen Hosp, Dept Oncol, Boston, MA 02114 USA. RP Kimball, AB (reprint author), Harvard Univ, Sch Med, Clin Unit Res Trials & Outcomes Skin CURTIS, 50 Staniford St,Suite 240, Boston, MA 02114 USA. EM harvardskinstudies@partners.org FU Roche; GlaxoSmithKline; Genentech FX Roche, GlaxoSmithKline, and Genentech funded the underlying clinical trials from which these data were derived. Our analysis was unfunded. NR 46 TC 45 Z9 45 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD FEB PY 2013 VL 24 IS 2 BP 530 EP 537 DI 10.1093/annonc/mds292 PG 8 WC Oncology SC Oncology GA 077VM UT WOS:000314057100038 PM 23035153 ER PT J AU Penel, N Demetri, GD Blay, JY Cousin, S Maki, RG Chawla, SP Judson, I von Mehren, M Schoffski, P Verweij, J Casali, P Rodenhuis, S Schutte, HJ Cassar, A Gomez, J Nieto, A Zintl, P Pontes, MJ Le Cesne, A AF Penel, N. Demetri, G. D. Blay, J. Y. Cousin, S. Maki, R. G. Chawla, S. P. Judson, I. von Mehren, M. Schoffski, P. Verweij, J. Casali, P. Rodenhuis, S. Schuette, H. J. Cassar, A. Gomez, J. Nieto, A. Zintl, P. Pontes, M. J. Le Cesne, A. TI Growth modulation index as metric of clinical benefit assessment among advanced soft tissue sarcoma patients receiving trabectedin as a salvage therapy SO ANNALS OF ONCOLOGY LA English DT Article DE growth modulation index; sarcoma; time-to-progression ratio; trabectedin ID GASTROINTESTINAL STROMAL TUMORS; PHASE-II; EUROPEAN ORGANIZATION; END-POINT; ANTICANCER AGENTS; OVARIAN-CANCER; TRIAL; PROGRESSION; ECTEINASCIDIN-743; 5-FLUOROURACIL AB The growth modulation index (GMI) is the ratio of time to progression with the nth line (TTPn) of therapy to the TTPn-1 with the n-1th line. GMI > 1.33 is considered as a sign of activity in phase II trials. This retrospective analysis evaluated the concordance between the GMI and the efficacy outcomes in 279 patients with advanced soft tissue sarcoma (ASTS) treated with trabectedin 1.5 mg/m superset of (24-h infusion every 3 weeks) in four phase II trials. One hundred and forty-two (51%) patients received one prior line and 137 >= 2 lines. The median TTPn was 2.8 months (range 0.2-26.8), whereas the median TTPn-1 was 4.0 months (0.3-79.5). The median GMI was 0.6 (0.0-14.4). Overall, 177 patients (63%) had a GMI < 1; 21 (8%) a GMI equal to 1-1.33 and 81 (29%) a GMI > 1.33, which correlated with the median overall survival in those patients (9.1, 13.9 and 23.8 months, respectively, P = 0.0005). A high concordance rate between the GMI and response rate (P < 0.0001) and progression-free survival (PFS, P < 0.0001) was observed. Good performance status (PS) was the only factor associated with GMI > 1.33 (PS = 0; P < 0.04). A high GMI was associated with favorable efficacy outcomes in patients treated with trabectedin. Further research is needed to assess GMI as an indicator in this setting. C1 [Penel, N.; Cousin, S.] Ctr Oscar Lambret, Dept Med Oncol, F-59020 Lille, France. [Demetri, G. D.] Dana Farber Canc Inst, Ludwig Ctr, Dept Med Oncol, Boston, MA 02115 USA. [Blay, J. Y.] Ctr Leon Berard, Dept Med Oncol, F-69373 Lyon, France. [Maki, R. G.] Mt Sinai Sch Med, Dept Med Oncol, New York, NY USA. [Chawla, S. P.] Santa Monica Oncol Ctr Santa Monica, Dept Med Oncol, Santa Monica, CA USA. [Judson, I.] Royal Marsden Hosp, Dept Med Oncol, London SW3 6JJ, England. [von Mehren, M.] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Schoffski, P.] Univ Hosp Gasthuisberg, Dept Med Oncol, B-3000 Louvain, Belgium. [Verweij, J.] Erasmus Univ, Dept Med Oncol, Med Ctr, Rotterdam, Netherlands. [Casali, P.] Ist Nazl Tumori, Dept Med Oncol, I-20133 Milan, Italy. [Rodenhuis, S.] Netherlands Canc Inst, Dept Med Oncol, Amsterdam, Netherlands. [Schuette, H. J.] Marien Hosp, Dept Med Oncol, Dusseldorf, Germany. [Cassar, A.] Novex Pharma, Sci Liaison Off, Levallois Perret, France. [Gomez, J.; Nieto, A.; Zintl, P.; Pontes, M. J.] Pharmamar, Dept Stat, Madrid, Spain. [Gomez, J.; Nieto, A.; Zintl, P.; Pontes, M. J.] Pharmamar, Med Affairs, Madrid, Spain. [Le Cesne, A.] Inst Gustave Roussy, Dept Med Oncol, Villejuif, France. RP Penel, N (reprint author), Ctr Oscar Lambret, Dept Gen Oncol, 3 Rue F Combemale, F-59020 Lille, France. EM n-penel@o-lambret.fr RI casali, Paolo Giovanni/D-1524-2017; Blay, Jean-Yves/N-3966-2016 OI casali, Paolo Giovanni/0000-0003-4056-8023; Blay, Jean-Yves/0000-0001-7190-120X FU PharmaMar SA FX AC, JG, AN, PZ and MJP are employed by PharmaMar SA. NP, GDD, JYB, RGM, SPC, IJ, MVM, PS, JV, PC, SR, HJS and ALC are investigators in the clinical trials funded by PharmaMar SA and have received research grant from PharmaMar SA. NR 29 TC 10 Z9 10 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD FEB PY 2013 VL 24 IS 2 BP 537 EP 542 DI 10.1093/annonc/mds470 PG 6 WC Oncology SC Oncology GA 077VM UT WOS:000314057100039 PM 23117071 ER PT J AU Cattaneo, Z Vecchi, T Fantino, M Herbert, AM Merabet, LB AF Cattaneo, Zaira Vecchi, Tomaso Fantino, Micaela Herbert, Andrew M. Merabet, Lotfi B. TI The effect of vertical and horizontal symmetry on memory for tactile patterns in late blind individuals SO ATTENTION PERCEPTION & PSYCHOPHYSICS LA English DT Article DE Symmetry; Tactile; Haptic; Late blind; Spatial memory; Reference frame ID BILATERAL SYMMETRY; HAPTIC DISCRIMINATION; UNFAMILIAR DISPLAYS; SPATIAL PROCESSES; PERCEPTION; ORIENTATION; STRATEGIES; IMAGERY; PICTURE; PEOPLE AB Visual stimuli that exhibit vertical symmetry are easier to remember than stimuli symmetric along other axes, an advantage that extends to the haptic modality as well. Critically, the vertical symmetry memory advantage has not been found in early blind individuals, despite their overall superior memory, as compared with sighted individuals, and the presence of an overall advantage for identifying symmetric over asymmetric patterns. The absence of the vertical axis memory advantage in the early blind may depend on their total lack of visual experience or on the effect of prolonged visual deprivation. To disentangle this issue, in this study, we measured the ability of late blind individuals to remember tactile spatial patterns that were either vertically or horizontally symmetric or asymmetric. Late blind participants showed better memory performance for symmetric patterns. An additional advantage for the vertical axis of symmetry over the horizontal one was reported, but only for patterns presented in the frontal plane. In the horizontal plane, no difference was observed between vertical and horizontal symmetric patterns, due to the latter being recalled particularly well. These results are discussed in terms of the influence of the spatial reference frame adopted during exploration. Overall, our data suggest that prior visual experience is sufficient to drive the vertical symmetry memory advantage, at least when an external reference frame based on geocentric cues (i.e., gravity) is adopted. C1 [Cattaneo, Zaira] Univ Milano Bicocca, Dept Psychol, Milan, Italy. [Cattaneo, Zaira; Vecchi, Tomaso] IRCCS Mondino, Brain Connect Ctr, Pavia, Italy. [Vecchi, Tomaso; Fantino, Micaela] Univ Pavia, Dept Psychol, I-27100 Pavia, Italy. [Herbert, Andrew M.] Rochester Inst Technol, Dept Psychol, Rochester, NY 14623 USA. [Merabet, Lotfi B.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Cattaneo, Z (reprint author), Univ Milano Bicocca, Dept Psychol, Milan, Italy. EM zaira.cattaneo@unimib.it NR 37 TC 5 Z9 5 U1 1 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1943-3921 J9 ATTEN PERCEPT PSYCHO JI Atten. Percept. Psychophys. PD FEB PY 2013 VL 75 IS 2 BP 375 EP 382 DI 10.3758/s13414-012-0393-x PG 8 WC Psychology; Psychology, Experimental SC Psychology GA 081BX UT WOS:000314291700014 PM 23150215 ER PT J AU Maramattom, LV Hari, PN Burns, LJ Carreras, J Arcese, W Cairo, MS Costa, LJ Fenske, TS Lill, M Freytes, CO Gale, RP Gross, TG Hale, GA Hamadani, M Holmberg, LA Hsu, JW Inwards, DJ Lazarus, HM Marks, DI Maloney, DG Maziarz, RT Montoto, S Rizzieri, DA Wirk, B Gajewski, JL AF Maramattom, Leena V. Hari, Parameswaran N. Burns, Linda J. Carreras, Jeanette Arcese, William Cairo, Mitchell S. Costa, Luciano J. Fenske, Timothy S. Lill, Michael Freytes, Cesar O. Gale, Robert Peter Gross, Thomas G. Hale, Gregory A. Hamadani, Mehdi Holmberg, Leona A. Hsu, Jack W. Inwards, David J. Lazarus, Hillard M. Marks, David I. Maloney, David G. Maziarz, Richard T. Montoto, Silvia Rizzieri, David A. Wirk, Baldeep Gajewski, James L. TI Autologous and Allogeneic Transplantation for Burkitt Lymphoma Outcomes and Changes in Utilization: A Report from the Center for International Blood and Marrow Transplant Research SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE AlloHCT; AutoHCT; Burkitt lymphoma ID ADULT BURKITT; LEUKEMIA; CHEMOTHERAPY; RADIATION; THERAPY AB Trends in utilization and outcomes after autologous or allogeneic hematopoietic cell transplantation (HCT) for Burkitt lymphoma were analyzed in 241 recipients reported to the Center for International Blood and Marrow Transplant Research between 1985 and 2007. The autologous HCT cohort had a higher proportion of chemotherapy-sensitive disease, peripheral blood grafts, and HCT in first complete remission (CR1). The use of autologous HCT has declined over time, with only 19% done after 2001. Overall survival at 5 years for the autologous cohort was 83% for those in CR1 and 31% for those not in CR1. Corresponding progression-free survival (PFS) was 78% and 27%, respectively. After allogeneic HCT, overall survival at 5 years was 53% and 20% for the CR1 and non-CR1 cohorts, whereas PFS was 50% and 19%, respectively. The most common cause of death was progressive lymphoma. Allogeneic HCT performed in a higher-risk subset (per National Comprehensive Cancer Network guidelines) resulted in a 5-year PFS of 27%. Autologous HCT resulted in a 5-year PFS of 44% in those undergoing transplantation in the second CR. (C) 2013 American Society for Blood and Marrow Transplantation. C1 [Maramattom, Leena V.; Hari, Parameswaran N.; Fenske, Timothy S.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Hari, Parameswaran N.; Fenske, Timothy S.] Med Coll Wisconsin, Dept Med, Div Hematol Oncol, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Burns, Linda J.] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Carreras, Jeanette] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Arcese, William] Univ Roma Tor Vergata, Rome Transplant Network, Rome, Italy. [Cairo, Mitchell S.] New York Med Coll, Valhalla, NY 10595 USA. [Costa, Luciano J.] Med Univ S Carolina, Charleston, SC 29425 USA. [Lill, Michael] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Freytes, Cesar O.] S Vet Hlth Care Syst, San Antonio, TX USA. [Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Gale, Robert Peter] Celgene Cord Blood Bank, Cedar Knolls, NJ USA. [Gross, Thomas G.] Nationwide Childrens Hosp, Columbus, OH USA. [Hale, Gregory A.] Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA. [Hamadani, Mehdi] W Virginia Univ Hosp Inc, Morgantown, WV USA. [Holmberg, Leona A.; Maloney, David G.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Hsu, Jack W.; Wirk, Baldeep] Shands HealthCare, Gainesville, FL USA. [Hsu, Jack W.] Univ Florida, Gainesville, FL USA. [Inwards, David J.] Mayo Clin Rochester, Rochester, MN USA. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Marks, David I.] Bristol Childrens Hosp, Bristol, Avon, England. [Maziarz, Richard T.; Gajewski, James L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Montoto, Silvia] Queen Mary Univ London, Barts Canc Inst, London, England. [Rizzieri, David A.] Duke Univ, Med Ctr, Durham, NC USA. RP Hari, PN (reprint author), Med Coll Wisconsin, POB 26509, Milwaukee, WI 53226 USA. EM phari@mcw.edu OI Hamadani, Mehdi/0000-0001-5372-510X; Hari, Parameswaran/0000-0002-8800-297X FU Public Health Service from the National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung and Blood Institute (NHLBI) [5U01HL069294]; National Institute of Allergy and Infectious Diseases (NIAID); NCI; Resources and Services Administration (HRSA/DHHS) [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; Allos, Inc.; Amgen, Inc.; Angioblast; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis Pharma; Leukemia & Lymphoma Society; Medical College of Wisconsin; Merck Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; RemedyMD; Sanofi; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience, Inc.; THERAKOS, 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 Allos, Inc.; Amgen, Inc.; Angioblast; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis Pharma; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; RemedyMD; Sanofi; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience, Inc.; THERAKOS, Inc.; and Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, or any other agency of the US Government. NR 14 TC 2 Z9 2 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2013 VL 19 IS 2 BP 173 EP 179 DI 10.1016/j.bbmt.2012.11.016 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 083DA UT WOS:000314441700004 PM 23200705 ER PT J AU Linsky, A Simon, SR AF Linsky, Amy Simon, Steven R. TI Medication discrepancies in integrated electronic health records SO BMJ QUALITY & SAFETY LA English DT Article ID ADVERSE DRUG EVENTS; PATIENT TRANSFER; CARE; SAFETY AB Introduction Medication discrepancies are associated with adverse drug events. Electronic health records (EHRs) may reduce discrepancies, especially if integrated with pharmacy dispensing. We determined the prevalence of discrepancies within a national healthcare system with EHR-pharmacy linkage to characterise the medications involved and to identify factors associated with discrepancies. Methods We conducted a retrospective cohort study of ambulatory care patients at Veterans Affairs Boston Healthcare System, April 2010-July 2011. The primary outcome was the presence of any medication discrepancy or specific types of discrepancies: commission-present in the record but not taken by patient; omission-not present in the record; duplication-present more than once; or alteration in dose or frequency-present but taken differently than documented. Results Sixty-two patients (60%) had at least one medication discrepancy. Prevalence of commissions, omissions, duplications and alterations were 36%, 27%, 11% and 19%, respectively. The involved medications differed by type of discrepancy, but non-opioid analgesics and herbal therapies were common among commissions and omissions. In adjusted analyses, an increasing number of medications was associated with more commissions (OR 1.2; 95% CI 1.1 to 1.3) and duplications (OR 1.2; 95% CI 1.1 to 1.4) and fewer omissions (OR 0.9; 95% CI 0.8 to 1.0). Discussion In a system with a well established EHR linked to pharmacy dispensing, medication discrepancies occurred in 60% of ambulatory clinic patients. Patients with a greater number of medications were more likely to have errors of commission and duplication, but less likely to have errors of omission. Our findings highlight that relying on EHRs alone will not ensure an accurate medication list and stress the need to review medication taking thoroughly with patients to capitalise on the full potential of EHRs. C1 [Linsky, Amy; Simon, Steven R.] VA Boston Healthcare Syst, Gen Internal Med Sect, Boston, MA 02130 USA. [Linsky, Amy; Simon, Steven R.] Boston Med Ctr, Gen Internal Med Sect, Boston, MA USA. [Linsky, Amy; Simon, Steven R.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Linsky, Amy; Simon, Steven R.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Linsky, Amy; Simon, Steven R.] Harvard Univ, Sch Med, Boston, MA USA. RP Linsky, A (reprint author), VA Boston Healthcare Syst, Gen Internal Med Sect, 150 S Huntington Ave,Bldg 9,Room 425 152G, Boston, MA 02130 USA. EM amy.linsky@va.gov OI Linsky, Amy/0000-0002-8090-3431 FU Boston Medical Center; Center for Organisation, Leadership, and Management Research at VA Boston Healthcare System FX The study was conducted using resources of the VA Boston Healthcare System. The work was initiated while Dr Linsky was a fellow supported by Boston Medical Center and the Center for Organisation, Leadership, and Management Research at VA Boston Healthcare System. NR 22 TC 9 Z9 9 U1 0 U2 11 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD FEB PY 2013 VL 22 IS 2 BP 103 EP 109 DI 10.1136/bmjqs-2012-001301 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 079ZV UT WOS:000314211900003 PM 23100547 ER PT J AU Moustafa, AA Gilbertson, MW Orr, SP Herzallah, MM Servatius, RJ Myers, CE AF Moustafa, Ahmed A. Gilbertson, Mark W. Orr, Scott P. Herzallah, Mohammad M. Servatius, Richard J. Myers, Catherine E. TI A model of amygdala-hippocampal-prefrontal interaction in fear conditioning and extinction in animals SO BRAIN AND COGNITION LA English DT Article DE Fear conditioning; Computational model; Hippocampus; Amygdala; Ventromedial prefrontal cortex; Extinction ID IBOTENIC ACID LESIONS; NEURAL-NETWORK MODEL; CONTEXTUAL FEAR; CENTRAL NUCLEUS; HEART-RATE; BASOLATERAL AMYGDALA; DORSAL HIPPOCAMPUS; NEUROCOMPUTATIONAL MODEL; BEHAVIORAL EXTINCTION; INTERCALATED NEURONS AB Empirical research has shown that the amygdala, hippocampus, and ventromedial prefrontal cortex (vmPFC) are involved in fear conditioning. However, the functional contribution of each brain area and the nature of their interactions are not clearly understood. Here, we extend existing neural network models of the functional roles of the hippocampus in classical conditioning to include interactions with the amygdala and prefrontal cortex. We apply the model to fear conditioning, in which animals learn physiological (e.g. heart rate) and behavioral (e.g. freezing) responses to stimuli that have been paired with a highly aversive event (e.g. electrical shock). The key feature of our model is that learning of these conditioned responses in the central nucleus of the amygdala is modulated by two separate processes, one from basolateral amygdala and signaling a positive prediction error, and one from the vmPFC, via the intercalated cells of the amygdala, and signaling a negative prediction error. In addition, we propose that hippocampal input to both vmPFC and basolateral amygdala is essential for contextual modulation of fear acquisition and extinction. The model is sufficient to account for a body of data from various animal fear conditioning paradigms, including acquisition, extinction, reacquisition, and context specificity effects. Consistent with studies on lesioned animals, our model shows that damage to the vmPFC impairs extinction, while damage to the hippocampus impairs extinction in a different context (e.g., a different conditioning chamber from that used in initial training in animal experiments). We also discuss model limitations and predictions, including the effects of number of training trials on fear conditioning. Published by Elsevier Inc. C1 [Moustafa, Ahmed A.] Univ Western Sydney, Marcs Inst Brain & Behav, Sch Social Sci & Psychol, Sydney, NSW, Australia. [Moustafa, Ahmed A.; Herzallah, Mohammad M.] Rutgers State Univ, Ctr Mol & Behav Neurosci, Newark, NJ 07102 USA. [Moustafa, Ahmed A.; Servatius, Richard J.; Myers, Catherine E.] New Jersey Hlth Care Syst, Dept Vet Affairs, E Orange, NJ USA. [Gilbertson, Mark W.] Manchester VA Med Ctr, Manchester, NH USA. [Gilbertson, Mark W.; Orr, Scott P.] Harvard Univ, Sch Med, Boston, MA USA. [Orr, Scott P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Herzallah, Mohammad M.] Al Quds Univ Abu Dis, Cognit Neurosci Lab, Beit Hanina, Israel. [Servatius, Richard J.; Myers, Catherine E.] Univ Med & Dent New Jersey, New Jersey Med Sch, Stress & Motivated Behav Inst, Newark, NJ 07103 USA. [Myers, Catherine E.] Rutgers State Univ, Dept Psychol, Newark, NJ 07102 USA. RP Moustafa, AA (reprint author), Univ Western Sydney, Sch Psychol, Sydney, NSW, Australia. EM a.moustafa@uws.edu.au OI Myers, Catherine/0000-0002-2776-4823 FU NSF/NIH Collaborative Research in Computational Neuroscience (CRCNS) Program; NIAAA [RO1 AA018737-01] FX This work was partially supported by the NSF/NIH Collaborative Research in Computational Neuroscience (CRCNS) Program and by NIAAA (RO1 AA018737-01). NR 168 TC 21 Z9 21 U1 1 U2 21 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 EI 1090-2147 J9 BRAIN COGNITION JI Brain Cogn. PD FEB PY 2013 VL 81 IS 1 BP 29 EP 43 DI 10.1016/j.bandc.2012.10.005 PG 15 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 079BP UT WOS:000314145500005 PM 23164732 ER PT J AU Liu, YH Malin, JL Diamant, AL Thind, A Maly, RC AF Liu, Yihang Malin, Jennifer L. Diamant, Allison L. Thind, Amardeep Maly, Rose C. TI Adherence to adjuvant hormone therapy in low-income women with breast cancer: the role of provider-patient communication SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Hormone therapy adherence; Low-income women ID MEDICALLY UNDERSERVED WOMEN; POSTMENOPAUSAL WOMEN; PHYSICIAN COMMUNICATION; MEDICATION NONADHERENCE; RACIAL DISPARITIES; TAMOXIFEN THERAPY; ENDOCRINE THERAPY; OLDER PATIENTS; CARE; DISCONTINUATION AB To assess the impact of patient-provider communication on adherence to tamoxifen (TAM) and aromatase inhibitors (AIs) 36 months after breast cancer (BC) diagnosis in a low-income population of women. California statewide surveys were conducted among 921 low-income women with BC at 6, 18, and 36 months after BC diagnosis. A subset of 303 women with stage I-III BC who initiated hormone treatment after diagnosis was identified. Bivariate and multivariate logistic regression analyses were performed, and adjusted adherence rates were calculated. The main outcome measure was self-reported hormone use at 36 months after BC diagnosis and the chief independent variables were patient-centered communication after diagnosis by patient report as measured by the Consumer Assessment of Healthcare Providers and Systems (CAHPS) and patients' self-efficacy in patient-physician interactions (PEPPI). Overall adherence to TAM/AI was relatively high (88 %). Adjusted rates of adherence were 59 and 94 % for patients with the lowest versus highest scores on the CAHPS communication scale (AOR = 1.22, P = 0.006) and 72 versus 91 % for patients with the lowest and highest rating of PEPPI (AOR = 1.04, P = 0.04). Having at least one comorbid condition also increased the odds of adherence to hormonal therapy (AOR = 3.14, P = 0.03). Having no health insurance and experiencing side-effects from hormone treatment were barriers for adherence (AOR = 0.12, P = 0.001; AOR = 0.26, P = 0.003, respectively). Patient-centered communication and perceived self-efficacy in patient-physician interaction were significantly associated with patient adherence to ongoing TAM/AI therapy among low-income women with BC. Interventions on patient-provider communication may provide opportunities to improve patient outcomes in this vulnerable population. C1 [Liu, Yihang; Maly, Rose C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Family Med, Los Angeles, CA 90024 USA. [Malin, Jennifer L.] VA Greater Los Angeles Healthcare Syst, Div Hematol Oncol, Los Angeles, CA USA. [Diamant, Allison L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Thind, Amardeep] Univ Western Ontario, Dept Family Med & Epidemiol & Biostat, London, ON, Canada. RP Maly, RC (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Family Med, 10880 Wilshire Blvd Ste 1800, Los Angeles, CA 90024 USA. EM rmaly@mednet.ucla.edu FU American Cancer Society [TURSG-02-081]; California Breast Cancer Research Program [7PB-0070]; National Cancer Institute [R01CA119197-01A1, R01CA140481-01A1] FX This study was funded by the American Cancer Society (# TURSG-02-081), the California Breast Cancer Research Program (# 7PB-0070), and the National Cancer Institute (#R01CA119197-01A1). Dr. Maly was additionally supported by the National Cancer Institute (#R01CA140481-01A1). NR 58 TC 32 Z9 32 U1 3 U2 21 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 FEB PY 2013 VL 137 IS 3 BP 829 EP 836 DI 10.1007/s10549-012-2387-8 PG 8 WC Oncology SC Oncology GA 076GN UT WOS:000313944600017 PM 23263740 ER PT J AU Rosovsky, R Hong, FX Tocco, D Connell, B Mitsiades, C Schlossman, R Ghobrial, I Lockridge, L Warren, D Bradwin, G Doyle, M Munshi, N Soiffer, RJ Anderson, KC Weller, E Richardson, P AF Rosovsky, Rachel Hong, Fangxin Tocco, Deanna Connell, Brendan Mitsiades, Constantine Schlossman, Robert Ghobrial, Irene Lockridge, Leslie Warren, Diane Bradwin, Gary Doyle, Mary Munshi, Nikhil Soiffer, Robert J. Anderson, Kenneth C. Weller, Edie Richardson, Paul TI Endothelial stress products and coagulation markers in patients with multiple myeloma treated with lenalidomide plus dexamethasone: an observational study SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE multiple myeloma; venous thromboembolism; dexamethasone; lenalidomide; endothelial markers ID VENOUS THROMBOSIS; COMBINATION THERAPY; THALIDOMIDE; IMMUNOMODULATION; DEFIBROTIDE; CC-4047; TRIAL AB In this prospective study of patients with relapsed or relapsed and refractory multiple myeloma (MM) treated with lenalidomide and dexamethasone, relationships between markers of endothelial stress and drug administration and incidence of venous thromboembolism (VTE) were assessed. Of 33 enrolled patients, laboratory and treatment data were available for 32 patients. Of these, 23 received pulsed dexamethasone (40 mg/day on days 1-4, 9-12 and 17-21 of each 28-day cycle) and 9 received weekly dexamethasone (40 mg/day on days 1, 8, 15 and 21 of each cycle). The overall incidence of VTE was 9%. A decreasing trend in markers values was observed with intercellular adhesion molecule (P = 0.05), fibrinogen (P = 0.008), plasminogen activator inhibitor-1 (P < 0.001), homocysteine (P = 0.002) and Pselectin (P < 0.001) during therapy. Compared with weekly dexamethasone, pulsed dexamethasone was associated with significantly greater variation in mean adjusted relative values of fibrinogen, P-selectin and vascular endothelial growth factor (P < 0.001 for all comparisons), although there was no apparent association with VTE incidence. Lenalidomide plus dexamethasone affects endothelial stress marker levels in patients with advanced MM. The higher variation seen with pulsed dexamethasone suggests greater endothelial stress with this approach. C1 [Rosovsky, Rachel] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rosovsky, Rachel; Hong, Fangxin; Mitsiades, Constantine; Schlossman, Robert; Ghobrial, Irene; Lockridge, Leslie; Bradwin, Gary; Munshi, Nikhil; Soiffer, Robert J.; Anderson, Kenneth C.; Weller, Edie; Richardson, Paul] Harvard Univ, Sch Med, Boston, MA USA. [Tocco, Deanna; Connell, Brendan; Mitsiades, Constantine; Schlossman, Robert; Ghobrial, Irene; Lockridge, Leslie; Warren, Diane; Munshi, Nikhil; Soiffer, Robert J.; Anderson, Kenneth C.; Weller, Edie; Richardson, Paul] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Div Hematol Malignancy, Boston, MA 02115 USA. [Bradwin, Gary] Childrens Hosp, Boston, MA 02115 USA. [Doyle, Mary] Instrumentat Lab, Lexington, MA USA. RP Rosovsky, R (reprint author), Massachusetts Gen Hosp, POB 246,55 Fruit St, Boston, MA 02114 USA. EM rprosovsky@partners.org FU Celgene; Rick Corman Multiple Myeloma Research Foundation; Celgene Corporation FX Celgene (Advisory Board, Research Support): I. Ghobrial, N. Munshi, K. C. Anderson and P. Richardson.; Support for this project was provided by the Rick Corman Multiple Myeloma Research Foundation and Celgene Corporation. The authors gratefully acknowledge Michelle Maglio for her extensive administrative support; Jacob Laubach MD for his review of the manuscript and contributions to the discussions; and the assistance of the Medical Arts Core, DFCI, Boston, MA, USA. NR 26 TC 5 Z9 6 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD FEB PY 2013 VL 160 IS 3 BP 351 EP 358 DI 10.1111/bjh.12152 PG 8 WC Hematology SC Hematology GA 073MH UT WOS:000313746600009 PM 23240658 ER PT J AU Zwicker, JI Liebman, HA Bauer, KA Caughey, T Campigotto, F Rosovsky, R Mantha, S Kessler, CM Eneman, J Raghavan, V Lenz, HJ Bullock, A Buchbinder, E Neuberg, D Furie, B AF Zwicker, Jeffrey I. Liebman, Howard A. Bauer, Kenneth A. Caughey, Thomas Campigotto, Federico Rosovsky, Rachel Mantha, Simon Kessler, Craig M. Eneman, Jonathan Raghavan, Vidya Lenz, Heinz-Joseph Bullock, Andrea Buchbinder, Elizabeth Neuberg, Donna Furie, Bruce TI Prediction and prevention of thromboembolic events with enoxaparin in cancer patients with elevated tissue factor-bearing microparticles: a randomized-controlled phase II trial (the Microtec study) SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE microparticles; venous thromboembolic events; cancer associated thrombosis; low molecular weight heparin ID FACTOR PROCOAGULANT ACTIVITY; CELL-DERIVED MICROPARTICLES; VENOUS THROMBOEMBOLISM; THROMBIN GENERATION; FIBRIN FORMATION; FLOW-CYTOMETRY; COMPETING RISK; P-SELECTIN; IN-VIVO; CHEMOTHERAPY AB Elevated levels of circulating tissue factor-bearing microparticles (TFMP) have been associated with an increased risk of developing venous thromboembolism (VTE) in cancer patients. We performed a randomized phase II study to evaluate the cumulative incidence of VTE in advanced cancer patients with lower levels of TFMP not receiving thromboprophylaxis and those with higher levels of circulating TFMP randomized to enoxaparin or observation. The cumulative incidence of VTE at 2 months in the higher TFMP group randomized to enoxaparin (N = 23) was 5.6% while the higher TFMP group observation arm (N = 11) was 27.3% (Gray test P = 0.06). The cumulative incidence of VTE in the low TFMP was 7.2% (N = 32). No major haemorrhages were observed in the enoxaparin arm. The median survival for patients with higher levels of TFMP followed by observation was 11.8 months compared with 17.8 months on enoxaparin (P = 0.58). In a prospective randomized trial, increased numbers of circulating TFMP detected by impedance flow cytometry identified cancer patients with a high incidence of VTE. Enoxaparin demonstrated a clear trend towards reducing the rate of VTE in patients with elevated levels of TFMP, with an overall rate of VTE similar in magnitude to the lower TFMP group. C1 [Zwicker, Jeffrey I.; Bauer, Kenneth A.; Furie, Bruce] Beth Israel Deaconess Med Ctr, Div Hemostasis & Thrombosis, Boston, MA 02215 USA. [Zwicker, Jeffrey I.; Bullock, Andrea; Buchbinder, Elizabeth] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Liebman, Howard A.; Lenz, Heinz-Joseph] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Bauer, Kenneth A.] Harvard Univ, Sch Med, Vet Affairs Boston Healthcare Syst, Boston, MA USA. [Caughey, Thomas; Raghavan, Vidya] Harvard Univ, Sch Med, Mt Auburn Hosp, Cambridge, MA 02138 USA. [Campigotto, Federico; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Rosovsky, Rachel] Harvard Univ, Sch Med, Massachusetts Gen Hosp, N Shore Canc Ctr, Danvers, MA USA. [Mantha, Simon] Lahey Clin Hosp, Burlington, MA USA. [Kessler, Craig M.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Eneman, Jonathan] York Hosp, York, ME USA. RP Zwicker, JI (reprint author), Beth Israel Deaconess Med Ctr, Div Hemostasis & Thrombosis, 330 Brookline Ave, Boston, MA 02215 USA. EM jzwicker@bidmc.harvard.edu OI Zwicker, Jeffrey/0000-0001-5810-6893 FU National Institutes of Health [K23 HL84052, R01 HL095084]; Sanofi FX This work was supported by grants from the National Institutes of Health, K23 HL84052 (JIZ) and R01 HL095084 (BF), as well as a research grant from Sanofi (JIZ). We thank Anita Rodrigues, Marie Mahony RN, Laurie Hornor RN, Lisa Fabry RN, and Kelly Tammaro PharmD for their efforts in clinical research coordination; Gus Alban and Leo Puljanowski and Beckman Coulter for cytometry technical support; Dr. Gary Horowitz for technical assistance with D-dimer analysis; Dr. Hing Wong at Altor Biosciences for the gift of humanized tissue factor antibody. We are indebted to the patients for participating in this trial and acknowledge the critical roles played by all the participating investigators and coordinators. NR 34 TC 56 Z9 58 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD FEB PY 2013 VL 160 IS 4 BP 530 EP 537 DI 10.1111/bjh.12163 PG 8 WC Hematology SC Hematology GA 077ZO UT WOS:000314068100013 PM 23240761 ER PT J AU Demay, MB AF Demay, Marie B. TI Physiological Insights from the Vitamin D Receptor Knockout Mouse SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE Alopecia; Ligand-independent; Osteomalacia; Rickets ID MINERAL ION HOMEOSTASIS; VDR-NULL MICE; 1,25-DIHYDROXYVITAMIN D-3; ABLATED MICE; HYPERTROPHIC CHONDROCYTES; EPIDERMAL DIFFERENTIATION; CALCIUM-ABSORPTION; HAIRLESS GENE; ANIMAL-MODEL; RICKETS AB Identification of vitamin D as a potent antirachitic factor almost a century ago prompted investigations aimed at addressing its mechanism of action and key target tissues. Studies in vitamin D deficiency models and in kindreds with impaired hormone activation and function were critical in identifying key steps in the vitamin D signaling pathway. Studies in humans with vitamin D receptor (VDR) mutations provided a tremendous amount of information regarding the role of this receptor in calcium and skeletal homeostasis. The availability of mouse models of VDR ablation provided an important tool for detailed molecular analyses of the pathophysiologic basis for the skeletal, parathyroid and cutaneous phenotypes observed in mice and humans with impaired VDR function. These investigations revealed that a critical action of the liganded receptor is the promotion of intestinal calcium absorption. Bypassing this defect by dietary or transgenic rescue prevents the severe skeletal phenotype of the VDR ablated mice, as well as the development of hyperparathyroidism. In contrast, intestine specific ablation of the receptor results in marked skeletal pathology. Like their human counterparts, VDR knockout mice develop alopecia. Studies in these mice demonstrated that the actions of the VDR required for cyclical regeneration of the hair follicle and prevention of alopecia were shown independent of 1,25-dihydroxyvitamin D demonstrating that the unliganded receptor has an important role in the cutaneous homeostasis. C1 Harvard Univ, Endocrine Unit, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Demay, MB (reprint author), Harvard Univ, Endocrine Unit, Massachusetts Gen Hosp, Sch Med, Thier 11,50 Blossom St, Boston, MA 02115 USA. EM demay@helix.mgh.harvard.edu FU National Institutes of Health [R01-DK-46974] FX This work was supported by a Grant from the National Institutes of Health R01-DK-46974. NR 45 TC 12 Z9 13 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD FEB PY 2013 VL 92 IS 2 SI SI BP 99 EP 105 DI 10.1007/s00223-012-9633-2 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 077RA UT WOS:000314043900003 PM 22903507 ER PT J AU Diyabalanage, HVK Granda, ML Hooker, JM AF Diyabalanage, Himashinie V. K. Granda, Michael L. Hooker, Jacob M. TI Combination therapy: Histone deacetylase inhibitors and platinum-based chemotherapeutics for cancer SO CANCER LETTERS LA English DT Review DE Histone deacetylase; Cisplatin; Cancer; Chemotherapy; HDAC inhibitor; Combination therapy; Platinum drug ID SUBEROYLANILIDE HYDROXAMIC ACID; T-CELL LYMPHOMA; PHASE-II TRIAL; HDAC INHIBITORS; OVARIAN-CANCER; VALPROIC ACID; CARCINOMA-CELLS; CLINICAL-APPLICATIONS; MOLECULAR-MECHANISMS; EPIGENETIC THERAPY AB One of the most promising strategies to increase the efficacy of standard chemotherapy drugs is by combining them with low doses of histone deacetylases inhibitors (HDACis). Regarded as chemosensitizers, the addition of well-tolerated doses of HDACis to platinum-based chemotherapeutics has been proven in vitro and in vivo in recent studies for many cancer types and stages. In this review, we discuss the most commonly used combinations of histone deacetylase inhibitors and platinum based drugs in the context of their possible mechanisms, efficiency, efficacy, and related drawbacks in preclinical and clinical studies. (c) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Diyabalanage, Himashinie V. K.; Granda, Michael L.; Hooker, Jacob M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Boston, MA 02129 USA. RP Hooker, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Boston, MA 02129 USA. EM hooker@nmr.mgh.harvard.edu OI Hooker, Jacob/0000-0002-9394-7708 FU NCI NIH HHS [T32 CA009502]; NCRR NIH HHS [S10 RR023385]; NIDA NIH HHS [R01 DA030321] NR 120 TC 19 Z9 19 U1 1 U2 45 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD FEB 1 PY 2013 VL 329 IS 1 BP 1 EP 8 DI 10.1016/j.canlet.2012.09.018 PG 8 WC Oncology SC Oncology GA 078CQ UT WOS:000314076100001 PM 23032720 ER PT J AU Micco, JA Hirshfeld-Becker, DR Henin, A Ehrenreich-May, J AF Micco, Jamie A. Hirshfeld-Becker, Dina R. Henin, Aude Ehrenreich-May, Jill TI Content Specificity of Threat Interpretation in Anxious and Non-Clinical Children SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE Content specificity; Threat interpretation; Interpretation bias; Child anxiety ID SEPARATION ANXIETY DISORDER; GENERALIZED-ANXIETY; SOCIAL PHOBIA; INTERPRETATION BIAS; CHILDHOOD ANXIETY; PANIC DISORDER; PERCEPTION ABNORMALITIES; EMOTIONAL INFORMATION; SOMATIC COMPLAINTS; DEPRESSION SCALE AB This study investigated content specificity of children's threat interpretations in a group of 40 clinically anxious (18 boys, 22 girls; ages 7-14 years) and a group of 40 non-clinical children (19 boys, 21 girls; ages 8-14 years). Associations between disorder-specific threat interpretations (in response to situations selected by each child) and each of six DSM-IV anxiety and depressive disorder symptom domains were examined for each group of children through multivariate regression analyses. Supporting theories of cognitive content specificity, results showed that for clinically anxious children, symptoms of social phobia and panic disorder were significantly and specifically predicted by threat interpretation in response to situations that corresponded to each disorder, while symptoms of separation anxiety were predicted by threat perception in situations relevant to separation anxiety and panic disorder. There was little evidence of cognitive content specificity within the non-clinical group of children. Implications for theories of development of interpretation biases associated with child anxiety disorders are discussed. C1 [Micco, Jamie A.; Hirshfeld-Becker, Dina R.; Henin, Aude] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. [Ehrenreich-May, Jill] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. RP Micco, JA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, 185 Alewife Brook Pkwy,Suite 2000, Cambridge, MA 02138 USA. EM jmicco@partners.org NR 49 TC 2 Z9 3 U1 1 U2 10 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD FEB PY 2013 VL 37 IS 1 BP 78 EP 88 DI 10.1007/s10608-012-9438-7 PG 11 WC Psychology, Clinical SC Psychology GA 077YD UT WOS:000314064400010 ER PT J AU Bui, E Simon, NM Robinaugh, DJ LeBlanc, NJ Wang, YJ Skritskaya, NA Mauro, C Shear, MK AF Bui, Eric Simon, Naomi M. Robinaugh, Donald J. LeBlanc, Nicole J. Wang, Yuanjia Skritskaya, Natalia A. Mauro, Christine Shear, M. Katherine TI PERILOSS DISSOCIATION, SYMPTOM SEVERITY, AND TREATMENT RESPONSE IN COMPLICATED GRIEF SO DEPRESSION AND ANXIETY LA English DT Article DE peritraumatic dissociation; complicated grief; treatment response; drop out; prediction ID POSTTRAUMATIC STRESS SYMPTOMS; PERITRAUMATIC DISSOCIATION; CHILDREN VICTIMS; TRAUMA; INDIVIDUALS; EXPERIENCES; ACCIDENT AB Background Complicated grief (CG) is a bereavement-specific syndrome characterized by traumatic and separation distress lasting over 6 months. Little is known about the role of dissociation experienced during or immediately after the loss of a loved one (i.e. periloss dissociation [PLD]) in CG. The present study aimed to examine the psychometric properties of the PLD-adapted Peritraumatic Dissociative Experiences Questionnaire and its association with symptom severity, treatment response, and drop-out rate. Methods PLD data collected as part of a randomized controlled trial of two loss-focused psychotherapy approaches for CG were examined. Treatment-seeking individuals with primary CG (n = 193) were assessed for PLD at the initial visit, 95 of whom were randomized and completed at least one treatment session. Results The PLD-adapted Peritraumatic Dissociative Experiences Questionnaire was found to be internally consistent (a = 0.91) with good convergent and divergent validity. After controlling for age, gender, time since loss, and current comorbid psychiatric diagnosis, self-reported PLD was associated with greater CG symptom severity (P < .01). However, contrary to our hypotheses, after controlling for age, baseline symptoms severity, psychiatric comorbidity, and treatment arm, PLD was predictive of better treatment response (P < .05) and lower study discontinuation (P < .01). Conclusions PLD may be useful in identifying individuals at risk for CG and those who might respond to psychotherapy. Additional research should investigate the relationship of PLD with treatment outcome for different treatment approaches, and whether PLD prospectively predicts the development of CG. C1 [Bui, Eric] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. [Bui, Eric; Simon, Naomi M.] Harvard Univ, Sch Med, Boston, MA USA. [Bui, Eric] Univ Toulouse, Toulouse, France. [Bui, Eric] CHU Toulouse, Toulouse, France. [Wang, Yuanjia; Skritskaya, Natalia A.; Mauro, Christine; Shear, M. Katherine] Columbia Univ, New York, NY USA. RP Bui, E (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, 1 Bowdoin Sq,6th Floor,Suite 650, Boston, MA 02114 USA. EM tebui@partners.org RI Bui, Eric/J-8347-2015 OI Bui, Eric/0000-0002-1413-6473 FU American Foundation for Suicide Prevention; Forest Laboratories; NIMH; DOD; GlaxoSmithKline; NARSAD Sepracor FX EB has received honoraria from Laboratoires Servier. NMS has research grants from American Foundation for Suicide Prevention, Forest Laboratories, NIMH, DOD, GlaxoSmithKline, NARSAD Sepracor and also has received honoraria for speaking/CME from MGH Psychiatry Academy. MKS has research grant from American Foundation for Suicide Prevention and NIMH. All other authors declare that they have no conflicts of interest. NR 24 TC 4 Z9 4 U1 0 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD FEB PY 2013 VL 30 IS 2 BP 123 EP 128 DI 10.1002/da.22029 PG 6 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 078QC UT WOS:000314113300004 PM 23212730 ER PT J AU Shah, RR Koniski, A Shinde, M Blythe, SA Fass, DM Haggarty, SJ Palis, J Klein, PS AF Shah, Rishita R. Koniski, Anne Shinde, Mansi Blythe, Shelby A. Fass, Daniel M. Haggarty, Stephen J. Palis, James Klein, Peter S. TI Regulation of Primitive Hematopoiesis by Class I Histone Deacetylases SO DEVELOPMENTAL DYNAMICS LA English DT Article DE class I HDACs; hematopoiesis ID VALPROIC ACID; EMBRYONIC BLOOD; XENOPUS-LAEVIS; MIDBLASTULA TRANSITION; VENTRAL MESODERM; CELL-DEVELOPMENT; GENE-EXPRESSION; GROWTH-FACTOR; ZEBRAFISH; GATA-1 AB Background: Histone deacetylases (HDACs) regulate multiple developmental processes and cellular functions. However, their roles in blood development have not been determined, and in Xenopus laevis a specific function for HDACs has yet to be identified. Here, we employed the class I selective HDAC inhibitor, valproic acid (VPA), to show that HDAC activity is required for primitive hematopoiesis. Results: VPA treatment during gastrulation resulted in a complete absence of red blood cells (RBCs) in Xenopus tadpoles, but did not affect development of other mesodermal tissues, including myeloid and endothelial lineages. These effects of VPA were mimicked by Trichostatin A (TSA), a well-established pan-HDAC inhibitor, but not by valpromide, which is structurally similar to VPA but does not inhibit HDACs. VPA also caused a marked, dose-dependent loss of primitive erythroid progenitors in mouse yolk sac explants at clinically relevant concentrations. In addition, VPA treatment inhibited erythropoietic development downstream of bmp4 and gata1 in Xenopus ectodermal explants. Conclusions: These findings suggest an important role for class I HDACs in primitive hematopoiesis. Our work also demonstrates that specific developmental defects associated with exposure to VPA, a significant teratogen in humans, arise through inhibition of class I HDACs. Developmental Dynamics 242:108121, 2013. (c) 2012 Wiley Periodicals,Inc. C1 [Shah, Rishita R.; Blythe, Shelby A.; Klein, Peter S.] Univ Penn, Cell & Mol Biol Grad Grp, Philadelphia, PA 19104 USA. [Koniski, Anne; Palis, James] Univ Rochester, Med Ctr, Dept Pediat, Ctr Pediat Biomed Res, Rochester, NY 14642 USA. [Shinde, Mansi; Klein, Peter S.] Univ Penn, Pharmacol Grad Grp, Philadelphia, PA 19104 USA. [Fass, Daniel M.; Haggarty, Stephen J.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Fass, Daniel M.; Haggarty, Stephen J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Klein, Peter S.] Univ Penn, Dept Med Hematol Oncol, Philadelphia, PA 19104 USA. RP Klein, PS (reprint author), Univ Penn, Dept Med Hematol Oncol, Philadelphia, PA 19104 USA. EM pklein@mail.med.upenn.edu OI Blythe, Shelby/0000-0003-4986-2579; Haggarty, Stephen J./0000-0002-7872-168X FU NIH [1R01GM076621, 1R01HL110806-01, R25 CA101871-07, R01DK09361, 1R01DA028301, R01DK 09361]; NCI [R25 CA101871-07] FX Contract grant sponsor: NIH; Contract grant numbers: 1R01GM076621; 1R01HL110806-01; R25 CA101871-07; R01DK09361; 1R01DA028301.; We thank Nancy Speck, Daniel Kessler, Michael May, Judy Meinkoth, and the members of the Klein Lab for their insights and encouragement. We also thank Mitch Weiss, Gerd Blobel, and Wei Tong for insightful comments. We thank Edward Holson for the synthesis of CI-994 and C60. This work was supported by the following NIH grants: 1R01GM076621 (P.S.K.), 1R01HL110806-01 (P.S.K.); R01DK 09361 (J.P.); and 1R01DA028301 (S.J.H.). In addition, R.S. was supported by the Cancer Pharmacology Training Grant R25 CA101871-07 from the NCI. NR 54 TC 4 Z9 5 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD FEB PY 2013 VL 242 IS 2 BP 108 EP 121 DI 10.1002/dvdy.23906 PG 14 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 076VE UT WOS:000313986100002 PM 23184530 ER PT J AU Saxon, AJ Ling, W Hillhouse, M Thomas, C Hasson, A Ang, A Doraimani, G Tasissa, G Lokhnygina, Y Leimberger, J Bruce, RD McCarthy, J Wiest, K McLaughlin, P Bilangi, R Cohen, A Woody, G Jacobs, P AF Saxon, Andrew J. Ling, Walter Hillhouse, Maureen Thomas, Christie Hasson, Albert Ang, Alfonso Doraimani, Geetha Tasissa, Gudaye Lokhnygina, Yuliya Leimberger, Jeff Bruce, R. Douglas McCarthy, John Wiest, Katharina McLaughlin, Paul Bilangi, Richard Cohen, Allan Woody, George Jacobs, Petra TI Buprenorphine/Naloxone and methadone effects on laboratory indices of liver health: A randomized trial SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Liver function; Buprenorphine; Methadone; Treatment outcome ID OPIOID DEPENDENCE; MAINTENANCE; HEPATITIS; ABUSE AB Background: Buprenorphine/naloxone (BUP) and methadone (MET) are efficacious treatments for opioid dependence, although concerns about a link between BUP and drug-induced hepatitis have been raised. This study compares the effects of BUP and MET on liver health in opioid-dependent participants. Methods: This was a randomized controlled trial of 1269 opioid-dependent participants seeking treatment at 8 federally licensed opioid treatment programs and followed for up to 32 weeks between May 2006 and August 2010; 731 participants met "evaluable" criteria defined as completing 24 weeks of medication and providing at least 4 blood samples for transaminase testing. Participants were randomly assigned to receive BUP or MET for 24 weeks. Shift table analysis determined how many evaluable participants moved between categories of low and elevated transaminase levels. Predictors of moving from low to high transaminase levels were identified. Results: Changes in transaminase levels did not differ by medication condition. Baseline infection with hepatitis C or B was the only significant predictor of moving from low to elevated transaminase levels; 9 BUP and 15 MET participants showed extreme liver test elevations and were more likely than those without extreme elevations to have seroconverted to both hepatitis B and C during the study, or to use illicit drugs during the first 8 weeks of treatment. MET participants were retained longer in treatment than BUP participants. Conclusions: This study demonstrated no evidence of liver damage during the initial 6 months of treatment in either condition. Physicians can prescribe either medication without major concern for liver injury. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Saxon, Andrew J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Ling, Walter; Hillhouse, Maureen; Thomas, Christie; Hasson, Albert; Ang, Alfonso; Doraimani, Geetha] Univ Calif Los Angeles, Integrated Subst Abuse Programs, Los Angeles, CA 90025 USA. [Tasissa, Gudaye; Lokhnygina, Yuliya; Leimberger, Jeff] Duke Clin Res Inst, Durham, NC 27705 USA. [Bruce, R. Douglas] Yale Univ, Sch Med, New Haven, CT 06510 USA. [McCarthy, John] Bivalley Med Clin Inc, Carmichael, CA 95838 USA. [Wiest, Katharina] CODA Inc, Portland, OR 97214 USA. [McLaughlin, Paul] Hartford Dispensary, Manchester, CT 06040 USA. [Bilangi, Richard] Connecticut Counseling Ctr, Danbury, CT 06810 USA. [Cohen, Allan] Bay Area Addict Res & Treatment, Sherman Oaks, CA 91403 USA. [Woody, George] Univ Penn, Sch Med, Philadelphia, PA 19106 USA. [Jacobs, Petra] NIDA, Clin Trials Network, Bethesda, MD 20892 USA. RP Hillhouse, M (reprint author), Univ Calif Los Angeles, Integrated Subst Abuse Programs, 1640 S Sepulveda Blvd,Suite 120, Los Angeles, CA 90025 USA. EM hillhous@ucla.edu FU Gilead Sciences, Inc; Merck Co; Bristol Myers Squibb; Boehringer Ingelheim; Reckitt Benckiser Pharmaceuticals; Abbott Laboratories; Pfizer, Inc FX Authors disclosing relevant financial interests, activities, relationships, and affiliations are: Andrew Saxon: Paid consultant to Reckitt Benckiser Pharmaceuticals; Walter Ling: Paid consultant to Reckitt Benckiser Pharmaceuticals; R. Douglas Bruce: Research grant support from Gilead Sciences, Inc., Merck & Co., Bristol Myers Squibb, Boehringer Ingelheim, Reckitt Benckiser Pharmaceuticals, Abbott Laboratories, Pfizer, Inc., and honorarium from Reckitt Benckiser Pharmaceuticals; Yuliya Lokhnygina: Paid consultant to Johnson & Johnson. All other authors report no financial or other possible conflicts of interest. NR 19 TC 25 Z9 25 U1 2 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD FEB 1 PY 2013 VL 128 IS 1-2 BP 71 EP 76 DI 10.1016/j.drugalcdep.2012.08.002 PG 6 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 081OO UT WOS:000314331700011 PM 22921476 ER PT J AU Schackman, BR Metsch, LR Colfax, GN Leff, JA Wong, A Scott, CA Feaster, DJ Gooden, L Matheson, T Haynes, LF Paltiel, AD Walensky, RP AF Schackman, Bruce R. Metsch, Lisa R. Colfax, Grant N. Leff, Jared A. Wong, Angela Scott, Callie A. Feaster, Daniel J. Gooden, Lauren Matheson, Tim Haynes, Louise F. Paltiel, A. David Walensky, Rochelle P. TI The cost-effectiveness of rapid HIV testing in substance abuse treatment: Results of a randomized trial SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Rapid HIV testing; Substance use; Cost-effectiveness ID HUMAN-IMMUNODEFICIENCY-VIRUS; UNITED-STATES; ANTIRETROVIRAL THERAPY; INFECTED PERSONS; CLINICAL-TRIALS; CARE; EFFICACY; PREVENTION; HIV/AIDS; LIFE AB Background: The President's National HIV/AIDS Strategy calls for coupling HIV screening and prevention services with substance abuse treatment programs. Fewer than half of US community-based substance abuse treatment programs make HIV testing available on-site or through referral. Methods: We measured the cost-effectiveness of three HIV testing strategies evaluated in a randomized trial conducted in 12 community-based substance abuse treatment programs in 2009: off-site testing referral, on-site rapid testing with information only, on-site rapid testing with risk-reduction counseling. Data from the trial included patient demographics, prior testing history, test acceptance and receipt of results, undiagnosed HIV prevalence (0.4%) and program costs. The Cost-Effectiveness of Preventing AIDS Complications (CEPAC) computer simulation model was used to project life expectancy, lifetime costs, and quality-adjusted life years (QALYs) for HIV-infected individuals. Incremental cost-effectiveness ratios (2009 US $/QALY) were calculated after adding costs of testing HIV-uninfected individuals; costs and QALYs were discounted at 3% annually. Results: Referral for off-site testing is less efficient (dominated) compared to offering on-site testing with information only. The cost-effectiveness ratio for on-site testing with information is $60,300/QALY in the base case, or $76,300/QALY with 0.1% undiagnosed HIV prevalence. HIV risk-reduction counseling costs $36 per person more without additional benefit. Conclusions: A strategy of on-site rapid HIV testing offer with information only in substance abuse treatment programs increases life expectancy at a cost-effectiveness ratio <$100,000/QALY. Policymakers and substance abuse treatment leaders should seek funding to implement on-site rapid HIV testing in substance abuse treatment programs for those not recently tested. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Schackman, Bruce R.; Leff, Jared A.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY 10065 USA. [Metsch, Lisa R.; Feaster, Daniel J.; Gooden, Lauren] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. [Colfax, Grant N.; Matheson, Tim] San Francisco Dept Publ Hlth, HIV Prevent & Res Sect, San Francisco, CA 94102 USA. [Wong, Angela; Scott, Callie A.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Haynes, Louise F.] Med Univ S Carolina, Div Clin Neurosci, Charleston, SC 29403 USA. [Paltiel, A. David] Yale Univ, Sch Publ Hlth, Div Hlth Policy & Adm, New Haven, CT 06510 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Schackman, BR (reprint author), Weill Cornell Med Coll, Dept Publ Hlth, 402 E 67th St, New York, NY 10065 USA. EM brs2006@med.cornell.edu RI Feaster, Daniel/I-6079-2013; OI Walensky, Rochelle P./0000-0002-8795-379X; Feaster, Daniel/0000-0002-6172-7460 FU National Institute on Drug Abuse [R01 DA027379, R01 DA015612]; National Drug Abuse Treatment Clinical Trials Network (CTN) [U10 DA013720, U10DA13720-09S, U10 DA020036, U10DA15815, U10DA13034, U10DA013038, U10 DA013732, U10 DA13036, U10 DA13727, U10DA015833, HHSN271200522081C, HHSN271200522071C]; National Institute of Mental Health [R01 MH065869]; National Institute of Allergy and Infectious Diseases [R37 A1042006] FX This research was supported by the National Institute on Drug Abuse (R01 DA027379; R01 DA015612), the National Drug Abuse Treatment Clinical Trials Network (CTN) (U10 DA013720, U10DA13720-09S, U10 DA020036, U10DA15815, U10DA13034, U10DA013038, U10 DA013732, U10 DA13036, U10 DA13727, U10DA015833, HHSN271200522081C, HHSN271200522071C); the National Institute of Mental Health (R01 MH065869), and the National Institute of Allergy and Infectious Diseases (R37 A1042006). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the views of the funding agencies or the U.S. government. NR 44 TC 14 Z9 14 U1 4 U2 24 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD FEB 1 PY 2013 VL 128 IS 1-2 BP 90 EP 97 DI 10.1016/j.drugalcdep.2012.08.009 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 081OO UT WOS:000314331700014 PM 22971593 ER PT J AU Ho, JM Blevins, JE AF Ho, Jacqueline M. Blevins, James E. TI Coming Full Circle: Contributions of Central and Peripheral Oxytocin Actions to Energy Balance SO ENDOCRINOLOGY LA English DT Review ID HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; CONDITIONED PLACE PREFERENCE; RECEPTOR GENE-EXPRESSION; C-FOS EXPRESSION; FOOD-INTAKE; BRAIN-STEM; GASTRIC DISTENSION; DEFICIENT MICE; NEUROHYPOPHYSEAL HORMONES; INTRACELLULAR CALCIUM AB The neuropeptide oxytocin has emerged as an important anorexigen in the regulation of energy balance. Its effects on food intake have largely been attributed to limiting meal size through interactions in key regulatory brain regions such as the hypothalamus and hindbrain. Pharmacologic and pair-feeding studies indicate that its ability to reduce body mass extends beyond that of food intake, affecting multiple factors that determine energy balance such as energy expenditure, lipolysis, and glucose regulation. Systemic administration of oxytocin recapitulates many of its effects when administered centrally, raising the questions of whether and to what extent circulating oxytocin contributes to energy regulation. Its therapeutic potential to treat metabolic conditions remains to be determined, but data from diet-induced and genetically obese rodent models as well as application of oxytocin in humans in other areas of research have revealed promising results thus far. (Endocrinology 154: 589-596, 2013) C1 [Ho, Jacqueline M.] Vet Affairs Puget Sound Hlth Care Syst, Off Res & Dev, Med Res Serv, Seattle, WA 98108 USA. Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. RP Ho, JM (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Off Res & Dev, Med Res Serv, 1660 S Columbian Way, Seattle, WA 98108 USA. EM jmh529@uw.edu FU Office of Research and Development, Medical Research Service, Department of Veterans Affairs; Department of Veterans Affairs; National Institutes of Health [T32DK007247-35] FX This work was supported by resources from the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, including the Department of Veterans Affairs Merit Review Research Program. Funding for this manuscript was provided by the Department of Veterans Affairs Merit Review Research Program (to J.E.B.) and a Trainee Fellowship under National Institutes of Health grant T32DK007247-35 (to J.M.H.). NR 99 TC 19 Z9 21 U1 2 U2 14 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 2013 VL 154 IS 2 BP 589 EP 596 DI 10.1210/en.2012-1751 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 076ME UT WOS:000313959800004 PM 23270805 ER PT J AU Giubellino, A Bullova, P Nolting, E Turkova, H Powers, JF Liu, QS Guichard, S Tischler, AS Grossman, AB Pacak, K AF Giubellino, Alessio Bullova, Petra Noelting, Svenja Turkova, Hana Powers, James F. Liu, Qingsong Guichard, Sylvie Tischler, Arthur S. Grossman, Ashley B. Pacak, Karel TI Combined Inhibition of mTORC1 and mTORC2 Signaling Pathways Is a Promising Therapeutic Option in Inhibiting Pheochromocytoma Tumor Growth: In Vitro and In Vivo Studies in Female Athymic Nude Mice SO ENDOCRINOLOGY LA English DT Article ID MALIGNANT PHEOCHROMOCYTOMA; DIFFERENTIAL EXPRESSION; NEUROENDOCRINE TUMORS; MAMMALIAN TARGET; KINASE INHIBITOR; ENDOCRINE TUMORS; CANCER; PARAGANGLIOMA; RAPAMYCIN; THERAPIES AB Several lines of evidence, including the recent discovery of novel susceptibility genes, point out an important role for the mammalian target of rapamycin (mTOR) signaling pathway in the development of pheochromocytoma. Analyzing a set of pheochromocytomas from patients with different genetic backgrounds, we observed and confirmed a significant overexpression of key mTOR complex (mTORC) signaling mediators. Using selective ATP-competitive inhibitors targeting both mTORC1 and mTORC2, we significantly arrested the in vitro cell proliferation and blocked migration of pheochromocytoma cells as a result of the pharmacological suppression of the Akt/mTOR signaling pathway. Moreover, AZD8055, a selective ATP-competitive dual mTORC1/2 small molecular inhibitor, significantly reduced the tumor burden in a model of metastatic pheochromocytoma using female athymic nude mice. This study suggests that targeting both mTORC1 and mTORC2 is a potentially rewarding strategy and supports the application of selective inhibitors in combinatorial drug regimens for metastatic pheochromocytoma. (Endocrinology 154: 646-655, 2013) C1 [Giubellino, Alessio; Bullova, Petra; Turkova, Hana; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod & Adult Endocrinol Program, NIH, Bethesda, MD 20892 USA. [Noelting, Svenja; Grossman, Ashley B.] Queen Mary Univ London, Barts & London Sch Med, Dept Endocrinol, William Harvey Res Inst, London EC1M 6BQ, England. [Powers, James F.; Tischler, Arthur S.] Tufts Med Ctr, Dept Pathol, Boston, MA 02111 USA. [Liu, Qingsong] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Guichard, Sylvie] AstraZeneca, Oncol iMed, Macclesfield SK10 4TG, Cheshire, England. [Grossman, Ashley B.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LE, England. RP Giubellino, A (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod & Adult Endocrinol Program, NIH, Bldg 10-CRC,1E-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM giubella@mail.nih.gov; karel@mail.nih.gov OI Giubellino, Alessio/0000-0002-5352-0662; liu, qing song/0000-0002-7829-2547 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; Department of Defense [W81XWH-11-1-0670] FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. J.F.P. and A. S. T. were supported by Grant W81XWH-11-1-0670 from the Department of Defense. NR 50 TC 18 Z9 19 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 2013 VL 154 IS 2 BP 646 EP 655 DI 10.1210/en.2012-1854 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 076ME UT WOS:000313959800010 PM 23307788 ER PT J AU Miao, J Wang, SB Wan, ZM Park, WM Xia, Q Wood, K Li, GA AF Miao, Jun Wang, Shaobai Wan, Zongmiao Park, Won Man Xia, Qun Wood, Kirkham Li, Guoan TI Motion characteristics of the vertebral segments with lumbar degenerative spondylolisthesis in elderly patients SO EUROPEAN SPINE JOURNAL LA English DT Article DE Lumbar spine; Degenerative spondylolisthesis; Vertebral kinematics; Disc degeneration; Spinal instability ID DISC DEGENERATION; DYNAMIC-MOTION; INSTABILITY; SPINE; ORIENTATION; KINEMATICS; HEIGHT AB Although some studies have reported on the kinematics of the lumbar segments with degenerative spondylolisthesis (DS), few data have been reported on the in vivo 6 degree-of-freedom kinematics of different anatomical structures of the diseased levels under physiological loading conditions. This research is to study the in vivo motion characteristics of the lumbar vertebral segments with L4 DS during weight-bearing activities. Nine asymptomatic volunteers (mean age 54.4) and 9 patients with L4 DS (mean age 73.4) were included. Vertebral kinematics was obtained using a combined MRI/CT and dual fluoroscopic imaging technique. During functional postures (supine, standing upright, flexion, and extension), disc heights, vertebral motion patterns and instability were compared between the two groups. Although anterior disc heights were smaller in the DS group than in the normal group, the differences were only significant at standing upright. Posterior disc heights were significantly smaller in DS group than in the normal group under all postures. Different vertebral motion patterns were observed in the DS group, especially in the left-right and cranial-caudal directions during flexion and extension of the body. However, the range of motions of the both groups were much less than the reported criteria of lumbar spinal instability. The study showed that lumbar vertebra with DS has disordered motion patterns. DS did not necessary result in vertebral instability. A restabilization process may have occurred and surgical treatment should be planned accordingly. C1 [Miao, Jun; Wang, Shaobai; Wan, Zongmiao; Park, Won Man; Wood, Kirkham; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02114 USA. [Miao, Jun; Xia, Qun] Tianjin Hosp, Dept Spinal Surg, Tianjin, Peoples R China. [Wang, Shaobai] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Wan, Zongmiao] Cent S Univ, Xiangya Hosp 2, Changsha, Hunan, Peoples R China. [Park, Won Man] Kyung Hee Univ, Dept Mech Engn, Yongin, South Korea. RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partner.org FU NIH [R21AR057 989]; China scholarship council FX This study was supported by NIH (R21AR057 989) and China scholarship council. NR 30 TC 8 Z9 12 U1 3 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0940-6719 J9 EUR SPINE J JI Eur. Spine J. PD FEB PY 2013 VL 22 IS 2 BP 425 EP 431 DI 10.1007/s00586-012-2428-3 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 077XU UT WOS:000314063500026 PM 22892705 ER PT J AU Drier, Y Lawrence, MS Carter, SL Stewart, C Gabriel, SB Lander, ES Meyerson, M Beroukhim, R Getz, G AF Drier, Yotam Lawrence, Michael S. Carter, Scott L. Stewart, Chip Gabriel, Stacey B. Lander, Eric S. Meyerson, Matthew Beroukhim, Rameen Getz, Gad TI Somatic rearrangements across cancer reveal classes of samples with distinct patterns of DNA breakage and rearrangement-induced hypermutability SO GENOME RESEARCH LA English DT Article ID HUMAN BREAST-CANCER; SEQUENCING REVEALS; GENOME; MUTATIONS; TRANSLOCATIONS; ARCHITECTURE; IDENTIFICATION; TRANSVERSIONS; ORGANIZATION; CHROMOSOMES AB Whole-genome sequencing using massively parallel sequencing technologies enables accurate detection of somatic rearrangements in cancer. Pinpointing large numbers of rearrangement breakpoints to base-pair resolution allows analysis of rearrangement microhomology and genomic location for every sample. Here we analyze 95 tumor genome sequences from breast, head and neck, colorectal, and prostate carcinomas, and from melanoma, multiple myeloma, and chronic lymphocytic leukemia. We discover three genomic factors that are significantly correlated with the distribution of rearrangements: replication time, transcription rate, and GC content. The correlation is complex, and different patterns are observed between tumor types, within tumor types, and even between different types of rearrangements. Mutations in the APC gene correlate with and, hence, potentially contribute to DNA breakage in late-replicating, low %GC, untranscribed regions of the genome. We show that somatic rearrangements display less microhomology than germline rearrangements, and that breakpoint loci are correlated with local hypermutability with a particular enrichment for C <-> G transversions. C1 [Drier, Yotam] Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel. [Drier, Yotam; Lawrence, Michael S.; Carter, Scott L.; Stewart, Chip; Gabriel, Stacey B.; Lander, Eric S.; Meyerson, Matthew; Beroukhim, Rameen; Getz, Gad] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Meyerson, Matthew; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Getz, G (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. EM gadgetz@broadinstitute.org RI Drier, Yotam/K-5208-2012 OI Drier, Yotam/0000-0003-1725-2995 FU NHGRI NIH HHS [U54 HG003067] NR 54 TC 49 Z9 50 U1 0 U2 18 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 FEB PY 2013 VL 23 IS 2 BP 228 EP 235 DI 10.1101/gr.141382.112 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 081LG UT WOS:000314323100002 PM 23124520 ER PT J AU Yu, ZT Chen, C Kling, DE Liu, B McCoy, JM Merighi, M Heidtman, M Newburg, DS AF Yu, Zhuo-Teng Chen, Ceng Kling, David E. Liu, Bo McCoy, John M. Merighi, Massimo Heidtman, Matthew Newburg, David S. TI The principal fucosylated oligosaccharides of human milk exhibit prebiotic properties on cultured infant microbiota SO GLYCOBIOLOGY LA English DT Article DE bifidobacteria; fucosylated oligosaccharides; human milk; prebiotic ID IN-VITRO FERMENTATION; REAL-TIME PCR; BIFIDOBACTERIUM-INFANTIS; ESCHERICHIA-COLI; BREAST-MILK; CONSUMPTION; PROTECTION; BACTERIA; PRIMERS; SAMPLES AB Breast-fed infant microbiota is typically rich in bifidobacteria. Herein, major human milk oligosaccharides (HMOS) are assessed for their ability to promote the growth of bifidobacteria and to acidify their environment, key features of prebiotics. During in vitro anaerobic fermentation of infant microbiota, supplementation by HMOS significantly decreased the pH even greater than supplementation by fructooligosaccharide (FOS), a prebiotic positive control. HMOS elevated lactate concentrations, increased the proportion of Bifidobacterium spp. in culture, and through their fermentation into organic acids, decreased the proportion of Escherichia and Clostridium perfringens. Three principal components of HMOS, 2'-fucosyllactose, lactodifucotetraose and 3-fucosyllactose, were consumed in these cultures. These three principal oligosaccharides of human milk were then individually tested as supplements for in vitro growth of four individual representative strains of infant gut microbes. Bifidobacterium longum JCM7007 and B. longum ATCC15697 efficiently consumed oligosaccharides and produced abundant lactate and short-chain fatty acids, resulting in significant pH reduction. The specificity of fermentation differed by microbe species and strain and by oligosaccharide structure. Escherichia coli K12 and C. perfringens did not utilize appreciable fucosylated oligosaccharides, and a typical mixture of organic acid fermentation products inhibited their growth. In summary, 2'-fucosyllactose, lactodifucotetraose, and 3-fucosyllactose, when cultured with B. longum JCM7007 and B. longum ATCC15697, exhibit key characteristics of a prebiotic in vitro. If these bifidobacteria are representative of pioneering or keystone species for human microbiota, fucosylated HMOS could strongly promote colonization and maintenance of a mutualist symbiotic microbiome. Thus, these simple glycans could mediate beneficial effects of human milk on infant health. C1 [Yu, Zhuo-Teng; Chen, Ceng; Liu, Bo; Newburg, David S.] Harvard Univ, Massachusetts Gen Hosp, Dept Pediat Gastroenterol & Nutr, Sch Med, Boston, MA 02129 USA. [McCoy, John M.; Merighi, Massimo; Heidtman, Matthew] Glycosyn LLC, Medford, MA 02155 USA. RP Newburg, DS (reprint author), Boston Coll, Program Glycobiol, Higgins Hall,140 Commonwealth Ave, Chestnut Hill, MA 02467 USA. EM david.newburg@bc.edu FU NIH [AI075563, HD013021, HD059140] FX This investigation was financially supported by the NIH grants AI075563, HD013021 and HD059140. NR 35 TC 51 Z9 52 U1 6 U2 74 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD FEB PY 2013 VL 23 IS 2 BP 169 EP 177 DI 10.1093/glycob/cws138 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 079DU UT WOS:000314151200004 PM 23028202 ER PT J AU Nuzzo, E Shensa, A Kim, KH Fine, MJ Barnett, TE Cook, R Primack, BA AF Nuzzo, Erin Shensa, Ariel Kim, Kevin H. Fine, Michael J. Barnett, Tracey E. Cook, Robert Primack, Brian A. TI Associations between hookah tobacco smoking knowledge and hookah smoking behavior among US college students SO HEALTH EDUCATION RESEARCH LA English DT Article ID HIGH-SCHOOL-STUDENTS; WATER-PIPE; CIGARETTE SMOKERS; CARBON-MONOXIDE; PREVALENCE; UNIVERSITY; NICOTINE; SUSCEPTIBILITY; CONSEQUENCES; NONRESPONSE AB Hookah tobacco smoking is increasing among US college students, including those who would not otherwise use tobacco. Part of hookah's appeal is attributed to the perception that hookah is less harmful than cigarettes. The aims of this study were to assess knowledge of harmful exposures associated with hookah smoking relative to cigarette smoking and to determine associations between this knowledge and hookah smoking outcomes. Students (N = 852) at the University of Florida were randomly sampled via e-mail to obtain information on demographics, hookah smoking behavior and knowledge of five exposures (e.g. tar and nicotine). Multivariable logistic regression models assessed independent associations between knowledge and hookah smoking outcomes. Of the five factual knowledge items asked, 475 (55.8%) of the respondents answered none correctly. In multivariable models, correct responses to any knowledge items were not associated with lower odds of hookah smoking or susceptibility to hookah smoking in the future. Although college students are largely unaware of the toxicant exposures associated with hookah smoking, there is little association between knowledge and hookah smoking behavior. C1 [Nuzzo, Erin; Shensa, Ariel; Fine, Michael J.; Primack, Brian A.] Univ Pittsburgh, Sch Educ, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15260 USA. [Kim, Kevin H.] Univ Pittsburgh, Sch Educ, Dept Educ Psychol, Pittsburgh, PA 15260 USA. [Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15213 USA. [Barnett, Tracey E.] Univ Florida, Dept Behav Sci & Community Hlth, Gainesville, FL 32610 USA. [Cook, Robert] Univ Florida, Dept Epidemiol, Gainesville, FL 32610 USA. [Primack, Brian A.] Univ Pittsburgh, Sch Med, Dept Pediat, Div Adolescent Med, Pittsburgh, PA 15213 USA. RP Primack, BA (reprint author), Univ Pittsburgh, Sch Educ, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15260 USA. EM bprimack@pitt.edu FU NCI NIH HHS [K07 CA114315, R01 CA140150, R01-CA140150] NR 38 TC 22 Z9 22 U1 1 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1153 J9 HEALTH EDUC RES JI Health Educ. Res. PD FEB PY 2013 VL 28 IS 1 BP 92 EP 100 DI 10.1093/her/cys095 PG 9 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 079EF UT WOS:000314152400009 PM 22987864 ER PT J AU Nagler, EM Pednekar, MS Viswanath, K Sinha, DN Aghi, MB Pischke, CR Ebbeling, CB Lando, HA Gupta, PC Sorensen, GC AF Nagler, Eve M. Pednekar, Mangesh S. Viswanath, Kasisomayajula Sinha, Dhirendra N. Aghi, Mira B. Pischke, Claudia R. Ebbeling, Cara B. Lando, Harry A. Gupta, Prakash C. Sorensen, Glorian C. TI Designing in the social context: using the social contextual model of health behavior change to develop a tobacco control intervention for teachers in India SO HEALTH EDUCATION RESEARCH LA English DT Article ID DIRECTIONS-SMALL-BUSINESS; WORKING-CLASS; CANCER PREVENTION; MULTIETHNIC POPULATIONS; FORMATIVE RESEARCH; SCHOOL-PERSONNEL; ORAL-CANCER; 2 REGIONS; WORKERS; PSYCHOLOGY AB This article provides a theory-based, step-by-step approach to intervention development and illustrates its application in India to design an intervention to promote tobacco-use cessation among school personnel in Bihar. We employed a five-step approach to develop the intervention using the Social Contextual Model of Health Behavior Change (SCM) in Bihar, which involved conducting formative research, classifying factors in the social environment as mediating mechanisms and modifying conditions, developing a creative brief, designing an intervention and refining the intervention based on pilot test results. The intervention engages users and non-users of tobacco, involves teachers in implementing and monitoring school tobacco control policies and maximizes teachers' role as change agents in schools and communities. Intervention components include health educator visits, discussions led by lead teachers, cessation assistance, posters and other educational materials and is implemented over the entire academic year. The intervention is being tested in Bihar government schools as part of a randomized-controlled trial. SCM was a useful framework for developing a tobacco control intervention that responded to teachers' lives in Bihar. C1 [Nagler, Eve M.; Viswanath, Kasisomayajula; Sorensen, Glorian C.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Pednekar, Mangesh S.; Gupta, Prakash C.] Healis Sekhsaria Inst Publ Hlth, Navi Mumbai 400614, India. [Sinha, Dhirendra N.] Sch Prevent Oncol, Patna 800001, Bihar, India. [Aghi, Mira B.] Healis Sekhsaria Inst Publ Hlth, New Delhi 110016, India. [Pischke, Claudia R.] Inst Epidemiol & Prevent Res BIPS, D-28359 Bremen, Germany. [Ebbeling, Cara B.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Lando, Harry A.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA. [Sorensen, Glorian C.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Nagler, EM (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. EM eve_nagler@dfci.harvard.edu FU NCI NIH HHS [5 K05 CA108663-05, 5R01CA120958-02, K05 CA108663, 2 R25 CA057713-06] NR 52 TC 6 Z9 6 U1 2 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1153 J9 HEALTH EDUC RES JI Health Educ. Res. PD FEB PY 2013 VL 28 IS 1 BP 113 EP 129 DI 10.1093/her/cys060 PG 17 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 079EF UT WOS:000314152400011 PM 22669010 ER PT J AU Flynn, AW Afilalo, J Agnihotri, AK Castrillo, C Shahian, DM Picard, MH AF Flynn, Aidan W. Afilalo, Jonathan Agnihotri, Arvind K. Castrillo, Cristina Shahian, David M. Picard, Michael H. TI Aortic sclerosis is associated with mortality and major morbidity in patients undergoing coronary artery bypass surgery SO HEART LA English DT Article ID VALVE SCLEROSIS; ECHOCARDIOGRAPHIC-ASSESSMENT; ANNULAR CALCIFICATION; EUROPEAN-ASSOCIATION; AMERICAN-SOCIETY; STENOSIS; DISEASE; RECOMMENDATIONS; HEART; GUIDELINES AB Objective In this study, we aim to investigate the association between aortic sclerosis and mortality and major morbidity in patients with established coronary artery disease undergoing coronary artery bypass grafting (CABG). Design Preoperative echocardiograms of consecutive patients undergoing isolated CABG between 2007 and 2009 (n=1150) were analysed, excluding patients without an echocardiogram in the 30 days prior to surgery (n=483). Using logistic regression, we evaluated the association between aortic sclerosis and inhospital mortality and major morbidity. Using Cox proportional hazards, the effect on long-term all-cause mortality was determined. Setting Massachusetts General Hospital, Boston. Patients Patients undergoing isolated CABG between 2007 and 2009. Interventions Analysis of echocardiograms. Main outcome measures Inhospital mortality and major morbidity, and long-term all-cause mortality. Results 627 patients were suitable for enrolment; 207 (33%) had significant aortic sclerosis. These patients had higher rates of traditional cardiovascular risk factors. Significant aortic sclerosis was associated with an increased risk of inhospital mortality or major morbidity (OR 1.95; 95% CI 1.25 to 3.04). Following adjustment for baseline clinical and echocardiographic variables, the association remained significant (OR 1.90; 95% CI 1.15 to 3.11). The HR for adjusted all-cause mortality was 2.52 (mean follow-up 2.7 years). Conclusions Aortic sclerosis is a common finding in patients undergoing CABG. In these patients, its presence is associated with a higher risk of inhospital mortality or major morbidity, and is associated with a higher risk of all-cause long-term mortality independent of other risk factors. C1 [Flynn, Aidan W.; Castrillo, Cristina; Picard, Michael H.] Harvard Univ, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, Boston, MA 02114 USA. [Afilalo, Jonathan] McGill Univ, Jewish Gen Hosp, Div Cardiol, Montreal, PQ H3T 1E2, Canada. [Afilalo, Jonathan] McGill Univ, Jewish Gen Hosp, Div Clin Epidemiol, Montreal, PQ H3T 1E2, Canada. [Agnihotri, Arvind K.; Shahian, David M.] Harvard Univ, Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02115 USA. [Shahian, David M.] Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Shahian, David M.] Harvard Univ, Ctr Qual & Safety, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Picard, MH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. EM mhpicard@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 25 TC 1 Z9 1 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD FEB PY 2013 VL 99 IS 4 BP 247 EP 252 DI 10.1136/heartjnl-2012-302957 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 079HR UT WOS:000314161700006 PM 23213174 ER PT J AU Romero-Perez, L Castilla, MA Lopez-Garcia, MA Diaz-Martin, J Biscuola, M Ramiro-Fuentes, S Oliva, E Matias-Guiu, X Prat, J Cano, A Moreno-Bueno, G Palacios, J AF Romero-Perez, Laura Angeles Castilla, Maria Angeles Lopez-Garcia, Maria Diaz-Martin, Juan Biscuola, Michele Ramiro-Fuentes, Susana Oliva, Esther Matias-Guiu, Xavier Prat, Jaime Cano, Amparo Moreno-Bueno, Gema Palacios, Jose TI Molecular events in endometrial carcinosarcomas and the role of high mobility group AT-hook 2 in endometrial carcinogenesis SO HUMAN PATHOLOGY LA English DT Article DE Endometrial carcinosarcoma; HMGA2; let-7b; Lin28B ID EPITHELIAL-MESENCHYMAL TRANSITION; MIXED MULLERIAN TUMORS; UTERINE CARCINOSARCOMAS; CANCER PROGRESSION; BREAST-CANCER; FACTOR BORIS; GENE HMGA2; EXPRESSION; TRANSFORMATION; CARCINOMAS AB The molecular events implicated in the development of endometrial carcinosarcoma remain poorly understood. Using complementary DNA microarrays, we analyzed a group of 15 endometrial carcinosarcomas and compared their gene expression profiles with those obtained from a group of 23 endometrioid endometrial carcinomas. We demonstrated changes in the expression of genes modulating processes such as the epithelial to mesenchymal transition, muscle differentiation, the expression of cancer/testis antigens, and immune response in endometrial carcinosarcomas. The high mobility group AT-hook 2 gene is an embryonic nuclear factor that mediates epithelial to mesenchymal transition in various tumor models, and it was among the genes overexpressed in endometrial carcinosarcomas. High mobility group AT-hook 2 overexpression was confirmed in 54% of endometrial carcinosarcomas by quantitative real time-polymerase chain reaction and immunohistochemistry. Moreover, we found, a significant inverse correlation between the expression of high mobility group AT-hook 2 and let-7b, a member of the let-7 family of microRNAs that represses high mobility group AT-hook 2 expression. These changes were also associated with overexpression of Lin28B, a suppressor of microRNA biogenesis that is implicated in cancer progression and metastasis. Finally, high mobility group AT-hook 2 overexpression, which was detected in less than 3% of endometrioid endometrial carcinomas, was observed in many nonendometrioid carcinomas (46% of 28 samples). This pattern of expression, restricted to nonendometrioid carcinomas and endometrial carcinosarcomas, reflects a role for high mobility group AT-hook 2 in endometrial carcinogenesis that is associated with aggressive phenotypes and points to its potential use as a marker to distinguish between endometrioid and nonendometrioid tumors. (c) 2013 Elsevier Inc. All rights reserved. C1 [Romero-Perez, Laura; Angeles Castilla, Maria; Angeles Lopez-Garcia, Maria; Diaz-Martin, Juan; Biscuola, Michele; Ramiro-Fuentes, Susana; Palacios, Jose] Univ Seville, CSIC, Hosp Univ Virgen del Rocio, Inst Biomed Sevilla IBiS,Dept Pathol, Seville 41013, Spain. [Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Matias-Guiu, Xavier] Univ Lleida, IRBLLEIDA, Hosp Univ Arnau de Vilanova, Dept Pathol & Mol Genet, Lleida 25198, Spain. [Prat, Jaime] Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona 08025, Spain. [Cano, Amparo; Moreno-Bueno, Gema] Inst Invest Sanitaria La Paz, Inst Invest Biomed Alberto Sols, Dept Bioquim, CSIC UAM,UAM,IdiPAZ, Madrid 28046, Spain. [Moreno-Bueno, Gema] Fdn MD Anderson Canc Ctr Madrid, Madrid 28033, Spain. [Palacios, Jose] Hosp Univ Ramon y Cajal, Dept Pathol, Madrid 28031, Spain. RP Palacios, J (reprint author), Hosp Univ Ramon y Cajal, Dept Pathol, Calle Colmenar Viejo 9, Madrid 28031, Spain. EM jose.palacios@salud.madrid.org RI Romero-Perez, Laura/C-8314-2015; Castilla, M Angeles/C-9454-2015; Diaz-Martin, Juan/F-4765-2015; IBIS, SARCOMAS/O-1893-2015; matias-guiu, xavier/C-3039-2009; IBIS, NEUROPEPTIDOS/H-7482-2016; Moreno-Bueno, Gema/K-9354-2016 OI Romero-Perez, Laura/0000-0003-3196-4382; matias-guiu, xavier/0000-0002-7201-6605; Moreno-Bueno, Gema/0000-0002-5030-6687 FU Instituto de Salud Carlos III (ISCIII) [PI07/90324, PI080971]; Ministerio de Ciencia e Innovacion (MCINN); European Development Regional Fund "A way to achieve Europe" EDRF [RD06/0020/0013]; Junta de Andalucia (Consejeria de Salud) [PI-0384/2007, PI0581/2009]; Consejeria de Innovacion (Proyecto de Excelencia) [P07-CVI-03100]; Asociacion Espanola Contra el Cancer, Red de Grupos estables en Oncologia (AECC); PFIS fellowship [F109/00193]; ISCIII [PI080971, RD06/0020/0013]; ISCIII-Red de Biobancos [RD09/0076/00085]; [FISPI10/00922]; [2009SGR794]; [RD06/0020/134]; [RD/0020/15] FX This work was supported by grants from the Instituto de Salud Carlos III (ISCIII; grant nos. PI07/90324 and PI080971) and the Ministerio de Ciencia e Innovacion (MCINN), cofinanced by the European Development Regional Fund "A way to achieve Europe" EDRF (grant no. RD06/0020/0013); the Junta de Andalucia (Consejeria de Salud, grant nos. PI-0384/2007 and PI0581/2009) and the Consejeria de Innovacion (Proyecto de Excelencia, grant no. P07-CVI-03100) to J. Pa.; grants FISPI10/00922, 2009SGR794, and RD06/0020/134 to X. M-G. and RD/0020/15 to J. Pr.; and by a grant from the Asociacion Espanola Contra el Cancer, Red de Grupos estables en Oncologia (AECC-2011) to X. M-G., J. Pr., and G. M-B. L. R-P. is a PhD student and a recipient of a PFIS fellowship (grant no. F109/00193). M. A. C. and J. D. are PhD researchers funded by the ISCIII (grant no. RD06/0020/0013) and the Consejeria de Salud de la Junta de Andalucia (PI0581/2009), respectively. M. B. is a researcher funded by the ISCIII-Red de Biobancos RD09/0076/00085. S. R-F. works as a laboratory technician supported by the ISCIII (PI080971). Tumor samples were obtained with the support of Xarxa Catalana de Bancs de Tumors, the Tumor Bank Platform of RTICC RD09/0076/00085 and RD09/0076/00059. NR 35 TC 14 Z9 14 U1 0 U2 21 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD FEB PY 2013 VL 44 IS 2 BP 244 EP 254 DI 10.1016/j.humpath.2012.05.013 PG 11 WC Pathology SC Pathology GA 082HM UT WOS:000314382900011 PM 22974476 ER PT J AU Rosado, FGN Tang, YW Hasserjian, RP McClain, CM Wang, B Mosse, CA AF Rosado, Flavia Guimaraes Nunes Tang, Yi-Wei Hasserjian, Robert Paul McClain, Colt M. Wang, Beverly Mosse, Claudio A. TI Kikuchi-Fujimoto lymphadenitis: role of parvovirus B-19, Epstein-Barr virus, human herpesvirus 6, and human herpesvirus 8 SO HUMAN PATHOLOGY LA English DT Article DE Kikuchi-Fugimoto; Viral; Lymphadenitis; Etiology; PCR; Parvovirus B-19; EBV; HHV-6; HHV-8 ID HISTIOCYTIC NECROTIZING LYMPHADENITIS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; REAL-TIME PCR; DISEASE; B19; DNA; INFECTION; CHILDREN AB Kikuchi-Fujimoto lymphadenitis is a self-limited disorder that typically presents in young females as painless cervical lymphadenopathy with fever, anemia, and leukopenia. The clinical manifestations and pathologic findings suggest a viral etiology, yet specific etiologic agents remain unknown. Although there are studies reporting positive associations between Kikuchi-Fujimoto lymphadenitis and parvovirus B19 and herpesviruses, other studies have failed to find an association with these viruses. To our knowledge, this current study is the largest study of Kikuchi-Fujimoto lymphadenitis in Western patients that used polymerase chain reaction testing for 4 different common viral pathogens often implicated as etiologic agents in Kikuchi-Fujimoto lymphadenitis. Archival material from 3 institutions was included, following confirmation of the diagnosis of Kikuchi-Fujimoto lymphadenitis by 2 independent pathologists. Polymerase chain reaction from the paraffin-embedded tissue sections for parvovirus B19, Epstein-Barr virus, human herpesvirus 6, and human herpesvirus 8 was performed. Eighteen cases of Kikuchi-Fujimoto lymphadenitis were analyzed, 12 of which (60%) were cervical lymph nodes. All the cases showed typical geographic necrosis with abundant apoptotic debris, although the degree of necrosis was variable. Polymerase chain reaction revealed a high prevalence of parvovirus B19 in the controls (44%); there were fewer positive cases seen in the Kikuchi-Fujimoto lymphadenitis cases (11%), but this did not reach statistical significance (P = .25).There were no significant differences between cases and controls in the prevalence of Epstein-Barr virus, human herpesvirus 6, and human herpesvirus 8 (P = .50 for all 3). Polymerase chain reaction failed to reveal a positive association between Kikuchi-Fujimoto lymphadenitis and 4 common suspected viral agents. These findings do not support a role for Epstein-Barr virus, human herpesvirus 6, human herpesvirus 8, or parvovirus B19 in the pathogenesis of Kikuchi-Fujimoto lymphadenitis. (c) 2013 Elsevier Inc. All rights reserved. C1 [Rosado, Flavia Guimaraes Nunes; McClain, Colt M.; Mosse, Claudio A.] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. [Tang, Yi-Wei] Mem Sloan Kettering Canc Ctr, Dept Lab Med, New York, NY 10065 USA. [Hasserjian, Robert Paul] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wang, Beverly] NYU, Dept Pathol, New York, NY 10016 USA. [Mosse, Claudio A.] VA Tennessee Valley Healthcare Syst, Pathol & Lab Med, Nashville, TN 37212 USA. RP Rosado, FGN (reprint author), Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. EM flaviarosado21@gmail.com OI Tang, Yi-Wei/0000-0003-4888-6771 NR 30 TC 12 Z9 15 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD FEB PY 2013 VL 44 IS 2 BP 255 EP 259 DI 10.1016/j.humpath.2012.05.016 PG 5 WC Pathology SC Pathology GA 082HM UT WOS:000314382900012 PM 22939574 ER PT J AU Babadi, B Tarokh, V AF Babadi, Behtash Tarokh, Vahid TI Spectral Distribution of Product of Pseudorandom Matrices Formed From Binary Block Codes SO IEEE TRANSACTIONS ON INFORMATION THEORY LA English DT Article DE Binary block codes; free probability theory; Levy distance; Marchenko-Pastur law; pseudorandom matrices; random matrix theory ID EIGENVALUES AB Let A is an element of {-1, 1}(Naxn) and B is an element of {-1, 1}(Nbxn) be two matrices whose rows are drawn i.i.d. from the codewords of the binary codes C-a and C-b of length n and dual distances d'a and d'b, respectively, under the mapping 0 bar right arrow 1 and 1 bar right arrow -1. It is proven that as n -> infinity with y(a) := n/N-a is an element of (0, infinity) and y(b) ; = n/Nb is an element of (0, infinity) fixed, the empirical spectral distribution of the matrix AB*/root NaNb resembles a universal distribution (closely related to the distribution function of the free multiplicative convolution of two members of the Marchenko-Pastur family of densities) in the sense of the Levy distance, if the asymptotic dual distances of the underlying binary codes are large enough. Moreover, an explicit upper bound on the Levy distance of the two distributions in terms of y(a), y(b), d'(a) and d'(b) is given. Under mild conditions, the upper bound is strengthened to the Kolmogorov distance of the underlying distributions. Numerical studies on the empirical spectral distribution of the product of random matrices from BCH and Gold codes are provided, which verify the validity of this result. C1 [Babadi, Behtash] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Babadi, Behtash] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Babadi, Behtash; Tarokh, Vahid] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. RP Babadi, B (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM behtash@nmr.mgh.harvard.edu; vahid@seas.harvard.edu FU John Simon Guggenheim Memorial Foundation FX This work was supported in part by a fellowship from the John Simon Guggenheim Memorial Foundation. The material in this paper was presented in part at the 2011 Allerton Conference on Communication, Control, and Computing, Monticello, IL [3]. NR 20 TC 1 Z9 1 U1 1 U2 7 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9448 EI 1557-9654 J9 IEEE T INFORM THEORY JI IEEE Trans. Inf. Theory PD FEB PY 2013 VL 59 IS 2 BP 970 EP 978 DI 10.1109/TIT.2012.2223812 PG 9 WC Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA 073FL UT WOS:000313728800017 ER PT J AU Richter, LL Miller, RM Hillman, JD Chiu, MW AF Richter, Laura L. Miller, Robert M. Hillman, Joseph D. Chiu, Melvin W. TI Bilateral thick crusts on the legs SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Editorial Material ID DERMATITIS NEGLECTA AB What is your diagnosis? C1 [Chiu, Melvin W.] Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Dept Med,Ctr Hlth Sci 52 121, Los Angeles, CA 90095 USA. [Hillman, Joseph D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Miller, Robert M.; Chiu, Melvin W.] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. RP Chiu, MW (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Dept Med,Ctr Hlth Sci 52 121, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM mchiu@mednet.ucla.edu NR 10 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD FEB PY 2013 VL 52 IS 2 BP 133 EP 135 DI 10.1111/j.1365-4632.2012.05678.x PG 3 WC Dermatology SC Dermatology GA 077ZW UT WOS:000314068900002 PM 23347299 ER PT J AU Worley, MJ Nitschmann, CC Shoni, M Rauh-Hain, JA Williams, KA Feltmate, CM AF Worley, Michael J., Jr. Nitschmann, Caroline C. Shoni, Melina Rauh-Hain, Jose Alejandro Williams, Kristina A. Feltmate, Colleen M. TI Preoperative Leukocytosis Imposes an Increased Risk of Recurrence and Death Among Patients With Nonendometrioid Endometrial Carcinoma SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE Nonendometrioid; Endometrial carcinoma; Preoperative leukocytosis ID COLONY-STIMULATING FACTOR; PAPILLARY SEROUS CARCINOMA; POOR-PROGNOSIS; CELL CARCINOMA; CANCER; CERVIX; CORPUS AB Objective: To evaluate the impact of preoperative leukocytosis among patients with nonendometrioid endometrial carcinoma. Methods: The medical records of all patients with nonendometrioid endometrial carcinoma who underwent surgical treatment between January 2005 and December 2010 were retrospectively reviewed. The patients were separated into 2 groups based on the presence or absence of preoperative leukocytosis (white blood cell count >= 10,000/mu L). The groups were then compared with respect to pathologic findings, progression-free survival, and overall survival. Results: A total of 222 patients were identified, and preoperative leukocytosis was observed in 33 patients (14.9%). The leukocytosis group was associated with a larger mean size of the primary tumor (6.8 vs 4.6 cm, P = 0.016) and a greater percentage of patients with cervical stromal involvement (36.4% vs 20.1%, P = 0.039), adnexal involvement (42.4% vs. 22.8%, P = 0.017), and pelvic/para-aortic lymph node involvement (50% vs 27.4%, P = 0.025). On multivariate analysis, preoperative leukocytosis was independently associated with an increased risk of recurrence (hazard ratio, 2.07; 95% confidence interval, 1.12-3.84) and an increased risk of death (hazard ratio, 3.33; 95% confidence interval, 2.01-5.53). Conclusions: Among patients with nonendometrioid endometrial carcinoma, preoperative leukocytosis is independently associated with an increased risk of recurrence and death. C1 [Worley, Michael J., Jr.; Shoni, Melina; Feltmate, Colleen M.] Brigham & Womens Hosp, Div Gynecol Oncol, Boston, MA 02115 USA. [Nitschmann, Caroline C.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Rauh-Hain, Jose Alejandro] Massachusetts Gen Hosp, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA 02114 USA. [Williams, Kristina A.] Harvard Univ, Sch Med, Boston, MA USA. RP Feltmate, CM (reprint author), Brigham & Womens Hosp, Div Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA. EM cfeltmate@partners.org NR 21 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD FEB PY 2013 VL 23 IS 2 BP 312 EP 317 DI 10.1097/IGC.0b013e31827da21b PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 080ZW UT WOS:000314284900015 PM 23358179 ER PT J AU Wasse, H Zhang, R Johansen, KL Kutner, N AF Wasse, Haimanot Zhang, Rebecca Johansen, Kirsten L. Kutner, Nancy TI ESRD patients using permanent vascular access report greater physical activity compared with catheter users SO INTERNATIONAL UROLOGY AND NEPHROLOGY LA English DT Article DE Dialysis vascular access; Physical function ID STAGE RENAL-DISEASE; AMBULATORY PATIENTS; DIALYSIS PATIENTS; HEMODIALYSIS; MORTALITY; SURVIVAL; EXERCISE; WAVE-2 AB Low levels of physical activity among end-stage renal disease (ESRD) patients are associated with increased risk of hospitalization and mortality, and contributors to low activity levels are important to identify. Among hemodialysis (HD) patients, use of a central venous catheter (CVC) might impede physical activity due to factors such as infection or patient fear of catheter dislodgement. This Comprehensive Dialysis Study surveyed patients who had recently started regular dialysis. Physical activity level was ascertained using responses to the Human Activity Profile (HAP) provided by 1,458 HD participants. We examined the association of vascular access type with patients' scores on HAP subscales measuring self-care and leg effort, two dimensions that are especially important for daily living. 32.6% of patients used an arteriovenous fistula (AVF), 11.5% used an arteriovenous graft, 51.8% used a CVC, and 4.1% used a CVC with another maturing access. Patients' self-care and leg effort scores differed by vascular access type and receipt of early nephrology care, and the mean self-care score of AVF users who received early care was similar to the mean score reported for healthy adults. Reported levels of self-care and leg effort activity were higher among incident HD patients using an AVF compared to those using a CVC. Future research should examine whether reinforcing the importance of regular physical activity in the pre-dialysis period, as well as wider early use of AVF in the HD population, may improve physical activity levels among ESRD patients. C1 [Wasse, Haimanot] Emory Univ, Sch Med, Div Nephrol, WMB, Atlanta, GA 30322 USA. [Wasse, Haimanot; Zhang, Rebecca; Johansen, Kirsten L.; Kutner, Nancy] Emory Univ, Rehabil Qual Life Special Studies Ctr, US Renal Data Syst, Atlanta, GA 30322 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA USA. RP Wasse, H (reprint author), Emory Univ, Sch Med, Div Nephrol, WMB, Room 338,1639 Pierce Dr, Atlanta, GA 30322 USA. EM hwasse@emory.edu FU National Institutes of Health [K23 DK65634, HHSN267200715004C, N01-DK-7-5004] FX The human activity profile was reproduced for use in the CDS with permission of the author, David Daughton. This work was supported in part by a National Institutes of Health Career Development Award K23 DK65634 (Haimanot Wasse) and by National Institutes of Health contract HHSN267200715004C, ADB No. N01-DK-7-5004. NR 15 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0301-1623 J9 INT UROL NEPHROL JI Int. Urol. Nephrol. PD FEB PY 2013 VL 45 IS 1 BP 199 EP 205 DI 10.1007/s11255-012-0137-9 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 081CD UT WOS:000314292500030 PM 22350837 ER PT J AU Aston-Mourney, K Zraika, S Udayasankar, J Subramanian, SL Green, PS Kahn, SE Hull, RL AF Aston-Mourney, Kathryn Zraika, Sakeneh Udayasankar, Jayalakshmi Subramanian, Shoba L. Green, Pattie S. Kahn, Steven E. Hull, Rebecca L. TI Matrix Metalloproteinase-9 Reduces Islet Amyloid Formation by Degrading Islet Amyloid Polypeptide SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-CELL APOPTOSIS; DIABETES-MELLITUS; TRANSGENIC MOUSE; PANCREATIC-ISLETS; FIBRIL FORMATION; HUMAN AMYLIN; PEPTIDE; MICE; INSULIN; HYPERGLYCEMIA AB Deposition of islet amyloid polypeptide ( IAPP) as amyloid is a pathological hallmark of the islet in type 2 diabetes, which is toxic to beta-cells. We previously showed that the enzyme neprilysin reduces islet amyloid deposition and thereby reduces beta-cell apoptosis, by inhibiting fibril formation. Two other enzymes, matrix metalloproteinase ( MMP)-2 and MMP-9, are extracellular gelatinases capable of degrading another amyloidogenic peptide, A beta, the constituent of amyloid deposits in Alzheimer disease. We therefore investigated whether MMP-2 and MMP-9 play a role in reducing islet amyloid deposition. MMP-2 and MMP-9 mRNA were present in mouse islets but only MMP-9 activity was detectable. In an islet culture model where human IAPP ( hIAPP) transgenic mouse islets develop amyloid but nontransgenic islets do not, a broad spectrum MMP inhibitor ( GM6001) and an MMP-2/9 inhibitor increased amyloid formation and the resultant beta-cell apoptosis. In contrast, a specific MMP-2 inhibitor had no effect on either amyloid deposition or beta-cell apoptosis. Mass spectrometry demonstrated that MMP-9 degraded amyloidogenic hIAPP but not nonamyloidogenic mouse IAPP. Thus, MMP-9 constitutes an endogenous islet protease that limits islet amyloid deposition and its toxic effects via degradation of hIAPP. Because islet MMP-9 mRNA levels are decreased in type 2 diabetic subjects, islet MMP-9 activity may also be decreased in human type 2 diabetes, thereby contributing to increased islet amyloid deposition and beta-cell loss. Approaches to increase islet MMP-9 activity could reduce or prevent amyloid deposition and its toxic effects in type 2 diabetes. C1 [Aston-Mourney, Kathryn; Zraika, Sakeneh; Udayasankar, Jayalakshmi; Subramanian, Shoba L.; Green, Pattie S.; Kahn, Steven E.; Hull, Rebecca L.] Vet Affairs Puget Sound Hlth Care Syst, Washington, WA 98108 USA. [Aston-Mourney, Kathryn; Zraika, Sakeneh; Udayasankar, Jayalakshmi; Subramanian, Shoba L.; Green, Pattie S.; Kahn, Steven E.; Hull, Rebecca L.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Aston-Mourney, Kathryn] Deakin Univ, Sch Med, Metab Res Unit, Waurn Ponds, Vic 3216, Australia. RP Hull, RL (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way 151, Seattle, WA 98108 USA. EM rhull@u.washington.edu OI Aston-Mourney, Kathryn/0000-0003-1412-6715; Kahn, Steven/0000-0001-7307-9002; Hull, Rebecca/0000-0001-9690-4087 FU Department of Veterans Affairs, Veterans Affairs Puget Sound Health Care System (Seattle, WA); National Institutes of Health [DK-075998, DK-074404, DK-080945, DK-017047, DK-007247]; American Diabetes Association Mentor-Based fellowship; University of Washington McAbee fellowship; Deakin University Alfred Deakin Postdoctoral research fellowship; Juvenile Diabetes Research Foundation FX This work was supported, in whole or in part, by the Department of Veterans Affairs, Veterans Affairs Puget Sound Health Care System (Seattle, WA) and National Institutes of Health Grants DK-075998 (to S. E. K.), DK-074404 (to R. L. H.), DK-080945 (to S. Z.), DK-017047 (to the Cellular and Molecular Imaging Core of the University of Washington Diabetes Research Center), and DK-007247.; Supported by an American Diabetes Association Mentor-Based fellowship, the University of Washington McAbee fellowship, and a Deakin University Alfred Deakin Postdoctoral research fellowship.; Supported by a Juvenile Diabetes Research Foundation postdoctoral fellowship. NR 36 TC 12 Z9 13 U1 0 U2 22 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 FEB 1 PY 2013 VL 288 IS 5 BP 3553 EP 3559 DI 10.1074/jbc.M112.438457 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 082NE UT WOS:000314397900060 PM 23229548 ER PT J AU Bloch, MJ Basile, JN AF Bloch, Michael J. Basile, Jan N. TI Analysis of Recent Papers in Hypertension Treatment of Obstructive Sleep Apnea With Continuous Positive Airway Pressure Appears to Decrease the Incidence of Incident Hypertension SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article ID ASSOCIATION C1 [Bloch, Michael J.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Seinsheimer Cardiovasc Hlth Program, Div Gen Internal Med Geriatr, Charleston, SC 29425 USA. [Bloch, Michael J.] Univ Nevada, Sch Med, MedSch Associates N, Dept Internal Med, Reno, NV 89520 USA. RP Bloch, MJ (reprint author), Univ Nevada, Sch Med, MedSch Associates N, Dept Internal Med, 1500 E 2nd St,Suite 302, Reno, NV 89520 USA. EM mbloch@aol.com NR 4 TC 1 Z9 1 U1 0 U2 0 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 FEB PY 2013 VL 15 IS 2 BP 85 EP 87 DI 10.1111/jch.12041 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 075PX UT WOS:000313900100001 PM 23339724 ER PT J AU Wiederhold, NP Najvar, LK Bocanegra, R Kirkpatrick, WR Patterson, TF Thornton, CR AF Wiederhold, Nathan P. Najvar, Laura K. Bocanegra, Rosie Kirkpatrick, William R. Patterson, Thomas F. Thornton, Christopher R. TI Interlaboratory and Interstudy Reproducibility of a Novel Lateral-Flow Device and Influence of Antifungal Therapy on Detection of Invasive Pulmonary Aspergillosis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID GALACTOMANNAN ENZYME-IMMUNOASSAY; NEUTROPENIC PATIENTS; RAPID SERODIAGNOSIS; MURINE MODEL; DIAGNOSIS; ASSAY; HIV; ANTIBODIES; FUMIGATUS AB Interest in lateral-flow devices (LFDs) as potential point-of-care assays for the diagnosis of infectious diseases has increased. Our objective was to evaluate the interlaboratory and interstudy reproducibility and the effects of antifungal therapy on an LFD developed for invasive pulmonary aspergillosis (IPA) detection. An established neutropenic guinea pig model of IPA caused by Aspergillus fumigatus was used. At predetermined time points (1 h and 3, 5, and 7 days postinoculation), blood and bronchoalveolar lavage (BAL) fluid were collected from infected and uninfected animals. In a separate experiment, guinea pigs were treated with posaconazole (10 mg/kg of body weight orally [p.o.] twice a day [BID]), voriconazole (10 mg/kg p.o. BID), liposomal amphotericin B (10 mg/kg intraperitoneally [i.p.] once a day [QD]), or caspofungin (2 mg/kg i.p. QD), and samples were collected on days 7 and 11. Each laboratory independently evaluated the IgG monoclonal antibody-based LFD. Galactomannan and (1 -> 3)-beta-D-glucan were also measured using commercially available kits. Good interlaboratory agreement was observed with the LFD, as the results for 97% (32/33) of the serum and 78.8% (26/33) of the BAL fluid samples from infected animals were in agreement. Good interstudy agreement was also observed. The serum sensitivity of each surrogate-marker assay was reduced in animals treated with antifungals. In contrast, these markers remained elevated within the BAL fluids of treated animals, which was consistent with the fungal burden and histopathology results. These results demonstrate that the LFD assay is reproducible between different laboratories and studies. However, the sensitivity of this assay and other markers of IPA may be reduced with serum in the presence of antifungal therapy. C1 [Wiederhold, Nathan P.; Najvar, Laura K.; Bocanegra, Rosie; Kirkpatrick, William R.; Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Wiederhold, Nathan P.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Najvar, Laura K.; Bocanegra, Rosie; Kirkpatrick, William R.; Patterson, Thomas F.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Thornton, Christopher R.] Univ Exeter, Exeter, Devon, England. RP Wiederhold, NP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. EM wiederholdn@uthscsa.edu OI Wiederhold, Nathan/0000-0002-2225-5122 FU National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID) [N01-AI-30041, HHSN272201000038I/HHSN27200002-task order A05, R21AI085393]; Pfizer; Schering-Plough; Merck; Basilea; Astellas FX This work was supported by contracts from the National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID; contract numbers N01-AI-30041 and HHSN272201000038I/HHSN27200002-task order A05) to T. F. Patterson and NIH/NIAID grant R21AI085393 to N. P. Wiederhold and C. R. Thornton.; N.P.W. has received research support from Pfizer, Schering-Plough, Merck, Basilea, and Astellas and has served on advisory boards for Merck, Astellas, Toyama, and Viamet. T.F.P. has received research grants to the UT Health Science Center at San Antonio from Astellas, Basilea, Merck, and Pfizer and has served as a consultant for Astellas, Basilea, Merck, Pfizer, and Toyama. C.R.T. has received support from Pfizer. None of the other authors has a conflict of interest. NR 26 TC 28 Z9 30 U1 0 U2 14 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 FEB PY 2013 VL 51 IS 2 BP 459 EP 465 DI 10.1128/JCM.02142-12 PG 7 WC Microbiology SC Microbiology GA 078OH UT WOS:000314108000012 PM 23175252 ER PT J AU Kulke, MH AF Kulke, Matthew H. TI Are Neuroendocrine Tumors Going Mainstream? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID ENDOCRINE TUMORS; GRADING SYSTEM; CLASSIFICATION C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kulke, MH (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA151532] NR 17 TC 5 Z9 6 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 FEB 1 PY 2013 VL 31 IS 4 BP 404 EP 405 DI 10.1200/JCO.2012.47.3884 PG 2 WC Oncology SC Oncology GA 078LG UT WOS:000314099800004 PM 23248246 ER PT J AU Zhu, AX Salem, R AF Zhu, Andrew X. Salem, Riad TI Combining Transarterial Chemoembolization With Radiofrequency Ablation for Hepatocellular Carcinoma: One Step Forward? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION; ETHANOL INJECTION; PHASE-II; THERAPY; SORAFENIB; SURVIVAL; COMBINATION; RADIOEMBOLIZATION; LIVER C1 [Zhu, Andrew X.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. RP Zhu, AX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. NR 28 TC 6 Z9 8 U1 0 U2 2 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 FEB 1 PY 2013 VL 31 IS 4 BP 406 EP 408 DI 10.1200/JCO.2012.46.1897 PG 3 WC Oncology SC Oncology GA 078LG UT WOS:000314099800005 PM 23269989 ER PT J AU Smith, DC Smith, MR Sweeney, C Elfiky, AA Logothetis, C Corn, PG Vogelzang, NJ Small, EJ Harzstark, AL Gordon, MS Vaishampayan, UN Haas, NB Spira, AI Lara, PN Lin, CC Srinivas, S Sella, A Schoffski, P Scheffold, C Weitzman, AL Hussain, M AF Smith, David C. Smith, Matthew R. Sweeney, Christopher Elfiky, Aymen A. Logothetis, Christopher Corn, Paul G. Vogelzang, Nicholas J. Small, Eric J. Harzstark, Andrea L. Gordon, Michael S. Vaishampayan, Ulka N. Haas, Naomi B. Spira, Alexander I. Lara, Primo N., Jr. Lin, Chia-Chi Srinivas, Sandy Sella, Avishay Schoeffski, Patrick Scheffold, Christian Weitzman, Aaron L. Hussain, Maha TI Cabozantinib in Patients With Advanced Prostate Cancer: Results of a Phase II Randomized Discontinuation Trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; LEUKEMIA GROUP-B; C-MET; PROGNOSTIC-SIGNIFICANCE; EXPRESSION; METASTASIS; INHIBITOR; RECEPTOR; VEGF; ANGIOGENESIS AB Purpose Cabozantinib (XL184) is an orally bioavailable tyrosine kinase inhibitor with activity against MET and vascular endothelial growth factor receptor 2. We evaluated the activity of cabozantinib in patients with castration-resistant prostate cancer (CRPC) in a phase II randomized discontinuation trial with an expansion cohort. Patients and Methods Patients received 100 mg of cabozantinib daily. Those with stable disease per RECIST at 12 weeks were randomly assigned to cabozantinib or placebo. Primary end points were objective response rate at 12 weeks and progression-free survival (PFS) after random assignment. Results One hundred seventy-one men with CRPC were enrolled. Random assignment was halted early based on the observed activity of cabozantinib. Seventy-two percent of patients had regression in soft tissue lesions, whereas 68% of evaluable patients had improvement on bone scan, including complete resolution in 12%. The objective response rate at 12 weeks was 5%, with stable disease in 75% of patients. Thirty-one patients with stable disease at week 12 were randomly assigned. Median PFS was 23.9 weeks (95% CI, 10.7 to 62.4 weeks) with cabozantinib and 5.9 weeks (95% CI, 5.4 to 6.6 weeks) with placebo (hazard ratio, 0.12; P < .001). Serum total alkaline phosphatase and plasma cross-linked C-terminal telopeptide of type I collagen were reduced by >= 50% in 57% of evaluable patients. On retrospective review, bone pain improved in 67% of evaluable patients, with a decrease in narcotic use in 56%. The most common grade 3 adverse events were fatigue (16%), hypertension (12%), and hand-foot syndrome (8%). Conclusion Cabozantinib has clinical activity in men with CRPC, including reduction of soft tissue lesions, improvement in PFS, resolution of bone scans, and reductions in bone turnover markers, pain, and narcotic use. J Clin Oncol 31:412-419. (C) 2012 by American Society of Clinical Oncology C1 [Smith, David C.; Hussain, Maha] Univ Michigan, Ann Arbor, MI 48109 USA. [Vaishampayan, Ulka N.] Wayne State Univ, Detroit, MI USA. [Smith, Matthew R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sweeney, Christopher; Elfiky, Aymen A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Logothetis, Christopher; Corn, Paul G.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Spira, Alexander I.] US Oncol Res, Houston, TX USA. [Vogelzang, Nicholas J.] US Oncol Comprehens Canc Ctr Nevada, Las Vegas, NV USA. [Small, Eric J.; Harzstark, Andrea L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Scheffold, Christian; Weitzman, Aaron L.] Exelixis, San Francisco, CA USA. [Lara, Primo N., Jr.] Univ Calif Davis, Ctr Comprehens Canc, Sacramento, CA 95817 USA. [Srinivas, Sandy] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Gordon, Michael S.] Pinnacle Oncol Hematol, Scottsdale, AZ USA. [Haas, Naomi B.] Abramson Canc Ctr, Philadelphia, PA USA. [Spira, Alexander I.] Virginia Canc Specialists, Fairfax, VA USA. [Lin, Chia-Chi] Natl Taiwan Univ Hosp, Taipei, Taiwan. [Sella, Avishay] Assaf Harofeh Med Ctr, IL-70300 Zerifin, Israel. [Schoeffski, Patrick] Katholieke Univ Leuven, Univ Hosp Leuven, Louvain, Belgium. RP Smith, DC (reprint author), 7302 CC SPC 5946,1500 Med Ctr Dr, Ann Arbor, MI 48109 USA. EM dcsmith@umich.edu FU Exelixis, South San Francisco, CA; Exelixis; Bayer Pharmaceuticals/Algeta; Progenics Pharmaceuticals; Tokai Pharmaceuticals; Johnson Johnson; Veridex; Astellas Pharma; Dendreon; sanofi-aventis; Biotechnology/Janssen Pharmaceutica; Genentech; GlaxoSmithKline; Pfizer; Polaris Group FX Supported by Exelixis, South San Francisco, CA.; David C. Smith, Exelixis; Matthew R. Smith, Exelixis; Christopher Sweeney, Exelixis; Christopher Logothetis, Exelixis; Nicholas J. Vogelzang, Exelixis, Bayer Pharmaceuticals/Algeta, Progenics Pharmaceuticals, Tokai Pharmaceuticals, Johnson & Johnson, Veridex, Astellas Pharma, Dendreon, sanofi-aventis; Michael S. Gordon, Exelixis; Primo N. Lara Jr, Cougar Biotechnology/Janssen Pharmaceutica, Exelixis, Genentech, GlaxoSmithKline, Pfizer, Polaris Group NR 28 TC 205 Z9 212 U1 0 U2 32 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 FEB 1 PY 2013 VL 31 IS 4 BP 412 EP 419 DI 10.1200/JCO.2012.45.0494 PG 8 WC Oncology SC Oncology GA 078LG UT WOS:000314099800007 PM 23169517 ER PT J AU San Miguel, JF Schlag, R Khuageva, NK Dimopoulos, MA Shpilberg, O Kropff, M Spicka, I Petrucci, MT Palumbo, A Samoilova, OS Dmoszynska, A Abdulkadyrov, KM Delforge, M Jiang, B Mateos, MV Anderson, KC Esseltine, DL Liu, K Deraedt, W Cakana, A van de Velde, H Richardson, PG AF San Miguel, Jesus F. Schlag, Rudolf Khuageva, Nuriet K. Dimopoulos, Meletios A. Shpilberg, Ofer Kropff, Martin Spicka, Ivan Petrucci, Maria Teresa Palumbo, Antonio Samoilova, Olga S. Dmoszynska, Anna Abdulkadyrov, Kudrat M. Delforge, Michel Jiang, Bin Mateos, Maria-Victoria Anderson, Kenneth C. Esseltine, Dixie-Lee Liu, Kevin Deraedt, William Cakana, Andrew van de Velde, Helgi Richardson, Paul G. TI Persistent Overall Survival Benefit and No Increased Risk of Second Malignancies With Bortezomib-Melphalan-Prednisone Versus Melphalan-Prednisone in Patients With Previously Untreated Multiple Myeloma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID STEM-CELL TRANSPLANTATION; INTERNATIONAL STAGING SYSTEM; LONG-TERM SURVIVAL; ELDERLY-PATIENTS; PLUS THALIDOMIDE; RANDOMIZED-TRIAL; CYTOGENETIC ABNORMALITIES; INDUCTION THERAPY; ACUTE-LEUKEMIA; PHASE-III AB Purpose This final analysis of the phase III VISTA trial (Velcade As Initial Standard Therapy in Multiple Myeloma: Assessment With Melphalan and Prednisone) was conducted to determine whether the overall survival (OS) benefit with bortezomib-melphalan-prednisone (VMP) versus melphalan-prednisone (MP) in patients with myeloma who were ineligible for transplantation was maintained after 5 years of follow-up and to explore the risk of second primary malignancies. Patients and Methods In all, 682 patients received up to nine 6-week cycles of VMP or MP and were then observed every 12 weeks or less. Data on second primary malignancies were collected by individual patient inquiries at all sites from 655 patients. Results After median follow-up of 60.1 months (range, 0 to 74 months), there was a 31% reduced risk of death with VMP versus MP (hazard ratio [HR], 0.695; P < .001; median OS 56.4 v 43.1 months). OS benefit with VMP was seen across prespecified patient subgroups (age >= 75 years, stage III myeloma, creatinine clearance < 60 mL/min). Sixty-three percent of VMP patients and 73% of MP patients had received subsequent therapy. Time to next therapy (median, 30.7 v 20.5 months; HR, 0.557; P < .001) was longer with VMP than with MP. Among patients who received subsequent therapies, survival from start of subsequent therapy was similar following VMP (median, 28.1 months) or MP (median, 26.8 months; HR, 0.914). Following VMP/MP, incidence proportions of hematologic malignancies (1%/1%) and solid tumors (5%/3%) and exposure-adjusted incidence rates (0.017/0.013 per patient-year) were similar and were consistent with background rates. Conclusion VMP resulted in a significant reduction in risk of death versus MP that was maintained after 5 years' follow-up and despite substantial use of novel-agent-based salvage therapies. There is no emerging safety signal for second primary malignancies following VMP. J Clin Oncol 31:448-455. (C) 2012 by American Society of Clinical Oncology C1 [San Miguel, Jesus F.; Mateos, Maria-Victoria] Hosp Univ Salamanca, Inst Invest Biomed Salamanca, Salamanca 37007, Spain. [San Miguel, Jesus F.; Mateos, Maria-Victoria] Univ Salamanca, Inst Biol Mol & Celular Canc, Consejo Super Invest Cient, E-37008 Salamanca, Spain. [Schlag, Rudolf] Praxisklin Dr Schlag, Wurzburg, Germany. [Kropff, Martin] Univ Munster, D-48149 Munster, Germany. [Khuageva, Nuriet K.] SP Botkin Moscow City Clin Hosp, Moscow, Russia. [Samoilova, Olga S.] Nizhnii Novgorod Reg Clin Hosp, Nizhnii Novgorod, Russia. [Abdulkadyrov, Kudrat M.] St Petersburg Clin Res Inst Hematol & Transfusiol, St Petersburg, Russia. [Dimopoulos, Meletios A.] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Shpilberg, Ofer] Rabin Med Ctr, Petah Tiqwa, Israel. [Spicka, Ivan] Charles Univ Prague, Prague, Czech Republic. [Petrucci, Maria Teresa] Univ Roma La Sapienza, Rome, Italy. [Palumbo, Antonio] Univ Turin, Turin, Italy. [Dmoszynska, Anna] Med Univ Lublin, Lublin, Poland. [Delforge, Michel] Belgian Hematol Soc, Myeloma Study Grp, Brussels, Belgium. [Deraedt, William; van de Velde, Helgi] Janssen Res & Dev, Beerse, Belgium. [Jiang, Bin] Peking Univ, Peoples Hosp, Beijing 100871, Peoples R China. [Anderson, Kenneth C.; Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Esseltine, Dixie-Lee] Millennium Pharmaceut Inc, Cambridge, MA USA. [Liu, Kevin] Janssen Res & Dev, Raritan, NJ USA. [Cakana, Andrew] Janssen Res & Dev, High Wycombe, Bucks, England. RP San Miguel, JF (reprint author), Hosp Univ Salamanca, Inst Invest Biomed Salamanca, Paseo San Vicente 58-182, Salamanca 37007, Spain. EM sanmigiz@usal.es OI SAN MIGUEL, JESUS/0000-0002-9183-4857; abdulkadyrov, kudrat/0000-0002-3771-909X FU Millennium Pharmaceuticals; Janssen Research Development; Janssen Global Services FX Supported by Millennium Pharmaceuticals, Janssen Research & Development, and Janssen Global Services. NR 48 TC 98 Z9 99 U1 0 U2 14 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 FEB 1 PY 2013 VL 31 IS 4 BP 448 EP 455 DI 10.1200/JCO.2012.41.6180 PG 8 WC Oncology SC Oncology GA 078LG UT WOS:000314099800012 PM 23233713 ER PT J AU Balboni, MJ Sullivan, A Amobi, A Phelps, AC Gorman, DP Zollfrank, A Peteet, JR Prigerson, HG VanderWeele, TJ Balboni, TA AF Balboni, Michael J. Sullivan, Adam Amobi, Adaugo Phelps, Andrea C. Gorman, Daniel P. Zollfrank, Angelika Peteet, John R. Prigerson, Holly G. VanderWeele, Tyler J. Balboni, Tracy A. TI Why Is Spiritual Care Infrequent at the End of Life? Spiritual Care Perceptions Among Patients, Nurses, and Physicians and the Role of Training SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; CANCER-PATIENTS; TREATMENT PREFERENCES; US PHYSICIANS; MEDICAL-CARE; NEAR-DEATH; ASSOCIATIONS; SATISFACTION; ONCOLOGY; RELIGION AB Purpose To determine factors contributing to the infrequent provision of spiritual care (SC) by nurses and physicians caring for patients at the end of life (EOL). Patients and Methods This is a survey-based, multisite study conducted from March 2006 through January 2009. All eligible patients with advanced cancer receiving palliative radiation therapy and oncology physician and nurses at four Boston academic centers were approached for study participation; 75 patients (response rate = 73%) and 339 nurses and physicians (response rate = 63%) participated. The survey assessed practical and operational dimensions of SC, including eight SC examples. Outcomes assessed five factors hypothesized to contribute to SC infrequency. Results Most patients with advanced cancer had never received any form of spiritual care from their oncology nurses or physicians (87% and 94%, respectively; P for difference = .043). Majorities of patients indicated that SC is an important component of cancer care from nurses and physicians (86% and 87%, respectively; P = .1). Most nurses and physicians thought that SC should at least occasionally be provided (87% and 80%, respectively; P = .16). Majorities of patients, nurses, and physicians endorsed the appropriateness of eight examples of SC (averages, 78%, 93%, and 87%, respectively; P = .01). In adjusted analyses, the strongest predictor of SC provision by nurses and physicians was reception of SC training (odds ratio [OR] = 11.20, 95% CI, 1.24 to 101; and OR = 7.22, 95% CI, 1.91 to 27.30, respectively). Most nurses and physicians had not received SC training (88% and 86%, respectively; P = .83). Conclusion Patients, nurses, and physicians view SC as an important, appropriate, and beneficial component of EOL care. SC infrequency may be primarily due to lack of training, suggesting that SC training is critical to meeting national EOL care guidelines. J Clin Oncol 31:461-467. (C) 2012 by American Society of Clinical Oncology C1 [Balboni, Michael J.; Peteet, John R.; Prigerson, Holly G.; Balboni, Tracy A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Balboni, Michael J.; Peteet, John R.; Prigerson, Holly G.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sullivan, Adam; VanderWeele, Tyler J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Zollfrank, Angelika] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Balboni, TA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dana 1101,450 Brookline Ave, Boston, MA 02115 USA. EM tbalboni@lroc.harvard.edu FU American Society of Clinical Oncology; Templeton Foundation; University of Chicago Program in Religion and Medicine Faculty Scholars Award FX Supported in part by an American Society of Clinical Oncology Young Investigator Award and Career Development Award (T. A. B.), a Templeton Foundation Award (T.J.V.), and a University of Chicago Program in Religion and Medicine Faculty Scholars Award (M.J.B.). NR 34 TC 63 Z9 64 U1 1 U2 23 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 FEB 1 PY 2013 VL 31 IS 4 BP 461 EP 467 DI 10.1200/JCO.2012.44.6443 PG 7 WC Oncology SC Oncology GA 078LG UT WOS:000314099800014 PM 23248245 ER PT J AU Sanoff, HK Carpenter, WR Sturmer, T Schrag, D AF Sanoff, Hanna K. Carpenter, William R. Stuermer, Til Schrag, Deborah TI Does Adjuvant Chemotherapy in Elderly Patients With Stage III Colon Cancer Really Save Lives? Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 [Sanoff, Hanna K.; Carpenter, William R.; Stuermer, Til] Univ N Carolina, Chapel Hill, NC 27515 USA. [Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sanoff, HK (reprint author), Univ N Carolina, Chapel Hill, NC 27515 USA. RI Carpenter, William/E-5125-2013 NR 6 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 FEB 1 PY 2013 VL 31 IS 4 BP 512 EP 513 DI 10.1200/JCO.2012.46.4859 PG 2 WC Oncology SC Oncology GA 078LG UT WOS:000314099800026 PM 23472263 ER PT J AU Garrett, LA Harmon, DC Schorge, JO AF Garrett, Leslie A. Harmon, David C. Schorge, John O. TI Embryonal Rhabdomyosarcoma of the Uterine Corpus SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INTERGROUP RHABDOMYOSARCOMA; SARCOMA BOTRYOIDES; CERVIX; THERAPY C1 [Garrett, Leslie A.; Harmon, David C.; Schorge, John O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Garrett, LA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 9 TC 2 Z9 2 U1 0 U2 2 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 FEB 1 PY 2013 VL 31 IS 4 BP E48 EP E50 DI 10.1200/JCO.2012.43.1841 PG 3 WC Oncology SC Oncology GA 078LG UT WOS:000314099800001 PM 23248250 ER PT J AU Niederdeppe, J Bigman, CA Gonzales, AL Gollust, SE AF Niederdeppe, Jeff Bigman, Cabral A. Gonzales, Amy L. Gollust, Sarah E. TI Communication About Health Disparities in the Mass Media SO JOURNAL OF COMMUNICATION LA English DT Article ID SOCIAL DETERMINANTS; ENTERTAINMENT-EDUCATION; CANCER COMMUNICATION; POPULATION HEALTH; UNITED-STATES; NEWS MEDIA; GROUP CUES; POLICY; INEQUALITIES; AWARENESS AB A variety of scholars have explored the role of communication in reducing, maintaining, and even widening health disparities, but comparatively less attention has focused on the content and effects of communication about health disparities in the mass media. This article aims to summarize the current state of knowledge about these issues by identifying key outcomes and audiences for mass-mediated communication about health disparities, describing what is known about public opinion about health disparities, reviewing selected research on the content and effects of mass-mediated communication about health disparities, and identifying priorities for future research to better understand the role of communication in shaping public support and collective action to reduce health disparities. C1 [Niederdeppe, Jeff; Bigman, Cabral A.; Gonzales, Amy L.; Gollust, Sarah E.] Cornell Univ, Dept Commun, Ithaca, NY 14850 USA. Dana Farber Canc Inst, Harvard Sch Publ Hlth, Cambridge, MA 02138 USA. Indiana Univ, Dept Telecommunicat, Bloomington, IN 47405 USA. Univ Minnesota Sch Publ Hlth, Minneapolis, MN 55455 USA. RP Niederdeppe, J (reprint author), Cornell Univ, Dept Commun, Ithaca, NY 14850 USA. EM jdn56@cornell.edu NR 80 TC 6 Z9 6 U1 4 U2 49 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9916 J9 J COMMUN JI J. Commun. PD FEB PY 2013 VL 63 IS 1 BP 8 EP 30 DI 10.1111/jcom.12003 PG 23 WC Communication SC Communication GA 079QC UT WOS:000314185400005 ER PT J AU Nagler, RH Ramanadhan, S Minsky, S Viswanath, K AF Nagler, Rebekah H. Ramanadhan, Shoba Minsky, Sara Viswanath, K. TI Recruitment and Retention for Community-Based eHealth Interventions with Populations of Low Socioeconomic Position: Strategies and Challenges SO JOURNAL OF COMMUNICATION LA English DT Article ID RESEARCH PARTICIPANTS; RESIDENTIAL-MOBILITY; HEALTH INFORMATION; PHYSICAL-ACTIVITY; DIGITAL-DIVIDE; CANCER; MINORITY; KNOWLEDGE; LESSONS; SEEKING AB Given persistent communication inequalities, it is important to develop interventions to improve Internet and health literacy among underserved populations. These goals drove the Click to Connect project, a community-based eHealth intervention that provided novice computer users of low socioeconomic position with broadband Internet access, training classes, a Web portal, and technical support. In this article, we describe the strategies used to recruit and retain this population, the budgetary implications of such strategies, and the challenges and successes we encountered. Results suggest that personal contact between study staff and participants and provision of in-depth technical support were central to successful recruitment and retention. Such investments are essential to realize the promise of eHealth with underserved populations. C1 [Nagler, Rebekah H.; Viswanath, K.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02215 USA. [Nagler, Rebekah H.; Ramanadhan, Shoba; Minsky, Sara; Viswanath, K.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA. RP Nagler, RH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02215 USA. EM rebekah_nagler@dfci.harvard.edu FU NCI NIH HHS [K05 CA108663, R01 CA122894, R25 CA057711] NR 42 TC 11 Z9 12 U1 4 U2 44 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9916 J9 J COMMUN JI J. Commun. PD FEB PY 2013 VL 63 IS 1 BP 201 EP 220 DI 10.1111/jcom.12008 PG 20 WC Communication SC Communication GA 079QC UT WOS:000314185400016 PM 23439871 ER PT J AU Kitch, BT DesRoches, C Lesser, C Cunningham, A Campbell, EG AF Kitch, Barrett T. DesRoches, Catherine Lesser, Cara Cunningham, Amy Campbell, Eric G. TI Systems model of physician professionalism in practice SO JOURNAL OF EVALUATION IN CLINICAL PRACTICE LA English DT Article DE costs; disclosure; errors; professionalism; systems ID MEDICAL PROFESSIONALISM; PERFORMANCE; MILLENNIUM; CHARTER; DOCTORS AB Rationale This article proposes a systems level conceptualization of physician professionalism that is embedded in and results from the characteristics of the organizations in which doctors work such as hospitals, group practices and physician organizations. Aims and objectives The goal of this study was to develop and test the systems model of professionalism. Methods In total, 25 interviews were conducted in Minneapolis and Miami. Job titles of the subjects included hospital presidents, medical directors, chairs of hospital departments, quality and safety directors, chief of quality improvement and practising physicians. The data from the interviews were coded and then sorted by members of the study team into major and minor themes. Results Virtually, all of the subjects were readily able to confirm aspects of the model by providing real-life examples of factors at the practice, hospital and market levels that they believed strongly influenced the extent to which physicians adhere, or fail to adhere, to the professional norms. Conclusions The systems model of professionalism was consistent with the views and experiences of physicians and administrators in two different geographic regions of the USA. If born out by further research, this model has implications for interventions aimed at improving professionalism as well as for professionalism as a field of study. C1 [DesRoches, Catherine; Campbell, Eric G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mongan Inst Hlth Policy, Boston, MA USA. [Lesser, Cara] ABIM Fdn, Fdn Programs, Philadelphia, PA USA. RP Kitch, BT (reprint author), NSMC, 81 Highland Ave, Salem, MA 01970 USA. EM bkitch@partners.org FU American Board of Internal Medicine Foundation FX The study was supported through a grant from the American Board of Internal Medicine Foundation. The foundation played a major role in all aspects of the study, including the study design, data collection, analyses and reporting. NR 20 TC 1 Z9 1 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1356-1294 J9 J EVAL CLIN PRACT JI J. Eval. Clin. Pract. PD FEB PY 2013 VL 19 IS 1 BP 1 EP 10 DI 10.1111/j.1365-2753.2011.01680.x PG 10 WC Health Care Sciences & Services; Medical Informatics; Medicine, General & Internal SC Health Care Sciences & Services; Medical Informatics; General & Internal Medicine GA 078QN UT WOS:000314114400001 PM 22435531 ER PT J AU Egede, LE Lynch, CP Gebregziabher, M Hunt, KJ Echols, C Gilbert, GE Mauldin, PD AF Egede, Leonard E. Lynch, Cheryl P. Gebregziabher, Mulugeta Hunt, Kelly J. Echols, Carrae Gilbert, Gregory E. Mauldin, Patrick D. TI Differential Impact of Longitudinal Medication Non-Adherence on Mortality by Race/Ethnicity among Veterans with Diabetes SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE medication non-adherence; veterans; diabetes; mortality; race/ethnicity ID RACIAL-DIFFERENCES; ADHERENCE; ADULTS; HEALTH; POPULATION; COHORT; HOSPITALIZATION; PREVALENCE; MELLITUS; US AB To examine the differential effect of medication non-adherence over time on all-cause mortality by race/ethnicity. Data on a longitudinal cohort of veterans with type 2 diabetes was examined. The main outcome was time to death. Primary independent variables were race/ethnicity and mean medication possession ratio (MPR) categorized into quintiles over the study period. Cox regression was used to model the association between time to death and MPR quintiles and race/ethnicity, adjusting for relevant covariates. The cohort of 629,563 veterans was followed for 5 years. After adjusting for all covariates, the hazard ratios (HR) for subjects in the lowest versus highest MPR quintile was 12.21 (95 % CI 11.89, 12.55) for non-Hispanic white (NHW), 10.01 (95 % CI 9.18, 10.91) for non-Hispanic black (NHB), 12.65 (95 % CI 11.10, 14.43) for Hispanic and 10.41 (95 % CI 9.06, 11.96) for Other race veterans. Furthermore, type of diabetes therapy (oral versus insulin) maintained a significant relationship with mortality that varied by racial/ethnic group. This study demonstrates the differential impact of medication non-adherence on mortality by race. It also demonstrates that type of diabetes therapy (insulin with or without oral agents) is associated with mortality and varies by racial/ethnic group. C1 [Egede, Leonard E.; Lynch, Cheryl P.; Gebregziabher, Mulugeta; Hunt, Kelly J.; Echols, Carrae; Gilbert, Gregory E.] Ralph H Johnson Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC 29425 USA. [Egede, Leonard E.; Lynch, Cheryl P.; Mauldin, Patrick D.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Gebregziabher, Mulugeta; Hunt, Kelly J.] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [Mauldin, Patrick D.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Mauldin, Patrick D.] Div Gen Internal Med & Geriatr, Charleston, SC USA. RP Egede, LE (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, POB 250593, Charleston, SC 29425 USA. EM Egedel@musc.edu RI Gilbert, Gregory/C-7735-2016; OI Gilbert, Gregory/0000-0003-0879-5496; Gebregziabher, Mulugeta/0000-0002-4826-481X FU VHA Health Services Research and Development (HSRD) program [IIR-06-219] FX This study was supported by grant #IIR-06-219 funded by the VHA Health Services Research and Development (HSR&D) program. The funding agency did not participate in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The manuscript represents the views of the authors and not those of the VA or HSR&D. All authors had access to the data and contributed to the manuscript NR 22 TC 13 Z9 13 U1 2 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2013 VL 28 IS 2 BP 208 EP 215 DI 10.1007/s11606-012-2200-8 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 077ZM UT WOS:000314067900011 PM 22948932 ER PT J AU Jena, AB Sun, E Goldman, DP AF Jena, Anupam B. Sun, Eric Goldman, Dana P. TI Confounding in the Association of Proton Pump Inhibitor Use With Risk of Community-Acquired Pneumonia SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE proton pump inhibitors; pneumonia; falsification testing ID GASTRIC-ACID; CHRONICALLY ILL; DRUG-USE; BACTERIAL; GASTROENTERITIS; POPULATION; INFECTION; THERAPY AB Use of proton pump inhibitors (PPIs) is associated with community-acquired pneumonia (CAP), an association which may be confounded by unobserved patient and prescriber characteristics. We assessed for confounding in the association between PPI use and CAP by using a 'falsification approach,' which estimated whether PPI use is also implausibly associated with other common medical conditions for which no known pathophysiologic link exists. Retrospective claims-based cohort study. Six private U.S. health plans. Individuals who filled at least one prescription for a PPI (N = 26,436) and those who never did (N = 28,054) over 11 years. Multivariate linear regression of the association between a filled prescription for a PPI and a diagnosis of CAP in each 3-month quarter. In falsification analyses, we tested for implausible associations between PPI use in each quarter and rates of osteoarthritis, chest pain, urinary tract infection (UTI), deep venous thrombosis (DVT), skin infection, and rheumatoid arthritis. Independent variables included an indicator for whether a prescription for a PPI was filled in a given quarter, and quarterly indicators for various co-morbidities, age, income, geographic location, and marital status. Compared to nonusers, those ever using a PPI had higher adjusted rates of CAP in quarters in which no prescription was filled (68 vs. 61 cases per 10,000 persons, p < 0.001). Similar associations were noted for all conditions (e.g. chest pain, 336 vs. 282 cases, p < 0.001; UTI, 151 vs. 139 cases, p < 0.001). Among those ever using a PPI, quarters in which a prescription was filled were associated with higher adjusted rates of CAP (111 vs. 68 cases per 10,000, p < 0.001) and all other conditions (e.g. chest pain, 597 vs. 336 cases, p < 0.001; UTI, 186 vs. 151 cases, p < 0.001), compared to quarters in which no prescription was filled. PPI use is associated with CAP, but also implausibly associated with common medical conditions. Observed associations between PPI use and CAP may be confounded. C1 [Jena, Anupam B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Jena, Anupam B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Jena, Anupam B.] Natl Bur Econ Res, Dept Med, Cambridge, MA 02138 USA. [Sun, Eric] Stanford Univ Hosp, Dept Anesthesia, Stanford, CA 94305 USA. [Goldman, Dana P.] Univ So Calif, Leonard Schaeffer Ctr Hlth Policy & Econ 7, Los Angeles, CA USA. RP Jena, AB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM jena@hcp.med.harvard.edu FU National Institute on Aging FX National Institute on Aging. The design, conduct, analysis, interpretation, and presentation of the data are the responsibility of the investigators, with no involvement from the funding sources. NR 30 TC 21 Z9 21 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2013 VL 28 IS 2 BP 223 EP 230 DI 10.1007/s11606-012-2211-5 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 077ZM UT WOS:000314067900013 PM 22956446 ER PT J AU Wee, CC Davis, RB Huskey, KW Jones, DB Hamel, MB AF Wee, Christina C. Davis, Roger B. Huskey, Karen W. Jones, Daniel B. Hamel, Mary B. TI Quality of Life Among Obese Patients Seeking Weight Loss Surgery: The Importance of Obesity-Related Social Stigma and Functional Status SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article ID BODY-MASS INDEX; BARIATRIC SURGERY; US ADULTS; HEALTH; CANCER; IMPACT; BMI; COMMUNITY; MORTALITY; TRENDS AB Obesity is a stigmatizing condition associated with adverse psychosocial consequences. The relative importance of weight stigma in reducing health utility or the value a person places on their current health state is unknown. We conducted a telephone survey of patients with obesity. All were seeking weight loss surgery at two bariatric centers (70 % response rate). We assessed patients' health utility (preference-based quality life measure) via a series of standard gamble scenarios assessing patients' willingness to risk death to lose various amounts of weight or achieve perfect health (range 0 to 1; 0 = death and 1 = most valued health/weight state). Multivariable models assessed associations among quality of life domains from the Short-form 36 (SF-36) and Impact of Weight on Quality of Life-lite (IWQOL-lite) and patients' health utility. Our study sample (n = 574) had a mean body mass index of 46.5 kg/m(2) and a mean health utility of 0.87, reflecting the group's average willingness to accept a 13 % risk of death to achieve their most desired health/weight state; utilities were highly variable, however, with 10 % reporting a utility of 1.00 and 27 % reporting a utility lower than 0.90. Among the IWQOL-lite subscales, Public Distress and Work Life were the only two subscales significantly associated with patients' utility after adjustment for sociodemographic factors. Among the SF-36 subscales, Role Physical, Physical Functioning, and Role Emotional were significantly associated with patients' utility. When the leading subscales on both IWQOL-lite and SF-36 were considered together, Role Physical, Public Distress, and to a lesser degree Role Emotional remained independently associated with patients' health utility. Patients seeking weight loss surgery report health utilities similar to those reported for people living with diabetes or with laryngeal cancer; however, utility values varied widely with more than a quarter of patients willing to accept more than a 10 % risk of death to achieve their most valued health/weight state. Interference with role functioning due to physical limitations and obesity-related social stigma were strong determinants of reduced health utility. C1 [Wee, Christina C.; Davis, Roger B.; Huskey, Karen W.; Hamel, Mary B.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Wee, Christina C.; Davis, Roger B.; Huskey, Karen W.; Jones, Daniel B.; Hamel, Mary B.] Harvard Univ, Sch Med, Boston, MA USA. [Jones, Daniel B.] Beth Israel Deaconess Med Ctr, Dept Surg, Div Gen Surg, Sect Minimally Invas Surg, Boston, MA 02215 USA. RP Wee, CC (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care, Boston, MA 02215 USA. EM cwee@bidmc.harvard.edu FU National Institute of Diabetes, Digestive and Kidney Diseases [R01 DK073302]; National Institute of Health [K24DK087932] FX This study was funded by the National Institute of Diabetes, Digestive and Kidney Diseases (R01 DK073302). Dr. Wee is also supported by a midcareer mentorship award from the National Institute of Health (K24DK087932). The sponsor had no role in the design or conduct of the study; the collection, management, analysis, and interpretation of the data; and the preparation, review, or approval of the manuscript. Dr. Wee conceived the research question, designed the study, obtained funding, supervised the conduct of the study, and drafted the manuscript. Drs. Jones and Wee facilitated the collection of the data. Ms. Huskey had full access to all the data, conducted all the analyses, and takes responsibility for the integrity of the data and accuracy of the data analysis. Dr. Davis provided statistical expertise and along with Drs. Hamel and Wee interpreted the data. All authors provided critical revision of the manuscript for intellectual content and approved the final manuscript. We thank the patients for participating in our study and thank the ABS study team for their efforts. NR 30 TC 18 Z9 18 U1 2 U2 21 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2013 VL 28 IS 2 BP 231 EP 238 DI 10.1007/s11606-012-2188-0 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 077ZM UT WOS:000314067900014 PM 22956443 ER PT J AU Barnes, DE Mehta, KM Boscardin, WJ Fortinsky, RH Palmer, RM Kirby, KA Landefeld, CS AF Barnes, Deborah E. Mehta, Kala M. Boscardin, W. John Fortinsky, Richard H. Palmer, Robert M. Kirby, Katharine A. Landefeld, C. Seth TI Prediction of Recovery, Dependence or Death in Elders Who Become Disabled During Hospitalization SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE functional status; disability; mortality; hospitalization; prognosis ID ACUTE MEDICAL ILLNESS; FUNCTIONAL DECLINE; OLDER-ADULTS; PROGNOSTIC INDEX; 1-YEAR MORTALITY; SCREENING TOOLS; ACUTE-CARE; RISK; VALIDATION; OUTCOMES AB Many older adults become dependent in one or more activities of daily living (ADLs: dressing, bathing, transferring, eating, toileting) when hospitalized, and their prognosis after discharge is unclear. To develop a prognostic index to estimate one-year probabilities of recovery, dependence or death in older hospitalized patients who are discharged with incident ADL dependence. Retrospective cohort study. 449 adults aged a parts per thousand yen 70 years hospitalized for acute illness and discharged with incident ADL dependence. Potential predictors included demographics (age, sex, race, education, marital status), functional measures (ADL dependencies, instrumental activities of daily living [IADL] dependencies, walking ability), chronic conditions (e.g., congestive heart failure, dementia, cancer), reason for admission (e.g., neurologic, cardiovascular), and laboratory values (creatinine, albumin, hematocrit). Multinomial logistic regression was used to develop a prognostic index for estimating the probabilities of recovery, disability or death over 1 year. Discrimination of the index was assessed for each outcome based on the c statistic. During the year following hospitalization, 36 % of patients recovered, 27 % remained dependent and 37 % died. Key predictors of recovery, dependence or death were age, sex, number of IADL dependencies 2 weeks prior to admission, number of ADL dependencies at discharge, dementia, cancer, number of other chronic conditions, reason for admission, and creatinine levels. The final prognostic index had good to excellent discrimination for all three outcomes based on the c statistic (recovery: 0.81, dependence: 0.72, death: 0.78). This index accurately estimated the probabilities of recovery, dependence or death in adults aged 70 years or older who were discharged with incident disability following hospitalization. This tool may be useful in clinical settings to guide care discussions and inform decision-making related to post-hospitalization care. C1 [Barnes, Deborah E.; Boscardin, W. John; Kirby, Katharine A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Barnes, Deborah E.; Boscardin, W. John; Kirby, Katharine A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Mehta, Kala M.] Stanford Univ, Stanford, CA 94305 USA. [Fortinsky, Richard H.] Univ Connecticut, Sch Med, Farmington, CT USA. [Palmer, Robert M.] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. [Landefeld, C. Seth] Univ Alabama Birmingham, Birmingham, AL USA. RP Barnes, DE (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. EM Deborah.barnes@ucsf.edu FU National Institutes of Health (Landefeld) [R01 AG029233, AG10418]; S. D. Bechtel, Jr. Foundation FX Support for this study was provided by the National Institutes of Health (Landefeld: R01 AG029233, AG10418) and the S. D. Bechtel, Jr. Foundation. NR 44 TC 18 Z9 18 U1 3 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2013 VL 28 IS 2 BP 261 EP 268 DI 10.1007/s11606-012-2226-y PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 077ZM UT WOS:000314067900018 PM 23054919 ER PT J AU Eckstrom, E Feeny, DH Walter, LC Perdue, LA Whitlock, EP AF Eckstrom, Elizabeth Feeny, David H. Walter, Louise C. Perdue, Leslie A. Whitlock, Evelyn P. TI Individualizing Cancer Screening in Older Adults: A Narrative Review and Framework for Future Research SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review DE older adults; cancer screening; patient preferences ID SERVICES TASK-FORCE; QUALITY-OF-LIFE; CLINICAL DECISION-MAKING; COLORECTAL-CANCER; BREAST-CANCER; MAMMOGRAPHY; WOMEN; PREVENTION; GUIDELINES; SURVIVAL AB Older adults often have multiple chronic conditions that may decrease additional life expectancy. Research evaluating the benefits and harms of screening must include consideration of competing morbidities and patient heterogeneity (beyond age), potentially increased harms of screening, and patient preferences. Other areas in need of additional research include the lack of evidence for older adults on the harms of screening tests; the overdiagnosis of disease; the burden of disease labeling; the effects of inaccurate test results; the harms of disease treatment; and harms related to prioritization of healthcare (e.g., for a particular patient, lifestyle counseling may be more important than screening). Nontraditional outcomes, such as the effects on family caregivers, are also relevant. Studies comparing trajectories of quality-adjusted survival with and without screening to assess net benefit are typically lacking. There is little evidence on the preferences of older adults for deciding whether to be screened, the process of being screened, and the health states associated with being or not being screened. To enhance the quality and quantity of evidence, older adults need to be enrolled in screening trials and clinical studies. Measures of functional status and health-related quality of life (HRQL) need to be included in trials, registries, and cohort studies. This article addresses these challenges, and presents a framework for what research is needed to better inform screening decisions in older adults. C1 [Eckstrom, Elizabeth] Oregon Hlth & Sci Univ, Dept Med, Div Gen Internal Med & Geriatr, Portland, OR 97201 USA. [Feeny, David H.; Perdue, Leslie A.; Whitlock, Evelyn P.] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA. [Walter, Louise C.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA. [Walter, Louise C.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Eckstrom, E (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Gen Internal Med Geriatr, 3181 SW Sam Jackson Pk Rd,L475, Portland, OR 97239 USA. EM eckstrom@ohsu.edu FU Agency for Health Care Research; National Cancer Institute; National Cancer Institute [R01 CA134425]; National Institute on Aging [K24AG041180] FX Agency for Health Care Research; National Cancer Institute (Dr. Eckstrom, Dr. Feeny, and Ms. Perdue). Dr. Walter's effort was supported by the National Cancer Institute (grant number R01 CA134425) and the National Institute on Aging (grant number K24AG041180). NR 44 TC 7 Z9 7 U1 0 U2 19 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2013 VL 28 IS 2 BP 292 EP 298 DI 10.1007/s11606-012-2227-x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 077ZM UT WOS:000314067900021 PM 23054920 ER PT J AU Chiovaro, J AF Chiovaro, Joe TI Haunted by the Unread SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material C1 Portland VA Med Ctr, Div Hosp Med, Dept Med, Portland, OR 97239 USA. RP Chiovaro, J (reprint author), Portland VA Med Ctr, Div Hosp Med, Dept Med, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM jchiovaro@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2013 VL 28 IS 2 BP 326 EP 327 DI 10.1007/s11606-012-2143-0 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 077ZM UT WOS:000314067900029 PM 22752590 ER PT J AU Bromley, SK Yan, S Tomura, M Kanagawa, O Luster, AD AF Bromley, Shannon K. Yan, Sha Tomura, Michio Kanagawa, Osami Luster, Andrew D. TI Recirculating Memory T Cells Are a Unique Subset of CD4(+) T Cells with a Distinct Phenotype and Migratory Pattern SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOID ORGANS; PERIPHERAL-TISSUES; IMMUNE-RESPONSE; IN-VIVO; LYMPHOCYTES; RECEPTOR; EGRESS; MICE; INFECTION; INTEGRIN AB Several populations of memory T cells have been described that differ in their migration and function. In this study, we have identified a unique subset of memory T cells, which we have named recirculating memory T cells (T-RCM). By exposing Kaede transgenic mouse skin to violet light, we tracked the fate of cutaneous T cells. One population of memory CD4(+) T cells remained in the skin. A second population migrated from the skin into draining lymph nodes (LNs) in a CCR7-dependent manner. These migrating CD4(+) T cells expressed a novel cell surface phenotype (CCR7(int/+)CD62L(int)CD69(-)CD103(+/-) E-selectin ligands(+)) that is distinct from memory T cell subsets described to date. Unlike memory T cell subsets that remain resident within tissues long-term, or that migrate either exclusively between lymphoid tissues or into peripheral nonlymphoid sites, CD4(+) T-RCM migrate from the skin into draining LNs. From the draining LNs, CD4(+) T-RCM reenter into the circulation, distal LNs, and sites of non-specific cutaneous inflammation. In addition, CD4(+) T-RCM upregulated CD40L and secreted IL-2 following polyclonal stimulation. Our results identify a novel subset of recirculating memory CD4(+) T cells equipped to deliver help to both distal lymphoid and cutaneous tissues. The Journal of Immunology, 2013, 190: 970-976. C1 [Bromley, Shannon K.; Yan, Sha; Luster, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Ctr Immunol & Inf, Boston, MA 02114 USA. [Tomura, Michio] Kyoto Univ, Ctr Innovat Immunoregulat Technol & Therapeut, Grad Sch Med, Kyoto 6068501, Japan. [Kanagawa, Osami] Akashi City Hosp, Akashi, Hyogo 6738501, Japan. RP Bromley, SK (reprint author), Massachusetts Gen Hosp, 149 13th St, Charlestown, MA 02129 USA. EM sbromley@helix.mgh.harvard.edu; aluster@mgh.harvard.edu FU National Institutes of Health [R01-CA069212, K01-AR053715]; Claflin Distinguished Scholar Award FX This work was supported by National Institutes of Health Grants R01-CA069212 (to A.D.L.) and K01-AR053715 (to S.K.B.) and by a Claflin Distinguished Scholar Award (to S.K.B.). NR 27 TC 52 Z9 52 U1 2 U2 14 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2013 VL 190 IS 3 BP 970 EP 976 DI 10.4049/jimmunol.1202805 PG 7 WC Immunology SC Immunology GA 074AM UT WOS:000313784200015 PM 23255361 ER PT J AU Bae, J Munshi, A Li, C Samur, M Prabhala, R Mitsiades, C Anderson, KC Munshi, NC AF Bae, Jooeun Munshi, Aditya Li, Cheng Samur, Mehmet Prabhala, Rao Mitsiades, Constantine Anderson, Kenneth C. Munshi, Nikhil C. TI Heat Shock Protein 90 Is Critical for Regulation of Phenotype and Functional Activity of Human T Lymphocytes and NK Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; HSP90 INHIBITORS; HSP90-SPECIFIC INHIBITOR; CANCER THERAPEUTICS; SIGNAL-TRANSDUCTION; MULTIPLE-MYELOMA; TYROSINE KINASES; MOLECULAR TARGET; ANTITUMOR AGENT; PLASMA-MEMBRANE AB The 90-kDa heat shock protein (Hsp90) has become an important therapeutic target with ongoing evaluation in a number of malignancies. Although Hsp90 inhibitors have a high therapeutic index with limited effects on normal cells, they have been described to inhibit dendritic cell function. However, its effect on human immune effector cells may have significant clinical implications, but remains unexplored. In this study, we have evaluated the effects of Hsp90 inhibition on human T lymphocyte and NK cells, including their Ag expression, activation, proliferation, and functional activities. These studies demonstrate that Hsp90 inhibition irreversibly downregulates cell surface expression of critical Ags (CD3, CD4, CD8), the costimulatory molecule (CD28, CD40L), and ab receptors on T lymphocytes, as well as activating receptors (CD2, CD11a, CD94, NKp30, NKp44, NKp46, KARp50.3) on NK cells. Hsp90 inhibition significantly reduced CD4 protein expression on T lymphocytes at both the cell surface and intracellular level, which was shown to be associated with aberrant regulation of Src-kinase p56(Lck). Downregulation of the Ags triggered by Hsp90 inhibition on CD3(+) T lymphocytes, both in CD4(+) and CD8(+) T cell subsets, was associated with a disruption in their cellular activation, proliferation, and/or IFN-gamma production, when the inhibition occurred either in activated or inactivated cells. In addition, downregulation of key activating receptors on NK cells following Hsp90 inhibition resulted in decreased cytotoxicity against tumor cells. Therefore, these observations demonstrate the need to closely monitor immune function in patients being treated with a Hsp90 inhibitor and may provide a potential therapeutic application in autoimmune diseases. The Journal of Immunology, 2013, 190: 1360-1371. C1 [Bae, Jooeun; Munshi, Aditya; Li, Cheng; Samur, Mehmet; Prabhala, Rao; Mitsiades, Constantine; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Munshi, Aditya; Li, Cheng; Samur, Mehmet] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. [Prabhala, Rao; Munshi, Nikhil C.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Munshi, NC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM nikhil_munshi@dfci.harvard.edu OI Munshi, Aditya/0000-0002-9111-7495 FU National Institutes of Health [RO1-124929, P50-100007, PO1-78378, PO1-155258, RO1-50947]; VA merit review grant FX This work was supported by National Institutes of Health Grant RO1-124929 and a VA merit review grant (to N.C.M.); National Institutes of Health Grants P50-100007, PO1-78378, and PO1-155258 (to N.C.M. and K.C.A.); and National Institutes of Health Grant RO1-50947 (to K.C.A.). NR 67 TC 20 Z9 20 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2013 VL 190 IS 3 BP 1360 EP 1371 DI 10.4049/jimmunol.1200593 PG 12 WC Immunology SC Immunology GA 074AM UT WOS:000313784200054 PM 23293352 ER PT J AU Hirachan, P Polnaszek, NM Martinez, M Wagner, B AF Hirachan, P. Polnaszek, N. M. Martinez, M. Wagner, B. TI ACUTE KIDNEY INJURY FOLLOWING RETROGRADE PYELOGRAM SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 21-23, 2013 CL New Orleans, LA SP Amer Federat Med Res, So Reg C1 [Hirachan, P.; Polnaszek, N. M.; Martinez, M.; Wagner, B.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Wagner, B.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2013 VL 61 IS 2 MA 258 BP 445 EP 446 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 079FO UT WOS:000314156100273 ER PT J AU Sewell, J Wagner, B AF Sewell, J. Wagner, B. TI NEPHROGENIC SYSTEMIC FIBROSIS: REDOX SENSITIVITY, DERMAL CCR7-EXPRESSING FIBROCYTES, AND EVIDENCE OF PULMONARY INVOLVEMENT IN A RAT MODEL SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 21-23, 2013 CL New Orleans, LA SP Amer Federat Med Res, So Reg C1 [Sewell, J.; Wagner, B.] Univ Texas Hlth Care Syst San Antonio, San Antonio, TX USA. [Wagner, B.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2013 VL 61 IS 2 MA 271 BP 449 EP 449 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 079FO UT WOS:000314156100286 ER PT J AU Jessee, R Weaver, F Chin, A Burns, S Svircev, J Hoenig, H Heggeness, M Carbone, L AF Jessee, R. Weaver, F. Chin, A. Burns, S. Svircev, J. Hoenig, H. Heggeness, M. Carbone, L. TI MANAGEMENT OF LOWER EXTREMITY FRACTURES IN MEN WITH SPINAL CORD INJURIES SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 21-23, 2013 CL New Orleans, LA SP Amer Federat Med Res, So Reg C1 [Jessee, R.; Carbone, L.] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA. [Weaver, F.; Chin, A.] Jr VA Hosp, Hines, IL USA. [Weaver, F.] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. [Burns, S.; Svircev, J.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Burns, S.; Svircev, J.] Univ Washington, Seattle, WA 98195 USA. [Hoenig, H.] Durham VAMC, Durham, NC USA. [Heggeness, M.] VA Med Ctr, Houston, TX USA. [Heggeness, M.] Baylor Coll Med, Houston, TX 77030 USA. [Carbone, L.] Memphis VA Med Ctr, Memphis, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2013 VL 61 IS 2 MA 297 BP 456 EP 456 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 079FO UT WOS:000314156100312 ER PT J AU Sewell, J Wagner, B AF Sewell, J. Wagner, B. TI NEPHROGENIC SYSTEMIC FIBROSIS: REDOX SENSITIVITY, DERMAL CCR7-EXPRESSING FIBROCYTES, AND EVIDENCE OF PULMONARY INVOLVEMENT IN A RAT MODEL SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 21-23, 2013 CL New Orleans, LA SP Amer Federat Med Res C1 [Sewell, J.; Wagner, B.] Univ Texas Hlth Care Syst San Antonio, San Antonio, TX USA. [Wagner, B.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2013 VL 61 IS 2 MA 393 BP 484 EP 484 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 079FO UT WOS:000314156100408 ER PT J AU Alge, J Karakala, N Neely, B Janech, M Arthur, J AF Alge, J. Karakala, N. Neely, B. Janech, M. Arthur, J. TI URINARY ANGIOTENSINOGEN: A PROGNOSTIC BIOMARKER OF ACUTE KIDNEY INJURY SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 21-23, 2013 CL New Orleans, LA SP Amer Federat Med Res, So Reg C1 [Alge, J.; Karakala, N.; Neely, B.; Janech, M.; Arthur, J.] Med Univ S Carolina, Charleston, SC 29425 USA. [Janech, M.; Arthur, J.] Ralph H Johnson VAMC, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2013 VL 61 IS 2 MA 504 BP 516 EP 516 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 079FO UT WOS:000314156100519 ER PT J AU Bhensdadia, N Hunt, K Lopes-Virella, M Tucker, M Neely, B Janech, M Arthur, J AF Bhensdadia, N. Hunt, K. Lopes-Virella, M. Tucker, M. Neely, B. Janech, M. Arthur, J. TI URINE HAPTOGLOBIN TO CREATININE RATIO PREDICTS WORSENING RENAL FUNCTIONS IN PATIENTS WITH TYPE 2 DIABETES SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 21-23, 2013 CL New Orleans, LA SP Amer Federat Med Res, So Reg C1 [Bhensdadia, N.; Hunt, K.; Lopes-Virella, M.; Tucker, M.; Neely, B.; Janech, M.; Arthur, J.] Med Univ S Carolina, Charleston, SC 29425 USA. [Lopes-Virella, M.; Janech, M.; Arthur, J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2013 VL 61 IS 2 MA 506 BP 517 EP 517 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 079FO UT WOS:000314156100521 ER PT J AU Davis, B Stewart, EH Clemans-Taylor, BL Centor, R Estrada, C AF Davis, B. Stewart, E. H. Clemans-Taylor, B. L. Centor, R. Estrada, C. TI A META-ANALYSIS OF THE RAPID ANTIGEN STREPTOCOCCUS TEST SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 21-23, 2013 CL New Orleans, LA SP Amer Federat Med Res, So Reg C1 [Davis, B.; Stewart, E. H.; Clemans-Taylor, B. L.; Centor, R.; Estrada, C.] Univ Alabama Birmingham, Birmingham, AL USA. [Estrada, C.] Birmingham VAMC, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2013 VL 61 IS 2 MA 527 BP 523 EP 523 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 079FO UT WOS:000314156100542 ER PT J AU Bryan, T Snyder, E Estrada, C Castiglioni, A AF Bryan, T. Snyder, E. Estrada, C. Castiglioni, A. TI EDUCATION IN DELIVERING PATIENT-CENTERED CARE: PROVIDER COMFORT LEVEL IN COUNSELING WOMEN AGES 40-49 REGARDING BREAST CANCER SCREENING OPTIONS SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 21-23, 2013 CL New Orleans, LA SP Amer Federat Med Res, So Reg C1 [Bryan, T.; Snyder, E.; Estrada, C.] Univ Alabama Birmingham, Birmingham, AL USA. [Castiglioni, A.] Univ Cent Florida, Coll Med, Tampa, FL USA. [Bryan, T.; Snyder, E.; Estrada, C.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2013 VL 61 IS 2 MA 528 BP 524 EP 524 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 079FO UT WOS:000314156100543 ER PT J AU Sullivan, G Vasterling, JJ Han, XT Tharp, AT Davis, T Deitch, EA Constans, JI AF Sullivan, Greer Vasterling, Jennifer J. Han, Xiaotong Tharp, Andra Teten Davis, Teri Deitch, Elizabeth A. Constans, Joseph I. TI Preexisting Mental Illness and Risk for Developing a New Disorder After Hurricane Katrina SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Hurricane Katrina; PTSD; disasters; preexisting mental illness ID POSTTRAUMATIC-STRESS-DISORDER; DISASTER VICTIMS SPEAK; NATURAL DISASTER; PSYCHIATRIC-DISORDERS; TRAUMA; DEPRESSION; MORTALITY AB To investigate predisaster mental illness as a risk factor of poor postdisaster mental health outcomes, veterans with (n = 249) and without (n = 250) preexisting mental illness residing in the Gulf Coast during Hurricane Katrina were surveyed after Katrina and screened for posttraumatic stress disorder (PTSD), depression, generalized anxiety disorder, and panic. Logistic regression examined the association between preexisting mental disorders and positive screens after the hurricane, adjusting for demographics and exposure to hurricane-related stressors. The odds of screening positive for any new mental disorder were 6.8 times greater for those with preexisting mental illness compared with those without preexisting mental illness. Among those with preexisting PTSD, the odds of screening positive for any new mental illness were 11.9 times greater; among those with schizophrenia, 9.1 times greater; and among those with affective disorders, 4.4 times greater. Persons with preexisting mental illnesses, particularly PTSD, should be considered a high-risk group for poor outcomes after a disaster. C1 [Sullivan, Greer; Han, Xiaotong; Davis, Teri; Constans, Joseph I.] Cent Arkansas Vet Healthcare Syst, VA S Cent Mental Illness Res Educ & Clin Ctr MIRE, N Little Rock, AR 72114 USA. [Sullivan, Greer; Han, Xiaotong] Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. [Vasterling, Jennifer J.] VA Boston Healthcare Syst, Psychol Serv, Boston, MA USA. [Vasterling, Jennifer J.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Vasterling, Jennifer J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Tharp, Andra Teten] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Deitch, Elizabeth A.] Univ New Orleans, Dept Management, New Orleans, LA 70148 USA. [Constans, Joseph I.] VA SE Louisiana Vet Hlth Care Syst, New Orleans, LA USA. [Constans, Joseph I.] Tulane Univ, Dept Psychiat & Behav Sci, New Orleans, LA 70118 USA. RP Sullivan, G (reprint author), Cent Arkansas Vet Healthcare Syst, VA S Cent Mental Illness Res Educ & Clin Ctr MIRE, 2200 Ft Roots Dr,Bldg 58, N Little Rock, AR 72114 USA. EM gsullivan@uams.edu FU VA South Central (VISN 16) Mental Illness Research, Education, and Clinical Center (MIRECC), North Little Rock, AR FX This work was funded by the VA South Central (VISN 16) Mental Illness Research, Education, and Clinical Center (MIRECC), North Little Rock, AR. The authors declare no conflict of interest. NR 29 TC 8 Z9 8 U1 0 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD FEB PY 2013 VL 201 IS 2 BP 161 EP 166 DI 10.1097/NMD.0b013e31827f636d PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 082CO UT WOS:000314369500015 PM 23364127 ER PT J AU Barker, FG AF Barker, Fred G., II TI Stroke, geography, and provider density SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material ID ASSOCIATION; MORTALITY; ADULTS; VOLUME; STATES C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. NR 14 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD FEB PY 2013 VL 118 IS 2 BP 428 EP 429 DI 10.3171/2012.7.JNS121120 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 076DY UT WOS:000313937900032 PM 23198832 ER PT J AU Adams, JM Fulmer, T AF Adams, Jeffrey M. Fulmer, Terry TI Influencing Collaborative Leadership An Interview With Dean Terry Fulmer SO JOURNAL OF NURSING ADMINISTRATION LA English DT Editorial Material C1 [Adams, Jeffrey M.] Massachusetts Gen Hosp, Ctr Innovat Care Delivery & Connell Res Scholar, Boston, MA 02114 USA. RP Adams, JM (reprint author), Massachusetts Gen Hosp, Ctr Innovat Care Delivery & Connell Res Scholar, 275 Cambridge St,POB 4, Boston, MA 02114 USA. EM Jadams9@partners.org NR 2 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD FEB PY 2013 VL 43 IS 2 BP 66 EP 68 DI 10.1097/NNA.0b013e31827f2090 PG 3 WC Nursing SC Nursing GA 079HM UT WOS:000314161200004 ER PT J AU Miller, AN Barei, DP Iaquinto, JM Ledoux, WR Beingessner, DM AF Miller, Anna N. Barei, David P. Iaquinto, Joseph M. Ledoux, William R. Beingessner, Daphne M. TI Iatrogenic Syndesmosis Malreduction via Clamp and Screw Placement SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE Ankle; syndesmosis; iatrogenic; malreduction ID ANKLE FRACTURES; OPERATIVE TREATMENT; FIXATION; STABILIZATION; INJURIES; REMOVAL AB Objectives: The purpose of this study was to assess the impact of variations in angulation of clamp placement to hold syndesmotic reduction and how subsequent syndesmotic screw placement affects malreduction of the syndesmosis. We hypothesized that an anatomic syndesmosis reduction cannot be reliably achieved with a clamp alone; and, inaccurate placement of intraoperative clamps and trans-syndesmotic screws after reduction can malreduce the ankle syndesmosis. Methods: After computed tomography scanning of the intact limbs, 14 cadaver legs were dissected; the syndesmosis was completely disrupted in all. Using planned drill holes, clamps were first placed at 0 degrees, 15 degrees, and 30 degrees angles from the fibula, then separate posterolateral, followed by lateral, screws were placed. After each intervention, the limb had a computed tomography scan so the fibular reduction could be evaluated precisely. Results: Clamps placed at 15 degrees and 30 degrees significantly displaced the fibula in external rotation and caused significant overcompression of the syndesmosis. Thirty-degree lateral screws caused significant anteromedial displacement, external rotation, and overcompression of the syndesmosis. The 15 degrees posterolateral screws also caused significant external rotation and overcompression of the syndesmosis. Conclusions: Our study demonstrates that intraoperative clamping and fixation can cause statistically significant malreduction of the syndesmosis. This article should alert clinicians that clamp and screw placement can cause iatrogenic malreduction of the syndesmosis and make them aware that these dangers occur with specific clamp and screw angles in particular. C1 [Miller, Anna N.] Wake Forest Univ, Bowman Gray Sch Med, Dept Orthopaed Surg, Winston Salem, NC 27157 USA. [Barei, David P.; Beingessner, Daphne M.] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. [Barei, David P.; Ledoux, William R.; Beingessner, Daphne M.] Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. [Iaquinto, Joseph M.; Ledoux, William R.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Seattle, WA USA. [Ledoux, William R.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. RP Miller, AN (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Orthopaed Surg, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM anmiller@wakehealth.edu RI Ledoux, William/K-6815-2015; OI Ledoux, William/0000-0003-4982-7714; Miller, Anna/0000-0002-7056-8502 FU University of Washington Department of Orthopaedic Surgery; Department of Veterans Affairs Rehabilitation Research and Development Center of Excellence FX Supported by the University of Washington Department of Orthopaedic Surgery and the Department of Veterans Affairs Rehabilitation Research and Development Center of Excellence. NR 22 TC 22 Z9 24 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-5339 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD FEB PY 2013 VL 27 IS 2 BP 100 EP 106 DI 10.1097/BOT.0b013e31825197cb PG 7 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 077VV UT WOS:000314058300013 PM 22549032 ER PT J AU Holgerson, PL Vestman, NR Claesson, R Ohman, C Domellof, M Tanner, ACR Hernell, O Johansson, I AF Holgerson, Pernilla L. Vestman, Nelly R. Claesson, Rolf Ohman, Carina Domellof, Magnus Tanner, Anne C. R. Hernell, Olle Johansson, Ingegerd TI Oral Microbial Profile Discriminates Breast-fed From Formula-fed Infants SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE breast-feeding; lactobacilli. Lactobacillus gasseri; microbiota; oral ID HYDROXYAPATITE IN-VITRO; UPPER RESPIRATORY-TRACT; MUTANS STREPTOCOCCI; HUMAN-MILK; LACTOBACILLUS-REUTERI; GUT MICROBIOME; BODY HABITATS; DENTAL-CARIES; CHILDREN; ADHESION AB Objectives: Little is known about the effect of diet on the oral microbiota of infants, although diet is known to affect the gut microbiota. The aims of the present study were to compare the oral microbiota in breast-fed and formula-fed infants, and investigate growth inhibition of streptococci by infant-isolated lactobacilli. Methods: A total of 207 mothers consented to participation of their 3-month-old infants. A total of 146 (70.5%) infants were exclusively and 38 (18.4%) partially breast-fed, and 23 (11.1%) were exclusively formula-fed. Saliva from all of their infants was cultured for Lactobacillus species, with isolate identifications from 21 infants. Lactobacillus isolates were tested for their ability to suppress Streptococcus mutans and S sanguinis. Oral swabs from 73 infants were analysed by the Human Oral Microbe Identification Microarray (HOMIM) and by quantitative polymerase chain reaction for Lactobacillus gasseri. Results: Lactobacilli were cultured from 27.8% of exclusively and partially breast-fed infants, but not from formula-fed infants. The prevalence of 14 HOMIM-detected taxa, and total salivary lactobacilli counts differed by feeding method. Multivariate modelling of HOMIM-detected bacteria and possible confounders clustered samples from breast-fed infants separately from formula-fed infants. The microbiota of breast-fed infants differed based on vaginal or C-section delivery. Isolates of L plantarum, L gasseri, and L vaginalis inhibited growth of the cariogenic S mutans and the commensal S sanguinis: L plantarum >L gasseri >L vaginalis. Conclusions: The microbiota of the mouth differs between 3-month-old breast-fed and formula-fed infants. Possible mechanisms for microbial differences observed include species suppression by lactobacilli indigenous to breast milk. C1 [Holgerson, Pernilla L.; Vestman, Nelly R.; Claesson, Rolf; Ohman, Carina; Johansson, Ingegerd] Umea Univ, Dept Odontol, SE-90187 Umea, Sweden. [Domellof, Magnus; Hernell, Olle] Umea Univ, Dept Clin Sci, SE-90187 Umea, Sweden. [Tanner, Anne C. R.] Harvard Univ, Sch Publ Hlth, Dept Mol Genet, Forsyth Inst, Boston, MA 02115 USA. RP Holgerson, PL (reprint author), Umea Univ, Dept Odontol, SE-90187 Umea, Sweden. EM pernilla.lif@odont.umu.se RI Domellof, Magnus/E-5307-2011 OI Domellof, Magnus/0000-0002-0726-7029 FU Vasterbotten County Council; Swedish Patent Revenue Foundation; Public Health Service Grant, National Institute of Dental and Craniofacial Research [DE-015847]; Henning and Johan Throne-Holst's Foundation FX The study was supported by grants from Vasterbotten County Council, the Swedish Patent Revenue Foundation, and by Public Health Service Grant DE-015847 (A.T.) from the National Institute of Dental and Craniofacial Research, and Henning and Johan Throne-Holst's Foundation (P.L.H.). NR 51 TC 34 Z9 35 U1 4 U2 48 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD FEB PY 2013 VL 56 IS 2 BP 127 EP 136 DI 10.1097/MPG.0b013e31826f2bc6 PG 10 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 078LE UT WOS:000314099600011 PM 22955450 ER PT J AU Moran, CJ Kelsey, PB Lauwers, GY Biller, JA AF Moran, Christopher J. Kelsey, Peter B. Lauwers, Gregory Y. Biller, Jeffrey A. TI Resection of Acquired Mucosal Web in Crohn Disease SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article ID COLONIC DIAPHRAGM DISEASE; ENDOSCOPIC MEMBRANECTOMY; DUODENAL DIAPHRAGM; ADULT C1 [Moran, Christopher J.; Biller, Jeffrey A.] MassGen Hosp Children, Div Pediat Gastroenterol Hepatol & Nutr, Dept Pediat, Boston, MA 02114 USA. [Kelsey, Peter B.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Moran, CJ (reprint author), MassGen Hosp Children, Div Pediat Gastroenterol Hepatol & Nutr, Dept Pediat, 55 Fruit St, Boston, MA 02114 USA. EM cjmoran@partners.org NR 8 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD FEB PY 2013 VL 56 IS 2 BP E8 EP E9 DI 10.1097/MPG.0b013e3182495b70 PG 2 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 078LE UT WOS:000314099600002 PM 22450147 ER PT J AU Bober, SL Giobbie-Hurder, A Emmons, KM Winer, E Partridge, A AF Bober, Sharon L. Giobbie-Hurder, Anita Emmons, Karen M. Winer, Eric Partridge, Ann TI Psychosexual Functioning and Body Image Following a Diagnosis of Ductal Carcinoma In Situ SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE DCIS; Psychosexual; Body Image; Breast Cancer ID QUALITY-OF-LIFE; BREAST-CANCER SURVIVORS; HEALTH; WOMEN; SURGERY; ADJUSTMENT; SEXUALITY; OUTCOMES; END AB Introduction. There has been exponential growth in diagnoses of ductal carcinoma in situ (DCIS) in the past decade, yet little is known about sexual functioning and body image in women after diagnosis of DCIS. This is of particular importance because many of the parallel treatment modalities also used to treat invasive breast cancer, e.g., surgery and hormonal therapy, have been shown to have a detrimental effect on psychosexual function. Aim. The aim was to explore changes in sexual function and body image after diagnosis and treatment of in situ cancer. Main Outcome Measures. Evidence-based self-report measures assessing psychosexual functioning and body image. Methods. Women diagnosed with DCIS within the past 3 months and who reported being sexually active completed measures assessing various aspects of psychosocial and sexual functioning and body image. Outcomes were evaluated at baseline, 9-, and 18-month time points. All statistical tests were two sided. Results. Three hundred four women completed this prospective survey. Overall, sexual function in women with DCIS appears to be very similar to women in the general population and does not seem to be significantly disrupted by a diagnosis of DCIS. Sexual function and body image were notably stable across the 18-month length of follow-up. Of those patients who underwent mastectomy, there were no differences in sexual satisfaction for patients who had reconstruction compared with patients who did not. Conclusion. Although it has been shown that women with DCIS have a number of psychosocial challenges, results from this large-scale prospective study of women suggest that sexual function and body image may not be significantly negatively affected by this diagnosis. Of note, these results were also the case for women who underwent mastectomy and hormonal therapy. These findings are reassuring for both patients and physicians in the context of decision making about treatment options. Bober SL, A Giobbie-Hurder, Emmons KM, Winer E, and Partridge A. Psychosexual functioning and body image following a diagnosis of ductal carcinoma in situ. J Sex Med **;**:****. C1 [Bober, Sharon L.; Emmons, Karen M.; Winer, Eric; Partridge, Ann] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Bober, Sharon L.; Emmons, Karen M.; Winer, Eric; Partridge, Ann] Harvard Univ, Sch Med, Boston, MA USA. [Giobbie-Hurder, Anita] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Bober, SL (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. EM Sharon_Bober@dfci.harvard.edu NR 31 TC 7 Z9 7 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD FEB PY 2013 VL 10 IS 2 BP 370 EP 377 DI 10.1111/j.1743-6109.2012.02852.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 078OC UT WOS:000314107400008 PM 22812628 ER PT J AU Hosain, GMM Latini, DM Kauth, M Goltz, HH Helmer, DA AF Hosain, G. M. Monawar Latini, David M. Kauth, Michael Goltz, Heather Honore Helmer, Drew A. TI Sexual Dysfunction among Male Veterans Returning from Iraq and Afghanistan: Prevalence and Correlates SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE Sexual Dysfunction; Veterans; Post-Traumatic Stress Disorder; Prevalence; Male; Young ID POSTTRAUMATIC-STRESS-DISORDER; MALE ERECTILE DYSFUNCTION; DEPRESSIVE SYMPTOMS; UNITED-STATES; INTIMATE-RELATIONSHIPS; WAR VETERANS; MEN; HYPERTENSION; SATISFACTION; PREDICTORS AB Introduction. Sexual dysfunction (SD) is not well described in the Iraq/Afghanistan veteran population despite high prevalence of multiple risk factors for this issue. Aim. To estimate the prevalence and examine the association of various sociodemographic, mental health, comorbid conditions and life style factors with sexual dysfunction in Iraq/Afghanistan veterans. Methods. This exploratory cross-sectional study was conducted using data from the VA administrative database. A total of 4,755 Iraq/Afghanistan veterans were identified who sought treatment from the Michael E. DeBakey Veterans Affairs Medical Center inpatient and outpatient clinic between September 2007 and August 2009. Main Outcome Measures. Sexual dysfunction was determined by ICD9-CM codes related to sexual health issues and/or by specific medications, primarily phosphodiesterase-5 inhibitors (PDE5i), prescribed for erectile dysfunction. Results. The overall prevalence of sexual dysfunction was 5.5% (N = 265). By age category, it was 3.6% (N = 145) for Iraq/Afghanistan veterans aged 1840 years and 15.7% (N = 120) for Iraq/Afghanistan veterans aged > 40 years, respectively. A multivariate logistic-regression model revealed that annual income, marital status, post-traumatic stress disorder, and hypertension were significant risk factors of SD (all P < 0.05) among younger Iraq/Afghanistan veterans, whereas among the older Iraq/Afghanistan veterans, being African American and having PTSD and hypertension were significant risk factors of SD (all P < 0.05). There was marked discrepancy between documented erectile dysfunction and prescription of a PDE5i. Conclusions. These data demonstrate that a significant proportion of Iraq/Afghanistan veterans have SD and that the risk factors differ between younger and older veterans. Our findings also suggest that SD is likely under-coded. To better identify the scope of the problem, systematic screening for sexual dysfunction may be appropriate perhaps as part of an initial post-deployment health evaluation. Hosain GMM, Latini DM, Kauth M, Goltz HH, and Helmer DA. Sexual dysfunction among male veterans returning from Iraq and Afghanistan: Prevalence and correlates. J Sex Med 2013;10:516-523. C1 [Hosain, G. M. Monawar; Latini, David M.; Kauth, Michael; Goltz, Heather Honore] Michael E DeBakey Vet Affairs Med Ctr 152, Houston VA HSR&D Ctr Excellence, Houston, TX 77030 USA. [Hosain, G. M. Monawar; Latini, David M.] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. [Kauth, Michael] S Cent Mental Illness Res Educ & Clin Ctr, Houston, TX USA. [Kauth, Michael] Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Goltz, Heather Honore] Univ Houston Downtown, Houston, TX USA. [Helmer, Drew A.] VA RRD Ctr Excellence & PrimeCare, Houston, TX USA. [Helmer, Drew A.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Hosain, GMM (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, Houston VA HSR&D Ctr Excellence, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM monawarhosain@gmail.com OI Latini, David/0000-0002-6161-4861; Goltz, Heather/0000-0002-2875-7764 FU NIH [K12 DK0083014] FX G. M. Monawar Hosain is working as an NIDDK K-12 scholar (NIH Grant K12 DK0083014). This work was also supported in part by the facilities and resources of 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. The NIH had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. NR 37 TC 21 Z9 21 U1 1 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD FEB PY 2013 VL 10 IS 2 BP 516 EP 523 DI 10.1111/j.1743-6109.2012.02978.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 078OC UT WOS:000314107400024 PM 23088675 ER PT J AU Passias, PG Wang, SL Kozanek, M Wang, SB Wang, C AF Passias, Peter G. Wang, Shenglin Kozanek, Michal Wang, Shaobai Wang, Chao TI Relationship Between the Alignment of the Occipitoaxial and Subaxial Cervical Spine in Patients With Congenital Atlantoxial Dislocations SO JOURNAL OF SPINAL DISORDERS & TECHNIQUES LA English DT Article DE atlantoaxial dislocation; alignment; occipitoaxial; subaxial; cervical; DDD ID RHEUMATOID-ARTHRITIS; OCCIPITOCERVICAL FUSION; FOLLOW-UP; INSTABILITY; ARTHRODESIS AB Study Design: Prospective radiographic analysis. Objective: This study aimed to characterize the relationship between the alignment of the occipitoaxial (OA) and the subaxial spine, establish normal parameters, and to determine the influence of upper cervical spine alignment on subaxial degenerative disc disease (DDD) and clinical outcomes in this population. Summary of Background Data: Previous studies reported that the alignments of the upper and lower cervical spine are closely interrelated in patients with atlantoaxial dislocations of a rheumatoid etiology. None have focused on congenital etiologies or included patients with OA kyphosis. The influence of the upper cervical alignment on subaxial (DDD) and outcomes is also unclear. Methods: Fifty-eight patients with congenital AAD undergoing surgical reduction and fusion were included. C0-C2 and C2-C7 angles were measured and DDD was assessed using plain radiographs. The relationship between the alignment of the OA joint and the subaxial cervical spine was evaluated, as well as the relationships between the cervical alignment, outcomes, and cervical DDD. Results: C0-2 improved from a mean of 1.59 +/- 17.3 degrees preoperatively to a mean of 15 +/- 9.8 degrees postoperatively (P < 0.001). C2-7 changed from a mean of 25.55 +/- 19.6 degrees to a mean of 14.2 +/- 14.4 degrees postoperatively (P < 0.001). The OA and subaxial alignment were negatively correlated in this population both before (r = -0.84; P < 0.001) and after (r = -0.64; P < 0.001) surgical treatment. There was an increased incidence of DDD postoperatively (P < 0.01), which was positively correlated with the postoperative C0-2 angle (r = 0.54; P < 0.001), but negatively correlated with the postoperative C2-7 angle (r = -0.79; P < 0.001). Conclusions: Changes in OA alignment before and after surgery are associated with changes in the subaxial spine. There is a high incidence of postoperative DDD in the subaxial spine that seems to be related to sagittal alignment after surgery. C1 [Passias, Peter G.] NYU, Hosp Joint Dis, New York Spine Inst, Langone Med Ctr, New York, NY USA. [Wang, Shenglin; Wang, Chao] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Combined Orthopaed Residency Program, Boston, MA USA. [Kozanek, Michal] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab, Boston, MA USA. [Kozanek, Michal; Wang, Shaobai; Wang, Chao] Peking Univ, Hosp 3, Dept Orthopaed, Beijing 100191, Peoples R China. RP Wang, C (reprint author), Peking Univ, Hosp 3, Dept Orthopaed, 49 N Garden St, Beijing 100191, Peoples R China. EM wangchaoo@ynet.com NR 19 TC 5 Z9 7 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1536-0652 J9 J SPINAL DISORD TECH JI J. Spinal Disord. Tech. PD FEB PY 2013 VL 26 IS 1 BP 15 EP 21 DI 10.1097/BSD.0b013e31823097f9 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 079HW UT WOS:000314162200009 PM 21959834 ER PT J AU Yao, Q Wang, SB Shin, JH Li, GA Wood, KB AF Yao, Qi Wang, Shaobai Shin, Jae-Hyuk Li, Guoan Wood, Kirkham Burwick TI Lumbar Facet Joint Motion in Patients With Degenerative Spondylolisthesis SO JOURNAL OF SPINAL DISORDERS & TECHNIQUES LA English DT Article DE degenerative lumbar spondylolisthesis; facet joint kinematics; facet orientation; facet joint osteoarthritis; disk degeneration ID SPINAL STENOSIS; DISC DISEASE; IN-VIVO; ORIENTATION; OSTEOARTHRITIS; DECOMPRESSION; ASSOCIATION; OUTCOMES; SYSTEM; GRADE AB Study Design: Controlled laboratory study. Objective: To investigate the in vivo biomechanical effect of degenerative lumbar spondylolisthesis (DLS) on the motion of the facet joint during various functional weight-bearing activities. Summary of Background Data: Although the morphologic changes of the facet joints in patients with DLS have been reported in a few studies, no data have been reported on the kinematics of these facet joints. Methods: Ten patients with DLS at L4-L5 were studied. Each patient underwent a magnetic resonance imaging scan to obtain 3-dimensional models of the lumbar vertebrae from L2-L5 and a dual fluoroscopic imaging scan in different postures: flexion-extension, left-right bending, and left-right torsion. The positions of the vertebrae were reproduced by matching the magnetic resonance imaging-based vertebral models to the fluoroscopic images. The kinematics of the facet joint and the ranges of motion were compared with those of healthy subjects and those of patients with degenerative disk diseases (DDD) previously published. Results: In DLS patients, the range of rotation of the facet joints was significantly less at the DLS level (L4-L5) than that at the adjacent levels (L2-L3 and L3-L4), whereas the range of translation was similar at all levels. The range of rotation at the facet joints of the DLS level decreased compared with those of both the DDD patients and healthy subjects at the corresponding vertebral level (L4-L5), whereas no significant difference was found in the range of translation. The range of motion of facet joints in DLS and in DDD patients was similar at the adjacent levels (L2-L3 and L3-L4). Conclusions: The range of rotation decreased at the facet joints at the DLS level (L4-L5) in patients compared with those in healthy subjects and DDD patients. This decrease in range of rotation implies that the DLS disease may cause restabilization of the joint. The data may help the selection of conservative treatment or different surgical techniques for the DLS patients. C1 [Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02114 USA. [Yao, Qi; Wang, Shaobai; Shin, Jae-Hyuk; Li, Guoan; Wood, Kirkham Burwick] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Yao, Qi] Capital Med Univ, Beijing Shijitan Hosp, Dept Orthopaed Surg, Beijing, Peoples R China. RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU NIH [R21AR057989]; National Natural, Science Foundation of China [81000796]; Beijing Nova Program [2011085]; China Scholarship Council [2011911025] FX Supported by partially the NIH (R21AR057989), National Natural, Science Foundation of China (81000796) and Beijing Nova Program (2011085), and China Scholarship Council (2011911025). NR 38 TC 2 Z9 4 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1536-0652 J9 J SPINAL DISORD TECH JI J. Spinal Disord. Tech. PD FEB PY 2013 VL 26 IS 1 BP E19 EP E27 DI 10.1097/BSD.0b013e31827a254f PG 9 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 079HW UT WOS:000314162200004 PM 23168388 ER PT J AU Sweeney, C AF Sweeney, Christopher TI Prostate cancer therapy: going forwards by going backwards SO LANCET ONCOLOGY LA English DT Editorial Material ID INCREASED SURVIVAL; TRIAL; CHEMOTHERAPY; MITOXANTRONE; PREDNISONE C1 Dana Farber Canc Inst, Boston, MA 02215 USA. RP Sweeney, C (reprint author), Dana Farber Canc Inst, Boston, MA 02215 USA. EM christopher_sweeney@dfci.harvard.edu NR 10 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD FEB PY 2013 VL 14 IS 2 BP 104 EP 105 DI 10.1016/S1470-2045(12)70591-0 PG 2 WC Oncology SC Oncology GA 079JP UT WOS:000314166700016 PM 23306099 ER PT J AU Choueiri, TK Pomerantz, MM Signoretti, S AF Choueiri, Toni K. Pomerantz, Mark M. Signoretti, Sabina TI Renal-cell carcinoma: a step closer to a new classification SO LANCET ONCOLOGY LA English DT Editorial Material ID THERAPY C1 [Choueiri, Toni K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Choueiri, TK (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM toni_choueiri@dfci.harvard.edu NR 9 TC 3 Z9 3 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD FEB PY 2013 VL 14 IS 2 BP 105 EP 107 DI 10.1016/S1470-2045(12)70599-5 PG 4 WC Oncology SC Oncology GA 079JP UT WOS:000314166700017 PM 23333115 ER PT J AU Farley, J Brady, WE Vathipadiekal, V Lankes, HA Coleman, R Morgan, MA Mannel, R Yamada, SD Mutch, D Rodgers, WH Birrer, M Gershenson, DM AF Farley, John Brady, William E. Vathipadiekal, Vinod Lankes, Heather A. Coleman, Robert Morgan, Mark A. Mannel, Robert Yamada, S. Diane Mutch, David Rodgers, William H. Birrer, Michael Gershenson, David M. TI Selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum: an open-label, single-arm, phase 2 study SO LANCET ONCOLOGY LA English DT Article ID PEGYLATED LIPOSOMAL DOXORUBICIN; PLATINUM-RESISTANT; CLINICAL BEHAVIOR; CANCER; TUMORS; CHEMOTHERAPY; MUTATIONS; CISPLATIN; PATTERNS; THERAPY AB Background Low-grade serous carcinoma of the ovary is chemoresistant but mutations in the MAPK pathway could be targeted to control tumour growth. We therefore assessed the safety and activity of selumetinib, an inhibitor of MEK1/2, for patients with this cancer. Methods In this open-label, single-arm phase 2 study, women (aged >= 18 years) with recurrent low-grade serous ovarian or peritoneal carcinoma were given selumetinib (50 mg twice daily, orally) until progression. The primary endpoint was the proportion of patients who had an objective tumour response according to RECIST version 1.1, assessed for all the treated patients. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00551070. Findings 52 patients were enrolled between Dec 17, 2007, and Nov 23, 2009. All were eligible for analyses. Eight (15%) patients had an objective response to treatment-one patient had a complete response and seven had partial responses. 34 (65%) patients had stable disease. There were no treatment-related deaths. Grade 4 toxicities were cardiac (one), pain (one), and pulmonary events (one). Grade 3 toxicities that occurred in more than one patient were gastrointestinal (13), dermatological (nine), metabolic (seven), fatigue (six), anaemia (four), pain (four), constitutional (three), and cardiac events (two). Interpretation Selumetinib is well tolerated, and is active in the treatment of recurrent low-grade serous carcinoma of the ovary or peritoneum. The findings suggest that inhibitors of the MAPK pathway warrant further investigation in these patients. C1 [Farley, John] Creighton Univ, Sch Med, St Josephs Hosp, Div Gynecol Oncol,Dept Obstet & Gynecol,Med Ctr, Phoenix, AZ 85013 USA. [Brady, William E.; Lankes, Heather A.] Roswell Pk Canc Inst, Gynecol Oncol Grp, Stat & Data Ctr, Buffalo, NY 14263 USA. [Vathipadiekal, Vinod; Birrer, Michael] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Coleman, Robert; Gershenson, David M.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol & Oncol, Houston, TX 77030 USA. [Morgan, Mark A.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Mannel, Robert] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Yamada, S. Diane] Univ Chicago, Gynecol Oncol Sect, Chicago, IL 60637 USA. [Mutch, David] Washington Univ, Sch Med, Dept Obstet & Gynecol, Div Gynecol Oncol, St Louis, MO 63110 USA. [Rodgers, William H.] Lenox Hill Hosp, Dept Pathol, New York, NY 10021 USA. RP Farley, J (reprint author), Creighton Univ, Sch Med, St Josephs Hosp, Div Gynecol Oncol,Dept Obstet & Gynecol,Med Ctr, 500 W Thomas Rd,Suite 600, Phoenix, AZ 85013 USA. EM John.farley@chw.edu OI Vathipadiekal, Vinod/0000-0002-8181-6890 FU National Cancer Institute [CA 27469]; GOG; GOG Statistical Office [CA 37517]; Cancer Therapy Evaluation Program of the National Cancer Institute FX DMG received funding from the National Cancer Institute (Cancer Therapy Evaluation Program) and the GOG. The other authors declare that they have no conflicts of interest.; This study was supported by National Cancer Institute grants to the GOG Administrative Office (CA 27469) and the GOG Statistical Office (CA 37517). The trial was sponsored by the Cancer Therapy Evaluation Program of the National Cancer Institute. The following GOG member institutions participated in the primary treatment studies: University of Mississippi Medical Center, University of California Medical Center at Irvine, Cleveland Clinic Foundation, Washington University School of Medicine, Memorial Sloan-Kettering Cancer Center, Columbus Cancer Council, MD Anderson Cancer Center, Fox Chase Cancer Center, University of Oklahoma, University of Chicago, Case Western Reserve University, Women and Infants Hospital, and Community Clinical Oncology Program. NR 24 TC 113 Z9 118 U1 0 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD FEB PY 2013 VL 14 IS 2 BP 134 EP 140 DI 10.1016/S1470-2045(12)70572-7 PG 7 WC Oncology SC Oncology GA 079JP UT WOS:000314166700026 PM 23261356 ER PT J AU Heng, DYC Xie, WL Regan, MM Harshman, LC Bjarnason, GA Vaishampayan, UN Mackenzie, M Wood, L Donskov, F Tan, MH Rha, SY Agarwal, N Kollmannsberger, C Rini, BI Choueiri, TK AF Heng, Daniel Y. C. Xie, Wanling Regan, Meredith M. Harshman, Lauren C. Bjarnason, Georg A. Vaishampayan, Ulka N. Mackenzie, Mary Wood, Lori Donskov, Frede Tan, Min-Han Rha, Sun-Young Agarwal, Neeraj Kollmannsberger, Christian Rini, Brian I. Choueiri, Toni K. TI External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study SO LANCET ONCOLOGY LA English DT Article ID INTERFERON-ALPHA; SURVIVAL; RECLASSIFICATION; SORAFENIB; INTERVAL; CANCER; TRIAL AB Background The International Metastatic Renal-Cell Carcinoma Database Consortium model offers prognostic information for patients with metastatic renal-cell carcinoma. We tested the accuracy of the model in an external population and compared it with other prognostic models. Methods We included patients with metastatic renal-cell carcinoma who were treated with first-line VEGF-targeted treatment at 13 international cancer centres and who were registered in the Consortium's database but had not contributed to the initial development of the Consortium Database model. The primary endpoint was overall survival. We compared the Database Consortium model with the Cleveland Clinic Foundation (CCF) model, the International Kidney Cancer Working Group (IKCWG) model, the French model, and the Memorial Sloan-Kettering Cancer Center (MSKCC) model by concordance indices and other measures of model fit. Findings Overall, 1028 patients were included in this study, of whom 849 had complete data to assess the Database Consortium model. Median overall survival was 18.8 months (95% 17.6-21.4). The predefined Database Consortium risk factors (anaemia, thrombocytosis, neutrophilia, hypercalcaemia, Karnofsky performance status <80%, and <1 year from diagnosis to treatment) were independent predictors of poor overall survival in the external validation set (hazard ratios ranged between 1.27 and 2.08, concordance index 0.71, 95% CI 0.68-0.73). When patients were segregated into three risk categories, median overall survival was 43.2 months (95% CI 31.4-50.1) in the favourable risk group (no risk factors; 157 patients), 22.5 months (18.7-25.1) in the intermediate risk group (one to two risk factors; 440 patients), and 7.8 months (6.5-9.7) in the poor risk group (three or more risk factors; 252 patients; p<0.0001; concordance index 0.664, 95% CI 0.639-0.689). 672 patients had complete data to test all five models. The concordance index of the CCF model was 0.662 (95% CI 0.636-0.687), of the French model 0.640 (0.614-0.665), of the IKCWG model 0.668 (0.645-0.692), and of the MSKCC model 0.657 (0.632-0.682). The reported versus predicted number of deaths at 2 years was most similar in the Database Consortium model compared with the other models. Interpretation The Database Consortium model is now externally validated and can be applied to stratify patients by risk in clinical trials and to counsel patients about prognosis. C1 [Heng, Daniel Y. C.] Univ Calgary, Tom Baker Canc Ctr, Calgary, AB T2N 4N2, Canada. [Xie, Wanling; Regan, Meredith M.; Choueiri, Toni K.] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Harshman, Lauren C.] Stanford Univ, Stanford Canc Inst, Stanford, CA 94305 USA. [Bjarnason, Georg A.] Sunnybrook Odette Canc Inst, Toronto, ON, Canada. [Vaishampayan, Ulka N.] Wayne State Univ, Detroit, MI USA. [Mackenzie, Mary] London Hlth Sci Ctr, London, ON, Canada. [Wood, Lori] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [Donskov, Frede] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. [Tan, Min-Han] Natl Canc Ctr, Inst Bioengn & Nanotechnol, Singapore, Singapore. [Rha, Sun-Young] Yonsei Univ Hosp, Seoul, South Korea. [Agarwal, Neeraj] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Kollmannsberger, Christian] BC Canc Agcy, Vancouver, BC, Canada. [Rini, Brian I.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. RP Heng, DYC (reprint author), Univ Calgary, Tom Baker Canc Ctr, Calgary, AB T2N 4N2, Canada. EM daniel.heng@albertahealthservices.ca OI Bjarnason, Georg Arnold/0000-0001-6903-5357; Donskov, Frede/0000-0002-8449-863X FU Bristol-Myers Squibb; Novartis; Genentech; Pfizer; GlaxoSmithKline; Bayer Korea FX DYCH has an advisory role at Aveo, Pfizer, Novartis, and Bayer. LCH has an advisory role at Novartis and Pfizer and has received research funding from Bristol-Myers Squibb, Novartis, and Genentech. GAB has a consultant and advisory role at Pfizer and has received honoraria and research funding from Pfizer. MM has an advisory role at Novartis and Pfizer and has received research funding from both. LW has an advisory role at Pfizer and Novartis and has received research funding from Pfizer, Novartis, and GlaxoSmithKline. UNV has received honoraria and research funding from Pfizer, Novartis, and GlaxoSmithKline. S-YR has an advisory role at Novartis, Pfizer, and GlaxoSmithKline, and has received research funding from Novartis and Bayer Korea. FD has received research funding from Novartis. CK has an advisory role at Pfizer, Novartis, and GlaxoSmithKline and has received honoraria and research funding from Pfizer, Novartis, and GlaxoSmithKline. BIR has an advisory role at Pfizer, GlaxoSmithKline, Aveo, Bayer, Onyx, and has received research funding from GlaxoSmithKline and Pfizer. TKC has received research funding from Pfizer and has an advisory role at Aveo, Pfizer, Novartis, GlaxoSmithKline, Genentech, Bayer, and Onyx. WX, MMR, M-HT, and NA declare that they have no conflicts of interest. NR 24 TC 150 Z9 154 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD FEB PY 2013 VL 14 IS 2 BP 141 EP 148 DI 10.1016/S1470-2045(12)70559-4 PG 8 WC Oncology SC Oncology GA 079JP UT WOS:000314166700027 PM 23312463 ER PT J AU Joffe, H AF Joffe, Hadine TI Antidepressant use after discontinuation of hormone therapy: what can one infer about post-hormone therapy depression? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID REPLACEMENT THERAPY; VASOMOTOR SYMPTOMS; MENOPAUSAL TRANSITION; PERIMENOPAUSAL WOMEN; ESTROGEN REPLACEMENT; PUBLICATION; TRIAL; PREDICTORS; CESSATION; DURATION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Womens Mental Hlth,Dept Psychiat, Boston, MA 02115 USA. RP Joffe, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Womens Mental Hlth,Dept Psychiat, Boston, MA 02115 USA. NR 24 TC 3 Z9 3 U1 1 U2 2 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 FEB PY 2013 VL 20 IS 2 BP 123 EP 125 DI 10.1097/gme.0b013e31828059d4 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 081SM UT WOS:000314342600003 PM 23340264 ER PT J AU Scott, NS AF Scott, Nandita S. TI Coronary artery calcium and exercise: does a relationship exist and does it matter? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID PHYSICAL-ACTIVITY; FUNCTIONAL-CAPACITY; SYNDROME-X; WOMEN; CALCIFICATION; METAANALYSIS; MORTALITY; DISEASE; GENDER; RISK C1 Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. RP Scott, NS (reprint author), Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. NR 20 TC 0 Z9 0 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 FEB PY 2013 VL 20 IS 2 BP 126 EP 127 DI 10.1097/gme.0b013e31827c44d2 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 081SM UT WOS:000314342600004 PM 23299705 ER PT J AU Trynka, G Sandor, C Han, B Xu, H Stranger, BE Liu, XS Raychaudhuri, S AF Trynka, Gosia Sandor, Cynthia Han, Buhm Xu, Han Stranger, Barbara E. Liu, X. Shirley Raychaudhuri, Soumya TI Chromatin marks identify critical cell types for fine mapping complex trait variants SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; DIABETES SUSCEPTIBILITY LOCI; RHEUMATOID-ARTHRITIS; T-CELLS; EXPRESSION; ENHANCERS; DISEASE; SCHIZOPHRENIA; METHYLATIONS; METAANALYSIS AB If trait-associated variants alter regulatory regions, then they should fall within chromatin marks in relevant cell types. However, it is unclear which of the many marks are most useful in defining cell types associated with disease and fine mapping variants. We hypothesized that informative marks are phenotypically cell type specific; that is, SNPs associated with the same trait likely overlap marks in the same cell type. We examined 15 chromatin marks and found that those highlighting active gene regulation were phenotypically cell type specific. Trimethylation of histone H3 at lysine 4 (H3K4me3) was the most phenotypically cell type specific (P < 1 x 10(-6)), driven by colocalization of variants and marks rather than gene proximity (P < 0.001). H3K4me3 peaks overlapped with 37 SNPs for plasma low-density lipoprotein concentration in the liver (P < 7 x 10(-5)), 31 SNPs for rheumatoid arthritis within CD4(+) regulatory T cells (P = 1 x 10(-4)), 67 SNPs for type 2 diabetes in pancreatic islet cells (P = 0.003) and the liver (P = 0.003), and 14 SNPs for neuropsychiatric disease in neuronal tissues (P = 0.007). We show how cell type-specific H3K4me3 peaks can inform the fine mapping of associated SNPs to identify causal variation. C1 [Trynka, Gosia; Sandor, Cynthia; Han, Buhm; Stranger, Barbara E.; Raychaudhuri, Soumya] Harvard Univ, Brigham & Womens Hosp, Div Genet, Sch Med, Boston, MA 02115 USA. [Trynka, Gosia; Sandor, Cynthia; Han, Buhm; Raychaudhuri, Soumya] Harvard Univ, Brigham & Womens Hosp, Div Rheumatol, Sch Med, Boston, MA 02115 USA. [Trynka, Gosia; Sandor, Cynthia; Han, Buhm; Raychaudhuri, Soumya] Partners Ctr Personalized Genet Med, Boston, MA USA. [Trynka, Gosia; Sandor, Cynthia; Han, Buhm; Stranger, Barbara E.; Raychaudhuri, Soumya] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Xu, Han; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Xu, Han; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Raychaudhuri, Soumya] Univ Manchester, Fac Med & Human Sci, Manchester, Lancs, England. RP Raychaudhuri, S (reprint author), Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. EM soumya@broadinstitute.org OI Trynka, Gosia/0000-0002-6955-9529; Stranger, Barbara/0000-0001-9021-7331 FU Rubicon grant from The Netherlands Organization for Scientific Research (NWO); Harvard University Milton Fund; Brigham and Women's Hospital; US NIH [K08AR055688, U01HG0070033, R01 HG004069]; Arthritis Foundation; NHGRI; NIH Roadmap Epigenomics Mapping Consortium FX We thank M. Daly, M. Kellis, D. Diogo, X. Hu, Y. Okada, R. Plenge, S. Ripke, G. Srivastava, E. Stahl and S. Sunyaev for critical feedback and discussion. G.T. is supported by the Rubicon grant from The Netherlands Organization for Scientific Research (NWO). B.E.S. and S.R. are supported by the Harvard University Milton Fund, and Brigham and Women's Hospital. S.R. is also supported by funds from the US NIH (K08AR055688 and U01HG0070033) and the Arthritis Foundation. X.S.L. is also supported by funds from the US NIH (R01 HG004069). We thank the ENCODE Project, supported by the NHGRI, and the NIH Roadmap Epigenomics Mapping Consortium for making data available. NR 55 TC 159 Z9 159 U1 3 U2 33 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 2013 VL 45 IS 2 BP 124 EP 130 DI 10.1038/ng.2504 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 081PB UT WOS:000314333000005 PM 23263488 ER PT J AU Chmielecki, J Crago, AM Rosenberg, M O'Connor, R Walker, SR Ambrogio, L Auclair, D McKenna, A Heinrich, MC Frank, DA Meyerson, M AF Chmielecki, Juliann Crago, Aimee M. Rosenberg, Mara O'Connor, Rachael Walker, Sarah R. Ambrogio, Lauren Auclair, Daniel McKenna, Aaron Heinrich, Michael C. Frank, David A. Meyerson, Matthew TI Whole-exome sequencing identifies a recurrent NAB2-STAT6 fusion in solitary fibrous tumors SO NATURE GENETICS LA English DT Article ID EXPRESSION; CANCER; MUTATIONS; NAB2; COREPRESSOR; ACTIVATION; GROWTH; STAT6 AB Solitary fibrous tumors (SFTs) are rare mesenchymal tumors. Here, we describe the identification of a NAB2-STAT6 fusion from whole-exome sequencing of 17 SFTs. Analysis in 53 tumors confirmed the presence of 7 variants of this fusion transcript in 29 tumors (55%), representing a lower bound for fusion frequency at this locus and suggesting that the NAB2-STAT6 fusion is a distinct molecular feature of SFTs. C1 [Chmielecki, Juliann; Walker, Sarah R.; Frank, David A.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chmielecki, Juliann; Rosenberg, Mara; Ambrogio, Lauren; Auclair, Daniel; McKenna, Aaron; Meyerson, Matthew] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA USA. [Crago, Aimee M.; O'Connor, Rachael] Mem Sloan Kettering Canc Ctr, Dept Surg, Sarcoma Biol Lab, New York, NY 10021 USA. [Walker, Sarah R.; Frank, David A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Walker, Sarah R.; Frank, David A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Heinrich, Michael C.] Portland Vet Affairs VA Med Ctr, Div Hematol & Med Oncol, Portland, OR USA. [Heinrich, Michael C.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM matthew_meyerson@dfci.harvard.edu OI Crago, Aimee/0000-0002-2965-752X; O'Connor, Rachael/0000-0002-6869-7954 FU Carlos Slim Health Institute in Mexico; Specialized Program of Research Excellence (SPORE) grant in Soft Tissue Sarcoma [P50 CA140146]; MSKCC [P01CA47179]; American Cancer Society AstraZeneca; Kristen Ann Carr Foundation FX We are grateful to the individuals with SFT who contributed material for this study. We thank members of the Genomics Platform at the Broad Institute for their technical expertise and M. Abazeed and A. Dulak for critically reviewing the manuscript. This work was conducted as part of the Slim Initiative for Genomic Medicine in the Americas (SIGMA), a project funded by the Carlos Slim Health Institute in Mexico. This work was supported by a Specialized Program of Research Excellence (SPORE) grant in Soft Tissue Sarcoma (P50 CA140146) and a P01 grant (P01CA47179) to S. Singer (MSKCC). J.C. is supported by an American Cancer Society AstraZeneca Postdoctoral Fellowship. A.M.C. is supported by a grant from the Kristen Ann Carr Foundation. M.M. is supported by generous donations from M.B. Zuckerman and Team Dragonfly of the Pan-Mass Challenge. Material was collected under institutional review board (IRB)-approved protocols at the Memorial Sloan-Kettering Cancer Center and the Oregon Health & Science University Biolibrary. All patients provided informed consent. NR 15 TC 122 Z9 129 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 2013 VL 45 IS 2 BP 131 EP 132 DI 10.1038/ng.2522 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 081PB UT WOS:000314333000006 PM 23313954 ER PT J AU Kottgen, A Albrecht, E Teumer, A Vitart, V Krumsiek, J Hundertmark, C Pistis, G Ruggiero, D O'Seaghdha, CM Haller, T Yang, Q Tanaka, T Johnson, AD Kutalik, Z Smith, AV Shi, JL Struchalin, M Middelberg, RPS Brown, MJ Gaffo, AL Pirastu, N Li, G Hayward, C Zemunik, T Huffman, J Yengo, L Zhao, JH Demirkan, A Feitosa, MF Liu, X Malerba, G Lopez, LM van der Harst, P Li, XZ Kleber, ME Hicks, AA Nolte, IM Johansson, A Murgia, F Wild, SH Bakker, SJL Peden, JF Dehghan, A Steri, M Tenesa, A Lagou, V Salo, P Mangino, M Rose, LM Lehtimaki, T Woodward, OM Okada, Y Tin, A Muller, C Oldmeadow, C Putku, M Czamara, D Kraft, P Frogheri, L Thun, GA Grotevendt, A Gislason, GK Harris, TB Launer, LJ McArdle, P Shuldiner, AR Boerwinkle, E Coresh, J Schmidt, H Schallert, M Martin, NG Montgomery, GW Kubo, M Nakamura, Y Tanaka, T Munroe, PB Samani, NJ Jacobs, DR Liu, K D'Adamo, P Ulivi, S Rotter, JI Psaty, BM Vollenweider, P Waeber, G Campbell, S Devuyst, O Navarro, P Kolcic, I Hastie, N Balkau, B Froguel, P Esko, T Salumets, A Khaw, KT Langenberg, C Wareham, NJ Isaacs, A Kraja, A Zhang, QY Wild, PS Scott, RJ Holliday, EG Org, E Viigimaa, M Bandinelli, S Metter, JE Lupo, A Trabetti, E Sorice, R Doring, A Lattka, E Strauch, K Theis, F Waldenberger, M Wichmann, HE Davies, G Gow, AJ Bruinenberg, M Stolk, RP Kooner, JS Zhang, WH Winkelmann, BR Boehm, BO Lucae, S Penninx, BW Smit, JH Curhan, G Mudgal, P Plenge, RM Portas, L Persico, I Kirin, M Wilson, JF Leach, IM van Gilst, WH Goel, A Ongen, H Hofman, A Rivadeneira, F Uitterlinden, AG Imboden, M von Eckardstein, A Cucca, F Nagaraja, R Piras, MG Nauck, M Schurmann, C Budde, K Ernst, F Farrington, SM Theodoratou, E Prokopenko, I Stumvoll, M Jula, A Perola, M Salomaa, V Shin, SY Spector, TD Sala, C Ridker, PM Kahonen, M Viikari, J Hengstenberg, C Nelson, CP Meschia, JF Nalls, MA Sharma, P Singleton, AB Kamatani, N Zeller, T Burnier, M Attia, J Laan, M Klopp, N Hillege, HL Kloiber, S Choi, H Pirastu, M Tore, S Probst-Hensch, NM Volzke, H Gudnason, V Parsa, A Schmidt, R Whitfield, JB Fornage, M Gasparini, P Siscovick, DS Polasek, O Campbell, H Rudan, I Bouatia-Naji, N Metspalu, A Loos, RJF van Duijn, CM Borecki, IB Ferrucci, L Gambaro, G Deary, IJ Wolffenbuttel, BHR Chambers, JC Marz, W Pramstaller, PP Snieder, H Gyllensten, U Wright, AF Navis, G Watkins, H Witteman, JCM Sanna, S Schipf, S Dunlop, MG Tonjes, A Ripatti, S Soranzo, N Toniolo, D Chasman, DI Raitakari, O Kao, WHL Ciullo, M Fox, CS Caulfield, M Bochud, M Gieger, C AF Koettgen, Anna Albrecht, Eva Teumer, Alexander Vitart, Veronique Krumsiek, Jan Hundertmark, Claudia Pistis, Giorgio Ruggiero, Daniela O'Seaghdha, Conall M. Haller, Toomas Yang, Qiong Tanaka, Toshiko Johnson, Andrew D. Kutalik, Zoltan Smith, Albert V. Shi, Julia Struchalin, Maksim Middelberg, Rita P. S. Brown, Morris J. Gaffo, Angelo L. Pirastu, Nicola Li, Guo Hayward, Caroline Zemunik, Tatijana Huffman, Jennifer Yengo, Loic Zhao, Jing Hua Demirkan, Ayse Feitosa, Mary F. Liu, Xuan Malerba, Giovanni Lopez, Lorna M. van der Harst, Pim Li, Xinzhong Kleber, Marcus E. Hicks, Andrew A. Nolte, Ilja M. Johansson, Asa Murgia, Federico Wild, Sarah H. Bakker, Stephan J. L. Peden, John F. Dehghan, Abbas Steri, Maristella Tenesa, Albert Lagou, Vasiliki Salo, Perttu Mangino, Massimo Rose, Lynda M. Lehtimaki, Terho Woodward, Owen M. Okada, Yukinori Tin, Adrienne Mueller, Christian Oldmeadow, Christopher Putku, Margus Czamara, Darina Kraft, Peter Frogheri, Laura Thun, Gian Andri Grotevendt, Anne Gislason, Gauti Kjartan Harris, Tamara B. Launer, Lenore J. McArdle, Patrick Shuldiner, Alan R. Boerwinkle, Eric Coresh, Josef Schmidt, Helena Schallert, Michael Martin, Nicholas G. Montgomery, Grant W. Kubo, Michiaki Nakamura, Yusuke Tanaka, Toshihiro Munroe, Patricia B. Samani, Nilesh J. Jacobs, David R., Jr. Liu, Kiang D'Adamo, Pio Ulivi, Sheila Rotter, Jerome I. Psaty, Bruce M. Vollenweider, Peter Waeber, Gerard Campbell, Susan Devuyst, Olivier Navarro, Pau Kolcic, Ivana Hastie, Nicholas Balkau, Beverley Froguel, Philippe Esko, Tonu Salumets, Andres Khaw, Kay Tee Langenberg, Claudia Wareham, Nicholas J. Isaacs, Aaron Kraja, Aldi Zhang, Qunyuan Wild, Philipp S. Scott, Rodney J. Holliday, Elizabeth G. Org, Elin Viigimaa, Margus Bandinelli, Stefania Metter, Jeffrey E. Lupo, Antonio Trabetti, Elisabetta Sorice, Rossella Doering, Angela Lattka, Eva Strauch, Konstantin Theis, Fabian Waldenberger, Melanie Wichmann, H-Erich Davies, Gail Gow, Alan J. Bruinenberg, Marcel Stolk, Ronald P. Kooner, Jaspal S. Zhang, Weihua Winkelmann, Bernhard R. Boehm, Bernhard O. Lucae, Susanne Penninx, Brenda W. Smit, Johannes H. Curhan, Gary Mudgal, Poorva Plenge, Robert M. Portas, Laura Persico, Ivana Kirin, Mirna Wilson, James F. Leach, Irene Mateo van Gilst, Wiek H. Goel, Anuj Ongen, Halit Hofman, Albert Rivadeneira, Fernando Uitterlinden, Andre G. Imboden, Medea von Eckardstein, Arnold Cucca, Francesco Nagaraja, Ramaiah Piras, Maria Grazia Nauck, Matthias Schurmann, Claudia Budde, Kathrin Ernst, Florian Farrington, Susan M. Theodoratou, Evropi Prokopenko, Inga Stumvoll, Michael Jula, Antti Perola, Markus Salomaa, Veikko Shin, So-Youn Spector, Tim D. Sala, Cinzia Ridker, Paul M. Kaehoenen, Mika Viikari, Jorma Hengstenberg, Christian Nelson, Christopher P. Meschia, James F. Nalls, Michael A. Sharma, Pankaj Singleton, Andrew B. Kamatani, Naoyuki Zeller, Tanja Burnier, Michel Attia, John Laan, Maris Klopp, Norman Hillege, Hans L. Kloiber, Stefan Choi, Hyon Pirastu, Mario Tore, Silvia Probst-Hensch, Nicole M. Voelzke, Henry Gudnason, Vilmundur Parsa, Afshin Schmidt, Reinhold Whitfield, John B. Fornage, Myriam Gasparini, Paolo Siscovick, David S. Polasek, Ozren Campbell, Harry Rudan, Igor Bouatia-Naji, Nabila Metspalu, Andres Loos, Ruth J. F. van Duijn, Cornelia M. Borecki, Ingrid B. Ferrucci, Luigi Gambaro, Giovanni Deary, Ian J. Wolffenbuttel, Bruce H. R. Chambers, John C. Maerz, Winfried Pramstaller, Peter P. Snieder, Harold Gyllensten, Ulf Wright, Alan F. Navis, Gerjan Watkins, Hugh Witteman, Jacqueline C. M. Sanna, Serena Schipf, Sabine Dunlop, Malcolm G. Toenjes, Anke Ripatti, Samuli Soranzo, Nicole Toniolo, Daniela Chasman, Daniel I. Raitakari, Olli Kao, W. H. Linda Ciullo, Marina Fox, Caroline S. Caulfield, Mark Bochud, Murielle Gieger, Christian CA LifeLines Cohort Study CARDIoGRAM Consortium DIAGRAM Consortium ICBP Consortium MAGIC Consortium TI Genome-wide association analyses identify 18 new loci associated with serum urate concentrations SO NATURE GENETICS LA English DT Article ID URIC-ACID LEVELS; CARDIOVASCULAR-DISEASE RISK; MOLECULAR PHYSIOLOGY; METABOLIC SYNDROME; GENETIC-LOCI; GOUT; HYPERURICEMIA; POPULATION; IDENTIFICATION; TRANSPORTER AB Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SEMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout. C1 [Koettgen, Anna; Hundertmark, Claudia] Freiburg Univ Hosp, Renal Div, Freiburg, Germany. [Koettgen, Anna; Tin, Adrienne; Coresh, Josef; Kao, W. H. Linda] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Albrecht, Eva; Strauch, Konstantin; Gieger, Christian] Helmholtz Zentrum Munchen, Inst Genet Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany. [Teumer, Alexander; Schurmann, Claudia; Ernst, Florian] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Vitart, Veronique; Hayward, Caroline; Huffman, Jennifer; Tenesa, Albert; Campbell, Susan; Navarro, Pau; Hastie, Nicholas; Farrington, Susan M.; Wright, Alan F.; Dunlop, Malcolm G.] Univ Edinburgh, Med Res Council MRC Human Genet Unit, MRC Inst Genet & Mol Med IGMM, Edinburgh, Midlothian, Scotland. [Krumsiek, Jan; Theis, Fabian] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Bioinformat & Syst Biol, Neuherberg, Germany. [Pistis, Giorgio; Sala, Cinzia; Toniolo, Daniela] Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy. [Ruggiero, Daniela; Sorice, Rossella; Ciullo, Marina] CNR, Inst Genet & Biophys A Buzzati Traverso, I-80125 Naples, Italy. [O'Seaghdha, Conall M.; Yang, Qiong; Johnson, Andrew D.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [O'Seaghdha, Conall M.; Yang, Qiong; Johnson, Andrew D.; Fox, Caroline S.] NHLBI, Ctr Populat Studies, Framingham, MA USA. [O'Seaghdha, Conall M.] Massachusetts Gen Hosp, Div Renal, Boston, MA 02114 USA. [Haller, Toomas; Esko, Tonu; Salumets, Andres; Perola, Markus; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Yang, Qiong; Liu, Xuan] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Tanaka, Toshiko; Metter, Jeffrey E.; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Kutalik, Zoltan] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland. [Kutalik, Zoltan] Swiss Inst Bioinformat, Lausanne, Switzerland. [Smith, Albert V.; Gislason, Gauti Kjartan; Gudnason, Vilmundur] Iceland Heart Assoc Res Inst, Kopavogur, Iceland. [Smith, Albert V.; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Shi, Julia; McArdle, Patrick; Shuldiner, Alan R.; Parsa, Afshin] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Struchalin, Maksim; Dehghan, Abbas; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Middelberg, Rita P. S.] Prince Charles Hosp, Dept Med, Chermside, Qld, Australia. [Middelberg, Rita P. S.; Martin, Nicholas G.; Montgomery, Grant W.; Whitfield, John B.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Brown, Morris J.] Univ Cambridge, Clin Pharmacol Unit, Cambridge, England. [Gaffo, Angelo L.] Univ Alabama Birmingham, Div Rheumatol, Birmingham, AL USA. [Gaffo, Angelo L.] Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Pirastu, Nicola; D'Adamo, Pio; Gasparini, Paolo] Univ Trieste, Inst Maternal & Child Hlth, Ist Ricovero & Cura Carattere Sci IRCCS Burlo Gar, Trieste, Italy. [Li, Guo; Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Zemunik, Tatijana; Kolcic, Ivana; Polasek, Ozren; Rudan, Igor] Univ Split, Fac Med, Split, Croatia. [Yengo, Loic; Froguel, Philippe; Bouatia-Naji, Nabila] Inst Pasteur, CNRS, UMR Genom & Mol Physiol Metab Dis 8199, F-59019 Lille, France. [Yengo, Loic] Univ Lille 1, Model Data Anal & Learning MODAL Team, Inst Natl Rech Informat & Automat INRIA Lille Nor, CNRS,UMR 8524,Lab Math, Lille, France. [Zhao, Jing Hua; Langenberg, Claudia; Wareham, Nicholas J.; Loos, Ruth J. F.] Addenbrookes Hosp, MRC Epidemiol Unit, Inst Metab Sci, Cambridge, England. [Demirkan, Ayse; Isaacs, Aaron; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Subdiv Genet Epidemiol, Rotterdam, Netherlands. [Feitosa, Mary F.; Kraja, Aldi; Zhang, Qunyuan; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA. [Malerba, Giovanni; Trabetti, Elisabetta] Univ Verona, Biol & Genet Sect, Dept Life & Reprod Sci, I-37100 Verona, Italy. [Lopez, Lorna M.; Davies, Gail; Gow, Alan J.; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland. [Lopez, Lorna M.; Gow, Alan J.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland. [van der Harst, Pim; Hillege, Hans L.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Li, Xinzhong] Univ London Imperial Coll Sci Technol & Med, Inst Clin Sci, Fac Med, London, England. [Kleber, Marcus E.] Ludwigshafen Risk & Cardiovasc Hlth LURIC, Freiburg, Germany. [Kleber, Marcus E.; Maerz, Winfried] Heidelberg Univ, Mannheim Inst Publ Hlth Social & Prevent Med, Med Fac Mannheim, Mannheim, Germany. [Hicks, Andrew A.; Pramstaller, Peter P.] European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy. [Hicks, Andrew A.; Pramstaller, Peter P.] Med Univ Lubeck, Affiliated Inst, Lubeck, Germany. [Nolte, Ilja M.; Stolk, Ronald P.; Snieder, Harold] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands. [Johansson, Asa] Univ Uppsala Hosp, Uppsala Clin Res Ctr, Uppsala, Sweden. [Johansson, Asa; Gyllensten, Ulf] Uppsala Univ, Dept Immunol Genet & Pathol, Rudbeck Lab, Uppsala, Sweden. [Murgia, Federico; Frogheri, Laura; Portas, Laura; Persico, Ivana; Pirastu, Mario; Tore, Silvia] CNR, Inst Populat Genet, Sassari, Italy. [Wild, Sarah H.; Kirin, Mirna; Wilson, James F.; Theodoratou, Evropi; Campbell, Harry; Rudan, Igor] Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Bakker, Stephan J. L.] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands. [Peden, John F.; Goel, Anuj; Ongen, Halit; Watkins, Hugh] Univ Oxford, Wellcome Trust Ctr Human Genet, Dept Cardiovasc Med, Oxford, England. [Steri, Maristella; Cucca, Francesco; Piras, Maria Grazia; Sanna, Serena] CNR, Ist Ric Genet & Biomed, Monserrato, Italy. [Tenesa, Albert] Univ Edinburgh, Roslin Inst, Edinburgh, Midlothian, Scotland. [Lagou, Vasiliki; Prokopenko, Inga] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Lagou, Vasiliki; Prokopenko, Inga] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Salo, Perttu; Perola, Markus; Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Mangino, Massimo; Spector, Tim D.] Kings Coll London, London WC2R 2LS, England. [Rose, Lynda M.; Ridker, Paul M.; Chasman, Daniel I.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Lehtimaki, Terho] Univ Tampere, Fimlab Labs, FIN-33101 Tampere, Finland. [Lehtimaki, Terho; Kaehoenen, Mika] Tampere Univ Hosp, Tampere, Finland. [Woodward, Owen M.] Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA. [Okada, Yukinori] RIKEN, Lab Stat Anal, Ctr Genom Med, Tokyo, Japan. [Okada, Yukinori] Univ Tokyo, Dept Allergy & Rheumatol, Grad Sch Med, Tokyo, Japan. [Mueller, Christian; Zeller, Tanja] Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, Hamburg, Germany. [Oldmeadow, Christopher; Holliday, Elizabeth G.; Attia, John] Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW 2300, Australia. [Putku, Margus; Esko, Tonu; Org, Elin; Laan, Maris; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia. [Czamara, Darina; Lucae, Susanne; Kloiber, Stefan] Max Planck Inst Psychiat, D-80804 Munich, Germany. [Kraft, Peter; Mudgal, Poorva] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Thun, Gian Andri; Imboden, Medea; Probst-Hensch, Nicole M.] Swiss Trop & Publ Hlth Inst, Basel, Switzerland. [Thun, Gian Andri; Imboden, Medea; Probst-Hensch, Nicole M.] Univ Basel, Basel, Switzerland. [Grotevendt, Anne; Nauck, Matthias; Budde, Kathrin] Ernst Moritz Arndt Univ Greifswald, Inst Clin Chem & Lab Med, Univ Med Greifswald, Greifswald, Germany. [Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Coresh, Josef; Kao, W. H. Linda] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Schmidt, Helena] Med Univ Graz, Inst Mol Biol & Biochem, Graz, Austria. [Schallert, Michael; Schmidt, Reinhold] Med Univ Graz, Dept Neurol, Sect Special Neurol, Graz, Austria. [Kubo, Michiaki] RIKEN, Lab Genotyping Dev, Ctr Genom Med, Yokohama, Kanagawa, Japan. [Nakamura, Yusuke] Univ Tokyo, Inst Med Sci, Lab Mol Med, Ctr Human Genome, Tokyo, Japan. [Tanaka, Toshihiro] RIKEN, Lab Cardiovasc Dis, Ctr Genom Med, Yokohama, Kanagawa, Japan. [Munroe, Patricia B.; Caulfield, Mark] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England. [Samani, Nilesh J.; Nelson, Christopher P.] Glenfield Gen Hosp, Leicester Natl Inst Hlth Res NIHR Biomed Res Unit, Leicester LE3 9QP, Leics, England. [Samani, Nilesh J.; Nelson, Christopher P.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England. [Jacobs, David R., Jr.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Liu, Kiang] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Ulivi, Sheila] IRCCS Burlo Garofolo Trieste, Intitute Maternal & Child Hlth, Trieste, Italy. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Med Genet Inst, Los Angeles, CA 90048 USA. [Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Dept Med, Seattle, WA USA. [Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Vollenweider, Peter; Waeber, Gerard] Univ Lausanne Hosp, Dept Med, Lausanne, Switzerland. [Devuyst, Olivier] Univ Zurich, Inst Physiol, Zurich Ctr Integrat Human Physiol ZIHP, Zurich, Switzerland. [Balkau, Beverley] Univ Paris 11, Unite Mixte Rech Sante UMRS 1018, Villejuif, France. [Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Dept Genom Common Dis, Sch Publ Hlth, Hammersmith Hosp, London, England. [Salumets, Andres] Competence Ctr Reprod Med & Biol, Tartu, Estonia. [Salumets, Andres] Univ Tartu, Dept Obstet & Gynecol, EE-50090 Tartu, Estonia. [Khaw, Kay Tee] Addenbrookes Hosp, Clin Gerontol Unit, Cambridge, England. [Wild, Philipp S.] Johannes Gutenberg Univ Mainz, Ctr Thrombosis & Hemostasis, Univ Med Ctr Mainz, D-55122 Mainz, Germany. [Wild, Philipp S.] Johannes Gutenberg Univ Mainz, Dept Med 2, Univ Med Ctr Mainz, D-55122 Mainz, Germany. [Scott, Rodney J.] Univ Newcastle, Sch Biomed Sci & Pharm, Newcastle, NSW 2300, Australia. [Viigimaa, Margus] Tallinn Univ Technol, Chair Med Phys, Dept Biomed Engn, Tallinn, Estonia. [Viigimaa, Margus] N Estonia Med Ctr, Ctr Cardiol, Tallinn, Estonia. [Bandinelli, Stefania] ASF, Geniatr Unit, Florence, Italy. [Lupo, Antonio] Univ Verona, Div Nephrol, Dept Med, I-37100 Verona, Italy. [Doering, Angela] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany. [Doering, Angela; Wichmann, H-Erich] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 1, Neuherberg, Germany. [Lattka, Eva; Waldenberger, Melanie; Klopp, Norman] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany. [Strauch, Konstantin] Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Wichmann, H-Erich] Univ Munich, Chair Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-80539 Munich, Germany. [Bruinenberg, Marcel] Univ Groningen, Univ Med Ctr Groningen, LifeLines Dept, Groningen, Netherlands. [Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Hammersmith Hosp, Fac Med, London, England. [Kooner, Jaspal S.; Zhang, Weihua; Chambers, John C.] Ealing Gen Hosp, Cath Lab Cardiol, Southall, Middx, England. [Zhang, Weihua; Chambers, John C.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Winkelmann, Bernhard R.] ClinPhen Study Ctr, Frankfurt, Germany. [Boehm, Bernhard O.] Univ Hosp, Div Endocrinol & Diabet, Dept Med, Ulm, Germany. [Penninx, Brenda W.; Smit, Johannes H.] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands. [Penninx, Brenda W.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands. [Penninx, Brenda W.] Leiden Univ, Dept Psychiat, Med Ctr, Leiden, Netherlands. [Curhan, Gary; Choi, Hyon] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA. [Plenge, Robert M.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Plenge, Robert M.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Plenge, Robert M.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Leach, Irene Mateo; van Gilst, Wiek H.] Univ Groningen, Univ Med Ctr Groningen, Div Expt Cardiol, Dept Cardiol, Groningen, Netherlands. [Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [von Eckardstein, Arnold] Univ Zurich Hosp, Inst Clin Chem, CH-8091 Zurich, Switzerland. [Nagaraja, Ramaiah] NIA, Lab Genet, Baltimore, MD 21224 USA. [Stumvoll, Michael; Toenjes, Anke] Univ Leipzig, Dept Med, D-04109 Leipzig, Germany. [Stumvoll, Michael; Toenjes, Anke] Univ Leipzig, Integrated Res & Treatment Ctr IFB Adipos Dis, D-04109 Leipzig, Germany. [Jula, Antti; Ripatti, Samuli] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Turku, Finland. [Perola, Markus; Ripatti, Samuli] Univ Helsinki, Inst Mol Med, Helsinki, Finland. [Shin, So-Youn; Ripatti, Samuli; Soranzo, Nicole] Wellcome Trust Sanger Inst, Cambridge, England. [Ridker, Paul M.; Chasman, Daniel I.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Kaehoenen, Mika] Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland. [Viikari, Jorma] Univ Turku, Dept Med, Turku, Finland. [Viikari, Jorma] Turku Univ Hosp, FIN-20520 Turku, Finland. [Hengstenberg, Christian] Univ Hosp Regensburg, Dept Internal Med 2, Regensburg, Germany. [Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Nalls, Michael A.; Singleton, Andrew B.] NIA, Mol Genet Sect, Neurogenet Lab, US NIH, Bethesda, MD 20892 USA. [Sharma, Pankaj] Univ London Imperial Coll Sci Technol & Med, Imperial Coll Cerebrovasc Res Unit, London, England. [Kamatani, Naoyuki] RIKEN, Lab Int Alliance, Ctr Genom Med, Yokohama, Kanagawa, Japan. [Burnier, Michel] Univ Lausanne Hosp, Nephrol Div, Dept Med, Lausanne, Switzerland. [Choi, Hyon] Boston Univ, Sch Med, Sect Rheumatol, Boston, MA 02118 USA. [Choi, Hyon] Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, Boston, MA 02118 USA. [Voelzke, Henry; Schipf, Sabine] Univ Med Greifswald, Inst Community Med, Greifswald, Germany. [Fornage, Myriam] Univ Texas Houston, Inst Mol Med, Houston, TX USA. [Fornage, Myriam] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Borecki, Ingrid B.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. [Gambaro, Giovanni] Catholic Univ, Renal Program, Inst Internal Med, Columbus Gemelli Univ Hosp, Rome, Italy. [Wolffenbuttel, Bruce H. R.] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands. [Maerz, Winfried] Synlab Ctr Lab Diagnost, Heidelberg, Germany. [Navis, Gerjan] Univ Groningen, Univ Med Ctr Groningen, Div Nephrol, Dept Internal Med, Groningen, Netherlands. [Toniolo, Daniela] CNR, Inst Mol Genet, I-27100 Pavia, Italy. [Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Bochud, Murielle] Univ Inst Social & Prevent Med, Lausanne, Switzerland. RP Kottgen, A (reprint author), Freiburg Univ Hosp, Renal Div, Freiburg, Germany. EM anna.koettgen@uniklinik-freiburg.de; veronique.vitart@igmm.ed.ac.uk; murielle.bochud@chuv.ch; christian.gieger@helmholtz-muenchen.de RI Colaus, PsyColaus/K-6607-2013; Farrington, Susan/C-7319-2013; Deary, Ian/C-6297-2009; Krumsiek, Jan/B-3961-2013; Pirastu, Nicola/G-4358-2011; Johnson, Andrew/G-6520-2013; Ulivi, Sheila/H-3700-2013; Gow, Alan/A-6070-2009; Rudan, Igor/I-1467-2012; Attia, John/F-5376-2013; Laan, Maris/A-4100-2011; Lagou, Vasiliki/N-8451-2013; mangino, massimo/F-5134-2011; Hayward, Caroline/M-8818-2016; BOUATIA-NAJI, NABILA/D-5863-2013; Dunlop, Malcolm/F-1973-2011; Yengo, Loic/D-2692-2017; Kolcic, Ivana/E-2713-2017; Feitosa, Mary/K-8044-2012; Hicks, Andrew/E-9518-2017; Gudnason, Vilmundur/K-6885-2015; Ripatti, Samuli/H-9446-2014; Wilson, James F/A-5704-2009; Polasek, Ozren/B-6002-2011; Montgomery, Grant/B-7148-2008; Rivadeneira, Fernando/O-5385-2015; Prokopenko, Inga/H-3241-2014; Tanaka, Toshihiro/J-9310-2014; Smith, Albert/K-5150-2015; Kubo, Michiaki/N-7947-2015; ruggiero, daniela/K-5638-2016; Schurmann, Claudia/L-1204-2016; Bochud, Murielle/A-3981-2010; Reischl, Eva/B-9311-2013; Waldenberger, Melanie/B-5355-2014; Gasparini, Paolo/B-6173-2014; d'Adamo, Adamo Pio/G-4064-2011; Theodoratou, Evropi/C-3430-2014; Singleton, Andrew/C-3010-2009; Yang, Qiong/G-5438-2014; Pramstaller, Peter/C-2357-2008; Johansson, Asa/G-5270-2011; Boehm, Bernhard/F-8750-2015; Salumets, Andres/J-2278-2015; Bakker, Stephan/J-4023-2015 OI Ulivi, Sheila/0000-0003-3606-835X; Gow, Alan/0000-0002-3320-4531; Rudan, Igor/0000-0001-6993-6884; Attia, John/0000-0001-9800-1308; Laan, Maris/0000-0002-8519-243X; Kleber, Marcus/0000-0003-0663-7275; Martin, Nicholas/0000-0003-4069-8020; Dehghan, Abbas/0000-0001-6403-016X; Watkins, Hugh/0000-0002-5287-9016; Theis, Fabian/0000-0002-2419-1943; Steri, Anna Maristella/0000-0001-5869-3872; Soranzo, Nicole/0000-0003-1095-3852; Gieger, Christian/0000-0001-6986-9554; Wolffenbuttel, Bruce H.R./0000-0001-9262-6921; Org, Elin/0000-0003-1451-9375; Esko, Tonu/0000-0003-1982-6569; Malerba, Giovanni/0000-0001-8705-8560; piras, maria grazia/0000-0001-9004-0900; sanna, serena/0000-0002-3768-1749; Kloiber, Stefan/0000-0002-6838-4114; mangino, massimo/0000-0002-2167-7470; Hayward, Caroline/0000-0002-9405-9550; Dunlop, Malcolm/0000-0002-3033-5851; Yengo, Loic/0000-0002-4272-9305; Kolcic, Ivana/0000-0001-7918-6052; Feitosa, Mary/0000-0002-0933-2410; Hicks, Andrew/0000-0001-6320-0411; Thun, Gian Andri/0000-0003-4436-3455; Pirastu, Nicola/0000-0002-5363-3886; Bouatia-Naji, Nabila/0000-0001-5424-2134; Navarro, Pau/0000-0001-5576-8584; Gudnason, Vilmundur/0000-0001-5696-0084; Ripatti, Samuli/0000-0002-0504-1202; Wilson, James F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862; Montgomery, Grant/0000-0002-4140-8139; Rivadeneira, Fernando/0000-0001-9435-9441; Prokopenko, Inga/0000-0003-1624-7457; Tanaka, Toshihiro/0000-0001-6201-9784; Smith, Albert/0000-0003-1942-5845; ruggiero, daniela/0000-0003-3898-7827; Schurmann, Claudia/0000-0003-4158-9192; Bochud, Murielle/0000-0002-5727-0218; Reischl, Eva/0000-0003-4055-8060; Waldenberger, Melanie/0000-0003-0583-5093; d'Adamo, Adamo Pio/0000-0001-9367-4909; Theodoratou, Evropi/0000-0001-5887-9132; Johansson, Asa/0000-0002-2915-4498; Salumets, Andres/0000-0002-1251-8160; Bakker, Stephan/0000-0003-3356-6791 FU Biotechnology and Biological Sciences Research Council [BB/F019394/1]; Cancer Research UK [12076, 14136]; Chief Scientist Office [CZB/4/710]; Intramural NIH HHS [Z01 AG000954-06]; Medical Research Council [G0401527, G0600237, G0700704, G1000143, G1002084, G9521010, MC_PC_U127592696, MC_U106179471, MC_U106188470, MC_U127527198, MC_U127592696, MR/K006584/1, MR/K026992/1]; NCATS NIH HHS [UL1 TR000124]; NCI NIH HHS [P01 CA087969, R01 CA047988]; NCRR NIH HHS [K12 RR023250, M01 RR016500, UL1 RR025005]; NHGRI NIH HHS [U01 HG004402, U01 HG004424, U01 HG004446, U01 HG004729]; NHLBI NIH HHS [HHSN268201100008C, HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, HHSN268201200036C, N01 HC025195, N01 HC045134, N01 HC095170, N01 HC095171, N01 HC095172, N01HC05187, N01HC45204, N01HC45205, N01HC48047, N01HC48048, N01HC48049, N01HC48050, N01HC55222, N01HC75150, N01HC85079, N01HC85086, N01HC95095, N02HL64278, R01 HL043851, R01 HL059367, R01 HL080295, R01 HL084099, R01 HL086694, R01 HL087641, R01 HL087652, R01 HL088119, R01 HL105756, U01 HL069757, U01 HL072515, U01 HL084756]; NIA NIH HHS [N01AG12100, N01AG12109, R01 AG015928, R01 AG018728, R01 AG020098, R01 AG023629, R01 AG027058]; NIAAA NIH HHS [K05 AA017688, P50 AA011998, R01 AA007535, R01 AA013320, R01 AA013321, R01 AA013326, R01 AA014041]; NIAMS NIH HHS [P60 AR047785, R01 AR056291, R21 AR056042]; NIDA NIH HHS [R01 DA012854]; NIDDK NIH HHS [P30 DK063491, P30 DK072488, P30 DK079637, P60 DK079637]; NIGMS NIH HHS [U01 GM074518]; NIMH NIH HHS [R01 MH066206]; Wellcome Trust [090532] NR 41 TC 163 Z9 174 U1 6 U2 83 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD FEB PY 2013 VL 45 IS 2 BP 145 EP 154 DI 10.1038/ng.2500 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 081PB UT WOS:000314333000009 PM 23263486 ER PT J AU Lu, Y Vitart, V Burdon, KP Khor, CC Bykhovskaya, Y Mirshahi, A Hewitt, AW Koehn, D Hysi, PG Ramdas, WD Zeller, T Vithana, EN Cornes, BK Tay, WT Tai, ES Cheng, CY Liu, JJ Foo, JN Saw, SM Thorleifsson, G Stefansson, K Dimasi, DP Mills, RA Mountain, J Ang, W Hoehn, R Verhoeven, VJM Grus, F Wolfs, R Castagne, R Lackner, KJ Springelkamp, H Yang, J Jonasson, F Leung, DYL Chen, LJ Tham, CCY Rudan, I Vatavuk, Z Hayward, C Gibson, J Cree, AJ MacLeod, A Ennis, S Polasek, O Campbell, H Wilson, JF Viswanathan, AC Fleck, B Li, XH Siscovick, D Taylor, KD Rotter, JI Yazar, S Ulmer, M Li, J Yaspan, BL Ozel, AB Richards, JE Moroi, SE Haines, JL Kang, JH Pasquale, LR Allingham, RR Ashley-Koch, A Mitchell, P Wang, JJ Wright, AF Pennell, C Spector, TD Young, TL Klaver, CCW Martin, NG Montgomery, GW Anderson, MG Aung, T Willoughby, CE Wiggs, JL Pang, CP Thorsteinsdottir, U Lotery, AJ Hammond, CJ van Duijn, CM Hauser, MA Rabinowitz, YS Pfeiffer, N Mackey, DA Craig, JE Macgregor, S Wong, TY AF Lu, Yi Vitart, Veronique Burdon, Kathryn P. Khor, Chiea Chuen Bykhovskaya, Yelena Mirshahi, Alireza Hewitt, Alex W. Koehn, Demelza Hysi, Pirro G. Ramdas, Wishal D. Zeller, Tanja Vithana, Eranga N. Cornes, Belinda K. Tay, Wan-Ting Tai, E. Shyong Cheng, Ching-Yu Liu, Jianjun Foo, Jia-Nee Saw, Seang Mei Thorleifsson, Gudmar Stefansson, Kari Dimasi, David P. Mills, Richard A. Mountain, Jenny Ang, Wei Hoehn, Rene Verhoeven, Virginie J. M. Grus, Franz Wolfs, Roger Castagne, Raphaele Lackner, Karl J. Springelkamp, Henriet Yang, Jian Jonasson, Fridbert Leung, Dexter Y. L. Chen, Li J. Tham, Clement C. Y. Rudan, Igor Vatavuk, Zoran Hayward, Caroline Gibson, Jane Cree, Angela J. MacLeod, Alex Ennis, Sarah Polasek, Ozren Campbell, Harry Wilson, James F. Viswanathan, Ananth C. Fleck, Brian Li, Xiaohui Siscovick, David Taylor, Kent D. Rotter, Jerome I. Yazar, Seyhan Ulmer, Megan Li, Jun Yaspan, Brian L. Ozel, Ayse B. Richards, Julia E. Moroi, Sayoko E. Haines, Jonathan L. Kang, Jae H. Pasquale, Louis R. Allingham, R. Rand Ashley-Koch, Allison Mitchell, Paul Wang, Jie Jin Wright, Alan F. Pennell, Craig Spector, Timothy D. Young, Terri L. Klaver, Caroline C. W. Martin, Nicholas G. Montgomery, Grant W. Anderson, Michael G. Aung, Tin Willoughby, Colin E. Wiggs, Janey L. Pang, Chi P. Thorsteinsdottir, Unnur Lotery, Andrew J. Hammond, Christopher J. van Duijn, Cornelia M. Hauser, Michael A. Rabinowitz, Yaron S. Pfeiffer, Norbert Mackey, David A. Craig, Jamie E. Macgregor, Stuart Wong, Tien Y. CA NEIGHBOR Consortium TI Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus SO NATURE GENETICS LA English DT Article ID OPEN-ANGLE GLAUCOMA; OSTEOGENESIS IMPERFECTA; OCULAR HYPERTENSION; ASIAN POPULATIONS; COMMON VARIANTS; BLUE SCLERA; GENE; MUTATIONS; COLLAGEN; IDENTIFICATION AB Central corneal thickness (CCT) is associated with eye conditions including keratoconus and glaucoma. We performed a meta-analysis on >20,000 individuals in European and Asian populations that identified 16 new loci associated with CCT at genome-wide significance (P < 5 x 10(-8)). We further showed that 2 CCT-associated loci, FOXO1 and FNDC3B, conferred relatively large risks for keratoconus in 2 cohorts with 874 cases and 6,085 controls (rs2721051 near FOXO1 had odds ratio (OR) = 1.62, 95% confidence interval (Cl) = 1.4-1.88, P = 2.7 x 10(-10), and rs4894535 in FNDC3B had OR = 1.47,95% Cl = 1.29-1.68, P = 4.9 x 10(-9)). FNDC3B was also associated with primary open-angle glaucoma (P = 5.6 x 10(-4); tested in 3 cohorts with 2,979 cases and 7,399 controls). Further analyses implicate the collagen and extracellular matrix pathways in the regulation of CCT. C1 [Lu, Yi; Martin, Nicholas G.; Montgomery, Grant W.; Macgregor, Stuart] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Vitart, Veronique; Hayward, Caroline; Wright, Alan F.] Univ Edinburgh, Med Res Council MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. [Burdon, Kathryn P.; Dimasi, David P.; Mills, Richard A.; Craig, Jamie E.] Flinders Univ S Australia, Dept Ophthalmol, Flinders Med Ctr, Adelaide, SA 5001, Australia. [Khor, Chiea Chuen; Vithana, Eranga N.; Cornes, Belinda K.; Tay, Wan-Ting; Cheng, Ching-Yu; Aung, Tin] Singapore Eye Res Inst, Singapore, Singapore. [Khor, Chiea Chuen; Vithana, Eranga N.; Cheng, Ching-Yu; Aung, Tin] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117595, Singapore. [Khor, Chiea Chuen; Tai, E. Shyong; Cheng, Ching-Yu; Liu, Jianjun; Saw, Seang Mei; Wong, Tien Y.] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore. [Khor, Chiea Chuen; Liu, Jianjun; Foo, Jia-Nee] ASTAR, Genome Inst Singapore, Human Genet, Singapore, Singapore. [Bykhovskaya, Yelena; Rabinowitz, Yaron S.] Cedars Sinai Med Ctr, Dept Surg, Regenerat Med Inst, Div Surg Res, Los Angeles, CA 90048 USA. [Mirshahi, Alireza; Hoehn, Rene; Grus, Franz; Pfeiffer, Norbert] Univ Med Ctr Mainz, Dept Ophthalmol, Mainz, Germany. [Hewitt, Alex W.; Mackey, David A.] Univ Melbourne, Ctr Eye Res Australia, Royal Victorian Eye & Ear Hosp, Melbourne, Vic, Australia. [Hewitt, Alex W.; Yazar, Seyhan; Mackey, David A.] Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Visual Sci, Perth, WA 6009, Australia. [Koehn, Demelza; Anderson, Michael G.] Univ Iowa, Dept Mol Physiol & Biophys, Iowa City, IA USA. [Hysi, Pirro G.; Spector, Timothy D.; Hammond, Christopher J.] Kings Coll London, Dept Twin Res & Genet Epidemiol, Sch Med, St Thomas Hosp, London WC2R 2LS, England. [Ramdas, Wishal D.; Verhoeven, Virginie J. M.; Wolfs, Roger; Springelkamp, Henriet; Klaver, Caroline C. W.] Erasmus MC, Dept Ophthalmol, Rotterdam, Netherlands. [Ramdas, Wishal D.; Verhoeven, Virginie J. M.; Wolfs, Roger; Springelkamp, Henriet; Klaver, Caroline C. W.; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Zeller, Tanja] Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, Hamburg, Germany. [Tai, E. Shyong] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 117595, Singapore. [Cheng, Ching-Yu] Duke Natl Univ Singapore, Grad Sch Med, Ctr Quantitat Med, Off Clin Sci, Singapore, Singapore. [Thorleifsson, Gudmar; Stefansson, Kari; Thorsteinsdottir, Unnur] deCODE Genet, Reykjavik, Iceland. [Stefansson, Kari; Jonasson, Fridbert; Thorsteinsdottir, Unnur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Mountain, Jenny] Univ Western Australia, Telethon Inst Child Hlth Res, Ctr Child Hlth Res, Perth, WA 6009, Australia. [Ang, Wei; Pennell, Craig] Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA 6009, Australia. [Castagne, Raphaele] Univ Paris 06, INSERM, UMRS 937, Paris, France. [Castagne, Raphaele] Sch Med, Paris, France. [Lackner, Karl J.] Univ Med Ctr Mainz, Mainz, Germany. [Yang, Jian] Univ Queensland, Diamantina Inst, Princess Alexandra Hosp, Brisbane, Qld, Australia. [Jonasson, Fridbert] Landspitali Natl Univ Hosp, Dept Ophthalmol, Reykjavik, Iceland. [Leung, Dexter Y. L.; Chen, Li J.; Tham, Clement C. Y.; Pang, Chi P.] Chinese Univ Hong Kong, Hong Kong Eye Hosp, Dept Ophthalmol & Visual Sci, Hong Kong, Hong Kong, Peoples R China. [Rudan, Igor; Campbell, Harry; Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Rudan, Igor; Polasek, Ozren] Univ Split, Sch Med, Croatian Ctr Global Hlth, Split, Croatia. [Vatavuk, Zoran] Hosp Sestre Milosrdnice, Dept Ophthalmol, Zagreb, Croatia. [Gibson, Jane; Ennis, Sarah] Univ Southampton, Fac Med, Genet Epidemiol & Genom Informat Grp, Southampton Gen Hosp, Southampton SO9 5NH, Hants, England. [Cree, Angela J.; Lotery, Andrew J.] Univ Southampton, Fac Med, Clin Neurosci Res Grp, Southampton Gen Hosp, Southampton SO9 5NH, Hants, England. [MacLeod, Alex; Lotery, Andrew J.] Southampton Gen Hosp, Southampton Eye Unit, Southampton SO9 4XY, Hants, England. [Polasek, Ozren] Univ Split, Dept Publ Hlth, Split, Croatia. [Viswanathan, Ananth C.] Moorfields Eye Hosp Natl Hlth Serv NHS Fdn Trust, Natl Inst Hlth Res NIHR Biomed Res Ctr, London, England. [Viswanathan, Ananth C.] Univ Coll London UCL Inst Ophthalmol, London, England. [Fleck, Brian] Princess Alexandra Eye Pavil, Edinburgh, Midlothian, Scotland. [Li, Xiaohui; Taylor, Kent D.; Rotter, Jerome I.] Cedars Sinai Med Ctr, Med Genet Inst, Los Angeles, CA 90048 USA. [Siscovick, David] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Ulmer, Megan; Ashley-Koch, Allison; Hauser, Michael A.] Duke Univ, Dept Med, Durham, NC USA. [Li, Jun; Ozel, Ayse B.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. [Yaspan, Brian L.; Haines, Jonathan L.] Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Nashville, TN 37212 USA. [Richards, Julia E.; Moroi, Sayoko E.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. [Kang, Jae H.; Pasquale, Louis R.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Pasquale, Louis R.; Wiggs, Janey L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Allingham, R. Rand; Wong, Tien Y.] Duke Univ, Sch Med, Dept Ophthalmol, Durham, NC USA. [Mitchell, Paul; Wang, Jie Jin] Univ Sydney, Ctr Vis Res, Dept Ophthalmol, Westmead, NSW 2145, Australia. [Mitchell, Paul; Wang, Jie Jin] Univ Sydney, Westmead Millennium Inst, Westmead, NSW 2145, Australia. [Young, Terri L.] Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC USA. [Young, Terri L.] Duke Natl Univ Singapore, Singapore, Singapore. [Anderson, Michael G.] Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA USA. [Aung, Tin] Singapore Natl Eye Ctr, Singapore, Singapore. [Willoughby, Colin E.] Queens Univ Belfast, Ctr Vis & Vasc Sci, Belfast, Antrim, North Ireland. [Rabinowitz, Yaron S.] Cedars Sinai Med Ctr, Cornea Genet Eye Inst, Los Angeles, CA 90048 USA. RP Macgregor, S (reprint author), Queensland Inst Med Res, Brisbane, Qld 4006, Australia. EM stuart.macgregor@qimr.edu.au; tien_yin_wong@nuhs.edu.sg RI Klaver, Caroline/A-2013-2016; Foo, Jia Nee/D-6069-2014; Rudan, Igor/I-1467-2012; Yang, Jian/A-5852-2010; Mackey, David/H-5340-2014; Hayward, Caroline/M-8818-2016; Pang, Chi/I-5388-2014; Wang, Jie Jin/P-1499-2014; Mitchell, Paul/P-1498-2014; Wilson, James F/A-5704-2009; Polasek, Ozren/B-6002-2011; Montgomery, Grant/B-7148-2008; Haines, Jonathan/C-3374-2012; Macgregor, Stuart/C-6442-2009; Hewitt, Alex/D-1936-2013; Cheng, Ching-Yu/K-7017-2013; Burdon, Kathryn/A-5026-2009; Anderson, Michael/B-4580-2009; Chen, Li Jia/I-5078-2014 OI Hohn, Rene /0000-0003-2870-1469; Ashley-Koch, Allison/0000-0001-5409-9155; Khor, Chiea Chuen/0000-0002-1128-4729; Hammond, Christopher/0000-0002-3227-2620; Tai, E Shyong/0000-0003-2929-8966; Martin, Nicholas/0000-0003-4069-8020; Foo, Jia Nee/0000-0001-9899-2308; Rudan, Igor/0000-0001-6993-6884; Yang, Jian/0000-0003-2001-2474; Mackey, David/0000-0001-7914-4709; Hayward, Caroline/0000-0002-9405-9550; Yazar, Seyhan/0000-0003-0994-6196; Carnes, Megan/0000-0002-7270-132X; Leung, Dexter/0000-0002-9830-3143; Wang, Jie Jin/0000-0001-9491-4898; Wilson, James F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862; Montgomery, Grant/0000-0002-4140-8139; Macgregor, Stuart/0000-0001-6731-8142; Hewitt, Alex/0000-0002-5123-5999; Cheng, Ching-Yu/0000-0003-0655-885X; Burdon, Kathryn/0000-0001-8217-1249; Anderson, Michael/0000-0001-5730-6105; Chen, Li Jia/0000-0003-3500-5840 FU Chief Scientist Office [CZB/4/438, CZB/4/710]; Department of Health [SRF/01/010]; Medical Research Council [MC_PC_U127561128]; NCATS NIH HHS [UL1 TR000124]; NEI NIH HHS [F32 EY021436, R01 EY018246, R01 EY018825, R01 EY022305] NR 49 TC 84 Z9 87 U1 4 U2 51 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 2013 VL 45 IS 2 BP 155 EP 163 DI 10.1038/ng.2506 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 081PB UT WOS:000314333000010 PM 23291589 ER PT J AU Huyghe, JR Jackson, AU Fogarty, MP Buchkovich, ML Stancakova, A Stringham, HM Sim, XL Yang, LY Fuchsberger, C Cederberg, H Chines, PS Teslovich, TM Romm, JM Ling, H McMullen, I Ingersoll, R Pugh, EW Doheny, KF Neale, BM Daly, MJ Kuusisto, J Scott, LJ Kang, HM Collins, FS Abecasis, GR Watanabe, RM Boehnke, M Laakso, M Mohlke, KL AF Huyghe, Jeroen R. Jackson, Anne U. Fogarty, Marie P. Buchkovich, Martin L. Stancakova, Alena Stringham, Heather M. Sim, Xueling Yang, Lingyao Fuchsberger, Christian Cederberg, Henna Chines, Peter S. Teslovich, Tanya M. Romm, Jane M. Ling, Hua McMullen, Ivy Ingersoll, Roxann Pugh, Elizabeth W. Doheny, Kimberly F. Neale, Benjamin M. Daly, Mark J. Kuusisto, Johanna Scott, Laura J. Kang, Hyun Min Collins, Francis S. Abecasis, Goncalo R. Watanabe, Richard M. Boehnke, Michael Laakso, Markku Mohlke, Karen L. TI Exome array analysis identifies new loci and low-frequency variants influencing insulin processing and secretion SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; COMMON VARIANTS; GLYCEMIC TRAITS; GLUCOSE; PROTEIN; POPULATION; EXPRESSION; RELEASE; GTPASES AB Insulin secretion has a crucial role in glucose homeostasis, and failure to secrete sufficient insulin is a hallmark of type 2 diabetes. Genome-wide association studies (GWAS) have identified loci contributing to insulin processing and secretion(1,2); however, a substantial fraction of the genetic contribution remains undefined. To examine low-frequency (minor allele frequency (MAF) 0.5-5%) and rare (MAF < 0.5%) nonsynonymous variants, we analyzed exome array data in 8,229 nondiabetic Finnish males using the Illumina HumanExome Beadchip. We identified low-frequency coding variants associated with fasting proinsulin concentrations at the SGSM2 and MADD GWAS loci and three new genes with low-frequency variants associated with fasting proinsulin or insulinogenic index: TBC1D30, KANK1 and PAM. We also show that the interpretation of single-variant and gene-based tests needs to consider the effects of noncoding SNPs both nearby and megabases away. This study demonstrates that exome array genotyping is a valuable approach to identify low-frequency variants that contribute to complex traits. C1 [Huyghe, Jeroen R.; Jackson, Anne U.; Stringham, Heather M.; Sim, Xueling; Yang, Lingyao; Fuchsberger, Christian; Teslovich, Tanya M.; Scott, Laura J.; Kang, Hyun Min; Abecasis, Goncalo R.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Fogarty, Marie P.; Buchkovich, Martin L.; Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Stancakova, Alena; Cederberg, Henna; Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio, Finland. [Stancakova, Alena; Cederberg, Henna; Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Chines, Peter S.; Collins, Francis S.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. [Romm, Jane M.; Ling, Hua; McMullen, Ivy; Ingersoll, Roxann; Pugh, Elizabeth W.; Doheny, Kimberly F.] Johns Hopkins Univ, Ctr Inherited Dis Res, Baltimore, MD USA. [Neale, Benjamin M.; Daly, Mark J.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Neale, Benjamin M.; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Neale, Benjamin M.; Daly, Mark J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. RP Mohlke, KL (reprint author), Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. EM mohlke@med.unc.edu RI Abecasis, Goncalo/B-7840-2010; OI Fuchsberger, Christian/0000-0002-5918-8947; Abecasis, Goncalo/0000-0003-1509-1825 FU Academy of Finland [124243]; Finnish Heart Foundation; Finnish Diabetes Foundation; Tekes [1510/31/06]; Commission of the European Community [HEALTH-F2-2007-201681]; US National Institutes of Health [DK093757, DK072193, DK062370, 1Z01 HG000024] FX This study was supported by the Academy of Finland (contract 124243) (to M.L.), the Finnish Heart Foundation (to M.L.), the Finnish Diabetes Foundation (to M.L.), Tekes (contract 1510/31/06) (to M.L.), the Commission of the European Community (HEALTH-F2-2007-201681) (to M.L.) and US National Institutes of Health grants DK093757 (to K.L.M.), DK072193 (to K.L.M.), DK062370 (to M.B.) and 1Z01 HG000024 (to F.S.C.). Genotyping was conducted at the Genetic Resources Core Facility (GRCF) at the Johns Hopkins Institute of Genetic Medicine. NR 31 TC 120 Z9 122 U1 1 U2 25 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 2013 VL 45 IS 2 BP 197 EP 201 DI 10.1038/ng.2507 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 081PB UT WOS:000314333000016 PM 23263489 ER PT J AU Kornblum, C Nicholls, TJ Haack, TB Scholer, S Peeva, V Danhauser, K Hallmann, K Zsurka, G Rorbach, J Iuso, A Wieland, T Sciacco, M Ronchi, D Comi, GP Moggio, M Quinzii, CM DiMauro, S Calvo, SE Mootha, VK Klopstock, T Strom, TM Meitinger, T Minczuk, M Kunz, WS Prokisch, H AF Kornblum, Cornelia Nicholls, Thomas J. Haack, Tobias B. Schoeler, Susanne Peeva, Viktoriya Danhauser, Katharina Hallmann, Kerstin Zsurka, Gabor Rorbach, Joanna Iuso, Arcangela Wieland, Thomas Sciacco, Monica Ronchi, Dario Comi, Giacomo P. Moggio, Maurizio Quinzii, Catarina M. DiMauro, Salvatore Calvo, Sarah E. Mootha, Vamsi K. Klopstock, Thomas Strom, Tim M. Meitinger, Thomas Minczuk, Michal Kunz, Wolfram S. Prokisch, Holger TI Loss-of-function mutations in MGME1 impair mtDNA replication and cause multisystemic mitochondrial disease SO NATURE GENETICS LA English DT Article ID PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; BASE EXCISION-REPAIR; DNA DEPLETION; PROTEIN; DEFICIENCY; GENE; POLG; MAINTENANCE; DELETIONS; TWINKLE AB Known disease mechanisms in mitochondria! DNA (mtDNA) maintenance disorders alter either the mitochondrial replication machinery (POLG, POLG2 and C10orf2)(1-3) or the biosynthesis pathways of deoxyribonucleoside 5'-triphosphates for mtDNA synthesis(4-11). However, in many of these disorders, the underlying genetic defect has yet to be discovered. Here, we identify homozygous nonsense and missense mutations in the orphan gene C20orf72 in three families with a mitochondrial syndrome characterized by external ophthalmoplegia, emaciation and respiratory failure. Muscle biopsies showed mtDNA depletion and multiple mtDNA deletions. C20orf72, hereafter MGME1 (mitochondrial genome maintenance exonuclease 1), encodes a mitochondria! RecB-type exonuclease belonging to the PD-(D/E)XK nuclease superfamily. We show that MGME1 cleaves single-stranded DNA and processes DNA flap substrates. Fibroblasts from affected individuals do not repopulate after chemically induced mtDNA depletion. They also accumulate intermediates of stalled replication and show increased levels of 7S DNA, as do MGME1-depleted cells. Thus, we show that MGME1-mediated mtDNA processing is essential for mitochondrial genome maintenance. C1 [Kornblum, Cornelia] Univ Bonn, Dept Neurol, Med Ctr, Bonn, Germany. [Nicholls, Thomas J.; Rorbach, Joanna; Minczuk, Michal] MRC, Mitochondrial Biol Unit, Cambridge, England. [Haack, Tobias B.; Danhauser, Katharina; Iuso, Arcangela; Wieland, Thomas; Strom, Tim M.; Meitinger, Thomas; Prokisch, Holger] Tech Univ Munich, Inst Human Genet, D-80290 Munich, Germany. [Haack, Tobias B.; Danhauser, Katharina; Iuso, Arcangela; Wieland, Thomas; Strom, Tim M.; Meitinger, Thomas; Prokisch, Holger] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Munich, Germany. [Schoeler, Susanne; Peeva, Viktoriya; Hallmann, Kerstin; Zsurka, Gabor; Kunz, Wolfram S.] Univ Bonn, Med Ctr, Dept Epileptol, Bonn, Germany. [Schoeler, Susanne; Peeva, Viktoriya; Hallmann, Kerstin; Zsurka, Gabor; Kunz, Wolfram S.] Univ Bonn, Med Ctr, Life & Brain Ctr, Bonn, Germany. [Sciacco, Monica; Moggio, Maurizio] Univ Milan, Fdn Ist Ricovero & Cura Carattere Sci IRCCS Ca Gr, Neuromuscular Unit, Osped Maggiore Policlin,Ctr Dino Ferrari, Milan, Italy. [Ronchi, Dario; Comi, Giacomo P.] Univ Milan, Fdn IRCCS Ca Granda, Neurol Unit, Osped Maggiore Policlin,Ctr Dino Ferrari, Milan, Italy. [Quinzii, Catarina M.; DiMauro, Salvatore] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA. [Calvo, Sarah E.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol & Med, Boston, MA 02114 USA. [Calvo, Sarah E.; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Calvo, Sarah E.; Mootha, Vamsi K.] Broad Inst, Cambridge, MA USA. [Klopstock, Thomas] Univ Munich, Dept Neurol, Friedrich Baur Inst, D-80539 Munich, Germany. RP Minczuk, M (reprint author), MRC, Mitochondrial Biol Unit, Cambridge, England. EM michal.minczuk@mrc-mbu.cam.ac.uk; wolfram.kunz@ukb.uni-bonn.de RI Prokisch, Holger/N-8964-2013; Meitinger, Thomas/O-1318-2015; Comi, Giacomo /K-5702-2016; Ronchi, Dario/K-8011-2016 OI Comi, Giacomo /0000-0002-1383-5248; Ronchi, Dario/0000-0002-6093-9816 FU Medical Research Council UK; German Bundesministerium fur Bildung und Forschung (BMBF) [SysMBo 0315494A]; E-Rare project GENOMIT [01GM1207]; German Network for mitochondrial disorders (mitoNET) [mitoNET 01GM0862, 01GM1113A, mitoNET 01GM0867, 01GM1113C, mitoNET 01GM0868]; Deutsche Forschungsgemeinschaft [SFB TR3 All, D12]; US National Institutes of Health [GM077465, GM097136]; Associazione Amici del Centro Dino Ferrari; University of Milan; Telethon project [GTB07001ER]; Eurobiobank project [QLTR-2001-02769]; Criobanca Automatizzata di Materiale Biologico [R.F.02.187] FX T.J.N. and M. Minczuk are grateful to S. Wood and I. Holt for stimulating discussions during the course of this work We are grateful to S. Beyer, K. Kappes-Horn, M. Stepien-Mering, E. Botz and R. Hellinger for technical assistance. We thank R. Wiesner (University of Cologne) for providing the TFAM antibody. This work was supported by the Medical Research Council UK (T.J.N., J.R. and M. Minczuk) and the German Bundesministerium fur Bildung und Forschung (BMBF) through funding of the Systems Biology of Metabotypes grant (SysMBo 0315494A), the E-Rare project GENOMIT (01GM1207) and the German Network for mitochondrial disorders (mitoNET), including C.K., T.K. (mitoNET 01GM0862 and 01GM1113A), T.M., H.P. (mitoNET 01GM0867 and 01GM1113C) and W.S.K. (mitoNET 01GM0868). W.S.K. was funded by the Deutsche Forschungsgemeinschaft (SFB TR3 All and D12). V.K.M. was supported by grants from the US National Institutes of Health (GM077465 and GM097136). The financial support of Associazione Amici del Centro Dino Ferrari, University of Milan, the Telethon project GTB07001ER, the Eurobiobank project QLTR-2001-02769 and R.F.02.187 Criobanca Automatizzata di Materiale Biologico to M.M. and M.S. are gratefully acknowledged. NR 28 TC 58 Z9 60 U1 3 U2 19 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 2013 VL 45 IS 2 BP 214 EP 219 DI 10.1038/ng.2501 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 081PB UT WOS:000314333000019 PM 23313956 ER PT J AU Liu, S Ren, JA Hong, ZW Yan, DS Gu, GS Han, G Wang, GF Ren, HJ Chen, J Li, JS AF Liu, Song Ren, Jianan Hong, Zhiwu Yan, Dongsheng Gu, Guosheng Han, Gang Wang, Gefei Ren, Huajian Chen, Jun Li, Jieshou TI Efficacy of Erythropoietin Combined With Enteral Nutrition for the Treatment of Anemia in Crohn's Disease: A Prospective Cohort Study SO NUTRITION IN CLINICAL PRACTICE LA English DT Article DE Crohn disease; anemia; erythropoietin; enteral nutrition; biological markers ID INFLAMMATORY-BOWEL-DISEASE; INTRAVENOUS IRON SUCROSE; DEFICIENCY ANEMIA; OXIDATIVE STRESS; FERROUS FUMARATE; MANAGEMENT; DIAGNOSIS; TRIPTOLIDE; COLITIS; IBD AB Background: Anemia is a common and serious complication in patients with inflammatory bowel disease. The present study was dedicated to evaluate the therapeutic efficacy of erythropoietin (EPO) combined with enteral nutrition (EN) in anemic Crohn's disease (CD) patients, in terms of hemoglobin level, treatment success rate, adverse events, and predictor of this therapy. Materials and Methods: We performed a prospective study in CD patients. On the basis of hemoglobin level, all enrolled patients were divided into anemic and nonanemic groups. The anemic group was further divided into EPO and non-EPO subgroups, depending on whether EPO was prescribed. Hematological and other parameters were measured initially and in the first 4 weeks after starting treatment. Results: In total, 109 patients (49 nonanemic and 60 anemic, including 38 EPO and 22 non-EPO) were included. The prevalence of anemia in CD was 55.05%. Age, disease behavior, Crohn's Disease Activity Index scores, C-reactive protein, and erythrocyte sedimentation rate were significantly different between anemic and nonanemic groups. An increase in hemoglobin level and a significant decrease in C-reactive protein level were observed in the EPO treatment group. Treatment success rate was 63.16% in the EPO group, whereas none of patients achieved treatment success in the non-EPO group. Conclusion: EPO combined with EN can improve the hemoglobin level in anemic CD patients. (Nutr Clin Pract. 2013;28:120-127) C1 [Liu, Song; Ren, Jianan; Hong, Zhiwu; Yan, Dongsheng; Gu, Guosheng; Wang, Gefei; Ren, Huajian; Chen, Jun; Li, Jieshou] Nanjing Univ, Sch Med, Jinling Hosp, Dept Gen Surg, Nanjing 210002, Jiangsu, Peoples R China. [Han, Gang] Jilin Univ, Gen Surg Ctr, Dept Gen Surg, Affiliated Hosp 2, Changchun, Jilin, Peoples R China. [Liu, Song] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Liu, Song] Harvard Univ, Sch Med, Boston, MA USA. RP Ren, JA (reprint author), Nanjing Univ, Sch Med, Jinling Hosp, Dept Gen Surg, 305 E Zhongshan Rd, Nanjing 210002, Jiangsu, Peoples R China. EM jiananr@gmail.com OI LIU, SONG/0000-0002-4780-9697; Ren, Jianan/0000-0002-7978-8093 FU Climb Program in Natural Science Foundation of Jiangsu Province for Distinguished Scholars [BK2010017] FX This work was supported by grants from the Climb Program in Natural Science Foundation of Jiangsu Province for Distinguished Scholars (No. BK2010017). NR 30 TC 8 Z9 8 U1 1 U2 17 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0884-5336 J9 NUTR CLIN PRACT JI Nutr. Clin. Pract. PD FEB PY 2013 VL 28 IS 1 BP 120 EP 127 DI 10.1177/0884533612462744 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 074PH UT WOS:000313824200013 PM 23064018 ER PT J AU Lee, MS Hang, JQ Zhang, FY Zheng, BY Su, L Zhao, Y Dai, HL Zhang, HX Christiani, DC AF Lee, Mi-Sun Hang, Jing-qing Zhang, Feng-ying Zheng, Bu-yong Su, Li Zhao, Yang Dai, He-lian Zhang, Hong-xi Christiani, David C. TI Household solid fuel use and pulmonary function in an urban population in Shanghai, China SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID INDOOR AIR-POLLUTION; LUNG-CANCER; OXIDATIVE STRESS; METABOLIC SYNDROME; RISK; INFLAMMATION; EXPOSURE; PARTICLES; CHILDREN; SMOKING AB Objectives We examined the association between household solid fuel exposure and lung function in a densely populated district in urban Shanghai, China. Methods Spirometry was performed in 12 506 subjects, aged 18 and over, residing in the Putuo District in Shanghai, China, in a cross-sectional survey. Exposure to solid fuel use at home was assessed by an administered questionnaire, estimating duration and total amount of solid fuel use at home during the lifetime. Results After adjusting for confounders, the subjects with exposure to household solid fuel had a 1.3% (95% CI 0.57 to 2.02) decrease in forced expiratory volume in 1 s (FEV1) percent predicted and 3.5% (95% CI 2.74 to 4.18) decrease in forced vital capacity (FVC) percent predicted, respectively. Trends towards decreased pulmonary function measures were seen for longer duration and greater amount of household fuel use at home, in the highest compared with lowest tertile (p values for trend <0.001). We observed decrease in FEV1 and FVC percent predicted across increase in tertile of body mass index in association with in-home solid fuel exposure. Conclusions This study suggests that in-home solid fuel exposure is associated with reduced lung function in an urban population. C1 [Lee, Mi-Sun; Su, Li; Zhao, Yang; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Environm & Occupat Med & Epidemiol Program, Dept Environm Hlth, Boston, MA 02115 USA. [Hang, Jing-qing; Zhang, Feng-ying; Zheng, Bu-yong; Dai, He-lian; Zhang, Hong-xi] Shanghai Putuo Dist Peoples Hosp, Shanghai, Peoples R China. [Christiani, David C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Environm & Occupat Med & Epidemiol Program, Dept Environm Hlth, 665 Huntington Ave,Bldg 1,Room 1401, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu FU National Institute of Environmental Health Science [ES000002]; National Institute for Occupational Safety and Health [R010421]; Shanghai Putuo District People's Hospital FX This study was supported by grants from the National Institute of Environmental Health Science (Grant ES000002); and the National Institute for Occupational Safety and Health (Grant R010421); and Shanghai Putuo District People's Hospital. NR 29 TC 3 Z9 3 U1 1 U2 8 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD FEB PY 2013 VL 70 IS 2 BP 120 EP 125 DI 10.1136/oemed-2011-100569 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 074FC UT WOS:000313797300008 PM 23155189 ER PT J AU Batey, LA Welt, CK Rohr, F Wessel, A Anastasoaie, V Feldman, HA Guo, CY Rubio-Gozalbo, E Berry, G Gordon, CM AF Batey, L. A. Welt, C. K. Rohr, F. Wessel, A. Anastasoaie, V. Feldman, H. A. Guo, C. -Y. Rubio-Gozalbo, E. Berry, G. Gordon, C. M. TI Skeletal health in adult patients with classic galactosemia SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE Bone density; Calcium; Galactosemia; Premature ovarian insufficiency; Vitamin D ID BONE TURNOVER; CHILDREN; ADOLESCENTS; DEFICIENCY; CALCIUM; WOMEN AB This study evaluated bone health in adults with galactosemia. Associations between bone mineral density (BMD) and nutritional and biochemical variables were explored. Calcium level predicted hip and spine BMD, and gonadotropin levels were inversely associated with spinal BMD in women. These results afford insights into management strategies for these patients. Bone loss is a complication of galactosemia. Dietary restriction, primary ovarian insufficiency in women, and disease-related alterations of bone metabolism may contribute. This study examined relationships between clinical factors and BMD in patients with galactosemia. This cross-sectional sample included 33 adults (16 women) with classic galactosemia, mean age 32.0 +/- 11.8 years. BMD was measured by dual-energy X-ray absorptiometry, and was correlated with age, height, weight, fractures, nutritional factors, hormonal status, and bone biomarkers. There was a significant difference in hip BMD between women and men (0.799 vs. 0.896 g/cm(2), p = 0.014). The percentage of subjects with BMD-Z <-2.0 was also greater for women than men [33 vs. 18 % (spine), 27 vs. 6 % (hip)], and more women reported sustaining fractures. Bivariate analyses yielded correlations between BMI and BMD-Z [at the hip in women (r = 0.58, p < 0.05) and spine in men (r = 0.53, p < 0.05)]. In women, weight was also correlated with BMD-Z (r = 0.57, p < 0.05 at hip), and C-telopeptides (r = -0.59 at spine and -0.63 hip, p < 0.05) and osteocalcin (r = -0.71 at spine and -0.72 hip, p < 0.05) were inversely correlated with BMD-Z. In final regression models, higher gonadotropin levels were associated with lower spinal BMD in women (p = 0.017); serum calcium was a significant predictor of hip (p = 0.014) and spine (p = 0.013) BMD in both sexes. Bone density in adults with galactosemia is low, indicating the potential for increased fracture risk, the etiology of which appears to be multifactorial. C1 [Batey, L. A.; Rohr, F.; Wessel, A.; Anastasoaie, V.; Feldman, H. A.; Berry, G.; Gordon, C. M.] Childrens Hosp Boston, Boston, MA USA. [Welt, C. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rubio-Gozalbo, E.] Maastricht Univ, Med Ctr, Dept Pediat, Maastricht, Netherlands. [Rubio-Gozalbo, E.] Maastricht Univ, Med Ctr, Lab Inherited Metab Dis, Maastricht, Netherlands. [Berry, G.] Manton Ctr Orphan Dis Res, Boston, MA USA. [Guo, C. -Y.] Natl Yang Ming Univ, Inst Publ Hlth, Taipei 112, Taiwan. [Gordon, C. M.] Childrens Hosp Boston, Div Adolescent Med & Endocrinol, Boston, MA 02115 USA. RP Gordon, CM (reprint author), Childrens Hosp Boston, Div Adolescent Med & Endocrinol, 300 Longwood Ave, Boston, MA 02115 USA. EM catherine.gordon@childrens.harvard.edu RI rubio, estela/H-1833-2011; OI Berry, Gerard/0000-0001-5299-3313; Welt, Corrine/0000-0002-8219-5504 FU Galactosemia Foundation FX The authors gratefully acknowledge all of the study participants and their families who made this study possible. We also thank Jamie Nydegger, CDT and Yailka Cardenas, CDT for the excellent technical assistance (Bone Health Program, Children's Hospital Boston) and Nicolle Quinn, MS RD (research dietitian, Clinical and Translational Study Unit, Children's Hospital Boston) for performing the food record analyses. This project was funded by the Galactosemia Foundation. NR 25 TC 3 Z9 4 U1 0 U2 7 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD FEB PY 2013 VL 24 IS 2 BP 501 EP 509 DI 10.1007/s00198-012-1983-0 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 080WI UT WOS:000314274400012 PM 22525982 ER PT J AU Fernandes, JR Samayoa, JC Broelsch, GF McCormack, MC Nicholls, AM Randolph, MA Mihm, MC Austen, WG AF Fernandes, Justin R. Samayoa, Juan C. Broelsch, G. Felix McCormack, Michael C. Nicholls, Alexa M. Randolph, Mark A. Mihm, Martin C. Austen, William G., Jr. TI Micro-Mechanical Fractional Skin Rejuvenation SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID CARBON-DIOXIDE LASER; INTENSE PULSED-LIGHT; PHOTOAGED SKIN; STRAND BREAKS; SHORT-TERM; YAG LASER; BURN SCAR; COLLAGEN; PHOTOTHERMOLYSIS; DERMABRASION AB Background: The most commonly performed skin rejuvenation procedure, laser resurfacing, is associated with adverse events and significant expense. The authors have developed a novel device that uses micro-coring needles to remove tissue in a fractional pattern and avoid the side effects of laser therapy. The authors compare the efficacy of these needles to standard needles in a pig model. Methods: One swine was treated with three needle types: standard hypodermic, solid hypodermic, and the authors' novel coring needles. Thirty-two 1 x 1-inch sites per flank received either 20 or 40 percent treatment coverage. Photographs were taken and punch biopsies were performed at days 0, 7, 28, 56, and 84. Biopsy specimens were evaluated for histology and collagen content. Results: All treatment sites healed quickly, with no evidence of scarring or infection. Coring sites were easily identified and contained increased fibroblast activity and newly synthesized collagen. At 1 month, the papillary dermis and epidermis of the coring sites were up to 196 percent thicker compared with controls (p < 0.001). The coring sites had enhanced undulating rete ridges-consistent with regeneration. At 3 months, a pronounced increase in collagen fibers and newly organized and augmented elastic fibers was seen. Enzyme-linked immunosorbent assay confirmed an 89 percent increase in collagen content in these coring sites (p < 0.001). Conclusions: This novel approach to skin rejuvenation was found to effectively induce the microscopic and biological endpoints of skin rejuvenation. This may provide a new modality for the safe and cost-effective treatment of age-related rhytides, skin laxity, photodamage, scarring, and striae. (Plast. Reconstr. Surg. 131: 216, 2013.) C1 [Austen, William G., Jr.] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. RP Austen, WG (reprint author), Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, 15 Parkman St,WAC 435, Boston, MA 02114 USA. EM wausten@partners.org NR 41 TC 2 Z9 2 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD FEB PY 2013 VL 131 IS 2 BP 216 EP 223 DI 10.1097/PRS.0b013e3182789afa PG 8 WC Surgery SC Surgery GA 081XL UT WOS:000314355700051 PM 23357983 ER PT J AU Okechukwu, CA Dutra, LM Bacic, J El Ayadi, A Emmons, KM AF Okechukwu, C. A. Dutra, L. M. Bacic, J. El Ayadi, A. Emmons, K. M. TI Home matters: Work and household predictors of smoking and cessation among blue-collar workers SO PREVENTIVE MEDICINE LA English DT Article DE Smoking; Occupational class; Blue-collar; Partner smoking ID WORKPLACE POLICIES; TOBACCO USE; ENVIRONMENT; RESTRICTIONS; DISPARITIES; POPULATION; BEHAVIORS; RELAPSE; GENDER; IMPACT AB Objective: This study examined the joint influence of work- and household-related variables on smoking behavior among a population representative sample of blue-collar workers with live-in partners. Methods: The study used data on 1389 blue-collar workers from the Tobacco Use Supplement to the United States Current Population Survey 2002 to 2003 longitudinal overlap sample. Unadjusted and adjusted logistical regression analyses, which employed sampling and replicate weights to account for sampling design, were run to estimate independent and joint effects of the predictors. Results: In adjusted analyses, partner smoking (OR = 4.97, 95%CI = 3.02-8.18) and complete and partial home smoking policy (OR = 0.16, 95%CI = 0.09-0.29 and OR = 0.39, 95%CI = 0.23-0.68, respectively) were significant predictors of smoking status, but worksite smoking policies and presence of a young child under 5 in the household were not (p > 0.05). Baseline complete home smoking ban was a significant predictor of subsequent cessation (OR = 3.49, 95%CI = 1.19-10.23), while partner smoking status, workplace smoking policy, and the presence of a young child in the home did not predict cessation (p > 0.05). Conclusion: Household-related variables were significant predictors of smoking status and cessation among blue-collar workers. Current efforts to decrease smoking in this group, which are mostly focused on work-related risk factors, should consider how to incorporate household risk factors. (c) 2012 Elsevier Inc. All rights reserved. C1 [Okechukwu, C. A.; Dutra, L. M.; Bacic, J.; El Ayadi, A.; Emmons, K. M.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Bacic, J.] Boston Univ, Dept Hlth Policy & Management, Sch Publ Hlth, Boston, MA 02118 USA. [Emmons, K. M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Okechukwu, CA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Kresge Bldg,7th Floor,677 Huntington Ave, Boston, MA 02115 USA. EM cokechuk@hsph.hatvard.edu FU NIMHD NIH HHS [L60 MD003645] NR 33 TC 4 Z9 5 U1 2 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD FEB PY 2013 VL 56 IS 2 BP 130 EP 134 DI 10.1016/j.ypmed.2012.12.005 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 082HJ UT WOS:000314382600008 PM 23262360 ER PT J AU Almony, A Nudleman, E Shah, GK Blinder, KJ Eliott, D Mittra, RA Tewari, A AF Almony, Arghavan Nudleman, Eric Shah, Gaurav K. Blinder, Kevin J. Eliott, Dean Mittra, Robert A. Tewari, Asheesh TI Untitled Reply SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Letter ID LARGE MACULAR HOLES C1 [Almony, Arghavan] Carolina Eye Associates, Southern Pines, NC USA. [Nudleman, Eric] William Beaumont Hosp, Royal Oak, MI 48072 USA. [Shah, Gaurav K.; Blinder, Kevin J.] Retina Inst, St Louis, MO USA. [Eliott, Dean] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Mittra, Robert A.] VitreoRetinal Surg, Minneapolis, MN USA. [Tewari, Asheesh] Wayne State Univ, Kresge Eye Inst, Detroit, MI USA. RP Almony, A (reprint author), Carolina Eye Associates, Southern Pines, NC USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD FEB PY 2013 VL 33 IS 2 BP 457 EP 458 DI 10.1097/IAE.0b013e31828451c9 PG 2 WC Ophthalmology SC Ophthalmology GA 081TI UT WOS:000314344800038 PM 23343824 ER PT J AU Marusyk, A Polyak, K AF Marusyk, Andriy Polyak, Kornelia TI Cancer Cell Phenotypes, in Fifty Shades of Grey SO SCIENCE LA English DT Editorial Material ID TUMOR HETEROGENEITY; STEM-CELLS C1 [Marusyk, Andriy] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Marusyk, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM kornelia_polyak@dfci.harvard.edu NR 8 TC 24 Z9 24 U1 2 U2 33 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 FEB 1 PY 2013 VL 339 IS 6119 BP 528 EP 529 DI 10.1126/science.1234415 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 080UR UT WOS:000314270000043 PM 23372002 ER PT J AU Yu, M Bardia, A Wittner, B Stott, SL Smas, ME Ting, DT Isakoff, SJ Ciciliano, JC Wells, MN Shah, AM Concannon, KF Donaldson, MC Sequist, LV Brachtel, E Sgroi, D Baselga, J Ramaswamy, S Toner, M Haber, DA Maheswaran, S AF Yu, Min Bardia, Aditya Wittner, Ben S. Stott, Shannon L. Smas, Malgorzata E. Ting, David T. Isakoff, Steven J. Ciciliano, Jordan C. Wells, Marissa N. Shah, Ajay M. Concannon, Kyle F. Donaldson, Maria C. Sequist, Lecia V. Brachtel, Elena Sgroi, Dennis Baselga, Jose Ramaswamy, Sridhar Toner, Mehmet Haber, Daniel A. Maheswaran, Shyamala TI Circulating Breast Tumor Cells Exhibit Dynamic Changes in Epithelial and Mesenchymal Composition SO SCIENCE LA English DT Article ID LUNG-CANCER; METASTASIS; TRANSITION; PROGRESSION; EMT; DISSEMINATION; PHENOTYPE AB Epithelial-mesenchymal transition (EMT) of adherent epithelial cells to a migratory mesenchymal state has been implicated in tumor metastasis in preclinical models. To investigate its role in human cancer, we characterized EMT in circulating tumor cells (CTCs) from breast cancer patients. Rare primary tumor cells simultaneously expressed mesenchymal and epithelial markers, but mesenchymal cells were highly enriched in CTCs. Serial CTC monitoring in 11 patients suggested an association of mesenchymal CTCs with disease progression. In an index patient, reversible shifts between these cell fates accompanied each cycle of response to therapy and disease progression. Mesenchymal CTCs occurred as both single cells and multicellular clusters, expressing known EMT regulators, including transforming growth factor (TGF)-beta pathway components and the FOXC1 transcription factor. These data support a role for EMT in the blood-borne dissemination of human breast cancer. C1 [Yu, Min; Bardia, Aditya; Wittner, Ben S.; Stott, Shannon L.; Smas, Malgorzata E.; Ting, David T.; Isakoff, Steven J.; Ciciliano, Jordan C.; Wells, Marissa N.; Concannon, Kyle F.; Donaldson, Maria C.; Sequist, Lecia V.; Brachtel, Elena; Sgroi, Dennis; Baselga, Jose; Ramaswamy, Sridhar; Haber, Daniel A.; Maheswaran, Shyamala] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Stott, Shannon L.; Shah, Ajay M.; Toner, Mehmet] Harvard Univ, Sch Med, Ctr Bioengn Med, Charlestown, MA 02129 USA. [Bardia, Aditya; Isakoff, Steven J.; Sequist, Lecia V.; Baselga, Jose; Ramaswamy, Sridhar; Haber, Daniel A.] Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. [Brachtel, Elena; Sgroi, Dennis] Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. [Toner, Mehmet; Maheswaran, Shyamala] Harvard Univ, Sch Med, Dept Surg, Charlestown, MA 02129 USA. [Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Haber, DA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM haber@helix.mgh.harvard.edu; maheswaran@helix.mgh.harvard.edu OI Ting, David/0000-0002-3261-2322 FU Breast Cancer Research Foundation; Stand Up To Cancer; Susan G. Komen for the Cure [KG090412]; NIBIB [EB008047]; NCI [CA129933]; National Cancer Institute-MGH Federal Share Program; Howard Hughes Medical Institute FX We are grateful to all the patients who participated in this study; we thank D. Juric, C. Koris, and the Massachusetts General Hospital (MGH) clinical research coordinators for help with clinical studies; A. Gilman, B. Brannigan, and M. Zeinali for technical support; F. Ozsolak and P. Milos (Helicos) for RNA sequencing; A. Forrest-Hay and Q. Nguyen (Affymetrix) for RNA-ISH reagents; L. Libby for mouse studies; and J. Walsh for expertise with microscopy. This work was supported by grants from the Breast Cancer Research Foundation (D. A. H.), Stand Up To Cancer (D. A. H., M. T., and S. M.), Susan G. Komen for the Cure KG090412 (S. M.), NIBIB EB008047 (M. T., D. A. H.), NCI CA129933 (D. A. H.), the National Cancer Institute-MGH Federal Share Program (S. M.), and the Howard Hughes Medical Institute (M.Y. and D. A. H.). The MGH and M. T. have filed a patent for the HB (Herringbone) microchip (U.S. patent 09816815.4). Sequencing data have been deposited in the Gene Expression Omnibus database (accession no. GSE41245). NR 29 TC 603 Z9 634 U1 45 U2 365 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 FEB 1 PY 2013 VL 339 IS 6119 BP 580 EP 584 DI 10.1126/science.1228522 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 080UR UT WOS:000314270000059 PM 23372014 ER PT J AU Gradus, JL Shipherd, JC Suvak, MK Giasson, HL Miller, M AF Gradus, Jaimie L. Shipherd, Jillian C. Suvak, Michael K. Giasson, Hannah L. Miller, Matthew TI Suicide Attempts and Suicide among Marines: A Decade of Follow-up SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID SEXUAL EXPERIENCES QUESTIONNAIRE; RISK-FACTORS; PSYCHOMETRIC PROPERTIES; PREVALENCE; MILITARY; HARASSMENT; VICTIMIZATION; AGGRESSION; PERSONNEL; ANXIETY AB Suicidal behavior among military personnel is of paramount public health importance because of the increased risk of death from suicide in this population. Pre- and post-Marine recruit training risk factors for suicide attempts among current and former Marines were examined in 10 years following recruit training. The characteristics of the subsample of current and former Marines who died by suicide during this time are also described. Stressful and traumatic life events (e.g., childhood physical, sexual, and emotional abuse, sexual harassment during recruit training) and pre-recruit training suicide attempts emerged as having strong associations with post-recruit training attempts. Half of those who died by suicide in the 10 years following recruit training endorsed at least one significant life stressor prior to joining the Marines. This study highlights the importance of screening for stressful and potentially traumatic experiences occurring both before and during military service as part of a comprehensive suicide risk assessment in military samples. C1 [Gradus, Jaimie L.; Shipherd, Jillian C.; Suvak, Michael K.; Giasson, Hannah L.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Gradus, Jaimie L.; Shipherd, Jillian C.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Gradus, Jaimie L.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Suvak, Michael K.] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. [Miller, Matthew] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Gradus, JL (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave,116B-3, Boston, MA 02130 USA. EM jaimie.gradus@va.gov OI Gradus, Jaimie/0000-0003-1459-5327 NR 28 TC 8 Z9 8 U1 4 U2 23 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 FEB PY 2013 VL 43 IS 1 BP 39 EP 49 DI 10.1111/j.1943-278X.2012.00126.x PG 11 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 079OR UT WOS:000314180600003 PM 23082753 ER PT J AU Velmahos, GC AF Velmahos, George C. TI Direct and Recurrent Inguinal Hernias Are Associated with Ventral Hernia Repair: A Database Study SO WORLD JOURNAL OF SURGERY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Velmahos, GC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM gvelmahos@partners.org NR 1 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD FEB PY 2013 VL 37 IS 2 BP 312 EP 312 DI 10.1007/s00268-012-1883-7 PG 1 WC Surgery SC Surgery GA 077KJ UT WOS:000314026300006 PM 23238798 ER PT J AU Ambrosy, AP Vaduganathan, M Mentz, RJ Greene, SJ Subacius, H Konstam, MA Maggioni, AP Swedberg, K Gheorghiade, M AF Ambrosy, Andrew P. Vaduganathan, Muthiah Mentz, Robert J. Greene, Stephen J. Subacius, Haris Konstam, Marvin A. Maggioni, Aldo P. Swedberg, Karl Gheorghiade, Mihai CA EVEREST Trial Investgators TI Clinical profile and prognostic value of low systolic blood pressure in patients hospitalized for heart failure with reduced ejection fraction: Insights from the Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST) trial SO AMERICAN HEART JOURNAL LA English DT Article ID MORTALITY; ASSOCIATION; UPDATE AB Background Systolic blood pressure (SBP) is related to the pathophysiologic development and progression of heart failure (HF) and is inversely associated with adverse outcomes during hospitalization for HF (HHF). The prognostic value of SBP after initiating inhospital therapy and the mode of death and etiology of cardiovascular readmissions based on SBP have not been well characterized in HHF. Methods A post hoc analysis was performed of the placebo group (n = 2061) of the EVEREST trial, which enrolled patients within 48 hours of admission for worsening HF with an ejection fraction (EF) <= 40% and an SBP >= 90 mm Hg, for a median followup of 9.9 months. Systolic blood pressure was measured at baseline, daily during hospitalization, and at discharge/day 7. Patients were divided into the following quartiles by SBP at baseline: <= 105, 106 to 119, 120 to 130, and >= 131 mm Hg. Outcomes were all-cause mortality (ACM) and the composite of cardiovascular mortality or HHF (CVM + HHF). The associations between baseline, discharge, and inhospital change in SBP and ACM and CVM + HHF were assessed using multivariable Cox proportional hazards regression models adjusted for known covariates. Results Median (25th, 75th) SBP at baseline was 120 (105, 130) mm Hg and ranged from 82 to 202 mm Hg. Patients with a lower SBP were younger and more likely to be male; had a higher prevalence of prior revascularization and ventricular arrhythmias; had a lower EF, worse renal function, higher natriuretic peptide concentrations, and wider QRS durations; and were more likely to require intravenous inotropes during hospitalization. Lower SBP was associated with increased mortality, driven by HF and sudden cardiac death, and cardiovascular hospitalization, primarily caused by HHF. After adjusting for potential confounders, SBP was inversely associated with risk of the coprimary end points both at baseline (ACM: hazard ratio [HR]/10-mm Hg decrease 1.15, 95% CI1.08-1.22; CVM + HHF: HR 1.09/10-mm Hg decrease, 95% CI 1.04-1.14) and at the time of discharge/ day 7 (ACM: HR 1.15/10-mm Hg decrease, 95% CI 1.08-1.22; CVM + HHF: HR 1.07/10-mm Hg decrease, 95% CI 1.02-1.13), but the association with inhospital SBP change was not significant. Conclusion Systolic blood pressure is an independent clinical predictor of morbidity and mortality after initial therapy during HHF with reduced EF. (Am Heart J 2013;165:216-25.) C1 [Ambrosy, Andrew P.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Vaduganathan, Muthiah] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Mentz, Robert J.] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA. [Greene, Stephen J.; Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. [Subacius, Haris] Northwestern Univ, Feinberg Sch Med, Dept Med, Div Cardiol, Chicago, IL 60611 USA. [Konstam, Marvin A.] Tufts Med Ctr, Dept Med, Div Cardiol, Boston, MA USA. [Maggioni, Aldo P.] ANMCO Res Ctr, Florence, Italy. [Swedberg, Karl] Univ Gothenburg, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden. RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, 645 N Michigan Ave,Suite 1006, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu FU Abbott Labs; Astellas; AstraZeneca; Bayer Schering PharmaAG; CorThera Inc; Cytokinetics Inc; DebioPharm SA; ErrekappaTerapeutici (Milan, Italy); Glaxo Smith Kline; JNJ; Medtronic; Novartis Pharma AG; Otsuka; Sigma Tau; Solvay Pharmaceuticals; Pericor Therapeutics FX Mihai Gheorghiade is a consultant for and/or has received research support from Abbott Labs, Astellas, AstraZeneca, Bayer Schering PharmaAG, CorThera Inc, Cytokinetics Inc, DebioPharm SA, ErrekappaTerapeutici (Milan, Italy), Glaxo Smith Kline, JNJ, Medtronic, Novartis Pharma AG, Otsuka, Sigma Tau, Solvay Pharmaceuticals, and Pericor Therapeutics. The other authors declare no conflicts of interest. NR 20 TC 22 Z9 22 U1 1 U2 9 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 FEB PY 2013 VL 165 IS 2 BP 216 EP 225 DI 10.1016/j.ahj.2012.11.004 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 078PS UT WOS:000314112300016 PM 23351825 ER PT J AU Tse, JY Nguyen, AT Le, LP Hoang, MP AF Tse, Julie Y. Nguyen, Anh T. Le, Long P. Hoang, Mai P. TI Microcystic Adnexal Carcinoma Versus Desmoplastic Trichoepithelioma: A Comparative Study SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE microcystic adnexal carcinoma; desmoplastic trichoepithelioma; CK19; CK17; epidermal growth factor receptor; immunohistochemistry ID BASAL-CELL CARCINOMA; FACTOR RECEPTOR GENE; OF-THE-LITERATURE; SEBACEOUS DIFFERENTIATION; CYTOKERATIN 15; MERKEL CELLS; STEM-CELLS; SKIN; EXPRESSION; MARKERS AB The histologic distinction between microcystic adnexal carcinoma (MAC) and desmoplastic trichoepithelioma (dTE) can be challenging in the setting of a superficial biopsy. However, accurate diagnosis has treatment implication because the standard of care for MAC is wide local excision but more conservative care for dTE. We reviewed the histologic features of 30 MAC and 39 dTE cases and performed cytokeratin (CK) 17, CK19, and epidermal growth factor receptor (EGFR) immunostains on 20 MACs and 18 dTEs. MAC cases occurred in older patients in comparison with dTE (median, 67 years vs. 34 years). The head and neck was the most commonly involved site, 88% and 89% for MAC and dTE, respectively. In addition to features previously reported as specific for MAC, such as skeletal muscle and subcutaneous tissue invasion, perineural invasion, and ductal differentiation, we found the presence of mitotic figures to be significantly more frequent in MAC cases (P < 0.0001). In contrast, the presence of keratocyst, keratin granuloma, and calcification was significantly more frequent in dTE cases (P < 0.0001). CK19 seems to be a helpful adjunct because its expression was seen in 70% (14/20) of MAC versus 22% (4/18) of dTE cases (P = 0.0044); however, the clinical usefulness in individual cases may be limited because of the overlapping immunoprofile. CK17 and EGFR expression was seen in all the MAC and dTE cases. Low polysomy of EGFR gene was observed in only one MAC case, suggesting that molecular mechanisms other than gene amplification play a role in EGFR overexpression. C1 [Tse, Julie Y.; Nguyen, Anh T.; Le, Long P.; Hoang, Mai P.] Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Hoang, MP (reprint author), Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,Warren 820, Boston, MA 02114 USA. EM mhoang@partners.org NR 34 TC 3 Z9 3 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD FEB PY 2013 VL 35 IS 1 BP 50 EP 55 DI 10.1097/DAD.0b013e31825988df PG 6 WC Dermatology SC Dermatology GA 078MR UT WOS:000314103600012 PM 22722464 ER PT J AU Zhang, GY Bai, HX Yang, L Ma, MH Su, YW Luo, YY Wen, HQ Lu, QJ Xiao, R AF Zhang, Guiying Bai, Harrison X. Yang, Li Ma, Michael H. Su, Yuwen Luo, Yangyang Wen, Haiquan Lu, Qianjin Xiao, Rong TI NK-/T-Cell Lymphoma Resembling Hydroa Vacciniforme With Positive CD4 Marker Expression: A Diagnostic Difficulty SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE CD4(+) lymphoma; hydroa vacciniforme; cutaneous NK-/T-cell lymphoma ID NATURAL-KILLER-CELL; NASAL-TYPE; CUTANEOUS LYMPHOMA; HEMATOLOGICAL NEOPLASMS; RECOGNIZED ENTITY; SKIN; INVOLVEMENT; WORKSHOP; CD56+; GENE AB A 35-year-old Chinese woman presented with a 2.5-year history of facial swelling in the left lower quadrant and a 10-month history of relapsing red papules and vesicles in the perioral area resembling hydroa vacciniforme. Histologically, a tissue biopsy showed a dense infiltration of medium-sized atypical lymphocytic cells expressing CD4 and CD56. A diagnosis of cutaneous NK-/T-cell lymphoma was made. The patient was treated with alpha-interferon, valaciclovir hydrochloride, and low-dose prednisone for 2 months. Her skin lesions and lymphoadenopathy resolved initially, but she succumbed to the disease shortly after starting chemotherapy treatment 11 months later. To our knowledge, this is the first case of CD4(+)CD56(+) NK-/T-cell lymphoma with clinical features resembling hydroa vacciniforme. C1 [Zhang, Guiying; Yang, Li; Su, Yuwen; Luo, Yangyang; Wen, Haiquan; Lu, Qianjin; Xiao, Rong] Cent S Univ, Dept Dermatol, Xiang Ya Hosp 2, Changsha 410011, Hunan, Peoples R China. [Bai, Harrison X.; Ma, Michael H.] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA. [Ma, Michael H.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Xiao, R (reprint author), Cent S Univ, Dept Dermatol, Xiang Ya Hosp 2, 139 Ren Min Middle Rd, Changsha 410011, Hunan, Peoples R China. EM xiaorong65@yahoo.com.cn NR 24 TC 2 Z9 2 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD FEB PY 2013 VL 35 IS 1 BP 94 EP 97 DI 10.1097/DAD.0b013e3182674895 PG 4 WC Dermatology SC Dermatology GA 078MR UT WOS:000314103600019 PM 22885552 ER PT J AU Fett, NM Teng, J Longley, BJ AF Fett, Nicole M. Teng, Joyce Longley, B. Jack TI Familial Urticaria Pigmentosa: Report of a Family and Review of the Role of KIT Mutations SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Review DE mastocytosis; urticarial pigmentosa; c-kit protooncogene; KIT tyrosine kinase ID GASTROINTESTINAL STROMAL TUMORS; C-KIT; GERMLINE MUTATION; PEDIATRIC MASTOCYTOSIS; CUTANEOUS MASTOCYTOSIS; DOMAIN MUTATIONS; DISEASE AB Cutaneous mastocytosis is a rare clinically heterogeneous disorder characterized by mast cell infiltration. Mastocytosis affects both children and adults and has been reported to occur in families. Recent data suggest that mutations in the c-kit protooncogene are causative of mastocytosis not only in adults but in children and familial cases as well; however, mutation analysis other than D816V is not widely available, making detection of causative mutations problematic. We present the case of a 33-year-old man with a 30-year history of persistent urticaria pigmentosa and his 2 affected children. Sequencing of KIT exons 8, 10, 11, and 17 was carried out on a skin biopsy specimen and mucosal swabs of the incident case and was negative for known KIT mutations. Additional work-up was deferred by the family. Presentation of this familial case of urticaria pigmentosa demonstrates the complexity of genetic evaluation in clinical settings. It suggests that mutations other than those reported in exons 8, 10, 11, and 17 may also result in familial mastocytosis. Presentation of this case also allows for review of the mechanism of action of causative KIT mutations and the recent literature supporting KIT mutations in childhood and familial mastocytosis. C1 [Fett, Nicole M.] Philadelphia VA Med Ctr, Dept Dermatol, Philadelphia, PA USA. [Fett, Nicole M.] Univ Penn, Dept Dermatol, Perelman Ctr Adv Med, Sch Med, Philadelphia, PA 19104 USA. [Teng, Joyce; Longley, B. Jack] Univ Wisconsin, Hosp & Clin, Dept Dermatol, Madison, WI 53792 USA. RP Fett, NM (reprint author), Univ Penn, Dept Dermatol, Perelman Ctr Adv Med, Sch Med, Suite 1-330A,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM nicole.fett@uphs.upenn.edu NR 22 TC 9 Z9 9 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD FEB PY 2013 VL 35 IS 1 BP 113 EP 116 DI 10.1097/DAD.0b013e31826330bf PG 4 WC Dermatology SC Dermatology GA 078MR UT WOS:000314103600024 PM 22892471 ER PT J AU Chlebicki, MP Safdar, N O'Horo, JC Maki, DG AF Chlebicki, Maciej Piotr Safdar, Nasia O'Horo, John Charles Maki, Dennis G. TI Preoperative chlorhexidine shower or bath for prevention of surgical site infection: A meta-analysis SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Review DE Antiseptic; Systematic review; Clean; Clean-contaminated ID WHOLE-BODY DISINFECTION; WOUND-INFECTION; CONTROLLED-TRIAL; PRISMA STATEMENT; POVIDONE-IODINE; CLINICAL-TRIALS; SURGERY; GLUCONATE; DETERGENT; PROPHYLAXIS AB Background: Chlorhexidine showering is frequently recommended as an important preoperative measure to prevent surgical site infection (SSI). However, the efficacy of this approach is uncertain. Methods: A search of electronic databases was undertaken to identify prospective controlled trials evaluating whole-body preoperative bathing with chlorhexidine versus placebo or no bath for prevention of SSI. Summary risk ratios were calculated using a DerSimonian-Laird random effects model and a Mantel-Haenzel dichotomous effects model. Results: Sixteen trials met inclusion criteria with a total of 17,932 patients: 7,952 patients received a chlorhexidine bath, and 9,980 patients were allocated to various comparator groups. Overall, 6.8% of patients developed SSI in the chlorhexidine group compared with 7.2% of patients in the comparator groups. Chlorhexidine bathing did not significantly reduce overall incidence of SSI when compared with soap, placebo, or no shower or bath (relative risk, 0.90; 95% confidence interval: 0.77-1.05, P = .19). Conclusions: Meta-analysis of available clinical trials suggests no appreciable benefit of preoperative whole-body chlorhexidine bathing for prevention of SSI. However, most studies omitted details of chlorhexidine application. Better designed trials with a specified duration and frequency of exposure to chlorhexidine are needed to determine whether preoperative whole-body chlorhexidine bathing reduces SSI. Copyright (C) 2013 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. C1 [Chlebicki, Maciej Piotr] Singapore Gen Hosp, Dept Infect Dis, Singapore, Singapore. [Safdar, Nasia] Univ Wisconsin, MFCB, Infect Dis Sect, Dept Med,Med Sch, Madison, WI 53705 USA. [Safdar, Nasia; Maki, Dennis G.] Univ Wisconsin Hosp & Clin, Infect Control Dept, Madison, WI 53792 USA. [Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [O'Horo, John Charles] Aurora Healthcare, Dept Grad Med Educ, Milwaukee, WI USA. RP Safdar, N (reprint author), Univ Wisconsin, MFCB, Infect Dis Sect, Dept Med,Med Sch, 1685 Highland Ave, Madison, WI 53705 USA. EM ns2@medicine.wisc.edu RI O'Horo, John/A-8787-2013; O'Horo, John/N-8681-2013 OI O'Horo, John/0000-0002-0880-4498; O'Horo, John/0000-0002-0880-4498 NR 42 TC 33 Z9 33 U1 1 U2 30 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD FEB PY 2013 VL 41 IS 2 BP 167 EP 173 DI 10.1016/j.ajic.2012.02.014 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 078NJ UT WOS:000314105500018 PM 22722008 ER PT J AU Ahmed, A Rich, MW Zile, M Sanders, PW Patel, K Zhang, Y Aban, IB Love, TE Fonarow, GC Aronow, WS Allman, RM AF Ahmed, Ali Rich, Michael W. Zile, Michael Sanders, Paul W. Patel, Kanan Zhang, Yan Aban, Inmaculada B. Love, Thomas E. Fonarow, Gregg C. Aronow, Wilbert S. Allman, Richard M. TI Renin-Angiotensin Inhibition in Diastolic Heart Failure and Chronic Kidney Disease SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Angiotensin-converting enzyme inhibitors; Angiotensin receptor blockers; Chronic kidney disease; Diastolic heart failure ID FUNCTIONAL RENAL-INSUFFICIENCY; CONVERTING-ENZYME-INHIBITION; PRESERVED EJECTION FRACTION; OLDER-ADULTS; SYSTOLIC FUNCTION; PROPENSITY SCORE; ATRIAL-FIBRILLATION; PRACTICE GUIDELINES; OUTCOMES; ASSOCIATION AB BACKGROUND: The role of renin-angiotensin inhibition in older patients with diastolic heart failure and chronic kidney disease remains unclear. METHODS: Of the 1340 patients (age >= 65 years) with diastolic heart failure (ejection fraction >= 45%) and chronic kidney disease (estimated glomerular filtration rate < 60 mL/min/1.73 m(2)), 717 received angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Propensity scores for the use of these drugs, estimated for each of the 1340 patients, were used to assemble a cohort of 421 pairs of patients, receiving and not receiving these drugs, who were balanced on 56 baseline characteristics. RESULTS: During more than 8 years of follow-up, all-cause mortality occurred in 63% and 69% of matched patients with chronic kidney disease receiving and not receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, respectively (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.70-0.97; P = .021). There was no association with heart failure hospitalization (HR, 0.98; 95% CI, 0.82-1.18; P = .816). Similar mortality reduction (HR, 0.81; 95% CI, 0.66-0.995; P = .045) occurred in a subgroup of matched patients with an estimated glomerular filtration rate less than 45 mL/min/1.73 m2. Among 207 pairs of propensity-matched patients without chronic kidney disease, the use of these drugs was not associated with mortality (HR, 1.03; 95% CI, 0.80-1.33; P = .826) or heart failure hospitalization (HR, 0.99; 95% CI, 0.76-1.30; P = .946). CONCLUSIONS: A discharge prescription for angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was associated with a significant reduction in all-cause mortality in older patients with diastolic heart failure and chronic kidney disease, including those with more advanced chronic kidney disease. Published by Elsevier Inc. The American Journal of Medicine (2013) 126, 150-161 C1 [Ahmed, Ali; Sanders, Paul W.; Patel, Kanan; Zhang, Yan; Aban, Inmaculada B.; Allman, Richard M.] Univ Alabama Birmingham, Birmingham, AL USA. [Ahmed, Ali; Sanders, Paul W.; Allman, Richard M.] Vet Affairs Med Ctr, Birmingham, AL USA. [Rich, Michael W.] Washington Univ, St Louis, MO USA. [Zile, Michael] Med Univ S Carolina, Charleston, SC 29425 USA. [Zile, Michael] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Love, Thomas E.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA. [Aronow, Wilbert S.] New York Med Coll, Valhalla, NY 10595 USA. RP Ahmed, A (reprint author), UAB Ctr Aging, CH19,Ste 219,1720 2nd Ave S, Birmingham, AL 35294 USA. EM aahmed@uab.edu OI Sanders, Paul/0000-0002-2915-5714 FU National Heart, Lung, and Blood Institute (NHLBI)/National Institutes of Health (NIH) [R01-HL085561, R01-HL085561-S]; NIH/NHLBI [R01-HL097047]; NIH/National Center for Research Resources [5UL1 RR025777]; NIH/National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK46199]; Department of Veterans Affairs FX The project was supported by Grant Numbers R01-HL085561 and R01-HL085561-S from the National Heart, Lung, and Blood Institute (NHLBI)/National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NHLBI or NIH. Dr Ahmed also is supported by NIH/NHLBI Grant R01-HL097047 and a generous gift from Jean B. Morris of Birmingham, Alabama. Dr Allman is supported by NIH/National Center for Research Resources Grant 5UL1 RR025777. Dr Sanders is supported by NIH/National Institute of Diabetes and Digestive and Kidney Diseases Grant R01-DK46199 and funding from the Department of Veterans Affairs. NR 41 TC 13 Z9 13 U1 0 U2 1 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 FEB PY 2013 VL 126 IS 2 BP 150 EP 161 DI 10.1016/j.amjmed.2012.06.031 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 072WP UT WOS:000313704500022 PM 23331442 ER PT J AU Pasquale, LR Loomis, SJ Kang, JH Yaspan, BL Abdrabou, W Budenz, DL Chen, TC Delbono, E Friedman, DS Gaasterland, D Gaasterland, T Grosskreutz, CL Lee, RK Lichter, PR Liu, YT McCarty, CA Moroi, SE Olson, LM Realini, T Rhee, DJ Schuman, JS Singh, K Vollrath, D Wollstein, G Zack, DJ Allingham, RR Pericak-Vance, MA Weinreb, RN Zhang, K Hauser, MA Richards, JE Haines, JL Wiggs, JL AF Pasquale, Louis R. Loomis, Stephanie J. Kang, Jae H. Yaspan, Brian L. Abdrabou, Wael Budenz, Donald L. Chen, Teresa C. Delbono, Elizabeth Friedman, David S. Gaasterland, Douglas Gaasterland, Terry Grosskreutz, Cynthia L. Lee, Richard K. Lichter, Paul R. Liu, Yutao McCarty, Catherine A. Moroi, Sayoko E. Olson, Lana M. Realini, Tony Rhee, Douglas J. Schuman, Joel S. Singh, Kuldev Vollrath, Douglas Wollstein, Gadi Zack, Donald J. Allingham, R. Rand Pericak-Vance, Margaret A. Weinreb, Robert N. Zhang, Kang Hauser, Michael A. Richards, Julia E. Haines, Jonathan L. Wiggs, Janey L. TI CDKN2B-AS1 Genotype-Glaucoma Feature Correlations in Primary Open-Angle Glaucoma Patients From the United States SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; BASE-LINE CHARACTERISTICS; REPLICATIVE SENESCENCE; SUSCEPTIBILITY LOCI; OPTIC DISC; POPULATION; VARIANTS; INHIBITORS; P15(INK4B); PRESSURE AB PURPOSE: To assess the association between single nucleotide polymorphisms (SNPs) of the gene region containing cyclin-dependent kinase inhibitor 2B antisense noncoding RNA (CDKN2B-AS1) and glaucoma features among primary open-angle glaucoma (POAG) patients. DESIGN: Retrospective observational case series. METHODS: We studied associations between 10 CDKN2B-AS1 SNPs and glaucoma features among 976 POAG cases from the Glaucoma Genes and Environment (GLAUGEN) study and 1971 cases from the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium. For each patient, we chose the feature from the eye with the higher value. We created cohort-specific multivariable models for glaucoma features and then meta-analyzed the results. RESULTS: For 9 of the 10 protective CDKN2B-AS1 SNPs with minor alleles associated with reduced disease risk (eg, the G allele at rs2157719), POAG patients carrying these minor alleles had smaller cup-to-disc ratio (0.05 units smaller per G allele at diagnosis; 95% CI: -0.08, -0.03; P = 6.23E-05) despite having higher intraocular pressure (IOP) (0.70 mm Hg higher per G allele at DNA collection; 95% CI: 0.40, 1.00; P = 5.45E-06). For the 1 adverse rs3217992 SNP with minor allele A associated with increased disease risk, POAG patients with A alleles had larger cup-to-disc ratio (0.05 units larger per A allele at diagnosis; 95% CI: 0.02, 0.07; P = 4.74E-04) despite having lower IOP (-0.57 mm Hg per A allele at DNA collection; 95% CI: -0.84, -0.29; P = 6.55E-05). CONCLUSION: Alleles of CDKN2B-AS1 SNPs, which influence risk of developing POAG, also modulate optic nerve degeneration among POAG patients, underscoring the role of CDKN2B-AS1 in POAG. (Am J Ophthalmol 2013;155:342-353. (c) 2013 by Elsevier Inc. All rights reserved.) C1 [Pasquale, Louis R.; Loomis, Stephanie J.; Abdrabou, Wael; Chen, Teresa C.; Delbono, Elizabeth; Grosskreutz, Cynthia L.; Rhee, Douglas J.; Wiggs, Janey L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Pasquale, Louis R.; Kang, Jae H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02114 USA. [Yaspan, Brian L.; Olson, Lana M.; Haines, Jonathan L.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN USA. [Budenz, Donald L.] Univ N Carolina, Dept Ophthalmol, Chapel Hill, NC USA. [Friedman, David S.; Zack, Donald J.] Johns Hopkins Univ Hosp, Wilmer Eye Inst, Baltimore, MD 21205 USA. [Gaasterland, Douglas] Eye Doctors Washington, Chevy Chase, MD USA. [Gaasterland, Terry] Univ Calif San Diego, Scripps Genome Ctr, San Diego, CA 92103 USA. [Lee, Richard K.; Pericak-Vance, Margaret A.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA. [Lichter, Paul R.; Moroi, Sayoko E.; Richards, Julia E.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. [Liu, Yutao; Allingham, R. Rand; Hauser, Michael A.] Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA. [McCarty, Catherine A.] Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI USA. [Realini, Tony] W Virginia Univ, Dept Ophthalmol, Inst Eye, Morgantown, WV 26506 USA. [Schuman, Joel S.; Wollstein, Gadi] Univ Pittsburgh, Dept Ophthalmol, UPMC Eye Ctr, Pittsburgh, PA 15260 USA. [Singh, Kuldev] Stanford Univ, Dept Ophthalmol, Palo Alto, CA 94304 USA. [Vollrath, Douglas] Stanford Univ, Dept Genet, Palo Alto, CA 94304 USA. [Weinreb, Robert N.; Zhang, Kang] Univ Calif San Diego, Dept Ophthalmol, La Jolla, CA 92093 USA. [Weinreb, Robert N.; Zhang, Kang] Univ Calif San Diego, Hamilton Glaucoma Ctr, La Jolla, CA 92093 USA. [Liu, Yutao; Hauser, Michael A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Richards, Julia E.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. RP Pasquale, LR (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Louis_Pasquale@meei.harvard.edu RI Haines, Jonathan/C-3374-2012; Schuman, Joel/K-7304-2012; OI Schuman, Joel/0000-0002-8885-3766; Zack, Don/0000-0002-7966-1973 FU Merck; Carl Zeiss Meditec; New World Medical; Harvard Catalyst group; National Institutes of Health (NIH); Agency for Healthcare Research; National Eye Institute (NEI); American Glaucoma Society; NEI; Alcon; NIH; Novartis; Nidek; Topcon; Aeries; Research to Prevent Blindness; Sramek Foundation; Allergan (Irvine, California); The Harvard Glaucoma Center of Excellence; Margolis fund (Boston, Massachusetts); Research to Prevent Blindness, Inc (New York, New York); The Glaucoma Research Foundation (San Francisco, California); American Health Assistance Foundation (Clarksburg, Maryland); Glaucoma Foundation (New York, New York); National Institutes of Health [CA87969, CA49449, CA55075, HL35464, NEI R01 EY015473, HHSN268200782096C]; National Human Genome Research Institute (Bethesda, Maryland) [HG004728, HG004424, HG004446]; National Eye Institute [HG005259-01]; The National Eye Institute (Bethesda, Maryland) through ARRA [3R01EY015872-05S1, 3R01EY019126-02S1]; National Institutes of Health (Bethesda, Maryland) [EY015543, EY006827, HL073389, EY13315, EY09611, EY009149, HG004608, EY008208, EY015473, EY012118, EY015682, EY011671, EY09580, EY013178, EY015872, EY010886, EY009847, EY011008, EY144428, EY144448, EY18660] FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST. Dr Pasquale has received funding from Merck for unrelated investigator-initiated research. He was also reimbursed for travel to an ARVO-Pfizer meeting on biomarkers in glaucoma research in May 2011. Dr T. Gaasterland has received an honorarium for a lecture given on glaucoma genomics by Sequenom. Dr Yaspan contributed to this research while he was at Vanderbilt University and is currently an employee of Genentech. He has no other financial conflicts to declare. Dr Grosskreutz is an employee of Novartis and retains stock options from her employer. She has no other financial conflicts to declare. The following coauthors declare the following financial activities for work outside the scope of the current publication. Dr Budenz is a consultant to Alcon Labs, Allergan, Santen, Ivantis, and Alimera. His institution receives grant support from Carl Zeiss Meditec and New World Medical. Dr Budenz is on the speakers bureau for Merck, Alcon, and Allergan. Dr Chen receives grant support from the Harvard Catalyst group, the National Institutes of Health (NIH), and the Agency for Healthcare Research. She also receives royalties from Elsevier for her role as a book editor. Dr Friedman is a consultant for Alcon, Bausch & Lomb, Merck, Pfizer, and QLT. Dr D. Gaasterland has been paid royalties as inventor of the G probe for Index. He also owns a small amount of IRIDEX stock. Dr Lee receives research support from National Eye Institute (NEI) and the American Glaucoma Society. He is also on the speakers bureaus of Merck and Pfizer. Dr Lee receives royalties from Pharmigen and has been reimbursed for meeting travel by Alcon. Dr Realini is a consultant for Alcon and received payment for manuscript preparation from this company. He is also on the speakers bureau for Lumenis. Dr Mono receives grant support from Merck and NEI as well as royalties from Lippicott. Dr Rhee is a consultant for Alcon, Allergan, Merck, Novagali, and Santen. He also receives grant support from Alcon and Merck. Dr Schuman receives grant support from the NIH and is an inventor on a patent (paid to University of Pittsburgh). He receives royalties from Carl Zeiss Meditec. Dr Singh is consultant to Alcon, Allergan, Santen, and Bausch & Lomb. Dr Wollstein receives grant support from NIH. Drs Allingham and Pericak-Vance receive grant support from NIH. Dr Zack retains Board membership with Alcon and has received grant support form Merck. Dr Weinreb is a consultant to Alcon, Allergan, Merck, Bausch & Lomb, Zeis Meditec and Optovue. He also receives grant support from Novartis, Nidek, Topcon, and Aeries. Dr Richards receives grant support from NIH, Research to Prevent Blindness, and the Sramek Foundation. She also receives royalties for authoring a textbook from Elsevier and has been reimbursed for travel to a Think Tank meeting by the Glaucoma Foundation, NYC.; Publication of this article was supported by the following: a Horizon Grant to MEEI from Allergan (Irvine, California) supported the collection of some glaucoma feature data. The Harvard Glaucoma Center of Excellence and Margolis fund (Boston, Massachusetts) support W.A., L.R.P., and J.L.W.. L.R.P., J.E.R., and J.L.W. are also supported by Research to Prevent Blindness, Inc (New York, New York). The Glaucoma Research Foundation (San Francisco, California), American Health Assistance Foundation (Clarksburg, Maryland), and the Glaucoma Foundation (New York, New York) support Y.L. The following National Institutes of Health grants support the maintenance of the Nurses Health Study and Health Professionals Follow-up, allowing these health professionals to contribute to this analysis: CA87969, CA49449, CA55075, HL35464, and NEI R01 EY015473 (L.R.P.). The following grants from the National Human Genome Research Institute (Bethesda, Maryland) supported GLAUGEN: HG004728 (L.R.P.), HG004424 (Broad Institute to support genotyping), HG004446 (C. Laurie, U. Washington, to support genotype data cleaning and analysis). Genotyping services for the NEIGHBOR study were provided by the Center for Inherited Disease Research (CIDR) and were supported by the National Eye Institute through grant HG005259-01 (J.L.W.). Additionally, CIDR is funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. The National Eye Institute (Bethesda, Maryland), through ARRA grants 3R01EY015872-05S1 (J.L.W.) and 3R01EY019126-02S1 (M.A.H.), supported the collection and processing of samples for the NEIGHBOR dataset. Funding for the collection of cases and controls was provided by National Institutes of Health (Bethesda, Maryland) grants: EY015543 (R.R.A.), EY006827 (D.G.), HL073389 (Hauser, E); EY13315 (M.A.H.); EY09611 (Hankinson, S), EY009149 (P.R.L.), HG004608 (C.A.M.), EY008208 (Medeiros, P), EY015473 (L.R.P.), EY012118 (M.A.P.V.), EY015682 (T.R.), EY011671 (J.E.R.) EY09580 (J.E.R.), EY013178 (J.S.S.), EY015872 (J.L.W.), EY010886 (J.L.W.), EY009847 (J.L.W.), EY011008 (Zangwill, L), EY144428 (K.Z.), EY144448 (K.Z.), EY18660 (K.Z.). NR 36 TC 18 Z9 18 U1 0 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD FEB PY 2013 VL 155 IS 2 BP 342 EP 353 DI 10.1016/j.ajo.2012.07.023 PG 12 WC Ophthalmology SC Ophthalmology GA 078YQ UT WOS:000314137400019 PM 23111177 ER PT J AU Jakobiec, FA Zakka, FR Perry, LP AF Jakobiec, Frederick A. Zakka, Fouad R. Perry, Lynn P. TI The Cytologic Composition of Dacryops: An Immunohistochemical Investigation of 15 Lesions Compared to the Normal Lacrimal Gland SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID DUCTAL CYSTS; BILATERAL DACRYOPS; WOLFRING DACRYOPS; CONJUNCTIVAL CYST; LIESEGANG RINGS; PALPEBRAL LOBE; CASE SERIES; TISSUE; ORBIT; MARSUPIALIZATION AB PURPOSE: To define the cytologic composition of the double-layered epithelial lining of dacryops (lacrimal duct cyst), improve histopathologic diagnosis, and better understand pathogenesis. DESIGN: Clinicopathologic retrospective study with immunohistochemical studies of 15 lesions compared with normal lacrimal gland. METHODS: Clinical data from 14 patients were reviewed and microscopy was performed with routine stains and immunohistochemical probes for epithelial membrane antigen (EMA), gross cystic disease fluid protein-15 (GCDFP-15), cytokeratin 7 (CK7), and smooth muscle actin (SMA). RESULTS: The major lacrimal gland was involved in 13 lesions; 2 lesions arose in an accessory gland of Krause. One case was bilateral; the average age of the patients was 50.7 years. Neither visual acuity nor motility was disturbed. No lesion was discovered to have recurred after excision. Microscopically, in all dacryops specimens goblet cells and luminal pseudoapocrine apical cytoplasmic projections were identified. Lacrimal acinar cells immunoreacted with GCDFP-15 and CK7, whereas the normal ducts and the epithelium of the dacryops lesions reacted diffusely only with CK7. SMA-positive myoepithelial cells were found in the acini but not in the normal ducts or dacryops epithelium. CONCLUSIONS: Negative GCDFP-15 staining ruled out apocrine metaplasia in dacryops. Normal ducts and dacryops showed no immunohistochemical evidence for the presence of myoepithelial cells. Pathogenetic theories of dacryops that implicate a failure of ductular "neuromuscular" contractility must therefore be revised. A dysfunction of the rich neural plexus around the ductules may play a role in the development of dacryops in conjunction with periductular inflammation and induced scarring. (Am J Ophthalmol 2013;155:380-396. (c) 2013 by Elsevier Inc. All rights reserved.) C1 [Jakobiec, Frederick A.; Zakka, Fouad R.; Perry, Lynn P.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Lab Ophthalm Pathol,Dept Ophthalmol, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Lab Ophthalm Pathol,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu FU Heed Foundation, Cleveland, Ohio FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST. The authors have no financial disclosures. L.P.P. is supported in part by the Heed Foundation, Cleveland, Ohio. Involved in design and conduct of the study (F.A.J.); collection, management, analysis, and interpretation of the data (F.A.J., F.R.Z., L.P.P.); and preparation, review, and approval of the manuscript (F.A.J., F.R.Z., L.P.P.). This retrospective study received prior Institutional Review Board approval to retrospectively review patient data and was conducted in compliance with the rules and regulations of the Health Insurance Portability and Accountability Act and in adherence to the Declaration of Helsinki and all federal and state laws. NR 72 TC 9 Z9 9 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD FEB PY 2013 VL 155 IS 2 BP 380 EP 396 DI 10.1016/j.ajo.2012.07.028 PG 17 WC Ophthalmology SC Ophthalmology GA 078YQ UT WOS:000314137400023 PM 23114708 ER PT J AU Sahani, DV Kambadakone, A Macari, M Takahashi, N Chari, S Fernandez-del Castillo, C AF Sahani, Dushyant V. Kambadakone, Avinash Macari, Michael Takahashi, Noaki Chari, Suresh Fernandez-del Castillo, Carlos TI Diagnosis and Management of Cystic Pancreatic Lesions SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE cystic pancreatic lesion; MDCT; MRI ID PAPILLARY-MUCINOUS NEOPLASM; POSITRON-EMISSION-TOMOGRAPHY; COMPUTED-TOMOGRAPHY; SEROUS-CYSTADENOMA; FOLLOW-UP; CLINICOPATHOLOGICAL FEATURES; MR CHOLANGIOPANCREATOGRAPHY; PATHOLOGICAL CORRELATION; DIFFERENTIAL-DIAGNOSIS; ENDOSCOPIC ULTRASOUND AB OBJECTIVE. The purpose of this review is to outline the management guidelines for the care of patients with cystic pancreatic lesions. CONCLUSION. The guidelines are as follows: Annual imaging surveillance is generally sufficient for benign serous cystadenomas smaller than 4 cm and for asymptomatic lesions. Asymptomatic thin-walled unilocular cystic lesions smaller than 3 cm or side-branch intraductal papillary mucinous neoplasms should be followed up with CT or MRI at 6 and 12 months interval after detection. Cystic lesions with more complex features or with growth rates greater than 1 cm/year should be followed more closely or recommended for resection if the patient's condition allows surgery. Symptomatic cystic lesions, neoplasms with high malignant potential, and lesions larger than 3 cm should be referred for surgical evaluation. Endoscopic ultrasound with fine-needle aspiration (FNA) biopsy can be used preoperatively to assess the risk of malignancy. C1 [Sahani, Dushyant V.; Kambadakone, Avinash] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Macari, Michael] NYU, Dept Radiol, Div Abdominal Imaging, Langone Med Ctr, New York, NY 10016 USA. [Takahashi, Noaki] Mayo Clin, Dept Radiol, Div Abdominal Imaging, Rochester, MN USA. [Chari, Suresh] Mayo Clin, Dept Med, Div Gastroenterol, Rochester, MN USA. [Fernandez-del Castillo, Carlos] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Pancreat Surg, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org NR 93 TC 34 Z9 37 U1 0 U2 8 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 2013 VL 200 IS 2 BP 343 EP 354 DI 10.2214/AJR.12.8862 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 076LG UT WOS:000313957400034 PM 23345356 ER PT J AU Gallotti, A Johnston, RP Bonaffini, PA Ingkakul, T Deshpande, V Fernandez-del Castillo, C Sahani, DV AF Gallotti, Anna Johnston, Rocio Perez Bonaffini, Pietro A. Ingkakul, Thun Deshpande, Vikram Fernandez-del Castillo, Carlos Sahani, Dushyant V. TI Incidental Neuroendocrine Tumors of the Pancreas: MDCT Findings and Features of Malignancy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE incidental lesions; MDCT; neuroendocrine tumors; pancreas; pancreatic malignancy ID ISLET-CELL TUMORS; ENDOCRINE TUMORS; SURGICAL-TREATMENT; HELICAL CT; NEOPLASMS; CLASSIFICATION; SURVIVAL; ANGIOGENESIS; PREDICTORS; DENSITY AB OBJECTIVE. The objective of our study was to evaluate the MDCT features of incidentally detected neuroendocrine tumors (NETs) of the pancreas, identify features that can predict tumor biology or aggressiveness and long-term outcome, and determine the incidence of "nonbenign" behavior. MATERIALS AND METHODS. In this retrospective study, 60 histologically verified pancreatic NETs incidentally detected with contrast-enhanced MDCT were included. Various MDCT features such as size, morphology, enhancement, and presence of calcifications were evaluated and were correlated with tumor biology on histopathology. The sensitivity, specificity, predictive values, and accuracy were calculated for MDCT features in predicting nonbenign biology and risk of recurrence. RESULTS. A total of 32 of 60 (53%) NETs were nonbenign: most were large (mean, 29.1 mm) with a solid or complex pattern. NET size of 3 cm or larger yielded a positive predictive value of 61% for nonbenign tumors and 100% when calcification was present. In 12 patients with recurrence, 92% of NETs were nonbenign. The presence of calcification, local invasion, main pancreatic duct dilatation, vascular invasion, and lymph node enlargement along with angioinvasion and a Ki-67 index greater than 2% on histology were associated with a nonbenign diagnosis and a higher risk of recurrence. CONCLUSION. Approximately 50% of incidental NETs show uncertain or malignant behavior. Solid tumors 3 cm or larger are commonly nonbenign; however, about 30% of tumors smaller than that size cutoff can be malignant. Nonbenign tumors and those with invasive features on MDCT have a higher incidence of recurrence. C1 [Gallotti, Anna] Univ Verona, Dept Radiol, Univ Hosp GB Rossi, I-37100 Verona, Italy. [Gallotti, Anna; Johnston, Rocio Perez; Bonaffini, Pietro A.; Sahani, Dushyant V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Bonaffini, Pietro A.] Univ Milano Bicocca, San Gerardo Hosp, Dept Diagnost Radiol, Monza, Italy. [Ingkakul, Thun; Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org RI Bonaffini, Pietro/M-8067-2016 OI Bonaffini, Pietro/0000-0001-5335-9429 NR 47 TC 13 Z9 15 U1 0 U2 4 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 2013 VL 200 IS 2 BP 355 EP 362 DI 10.2214/AJR.11.8037 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 076LG UT WOS:000313957400035 PM 23345357 ER PT J AU Drubach, LA Zurakowski, D Palmer, EL Tracy, DA Lee, EY AF Drubach, Laura A. Zurakowski, David Palmer, Edwin L., III Tracy, Donald A. Lee, Edward Y. TI Utility of Salivagram in Pulmonary Aspiration in Pediatric Patients: Comparison of Salivagram and Chest Radiography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE chest radiography; pediatric patients; pulmonary aspiration; salivagram ID RADIONUCLIDE SALIVAGRAM; CHILDREN; AGREEMENT; SIALORRHEA; PNEUMONIA AB OBJECTIVE. The purpose of our study was to correlate the results of the radionuclide salivagram with the corresponding chest radiography findings on patients being evaluated for salivary aspiration to determine the utility of the salivagram. MATERIALS AND METHODS. We identified 222 patients younger than 21 years who underwent salivagram and chest radiography within 3 months of each other. Salivagrams were blindly interpreted by two readers and chest radiographs were blindly interpreted by two other readers. The kappa coefficient with 95% CI was used to measure the level of interobserver agreement. Multivariate logistic regression was applied to determine whether age, sex, and neurologic diagnosis were predictors of a positive salivagram, with the odds ratio used to estimate association. RESULTS. Interobserver agreement on salivagram interpretation was excellent (kappa = 0.988; p < 0.0001; 95% CI, 0.968-1.000). Interobserver agreement on chest radiography interpretation was excellent (kappa = 0.905; p < 0.0001; 95% CI, 0.845-0.965). The salivagram was positive for aspiration in 55 patients (25%). Chest radiography was positive in 54 patients (24%). When the interpretations of the salivagram (normal or abnormal) were compared with interpretations of the chest radiograph (normal or abnormal), there were 213 agreements and nine disagreements (intermethod agreement kappa = 0.891; p < 0.0001; 95% CI, 0.831-0.952). Independent of age (p = 0.80) and sex (p = 0.31), patients with a neurologic diagnosis had odds of a positive salivagram 5.6 times higher than other diagnoses (odds ratio = 5.6; 95% CI, 2.5-13.1; p < 0.0001). CONCLUSION. Infants with abnormal findings on salivagrams also had a high rate of abnormal findings on chest radiographs, which may indicate that some of the lung disease may be due to aspirated saliva. Salivagrams may be useful in children at risk of aspiration to identify those in whom intervention may help minimize the consequences of aspiration. C1 [Drubach, Laura A.] Childrens Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02115 USA. [Drubach, Laura A.; Zurakowski, David; Palmer, Edwin L., III; Tracy, Donald A.; Lee, Edward Y.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Zurakowski, David] Childrens Hosp, Dept Anesthesia, Div Biostat, Boston, MA 02115 USA. [Palmer, Edwin L., III] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. [Tracy, Donald A.; Lee, Edward Y.] Childrens Hosp, Dept Radiol, Div Thorac Imaging, Boston, MA 02115 USA. RP Lee, EY (reprint author), Childrens Hosp, Dept Radiol, Div Thorac Imaging, 300 Longwood Ave, Boston, MA 02115 USA. EM edward.lee@childrens.harvard.edu NR 26 TC 4 Z9 4 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 2013 VL 200 IS 2 BP 437 EP 441 DI 10.2214/AJR.12.8792 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 076LG UT WOS:000313957400046 PM 23345368 ER PT J AU Hunt, KJ Gebregziabher, M Lynch, CP Echols, C Mauldin, PD Egede, LE AF Hunt, Kelly J. Gebregziabher, Mulugeta Lynch, Cheryl P. Echols, Carrae Mauldin, Patrick D. Egede, Leonard E. TI Impact of diabetes control on mortality by race in a national cohort of veterans SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Type 2 diabetes; Race; Hemoglobin A1c; Retrospective cohort; Medication adherence; Mortality ID ALL-CAUSE MORTALITY; MEDICATION ADHERENCE; HEMOGLOBIN A(1C); CARDIOVASCULAR-DISEASE; LONGITUDINAL COHORT; RACIAL-DIFFERENCES; GLUCOSE CONTROL; DRUG-THERAPY; TYPE-2; MELLITUS AB Purpose: The association between glycated hemoglobin (HbA1c), medication use/adherence, and mortality stratified by race/ethnicity was examined in a national cohort of veterans with type 2 diabetes. Methods: A total of 892,223 veterans with diabetes in 2002 were followed through 2006. HbA1c category was the main exposure (i.e., HbA1c <7%, HbA1c 7%-8% [reference], HbA1c 8%-9%, and HbA1c >9%). Covariates included age, sex, marital status, rural/urban residence, geographic region, number of comorbidities, and diabetes medication use/adherence (i.e., adherent, medication possession ratio >= 80%; nonadherent; and nonusers). HbA1c and medication use/adherence varied over time, and Cox regression models accounting for time-varying variables were used. Results: In nonmedication users, HbA1c greater than 9% predicted higher mortality risk relative to HbA1c of 7%-8% in non-Hispanic whites (hazard ratio [HR], 1.55; 95% confidence interval [95% CI], 1.43-1.69), non-Hispanic blacks (NHB) (HR, 1.58; 95% CI, 1.34-1.87), and Hispanics (HR, 2.22; 95% CI, 1.75-2.82). In contrast, in nonadherent medication users, HbA1c less than 7% predicted higher mortality risk in NHB (HR, 1.12; 95% CI, 1.05-1.20), whereas HbA1c greater than 9% only predicted mortality in non-Hispanic whites (HR, 1.11; 95% CI, 1.06-1.16). In adherent medication users, HbA1c less than 7% predicted higher mortality in NHB (HR, 1.18; 95% CI, 1.07-1.31), whereas HbA1c greater than 9.0% predicted higher mortality risk across all race/ethnic groups. Conclusion: We found evidence for racial/ethnic differences in the association between glycemic control and mortality, which varied by medication use/adherence. (c) 2013 Elsevier Inc. All rights reserved. C1 [Hunt, Kelly J.; Gebregziabher, Mulugeta; Lynch, Cheryl P.; Echols, Carrae; Mauldin, Patrick D.; Egede, Leonard E.] Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Ralph H Johnson Dept, Charleston, SC 29403 USA. [Hunt, Kelly J.; Gebregziabher, Mulugeta] Med Univ S Carolina, Dept Med, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [Hunt, Kelly J.; Lynch, Cheryl P.; Echols, Carrae; Mauldin, Patrick D.; Egede, Leonard E.] Med Univ S Carolina, Dept Med, Div Gen Internal Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Dept Med, Div Gen Internal Med, Ctr Hlth Dispar Res, 135 Rutledge Ave,MSC 593, Charleston, SC 29425 USA. EM egedel@musc.edu OI Gebregziabher, Mulugeta/0000-0002-4826-481X FU VHA Health Services Research and Development program; [IIR-06-219] FX This study was supported by grant IIR-06-219 funded by the VHA Health Services Research and Development program. The funding agency did not participate in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 39 TC 6 Z9 6 U1 2 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD FEB PY 2013 VL 23 IS 2 BP 74 EP 79 DI 10.1016/j.annepidem.2012.11.002 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 074WO UT WOS:000313846000007 PM 23238350 ER PT J AU Vaduganathan, M AF Vaduganathan, Muthiah TI The Perils of Long Surgical Experiences: Changes in Case Mix Over Time SO ANNALS OF THORACIC SURGERY LA English DT Letter ID AORTIC-VALVE-REPLACEMENT; OUTCOMES C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Vaduganathan, M (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St,GRB 740, Boston, MA 02114 USA. EM mvaduganathan@partners.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD FEB PY 2013 VL 95 IS 2 BP 771 EP 772 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 074DF UT WOS:000313792000083 PM 23336903 ER PT J AU Wiederhold, NP Najvar, LK Bocanegra, R Kirkpatrick, WR Sorrell, TC Patterson, TF AF Wiederhold, Nathan P. Najvar, Laura K. Bocanegra, Rosie Kirkpatrick, William R. Sorrell, Tania C. Patterson, Thomas F. TI Limited Activity of Miltefosine in Murine Models of Cryptococcal Meningoencephalitis and Disseminated Cryptococcosis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INDIAN VISCERAL LEISHMANIASIS; WORLD CUTANEOUS LEISHMANIASIS; AMPHOTERICIN-B; FUNGICIDAL ACTIVITY; ORAL MILTEFOSINE; IN-VITRO; MENINGITIS; FLUCONAZOLE; HEXADECYLPHOSPHOCHOLINE; FLUCYTOSINE AB Miltefosine is an alkyl phosphocholine with good oral bioavailability and in vitro activity against Cryptococcus species that has gained interest as an additional agent for cryptococcal infections. Our objective was to further evaluate the in vivo efficacy of miltefosine in experimental in vivo models of cryptococcal meningoencephalitis and disseminated cryptococcosis. Mice were infected intracranially or intravenously with either C. neoformans USC1597 or H99. Miltefosine treatment (1.8 to 45 mg/kg of body weight orally once daily) began at either 1 h or 1 day postinoculation. Fluconazole (10 mg/kg orally twice daily) or amphotericin B deoxycholate (3 mg/kg intraperitoneally once daily) served as positive controls. In our standard models, miltefosine did not result in significant improvements in survival or reductions in fungal burden against either C. neoformans isolate. There was a trend toward improved survival with miltefosine at 7.2 mg/kg against disseminated cryptococcosis with the H99 strain but only at a low infecting inoculum. In contrast, both fluconazole and amphotericin B significantly improved survival in mice with cryptococcal meningoencephalitis and disseminated cryptococcosis due to USC1597. Amphotericin B also improved survival against both cryptococcal infections caused by H99. Combination therapy with miltefosine demonstrated neither synergy nor antagonism in both models. These results demonstrate limited efficacy of miltefosine and suggest caution with the potential use of this agent for the treatment of C. neoformans infections. C1 [Wiederhold, Nathan P.; Najvar, Laura K.; Bocanegra, Rosie; Kirkpatrick, William R.; Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Wiederhold, Nathan P.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Najvar, Laura K.; Bocanegra, Rosie; Kirkpatrick, William R.; Patterson, Thomas F.] S Texas Vet Hlth Care Adm, San Antonio, TX USA. [Sorrell, Tania C.] Sydney Emerging Infect & Biosecur Inst, Sydney, NSW, Australia. [Sorrell, Tania C.] Univ Sydney, Sydney, NSW 2006, Australia. [Sorrell, Tania C.] Westmead Millennium Inst, Sydney, NSW, Australia. RP Wiederhold, NP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. EM wiederholdn@uthscsa.edu OI Wiederhold, Nathan/0000-0002-2225-5122 FU National Institutes of Health/National Institute of Allergy and Infectious Diseases [N01-AI-25475]; Pfizer; Schering-Plough; Merck; Basilea; Astellas FX This work was supported by a contract from the National Institutes of Health/National Institute of Allergy and Infectious Diseases (N01-AI-25475) to T.F.P. T.C.S. is a Sydney Medical School Foundation Fellow.; N.P.W. has received research support from Pfizer, Schering-Plough, Merck, Basilea, and Astellas and has served on advisory boards for Merck, Astellas, Toyama, and Viamet. T.F.P. has received research grants to UT Health Science Center San Antonio from Astellas, Basilea, Merck, and Pfizer and has been a consultant for Astellas, Basilea, Merck, Pfizer, and Toyama. We have no other conflicts of interest. NR 30 TC 10 Z9 10 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD FEB PY 2013 VL 57 IS 2 BP 745 EP 750 DI 10.1128/AAC.01624-12 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 075ON UT WOS:000313896500008 PM 23165465 ER PT J AU Halford, C Gonzalez, R Campuzano, S Hu, B Babbitt, JT Liu, J Wang, J Churchill, BM Haake, DA AF Halford, Colin Gonzalez, Rodrigo Campuzano, Susana Hu, Bo Babbitt, Jane T. Liu, Jun Wang, Joseph Churchill, Bernard M. Haake, David A. TI Rapid Antimicrobial Susceptibility Testing by Sensitive Detection of Precursor rRNA Using a Novel Electrochemical Biosensing Platform SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CLINICAL URINE SPECIMENS; AMBIENT-TEMPERATURE; UROPATHOGENS; HYBRIDIZATION AB Precursor rRNA (pre-rRNA) is an intermediate stage in the formation of mature rRNA and is a useful marker for cellular metabolism and growth rate. We developed an electrochemical sensor assay for Escherichia coli pre-rRNA involving hybridization of capture and detector probes with tail sections that are spliced away during rRNA maturation. A ternary self-assembled monolayer (SAM) prepared on gold electrode surfaces by coassembly of thiolated capture probes with hexanedithiol and posttreatment with 6-mercapto-1-hexanol minimized the background signal and maximized the signal-to-noise ratio. Inclusion of internal calibration controls allowed accurate estimation of the pre-rRNA copy number per cell. As expected, the ratio of pre-rRNA to mature rRNA was low during stationary phase and high during log phase. Pre-rRNA levels were highly dynamic, ranging from 2 copies per cell during stationary phase to similar to 1,200 copies per cell within 60 min of inoculation into fresh growth medium. Specificity of the assay for pre-rRNA was validated using rifampin and chloramphenicol, which are known inhibitors of pre-rRNA synthesis and processing, respectively. The DNA gyrase inhibitor, ciprofloxacin, was found to act similarly to rifampin; a decline in pre-rRNA was detectable within 15 min in ciprofloxacin-susceptible bacteria. Assays for pre-rRNA provide insight into cellular metabolism and are promising predictors of antibiotic susceptibility. C1 [Halford, Colin; Gonzalez, Rodrigo; Babbitt, Jane T.; Haake, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Halford, Colin; Churchill, Bernard M.; Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Babbitt, Jane T.; Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. [Campuzano, Susana; Wang, Joseph] Univ Calif San Diego, Dept Nanoengn, La Jolla, CA 92093 USA. [Hu, Bo; Liu, Jun] Univ Texas Med Sch Houston, Dept Pathol & Lab Med, Houston, TX USA. RP Haake, DA (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. EM dhaake@ucla.edu RI Campuzano Ruiz, Susana/C-6448-2011; Wang, Joseph/C-6175-2011 FU National Institute of Allergy and Infectious Diseases [AI075565]; Wendy and Ken Ruby Fund for Excellence in Pediatric Urology Research; Welch Foundation [AU-1714] FX This study was supported by Cooperative Agreement Award AI075565 (to D.A.H.) from the National Institute of Allergy and Infectious Diseases and by the Wendy and Ken Ruby Fund for Excellence in Pediatric Urology Research. B.M.C. is the Judith and Robert Winston Chair in Pediatric Urology. B.H. and J.L. were supported by a grant from Welch Foundation (AU-1714). NR 18 TC 4 Z9 4 U1 1 U2 19 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD FEB PY 2013 VL 57 IS 2 BP 936 EP 943 DI 10.1128/AAC.00615-12 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 075ON UT WOS:000313896500033 PM 23229486 ER PT J AU Saremi, A Schwenke, DC Buchanan, TA Hodis, HN Mack, WJ Banerji, M Bray, GA Clement, SC Henry, RR Kitabchi, AE Mudaliar, S Ratner, RE Stentz, FB Musi, N Tripathy, D DeFronzo, RA Reaven, PD AF Saremi, Aramesh Schwenke, Dawn C. Buchanan, Thomas A. Hodis, Howard N. Mack, Wendy J. Banerji, MaryAnn Bray, George A. Clement, Stephen C. Henry, Robert R. Kitabchi, Abbas E. Mudaliar, Sunder Ratner, Robert E. Stentz, Frankie B. Musi, Nicolas Tripathy, Devjit DeFronzo, Ralph A. Reaven, Peter D. TI Pioglitazone Slows Progression of Atherosclerosis in Prediabetes Independent of Changes in Cardiovascular Risk Factors SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE carotid atherosclerosis progression; impaired glucose tolerance; insulin resistance; inflammation; pioglitazone ID IMPAIRED GLUCOSE-TOLERANCE; TYPE-2 DIABETES-MELLITUS; ACTIVATED-RECEPTOR-GAMMA; INTIMA-MEDIA THICKNESS; RANDOMIZED CONTROLLED-TRIAL; SMOOTH-MUSCLE-CELLS; PPAR-GAMMA; INSULIN SENSITIVITY; SUBCLINICAL ATHEROSCLEROSIS; CORONARY ATHEROSCLEROSIS AB Objective-To determine whether changes in standard and novel risk factors during the Actos Now for Prevention of Diabetes trial explained the slower rate of carotid intima media thickness (CIMT) progression with pioglitazone treatment in persons with prediabetes. Methods and Results-CIMT was measured in 382 participants at the beginning and up to 3 additional times during follow-up of the Actos Now for Prevention of Diabetes trial. During an average follow-up of 2.3 years, the mean unadjusted annual rate of CIMT progression was significantly (P=0.01) lower with pioglitazone treatment (4.76x10(-3) mm/year; 95% CI: 2.39x10(-3)-7.14x10(-3) mm/year) compared with placebo (9.69x10(-3) mm/year; 95% CI: 7.24x10(-3)-12.15x10(-3) mm/year). High-density lipoprotein cholesterol, fasting and 2-hour glucose, HbA(1c), fasting insulin, Matsuda insulin sensitivity index, adiponectin, and plasminogen activator inhibitor-1 levels improved significantly with pioglitazone treatment compared with placebo (P<0.001). However, the effect of pioglitazone on CIMT progression was not attenuated by multiple methods of adjustment for traditional, metabolic, and inflammatory risk factors and concomitant medications, and was independent of changes in risk factors during pioglitazone treatment. Conclusion-Pioglitazone slowed progression of CIMT, independent of improvement in hyperglycemia, insulin resistance, dyslipidemia, and systemic inflammation in prediabetes. These results suggest a possible direct vascular benefit of pioglitazone. (Arterioscler Thromb Vasc Biol. 2013;33:393-399.) C1 [Saremi, Aramesh; Schwenke, Dawn C.; Reaven, Peter D.] Phoenix Vet Affair VA Hlth Care Syst, Phoenix, AZ USA. [Buchanan, Thomas A.; Hodis, Howard N.; Mack, Wendy J.] Univ So Calif, Sch Med, Los Angeles, CA USA. [Banerji, MaryAnn] SUNY Hlth Sci Ctr, Brooklyn, NY USA. [Bray, George A.] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Clement, Stephen C.] Georgetown Univ, Washington, DC USA. [Henry, Robert R.; Mudaliar, Sunder] San Diego VA Hlth Care Syst, San Diego, CA USA. [Henry, Robert R.; Mudaliar, Sunder] Univ San Diego, San Diego, CA 92110 USA. [Kitabchi, Abbas E.; Stentz, Frankie B.] Univ Tennessee, Memphis, TN USA. [Ratner, Robert E.] Medstar Res Inst, Hyattsville, MD USA. [Musi, Nicolas; Tripathy, Devjit; DeFronzo, Ralph A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Musi, Nicolas] S Texas Vet Healthcare Syst, San Antonio, TX USA. RP Reaven, PD (reprint author), Carl T Hayden VAMC 111E, Diabet Program, 650 E Indian Sch Rd, Phoenix, AZ 85012 USA. EM Peter.Reaven@va.gov FU Takeda Pharmaceuticals [NCT00220961]; office of Research and Development, Medical Research Service, Department of Veterans Affairs; BMS; Novartis; Boehringer Ingelheim; Sanofi-Aventis; Merck; Roche; Takeda; Amylin; Eli Lilly; Daiichi-Sankyo; NovoNordisk; Genentech-Roche; GlaxoSmithKline; Bayhill; Halozyme; Integrium; Takeda Pharmaceuticals FX This investigator-initiated study was supported by a grant from Takeda Pharmaceuticals. (ClinicalTrial.gov number, NCT00220961). This work was supported in part by the office of Research and Development, Medical Research Service, Department of Veterans Affairs. We are grateful to ACT NOW study participants, study staff, and investigators. The contents of this article do not repre-sent the views of the Department of Veterans Affairs or the U.S. Government.; Dr Banerji reports receiving consulting fees from BMS, Novartis, Boehringer Ingelheim, Sanofi-Aventis, Merck, and Roche, and lecture fees from Merck and Sanofi-Aventis; Dr Buchanan reports receiving consulting fees and lecture fees from Takeda and reports that the University of Southern California Keck School of Medicine has received grant support from Takeda; Dr DeFronzo reports receiving payments for board membership from Amylin, Takeda, ISIS, and Boehringer Ingelheim and reports that the University of Texas Health Science Center at San Antonio has received grant support from Takeda, Amylin, and Eli Lilly; Dr Henry reports receiving consulting fees, lecture fees, and payment for expert testimony from Takeda; Dr Musi reports receiving consulting fees from Merck, Daiichi-Sankyo, Takeda, and Novartis; Dr Ratner reports that the Medstar Research Institute has received consulting fees from Amylin, NovoNordisk, Sanofi-Aventis, and Genentech-Roche and grant support from Amylin, NovoNordisk, GlaxoSmithKline, Bayhill, Halozyme, and Integrium; Dr Reaven reports receiving consulting fees from BMS and Gilead, lecture fees from Merck and Amylin, and payment for the development of educational presentations from Amylin, and that the Carl T. Hayden Veterans Affairs Medical Center has received grant support from Amylin; and Dr Tripathy reports receiving grant support from Takeda Pharmaceuticals. No other potential conflict of interest relevant to this article was reported. NR 40 TC 33 Z9 33 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD FEB PY 2013 VL 33 IS 2 BP 393 EP + DI 10.1161/ATVBAHA.112.300346 PG 16 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 073MS UT WOS:000313747700035 PM 23175674 ER PT J AU Dhonnchadha, BAN Lin, A Leite-Morris, KA Kaplan, GB Man, HY Kantak, KM AF Dhonnchadha, B. A. Nic Lin, A. Leite-Morris, K. A. Kaplan, G. B. Man, H. Y. Kantak, K. M. TI Alterations in expression and phosphorylation of GluA1 receptors following cocaine-cue extinction learning SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Basolateral amygdala; Cocaine; Cocaine-cue extinction learning; GluA1 receptor; Self-administration; Ventromedial prefrontal cortex ID MEDIAL PREFRONTAL CORTEX; AMPA RECEPTORS; SYNAPTIC PLASTICITY; PKA PHOSPHORYLATION; FEAR; TRAFFICKING; SUBUNIT; MEMORY; FOS AB Brain regional analyses of total GluA1 and GluA1-pSer(845) were used to delineate plasticity of the AMPA receptor in conjunction with cocaine-cue extinction learning. Rats were trained to self-administer cocaine paired with a 2-s light cue and later underwent a single 2 h extinction session for which cocaine was withheld but response-contingent cues were presented. Control groups received yoked-saline sessions or received cocaine self-administration training without undergoing extinction training. Extinction-related increases and decreases, respectively, in total GluA1 were observed in the ventromedial prefrontal cortex (vmPFC) and basolateral amygdala (BLA). Phosphorylation of GluA1 at Ser(845) was increased in the vmPFC and nucleus accumbens (NAc). Though total GluA1 did not change in NAc, there was a positive association between the number of responses during extinction training and the magnitude of total GluA1 in NAc. No significant changes were evident in the dorsal hippocampus. We conclude that the BLA and vmPFC, in particular, appear to be loci for the inhibition of learned behavior induced via extinction training, but each site may have different signaling functions for cocaine-cue extinction learning. (c) 2012 Elsevier B.V. All rights reserved. C1 [Dhonnchadha, B. A. Nic; Kantak, K. M.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Lin, A.; Man, H. Y.] Boston Univ, Dept Biol, Boston, MA 02215 USA. [Leite-Morris, K. A.; Kaplan, G. B.] VA Boston Healthcare, Res Serv, Boston, MA USA. [Leite-Morris, K. A.; Kaplan, G. B.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Leite-Morris, K. A.; Kaplan, G. B.] Boston Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02215 USA. RP Kantak, KM (reprint author), Boston Univ, Dept Psychol, 64 Cummington Mall, Boston, MA 02215 USA. EM kkantak@bu.edu OI Leite-Morris, Kimberly/0000-0003-3407-7375 FU Boston University Center for Neuroscience; [DA011716] FX This study was supported by seed funding from the Boston University Center for Neuroscience and DA011716. We thank Ms. Jamie Gauthier for assistance with data collection. NR 25 TC 8 Z9 8 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 EI 1872-7549 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD FEB 1 PY 2013 VL 238 BP 119 EP 123 DI 10.1016/j.bbr.2012.10.012 PG 5 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 078ZE UT WOS:000314138800016 ER PT J AU Courtwright, A AF Courtwright, Andrew TI STIGMATIZATION AND PUBLIC HEALTH ETHICS SO BIOETHICS LA English DT Article DE contractualism; denormalization; Martha Nussbaum; public health ethics; social identity; stigma ID STIGMA; TUBERCULOSIS; PREJUDICE; OBESITY AB Encouraged by the success of smoking denormalization strategies as a tobacco-control measure, public health institutions are adopting a similar approach to other health behaviors. For example, a recent controversial ad campaign in New York explicitly aimed to denormalize HIV/AIDS amongst gay men. Authors such as Scott Burris have argued that efforts like this are tantamount to stigmatization and that such stigmatization is unethical because it is dehumanizing. Others have offered a limited endorsement of denormalization/stigmatization campaigns as being justified on consequentialist grounds; namely, that the potential public health benefits outweigh any stigmatizing side effects. In this paper, I examine and reject the blanket condemnation of stigmatization efforts in public health. I argue that the moral status of such efforts are best evaluated within a contractualist, as opposed to a consequentialist, framework. Contractualism in public health ethics asks whether a particular stigmatizing policy could be justified to reasonable individuals who do not know whether they will be affected by that policy. Using this approach, I argue that it is sometimes permissible for public health institutions to engage in health-related stigmatization. RP Courtwright, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Internal Med,Womens Hlth Associates, Yawkey 4B,55 Fruit St, Boston, MA 02114 USA. EM acourtwright@partners.org NR 25 TC 7 Z9 7 U1 2 U2 32 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-9702 J9 BIOETHICS JI Bioethics PD FEB PY 2013 VL 27 IS 2 BP 74 EP 80 DI 10.1111/j.1467-8519.2011.01904.x PG 7 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 070MO UT WOS:000313511300004 PM 21797912 ER PT J AU Liu, R Gilmore, DM Zubris, KAV Xu, XY Catalano, PJ Padera, RF Grinstaff, MW Colson, YL AF Liu, Rong Gilmore, Denis M. Zubris, Kimberly Ann V. Xu, Xiaoyin Catalano, Paul J. Padera, Robert F. Grinstaff, Mark W. Colson, Yolonda L. TI Prevention of nodal metastases in breast cancer following the lymphatic migration of paclitaxel-loaded expansile nanoparticles SO BIOMATERIALS LA English DT Article DE Nanoparticle; Drug delivery; Polymer; Metastases; Breast cancer; Lymphatic ID EPITHELIAL OVARIAN-CANCER; DRUG-DELIVERY; CHEMOTHERAPY; TUMORS; MODEL; RECURRENCE; MORBIDITY; EFFICACY; CARRIERS; THERAPY AB Although breast cancer patients with localized disease exhibit an excellent long-term prognosis, up to 40% of patients treated with local resection alone may harbor occult nodal metastatic disease leading to increased locoregional recurrence and decreased survival. Given the potential for targeted drug delivery to result in more efficacious locoregional control with less morbidity, the current study assessed the ability of drug-loaded polymeric expansile nanoparticles (eNP) to migrate from the site of tumor to regional lymph nodes, locally deliver a chemotherapeutic payload, and prevent primary tumor growth as well as lymph node metastases. Expansile nanoparticles entered tumor cells and paclitaxel-loaded eNP (Pax-eNP) exhibited dose-dependent cytotoxicity in vitro and significantly decreased tumor doubling time in vivo against human triple negative breast cancer in both microscopic and established murine breast cancer models. Furthermore, migration of Pax-eNP to axillary lymph nodes resulted in higher intranodal paclitaxel concentrations and a significantly lower incidence of lymph node metastases. These findings demonstrate that lymphatic migration of drug-loaded eNP provides regionally targeted delivery of chemotherapy to both decrease local tumor growth and strategically prevent the development of nodal metastases within the regional tumor-draining lymph node basin. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Liu, Rong; Gilmore, Denis M.; Colson, Yolonda L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Thorac Surg,Dept Surg, Boston, MA 02115 USA. [Zubris, Kimberly Ann V.; Grinstaff, Mark W.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Zubris, Kimberly Ann V.; Grinstaff, Mark W.] Boston Univ, Dept Chem, Boston, MA 02215 USA. [Xu, Xiaoyin] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Catalano, Paul J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Padera, Robert F.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Colson, YL (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Thorac Surg,Dept Surg, 75 Francis St,PBB 544, Boston, MA 02115 USA. EM mgrin@bu.edu; ycolson@partners.org FU Center for Integration of Medicine and Innovative Technologies (CIMIT) [07-004]; National Science Foundation [DMR-1006601, CNS-0958345]; Boston University's Nanomedicine Program and Cross-Disciplinary Training in Nanotechnology for Cancer [NIH R25 CA153955]; Brigham and Women's Hospital; Boston University FX This work was supported in part by the Center for Integration of Medicine and Innovative Technologies (CIMIT #07-004), National Science Foundation (DMR-1006601 and CNS-0958345), the Boston University's Nanomedicine Program and Cross-Disciplinary Training in Nanotechnology for Cancer (NIH R25 CA153955), Brigham and Women's Hospital, and Boston University. The authors wish to express appreciation for the excellent care provided by the staff at the Animal Resources Facility at Dana-Farber Cancer Institute, and to acknowledge the contributions of the Confocal Core Facility at Beth Israel Deaconess Medical Center under the direction of Lay-Hong Ang. NR 41 TC 23 Z9 23 U1 1 U2 50 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 EI 1878-5905 J9 BIOMATERIALS JI Biomaterials PD FEB PY 2013 VL 34 IS 7 BP 1810 EP 1819 DI 10.1016/j.biomaterials.2012.11.038 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 078GV UT WOS:000314087600007 PM 23228419 ER PT J AU Slopen, N McLaughlin, KA Dunn, EC Koenen, KC AF Slopen, Natalie McLaughlin, Katie A. Dunn, Erin C. Koenen, Karestan C. TI Childhood adversity and cell-mediated immunity in young adulthood: Does type and timing matter? SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE Cell-mediated immune response; Epstein-Barr Virus (EBV) antibody titers; Childhood adversity; Child abuse; Socioeconomic status; National Longitudinal Study of Adolescent Health (Add Health) ID EPSTEIN-BARR-VIRUS; EARLY-LIFE; PSYCHOLOGICAL STRESS; SOCIOECONOMIC-STATUS; HEALTH OUTCOMES; INFECTIOUS-DISEASE; ANTIBODY-LEVELS; MENTAL-HEALTH; MALTREATMENT; INFLAMMATION AB Childhood adversity can have powerful effects on health over the life course. Persistent changes in cell-mediated immune function may be one pathway linking adverse childhood experiences with later disease risk. However, limited research has examined childhood adversity in relation to cell-mediated immune function, and in particular, immune response to latent viruses in adulthood. The present study investigated the association of two types of childhood adversity, socioeconomic disadvantage during adolescence and abuse prior to age 18, with Epstein-Barr Virus (EBV) antibody titers in a large nationally representative sample of young adults aged 24-32 years. Data were drawn from the National Longitudinal Study on Adolescent Health, Wave 4 (n = 13,162). We examined the associations of three indicators of adolescent SES (parental education, household income, and occupational status) and frequency and timing of physical and sexual abuse with EBV antibodies, controlling for age, sex, race/ethnicity, and presence of a smoker in the household during adolescence. Lower parental occupational status and some categories of lower education were associated with elevated EBV antibodies (p < .05), and individuals who reported sexual abuse that occurred more than 10 times had elevated EBV antibodies relative to individuals who were not sexually abused (p = 0.03). Among individuals exposed to physical abuse, those who were first abused at age 3-5 years had heightened EBV antibodies relative to those first abused during adolescence (p = 0.004). This study extends prior research linking early adversity and immune function, and provides initial evidence that childhood adversity has a persistent influence on immune responses to latent infection in adulthood. (C) 2012 Elsevier Inc. All rights reserved. C1 [Slopen, Natalie] Harvard Univ, Ctr Developing Child, Cambridge, MA 02138 USA. [McLaughlin, Katie A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Dunn, Erin C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Koenen, Karestan C.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY 10032 USA. RP Slopen, N (reprint author), Harvard Univ, Ctr Developing Child, 50 Church St,4th Floor, Cambridge, MA 02138 USA. EM nslopen@hsph.harvard.edu RI Koenen, Karestan/K-5402-2014; OI Koenen, Karestan/0000-0003-3293-4281; McLaughlin, Katie/0000-0002-1362-2410 FU Robert Wood Johnson Foundation; Eunice Kennedy Shriver National Institute of Child Health and Human Development [P01-HD31921] FX This research was funded by a postdoctoral fellowship to the first author from the Robert Wood Johnson Foundation to support the Early Childhood Innovation Project. This research uses data from Add Health, a program project directed by Kathleen Mullan Harris and designed by J. Richard Udry, Peter S. Bearman, and Kathleen Mullan Harris at the University of North Carolina at Chapel Hill, and funded by Grant P01-HD31921 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, with cooperative funding from 23 other federal agencies and foundations. Special acknowledgment is due Ronald R. Rindfuss and Barbara Entwisle for assistance in the original design. Information on how to obtain the Add Health data files is available on the Add Health website (http://www.cpc.unc.edu/addhealth). No direct support was received from Grant P01-HD31921 for this analysis. NR 77 TC 23 Z9 25 U1 8 U2 38 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD FEB PY 2013 VL 28 BP 63 EP 71 DI 10.1016/j.bbi.2012.10.018 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 076YV UT WOS:000313996000008 PM 23108062 ER PT J AU Irwin, KE Greer, JA Khatib, J Temel, JS Pirl, WF AF Irwin, Kelly E. Greer, Joseph A. Khatib, Jude Temel, Jennifer S. Pirl, William F. TI Early palliative care and metastatic non-small cell lung cancer: Potential mechanisms of prolonged survival SO CHRONIC RESPIRATORY DISEASE LA English DT Article DE Early palliative care; survival; lung cancer; advanced cancer ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; CLINICAL-TRIALS; MEDICINE CONSULTATION; ELDERLY-PATIENTS; REPORTED HEALTH; MARITAL-STATUS; DEPRESSION; INTERVENTION; OUTCOMES AB Patients with advanced cancer experience a significant burden of physical symptoms and psychological distress at the end of life, and many elect to receive aggressive cancer-directed therapy. The goal of palliative care is to relieve suffering and promote quality of life (QOL) for patients and families. Traditionally, both the public and medical community have conceptualized the need for patients to make a choice between pursuing curative therapy or receiving palliative care. However, practice guidelines from the World Health Organization and leadership from the oncology and palliative care communities advocate a different model of palliative care that is introduced from the point of diagnosis of life-threatening illness. Early palliative care has been shown to provide benefits in QOL, mood, and health care utilization. Additionally, preliminary research has suggested that in contrast to fears about palliative care hastening death, referral to palliative care earlier in the course of illness may have the potential to lengthen survival, particularly in patients with advanced nonsmall-cell lung cancer. This review summarizes the literature on potential survival benefits of palliative care and presents a model of how early integrated palliative care could potentially influence survival in patients with advanced cancer. C1 [Irwin, Kelly E.; Greer, Joseph A.; Temel, Jennifer S.; Pirl, William F.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Khatib, Jude] Royal Coll Surgeons Ireland, Dublin 2, Ireland. RP Pirl, WF (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM wpirl@partners.org NR 58 TC 24 Z9 25 U1 2 U2 23 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1479-9723 J9 CHRON RESP DIS JI Chronic Respir. Dis. PD FEB PY 2013 VL 10 IS 1 BP 35 EP 47 DI 10.1177/1479972312471549 PG 13 WC Respiratory System SC Respiratory System GA 078UW UT WOS:000314126200006 PM 23355404 ER PT J AU Bragdon, CR Doerner, M Martell, J Jarrett, B Palm, H Malchau, H AF Bragdon, Charles R. Doerner, Michael Martell, John Jarrett, Bryan Palm, Henrik Malchau, Henrik CA Multicenter Study Grp TI The 2012 John Charnley Award: Clinical Multicenter Studies of the Wear Performance of Highly Crosslinked Remelted Polyethylene in THA SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID MOLECULAR-WEIGHT POLYETHYLENE; TOTAL HIP-ARTHROPLASTY; FEMORAL-HEAD PENETRATION; TOTAL JOINT ARTHROPLASTY; RADIOSTEREOMETRIC ANALYSIS; UNCEMENTED SOCKETS; ACETABULAR LINER; 3RD-BODY WEAR; FOLLOW-UP; IN-VITRO AB Highly crosslinked polyethylene (HXLPE) in THA was developed to reduce particle-induced periprosthetic osteolysis. A series of clinical studies were initiated to determine the clinical efficacy as judged by patient-reported scores, radiographic osteolysis, and wear analysis of one form of HXLPE. The purposes of this series of studies were to (1) determine the wear rates of one form of HXLPE; (2) report long-term (7-10 years) patient-reported outcome measures; (3) assess the effect of femoral head size on wear; and (4) determine the incidence of periprosthetic osteolysis. A single-center and two multicenter studies were conducted on 768 primary patients (head size 26-36 mm) undergoing THA at eight medical centers. Patient-reported outcome scores, radiographic grading for osteolysis, and radiographic wear evaluation were performed. Serial plain radiographs showed no periprosthetic osteolysis in the three studies. The average femoral head penetration rates did not correlate with time in vivo for patients with standard femoral head sizes. Although there was an indication of higher wear in patients with 36-mm diameter femoral heads, it was below the threshold for producing osteolysis. The introduction of this HXLPE substantially improved the prognosis of patients after THA up to 13 years as judged by clinical scores, incidence of osteolysis, and polyethylene wear measurements. Level III, therapeutic study. See the Guideline for Authors for a complete description of levels of evidence. C1 [Bragdon, Charles R.; Doerner, Michael; Jarrett, Bryan; Malchau, Henrik] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. [Martell, John] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Palm, Henrik] Hvidovre Univ Hosp, Copenhagen, Denmark. RP Bragdon, CR (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, 55 Fruit St,GRJ 1126, Boston, MA 02114 USA. EM cbragdon@partners.org OI Malchau, Henrik/0000-0002-4291-2441 FU Zimmer Inc; Curing Hip Disease Fund; DePuy; William H. Harris Foundation FX Sahlgrenska University Hospital, Gothenburg, Sweden One of the authors (CDV) certifies he has or may receive payments or benefits, in any one year, an amount in excess of $10,000 from a commercial entity (Biomet, Warsaw, IN, USA, and Smith & Nephew, Memphis TN, USA). One of the authors (KB) certifies that he has or may receive payments or benefits, during the study period, an amount of more than $1,000,001 from Zimmer Inc (Warsaw, IN, USA) and DePuy Ortho Inc (Warsaw, IN, USA). One of the authors (DB) certifies that he has or may receive payments or benefits, during the study period, an amount of more than $1,000,001 from DePuy Ortho Inc. The institution of two contributors (PL, DB) receives research funds From (DePuy Ortho Inc or Zimmer Inc). The institution of one or more of the authors (CRB, MD, BJ, YMK, HM, PEJ, DB, JC) received funding from Zimmer Inc, Curing Hip Disease Fund, DePuy, and/or the William H. Harris Foundation. Seven contributors (JC, MD, YMK, BJ, PEJ, HP, HM) certifies that he or she, or a member of their immediate family, has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. NR 55 TC 36 Z9 36 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD FEB PY 2013 VL 471 IS 2 BP 393 EP 402 DI 10.1007/s11999-012-2604-0 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 074FO UT WOS:000313798500010 PM 23070661 ER PT J AU Bozic, KJ Ong, K Lau, E Berry, DJ Vail, TP Kurtz, SM Rubash, HE AF Bozic, Kevin J. Ong, Kevin Lau, Edmund Berry, Daniel J. Vail, Thomas P. Kurtz, Steven M. Rubash, Harry E. TI Estimating Risk in Medicare Patients With THA: An Electronic Risk Calculator for Periprosthetic Joint Infection and Mortality SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TOTAL HIP-ARTHROPLASTY; QUALITY-OF-LIFE; POSTOPERATIVE MORTALITY; KNEE; REPLACEMENT; OSTEOARTHRITIS AB Although risk factors for periprosthetic joint infection (PJI) and mortality after total hip arthroplasty (THA) have been identified, interactions between specific patient risk factors are poorly understood. Therefore, it is difficult for surgeons to counsel patients on their individual risk of PJI or mortality after THA. We evaluated the interaction between patient clinical and demographic factors on the risk of PJI and mortality after THA and developed an electronic risk calculator for estimating the patient-specific risk of PJI and mortality in Medicare patients with THA. We used the Medicare 5% sample claims database to calculate the risk of PJI within 2 years and mortality within 90 days after THA in 53,252 Medicare patients with primary THAs between 1998 and 2009. Logistic regression using 29 comorbid conditions, age, sex, race, and socioeconomic status were used as inputs to develop an electronic risk calculator to estimate patient-specific risk of PJI and mortality after THA. The overall 2-year risk of PJI and 90-day risk of mortality after primary THA were 2.07% and 1.30%, respectively. White women aged 70 to 74 years with alcohol abuse, depression, electrolyte disorder, peptic ulcer disease, urinary tract infection, rheumatologic disease, preoperative anemia, cardiopulmonary (cardiac arrhythmia, congestive heart failure, ischemic heart disease, chronic pulmonary disease) comorbidities, and peripheral vascular disease were at highest risk for PJI. White women aged 65 to 69 years with electrolyte disorder, hemiplegia/paraplegia, hypertension, hypothyroidism, metastatic tumor, preoperative anemia, coagulopathy, cardiopulmonary (congestive heart failure, chronic pulmonary disease) and psychiatric (psychoses, depression) comorbidities, malignancies, and peripheral vascular disease were at highest risk for mortality. An electronic risk calculator was developed to estimate the risk of PJI and mortality in Medicare patients with THA. This electronic risk calculator can be used to counsel Medicare patients regarding their patient-specific risks of PJI and mortality after THA. Level II, prognostic study. See the Instructions for Authors for a complete description of levels of evidence. C1 [Bozic, Kevin J.; Vail, Thomas P.] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. [Bozic, Kevin J.] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94143 USA. [Ong, Kevin; Kurtz, Steven M.] Exponent Inc, Philadelphia, PA USA. [Lau, Edmund] Exponent Inc, Menlo Pk, CA USA. [Berry, Daniel J.] Mayo Clin, Dept Orthopaed Surg, Rochester, MN USA. [Rubash, Harry E.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Bozic, KJ (reprint author), Univ Calif San Francisco, Dept Orthopaed Surg, 500 Parnassus,MU 320W, San Francisco, CA 94143 USA. EM kevin.bozic@ucsf.edu FU Orthopaedic Research and Education Foundation (Rosemont, IL, USA); Exponent, Inc (Philadelphia, PA, USA); Exponent, Inc.; DePuy Orthopaedics, Inc (Warsaw, IN, USA); DePuy Orthopaedics, Inc.; Zimmer, Inc (Warsaw, IN, USA) FX The institution of one or more of the authors (KJB) has received, during the study period, funding from the Orthopaedic Research and Education Foundation (Rosemont, IL, USA). One of the authors (SMK) certifies that he has received or may receive payments or benefits, during the study period, an amount in excess of $100,000, from Exponent, Inc (Philadelphia, PA, USA). One of the authors (KO) certifies that he has received or may receive payments or benefits, during the study period, an amount in excess of $100,000, from Exponent, Inc. One of the authors (EL) certifies that he has received or may receive payments or benefits, during the study period, an amount in excess of $100,000, from Exponent, Inc. One of the authors (DJB) certifies that he has received or may receive payments or benefits, during the study period, an amount in excess of $100,000, from DePuy Orthopaedics, Inc (Warsaw, IN, USA). One of the authors (TPV) certifies that he has received or may receive payments or benefits, during the study period, an amount in excess of $10,000, from DePuy Orthopaedics, Inc. One of the authors (HER) certifies that he has received or may receive payments or benefits, during the study period, an amount in excess of $100,000, from Zimmer, Inc (Warsaw, IN, USA). NR 16 TC 39 Z9 39 U1 0 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD FEB PY 2013 VL 471 IS 2 BP 574 EP 583 DI 10.1007/s11999-012-2605-z PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 074FO UT WOS:000313798500033 PM 23179112 ER PT J AU Jain, NB Kuye, I Higgins, LD Warner, JJP AF Jain, Nitin B. Kuye, Ifedayo Higgins, Laurence D. Warner, Jon J. P. TI Surgeon Volume is Associated With Cost and Variation in Surgical Treatment of Proximal Humeral Fractures SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TOTAL HIP-REPLACEMENT; SHOULDER ARTHROPLASTY; HOSPITAL VOLUME; TERM OUTCOMES; UNITED-STATES; CARE; CLASSIFICATION; HEMIARTHROPLASTY; REPRODUCIBILITY; MORBIDITY AB The issue of rising costs will likely dominate the healthcare debate in the forthcoming years. We assessed factors including surgeon volume that were associated with lower hospital costs and variations in surgical treatment for proximal humeral fractures. We used national databases for 2001 to 2008 to extract information on 25,731 patients undergoing surgery for proximal humeral fractures. We calculated hospital cost by converting hospital charges based on the hospital accounting reports collected by the Centers for Medicare & Medicaid Services. In a multivariate linear regression analysis, higher surgeon volume, open reduction and internal fixation (versus hemiarthroplasty), and lower burden of comorbidities were associated with lower hospital cost. Higher surgeon volume was linearly associated with lower hospital costs such that, on average, adjusting for all other factors, a surgeon performing 20 shoulder arthroplasties per year saves a hospital approximately US $1800 per surgery. Factors associated with higher utilization of hemiarthroplasty included high surgeon volume (odds ratio [OR] = 1.46; 95% CI = 1.43, 1.97; as compared with low surgeon volume) and earlier years of our study period (OR = 0.61; 95% CI = 0.56, 0.66; for hemiarthroplasty in 2007-2008 versus 2001-2002). Higher surgeon volume was associated with lower hospital costs for proximal humeral fractures. Therefore, policies on minimum volume requirements by hospitals may result in substantial cost savings. There is provider-based practice variation in the surgical treatment of proximal humeral fractures and evidence-based guidelines in this area are needed. Level III, economic analysis. See Instructions for Authors for a complete description of levels of evidence. C1 [Jain, Nitin B.] Brigham & Womens Hosp, Orthoped & Arthrit Ctr Outcomes Res, Boston, MA 02115 USA. [Jain, Nitin B.; Kuye, Ifedayo; Higgins, Laurence D.; Warner, Jon J. P.] Harvard Univ, Sch Med, Harvard Shoulder Serv, Boston, MA USA. [Jain, Nitin B.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Jain, Nitin B.; Kuye, Ifedayo; Higgins, Laurence D.] Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Warner, Jon J. P.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Jain, NB (reprint author), Brigham & Womens Hosp, Orthoped & Arthrit Ctr Outcomes Res, 75 Francis St,BC-4-016, Boston, MA 02115 USA. EM njain1@partners.org FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [1K23AR059199]; Foundation for Physical Medicine and Rehabilitation (Rosemont, IL, USA); Biomedical Research Institute (Boston, MA, USA) FX One of the authors (NBJ) certifies that he, or a member of his immediate family, has received or may receive payments or benefits, during the study period, from National Institute of Arthritis and Musculoskeletal and Skin Diseases Project Number 1K23AR059199, Foundation for Physical Medicine and Rehabilitation (Rosemont, IL, USA), and Biomedical Research Institute (Boston, MA, USA). NR 46 TC 14 Z9 14 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD FEB PY 2013 VL 471 IS 2 BP 655 EP 664 DI 10.1007/s11999-012-2481-6 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 074FO UT WOS:000313798500044 PM 22826013 ER PT J AU Larkin, ME Beauharnais, CC Magyar, K Macey, L Grennan, KB Boykin, EE Russell, SJ AF Larkin, Mary E. Beauharnais, Catherine C. Magyar, Kendra Macey, Laurel Grennan, Kerry B. Boykin, Emily E. Russell, Steven J. TI Obtaining surrogate consent for a minimal-risk research study in the intensive care unit setting SO CLINICAL TRIALS LA English DT Article AB Background Obtaining surrogate consent for clinical research studies conducted in the intensive care unit (ICU) setting is logistically challenging. Purpose To determine whether differences in proportions consenting to trial enrollment existed among patients eligible to consent directly versus those requiring surrogate decision makers in a minimal-risk study to evaluate the accuracy of continuous glucose monitoring in the ICU setting. Methods Low initial enrollment rates prompted a detailed tracking of the screening and consent process. We analyzed the subset of eligible patients identified during a single year to document whether they were approached about trial enrollment, whether they consented or declined, the reasons for declining, and the method of consent (self or surrogate). The proportion of participants who consented and the reasons for declining were compared for self-consenting and surrogate-consenting participants. Results Of the 3041 patients screened, one-third (n = 982) were eligible; 119 of the 982 were approached regarding enrollment. Absence of a surrogate accounted for the majority of eligible patients (726; 84%) not approached. The most common reasons for refusal in the self versus surrogate groups included feeling overwhelmed (13% vs 24%), fear of discomfort (22% vs 12%), and fear of risk (7% vs 4%). Of the 57 eligible patients capable of consenting directly, 11 (19%) enrolled versus 12 (19%) of the 62 who required surrogate consent. When recruitment hours were expanded to include evening time, more eligible patients or their surrogates could be approached than during the day-shift hours alone. Consent was obtained for a larger proportion of potential participants with a history of diabetes (40%) than for those without a history of diabetes (14%). Limitations The findings are from a subset of the entire study sample; data were available only for participants who could be approached, who may have differed from those who could not be approached. Conclusions Surrogate and self-consent rates were similar. Surrogate unavailability was a major barrier to enrollment; overlap of staffing with usual visiting hours should be considered when planning trials in the ICU. Clinical Trials 2012; 10: 93-96. http://ctj.sagepub.com C1 [Larkin, Mary E.; Beauharnais, Catherine C.; Magyar, Kendra; Macey, Laurel; Grennan, Kerry B.; Boykin, Emily E.; Russell, Steven J.] Massachusetts Gen Hosp, Diabet Res Ctr, Boston, MA 02114 USA. RP Larkin, ME (reprint author), Massachusetts Gen Hosp, Diabet Res Ctr, 50 Staniford St,Ste 301, Boston, MA 02114 USA. EM mlarkin1@partners.org FU Abbott Diabetes Care; R01 [5R01DK085633-03] FX This work was funded by a grant from Abbott Diabetes Care for an investigator-initiated study of continuous glucose monitoring (to SJ Russell, MGH Principal Investigator) and from R01 (#5R01DK085633-03) to Edward Damiano (with SJR as MGH Principal Investigator). NR 7 TC 2 Z9 2 U1 0 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD FEB PY 2013 VL 10 IS 1 BP 93 EP 96 DI 10.1177/1740774512464727 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 075RT UT WOS:000313904900012 PM 23169873 ER PT J AU Hinton, DE Pich, V Hofmann, SG Otto, MW AF Hinton, Devon E. Pich, Vuth Hofmann, Stefan G. Otto, Michael W. TI Acceptance and Mindfulness Techniques as Applied to Refugee and Ethnic Minority Populations With PTSD: Examples From "Culturally Adapted CBT" SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article DE acceptance; mindfulness; PTSD; cross-cultural ID TREATMENT-RESISTANT PTSD; CAMBODIAN REFUGEES; EMOTION REGULATION; INITIAL VALIDATION; PANIC-ATTACKS; SCALE; PERSPECTIVE; COMPASSION; MEDITATION; MECHANISMS AB In this article we illustrate how we utilize acceptance and mindfulness techniques in our treatment (Culturally Adapted CBT, or CA-CBT) for traumatized refugees and ethnic minority populations. We present a Nodal Network Model (NNM) of Affect to explain the treatment's emphasis on body-centered mindfulness techniques and its focus on psychological flexibility. We explain the definition of mindfulness that guides our treatment, and we outline a typology of mindfulness states and show how many of the techniques in our treatment can be analyzed by these categories. We argue that acceptance and mindfulness are therapeutic for refugees and minority populations for several reasons. These include their increasing psychological flexibility, decreasing somatic distress, decreasing rumination, serving as emotion regulation techniques, decreasing the attentional bias to threat, and forming part of a new adaptive processing mode (which in CA-CBT centers on psychological flexibility). We describe the specific ways we teach acceptance and mindfulness with Latino and Southeast Asian refugee populations and present case examples of the treatment of a traumatized Latino and Cambodian patient. C1 [Hinton, Devon E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Hinton, Devon E.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Hinton, Devon E.; Pich, Vuth] Arbour Counseling Serv, Lowell, MA USA. [Hofmann, Stefan G.; Otto, Michael W.] Boston Univ, Boston, MA 02215 USA. RP Hinton, DE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM devon_hinton@hms.harvard.edu RI Hofmann, Stefan/B-8769-2014 OI Hofmann, Stefan/0000-0002-3548-9681 NR 44 TC 13 Z9 13 U1 4 U2 47 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD FEB PY 2013 VL 20 IS 1 BP 33 EP 46 PG 14 WC Psychology, Clinical SC Psychology GA 073UY UT WOS:000313769800004 ER PT J AU Otis, JD AF Otis, John D. TI Chronic Pain: An Integrated Biobehavioral Approach SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Book Review AB Chronic pain is a significant health-care problem that impacts millions of Americans and costs our economy billions of dollars each year. Research indicates that cognitive behavioral therapy (CBT) can be an effective approach for teaching individuals with chronic pain ways of managing their pain more effectively. In Chronic Pain: An Integrated Biobehavioral Approach, Drs. Dennis Turk and Herta Nor (2011) provide a well-written and clear product that skillfully integrates pain-relevant science and research with information that is directly relevant for clinical practice. This book is highly recommended for any clinician interested in working with patients who have chronic pain. C1 [Otis, John D.] VA Boston Healthcare Syst, Boston, MA 02130 USA. RP Otis, JD (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA. EM John.Otis@va.gov NR 3 TC 0 Z9 0 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD FEB PY 2013 VL 20 IS 1 BP 117 EP 118 PG 2 WC Psychology, Clinical SC Psychology GA 073UY UT WOS:000313769800013 ER PT J AU Anzueto, A Restrepo, MI Pugh, MJV Wilson, BZ Mortensen, EM AF Anzueto, Antonio Restrepo, Marcos I. Pugh, Mary Jo V. Wilson, Bryan Z. Mortensen, Eric M. TI Severe Community-Acquired Pneumonia: Don't Get Rid of Fluoroquinolone reply SO CRITICAL CARE MEDICINE LA English DT Letter C1 [Anzueto, Antonio; Restrepo, Marcos I.; Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, VERDICT S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol, San Antonio, TX 78229 USA. [Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biostat, San Antonio, TX 78229 USA. [Wilson, Bryan Z.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Mortensen, Eric M.] VA N Texas Hlth Care Syst, Dallas, TX USA. [Mortensen, Eric M.] Univ Texas SW, Dallas, TX USA. RP Anzueto, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, VERDICT S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RI Restrepo, Marcos/H-4442-2014 FU NHLBI NIH HHS [K23 HL096054] NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD FEB PY 2013 VL 41 IS 2 BP E16 EP E17 DI 10.1097/CCM.0b013e318277103a PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 078NO UT WOS:000314106000006 PM 23353969 ER PT J AU Wedel, SK Orr, RA Frakes, MA Conn, AKT AF Wedel, Suzanne K. Orr, Richard A. Frakes, Michael A. Conn, Alasdair K. T. TI Improving the Incomplete Infrastructure for Interhospital Patient Transfer SO CRITICAL CARE MEDICINE LA English DT Letter ID MEDICARE BENEFICIARIES; TRANSPORT; CARE; CERTIFICATION; HOSPITALS; EVENTS C1 [Wedel, Suzanne K.; Frakes, Michael A.] Boston MedFlight, Boston, MA USA. [Wedel, Suzanne K.] Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. [Orr, Richard A.] Univ Pittsburgh, Sch Med, Dept Crit Care Med & Pediat, Pittsburgh, PA USA. [Conn, Alasdair K. T.] Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA 02114 USA. [Conn, Alasdair K. T.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Wedel, SK (reprint author), Boston MedFlight, Boston, MA USA. NR 10 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD FEB PY 2013 VL 41 IS 2 BP E21 EP E22 DI 10.1097/CCM.0b013e318275861e PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 078NO UT WOS:000314106000014 PM 23353977 ER PT J AU Wei, NJ Wexler, DJ Nathan, DM Grant, RW AF Wei, N. J. Wexler, D. J. Nathan, D. M. Grant, R. W. TI Intensification of diabetes medication and risk for 30-day readmission SO DIABETIC MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; HOSPITAL ADMISSION; HEMOGLOBIN A1C; PRIMARY-CARE; DIAGNOSIS; SERVICE; DISCONTINUATION; HYPERGLYCEMIA; PREVALENCE; MORTALITY AB Aim To examine the association of in-hospital diabetes regimen intensification with subsequent 30-day risk for unplanned readmission/emergency department admission. Methods We retrospectively studied 1949 adults with Type 2 diabetes receiving primary care within an academic health network admitted to the hospital between January 2007 and December 2009. Glucose therapy intensification was defined as new start of insulin or oral hypoglycaemic agents, or addition of prandial insulin or insulin mixtures. The association of glucose therapy intensification with subsequent 30-day risk for unplanned readmission/emergency department admission was examined, with focus on medicine service patients with poorly controlled glycaemia (baseline HbA1c = 64 mmol/mol). Results One in six patients (324/1949, 17%) had early readmission/emergency department admission. Compared with patients without early readmission, readmitted patients were more often male (58 vs. 52%, P = 0.03), had higher Charlson co-morbidity score [mean (sd) 3.0 (2.0) vs. 2.8 (1.8), P = 0.02], longer length of stay [5 (4.4) vs. 3.9 (3.3) days, P < 0.01] and were more often discharged home with nursing services (38 vs. 32%, P = 0.03). Overall, glucose therapy intensification was not associated with early hospital readmission/emergency department admission (odds ratio 0.94, 95% CI 0.641.37, P = 0.74). However, among medicine service patients with baseline HbA1c = 64 mmol/mol (8%), glucose therapy intensification was associated with a significantly decreased early readmission risk (adjusted odds ratio 0.33, 95% CI 0.120.88, P = 0.03) and lower post-discharge HbA1c {mean decrease (sd): 20 (26) mmol/mol [1.8 (2.4)%] vs. 7 (15) mmol/mol [0.6 (1.4)%], P < 0.01}. Conclusions Diabetes medical regimen intensification during hospitalization was not associated with early readmission. Among patients with elevated HbA1c, glucose therapy intensification was associated with a decreased 30-day readmission/emergency department admission risk and lower outpatient HbA1c levels. Our findings support the safety and durable impact of diabetes regimen optimization during hospital admission. C1 [Wei, N. J.; Wexler, D. J.; Nathan, D. M.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Wei, N. J.; Wexler, D. J.; Nathan, D. M.] Harvard Univ, Sch Med, Boston, MA USA. [Grant, R. W.] Kaiser Permanente, Div Res, Oakland, CA USA. RP Wei, NJ (reprint author), Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. EM ncwei@partners.org OI Grant, Richard/0000-0002-6164-8025 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [T32 DK007-028]; NIDDK [K23-DK 080-28]; Charlton Fund for Innovative Research in Diabetes FX NJW is supported by a National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) training grant (T32 DK007-028). DJW is supported by a NIDDK Patient-Oriented Research Career Development Award (K23-DK 080-28). DMN is supported in part by the Charlton Fund for Innovative Research in Diabetes. NR 26 TC 6 Z9 6 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD FEB PY 2013 VL 30 IS 2 BP E56 EP E62 DI 10.1111/dme.12061 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 075HV UT WOS:000313876500004 PM 23126686 ER PT J AU Tirado, A Wu, T Noble, VE Huang, C Lewiss, RE Martin, JA Murphy, MC Sivitz, A AF Tirado, Alfredo Wu, Teresa Noble, Vicki E. Huang, Calvin Lewiss, Resa E. Martin, Jennifer A. Murphy, Michael C. Sivitz, Adam TI Ultrasound-Guided Procedures in the Emergency Department-Diagnostic and Therapeutic Asset SO EMERGENCY MEDICINE CLINICS OF NORTH AMERICA LA English DT Article DE Ultrasound; Procedures; Pericardiocentesis; Abscess; Lumbar puncture; Paracentesis; Arthrocentesis; Thoracentesis ID SOFT-TISSUE INFECTIONS; FOREIGN-BODIES; LUMBAR PUNCTURE; EPIDURAL-ANESTHESIA; SONOGRAPHIC DETECTION; BEDSIDE SONOGRAPHY; JOINT EFFUSIONS; LOCALIZATION; PERICARDIOCENTESIS; ULTRASONOGRAPHY AB Bedside ultrasound is an extremely valuable and rapidly accessible diagnostic and therapeutic modality in potentially life- and limb-threatening situations in the emergency department. In this report, the authors discuss the role of ultrasound in quick assessment of pathologic conditions and its use to aid in diagnostic and therapeutic interventions. C1 [Tirado, Alfredo] Florida Hosp E Orlando, Dept Emergency Med, Orlando, FL 32822 USA. [Wu, Teresa] Univ Arizona, Coll Med, Maricopa Med Ctr, Dept Emergency Med,EM Residency Program, Phoenix, AZ 85008 USA. [Noble, Vicki E.; Huang, Calvin] Harvard Univ, Massachusetts Gen Hosp, Dept Emergency Med, Emergency Ultrasound Div, Boston, MA 02114 USA. [Lewiss, Resa E.; Martin, Jennifer A.] St Lukes Roosevelt Hosp, Dept Emergency Med, Emergency Ultrasound Div, New York, NY 10025 USA. [Murphy, Michael C.] Harvard Univ, Sch Med, Mt Auburn Hosp, Dept Emergency Med, Cambridge, MA 02138 USA. [Sivitz, Adam] Univ Med & Dent New Jersey, Newark Beth Israel Med Ctr, Newark, NJ 07112 USA. [Sivitz, Adam] Univ Med & Dent New Jersey, Childrens Hosp New Jersey, Newark, NJ 07112 USA. RP Tirado, A (reprint author), Florida Hosp E Orlando, Dept Emergency Med, 7727 Lake Underhill Rd, Orlando, FL 32822 USA. EM tirado_alfredo@yahoo.com NR 68 TC 10 Z9 10 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8627 J9 EMERG MED CLIN N AM JI Emerg. Med. Clin. N. Am. PD FEB PY 2013 VL 31 IS 1 BP 117 EP + DI 10.1016/j.emc.2012.09.009 PG 34 WC Emergency Medicine SC Emergency Medicine GA 067RL UT WOS:000313312700007 PM 23200331 ER PT J AU Erqou, S Lee, CTC Suffoletto, M Echouffo-Tcheugui, JB de Boer, RA van Melle, JP Adler, AI AF Erqou, Sebhat Lee, Chee-Tin Christine Suffoletto, Matthew Echouffo-Tcheugui, Justin B. de Boer, Rudolf A. van Melle, Joost P. Adler, Amanda I. TI Association between glycated haemoglobin and the risk of congestive heart failure in diabetes mellitus: systematic review and meta-analysis SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Review DE Heart failure; Diabetes; Epidemiology; HbA(1c); Hyperglycaemia; Meta-analysis; Risk factor; Systematic review ID GLYCEMIC CONTROL; ATHEROSCLEROSIS RISK; TASK-FORCE; TYPE-2; DISEASE; GLUCOSE; HOSPITALIZATION; CARDIOMYOPATHY; COLLABORATION; COMPLICATIONS AB Clinical trials to date have not provided definitive evidence regarding the effects of glucose lowering on the incidence of congestive heart failure (CHF). We synthesized available prospective epidemiological data on the association between glycaemia measured by haemoglobin A(1c) (HbA(1c)) and incident CHF in individuals with diabetes. We searched electronic databases and reference lists of selected articles for relevant prospective epidemiological studies. We abstracted data from relevant studies using standardized forms and obtained additional data from investigators when required. We pooled study-specific relative risk estimates using random-effects model meta-analysis. Of the 1044 citations identified, we included 10 studies comprising 178 929 participants with diabetes and 14 176 incident CHF cases. Five studies included only patients with type 2 diabetes, four studies had predominantly patients with type 2 diabetes, and one study included only patients with type 1 diabetes. All studies except one showed an increased risk of CHF with higher HbA(1c). The overall adjusted risk ratio (RR) for CHF was 1.15 [95 confidence interval (CI) 1.101.21] for each percentage point higher HbA(1c). There was substantial heterogeneity across the 10 studies (I-2: 83; 95 CI 6991; P 0.001) not explained by available study-level characteristics such as study design or average HbA(1c) level. In seven studies reporting RRs with more than one degree of adjustment, the association was minimally altered after adjustment for several cardiovascular risk factors. In observational studies of individuals with diabetes, a higher HbA(1c) level was associated with a significantly increased incidence of CHF. C1 [Erqou, Sebhat] Univ Pittsburgh, Med Ctr, Dept Internal Med, Pittsburgh, PA 15213 USA. [Lee, Chee-Tin Christine] Univ Toronto, Dept Nutr Sci, Toronto, ON M5S 1A1, Canada. [Suffoletto, Matthew] Vet Affairs Pittsburgh Hlth Care Syst, Dept Cardiol, Pittsburgh, PA USA. [Echouffo-Tcheugui, Justin B.] Emory Univ, Rollins Sch Publ Hlth, Dept Global Hlth, Atlanta, GA 30322 USA. [de Boer, Rudolf A.; van Melle, Joost P.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 AB Groningen, Netherlands. [Adler, Amanda I.] Addenbrookes Hosp, Inst Metab Sci, Cambridge, England. RP Erqou, S (reprint author), Univ Pittsburgh, Med Ctr, Dept Internal Med, Pittsburgh, PA 15213 USA. EM sebhaterqou@googlemail.com NR 40 TC 17 Z9 17 U1 0 U2 12 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 FEB PY 2013 VL 15 IS 2 BP 185 EP 193 DI 10.1093/eurjhf/hfs156 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 074RV UT WOS:000313831900010 PM 23099356 ER PT J AU Lim, K Merfeld, DM AF Lim, Koeun Merfeld, Daniel M. TI Signal detection theory and vestibular perception: II. Fitting perceptual thresholds as a function of frequency (vol 222, pg 303, 2012) SO EXPERIMENTAL BRAIN RESEARCH LA English DT Correction C1 [Lim, Koeun; Merfeld, Daniel M.] Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. [Merfeld, Daniel M.] Harvard Univ, Sch Med, Boston, MA USA. RP Merfeld, DM (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, 243 Charles St,Suite 421, Boston, MA 02114 USA. EM koeunlim@mit.edu; dan_merfeld@meei.harvard.edu NR 1 TC 0 Z9 0 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD FEB PY 2013 VL 224 IS 3 BP 501 EP 501 DI 10.1007/s00221-012-3306-2 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 077PO UT WOS:000314040000018 ER PT J AU Young, RH AF Young, Robert H. TI Dr Robert E. Scully - Obituary SO HISTOPATHOLOGY LA English DT Biographical-Item C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Young, RH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 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 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD FEB PY 2013 VL 62 IS 3 BP 525 EP 527 DI 10.1111/his.12074 PG 3 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 075US UT WOS:000313913000020 PM 23339368 ER PT J AU Chirinos, JA Segers, P Rietzschel, ER De Buyzere, ML Raja, MW Claessens, T De Bacquer, D Sutton, MSJ Gillebert, TC AF Chirinos, Julio A. Segers, Patrick Rietzschel, Ernst R. De Buyzere, Marc L. Raja, Muhammad W. Claessens, Tom De Bacquer, Dirk Sutton, Martin St. John Gillebert, Thierry C. CA Asklepios Investigators TI Early and Late Systolic Wall Stress Differentially Relate to Myocardial Contraction and Relaxation in Middle-Aged Adults The Asklepios Study SO HYPERTENSION LA English DT Article DE afterload; diastolic function; loading sequence; myocardial function; myocardial wall stress; systolic function; tissue Doppler imaging ID LEFT-VENTRICULAR RELAXATION; WAVE REFLECTION MAGNITUDE; INTACT CANINE HEART; LOADING SEQUENCE; DEPENDENT RELAXATION; CARDIAC-MUSCLE; ARTERIAL LOAD; PRESSURE FALL; DETERMINANTS; VELOCITY AB Experimental studies implicate late systolic load as a determinant of impaired left-ventricular relaxation. We aimed to assess the relationship between the myocardial loading sequence and left-ventricular contraction and relaxation. Time-resolved central pressure and time-resolved left-ventricular geometry were measured with carotid tonometry and speckle-tracking echocardiography, respectively, for computation of time-resolved ejection-phase myocardial wall stress (EP-MWS) among 1214 middle-aged adults without manifest cardiovascular disease from the general population. Early diastolic annular velocity and systolic annular velocities were measured with tissue Doppler imaging, and segment-averaged longitudinal strain was measured with speckle-tracking echocardiography. After adjustment for age, sex, and potential confounders, late EP-MWS was negatively associated with early diastolic mitral annular velocity (standardized beta=-0.25; P<0.0001) and mitral inflow propagation velocity (standardized beta=-0.13; P=0.02). In contrast, early EP-MWS was positively associated with early diastolic mitral annular velocity (standardized beta=0.18; P<0.0001) and mitral inflow propagation velocity (standardized beta=0.22; P<0.0001). A higher late EP-MWS predicted a lower systolic mitral annular velocity (standardized beta=-0.31; P<0.0001) and lesser myocardial longitudinal strain (standardized beta=0.32; P<0.0001), whereas a higher early EP-MWS was associated with a higher systolic mitral annular velocity (standardized beta=0.16; P=0.002) and greater longitudinal strain (standardized beta=-0.24; P=0.002). The loading sequence remained independently associated with early diastolic mitral annular velocity after adjustment for systolic mitral annular velocity or systolic longitudinal strain. In the context of available experimental data, our findings support the role of the myocardial loading sequence as a determinant of left-ventricular systolic and diastolic function. A loading sequence characterized by prominent late systolic wall stress was associated with lower longitudinal systolic function and diastolic relaxation. (Hypertension. 2013;61:296-303.). circle Online Data Supplement C1 [Chirinos, Julio A.; Raja, Muhammad W.; Sutton, Martin St. John] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Chirinos, Julio A.; Raja, Muhammad W.; Sutton, Martin St. John] Univ Penn, Philadelphia, PA 19104 USA. [Segers, Patrick; Claessens, Tom] Univ Ghent, Inst Biomed Technol, B-9000 Ghent, Belgium. [Rietzschel, Ernst R.; De Bacquer, Dirk] Univ Ghent, Dept Publ Hlth, B-9000 Ghent, Belgium. [Rietzschel, Ernst R.; De Buyzere, Marc L.; Gillebert, Thierry C.] Ghent Univ Hosp, Dept Cardiovasc Dis, Ghent, Belgium. [Claessens, Tom] Univ Coll Ghent, Dept Mech, Ghent, Belgium. RP Chirinos, JA (reprint author), 3800 Woodland Ave,Rm 8B111, Philadelphia, PA 19104 USA. EM Julio.chirinos@uphs.upenn.edu RI Claessens, Tom/B-2737-2009; OI Claessens, Tom/0000-0002-3182-6820; Gillebert, Thierry/0000-0002-3832-919X FU Fonds voor Wetenschappelijk Onderzoek Vlaanderen [G.0.838.10]; Edna G. Kynett Memorial Foundation; National Institutes of Health; American Heart Association FX This study was supported by Fonds voor Wetenschappelijk Onderzoek Vlaanderen grant G.0.838.10 and Edna G. Kynett Memorial Foundation (Dr Chirinos).; Dr Chirinos has received significant (>$ 10 000) grants from the National Institutes of Health and the American Heart Association for research studies related to arterial hemodynamics and has received minor support (equipment loans) from Atcor Medical, Cardiodynamics, and APC cardiovascular. NR 38 TC 30 Z9 30 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD FEB PY 2013 VL 61 IS 2 BP 296 EP 303 DI 10.1161/HYPERTENSIONAHA.111.00530 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 073JU UT WOS:000313740100026 PM 23283359 ER PT J AU Reeves, RM Ong, FR Matheny, ME Denny, JC Aronsky, D Gobbel, GT Montella, D Speroff, T Brown, SH AF Reeves, Ruth M. Ong, Ferdo R. Matheny, Michael E. Denny, Joshua C. Aronsky, Dominik Gobbel, Glenn T. Montella, Diane Speroff, Theodore Brown, Steven H. TI Detecting temporal expressions in medical narratives SO INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS LA English DT Article DE Event sequence; TimeML; Temporal reasoning; Narration; Natural language processing ID DISCHARGE SUMMARIES; CLASSIFICATION; ARCHITECTURE; INFORMATION; KNOWLEDGE; SYSTEM; TEXT AB Background: Clinical practice and epidemiological information aggregation require knowing when, how long, and in what sequence medically relevant events occur. The Temporal Awareness and Reasoning Systems for Question Interpretation (TARSQI) Toolkit (TTK) is a complete, open source software package for the temporal ordering of events within narrative text documents. TTK was developed on newspaper articles. We extended TTK to support medical notes using veterans' affairs (VA) clinical notes and compared it to TTK. Methods: We used a development set consisting of 200 VA clinical notes to modify and append rules to TTK's time tagger, creating Med-TTK. We then evaluated the performances of TTK and Med-TTK on an independent random selection of 100 clinical notes. Evaluation tasks were to identify and classify time-referring expressions as one of four temporal classes (DATE, TIME, DURATION, and SET). The reference standard for this test set was generated by dual human manual review with disagreements resolved by a third reviewer. Outcome measures included recall and precision for each class, and inter-rater agreement scores. Results: There were 3146 temporal expressions in the reference standard. TTK identified 1595 temporal expressions. Recall was 0.15 (95% confidence interval [CI] 0.12-0.15) and precision was 0.27 (95% CI 0.25-0.29) for TTK. Med-TTK identified 3174 expressions. Recall was 0.86 (95% CI 0.84-0.87) and precision was 0.85 (95% CI 0.84-0.86) for Med-TTK. Conclusion: The algorithms for identifying and classifying temporal expressions in medical narratives developed within Med-TTK significantly improved performance compared to TTK. Natural language processing applications such as Med-TTK provide a foundation for meaningful longitudinal mapping of patient history events among electronic health records. The tool can be accessed at the following site: http://code.google.com/p/med-ttk/. (c) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Reeves, Ruth M.; Matheny, Michael E.; Gobbel, Glenn T.; Speroff, Theodore; Brown, Steven H.] Tennessee Valley Healthcare Syst, Dept Vet Affairs, Geriatr Res Educ & Clin Ctr, Nashville, TN USA. [Reeves, Ruth M.; Ong, Ferdo R.; Matheny, Michael E.; Denny, Joshua C.; Aronsky, Dominik; Gobbel, Glenn T.; Montella, Diane; Brown, Steven H.] Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN USA. [Matheny, Michael E.; Speroff, Theodore] Vanderbilt Univ, Sch Med, Dept Med, Div Gen Internal Med, Nashville, TN 37212 USA. [Matheny, Michael E.; Speroff, Theodore] Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN USA. [Montella, Diane; Brown, Steven H.] Vet Hlth Adm, Dept Vet Affairs, Off Informat & Analyt, Nashville, TN USA. RP Reeves, RM (reprint author), US Dept Vet Affairs, Tennessee Valley Healthcare Syst, 1310 24th Ave S, Nashville, TN 37212 USA. EM ruth.reeves2@va.gov OI Matheny, Michael/0000-0003-3217-4147 FU VA Medical Informatics Fellowship, Office of Academic Affiliations; Veterans Health Administration HSR&D Career Development Award [CDA-08-020]; Veterans Health Consortium for Health Informatics Research (CHIR) [HIR 09-001, HIR 09-003]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development FX The research reported here began with the 2009 Medical Informatics Master's Thesis of Dr. Ferdo Ong who initiated his research with an interest in adapting TTK for eventual clinical usage. This thesis entitled "The Tarsqi Toolkit's Recognition of Temporal Expressions within Medical Documents" is available at http://etd.library.vanderbilt.edu/available/etd-05242010-101636/. Drs. Reeves, Montella and Ong were supported by VA Medical Informatics Fellowship, Office of Academic Affiliations. Dr. Matheny is supported by the Veterans Health Administration HSR&D Career Development Award CDA-08-020. Drs. Matheny and Speroff and Gobbel are supported by the Veterans Health Consortium for Health Informatics Research (CHIR) awards HIR 09-001 and HIR 09-003.; This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development with resources and the use of facilities at the VA Tennessee Valley Healthcare System. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 54 TC 12 Z9 12 U1 1 U2 15 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1386-5056 J9 INT J MED INFORM JI Int. J. Med. Inform. PD FEB PY 2013 VL 82 IS 2 BP 118 EP 127 DI 10.1016/j.ijmedinf.2012.04.006 PG 10 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 078RJ UT WOS:000314116700006 PM 22595284 ER PT J AU Ohning, GV AF Ohning, Gordon V. TI Intestinal Mucins The First Line of Defense SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Editorial Material ID INFLAMMATORY-BOWEL-DISEASE; MECHANISMS C1 Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, W Los Angeles VA Healthcare Ctr, Los Angeles, CA 90073 USA. RP Ohning, GV (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, W Los Angeles VA Healthcare Ctr, Bld 115,Rm 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM gordon.ohning@va.gov NR 10 TC 0 Z9 0 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD FEB PY 2013 VL 47 IS 2 BP 104 EP 105 DI 10.1097/MCG.0b013e3182713185 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 075UP UT WOS:000313912700005 PM 23314666 ER PT J AU Onozato, ML Hammond, S Merren, M Yagi, Y AF Onozato, Maristela L. Hammond, Stephen Merren, Mark Yagi, Yukako TI Evaluation of a completely automated tissue-sectioning machine for paraffin blocks SO JOURNAL OF CLINICAL PATHOLOGY LA English DT Article AB Tissue-sectioning automation can be a resourceful tool in processing anatomical pathology specimens. The advantages of an automated system compared with traditional manual sectioning are the invariable thickness, uniform orientation and fewer tissue-sectioning artefacts. This short report presents the design of an automated tissue-sectioning device and compares the sectioned specimens with normal manual tissue sectioning performed by an experienced histology technician. The automated system was easy to use, safe and the sectioned material showed acceptable quality with well-preserved morphology and tissue antigenicity. It is expected that the turnaround time will be improved in the near future. C1 [Onozato, Maristela L.; Yagi, Yukako] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Pathol, Pathol Informat & Commun Technol PICT Lab, Boston, MA 02114 USA. [Onozato, Maristela L.; Merren, Mark; Yagi, Yukako] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hammond, Stephen] Boston Univ, Dept Pathol, Boston, MA 02215 USA. RP Onozato, ML (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, PICT Lab,Dept Pathol, 101 Merrimac St,Suite 820, Boston, MA 02114 USA. EM likaono@gmail.com NR 4 TC 3 Z9 3 U1 1 U2 5 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0021-9746 J9 J CLIN PATHOL JI J. Clin. Pathol. PD FEB PY 2013 VL 66 IS 2 BP 151 EP 154 DI 10.1136/jclinpath-2011-200205 PG 4 WC Pathology SC Pathology GA 078NM UT WOS:000314105800011 PM 21900334 ER PT J AU Kar, HL O'Leary, KD AF Kar, Heidi L. O'Leary, K. Daniel TI Patterns of Psychological Aggression, Dominance, and Jealousy within Marriage SO JOURNAL OF FAMILY VIOLENCE LA English DT Article DE Emotional abuse; Intimate-partner violence; Partner aggression; Control; Bilateral aggression ID RISK YOUNG COUPLES; PHYSICAL AGGRESSION; DOMESTIC VIOLENCE; PARTNER VIOLENCE; GENDER; CONFLICT; DEPRESSION; FREQUENCY; EMOTIONS; SYMMETRY AB Few empirical studies with representative samples have focused on the gendered aspect of psychological aggression and its sub-constructs of dominance and jealousy. Those that do report on gender differences, often fail to report on important dyadic factors such as whether the aggression is unilateral or bilateral in nature. Differences in psychological aggression, dominance, and jealousy constructs were assessed in a representative sample of 453 married parents. Overall, women had significantly higher dominance, jealousy, and psychological aggression scores. Both male and female respondents in relationships where there was bi-directional severe psychological aggression demonstrated higher mean levels of severe psychological aggression, dominance, and jealousy than did their counterparts who were unilaterally severely aggressive. This is the first study to demonstrate that bilateral psychological aggression is associated with higher mean levels of psychological aggression, dominance, and jealousy scores for both male and female partners than unilateral aggression. Contrary to our hypothesis, there was no differential impact of severe psychological aggression by gender. C1 [Kar, Heidi L.] San Francisco VA Med Ctr, Psychol Serv 116B, San Francisco, CA 94121 USA. [O'Leary, K. Daniel] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. RP Kar, HL (reprint author), San Francisco VA Med Ctr, Psychol Serv 116B, 4150 Clement St, San Francisco, CA 94121 USA. EM Heidi.Kar@va.gov NR 72 TC 2 Z9 2 U1 6 U2 55 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7482 J9 J FAM VIOLENCE JI J. Fam. Violence PD FEB PY 2013 VL 28 IS 2 BP 109 EP 119 DI 10.1007/s10896-012-9492-7 PG 11 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 077LL UT WOS:000314029100001 ER PT J AU Jin, BJ Thiagarajah, JR Verkman, AS AF Jin, Byung-Ju Thiagarajah, Jay R. Verkman, A. S. TI Convective washout reduces the antidiarrheal efficacy of enterocyte surface-targeted antisecretory drugs SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article ID POLYCYSTIC KIDNEY-DISEASE; SMALL INTESTINAL MUCOSA; CFTR INHIBITORS; FLUID SECRETION; CYSTIC-FIBROSIS; CHOLERA-TOXIN; ENTEROTOXIN; ABSORPTION; TRANSPORT; DIARRHEA AB Secretory diarrheas such as cholera are a major cause of morbidity and mortality in developing countries. We previously introduced the concept of antisecretory therapy for diarrhea using chloride channel inhibitors targeting the cystic fibrosis transmembrane conductance regulator channel pore on the extracellular surface of enterocytes. However, a concern with this strategy is that rapid fluid secretion could cause convective drug washout that would limit the efficacy of extracellularly targeted inhibitors. Here, we developed a convection-diffusion model of washout in an anatomically accurate three-dimensional model of human intestine comprising cylindrical crypts and villi secreting fluid into a central lumen. Input parameters included initial lumen flow and inhibitor concentration, inhibitor dissociation constant (K-d), crypt/villus secretion, and inhibitor diffusion. We modeled both membrane-impermeant and permeable inhibitors. The model predicted greatly reduced inhibitor efficacy for high crypt fluid secretion as occurs in cholera. We conclude that the antisecretory efficacy of an orally administered membrane-impermeant, surface-targeted inhibitor requires both (a) high inhibitor affinity (low nanomolar K-d) to obtain sufficiently high luminal inhibitor concentration (>100-fold K-d), and (b) sustained high luminal inhibitor concentration or slow inhibitor dissociation compared with oral administration frequency. Efficacy of a surface-targeted permeable inhibitor delivered from the blood requires high inhibitor permeability and blood concentration (relative to K-d). C1 [Jin, Byung-Ju; Thiagarajah, Jay R.; Verkman, A. S.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Jin, Byung-Ju; Thiagarajah, Jay R.; Verkman, A. S.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. [Thiagarajah, Jay R.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Verkman, AS (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. EM alan.verkman@ucsf.edu FU National Institutes of Health [DK72517, EB00415, HL73856, DK35124, EY13574] FX This work was supported by National Institutes of Health grants DK72517, EB00415, HL73856, DK35124, and EY13574. NR 29 TC 11 Z9 11 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD FEB PY 2013 VL 141 IS 2 BP 261 EP 272 DI 10.1085/jgp.201210885 PG 12 WC Physiology SC Physiology GA 079HI UT WOS:000314160800011 PM 23359285 ER PT J AU Raskin, KA Schwab, JH Mankin, HJ Springfield, DS Hornicek, FJ AF Raskin, Kevin A. Schwab, Joseph H. Mankin, Henry J. Springfield, Dempsey S. Hornicek, Francis J. TI Giant Cell Tumor of Bone SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Review ID GENE-EXPRESSION; CRYOSURGERY; MANAGEMENT; CURETTAGE; THERAPY; LESIONS AB Giant cell tumor (GOT) of bone is one type of giant cell-rich lesion of bone. This benign mesenchymal tumor has characteristic multinuclear giant cells. Mononuclear stromal cells are the physiologically active and diagnostic cell type. Most GCTs are located in the epiphyseal regions of long bones. The axial skeleton primarily the sacrum is a secondary site of involvement. Most patients present with pain, swelling, joint effusion, and disability in the third and fourth decades of life. Imaging studies are important for tumor staging and radiographic grading. Typically, these clinically active but slow-growing tumors are confined to bone, with relatively well-defined radiographic borders. Monostotic disease is most common. Metastatic spread to the lungs is rare. Extended intralesional curettage with or without adjuvant therapy is the primary treatment choice. Local recurrence is seen in <= 20% of cases, and a second local intralesional procedure is typically sufficient in cases that are detected early. Medical therapies include diphosphonates and denosumab. Denosumab has been approved for use in osteoporosis as well as breast and prostate cancer metastatic to bone. Medical therapy and radiotherapy can alter the management of GOT of bone, especially in multifocal disease, local recurrences, and bulky central/axial disease. C1 [Raskin, Kevin A.; Schwab, Joseph H.; Mankin, Henry J.; Springfield, Dempsey S.; Hornicek, Francis J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Raskin, KA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. FU Globus Medical; Stryker FX Dr. Raskin or an immediate family member serves as an unpaid consultant to KCI. Dr. Schwab or an immediate family member is a member of a speakers' bureau or has made paid presentations on behalf of Synthes and Stryker Spine; serves as a paid consultant to or is an employee of Biom'Up; has received nonincome support (such as equipment or services), commercially derived honoraria, or other non-research-related funding (such as paid travel) from Globus Medical and Stryker; and serves as a board member, owner, officer, or committee member of Biom'Up. Dr. Springfield or an immediate family member has stock or stock options held in Johnson & Johnson and Merck. Dr. Hornicek or an immediate family member serves as a paid consultant to or is an employee of Stryker, Stryker Spine, and AO Spine; has received research or institutional support from Stryker; and serves as a board member, owner, officer, or committee member of the American Association of Tissue Banks. Neither Dr. Mankin nor any immediate family member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or indirectly to the subject of this article. NR 35 TC 43 Z9 46 U1 1 U2 15 PU AMER ACAD ORTHOPAEDIC SURGEONS PI ROSEMENT PA 6300 N RIVER ROAD, ROSEMENT, IL 60018-4262 USA SN 1067-151X J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD FEB PY 2013 VL 21 IS 2 BP 118 EP 126 DI 10.5435/JAAOS-21-02-118 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 079TS UT WOS:000314195700008 PM 23378375 ER PT J AU Sheth, RA Hesketh, R Deipolyi, AR Oklu, R AF Sheth, Rahul A. Hesketh, Robin Deipolyi, Amy R. Oklu, Rahmi TI Circulating Tumor Cells: Personalized Medicine in Interventional Oncology? SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Review ID METASTATIC BREAST-CANCER; PROSTATE-CANCER; LUNG-CANCER; COLORECTAL-CANCER; PERIPHERAL-BLOOD; SURVIVAL; EVOLUTION; ADENOCARCINOMA; PERSPECTIVE; PROGRESSION AB Innovative technologic advancements have expanded the ability of interventional radiologists to capture and visualize directly tumor cells that have intravasated into the circulation. The detection of these circulating tumor cells (CTCs) is revolutionizing the understanding of the pathogenesis of metastasis and is paving the way for exquisitely sensitive techniques to detect malignancy, monitor recurrence, and prognosticate outcomes. In this review, the prevailing theories on the pathobiology of metastasis and the tools that have been developed to investigate CTCs are summarized. The tremendous impact CTCs are likely to have in oncology is discussed, with particular emphasis on their relevance to interventional oncology. C1 [Sheth, Rahul A.; Deipolyi, Amy R.; Oklu, Rahmi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Imaging,Div Vasc Imaging & Intervent, Boston, MA 02114 USA. [Hesketh, Robin] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England. RP Oklu, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Imaging,Div Vasc Imaging & Intervent, 55 Fruit St,290 Gray Bigelow, Boston, MA 02114 USA. EM roklu@partners.org OI Deipolyi, Amy/0000-0003-3144-386X NR 45 TC 2 Z9 2 U1 0 U2 16 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 FEB PY 2013 VL 24 IS 2 BP 221 EP 228 DI 10.1016/j.jvir.2012.10.018 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 078HC UT WOS:000314088300011 PM 23265726 ER PT J AU Kalva, SP Pectasides, M Yeddula, K Ganguli, S Blaszkowsky, LS Zhu, AX AF Kalva, Sanjeeva P. Pectasides, Melina Yeddula, Kalpana Ganguli, Suvranu Blaszkowsky, Lawrence S. Zhu, Andrew X. TI Factors Affecting Survival following Chemoembolization with Doxorubicin-eluting Microspheres for Inoperable Hepatocellular Carcinoma SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION; RANDOMIZED CONTROLLED TRIAL; PROGNOSTIC-FACTORS; TRANSARTERIAL CHEMOEMBOLIZATION; MULTIVARIATE-ANALYSIS; LIPIODOL CHEMOEMBOLIZATION; Y-90 RADIOEMBOLIZATION; RISK-FACTORS; PHASE-II; BEADS AB Purpose: To assess factors associated with better overall survival (OS) and progression-free survival (PFS) following chemoembolization with doxorubicin-eluting microspheres for inoperable hepatocellular carcinoma (HCC) Materials and Methods: Data of 130 patients (104 men;, median age, 62 y) with inoperable HCC who underwent successful DEB chemoembolization with 100-300 -mu m LC Bead particles loaded with 50 mg doxorubicin per vial were reviewed following human research committee approval. Effects of various clinical, imaging, and response factors on OS and PFS were assessed by univariate Kaplan-Meier survival. analysis. Multiple Cox regression with backward elimination was performed for terms found significant (P <= .05) on univariate analysis. Results: The number of DEB chemoembolization procedures per patient ranged from one to four (mean, 2 +/- 1). The median PFS and OS were 5.7 months (95% confidence interval, 4.6-7.6 mo) and 14.7 months (95% confidence interval; 12.3-19.7 mo), respectively. On multivariate Cox regression, Canter of the Liver Italian Program (CLIP) store of 1 or lower, necrosis of More than 50%, and response or stable disease per Response Evaluation Criteria hi Solid Tumors after DEB chemoembolization were associated with better PFS. CLIP score of 1 or lower, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1 or lower, absence of portal vein (PV) thrombosis, and necrosis greater than 50% following DEB chemoembolization were associated with better OS. Conclusions: CLIP score of 1 or lower and necrosis of more than 50% are independent variables affecting PPS. and OS after DEB chemoembolization, whereas absence of PV thrombosis,and ECOG PS of 1 or lower affected OS but riot PFS C1 [Kalva, Sanjeeva P.] Massachusetts Gen Hosp, Ctr Image Guided Canc Therapy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Kalva, SP (reprint author), Massachusetts Gen Hosp, Ctr Image Guided Canc Therapy, GRB-297,55 Fruit St, Boston, MA 02114 USA. EM skalva@partners.org NR 57 TC 5 Z9 5 U1 0 U2 5 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 FEB PY 2013 VL 24 IS 2 BP 257 EP 265 DI 10.1016/j.jvir.2012.10.021 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 078HC UT WOS:000314088300016 PM 23369560 ER PT J AU Gupta, PK Ramanan, B MacTaggart, JN Sundaram, A Fang, X Gupta, H Johanning, JM Pipinos, II AF Gupta, Prateek K. Ramanan, Bala MacTaggart, Jason N. Sundaram, Abhishek Fang, Xiang Gupta, Himani Johanning, Jason M. Pipinos, Iraklis I. TI Risk index for predicting perioperative stroke, myocardial infarction, or death risk in asymptomatic patients undergoing carotid endarterectomy SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-College-of-Surgeons CY OCT 03, 2012 CL Chicago, IL SP Amer Coll Surg ID CARDIAC RISK; ARTERIAL-DISEASE; LOWER-EXTREMITY; BYPASS-SURGERY; SURGICAL CARE; YOUNG-ADULTS; MORTALITY; VALIDATION; ADJUSTMENT; QUALITY AB Objective: The latest guidelines recommend performance of carotid endarterectomy (CEA) on asymptomatic patients with high-grade carotid stenosis, only if the combined perioperative stroke, myocardial infarction (MI), or death risk is <= 3%. Our objective was to develop and validate a risk index to estimate the combined risk of perioperative stroke, MI, or death in asymptomatic patients undergoing elective CEA. Methods: Asymptomatic patients who underwent an elective CEA (n = 17,692) were identified from the 2005-2010 National Surgical Quality Improvement Program, a multicenter, prospective database. Multivariable logistic regression analysis was performed with primary outcome of interest being the composite of any stroke, MI, or death during the 30-day periprocedural period. Bootstrapping was used for internal validation. A risk index was created by assigning weighted points to each predictor using the beta-coefficients from the regression analysis. Results: Fifty-eight percent of the patients were men with a median age of 72 years. Thirty-day incidences of stroke, MI, and death were 0.9% (n = 167), 0.6% (n = 108), and 0.4% (n = 72), respectively. The combined 30-day stroke, MI, or death incidence was 1.8%(n = 324). On multivariable analysis, six independent predictors were identified and a risk index created by assigning weighted points to each predictor using the b-coefficients from the regression analysis. The predictors included age in years (<60: 0 point; 60-69: -1 point; 70-79: -1 point; >= 80: 2 points), dyspnea (2 points), chronic obstructive pulmonary disease (3 points), previous peripheral revascularization or amputation (3 points), recent angina within 1 month (4 points), and dependent functional status (5 points). Patients were classified as low(<3%), intermediate (3%-6%), or high (>6%) risk for combined 30-day stroke, MI, or death, based on a total point score of <4, 4-7, and >7, respectively. There were 15,249 patients (86.2%) in the low-risk category, 2233 (12.6%) in the intermediate-risk category, and 210 (1.2%) in the high-risk category. Conclusions: The validated risk index can help identify asymptomatic patients who are at greatest risk for 30-day stroke, MI, and death after CEA, thereby aiding patient selection. (J Vasc Surg 2013; 57: 318-26.) C1 [Gupta, Prateek K.] Univ Wisconsin Hosp & Clin, Dept Surg, Madison, WI 53792 USA. [Gupta, Himani] William S Middleton Mem Vet Adm Med Ctr, Dept Med, Madison, WI USA. [Ramanan, Bala; Sundaram, Abhishek] Creighton Univ, Dept Surg, Omaha, NE 68178 USA. [MacTaggart, Jason N.; Johanning, Jason M.; Pipinos, Iraklis I.] Univ Nebraska, Med Ctr, Dept Surg, Omaha, NE 68154 USA. [MacTaggart, Jason N.; Johanning, Jason M.; Pipinos, Iraklis I.] VA Nebraska & Western Iowa Hlth Care Syst, Omaha, NE 68154 USA. [Fang, Xiang] Creighton Univ, Biostat Core, Omaha, NE 68178 USA. RP Pipinos, II (reprint author), Univ Nebraska, Med Ctr, Dept Surg, Omaha, NE 68154 USA. EM ipipinos@unmc.edu FU NIA NIH HHS [R01 AG034995] NR 34 TC 19 Z9 20 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD FEB PY 2013 VL 57 IS 2 BP 318 EP 326 DI 10.1016/j.jvs.2012.08.116 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 073NX UT WOS:000313750800003 PM 23159474 ER PT J AU Doores, KJ Huber, M Le, KM Wang, SK Doyle-Cooper, C Cooper, A Pantophlet, R Wong, CH Nemazee, D Burton, DR AF Doores, Katie J. Huber, Michael Le, Khoa M. Wang, Sheng-Kai Doyle-Cooper, Colleen Cooper, Anthony Pantophlet, Ralph Wong, Chi-Huey Nemazee, David Burton, Dennis R. TI 2G12-Expressing B Cell Lines May Aid in HIV Carbohydrate Vaccine Design Strategies SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; GERMLINE ANTIBODY RECOGNITION; NEUTRALIZING ANTIBODIES; GLYCAN SHIELD; 2G12 RECOGNIZES; DOMAIN EXCHANGE; EPITOPE; POTENT; BROAD; GP120 AB The highly conserved cluster of high-mannose glycans on the HIV-1 envelope glycoprotein, gp120, has been highlighted as a target for neutralizing antibodies. 2G12, the first HIV-1 antiglycan neutralizing antibody described, binds with an unusual domain-exchanged structure that creates a high-affinity multivalent binding surface. It is an interesting challenge for rational vaccine design to generate immunogens capable of eliciting domain-exchanged 2G12-like responses. We recently showed that di-mannose recognition by the variable domains of 2G12 is independent of domain exchange but that exchange is critical for virus neutralization. Carbohydrate-based immunogens aimed at inducing 2G12-like antibodies may need to drive both di-mannose recognition and domain exchange through interactions with B cell receptors. Here we assessed the ability of such immunogens to activate mouse B cell lines displaying domain-exchanged wild-type 2G12 (2G12 WT), a non-domain-exchanged Y-shaped variant (2G12 I19R), and germ line 2G12 (2G12 gl). We show that several immunogens, including heat-killed yeast and bacteria, can activate both 2G12 WT and 2G12 I19R B cells. However, only discrete clusters of high-mannose glycans, as on recombinant forms of the HIV-1 envelope trimer and oligodendrons, activate 2G12 WT B cells. Furthermore, no immunogen tested activated 2G12 gl cells. Our results support the hypothesis that in order to drive domain exchange of an antimannose antibody response, a boost with an immunogen displaying discrete clusters of high-mannose glycans not recognized by conventional Y-shaped antibodies will be required. Additionally, a molecule capable of activating 2G12 gl cells might also be required. The results highlight broadly neutralizing antibody-expressing mouse B cells as potentially useful tools for carbohydrate immunogen screening. C1 [Doores, Katie J.; Huber, Michael; Le, Khoa M.; Doyle-Cooper, Colleen; Cooper, Anthony; Nemazee, David; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Wang, Sheng-Kai; Wong, Chi-Huey] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. [Wang, Sheng-Kai; Wong, Chi-Huey] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. [Burton, Dennis R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. [Burton, Dennis R.] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Design, La Jolla, CA 92037 USA. [Doores, Katie J.; Huber, Michael; Burton, Dennis R.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Pantophlet, Ralph] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. [Pantophlet, Ralph] Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada. RP Burton, DR (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. EM burton@scripps.edu RI Huber, Michael/B-8509-2015; OI Doores, Katie/0000-0002-5507-1725 FU International AIDS Vaccine Initiative through the Neutralizing Antibody Consortium; National Institute of Allergy and Infectious Diseases, NIH [5R01 AI033292, 5U01 AI078224, AI073148, UM1AI100663]; Ragon Institute of MGH, MIT, and Harvard FX This work was funded by the International AIDS Vaccine Initiative through the Neutralizing Antibody Consortium, the National Institute of Allergy and Infectious Diseases, NIH (grants 5R01 AI033292, 5U01 AI078224, AI073148, and UM1AI100663), and the Ragon Institute of MGH, MIT, and Harvard. NR 40 TC 7 Z9 7 U1 0 U2 24 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 FEB PY 2013 VL 87 IS 4 BP 2234 EP 2241 DI 10.1128/JVI.02820-12 PG 8 WC Virology SC Virology GA 078BB UT WOS:000314072000029 PM 23221565 ER PT J AU Iezzoni, LI AF Iezzoni, Lisa I. TI Imperatives for HSR Addressing Individuals With Disabilities-The Canaries in Health Care's Coal Mine SO MEDICAL CARE LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dept Med, Mongan Inst Hlth Policy,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Iezzoni, LI (reprint author), Harvard Univ, Sch Med, Dept Med, Mongan Inst Hlth Policy,Massachusetts Gen Hosp, 50 Staniford St,Room 901B, Boston, MA 02114 USA. EM liezzoni@partners.org NR 14 TC 4 Z9 4 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD FEB PY 2013 VL 51 IS 2 BP 133 EP 136 DI 10.1097/MLR.0b013e31827da9b9 PG 4 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 078LW UT WOS:000314101400004 PM 23254696 ER PT J AU Sullivan, JL Shwartz, M Burgess, JF Pekoz, EA Christiansen, CL Gerena-Melia, M Berlowitz, D AF Sullivan, Jennifer L. Shwartz, Michael Burgess, James F., Jr. Pekoez, Erol A. Christiansen, Cindy L. Gerena-Melia, Mariana Berlowitz, Dan TI Person-centered Care Practices and Quality in Department of Veterans Affairs Nursing Homes Is There a Relationship? SO MEDICAL CARE LA English DT Article DE nursing home quality; nursing home culture change; person-centered care ID CULTURE-CHANGE; OUTCOMES; STAFF AB Objective: To examine variation in culture change to a person-centered care (PCC) model, and the association between culture change and a composite measure of quality in 107 Department of Veterans Affairs nursing homes. Methods: We examined the relationship between a composite quality measure calculated from 24 quality indicators (QIs) from the Minimum Data Set (that measure unfavorable events), and PCC summary scores calculated from the 6 domains of the Artifact of Culture Change Tool, using 3 different methods of calculating the summary scores. We also use a Bayesian hierarchical model to analyze the relationship between a latent construct measuring extent of culture change and the composite quality measure. Results: Using the original Artifacts scores, the highest performing facility has a 2.9 times higher score than the lowest. There is a statistically significant relationship between the composite quality measure and each of the 3 summary Artifacts scores. Depending on whether original scores, standardized scores, or optimal scores are used, a facility at the 10th percentile in terms of culture change compared with one at the 90th percentile has 8.0%, 8.9%, or 10.3% more QI events. When PCC implementation is considered as a latent construct, 18 low performance PCC facilities have, on an average, 16.3% more QI events than 13 high performance facilities. Conclusions: Our results indicate that culture change to a PCC model is associated with higher Minimum Data Set-based quality. Longitudinal data are needed to better assess whether there is a causal relationship between the extent of culture change and quality. C1 [Sullivan, Jennifer L.; Shwartz, Michael; Burgess, James F., Jr.; Pekoez, Erol A.] VA Boston Healthcare Syst, COLMR, Boston, MA 02130 USA. [Sullivan, Jennifer L.; Burgess, James F., Jr.; Christiansen, Cindy L.; Berlowitz, Dan] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Shwartz, Michael; Pekoez, Erol A.] Boston Univ, Sch Management, Boston, MA 02215 USA. [Gerena-Melia, Mariana] Univ Massachusetts, Amherst, MA 01003 USA. [Berlowitz, Dan] CHQOER Edith Nourse Rogers Mem VAMC, Bedford, MA USA. RP Sullivan, JL (reprint author), VA Boston Healthcare Syst, COLMR, 150 S Huntington Ave,152M, Boston, MA 02130 USA. EM jennifer.sullivan@va.gov OI Burgess, James/0000-0002-6646-7071; Christiansen, Cindy/0000-0001-9951-480X; Sullivan, Jennifer/0000-0003-2906-2232 FU Veterans Health Administration HSRD [IIR-06-260] FX Funded by Veterans Health Administration HSR&D grant IIR-06-260. NR 35 TC 9 Z9 9 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD FEB PY 2013 VL 51 IS 2 BP 165 EP 171 DI 10.1097/MLR.0b013e3182763230 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 078LW UT WOS:000314101400009 PM 23132200 ER PT J AU Epstein, AJ Busch, SH Busch, AB Asch, DA Barry, CL AF Epstein, Andrew J. Busch, Susan H. Busch, Alisa B. Asch, David A. Barry, Colleen L. TI Does Exposure to Conflict of Interest Policies in Psychiatry Residency Affect Antidepressant Prescribing? SO MEDICAL CARE LA English DT Article DE drug utilization; pharmaceutical policy; physician practice patterns; psychiatry ID ACADEMIC MEDICAL-CENTERS; PHARMACEUTICAL REPRESENTATIVES; NATIONAL-SURVEY; PRESCRIPTION DRUGS; PHYSICIANS; INDUSTRY; ATTITUDES; BEHAVIOR; INFORMATION AB Background: Academic medical institutions have instituted conflict of interest (COI) policies in response to concerns about pharmaceutical industry influence. Objective: To determine whether exposure to COI policies during psychiatry residency training affects psychiatrists' antidepressant prescribing patterns after graduation. Research Design: We used 2009 physician-level national administrative prescribing data from IMS Health for 1652 psychiatrists from 162 residency programs. We used difference-in-differences estimation to compare antidepressant prescribing based on graduation before (2001) or after (2008) COI policy adoption across residency program groups with maximally, moderately, and minimally restrictive COI policies. The primary outcomes were shares of psychiatrists' prescribing of heavily promoted, brand reformulated, and brand antidepressants. Results: Rates of prescribing heavily promoted, brand reformulated, and brand antidepressants in 2009 were lower among post-COI graduates than pre-COI graduates at all levels of COI restrictiveness. However, differences between pre-COI and post-COI graduates' prescribing of heavily promoted medications were larger for maximally restrictive programs than both minimally restrictive programs [- 4.3 percentage points; 95% confidence interval (CI), - 7.0, - 1.6] and moderately restrictive programs (- 3.6 percentage points; 95% CI, - 6.2, - 1.1). The difference in prescribing reformulations was larger for maximally restrictive programs than minimally restrictive programs (- 3.0 percentage points; 95% CI, - 5.3, - 0.7). Results were consistent for prescribing of brand drugs. Conclusions: This study provides the first empirical evidence of the effects of COI policies. Our results suggest that COI policies can help inoculate physicians against persuasive aspects of pharmaceutical promotion. Further research should assess whether these policies affect other drug classes and physician specialties similarly. C1 [Epstein, Andrew J.; Asch, David A.] Univ Penn, Dept Vet Affairs, Ctr Hlth Equ Res & Promot, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Epstein, Andrew J.; Asch, David A.] Univ Penn, Dept Med, Div Gen Internal Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Epstein, Andrew J.; Asch, David A.; Barry, Colleen L.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Busch, Susan H.] Yale Univ, Sch Publ Hlth, Dept Hlth Policy & Adm, New Haven, CT USA. [Busch, Alisa B.] McLean Hosp, Belmont, MA 02178 USA. [Busch, Alisa B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Barry, Colleen L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. RP Epstein, AJ (reprint author), Univ Penn, Dept Med, Div Gen Internal Med, Perelman Sch Med, 423 Guardian Dr, Philadelphia, PA 19104 USA. EM eandrew@mail.med.upenn.edu OI Asch, David/0000-0002-7970-286X NR 32 TC 23 Z9 23 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD FEB PY 2013 VL 51 IS 2 BP 199 EP 203 DI 10.1097/MLR.0b013e318277eb19 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 078LW UT WOS:000314101400014 PM 23142772 ER PT J AU Catalano, PJ Ayanian, JZ Weeks, JC Kahn, KL Landrum, MB Zaslavsky, AM Lee, J Pendergast, J Harrington, DP AF Catalano, Paul J. Ayanian, John Z. Weeks, Jane C. Kahn, Katherine L. Landrum, Mary Beth Zaslavsky, Alan M. Lee, Jeannette Pendergast, Jane Harrington, David P. CA Canc Care Outcomes Res Surveillanc TI Representativeness of Participants in the Cancer Care Outcomes Research and Surveillance Consortium Relative to the Surveillance, Epidemiology, and End Results Program SO MEDICAL CARE LA English DT Article DE lung cancer; colorectal cancer; cancer populations ID POPULATION; GENERALIZABILITY AB Background: The research goals of the Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium are to determine how characteristics and beliefs of patients, providers, and health care organizations influence the treatments and outcomes of individuals with newly diagnosed lung and colorectal cancers. As CanCORS results will inform national policy, it is important to know how they generalize to the United States population with these cancers. Research Design: This study assessed the representativeness of the CanCORS cohort of 10,547 patients with lung cancer (LC) or colorectal cancer (CRC) enrolled between 2003 and 2005. We compared characteristics (sex, race, age, and disease stage) with the Surveillance, Epidemiology, and End Results (SEER) population of 234,464 patients with new onset of these cancers during the CanCORS recruitment period. Results: The CanCORS sample is well matched to the SEER Program for both cancers. In CanCORS, 41% LC/47% CRC were female versus 47% LC/49% CRC in SEER. African American, Hispanic, and Asian cases differed by no more than 5 percentage points between CanCORS and SEER. The SEER population is slightly older, with the percentage of patients older than 75 years 33.1% LC/37.3% CRC in SEER versus 26.9% LC/29.4% in CanCORS, and also has a slightly higher proportion of early stage patients. We also found that the CanCORS cohort was representative within specific SEER regions that map closely to CanCORS sites. Conclusions: This study demonstrates that the CanCORS Consortium was successful in enrolling a demographically representative sample within the CanCORS regions. C1 [Catalano, Paul J.; Harrington, David P.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Catalano, Paul J.; Harrington, David P.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Ayanian, John Z.; Landrum, Mary Beth; Zaslavsky, Alan M.] Harvard Univ, Sch Publ Hlth, Dept Hlth Care Policy, Boston, MA 02115 USA. [Ayanian, John Z.] Womens Hosp Med Ctr, Div Gen Med, Boston, MA USA. [Weeks, Jane C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kahn, Katherine L.] RAND Corp, Santa Monica, CA USA. [Kahn, Katherine L.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Lee, Jeannette] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. [Pendergast, Jane] Univ Iowa, Coll Publ Hlth, Dept Biostat, Iowa City, IA USA. RP Catalano, PJ (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02215 USA. EM pcata@jimmy.harvard.edu FU National Cancer Institute (NCI) [U01 CA093344]; Primary Data Collection and Research Centers at the Harvard Medical School and Northern California Cancer Center [U01 CA093324]; Dana-Farber Cancer Institute and Cancer Research Network [U01 CA093332]; RAND and University of California, Los Angeles [U01 CA093348]; University of Alabama at Birmingham [U01 CA093329]; University of Iowa [U01 CA093339]; University of North Carolina [U01 CA093326]; Department of Veteran's Affairs [U01 CDA093344 (MOU), HARQ 03-438MO-03] FX The Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium was supported by grants from the National Cancer Institute (NCI) to the Statistical Coordinating Center at the Dana-Farber Cancer Institute (U01 CA093344) and the Primary Data Collection and Research Centers at the Harvard Medical School and Northern California Cancer Center (U01 CA093324); Dana-Farber Cancer Institute and Cancer Research Network (U01 CA093332); RAND and University of California, Los Angeles (U01 CA093348); University of Alabama at Birmingham (U01 CA093329); University of Iowa (U01 CA093339); University of North Carolina (U01 CA093326); and by a Department of Veteran's Affairs grant to the Durham VA Medical Center (U01 CDA093344 (MOU) and HARQ 03-438MO-03). NR 9 TC 45 Z9 45 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD FEB PY 2013 VL 51 IS 2 BP E9 EP E15 DI 10.1097/MLR.0b013e318222a711 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 078LW UT WOS:000314101400001 PM 22406968 ER PT J AU Dusseault-Belanger, F Cohen, AA Hivert, MF Courteau, J Vanasse, A AF Dusseault-Belanger, Francis Cohen, Alan A. Hivert, Marie-France Courteau, Josiane Vanasse, Alain TI Validating Metabolic Syndrome Through Principal Component Analysis in a Medically Diverse, Realistic Cohort SO METABOLIC SYNDROME AND RELATED DISORDERS LA English DT Article ID INSULIN-RESISTANCE SYNDROME; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; DIABETES-MELLITUS; SYNDROME-X; RISK; ADULTS; WOMEN AB Background: The concept of metabolic syndrome has been subject to etiological and clinical controversies in recent years. Associations among the five risk factors (obesity, hypertension, hyperglycemia, high triglyceride levels, and low high-density lipoprotein cholesterol) may help establish the validity of the concept, especially in a cohort representative of an actual population. Methods: We used principal component analysis (PCA) to analyze the structure of the physiological components of metabolic syndrome in 7213 patients contained in an administrative database for the Centre Hospitalier Universitaire de Sherbrooke in Sherbrooke, Quebec, a realistic cohort with diverse medical histories. We validated the results by repeating the analysis on stratified and random subgroups of patients, and on different combinations of risk factors. The first axis of the PCA was used to predict coronary heart disease (CHD) and diabetes. Results: The two first axes explained 53% of the variance. The first axis (33%) was associated in the expected direction with all five predictor variables, consistent with its interpretation as metabolic syndrome. The first axis was more predictive of subsequent CHD and diabetes than the formal definition of metabolic syndrome. Conclusions: These results suggest that the concept of metabolic syndrome accurately captures an existing underlying physiological process. A continuous indicator could be constructed to identify metabolic syndrome more accurately, thus improving risk assessment for CHD and diabetes mellitus. Metabolic syndrome can be measured well even without all five predictors. However, discrepancies with other studies suggest that our results may not be generalizable, perhaps because our cohort tends to be sicker. C1 [Dusseault-Belanger, Francis] Univ Sherbrooke, Dept Math, Sherbrooke, PQ J1K 2R1, Canada. [Dusseault-Belanger, Francis; Cohen, Alan A.; Hivert, Marie-France; Courteau, Josiane; Vanasse, Alain] Univ Sherbrooke, Ctr Rech Clin Etienne Lebel Ctr Hosp, Sherbrooke, PQ J1K 2R1, Canada. [Cohen, Alan A.; Vanasse, Alain] Univ Sherbrooke, Dept Med Famille, Sherbrooke, PQ J1K 2R1, Canada. [Cohen, Alan A.] Inst Univ Geriatrie Sherbrooke, Ctr Rech Vieillissement, Ctr Sante & Serv Sociaux, Sherbrooke, PQ, Canada. [Hivert, Marie-France] Univ Sherbrooke, Dept Med, Sherbrooke, PQ J1K 2R1, Canada. [Hivert, Marie-France] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Cohen, AA (reprint author), Grp Rech PRIMUS, 3001,12E Ave Nord, Sherbrooke, PQ J1H 5N4, Canada. EM alan.cohen@usherbrooke.ca FU Fonds de Recherche en Sante du Quebec (FRSQ); Canadian Diabetes Association FX The Centre de Recherche Clinique Etienne-LeBel and the Centre de Recherche sur le Vieillissement are two clinical research centers supported by the Fonds de Recherche en Sante du Quebec (FRSQ). Marie-France Hivert is supported by an FRSQ Scholar Award (junior 1 level) and a Canadian Diabetes Association Clinical Scientist award. Alain Vanasse receives a career award form the FRSQ as a senior clinician scholar. NR 26 TC 3 Z9 3 U1 0 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-4196 J9 METAB SYNDR RELAT D JI Metab. Syndr. Relat. Disord. PD FEB PY 2013 VL 11 IS 1 BP 21 EP 28 DI 10.1089/met.2012.0094 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 076OF UT WOS:000313965200005 PM 22978288 ER PT J AU Stanley, T Bredella, MA Pierce, L Misra, M AF Stanley, Takara Bredella, Miriam A. Pierce, Lisa Misra, Madhusmita TI The Ratio of Parathyroid Hormone to Vitamin D Is a Determinant of Cardiovascular Risk and Insulin Sensitivity in Adolescent Girls SO METABOLIC SYNDROME AND RELATED DISORDERS LA English DT Article ID 25-HYDROXYVITAMIN D CONCENTRATIONS; CYTOKINE-INDUCED APOPTOSIS; 1,25 DIHYDROXYVITAMIN D-3; METABOLIC SYNDROME; MORBIDLY OBESE; GROWTH-HORMONE; D DEFICIENCY; RESISTANCE; WOMEN; ADIPOSITY AB Background: Vitamin D insufficiency and higher testosterone are common in obese girls and may adversely affect glucose homeostasis and cardiovascular risk. Data are conflicting regarding the impact of parathyroid hormone (PTH) on these factors. Our objective was to determine associations of 25-hydroxyvitamin D (25-OHD), PTH, and testosterone with measures of glucose homeostasis and cardiovascular risk in adolescent girls after controlling for regional adiposity, with the hypothesis that lower 25-OHD, a higher PTH or PTH/25-OHD ratio, and higher testosterone would be associated with lower insulin sensitivity and greater cardiovascular risk. Methods: A total of 15 obese girls and 15 matched normal weight controls (12-18 years) underwent fasting measurements of 25-OHD, PTH, testosterone, sex hormone-binding globulin (SHBG), high-sensitivity C-reactive protein (hsCRP), oral glucose tolerance testing, and quantification of visceral (VAT) and subcutaneous (SAT) fat by magnetic resonance imaging (MRI). Results: There were no associations of 25-OHD with measures of glucose homeostasis or hsCRP. In contrast, PTH and PTH/25-OHD were associated negatively with homeostasis model assessment of insulin resistance (HOMA-IR) and positively with quantitative insulin sensitivity check index (QUICKI) in obese girls but not controls. These associations remained significant after controlling for body mass index standard deviation score (BMI-SDS), but not for VAT. On regression modeling, PTH/25-OHD was positively associated with hsCRP after controlling for BMI-SDS or VAT. Free testosterone positively predicted the corrected insulin response. Conclusions: In obese girls, PTH/25-OHD is positively associated with measures of insulin sensitivity and hsCRP. Further studies are needed to investigate the relationship between PTH and glucose homeostasis in obesity. C1 [Stanley, Takara; Pierce, Lisa; Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Stanley, Takara; Misra, Madhusmita] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. [Bredella, Miriam A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457, Boston, MA 02114 USA. EM mmisra@partners.org FU National Institutes of Health [5P30DK4620-15, 1 UL1 RR025758] FX This study was supported in part by grants National Institutes of Health grants 5P30DK4620-15 and 1 UL1 RR025758. NR 40 TC 8 Z9 8 U1 0 U2 8 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-4196 EI 1557-8518 J9 METAB SYNDR RELAT D JI Metab. Syndr. Relat. Disord. PD FEB PY 2013 VL 11 IS 1 BP 56 EP 62 DI 10.1089/met.2012.0102 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 076OF UT WOS:000313965200010 PM 23130887 ER PT J AU Gesty-Palmer, D Yuan, L Martin, B Wood, WH Lee, MH Janech, MG Tsoi, LC Zheng, WJ Luttrell, LM Maudsley, S AF Gesty-Palmer, Diane Yuan, Ling Martin, Bronwen Wood, William H., III Lee, Mi-Hye Janech, Michael G. Tsoi, Lam C. Zheng, W. Jim Luttrell, Louis M. Maudsley, Stuart TI beta-Arrestin-Selective G Protein-Coupled Receptor Agonists Engender Unique Biological Efficacy in Vivo SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PARATHYROID-HORMONE PTH; SIGNALING PATHWAYS; BONE-FORMATION; ACTIVATION; BETA-ARRESTIN-2; MICE; KINASE; CELLS; BINDING; CANCER AB Biased G protein-coupled receptor agonists are orthosteric ligands that possess pathway-selective efficacy, activating or inhibiting only a subset of the signaling repertoire of their cognate receptors. In vitro, D-Trp(12), Tyr(34)-bPTH(7-34) [bPTH(7-34)], a biased agonist for the type 1 PTH receptor, antagonizes receptor-G protein coupling but activates arrestin-dependent signaling. In vivo, both bPTH(7-34) and the conventional agonist hPTH(1-34) stimulate anabolic bone formation. To understand how two PTH receptor ligands with markedly different in vitro efficacy could elicit similar in vivo responses, we analyzed transcriptional profiles from calvarial bone of mice treated for 8 wk with vehicle, bPTH(7-34) or hPTH(1-34). Treatment of wild-type mice with bPTH(7-34) primarily affected pathways that promote expansion of the osteoblast pool, notably cell cycle regulation, cell survival, and migration. These responses were absent in beta-arrestin2-null mice, identifying them as downstream targets of beta-arrestin2-mediated signaling. In contrast, hPTH(1-34) primarily affected pathways classically associated with enhanced bone formation, including collagen synthesis and matrix mineralization. hPTH(1-34) actions were less dependent on beta-arrestin2, as might be expected of a ligand capable of G protein activation. In vitro, bPTH(7-34) slowed the rate of preosteoblast proliferation, enhanced osteoblast survival when exposed to an apoptotic stimulus, and stimulated cell migration in wild-type, but not beta-arrestin2-null, calvarial osteoblasts. These results suggest that bPTH(7-34) and hPTH(1-34) affect bone mass in vivo through predominantly separate genomic mechanisms created by largely distinct receptor-signaling networks and demonstrate that functional selectivity can be exploited to change the quality of G protein-coupled receptor efficacy. (Molecular Endocrinology 27: 296-314, 2013) C1 [Gesty-Palmer, Diane; Yuan, Ling] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Martin, Bronwen; Maudsley, Stuart] NIA, NIH, Receptor Pharmacol Unit, Baltimore, MD 21224 USA. [Wood, William H., III] NIA, NIH, Gene Express & Genom Unit, Baltimore, MD 21224 USA. [Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. [Tsoi, Lam C.; Zheng, W. Jim; Luttrell, Louis M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Janech, Michael G.; Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Luttrell, LM (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, 96 Jonathan Lucas St,Suite 816 CSB,MSC 624, Charleston, SC 29425 USA. EM luttrell@musc.edu OI Janech, Michael/0000-0002-3202-4811 FU National Institutes of Health [DK64353, DK55524, HD043446]; Arthritis Foundation; Research Services of the Charleston, South Carolina; Research Services of the Charleston, Durham; North Carolina Veterans Affairs Medical Centers; Neph-cure Young Investigator; Department of Veterans Affairs Career Development Awards; National Institute on Aging Intramural Research Program of the NIH FX This work was supported by National Institutes of Health Grants DK64353 (to L.M.L./D.G.-P.), DK55524 (to L.M.L.), HD043446 (to D.G.-P.), the Arthritis Foundation (to D.G.-P.), and the Research Services of the Charleston, South Carolina and Durham, North Carolina Veterans Affairs Medical Centers (to L.M.L., M.G.J., and D.G.-P.). M.G.J. was supported by Neph-cure Young Investigator and Department of Veterans Affairs Career Development Awards. This work was supported in part by the National Institute on Aging Intramural Research Program of the NIH (to S.M., B.M., and W.W.). NR 68 TC 28 Z9 28 U1 1 U2 11 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD FEB PY 2013 VL 27 IS 2 BP 296 EP 314 DI 10.1210/me.2012-1091 PG 19 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 078RK UT WOS:000314116900010 PM 23315939 ER PT J AU Saha, D Takahashi, K de Prost, N Winkler, T Pinilla-Vera, M Baron, RM Melo, MFV AF Saha, Dalia Takahashi, Kazue de Prost, Nicolas Winkler, Tilo Pinilla-Vera, Miguel Baron, Rebecca M. Melo, Marcos F. Vidal TI Micro-Autoradiographic Assessment of Cell Types Contributing to 2-Deoxy-2-[F-18]Fluoro-d-Glucose Uptake During Ventilator-Induced and Endotoxemic Lung Injury SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE Micro-autoradiography; 2-Deoxy-2-[F-18]fluoro-D-glucose; Positron emission tomography; Ventilator-induced lung injury; Acute lung injury; Endotoxin lung injury; Neutrophil; Macrophage; Type 2 epithelial cell; Lung ID RESPIRATORY-DISTRESS-SYNDROME; POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO MEASUREMENT; MECHANICAL VENTILATION; METABOLIC-ACTIVITY; CYTOKINE RELEASE; EPITHELIAL-CELLS; P-SELECTIN; FDG-PET; INFLAMMATION AB The aim of the study was to use micro-autoradiography to investigate the lung cell types responsible for 2-deoxy-2-[F-18]fluoro-d-glucose (FDG) uptake in murine models of acute lung injury (ALI). C57/BL6 mice were studied in three groups: controls, ventilator-induced lung injury (VILI), and endotoxin. VILI was produced by high tidal volumes and zero end-expiratory pressure and endotoxin ALI, by intranasal administration. Following FDG injection, the lungs were processed and exposed to autoradiographic emulsion. Grain density over cells was used to quantify FDG uptake. Neutrophils, macrophages, and type 2 epithelial cells presented higher grain densities during VILI and endotoxin ALI than controls. Remarkably, cell grain density in specific cell types was dependent on the injury mechanism. Whereas macrophages showed high grain densities during endotoxin ALI, similar to those exhibited by neutrophils, type 2 epithelial cells demonstrated the second highest grain density (with neutrophils as the highest) during VILI. In murine models of VILI and endotoxin ALI, FDG uptake occurs not only in neutrophils but also in macrophages and type 2 epithelial cells. FDG uptake by individual cell types depends on the mechanism underlying ALI. C1 [Saha, Dalia; de Prost, Nicolas; Winkler, Tilo; Melo, Marcos F. Vidal] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Takahashi, Kazue] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Dev Immunol,Dept Pediat, Boston, MA 02114 USA. [Pinilla-Vera, Miguel; Baron, Rebecca M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med Pulm & Crit Care, Boston, MA 02114 USA. RP Melo, MFV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM mvidalmelo@partners.org RI Winkler, Tilo/B-5337-2009; OI Winkler, Tilo/0000-0002-7276-5550; de Prost, Nicolas/0000-0002-4833-4320 FU National Heart, Lung, and Blood Institute/National Institutes of Health [HL 5R01HL086827] FX This work was partially supported by the National Heart, Lung, and Blood Institute/National Institutes of Health grant HL 5R01HL086827. We would like to express our profound gratitude to Dr. Rosemary Jones and Diane E. Capen for the guidance and criticism on the experiments and manuscript. We would also like to thank Dr. Mauro Tucci for performance of pilot studies, Steve Weise for the technical aspects in manipulation of FDG samples, and Teri Bowman for assistance with methodology for immunohistochemistry. NR 35 TC 15 Z9 15 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD FEB PY 2013 VL 15 IS 1 BP 19 EP 27 DI 10.1007/s11307-012-0575-x PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 077MY UT WOS:000314033000004 PM 22752654 ER PT J AU Fu, MY Brewer, S Olafsen, T Wu, AM Gordon, LK Said, J Braun, J Wadehra, M AF Fu, Maoyong Brewer, Sarah Olafsen, Tove Wu, Anna M. Gordon, Lynn K. Said, Jonathan Braun, Jonathan Wadehra, Madhuri TI Positron Emission Tomography Imaging of Endometrial Cancer Using Engineered Anti-EMP2 Antibody Fragments SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE Epithelial membrane protein-2; Endometrial cancer; PET imaging; Minibody; Copper-64 ID EPITHELIAL MEMBRANE PROTEIN-2; IN-VIVO; SURFACE EXPRESSION; EMP2; COMPLEXES; PET; ANTIGEN; TUMORIGENICITY; XENOGRAFTS; PROSTATE AB As imaging of the cell surface tetraspan protein epithelial membrane protein-2 (EMP2) expression in malignant tumors may provide important prognostic and predictive diagnostic information, the goal of this study is to determine if antibody fragments to EMP2 may be useful for imaging EMP2 positive tumors. The normal tissue distribution of EMP2 protein expression was evaluated by immunohistochemistry and found to be discretely expressed in both mouse and human tissues. To detect EMP2 in tumors, a recombinant human anti-EMP2 minibody (scFv-hinge-C(H)3 dimer; 80 kDa) was designed to recognize a common epitope in mice and humans and characterized. In human tumor cell lines, the antibody binding induced EMP2 internalization and degradation, prompting the need for a residualizing imaging strategy. Following conjugation to DOTA (1,4,7,10-tetraazacyclododecane-N,N',N',N'aEuro(3)-tetraacetic acid), the minibody was radiolabeled with Cu-64 (t (1/2) = 12.7 h) and evaluated in mice as a positron emission tomography (PET) imaging agent for human EMP2-expressing endometrial tumor xenografts. The residualizing agent, Cu-64-DOTA anti-EMP2 minibody, achieved high uptake in endometrial cancer xenografts overexpressing EMP2 (10.2 +/- 2.6, percent injected dose per gram (%ID/g) +/- SD) with moderate uptake in wild-type HEC1A tumors (6.0 +/- 0.1). In both cases, precise tumor delineation was observed from the PET images. In contrast, low uptake was observed with anti-EMP2 minibodies in EMP2-negative tumors (1.9 +/- 0.5). This new immune-PET agent may be useful for preclinical assessment of anti-EMP2 targeting in vivo. It may also have value for imaging of tumor localization and therapeutic response in patients with EMP2-positive malignancies. C1 [Fu, Maoyong; Brewer, Sarah; Said, Jonathan; Braun, Jonathan; Wadehra, Madhuri] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Olafsen, Tove; Wu, Anna M.; Braun, Jonathan] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Wu, Anna M.; Said, Jonathan; Braun, Jonathan; Wadehra, Madhuri] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Gordon, Lynn K.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. [Gordon, Lynn K.] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Surg, Los Angeles, CA 90099 USA. RP Wadehra, M (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. EM mwadehra@mednet.ucla.edu FU NIH [HD48540, R21 CA131756, CA016042, R24 CA86307] FX This work was supported by NIH grants HD48540 (J. Braun), R21 CA131756 (M. Wadehra), CA016042 (University of California at Los Angeles Jonsson Comprehensive Cancer Center flow cytometry core), and R24 CA86307 (Production of 64Cu at Washington University School of Medicine). A.M.W., J.S., J.B., and M.W. are members of the Jonsson Comprehensive Cancer Center. We are especially grateful to Dr. David Ho and Arye Lipman in ImaginAb, Inc. for the assistance with minibody KS83 construction and Dr. David Stout and Waldemar Ladno at the Crump Institute for Molecular Imaging at UCLA (U24 CA092865) for the assistance with the small animal PET/CT scans. NR 43 TC 4 Z9 5 U1 0 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD FEB PY 2013 VL 15 IS 1 BP 68 EP 78 DI 10.1007/s11307-012-0558-y PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 077MY UT WOS:000314033000009 PM 22585360 ER PT J AU Lee, MN Roy, M Ong, SE Mertins, P Villani, AC Li, WB Dotiwala, F Sen, J Doench, JG Orzalli, MH Kramnik, I Knipe, DM Lieberman, J Carr, SA Hacohen, N AF Lee, Mark N. Roy, Matthew Ong, Shao-En Mertins, Philipp Villani, Alexandra-Chloe Li, Weibo Dotiwala, Farokh Sen, Jayita Doench, John G. Orzalli, Megan H. Kramnik, Igor Knipe, David M. Lieberman, Judy Carr, Steven A. Hacohen, Nir TI Identification of regulators of the innate immune response to cytosolic DNA and retroviral infection by an integrative approach SO NATURE IMMUNOLOGY LA English DT Article ID AICARDI-GOUTIERES-SYNDROME; EXONUCLEASE TREX1; NUCLEIC-ACID; RIG-I; AUTOIMMUNE-DISEASE; INTRACELLULAR DNA; CELL-DEATH; MUTATIONS; PROTEINS; PATHWAY AB The innate immune system senses viral DNA that enters mammalian cells, or in aberrant situations self-DNA, and triggers type I interferon production. Here we present an integrative approach that combines quantitative proteomics, genomics and small molecule perturbations to identify genes involved in this pathway. We silenced 809 candidate genes, measured the response to dsDNA and connected resulting hits with the known signaling network. We identified ABCF1 as a critical protein that associates with dsDNA and the DNA-sensing components HMGB2 and IFI204. We also found that CDC37 regulates the stability of the signaling molecule TBK1 and that chemical inhibition of the CDC37-HSP90 interaction and several other pathway regulators potently modulates the innate immune response to DNA and retroviral infection. C1 [Lee, Mark N.; Roy, Matthew; Ong, Shao-En; Mertins, Philipp; Villani, Alexandra-Chloe; Li, Weibo; Doench, John G.; Carr, Steven A.; Hacohen, Nir] Broad Inst MIT & Harvard, Cambridge, MA USA. [Lee, Mark N.; Roy, Matthew; Li, Weibo; Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. [Lee, Mark N.; Roy, Matthew; Hacohen, Nir] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Dotiwala, Farokh; Lieberman, Judy] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. [Dotiwala, Farokh; Lieberman, Judy] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Dotiwala, Farokh; Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Sen, Jayita; Orzalli, Megan H.; Knipe, David M.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Kramnik, Igor] Boston Univ, Sch Med, Dept Med, Natl Emerging Infect Dis Lab,Pulm Ctr, Boston, MA 02118 USA. RP Hacohen, N (reprint author), Broad Inst MIT & Harvard, Cambridge, MA USA. EM nhacohen@partners.org RI Lieberman, Judy/A-2717-2015; OI Kramnik, Igor/0000-0001-6511-9246; Doench, John/0000-0002-3707-9889 FU US National Human Genome Research Institute [HG005062]; US National Institutes of Health [DP2OD002230]; National Institutes of Health; GlaxoSmithKline Immune Disease Institute; National Institute of Allergy and Infectious Diseases [AI102816] FX We are grateful to Y.J. Crow for AGS patient fibroblasts and control cells; T. Lindahl for Trex1-/- MEFs and wild-type control MEFs; D. Sabatini and D. Kwiatkowski for p53-/- MEFs; N.A. DeLuca for HSV-1 d109 virus; C. Shamu (Institute of Chemistry and Cell Biology at Harvard Medical School) for the siRNA library and expert advice; The RNAi Consortium at the Broad Institute for assistance with siRNA screening; J. Qiao for assistance with mass spectrometry; M. Rooney and C. Ye for advice about statistical analyses; D. Londono for help with microscopy; J. Kagan, N. Haining, L. Glimcher and M. Brenner for valuable discussions; and W.F. Pendergraft III and other members of the Hacohen laboratory for critical review of the manuscript. This work was supported by the US National Human Genome Research Institute grant HG005062 and US National Institutes of Health Director's New Innovator award DP2OD002230 (N.H.). M.N.L. is supported by a National Institutes of Health Medical Scientist Training Program fellowship; F.D. by a GlaxoSmithKline Immune Disease Institute fellowship; and J.L. by National Institute of Allergy and Infectious Diseases grant AI102816. NR 40 TC 32 Z9 33 U1 2 U2 26 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD FEB PY 2013 VL 14 IS 2 BP 179 EP 185 DI 10.1038/ni.2509 PG 7 WC Immunology SC Immunology GA 075WR UT WOS:000313918400013 PM 23263557 ER PT J AU Bourne, SK Sheth, SA Neal, J Strong, C Mian, MK Cosgrove, GR Eskandar, EN Dougherty, DD AF Bourne, Sarah K. Sheth, Sameer A. Neal, Jonathan Strong, Christian Mian, Matthew K. Cosgrove, G. Rees Eskandar, Emad N. Dougherty, Darin D. TI Beneficial Effect of Subsequent Lesion Procedures After Nonresponse to Initial Cingulotomy for Severe, Treatment-Refractory Obsessive-Compulsive Disorder SO NEUROSURGERY LA English DT Article DE Cingulotomy; Obsessive-compulsive disorder; Psychosurgery; Subcaudate tractotomy ID TERM-FOLLOW-UP; STEREOTACTIC LIMBIC LEUCOTOMY; ANTERIOR CINGULOTOMY; CEREBRAL GLUCOSE; LEUKOTOMY; PREVALENCE; METABOLISM; DEPRESSION AB BACKGROUND: Anterior cingulotomy (AC) can be an effective therapy for patients with severe obsessive-compulsive disorder who are refractory to traditional medical therapy. For patients who do not respond to AC, the benefit of additional lesion procedures vs continued medical management remains unknown. OBJECTIVE: To determine whether a second lesion procedure is beneficial after unsuccessful initial AC. METHODS: In this retrospective cohort study, we reviewed the records of 31 patients who were nonresponders to initial AC. Full response was defined as at least a 35% decrease and partial response as a 25% to 34% decrease in Yale-Brown Obsessive-Compulsive Scale scores. Yale-Brown Obsessive-Compulsive Scale change was compared between patients who underwent additional surgery and those treated nonsurgically. In addition, for patients who underwent additional surgery, we compared the benefit of subcaudate tractotomy with repeat AC (extension of the initial lesion) as the second procedure. RESULTS: Nineteen patients underwent a second surgery and 12 patients continued nonsurgical therapy. Fifty-three percent of patients who received additional surgery were full responders and 21% were partial responders at the most recent follow-up compared with 17% full responders and 25% partial responders among those who continued conventional therapy (P = .02). Of the patients who underwent an additional surgery, there were 64% full and 9% partial responders in the subcaudate tractotomy group compared with 38% full and 38% partial responders in the repeat AC group (P = .04). CONCLUSION: Second lesion surgery can be a safe and effective therapy for patients who do not respond to initial AC. Subcaudate tractotomy may confer a higher response rate than repeat cingulotomy. C1 [Bourne, Sarah K.; Sheth, Sameer A.; Neal, Jonathan; Strong, Christian; Mian, Matthew K.; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Dougherty, Darin D.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Bourne, Sarah K.] Vanderbilt Univ Sch Med, Nashville, TN USA. [Cosgrove, G. Rees] Brown Univ, Warren Alpert Med Sch, Dept Neurosurg, Providence, RI 02912 USA. RP Dougherty, DD (reprint author), Massachusetts Gen Hosp E, Dept Psychiat, 149 13th St,Room 2612, Charlestown, MA 02129 USA. EM ddougherty@partners.org FU Howard Hughes Medical Institute Medical Fellows Program FX S.K. Bourne received funding support from Howard Hughes Medical Institute Medical Fellows Program. The authors have no personal financial or institutional interest in any of the drugs, materials, or devices described in this article. NR 27 TC 10 Z9 10 U1 4 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD FEB PY 2013 VL 72 IS 2 BP 196 EP 202 DI 10.1227/NEU.0b013e31827b9c7c PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 073HP UT WOS:000313734400032 PM 23147780 ER PT J AU Gowrishankar, TR Smith, KC Weaver, JC AF Gowrishankar, Thiruvallur R. Smith, Kyle C. Weaver, James C. TI Transport-Based Biophysical System Models of Cells for Quantitatively Describing Responses to Electric Fields SO PROCEEDINGS OF THE IEEE LA English DT Review DE Distributed transport model; electroporation (EP); meshed transport networks (MTNs); transport lattice ID PLANAR BILAYER-MEMBRANES; SOLID TUMOR TREATMENT; SINGLE-CELL; IRREVERSIBLE ELECTROPORATION; SUPRA-ELECTROPORATION; ASYMPTOTIC MODEL; ORGANELLES; VOLTAGE; PULSES; MECHANISMS AB In this paper, we review computational methods based on spatially distributed transport models that we have used to describe biological cell system responses to electric fields. Application to electroporation (EP) is emphasized, as it is increasingly used experimentally, but is not well understood quantitatively. We argue that Cartesian transport lattices (CTLs) and meshed transport networks (MTNs) are appropriate for describing transport in cellular systems generally. The approach is based on mathematical descriptions of transport in 1-D, which are then assigned to intranodal regions in 1-D, 2-D, and 3-D cell system geometries. Electrical behavior is based on nonspecific charge movement. Descriptions of heat transfer and both molecular and ionic transport have also been examined. This approach allows both traditional, idealized geometries [e. g., cylindrical, spherical plasma membrane (PM)] and also more realistic, irregular cell shapes and sizes to be used approximately, with little difference in computational difficulty. The more complex (active) local membrane models are similar to "agents" in agent-based modeling, in the sense that it is the individual responses of interactions within local regions that yield overall system behavior, which can be emergent and nonintuitive. Cell system models may be useful for screening of EP candidate combinations of pulse parameters, cell characteristics, and molecular transport properties with the goal of optimizing existing experimental protocols and possibly discovering new effects and applications. C1 [Gowrishankar, Thiruvallur R.; Smith, Kyle C.; Weaver, James C.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Smith, Kyle C.] Massachusetts Gen Hosp, Ctr Engn & Med, Boston, MA 02114 USA. RP Gowrishankar, TR (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM jcw@mit.edu FU National Institutes of Health [GM063857] FX Manuscript received September 23, 2011; revised February 27, 2012 and April 24, 2012; accepted May 5, 2012. Date of publication July 16, 2012; date of current version January 16, 2013. This work was supported by the National Institutes of Health under Grant GM063857. NR 47 TC 7 Z9 7 U1 2 U2 27 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9219 J9 P IEEE JI Proc. IEEE PD FEB PY 2013 VL 101 IS 2 SI SI BP 505 EP 517 DI 10.1109/JPROC.2012.2200289 PG 13 WC Engineering, Electrical & Electronic SC Engineering GA 073DT UT WOS:000313724400023 ER PT J AU Tuzer, F Madani, N Kamanna, K Zentner, I LaLonde, J Holmes, A Upton, E Rajagopal, S McFadden, K Contarino, M Sodroski, J Chaiken, I AF Tuzer, Ferit Madani, Navid Kamanna, Kantharaju Zentner, Isaac LaLonde, Judith Holmes, Andrew Upton, Elizabeth Rajagopal, Srivats McFadden, Karyn Contarino, Mark Sodroski, Joseph Chaiken, Irwin TI HIV-1 ENV gp120 structural determinants for peptide triazole dual receptor site antagonism SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE entry inhibitor; KR21; dual antagonism; binding site ID IMMUNODEFICIENCY-VIRUS TYPE-1; SMALL-MOLECULE INHIBITORS; CD4 BINDING-SITE; ENVELOPE GLYCOPROTEIN; VIROLOGICAL FAILURE; ENTRY INHIBITORS; ANTIBODY; AFFINITY; CONFORMATION; BIOSENSOR AB Despite advances in HIV therapy, viral resistance and side-effects with current drug regimens require targeting new components of the virus. Dual antagonist peptide triazoles (PT) are a novel class of HIV-1 inhibitors that specifically target the gp120 component of the viral spike and inhibit its interaction with both of its cell surface protein ligands, namely the initial receptor CD4 and the co-receptor (CCR5/CXCR4), thus preventing viral entry. Following an initial survey of 19 gp120 alanine mutants by ELISA, we screened 11 mutants for their importance in binding to, and inhibition by the PT KR21 using surface plasmon resonance. Key mutants were purified and tested for their effects on the peptide's affinity and its ability to inhibit binding of CD4 and the co-receptor surrogate mAb 17b. Effects of the mutations on KR21 viral neutralization were measured by single-round cell infection assays. Two mutations, D474A and T257A, caused large-scale loss of KR21 binding, as well as losses in both CD4/17b and viral inhibition by KR21. A set of other Ala mutants revealed more moderate losses in direct binding affinity and inhibition sensitivity to KR21. The cluster of sensitive residues defines a PT functional epitope. This site is in a conserved region of gp120 that overlaps the CD4 binding site and is distant from the co-receptor/17b binding site, suggesting an allosteric mode of inhibition for the latter. The arrangement and sequence conservation of the residues in the functional epitope explain the breadth of antiviral activity, and improve the potential for rational inhibitor development. Proteins 2013. (C) 2012 Wiley Periodicals, Inc. C1 [Tuzer, Ferit; Kamanna, Kantharaju; Zentner, Isaac; Holmes, Andrew; Upton, Elizabeth; Contarino, Mark; Chaiken, Irwin] Drexel Univ, Coll Med, Dept Biochem & Mol Biol, Philadelphia, PA 19102 USA. [Madani, Navid; Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [LaLonde, Judith] Bryn Mawr Coll, Dept Chem, Bryn Mawr, PA 19010 USA. [Rajagopal, Srivats] Syngene Int, Div Biol, Bangalore, Karnataka, India. [McFadden, Karyn] Duke Univ, Dept Mol Genet & Microbiol, Med Ctr, Durham, NC 27710 USA. RP Chaiken, I (reprint author), New Coll Bldg,Room 11101,245 N 15th St, Philadelphia, PA 19102 USA. EM ichaiken@drexelmed.edu FU NIH [P01 GM 56550]; Ragon Institute of MGH, MIT and Harvard; International AIDS Vaccine Initiative; Center for HIV/AIDS Vaccine Immunology FX Grant sponsor: NIH; Grant number: P01 GM 56550; Grant sponsor: Ragon Institute of MGH, MIT and Harvard, the International AIDS Vaccine Initiative, the Center for HIV/AIDS Vaccine Immunology, the late William F. McCarty-Cooper (to J.S.). NR 34 TC 8 Z9 8 U1 0 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0887-3585 J9 PROTEINS JI Proteins PD FEB PY 2013 VL 81 IS 2 BP 271 EP 290 DI 10.1002/prot.24184 PG 20 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 074KP UT WOS:000313811700008 PM 23011758 ER PT J AU Asami, T Saito, Y Whitford, TJ Makris, N Niznikiewicz, M McCarley, RW Shenton, ME Kubicki, M AF Asami, Takeshi Saito, Yukiko Whitford, Thomas J. Makris, Nikos Niznikiewicz, Margaret McCarley, Robert W. Shenton, Martha E. Kubicki, Marek TI Abnormalities of middle longitudinal fascicle and disorganization in patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; DTI; FA; Middle longitudinal fascicle; Disorganization; Attention deficit ID POSITRON-EMISSION-TOMOGRAPHY; SYNDROME SCALE PANSS; AUDITORY HALLUCINATIONS; SYNAPTIC PLASTICITY; CORPUS-CALLOSUM; TEMPORAL-LOBE; HUMAN BRAIN; DIFFUSION; PSYCHOSIS; SYMPTOMS AB Introduction: The middle longitudinal fascicle (MdLF) is a long association fiber connecting the superior temporal gyrus (STG) and temporal pole with the angular gyrus through the white matter of the STG, structures which are known to play a crucial role in the pathology of schizophrenia. Functions of MdLF are thought to be related to language and thought processing in the left hemisphere, and with attention in the right hemisphere. While deficits of these functions are core clinical features of schizophrenia, no study has investigated the structural abnormalities of MdLF in schizophrenia. Method: 3 T diffusion tensor data was acquired from twenty-six patients with schizophrenia and twenty-five healthy control subjects. Streamline tractography technique was used to extract MdLF. Fractional anisotropy (FA) was compared between the two groups. In addition, relationships were investigated between FA in the left MdLF and the Disorganized Thoughts Factor derived from the Positive and Negative Symptom Scale five factor model, and between FA in the right MdLF and the Poor Attention. Result: Relative to control subjects, the patients with chronic schizophrenia showed significant mean FA reductions in the bilateral MdLF. The FA of the left MdLF demonstrated a significant negative association with the Disorganized Thoughts Factor, and the FA of the right MdLF showed a significant negative relationship with the Poor Attention. Conclusions: This study provides new evidence for structural deficits in the bilateral MdLF in patients with chronic schizophrenia. It further demonstrates the contribution of these abnormalities to the core clinical features - especially to disorganization and attention deficit. (C) 2012 Elsevier B. V. All rights reserved. C1 [Asami, Takeshi; Niznikiewicz, Margaret; McCarley, Robert W.; Shenton, Martha E.; Kubicki, Marek] Harvard Univ, Sch Med, Boston Vet Affairs Healthcare Syst,Brockton Div, Lab Neurosci,Clin Neurosci Div,Dept Psychiat, Brockton, MA 02401 USA. [Asami, Takeshi; Saito, Yukiko; Whitford, Thomas J.; Shenton, Martha E.; Kubicki, Marek] Harvard Univ, Sch Med, Brigham & Womens Hosp, Psychiat Neuroimaging Lab,Dept Psychiat, Boston, MA 02215 USA. [Whitford, Thomas J.] Univ New S Wales, Sch Psychol, Sydney, NSW, Australia. [Makris, Nikos] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Psychiat, Ctr Morphometr Anal,Athinoula A Martinos Ctr Biom, Boston, MA 02215 USA. [Makris, Nikos] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Neurol, Ctr Morphometr Anal,Athinoula A Martinos Ctr Biom, Boston, MA 02215 USA. [Makris, Nikos] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol Serv, Ctr Morphometr Anal,Athinoula A Martinos Ctr Biom, Boston, MA 02215 USA. [Makris, Nikos] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Shenton, Martha E.; Kubicki, Marek] Harvard Univ, Sch Med, Brigham & Womens Hosp, Surg Planning Lab,MRI Div,Dept Radiol, Boston, MA 02215 USA. RP Kubicki, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Psychiat Neuroimaging Lab,Dept Psychiat, 1249 Boylston St, Boston, MA 02215 USA. EM kubicki@bwh.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU National Institute of Health [K05 MH070047, R01 MH 50740, R01 MH 40799, R01MH 074794, P50MH 080272-CIDAR, R21MH084041, R01DA027804]; ARRA-NIH-NCCAM; Department of Veterans Affairs; VA Schizophrenia Center; National Alliance for Medical Image Computing (NA-MIC); National Institutes of Health Roadmap for Medical Research [U54 EB005149]; National Health and Medical Research Council of Australia [520627]; National Alliance for Research on Schizophrenia and Depression (NARSAD) FX This study was supported, in part, by grants from the National Institute of Health (K05 MH070047 and R01 MH 50740 to MES, R01 MH 40799 to RWM, R01MH 074794 to MK, P50MH 080272-CIDAR award to RWM, MES, MK; R21MH084041, R01DA027804 and ARRA-NIH-NCCAM to NM), the Department of Veterans Affairs Merit Awards (MES, RWM), and the VA Schizophrenia Center Grant (RWM/MES/MK). This work is also, in part, supported by the National Alliance for Medical Image Computing (NA-MIC), the latter a grant supported through the National Institutes of Health Roadmap for Medical Research, Grant U54 EB005149 (MK). TJW is supported by an Overseas-Based Biomedical Training Fellowship from the National Health and Medical Research Council of Australia (#520627), and a Young Investigator Award from the National Alliance for Research on Schizophrenia and Depression (NARSAD). NR 51 TC 9 Z9 9 U1 3 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB PY 2013 VL 143 IS 2-3 BP 253 EP 259 DI 10.1016/j.schres.2012.11.030 PG 7 WC Psychiatry SC Psychiatry GA 072GX UT WOS:000313659000004 PM 23290607 ER PT J AU Zhuo, KM Lu, Y Yang, ZL Fan, XD Song, ZH Liao, LW Ji, CF Zhu, DM Yu, SY Yan, C Chan, RCK Goff, DC Xu, YF Liu, DT AF Zhuo, Kaiming Lu, Yun Yang, Zhiliang Fan, Xiaoduo Song, Zhenhua Liao, Liwei Ji, Chenfeng Zhu, Dianming Yu, Shunying Yan, Chao Chan, Raymond C. K. Goff, Donald C. Xu, Yifeng Liu, Dengtang TI Prospective memory performance in patients with drug-naive, first-episode psychosis SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Prospective memory; Schizophrenia; First-episode ID RETROSPECTIVE-MEMORY; COGNITIVE IMPAIRMENT; WORKING-MEMORY; SCHIZOPHRENIA; NEUROCOGNITION; DEFICITS; METAANALYSIS; PREDICTORS; SYMPTOMS; CORE AB Schizophrenia is associated with an impairment of prospective memory (PM) which refers to the ability to remember to carry out an intended action in the future. However, most of these studies were limited to chronic samples. The current study examined the event-based PM and time-based PM using a dual-task paradigm in 22 drug-naive, first-episode psychosis (FEP) patients and 23 healthy controls. Results indicated that FEP patients performed significantly poorer than healthy controls in both event-based and time-based PM. However, the significant difference in time-based PM disappeared after controlling for working memory. Correlation analysis indicated that both types of PM did not correlate with positive symptoms or negative symptoms, duration of illness, or duration of untreated psychosis. However, time-based PM was correlated with the general psychopathology subscale of the PANSS. Taken together, these findings suggest that PM deficits are present in drug-naive FEP patients; impairment of event-based PM appears to occur independently, whereas time-based PM impairment may be, in part, a secondary consequence of a working memory deficit. (C) 2012 Elsevier B. V. All rights reserved. C1 [Zhuo, Kaiming; Lu, Yun; Song, Zhenhua; Liao, Liwei; Ji, Chenfeng; Zhu, Dianming; Yu, Shunying; Xu, Yifeng; Liu, Dengtang] Shanghai Jiao Tong Univ, Sch Med, Shanghai Mental Hlth Ctr, Schizophrenia Program,Dept Psychiat, Shanghai 200030, Peoples R China. [Yang, Zhiliang; Liu, Dengtang] E China Normal Univ, Dept Psychol, Shanghai 200062, Peoples R China. [Fan, Xiaoduo] Harvard Univ, Sch Med, Dept Psychiat, Schizophrenia Program,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Yan, Chao; Chan, Raymond C. K.] Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Neuropsychol & Appl Cognit Neurosci Lab, Beijing 100101, Peoples R China. [Goff, Donald C.] NYU, Med Ctr, Nathan S Kline Inst Psychiat Res, New York, NY 10016 USA. RP Xu, YF (reprint author), Shanghai Jiao Tong Univ, Sch Med, Shanghai Mental Hlth Ctr, Schizophrenia Program,Dept Psychiat, 600 Wan Ping Nan Rd, Shanghai 200030, Peoples R China. EM hyyyyb@gmail.com; erliu110@126.com FU Science and Technology Commission of Shanghai Municipality [11ZR1431600]; China Postdoctoral Science Foundation [20080430634]; National Key Clinical Disciplines at Shanghai Mental Health Center (OMA-MH) [2011-873] FX This work was supported by a grant 11ZR1431600 from the Science and Technology Commission of Shanghai Municipality to Dr Liu and a grant 20080430634 from China Postdoctoral Science Foundation to Dr Liu. It was also supported by National Key Clinical Disciplines at Shanghai Mental Health Center (OMA-MH, 2011-873). NR 47 TC 7 Z9 9 U1 2 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB PY 2013 VL 143 IS 2-3 BP 285 EP 290 DI 10.1016/j.schres.2012.12.002 PG 6 WC Psychiatry SC Psychiatry GA 072GX UT WOS:000313659000008 PM 23267733 ER PT J AU Zhang, XY Chen, DC Xiu, MH De Yang, F Tan, YL He, SC Kosten, TA Kosten, TR AF Zhang, Xiang Yang Chen, Da Chun Xiu, Mei Hong De Yang, Fu Tan, Yun Long He, Shuchang Kosten, Therese A. Kosten, Thomas R. TI Thioredoxin, a novel oxidative stress marker and cognitive performance in chronic and medicated schizophrenia versus healthy controls SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Cognition; Oxidative stress; Psychopathology ID FREE-RADICAL PATHOLOGY; SUPEROXIDE-DISMUTASE; 1ST-EPISODE SCHIZOPHRENIA; NEUROPSYCHOLOGICAL STATUS; PLASMA THIOREDOXIN; REPEATABLE BATTERY; TARDIVE-DYSKINESIA; LIPID-PEROXIDATION; DIFFERENT FORMS; PSYCHOSIS AB Oxidative stress-induced damage to neurons may contribute to cognitive deficits during aging and in neuro-degenerative disorders. Schizophrenia has a range of cognitive deficits that may evolve from oxidative stress. Thioredoxin (TRX), a redox-regulating protein with antioxidant activity recognized as an oxidative-stress marker has recently been found to be involved in pathogenesis and psychopathology of schizophrenia. The aim of this study was to examine the association of TRX with cognitive deficits in schizophrenia. We recruited 45 chronic schizophrenic patients and 66 healthy control subjects and examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum TRX in both groups. Schizophrenic symptoms were assessed using the positive and negative syndrome scale (PANSS). We found no significant difference in TRX levels between patients and healthy controls. Cognitive scores on the RBANS and four of its five subscales (all p<0.001) except for the Visuospatial/Constructional index (p>0.05) were significantly lower in schizophrenic patients than normal controls. For the patients, TRX was inversely associated with the Attention domain of cognitive deficits in schizophrenia; however, TRX was positively associated with Attention in controls. The significantly lower TRX levels in attention impaired schizophrenia compared to controls suggest that oxidative stress may be involved in the cognitive impairment, especially attention in schizophrenia. The differential association of TRX and cognitive performance in schizophrenia and controls may be related to the impaired oxidative stress status of schizophrenia patients. (C) 2012 Elsevier B. V. All rights reserved. C1 [Zhang, Xiang Yang; Kosten, Therese A.; Kosten, Thomas R.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Zhang, Xiang Yang; Kosten, Therese A.; Kosten, Thomas R.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Zhang, Xiang Yang; Chen, Da Chun; Xiu, Mei Hong; De Yang, Fu; Tan, Yun Long; Kosten, Thomas R.] Peking Univ, Beijing HuiLongGuan Hosp, Beijing 100871, Peoples R China. [He, Shuchang] Peking Univ, Dept Psychol, Beijing 100871, Peoples R China. RP Zhang, XY (reprint author), VA Med Ctr, Res Bldg 109,Room 130,2002 Holcombe Blvd, Houston, TX 77030 USA. EM xyzhang@bcm.edu; kosten@bcm.edu FU Stanley Medical Research Institute [03T-459, 05T-726]; Department of Veterans Affairs; VISN 16; Mental Illness Research, Education and Clinical Center (MIRECC); United States National Institute of Health [K05-DA0454, P50-DA18827, U01-MH79639] FX Funding for this study was provided by grants from the Stanley Medical Research Institute (03T-459 and 05T-726), the Department of Veterans Affairs, VISN 16, Mental Illness Research, Education and Clinical Center (MIRECC), and United States National Institute of Health (K05-DA0454, P50-DA18827 and U01-MH79639). These sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 62 TC 17 Z9 18 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB PY 2013 VL 143 IS 2-3 BP 301 EP 306 DI 10.1016/j.schres.2012.11.017 PG 6 WC Psychiatry SC Psychiatry GA 072GX UT WOS:000313659000011 PM 23238053 ER PT J AU Jahshan, C Wynn, JK Green, MF AF Jahshan, Carol Wynn, Jonathan K. Green, Michael F. TI Relationship between auditory processing and affective prosody in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Auditory processing; Affective prosody; Mismatch negativity; P300 ID FACIAL AFFECT RECOGNITION; MISMATCH NEGATIVITY; SENSORY CONTRIBUTIONS; VOCAL EXPRESSION; COGNITION; PERCEPTION; DEFICITS; DISCRIMINATION; COMMUNICATION; METAANALYSIS AB Patients with schizophrenia have well-established deficits in their ability to identify emotion from facial expression and tone of voice. In the visual modality, there is strong evidence that basic processing deficits contribute to impaired facial affect recognition in schizophrenia. However, few studies have examined the auditory modality for mechanisms underlying affective prosody identification. In this study, we explored links between different stages of auditory processing, using event-related potentials (ERPs), and affective prosody detection in schizophrenia. Thirty-six schizophrenia patients and 18 healthy control subjects received tasks of affective prosody, facial emotion identification, and tone matching, as well as two auditory oddball paradigms, one passive for mismatch negativity (MMN) and one active for P300. Patients had significantly reduced MMN and P300 amplitudes, impaired auditory and visual emotion recognition, and poorer tone matching performance, relative to healthy controls. Correlations between ERP and behavioral measures within the patient group revealed significant associations between affective prosody recognition and both MMN and P300 amplitudes. These relationships were modality specific, as MMN and P300 did not correlate with facial emotion recognition. The two ERP waves accounted for 49% of the variance in affective prosody in a regression analysis. Our results support previous suggestions of a relationship between basic auditory processing abnormalities and affective prosody dysfunction in schizophrenia, and indicate that both relatively automatic pre-attentive processes (MMN) and later attention-dependent processes (P300) are involved with accurate auditory emotion identification. These findings provide support for bottom-up (e. g., perceptually based) cognitive remediation approaches. Published by Elsevier B.V. C1 VA Greater Los Angeles Healthcare Syst, Sierra Pacific Mental Illness Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. RP Jahshan, C (reprint author), VA Greater Los Angeles Healthcare Syst, MIRECC, Bldg 210,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM caroljahshan@hotmail.com RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 FU Department of Veterans Affairs Sierra Pacific Mental Illness Research, Education and Clinical Center (MIRECC); National Institute of Mental Health [MH065707]; Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment FX Funding for this study was provided by grants from the Department of Veterans Affairs Sierra Pacific Mental Illness Research, Education and Clinical Center (MIRECC) and the National Institute of Mental Health (MH065707 to MFG). The MIRECC and NIH had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.; Writing of this manuscript was supported by the Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment. The authors would like to thank Crystal Gibson, Cory Tripp, Katie Weiner, Mark McGee, Christen Waldon and Amanda Bender for their assistance with recruitment and testing. The authors would also like to thank Petri Laukka, Ph.D. and David I. Leitman, Ph.D. for providing the affective prosody task and tone matching task, respectively. NR 42 TC 17 Z9 17 U1 0 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB PY 2013 VL 143 IS 2-3 BP 348 EP 353 DI 10.1016/j.schres.2012.11.025 PG 6 WC Psychiatry SC Psychiatry GA 072GX UT WOS:000313659000018 PM 23276478 ER PT J AU Antonius, D Kline, B Sinclair, SJ White-Ajmani, M Gianfagna, S Malaspina, D Tremeau, F AF Antonius, Daniel Kline, Brian Sinclair, Samuel Justin White-Ajmani, Mandi Gianfagna, Sara Malaspina, Dolores Tremeau, Fabien TI Deficits in implicit facial recognition of fear in aggressive patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Letter ID METAANALYSIS C1 [Antonius, Daniel] SUNY Buffalo, Dept Psychiat, Erie Cty Med Ctr, Buffalo, NY 14125 USA. [Antonius, Daniel] Erie Cty Forens Mental Hlth Serv, Buffalo, NY USA. [Antonius, Daniel; White-Ajmani, Mandi; Malaspina, Dolores; Tremeau, Fabien] NYU, Sch Med, Inst Social & Psychiat Initiat InSPIRES, New York, NY USA. [Sinclair, Samuel Justin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sinclair, Samuel Justin] Harvard Univ, Sch Med, Psychol Evaluat & Res Lab PEaRL, Boston, MA USA. [Gianfagna, Sara] Georgetown Univ, Washington, DC USA. [Malaspina, Dolores] Creedmoor Psychiat Ctr, Queens Village, NY USA. [Tremeau, Fabien] Nathan S Kline Inst Psychiat Res, Orangeburg, NY USA. RP Antonius, D (reprint author), SUNY Buffalo, Dept Psychiat, Erie Cty Med Ctr, 462 Grider St, Buffalo, NY 14125 USA. EM danielan@buffalo.edu FU NIMH NIH HHS [5K24MH001699-10, K24 MH001699, R01 MH066428, R01MH066428] NR 10 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB PY 2013 VL 143 IS 2-3 BP 401 EP 402 DI 10.1016/j.schres.2012.11.038 PG 2 WC Psychiatry SC Psychiatry GA 072GX UT WOS:000313659000030 PM 23276483 ER PT J AU Mavandadi, S Rook, KS Newsom, JT Oslin, DW AF Mavandadi, Shahrzad Rook, Karen S. Newsom, Jason T. Oslin, David W. TI Suicidal ideation and social exchanges among at-risk veterans referred for a behavioral health assessment SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY LA English DT Article DE Suicide; Positive social exchanges; Negative social exchanges; Mental health; Veterans ID PSYCHOLOGICAL DISTRESS; RELATIVE IMPORTANCE; COMMUNITY SAMPLE; DEPRESSION; POPULATION; AFFAIRS; SUPPORT; STRESS; ADULTS; LIFE AB The current study examined the independent association between positive (e.g., emotional and instrumental support) and negative (e.g., insensitive behavior, unwanted advice from others) social exchanges and suicidal ideation among veterans referred for a behavioral health assessment. The sample included 606 veterans [mean age = 54.96 (SD = 14.96)] referred by primary care for a clinical mental health/substance abuse (MH/SA) assessment following a positive MH/SA screen. Data on sociodemographics, MH/SA conditions (e.g., depression, PTSD, anxiety, and alcohol abuse), the self-reported frequency of positive and negative social exchanges, and suicidal ideation were extracted from clinical interviews and evaluated. Veterans were primarily male, non-married, and had adequate financial resources, and approximately half were White. 74.4 and 20.3 % met criteria for a MH/SA condition and suicidal ideation, respectively. Multiple logistic regression analyses revealed that, adjusting for sociodemographics, physical functioning, and comorbid MH/SA conditions, veterans reporting more frequent negative exchanges with network members were significantly more likely to report suicidal ideation. Positive exchanges, in contrast, were not significantly related to the outcome. Inadequate finances and MH/SA conditions also were significantly related to suicidal ideation. Findings highlight the value of exploring the quality of social exchanges among veterans in primary care who screen positive for behavioral health issues, as such information has the potential to inform screening and intervention efforts aimed at reducing suicidal ideation. C1 [Mavandadi, Shahrzad; Oslin, David W.] Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. [Mavandadi, Shahrzad; Oslin, David W.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Rook, Karen S.] Univ Calif Irvine, Sch Social Ecol, Dept Psychol & Social Behav, Irvine, CA 92697 USA. [Newsom, Jason T.] Portland State Univ, Sch Community Hlth, Inst Aging, Portland, OR 97207 USA. RP Mavandadi, S (reprint author), Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, 3900 Woodland Ave,B215, Philadelphia, PA 19104 USA. EM Shahrzad.Mavandadi@va.gov FU VISN 4 Mental Illness Research, Education, and Clinical Center (MIRECC) at the Philadelphia Veterans Affairs Medical Center (PVAMC); VA Office of Research and Development FX This work was supported by the VISN 4 Mental Illness Research, Education, and Clinical Center (MIRECC) at the Philadelphia Veterans Affairs Medical Center (PVAMC) and VA Office of Research and Development. The content of this article does not reflect the views of the VHA or of the Government. NR 58 TC 6 Z9 6 U1 4 U2 26 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0933-7954 EI 1433-9285 J9 SOC PSYCH PSYCH EPID JI Soc. Psychiatry Psychiatr. Epidemiol. PD FEB PY 2013 VL 48 IS 2 BP 233 EP 243 DI 10.1007/s00127-012-0534-5 PG 11 WC Psychiatry SC Psychiatry GA 074LR UT WOS:000313814500007 PM 22722536 ER PT J AU Falcone, GJ Biffi, A Devan, WJ Brouwers, HB Anderson, CD Valant, V Ayres, AM Schwab, K Rost, NS Goldstein, JN Viswanathan, A Greenberg, SM Selim, M Meschia, JF Brown, DL Worrall, BB Silliman, SL Tirschwell, DL Rosand, J AF Falcone, Guido J. Biffi, Alessandro Devan, William J. Brouwers, H. Bart Anderson, Christopher D. Valant, Valerie Ayres, Alison M. Schwab, Kristin Rost, Natalia S. Goldstein, Joshua N. Viswanathan, Anand Greenberg, Steven M. Selim, Magdy Meschia, James F. Brown, Devin L. Worrall, Bradford B. Silliman, Scott L. Tirschwell, David L. Rosand, Jonathan CA GOCHA Investigators TI Burden of Blood Pressure-Related Alleles Is Associated With Larger Hematoma Volume and Worse Outcome in Intracerebral Hemorrhage SO STROKE LA English DT Article DE common genetic variants; genetic risk score; hypertension; ICH volume; intracerebral hemorrhage ID GENOME-WIDE ASSOCIATION; CEREBRAL-HEMORRHAGE; RISK; HYPERTENSION; REDUCTION; INTERACT; GENOTYPE; ADULTS; TRIAL AB Background and Purpose-Intracerebral hemorrhage (ICH) is the acute manifestation of a progressive disease of the cerebral small vessels. The severity of this disease seems to influence not only risk of ICH but also the size of the hematoma. As the burden of high blood pressure-related alleles is associated with both hypertension-related end-organ damage and risk of ICH, we sought to determine whether this burden influences ICH baseline hematoma volume. Methods-Prospective study in subjects of European descent with supratentorial ICH who underwent genome-wide genotyping. Forty-two single nucleotide polymorphisms associated with high blood pressure were identified from a publicly available database. A genetic risk score was constructed based on these single nucleotide polymorphisms. The score was used as the independent variable in univariate and multivariate regression models for admission ICH volume and poor clinical outcome (modified Rankin Scale, 3-6). Results-A total of 323 ICH cases were enrolled in the study (135 deep and 188 lobar intracranial hematomas). The blood pressure-based genetic risk score was associated with both baseline hematoma volume and poor clinical outcome specifically in deep ICH. In multivariate regression analyses, each additional SD of the score increased mean deep ICH volume by 28% (or 2.7 mL increase; beta=0.28; SE=0.11; P=0.009) and risk of poor clinical outcome by 71% (odds ratio, 1.71; 95% confidence interval, 1.05-2.80; P=0.03). Conclusions-Increasing numbers of high blood pressure-related alleles are associated with mean baseline hematoma volume and poor clinical outcome in ICH. These findings suggest that the small vessel vasculopathy responsible for the occurrence of the hemorrhage also influences its volume. (Stroke. 2013; 44: 321-326.) C1 [Falcone, Guido J.; Biffi, Alessandro; Devan, William J.; Brouwers, H. Bart; Anderson, Christopher D.; Valant, Valerie; Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Falcone, Guido J.; Biffi, Alessandro; Devan, William J.; Brouwers, H. Bart; Anderson, Christopher D.; Valant, Valerie; Ayres, Alison M.; Schwab, Kristin; Rost, Natalia S.; Viswanathan, Anand; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Hemorrhag Stroke Res Grp, Boston, MA 02114 USA. [Falcone, Guido J.; Biffi, Alessandro; Devan, William J.; Brouwers, H. Bart; Anderson, Christopher D.; Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. [Falcone, Guido J.; Biffi, Alessandro; Devan, William J.; Brouwers, H. Bart; Anderson, Christopher D.; Rost, Natalia S.; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Falcone, Guido J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Selim, Magdy] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Brown, Devin L.] Univ Michigan Hlth Syst, Dept Neurol, Stroke Program, Ann Arbor, MI USA. [Worrall, Bradford B.] Univ Virginia Hlth Syst, Dept Neurol & Publ Hlth Sci, Charlottesville, VA USA. [Silliman, Scott L.] Univ Florida, Coll Med, Dept Neurol, Jacksonville, FL USA. [Tirschwell, David L.] Univ Washington, Harborview Med Ctr, Stroke Ctr, Seattle, WA 98104 USA. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 6818, Boston, MA 02114 USA. EM jrosand@partners.org RI Goldstein, Joshua/H-8953-2016; Falcone, Guido/L-2287-2016; OI Falcone, Guido/0000-0002-6407-0302; Brown, Devin/0000-0002-9815-3421; Anderson, Christopher/0000-0002-0053-2002 FU National Institutes of Health (NIH)-National Institute of Neurological Disorders and Stroke (NINDS) [R01NS059727]; Keane Stroke Genetics Research Fund; Edward and Maybeth Sonn Research Fund; University of Michigan General Clinical Research Center [M01 RR000042]; National Center for Research Resources; NIH-NINDS [5U54NS057405 (DECIPHER)]; American Heart Association/Bugher Foundation Centers for Stroke Prevention Research [0775010 N]; NIH-NINDS Specialized Programs of Translational Research in Acute Stroke fellowship [P50NS051343]; NIH; NINDS; National Institutes of Health; American Heart Association; [NIH-K23NS059774] FX Genetics of Cerebral Hemorrhage on Anticoagulation: This study was funded by National Institutes of Health (NIH)-National Institute of Neurological Disorders and Stroke (NINDS) Grants R01NS059727, the Keane Stroke Genetics Research Fund, the Edward and Maybeth Sonn Research Fund, by the University of Michigan General Clinical Research Center (M01 RR000042) and by a grant from the National Center for Research Resources.; DECIPHER Study: This study is funded by NIH-NINDS Grant 5U54NS057405 (DECIPHER). Dr Goldstein was supported by the NIH-K23NS059774. Drs Biffi and Anderson were supported in part by the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (0775010 N). Dr Brouwers was supported by the NIH-NINDS Specialized Programs of Translational Research in Acute Stroke fellowship Grant P50NS051343.; Steven M. Greenberg received a research grant from the NIH, received honoraria from Medtronic and Pfizer, and is a consultant/on the advisory board of Hoffman-La Roche, Janssen Alzheimer Immunotherapy, and Bristol-Myers Squibb Company; Joshua N. Goldstein received a research grant from the NINDS and is a consultant/on the advisory board of CSL Behring. Jonathan Rosand received a research grant from the National Institutes of Health and the American Heart Association. The other authors have no conflicts to report. NR 23 TC 11 Z9 12 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 BP 321 EP + DI 10.1161/STROKEAHA.112.675181 PG 10 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 073PK UT WOS:000313754800016 PM 23321443 ER PT J AU Sirimarco, G Amarenco, P Labreuche, J Touboul, PJ Alberts, M Goto, S Rother, J Mas, JL Bhatt, DL Steg, PG AF Sirimarco, Gaia Amarenco, Pierre Labreuche, Julien Touboul, Pierre-Jean Alberts, Mark Goto, Shinya Rother, Joachim Mas, Jean-Louis Bhatt, Deepak L. Steg, Philippe Gabriel CA REACH Registry Investigators TI Carotid Atherosclerosis and Risk of Subsequent Coronary Event in Outpatients With Atherothrombosis SO STROKE LA English DT Article DE atherosclerosis; carotid plaque; coronary disease ID INTIMA-MEDIA THICKNESS; ARTERY-DISEASE; CARDIOVASCULAR-DISEASE; PREDICTIVE-VALUE; ANGINA-PECTORIS; STROKE; PLAQUE; PREVALENCE; RATES; DETERMINANTS AB Background and Purpose-The presence of carotid plaque reflects overall atherosclerotic burden and may predict coronary artery disease events. We examined the association among carotid atherosclerosis, history of atherothrombotic events, and risk of coronary events. Methods-Among 45 227 patients in the Reduction of Atherothrombosis for Continued Health (REACH) Registry with 4-year follow-up, 23 364 patients with information on carotid atherosclerosis at baseline were analyzed. The primary outcome was the composite of first occurrence of cardiovascular death, myocardial infarction, or coronary hospitalization. Results-The carotid atherosclerosis was present in 46% of patients (n=10 725) and was associated with increasing conventional cardiovascular risk factors and extent of symptomatic vascular disease. During 4-year follow-up, 4304 patients experienced >= 1 coronary event. After adjustment for cardiovascular risk factors and geographic region, the risk of coronary events increased by 22% (95% confidence interval [CI], 14%-30%) in patients with versus without carotid atherosclerosis. The relative increase was 18% (95% CI, -7%-51%) in patients enrolled with multiple risk factors only, 25% (95% CI, 16%-35%) in patients with coronary artery disease, 46% (95% CI, 28%-65%) in patients with cerebrovascular disease, and 37% (95% CI, 17%-60%) in patients with peripheral artery disease. Carotid atherosclerosis was associated with increased risk, even among patients with previous myocardial infarction but no known stroke (P=0.001) or among patients with previous stroke but no known myocardial infarction (P<0.001). Conclusions-Carotid atherosclerosis was an independent predictor of coronary events across all types of symptomatic vascular disease and had an incremental effect on risk regardless of risk factors or location of vessel disease. (Stroke. 2013;44:373-379.) C1 [Sirimarco, Gaia; Amarenco, Pierre; Touboul, Pierre-Jean] Univ Paris Diderot, Hop Bichat Claude Bernard, AP HP, Dept Neurol, Paris, France. [Sirimarco, Gaia; Amarenco, Pierre; Touboul, Pierre-Jean] Univ Paris Diderot, Hop Bichat Claude Bernard, AP HP, Stroke Ctr, Paris, France. [Amarenco, Pierre; Labreuche, Julien; Touboul, Pierre-Jean; Steg, Philippe Gabriel] Univ Paris Diderot, Hop Bichat Claude Bernard, AP HP, INSERM U 698, Paris, France. [Steg, Philippe Gabriel] Univ Paris Diderot, Hop Bichat Claude Bernard, AP HP, Dept Cardiol, Paris, France. [Alberts, Mark] Northwestern Univ, Feinberg Sch Med, Dept Neurol, Chicago, IL 60611 USA. [Goto, Shinya] Tokai Univ, Sch Med, Dept Med Cardiol, Isehara, Kanagawa 25911, Japan. [Rother, Joachim] Klinikum Minden, Hannover Med Sch, Dept Neurol, Minden, Germany. [Mas, Jean-Louis] Paris Descartes Univ, St Anne Hosp, Stroke Unit, Neurol Dept,INSERM UMR S 894, Paris, France. [Bhatt, Deepak L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Steg, PG (reprint author), Hop Bichat Claude Bernard, Dept Cardiol, 46 Rue Henri Huchard, F-75877 Paris 18, France. EM gabriel.steg@bch.aphp.fr FU SOS-ATTAQUE CEREBRALE Association; Sanofi-Aventis; Bristol-Myers Squibb; Waksman Foundation (Tokyo, Japan); Boehringer Ingelheim; Otsuka; Daiichi-Sankyo; Amarin; AstraZeneca; Eisai; Ethicon; Medtronic; Medicines Company; FlowCo; PLx Pharma; Takeda FX Drs Lloyd and Rushton-Smith provided editorial help in checking language and formatting the final version of the manuscript. They were funded by SOS-ATTAQUE CEREBRALE Association.; The Reduction of Atherothrombosis for Continued Health Registry (REACH) is sponsored by Sanofi-Aventis, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan). The REACH Registry is endorsed by the World Heart Federation.; P.-J. Touboul is involved in medical research and development in the IMT company and received royalties for intellectual property of IMT software. S. Goto received significant amount of honoraria from Sanofi-Aventis and AstraZenneca, and also received a significant amount of research grants from Sanofi-Aventis, Boehringer Ingelheim, Otsuka, and Daiichi-Sankyo. D.L. Bhatt is a member of the Advisory Board for Medscape Cardiology, is on the Board of Directors for: Boston VA Research Institute and Society of Chest Pain Centers, is Chair for American Heart Association Get With The Guidelines Science Subcommittee, received Honoraria from American College of Cardiology (Editor, Clinical Trials, and Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), and WebMD (CME steering committees) is Senior Associate Editor for Journal of Invasive Cardiology, received research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi-Aventis, and The Medicines Company, and performed unfunded research for FlowCo, PLx Pharma, and Takeda. NR 34 TC 13 Z9 17 U1 5 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 BP 373 EP + DI 10.1161/STROKEAHA.112.673129 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 073PK UT WOS:000313754800024 PM 23306325 ER PT J AU Chroinin, DN Asplund, K Asberg, S Callaly, E Cuadrado-Godia, E Diez-Tejedor, E Di Napoli, M Engelter, ST Furie, KL Giannopoulos, S Gotto, AM Hannon, N Jonsson, F Kapral, MK Marti-Fabregas, J Martinez-Sanchez, P Milionis, HJ Montaner, J Muscari, A Pikija, S Probstfield, J Rost, NS Thrift, AG Vemmos, K Kelly, PJ AF Chroinin, Danielle Ni Asplund, Kjell Asberg, Signild Callaly, Elizabeth Cuadrado-Godia, Elisa Diez-Tejedor, Exuperio Di Napoli, Mario Engelter, Stefan T. Furie, Karen L. Giannopoulos, Sotirios Gotto, Antonio M., Jr. Hannon, Niamh Jonsson, Fredrik Kapral, Moira K. Marti-Fabregas, Joan Martinez-Sanchez, Patricia Milionis, Haralampos J. Montaner, Joan Muscari, Antonio Pikija, Slaven Probstfield, Jeffrey Rost, Natalia S. Thrift, Amanda G. Vemmos, Konstantinos Kelly, Peter J. TI Statin Therapy and Outcome After Ischemic Stroke Systematic Review and Meta-Analysis of Observational Studies and Randomized Trials SO STROKE LA English DT Review DE cerebral infarction; ischemia; neuroprotective agents; outcomes assessment; stroke; therapy ID COA REDUCTASE INHIBITOR; NITRIC-OXIDE SYNTHASE; TISSUE-PLASMINOGEN ACTIVATOR; FOCAL CEREBRAL-ISCHEMIA; INFARCT VOLUME; ACUTE-PHASE; INTRAVENOUS THROMBOLYSIS; LOWERING TREATMENT; LIPID PROFILE; PRETREATMENT AB Background and Purpose-Although experimental data suggest that statin therapy may improve neurological outcome after acute cerebral ischemia, the results from clinical studies are conflicting. We performed a systematic review and meta-analysis investigating the relationship between statin therapy and outcome after ischemic stroke. Methods-The primary analysis investigated statin therapy at stroke onset (prestroke statin use) and good functional outcome (modified Rankin score 0 to 2) and death. Secondary analyses included the following: (1) acute poststroke statin therapy (<= 72 hours after stroke), and (2) thrombolysis-treated patients. Results-The primary analysis included 113 148 subjects (27 studies). Among observational studies, statin treatment at stroke onset was associated with good functional outcome at 90 days (pooled odds ratio [OR], 1.41; 95% confidence interval [CI], 1.29-1.56; P<0.001), but not 1 year (OR, 1.12; 95% CI, 0.9-1.4; P=0.31), and with reduced fatality at 90 days (pooled OR, 0.71; 95% CI, 0.62-0.82; P<0.001) and 1 year (OR, 0.80;95% CI, 0.67-0.95; P=0.01). In the single randomized controlled trial reporting 90-day functional outcome, statin treatment was associated with good outcome (OR, 1.5; 95% CI, 1.0-2.24; P=0.05). No reduction in fatality was observed on meta-analysis of data from 3 randomized controlled trials (P=0.9). In studies restricted to of thrombolysis-treated patients, an association between statins and increased fatality at 90 days was observed (pooled OR, 1.25; 95% CI, 1.02-1.52; P=0.03, 3 studies, 4339 patients). However, this association was no longer present after adjusting for age and stroke severity in the largest study (adjusted OR, 1.14; 95% CI, 0.90-1.44; 4012 patients). Conclusion-In the largest meta-analysis to date, statin therapy at stroke onset was associated with improved outcome, a finding not observed in studies restricted to thrombolysis-treated patients. Randomized trials of statin therapy in acute ischemic stroke are needed. (Stroke. 2013;44:448-456.) C1 [Chroinin, Danielle Ni; Callaly, Elizabeth; Hannon, Niamh; Kelly, Peter J.] Natl Univ Ireland Univ Coll Dublin, Neurovasc Unit Appl Translat Res & Therapeut, Mater Univ Hosp, Dublin Acad Med Ctr, Dublin, Ireland. [Asplund, Kjell; Jonsson, Fredrik] Umea Univ Hosp, Dept Med, S-90185 Umea, Sweden. [Asberg, Signild] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Cuadrado-Godia, Elisa] Hosp del Mar IMIM, Dept Neurol, Barcelona, Spain. [Diez-Tejedor, Exuperio; Martinez-Sanchez, Patricia] Univ Autonoma Madrid, Dept Neurol, La Paz Univ Hosp, Madrid, Spain. [Diez-Tejedor, Exuperio; Martinez-Sanchez, Patricia] Univ Autonoma Madrid, Stroke Ctr, La Paz Univ Hosp, Madrid, Spain. [Di Napoli, Mario] San Camillo deLellis Gen Hosp, Neurol Serv, Rieti, Italy. [Di Napoli, Mario] Ctr Cardiovasc Med & Cerebrovasc Dis Prevent, SMDN, Laquila, Italy. [Engelter, Stefan T.] Univ Basel Hosp, Dept Neurol, Basel, Switzerland. [Furie, Karen L.; Rost, Natalia S.] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA. [Giannopoulos, Sotirios; Milionis, Haralampos J.] Univ Ioannina, Sch Med, GR-45110 Ioannina, Greece. [Gotto, Antonio M., Jr.] Weill Cornell Med Coll, New York, NY USA. [Kapral, Moira K.] Toronto Gen Hosp, Inst Clin Evaluat Sci, Toronto, ON, Canada. [Marti-Fabregas, Joan] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Montaner, Joan] Autonomous Univ Barcelona, Hosp Vall dHebron, Barcelona, Spain. [Montaner, Joan] Autonomous Univ Barcelona, Vall dHebron Res Inst VHIR, Barcelona, Spain. [Muscari, Antonio] Univ Bologna, S Orsola Malpighi Hosp, Bologna, Italy. [Pikija, Slaven] Gen Hosp Varazdin, Varazhdin, Croatia. [Probstfield, Jeffrey] Univ Washington, Dept Med, Seattle, WA USA. [Probstfield, Jeffrey] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Thrift, Amanda G.] Monash Univ, Monash Med Ctr, Stroke & Ageing Res Ctr, Dept Med, Clayton, Vic, Australia. [Thrift, Amanda G.] Natl Stroke Res Inst, Heidelberg, Vic, Australia. [Vemmos, Konstantinos] Univ Athens, Dept Therapeut, Alexandra Hosp, GR-10679 Athens, Greece. RP Chroinin, DN (reprint author), Natl Univ Ireland Univ Coll Dublin, Neurovasc Unit Appl Translat Res & Therapeut, Mater Univ Hosp, Dublin Acad Med Ctr, Dublin, Ireland. EM dmmnic@umail.ucc.ie RI Thrift, Amanda/I-6251-2012; Di Napoli, Mario/J-6418-2014; Montaner, Joan/D-3063-2015; IBIS, NEUROVASCULAR/O-1855-2015; Martinez-Sanchez, Patricia/O-5687-2016; OI Thrift, Amanda/0000-0001-8533-4170; Di Napoli, Mario/0000-0001-9609-4926; Martinez-Sanchez, Patricia/0000-0003-1945-4435; Diez Tejedor, Exuperio/0000-0003-2295-1707; Asberg, Signild/0000-0001-8693-1014 FU National Institutes of Health/NINDS [K23NS064052]; National Health and Medical Research Council of Australia [438700]; Irish Health Services Executive; National Lottery of Ireland; Servier; Boehringer Ingelheim; Pfizer Inc; Sanofi-aventis; Shire plc; Kaethe-Zingg-Schwichtenberg-Fonds of the Swiss Academy of Medical Sciences; Swiss Heart Foundation; Swiss National Funds; Health Research Board of Ireland; Irish Heart Foundation; Instituto de Salud Carlo III FX Dr Rost is supported by the National Institutes of Health/NINDS (K23NS064052). Dr Thrift is supported by a Senior Research Fellowship from the National Health and Medical Research Council of Australia (Grant 438700). Funding was also received by the Neurovascular Unit for Applied Translational Research and Therapeutics, Dublin from the Irish Health Services Executive, National Lottery of Ireland, and an unrestricted educational grant for stroke research and education from Servier. Funding sources were not involved in the design, conduct, analysis, or reporting of the study findings.; Dr Diez-Tejedor has collaborated as a clinical advisor, preclinical and clinical trial researcher, or as a speaker with the following companies: Astra-Zeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Cellerix, Ferrer Grupo, Pfizer, Sanofi, Sygnis Pharma AG, Roche, and EVER Neuro Pharma. Dr Engelter has received funding for travel or speaker honoraria from Boehringer Ingelheim, Pfizer Inc, Sanofi-aventis, and Shire plc; serves on scientific advisory boards for Bayer and Boehringer Ingelheim and on the editorial board of Stroke. He has received research support from the Kaethe-Zingg-Schwichtenberg-Fonds of the Swiss Academy of Medical Sciences, the Swiss Heart Foundation, and Swiss National Funds. Dr Gotto Jr is a consultant for Kowa and Merck, and he serves on the Board of Directors for Aegerion Pharmaceuticals and Arisph Pharmaceuticals. He is a member of advisory boards for DuPont and Vatera Capital. Dr Hannon is funded by the Health Research Board of Ireland. Dr Kapral holds a Career Investigator Award from the Heart and Stroke Foundation of Canada. Dr Kelly is the recipient of a Clinician Scientist Award from the Health Research Board of Ireland and research funding from the Irish Heart Foundation. Dr has collaborated as clinical trial researcher with the following companies: Astra-Zeneca, Bayer, Bristol-Myers Squibb, Ferrer Grupo, Pfizer, Sanofi and Roche. Dr Montaner is the Principal Investigator of the project: EC07/90195: Strategies to improve safety and efficacy of the treatment with simvastatin in the acute phase of ischemic stroke: STARS trial, funded by the Instituto de Salud Carlo III, through a call for nonprofit drugs independent research. The other authors report no conflicts. NR 75 TC 25 Z9 26 U1 0 U2 29 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 BP 448 EP 456 DI 10.1161/STROKEAHA.112.668277 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 073PK UT WOS:000313754800036 ER PT J AU Hanchate, AD Schwamm, LH Huang, W Hylek, EM AF Hanchate, Amresh D. Schwamm, Lee H. Huang, Wei Hylek, Elaine M. TI Comparison of Ischemic Stroke Outcomes and Patient and Hospital Characteristics by Race/Ethnicity and Socioeconomic Status SO STROKE LA English DT Article DE ethnicity; ischemic stroke; inpatient mortality; length of stay; race; risk factors; socioeconomic status ID ATHEROSCLEROSIS RISK; NORTHERN MANHATTAN; ETHNIC DISPARITIES; MEXICAN-AMERICANS; MEDICARE PATIENTS; HEALTH-CARE; FOLLOW-UP; MORTALITY; POPULATION; QUALITY AB Background and Purpose-Current literature provides mixed evidence on disparities by race/ethnicity and socioeconomic status in discharge outcomes after hospitalization for acute ischemic stroke. Using comprehensive data from 8 states, we sought to compare inpatient mortality and length of stay by race/ethnicity and socioeconomic status. Methods-We examined all 2007 hospitalizations for acute ischemic stroke in all nonfederal acute care hospitals in Arizona, California, Florida, Maine, New Jersey, New York, Pennsylvania, and Texas. Population was stratified by race/ethnicity (non-Hispanic whites, non-Hispanic blacks, and Hispanics) and socioeconomic status, measured by median income of patient zip code. For each stratum, we estimated risk-adjusted rates of inpatient mortality and longer length of stay (greater than median length of stay). We also compared the hospitals where these subpopulations received care. Results-Hispanic and black patients accounted for 14% and 12% of all ischemic stroke admissions (N=147 780), respectively, and had lower crude inpatient mortality rates (Hispanic=4.5%, blacks=4.4%; all P<0.001) compared with white patients (5.8%). Hispanic and black patients were younger and fewer had any form of atrial fibrillation. Adjusted for patient risk, inpatient mortality was similar by race/ethnicity, but was significantly higher for low-income area patients than that for high-income area patients (odds ratio, 1.08; 95% confidence interval, 1.02-1.15). Risk-adjusted rates of longer length of stay were higher among minority and low-income area populations. Conclusions-Risk-adjusted inpatient mortality was similar among patients by race/ethnicity but higher among patients from lower income areas. However, this pattern was not evident in sensitivity analyses, including the use of mechanical ventilation as a partial surrogate for stroke severity. (Stroke. 2013;44:469-476.) C1 [Hanchate, Amresh D.] VA Boston Healthcare Syst, Boston, MA USA. [Hanchate, Amresh D.; Hylek, Elaine M.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Schwamm, Lee H.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Huang, Wei] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02118 USA. [Hylek, Elaine M.] Boston Med Ctr, Boston, MA USA. RP Hanchate, AD (reprint author), Boston Univ, Sch Med, Gen Internal Med Sect, 801 Massachusetts Ave,2092, Boston, MA 02118 USA. EM hanchate@bu.edu OI Hanchate, Amresh/0000-0002-7038-4463; Schwamm, Lee/0000-0003-0592-9145 FU National Institutes of Health [1R21NS062677, 1R01HL106029-01] FX This research has been funded by National Institutes of Health grants 1R21NS062677 (PI=Dr Hanchate) and 1R01HL106029-01 (principal investigator=Dr Hylek). NR 41 TC 9 Z9 10 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 BP 469 EP + DI 10.1161/STROKEAHA.112.669341 PG 21 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 073PK UT WOS:000313754800039 PM 23306327 ER PT J AU Campos, F Qin, T Castillo, J Seo, JH Arai, K Lo, EH Waeber, C AF Campos, Francisco Qin, Tao Castillo, Jose Seo, Ji Hae Arai, Ken Lo, Eng H. Waeber, Christian TI Fingolimod Reduces Hemorrhagic Transformation Associated With Delayed Tissue Plasminogen Activator Treatment in a Mouse Thromboembolic Model SO STROKE LA English DT Article DE fingolimod; hemorrhage; stroke; tPA; thromboembolic model ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; SPHINGOSINE 1-PHOSPHATE RECEPTOR; ACUTE ISCHEMIC-STROKE; BLOOD-BRAIN-BARRIER; CEREBRAL-ISCHEMIA; MULTIPLE-SCLEROSIS; LASER SPECKLE; FTY720; RECANALIZATION; REPERFUSION AB Background and Purpose-The sphingosine 1-phosphate receptor agonist fingolimod reduces infarct size in rodent models of stroke and enhances blood-brain barrier integrity. Based on these observations, we hypothesized that combination of fingolimod with tissue plasminogen activator (tPA) would reduce the risk of hemorrhagic transformation associated with delayed administration of tPA. Methods-We evaluated the effects of fingolimod in a mouse model of thromboembolic stroke, in which both the beneficial effect of reperfusion associated with early tPA treatment and hemorrhagic transformation associated with delayed administration mimic clinical observations in humans. Results-Our results demonstrate that fingolimod treatment attenuates the neurological deficit and reduces infarct volume after in situ thromboembolic occlusion of the middle cerebral artery. Combination of fingolimod and tPA improves the neurological outcome of the thrombolytic therapy and reduces the risk of hemorrhagic transformation associated with delayed administration of tPA. Conclusion-This study confirms the protective efficacy of fingolimod as a treatment against ischemic stroke in another rodent model of stroke (thromboembolic occlusion), and suggests that fingolimod could potentially be used in combination with tPA to reduce the risk of brain hemorrhage. (Stroke. 2013;44:505-511.) C1 [Campos, Francisco; Qin, Tao; Waeber, Christian] Massachusetts Gen Hosp, Stroke Res Lab, Dept Radiol, Charlestown, MA USA. [Campos, Francisco; Castillo, Jose] Univ Santiago de Compostela, Clin Neurosci Res Lab, Univ Clin Hosp, Dept Neurol,IDIS, Santiago De Compostela, Spain. [Seo, Ji Hae; Arai, Ken; Lo, Eng H.] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA USA. [Seo, Ji Hae; Arai, Ken; Lo, Eng H.] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA USA. RP Waeber, C (reprint author), Natl Univ Ireland Univ Coll Cork, Room 1-26,Cavanagh Pharm Bldg,Coll Rd, Cork, Ireland. EM c.waeber@ucc.ie RI Waeber, Christian/A-8333-2009; OI Waeber, Christian/0000-0001-6078-0027; Castillo, Jose/0000-0002-6685-3001 FU NIH [NS049263, NS055104]; Interdepartmental Neuroscience Center [P30NS045776]; Spanish Ministry of Science and Innovation [SAF2011-30517]; RENEVAS [RD06/0026/000]; Conselleria de Industria, Xunta de Galicia (Programa Angeles Alvarino) FX This work was supported by NIH grants (NS049263 and NS055104) to CW and grant P30NS045776 (Interdepartmental Neuroscience Center). Spanish Ministry of Science and Innovation SAF2011-30517 AND RENEVAS (RD06/0026/000). Furthermore, FC is the recipient of a fellowship from the Conselleria de Industria, Xunta de Galicia (Programa Angeles Alvarino). NR 32 TC 28 Z9 31 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 BP 505 EP + DI 10.1161/STROKEAHA.112.679043 PG 16 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 073PK UT WOS:000313754800044 PM 23287783 ER PT J AU Richards, A Cheng, EM AF Richards, Adam Cheng, Eric M. TI Stroke Risk Calculators in the Era of Electronic Health Records Linked to Administrative Databases SO STROKE LA English DT Review DE cardiovascular disease; database management systems; electronic health records; epidemiology; risk assessment; stroke ID CORONARY-HEART-DISEASE; GLOBAL CARDIOVASCULAR RISK; TRANSIENT ISCHEMIC ATTACK; ATRIAL-FIBRILLATION; PRIMARY-CARE; SOCIOECONOMIC-STATUS; NATIONWIDE COHORT; VALIDATION; PREDICTION; SCORES C1 [Richards, Adam; Cheng, Eric M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Cheng, Eric M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Cheng, EM (reprint author), VA Greater Los Angeles, Dept Neurol, 11301 Wilshire Blvd,ML 127, Los Angeles, CA 90073 USA. EM eric.cheng@va.gov FU National Institutes of Health/National Institute of Neurological Disorders and Stroke [K23NS058571]; UCLA Outcomes Research Center; American Heart Association Pharmaceutical Roundtable FX Dr Cheng is supported by a Career Development Award from National Institutes of Health/National Institute of Neurological Disorders and Stroke (K23NS058571). Drs Cheng and Richards are supported by the UCLA Outcomes Research Center, funded through the American Heart Association Pharmaceutical Roundtable and David and Stevie Spina. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 40 TC 2 Z9 3 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 BP 564 EP 569 DI 10.1161/STROKEAHA.111.649798 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 073PK UT WOS:000313754800059 PM 23204057 ER PT J AU Wahlster, L Arimon, M Nasser-Ghodsi, N Post, KL Serrano-Pozo, A Uemura, K Berezovska, O AF Wahlster, Lara Arimon, Muriel Nasser-Ghodsi, Navine Post, Kathryn Leigh Serrano-Pozo, Alberto Uemura, Kengo Berezovska, Oksana TI Presenilin-1 adopts pathogenic conformation in normal aging and in sporadic Alzheimer's disease SO ACTA NEUROPATHOLOGICA LA English DT Article DE Alzheimer's disease; Aging; Presenilin-1; Amyloid beta; Oxidative stress ID AMYLOID-BETA-PROTEIN; MILD COGNITIVE IMPAIRMENT; GAMMA-SECRETASE ACTIVITY; IN-VIVO; OXIDATIVE STRESS; FRONTOTEMPORAL DEMENTIA; LIPID-PEROXIDATION; PRECURSOR PROTEIN; SYNAPSE LOSS; MOUSE MODEL AB Accumulation of amyloid-beta (A beta) and neurofibrillary tangles in the brain, inflammation and synaptic and neuronal loss are some of the major neuropathological hallmarks of Alzheimer's disease (AD). While genetic mutations in amyloid precursor protein and presenilin-1 and -2 (PS1 and PS2) genes cause early-onset familial AD, the etiology of sporadic AD is not fully understood. Our current study shows that changes in conformation of endogenous wild-type PS1, similar to those found with mutant PS1, occur in sporadic AD brain and during normal aging. Using a mouse model of Alzheimer's disease (Tg2576) that overexpresses the Swedish mutation of amyloid precursor protein but has normal levels of endogenous wild-type presenilin, we report that the percentage of PS1 in a pathogenic conformation increases with age. Importantly, we found that this PS1 conformational shift is associated with amyloid pathology and precedes amyloid-beta deposition in the brain. Furthermore, we found that oxidative stress, a common stress characteristic of aging and AD, causes pathogenic PS1 conformational change in neurons in vitro, which is accompanied by increased A beta 42/40 ratio. The results of this study provide important information about the timeline of pathogenic changes in PS1 conformation during aging and suggest that structural changes in PS1/gamma-secretase may represent a molecular mechanism by which oxidative stress triggers amyloid-beta accumulation in aging and in sporadic AD brain. C1 [Wahlster, Lara; Arimon, Muriel; Nasser-Ghodsi, Navine; Post, Kathryn Leigh; Serrano-Pozo, Alberto; Uemura, Kengo; Berezovska, Oksana] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,MassGen Inst Neurodegenerat Dis MIND, Charlestown, MA 02129 USA. RP Berezovska, O (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,MassGen Inst Neurodegenerat Dis MIND, CNY 114,16th St, Charlestown, MA 02129 USA. EM wahlster@stud.uni-heidelberg.de; Arimon.Muriel@mgh.harvard.edu; NNasserghodsi@gmail.com; klpost@partners.org; ASerrano1@partners.org; ueken@kuhp.kyoto-u.ac.jp; OBerezovska@partners.org RI SERRANO-POZO, ALBERTO/F-5119-2013; Arimon, Muriel/I-4054-2015; OI Arimon, Muriel/0000-0002-0894-3324; SERRANO-POZO, ALBERTO/0000-0003-0899-7530 FU National Institutes of Health [AG15379]; German National Academic Foundation ("Studienstiftung des deutschen Volkes"); Fundacion Ibercaja (Zaragoza, Spain); Fundacion Alfonso Martin Escudero (Madrid, Spain) FX We thank Dr. Bradley T. Hyman, Dr. Matthew Frosch, Karlotta Fitch, and the Alzheimer's Disease Research Center for providing the human brain tissue that was used in this study. This work was supported by National Institutes of Health Grant [AG15379 to O.B.]; the German National Academic Foundation ("Studienstiftung des deutschen Volkes") [scholarship to L. W.]; the Fundacion Ibercaja (Zaragoza, Spain) [fellowship to M. A.]; the Fundacion Alfonso Martin Escudero (Madrid, Spain) [fellowship to A.S.P.]. NR 73 TC 20 Z9 20 U1 1 U2 24 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD FEB PY 2013 VL 125 IS 2 BP 187 EP 199 DI 10.1007/s00401-012-1065-6 PG 13 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 074DS UT WOS:000313793400002 PM 23138650 ER PT J AU Byatt, N Deligiannidis, KM Freeman, MP AF Byatt, N. Deligiannidis, K. M. Freeman, M. P. TI Antidepressant use in pregnancy: a critical review focused on risks and controversies SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Review DE antidepressant; in utero; teratogenicity; postnatal adaptation syndrome; persistent pulmonary hypertension ID SEROTONIN-REUPTAKE INHIBITORS; PERSISTENT PULMONARY-HYPERTENSION; IN-UTERO EXPOSURE; MAJOR CONGENITAL-MALFORMATIONS; REPEAT CESAREAN DELIVERY; MATERNAL USE; PRENATAL EXPOSURE; BIRTH OUTCOMES; NEONATAL OUTCOMES; WITHDRAWAL SYNDROME AB Objective Conflicting data have led to controversy regarding antidepressant use during pregnancy. The objectives of this study are to i) review the risks of untreated depression and anxiety, ii) review the literature on risks of exposure to antidepressants during pregnancy, iii) discuss the strengths and weaknesses of the different study designs used to evaluate those risks, and iv) provide clinical recommendations. Method MEDLINE/PubMed was searched for reports and studies on the risk of first-trimester teratogenicity, postnatal adaptation syndrome (PNAS), and persistent pulmonary hypertension (PPHN) with in utero antidepressant exposure. Results While some individual studies suggest associations between some specific major malformations, the findings are inconsistent. Therefore, the absolute risks appear small. PNAS occurs in up to 30% of neonates exposed to antidepressants. In some studies, PPHN has been weakly associated with in utero antidepressant exposure, while in other studies, there has been no association. Conclusion Exposures of concern include that of untreated maternal illness as well as medication exposure. It is vital to have a careful discussion, tailored to each patient, which incorporates the evidence to date and considers methodological and statistical limitations. Past medication trials, previous success with symptom remission, and women's preference should guide treatment decisions. C1 [Byatt, N.; Deligiannidis, K. M.] Univ Massachusetts, Sch Med, UMass Mem Med Ctr,Ctr Psychopharmacol Res & Treat, Depress Specialty Clin,Womens Mental Hlth Special, Worcester, MA 01655 USA. [Freeman, M. P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat Perinatal & Reprod Psychiat Program, Boston, MA USA. RP Byatt, N (reprint author), Univ Massachusetts, Sch Med, UMass Mem Med Ctr,Ctr Psychopharmacol Res & Treat, Depress Specialty Clin,Womens Mental Hlth Special, 55 Lake Ave N, Worcester, MA 01655 USA. EM nancy.byatt@umassmemorial.org RI Deligiannidis, Kristina/C-3654-2014; OI Deligiannidis, Kristina/0000-0001-7439-2236; Byatt, Nancy/0000-0002-4010-8919 FU NCATS NIH HHS [KL2 TR000160, UL1 TR000161] NR 160 TC 52 Z9 53 U1 5 U2 52 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD FEB PY 2013 VL 127 IS 2 BP 94 EP 114 DI 10.1111/acps.12042 PG 21 WC Psychiatry SC Psychiatry GA 070FT UT WOS:000313492300002 PM 23240634 ER PT J AU Yaffe, K Ackerson, L Hoang, TD Go, AS Maguire, MG Ying, GS Daniel, E Bazzano, LA Coleman, M Cohen, DL Kusek, JW Ojo, A Seliger, S Xie, DW Grunwald, JE AF Yaffe, Kristine Ackerson, Lynn Hoang, Tina D. Go, Alan S. Maguire, Maureen G. Ying, Gui-Shuang Daniel, Ebenezer Bazzano, Lydia A. Coleman, Martha Cohen, Debbie L. Kusek, John W. Ojo, Akinlolu Seliger, Stephen Xie, Dawei Grunwald, Juan E. CA CRIC Study Investigators TI Retinopathy and Cognitive Impairment in Adults With CKD SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Chronic kidney disease; cognitive impairment; retinopathy ID RETINAL MICROVASCULAR ABNORMALITIES; CHRONIC KIDNEY-DISEASE; SMALL-VESSEL DISEASE; GLOMERULAR-FILTRATION-RATE; CARDIOVASCULAR HEALTH; ATHEROSCLEROSIS RISK; ELDERLY POPULATION; RENAL-DISEASE; OLDER-ADULTS; FOLLOW-UP AB Background: Retinal microvascular abnormalities have been associated with cognitive impairment, possibly serving as a marker of cerebral small-vessel disease. This relationship has not been evaluated in persons with chronic kidney disease (CKD), a condition associated with increased risk of both retinal pathology and cognitive impairment. Study Design: Cross-sectional study. Setting & Participants: 588 participants 52 years or older with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study. Predictor: Retinopathy graded using the Early Treatment Diabetic Retinopathy Study severity scale and diameters of retinal vessels. Outcomes: Neuropsychological battery of 6 cognitive tests. Measurements: Logistic regression models were used to evaluate the association of retinopathy, individual retinopathy features, and retinal vessel diameters with cognitive impairment (<= 1 SD from the mean), and linear regression models were used to compare cognitive test scores across levels of retinopathy, adjusting for age, race, sex, education, and medical comorbid conditions. Results: The mean age of the cohort was 65.3 +/- 5.6 (SD) years, 51.9% were nonwhite, and 52.6% were men. The prevalence of retinopathy was 30.1%, and the prevalence of cognitive impairment was 14.3%. Compared with those without retinopathy, participants with retinopathy had an increased likelihood of cognitive impairment on executive function (35.1% vs 11.5%; OR, 3.4 [ 95% CI, 2.0-6.0]), attention (26.7% vs 7.3%; OR, 3.0 [ 95% CI, 1.8-4.9]), and naming (26.0% vs 10.0%; OR, 2.1 [ 95% CI, 1.2-3.4]) after multivariable adjustment. Increased level of retinopathy also was associated with lower cognitive performance on executive function and attention. Microaneurysms were associated with cognitive impairment on some domains, but there were no significant associations with other retinal measures after multivariable adjustment. Limitations: Unknown temporal relationship between retinopathy and impairment. Conclusions: In adults with CKD, retinopathy is associated with poor performance on several cognitive domains, including executive function and attention. Evaluation of retinal microvascular abnormalities may be a promising tool for identifying patients with CKD who are at increased risk of cognitive impairment. Am J Kidney Dis. 61(2): 219-227. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94121 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Ackerson, Lynn; Go, Alan S.] Kaiser Permanente, Div Res, Oakland, CA USA. [Hoang, Tina D.] No Calif Inst Res & Educ, San Francisco, CA USA. [Maguire, Maureen G.; Ying, Gui-Shuang; Daniel, Ebenezer; Grunwald, Juan E.] Univ Penn, Dept Ophthalmol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Bazzano, Lydia A.] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA. [Coleman, Martha] Univ Hosp Cleveland, Cleveland Clin Fdn, Cleveland, OH 44106 USA. [Cohen, Debbie L.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kusek, John W.] NIDDKD, Div Kidney Urol & Hematol Dis, Bethesda, MD USA. [Ojo, Akinlolu] Univ Michigan Hlth Syst, Dept Internal Med, Ann Arbor, MI USA. [Ojo, Akinlolu] Univ Michigan Hlth Syst, Dept Nephrol, Ann Arbor, MI USA. [Seliger, Stephen] Univ Maryland, Sch Med, Div Nephrol, Baltimore, MD 21201 USA. [Xie, Dawei] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, Box 181,4150 Clement St, San Francisco, CA 94121 USA. EM kristine.yaffe@ucsf.edu OI Daniel, Ebenezer/0000-0002-2027-2316 FU National Institutes of Health (NIH) [U01 DK060980, U01 DK060902, U01 DK060963, U01 DK060984, U01 DK060990, U01 DK061021, U01 DK061022]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [UL1 RR-024134, UL1 RR-025005, MO1 RR-16500, UL1 RR-024989, MO1 RR-000042, UL1 RR-024986, UL1 RR-029879, UL1 RR-024131]; NIDDK grant [R01 DK069406]; NIH [R01 DK74151]; Vivian S. Lasko Research Fund; Nina C. Mackall Trust, and Research to Prevent Blindness FX The CRIC Study is funded by National Institutes of Health (NIH) grants U01 DK060980, U01 DK060902, U01 DK060963, U01 DK060984, U01 DK060990, U01 DK061021, and U01 DK061022 and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grants UL1 RR-024134, UL1 RR-025005, MO1 RR-16500, UL1 RR-024989, MO1 RR-000042, UL1 RR-024986, UL1 RR-029879, and UL1 RR-024131. The ancillary studies also were supported by NIDDK grant R01 DK069406, which was administered by the Northern California Institute for Research and Education and with resources of the Veterans Affairs Medical Center, San Francisco, CA, and by NIH R01 DK74151, Vivian S. Lasko Research Fund, Nina C. Mackall Trust, and Research to Prevent Blindness. NR 47 TC 9 Z9 10 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD FEB PY 2013 VL 61 IS 2 BP 219 EP 227 DI 10.1053/j.ajkd.2012.10.006 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 071KP UT WOS:000313591800008 PM 23206534 ER PT J AU La Fountaine, MF Rivera, DR Radulovic, M Bauman, WA AF La Fountaine, Michael F. Rivera, Dwindally Rosado Radulovic, Miroslav Bauman, William A. TI The Hemodynamic Actions of Insulin Are Blunted in the Sublesional Microvasculature of Healthy Persons with Spinal Cord Injury SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Iontophoresis; Insulin; Autonomic; Laser Doppler Flowmetry; Skin Blood Flow ID SKELETAL-MUSCLE VASODILATION; NITRIC-OXIDE RELEASE; CARDIOVASCULAR-DISEASE; ENDOTHELIAL FUNCTION; GLUCOSE-INTOLERANCE; BLOOD-FLOW; SKIN; RESISTANCE; HUMANS; RISK AB La Fountaine MF, Rivera DR, Radulovic M, Bauman WA: The hemodynamic actions of insulin are blunted in the sublesional microvasculature of healthy persons with spinal cord injury. Am J Phys Med Rehabil 2013;92:127-135. Objective: The aim of this study was to gain a better understanding of the hemodynamic actions of insulin on cutaneous microcirculation in persons with spinal cord injury (SCI). Design: A prospective, open-label, nonrandomized, placebo-controlled investigation was performed in an otherwise healthy cohort of persons with SCI (n = 10) and in an age- and sex-matched cohort of control subjects whose neurologic function is intact (n = 10). Laser Doppler flowmetry characterized the peak blood perfusion unit (BPU) response (percent change from baseline) to insulin or placebo iontophoresis above and below the neurologic level of injury. Results: Placebo iontophoresis did not result in any statistically significant changes in BPU. In the arm, insulin iontophoresis resulted in a 20% mean increase in BPU (P < 0.05) in the control group and a 9% mean increase in the SCI group (P = 0.14). In the leg, insulin iontophoresis resulted in an 81% (P < 0.01) mean increase in BPU in the control group and a 29% (P < 0.001) mean increase in BPU in the SCI group. The relative effect of insulin on the lower extremity BPU response was significantly greater (P < 0.05) in the control group compared with the SCI group (77% vs. 35%, respectively). Conclusions: The hemodynamic actions of insulin are markedly blunted in the sublesional microvasculature of persons with SCI, most likely as a result of impaired sublesional sympathetic nervous system control. C1 [La Fountaine, Michael F.; Rivera, Dwindally Rosado; Radulovic, Miroslav; Bauman, William A.] James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA. [La Fountaine, Michael F.; Radulovic, Miroslav; Bauman, William A.] James J Peters VA Med Ctr, Med Serv, Bronx, NY 10468 USA. [La Fountaine, Michael F.; Bauman, William A.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Radulovic, Miroslav] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. [La Fountaine, Michael F.] Seton Hall Univ, Dept Phys Therapy, Sch Hlth & Med Sci, S Orange, NJ 07079 USA. RP La Fountaine, MF (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. FU Veterans Affairs Rehabilitation Research & Development National Center of Excellence for the Medical Consequences of Spinal Cord Injury [B9212-C]; James J. Peters VA Medical Center; James J. Peters VA Medical Center, Bronx, NY; Department of Veterans Affairs Rehabilitation Research & Development Service FX Funded by the Veterans Affairs Rehabilitation Research & Development National Center of Excellence for the Medical Consequences of Spinal Cord Injury (#B9212-C) and James J. Peters VA Medical Center.; The authors thank James J. Peters VA Medical Center, Bronx, NY, and the Department of Veterans Affairs Rehabilitation Research & Development Service for their support. NR 31 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD FEB PY 2013 VL 92 IS 2 BP 127 EP 135 DI 10.1097/PHM.0b013e31827d63ee PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 072KA UT WOS:000313668600004 PM 23328885 ER PT J AU Wang, QM Wei, Y Zheng, Y Waeber, C AF Wang, Qing Mei Wei, Ying Zheng, Yi Waeber, Christian TI Efficacy of Combined Atorvastatin and Sildenafil in Promoting Recovery After Ischemic Stroke in Mice SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Stroke; Atorvastatin; Sildenafil; Recovery; Angiogenesis ID FUNCTIONAL RECOVERY; CEREBRAL-ISCHEMIA; NEUROGENESIS; STATIN; ANGIOGENESIS; INJURY; RATS; INFLAMMATION; SIMVASTATIN; PROTECTION AB Wang QM, Wei Y, Zheng Y, Waeber C: Efficacy of combined atorvastatin and sildenafil in promoting recovery after ischemic stroke in mice. Am J Phys Med Rehabil 2013;92:143-150. Objective: The aim of this study was to test the hypothesis that a combination of atorvastatin and sildenafil promotes recovery in an additive manner after ischemic stroke in mice. Design: Adult C57BL/6 mice (n = 67) were subjected to transient middle cerebral artery occlusion. Vehicle-control (H2O), atorvastatin (0.3 mg/kg), sildenafil (0.3 mg/kg), or combined atorvastatin (0.3 mg/kg) and sildenafil (0.3 mg/kg) were administrated via oral gavage daily for 6 days starting 24 hrs after ischemia. Behavioral studies including neurologic score and adhesive removal test were performed before surgery and on postoperative days 1 and 7; cylinder test was performed before surgery and on postoperative day 7. Mice were killed after 7 days and brain slices were stained with hematoxylin and eosin to measure the infarct volume. Results: The combination group performed significantly better in the adhesive removal test (mean +/- SD) (50 +/- 54 secs) as compared with the control group (147 +/- 109 secs) (P < 0.05) and to atorvastatin (144 +/- 102 secs) (P < 0.05) but did not show statistically significant improvement as compared with sildenafil (107 +/- 115 secs) (P = 0.148). There were no significant differences among the groups in neurologic score and cylinder test. There was no significant difference in the infarct volume. Conclusions: The data suggest that combined atorvastatin and sildenafil generates a better functional outcome as compared with atorvastatin-only treatment, but not sildenafil-only treatment, in one of multiple variables tested. C1 [Wang, Qing Mei] Harvard Univ, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Sch Med, Boston, MA 02114 USA. [Wei, Ying; Zheng, Yi; Waeber, Christian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wang, QM (reprint author), Harvard Univ, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Sch Med, 125 Nashua St, Boston, MA 02114 USA. RI Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 FU Rehabilitation Medicine Scientist Training Program FX The authors disclosure unlabeled use of pharmaceutical products on the animals in this study. No human subjects were involved. Dr Qing Mei Wang is funded by the Rehabilitation Medicine Scientist Training Program. There is no financial disclosure from any of the authors. NR 30 TC 4 Z9 6 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD FEB PY 2013 VL 92 IS 2 BP 143 EP 150 DI 10.1097/PHM.0b013e3182643f1a PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 072KA UT WOS:000313668600006 PM 22854903 ER PT J AU Elias, JA Morgenroth, DC AF Elias, Joseph Abraham Morgenroth, David Crespi TI Amputee Care Education in Physical Medicine and Rehabilitation Residency Programs SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Residency; Amputee; Education; Physical Medicine and Rehabilitation ID LOWER-LIMB AMPUTATIONS; MUSCULOSKELETAL EDUCATION; INPATIENT REHABILITATION; UNITED-STATES; BACK-PAIN; PREVALENCE; OSTEOARTHRITIS; SERVICES; KNEE AB Elias JA, Morgenroth DC: Amputee care education in physical medicine and rehabilitation residency programs. Am J Phys Med Rehabil 2013;92:157-162. Objective: The aim of this study was to assess amputee care-related educational offerings and barriers to further educational opportunities in United States physical medicine and rehabilitation residency programs. Design: A two-part survey was distributed to all United States physical medicine and rehabilitation residency program directors. Part 1 assessed the use of educational tools in amputee education. Part 2 assessed the potential barriers to amputee care-related education. Results: Sixty-nine percent of the program directors responded. Seventy-five percent or more of the programs that responded have didactic lectures; grand rounds; reading lists; self-assessment exam review; gait analysis training; training with prosthetists; faculty with amputee expertise; and amputee care during inpatient, outpatient, and consult rotations. Less than 25% of the programs use intranet resources. No more than 14% of the programs said any one factor was a major barrier. However, some of the most prominent major barriers were limited faculty number, finances, and patient volume. The factors many of the programs considered somewhat of a barrier included lack of national standardized resources for curriculum, resident time, and faculty time. Conclusions: This study identified the most commonly used amputee educational opportunities and methods in physical medicine and rehabilitation residencies as well as the barriers to furthering resident amputee education. Developing Web-based resources on amputee care and increasing awareness of physiatrists as perioperative consultants could improve resident amputee education and have important implications toward optimizing care of individuals with amputation. C1 [Elias, Joseph Abraham; Morgenroth, David Crespi] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Morgenroth, David Crespi] Dept Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Morgenroth, DC (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way,RCS-117, Seattle, WA 98108 USA. OI Morgenroth, David/0000-0002-0226-7775 NR 24 TC 1 Z9 1 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD FEB PY 2013 VL 92 IS 2 BP 157 EP 162 DI 10.1097/PHM.0b013e318269d7c8 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 072KA UT WOS:000313668600008 PM 23334616 ER PT J AU Ip, PPC Irving, JA McCluggage, WG Clement, PB Young, RH AF Ip, Philip P. C. Irving, Julie A. McCluggage, W. Glenn Clement, Philip B. Young, Robert H. TI Papillary Proliferation of the Endometrium A Clinicopathologic Study of 59 Cases of Simple and Complex Papillae Without Cytologic Atypia SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE papillary proliferation; papillary endometrial hyperplasia; papillary carcinoma; endometrial carcinoma; endometrial polyp; mucinous hyperplasia; Lehman and Hart ID WELL-DIFFERENTIATED CARCINOMA; K-RAS MUTATIONS; MICROSATELLITE INSTABILITY; MUCINOUS ADENOCARCINOMA; DIAGNOSTIC PITFALLS; SEROUS CARCINOMA; SYNCYTIAL CHANGE; HYPERPLASIA; PATHOLOGY; CRITERIA AB Papillary proliferation of the endometrium (PPE) without cytologic atypia is uncommon and has only been studied in detail by Lehman and Hart in 2001. On histologic examination, PPE ranges from simple papillae with fibrovascular cores, often involving the surface of endometrial polyps, to complex intracystic proliferations; some consider the latter to be analogous to nonatypical complex hyperplasia. To further characterize PPE, with emphasis on the risk of and features associated with concurrent or subsequent neoplasia, the clinicopathologic features of 59 cases without cytologic atypia were studied. The cases were classified into 2 groups according to the degree of architectural complexity and extent of proliferation. Group 1 consisted of those with localized simple papillae. Simple papillae were defined as those with short, predominantly nonbranching stalks; those with occasional secondary branches and/or detached papillae were also included in this group. Localized proliferations were those with 1 or 2 foci involving the surface or the subjacent glands of polyps or nonpolypoid endometrium. Group 2 consisted of those with complex papillae and/or those with diffuse and crowded intracystic papillae. Complex papillae were those with either short or long stalks, with frequent secondary and complex branches. Diffuse proliferation was defined as presence of 3 or more foci within a specimen or involvement of > 50% of the endometrial polyp by simple or complex PPE. Any coexistent or subsequent hyperplasia of conventional type (World Health Organization classification) or adenocarcinoma was recorded. The age of patients ranged from 23 to 82 years (median, 53 y); 36 (61%) were postmenopausal. The majority presented with abnormal vaginal bleeding. Sixteen patients (27%) were receiving hormonal preparations including 5 who were treated with a progestogen for preexisting endometrial hyperplasia or low-grade endometrioid adenocarcinoma. The histologic diagnosis of PPE was made in 49 biopsies and in 10 hysterectomy specimens. Thirty-six cases (61%) were classified as group 1 and 23 (39%) as group 2. In 47 cases (80%), there was a coexisting endometrial polyp, 39 (66%) of which were involved by the PPE. Fifty-three cases (90%) had coexisting epithelial metaplastic changes, 41 (77%) of which were involved by the PPE. The most common type of metaplasia was mucinous (41 of 59 cases, or 69%). Follow-up information was known for 46 patients (78%). Coexistent or subsequent nonatypical and atypical hyperplasia was found in 8 (17%) and 6 cases (13%), respectively. In 6 of the 46 cases (13%), a low-grade endometrioid adenocarcinoma was present either in the original specimen or during follow-up. In contrast to group 1 PPE, those with group 2 features were significantly associated with concurrent or subsequent premalignant lesions (non-atypical and atypical hyperplasia) or carcinoma (P < 0.0001). This study indicates that localized and architecturally simple PPEs confined to a completely removed polyp are usually associated with a benign outcome and may be appropriately labeled as "benign papillary proliferation of the endometrium." Lesions with architecturally complex papillae, especially when extensive, have an increased risk of concurrent or subsequent endometrial hyperplasia and carcinoma and should probably be regarded as analogous to atypical complex hyperplasia, and the term "complex papillary hyperplasia" is appropriate. As the distinction between simple and complex PPE may be difficult in small endometrial aspirational samples, consideration for curettage should be given to ascertain whether the lesion has been completely removed. C1 [Ip, Philip P. C.] Univ Hong Kong, Queen Mary Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China. [Irving, Julie A.] Royal Jubilee Hosp, Dept Pathol, Victoria, BC, Canada. [Clement, Philip B.] Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. [McCluggage, W. Glenn] Belfast Hlth & Social Care Trust, Dept Pathol, Belfast, Antrim, North Ireland. [Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Lab, Boston, MA USA. RP Ip, PPC (reprint author), Univ Hong Kong, Queen Mary Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China. EM philipip@pathology.hku.hk NR 52 TC 9 Z9 9 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD FEB PY 2013 VL 37 IS 2 BP 167 EP 177 DI 10.1097/PAS.0b013e318272d428 PG 11 WC Pathology; Surgery SC Pathology; Surgery GA 071FY UT WOS:000313576200002 PM 23211295 ER PT J AU Onozato, ML Kovach, AE Yeap, BY Morales-Oyarvide, V Klepeis, VE Tammireddy, S Heist, RS Mark, EJ Dias-Santagata, D Iafrate, AJ Yagi, Y Mino-Kenudson, M AF Onozato, Maristela L. Kovach, Alexandra E. Yeap, Beow Y. Morales-Oyarvide, Vicente Klepeis, Veronica E. Tammireddy, Swathi Heist, Rebecca S. Mark, Eugene J. Dias-Santagata, Dora Iafrate, A. John Yagi, Yukako Mino-Kenudson, Mari TI Tumor Islands in Resected Early-stage Lung Adenocarcinomas are Associated With Unique Clinicopathologic and Molecular Characteristics and Worse Prognosis SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE lung adenocarcinoma; 3D; intra-alveolar; tumor islands; prognosis ID SIGNIFICANTLY POOR-PROGNOSIS; DISTINCT PATHOLOGICAL MARKER; MICROPAPILLARY PATTERN; INTERNATIONAL-ASSOCIATION; HISTOLOGIC SUBTYPE; CANCER; CLASSIFICATION; COMPONENT; BRONCHIOLOALVEOLAR; EXPRESSION AB Tumor islands-large collections of tumor cells isolated within alveolar spaces-can be seen in lung adenocarcinomas. Recently we observed by 3-dimensional reconstruction that these structures were connected with each other and with the main tumor in different tissue planes, raising the possibility of tumor islands being a means of extension. However, the clinical and prognostic significance of tumor islands remains unknown. In this study, we compared clinicopathologic and molecular characteristics and prognosis of stages I to II lung adenocarcinomas with tumor islands (n = 58) and those without (n = 203). Lung adenocarcinomas with tumor islands were more likely to occur in smokers, exhibit higher nuclear grade and a solid or micropapillary pattern of growth, and harbor KRAS mutations. In contrast, lung adenocarcinomas without tumor islands were more likely to present as minimally invasive adenocarcinoma, show a lepidic pattern of growth, and harbor EGFR mutations. Although there was no difference in stage, the prognosis of lung adenocarcinomas with tumor islands was significantly worse than those without. The 5-year recurrence-free survival for patients with tumor islands and those without was 44.6% and 74.4%, respectively (log rank P = 0.010). The survival difference remained significant (P < 0.020) by multivariate analysis, and the presence of tumor islands was associated with almost 2-fold increase in the risk of recurrence. Even in the stage IA cohort, more than half of the patients with tumor islands experienced recurrence within 5 years. Thus, aggressive surveillance and/or further intervention may be indicated for patients whose tumors exhibit tumor islands. C1 [Onozato, Maristela L.; Kovach, Alexandra E.; Morales-Oyarvide, Vicente; Klepeis, Veronica E.; Mark, Eugene J.; Dias-Santagata, Dora; Iafrate, A. John; Yagi, Yukako; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Yeap, Beow Y.; Tammireddy, Swathi; Heist, Rebecca S.; Dias-Santagata, Dora; Iafrate, A. John; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Yeap, Beow Y.; Heist, Rebecca S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Mark, Eugene J.; Dias-Santagata, Dora; Iafrate, A. John; Yagi, Yukako; Mino-Kenudson, Mari] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Mino-Kenudson, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 122, Boston, MA 02114 USA. EM mminokenudson@partners.org FU National Cancer Institute Lung SPORE [P50-CA090578] FX B.Y. was supported by grants from the National Cancer Institute Lung SPORE P50-CA090578. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. NR 27 TC 21 Z9 22 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD FEB PY 2013 VL 37 IS 2 BP 287 EP 294 DI 10.1097/PAS.0b013e31826885fb PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 071FY UT WOS:000313576200017 PM 23095504 ER PT J AU Montecucco, F Bauer, I Braunersreuther, V Bruzzone, S Akhmedov, A Luscher, TF Speer, T Poggi, A Mannino, E Pelli, G Galan, K Bertolotto, M Lenglet, S Garuti, A Montessuit, C Lerch, R Pellieux, C Vuilleumier, N Dallegri, F Mage, J Sebastian, C Mostoslavsky, R Gayet-Ageron, A Patrone, F Mach, F Nencioni, A AF Montecucco, Fabrizio Bauer, Inga Braunersreuther, Vincent Bruzzone, Santina Akhmedov, Alexander Luescher, Thomas F. Speer, Timo Poggi, Alessandro Mannino, Elena Pelli, Graziano Galan, Katia Bertolotto, Maria Lenglet, Sebastien Garuti, Anna Montessuit, Christophe Lerch, Rene Pellieux, Corinne Vuilleumier, Nicolas Dallegri, Franco Mage, Jacqueline Sebastian, Carlos Mostoslavsky, Raul Gayet-Ageron, Angele Patrone, Franco Mach, Francois Nencioni, Alessio TI Inhibition of Nicotinamide Phosphoribosyltransferase Reduces Neutrophil-Mediated Injury in Myocardial Infarction SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID COLONY-ENHANCING FACTOR; CARDIAC MYOCYTES; OXIDATIVE STRESS; NAD; ISCHEMIA/REPERFUSION; VISFATIN; HEART; MICE; ATHEROSCLEROSIS; LYMPHOCYTES AB Aims: Nicotinamide phosphoribosyltransferase (Nampt) is a key enzyme for nicotinamide adenine dinucleotide (NAD(+)) biosynthesis, and recent evidence indicates its role in inflammatory processes. Here, we investigated the potential effects of pharmacological Nampt inhibition with FK866 in a mouse myocardial ischemia/reperfusion model. In vivo and ex vivo mouse myocardial ischemia/reperfusion procedures were performed. Results: Treatment with FK866 reduced myocardial infarct size, neutrophil infiltration, and reactive oxygen species (ROS) generation within infarcted hearts in vivo in a mouse model of ischemia and reperfusion. The benefit of FK866 was not shown in the Langendorff model (ex vivo model of working heart without circulating leukocytes), suggesting a direct involvement of these cells in cardiac injury. Sera from FK866-treated mice showed reduced circulating levels of the neutrophil chemoattractant CXCL2 and impaired capacity to prime migration of these cells in vitro. The release of CXCL8 (human homolog of murine chemokine CXCL2) by human peripheral blood mononuclear cells (PBMCs) and Jurkat cells was also reduced by FK866, as well as by sirtuin (SIRT) inhibitors and SIRT6 silencing, implying a pivotal role for this NAD(+)-dependent deacetylase in the production of this chemokine. Innovation: The pharmacological inhibition of Nampt might represent an effective approach to reduce neutrophilic inflammation-and oxidative stress-mediated tissue damage in early phases of reperfusion after a myocardial infarction. Conclusions: Nampt inhibition appears as a new strategy to dampen CXCL2-induced neutrophil recruitment and thereby reduce neutrophil-mediated tissue injury in mice. Antioxid. Redox Signal. 18, 630-641. C1 [Montecucco, Fabrizio; Braunersreuther, Vincent; Pelli, Graziano; Galan, Katia; Lenglet, Sebastien; Montessuit, Christophe; Lerch, Rene; Pellieux, Corinne; Mage, Jacqueline; Mach, Francois] Univ Hosp Geneva, Div Cardiol, Fdn Med Res, Fac Med,Dept Internal Med, CH-1211 Geneva, Switzerland. [Vuilleumier, Nicolas] Univ Hosp Geneva, Dept Genet & Lab Med, Div Lab Med, CH-1211 Geneva, Switzerland. [Gayet-Ageron, Angele] Univ Hosp Geneva, Div Clin Epidemiol, CH-1211 Geneva, Switzerland. [Bauer, Inga; Bertolotto, Maria; Garuti, Anna; Dallegri, Franco; Patrone, Franco; Nencioni, Alessio] Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy. [Bruzzone, Santina; Mannino, Elena] Univ Genoa, Biochem Sect, Dept Expt Med, Genoa, Italy. [Akhmedov, Alexander; Luescher, Thomas F.; Speer, Timo] Univ Zurich Hosp, Ctr Cardiovasc, CH-8091 Zurich, Switzerland. [Poggi, Alessandro] Natl Inst Canc Res, Unit Mol Oncol & Angiogenesis, Genoa, Italy. [Sebastian, Carlos; Mostoslavsky, Raul] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. RP Montecucco, F (reprint author), Univ Hosp Geneva, Div Cardiol, Dept Med, Fdn Med Res, 64 Ave Roseraie, CH-1211 Geneva, Switzerland. EM fabrizio.montecucco@unige.ch RI Montessuit, Christophe/B-5650-2011; LENGLET, Sebastien/N-8923-2013; Bruzzone, Santina/A-4264-2015; Poggi, Alessandro/K-6664-2016; Montecucco, Fabrizio/K-8543-2016; OI Montessuit, Christophe/0000-0002-2580-7711; LENGLET, Sebastien/0000-0002-4853-8163; Bruzzone, Santina/0000-0003-2034-3716; Poggi, Alessandro/0000-0002-1860-430X; Montecucco, Fabrizio/0000-0003-0823-8729; Gayet-Ageron, Angele/0000-0002-6164-9693; DALLEGRI, FRANCO/0000-0001-9537-4547; Speer, Thimoteus/0000-0002-2491-6393; Bertolotto, Maria Bianca/0000-0002-4889-8046 FU EU [201668]; AtheroRemo; Novartis Foundation; Swiss National Science Foundation [310030B-133127]; Montecucco [32003B-134963/1]; Associazione Italiana per la Ricerca sul Cancro; Associazione Italiana per la Lotta alle Leucemie/Linfomi e al Mieloma; University of Genoa FX This research was funded by EU FP7, Grant number 201668, AtheroRemo and by Novartis Foundation to Mach, by grants from the Swiss National Science Foundation (to Mach [# 310030B-133127] and Montecucco [# 32003B-134963/1]), by the Associazione Italiana per la Ricerca sul Cancro (to Nencioni and Bauer), by the Associazione Italiana per la Lotta alle Leucemie/Linfomi e al Mieloma, and by the University of Genoa. NR 36 TC 38 Z9 43 U1 0 U2 16 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD FEB PY 2013 VL 18 IS 6 BP 630 EP 641 DI 10.1089/ars.2011.4487 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 072LV UT WOS:000313673400004 PM 22452634 ER PT J AU Huang, YY Vecchio, D Avci, P Yin, R Garcia-Diaz, M Hamblin, MR AF Huang, Ying-Ying Vecchio, Daniela Avci, Pinar Yin, Rui Garcia-Diaz, Maria Hamblin, Michael R. TI Melanoma resistance to photodynamic therapy: new insights SO BIOLOGICAL CHEMISTRY LA English DT Review DE antitumor immune response; depigmentation; drug efflux systems; melanoma; melanosomes; photodynamic therapy; photosensitizers; resistance mechanisms ID IN-SITU PHOTOIMMUNOTHERAPY; B16 PIGMENTED MELANOMA; MALIGNANT-MELANOMA; METASTATIC MELANOMA; DRUG-RESISTANCE; CHLORIN E(6); CELL LINES; SKIN; HYPERICIN; REPAIR AB Melanoma is the most dangerous form of skin cancer, with a steeply rising incidence and a poor prognosis in its advanced stages. Melanoma is highly resistant to traditional chemotherapy and radiotherapy, although modern targeted therapies such as BRAF inhibitors are showing some promise. Photodynamic therapy (PDT, the combination of photosensitizing dyes and visible light) has been tested in the treatment of melanoma with some promising results, but melanoma is generally considered to be resistant to it. Optical interference by the highly-pigmented melanin, the antioxidant effect of melanin, the sequestration of photosensitizers inside melanosomes, defects in apoptotic pathways, and the efflux of photosensitizers by ATP-binding cassette transporters have all been implicated in melanoma resistance to PDT. Approaches to overcoming melanoma resistance to PDT include: the discovery of highly active photosensitizers absorbing in the 700-800-nm near infrared spectral region; interventions that can temporarily reduce the amount or pigmentation of the melanin; compounds that can reverse apoptotic defects or inhibit drug-efflux of photosensitizers; and immunotherapy approaches that can take advantage of the ability of PDT to activate the host immune system against the tumor being treated. C1 [Huang, Ying-Ying; Vecchio, Daniela; Avci, Pinar; Yin, Rui; Garcia-Diaz, Maria; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Huang, Ying-Ying; Vecchio, Daniela; Yin, Rui; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Huang, Ying-Ying] Guangxi Med Univ, Dept Pathol, Nanning, Guangxi, Peoples R China. [Yin, Rui] Third Mil Med Univ, Southwest Hosp, Dept Dermatol, Chongqing, Peoples R China. [Garcia-Diaz, Maria] Ramon Llull Univ, IQS Sch Engn, Mol Engn Grp, Barcelona, Spain. [Garcia-Diaz, Maria] Univ Barcelona, Dept Biochem & Mol Biol, Barcelona, Spain. [Hamblin, Michael R.] Harvard MIT, Div Hlth Sci & Technol, Cambridge, MA USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Huang, Ying-ying/G-3153-2011; Garcia-Diaz, Maria/J-9202-2014; OI Huang, Ying-ying/0000-0003-3066-6981; Garcia-Diaz, Maria/0000-0002-4794-5437; Hamblin, Michael/0000-0001-6431-4605 FU US National Institutes of Health [R01AI050875]; Fondazione MPS, Italy; National Natural Science Foundation of China [81172495]; Comissionat per a Universitats i Recerca del Departament d'Innovacio, Universitats i Empresa de la Generalitat de Catalunya i del Fons Social Europeu FX This work was supported by the US National Institutes of Health (R01AI050875). D. V. was supported by Fondazione MPS, Italy. R. Y. was supported by National Natural Science Foundation of China (Grant No: 81172495), M. G.-D. was supported by a predoctoral fellowship from the Comissionat per a Universitats i Recerca del Departament d'Innovacio, Universitats i Empresa de la Generalitat de Catalunya i del Fons Social Europeu. NR 56 TC 20 Z9 21 U1 4 U2 70 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1431-6730 J9 BIOL CHEM JI Biol. Chem. PD FEB PY 2013 VL 394 IS 2 BP 239 EP 250 DI 10.1515/hsz-2012-0228 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 070PR UT WOS:000313522800008 PM 23152406 ER PT J AU Seton, M Jupner, H AF Seton, Margaret Juepner, Harald TI Autosomal dominant hypophosphatemic rickets in an 85 year old woman: Characterization of her disease from infancy through adulthood SO BONE LA English DT Article DE Autosomal dominant hypophosphatemic rickets; Osteomalacia; Fibroblast growth factor 23 (FGF23); Renal phosphate wasting; Metabolic bone disease ID PROTEOLYTIC CLEAVAGE; GENE-EXPRESSION; IRON-DEFICIENCY; NPT2A GENE; IN-VIVO; PHOSPHATE; FGF23; FIBROBLAST-GROWTH-FACTOR-23; MUTATIONS; RESISTANT AB Background: Autosomal dominant hypophosphatemic rickets (ADHR) is a rare genetic disorder of phosphate homeostasis characterized, when severely expressed, by osteomalacia, suppressed levels of calcitriol, and renal phosphate wasting due to elevated levels of fibroblast growth factor 23 (FGF23). The disease is caused by heterozygous FGF23 mutations at the RXXR site that prevent cleavage of the intact hormone. Objectives: An FGF23 mutation was identified in the proband an 85-year-old woman with elevated FGF23 levels, and her clinical course was characterized. Medical records revealed she was treated for rickets as an infant. She was then asymptomatic until soon after her 4th pregnancy, when she suffered incapacitating bone pain and weakness, age 37. Symptoms remitted with brief treatment. Results: The proband and one son, but not other family members, were found to be heterozygous for the R176Q mutation in FGF23. Expression of this germ line mutation was strikingly different in both individuals in terms of skeletal health, FGF23 levels and disease activity. Conclusions: The identified FGF23 mutation in two members of this family raises questions about molecular mechanisms that have led to intermittent increases in FGF23 synthesis and secretion, and disease expression. (C) 2012 Elsevier Inc. All rights reserved. C1 [Seton, Margaret] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Juepner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Seton, M (reprint author), Massachusetts Gen Hosp, Bulfinch 165,55 Fruit St, Boston, MA 02114 USA. EM mseton@partners.org; jueppner@helix.mgh.harvard.edu FU NIDDK NIH HHS [R01 DK046718] NR 26 TC 3 Z9 3 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD FEB PY 2013 VL 52 IS 2 BP 640 EP 643 DI 10.1016/j.bone.2012.11.012 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 071PW UT WOS:000313607700014 PM 23174215 ER PT J AU Ciaranello, AL Perez, F Engelsmann, B Walensky, RP Mushavi, A Rusibamayila, A Keatinge, J Park, JE Maruva, M Cerda, R Wood, R Dabis, F Freedberg, KA AF Ciaranello, Andrea L. Perez, Freddy Engelsmann, Barbara Walensky, Rochelle P. Mushavi, Angela Rusibamayila, Asinath Keatinge, Jo Park, Ji-Eun Maruva, Matthews Cerda, Rodrigo Wood, Robin Dabis, Francois Freedberg, Kenneth A. TI Cost-effectiveness of World Health Organization 2010 Guidelines for Prevention of Mother-to-Child HIV Transmission in Zimbabwe SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE HIV; mother-to-child transmission; PMTCT; pediatric HIV; cost-effectiveness ID SINGLE-DOSE NEVIRAPINE; ANTIRETROVIRAL THERAPY PROGRAMS; SUB-SAHARAN AFRICA; SOUTH-AFRICA; RANDOMIZED-TRIAL; INFECTED CHILDREN; POOLED ANALYSIS; PREGNANT-WOMEN; FOLLOW-UP; POSTPARTUM WOMEN AB Background. In 2010, the World Health Organization (WHO) released revised guidelines for prevention of mother-to-child human immunodeficiency virus (HIV) transmission (PMTCT). We projected clinical impacts, costs, and cost-effectiveness of WHO-recommended PMTCT strategies in Zimbabwe. Methods. We used Zimbabwean data in a validated computer model to simulate a cohort of pregnant, HIV-infected women (mean age, 24 years; mean CD4 count, 451 cells/mu L; subsequent 18 months of breastfeeding). We simulated guideline-concordant care for 4 PMTCT regimens: single-dose nevirapine (sdNVP); WHO-recommended Option A, WHO-recommended Option B, and Option B+ (lifelong maternal 3-drug antiretroviral therapy regardless of CD4). Outcomes included maternal and infant life expectancy (LE) and lifetime healthcare costs (2008 US dollars [USD]). Incremental cost-effectiveness ratios (ICERs, in USD per year of life saved [YLS]) were calculated from combined (maternal + infant) discounted costs and LE. Results. Replacing sdNVP with Option A increased combined maternal and infant LE from 36.97 to 37.89 years and would reduce lifetime costs from $5760 to $5710 per mother-infant pair. Compared with Option A, Option B further improved LE (38.32 years), and saved money within 4 years after delivery ($ 5630 per mother-infant pair). Option B+ (LE, 39.04 years; lifetime cost, $ 6620 per mother-infant pair) improved maternal and infant health, with an ICER of $ 1370 per YLS compared with Option B. Conclusions. Replacing sdNVP with Option A or Option B will improve maternal and infant outcomes and save money; Option B increases health benefits and decreases costs compared with Option A. Option B+ further improves maternal outcomes, with an ICER (compared with Option B) similar to many current HIV-related healthcare interventions. C1 [Ciaranello, Andrea L.; Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Walensky, Rochelle P.; Rusibamayila, Asinath; Park, Ji-Eun; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Cerda, Rodrigo] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Walensky, Rochelle P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. [Perez, Freddy; Dabis, Francois] Univ Bordeaux, Inst Sante Publ Epidemiol & Dev, Bordeaux, France. [Perez, Freddy; Dabis, Francois] Ctr INSERM, Epidemiol Biostat U897, Bordeaux, France. [Perez, Freddy] Pan Amer Hlth Org, HIV AIDS Unit, Washington, DC USA. [Engelsmann, Barbara] Org Publ Hlth Intervent & Dev, Harare, Zimbabwe. [Mushavi, Angela] Minist Hlth & Child Welf, Harare, Zimbabwe. [Keatinge, Jo; Maruva, Matthews] US Agcy Int Dev, Harare, Zimbabwe. [Wood, Robin] Univ Cape Town, Inst Infect Dis & Mol Med, Desmond Tutu HIV Ctr, ZA-7700 Rondebosch, South Africa. RP Ciaranello, AL (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Med Practice Evaluat Ctr, 50 Staniford St,9th Fl, Boston, MA 02114 USA. EM aciaranello@partners.org RI 杜, 美晨/S-4063-2016; OI 杜, 美晨/0000-0002-1562-1155; Walensky, Rochelle P./0000-0002-8795-379X FU Elizabeth Glaser Pediatric AIDS Foundation; National Institute of Allergy and Infectious Diseases; National Institute of Child Health and Human Development, National Institutes of Health [K01 AI078754, K24 AI062476, R01 AI058736]; Harvard University Center for AIDS Research FX This work was supported by the Elizabeth Glaser Pediatric AIDS Foundation; the National Institute of Allergy and Infectious Diseases and the National Institute of Child Health and Human Development, National Institutes of Health (K01 AI078754 to A. L. C.; K24 AI062476 to K. A. F.; R01 AI058736 to R. P. W., A. R., J.-E. P., K. A. F; IMPAACT network to R. P. W., J.-E. P., K. A. F.); and Harvard University Center for AIDS Research (to K. A. F., R. P. W.). The funders had no role in study design, interpretation of results, or decision to publish. NR 99 TC 29 Z9 29 U1 3 U2 26 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 FEB 1 PY 2013 VL 56 IS 3 BP 430 EP 446 DI 10.1093/cid/cis858 PG 17 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 071TM UT WOS:000313617400025 PM 23204035 ER PT J AU Thoonen, R Sips, PY Bloch, KD Buys, ES AF Thoonen, Robrecht Sips, Patrick Y. Bloch, Kenneth D. Buys, Emmanuel S. TI Pathophysiology of Hypertension in the Absence of Nitric Oxide/Cyclic GMP Signaling SO CURRENT HYPERTENSION REPORTS LA English DT Article DE Cyclic guanosine monophosphate; Blood pressure; Hypertension; Cardiovascular function; Soluble guanylate cyclase; Nitric oxide; Mutant mice; Genetic variants; Renin-angiotensin-aldosterone signaling; Gender; S-nitrosylation; Therapeutics ID SOLUBLE GUANYLATE-CYCLASE; DEPENDENT PROTEIN-KINASE; VASCULAR SMOOTH-MUSCLE; ENDOTHELIAL NO SYNTHASE; CARDIOMYOCYTE-SPECIFIC OVEREXPRESSION; SYSTEMIC VASODILATOR RESPONSES; S-NITROSOGLUTATHIONE REDUCTASE; GENOME-WIDE ASSOCIATION; CINACIGUAT BAY 58-2667; DOUBLE-KNOCKOUT MICE AB The nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling system is a well-characterized modulator of cardiovascular function, in general, and blood pressure, in particular. The availability of mice mutant for key enzymes in the NO-cGMP signaling system facilitated the identification of interactions with other blood pressure modifying pathways (e.g. the renin-angiotensin-aldosterone system) and of gender-specific effects of impaired NO-cGMP signaling. In addition, recent genome-wide association studies identified blood pressure-modifying genetic variants in genes that modulate NO and cGMP levels. Together, these findings have advanced our understanding of how NO-cGMP signaling regulates blood pressure. In this review, we will summarize the results obtained in mice with disrupted NO-cGMP signaling and highlight the relevance of this pathway as a potential therapeutic target for the treatment of hypertension. C1 [Thoonen, Robrecht] Tufts Med Ctr, Mol Cardiol Res Inst, Mol Cardiol Res Ctr, Boston, MA 02111 USA. [Sips, Patrick Y.] Harvard Univ, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, Massachusetts Gen Hosp,Med Sch, Charlestown, MA 02129 USA. [Bloch, Kenneth D.; Buys, Emmanuel S.] Harvard Univ, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. RP Buys, ES (reprint author), Harvard Univ, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, Massachusetts Gen Hosp,Med Sch, 55 Fruit St,Thier 511B, Boston, MA 02114 USA. EM rthoonen@tuftsmedicalcenter.org; psips@partners.org; kdbloch@partners.org; ebuys@partners.org OI Sips, Patrick/0000-0001-9241-5980 FU NEI NIH HHS [R01 EY022746, R21 EY020987] NR 145 TC 14 Z9 15 U1 1 U2 14 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 FEB PY 2013 VL 15 IS 1 BP 47 EP 58 DI 10.1007/s11906-012-0320-5 PG 12 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 070OE UT WOS:000313518100008 PM 23233080 ER PT J AU Bowden, MG Woodbury, ML Duncan, PW AF Bowden, Mark G. Woodbury, Michelle L. Duncan, Pamela W. TI Promoting neuroplasticity and recovery after stroke: future directions for rehabilitation clinical trials SO CURRENT OPINION IN NEUROLOGY LA English DT Review DE neuroplasticity; recovery; rehabilitation; stroke ID DIRECT-CURRENT STIMULATION; CONSTRAINT-INDUCED MOVEMENT; RANDOMIZED CONTROLLED-TRIAL; NONINVASIVE CORTICAL STIMULATION; ADULT SQUIRREL-MONKEYS; MOTOR CORTEX; NEURAL PLASTICITY; AMBULATORY FUNCTION; DC-STIMULATION; BRAIN-INJURY AB Purpose of review The purpose is to establish a theoretical framework by which new interventions for poststroke rehabilitation may be developed incorporating knowledge of neuroplasticity and the critical ingredients of rehabilitation. Recent findings Large phase III randomized controlled trials (RCTs) are rare in neurorehabilitation, and the results of those that have been completed are perplexing because the experimental and control treatments were not different when matched for activity level. In addition, the outcome measures used to define treatment effects reflected behavioral endpoints, but did not reveal how neuroplastic mechanisms or other mechanistic factors may have contributed to the treatment response. Knowledge of both the neurophysiologic basis of recovery and key elements of interventions that drive motor learning, such as intensity and task progression, are critical for optimizing future poststroke motor rehabilitation clinical trials. Summary Future neurorehabilitation RCTs require a better understanding of the interaction of interventions and neurophysiological recovery in order to target interventions at specific neurophysiologic substrates, develop a more clear understanding of the impact of intervention parameters (e.g. dose, intensity), and advance discussions regarding optimal ways to partner medical and rehabilitation interventions in order to improve outcomes. C1 [Bowden, Mark G.; Woodbury, Michelle L.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. [Bowden, Mark G.; Woodbury, Michelle L.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Bowden, Mark G.] Med Univ S Carolina, Div Phys Therapy, Charleston, SC 29425 USA. [Woodbury, Michelle L.] Med Univ S Carolina, Div Occupat Therapy, Charleston, SC 29425 USA. [Duncan, Pamela W.] Wake Forest Baptist Med Ctr, Dept Neurol, Winston Salem, NC USA. RP Bowden, MG (reprint author), Med Univ S Carolina, Ralph H Johnson VA Med Ctr, 77 President St,MSC 700, Charleston, SC 29425 USA. EM bowdenm@musc.edu FU Ralph H. Johnson Veterans Affairs Medical Center; Department of Veterans Affairs Office of Research and Development [B-7177M, B-6332W]; South Carolina Clinical and Translational Research Institute Discovery Grant; American Heart Association Innovative Research Grant FX This work was supported in part by the Ralph H. Johnson Veterans Affairs Medical Center and the Department of Veterans Affairs Office of Research and Development, Rehabilitation Research and Development; Career Development-1 Award (B-7177M), PI: M. G. Bowden; Career Development-2 Award (B-6332W), PI: M.L. Woodbury.; None of the authors has a conflict of interest with this manuscript. Dr Duncan has been involved with private industry, notably she has received honorarium for consulting with Allergan to develop a post stroke disability measures and with Glaxo to design phase 2 trials to enhance stroke recovery. The authors are supported by the following grants: South Carolina Clinical and Translational Research Institute Discovery Grant; American Heart Association Innovative Research Grant. NR 57 TC 20 Z9 22 U1 1 U2 51 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD FEB PY 2013 VL 26 IS 1 BP 37 EP 42 DI 10.1097/WCO.0b013e32835c5ba0 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 070XI UT WOS:000313547000005 PM 23254556 ER PT J AU Rodriguez-Galindo, C Friedrich, P Morrissey, L Frazier, L AF Rodriguez-Galindo, Carlos Friedrich, Paola Morrissey, Lisa Frazier, Lindsay TI Global challenges in pediatric oncology SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE global health; low-income and middle-income countries; pediatric cancer ID ACUTE LYMPHOBLASTIC-LEUKEMIA; LOW-INCOME COUNTRIES; TREATMENT-RELATED MORTALITY; PALLIATIVE-CARE SERVICES; CHILDHOOD-CANCER; CENTRAL-AMERICA; BURKITT-LYMPHOMA; NURSING-EDUCATION; WILMS-TUMOR; EL SALVADOR AB Purpose of review Reduction of child mortality is one of the Millennium Development Goals; as low-income and middle-income countries (LMICs) advance toward the achievement of this goal, initiatives aimed at reducing the burden of noncommunicable diseases, including childhood cancer, need to be developed. Recent findings Approximately 200 000 children and adolescents are diagnosed with cancer every year worldwide; of those, 80% live in LMICs, which account for 90% of the deaths. Lack of quality population-based cancer registries in LMICs limits our knowledge of the epidemiology of pediatric cancer; however, available information showing variations in incidence may indicate unique interactions between environmental and genetic factors that could provide clues to cause. Outcome of children with cancer in LMICs is dictated by late presentation and underdiagnosis, high abandonment rates, high prevalence of malnutrition and other comorbidities, suboptimal supportive and palliative care, and limited access to curative therapies. Initiatives integrating program building with education of healthcare providers and research have proven to be successful in the development of regional capacity. Intensity-graduated treatments adjusted to the local capacity have been developed. Summary Childhood cancer burden is shifted toward LMICs; global initiatives directed at pediatric cancer care and control are urgently needed. International partnerships facilitating stepwise processes that build capacity while incorporating epidemiology and health services research and implementing intensity-graduated treatments have been shown to be effective. C1 [Rodriguez-Galindo, Carlos; Friedrich, Paola; Morrissey, Lisa; Frazier, Lindsay] Harvard Univ, Sch Med, Div Hematol Oncol, Dana Farber Childrens Hosp Canc Ctr, Boston, MA USA. [Rodriguez-Galindo, Carlos; Friedrich, Paola; Frazier, Lindsay] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Rodriguez-Galindo, C (reprint author), Dana Farber Canc Inst, 450 Brookline Ave SW350, Boston, MA 02215 USA. EM carlos_rodriguez-galindo@dfci.harvard.edu OI Friedrich, Paola/0000-0002-5265-3113 NR 82 TC 29 Z9 34 U1 2 U2 36 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 EI 1531-698X J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD FEB PY 2013 VL 25 IS 1 BP 3 EP 15 DI 10.1097/MOP.0b013e32835c1cbe PG 13 WC Pediatrics SC Pediatrics GA 069DC UT WOS:000313414400002 PM 23295716 ER PT J AU Van Eeghen, AM Pulsifer, MB Merker, VL Neumeyer, AM Van Eeghen, EE Thibert, RL Cole, AJ Leigh, FA Plotkin, SR Thiele, EA AF Van Eeghen, Agnies M. Pulsifer, Margaret B. Merker, Vanessa L. Neumeyer, Ann M. Van Eeghen, Elmer E. Thibert, Ronald L. Cole, Andrew J. Leigh, Fawn A. Plotkin, Scott R. Thiele, Elizabeth A. TI Understanding relationships between autism, intelligence, and epilepsy: a cross-disorder approach SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; PERVASIVE DEVELOPMENTAL DISORDERS; INFANTILE SPASMS; DOWN-SYNDROME; FRAGILE-X; CHILDREN; SPECTRUM; INDIVIDUALS; DEFINITION; MUTATIONS AB Aim As relationships between autistic traits, epilepsy, and cognitive functioning remain poorly understood, these associations were explored in the biologically related disorders tuberous sclerosis complex (TSC), neurofibromatosis type 1 (NF1), and epilepsy. Method The Social Responsiveness Scale (SRS), a quantitative measure of autistic traits, was distributed to caregivers or companions of patients with TSC, NF1, and childhood-onset epilepsy of unknown cause (EUC), and these results were compared with SRS data from individuals with idiopathic autism spectrum disorders (ASDs) and their unaffected siblings. Scores and trait profiles of autistic features were compared with cognitive outcomes, epilepsy variables, and genotype. Results A total of 180 SRS questionnaires were completed in the TSC, NF1, and EUC outpatient clinics at the Massachusetts General Hospital (90 females, 90 males; mean age 21y, range 463y), and SRS data from 210 patients with ASD recruited from an autism research collaboration (167 males, 43 females; mean age 9y, range 422y) and 130 unaffected siblings were available. Regression models showed a significant association between SRS scores and intelligence outcomes (p<0.001) and various seizure variables (p<0.02), but not with a specific underlying disorder or genotype. The level of autistic features was strongly associated with intelligence outcomes in patients with TSC and epilepsy (p<0.01); in patients with NF1 these relationships were weaker (p=0.25). For all study groups, autistic trait subdomains covaried with neurocognitive comorbidity, with endophenotypes similar to that of idiopathic autism. Interpretation Our data show that in TSC and childhood-onset epilepsy, the severity and phenotype of autistic features are inextricably linked with intelligence and epilepsy outcomes. Such relationships were weaker for individuals with NF1. Findings suggest that ASDs are not specific in these conditions. C1 [Van Eeghen, Agnies M.; Van Eeghen, Elmer E.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Carol & James Herscot Ctr Tuberous Sclerosis Comp, Boston, MA 02114 USA. [Van Eeghen, Agnies M.] Erasmus MC, Expertise Ctr Neurodev Disorders, ENCORE, Dept Neurosci, Rotterdam, Netherlands. [Pulsifer, Margaret B.] Massachusetts Gen Hosp, Dept Psychiat, Psychol Assessment Ctr, Boston, MA 02114 USA. [Merker, Vanessa L.; Leigh, Fawn A.; Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Neumeyer, Ann M.] Massachusetts Gen Hosp, Dept Neurol, Lurie Ctr Autism, Boston, MA 02114 USA. [Thibert, Ronald L.] Massachusetts Gen Hosp, Dept Neurol, Pediat Epilepsy Serv, Boston, MA 02114 USA. [Cole, Andrew J.] Massachusetts Gen Hosp, Dept Neurol, Epilepsy Serv, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Carol & James Herscot Ctr Tuberous Sclerosis, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM ethiele@partners.org OI Merker, Vanessa/0000-0002-4542-5227 FU Herscot Center for Tuberous Sclerosis Complex; NIH/NINDS [P01 NS024279] FX We are grateful to the families and individuals who agreed to participate in this study and the Autism Consortium for their valuable time and effort. We are grateful to the Autism Consortium for access to the data analyzed here, and for the support from Christine Ferrone and Roksana Sasanfar for assisting with the Autism Consortium data collection. We thank Zaida Ortega, Christina Anagnos, Jill Beamon, and Joseph Nimon for assisting with distribution and scoring of the questionnaires. Lastly, we are grateful to the MGH Department of Biostatistics for assistance with statistical analysis. This study was sponsored by the Herscot Center for Tuberous Sclerosis Complex, and NIH/NINDS P01 NS024279. NR 46 TC 31 Z9 31 U1 1 U2 37 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0012-1622 J9 DEV MED CHILD NEUROL JI Dev. Med. Child Neurol. PD FEB PY 2013 VL 55 IS 2 BP 146 EP 153 DI 10.1111/dmcn.12044 PG 8 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 073FT UT WOS:000313729600013 PM 23205844 ER PT J AU Saylor, PJ Armstrong, AJ Fizazi, K Freedland, S Saad, F Smith, MR Tombal, B Pienta, K AF Saylor, Philip J. Armstrong, Andrew J. Fizazi, Karim Freedland, Stephen Saad, Fred Smith, Matthew R. Tombal, Bertrand Pienta, Kenneth TI New and Emerging Therapies for Bone Metastases in Genitourinary Cancers SO EUROPEAN UROLOGY LA English DT Review DE Prostate cancer; Bladder cancer; Urothelial cancer; Bone metastases; Zoledronic acid; Denosumab; Radium-223 ID RESISTANT PROSTATE-CANCER; RENAL-CELL CARCINOMA; PLACEBO-CONTROLLED TRIAL; ORAL SODIUM CLODRONATE; PHASE-II TRIAL; ZOLEDRONIC ACID; DOUBLE-BLIND; SKELETAL COMPLICATIONS; OSTEOCLAST DIFFERENTIATION; BREAST-CANCER AB Context: Bone metastases are a common feature of advanced genitourinary malignancies and a prominent cause of morbidity and mortality. Objective: The objective of this review is to discuss the incidence, pathophysiology, and management of bone metastases in the most prevalent genitourinary malignancies. Evidence acquisition: We reviewed the relevant medical literature, with a particular emphasis on prospective randomized controlled trials. Much of the relevant clinical trial data focus on prostate cancer (PCa). We provide a nonsystematic review and our perspective on the available data. Evidence synthesis: Clinical manifestations can include pain, hypercalcemia, pathologic fractures, and spinal cord compression. Optimal systemic therapy for skeletal metastases often features a combination of disease-specific therapy and bone-targeted therapy. Some agents, such as the radiopharmaceutical radium-223, blur the line between those categories. Osteoclast inhibition is a validated strategy in the management of selected patients with bone metastases. Zoledronic acid, a bisphosphonate, is approved for the prevention of skeletal events caused by solid tumors metastatic to bone. Denosumab is a fully human monoclonal antibody that inactivates receptor activator of nuclear factor-kappa B ligand and is approved for the same indication. Beta-emitting radiopharmaceuticals can be effective for the palliation of pain caused by bone metastases, but their use is often limited by marrow suppression. The alpha-emitting radiopharmaceutical radium-223 has recently been shown to improve overall survival and prevent skeletal events in select men with castration-resistant PCa metastatic to bone. Multiple ongoing clinical trials are designed to examine the potential for therapeutic inhibition of additional targets such as Src and hepatocyte growth factor (MET). Conclusions: Bone metastases cause considerable morbidity and mortality among patients with genitourinary malignancies. Optimal management requires consideration of bone-targeted therapy as well as disease-specific therapy. Further research is needed to optimize the use of existing agents and to define the therapeutic potential of novel targets. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved. C1 [Saylor, Philip J.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA. [Armstrong, Andrew J.] Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC USA. [Armstrong, Andrew J.] Duke Univ, Med Ctr, Duke Prostate Ctr, Durham, NC USA. [Fizazi, Karim] Inst Gustave Roussy, Dept Canc Med, Villejuif, France. [Freedland, Stephen] VA Med Ctr, Dept Surg, Durham, NC USA. [Freedland, Stephen] Duke Univ, Dept Surg & Pathol, Div Urol Surg, Durham, NC USA. [Saad, Fred] Ctr Hosp Univ Montreal, Montreal, PQ, Canada. [Tombal, Bertrand] Catholic Univ Louvain, Clin Univ St Luc, Serv Urol, B-1200 Brussels, Belgium. [Pienta, Kenneth] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. RP Saylor, PJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, 55 Fruit St,Yawkey 7E, Boston, MA 02114 USA. EM psaylor@partners.org RI Pienta, Kenneth/E-7679-2015 OI TOMBAL, Bertrand/0000-0002-0093-8408; Pienta, Kenneth/0000-0002-4138-2186 FU Novartis; Prostate Cancer Foundation; US National Institutes of Health [5K24CA121990-02] FX Philip J. Saylor certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Dr Armstrong is a speaker for and on the advisory board of Amgen and has received research support from Novartis. Dr Fizazi participates on the advisory boards of or is a speaker for Amgen, Novartis, Exelixis, and Bayer. Dr Freedland is a speaker and consultant for Amgen and Janssen. Dr Saad is a consultant and researcher for Amgen and Novartis. Dr Saylor is supported by a Young Investigator Award from the Prostate Cancer Foundation. Dr Smith is supported by a US National Institutes of Health K24 Midcareer Investigator Award (5K24CA121990-02) and awards from the Prostate Cancer Foundation and is a consultant for Amgen and Bayer. Dr Tombal is an advisor and consultant to Amgen. NR 81 TC 24 Z9 25 U1 1 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD FEB PY 2013 VL 63 IS 2 BP 309 EP 320 DI 10.1016/j.eururo.2012.10.007 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 071FE UT WOS:000313572100026 PM 23201471 ER PT J AU Saini, N Mahindra, A AF Saini, Neeraj Mahindra, Anuj TI Novel immunomodulatory compounds in multiple myeloma SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE IMiDs; lenalidomide; multiple myeloma; pomalidomide ID STEM-CELL TRANSPLANTATION; LENALIDOMIDE PLUS DEXAMETHASONE; PHASE-II TRIALS; NF-KAPPA-B; COMBINATION THERAPY; MULTICENTER PHASE-2; INDUCTION THERAPY; DRUG-RESISTANCE; THALIDOMIDE; MOBILIZATION AB Introduction: The treatment options for patients with multiple myeloma (MM) remain limited. Immunomodulatory agents (IMiDs), such as thalidomide and lenalidomide, have changed the landscape in the treatment of patients with MM while newer IMiDs such as pomalidomide are showing promise in early clinical trials. Areas covered: This review focuses on the biologic rationales of IMiDs and the clinical results supporting their use in MM. It includes data on the new IMiD, pomalidomide and also explores the possible utility of combining IMiDs with other agents. A PubMed search and abstracts from oncology scientific meetings (ASCO and ASH) of articles related to IMiDs and MM was conducted. Expert opinion: IMiDs have shown clinical activity as single agents and in combination. Thalidomide was the first in class drug. Lenalidomide has a better toxicity profile than thalidomide. Pomalidomide may overcome resistance to lenalidomide indicating differences in their mechanisms of action and resistance. Molecular biomarkers may allow us to identify patients who will respond to IMiDs. C1 [Saini, Neeraj] N Shore Med Ctr, Boston, MA USA. [Mahindra, Anuj] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mahindra, A (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM amahindra@partners.org OI saini, Neeraj/0000-0001-7435-0933 NR 56 TC 5 Z9 5 U1 0 U2 8 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD FEB PY 2013 VL 22 IS 2 BP 207 EP 215 DI 10.1517/13543784.2013.749235 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 071KR UT WOS:000313592000004 PM 23265189 ER PT J AU Thakurathi, N Vincenzi, B Henderson, DC AF Thakurathi, Neelam Vincenzi, Brenda Henderson, David C. TI Assessing the prospect of donepezil in improving cognitive impairment in patients with schizophrenia SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Editorial Material DE acetylcholinesterase inhibitor; atypical antipsychotics; cognitive impairments; donepezil; schizophrenia ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; ADJUNCTIVE TREATMENT; FUNCTIONAL CONSEQUENCES; NEUROCOGNITIVE DEFICITS; STABLE SCHIZOPHRENIA; WORKING-MEMORY; GALANTAMINE; RISPERIDONE; NICOTINE AB Introduction: Even though cognitive impairment is manifested in almost all patients with schizophrenia, the Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE) study showed no significant difference between first- and second-generation psychotropic drugs in improving cognitive abilities. Discovering new drugs that can improve impaired cognition, thus, is an attractive treatment target for patients with schizophrenia. Areas covered: This article briefly reviews about donepezil, a highly selective (IC50 = 6.7 nM) centrally acting reversible acetylcholinesterase inhibitor that has been approved by FDA for treating cognitive deficit states such as in Alzheimer's disease and its uses in clinical trials for the treatment of schizophrenia. The literature search included PubMed and Cochrane library with the following words: donepezil, schizophrenia and cognitive impairments. Expert opinion: The results of several clinical trials utilizing donepezil as an adjunct to second-generation antipsychotic drugs targeting cognitive deficits in schizophrenia subjects have been disappointing and would not lead clinicians to consider this as a potential treatment option. While longer randomized controlled trials, increase dosage and selected groups of patients at different stage of cognitive impairment may provide a better understanding of the potential for this drug in addressing cognitive deficits, results to date have not been encouraging. C1 [Thakurathi, Neelam; Vincenzi, Brenda; Henderson, David C.] Massachusetts Gen Hosp, Schizophrenia Clin & Res Program, Boston, MA 02114 USA. [Henderson, David C.] Harvard Univ, Sch Med, Freedom Trail Clin, Boston, MA 02114 USA. RP Henderson, DC (reprint author), Massachusetts Gen Hosp, Schizophrenia Clin & Res Program, Boston, MA 02114 USA. EM dchenderson@partners.org NR 47 TC 6 Z9 6 U1 0 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD FEB PY 2013 VL 22 IS 2 BP 259 EP 265 DI 10.1517/13543784.2013.750650 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 071KR UT WOS:000313592000008 PM 23215841 ER PT J AU Chen, H Meigs, JB Dupuis, J AF Chen, Han Meigs, James B. Dupuis, Josee TI Sequence Kernel Association Test for Quantitative Traits in Family Samples SO GENETIC EPIDEMIOLOGY LA English DT Article DE rare variant analysis; quantitative traits; family samples; heritability; linear mixed effects model ID HAPLOTYPE RELATIVE RISK; COMMON DISEASES; RARE VARIANTS; MODELS AB A large number of rare genetic variants have been discovered with the development in sequencing technology and the lowering of sequencing costs. Rare variant analysis may help identify novel genes associated with diseases and quantitative traits, adding to our knowledge of explaining heritability of these phenotypes. Many statistical methods for rare variant analysis have been developed in recent years, but some of them require the strong assumption that all rare variants in the analysis share the same direction of effect, and others requiring permutation to calculate the P-values are computer intensive. Among these methods, the sequence kernel association test (SKAT) is a powerful method under many different scenarios. It does not require any assumption on the directionality of effects, and statistical significance is computed analytically. In this paper, we extend SKAT to be applicable to family data. The family-based SKAT (famSKAT) has a different test statistic and null distribution compared to SKAT, but is equivalent to SKAT when there is no familial correlation. Our simulation studies show that SKAT has inflated type I error if familial correlation is inappropriately ignored, but has appropriate type I error if applied to a single individual per family to obtain an unrelated subset. In contrast, famSKAT has the correct type I error when analyzing correlated observations, and it has higher power than competing methods in many different scenarios. We illustrate our approach to analyze the association of rare genetic variants using glycemic traits from the Framingham Heart Study. C1 [Chen, Han; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA. RP Chen, H (reprint author), 801 Massachusetts Ave,3rd Floor, Boston, MA 02118 USA. EM hanchen@bu.edu OI Dupuis, Josee/0000-0003-2871-3603; Chen, Han/0000-0002-9510-4923 FU NIH [R01 DK078616, U01 DK85526, K24 DK080140]; National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-25195]; Affymetrix, Inc. [N02-HL-6-4278]; Boston University [N01-HC-25195] FX Contract grant sponsor: NIH; Contract grant numbers: R01 DK078616; U01 DK85526; K24 DK080140; Contract grant sponsor: National Heart, Lung, and Blood Institute (NHLBI); Contract grant number: N01-HC-25195; Contract grant sponsor: Affymetrix, Inc.; Contract grant number: N02-HL-6-4278.; The authors thank Dr. Thomas Lumley for his insights into Kuonen's saddlepoint method. This research was partially supported by NIH awards R01 DK078616, U01 DK85526, and K24 DK080140. A portion of this research was conducted using the Linux Clusters for Genetic Analysis (LinGA) computing resources at Boston University Medicine Campus. The Framingham Heart Study is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University (Contract No. N01-HC-25195). This work was partially supported by a contract with Affymetrix, Inc. for genotyping services (Contract No. N02-HL-6-4278). NR 22 TC 72 Z9 74 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD FEB PY 2013 VL 37 IS 2 BP 196 EP 204 DI 10.1002/gepi.21703 PG 9 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 074AK UT WOS:000313784000008 PM 23280576 ER PT J AU Minelli, C De Grandi, A Weichenberger, CX Gogele, M Modenese, M Attia, J Barrett, JH Boehnke, M Borsani, G Casari, G Fox, CS Freina, T Hicks, AA Marroni, F Parmigiani, G Pastore, A Pattaro, C Pfeufer, A Ruggeri, F Schwienbacher, C Taliun, D Pramstaller, PP Domingues, FS Thompson, JR AF Minelli, Cosetta De Grandi, Alessandro Weichenberger, Christian X. Goegele, Martin Modenese, Mirko Attia, John Barrett, Jennifer H. Boehnke, Michael Borsani, Giuseppe Casari, Giorgio Fox, Caroline S. Freina, Thomas Hicks, Andrew A. Marroni, Fabio Parmigiani, Giovanni Pastore, Andrea Pattaro, Cristian Pfeufer, Arne Ruggeri, Fabrizio Schwienbacher, Christine Taliun, Daniel Pramstaller, Peter P. Domingues, Francisco S. Thompson, John R. TI Importance of Different Types of Prior Knowledge in Selecting Genome-Wide Findings for Follow-Up SO GENETIC EPIDEMIOLOGY LA English DT Article DE gene prioritization; genome-wide association studies; bioinformatics databases ID SCALE ASSOCIATION ANALYSIS; SUSCEPTIBILITY LOCI; GENE PRIORITIZATION; HUMAN-DISEASE; DATABASE; MOUSE; REPLICATION; PATHWAY; INCONSISTENCY; METAANALYSES AB Biological plausibility and other prior information could help select genome-wide association (GWA) findings for further follow-up, but there is no consensus on which types of knowledge should be considered or how to weight them. We used experts opinions and empirical evidence to estimate the relative importance of 15 types of information at the single-nucleotide polymorphism (SNP) and gene levels. Opinions were elicited from 10 experts using a two-round Delphi survey. Empirical evidence was obtained by comparing the frequency of each type of characteristic in SNPs established as being associated with seven disease traits through GWA meta-analysis and independent replication, with the corresponding frequency in a randomly selected set of SNPs. SNP and gene characteristics were retrieved using a specially developed bioinformatics tool. Both the expert and the empirical evidence rated previous association in a meta-analysis or more than one study as conferring the highest relative probability of true association, whereas previous association in a single study ranked much lower. High relative probabilities were also observed for location in a functional protein domain, although location in a region evolutionarily conserved in vertebrates was ranked high by the data but not by the experts. Our empirical evidence did not support the importance attributed by the experts to whether the gene encodes a protein in a pathway or shows interactions relevant to the trait. Our findings provide insight into the selection and weighting of different types of knowledge in SNP or gene prioritization, and point to areas requiring further research. C1 [Minelli, Cosetta; De Grandi, Alessandro; Weichenberger, Christian X.; Goegele, Martin; Modenese, Mirko; Freina, Thomas; Hicks, Andrew A.; Pattaro, Cristian; Schwienbacher, Christine; Taliun, Daniel; Pramstaller, Peter P.; Domingues, Francisco S.] European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy. [Attia, John] Univ Newcastle, Hunter Med Res Inst, Ctr Clin Epidemiol & Biostatist, Newcastle, NSW 2300, Australia. [Attia, John] John Hunter Hosp, Dept Gen Med, Newcastle, NSW, Australia. [Barrett, Jennifer H.] Univ Leeds, Sect Epidemiol & Biostat, Leeds Inst Mol Med, Leeds, W Yorkshire, England. [Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Boehnke, Michael] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Borsani, Giuseppe] Univ Brescia, Dept Biomed Sci & Biotechnol, Brescia, Italy. [Casari, Giorgio] Univ Vita Salute San Raffaele, Milan, Italy. [Casari, Giorgio] Ctr Translat Genom & Bioinformat, Milan, Italy. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA. [Marroni, Fabio] Inst Appl Genom, Udine, Italy. [Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Pastore, Andrea] Ca Foscari Venezia Univ, Dept Econ, Venice, Italy. [Pfeufer, Arne] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munich, Dept Bioinformat & Syst Biol IBIS, Neuherberg, Germany. [Ruggeri, Fabrizio] Inst Appl Math & Informat Technol, Natl Res Council, Milan, Italy. [Pramstaller, Peter P.] Cent Hosp, Dept Neurol, Bolzano, Italy. [Pramstaller, Peter P.] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. [Thompson, John R.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England. RP Minelli, C (reprint author), EURAC Res, Ctr Biomed, Viale Druso 1, I-39100 Bolzano, Italy. EM cosetta.minelli@eurac.edu RI Pfeufer, Arne/B-6634-2013; Attia, John/F-5376-2013; Pramstaller, Peter/C-2357-2008; Ruggeri, Fabrizio/A-9383-2012; Hicks, Andrew/E-9518-2017; OI Barrett, Jenny/0000-0002-1720-7724; Borsani, Giuseppe/0000-0003-0110-1148; Attia, John/0000-0001-9800-1308; Ruggeri, Fabrizio/0000-0002-7655-6254; Hicks, Andrew/0000-0001-6320-0411; CASARI, Giorgio/0000-0002-0115-8980; Marroni, Fabio/0000-0002-1556-5907 FU Department for Promotion of Educational Policies, Universities and Research of the Autonomous Province of Bolzano, South Tyrol, Italy; NIH [HG000376] FX All researchers from the Center for Biomedicine at EURAC were supported by the Department for Promotion of Educational Policies, Universities and Research of the Autonomous Province of Bolzano, South Tyrol, Italy; M. B. was supported by NIH grant HG000376. None of the authors declare any conflict of interest. NR 47 TC 4 Z9 6 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD FEB PY 2013 VL 37 IS 2 BP 205 EP 213 DI 10.1002/gepi.21705 PG 9 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 074AK UT WOS:000313784000009 PM 23307621 ER PT J AU Thompson, JR Gogele, M Weichenberger, CX Modenese, M Attia, J Barrett, JH Boehnke, M De Grandi, A Domingues, FS Hicks, AA Marroni, F Pattaro, C Ruggeri, F Borsani, G Casari, G Parmigiani, G Pastore, A Pfeufer, A Schwienbacher, C Taliun, D Fox, CS Pramstaller, PP Minelli, C AF Thompson, John R. Goegele, Martin Weichenberger, Christian X. Modenese, Mirko Attia, John Barrett, Jennifer H. Boehnke, Michael De Grandi, Alessandro Domingues, Francisco S. Hicks, Andrew A. Marroni, Fabio Pattaro, Cristian Ruggeri, Fabrizio Borsani, Giuseppe Casari, Giorgio Parmigiani, Giovanni Pastore, Andrea Pfeufer, Arne Schwienbacher, Christine Taliun, Daniel Fox, Caroline S. Pramstaller, Peter P. Minelli, Cosetta CA CKDGen Consortium TI SNP Prioritization Using a Bayesian Probability of Association SO GENETIC EPIDEMIOLOGY LA English DT Article DE replication; prior knowledge; genome-wide studies ID GENOME-WIDE ASSOCIATION; CHRONIC KIDNEY-DISEASE; STATISTICAL-METHODS; POSITIVE REPORT; FALSE; EPIDEMIOLOGY; DISCOVERY AB Prioritization is the process whereby a set of possible candidate genes or SNPs is ranked so that the most promising can be taken forward into further studies. In a genome-wide association study, prioritization is usually based on the P-values alone, but researchers sometimes take account of external annotation information about the SNPs such as whether the SNP lies close to a good candidate gene. Using external information in this way is inherently subjective and is often not formalized, making the analysis difficult to reproduce. Building on previous work that has identified 14 important types of external information, we present an approximate Bayesian analysis that produces an estimate of the probability of association. The calculation combines four sources of information: the genome-wide data, SNP information derived from bioinformatics databases, empirical SNP weights, and the researchers subjective prior opinions. The calculation is fast enough that it can be applied to millions of SNPS and although it does rely on subjective judgments, those judgments are made explicit so that the final SNP selection can be reproduced. We show that the resulting probability of association is intuitively more appealing than the P-value because it is easier to interpret and it makes allowance for the power of the study. We illustrate the use of the probability of association for SNP prioritization by applying it to a meta-analysis of kidney function genome-wide association studies and demonstrate that SNP selection performs better using the probability of association compared with P-values alone. C1 [Thompson, John R.; CKDGen Consortium] Univ Leicester, Dept Hlth Sci, Leicester LE1 7RH, Leics, England. [Goegele, Martin; Weichenberger, Christian X.; Modenese, Mirko; De Grandi, Alessandro; Domingues, Francisco S.; Hicks, Andrew A.; Pattaro, Cristian; Schwienbacher, Christine; Taliun, Daniel; Pramstaller, Peter P.; Minelli, Cosetta] European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy. [Attia, John] Univ Newcastle, Hunter Med Res Inst, Ctr Clin Epidemiol & Biostat, Newcastle, NSW 2300, Australia. [Attia, John] John Hunter Hosp, Dept Gen Med, Newcastle, NSW, Australia. [Barrett, Jennifer H.] Univ Leeds, Leeds Inst Mol Med, Sect Epidemiol & Biostat, Leeds, W Yorkshire, England. [Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Boehnke, Michael] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Marroni, Fabio] Inst Appl Genom, Udine, Italy. [Ruggeri, Fabrizio] Inst Appl Math & Informat Technol, Natl Res Council, Milan, Italy. [Borsani, Giuseppe] Univ Brescia, Dept Biomed Sci & Biotechnol, Brescia, Italy. [Casari, Giorgio] Univ Vita Salute San Raffaele, Milan, Italy. [Casari, Giorgio] Ctr Translat Genom & Bioinformat, Milan, Italy. [Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Pastore, Andrea] Ca Foscari Venezia Univ, Dept Econ, Venice, Italy. [Pfeufer, Arne] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munich, Dept Bioinformat & Syst Biol IBIS, Neuherberg, Germany. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA. [Pramstaller, Peter P.] Cent Hosp, Dept Neurol, Bolzano, Italy. [Pramstaller, Peter P.] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. RP Thompson, JR (reprint author), Univ Leicester, Dept Hlth Sci, Room 214F,Adrian Bldg, Leicester LE1 7RH, Leics, England. EM john.thompson@le.ac.uk RI Pfeufer, Arne/B-6634-2013; Attia, John/F-5376-2013; Pramstaller, Peter/C-2357-2008; Ruggeri, Fabrizio/A-9383-2012; Hicks, Andrew/E-9518-2017; OI Borsani, Giuseppe/0000-0003-0110-1148; Attia, John/0000-0001-9800-1308; Ruggeri, Fabrizio/0000-0002-7655-6254; Hicks, Andrew/0000-0001-6320-0411; CASARI, Giorgio/0000-0002-0115-8980; Marroni, Fabio/0000-0002-1556-5907; Barrett, Jenny/0000-0002-1720-7724 FU Department for Promotion of Educational Policies, Universities and Research of the Autonomous Province of Bolzano, South Tyrol, Italy; NIH [HG000376] FX All researchers from the Center for Biomedicine at EURAC were supported by the Department for Promotion of Educational Policies, Universities and Research of the Autonomous Province of Bolzano, South Tyrol, Italy; Michael Boehnke was supported by NIH grant HG000376. None of the authors declares any conflict of interest. NR 22 TC 1 Z9 3 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD FEB PY 2013 VL 37 IS 2 BP 214 EP 221 DI 10.1002/gepi.21704 PG 8 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 074AK UT WOS:000313784000010 PM 23280596 ER PT J AU Van Houtven, CH Thorpe, JM Chestnutt, D Molloy, M Boling, JC Davis, LL AF Van Houtven, Courtney Harold Thorpe, Joshua M. Chestnutt, Deborah Molloy, Margory Boling, John C. Davis, Linda Lindsey TI Do Nurse-Led Skill Training Interventions Affect Informal Caregivers' Out-of-Pocket Expenditures? SO GERONTOLOGIST LA English DT Article DE Cost analysis; Intervention study; Nurses/midwives/nursing; Alzheimer's disease; Parkinson's disease; Average treatment effect ID RANDOMIZED CONTROLLED-TRIAL; ALZHEIMERS-DISEASE; HOME PLACEMENT; CARE; DEMENTIA; COST; BURDEN; CANCER; METAANALYSIS AB Purpose of the Study: This paper is a report of a study of the Assistance, Support, and Self-health Initiated through Skill Training (ASSIST) randomized control trial. The aim of this paper is to understand whether participating in ASSIST significantly changed the out-of-pocket (OOP) costs for family caregivers of Alzheimer's disease (AD) or Parkinson's disease (PD) patients. Design and Methods: Secondary analysis of randomized control trial data, calculating average treatment effects of the intervention on OOP costs. Enrollment in the ASSIST trial occurred between 2002 and 2007 at 2 sites: Durham, North Carolina, and Birmingham, Alabama. We profile OOP costs for caregivers who participated in the ASSIST study and use 2-part expenditure models to examine the average treatment effect of the intervention on caregiver OOP expenditures. Results: ASSIST-trained AD and PD caregivers reported monthly OOP expenditures that averaged $500-$600. The intervention increased the likelihood of caregivers spending any money OOP by 26 percentage points over usual care, but the intervention did not significantly increase overall OOP costs. Implications: The ASSIST intervention was effective and inexpensive to the caregiver in direct monetary outlays; thus, there are minimal unintended consequences of the trial on caregiver financial well-being. C1 [Van Houtven, Courtney Harold] Durham VA, Ctr Excellence Hlth Serv Res Primary Care, Durham, NC 27705 USA. [Van Houtven, Courtney Harold] Duke Univ, Dept Med, Durham, NC USA. [Thorpe, Joshua M.] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA 15260 USA. [Thorpe, Joshua M.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Chestnutt, Deborah] Ralph H Johnson Charleston Vet Adm Hosp, VA Nurse Acad, Charleston, SC USA. [Molloy, Margory] Duke Univ, Sch Nursing, Ctr Nursing Discovery, Durham, NC USA. RP Van Houtven, CH (reprint author), Durham VA, Ctr Excellence Hlth Serv Res Primary Care, 508 Fulton St, Durham, NC 27705 USA. EM courtney.vanhoutven@duke.edu RI Thorpe, Joshua/C-1188-2013 FU NINR NIH HHS [R01 NR 008285, R01 NR008285] NR 36 TC 3 Z9 3 U1 2 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD FEB PY 2013 VL 53 IS 1 BP 60 EP 70 DI 10.1093/geront/gns045 PG 11 WC Gerontology SC Geriatrics & Gerontology GA 071RV UT WOS:000313612800007 PM 22459694 ER PT J AU Goodman, KA Khalid, N Kachnic, LA Minsky, BD Crozier, C Owen, JB Devlin, PM Thomas, CR AF Goodman, Karyn A. Khalid, Najma Kachnic, Lisa A. Minsky, Bruce D. Crozier, Cheryl Owen, Jean B. Devlin, Phillip M. Thomas, Charles R., Jr. TI Quality Research in Radiation Oncology Analysis of Clinical Performance Measures in the Management of Gastric Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID POSTOPERATIVE CHEMORADIOTHERAPY; LOCAL-CONTROL; RADIOTHERAPY; CHEMOTHERAPY; CARCINOMA; ADENOCARCINOMA; PROLONGATION; PATTERNS; SURGERY; CARE AB Background: The specific aim was to determine national patterns of radiation therapy (RT) practice in patients treated for stage IB-IV (nonmetastatic) gastric cancer (GC). Methods and Materials: A national process survey of randomly selected US RT facilities was conducted which retrospectively assessed demographics, staging, geographic region, practice setting, and treatment by using on-site record review of eligible GC cases treated from 2005 to 2007. Three clinical performance measures (CPMs), (1) use of computed tomography (CT)-based treatment planning; (2) use of dose volume histograms (DVHs) to evaluate RT dose to the kidneys and liver; and (3) completion of RT within the prescribed time frame; and emerging quality indicators, (i) use of intensity modulated RT (IMRT); (ii) use of image-guided tools (IGRT) other than CT for RT target delineation; and (iii) use of preoperative RT, were assessed. Results: CPMs were computed for 250 eligible patients at 45 institutions (median age, 62 years; 66% male; 60% Caucasian). Using 2000 American Joint Committee on Cancer criteria, 13% of patients were stage I, 29% were stage II, 32% were stage IIIA, 10% were stage IIIB, and 12% were stage IV. Most patients (43%) were treated at academic centers, 32% were treated at large nonacademic centers, and 25% were treated at small to medium sized facilities. Almost all patients (99.5%) underwent CT-based planning, and 75% had DVHs to evaluate normal tissue doses to the kidneys and liver. Seventy percent of patients completed RT within the prescribed time frame. IMRT and IGRT were used in 22% and 17% of patients, respectively. IGRT techniques included positron emission tomography (n=20), magnetic resonance imaging (n=1), respiratory gating and 4-dimensional CT (n=22), and on-board imaging (n=10). Nineteen percent of patients received preoperative RT. Conclusions: This analysis of radiation practice patterns for treating nonmetastatic GC indicates widespread adoption of CT-based planning with use of DVH to evaluate normal tissue doses. Most patients completed adjuvant RT in the prescribed time frame. IMRT and IGRT were not routinely incorporated into clinical practice during the 2005-2007 period. These data will be a benchmark for future Quality Research in Radiation Oncology GC surveys. (C) 2013 Elsevier Inc. C1 [Goodman, Karyn A.] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10065 USA. [Khalid, Najma; Crozier, Cheryl; Owen, Jean B.] Amer Coll Radiol, Clin Res Ctr, Philadelphia, PA USA. [Kachnic, Lisa A.] Boston Univ, Med Ctr, Dept Radiat Oncol, Boston, MA USA. [Minsky, Bruce D.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Devlin, Phillip M.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Thomas, Charles R., Jr.] Oregon Hlth & Sci Univ, Knight Canc Inst, Dept Radiat Med, Portland, OR 97201 USA. RP Goodman, KA (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, 1275 York Ave, New York, NY 10065 USA. EM goodmank@mskcc.org FU National Institutes of Health National Cancer Institute [CA065435] FX Quality Research in Radiation Oncology is supported by National Institutes of Health National Cancer Institute grant CA065435. NR 20 TC 1 Z9 2 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 2013 VL 85 IS 2 BP 355 EP 362 DI 10.1016/j.ijrobp.2012.08.021 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 072BB UT WOS:000313642000022 PM 23040221 ER PT J AU Halasz, LM Weeks, JC Neville, BA Taback, N Punglia, RS AF Halasz, Lia M. Weeks, Jane C. Neville, Bridget A. Taback, Nathan Punglia, Rinaa S. TI Use of Stereotactic Radiosurgery for Brain Metastases From Non-Small Cell Lung Cancer in the United States SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID COST-EFFECTIVENESS; RADIATION-THERAPY; SURGICAL RESECTION; COMORBIDITY INDEX; RADIOTHERAPY; VALIDATION; TRIAL; HEAD AB Purpose: The indications for treatment of brain metastases from non-small cell lung cancer (NSCLC) with stereotactic radiosurgery (SRS) remain controversial. We studied patterns, predictors, and cost of SRS use in elderly patients with NSCLC. Methods and Materials: Using the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we identified patients with NSCLC who were diagnosed with brain metastases between 2000 and 2007. Our cohort included patients treated with radiation therapy and not surgical resection as initial treatment for brain metastases. Results: We identified 7684 patients treated with radiation therapy within 2 months after brain metastases diagnosis, of whom 469 (6.1%) cases had billing codes for SRS. Annual SRS use increased from 3.0% in 2000 to 8.2% in 2005 and varied from 3.4% to 12.5% by specific SEER registry site. After controlling for clinical and sociodemographic characteristics, we found SRS use was significantly associated with increasing year of diagnosis, specific SEER registry, higher socioeconomic status, admission to a teaching hospital, no history of participation in low-income state buy-in programs (a proxy for Medicaid eligibility), no extracranial metastases, and longer intervals from NSCLC diagnosis. The average cost per patient associated with radiation therapy was 2.19 times greater for those who received SRS than for those who did not. Conclusions: The use of SRS in patients with metastatic NSCLC increased almost 3-fold from 2000 to 2005. In addition, we found significant variations in SRS use across SEER registries and socioeconomic quartiles. National practice patterns in this study suggested both a lack of consensus and an overall limited use of the approach among elderly patients before 2008. (C) 2013 Elsevier Inc. C1 [Halasz, Lia M.] Univ Washington, Dept Radiat Oncol, Seattle, WA 98195 USA. [Halasz, Lia M.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA USA. [Weeks, Jane C.; Neville, Bridget A.; Taback, Nathan] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. [Punglia, Rinaa S.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Halasz, LM (reprint author), Univ Washington, Dept Radiat Oncol, 1959 NE Pacific St,Box 356043, Seattle, WA 98195 USA. EM lhalasz@uw.edu FU Joint Center for Radiation Therapy, Boston, MA FX This study was supported by a grant from the Joint Center for Radiation Therapy, Boston, MA, and was presented at the 53rd Annual Meeting of the American Society for Radiation Oncology (ASTRO) in Miami Beach, Florida, Oct 2-6, 2011. NR 23 TC 13 Z9 14 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 2013 VL 85 IS 2 BP E109 EP E116 DI 10.1016/j.ijrobp.2012.08.007 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 072BB UT WOS:000313642000002 PM 23058058 ER PT J AU Hegde, JV Chen, MH Mulkern, RV Fennessy, FM D'Amico, AV Tempany, CMC AF Hegde, John V. Chen, Ming-Hui Mulkern, Robert V. Fennessy, Fiona M. D'Amico, Anthony V. Tempany, Clare M. C. TI Preoperative 3-Tesla Multiparametric Endorectal Magnetic Resonance Imaging Findings and the Odds of Upgrading and Upstaging at Radical Prostatectomy in Men With Clinically Localized Prostate Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID ANDROGEN DEPRIVATION; INCREMENTAL VALUE; EXTRACAPSULAR EXTENSION; RADIATION-THERAPY; RANDOMIZED-TRIAL; MR; RADIOTHERAPY; PREDICTION; SUPPRESSION; STAGE AB Purpose: To investigate whether 3-T esla (3T) multiparametric endorectal MRI (erMRI) can add information to established predictors regarding occult extraprostatic or high-grade prostate cancer (PC) in men with clinically localized PC. Methods and Materials: At a single academic medical center, this retrospective study's cohort included 118 men with clinically localized PC who underwent 3T multiparametric erMRI followed by radical prostatectomy, from 2008 to 2011. Multivariable logistic regression analyses in all men and in 100 with favorable-risk PC addressed whether erMRI evidence of T3 disease was associated with prostatectomy T3 or Gleason score (GS) 8-10 (in patients with biopsyGS <= 7) PC, adjusting for age, prostate-specific antigen level, clinical T category, biopsy GS, and percent positive biopsies. Results: The accuracy of erMRI prediction of extracapsular extension and seminal vesicle invasion was 75% and 95%, respectively. For all men, erMRI evidence of a T3 lesion versus T2 was associated with an increased odds of having pT3 disease (adjusted odds ratio [AOR] 4.81, 95% confidence interval [CI] 1.36-16.98, P = .015) and pGS 8-10 (AOR 5.56, 95% CI 1.10-28.18, P = .038). In the favorable-risk population, these results were AOR 4.14 (95% CI 1.03-16.56), P = .045 and AOR 7.71 (95% CI 1.36-43.62), P = .021, respectively. Conclusions: Three-Tesla multiparametric erMRI in men with favorable-risk PC provides information beyond that contained in known preoperative predictors about the presence of occult extraprostatic and/or high-grade PC. If validated in additional studies, this information can be used to counsel men planning to undergo radical prostatectomy or radiation therapy about the possible need for adjuvant radiation therapy or the utility of adding hormone therapy, respectively. (C) 2013 Elsevier Inc. C1 [Hegde, John V.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Mulkern, Robert V.] Childrens Hosp Boston, Dept Radiol, Boston, MA USA. [Fennessy, Fiona M.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Tempany, Clare M. C.] Brigham & Womens Hosp, Dept Radiol, Surg Planning Lab, Div MRI, Boston, MA 02115 USA. RP Tempany, CMC (reprint author), Brigham & Womens Hosp, Dept Radiol, Surg Planning Lab, Div MRI, L1 050,75 Francis St, Boston, MA 02115 USA. EM ctempany@bwh.harvard.edu FU National Institutes of Health [P01CA067165, R01CA111288, P41RR019703, R01CA109246, U01CA151261]; National Institute of Biomedical Imaging and Bioengineering [P41EB015898]; Harvard Medical School FX Research support was received from the National Institutes of Health (grants P01CA067165, R01CA111288, P41RR019703, R01CA109246, and U01CA151261), the National Institute of Biomedical Imaging and Bioengineering (grant P41EB015898), and a medical student research fellowship provided by Harvard Medical School. NR 23 TC 19 Z9 19 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 2013 VL 85 IS 2 BP E101 EP E107 DI 10.1016/j.ijrobp.2012.08.032 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 072BB UT WOS:000313642000001 PM 23040223 ER PT J AU Nakamura, K Hirano, K Wu, SM AF Nakamura, Kenta Hirano, Ken-ichi Wu, Sean M. TI iPS Cell Modeling of Cardiometabolic Diseases SO JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH LA English DT Article DE Cardiometabolic disease; Induced pluripotent stem cell; Disease modeling; Storage disease ID PLURIPOTENT STEM-CELLS; ADIPOSE TRIGLYCERIDE LIPASE; LIPID STORAGE DISEASE; ACTIVATED PROTEIN-KINASE; CHANARIN-DORFMAN-SYNDROME; CORONARY-HEART-DISEASE; ZINC-FINGER NUCLEASES; GLYCOGEN-STORAGE; HYPERTROPHIC CARDIOMYOPATHY; CARDIOVASCULAR-DISEASE AB Cardiometabolic diseases encompass simple monogenic enzyme deficiencies with well-established pathogenesis and clinical outcomes to complex polygenic diseases such as the cardiometabolic syndrome. The limited availability of relevant human cell types such as cardiomyocytes has hampered our ability to adequately model and study pathways or drugs relevant to these diseases in the heart. The recent discovery of induced pluripotent stem (iPS) cell technology now offers a powerful opportunity to establish translational platforms for cardiac disease modeling, drug discovery, and pre-clinical testing. In this article, we discuss the excitement and challenges of modeling cardiometabolic diseases using iPS cell and their potential to revolutionize translational research. C1 [Wu, Sean M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Div Cardiol,Dept Med, Boston, MA 02114 USA. [Hirano, Ken-ichi] Osaka Univ, Grad Sch Med, Dept Cardiovasc Med, Osaka, Japan. [Wu, Sean M.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Wu, SM (reprint author), Stanford Univ, Lokey Stem Cell Bldg,265 Campus Dr,Room G1120A, Stanford, CA 94305 USA. EM knakamura@partners.org; smwu@partners.org FU NIH; NIH/NHLBI FX The authors would like to thank Ms. Karolina Plonowska for her editorial assistance. This work was funded by NIH Officer of the Director and NIH/NHLBI to S. M. W. We apologize for our inability to cite many excellent studies in this area due to space constraints. NR 74 TC 7 Z9 7 U1 2 U2 21 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1937-5387 J9 J CARDIOVASC TRANSL JI J. Cardiovasc. Transl. Res. PD FEB PY 2013 VL 6 IS 1 SI SI BP 46 EP 53 DI 10.1007/s12265-012-9413-4 PG 8 WC Cardiac & Cardiovascular Systems; Medicine, Research & Experimental SC Cardiovascular System & Cardiology; Research & Experimental Medicine GA 072GM UT WOS:000313657700006 PM 23070616 ER PT J AU Gao, B Chen, W Hao, L Zhu, G Feng, S Ci, H Zhou, X Stashenko, P Li, YP AF Gao, B. Chen, W. Hao, L. Zhu, G. Feng, S. Ci, H. Zhou, X. Stashenko, P. Li, Y. P. TI Inhibiting Periapical Lesions through AAV-RNAi Silencing of Cathepsin K SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE endodontic disease; inflammation; bone resorption; dental caries; osteoclast; gene therapy ID PERIODONTAL-LIGAMENT CELLS; APICAL PERIODONTITIS; BONE-RESORPTION; DENTAL-PULP; DISEASE; RANKL; GENE; DIFFERENTIATION; PYCNODYSOSTOSIS; PATHOGENESIS AB Dental caries, one of the most prevalent infectious diseases worldwide, affects approximately 80% of children and the majority of adults. Dental caries may result in endodontic disease, leading to dental pulp necrosis, periapical inflammation and bone resorption, severe pain, and tooth loss. Periapical inflammation may also increase inflammation in other parts of the body. Although many studies have attempted to develop therapies for this disease, there is still an urgent need for effective treatments. In this study, we applied a novel gene therapeutic approach using recombinant adeno-associated virus (AAV)-mediated RNAi knockdown of Cathepsin K (Ctsk) gene expression, to target osteoclasts and periapical bone resorption in a mouse model. We found that AAV-sh-Cathepsin K (AAV-sh-Ctsk) impaired osteoclast function in vivo and furthermore reduced bacterial infection-stimulated bone resorption by 88%. Reduced periapical lesion size was accompanied by decreases in mononuclear leukocyte infiltration and inflammatory cytokine expression. Our study shows that AAV-RNAi silencing of Cathepsin K in periapical tissues can significantly reduce endodontic disease development, bone destruction, and inflammation in the periapical lesion. This is the first demonstration that AAV-mediated RNAi knockdown gene therapy may significantly reduce the severity of endodontic disease. C1 [Gao, B.; Hao, L.; Zhou, X.] Sichuan Univ, W China Coll Stomatol, State Key Lab Oral Dis, Chengdu, Sichuan, Peoples R China. [Gao, B.; Chen, W.; Hao, L.; Zhu, G.; Feng, S.; Ci, H.; Li, Y. P.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Stashenko, P.] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA USA. RP Chen, W (reprint author), Univ Alabama Birmingham, Dept Pathol, SHEL 810,1825 Univ Blvd, Birmingham, AL 35294 USA. EM wechen@uab.edu; ypli@uab.edu FU NIH [RC1-DE-020533-01] FX We thank Ms. Christie Paulson and Mr. Zach Nolen for their excellent assistance with the manuscript. We also thank Drs. Sergei Musatov and Sonoko Ogawa for kindly providing the AAV-H1-shRNA-luc-YFP and AAV-H1 vectors and for helpful suggestions. We appreciate the assistance of the Center for Metabolic Bone Disease at the University of Alabama at Birmingham (P30 AR046031). We are also grateful for the assistance of the Small Animal Phenotyping Core, Metabolism Core, and Neuroscience Molecular Detection Core Laboratory at the University of Alabama at Birmingham (P30 NS0474666). This work was supported by NIH grant RC1-DE-020533-01 (Y.P.L.). The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 30 TC 15 Z9 15 U1 1 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD FEB PY 2013 VL 92 IS 2 BP 180 EP 186 DI 10.1177/0022034512468757 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 071XE UT WOS:000313629700014 PM 23166044 ER PT J AU Valsangkar, NP Bush, DM Michaelson, JS Ferrone, CR Wargo, JA Lillemoe, KD Fernandez-del Castillo, C Warshaw, AL Thayer, SP AF Valsangkar, Nakul P. Bush, Devon M. Michaelson, James S. Ferrone, Cristina R. Wargo, Jennifer A. Lillemoe, Keith D. Fernandez-del Castillo, Carlos Warshaw, Andrew L. Thayer, Sarah P. TI N0/N1, PNL, or LNR? The Effect of Lymph Node Number on Accurate Survival Prediction in Pancreatic Ductal Adenocarcinoma SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Pancreatic cancer; Lymph node ratio; Staging; Survival ID EXTENDED RETROPERITONEAL LYMPHADENECTOMY; CURATIVE RESECTION; PROGNOSTIC-FACTOR; PERIAMPULLARY ADENOCARCINOMA; DISTAL GASTRECTOMY; SINGLE-INSTITUTION; HEAD CANCER; RATIO; PANCREATICODUODENECTOMY; CARCINOMA AB We evaluated the prognostic accuracy of LN variables (N0/N1), numbers of positive lymph nodes (PLN), and lymph node ratio (LNR) in the context of the total number of examined lymph nodes (ELN). Patients from SEER and a single institution (MGH) were reviewed and survival analyses performed in subgroups based on numbers of ELN to calculate excess risk of death (hazard ratio, HR). In SEER and MGH, higher numbers of ELN improved the overall survival for N0 patients. The prognostic significance (N0/N1) and PLN were too variable as the importance of a single PLN depended on the total number of LN dissected. LNR consistently correlated with survival once a certain number of lymph nodes were dissected (a parts per thousand yen13 in SEER and a parts per thousand yen17 in the MGH dataset). Better survival for N0 patients with increasing ELN likely represents improved staging. PLN have some predictive value but the ELN strongly influence their impact on survival, suggesting the need for a ratio-based classification. LNR strongly correlates with outcome provided that a certain number of lymph nodes is evaluated, suggesting that the prognostic accuracy of any LN variable depends on the total number of ELN. C1 [Valsangkar, Nakul P.; Ferrone, Cristina R.; Wargo, Jennifer A.; Lillemoe, Keith D.; Fernandez-del Castillo, Carlos; Warshaw, Andrew L.; Thayer, Sarah P.] Massachusetts Gen Hosp, Dept Surg & Andrew L Warshaw, Inst Pancreat Canc Res, Boston, MA 02114 USA. [Valsangkar, Nakul P.; Bush, Devon M.; Michaelson, James S.; Ferrone, Cristina R.; Wargo, Jennifer A.; Lillemoe, Keith D.; Fernandez-del Castillo, Carlos; Warshaw, Andrew L.; Thayer, Sarah P.] Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Lab Quantitat Med, Boston, MA 02114 USA. [Thayer, Sarah P.] Massachusetts Gen Hosp, Dept Surg, Pancreat Biol Lab, Boston, MA 02114 USA. RP Thayer, SP (reprint author), Massachusetts Gen Hosp, Dept Surg, Pancreat Biol Lab, 15 Parkman St,WACC 460, Boston, MA 02114 USA. EM sthayer@partners.org FU National Cancer Institute [CA117969, CA127003]; Institute for Pancreatic Cancer Research FX We thank Andrew Liss, Ph.D. for his scientific and editorial support. This study was supported by the Andrew L. Warshaw, M.D., Institute for Pancreatic Cancer Research and grants CA117969 and CA127003 from the National Cancer Institute. NR 44 TC 43 Z9 47 U1 0 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD FEB PY 2013 VL 17 IS 2 BP 257 EP 266 DI 10.1007/s11605-012-1974-7 PG 10 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 072FY UT WOS:000313656100008 PM 23229885 ER PT J AU Enamandram, M Kimball, AB AF Enamandram, Monica Kimball, Alexa B. TI Psoriasis Epidemiology: The Interplay of Genes and the Environment SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material ID PREVALENCE AB Psoriasis is a common chronic dermatological disease whose prevalence varies among different populations worldwide. In epidemiological studies, the factors that potentially account for this variability include climate, genetic susceptibility, and environmental antigen exposure. In this issue, Parisi et al. performed a systematic review to explore the global prevalence and incidence of psoriasis. Journal of Investigative Dermatology (2013) 133, 287-289. doi:10.1038/jid.2012.434 C1 [Enamandram, Monica; Kimball, Alexa B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. RP Kimball, AB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, 50 Staniford St,Suite 240, Boston, MA 02114 USA. EM harvardskinstudies@pattners.org NR 10 TC 20 Z9 27 U1 0 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 2013 VL 133 IS 2 BP 287 EP 289 DI 10.1038/jid.2012.434 PG 3 WC Dermatology SC Dermatology GA 072JU UT WOS:000313668000004 PM 23318785 ER PT J AU Chen, L Wu, JJ Pier, E Zhao, Y Shen, Z AF Chen, Ling Wu, Jinjin Pier, Eric Zhao, Yun Shen, Zhu TI mTORC2-PKB alpha/Akt1 Serine 473 Phosphorylation Axis Is Essential for Regulation of FOXP3 Stability by Chemokine CCL3 in Psoriasis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID MACROPHAGE INFLAMMATORY PROTEIN-1; CELLS IN-VIVO; T-CELLS; IFN-GAMMA; EXPRESSION; AKT; PROLIFERATION; CYTOKINES; SIN1; FIBROBLASTS AB The connection between infections and acute guttate psoriasis (AGP) outbreaks/chronic plaque psoriasis (CPP) exacerbation has been known for years. Impaired function of FOXP3 + Tregs in psoriasis has been identified. However, the mechanisms behind these two observations have not been fully interpreted. In the present study, we provide evidence to support chemokine CCL3 as one of the vital links between infections and FOXP3 stability in the psoriatic microenvironment. We found that serum CCL3, strongly induced by microorganism infections including streptococcus, was closely correlated with FOXP3 levels in CD4 + CD25 + T cells of patients with psoriasis. CCL3 manipulated FOXP3 stability in a concentration-dependent bidirectional manner. High-concentration CCL3 decreased FOXP3 stability by promoting FOXP3's degradation through K48-linkage ubiquitination. This degradation was mainly dependent on upregulation of Serine 473 phosphorylation of the PKB alpha/Akt1 isoform, and almost independent of mTORC1 (mammalian target of rapamycin complex 1) activity. On the other hand, low-concentration CCL3 could enhance FOXP3 stability by the maintenance of the PKC pathway and the restriction of the PKB/Akt pathway. We further demonstrated that enhancing FOXP3 stability by low-concentration CCL3 attributed, at least partly, to the prevention of cytoplasmic Sin1, a vital component of mTORC2, nuclear translocation. Our results suggest vital roles for CCL3-mTORC2-isoform PKB/Akt1 S473 phosphorylation axis in FOXP3 + Tregs and the development of psoriasis. Journal of Investigative Dermatology (2013) 133, 418-428; doi:10.1038/jid.2012.333; published online 6 December 2012 C1 [Chen, Ling; Wu, Jinjin] Third Mil Med Univ, Daping Hosp, Dept Dermatol, Chongqing 400038, Peoples R China. [Pier, Eric] Tufts Univ, Sch Med, Tufts Med Ctr, Boston, MA 02111 USA. [Zhao, Yun] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Shen, Zhu] Third Mil Med Univ, Southwest Hosp, Dept Dermatol, Chongqing 400038, Peoples R China. [Shen, Zhu] Third Mil Med Univ, Southwest Hosp, Ctr Clin Immunol, Chongqing 400038, Peoples R China. RP Shen, Z (reprint author), Third Mil Med Univ, Southwest Hosp, Dept Dermatol, 30 Gaotanyan Main St, Chongqing 400038, Peoples R China. EM zhushencq@gmail.com FU National Natural Science Foundation of China [30801013, 81072502]; Natural Science Foundation Project of CQ CSTC [CSTC 2009BA5010]; Project for Medical Science Development of PLA [CWS12J027] FX We wish to thank all the patients and healthy donors who have assisted in this study. We also thank Dr Tangyou Zhu and Shuqian Tang (Third Military Medical University) for the help in immunohistochemistry. We thank Kah-Leong LIM (National University of Singapore), Pan Zheng (University of Michigan School of Medicine and Cancer Center), Philip N. Tsichlis (Tufts University School of Medicine), Estela Jacinto (UMDNJ-Robert Wood Johnson Medical School), and Joseph G. Sodroski (Harvard Medical School) for the plasmids, cells and regents. This work was supported by the National Natural Science Foundation of China (No. 30801013, Ling Chen; No. 81072502, Zhu Shen), the Natural Science Foundation Project of CQ CSTC (No. CSTC 2009BA5010, Zhu Shen), and the Project for Medical Science Development of PLA (No. CWS12J027, Ling Chen). NR 45 TC 10 Z9 11 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 2013 VL 133 IS 2 BP 418 EP 428 DI 10.1038/jid.2012.333 PG 11 WC Dermatology SC Dermatology GA 072JU UT WOS:000313668000021 PM 23223135 ER PT J AU Liu, WM Luo, YC Dunn, JH Norris, DA Dinarello, CA Fujita, M AF Liu, Weimin Luo, Yuchun Dunn, Jeffrey H. Norris, David A. Dinarello, Charles A. Fujita, Mayumi TI Dual Role of Apoptosis-Associated Speck-Like Protein Containing a CARD (ASC) in Tumorigenesis of Human Melanoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID KAPPA-B ACTIVATION; ABERRANT METHYLATION; TMS1/ASC; CANCER; CELLS; INFLAMMASOME; ADAPTER; FAMILY; GENE AB Apoptosis-associated Speck-like protein containing a CARD (caspase recruitment domain) (ASC) was originally named because it triggered apoptosis in certain tumors. More recently, however, ASC was found to be a central adaptor protein of inflammasome, which mediates the secretion of protumorigenic inflammation. Here we examined the role of ASC in tumorigenesis of human melanoma. Compared with primary melanoma, ASC protein expression was generally downregulated in metastatic melanoma. Although overexpressing ASC in metastatic melanoma showed no effects on cell viability, silencing ASC with short hairpin RNA induced Cl cell cycle arrest, reduced cell viability, and suppressed tumorigenesis in metastatic melanoma. On the other hand, silencing ASC in primary melanoma reduced cell death, increased cell viability, and enhanced tumorigenesis. In primary and metastatic melanoma cells, ASC knockdown inhibited inflammasome-mediated caspase-1 activity and IL-1 beta secretion. However, phosphorylated I kappa B kinase (IKK)alpha/beta expression and NF-kappa B activity were suppressed in metastatic melanoma and enhanced in primary melanoma after ASC knockdown. These findings suggest stage-dependent dual roles of ASC in tumorigenesis. ASC expression in primary melanoma inhibits tumorigenesis by reducing IKK alpha/beta phosphorylation and inhibiting NF-kappa B activity. In metastatic melanoma, on the other hand, this inhibitory effect is diminished, and ASC induces tumorigenic pathways through enhanced NF-kappa B activity and inflammasome-mediated IL-1 beta secretion. Journal of Investigative Dermatology (2013) 133, 518-527; doi:10.1038/jid.2012.317; published online 30 August 2012 C1 [Liu, Weimin; Luo, Yuchun; Dunn, Jeffrey H.; Norris, David A.; Fujita, Mayumi] Univ Colorado Denver, Dept Dermatol, Sch Med, Aurora, CO 80045 USA. [Norris, David A.; Fujita, Mayumi] Denver Vet Affairs Med Ctr, Denver, CO USA. [Dinarello, Charles A.] Univ Colorado Denver, Dept Med, Sch Med, Aurora, CO 80045 USA. RP Fujita, M (reprint author), Univ Colorado Denver, Dept Dermatol, Sch Med, Mail Stop 8127,12801 E 17th Ave,RC-1 S,Room 4124, Aurora, CO 80045 USA. EM mayumi.fujita@ucdenver.edu RI Luo, Yuchun/B-8683-2014 FU Veterans Affairs Merit Review Award; US National Institutes of Health [P30CA046934, P30AR057212]; Dermatology Foundation; Wendy Will Case Cancer Fund grant; Cancer League of Colorado; Tadamitsu Cancer Research Fund FX We thank the University of Colorado Denver (UCD) melanoma tissue bank for providing human melanoma samples, the University of Colorado Cancer Center (UCCC) and the Skin Disease Research Center (SDRC) flow core (Alistaire S. Acosta and Karen Helm) for helping with FACS, and IHCtech LLC for helping with immunohistochemical staining. We also thank Xianzhong Meng, MD, PhD (Department of Surgery, UCD), and Advance Light Microscopy Core Facility of UCD for technical support of microscopic analysis, and Manjinder Kaur, PhD (Department of Dermatology, UCD), for critically reviewing the manuscript. This work was supported, in whole or in part, by a Veterans Affairs Merit Review Award (to M.F.), US National Institutes of Health grants P30CA046934 (Flow Core of the UCCC) and P30AR057212 (Flow Core of the SDRC), Dermatology Foundation (to M.F.), Wendy Will Case Cancer Fund grant (to M.F.), Cancer League of Colorado (to M.F.), and Tadamitsu Cancer Research Fund (to M.F.). The funders had no role in study design, data collection, analysis and interpretation, manuscript preparation, or decision to submit the manuscript. NR 17 TC 23 Z9 23 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 2013 VL 133 IS 2 BP 518 EP 527 DI 10.1038/jid.2012.317 PG 10 WC Dermatology SC Dermatology GA 072JU UT WOS:000313668000031 PM 22931929 ER PT J AU Zuckerman, KE Perrin, JM Hobrecker, K Donelan, K AF Zuckerman, Katharine E. Perrin, James M. Hobrecker, Karin Donelan, Karen TI Barriers to Specialty Care and Specialty Referral Completion in the Community Health Center Setting SO JOURNAL OF PEDIATRICS LA English DT Article ID LOW-INCOME PARENTS; CHILD-CARE; DISPARITIES; FAMILIES; SERVICES; ACCESS; NEEDS; TIME AB Objective To assess the frequency of barriers to specialty care and to assess which barriers are associated with an incomplete specialty referral (not attending a specialty visit when referred by a primary care provider) among children seen in community health centers. Study design Two months after their child's specialty referral, 341 parents completed telephone surveys assessing whether a specialty visit was completed and whether they experienced any of 10 barriers to care. Family/community barriers included difficulty leaving work, obtaining childcare, obtaining transportation, and inadequate insurance. Health care system barriers included getting appointments quickly, understanding doctors and nurses, communicating with doctors' offices, locating offices, accessing interpreters, and inconvenient office hours. We calculated barrier frequency and total barriers experienced. Using logistic regression, we assessed which barriers were associated with incomplete referral, and whether experiencing >= 4 barriers was associated with incomplete referral. Results A total of 22.9% of families experienced incomplete referral. 42.0% of families encountered 1 or more barriers. The most frequent barriers were difficulty leaving work, obtaining childcare, and obtaining transportation. On multivariate analysis, difficulty getting appointments quickly, difficulty finding doctors' offices, and inconvenient office hours were associated with incomplete referral. Families experiencing >= 4 barriers were more likely than those experiencing <= 3 barriers to have incomplete referral. Conclusion Barriers to specialty care were common and associated with incomplete referral. Families experiencing many barriers had greater risk of incomplete referral. Improving family/community factors may increase satisfaction with specialty care; however, improving health system factors may be the best way to reduce incomplete referrals. (J Pediatr 2013;162:409-14). C1 [Zuckerman, Katharine E.] Oregon Hlth & Sci Univ, Div Gen Pediat, Child & Adolescent Hlth Measurement Initiat, Mail Code CDRC P, Portland, OR 97239 USA. [Perrin, James M.] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. [Hobrecker, Karin] Massachusetts Gen Hosp, Patient Care Serv, Boston, MA 02114 USA. [Donelan, Karen] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP Zuckerman, KE (reprint author), Oregon Hlth & Sci Univ, Div Gen Pediat, Child & Adolescent Hlth Measurement Initiat, Mail Code CDRC P, 707 SW Gaines St, Portland, OR 97239 USA. EM zuckerma@ohsu.edu FU Controlled Risk Insurance Company-Risk Management Foundation; National Research Service Award from the Health Resources and Services Administration, Department of Health and Human Services [T32 HP10018]; CRICO-Risk Management Foundation FX Supported by a grant from the Controlled Risk Insurance Company-Risk Management Foundation to K.Z. K.Z.'s effort also was partially funded by a National Research Service Award (T32 HP10018) from the Health Resources and Services Administration, Department of Health and Human Services, to the Harvard Pediatric Health Services Research Fellowship. The authors declare no conflicts of interest.; We thank all of the community health center parents, providers, and administrators for their participation in the project. We additionally thank Esteban Barreto, Xin Cai, Gibran Minero, Michelle Connolly, Dianali Rivera, Tara Bryant, and Odeviz Soto for their assistance with data collection. The efforts of E.B., X.C., D.R., T.B., and O.S. were funded by a grant from the CRICO-Risk Management Foundation. NR 22 TC 10 Z9 10 U1 1 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD FEB PY 2013 VL 162 IS 2 BP 409 EP + DI 10.1016/j.jpeds.2012.07.022 PG 7 WC Pediatrics SC Pediatrics GA 071GX UT WOS:000313579900037 PM 22929162 ER PT J AU Di Eusanio, M Trimarchi, S Patel, HJ Hutchison, S Suzuki, T Peterson, MD Di Bartolomeo, R Folesani, G Pyeritz, RE Braverman, AC Montgomery, DG Isselbacher, EM Nienaber, CA Eagle, KA Fattori, R AF Di Eusanio, Marco Trimarchi, Santi Patel, Himanshu J. Hutchison, Stuart Suzuki, Toru Peterson, Mark D. Di Bartolomeo, Roberto Folesani, Gianluca Pyeritz, Reed E. Braverman, Alan C. Montgomery, Daniel G. Isselbacher, Eric M. Nienaber, Christoph A. Eagle, Kim A. Fattori, Rossella TI Clinical presentation, management, and short-term outcome of patients with type A acute dissection complicated by mesenteric malperfusion: Observations from the International Registry of Acute Aortic Dissection SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID STRATEGIES; REPAIR; IRAD AB Background: Few data exist on clinical/imaging characteristics, management, and outcomes of patients with type A acute dissection and mesenteric malperfusion. Methods: Patients with type A acute dissection enrolled in the International Registry for Acute Dissection (IRAD) were evaluated to assess differences in clinical features, management, and in-hospital outcomes according to the presence/absence of mesenteric malperfusion. A mortality model was used to identify predictors of in-hospital mortality in patients with mesenteric malperfusion. Results: Mesenteric malperfusion was detected in 68 (3.7%) of 1809 patients with type A acute dissection. Patients with mesenteric malperfusion were more likely to be older and to have coma, cerebrovascular accident, spinal cord ischemia, acute renal failure, limb ischemia, and any pulse deficit. They were less likely to undergo surgical/hybrid treatment (52.9% vs 87.9%) and more likely to receive only medical (30.9% vs 11.6%) or endovascular (16.2% vs 0.5%) management (P < .001). Overall in-hospital mortality was 63.2% and 23.8% in patients with and without mesenteric malperfusion, respectively (P <. 001). In-hospital mortality of patients with mesenteric malperfusion receiving medical, endovascular, and surgical/hybrid therapy was 95.2%, 72.7%, and 41.7%, respectively (P <. 001). At multivariate analysis, male gender (odds ratio [OR], 1.7; P = .002), age (OR, 1.1/y; P = .002), and renal failure (OR, 5.9; P = .020) were predictors of mortality whereas surgical/hybrid management (OR, 0.1; P = .005) was associated with better outcome. Conclusions: Type A acute aortic dissection complicated by mesenteric malperfusion is a rare but ominous complication carrying a high risk of hospital mortality. Surgical/hybrid therapy, although associated with 2-fold hospital mortality, appears to be associated with better long-term outcomes in the management of type A acute aortic dissection in this setting. (J Thorac Cardiovasc Surg 2013;145:385-90) C1 [Di Eusanio, Marco; Di Bartolomeo, Roberto; Folesani, Gianluca; Fattori, Rossella] Univ Bologna, St Orsola Malpighi Hosp, Dept Cardiovasc Surg, I-40128 Bologna, Italy. [Trimarchi, Santi] IRCCS Policlin San Donato, Cardiovasc Ctr E Malan, San Donato Milanese, Italy. [Patel, Himanshu J.] Univ Michigan, Dept Cardiac Surg, Ann Arbor, MI 48109 USA. [Hutchison, Stuart] Univ Calgary, Med Ctr, Dept Cardiol, Calgary, AB, Canada. [Suzuki, Toru] Univ Tokyo, Tokyo, Japan. [Peterson, Mark D.] St Michaels Hosp, Div Cardiac Surg, Toronto, ON M5B 1W8, Canada. [Pyeritz, Reed E.] Univ Penn, Sch Med, Div Med Genet, Philadelphia, PA 19104 USA. [Braverman, Alan C.] Washington Univ, Sch Med, Div Cardiovasc, St Louis, MO 63110 USA. [Montgomery, Daniel G.; Eagle, Kim A.] Univ Michigan, Dept Cardiol, Ann Arbor, MI 48109 USA. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA. [Nienaber, Christoph A.] Univ Hosp Eppendorf Rostock, Dept Internal Med, Rostock, Germany. RP Di Eusanio, M (reprint author), Univ Bologna, Dept Cardiac Surg, Policlin St Orsola Malpighi, Pad 25,Via Massarenti 9, I-40128 Bologna, Italy. EM marco.dieusanio2@unibo.it RI Trimarchi, Santi/J-7361-2016; OI Trimarchi, Santi/0000-0001-5996-3264; di bartolomeo, roberto/0000-0003-3965-5779 NR 18 TC 41 Z9 43 U1 1 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD FEB PY 2013 VL 145 IS 2 BP 385 EP U417 DI 10.1016/j.jtcvs.2012.01.042 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 071YO UT WOS:000313634700016 PM 22341418 ER PT J AU Haim, H Salas, I Sodroski, J AF Haim, Hillel Salas, Ignacio Sodroski, Joseph TI Proteolytic Processing of the Human Immunodeficiency Virus Envelope Glycoprotein Precursor Decreases Conformational Flexibility SO JOURNAL OF VIROLOGY LA English DT Article ID PROXIMAL EXTERNAL REGION; HUMAN MONOCLONAL-ANTIBODIES; NEUTRALIZING ANTIBODIES; TYPE-1 NEUTRALIZATION; HIV-1 GP120; EPITOPE EXPOSURE; STRUCTURAL BASIS; AIDS PATIENTS; HTLV-III; GP41 AB The mature envelope glycoprotein (Env) spike on the surface of human immunodeficiency virus type 1 (HIV-1) virions is derived by proteolytic cleavage of a trimeric gp160 glycoprotein precursor. Remarkably, proteolytic processing of the HIV-1 Env precursor results in changes in Env antigenicity that resemble those associated with glutaraldehyde fixation. Apparently, proteolytic processing of the HIV-1 Env precursor decreases conformational flexibility of the Env trimeric complex, differentially affecting the integrity/accessibility of epitopes for neutralizing and nonneutralizing antibodies. C1 [Haim, Hillel; Salas, Ignacio; Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Microbiol & Immunob, Boston, MA 02115 USA. [Sodroski, Joseph] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Microbiol & Immunob, 44 Binney St, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU NRSA [NIH T32 AI007386]; National Institutes of Health [AI24755, AI67854, AI060354]; International AIDS Vaccine Initiative FX H.H. was supported by an NRSA postdoctoral training program in AIDS research (NIH T32 AI007386). The National Institutes of Health (AI24755, AI67854, and CFAR award AI060354), the International AIDS Vaccine Initiative, and the late William F. McCarty-Cooper supported this research. NR 73 TC 19 Z9 19 U1 0 U2 12 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 FEB PY 2013 VL 87 IS 3 BP 1884 EP 1889 DI 10.1128/JVI.02765-12 PG 6 WC Virology SC Virology GA 071AR UT WOS:000313558100053 PM 23175369 ER PT J AU Fok, WC Zhang, YQ Salmon, AB Bhattacharya, A Gunda, R Jones, D Ward, W Fisher, K Richardson, A Perez, VI AF Fok, Wilson C. Zhang, Yiqiang Salmon, Adam B. Bhattacharya, Arunabh Gunda, Rakesh Jones, Dean Ward, Walter Fisher, Kathleen Richardson, Arlan Perez, Viviana I. TI Short-Term Treatment With Rapamycin and Dietary Restriction Have Overlapping and Distinctive Effects in Young Mice SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Rapamycin; Dietary restriction; mTOR; Autophagy; Gene expression ID GLUTATHIONE REDOX STATE; GENETICALLY HETEROGENEOUS MICE; EXTENDS LIFE-SPAN; CELL-CYCLE ARREST; CALORIE RESTRICTION; OXIDATIVE STRESS; RAT HEPATOCYTES; MTOR INHIBITION; UREA CYCLE; LONGEVITY AB Because rapamycin, an inhibitor of the nutrient sensor mammalian target of rapamycin, and dietary restriction both increase life span of mice, it has been hypothesized that they act through similar mechanisms. To test this hypothesis, we compared various biological parameters in dietary restriction mice (40% food restriction) and mice fed rapamycin (14 ppm). Both treatments led to a significant reduction in mammalian target of rapamycin signaling and a corresponding increase in autophagy. However, we observed striking differences in fat mass, insulin sensitivity, and expression of cell cycle and sirtuin genes in mice fed rapamycin compared with dietary restriction. Thus, although both treatments lead to significant downregulation of mammalian target of rapamycin signaling, these two manipulations have quite different effects on other physiological functions suggesting that they might increase life span through a common pathway as well as pathways that are altered differently by dietary restriction and rapamycin. C1 [Fok, Wilson C.; Richardson, Arlan; Perez, Viviana I.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Zhang, Yiqiang; Salmon, Adam B.; Bhattacharya, Arunabh; Gunda, Rakesh; Ward, Walter; Fisher, Kathleen; Richardson, Arlan; Perez, Viviana I.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Zhang, Yiqiang; Ward, Walter; Fisher, Kathleen] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Salmon, Adam B.] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Salmon, Adam B.; Richardson, Arlan] S Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX USA. [Jones, Dean] Emory Univ, Sch Med, Dept Med,Clin Biomarkers Lab, Div Pulm Allergy & Crit Care Med, Atlanta, GA USA. RP Perez, VI (reprint author), Oregon State Univ, Dept Biochem & Biophys, Linus Pauling Inst, Linus Pauling Sci Ctr 307, Corvallis, OR 97331 USA. EM viviana.perez@oregonstate.edu OI Fok, Wilson Chun Yim/0000-0003-3289-2093 FU San Antonio Nathan Shock Aging Center [1P30-AG-13319]; National Institutes of Health (NIH) [AG036613]; NIH [AG021890]; Ellison Medical Foundation FX Financial support was provided by The San Antonio Nathan Shock Aging Center (1P30-AG-13319 to A.R.), National Institutes of Health (NIH) RC2 Grand Opportunity grant (AG036613 to A.R.), NIH T32 Training Grant (AG021890 to W.C.F.), and The Ellison Medical Foundation (to V.I.P.). NR 55 TC 21 Z9 21 U1 1 U2 24 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD FEB PY 2013 VL 68 IS 2 BP 108 EP 116 DI 10.1093/gerona/gls127 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 069YW UT WOS:000313474000002 PM 22570137 ER PT J AU Baddley, JW Andes, DR Marr, KA Kauffman, CA Kontoyiannis, DP Ito, JI Schuster, MG Brizendine, KD Patterson, TF Lyon, GM Boeckh, M Oster, RA Chiller, T Pappas, PG AF Baddley, John W. Andes, David R. Marr, Kieren A. Kauffman, Carol A. Kontoyiannis, Dimitrios P. Ito, James I. Schuster, Mindy G. Brizendine, Kyle D. Patterson, Thomas F. Lyon, G. Marshall Boeckh, Michael Oster, Robert A. Chiller, Tom Pappas, Peter G. TI Antifungal therapy and length of hospitalization in transplant patients with invasive aspergillosis SO MEDICAL MYCOLOGY LA English DT Article DE aspergillosis; combination therapy; voriconazole; Aspergillus ID HEMATOPOIETIC STEM-CELL; SURVEILLANCE NETWORK TRANSNET; FUNGAL-INFECTIONS; IMMUNOCOMPROMISED PATIENTS; UNITED-STATES; AMPHOTERICIN-B; MORTALITY; RECIPIENTS; OUTCOMES; COSTS AB The impact of antifungal therapy on economic outcomes in patients with invasive aspergillosis (IA) needs further exploration. The purpose of this study was to describe antifungal therapy and factors associated with hospital length of stay (LOS) in transplant patients with IA. Patients were enrolled from March 2001 to October 2005 and IA cases identified through March 2006 from a sub-group of patients in the Transplant Associated Infection Surveillance Network (TRANSNET). Factors associated with hospital LOS were determined by logistic regression analysis. Of 361 patients, the mean age was 49 years, 60.7% were male, and 63% were hematopoietic stem cell transplantation (HSCT) recipients. Primary monotherapy was used in 233 (64.5%) patients, of which voriconazole (93/233, 39.9%) was most commonly used antifungal. Primary combination therapy was used in 128 (35.4%) of 361 patients, with voriconazole plus caspofungin (81/361, 22.4%) the most frequently employed. Mean duration of therapy was 115 days (HSCT 109.7; solid organ transplant [SOT] 125.3). Mean hospital LOS was 35.3 days (HSCT 38.7; SOT 29.7). Regression analysis identified disseminated IA, neutropenia, malnutrition and length of ICU stay as factors associated with increased hospital LOS. Initial voriconazole use was associated with decreased LOS. Further investigation on impact of antifungal therapy on economic outcomes is needed. C1 [Baddley, John W.] Univ Alabama Birmingham, Div Infect Dis, Dept Med, Birmingham, AL 35294 USA. [Baddley, John W.; Brizendine, Kyle D.; Oster, Robert A.; Pappas, Peter G.] Birmingham VA Med Ctr, Birmingham, AL USA. [Andes, David R.] Univ Wisconsin, Dept Med, Madison, WI USA. [Marr, Kieren A.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Kauffman, Carol A.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Kauffman, Carol A.] Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Dept Med, Houston, TX 77030 USA. [Ito, James I.] City Hope Natl Med Ctr, Dept Med, Los Angeles, CA USA. [Schuster, Mindy G.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Patterson, Thomas F.] S Texas Vet Healthcare Syst, San Antonio, TX USA. [Lyon, G. Marshall] Emory Univ, Dept Med, Atlanta, GA 30322 USA. [Boeckh, Michael] Fred Hutchinson Canc Res Ctr, Dept Med, Seattle, WA 98104 USA. [Chiller, Tom] Ctr Dis Control, Mycot Dis Branch, Atlanta, GA 30333 USA. RP Baddley, JW (reprint author), Univ Alabama Birmingham, Div Infect Dis, Dept Med, 1900 Univ Blvd,229 Tinsley Harrison Tower, Birmingham, AL 35294 USA. EM jbaddley@uab.edu FU Centers for Disease Control (CDC); Astellas; Pfizer; Merck; Schering Plough; NIH [K23AI064613, K24AI085118]; Schering-Plough; Astella Pharma Inc.; Enzon Pharmaceuticals; Merck and Co., Inc.; Basilea; Qiagen; T2 Biosystems FX TRANSNET was sponsored by the Centers for Disease Control (CDC), Astellas, Pfizer, Merck, and Schering Plough. Pfizer sponsored additional treatment data collection. The findings and conclusions in this article are those of the authors and do not necessarily represent the views of the Centers of Disease Control and Prevention.; JWB was sponsored in part by NIH K23AI064613. He is on the advisory board or consulting for Pfizer and Merck. DRA receives research grants from Merck, Astellas and Pfizer and is a consultant for Astellas, Novartis, Merck, Schering Plough. KAM is sponsored in part by NIH K24AI085118 and receives research grants from Merck, Astellas and Pfizer. He is on the advisory board or consulting for Astellas, Basilea, Merck, Pfizer, Schering Plough. CAK receives research grants from Merck and is on the data adjudication Board, Pfizer, and the Data Safety Monitoring Board, Merck. DPK has received research support and honoraria from Schering-Plough, Pfizer, Astella Pharma Inc., Enzon Pharmaceuticals, and Merck and Co., Inc. JII is on the speakers' bureaux for Astellas, Enzon, Merck, Pfizer, Schering-Plough and is a consultant for Enzon, Sigma Tau. TFP receives research grants from Astellas, Basilea, Merck, Pfizer and Schering-Plough and is on the advisory boards or consulting for Astellas, Basilea, Merck, Pfizer and Toyoma. GML is on the advisory board for Merck and receives research funding from Pfizer, Astellas and Qiagen. PGP receives research support and is an ad hoc advisor for Merck, Pfizer, Astellas, Basilea and T2 Biosystems. The remaining authors have no conflicts of interest for this subject matter. The authors alone are responsible for the content and writing of the paper. NR 20 TC 13 Z9 14 U1 2 U2 9 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD FEB PY 2013 VL 51 IS 2 BP 128 EP 135 DI 10.3109/13693786.2012.690108 PG 8 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 072MQ UT WOS:000313676100003 PM 22680976 ER PT J AU Li, XJ Uemura, K Hashimoto, T Nasser-Ghodsi, N Arimon, M Lill, CM Palazzolo, I Krainc, D Hyman, BT Berezovska, O AF Li, Xuejing Uemura, Kengo Hashimoto, Tadafumi Nasser-Ghodsi, Navine Arimon, Muriel Lill, Christina M. Palazzolo, Isabella Krainc, Dimitri Hyman, Bradley T. Berezovska, Oksana TI Neuronal activity and secreted amyloid beta lead to altered amyloid beta precursor protein and presenilin 1 interactions SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Alzheimer's disease; Presenilin 1; Amyloid beta precursor protein; FLIM (fluorescence lifetime imaging microscopy); Neuronal activity ID ALZHEIMERS-DISEASE; SYNAPTIC PLASTICITY; ALPHA-SECRETASE; A-BETA; IN-VIVO; ACTIVATION; PROMOTES; PEPTIDE; CONFORMATION; DEPOSITION AB Deposition of amyloid beta (A beta) containing plaques in the brain is one of the neuropathological hallmarks of Alzheimer's disease (AD). It has been suggested that modulation of neuronal activity may alter A beta production in the brain. We postulate that these changes in A beta production are due to changes in the rate-limiting step of A beta generation, APP cleavage by gamma-secretase. By combining biochemical approaches with fluorescence lifetime imaging microscopy, we found that neuronal inhibition decreases endogenous APP and PSI interactions, which correlates with reduced A beta production. By contrast, neuronal activation had a two-phase effect: it initially enhanced APP-PS1 interaction leading to increased A beta production, which followed by a decrease in the APP and PS1 proximity/interaction. Accordingly, treatment of neurons with naturally secreted A beta isolated from AD brain or with synthetic A beta resulted in reduced APP and PS1 proximity. Moreover, applying low concentration of A beta(42) to cultured neurons inhibited de novo A beta synthesis. These data provide evidence that neuronal activity regulates endogenous APP-PSI interactions, and suggest a model of a product-enzyme negative feedback. Thus, under normal physiological conditions A beta may impact its own production by modifying gamma-secretase cleavage of APP. Disruption of this negative modulation may cause A beta overproduction leading to neurotoxicity. (C) 2012 Elsevier Inc. All rights reserved. C1 [Li, Xuejing; Hashimoto, Tadafumi; Nasser-Ghodsi, Navine; Arimon, Muriel; Palazzolo, Isabella; Krainc, Dimitri; Hyman, Bradley T.; Berezovska, Oksana] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurobiol Alzheimers Dis Lab, Charlestown, MA 02129 USA. [Uemura, Kengo] Kyoto Univ, Grad Sch Med, Dept Neurol, Kyoto 6068507, Japan. [Lill, Christina M.] Johannes Gutenberg Univ Mainz, Dept Neurol, D-55122 Mainz, Germany. RP Berezovska, O (reprint author), Dept Neurol, Alzheimer Unit, 114-16th St, Charlestown, MA 02129 USA. EM oberezovska@partners.org RI Arimon, Muriel/I-4054-2015; Lill, Christina/J-9449-2015 OI Arimon, Muriel/0000-0002-0894-3324; Lill, Christina/0000-0002-2805-1307 FU National Institutes of Health [AG015379]; Deutscher Akademischer Austauschdienst (DAAD) FX This work was supported by National Institutes of Health Grant AG015379 (B.T.H., O.B.), and fellowship from the Deutscher Akademischer Austauschdienst (DAAD) to CML. NR 34 TC 5 Z9 5 U1 1 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD FEB PY 2013 VL 50 BP 127 EP 134 DI 10.1016/j.nbd.2012.10.002 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 073QR UT WOS:000313758100014 PM 23064434 ER PT J AU Conforti, P Camnasio, S Mutti, C Valenza, M Thompson, M Fossale, E Zeitlin, S MacDonald, ME Zuccato, C Cattaneo, E AF Conforti, Paola Camnasio, Stefano Mutti, Cesare Valenza, Marta Thompson, Morgan Fossale, Elisa Zeitlin, Scott MacDonald, Marcy E. Zuccato, Chiara Cattaneo, Elena TI Lack of huntingtin promotes neural stem cells differentiation into glial cells while neurons expressing huntingtin with expanded polyglutamine tracts undergo cell death SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Huntington's disease; Neuronal differentiation; polyQ; Mouse knock-in neural stem cells ID DISEASE GENE HOMOLOG; KNOCK-IN MOUSE; MUTANT HUNTINGTIN; NS CELLS; NEUROTROPHIC FACTOR; STRIATAL CELLS; BDNF LEVELS; MODEL; REPEAT; TRANSCRIPTION AB Huntington's disease (HD) is a neurodegenerative disorder that affects muscle coordination and diminishes cognitive abilities. The genetic basis of the disease is an expansion of CAG repeats in the Huntingtin (Htt) gene. Here we aimed to generate a series of mouse neural stem (NS) cell lines that carried varying numbers of CAG repeats in the mouse Htt gene (Hdh CAG knock-in NS cells) or that had Hdh null alleles (Hdh knock-out NS cells). Towards this end, Hdh CAG knock-in mouse ES cell lines that carried an Htt gene with 20, 50, 111, or 140 CAG repeats or that were Htt null were neuralized and converted into self-renewing NS cells. The resulting NS cell lines were immunopositive for the neural stem cell markers NESTIN, SOX2, and BLBP and had similar proliferative rates and cell cycle distributions. After 14 days in vitro, wild-type NS cells gave rise to cultures composed of 70% MAP2(+) neurons and 30% GFAP(+) astrocytes. In contrast, NS cells with expanded CAG repeats underwent neuronal cell death, with only 38% +/- 15% of the MAP2(+) cells remaining at the end of the differentiation period. Cell death was verified by increased caspase 3/7 activity on day 14 of the neuronal differentiation protocol. Interestingly, Hdh knock-out NS cells treated using the same neuronal differentiation protocol showed a dramatic increase in the number of GFAP(+) cells on day 14 (61% +/- 20% versus 24% +/- 10% in controls), and a massive decrease of MAP2(+) neurons (30% +/- 11% versus 64% +/- 17% in controls). Both Hdh CAG knock-in NS cells and Hdh knock-out NS cells showed reduced levels of Bdnf mRNA during neuronal differentiation, in agreement with data obtained previously in HD mouse models and in post-mortem brain samples from HD patients. We concluded that Hdh CAG knock-in and Hdh knock-out NS cells have potential as tools for investigating the roles of normal and mutant HTT in differentiated neurons and glial cells of the brain. (C) 2012 Elsevier Inc. All rights reserved. C1 [Conforti, Paola; Camnasio, Stefano; Mutti, Cesare; Valenza, Marta; Zuccato, Chiara; Cattaneo, Elena] Univ Milan, Ctr Stem Cell Res, I-20113 Milan, Italy. [Thompson, Morgan; Fossale, Elisa; MacDonald, Marcy E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Zeitlin, Scott] Univ Virginia, Sch Med, Dept Neurosci, Charlottesville, VA 22908 USA. RP Cattaneo, E (reprint author), Univ Milan, Ctr Stem Cell Res, Via Balzaretti 9, I-20113 Milan, Italy. EM elena.cattaneo@unimi.it OI CATTANEO, ELENA/0000-0002-0755-4917; ZUCCATO, CHIARA/0000-0003-1771-3392; VALENZA, MARTA/0000-0002-7048-9257 FU STEM-HD (EU-FP6); Fondazione Cariplo (Italy); NIH [NINDS 32765]; Huntington's Disease Society of America Coalition for the Cure (Normal Huntingtin Function Team) FX This research was supported in part by STEM-HD (EU-FP6) and Fondazione Cariplo (Italy) and by NIH grant NINDS 32765 and, in its inception, the Huntington's Disease Society of America Coalition for the Cure (Normal Huntingtin Function Team). We acknowledge the contribution of Unicredit Banca S.p.A. (Italy) and Tavola Valdese (Italy). NR 59 TC 14 Z9 15 U1 0 U2 32 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 EI 1095-953X J9 NEUROBIOL DIS JI Neurobiol. Dis. PD FEB PY 2013 VL 50 BP 160 EP 170 DI 10.1016/j.nbd.2012.10.015 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 073QR UT WOS:000313758100018 PM 23089356 ER PT J AU Schacht, JP Anton, RF Voronin, KE Randall, PK Li, XB Henderson, S Myrick, H AF Schacht, Joseph P. Anton, Raymond F. Voronin, Konstantin E. Randall, Patrick K. Li, Xingbao Henderson, Scott Myrick, Hugh TI Interacting Effects of Naltrexone and OPRM I and DAT I Variation on the Neural Response to Alcohol Cues SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE alcoholism; opioid antagonist; functional neuroimaging; SNP; VNTR ID OPIOID RECEPTOR GENE; DOPAMINE TRANSPORTER GENE; CLINICAL LABORATORY PARADIGM; NUCLEUS-ACCUMBENS; VENTRAL STRIATUM; 3'-UNTRANSLATED REGION; DEPENDENT SUBJECTS; SOCIAL DRINKERS; VARIABLE NUMBER; HEAVY DRINKERS AB Variation at a single nucleotide polymorphism in the mu-opioid receptor gene (OPRM I), Al 18G (Asn40Asp), may moderate naltrexone (NTX) effects in alcohol dependence. Both NTX and Al 18G variation have also been reported to affect alcohol cue-elicited brain activation. This study investigated whether sub-acute NTX treatment and Al 18G genotype interacted in their effects on cue-elicited activation of the ventral striatum (VS), medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC). Secondarily, variation at a variable number tandem repeat polymorphism in the dopamine transporter gene (DAT I/SLC6A3), which has been associated with increased reward-related activation in VS, was analyzed as a moderator of medication and Al 18G effects. Seventy-four non-treatment-seeking alcohol-dependent individuals, half preselected to carry at least one copy of the Al 18G G (Asp) allele, were randomized to NTX (50 mg) or placebo for 7 days, and performed an fMRI alcohol cue reactivity task on day 6. Region-of-interest analyses indicated no main effects of medication or Al 18G genotype. However, these factors interacted in their effects on OFC activation, such that, among NTX-treated individuals, G-allele carriers had less activation than A-allele homozygotes. DAT I variation also moderated medication/Al 18G effects. There was a three-way interaction between medication and Al 18G and DAT I genotypes on VS activation, such that, among G-allele carriers who received NTX, DATI 10-repeat-allele (10R) homozygotes had less activation than 9-repeat-allele (9R) carriers. Further, IOR homozygotes who received NIX had less mPFC activation than 9R carriers. Polymorphic variation in OPRM I and DATI should be considered in future studies of NTX, particularly regarding its effects on reward processing. Neuropsychopharmacology (2013) 38, 414-422; doi:10.1038/npp.2012.195; published online 3 October 2012 C1 [Schacht, Joseph P.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Ctr Drug & Alcohol Programs, Charleston, SC 29425 USA. [Myrick, Hugh] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Schacht, JP (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Ctr Drug & Alcohol Programs, MSC 861, Charleston, SC 29425 USA. EM schacht@musc.edu FU National Institute on Alcohol Abuse and Alcoholism (the Charleston Alcohol Research Center) [P50 AA010761, T32 AA007474, K05 AA017435]; Eli Lilly; Schering Plough; Lundbeck; Alkermes; GlaxoSmithKline; Johnson Johnson; Abbott Laboratories; Merck; NIDA FX This work was supported by grants from the National Institute on Alcohol Abuse and Alcoholism: P50 AA010761 (the Charleston Alcohol Research Center), T32 AA007474 (to Dr Schacht), and K05 AA017435 (to Dr Anton). Portions were presented in a symposium at the 35th Annual Meeting of the Research Society on Alcoholism (June, 2012, San Francisco, CA).; Dr Anton reports as being a consultant or on the scientific advisory board for Eli Lilly, GlaxoSmithKline, Alkermes, Lundbeck, and Roche for the past 3 years. Additionally, as part of the Alcohol Clinical Trials Initiative workgroup (ACTIVE), he has received support from Eli Lilly, Schering Plough, Lundbeck, Alkermes, GlaxoSmithKline, Johnson & Johnson, and Abbott Laboratories. He has also received research contracts/grants from Eli Lilly and Merck. He is a stockholder in Alcomed, which has received Small Business Technology Transfer Research support from NIDA. Dr Myrick reports serving on speakers' bureaus for Bristol-Myers Squibb and Alkermes. All other authors declare no conflict of interest. NR 65 TC 33 Z9 33 U1 8 U2 22 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD FEB PY 2013 VL 38 IS 3 BP 414 EP 422 DI 10.1038/npp.2012.195 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 073VK UT WOS:000313771000005 PM 23032071 ER PT J AU Theodoroff, SM Folmer, RL AF Theodoroff, Sarah M. Folmer, Robert L. TI Repetitive Transcranial Magnetic Stimulation as a Treatment for Chronic Tinnitus: A Critical Review SO OTOLOGY & NEUROTOLOGY LA English DT Review DE Repetitive transcranial magnetic stimulation; Tinnitus; Transcranial magnetic stimulation ID POSTTRAUMATIC-STRESS-DISORDER; DORSAL COCHLEAR NUCLEUS; LOW-FREQUENCY RTMS; AUDITORY-CORTEX; PREMOTOR CORTEX; NEURAL ACTIVITY; MOTOR CORTEX; FOLLOW-UP; SUPPRESSION; DEPRESSION AB Objective: Because chronic tinnitus is a condition that negatively impacts the quality of life for millions of people worldwide, a safe and effective treatment for tinnitus has been sought for decades. However, a true "cure'' for the most common causes of tinnitus remains elusive. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive procedure, has shown potential for reducing patients' perception or severity of tinnitus. This article provides background information about rTMS and reviews studies that investigated rTMS as a treatment for chronic tinnitus. Data Sources: PubMed and Medline databases (National Center for Biotechnology Information, U.S. National Library of Medicine) were searched for the terms repetitive transcranial magnetic stimulation, tinnitus, TMS, and rTMS in articles published from 1980 to 2012. Study Selection: Articles included in this review were selected to represent a sampling of rTMS methodologies that have been used with tinnitus patients. Data Extraction: Data extraction included sample size, TMS stimulation frequency, TMS stimulation intensity, number of pulses administered per session, number of TMS sessions, and method of tinnitus assessment. Data Synthesis: Because of the heterogeneity of the studies reviewed, most of which had small populations of subjects, it was not appropriate to perform a meta-analysis. A systematic review of the literature was conducted to summarize and critique published research results. Conclusion: Although optimism for the clinical use of rTMS as an effective treatment for tinnitus remains high among many researchers, clinicians, and patients, several key questions and procedural issues remain unresolved. Suggestions for improving rTMS research protocols are described and discussed. C1 [Theodoroff, Sarah M.; Folmer, Robert L.] Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Portland, OR 97239 USA. [Theodoroff, Sarah M.; Folmer, Robert L.] Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA. RP Folmer, RL (reprint author), Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, 3710 SWUS Vet Hosp Rd NCRAR, Portland, OR 97239 USA. EM Robert.Folmer@va.gov FU U.S. Department of Veterans Affairs Rehabilitation Research and Development (RRD) Service; National Center for Rehabilitative Auditory Research at Portland VA Medical Center FX This research was supported by a grant from the U.S. Department of Veterans Affairs Rehabilitation Research and Development (RR&D) Service. Additional support was provided by the National Center for Rehabilitative Auditory Research at Portland VA Medical Center. NR 78 TC 20 Z9 24 U1 6 U2 39 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD FEB PY 2013 VL 34 IS 2 BP 199 EP 208 DI 10.1097/MAO.0b013e31827b4d46 PG 10 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 073YH UT WOS:000313778500004 PM 23444467 ER PT J AU Milojcic, R Guinan, JJ Rauch, SD Herrmann, BS AF Milojcic, Rupprecht Guinan, John J., Jr. Rauch, Steven D. Herrmann, Barbara S. TI Vestibular Evoked Myogenic Potentials in Patients With Superior Semicircular Canal Dehiscence SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Superior semicircular canal dehiscence; Vestibular evoked myogenic potential; Air bone gap ID AIR-BONE GAP; TULLIO PHENOMENON; HYPERSENSITIVITY; VERTIGO; SOUND AB Objective: To compare the audiometric and cervical vestibular evoked muscle potential (cVEMP) outcomes of ears with superior canal dehiscence (SSCD) to outcomes from normal ears and the unaffected ears of unilateral SSCD patients. Study Design: Retrospective review of clinical testing outcomes. Setting: Tertiary care specialty teaching hospital. Patients: Three subject groups were used: 21 ears of healthy subjects, ages 21 to 52 years; 58 affected SSCD ears in patients, ages 15 to 65 years; and 26 unaffected ears of unilateral SSCD patients, ages 15 to 65 years. Main Outcome Measure: Results of pure-tone audiometry and cervical vestibular evoked muscle potential (cVEMP) testing. Results: SSCD ears differed from normal ears or unaffected ears of unilateral SSCD patients in 2 ways: 1) they had significantly larger air-bone gaps at 250 and 500 Hz, resulting in poorer air-conduction thresholds at those frequencies, and 2) their cVEMP thresholds at 500 Hz were significantly lower. When the cVEMP threshold was adjusted for the size of the air-bone gap on the audiogram, cVEMP thresholds were significantly lower for 250-, 500-, and 1,000-Hz tone bursts compared with the other subject groups. Logistic regression indicated that the probability of predicting SSCD from the cVEMP thresholds was significant. cVEMP tuning was unaffected by SSCD. Conclusion: Combining 2 features associated with SSCD, the presence of an air-bone gap and the lower cVEMP threshold, into one variable, an adjusted cVEMP threshold, better separated SSCD ears from normal or unaffected SSCD ears. A probability predictive function from logistic regression of the adjusted cVEMP may be clinically applicable. C1 [Milojcic, Rupprecht; Guinan, John J., Jr.; Rauch, Steven D.; Herrmann, Barbara S.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Herrmann, Barbara S.] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. [Milojcic, Rupprecht; Rauch, Steven D.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Guinan, John J., Jr.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Milojcic, Rupprecht] Univ Erlangen Nurnberg, Dept Otorhinolaryngol Head & Neck Surg, Bavaria, Germany. RP Herrmann, BS (reprint author), Massachusetts Eye & Ear Infirm, Dept Audiol, 243 Charles St, Boston, MA 02114 USA. EM barbara_herrmann@meei.harvard.edu NR 25 TC 6 Z9 6 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD FEB PY 2013 VL 34 IS 2 BP 360 EP 367 DI 10.1097/MAO.0b013e31827b4fb5 PG 8 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 073YH UT WOS:000313778500027 PM 23444482 ER PT J AU Berthold, HK Berneis, K Mantzoros, CS Krone, W Gouni-Berthold, I AF Berthold, Heiner K. Berneis, Kaspar Mantzoros, Christos S. Krone, Wilhelm Gouni-Berthold, Ioanna TI Effects of simvastatin and ezetimibe on interleukin-6 and high-sensitivity C-reactive protein SO SCANDINAVIAN CARDIOVASCULAR JOURNAL LA English DT Article DE anti-inflammatory effects; ezetimibe; high-sensitivity C-reactive protein; interleukin-6; pleiotropic effects; simvastatin; statins ID LOW-DENSITY-LIPOPROTEIN; RANDOMIZED-TRIAL; HEALTHY-MEN; AND/OR SIMVASTATIN; CHOLESTEROL; COMBINATION; DISEASE; LDL; HYPERCHOLESTEROLEMIA; ATORVASTATIN AB Objectives. Statins decrease cardiovascular events mainly by lowering cholesterol but anti-inflammatory effects also play a role. The effects of the cholesterol absorption inhibitor ezetimibe on markers of inflammation remain unclear. We performed an exploratory post-hoc analysis whether these drugs influence the pro-inflammatory markers interleukin-6 and high-sensitivity C-reactive protein in subjects with very-low cardiovascular risk. Design. Single center, randomized, parallel 3-group study in 72 healthy men without apparent cardiovascular disease (age 32 +/- 9 years, BMI 25.7 +/- 3.2 kg/m(2)). Each group of 24 subjects received a 14-day treatment with either simvastatin 40 mg, ezetimibe 10 mg, or their combination. Results. Baseline IL-6 and hsCRP concentrations in the total cohort were 0.72 +/- 0.57 ng/l and 0.40 +/- 0.65 mg/l, respectively, with no differences between the 3 groups. Median changes (interquartile range) in IL-6 and hsCRP concentrations were -22% (-43 to 0%) and -30% (-44 to +19%) after simvastatin, -5% (-36 to +30%) and +9% (-22 to +107%) after ezetimibe, and +15% (-15 to +86%) and +1 (-30 to +49%) after the combination. Using a generalized linear model, the multivariable adjusted overall P-values for these changes were 0.008 (IL-6) and 0.1 (hsCRP). Conclusions. Simvastatin decreases the pro-inflammatory markers IL-6 and almost significantly hsCRP while ezetimibe monotherapy or the combination with simvastatin has no effect. C1 [Berthold, Heiner K.] Charite Univ Med Berlin, Evangel Geriatr Ctr Berlin EGZB, D-13347 Berlin, Germany. [Berthold, Heiner K.] Charite Univ Med Berlin, Lipid Clin, Interdisciplinary Metab Ctr, D-13347 Berlin, Germany. [Berneis, Kaspar] Univ Zurich Hosp, Div Endocrinol Diabet & Clin Nutr, CH-8091 Zurich, Switzerland. [Mantzoros, Christos S.] Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA USA. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Beth Israel Med Ctr, Boston, MA USA. [Mantzoros, Christos S.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Krone, Wilhelm; Gouni-Berthold, Ioanna] Univ Cologne, Ctr Endocrinol Diabet & Prevent Med, D-50931 Cologne, Germany. RP Berthold, HK (reprint author), Charite Univ Med Berlin, Evangel Geriatr Ctr Berlin EGZB, Reinickendorfer Str 61, D-13347 Berlin, Germany. EM heiner.berthold@charite.de RI Berthold, Heiner/E-6017-2011 OI Berthold, Heiner/0000-0002-1457-2216 FU Bayer Health Care; MSD Sharp & Dohme (Munich, Germany); Wilhelm-Doerenkamp Foundation (Cologne, Germany) FX W.K. has served on advisory boards of MSD Sharp & Dohme/Essex and has received consultation honoraria from Pfizer, Bayer and Astra-Zeneca. I. G. B. has received research grants from Bayer Health Care and honoraria and travel expenses from Genzyme, MSD Sharp & Dohme, Novartis and Otsuka. None of the other authors have 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. No writing assistance was utilized in the production of this manuscript. The authors alone are responsible for the content and writing of the paper.; The parent trial (10) was supported in part by an investigator-initiated grant from MSD Sharp & Dohme (Munich, Germany) and the Wilhelm-Doerenkamp Foundation (Cologne, Germany). The present study was sponsored by the Wilhelm-Doerenkamp Foundation (Cologne, Germany). The sponsors had neither an influence on design and conduct of the study, collection and interpretation of the data nor on the preparation of the manuscript. NR 30 TC 4 Z9 4 U1 0 U2 11 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1401-7431 J9 SCAND CARDIOVASC J JI Scand. Cardiovasc. J. PD FEB PY 2013 VL 47 IS 1 BP 20 EP 27 DI 10.3109/14017431.2012.734635 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 072NK UT WOS:000313678500003 PM 23013513 ER PT J AU Knoll, BM Hellmann, M Kotton, CN AF Knoll, Bettina M. Hellmann, Matt Kotton, Camille N. TI Vancomycin-resistant Enterococcus faecium meningitis in adults: Case series and review of the literature SO SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES LA English DT Review DE Vancomycin-resistant Enterococcus faecium; meningitis ID GRAM-POSITIVE COCCI; INTRAVENTRICULAR QUINUPRISTIN/DALFOPRISTIN; QUINUPRISTIN-DALFOPRISTIN; SHUNT INFECTION; DAPTOMYCIN; COMBINATION; THERAPY AB Background: Vancomycin-resistant Enterococcus faecium (VR E. faecium) is a rare cause of meningitis and is associated with substantial mortality. Limited therapeutic options are available for the treatment of VR E. faecium meningitis. The optimum therapy has not been established. Methods: We retrospectively identified adult cases of meningitis due to VR E. faecium that occurred at the Massachusetts General Hospital from 1999 to 2011 and performed a literature search for published adult cases using Medline and Embase. Results: At our institution, 4 cases of meningitis due to VR E. faecium were identified. Three out of our 4 cases were successfully treated with linezolid in combination with rifampicin, or with daptomycin in combination with quinupristin - dalfopristin (QD), and 1 out of 4 with linezolid monotherapy. The literature search yielded 18 cases published to date. Published cases showed bacterial cure with linezolid, chloramphenicol or QD (intravenous (IV) and intrathecal (IT)) monotherapy, or linezolid in combination with ampicillin, gentamicin, rifampicin or chloramphenicol, or daptomycin in combination with gentamicin or QD. Conclusions: Bacterial cure of meningitis due to VR E. faecium can be achieved with various antimicrobial drugs used as monotherapy or in combination. IT in addition to IV therapy should be considered dependent on the pharmacological properties of the drugs. We also reported the successful treatment of a case with a vancomycin-resistant, linezolid-intermediate isolate with QD and daptomycin. The paucity of cases with this clinical syndrome does not allow the identification of an optimal treatment regimen. C1 [Knoll, Bettina M.; Kotton, Camille N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Infect Dis Div, Dept Transplant & Immunocompromised Host Infect D, Boston, MA 02114 USA. [Hellmann, Matt] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. RP Knoll, BM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Infect Dis Div, Dept Transplant & Immunocompromised Host Infect D, 55 Fruit St,Cox 5, Boston, MA 02114 USA. EM bknoll@partners.org NR 33 TC 8 Z9 11 U1 1 U2 8 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0036-5548 J9 SCAND J INFECT DIS JI Scand. J. Infect. Dis. PD FEB PY 2013 VL 45 IS 2 BP 131 EP 139 DI 10.3109/00365548.2012.717711 PG 9 WC Infectious Diseases SC Infectious Diseases GA 072MZ UT WOS:000313677200008 PM 22992165 ER PT J AU Smith, BL AF Smith, Barbara L. TI Neoadjuvant Versus Adjuvant Systemic Therapy for Operable Breast Cancer Equivalent Outcomes? SO ANNALS OF SURGERY LA English DT Editorial Material ID PREOPERATIVE CHEMOTHERAPY; B-18 C1 Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. RP Smith, BL (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, 55 Fruit St, Boston, MA 02114 USA. EM blsmith1@partners.org NR 7 TC 4 Z9 5 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD FEB PY 2013 VL 257 IS 2 BP 180 EP 181 DI 10.1097/SLA.0b013e318280a688 PG 2 WC Surgery SC Surgery GA 068IX UT WOS:000313361300002 PM 23291659 ER PT J AU Lin, PY Roche-Labarbe, N Dehaes, M Fenoglio, A Grant, PE Franceschini, MA AF Lin, Pei-Yi Roche-Labarbe, Nadege Dehaes, Mathieu Fenoglio, Angela Grant, P. Ellen Franceschini, Maria Angela TI Regional and Hemispheric Asymmetries of Cerebral Hemodynamic and Oxygen Metabolism in Newborns SO CEREBRAL CORTEX LA English DT Article DE brain development; cerebral asymmetry; diffuse correlation spectroscopy; near-infrared spectroscopy; newborns ID NEAR-INFRARED SPECTROSCOPY; DIFFUSE CORRELATION SPECTROSCOPY; POSITRON-EMISSION-TOMOGRAPHY; BLOOD-FLOW; FREQUENCY-DOMAIN; PRETERM INFANTS; OPTICAL-PROPERTIES; BRAIN-DEVELOPMENT; NEONATAL BRAIN; SEXUAL-DIMORPHISM AB Understanding the evolution of regional and hemispheric asymmetries in the early stages of life is essential to the advancement of developmental neuroscience. By using 2 noninvasive optical methods, frequency-domain near-infrared spectroscopy and diffuse correlation spectroscopy, we measured cerebral hemoglobin oxygenation (SO2), blood volume (CBV), an index of cerebral blood flow (CBFi), and the metabolic rate of oxygen (CMRO2i) in the frontal, temporal, and parietal regions of 70 premature and term newborns. In concordance with results obtained using more invasive imaging modalities, we verified both hemodynamic (CBV, CBFi, and SO2) and metabolic (CMRO2i) parameters were greater in the temporal and parietal regions than in the frontal region and that these differences increased with age. In addition, we found that most parameters were significantly greater in the right hemisphere than in the left. Finally, in comparing age-matched males and females, we found that males had higher CBFi in most cortical regions, higher CMRO2i in the frontal region, and more prominent right-left CBFi asymmetry. These results reveal, for the first time, that we can detect regional and hemispheric asymmetries in newborns using noninvasive optical techniques. Such a bedside screening tool may facilitate early detection of abnormalities and delays in maturation of specific cortical areas. C1 [Lin, Pei-Yi; Roche-Labarbe, Nadege; Franceschini, Maria Angela] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Opt Div,Athinoula Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Lin, Pei-Yi] Natl Cheng Kung Univ, Dept Biomed Engn, Tainan 70101, Taiwan. [Dehaes, Mathieu; Fenoglio, Angela; Grant, P. Ellen] Harvard Univ, Sch Med, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Childrens Hosp Boston, Boston, MA 02115 USA. RP Franceschini, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Opt Div,Athinoula Martinos Ctr Biomed Imaging, Bldg 149,13th St, Boston, MA 02129 USA. EM mari@nmr.mgh.harvard.edu RI Roche-Labarbe, Nadege/N-9101-2015 OI Roche-Labarbe, Nadege/0000-0002-5010-0400 FU National Institute of Health [R01-HD042908, R21-HD058725, P41-RR14075]; National Science council of Republic of China [NSC 100-2321-B-006 -018]; Clinical Translational Science Award [UL1RR025758] FX National Institute of Health (R01-HD042908, R21-HD058725, and P41-RR14075) and National Science council of Republic of China (NSC 100-2321-B-006 -018 to P.-Y.L.); We thank Marcia Kocienski-Filip for her assistance during measurements, which is supported by the Clinical Translational Science Award UL1RR025758 to Harvard University and Brigham and Women's Hospital from the National Center for Research Resources. We thank Bruce Rosen, David Boas, Maddy Artunduaga, Alpna Aggarwal, Sarah M. Barnett, Kalpathy S. Krishnamoorthy, Linda J. Van Marter, Robert M. Insoft, Jonathan H. Cronin, Elizabeth A. Warren, and the neonatal intensive care units staff for help and support on the project. We thank Dr George Cowan for guidance in pursuing this project. We also thank Gary Boas for editing the manuscript. 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. Conflict of Interest : None declared. NR 81 TC 15 Z9 16 U1 4 U2 18 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD FEB PY 2013 VL 23 IS 2 BP 339 EP 348 DI 10.1093/cercor/bhs023 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 070RX UT WOS:000313529600010 PM 22328446 ER PT J AU Caronia, LM Dwyer, AA Hayden, D Amati, F Pitteloud, N Hayes, FJ AF Caronia, Lisa M. Dwyer, Andrew A. Hayden, Douglas Amati, Francesca Pitteloud, Nelly Hayes, Frances J. TI Abrupt decrease in serum testosterone levels after an oral glucose load in men: implications for screening for hypogonadism SO CLINICAL ENDOCRINOLOGY LA English DT Article ID SEX-HORMONES; INSULIN SENSITIVITY; LUTEINIZING-HORMONE; PLASMA LEPTIN; HEALTHY-MEN; SECRETION; RESPONSES; INHIBITION; RESISTANCE; PITUITARY AB Objective This study examines the physiological impact of a glucose load on serum testosterone (T) levels in men with varying glucose tolerance (GT). Design Cross-sectional study. Patients and Methods 74 men (1974 years, mean 51.4 +/- 1.4 years) underwent a standard 75-g oral glucose tolerance test with blood sampling at 0, 30, 60, 90 and 120 min. Fasting serum glucose, insulin, total T (and calculated free T), LH, SHBG, leptin and cortisol were measured. Results 57% of the men had normal GT, 30% had impaired GT and 13% had newly diagnosed type 2 diabetes. Glucose ingestion was associated with a 25% decrease in mean T levels (delta = -4.2 +/- 0.3 nm, P < 0.0001). T levels remained suppressed at 120 min compared with baseline (13.7 +/- 0.6 vs 16.5 +/- 0.7 nm, P < 0.0001) and did not differ across GT or BMI. Of the 66 men with normal T levels at baseline, 10 (15%) had levels that decreased to the hypogonadal range (<9.7 nm) at one or more time points. SHBG, LH and cortisol levels were unchanged. Leptin levels decreased from baseline at all time points (P < 0.0001). Conclusions Glucose ingestion induces a significant reduction in total and free T levels in men, which is similar across the spectrum of glucose tolerance. This decrease in T appears to be because of a direct testicular defect, but the absence of compensatory changes in LH suggests an additional central component. Men found to have low nonfasting T levels should be re-evaluated in the fasting state. C1 [Caronia, Lisa M.] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. [Dwyer, Andrew A.; Pitteloud, Nelly] CHU Vaudois, Endocrinol Diabet & Metab Serv, CH-1011 Lausanne, Switzerland. [Hayden, Douglas] Massachusetts Gen Hosp, Gen Clin Res Ctr, Dept Biostat, Boston, MA 02114 USA. [Amati, Francesca] Univ Lausanne, Dept Physiol, Lausanne, Switzerland. [Hayes, Frances J.] St Vincents Univ Hosp, Dept Endocrinol, Dublin 4, Ireland. RP Hayes, FJ (reprint author), St Vincents Univ Hosp, Dept Endocrinol, Elm Pk, Dublin 4, Ireland. EM f.hayes@st-vincents.ie RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014; OI Dwyer, Andrew/0000-0002-7023-6794; Amati, Francesca/0000-0002-1731-0262 FU NIH [RO1 DK-71168]; American Diabetes Association; [M01-RR-01066] FX The authors have no conflicting interests or financial disclosures to declare. This work was supported by NIH RO1 DK-71168 (FJH) and a Career Development Award from the American Diabetes Association (FJH) and M01-RR-01066. This study was registered at ClinicalTrials.gov (NCT00433173). NR 34 TC 17 Z9 17 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD FEB PY 2013 VL 78 IS 2 BP 291 EP 296 DI 10.1111/j.1365-2265.2012.04486.x PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 067AT UT WOS:000313264900020 PM 22804876 ER PT J AU Young, BC Ecker, JL AF Young, Brett C. Ecker, Jeffrey L. TI Fetal Macrosomia and Shoulder Dystocia in Women with Gestational Diabetes: Risks Amenable to Treatment? SO CURRENT DIABETES REPORTS LA English DT Article DE Gestational diabetes; Hyperglycemia; Fetal macrosomia; Shoulder dystocia ID INTERNATIONAL WORKSHOP-CONFERENCE; PREGNANCY OUTCOMES; GLUCOSE-TOLERANCE; OBJECTIVE DEFINITION; BIRTH-WEIGHT; MELLITUS; INTOLERANCE; POPULATION; DELIVERY; TRIAL AB Fetal macrosomia and maternal diabetes are independent risk factors for shoulder dystocia, an obstetrical emergency that may cause permanent neonatal injury. Randomized trials of glycemic control in pregnancies complicated by gestational diabetes reveal decreased rates of macrosomia and shoulder dystocia among those treated. However, definitions of gestational diabetes vary and a specific glycemic threshold for clinically significant risk reduction remains to be delineated. This review discusses risks associated with gestational diabetes including macrosomia (birth weight above 4000-4500 g) and delivery-related morbidity, specifically, shoulder dystocia. Subsequently, we will review recent randomized trials assessing the impact of glycemic control on these delivery-related morbidities. Finally, we will examine a large observational study that found associations with delivery-related morbidity and hyperglycemia below current diabetic thresholds, observations which may suggest reexamination of current diagnosis guidelines for gestational diabetes. C1 [Young, Brett C.; Ecker, Jeffrey L.] Massachusetts Gen Hosp, Div Maternal Fetal Med, Boston, MA 02114 USA. RP Young, BC (reprint author), Massachusetts Gen Hosp, Div Maternal Fetal Med, 55 Fruit St,Founders 4th Floor, Boston, MA 02114 USA. EM byoung1@partners.org; jecker@partners.org NR 41 TC 9 Z9 9 U1 2 U2 9 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD FEB PY 2013 VL 13 IS 1 BP 12 EP 18 DI 10.1007/s11892-012-0338-8 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 069LJ UT WOS:000313437300003 PM 23076441 ER PT J AU Hawkins, K Donihi, AC Korytkowski, MT AF Hawkins, Kara Donihi, Amy C. Korytkowski, Mary T. TI Glycemic Management in Medical and Surgical Patients in the Non-ICU Setting SO CURRENT DIABETES REPORTS LA English DT Article DE Type 1 diabetes; Type 2 diabetes; Hyperglycemia; Inpatients; Insulin; Perioperative care; Continuity of patient care; Glycemic management; Medical and surgical patients; Non-ICU setting ID INTENSIVE INSULIN THERAPY; CRITICALLY-ILL PATIENTS; HOSPITALIZED-PATIENTS; RANDOMIZED-TRIAL; GLUCOSE CONTROL; PUMP THERAPY; INPATIENT; CARE; HYPERGLYCEMIA; HYPOGLYCEMIA AB Hyperglycemia is commonly observed in hospitalized patients with and without previously known diabetes and is associated with adverse outcomes. For this reason, measurement of blood glucose (BG) is recommended for all patients at admission. Measurement of an A1C identifies patients with either newly recognized diabetes or uncontrolled diabetes. Current guidelines advise fasting and premeal BG < 140 mg/dl, with maximal random BG < 180 mg/dl for the majority of noncritically ill patients. Rational use of basal bolus insulin (BBI) regimens is effective in achieving these glycemic goals, with low risk for hypoglycemia. The safety of BBI relies upon provider knowledge for initiation and adjustment of insulin doses for changes in nutritional status or use of medications affecting glucose metabolism. Smooth transition of care to the outpatient setting is facilitated by providing oral and written instructions regarding timing and dosing of insulin, as well as education in basic skills for home management. C1 [Hawkins, Kara] VA Pittsburgh Healthcare Syst, Div Endocrinol, Dept Med, Pittsburgh, PA USA. [Donihi, Amy C.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15213 USA. [Korytkowski, Mary T.] Univ Pittsburgh, Dept Med, Med Ctr, Div Endocrinol, Pittsburgh, PA 15213 USA. RP Korytkowski, MT (reprint author), Univ Pittsburgh, Dept Med, Med Ctr, Div Endocrinol, Room 560,3601 5th Ave, Pittsburgh, PA 15213 USA. EM mtk7@pitt.edu FU Sanofi-Aventis FX K. Hawkins, none; A. C. Donihi, none; M. T. Korytkowski has a board membership with the American Diabetes Association (volunteer position), was a consultant for Regeneron, and has received grant support and honoraria from Sanofi-Aventis. NR 49 TC 6 Z9 6 U1 0 U2 13 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD FEB PY 2013 VL 13 IS 1 BP 96 EP 106 DI 10.1007/s11892-012-0340-1 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 069LJ UT WOS:000313437300014 PM 23100037 ER PT J AU Alschuler, KN Otis, JD AF Alschuler, K. N. Otis, J. D. TI Significant others' responses to pain in veterans with chronic pain and clinical levels of post-traumatic stress disorder symptomatology SO EUROPEAN JOURNAL OF PAIN LA English DT Article ID COMORBID CHRONIC PAIN; EMOTIONAL DISTRESS; MUTUAL MAINTENANCE; SYMPTOMS; DISABILITY; BEHAVIORS; SEVERITY; SOLDIERS; HEALTH; IMPACT AB Background Pain and post-traumatic stress disorder (PTSD) are two of the most common health complaints among US veterans. Studies suggest that the co-morbidity of these disorders exacerbates veterans experiences of chronic pain. Although a limited number of papers have reviewed reasons for this exacerbation, no studies have explored the potential contribution of significant others responses to veterans experience of pain in the context of PTSD symptomatology. The purpose of this study was to explore whether significant others responses to chronic pain differed for veterans with and without clinical levels of PTSD symptoms. It was hypothesized that veterans who presented with higher levels of PTSD symptomatology would report higher levels of punishing responses to their pain from significant others. Methods Participants were 184 veterans who completed self-report questionnaires as part of their participation in a Psychology Pain Management program at a Department of Veterans Affairs healthcare facility. Results Supporting our hypothesis, PTSD symptoms in veterans were associated with higher levels of punishing responses to pain from their significant others. Further, veterans who reported clinically significant levels of PTSD symptoms garnered more punishing responses to pain when compared with veterans with subclinical levels of PTSD symptomatology. Punishing responses to pain were associated with greater pain-related disability among veterans. Conclusions The presence of more punishing responses may impact the cognitive-behavioural components of the chronic pain experience. For example, it may worsen negative affect, which can thus impact the fear-avoidance model. Further discussion focuses on the implications of these results, including guidelines for clinical applications. C1 [Alschuler, K. N.] Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98195 USA. [Otis, J. D.] VA Boston Healthcare Syst, Boston, MA USA. [Otis, J. D.] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Alschuler, KN (reprint author), Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98195 USA. EM kalschul@uw.edu OI Otis, John/0000-0002-5441-7421 FU Department of Veterans Affairs, Veterans Health Administration, Rehabilitation, Research and Development Service (RR&D), VA Merit Review Grant [C3322R]; Research Service of the VA Boston Healthcare System FX This work was supported by a Department of Veterans Affairs, Veterans Health Administration, Rehabilitation, Research and Development Service (RR&D), VA Merit Review Grant (C3322R) and by the Research Service of the VA Boston Healthcare System. NR 44 TC 6 Z9 8 U1 1 U2 16 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1090-3801 J9 EUR J PAIN JI Eur. J. Pain PD FEB PY 2013 VL 17 IS 2 BP 245 EP 254 DI 10.1002/j.1532-2149.2012.00180.x PG 10 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 067KN UT WOS:000313293000011 PM 22718501 ER PT J AU Adler, A Wegscheider, K Lieberman, D Aminalai, A Aschenbeck, J Drossel, R Mayr, M Mross, M Scheel, M Schroder, A Gerber, K Stange, G Roll, S Gauger, U Wiedenmann, B Altenhofen, L Rosch, T AF Adler, Andreas Wegscheider, Karl Lieberman, David Aminalai, Alireza Aschenbeck, Jens Drossel, Rolf Mayr, Michael Mross, Michael Scheel, Mathias Schroeder, Andreas Gerber, Katharina Stange, Gabriela Roll, Stephanie Gauger, Ulrich Wiedenmann, Bertram Altenhofen, Lutz Rosch, Thomas TI Factors determining the quality of screening colonoscopy: a prospective study on adenoma detection rates, from 12 134 examinations (Berlin colonoscopy project 3, BECOP-3) SO GUT LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; HIGH-DEFINITION; WIDE-ANGLE; PROSPECTIVE MULTICENTER; COLORECTAL NEOPLASIA; SURGICAL MORTALITY; HOSPITAL VOLUME; WITHDRAWAL TIME; POLYP DETECTION; UNITED-STATES AB Background Screening colonoscopy (SC) outcome quality is best determined by the adenoma detection rate (ADR). The substantial variability in the ADRs between endoscopists may reflect different skills, experience and/or equipment. Objective To analyse the potential factors that may influence ADR variance, including case volume. Design 12 134 consecutive SCs (mean age 64.5 years, 47% men) from 21 Berlin private-practice colonoscopists were prospectively studied during 18 months. The data were analysed using a two-level mixed linear model to adequately address the characteristics of patients and colonoscopists. The ADR was regressed after considering the following factors: sex, age, bowel cleanliness, NSAID intake, annual SC case volume, lifetime experience, instrument withdrawal times, instrument generations used, and the number of annual continuing medical education (CME) meetings attended by the physician. The case volume was also retrospectively analysed from the 2007 national SC registry data (312 903 colonoscopies and 1004 colonoscopists). Results The patient factors that correlated with the ADR were sex, age (p<0.001) and low quality of bowel preparation (p=0.005). The factors that were related to the colonoscopists were the number of CME meetings attended (p=0.012) and instrument generation (p=0.001); these factors accounted for approximately 40% of the interphysician variability. Within a narrow range (6-11 min), the withdrawal time was not correlated with the ADR. Annual screening case volume did not correlate with the ADR, and this finding was confirmed by the German registry data. Conclusions The outcome quality of screening colonoscopies is mainly influenced by individual colonoscopist factors (ie, CME activities) and instrument quality. C1 [Adler, Andreas; Stange, Gabriela] Charite, Campus Virchow Hosp, D-13353 Berlin, Germany. [Wegscheider, Karl] Univ Hosp Hamburg Eppendorf, Dept Med Biometry & Epidemiol, D-20246 Hamburg, Germany. [Lieberman, David] Portland VA Med Ctr, Div Gastroenterol, Portland, OR USA. [Gerber, Katharina; Rosch, Thomas] Univ Hosp Hamburg Eppendorf, Dept Interdisciplinary Endoscopy, Berlin Study Grp Off, D-20246 Hamburg, Germany. [Roll, Stephanie] Charite, Campus Mitte Hosp, Inst Social Med Epidemiol & Hlth Econ, D-13353 Berlin, Germany. [Gauger, Ulrich] Berlin Stat Off, Berlin, Germany. [Wiedenmann, Bertram] Charite, Campus Virchow Klinikum, MED KLIN MS Hepatol U Gastroenterol, D-13353 Berlin, Germany. [Altenhofen, Lutz] Cent Res Inst Ambulatory Hlth Care, Berlin, Germany. RP Rosch, T (reprint author), Univ Hosp Hamburg Eppendorf, Dept Interdisciplinary Endoscopy, Berlin Study Grp Off, Martinistr 52, D-20246 Hamburg, Germany. EM t.roesch@uke.de FU Deutsche Krebshilfe e.V. [108166]; Olympus; Pentax; Falk Companies FX The Berlin Colonoscopy Screening Study was supported by a grant from Deutsche Krebshilfe e.V. (no. 108166) and by unrestricted grants from Olympus, Pentax and Falk Companies. There was no influence on study design, performance, data analysis or the writing of the manuscript. NR 33 TC 76 Z9 77 U1 0 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD FEB PY 2013 VL 62 IS 2 BP 236 EP 241 DI 10.1136/gutjnl-2011-300167 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 067AQ UT WOS:000313264400009 PM 22442161 ER PT J AU Kastrinos, F Steyerberg, EW Balmana, J Mercado, R Gallinger, S Haile, R Casey, G Hopper, JL LeMarchand, L Lindor, NM Newcomb, PA Thibodeau, SN Syngal, S AF Kastrinos, Fay Steyerberg, Ewout W. Balmana, Judith Mercado, Rowena Gallinger, Steven Haile, Robert Casey, Graham Hopper, John L. LeMarchand, Loic Lindor, Noralane M. Newcomb, Polly A. Thibodeau, Stephen N. Syngal, Sapna CA Colon Canc Family Registry TI Comparison of the clinical prediction model PREMM1,2,6 and molecular testing for the systematic identification of Lynch syndrome in colorectal cancer SO GUT LA English DT Article ID REVISED BETHESDA GUIDELINES; MISMATCH-REPAIR GENES; MICROSATELLITE INSTABILITY; GERMLINE MUTATIONS; COLON-CANCER; COST-EFFECTIVENESS; FAMILY-REGISTRY; CRITERIA; HISTORY; MLH1 AB Background Lynch syndrome is caused by germline mismatch repair (MMR) gene mutations. The PREMM1,2,6 model predicts the likelihood of a MMR gene mutation based on personal and family cancer history. Objective To compare strategies using PREMM1,2,6 and tumour testing (microsatellite instability (MSI) and/or immunohistochemistry (IHC) staining) to identify mutation carriers. Design Data from population-based or clinic-based patients with colorectal cancers enrolled through the Colon Cancer Family Registry were analysed. Evaluation included MSI, IHC and germline mutation analysis for MLH1, MSH2, MSH6 and PMS2. Personal and family cancer histories were used to calculate PREMM1,2,6 predictions. Discriminative ability to identify carriers from non-carriers using the area under the receiver operating characteristic curve (AUC) was assessed. Predictions were based on logistic regression models for (1) cancer assessment using PREMM1,2,6, (2) MSI, (3) IHC for loss of any MMR protein expression, (4) MSI + IHC, (5) PREMM1,2,6 + MSI, (6) PREMM1,2,6 + IHC, (7) PREMM1,2,6 + IHC + MSI. Results Among 1651 subjects, 239 (14%) had mutations (90 MLH1, 125 MSH2, 24 MSH6). PREMM1,2,6 discriminated well with AUC 0.90 (95% CI 0.88 to 0.92). MSI alone, IHC alone, or MSI + IHC each had lower AUCs: 0.77, 0.82 and 0.82, respectively. The added value of IHC + PREMM1,2,6 was slightly greater than PREMM1,2,6 + MSI (AUC 0.94 vs 0.93). Adding MSI to PREMM1,2,6 + IHC did not improve discrimination. Conclusion PREMM1,2,6 and IHC showed excellent performance in distinguishing mutation carriers from non-carriers and performed best when combined. MSI may have a greater role in distinguishing Lynch syndrome from other familial colorectal cancer subtypes among cases with high PREMM1,2,6 scores where genetic evaluation does not disclose a MMR mutation. C1 [Kastrinos, Fay] Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA. [Kastrinos, Fay] Columbia Univ, Med Ctr, Div Liver & Digest Dis, New York, NY 10032 USA. [Steyerberg, Ewout W.] Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands. [Balmana, Judith] Univ Autonoma Barcelona, Dept Med Oncol, Hosp Vall dHebron, Dept Med, E-08193 Barcelona, Spain. [Mercado, Rowena; Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Gallinger, Steven] Univ Toronto, Dr Zane Cohen Digest Dis Clin Res Ctr, Mt Sinai Hosp, Toronto, ON M5S 1A1, Canada. [Gallinger, Steven] Univ Toronto, Dept Surg, Toronto, ON M5S 1A1, Canada. [Haile, Robert; Casey, Graham] USC Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. [Hopper, John L.] Univ Melbourne, Dept Publ Hlth, Carlton, Vic 3053, Australia. [LeMarchand, Loic] Univ Hawaii, Div Epidemiol, Ctr Canc, Honolulu, HI 96822 USA. [Lindor, Noralane M.] Mayo Clin, Dept Med Genet, Rochester, MN USA. [Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Newcomb, Polly A.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Syngal, Sapna] Harvard Univ, Sch Med, Boston, MA USA. RP Kastrinos, F (reprint author), Columbia Univ, Med Ctr, Div Liver & Digest Dis, 630 W 168th St, New York, NY 10032 USA. EM fk18@columbia.edu RI Gallinger, Steven/E-4575-2013; OI Steyerberg, Ewout/0000-0002-7787-0122 FU National Cancer Institute [K07 CA151769-02, R01 CA132829, K24 CA113433]; National Institutes of Health [CA95-011] FX This work was supported by the National Cancer Institute (K07 CA151769-02 to FK; R01 CA132829 and K24 CA113433 to SS), National Institutes of Health under RFA # CA95-011 and through cooperative agreements with members of the Colon Cancer Family Registry and PIs. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the CFRs, nor does mention of trade names, commercial products, or organisations imply endorsement by the US Government or the CFR. The study sponsors/funders had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. NR 35 TC 24 Z9 24 U1 0 U2 14 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD FEB PY 2013 VL 62 IS 2 BP 272 EP 279 DI 10.1136/gutjnl-2011-301265 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 067AQ UT WOS:000313264400013 PM 22345660 ER PT J AU Lopez, L Jha, AK AF Lopez, Lenny Jha, Ashish K. TI Outcomes for Whites and Blacks at Hospitals That Disproportionately Care for Black Medicare Beneficiaries SO HEALTH SERVICES RESEARCH LA English DT Article DE Black-serving hospitals; mortality; disparities AB Objective Hospital care for blacks is concentrated among a small number of hospitals and whether they have worse outcomes across common medical conditions is unknown. Data Source We used the 2007 100% Medicare file to calculate 30- and 90-day mortality rates for white and black patients admitted for acute myocardial infarction (AMI), congestive heart failure (CHF), or pneumonia. Study Design We ranked all hospitals in the country by their proportion of discharged black patients and identified the top 10 percent of these hospitals as black serving. We examined race-specific adjusted mortality rates and adjusted for differences in hospital characteristics. Principal Findings At 30 days, black-serving hospitals had, compared with nonblack-serving hospitals, similar mortality for AMI, lower mortality for CHF, and higher mortality for pneumonia. At 90 days, mortality was higher at black-serving hospitals for both AMI and pneumonia and comparable for CHF compared with nonblack-serving hospitals. White patients had worse outcomes at black-serving hospitals for two conditions at 30 days and all three conditions at 90 days. Blacks also had worse outcomes at black-serving hospitals. Conclusions Hospitals with a high proportion of black patients had worse outcomes than other hospitals for both their white and black elderly patients. C1 [Lopez, Lenny] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Lopez, Lenny] Massachusetts Gen Hosp, Dept Med, Dispar Solut Ctr, Boston, MA 02114 USA. [Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Lopez, L (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM llopez1@partners.org NR 0 TC 6 Z9 6 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD FEB PY 2013 VL 48 IS 1 BP 114 EP 128 DI 10.1111/j.1475-6773.2012.01445.x PG 15 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 066WT UT WOS:000313253100007 PM 22816447 ER PT J AU Slade, EP McCarthy, JF Valenstein, M Visnic, S Dixon, LB AF Slade, Eric P. McCarthy, John F. Valenstein, Marcia Visnic, Stephanie Dixon, Lisa B. TI Cost Savings from Assertive Community Treatment Services in an Era of Declining Psychiatric Inpatient Use SO HEALTH SERVICES RESEARCH LA English DT Article DE Assertive community treatment; inpatient use; serious mental illness ID CRITICAL TIME INTERVENTION; MENTAL-HOSPITAL TREATMENT; INSTRUMENTAL VARIABLES; CAUSAL INFERENCE; BEHAVIORAL-MODEL; HEALTH TREATMENT; MEDICAL-CARE; ILLNESS; HOMELESSNESS; PROGRAM AB Objective To assess, during a period of decreasing psychiatric inpatient utilization, cost savings from Assertive Community Treatment (ACT) programs for individuals with severe mental illnesses. Data Source U.S. Department of Veterans Affairs' (VA) national administrative data for entrants into ACT programs. Study Design An observational study of the effects of ACT enrollment on mental health inpatient utilization and costs in the first 12 months following enrollment. ACT enrollees (N = 2010) were propensity score matched to ACT-eligible non-enrollees (N = 4020). An instrumental variables generalized linear regression approach was used to estimate enrollment effects. Results Instrumental variables estimates indicate that between FY2001 and FY2004, entry into ACT resulted in a net increase of $4529 in VA costs. Trends in inpatient use among ACT program entrants suggest this effect remained stable after FY2004. However, eligibility for ACT declined 37 percent, because fewer patients met an eligibility standard based on high prior psychiatric inpatient use. Conclusions Savings from ACT programs depend on new enrollees' intensity of psychiatric inpatient utilization prior to entering the ACT program. Although a program eligibility standard based on prior psychiatric inpatient use helped to sustain the savings from VA ACT programs, over time, it also resulted in an unintended narrowing of program eligibility. C1 [Slade, Eric P.; Dixon, Lisa B.] US Dept Vet Affairs, VA Capitol Healthcare Network VISN 5, Mental Illness Res Educ & Clin Ctr, Baltimore, MD 21201 USA. [Slade, Eric P.; Dixon, Lisa B.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. [McCarthy, John F.; Valenstein, Marcia] US Dept Vet Affairs, VA Serious Mental Illness Treatment Resource & Ev, Ann Arbor, MI USA. [McCarthy, John F.; Valenstein, Marcia] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI 48109 USA. [Visnic, Stephanie] US Dept Vet Affairs, Serious Mental Illness Treatment Resource & Evalu, Ann Arbor, MI USA. RP Slade, EP (reprint author), US Dept Vet Affairs, VA Capitol Healthcare Network VISN 5, Mental Illness Res Educ & Clin Ctr, 737 W Lombard St,Room 526, Baltimore, MD 21201 USA. EM eslade@psych.umaryland.edu FU U.S. Department of Veterans Affairs (VA) Health Services Research & Development Service [IIR-06-115] FX This project was supported by grant IIR-06-115 from the U.S. Department of Veterans Affairs (VA) Health Services Research & Development Service. Data for this project were generously provided by the VA New England Performance Evaluation Center (NEPEC), the VA Serious Mental Illness Treatment Resource and Evaluation Center (SMITREC), and the VA Health Economics Resource Center (HERC). The authors also thank Rosalinda Ignacio, Deborah Welsh, and Lan Li for outstanding data analysis; Alan Bellack at the VA VISN5 MIRECC and Frederic Blow at the VA SMITREC for their leadership and support of this project; and Robert Rosenheck at the VA NEPEC for many helpful suggestions on an earlier version of the manuscript. None of the authors has a financial or other conflict. NR 59 TC 6 Z9 6 U1 2 U2 25 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD FEB PY 2013 VL 48 IS 1 BP 195 EP 217 DI 10.1111/j.1475-6773.2012.01420.x PG 23 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 066WT UT WOS:000313253100011 PM 22594523 ER PT J AU Molis, MR Diedesch, A Gallun, F Leek, MR AF Molis, Michelle R. Diedesch, Anna Gallun, Frederick Leek, Marjorie R. TI Vowel Identification by Amplitude and Phase Contrast SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE spectral contrast; formants; hearing impairment; frequency selectivity; phase; vowel identification ID HEARING-IMPAIRED LISTENERS; SPECTRAL CONTRAST; COMPONENT PHASE; ENHANCEMENT; NOISE; MODEL; INTELLIGIBILITY; PERCEPTION; FREQUENCY; SPEECH AB Vowel identification is largely dependent on listeners' access to the frequency of two or three peaks in the amplitude spectrum. Earlier work has demonstrated that, whereas normal-hearing listeners can identify harmonic complexes with vowel-like spectral shapes even with very little amplitude contrast between "formant" components and remaining harmonic components, listeners with hearing loss require greater amplitude differences. This is likely the result of the poor frequency resolution that often accompanies hearing loss. Here, we describe an additional acoustic dimension for emphasizing formant versus non-formant harmonics that may supplement amplitude contrast information. The purpose of this study was to determine whether listeners were able to identify "vowel-like" sounds using temporal (component phase) contrast, which may be less affected by cochlear loss than spectral cues, and whether overall identification improves when congruent temporal and spectral information are provided together. Five normal-hearing and five hearing-impaired listeners identified three vowels over many presentations. Harmonics representing formant peaks were varied in amplitude, phase, or a combination of both. In addition to requiring less amplitude contrast, normal-hearing listeners could accurately identify the sounds with less phase contrast than required by people with hearing loss. However, both normal-hearing and hearing-impaired groups demonstrated the ability to identify vowel-like sounds based solely on component phase shifts, with no amplitude contrast information, and they also showed improved performance when congruent phase and amplitude cues were combined. For nearly all listeners, the combination of spectral and temporal information improved identification in comparison to either dimension alone. C1 [Molis, Michelle R.; Diedesch, Anna; Gallun, Frederick; Leek, Marjorie R.] Portland VA Med Ctr, VA RR&D Natl Ctr Rehabilitat Auditory Res NCRAR, Portland, OR 97207 USA. [Molis, Michelle R.; Gallun, Frederick; Leek, Marjorie R.] Oregon Hlth & Sci Univ, Oregon Hearing Res Ctr, Portland, OR 97239 USA. RP Molis, MR (reprint author), Portland VA Med Ctr, VA RR&D Natl Ctr Rehabilitat Auditory Res NCRAR, 3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. EM michelle.molis@va.gov RI Gallun, Frederick/G-3792-2012 OI Gallun, Frederick/0000-0002-4145-2199 FU NIDCD [R01 DC 00626, T35 DC008764]; Department of Veterans Affairs Rehabilitation Research & Development Service [C6116W, C4963W]; Senior Research Career Scientist [C4042L] FX This research was supported by grant no. R01 DC 00626 [PI: Leek] from the NIDCD. Diedesch was supported by T35 DC008764 [PI: Leek], also from the NIDCD. Support was also provided by the Department of Veterans Affairs Rehabilitation Research & Development Service [Career Development grants C6116W (Molis) and C4963W (Gallun), and Senior Research Career Scientist award C4042L ( Leek)]. The work was supported with resources and the use of facilities at the Portland VA Medical Center. The contents of this article do not represent the views of the Department of Veterans Affairs or the United States Government. NR 23 TC 0 Z9 0 U1 0 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD FEB PY 2013 VL 14 IS 1 BP 125 EP 137 DI 10.1007/s10162-012-0352-1 PG 13 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 068LZ UT WOS:000313369500010 PM 23007720 ER PT J AU Guyatt, GH Oxman, AD Santesso, N Helfand, M Vist, G Kunz, R Brozek, J Norris, S Meerpohl, J Djulbegovic, B Alonso-Coello, P Post, PN Busse, JW Glasziou, P Christensen, R Schunemann, HJ AF Guyatt, Gordon H. Oxman, Andrew D. Santesso, Nancy Helfand, Mark Vist, Gunn Kunz, Regina Brozek, Jan Norris, Susan Meerpohl, Joerg Djulbegovic, Ben Alonso-Coello, Pablo Post, Piet N. Busse, Jason W. Glasziou, Paul Christensen, Robin Schuenemann, Holger J. TI GRADE guidelines: 12. Preparing Summary of Findings tables-binary outcomes SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE GRADE; Summary of findings; Evidence profile; Confidence in estimates; Quality of evidence; Systematic reviews ID SULFONYLUREA-INDUCED HYPOGLYCEMIA; NATURAL FREQUENCIES; COCHRANE REVIEWS; CLINICAL-TRIALS; QUALITY; METAANALYSIS; OCTREOTIDE; DIFFERENCE AB (SoF) tables present, for each of the seven (or fewer) most important outcomes, the following: the number of studies and number of participants; the confidence in effect estimates (quality of evidence); and the best estimates of relative and absolute effects. Potentially challenging choices in preparing SoF table include using direct evidence (which may have very few events) or indirect evidence (from a surrogate) as the best evidence for a treatment effect. If a surrogate is chosen, it must be labeled as substituting for the corresponding patient-important outcome. Another such choice is presenting evidence from low-quality randomized trials or high-quality observational studies. When in doubt, a reasonable approach is to present both sets of evidence; if the two bodies of evidence have similar quality but discrepant results, one would rate down further for inconsistency. For binary outcomes, relative risks (RRs) are the preferred measure of relative effect and, in most instances, are applied to the baseline or control group risks to generate absolute risks. Ideally, the baseline risks come from observational studies including representative patients and identifying easily measured prognostic factors that define groups at differing risk. In the absence of such studies, relevant randomized trials provide estimates of baseline risk. When confidence intervals (CIs) around the relative effect include no difference, one may simply state in the absolute risk column that results fail to show a difference, omit the point estimate and report only the CIs, or add a comment emphasizing the uncertainty associated with the point estimate. (C) 2013 Elsevier Inc. All rights reserved. C1 [Guyatt, Gordon H.; Santesso, Nancy; Brozek, Jan; Busse, Jason W.; Schuenemann, Holger J.] McMaster Univ, Dept Clin Epidemiol & Biostat, W Hamilton, ON L8N 3Z5, Canada. [Guyatt, Gordon H.; Santesso, Nancy; Brozek, Jan; Busse, Jason W.; Schuenemann, Holger J.] McMaster Univ, Dept Med, W Hamilton, ON L8N 3Z5, Canada. [Oxman, Andrew D.; Vist, Gunn] Norwegian Knowledge Ctr Hlth Serv, N-0130 Oslo, Norway. [Helfand, Mark] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Oregon Evidence Based Practice Ctr, Portland, OR 97201 USA. [Kunz, Regina] Univ Basel Hosp, Basel Inst Clin Epidemiol, CH-4031 Basel, Switzerland. [Norris, Susan] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA. [Meerpohl, Joerg] Univ Med Ctr Freiburg, Inst Med Biometry & Med Informat, German Cochrane Ctr, D-79104 Freiburg, Germany. [Meerpohl, Joerg] Univ Med Ctr Freiburg, Dept Pediat & Adolescent Med, Div Pediat Hematol & Oncol, D-79106 Freiburg, Germany. [Djulbegovic, Ben] Univ S Florida, Ctr Evidence Based Med & Hlth Outcomes Res, Tampa, FL 33612 USA. [Djulbegovic, Ben] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Hematol, Tampa, FL 33612 USA. [Djulbegovic, Ben] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Hlth Outcomes & Behav, Tampa, FL 33612 USA. [Alonso-Coello, Pablo] CIBRESP IIB St Pau, Iberoamer Cochrane Ctr, Barcelona 08041, Spain. [Alonso-Coello, Pablo] Hosp St Pau Creu & St Pau, Epidemiol & Publ Hlth CIBER CIBERESP, Barcelona 08041, Spain. [Post, Piet N.] Dutch Inst Healthcare Improvement CBO, Utrecht, Netherlands. [Busse, Jason W.] Inst Work & Hlth, Toronto, ON M5G 2E9, Canada. [Glasziou, Paul] Bond Univ, Fac Hlth Sci, Ctr Res Evidence Based Practice, Gold Coast, Qld 4229, Australia. [Christensen, Robin] Copenhagen Univ Hosp, Parker Inst, Musculoskeletal Stat Unit, Frederiksberg, Denmark. RP Guyatt, GH (reprint author), McMaster Univ, CLAR Res Grp, Dept Clin Epidemiol, Room 2C12,1200 Main St, W Hamilton, ON L8N 3Z5, Canada. EM guyatt@mcmaster.ca RI Djulbegovic, Benjamin/I-3661-2012; Meerpohl, Joerg/J-4224-2013; Glasziou, Paul/A-7832-2008; OI Djulbegovic, Benjamin/0000-0003-0671-1447; Meerpohl, Joerg/0000-0002-1333-5403; Glasziou, Paul/0000-0001-7564-073X; Busse, Jason/0000-0002-0178-8712 NR 38 TC 125 Z9 129 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD FEB PY 2013 VL 66 IS 2 BP 158 EP 172 DI 10.1016/j.jclinepi.2012.01.012 PG 15 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 068PK UT WOS:000313378500007 PM 22609141 ER PT J AU Vitali, M Tedeschini, E Mistretta, M Fehling, K Aceti, F Ceccanti, M Fava, M AF Vitali, Mario Tedeschini, Enrico Mistretta, Martino Fehling, Kiki Aceti, Franca Ceccanti, Mauro Fava, Maurizio TI Adjunctive Pregabalin in Partial Responders With Major Depressive Disorder and Residual Anxiety SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE adjunctive pregabalin; antidepressants; residual anxiety; MDD; partial responders ID PLACEBO-CONTROLLED TRIAL; STAR-ASTERISK-D; DOUBLE-BLIND; SYMPTOMS; FIBROMYALGIA; MULTICENTER; EFFICACY AB Background: Anxiety symptoms in depression result often in treatment resistance, residual symptoms, and persistent functional impairment. Objective: To assess the effectiveness and safety of adjunctive pregabalin to antidepressants for residual anxiety in patients with major depressive disorder (MDD). Methods: A retrospective chart review was conducted to identify partial responders among patients with MDD with residual anxiety. Twenty such patients (age, 58.4 +/- 11.2 years; 15 women; baseline Hamilton Depression Rating Scale [HDRS], 17.1 +/- 3.5) who received adjunctive pregabalin for residual anxiety were included. Antidepressants augmented were the selective serotonin reuptake inhibitors (n = 12), mirtazapine (n = 2), and selective serotonin-norepinephrine reuptake inhibitors (n = 6). Results: Twenty patients received at least 4 weeks of pregabalin treatment after 8 weeks of antidepressant therapy. At week 1 (9 weeks after initiating treatment), pregabalin was prescribed at a mean +/- SD dose of 71.2 +/- 31.7 mg, and the mean maximum pregabalin dose prescribed was 156.2 +/- 76.5 mg (range, 75-300 mg). At week 8, there were 13 responders (13/20 [65%]), and 7 of these 13 patients achieved remission (HDRS17 < 8). There were significant decreases in HDRS scores (13.5 +/- 3.1 vs 9.1 +/- 2.9, P < 0.000), and HDRS anxiety/somatization subscale scores (6.3 +/- 2 to 3.6 +/- 1.7, P < 0.000). Adverse effects included somnolence (n = 7), weight gain (n = 3), dizziness (n = 4), dry mouth (n = 6), edema (n = 3), blurred vision (n = 3), difficulty with concentration/attention (n = 8), headache (n = 6), and diarrhea (n = 5). Conclusions: The results suggest a possible augmentation role for pregabalin when used in conjunction with conventional antidepressants for residual anxiety in MDD. C1 [Vitali, Mario; Ceccanti, Mauro] Univ Roma La Sapienza, Dept Clin Med, Rome, Italy. [Vitali, Mario; Fava, Maurizio] Harvard Univ, Dept Psychiat, Cambridge, MA 02138 USA. [Vitali, Mario; Fehling, Kiki; Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Tedeschini, Enrico] Modena & Reggio Emilia Univ, Dept Psychiat, Modena, Italy. [Tedeschini, Enrico] Modena & Reggio Emilia Univ, Dept Psychiat, Reggio Emilia, Italy. [Mistretta, Martino; Aceti, Franca] Univ Roma La Sapienza, Dept Psychiat, Rome, Italy. RP Vitali, M (reprint author), DCRP, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM vitalimario@yahoo.it OI Aceti, Franca/0000-0002-8245-8466; CECCANTI, Mauro/0000-0001-9981-8715 FU Merck Serono; CT San Remo; Lippincott; Williams & Wilkins for Handbook of Psychiatric Drug Therapy; Wolters Kluwer Health Inc; World Scientific Publishing Co Pte Ltd.; MGH CPFQ; SFI; ATRQ; DESS; SAFER; Abbott Laboratories; Alkermes; Aspect Medical Systems; AstraZeneca; BioResearch; Brain Cells, Inc; Bristol-Myers Squibb Company; Cephalon; Clinical Trial Solutions, LLC; Eli Lilly Company; Forest Pharmaceuticals Inc; Ganeden; GlaxoSmithKline; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Lundbeck; NARSAD; NCCAM; NIDA; NIMH; Novartis; Organon Inc; PamLab, LLC; Pfizer Inc; Pharmavite; Roche; Sanofi-Aventis; Servier; Shire; Solvay Pharmaceuticals, Inc; Synthelabo; Wyeth-Ayerst Laboratories FX Dr Ceccanti has served as a consultant to Merck Serono, Lundbeck, and CT San Remo. He has received research support from Merck Serono and CT San Remo. Dr Vitali has served as a consultant to Laboratorio CT San Remo. Dr Fava acts as a board member for Eisai, EnVivo, GenOmind, Psylin, Scherring-Plough, BMS/Otsuka, Johnson & Johnson, PsychoGenics, Neuronetics, Brain Cells Inc, Ganeden, Lundbeck/Takeda, NIDA, Transcept; acts as a consultant for Abbott Laboratories, Amarin, Aspect Medical Systems, AstraZeneca, Auspex Pharmaceuticals, Bayer AG, Best Practice Project Management, Inc, BioMarin Pharmaceuticals, Inc, Biovail Pharmaceuticals, Inc, Brain Cells, 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, 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. Pharmaceuticals Inc, Adamed, Co, Advanced Meeting Partners, American Psychiatric Association, American Society of Clinical Psychopharmacology, AstraZeneca, 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, Wyeth-Ayerst Laboratories; has grants with NIMH, NCCAM, NIH, NIDA, BMS, Ganeden, Johnson & Johnson; receives royalties from Lippincott, Williams & Wilkins for Handbook of Psychiatric Drug Therapy; from Wolters Kluwer Health Inc, and from World Scientific Publishing Co Pte Ltd. Dr Fava also receives copyright royalties for MGH CPFQ, SFI, ATRQ, DESS, and SAFER; and receives research support from Abbott Laboratories, Alkermes, Aspect Medical Systems, AstraZeneca, BioResearch, Brain Cells, Inc, Bristol-Myers Squibb Company, Cephalon, Clinical Trial Solutions, LLC, Eli Lilly & Company, Forest Pharmaceuticals Inc, Ganeden, GlaxoSmithKline, J & J Pharmaceuticals (personal $5500 in 2010), Lichtwer Pharma GmbH, Lorex Pharmaceuticals, Lundbeck (personal $ 1500 in 2010) NARSAD, NCCAM, NIDA, NIMH, Novartis, Organon Inc, PamLab, LLC, Pfizer Inc (personal $ 3500 in 2011), Pharmavite, Roche, Sanofi-Aventis, Servier (2000 Euro in 2011) Shire, Solvay Pharmaceuticals, Inc, Synthelabo, and Wyeth-Ayerst Laboratories. The other authors declare no financial or other conflicts of interest. NR 29 TC 5 Z9 5 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 2013 VL 33 IS 1 BP 95 EP 98 DI 10.1097/JCP.0b013e31827b9351 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 064YR UT WOS:000313112400018 PM 23277244 ER PT J AU Wight, RG Aneshensel, CS Barrett, C Ko, M Chodosh, J Karlamangla, AS AF Wight, Richard G. Aneshensel, Carol S. Barrett, Christopher Ko, Michelle Chodosh, Joshua Karlamangla, Arun S. TI Urban neighbourhood unemployment history and depressive symptoms over time among late middle age and older adults SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID HEALTH; RETIREMENT AB Background Little is known about how a neighbourhood's unemployment history may set the stage for depressive symptomatology. This study examines the effects of urban neighbourhood unemployment history on current depressive symptoms and subsequent symptom trajectories among residentially stable late middle age and older adults. Contingent effects between neighbourhood unemployment and individual-level employment status (ie, cross-level interactions) are also assessed. Methods Individual-level survey data are from four waves (2000, 2002, 2004 and 2006) of the original cohort of the nationally representative US Health and Retirement Study. Neighbourhoods are operationalised with US Census tracts for which historical average proportion unemployed between 1990 and 2000 and change in proportion unemployed between 1990 and 2000 are used to characterise the neighbourhood's unemployment history. Hierarchical linear regressions estimate three-level (time, individual and neighbourhood) growth models. Results Symptoms in 2000 are highest among those residing in neighbourhoods characterised by high historical average unemployment beginning in 1990 and increasing unemployment between 1990 and 2000, net of a wide range of socio-demographic controls including individual-level employment status. These neighbourhood unemployment effects are not contingent upon individual-level employment status in 2000. 6-year trajectories of depressive symptoms decrease over time on average but are not significantly influenced by the neighbourhood's unemployment history. Conclusions Given the current US recession, future studies that do not consider historical employment conditions may underestimate the mental health impact of urban neighbourhood context. The findings suggest that exposure to neighbourhood unemployment earlier in life may be consequential to mental health later in life. C1 [Wight, Richard G.; Aneshensel, Carol S.; Barrett, Christopher] Univ Calif Los Angeles, Dept Community Hlth Sci, Fielding Sch Publ Hlth, Los Angeles, CA 90095 USA. [Ko, Michelle] Univ Calif Los Angeles, Dept Hlth Serv, Fielding Sch Publ Hlth, Los Angeles, CA 90095 USA. [Chodosh, Joshua; Karlamangla, Arun S.] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Los Angeles, CA 90095 USA. [Chodosh, Joshua] VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. RP Wight, RG (reprint author), Univ Calif Los Angeles, Dept Community Hlth Sci, Fielding Sch Publ Hlth, 650 Charles Young Dr,Box 951772, Los Angeles, CA 90095 USA. EM rwight@ucla.edu OI Chodosh, Joshua/0000-0001-7784-4306 FU National Institute on Aging [R01AG022537] FX The project described was supported by award number R01AG022537 (CSA, Principal Investigator) from the National Institute on Aging. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Aging or the National Institutes of Health. NR 31 TC 12 Z9 12 U1 1 U2 28 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD FEB PY 2013 VL 67 IS 2 BP 153 EP 158 DI 10.1136/jech-2012-201537 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 068AC UT WOS:000313335900007 PM 22918896 ER PT J AU Andriole, GL McCullum-Hill, C Sandhu, GS Crawford, ED Barry, MJ Cantor, A AF Andriole, Gerald L. McCullum-Hill, Christie Sandhu, Gurdarshan S. Crawford, E. David Barry, Michael J. Cantor, Alan CA CAMUS Study Grp TI The Effect of Increasing Doses of Saw Palmetto Fruit Extract on Serum Prostate Specific Antigen: Analysis of the CAMUS Randomized Trial SO JOURNAL OF UROLOGY LA English DT Article DE permixon; Serenoa; prostate-specific antigen; prostatic hyperplasia ID URINARY-TRACT SYMPTOMS; SERENOA-REPENS; ANDROGEN RECEPTOR; HYPERPLASIA; MEN; PHYTOTHERAPY; POLYMORPHISMS; ASSOCIATION; FINASTERIDE; PSA AB Purpose: Saw palmetto extracts are used to treat lower urinary tract symptoms in men despite level I evidence that saw palmetto is ineffective in reducing these lower urinary tract symptoms. We determined whether higher doses of saw palmetto as studied in the CAMUS (Complementary and Alternative Medicine for Urologic Symptoms) trial affect serum prostate specific antigen levels. Materials and Methods: The CAMUS trial was a randomized, placebo controlled, double-blind, multicenter, North American trial conducted between June 5, 2008 and October 10, 2012, in which 369 men older than 45 years with an AUA symptom score of 8 to 24 were randomly assigned to placebo or dose escalation of saw palmetto, which consisted of 320 mg for the first 24 weeks, 640 mg for the next 24 weeks and 960 mg for the last 24 weeks of this 72-week trial. Serum prostate specific antigen levels were obtained at baseline and at weeks 24, 48 and 72, and were compared between treatment groups using the pooled t test and Fisher's exact test. Results: Serum prostate specific antigen was similar at baseline for the placebo (mean +/- SD 1.93 +/- 1.59 ng/ml) and saw palmetto groups (2.20 +/- 1.95, p = 0.16). Changes in prostate specific antigen during the study were similar, with a mean change in the placebo group of 0.16 +/- 1.08 ng/ml and 0.23 +/- 0.83 ng/ml in the saw palmetto group (p = 0.50). In addition, no differential effect on serum prostate specific antigen was observed between treatment arms when the groups were stratified by baseline prostate specific antigen. Conclusions: Saw palmetto extract does not affect serum prostate specific antigen more than placebo, even at relatively high doses. C1 [Andriole, Gerald L.; Sandhu, Gurdarshan S.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA. [McCullum-Hill, Christie; Cantor, Alan] Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL USA. [Crawford, E. David] Univ Colorado, Div Urol, Denver, CO 80202 USA. [Barry, Michael J.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Andriole, GL (reprint author), Washington Univ, Sch Med, Div Urol Surg, 4960 Childrens Pl,Campus Box 8242, St Louis, MO 63110 USA. EM andrioleg@wustl.edu FU National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases [U01 DK63795, U01 DK63797, U01 DK63825, U01 DK63835, U01 DK63866, U01 DK63833, U01 DK63862, U01 DK63840, U01 DK63883, U01 DK63831, U01 DK63778, U01 DK63788]; National Center for Complementary and Alternative Medicine; Office of Dietary Supplements, NIH FX Supported by cooperative agreements from the National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases U01 DK63795, U01 DK63797, U01 DK63825, U01 DK63835, U01 DK63866, U01 DK63833, U01 DK63862, U01 DK63840, U01 DK63883, U01 DK63831, U01 DK63778 and U01 DK63788. Also supported by the National Center for Complementary and Alternative Medicine, and the Office of Dietary Supplements, NIH. NR 24 TC 5 Z9 5 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD FEB PY 2013 VL 189 IS 2 BP 486 EP 492 DI 10.1016/j.juro.2012.09.037 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 069VI UT WOS:000313464800024 PM 23253958 ER PT J AU Anderson, CB Penson, DF Ni, SH Makarov, DV Barocas, DA AF Anderson, Christopher B. Penson, David F. Ni, Shenghua Makarov, Danil V. Barocas, Daniel A. TI Centralization of Radical Prostatectomy in the United States SO JOURNAL OF UROLOGY LA English DT Article DE prostatectomy; prostatic neoplasms; trends; robotics ID HOSPITAL VOLUME; OPERATIVE MORTALITY; POTENTIAL BENEFITS; SURGERY; CANCER; TRENDS; ASSOCIATION; TECHNOLOGY; PATTERNS; OUTCOMES AB Purpose: Radical prostatectomy is a common treatment for organ confined prostate cancer and its use is increasing. We examined how the increased volume is being distributed and what hospital characteristics are associated with increasing volume. Materials and Methods: We identified all men age 40 to less than 80 years who underwent radical prostatectomy for prostate cancer from 2000 to 2008 in the NIS (Nationwide Inpatient Sample) (586,429). Ownership of a surgical robot was determined using the 2007 AHA (American Hospital Association) Annual Survey. The association between hospital radical prostatectomy volume and hospital characteristics, including ownership of a robot, was explored using multivariate linear regression. Results: From 2000 to 2008 there was a 74% increase in the number of radical prostatectomies performed (p = 0.05) along with a 19% decrease in the number of hospitals performing radical prostatectomy (p < 0.001), resulting in an increase in annual hospital radical prostatectomy volume (p = 0.009). Several hospital variables were associated with greater radical prostatectomy volume including teaching status, urban location, large bed size and ownership of a robot in 2007. On multivariate analysis the year, teaching status, large bed size, urban location and presence of a robot were associated with higher hospital radical prostatectomy volume. Conclusions: Use of radical prostatectomy increased significantly between 2000 and 2008, most notably after 2005. The increase in radical prostatectomy resulted in centralization to select hospitals, particularly those in the top radical prostatectomy volume quartile and those investing in robotic technology. Our findings support the hypothesis that hospitals with the greatest volume increases are specialty centers already performing a high volume of radical prostatectomy procedures. C1 [Anderson, Christopher B.; Penson, David F.; Ni, Shenghua; Barocas, Daniel A.] Vanderbilt Univ, Med Ctr, Dept Urol Surg, Nashville, TN 37232 USA. [Penson, David F.; Barocas, Daniel A.] Vanderbilt Univ, Med Ctr, Ctr Surg Qual & Outcomes Res, Nashville, TN 37232 USA. [Penson, David F.] Tennessee Valley Geriatr Res Educ & Clin Ctr DFP, US Dept Vet Affairs, Nashville, TN USA. [Makarov, Danil V.] NYU, Sch Med, Dept Urol, New York, NY 10003 USA. [Makarov, Danil V.] New York Harbor Healthcare Syst, US Dept Vet Affairs, New York, NY USA. RP Anderson, CB (reprint author), Vanderbilt Univ, Med Ctr, Dept Urol Surg, A-1302 Med Ctr N, Nashville, TN 37232 USA. EM c.anderson@vanderbilt.edu RI Ni, Shenghua/E-7300-2013; OI Ni, Shenghua/0000-0002-8411-9126; Makarov, Danil/0000-0002-0565-9272 FU Agency for Healthcare Research and Quality [1 R01 HS019356-01] FX Supported by Grant 1 R01 HS019356-01 from the Agency for Healthcare Research and Quality (DFP) NR 28 TC 15 Z9 15 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD FEB PY 2013 VL 189 IS 2 BP 500 EP 506 DI 10.1016/j.juro.2012.10.012 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 069VI UT WOS:000313464800027 PM 23069384 ER PT J AU Bianchi, G Ghobrial, IM AF Bianchi, Giada Ghobrial, Irene M. TI Molecular mechanisms of effectiveness of novel therapies in multiple myeloma SO LEUKEMIA & LYMPHOMA LA English DT Review DE Multiple myeloma; novel therapies; microenvironment ID PROTEASOME INHIBITOR PS-341; UNFOLDED PROTEIN RESPONSE; BONE-MARROW MICROENVIRONMENT; MHC CLASS-I; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; REGULATES AGGRESOME FORMATION; PLASMA-CELL DIFFERENTIATION; TRANSCRIPTION FACTOR XBP-1; CHEMOKINE RECEPTOR CXCR4; NON-HODGKINS-LYMPHOMA AB The prognosis of patients with multiple myeloma (MM) has radically changed over the past two decades mostly due to the introduction of novel pharmacologic treatments such as thalidomide, bortezomib and lenalidomide. These drugs were the first new anti-myeloma agents since the 1950s, and represented a landmark step in the race for the cure of MM and the paradigm of effectiveness of bench-to-bedside research. Compared to a median overall survival of 2-3 years in the mid-1950s, patients with MM have nowadays an expected median survival of 7-8 years. Novel agents have not only extended the life expectancy of patients with MM, but also shed light on the necessity of further understanding the biology of MM in order to design more effective, less toxic therapies. Basic research has provided a critical mass of information about the molecular and cellular biology of MM, particularly the pivotal pathogenetic role of the bone marrow niche. Several novel drugs, designed to specifically target MM in the context of its microenvironment, are currently in clinical trials and hold great promise for improving the MM treatment armamentarium and overcoming resistance. In this article we review the biological basis of effectiveness of anti-myeloma agents with an emphasis on experimental drugs. C1 [Bianchi, Giada] Mayo Clin, Dept Internal Med, Rochester, MN USA. [Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Ghobrial, IM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM Irene_Ghobrial@dfci.harvard.edu NR 196 TC 7 Z9 7 U1 1 U2 29 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD FEB PY 2013 VL 54 IS 2 BP 229 EP 241 DI 10.3109/10428194.2012.706287 PG 13 WC Oncology; Hematology SC Oncology; Hematology GA 067HR UT WOS:000313285400008 PM 22897729 ER PT J AU Cea, M Cagnetta, A Cirmena, G Garuti, A Rocco, I Palermo, C Pierri, I Reverberi, D Nencioni, A Ballestrero, A Gobbi, M Carella, AM Patrone, F AF Cea, Michele Cagnetta, Antonia Cirmena, Gabriella Garuti, Anna Rocco, Ilaria Palermo, Claudia Pierri, Ivana Reverberi, Daniele Nencioni, Alessio Ballestrero, Alberto Gobbi, Marco Carella, Angelo Michele Patrone, Franco TI Tracking molecular relapse of chronic myeloid leukemia by measuring Hedgehog signaling status SO LEUKEMIA & LYMPHOMA LA English DT Article DE Chronic myeloid leukemia; molecular monitoring; leukemic stem cell; resistance to treatment ID CANCER STEM-CELLS; CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; KINASE DOMAIN MUTATIONS; PANCREATIC-CANCER; WORKING PARTY; IMATINIB; PATHWAY; CHEMOTHERAPY; INHIBITION AB Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by the expansion of a leukemic stem cell (LSC) clone, carring a Philadelphia translocation, able to overcome the non-malignant hematopoietic stem cells. The tyrosine kinase inhibitors (TKIs) imatinib, nilotinib and dasatinib are gold-standard for CML treatment. Each shows an impressive rate of complete cytogenetic response in chronic phase (CP)-CML. However, relapse and treatment failure are major problems with long-term use of TKIs. A polymerase chain reaction (PCR) assay to detect the mRNA expression of BCR-ABL1 represents the main molecular approach to monitoring response to treatment. However, using this analysis it is currently not possible to prospectively identify patients whose disease will relapse due to LSC reappearance. The aim of our study was to investigate whether the mRNA expression analysis of two Hedgehog (Hh) stemness signaling molecules, Smoothened (SMO) and Patched-1 (PTCH1), could predict upcoming molecular relapse. At the time of diagnosis, patients with high Sokal risk (n = 12) showed higher and lower levels of SMO and PTCH1, respectively (p = 0.0132), compared with patients with different Sokal scores (p = 0.0316 for intermediate risk and p = 0.0340 for low risk). These data suggest that Hh signaling was functionally more active in this risk group at the time of diagnosis. Furthermore, the kinetics of Hh signaling activity during the individual medical history correlated with BCR-ABL1 mRNA level and with upcoming molecular relapse. Also, mutation analysis of BCR-ABL1 revealed that activation of Hh signaling precedes molecular relapse by several months, mostly in patients carrying the gatekeeper mutation T315I. Importantly, in vitro data showed a synergistic effect of chemical inhibitors of Hh signaling and TKIs in both wild-type and resistant (T315I) CML cell lines. Collectively our data show that monitoring Hh pathway activity contemporaneously with BCR-ABL1 mRNA level may improve the chance of early detection of patients who will experience a relapse (mainly in the high Sokal risk group), paving the way for an innovative management of this hematologic malignancy. C1 [Cea, Michele; Cagnetta, Antonia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Cea, Michele; Cagnetta, Antonia] Harvard Univ, Sch Med, Boston, MA USA. [Cea, Michele; Cagnetta, Antonia; Pierri, Ivana; Gobbi, Marco; Carella, Angelo Michele] IRCCSAOU San Martino IST, Dept Hematol & Oncol, Genoa, Italy. [Cirmena, Gabriella; Garuti, Anna; Rocco, Ilaria; Palermo, Claudia; Nencioni, Alessio; Ballestrero, Alberto; Patrone, Franco] IRCCSAOU San Martino IST, Dept Internal Med, Genoa, Italy. [Reverberi, Daniele] Natl Canc Inst, Med Oncol Div C, Genoa, Italy. RP Cea, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Mayer 551, Boston, MA 02115 USA. EM Michele_Cea@dfci.harvard.edu FU American Italian Cancer Foundation; Fondazione Italiana Ricerca sul Cancro; Associazione Cristina Bassi Onlus; Associazione Italiana per la Ricerca sul Cancro FX M.C. was supported by the American Italian Cancer Foundation and by Fondazione Italiana Ricerca sul Cancro; A. C. was supported by the Associazione Cristina Bassi Onlus. NR 39 TC 4 Z9 5 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD FEB PY 2013 VL 54 IS 2 BP 342 EP 352 DI 10.3109/10428194.2012.708752 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA 067HR UT WOS:000313285400024 PM 22762548 ER PT J AU McCormack, SE Shaham, O McCarthy, MA Deik, AA Wang, TJ Gerszten, RE Clish, CB Mootha, VK Grinspoon, SK Fleischman, A AF McCormack, S. E. Shaham, O. McCarthy, M. A. Deik, A. A. Wang, T. J. Gerszten, R. E. Clish, C. B. Mootha, V. K. Grinspoon, S. K. Fleischman, A. TI Circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents SO PEDIATRIC OBESITY LA English DT Article DE Branched-chain amino acids; insulin resistance; metabolomics; paediatric obesity ID FASTING PLASMA-GLUCOSE; PROTEIN-METABOLISM; LEUCINE TURNOVER; WEIGHT-LOSS; SENSITIVITY; PUBERTY; HUMANS; SECRETION; SIGNATURE; EXERCISE AB What is already known about this subject Circulating concentrations of branched-chain amino acids (BCAAs) can affect carbohydrate metabolism in skeletal muscle, and therefore may alter insulin sensitivity. BCAAs are elevated in adults with diet-induced obesity, and are associated with their future risk of type 2 diabetes even after accounting for baseline clinical risk factors. What this study adds Increased concentrations of BCAAs are already present in young obese children and their metabolomic profiles are consistent with increased BCAA catabolism. Elevations in BCAAs in children are positively associated with insulin resistance measured 18 months later, independent of their initial body mass index. Background Branched-chain amino acid (BCAA) concentrations are elevated in response to overnutrition, and can affect both insulin sensitivity and secretion. Alterations in their metabolism may therefore play a role in the early pathogenesis of type 2 diabetes in overweight children. Objective To determine whether paediatric obesity is associated with elevations in fasting circulating concentrations of BCAAs (isoleucine, leucine and valine), and whether these elevations predict future insulin resistance. Methods Sixty-nine healthy subjects, ages 818 years, were enrolled as a cross-sectional cohort. A subset of subjects who were pre- or early-pubertal, ages 813 years, were enrolled in a prospective longitudinal cohort for 18 months (n?=?17 with complete data). Results Elevations in the concentrations of BCAAs were significantly associated with body mass index (BMI) Z-score (Spearman's Rho 0.27, P?=?0.03) in the cross-sectional cohort. In the subset of subjects that followed longitudinally, baseline BCAA concentrations were positively associated with homeostasis model assessment for insulin resistance measured 18 months later after controlling for baseline clinical factors including BMI Z-score, sex and pubertal stage (P?=?0.046). Conclusions Elevations in the concentrations of circulating BCAAs are significantly associated with obesity in children and adolescents, and may independently predict future insulin resistance. C1 [McCormack, S. E.; McCarthy, M. A.; Grinspoon, S. K.; Fleischman, A.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [McCormack, S. E.; McCarthy, M. A.; Grinspoon, S. K.; Fleischman, A.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [McCormack, S. E.; McCarthy, M. A.; Grinspoon, S. K.; Fleischman, A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [McCormack, S. E.; Fleischman, A.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Shaham, O.; Deik, A. A.; Gerszten, R. E.; Clish, C. B.; Mootha, V. K.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Shaham, O.] IBM Res, Haifa, Israel. [Mootha, V. K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Mootha, V. K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Wang, T. J.; Gerszten, R. E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Wang, T. J.; Gerszten, R. E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Wang, T. J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Wang, T. J.] Boston Univ, Sch Med, Framingham, MA USA. RP Fleischman, A (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON 207, Boston, MA 02114 USA. EM afleischman@partners.org FU National Institutes of Health [K23 DK080658, K24 DK064545, 5R01 DK081572-03, R01 DK081457]; Harvard Clinical and Translational Science Center, from the National Center for Research Resources [1 UL1 RR025758-03, M01-RR-01066]; Harvard Clinical Nutrition Research Center Pilot/Feasibility Project grant [5P30DK040561-15]; Genentech Clinical Scholars Award from the Lawson Wilkins Endocrinology Society FX This work was supported by grants from the National Institutes of Health (K23 DK080658 [A.F.], K24 DK064545 [S.K.G.], 5R01 DK081572-03 [R.E.G. and T.J.W.] and R01 DK081457 [V.K.M.]), and a gift from Nestle Research Center to the Broad Institute. The project was also supported by grant numbers 1 UL1 RR025758-03 and M01-RR-01066, 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.) In addition, the study was supported by a Harvard Clinical Nutrition Research Center Pilot/Feasibility Project grant (5P30DK040561-15) (A.F.), a Genentech Clinical Scholars Award from the Lawson Wilkins Endocrinology Society (A.F.), a gift from the Henry T. Zarrow Foundation (A.F.) and the Career Development Award (A.F.) from the Children's Hospital Boston. NR 45 TC 93 Z9 94 U1 6 U2 59 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-6310 J9 PEDIATR OBES JI Pediatr. Obes. PD FEB PY 2013 VL 8 IS 1 BP 52 EP 61 DI 10.1111/j.2047-6310.2012.00087.x PG 10 WC Pediatrics SC Pediatrics GA 066YL UT WOS:000313258300009 PM 22961720 ER PT J AU Hakimi, K Spanier, D AF Hakimi, Kevin Spanier, David TI Electrodiagnosis of Cervical Radiculopathy SO PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA LA English DT Article DE Cervical; Radiculopathy; Electrodiagnosis; Electromyography ID FLEXOR CARPI RADIALIS; ASYMPTOMATIC SUBJECTS; H-REFLEX; UTILITY; ROOT; ELECTROMYOGRAPHY; EPIDEMIOLOGY; MYELOGRAPHY; DIAGNOSIS; STENOSIS AB Cervical radiculopathy is a common diagnosis with a peak onset in the fifth decade. The most commonly affected nerve root is C7, C6, and C8. The etiology is often compressive, but may arise from noncompressive sources. Patients commonly complain of pain, weakness, numbness, and/or tingling. Examination may reveal sensory or motor disturbance in-a dermatomal/myotomal distribution. Neural compression and tension signs may be positive. Diagnostic tests include imaging and electrodiagnostic study. Electrodiagnostic study serves as an extension of the neurologic examination. Electrodiagnostic findings can be useful for patients with atypical symptoms, potential pain-mediated weakness, and nonfocal imaging findings. C1 [Hakimi, Kevin; Spanier, David] VA Puget Sound, Rehabil Care Serv RCS 117, Dept Rehabil Med, Rehabil Care Serv, Seattle, WA 98108 USA. RP Hakimi, K (reprint author), VA Puget Sound, Rehabil Care Serv RCS 117, Dept Rehabil Med, Rehabil Care Serv, 1660 S Columbian Way, Seattle, WA 98108 USA. EM khakimi@uw.edu NR 24 TC 5 Z9 5 U1 3 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1047-9651 J9 PHYS MED REH CLIN N JI Phys. Med. Rehabil. Clin. N. Am. PD FEB PY 2013 VL 24 IS 1 BP 1 EP + DI 10.1016/j.pmr.2012.08.012 PG 13 WC Rehabilitation SC Rehabilitation GA 065KA UT WOS:000313146000003 PM 23177027 ER PT J AU Brooks-Worrell, BM Palmer, JP AF Brooks-Worrell, B. M. Palmer, J. P. TI Attenuation of islet-specific T cell responses is associated with C-peptide improvement in autoimmune type 2 diabetes patients SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE autoimmunity; PPAR-; rosiglitazone; T cells; type 2 diabetes ID PROLIFERATOR-ACTIVATED-RECEPTOR; PPAR-GAMMA AGONISTS; PROGRESSIVE MULTIPLE-SCLEROSIS; TRANSCRIPTION FACTOR; IMMUNE-RESPONSES; INTERLEUKIN-12; ENCEPHALOMYELITIS; INFLAMMATION; LYMPHOCYTES; DISEASES AB The clinical efficacy of peroxisome proliferator-activated receptor gamma (PPAR-?) agonists in cell-mediated autoimmune diseases results from down-regulation of inflammatory cytokines and autoimmune effector cells. T cell islet autoimmunity has been demonstrated to be common in patients with phenotypic type 2 diabetes mellitus (T2DM) and islet-specific T cells (T+) to be correlated positively with more severe beta cell dysfunction. We hypothesized that the beneficial effects of the PPAR-? agonist, rosiglitazone, therapy in autoimmune T2DM patients is due, in part, to the immunosuppressive properties on the islet-specific T cell responses. Twenty-six phenotypic T2DM patients positive for T cell islet autoimmunity (T+) were identified and randomized to rosiglitazone (n?=?12) or glyburide (n?=?14). Beta cell function, islet-specific T cell responses, interleukin (IL)-12 and interferon (IFN)-? responses and islet autoantibodies were followed for 36 months. Patients treated with rosiglitazone demonstrated significant (P? 90 consecutive days). Results: During the study year, 35% of the sample received an opioid prescription and 5% received COT. Most first opioid prescriptions were written by primary care clinicians. Veterans prescribed COT were younger, had greater pain intensity, and high rates of psychiatric and substance use disorders compared with veterans in the other 2 groups. Among patients receiving COT, 29% were prescribed long-acting opioids, 37% received 1 or more urine drug screens, and 24% were prescribed benzodiazepines. Adjusting for age, sex, and baseline pain intensity, major depression [odds ratio 1.24 (1.10-1.39); 1.48 (1.14-1.93)], and nicotine dependence [1.34 (1.17-1.53); 2.02 (1.53-2.67)] were associated with receiving any opioid prescription and with COT, respectively. Discussion: Opioid initiations are common among veterans with persistent pain, but most veterans are not prescribed opioids long-term. Psychiatric disorders and substance use disorders are associated with receiving COT. Many Veterans receiving COT are concurrently prescribed benzodiazepines and many do not receive urine drug screening; additional study regarding practices that optimize safety of COT in this population is indicated. C1 [Dobscha, Steven K.; Morasco, Benjamin J.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR USA. [Dobscha, Steven K.; Morasco, Benjamin J.; Macey, Tara] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Ctr Occupat & Environm Toxicol, Portland, OR 97201 USA. [Dobscha, Steven K.; Morasco, Benjamin J.; Duckart, Jonathan P.] Portland VA Med Ctr, Ctr Study Chron Comorbid Mental & Phys Disorders, Portland, OR USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR 97201 USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Dept Internal Med, Portland, OR 97201 USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Deyo, Richard A.] Kaiser Permanente Ctr Hlth Res, Portland, OR 90034 USA. RP Dobscha, SK (reprint author), Portland VA Med Ctr P3MHADM, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM steven.dobscha@va.gov FU National Institute on Drug Abuse, Bethesda, MD [K23DA023467]; VA Health Services Research and Development Service, Portland, OR [REA 06-174] FX Supported with resources and the use of facilities at the Portland VA Medical Center, Portland, OR. B.J.M. received support from award K23DA023467 from the National Institute on Drug Abuse, Bethesda, MD. J.P.D. was supported by grant REA 06-174 from the VA Health Services Research and Development Service, Portland, OR. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs or the National Institutes of Health. The authors declare no conflict of interest. NR 43 TC 35 Z9 36 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0749-8047 J9 CLIN J PAIN JI Clin. J. Pain PD FEB PY 2013 VL 29 IS 2 BP 102 EP 108 DI 10.1097/AJP.0b013e3182490bdb PG 7 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 063VK UT WOS:000313029900003 PM 23269280 ER PT J AU Hwang, U Platts-Mills, TF AF Hwang, Ula Platts-Mills, Timothy F. TI Acute Pain Management in Older Adults in the Emergency Department SO CLINICS IN GERIATRIC MEDICINE LA English DT Article DE Pain; Geriatrics; Emergency medicine; Pain assessment; Analgesics ID RANDOMIZED CONTROLLED-TRIAL; POSTOPERATIVE PAIN; HIP FRACTURE; PHARMACOLOGICAL MANAGEMENT; MUSCULOSKELETAL PAIN; COMPARATIVE SAFETY; COPING SKILLS; CARE; MEDICATION; ANALGESIA AB Effective treatment of acute pain in older patients is a common challenge faced by emergency providers. Because older adults are at increased risk for adverse events associated with systemic analgesics, pain treatment must proceed cautiously. Essential elements to quality acute pain care include an early initial assessment for the presence of pain, selection of an analgesic based on patient-specific risks and preferences, and frequent reassessments and retreatments as needed. This article describes current knowledge regarding the assessment and treatment of acute pain in older adults. C1 [Hwang, Ula] Mt Sinai Sch Med, Dept Emergency Med, New York, NY 10029 USA. [Hwang, Ula] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Hwang, Ula] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Platts-Mills, Timothy F.] Univ N Carolina, Dept Emergency Med, Chapel Hill, NC USA. [Platts-Mills, Timothy F.] Univ N Carolina, Dept Anesthesiol, Chapel Hill, NC USA. RP Hwang, U (reprint author), Mt Sinai Sch Med, Dept Emergency Med, 1 Gustave L Levy Pl,Box 1620, New York, NY 10029 USA. EM ula.hwang@mountsinai.org FU National Institute on Aging [AG031218, AG040734]; National Center for Research Resources through North Carolina Translational and Clinical Science Institute [KL2 TR000084, UL1 TR000083] FX Ula Hwang is supported by a K23 (AG031218) and R21 (AG040734) from the National Institute on Aging to study pain care for older adults in the ED setting. Dr Platts-Mills is supported by Award Number KL2 TR000084 and UL1 TR000083 from the National Center for Research Resources through the North Carolina Translational and Clinical Science Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources, the National Institutes of Health, or the North Carolina Translational and Clinical Science Institute. NR 71 TC 8 Z9 8 U1 3 U2 17 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0690 EI 1879-8853 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD FEB PY 2013 VL 29 IS 1 BP 151 EP + DI 10.1016/j.cger.2012.10.006 PG 15 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 058HK UT WOS:000312624500009 PM 23177605 ER PT J AU Lo, AX Harada, CN AF Lo, Alexander X. Harada, Caroline N. TI Geriatric Dizziness Evolving Diagnostic and Therapeutic Approaches for the Emergency Department SO CLINICS IN GERIATRIC MEDICINE LA English DT Article DE Dizziness; Geriatrics; Vertigo; Stroke ID PAROXYSMAL POSITIONAL VERTIGO; NATIONALLY REPRESENTATIVE SAMPLE; TRANSIENT ISCHEMIC ATTACK; ACUTE VESTIBULAR SYNDROME; CROSS-SECTIONAL ANALYSIS; PRIMARY-CARE; PERSISTENT DIZZINESS; ELDERLY-PATIENTS; EPLEY MANEUVER; DIZZY PATIENT AB Dizziness affects one in five people over the age of 65 years and is associated with substantial healthcare costs. Serious causes of dizziness are found in 20% of patients over 50 years. The approach to the patient with dizziness is challenging as physical exam and diagnostic tests have suboptimal sensitivities. The risk of vascular events is higher in the first 30 days than after, suggesting some missed diagnoses. Medications and vestibular rehabilitation may serve as treatment options for dizziness, but data on their efficacy in older patients is lacking. C1 [Lo, Alexander X.] Univ Alabama Birmingham, Dept Emergency Med, Birmingham, AL 35249 USA. [Harada, Caroline N.] Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. [Harada, Caroline N.] Univ Alabama Birmingham, Dept Med, Div Gerontol Geriatr & Palliat Care, Birmingham, AL 35249 USA. RP Lo, AX (reprint author), Univ Alabama Birmingham, Dept Emergency Med, OHB 251,619 19th St S, Birmingham, AL 35249 USA. EM alexanderlo@uabmc.edu FU John Hartford Foundation FX Supported by a grant from the John Hartford Foundation. NR 107 TC 3 Z9 6 U1 4 U2 14 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD FEB PY 2013 VL 29 IS 1 BP 181 EP + DI 10.1016/j.cger.2012.10.004 PG 25 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 058HK UT WOS:000312624500011 PM 23177607 ER PT J AU Pawlowski, J AF Pawlowski, John TI Anesthetic considerations for interventional pulmonary procedures SO CURRENT OPINION IN ANESTHESIOLOGY LA English DT Review DE anesthesia; bronchoscopy; pleuroscopy; pulmonology; sedation; total intravenous ID FREQUENCY JET VENTILATION; BRONCHIAL THERMOPLASTY; BRONCHOSCOPY; REDUCTION; SURGERY; AIRWAY; ASTHMA; STENT AB Purpose of review To discuss the anesthetic considerations of various procedures now performed by the interventional pulmonologist. With recent technological advances, many of these procedures represent acceptable alternatives to the invasive surgical procedures. For example, the placement of endobronchial valves can substitute for lung reduction surgery and can greatly reduce the postoperative recovery period. However, many of these complex procedures require anesthesia services. The nature and indication for the procedure as well as the patient's overall health will have an impact on the anesthetic choice. Recent findings New studies have documented common complications from interventional pulmonology procedures and recent ways to avoid these complications have been suggested. Strategies to avoid obstruction, bleeding, pneumothorax and air embolism are discussed in this article. Potential benefits of high frequency jet ventilation in reducing airway pressures and, perhaps, barotraumas are cited. Novel interventional pulmonary procedures are described. Summary As the array of diagnostic and therapeutic pulmonary interventions is expanding, the types of anesthetic techniques and ventilatory modes are varying to fit the procedural requirements. Some pulmonary procedures are best accomplished in the lightly sedated patient, who is breathing spontaneously, whereas procedures that use the working channel of a rigid bronchoscope are better performed in the patient under general anesthesia and mechanical ventilation that often use jet ventilation to minimize respiratory movements. C1 Dept Anesthesia, Boston, MA 02215 USA. RP Pawlowski, J (reprint author), Dept Anesthesia, CC539 Beth Israel Deaconess Med Ctr,1 Deaconess R, Boston, MA 02215 USA. EM jpawlows@bidmc.harvard.edu NR 22 TC 7 Z9 7 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0952-7907 J9 CURR OPIN ANESTHESIO JI Curr. Opin. Anesthesiol. PD FEB PY 2013 VL 26 IS 1 BP 6 EP 12 DI 10.1097/ACO.0b013e32835bd0aa PG 7 WC Anesthesiology SC Anesthesiology GA 062WG UT WOS:000312953900002 PM 23235522 ER PT J AU Albrechtsen, A Grarup, N Li, Y Sparso, T Tian, G Cao, H Jiang, T Kim, SY Korneliussen, T Li, Q Nie, C Wu, R Skotte, L Morris, AP Ladenvall, C Cauchi, S Stancakova, A Andersen, G Astrup, A Banasik, K Bennett, AJ Bolund, L Charpentier, G Chen, Y Dekker, JM Doney, ASF Dorkhan, M Forsen, T Frayling, TM Groves, CJ Gui, Y Hallmans, G Hattersley, AT He, K Hitman, GA Holmkvist, J Huang, S Jiang, H Jin, X Justesen, JM Kristiansen, K Kuusisto, J Lajer, M Lantieri, O Li, W Liang, H Liao, Q Liu, X Ma, T Ma, X Manijak, MP Marre, M Mokrosinski, J Morris, AD Mu, B Nielsen, AA Nijpels, G Nilsson, P Palmer, CNA Rayner, NW Renstrom, F Ribel-Madsen, R Robertson, N Rolandsson, O Rossing, P Schwartz, TW Slagboom, PE Sterner, M Tang, M Tarnow, L Tuomi, T van't Riet, E van Leeuwen, N Varga, TV Vestmar, MA Walker, M Wang, B Wang, Y Wu, H Xi, F Yengo, L Yu, C Zhang, X Zhang, J Zhang, Q Zhang, W Zheng, H Zhou, Y Altshuler, D 't Hart, LM Franks, PW Balkau, B Froguel, P McCarthy, MI Laakso, M Groop, L Christensen, C Brandslund, I Lauritzen, T Witte, DR Linneberg, A Jorgensen, T Hansen, T Wang, J Nielsen, R Pedersen, O AF Albrechtsen, A. Grarup, N. Li, Y. Sparso, T. Tian, G. Cao, H. Jiang, T. Kim, S. Y. Korneliussen, T. Li, Q. Nie, C. Wu, R. Skotte, L. Morris, A. P. Ladenvall, C. Cauchi, S. Stancakova, A. Andersen, G. Astrup, A. Banasik, K. Bennett, A. J. Bolund, L. Charpentier, G. Chen, Y. Dekker, J. M. Doney, A. S. F. Dorkhan, M. Forsen, T. Frayling, T. M. Groves, C. J. Gui, Y. Hallmans, G. Hattersley, A. T. He, K. Hitman, G. A. Holmkvist, J. Huang, S. Jiang, H. Jin, X. Justesen, J. M. Kristiansen, K. Kuusisto, J. Lajer, M. Lantieri, O. Li, W. Liang, H. Liao, Q. Liu, X. Ma, T. Ma, X. Manijak, M. P. Marre, M. Mokrosinski, J. Morris, A. D. Mu, B. Nielsen, A. A. Nijpels, G. Nilsson, P. Palmer, C. N. A. Rayner, N. W. Renstrom, F. Ribel-Madsen, R. Robertson, N. Rolandsson, O. Rossing, P. Schwartz, T. W. Slagboom, P. E. Sterner, M. Tang, M. Tarnow, L. Tuomi, T. van't Riet, E. van Leeuwen, N. Varga, T. V. Vestmar, M. A. Walker, M. Wang, B. Wang, Y. Wu, H. Xi, F. Yengo, L. Yu, C. Zhang, X. Zhang, J. Zhang, Q. Zhang, W. Zheng, H. Zhou, Y. Altshuler, D. 't Hart, L. M. Franks, P. W. Balkau, B. Froguel, P. McCarthy, M. I. Laakso, M. Groop, L. Christensen, C. Brandslund, I. Lauritzen, T. Witte, D. R. Linneberg, A. Jorgensen, T. Hansen, T. Wang, J. Nielsen, R. Pedersen, O. CA DESIR Study Grp DIAGRAM Consortium TI Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes SO DIABETOLOGIA LA English DT Article DE Exome sequencing; Genetic epidemiology; Genetics; Lipids; Next-generation sequencing; Obesity; Type 2 diabetes ID GENOME-WIDE ASSOCIATION; DIABETES SUSCEPTIBILITY LOCI; DE-NOVO MUTATIONS; GLUCOSE-HOMEOSTASIS; IDENTIFIES 6; VARIANTS; RISK; METAANALYSIS; INDIVIDUALS; EFFICIENT AB Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) > 1% with common metabolic phenotypes. The study comprised three stages. We performed medium-depth (8x) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI > 27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case-control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans. Exome sequencing identified 70,182 polymorphisms with MAF > 1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 x 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 x 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 x 10(-10)). We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits. C1 [Albrechtsen, A.; Korneliussen, T.; Skotte, L.; Nielsen, R.] Univ Copenhagen, Ctr Bioinformat, Fac Sci, DK-2100 Copenhagen O, Denmark. [Grarup, N.; Sparso, T.; Andersen, G.; Banasik, K.; Holmkvist, J.; Justesen, J. M.; Manijak, M. P.; Mokrosinski, J.; Ribel-Madsen, R.; Schwartz, T. W.; Vestmar, M. A.; Hansen, T.; Wang, J.; Pedersen, O.] Univ Copenhagen, Novo Nordisk Fdn, Ctr Basic Metab Res, Fac Hlth & Med Sci, DK-2100 Copenhagen O, Denmark. [Li, Y.; Cao, H.; Jiang, T.; Li, Q.; Nie, C.; Wu, R.; Chen, Y.; Gui, Y.; Huang, S.; Jiang, H.; Jin, X.; Li, W.; Liang, H.; Liao, Q.; Liu, X.; Ma, T.; Ma, X.; Mu, B.; Tang, M.; Wang, B.; Wang, Y.; Wu, H.; Xi, F.; Yu, C.; Zhang, X.; Zhang, J.; Zhang, Q.; Zhang, W.; Zheng, H.; Zhou, Y.; Wang, J.] BGI Shenzhen, Shenzhen 518083, Peoples R China. [Tian, G.] BGI Tianjin, Tianjin, Peoples R China. [Kim, S. Y.; Nielsen, R.] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA. [Morris, A. P.; Rayner, N. W.; Robertson, N.; McCarthy, M. I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Ladenvall, C.; Dorkhan, M.; Sterner, M.; Groop, L.] Lund Univ, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden. [Ladenvall, C.; Dorkhan, M.; Sterner, M.; Groop, L.] Lund Univ, Ctr Diabet, Malmo, Sweden. [Cauchi, S.; Yengo, L.; Froguel, P.] Inst Pasteur, Ctr Immunol & Biol Parasitaire, CNRS, UMR Genom & Metab Dis 8199, F-59019 Lille, France. [Stancakova, A.; Kuusisto, J.; Laakso, M.] Univ Eastern Finland, Dept Med, Kuopio, Finland. [Stancakova, A.; Kuusisto, J.; Laakso, M.] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Astrup, A.] Univ Copenhagen, Dept Human Nutr, Fac Sci, DK-2100 Copenhagen O, Denmark. [Bennett, A. J.; Groves, C. J.; Rayner, N. W.; Robertson, N.; McCarthy, M. I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Bolund, L.] Aarhus Univ, Inst Human Genet, DK-8000 Aarhus, Denmark. [Charpentier, G.] Corbeil Essonnes Hosp, Dept Endocrinol Diabetol, Corbeil Essonnes, France. [Dekker, J. M.; Nijpels, G.; van't Riet, E.] Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands. [Doney, A. S. F.; Morris, A. D.; Palmer, C. N. A.] Univ Dundee, Diabet Res Ctr, Biomed Res Inst, Ninewells Hosp, Dundee, Scotland. [Doney, A. S. F.; Morris, A. D.; Palmer, C. N. A.] Univ Dundee, Pharmacogen Ctr, Biomed Res Inst, Ninewells Hosp, Dundee, Scotland. [Forsen, T.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Forsen, T.] Vasa Hlth Care Ctr, Vaasa, Finland. [Frayling, T. M.; Hattersley, A. T.] Univ Exeter, Inst Biomed & Clin Sci, Peninsula Med Sch, Exeter, Devon, England. [Hallmans, G.; Rolandsson, O.; Franks, P. W.] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [He, K.] Chinese Peoples Liberat Army Gen Hosp, Beijing, Peoples R China. [Hitman, G. A.] Queen Mary Univ London, Ctr Diabet, Blizard Inst, London, England. [Holmkvist, J.] Vipergen Aps, Copenhagen, Denmark. [Huang, S.] S China Univ Technol, Sch Biosci & Biotechnol, Guangzhou, Guangdong, Peoples R China. [Kristiansen, K.; Wang, J.] Univ Copenhagen, Fac Sci, Dept Biol, DK-2100 Copenhagen O, Denmark. [Lajer, M.; Rossing, P.; Tarnow, L.; Witte, D. R.] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Lantieri, O.; DESIR Study Grp] Inst Inter Reg Sante IRSA, La Riche, France. [Marre, M.] Bichat Claude Bernard Univ Hosp, AP HP, Dept Endocrinol Diabetol & Nutr, Paris, France. [Marre, M.] Univ Paris 07, INSERM, U695, Paris, France. [Mokrosinski, J.; Schwartz, T. W.; Vestmar, M. A.] Univ Copenhagen, Mol Pharmacol Lab, Dept Pharmacol, Fac Hlth & Med Sci, DK-2100 Copenhagen O, Denmark. [Nielsen, A. A.; Brandslund, I.] Vejle Hosp, Dept Clin Biochem, Vejle, Denmark. [Nilsson, P.] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Renstrom, F.; Varga, T. V.; Franks, P. W.] Lund Univ, Skana Univ Hosp, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden. [Slagboom, P. E.; 't Hart, L. M.] Leiden Univ, Med Ctr, Sect Mol Epidemiol, Leiden, Netherlands. [Slagboom, P. E.] Netherlands Ctr Hlth Ageing, Leiden, Netherlands. [Tuomi, T.] Helsinki Univ Hosp, Dept Med, Helsinki, Finland. [Tuomi, T.] Folkhalsan Res Ctr, Helsinki, Finland. [van Leeuwen, N.; 't Hart, L. M.] Leiden Univ, Med Ctr, Dept Mol Cell Biol, Leiden, Netherlands. [Walker, M.] Newcastle Univ, Diabet Res Grp, Sch Clin Med Sci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Altshuler, D.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Altshuler, D.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Franks, P. W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Balkau, B.] INSERM, U1018, CESP, Villejuif, France. [Froguel, P.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England. [McCarthy, M. I.] Churchill Hosp, Oxford Natl Inst Hlth Res, Biomed Res Ctr, Oxford OX3 7LJ, England. [Christensen, C.] Vejle Hosp, Dept Internal Med & Endocrinol, Vejle, Denmark. [Brandslund, I.] Univ So Denmark, Inst Reg Hlth Res, Odense, Denmark. [Lauritzen, T.] Aarhus Univ, Dept Gen Practice, Aarhus, Denmark. [Linneberg, A.; Jorgensen, T.] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark. [Jorgensen, T.] Aalborg Univ, Fac Med, Aalborg, Denmark. [Hansen, T.] Univ So Denmark, Fac Hlth Sci, Odense, Denmark. [Nielsen, R.] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA. [Pedersen, O.] Aarhus Univ, Fac Hlth Sci, Aarhus, Denmark. [Pedersen, O.] Hagedorn Res Inst, Gentofte, Denmark. [Pedersen, O.] Univ Copenhagen, Inst Biomed Sci, Fac Hlth & Med Sci, DK-2100 Copenhagen O, Denmark. RP Pedersen, O (reprint author), Univ Copenhagen, Novo Nordisk Fdn, Ctr Basic Metab Res, Fac Hlth & Med Sci, DIKU Bldg,Univ Pk 1, DK-2100 Copenhagen O, Denmark. EM wangj@genomics.org.cn; rasmus_nielsen@berkeley.edu; oluf@hagedorn.dk RI Slagboom, P. Eline/R-4790-2016; Yengo, Loic/D-2692-2017; Skotte, Line/F-7359-2014; Wang, Jun/B-9503-2016; Palmer, Colin/C-7053-2008; Nielsen, Rasmus/D-4405-2009; Banasik, Karina/G-1728-2013; Albrechtsen, Anders/K-4281-2013; Altshuler, David/A-4476-2009; Korneliussen, Thorfinn Sand/F-6421-2014; Witte, Daniel/C-1722-2008; Kristiansen, Karsten/J-5148-2014; Wang, Jun/C-8434-2016; Grarup, Niels/K-2807-2015; Justesen, Johanne Marie/L-6023-2015; Study, GoDARTS/K-9448-2016 OI Linneberg, Allan/0000-0002-0994-0184; Franks, Paul/0000-0002-0520-7604; rossing, peter/0000-0002-1531-4294; Tuomi, Tiinamaija/0000-0002-8306-6202; Jorgensen, Torben/0000-0001-9453-2830; Varga, Tibor/0000-0002-2383-699X; Hattersley, Andrew/0000-0001-5620-473X; Slagboom, P. Eline/0000-0002-2875-4723; Yengo, Loic/0000-0002-4272-9305; Skotte, Line/0000-0002-7398-1271; Wang, Jun/0000-0002-2113-5874; Marre, Michel/0000-0002-3071-1837; Zeggini, Eleftheria/0000-0003-4238-659X; Mokrosinski, Jacek/0000-0001-5008-0457; Palmer, Colin/0000-0002-6415-6560; Nielsen, Rasmus/0000-0003-0513-6591; Albrechtsen, Anders/0000-0001-7306-031X; Altshuler, David/0000-0002-7250-4107; Korneliussen, Thorfinn Sand/0000-0001-7576-5380; Witte, Daniel/0000-0002-0769-2922; Kristiansen, Karsten/0000-0002-6024-0917; Wang, Jun/0000-0002-8540-8931; Grarup, Niels/0000-0001-5526-1070; Justesen, Johanne Marie/0000-0002-0484-8522; FU Lundbeck Foundation; Novo Nordisk Foundation; Danish Council for Independent Research (Medical Sciences); Danish Research Council; Danish Centre for Health Technology Assessment; Novo Nordisk Inc.; Research Foundation of Copenhagen County; Ministry of Internal Affairs and Health; Danish Heart Foundation; Danish Pharmaceutical Association; Augustinus Foundation; Ib Henriksen Foundation; Becket Foundation; Danish Diabetes Association; Velux Foundation; Danish Medical Research Council; Danish Agency for Science, Technology and Innovation; Aase and Ejner Danielsens Foundation; ALK-Abello, (Horsholm, Denmark); Research Centre for Prevention and Health (the Capital Region of Denmark); Academy of Finland; Finnish Diabetes Research Foundation; Finnish Cardiovascular Research Foundation; EVO grant from the Kuopio University Hospital [5263]; Diabetes UK; BDA Research; UK Medical Research Council [G0000649]; Wellcome Trust [GR072960, 076113/C/04/Z, 06854/Z/02/Z, 083270, 081682/Z/06/Z]; NIHR [RP-PG-0310-1002]; Medical Research Council [G0000934]; EU [ENGAGE: HEALTH-F4-2007-201413]; Oxford NIHR Biomedical Research Centre; Dutch Diabetes Research Foundation [2006.00.060]; Bio-banking and Biomolecular Research Infrastructure the Netherlands (BBMRI-NL); Inserm; CNAMTS; Novartis; Lilly; sanofi-aventis; Inserm (Reseaux en Sante Publique, Interactions entre les determinants de la sante, Cohortes Sante TGIR); Association Diabete Risque Vasculaire; Federation Francaise de Cardiologie, La Fondation de France; ALFEDIAM; ONIVINS; Societe Francophone du Diabete; Ardix Medical; Bayer Diagnostics; Becton Dickinson; Cardionics; Merck Sante; Novo Nordisk; Pierre Fabre; Roche; Topcon; Swedish Research Foundation [Dnr-349-2006-6589, 2009-1039, 521-2010-3490]; Knut & Alice Wallenberg Foundation; Sigrid Juselius Foundation; Folkhalsan Research Foundation; Finnish Medical Society; Swedish Heart-Lung Foundation; Swedish Diabetes Association; Pahlssons Foundation; Swedish Research Council; Umea University; Heart Foundation of Northern Sweden FX This project was funded by the Lundbeck Foundation and produced by The Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention and Care (LuCamp, www.lucamp.org). The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk). Further funding came from the Danish Council for Independent Research (Medical Sciences).; The Inter99 was initiated by Torben Jorgensen (PI), Knut Borch-Johnsen (co-PI), Hans Ibsen and Troels F. Thomsen. The steering committee comprises the former two and Charlotta Pisinger. The study was financially supported by research grants from the Danish Research Council, the Danish Centre for Health Technology Assessment, Novo Nordisk Inc., Research Foundation of Copenhagen County, Ministry of Internal Affairs and Health, the Danish Heart Foundation, the Danish Pharmaceutical Association, the Augustinus Foundation, the Ib Henriksen Foundation, the Becket Foundation, and the Danish Diabetes Association.; The Health2006 was initiated by Allan Linneberg (PI) and Torben Jorgensen (co-PI). The study was financially supported by grants from the Velux Foundation, The Danish Medical Research Council, Danish Agency for Science, Technology and Innovation, The Aase and Ejner Danielsens Foundation, ALK-Abello, (Horsholm, Denmark) and Research Centre for Prevention and Health (the Capital Region of Denmark).; In Finland this work has been supported by the following grants to M. Laakso: Academy of Finland, the Finnish Diabetes Research Foundation, the Finnish Cardiovascular Research Foundation, and EVO grant from the Kuopio University Hospital (5263).; In the UK the Collection of the UK type 2 diabetes cases was supported by Diabetes UK, BDA Research and the UK Medical Research Council (Biomedical Collections Strategic Grant G0000649). The UK Type 2 Diabetes Genetics Consortium collection was supported by the Wellcome Trust (Biomedical Collections Grant GR072960). We acknowledge use of DNA from The UK Blood Services collection of Common Controls (UKBS-CC collection), funded by the Wellcome Trust grant 076113/C/04/Z and by NIHR programme grant to NHSBT (RP-PG-0310-1002). The collection was established as part of the Wellcome Trust Case Control Consortium (WTCCC). For the 1958 Birth Cohort, venous blood collection was funded by the Medical Research Council grant G0000934 (awarded under the Health of the Public initiative), peripheral blood lymphocyte preparation by Juvenile Diabetes Research Foundation/Wellcome Trust and the cell-line production, DNA extraction and processing by the Wellcome Trust grant 06854/Z/02/Z. The genotyping was supported by the Wellcome Trust (083270) and EU (ENGAGE: HEALTH-F4-2007-201413). A. P. Morris is a Wellcome Trust Senior Fellow (081682/Z/06/Z) and M. McCarthy receives funding from the Oxford NIHR Biomedical Research Centre. We acknowledge the contribution of M. Sampson.; In the Netherlands the work in this study was financially supported by the Dutch Diabetes Research Foundation grant 2006.00.060 and Bio-banking and Biomolecular Research Infrastructure the Netherlands (BBMRI-NL).; The D. E. S. I. R. cohort was supported by co-operative contracts between Inserm, CNAMTS, Novartis, Lilly and sanofi-aventis, by Inserm (Reseaux en Sante Publique, Interactions entre les determinants de la sante, Cohortes Sante TGIR 2008), by the Association Diabete Risque Vasculaire, the Federation Francaise de Cardiologie, La Fondation de France, ALFEDIAM, ONIVINS, Societe Francophone du Diabete; Ardix Medical, Bayer Diagnostics, Becton Dickinson, Cardionics, Lilly, Merck Sante, Novo Nordisk, Pierre Fabre, Roche, sanofi-aventis, Topcon.; Work in Sweden was supported by grants from the Swedish Research Foundation (Dnr-349-2006-6589, 2009-1039, 521-2010-3490) and Knut & Alice Wallenberg Foundation.; Work in Finland was supported by grants from the Sigrid Juselius Foundation, Folkhalsan Research Foundation and the Finnish Medical Society.; The Gene-Lifestyle interactions And Complex traits Involved in Elevated Disease Risk (GLACIER) study is nested within the Northern Swedish Health and Disease Study cohort and the Vasterbotten Intervention Programme (VIP). The research programme was approved by the Ethical Review Board in Umea, Sweden. We are indebted to the study participants who dedicated their time and samples to these studies. We also thank the VIP and Umea Medical Biobank staff for biomedical data collection and preparation. We specifically thank angstrom. Agren (Umea Medical Biobank) for data organisation, and K. Enqvist and T. Johansson (Vasterbottens County Council) for expert technical assistance with DNA preparation. The GLACIER Study was funded by project grants from Novo Nordisk (P. W. Franks [PWF]), the Swedish Heart-Lung Foundation (PWF), the Swedish Diabetes Association (to PWF), Pahlssons Foundation (PWF), the Swedish Research Council (PWF), Umea University Career Development Award (PWF) and The Heart Foundation of Northern Sweden (PWF). NR 31 TC 48 Z9 48 U1 1 U2 47 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD FEB PY 2013 VL 56 IS 2 BP 298 EP 310 DI 10.1007/s00125-012-2756-1 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 064LD UT WOS:000313075500010 PM 23160641 ER PT J AU Pinho, DF Kulkarni, NM Krishnaraj, A Kalva, SP Sahani, DV AF Pinho, Daniella F. Kulkarni, Naveen M. Krishnaraj, Arun Kalva, Sanjeeva P. Sahani, Dushyant V. TI Initial experience with single-source dual-energy CT abdominal angiography and comparison with single-energy CT angiography: image quality, enhancement, diagnosis and radiation dose SO EUROPEAN RADIOLOGY LA English DT Article DE Dual-energy CT; CT angiography; Multidetector CT; Radiation dose; Unenhanced virtual images ID ROW HELICAL CT; MULTIDETECTOR CT; ENDOVASCULAR REPAIR; AORTIC-ANEURYSM; TOMOGRAPHY; ENDOLEAKS; RECONSTRUCTIONS; DISEASE; PHANTOM AB To assess image quality of virtual monochromatic spectral (VMS) images, compared to single-energy (SE) CT, and to evaluate the feasibility of material density imaging in abdominal aortic disease. In this retrospective study, single-source (ss) dual-energy (DE) CT of the aorto-iliac system in 35 patients (32 male, mean age 76.5 years) was compared to SE-CT. By post-processing the data from ssDECT, VMS images at different energies and material density water (WD) images were generated. The image quality parameters were rated on 5-point scales. The aorto-iliac attenuation and contrast-to-noise ratio (CNR) were recorded. Quality of WD images was compared to true unenhanced (TNE) images. Radiation dose was recorded and statistical analysis was performed. Image quality and noise were better at 70 keV (P < 0.01). Renal artery branch visualisation was better at 50 keV (P < 0.005). Attenuation and CNR were higher at 50 and 70 keV (P < 0.0001). The WD images had diagnostic quality but higher noise than TNE images (P < 0.0001). Radiation dose was lower using single-phase ssDECT compared to dual-phase SE-CT (P < 0.0001). 70-keV images from ssDECT provide higher contrast enhancement and improved image quality for aorto-iliac CT when compared to SE-CT at 120 kVp. WD images are an effective substitute for TNE images with a potential for dose reduction. aEuro cent Multi-detector computed tomography (MDCT) angiography is now a routine procedure. aEuro cent Single-source dual-energy CT (ssDECT) can provide simultaneous data with different kilovoltages. aEuro cent 70 keV images showed better image quality than conventional single-energy (SE) CT. aEuro cent 70 keV images exhibited less image noise in comparison to SE-CT. C1 [Pinho, Daniella F.; Kulkarni, Naveen M.; Krishnaraj, Arun; Sahani, Dushyant V.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Pinho, Daniella F.] Hosp Israelita Albert Einstein, Dept Imaging, Sao Paulo, Brazil. [Kalva, Sanjeeva P.] Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM daniffcpinho@gmail.com; naveenkul@gmail.com; akrishnaraj99@gmail.com; skalva@partners.org; dsahani@partners.org FU GE Healthcare FX DVS has received grant support from GE Healthcare in the past but not related to this study. NR 30 TC 38 Z9 46 U1 0 U2 19 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD FEB PY 2013 VL 23 IS 2 BP 351 EP 359 DI 10.1007/s00330-012-2624-x PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 061WZ UT WOS:000312882200008 PM 22918562 ER PT J AU White, NS Leergaard, TB D'Arceuil, H Bjaalie, JG Dale, AM AF White, Nathan S. Leergaard, Trygve B. D'Arceuil, Helen Bjaalie, Jan G. Dale, Anders M. TI Probing tissue microstructure with restriction spectrum imaging: Histological and theoretical validation SO HUMAN BRAIN MAPPING LA English DT Article DE diffusion MRI; DTI; HARDI; DSI; FOD; fiber orientation; tractography; histology; cerebellum; cerebral cortex; striatum; basal ganglia; rat ID DIFFUSION-WEIGHTED MRI; FIBER ORIENTATION DISTRIBUTIONS; AXON DIAMETER DISTRIBUTION; BRAIN EXTRACELLULAR-SPACE; SPHERICAL DECONVOLUTION; OSMOTIC CHALLENGE; NERVOUS-SYSTEM; RAT NEOCORTEX; SINGLE-CELL; CORTEX AB Water diffusion magnetic resonance imaging (dMRI) is a powerful tool for studying biological tissue microarchitectures in vivo. Recently, there has been increased effort to develop quantitative dMRI methods to probe both length scale and orientation information in diffusion media. Diffusion spectrum imaging (DSI) is one such approach that aims to resolve such information based on the three-dimensional diffusion propagator at each voxel. However, in practice, only the orientation component of the propagator function is preserved when deriving the orientation distribution function. Here, we demonstrate how a straightforward extension of the linear spherical deconvolution (SD) model can be used to probe tissue orientation structures over a range (or spectrum) of length scales with minimal assumptions on the underlying microarchitecture. Using high b-value Cartesian q-space data on a rat brain tissue sample, we demonstrate how this restriction spectrum imaging (RSI) model allows for separating the volume fraction and orientation distribution of hindered and restricted diffusion, which we argue stems primarily from diffusion in the extraneurite and intraneurite water compartment, respectively. Moreover, we demonstrate how empirical RSI estimates of the neurite orientation distribution and volume fraction capture important additional structure not afforded by traditional DSI or fixed-scale SD-like reconstructions, particularly in gray matter. We conclude that incorporating length scale information in geometric models of diffusion offers promise for advancing state-of-the-art dMRI methods beyond white matter into gray matter structures while allowing more detailed quantitative characterization of water compartmentalization and histoarchitecture of healthy and diseased tissue. Hum Brain Mapp, 2013. (C) 2012 Wiley Periodicals, Inc. C1 [White, Nathan S.; Dale, Anders M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Leergaard, Trygve B.; Bjaalie, Jan G.] Univ Oslo, Inst Basic Med Sci, Ctr Mol Biol & Neurosci, Oslo, Norway. [D'Arceuil, Helen] Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP White, NS (reprint author), Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. EM nswhite@ucsd.edu OI Leergaard, Trygve B./0000-0001-5965-8470 FU Research Council of Norway; NIH/NIBIB [R01-EB00790]; NIH/NCRR [P41-RR14075, U24-RR021382, S10-RR016811]; NIH/NINDS [R01-NS41285]; NIH/NIDA [RC2-DA029475] FX Contract grant sponsor: The Research Council of Norway; Contract grant sponsor: NIH/NIBIB; Contract grant number: R01-EB00790; Contract grant sponsor: NIH/NCRR; Contract grant numbers: P41-RR14075, U24-RR021382, S10-RR016811; Contract grant sponsor: NIH/NINDS; Contract grant number: R01-NS41285; Contract grant sponsor: NIH/NIDA; Contract grant numbers: RC2-DA029475 NR 76 TC 41 Z9 41 U1 0 U2 34 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD FEB PY 2013 VL 34 IS 2 BP 327 EP 346 DI 10.1002/hbm.21454 PG 20 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 064ZM UT WOS:000313115000007 PM 23169482 ER PT J AU Baxter, RM Dai, TH Kimball, J Wang, E Hamblin, MR Wiesmann, WP McCarthy, SJ Baker, SM AF Baxter, Ruth M. Dai, Tianhong Kimball, Jess Wang, Eugenia Hamblin, Michael R. Wiesmann, William P. McCarthy, Simon J. Baker, Shenda M. TI Chitosan dressing promotes healing in third degree burns in mice: Gene expression analysis shows biphasic effects for rapid tissue regeneration and decreased fibrotic signaling SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE chitosan; wound healing; TGF ss 1; expression profiling; biomarkers ID TIME RT-PCR; ACETATE BANDAGE; WOUNDS; COLLAGEN; MODEL; ACCELERATOR; MEMBRANE; PROTEINS; SURGERY; DISEASE AB Burns are a significant health challenge and healing can result in scar formation. Chitosan, a derivative of chitin, has been used to promote wound healing. In this study we used gene expression profiling in a mouse model of full thickness cutaneous burn to assess the benefits of treating with a chitosan lactate dressing. Three days after wounding mice treated with chitosan showed increased expression of genes associated with formation of granulation tissue. At a later time point, seven days after wounding, genes that initially showed increased expression were now down-regulated, and there was increased expression of genes involved in remodeling suggesting that the chitosan treatment results in accelerated healing. Quantitative RT-PCR showed modulated mRNA levels for TGF beta 1 by the chitosan dressing. TGF beta 1 initially promotes healing but extended activity can result in scarring. Importantly we found that expression was elevated at day three, but decreased at day seven suggesting that chitosan treatment will not result in scar formation, and may even be beneficial in preventing scar formation. Additionally, the biphasic regulation of expression of TGF beta 1 could be a powerful biomarker for future studies of the wound-healing potential of chitosan based and other treatments for burn wounds. (c) 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013. C1 [Baxter, Ruth M.; Wiesmann, William P.; Baker, Shenda M.] Synedgen Inc, Claremont, CA USA. [Dai, Tianhong; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Dai, Tianhong; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Kimball, Jess; McCarthy, Simon J.] Hemcon Med Technol Inc, Portland, OR USA. [Wang, Eugenia] Adv Genom Technol LLC, Louisville, KY USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Baxter, RM (reprint author), Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA. EM rbaxter@mednet.ucla.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NIH [R01AI050875]; Airlift Research Foundation Extremity Trauma Research Grant [109421]; US Army MRMC [W81XWH-08-2-0120] FX Contract grant sponsor: NIH (M. R. Hamblin); contract grant number: Grant R01AI050875; Contract grant sponsor: Airlift Research Foundation Extremity Trauma Research Grant (Tianhong Dai); contract grant number: 109421; Contract grant sponsor: Contract W81XWH-08-2-0120 from the US Army MRMC (Research at HemCon and Synedgen) NR 53 TC 11 Z9 12 U1 3 U2 31 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1549-3296 EI 1552-4965 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD FEB PY 2013 VL 101 IS 2 BP 340 EP 348 DI 10.1002/jbm.a.34328 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 059TK UT WOS:000312728000004 PM 22847951 ER PT J AU Waak, K Zaremba, S Eikermann, M AF Waak, Karen Zaremba, Sebastian Eikermann, Matthias TI Muscle strength measurement in the intensive care unit: Not everything that can be counted counts SO JOURNAL OF CRITICAL CARE LA English DT Editorial Material ID ICU-ACQUIRED PARESIS; HANDGRIP STRENGTH; MORTALITY; SCORE C1 [Waak, Karen] Massachusetts Gen Hosp, Dept Phys & Occupat Therapy Serv, Boston, MA 02114 USA. [Zaremba, Sebastian; Eikermann, Matthias] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Zaremba, Sebastian] Univ Klinikum Bonn, Neurol Klin, Bonn, Germany. [Eikermann, Matthias] Essen Duisburg Univ, Klin Anaesthesiol & Intens Med, Essen, Germany. RP Waak, K (reprint author), Massachusetts Gen Hosp, Dept Phys & Occupat Therapy Serv, Boston, MA 02114 USA. EM meikermann@partners.org NR 12 TC 4 Z9 4 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0883-9441 J9 J CRIT CARE JI J. Crit. Care PD FEB PY 2013 VL 28 IS 1 BP 96 EP 98 DI 10.1016/j.jcrc.2012.08.014 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 062UY UT WOS:000312949700015 PM 23102532 ER PT J AU Chang, CY Huang, AJ AF Chang, Connie Y. Huang, Ambrose J. TI MR Imaging of Normal Hip Anatomy SO MAGNETIC RESONANCE IMAGING CLINICS OF NORTH AMERICA LA English DT Article DE Hip; Normal; Anatomy; Labrum; Anatomic variant ID MAGNETIC-RESONANCE ARTHROGRAPHY; ACETABULAR LABRAL TEARS; ARTICULAR-CARTILAGE; ASYMPTOMATIC HIPS; SYNOVIAL PLICAE; NORMAL VARIANT; FEMORAL-HEAD; ADULT HIP; PAIN; MUSCLE AB Understanding normal anatomy of the hip is important for diagnosing its pathology. MR arthrography is more sensitive for the detection of intra-articular pathology than noncontrast MR imaging. Important elements of the osseous structures on MR imaging include the alignment and the marrow. Acetabular ossicles may be present. Normal variations involving the cartilage include the supra-acetabular fossa and the stellate lesion. Important muscles of the hip are the sartorius, rectus femoris, iliopsoas, gluteus minimus and medius, adductors, and hamstrings. The iliofemoral, ischiofemoral, and pubofemoral ligaments represent thickenings of the joint capsule that reinforce and stabilize the hip joint. Normal variations in the labrum include labral sulcus and absent labrum. The largest nerves in the hip and thigh are the sciatic nerve, the femoral nerve, and the obturator nerve. C1 [Chang, Connie Y.; Huang, Ambrose J.] Harvard Univ, Massachusetts Gen Hosp, Div Musculoskeletal Imaging & Intervent, Dept Radiol,Sch Med, Boston, MA 02114 USA. RP Chang, CY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Musculoskeletal Imaging & Intervent, Dept Radiol,Sch Med, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA. EM cychang@partners.org NR 59 TC 8 Z9 10 U1 3 U2 16 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1064-9689 J9 MAGN RESON IMAGING C JI Magn. Reson. Imaging Clin. N. Am. PD FEB PY 2013 VL 21 IS 1 BP 1 EP + DI 10.1016/j.mric.2012.08.006 PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058FJ UT WOS:000312619200003 PM 23168179 ER PT J AU Bredella, MA AF Bredella, Miriam A. TI Imaging of the Hip Preface SO MAGNETIC RESONANCE IMAGING CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 [Bredella, Miriam A.] Massachusetts Gen Hosp, Dept Radiol Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. [Bredella, Miriam A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol Musculoskeletal Imaging & Intervent, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA. EM mbredella@partners.org NR 0 TC 0 Z9 0 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 1064-9689 J9 MAGN RESON IMAGING C JI Magn. Reson. Imaging Clin. N. Am. PD FEB PY 2013 VL 21 IS 1 BP XIII EP XIV DI 10.1016/j.mric.2012.09.007 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058FJ UT WOS:000312619200002 PM 23168193 ER PT J AU Bredella, MA Ulbrich, EJ Stoller, DW Anderson, SE AF Bredella, Miriam A. Ulbrich, Erika J. Stoller, David W. Anderson, Suzanne E. TI Femoroacetabular Impingement SO MAGNETIC RESONANCE IMAGING CLINICS OF NORTH AMERICA LA English DT Article DE Femoroacetabular impingement; Hip; Imaging; Magnetic resonance imaging; Radiographs ID FEMORO-ACETABULAR IMPINGEMENT; MR ARTHROGRAPHIC FINDINGS; HEAD-NECK JUNCTION; YOUNG-ADULTS; HIP-JOINT; ASYMPTOMATIC VOLUNTEERS; PERIACETABULAR OSTEOTOMY; RADIOGRAPHIC FINDINGS; SURGICAL DISLOCATION; EARLY OSTEOARTHRITIS AB Femoroacetabular impingement (FAI) is a common cause of early-onset osteoarthritis of the hip. It can be caused by morphologic abnormalities involving the proximal femur or acetabulum, leading to abnormal abutment of the femoral head-neck against the acetabular rim. This repetitive trauma causes mechanical wear of the labrum and articular cartilage, leading to osteoarthritis of the hip. Magnetic resonance imaging is an accurate noninvasive imaging modality that can detect acetabular labral lesions and adjacent cartilage damage, and is able to detect underlying subtle anatomic variations of the femoral head-neck junction and acetabulum associated with FAI. C1 [Bredella, Miriam A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Musculoskeletal Radiol & Intervent,Dept Radio, Boston, MA 02114 USA. [Ulbrich, Erika J.] Univ Zurich Hosp, Dept Diagnost & Intervent Radiol, CH-8091 Zurich, Switzerland. [Stoller, David W.] Calif Pacific Med Ctr, Natl Orthopaed Imaging Associates, San Francisco, CA USA. [Stoller, David W.] Calif Pacific Med Ctr, MRI, San Francisco, CA USA. [Stoller, David W.] Johns Hopkins Univ, Dept Radiol, Sch Med, Baltimore, MD 21287 USA. [Anderson, Suzanne E.] Univ Notre Dame Australia, Sch Med Sydney, Sydney, NSW, Australia. RP Bredella, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Musculoskeletal Radiol & Intervent,Dept Radio, 55 Fruit St,Yawkey Bldg 6400, Boston, MA 02114 USA. EM mbredella@partners.org NR 90 TC 9 Z9 9 U1 1 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1064-9689 J9 MAGN RESON IMAGING C JI Magn. Reson. Imaging Clin. N. Am. PD FEB PY 2013 VL 21 IS 1 BP 45 EP + DI 10.1016/j.mric.2012.08.012 PG 21 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058FJ UT WOS:000312619200006 PM 23168182 ER PT J AU Taneja, AK Bredella, MA Torriani, M AF Taneja, Atul K. Bredella, Miriam A. Torriani, Martin TI Ischiofemoral Impingement SO MAGNETIC RESONANCE IMAGING CLINICS OF NORTH AMERICA LA English DT Article DE Hip pain; Ischiofemoral impingement; Quadratus femoris; Ischium; Lesser trochanter ID QUADRATUS FEMORIS MUSCLE; LESSER TROCHANTER; HIP PAIN; TEAR; MRI AB Ischiofemoral impingement is a syndrome defined by hip pain associated with narrowing of the space between ischial tuberosity and lesser trochanter. This phenomenon leads to abnormalities of the quadratus femoris muscle, ranging from deformity and edema to tears and atrophy. This review article presents an up-to-date discussion and imaging findings of ischiofemoral impingement, along with its related anatomy, clinical presentation, differential diagnosis and treatment. C1 [Taneja, Atul K.; Bredella, Miriam A.; Torriani, Martin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Torriani, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM mtorriani@hms.harvard.edu RI Taneja, Atul/N-3133-2014 OI Taneja, Atul/0000-0002-4655-2033 NR 11 TC 17 Z9 17 U1 0 U2 12 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1064-9689 EI 1557-9786 J9 MAGN RESON IMAGING C JI Magn. Reson. Imaging Clin. N. Am. PD FEB PY 2013 VL 21 IS 1 BP 65 EP + DI 10.1016/j.mric.2012.08.005 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058FJ UT WOS:000312619200007 PM 23168183 ER PT J AU Campe, CB Palmer, WE AF Campe, Carson B. Palmer, William E. TI MR Imaging of Metal-on-Metal Hip Prostheses SO MAGNETIC RESONANCE IMAGING CLINICS OF NORTH AMERICA LA English DT Article DE MR imaging; Metal artifact reduction; Hip arthroplasty; Metal-on-metal; Pseudotumor ID RESURFACING ARTHROPLASTY; INFLAMMATORY PSEUDOTUMOR; ARTIFACT REDUCTION; PERIPROSTHETIC OSTEOLYSIS; ASYMPTOMATIC PATIENTS; JOINT REPLACEMENT; EARLY FAILURE; FOLLOW-UP; IMPLANTS; COMPONENTS AB Metal-on-metal (MoM) hip arthroplasty was expected to provide benefits over metal-on-polyethylene systems. After widespread placement of MoM implants, outcomes have been disappointing. MoM implants are associated with higher serum levels of metal ions, adverse periarticular soft tissue reactions, and increased long-term failure rates. In light of these findings, it is crucial that patients with MoM implants be closely monitored for adverse effects. MR imaging is ideally suited for assessment of these patients and complements standard clinical evaluation and laboratory testing. This article reviews the background of MoM implants, emerging data on complications, strategies for using MR imaging, and MR imaging findings in patients with reaction to metal. C1 [Campe, Carson B.; Palmer, William E.] Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging, Boston, MA 02114 USA. RP Palmer, WE (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging, 55 Fruit St, Boston, MA 02114 USA. EM wpalmer@partners.org NR 69 TC 4 Z9 6 U1 1 U2 16 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1064-9689 J9 MAGN RESON IMAGING C JI Magn. Reson. Imaging Clin. N. Am. PD FEB PY 2013 VL 21 IS 1 BP 155 EP + DI 10.1016/j.mric.2012.09.005 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058FJ UT WOS:000312619200013 PM 23168189 ER PT J AU Gilman, SE Trinh, NH Smoller, JW Fava, M Murphy, JM Breslau, J AF Gilman, S. E. Trinh, N. -H. Smoller, J. W. Fava, M. Murphy, J. M. Breslau, J. TI Psychosocial stressors and the prognosis of major depression: a test of Axis IV SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Axis IV; depression; DSM-IV; prognosis; psychosocial stress ID PSYCHIATRIC DIAGNOSTIC MODULES; GENERAL-POPULATION SAMPLE; CORONARY-HEART-DISEASE; ALCOHOL-USE-DISORDER; DSM-III; LIFE EVENTS; RISK-FACTORS; ANTIDEPRESSANT TREATMENT; CHILDHOOD ADVERSITY; MULTIAXIAL SYSTEM AB Background. Axis IV is for reporting 'psychosocial and environmental problems that may affect the diagnosis, treatment and prognosis of mental disorders'. No studies have examined the prognostic value of Axis IV in DSM-IV. Method. We analyzed data from 2497 participants in the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) with major depressive episode (MDE). We hypothesized that psychosocial stressors predict a poor prognosis of MDE. Secondarily, we hypothesized that psychosocial stressors predict a poor prognosis of anxiety and substance use disorders. Stressors were defined according to DSM-IV's taxonomy, and empirically using latent class analysis (LCA). Results. Primary support group problems, occupational problems and childhood adversity increased the risks of depressive episodes and suicidal ideation by 20-30%. Associations of the empirically derived classes of stressors with depression were larger in magnitude. Economic stressors conferred a 1.5-fold increase in risk for a depressive episode [95% confidence interval (CI) 1.2-1.9]; financial and interpersonal instability conferred a 1.3-fold increased risk of recurrent depression (95% CI 1.1-1.6). These two classes of stressors also predicted the recurrence of anxiety and substance use disorders. Stressors were not related to suicidal ideation independent from depression severity. Conclusions. Psychosocial and environmental problems are associated with the prognosis of MDE and other Axis I disorders. Although DSM-IV's taxonomy of stressors stands to be improved, these results provide empirical support for the prognostic value of Axis IV. Future work is needed to determine the reliability of Axis IV assessments in clinical practice, and the usefulness of this information to improving the clinical course of mental disorders. C1 [Gilman, S. E.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Gilman, S. E.; Smoller, J. W.; Murphy, J. M.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Gilman, S. E.; Trinh, N. -H.; Smoller, J. W.; Fava, M.; Murphy, J. M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Trinh, N. -H.; Smoller, J. W.; Fava, M.; Murphy, J. M.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Breslau, J.] RAND Corp, Pittsburgh, PA USA. RP Gilman, SE (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 677 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 [MH085050, MH087544]; Abbott Laboratories; Alkermes, Inc.; Aspect Medical Systems; AstraZeneca; BioResearch; BrainCells Inc.; Bristol-Myers Squibb; Cephalon, Inc.; CeNeRx BioPharma; Clinical Trials Solutions, LLC; Clintara, LLC; Covidien; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; GlaxoSmithKline; Icon Clinical Research; i3 Innovus/Ingenix; Johnson & Johnson Pharmaceutical Research Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; National Alliance for Research on Schizophrenia and Depression (NARSAD); National Center for Complementary and Alternative Medicine (NCCAM); National Institute of Drug Abuse (NIDA); National Institute of Mental Health (NIMH); Novartis AG; Organon Pharmaceuticals; PamLab, LLC.; Pfizer Inc.; Pharmavite(R) LLC; Photothera; Roche; RCT Logic, LLC; Sanofi-Aventis US LLC; Shire; Solvay Pharmaceuticals, Inc.; Synthelabo; Wyeth-Ayerst Laboratories; Adamed, Co; Advanced Meeting Partners; American Psychiatric Association; American Society of Clinical Psychopharmacology; Belvoir Media Group; Boehringer Ingelheim GmbH; CME Institute/Physicians Postgraduate Press, Inc.; Imedex, LLC; MGH Psychiatry Academy/Primedia; MGH Psychiatry Academy/Reed Elsevier; PharmaStar; United BioSource, Corp.; WyethAyerst Laboratories FX We sincerely appreciate the contributions of K. McGaffigan for data management and statistical programming, and R. Hawrusik for research assistance. This research was supported in part by grants MH085050 and MH087544 from the National Institutes of Health.; Dr M. Fava has received research support from Abbott Laboratories; Alkermes, Inc.; Aspect Medical Systems; AstraZeneca; BioResearch; BrainCells Inc.; Bristol-Myers Squibb; Cephalon, Inc.; CeNeRx BioPharma; Clinical Trials Solutions, LLC; Clintara, LLC; Covidien; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; GlaxoSmithKline; Icon Clinical Research; i3 Innovus/Ingenix; Johnson & Johnson Pharmaceutical Research & Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; National Alliance for Research on Schizophrenia and Depression (NARSAD); National Center for Complementary and Alternative Medicine (NCCAM); National Institute of Drug Abuse (NIDA); National Institute of Mental Health (NIMH); Novartis AG; Organon Pharmaceuticals; PamLab, LLC.; Pfizer Inc.; Pharmavite (R) LLC; Photothera; Roche; RCT Logic, LLC; Sanofi-Aventis US LLC; Shire; Solvay Pharmaceuticals, Inc.; Synthelabo; and Wyeth-Ayerst Laboratories. He has served as advisor or consultant to Abbott Laboratories; Affectis Pharmaceuticals AG; Alkermes, Inc.; Amarin Pharma Inc.; Aspect Medical Systems; AstraZeneca; Auspex Pharmaceuticals; Bayer AG; Best Practice Project Management, Inc.; BioMarin Pharmaceuticals, Inc.; Biovail Corporation; BrainCells Inc.; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon, Inc.; Clinical Trials Solutions, LLC; CNS Response, Inc.; Compellis Pharmaceuticals; Cypress Pharmaceutical, Inc.; DiagnoSearch Life Sciences (P) Ltd.; Dinippon Sumitomo Pharma Co. Inc.; Dov Pharmaceuticals, Inc.; Edgemont Pharmaceuticals, Inc.; Eisai Inc.; Eli Lilly and Company; ePharmaSolutions; EPIX Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Fabre-Kramer Pharmaceuticals, Inc.; Forest Pharmaceuticals, Inc.; GenOmind, LLC; GlaxoSmithKline; Grunenthal GmbH; i3 Innovus/Ingenis; Janssen Pharmaceutica; Jazz Pharmaceuticals, Inc.; Johnson & Johnson Pharmaceutical Research & Development, LLC; Knoll Pharmaceuticals Corp.; Labopharm Inc.; Lorex Pharmaceuticals; Lundbeck Inc.; MedAvante, Inc.; Merck & Co., Inc.; MSI Methylation Sciences, Inc.; Naurex, Inc.; Neuronetics, Inc.; NextWave Pharmaceuticals; Novartis AG; Nutrition 21; Orexigen Therapeutics, Inc.; Organon Pharmaceuticals; Otsuka Pharmaceuticals; PamLab, LLC.; Pfizer Inc.; PharmaStar; Pharmavite (R) LLC.; PharmoRx Therapeutics; Precision Human Biolaboratory; Prexa Pharmaceuticals, Inc.; Puretech Ventures; PsychoGenics; Psylin Neurosciences, Inc.; Rexahn Pharmaceuticals, Inc.; Ridge Diagnostics, Inc.; Roche; RCT Logic, LLC; Sanofi-Aventis US LLC.; Sepracor Inc.; Servier Laboratories; Schering-Plough Corporation; Solvay Pharmaceuticals, Inc.; Somaxon Pharmaceuticals, Inc.; Somerset Pharmaceuticals, Inc.; Sunovion Pharmaceuticals; Supernus Pharmaceuticals, Inc.; Synthelabo; Takeda Pharmaceutical Company Limited; Tal Medical, Inc.; Tetragenex Pharmaceuticals, Inc.; TransForm Pharmaceuticals, Inc.; Transcept Pharmaceuticals, Inc.; and Vanda Pharmaceuticals, Inc. He has received speaking or publishing fees from Adamed, Co; Advanced Meeting Partners; American Psychiatric Association; American Society of Clinical Psychopharmacology; AstraZeneca; Belvoir Media Group; Boehringer Ingelheim GmbH; Bristol-Myers Squibb; Cephalon, Inc.; CME Institute/Physicians Postgraduate Press, Inc.; Eli Lilly and Company; Forest Pharmaceuticals, Inc.; GlaxoSmithKline; Imedex, LLC; MGH Psychiatry Academy/Primedia; MGH Psychiatry Academy/Reed Elsevier; Novartis AG; Organon Pharmaceuticals; Pfizer Inc.; PharmaStar; United BioSource, Corp.; ; and WyethAyerst Laboratories. He owns stock in Compellis. He has a received royalty, patent or other income from a patent for Sequential Parallel Comparison Design (SPCD) and a patent application for a combination of azapirones and bupropion in major depressive disorder (MDD), copyright royalties for the MGH Cognitive and Physical Functioning Questionnaire (CPFQ), Sexual Functioning Inventory (SFI), Antidepressant Treatment Response Questionnaire (ATRQ), Discontinuation-Emergent Signs and Symptoms (DESS), and SAFER. He has a patent for research and licensing of SPCD with RCT Logic; Lippincott, Williams & Wilkins; and World Scientific Publishing Co. Pte. Ltd. NR 54 TC 18 Z9 18 U1 2 U2 31 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD FEB PY 2013 VL 43 IS 2 BP 303 EP 316 DI 10.1017/S0033291712001080 PG 14 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 064IB UT WOS:000313066400007 PM 22640506 ER PT J AU Breslau, N Troost, JP Bohnert, K Luo, Z AF Breslau, N. Troost, J. P. Bohnert, K. Luo, Z. TI Influence of predispositions on post-traumatic stress disorder: does it vary by trauma severity? SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Epidemiology; post-traumatic stress disorder; predispositions; sexual assault; trauma ID NATIONAL COMORBIDITY SURVEY; SEX-DIFFERENCES; YOUNG-ADULTS; DSM-IV; EXPOSURE; RISK; COMMUNITY; EVENTS; PTSD; INTELLIGENCE AB Background. Only a minority of trauma victims (< 10%) develops post-traumatic stress disorder (PTSD), suggesting that victims vary in predispositions to the PTSD response to traumas. It is assumed that the influence of predispositions is inversely related to trauma severity : when trauma is extreme predispositions are assumed to play a secondary role. This assumption has not been tested. We estimate the influence of key predispositions on PTSD induced by an extreme trauma - associated with a high percentage of PTSD - (sexual assault), relative to events of lower magnitude (accidents, disaster, and unexpected death of someone close). Method. The National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) is representative of the adult population of the USA. A total of 34 653 respondents completed the second wave in which lifetime PTSD was assessed. We conducted three series of multinomial logistic regressions, comparing the influence of six predispositions on the PTSD effect of sexual assault with each comparison event. Three pre-existing disorders and three parental history variables were examined. Results. Predispositions predicted elevated PTSD risk among victims of sexual assault as they did among victims of comparison events. We detected no evidence that the influence of predispositions on PTSD risk was significantly lower when the event was sexual assault, relative to accidents, disasters and unexpected death of someone close. Conclusions. Important predispositions increase the risk of PTSD following sexual assault as much as they do following accidents, disaster, and unexpected death of someone close. Research on other predispositions and alternative classifications of event severity would be illuminating. Received 13 March 2012; Revised 25 April 2012; Accepted 30 April 2012; First published online 18 June 2012 C1 [Breslau, N.; Troost, J. P.; Luo, Z.] Michigan State Univ, Coll Human Med, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Bohnert, K.] US Dept Vet Affairs, Serious Mental Illness Treatment Resource & Evalu, Ann Arbor, MI USA. RP Breslau, N (reprint author), Michigan State Univ, Coll Human Med, Dept Epidemiol & Biostat, B645 W Fee Hall, E Lansing, MI 48824 USA. EM breslau@epi.msu.edu FU National Institutes of Health, in Bethesda, MD [MH44586, MH071395, MH092737] FX This study was supported by grants no. MH44586 (N.B.), no. MH071395 (N.B.) and no. MH092737 (Z.L.) from the National Institutes of Health, in Bethesda, MD. NR 37 TC 11 Z9 11 U1 1 U2 36 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD FEB PY 2013 VL 43 IS 2 BP 381 EP 390 DI 10.1017/S0033291712001195 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 064IB UT WOS:000313066400014 PM 22703614 ER PT J AU Kirchhoff, AC Kuhlthau, K Pajolek, H Leisenring, W Armstrong, GT Robison, LL Park, ER AF Kirchhoff, Anne C. Kuhlthau, Karen Pajolek, Hannah Leisenring, Wendy Armstrong, Greg T. Robison, Leslie L. Park, Elyse R. TI Employer-sponsored health insurance coverage limitations: results from the Childhood Cancer Survivor Study SO SUPPORTIVE CARE IN CANCER LA English DT Article DE Employer-sponsored health insurance; Childhood cancer survivors; Affordable Care Act; Insurance reform ID AFFORDABLE CARE ACT; LONG-TERM SURVIVORS; ADULT SURVIVORS; WORKERS; UNEMPLOYMENT; ILLNESS AB The Affordable Care Act (ACA) will expand health insurance options for cancer survivors in the USA. It is unclear how this legislation will affect their access to employer-sponsored health insurance (ESI). We describe the health insurance experiences for survivors of childhood cancer with and without ESI. We conducted a series of qualitative interviews with 32 adult survivors from the Childhood Cancer Survivor Study to assess their employment-related concerns and decisions regarding health insurance coverage. Interviews were performed from August to December 2009 and were recorded, transcribed, and content analyzed using NVivo 8. Uninsured survivors described ongoing employment limitations, such as being employed at part-time capacity, which affected their access to ESI coverage. These survivors acknowledged they could not afford insurance without employer support. Survivors on ESI had previously been denied health insurance due to their preexisting health conditions until they obtained coverage through an employer. Survivors feared losing their ESI coverage, which created a disincentive to making career transitions. Others reported worries about insurance rescission if their cancer history was discovered. Survivors on ESI reported financial barriers in their ability to pay for health care. Childhood cancer survivors face barriers to obtaining ESI. While ACA provisions may mitigate insurance barriers for cancer survivors, many will still face cost barriers to affording health care without employer support. C1 [Kirchhoff, Anne C.] Univ Utah, Huntsman Canc Inst, Ctr Childrens Canc Res, Salt Lake City, UT 84112 USA. [Kirchhoff, Anne C.] Univ Utah, Huntsman Canc Inst, Canc Control & Populat Sci Res Program, Salt Lake City, UT 84112 USA. [Kirchhoff, Anne C.] Univ Utah, Dept Pediat, Salt Lake City, UT 84112 USA. [Kuhlthau, Karen; Pajolek, Hannah; Park, Elyse R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Leisenring, Wendy] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Leisenring, Wendy] Univ Washington, Seattle, WA 98195 USA. [Armstrong, Greg T.; Robison, Leslie L.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. RP Kirchhoff, AC (reprint author), Univ Utah, Dept Pediat, 2000 Circle Hope, Salt Lake City, UT 84112 USA. EM anne.kirchhoff@hci.utah.edu FU Lance Armstrong Foundation; National Cancer Institute [U24-CA55727] FX This study was supported by the Lance Armstrong Foundation and National Cancer Institute (U24-CA55727). NR 30 TC 7 Z9 7 U1 0 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD FEB PY 2013 VL 21 IS 2 BP 377 EP 383 DI 10.1007/s00520-012-1523-7 PG 7 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 065RA UT WOS:000313165100004 PM 22717916 ER PT J AU Trevino, KM Fasciano, K Block, S Prigerson, HG AF Trevino, K. M. Fasciano, K. Block, S. Prigerson, H. G. TI Correlates of social support in young adults with advanced cancer SO SUPPORTIVE CARE IN CANCER LA English DT Article DE Young adult; Social support; Quality of life; Grief; Cancer; Oncology ID QUALITY-OF-LIFE; ADVANCED BREAST-CANCER; PSYCHOSOCIAL ISSUES; COPING STRATEGIES; COMPLICATED GRIEF; SYMPTOM DISTRESS; PALLIATIVE CARE; THE-LITERATURE; ADOLESCENTS; DEPRESSION AB This study examined the relationship between perceived social support, quality of life (QoL), and grief in young adults with advanced cancer. Seventy-one young adults (20-40 years) with advanced cancer were administered measures of social support, QoL, and grief. Regression analyses examined the relationship between social support and QoL and grief. Higher levels of total social support were associated with better psychological and existential QoL and less severe grief. Availability of someone to talk to about problems was also associated with better psychological and existential QoL and less severe grief. Tangible support was associated with better psychological and existential QoL. Availability of someone to engage in activities with was only associated with better existential QoL. These results suggest that enhancing social support may improve psychological well-being in this population. In addition, specific types of social support may be particularly relevant to the psychological well-being of young adults with advanced cancer. C1 [Trevino, K. M.; Fasciano, K.; Block, S.; Prigerson, H. G.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Trevino, K. M.; Fasciano, K.; Block, S.; Prigerson, H. G.] Harvard Univ, Sch Med, Boston, MA USA. [Trevino, K. M.; Fasciano, K.; Block, S.; Prigerson, H. G.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Prigerson, HG (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Dana 1134, Boston, MA 02215 USA. EM holly_prigerson@dfci.harvard.edu FU National Institute of Mental Health [MH63892]; National Cancer Institute; the Adolescent and Young Adults with Cancer Closing the Gap Fund [CA106370, CA156732]; Center for Psycho-Oncology and Palliative Care Research, Dana-Farber Cancer Institute FX This research was supported in part by the following grants to Dr. Prigerson: MH63892 from the National Institute of Mental Health and CA106370 and CA156732 from the National Cancer Institute; the Adolescent and Young Adults with Cancer Closing the Gap Fund; and the Center for Psycho-Oncology and Palliative Care Research, Dana-Farber Cancer Institute. NR 43 TC 8 Z9 8 U1 3 U2 25 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD FEB PY 2013 VL 21 IS 2 BP 421 EP 429 DI 10.1007/s00520-012-1536-2 PG 9 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 065RA UT WOS:000313165100009 PM 22790223 ER PT J AU Dennis, ER Bussiere, MR Niemierko, A Lu, MW Fullerton, BC Loeffler, JS Shih, HA AF Dennis, Elizabeth R. Bussiere, Marc R. Niemierko, Andrzej Lu, Michael W. Fullerton, Barbara C. Loeffler, Jay S. Shih, Helen A. TI A Comparison of Critical Structure Dose and Toxicity Risks in Patients with Low Grade Gliomas Treated with IMRT versus Proton Radiation Therapy SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Article DE Proton therapy; Low grade glioma; Dosimetric comparison; Modeling; NTCP; Late effects ID RADIOTHERAPY; OLIGODENDROGLIOMA; DISTRIBUTIONS; LESIONS; PHOTON; BEAMS AB Proton therapy offers dosimetric advantage of decreased dose to non-target tissues. This study explored the potential benefits of proton radiation therapy versus photon based intensity modulated radiation therapy (IMRT) for patients with low grade gliomas (LGG) through dosimetric comparison and biological modeling of potential radiation-induced toxicities. Eleven patients were treated with fractionated proton radiation therapy on a prospective protocol assessing for feasibility and treatment toxicity of proton radiation therapy in patients with LGG. IMRT treatment plans were created for each patient using the same CT planning data set and defined structures. The prescription dose to the clinical target volume (CTV) was 54 Gy(RBE). The toxicity risk of IMRT and protons was estimated based upon equivalent uniform dose (EUD) and normal tissue complication probability (NTCP) modeling. The risk of secondary tumors for each modality was estimated. Proton EUD for most immediate normal tissue structures was between 10-20 Gy lower than the EUD delivered by IMRT. However, the difference in NTCP was negligible for both modalities. The mean excess risk of proton radiation-induced second tumor in the brain per 10,000 cases per year is 47 (range 11-83), while the mean risk for IMRT is 106 (range 70-134). The mean ratio of excess risk IMRT/protons is 2.2 (range 1.6-6.5), demonstrating that the risk of secondary tumors is consistently higher for IMRT. Proton therapy effectively reduces the dose to surrounding normal tissues in LGG patients. IMRT has a twofold higher risk of secondary intracranial tumors as compared to proton therapy. In most cases, NTCP is negligible for both modalities. The benefit of proton therapy over IMRT may be more substantial in patients with tumors in proximity to critical structures. C1 [Dennis, Elizabeth R.; Bussiere, Marc R.; Niemierko, Andrzej; Lu, Michael W.; Fullerton, Barbara C.; Loeffler, Jay S.; Shih, Helen A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Niemierko, Andrzej; Fullerton, Barbara C.; Loeffler, Jay S.; Shih, Helen A.] Harvard Univ, Sch Med, Boston, MA USA. RP Shih, HA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 30 Fruit St,Room 108, Boston, MA 02114 USA. EM hshih@partners.org NR 14 TC 8 Z9 8 U1 1 U2 9 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 1533-0346 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD FEB PY 2013 VL 12 IS 1 BP 1 EP 9 DI 10.7785/tcrt.2012.500276 PG 9 WC Oncology SC Oncology GA 058AX UT WOS:000312607600001 PM 22775339 ER PT J AU Eisner, BH Goldfarb, DS Pareek, G AF Eisner, Brian H. Goldfarb, David S. Pareek, Gyan TI Pharmacologic Treatment of Kidney Stone Disease SO UROLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Allopurinol; Citrate; Medication; Nephrolithiasis; Prevention; Thiazides; Uric acid ID MEDICAL-EXPULSIVE THERAPY; LOWER URETERAL STONES; HYPOCITRATURIC CALCIUM NEPHROLITHIASIS; UPPER TRACT INFECTION; DOUBLE-BLIND-TRIAL; RANDOMIZED-TRIAL; OXALOBACTER-FORMIGENES; ACETOHYDROXAMIC ACID; POTASSIUM CITRATE; UNITED-STATES AB This article reviews the data on pharmacologic treatment of kidney stone disease, with a focus on prophylaxis against stone recurrence. One of the most effective and important therapies for stone prevention, an increase in urine volume, is not discussed because this is a dietary and not a pharmacologic intervention. Also reviewed are medical expulsive therapy used to improve the spontaneous passage of ureteral stones and pharmacologic treatment of symptoms associated with ureteral stents. The goal is to review the literature with a focus on the highest level of evidence (ie, randomized controlled trials). C1 [Eisner, Brian H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Goldfarb, David S.] NYU, Sch Med, New York Harbor VA Healthcare Syst, Nephrol Sect, New York, NY 10010 USA. [Pareek, Gyan] Brown Univ, Warren Alpert Med Sch, Dept Urol, Providence, RI 02903 USA. RP Eisner, BH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org OI Goldfarb, David/0000-0002-9215-1273 NR 94 TC 7 Z9 14 U1 2 U2 19 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0094-0143 J9 UROL CLIN N AM JI Urol. Clin. N. Am. PD FEB PY 2013 VL 40 IS 1 BP 21 EP + DI 10.1016/j.ucl.2012.09.013 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 065GZ UT WOS:000313138100005 PM 23177632 ER PT J AU Stone, RM Appelbaum, FR St Couban Erba, H Larson, RA Little, R Tallman, MS AF Stone, R. M. Appelbaum, F. R. St Couban Erba, H. Larson, R. A. Little, R. Tallman, M. S. TI North American Cooperative Trials in AML SO ANNALS OF HEMATOLOGY LA English DT Meeting Abstract ID LEUKEMIA C1 [Stone, R. M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Appelbaum, F. R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [St Couban] Dalhousie Univ, Halifax, NS, Canada. [St Couban] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [Erba, H.] Univ Alabama Birmingham, Birmingham, AL USA. [Larson, R. A.] Univ Chicago, Chicago, IL 60637 USA. [Little, R.] NCI, Canc Therapy & Evaluat Program, Bethesda, MD 20892 USA. [Tallman, M. S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-5555 EI 1432-0584 J9 ANN HEMATOL JI Ann. Hematol. PD FEB PY 2013 VL 92 SU 1 BP S56 EP S58 PG 3 WC Hematology SC Hematology GA AT4UP UT WOS:000344939100098 ER PT J AU Weinstock, D AF Weinstock, D. TI Down Syndrome and the Epigenome in ALL SO ANNALS OF HEMATOLOGY LA English DT Meeting Abstract C1 [Weinstock, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-5555 EI 1432-0584 J9 ANN HEMATOL JI Ann. Hematol. PD FEB PY 2013 VL 92 SU 1 BP S59 EP S59 PG 1 WC Hematology SC Hematology GA AT4UP UT WOS:000344939100101 ER PT J AU Rahimy, E Law, SK AF Rahimy, Ehsan Law, Simon K. TI Orbital inflammation after zoledronate infusion: an emerging complication SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE LA English DT Letter ID BISPHOSPHONATES; DISEASE C1 [Rahimy, Ehsan; Law, Simon K.] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. [Law, Simon K.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Law, SK (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. EM law@jsei.ucla.edu NR 5 TC 2 Z9 2 U1 0 U2 1 PU CANADIAN OPHTHAL SOC PI OTTAWA PA 1525 CARLING AVE SUITE 610, OTTAWA, ONTARIO K1Z 8R9, CANADA SN 0008-4182 EI 1715-3360 J9 CAN J OPHTHALMOL JI Can. J. Opthalmol.-J. Can. Opthalmol. PD FEB PY 2013 VL 48 IS 1 BP E11 EP E12 DI 10.1016/j.jcjo.2012.09.011 PG 3 WC Ophthalmology SC Ophthalmology GA AA5NR UT WOS:000331147200008 PM 23419305 ER PT J AU Beadling, C Patterson, J Justusson, E Nelson, D Pantaleo, MA Hornick, JL Chacon, M Corless, CL Heinrich, MC AF Beadling, Carol Patterson, Janice Justusson, Emily Nelson, Dylan Pantaleo, Maria A. Hornick, Jason L. Chacon, Matias Corless, Christopher L. Heinrich, Michael C. TI Gene expression of the IGF pathway family distinguishes subsets of gastrointestinal stromal tumors wild type for KIT and PDGFRA SO CANCER MEDICINE LA English DT Article DE Gastrointestinal stromal tumor; IGF1R; wild type AB Gastrointestinal stromal tumors (GISTs) arise from the interstitial cells of Cajal (ICCs) and are the most common mesenchymal neoplasm of the gastrointestinal tract. While the majority of GISTs harbor activating mutations in either the v-kit Hardy-Zuckerman feline sarcoma viral oncogene homolog (KIT) or platelet-derived growth factor receptor alpha (PDGFRA) tyrosine kinases, approximately 10-15% of adult GISTs and 85% of pediatric GISTs lack such mutations. These "wild-type" GISTs have been reported to express high levels of the insulin-like growth factor 1 receptor (IGF1R), and IGF1R-targeted therapy of wild-type GISTs is being evaluated in clinical trials. However, it is not clear that all wild-type GISTs express IGF1R, because studies to date have predominantly focused on a particular subtype of gastric wild-type GIST that is deficient in the mitochondrial succinate dehydrogenase (SDH) complex. This study of a series of 136 GISTs, including 72 wild-type specimens, was therefore undertaken to further characterize wild-type GIST subtypes based on the relative expression of transcripts encoding IGF1R. Additional transcripts relevant to GIST biology were also evaluated, including members of the IGF-signaling pathway (IGF1, IGF2, and insulin receptor [INSR]), neural markers (CDH2 [CDH: Cadherin], neurofilament, light polypeptide, LHX2 [LHX: LIM homeobox], and KIRREL3 [KIRREL: kin of IRRE like]), KIT, PDGFRA, CD34, and HIF1A. Succinate dehydrogenase complex, subunit B protein expression was also assessed as a measure of SDH complex integrity. In addition to the previously described SDH-deficient, IGF1R high wild-type GISTs, other SDH-intact wild-type subpopulations were defined by high relative expression of IGF1R, neural markers, IGF1 and INSR, or low IGF1R coupled with high IGF2. These results underscore the complexity and heterogeneity of wild-type GISTs that will need to be factored into molecularly-targeted therapeutic strategies. C1 [Beadling, Carol; Patterson, Janice; Justusson, Emily; Nelson, Dylan; Corless, Christopher L.; Heinrich, Michael C.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Beadling, Carol; Heinrich, Michael C.] Oregon Hlth & Sci Univ, Div Hematol & Oncol, Portland, OR 97201 USA. [Pantaleo, Maria A.] Univ Bologna, Dept Hematol & Oncol Sci, S Orsola Malpighi Hosp, I-40126 Bologna, Italy. [Hornick, Jason L.] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Chacon, Matias] GATE D, Buenos Aires, DF, Argentina. [Corless, Christopher L.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. [Heinrich, Michael C.] Portland VA Med Ctr, Portland, OR USA. RP Heinrich, MC (reprint author), 3710 SW US Vet Hosp Rd,R&D 19, Portland, OR 97239 USA. EM Heinrich@ohsu.edu OI Patterson, Janice/0000-0002-8969-2933; PANTALEO, MARIA ABBONDANZA/0000-0002-0177-6957 FU GIST Cancer Research Fund; BP Lester Foundation; Life Raft Group; VA Merit Review Grant FX This study was supported, in part, by funds from the GIST Cancer Research Fund, the BP Lester Foundation, and the Life Raft Group (M. C. H. and C. L. C.). M. C. H. is a recipient of a VA Merit Review Grant. NR 45 TC 11 Z9 13 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2045-7634 J9 CANCER MED-US JI Cancer Med. PD FEB PY 2013 VL 2 IS 1 BP 21 EP 31 DI 10.1002/cam4.57 PG 11 WC Oncology SC Oncology GA V36KH UT WOS:000209210500003 PM 24133624 ER PT J AU Niessner, H Forschner, A Klumpp, B Honegger, JB Witte, M Bornemann, A Dummer, R Adam, A Bauer, J Tabatabai, G Flaherty, K Sinnberg, T Beck, D Leiter, U Mauch, C Roesch, A Weide, B Eigentler, T Schadendorf, D Garbe, C Kulms, D Quintanilla-Martinez, L Meier, F AF Niessner, Heike Forschner, Andrea Klumpp, Bernhard Honegger, Juergen B. Witte, Maria Bornemann, Antje Dummer, Reinhard Adam, Annemarie Bauer, Juergen Tabatabai, Ghazaleh Flaherty, Keith Sinnberg, Tobias Beck, Daniela Leiter, Ulrike Mauch, Cornelia Roesch, Alexander Weide, Benjamin Eigentler, Thomas Schadendorf, Dirk Garbe, Claus Kulms, Dagmar Quintanilla-Martinez, Leticia Meier, Friedegund TI Targeting hyperactivation of the AKT survival pathway to overcome therapy resistance of melanoma brain metastases SO CANCER MEDICINE LA English DT Article DE AKT; BRAF inhibitors; brain metastasis; melanoma; therapy resistance AB Brain metastases are the most common cause of death in patients with metastatic melanoma, and the RAF-MEK-ERK and PI3K-AKT signaling pathways are key players in melanoma progression and drug resistance. The BRAF inhibitor vemurafenib significantly improved overall survival. However, brain metastases still limit the effectiveness of this therapy. In a series of patients, we observed that treatment with vemurafenib resulted in substantial regression of extracerebral metastases, but brain metastases developed. This study aimed to identify factors that contribute to treatment resistance in brain metastases. Matched brain and extracerebral metastases from melanoma patients had identical ERK, p-ERK, and AKT immunohistochemistry staining patterns, but there was hyperactivation of AKT (p-AKT) and loss of PTEN expression in the brain metastases. Mutation analysis revealed no differences in BRAF, NRAS, or KIT mutation status in matched brain and extracerebral metastases. In contrast, AKT, p-AKT, and PTEN expression was identical in monolayer cultures derived from melanoma brain and extracerebral metastases. Furthermore, melanoma cells stimulated by astrocyte-conditioned medium showed higher AKT activation and invasiveness than melanoma cells stimulated by fibroblast-conditioned medium. Inhibition of PI3K-AKT signaling resensitized melanoma cells isolated from a vemurafenib-resistant brain metastasis to vemurafenib. Brain-derived factors appear to induce hyperactivation of the AKT survival pathway and to promote the survival and drug resistance of melanoma cells in the brain. Thus, inhibition of PI3K-AKT signaling shows potential for enhancing and/or prolonging the antitumor effect of BRAF inhibitors or other anticancer agents in melanoma brain metastases. C1 [Niessner, Heike; Forschner, Andrea; Bauer, Juergen; Sinnberg, Tobias; Beck, Daniela; Leiter, Ulrike; Weide, Benjamin; Eigentler, Thomas; Garbe, Claus; Meier, Friedegund] Univ Tubingen, Div Dermatol Oncol, Dept Dermatol, D-72076 Tubingen, Germany. [Klumpp, Bernhard] Univ Tubingen, Dept Diagnost & Intervent Radiol, D-72076 Tubingen, Germany. [Honegger, Juergen B.] Univ Tubingen, Dept Neurosurg, D-72076 Tubingen, Germany. [Witte, Maria] Univ Tubingen, Dept Surg, D-72076 Tubingen, Germany. [Bornemann, Antje] Univ Tubingen, Dept Neuropathol, D-72076 Tubingen, Germany. [Dummer, Reinhard] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. [Adam, Annemarie; Quintanilla-Martinez, Leticia] Univ Tubingen, Inst Pathol, D-72076 Tubingen, Germany. [Tabatabai, Ghazaleh] Univ Zurich Hosp, Dept Neurol, CH-8091 Zurich, Switzerland. [Flaherty, Keith] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Mauch, Cornelia] Univ Cologne, Dept Dermatol, Cologne, Germany. [Roesch, Alexander] Univ Homburg, Dept Dermatol, Homburg, Germany. [Schadendorf, Dirk] Univ Essen Gesamthsch, Dept Dermatol, Essen, Germany. [Kulms, Dagmar] Univ Dresden, Dept Dermatol, Dresden, Germany. RP Meier, F (reprint author), Univ Tubingen, Div Dermatol Oncol, Dept Dermatol, Liebermeisterstr 25, D-72076 Tubingen, Germany. EM friedegund.meier@med.uni-tuebingen.de RI Weide, Benjamin/N-3698-2013; Eigentler, Thomas/K-8570-2015; Bauer, Jurgen/B-4656-2008; Tabatabai, Ghazaleh/A-6365-2015 OI Eigentler, Thomas/0000-0003-0019-2770; Bauer, Jurgen/0000-0001-8789-1536; Tabatabai, Ghazaleh/0000-0003-3702-923X FU Deutsche Forschungsgemeinschaft [SFB 773] FX Deutsche Forschungsgemeinschaft SFB 773 (H. N., G. T., F. M.). NR 27 TC 35 Z9 37 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2045-7634 J9 CANCER MED-US JI Cancer Med. PD FEB PY 2013 VL 2 IS 1 BP 76 EP 85 DI 10.1002/cam4.50 PG 10 WC Oncology SC Oncology GA V36KH UT WOS:000209210500009 PM 24133630 ER PT J AU Gameiro, P Metelo, A Perez-Carro, R Alexandra, A Wang, ZW Rathmell, KW Olumi, A Lopez-Larrubia, P Stephanopoulos, G Illopoulos, O AF Gameiro, Paulo Metelo, Ana Perez-Carro, Rojo Alexandra, Arreola Wang, Zongwei Rathmell, Kimryn W. Olumi, Aria Lopez-Larrubia, Pilar Stephanopoulos, Gregory Illopoulos, Othon TI Hypoxia inducible factor (HIF) promotes reductive carboxylation by regulating citrate levels and renders VHL-deficient and hypoxic cells sensitive to glutamine deprivation SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Gameiro, Paulo; Metelo, Ana; Illopoulos, Othon] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. [Perez-Carro, Rojo; Lopez-Larrubia, Pilar] Inst Invest Biomed Alberto Sols, Madrid, Spain. [Alexandra, Arreola; Rathmell, Kimryn W.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Wang, Zongwei; Olumi, Aria] Massachusetts Gen Hosp, Urol, Boston, MA 02114 USA. [Stephanopoulos, Gregory] MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2013 VL 73 SU 3 MA B1 DI 10.1158/1538-7445.TIM2013-B1 PG 2 WC Oncology SC Oncology GA V40RT UT WOS:000209496400084 ER PT J AU Yoshikawa, K Matsumoto, Y Ito, J Shiojiri, Y Reinherz, E Toi, M AF Yoshikawa, Kiyotsugu Matsumoto, Yoshiaki Ito, Junji Shiojiri, Yoshie Reinherz, Ellis Toi, Masakazu TI Application of sensitive EMT reporter to identification of breast cancer stem cell-related genes SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Yoshikawa, Kiyotsugu; Matsumoto, Yoshiaki; Ito, Junji; Shiojiri, Yoshie; Toi, Masakazu] Kyoto Univ, Grad Sch Med, Kyoto, Japan. [Reinherz, Ellis] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2013 VL 73 SU 3 MA C84 DI 10.1158/1538-7445.TIM2013-C84 PG 2 WC Oncology SC Oncology GA V40RT UT WOS:000209496400230 ER PT J AU Yu, M Bardia, A Wittner, B Stott, S Smas, M Ting, D Isakoff, S Cicillano, J Wells, M Shah, A Concannon, K Donaldson, M Sequiet, L Brachtel, E Sgrol, D Baseiga, J Ramaswamy, S Toner, M Haber, D Maheswaran, S AF Yu, Min Bardia, Aditya Wittner, Ben Stott, Shannon Smas, Malgorzata Ting, David Isakoff, Steven Cicillano, Jordan Wells, Marissa Shah, Ajay Concannon, Kyle Donaldson, Maria Sequiet, Lecia Brachtel, Elena Sgrol, Dennis Baseiga, Jose Ramaswamy, Sridhar Toner, Mehmet Haber, Daniel Maheswaran, Shyamala TI Circulating tumor cells in human breast cancer exhibit dynamic changes in epithelial and mesenchymal composition SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Yu, Min; Bardia, Aditya; Wittner, Ben; Stott, Shannon; Smas, Malgorzata; Ting, David; Isakoff, Steven; Cicillano, Jordan; Wells, Marissa; Shah, Ajay; Concannon, Kyle; Donaldson, Maria; Sequiet, Lecia; Brachtel, Elena; Sgrol, Dennis; Baseiga, Jose; Ramaswamy, Sridhar; Toner, Mehmet; Haber, Daniel; Maheswaran, Shyamala] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2013 VL 73 SU 3 MA A75 DI 10.1158/1538-7445.TIM2013-A75 PG 2 WC Oncology SC Oncology GA V40RT UT WOS:000209496400061 ER PT J AU Gitajn, IL Toussaint, RJ Kwon, JY AF Gitajn, I. Leah Toussaint, Rull James Kwon, John Y. TI Assessing Accuracy of Sustentaculum Screw Placement During Calcaneal Fixation SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE calcaneus fracture; sustentaculum; Harris heel view ID DISPLACED INTRAARTICULAR FRACTURES; OPERATIVE TREATMENT; INTERNAL-FIXATION; NONOPERATIVE TREATMENT; SURGICAL-MANAGEMENT; REDUCTION; TRIAL AB Background: The aim of this study was to determine the ability of the Harris heel view to confirm placement of the sustentacular screw during calcaneal fixation. Methods: A 4.0 cancellous screw was placed in a cadaveric specimen, from lateral to medial in 5 configurations: (1) within the sustentaculum, (2) misdirected inferiorly to sustentaculum, (3) misdirected superiorly to sustentaculum, (4) misdirected anteriorly to sustentaculum, and (5) misdirected posteriorly to sustentaculum. Harris heel views were obtained at 5 angulations and were analyzed to determine screw placement. Results: A screw placed anatomically was radiographically confirmed by the Harris heel view to be within the sustentaculum in all views. An inferiorly misdirected screw appeared radiographically within the sustentaculum at 30, 40 and 50 degrees but was confirmed misplaced on the 10- and 20-degree views. A posteriorly misdirected screw was confirmed misplaced on all 5 views. An anteriorly misdirected screw appeared radiographically within the sustentaculum on the 10-degree view but was confirmed misplaced on all other views. A superiorly misdirected screw was confirmed misplaced on all views. Conclusions: Clinicians should be aware that several specific axial heel views are required to verify placement of the sustentacular screw. An inferiorly misdirected screw will appear to be within the sustentaculum with the standard Harris heel view. C1 [Gitajn, I. Leah; Toussaint, Rull James; Kwon, John Y.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Gitajn, IL (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. EM igitajn@partners.org NR 24 TC 4 Z9 6 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1071-1007 EI 1944-7876 J9 FOOT ANKLE INT JI Foot Ankle Int. PD FEB PY 2013 VL 34 IS 2 BP 282 EP 286 DI 10.1177/1071100712467617 PG 5 WC Orthopedics SC Orthopedics GA 298EG UT WOS:000330306300019 PM 23413070 ER PT J AU Blanch, L Sales, B Montanya, J Lucangelo, U Garcia-Esquirol, O Villagra, A Chacon, E Estruga, A Borelli, M Burgueno, MJ Olivia, JC Fernandez, R Villar, J Kacmarek, R Murias, G AF Blanch, Lluis Sales, Bernat Montanya, Jaume Lucangelo, Umberto Garcia-Esquirol, Oscar Villagra, Ana Chacon, Encarna Estruga, Anna Borelli, Massimo Burgueno, Ma Jose Olivia, Joan C. Fernandez, Rafael Villar, Jesus Kacmarek, Robert Murias, Gaston TI Validation of the Better Care system to detect ineffective efforts during expiration in mechanically ventilated patients: a pilot study (vol 38, pg 772, 2012) SO INTENSIVE CARE MEDICINE LA English DT Correction C1 Univ Autonoma Barcelona, Corporacio Sanitaria Univ Parc Tauli, Hosp Sabadell, Crit Care Ctr, E-08208 Sabadell, Spain. CIBER Enfermedades Resp, ISCii, Madrid, Spain. Univ Autonoma Barcelona, Corporacio Sanitaria Univ Parc Tauli, Fundacio Parc Tauli, E-08208 Sabadell, Spain. Trieste Univ, Cattinara Hosp, Dept Perioperat Med Intens Care & Emergency, Trieste, Italy. Hosp Univ Dr Negrin, Multidisciplinary Organ Dysfunct Evaluat Res, Res Unit, Las Palmas Gran Canaria, Spain. Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Clin Bazterrica & Clin Santa Isabel, Buenos Aires, DF, Argentina. RP Blanch, L (reprint author), Univ Autonoma Barcelona, Corporacio Sanitaria Univ Parc Tauli, Hosp Sabadell, Crit Care Ctr, Parc Tauli, E-08208 Sabadell, Spain. EM lblanch@tauli.cat NR 1 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD FEB PY 2013 VL 39 IS 2 BP 341 EP 341 DI 10.1007/s00134-012-2744-4 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 087MG UT WOS:000314765000018 ER PT J AU Braunwald, E AF Braunwald, Eugene TI Heart Failure SO JACC-HEART FAILURE LA English DT Review DE biomarkers; calcium cycling; cardiovascular disease; heart failure; left ventricular assist device; review AB Despite major improvements in the treatment of virtually all cardiac disorders, heart failure (HF) is an exception, in that its prevalence is rising, and only small prolongations in survival are occurring. An increasing fraction, especially older women with diabetes, obesity, and atrial fibrillation exhibit HF with preserved systolic function. Several pathogenetic mechanisms appear to be operative in HF. These include increased hemodynamic overload, ischemia-related dysfunction, ventricular remodeling, excessive neurohumoral stimulation, abnormal myocyte calcium cycling, excessive or inadequate proliferation of the extracellular matrix, accelerated apoptosis, and genetic mutations. Biomarkers released as a consequence of myocardial stretch, imbalance between formation and breakdown of extracellular matrix, inflammation, and renal failure are useful in the identification of the pathogenetic mechanism and, when used in combination, may become helpful in estimating prognosis and selecting appropriate therapy. Promising new therapies that are now undergoing intensive investigation include an angiotensin receptor neprilysin inhibitor, a naturally-occurring vasodilator peptide, a myofilament sensitizer and several drugs that enhance Ca++ uptake by the sarcoplasmic reticulum. Cell therapy, using autologous bone marrow and cardiac progenitor cells, appears to be promising, as does gene therapy. Chronic left ventricular assistance with continuous flow pumps is being applied more frequently and successfully as destination therapy, as a bridge to transplantation, and even as a bridge to recovery and explantation. While many of these therapies will improve the care of patients with HF, significant reductions in prevalence will require vigorous, multifaceted, preventive approaches. (C) 2013 by the American College of Cardiology Foundation C1 [Braunwald, Eugene] Brigham & Womens Hosp, Dept Med, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. [Braunwald, Eugene] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Braunwald, E (reprint author), TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 201 TC 170 Z9 178 U1 5 U2 26 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1779 EI 2213-1787 J9 JACC-HEART FAIL JI JACC-Heart Fail. PD FEB PY 2013 VL 1 IS 1 BP 1 EP 20 DI 10.1016/j.jchf.2012.10.002 PG 20 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V41GS UT WOS:000209535300001 PM 24621794 ER PT J AU Addison, W Fu, M Yang, H Lin, Z Gori, F Baron, R AF Addison, William Fu, Martin Yang, Helen Lin, Zhao Gori, Francesca Baron, Roland TI Transcriptional control of bone and fat lineage determination by Zinc finger protein 521 (Zfp521) SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Addison, William; Fu, Martin; Yang, Helen; Lin, Zhao; Baron, Roland] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Addison, William; Fu, Martin; Yang, Helen; Lin, Zhao; Baron, Roland] Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA. [Gori, Francesca] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SU0244 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035805032 ER PT J AU Atanasovska, B Oei, L Medina, C Campos, N Estrada, K Hofman, A Aubry-rozier, B Zillikens, C Uitterlinden, A Oei, E Hans, D Rivadeneira, F AF Atanasovska, Biljana Oei, Ling Medina, Carolina Campos, Natalia Estrada, Karol Hofman, Albert Aubry-rozier, Berengere Zillikens, Carola Uitterlinden, Andre Oei, Edwin Hans, Didier Rivadeneira, Fernando TI Prediction of vertebral fracture by Trabecular Bone Score in elderly women of The Rotterdam Study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Atanasovska, Biljana; Medina, Carolina; Campos, Natalia] Erasmus MC, Rotterdam, Netherlands. [Oei, Ling; Rivadeneira, Fernando] Erasmus Univ, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Estrada, Karol] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Hofman, Albert] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Aubry-rozier, Berengere; Hans, Didier] Univ Lausanne Hosp, Lausanne, Switzerland. [Uitterlinden, Andre] Genet Lab, Utrecht, Netherlands. RI Rivadeneira, Fernando/O-5385-2015; Oei, Ling/E-8163-2013 OI Rivadeneira, Fernando/0000-0001-9435-9441; Oei, Ling/0000-0003-3523-458X 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA 1107 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035800108 ER PT J AU Bahar, H Maeda, A Reyes, M Dean, T Schipani, E Kostenuik, P Potts, J Gardella, T AF Bahar, Hila Maeda, Akira Reyes, Monica Dean, Thomas Schipani, Ernestina Kostenuik, Paul Potts, John Gardella, Thomas TI RANKL-Dependent and -Independent Mechanisms of Acute Calcemic Responses to PTH(1-34) SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Bahar, Hila; Maeda, Akira; Reyes, Monica; Dean, Thomas; Potts, John; Gardella, Thomas] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bahar, Hila] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Schipani, Ernestina] Univ Michigan, Ann Arbor, MI 48109 USA. [Kostenuik, Paul] Amgen Inc, Thousand Oaks, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA LB-SA11 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035800247 ER PT J AU Bergwitz, C Reyes, M Sharma, A Carpenter, T Janner, M Biggin, A Tuchman, S Baluarte, HJ Ichikawa, S Munns, C Jueppner, H AF Bergwitz, Clemens Reyes, Monica Sharma, Amita Carpenter, Thomas Janner, Marco Biggin, Andrew Tuchman, Shamir Baluarte, H. Jorge Ichikawa, Shoji Munns, Craig Jueppner, Harald TI Increased Frequency of Renal Stones and Nephrocalcinosis in Heterozygous and Homozygous Carriers of Sequence Variations in SLC34A3/NPT2c SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Bergwitz, Clemens; Reyes, Monica; Sharma, Amita; Jueppner, Harald] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bergwitz, Clemens] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Carpenter, Thomas] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Janner, Marco] Univ Childrens Hosp, Zurich, Switzerland. [Biggin, Andrew; Munns, Craig] Childrens Hosp Westmead, Westmead, NSW, Australia. [Tuchman, Shamir] Childrens Natl Med Ctr, Washington, DC USA. [Baluarte, H. Jorge] Childrens Hosp Philadelphia, Philadelphia, PA USA. [Ichikawa, Shoji] Indiana Univ Sch Med, Indianapolis, IN 46202 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA MO0173 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035801207 ER PT J AU Bilezikian, J Hoff, L Vokes, T Rothman, J Clarke, B Mannstadt, M Lagast, H Shoback, D AF Bilezikian, John Hoff, Leanne Vokes, Tamara Rothman, Jeffrey Clarke, Bart Mannstadt, Michael Lagast, Hjalmar Shoback, Dolores TI Changes in Bone Turnover Markers and Bone Mineral Density with Recombinant Human Parathyroid Hormone, rhPTH(1-84), in Hypoparathyroidism: Potential Utility as Surrogate Endpoints for Monitoring - the REPLACE Study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Bilezikian, John] Columbia Univ, Coll Phys & Surg, New York, NY 10027 USA. [Vokes, Tamara] Univ Chicago, Chicago, IL 60637 USA. [Rothman, Jeffrey] Staten Isl Univ Hosp, New York, NY USA. [Clarke, Bart] Mayo Clin, Coll Med, Rochester, MN USA. [Mannstadt, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mannstadt, Michael] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Lagast, Hjalmar] NPS Pharmaceut Inc, Bedminster Township, NJ USA. [Shoback, Dolores] Univ Calif San Francisco, Vet Affairs Med Ctr, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SA0175 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035803093 ER PT J AU Bischoff, D Zhu, JH Makhijani, N Yamaguchi, D AF Bischoff, David Zhu, Jian-hua Makhijani, Nalini Yamaguchi, Dean TI Induction of CXC Chemokines in Human Mesenchymal Stem Cells (hMSCs) by Stimulation with Secreted Frizzled-Related Proteins (sFRPs) SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Bischoff, David; Zhu, Jian-hua; Makhijani, Nalini; Yamaguchi, Dean] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SU0153 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035804219 ER PT J AU Chubb, R Sinha, P Aarnisalo, P Johnson, R Poulton, I Chen, M Weinstein, L Sims, N Kronenberg, H Wu, J AF Chubb, Rhiannon Sinha, Partha Aarnisalo, Piia Johnson, Rachelle Poulton, Ingrid Chen, Min Weinstein, Lee Sims, Natalie Kronenberg, Henry Wu, Joy TI Intermittent PTH Increases Bone Formation but Not Bone Mass in Osteopenic Mice Lacking Gsa in Osteoblasts SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Chubb, Rhiannon; Sinha, Partha; Kronenberg, Henry] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Aarnisalo, Piia] Univ Helsinki, FIN-00014 Helsinki, Finland. [Aarnisalo, Piia] Univ Helsinki, Cent Hosp, FIN-00014 Helsinki, Finland. [Johnson, Rachelle; Poulton, Ingrid; Sims, Natalie] St Vincents Inst Med Res, Fitzroy, Vic, Australia. [Chen, Min; Weinstein, Lee] NIDDKD, Bethesda, MD USA. [Wu, Joy] Stanford Univ, Sch Med, Stanford, CA 94305 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SA0202 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035800155 ER PT J AU De Giacomo, A Teich, J Demay, M Morgan, E Gerstenfeld, L Einhorn, T AF De Giacomo, Anthony Teich, Joshua Demay, Marie Morgan, Elise Gerstenfeld, Louis Einhorn, Thomas TI Nutritionally Induced Delayed Union Model of Femur Fractures In Mice SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [De Giacomo, Anthony; Teich, Joshua; Gerstenfeld, Louis] Boston Univ, Sch Med, Boston, MA 02215 USA. [Demay, Marie] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Demay, Marie] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Morgan, Elise] Boston Univ, Boston, MA 02215 USA. [Einhorn, Thomas] Boston Med Ctr, 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SU0106 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035804172 ER PT J AU Diem, S Joffe, H Larson, J Guthrie, K Tsai, J Lacroix, A Ensrud, K Leder, B AF Diem, Susan Joffe, Hadine Larson, Joseph Guthrie, Katherine Tsai, Joy Lacroix, Andrea Ensrud, Kristine Leder, Benjamin TI Effects of Escitalopram on Biochemical Markers of Bone Turnover: A Randomized Controlled Trial SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Diem, Susan; Ensrud, Kristine] Univ Minnesota, Minneapolis, MN 55455 USA. [Joffe, Hadine; Tsai, Joy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Larson, Joseph; Guthrie, Katherine; Lacroix, Andrea] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Ensrud, Kristine] Minneapolis VA Hlth Care Syst, Minneapolis, MN USA. [Leder, Benjamin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA MO0347 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035802080 ER PT J AU Estrada, K Liu, CT Cheng, CH Medina-Gomez, C Zhou, YH Oei, L Hofman, A Zillikens, C Karasik, D Uitterlinden, A Cupples, LA Kiel, D Rivadeneira, F Hsu, YH AF Estrada, Karol Liu, Ching-Ti Cheng, Chia-Ho Medina-Gomez, Carolina Zhou, Yanhua Oei, Ling Hofman, Albert Zillikens, Carola Karasik, David Uitterlinden, Andre Cupples, L. Adrienne Kiel, Douglas Rivadeneira, Fernando Hsu, Yi-Hsiang TI Protein-Coding Less-Common Variants Are Associated with BMD: An Exome-Chip Meta-Analysis of Adult Caucasians SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Estrada, Karol] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Liu, Ching-Ti; Zhou, Yanhua; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Cheng, Chia-Ho; Hsu, Yi-Hsiang] Hebrew SeniorLife Inst Aging Res, Roslindale, MA USA. [Medina-Gomez, Carolina] Erasmus MC, Rotterdam, Netherlands. [Oei, Ling; Hofman, Albert; Zillikens, Carola; Rivadeneira, Fernando] Erasmus Univ, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Karasik, David; Kiel, Douglas] Hebrew SeniorLife, Roslindale, MA USA. [Karasik, David] Bar Ilan Univ, IL-52100 Ramat Gan, Israel. [Hsu, Yi-Hsiang] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RI Rivadeneira, Fernando/O-5385-2015; Oei, Ling/E-8163-2013 OI Rivadeneira, Fernando/0000-0001-9435-9441; Oei, Ling/0000-0003-3523-458X 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA 1067 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035800068 ER PT J AU Fazeli, P Wang, I Miller, K Finkelstein, J Bouxsein, M Klibanski, A AF Fazeli, Pouneh Wang, Irene Miller, Karen Finkelstein, Joel Bouxsein, Mary Klibanski, Anne TI Teriparatide increases bone formation and bone mineral density in adult women with anorexia nervosa SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Fazeli, Pouneh; Wang, Irene; Miller, Karen; Finkelstein, Joel] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fazeli, Pouneh] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Bouxsein, Mary] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Klibanski, Anne] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA LB-SA33 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035801003 ER PT J AU Fulzele, K Dedic, C Liu, XL Pajevic, PD AF Fulzele, Keertik Dedic, Christopher Liu, Xiaolong Pajevic, Paola Divieti TI Treatment With Anti-sclerostin Antibody Restores Endosteal Osteoblasts in Osteocyte-specific Gs alpha-KO Mice SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Fulzele, Keertik; Pajevic, Paola Divieti] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fulzele, Keertik; Dedic, Christopher; Liu, Xiaolong; Pajevic, Paola Divieti] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Dedic, Christopher; Liu, Xiaolong] Massachusetts Gen Hosp, Endocrine Unit, 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA 1116 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035800117 ER PT J AU Garr, J Marengi, D Saini, V Liu, XL Pajevic, PD AF Garr, Jenna Marengi, Dean Saini, Vaibhav Liu, Xiaolong Pajevic, Paola Divieti TI Role of PTH/PTHrP Receptor Signaling in Osteocytes in Ovariectomy-Induced Osteopenia SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Garr, Jenna; Marengi, Dean; Liu, Xiaolong; Pajevic, Paola Divieti] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Saini, Vaibhav] Harvard Univ, Sch Med, MGH, Cambridge, MA 02138 USA. [Pajevic, Paola Divieti] Harvard Univ, Sch Med, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SA0125 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035800136 ER PT J AU Giampietro, P Sweetser, D Stoddard, A Blank, R Stephan, M Raggio, C Rasmussen, K Pickart, M Sund, S Broeckel, U AF Giampietro, Philip Sweetser, David Stoddard, Alex Blank, Robert Stephan, Mark Raggio, Cathleen Rasmussen, Kristen Pickart, Michael Sund, Sarah Broeckel, Ulrich TI Whole Exome Sequencing Reveals a Pathogenic Mutation in a Kindred with Congenital Kyphosis and Anterior Fontanelle Patency SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Giampietro, Philip] Univ Wisconsin, Dept Pediat, Madison, WI 53706 USA. [Sweetser, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stoddard, Alex; Blank, Robert; Broeckel, Ulrich] Med Coll Wisconsin, Milwaukee, WI USA. [Stephan, Mark] Madigan Army Med Ctr, Tacoma, WA USA. [Raggio, Cathleen] Hosp Special Surg, New York, NY USA. [Rasmussen, Kristen] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA. [Pickart, Michael] Concordia Univ, Portland, OR USA. [Sund, Sarah] Univ Wisconsin, Madison, WI 53706 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA 1007 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035800008 ER PT J AU Idelevich, A Sato, K Rowe, G Gori, F Baron, R AF Idelevich, Anna Sato, Kazusa Rowe, Glenn Gori, Francesca Baron, Roland TI Inhibition of AP-1 in specific hypothalamic neurons increases both energy expenditure and bone density in mice SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Idelevich, Anna] Harvard Univ, Cambridge, MA 02138 USA. [Sato, Kazusa] Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA. [Rowe, Glenn; Baron, Roland] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Gori, Francesca] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA 1043 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035800044 ER PT J AU Kedlaya, R Pajevic, PD Robling, A AF Kedlaya, Rajendra Pajevic, Paola Divieti Robling, Alexander TI Adult-onset deletion of beta-catenin in 10kbDmp1-expressing cells prevents intermittent PTH-induced bone gain SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Kedlaya, Rajendra; Robling, Alexander] Indiana Univ, Bloomington, IN 47405 USA. [Pajevic, Paola Divieti] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pajevic, Paola Divieti] Harvard Univ, Sch Med, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA 1059 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035800060 ER PT J AU LaRue, A Parthiban, B Cumbee, JL Borke, J Ogawa, M Mehrotra, M AF LaRue, Amanda Parthiban, Beneta Cumbee, Jasper L. Borke, James Ogawa, Makio Mehrotra, Meenal TI Contribution of Hematopoietic Stem Cells to Dental Tissues SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [LaRue, Amanda] Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 USA. [Parthiban, Beneta; Cumbee, Jasper L.; Ogawa, Makio] MUSC, Charleston, SC USA. [Borke, James] Western Univ Hlth Sci, Pomona, CA USA. [Mehrotra, Meenal] Med Univ South Carolina & Res Serv, Ralph H Johnson VAMC, Charleston, SC 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SA0105 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035803037 ER PT J AU Leder, B Uihlein, A Tsai, J Neer, R Siwila-Sackman, E Zhu, YL Foley, K Lee, H Burnett-Bowie, SA AF Leder, Benjamin Uihlein, Alexander Tsai, Joy Neer, Robert Siwila-Sackman, Erica Zhu, Yuli Foley, Katelyn Lee, Hang Burnett-Bowie, Sherri-Ann TI The DATA Extension Study: 2 Years of Combined Denosumab and Teriparatide in Postmenopausal Women with Osteoporosis: A Randomized Controlled Trial SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Leder, Benjamin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Uihlein, Alexander] Northwestern Mem Fac Fdn, Chicago, IL USA. [Tsai, Joy; Neer, Robert; Siwila-Sackman, Erica; Zhu, Yuli; Foley, Katelyn; Lee, Hang; Burnett-Bowie, Sherri-Ann] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA 1019 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035800020 ER PT J AU Lewis, J Estrada, K Uitterlinden, A Rivadeneira, F Prince, R AF Lewis, Joshua Estrada, Karol Uitterlinden, Andre Rivadeneira, Fernando Prince, Richard TI Interaction of a single genotype and body mass index for prediction of hip fracture risk: a prospective cohort study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Lewis, Joshua] Univ Western Australia, Sir Charles Gairdner Hosp, Nedlands, WA 6009, Australia. [Estrada, Karol] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Rivadeneira, Fernando] Erasmus Univ, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Prince, Richard] Sir Charles Gairdner Hosp, Nedlands, WA, Australia. 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SU0334 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035805120 ER PT J AU Lisse, T Luderer, H Gori, F Demay, M AF Lisse, Thomas Luderer, Hilary Gori, Francesca Demay, Marie TI The vitamin D receptor is required for activation of the canonical Wnt and Hedgehog signaling pathways in keratinocytes SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Lisse, Thomas; Luderer, Hilary; Demay, Marie] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lisse, Thomas; Demay, Marie] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Gori, Francesca] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA MO0456 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035802189 ER PT J AU Liu, E Raimann, A Zhu, E Demay, M AF Liu, Eva Raimann, Adalbert Zhu, Eric Demay, Marie TI C-raf is Required for Normal Postnatal Growth Plate Maturation SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Liu, Eva] Brigham & Womens Hosp, Boston, MA 02115 USA. [Liu, Eva; Zhu, Eric; Demay, Marie] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Raimann, Adalbert] Med Univ Vienna, Vienna, Austria. [Demay, Marie] Harvard Univ, Sch Med, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SU0083 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035804150 ER PT J AU Liu, E Gori, F Demay, M AF Liu, Eva Gori, Francesca Demay, Marie TI Phosphate regulates signaling molecules and apoptotic proteins in hypertrophic chondrocytes SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Liu, Eva] Brigham & Womens Hosp, Boston, MA 02115 USA. [Liu, Eva; Demay, Marie] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gori, Francesca] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Demay, Marie] Harvard Univ, Sch Med, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SA0090 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035803023 ER PT J AU Liu, XW Nagano, K Saito, H Baron, R Gori, F AF Liu, Xianwen Nagano, Kenichi Saito, Hiroaki Baron, Roland Gori, Francesca TI Wnt16 Deletion Differentially Affects Cortical and Trabecular Bone: Increased Cortical Bone Resorption, Porosity and Fracture in Wnt16 Knockout Mice SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Liu, Xianwen; Nagano, Kenichi; Saito, Hiroaki] Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA. [Baron, Roland] Harvard Univ, Sch Med & Dent Med, Cambridge, MA 02138 USA. [Gori, Francesca] Harvard Univ, Sch Dent 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA 1057 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035800058 ER PT J AU Liu, XH Kang, H Dang, A Kim, H Nissenson, R Halloran, B AF Liu, Xuhui Kang, Heejae Dang, Alexis Kim, Hubert Nissenson, Robert Halloran, Bernard TI A Novel Mouse Model of Heterotopic Ossification with Spinal Cord Injury SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Liu, Xuhui; Dang, Alexis; Kim, Hubert; Nissenson, Robert] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Kang, Heejae] San Francisco VA Med Ctr, San Francisco, CA USA. [Nissenson, Robert] VA Med Ctr, Portland, VA USA. [Halloran, Bernard] VA Med Ctr, Portland, VA 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA MO0191 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035801225 ER PT J AU Mannstadt, M Nesbit, MA Howles, S Rogers, A Thakker, R Jueppner, H AF Mannstadt, Michael Nesbit, M. Andrew Howles, Sarah Rogers, Angela Thakker, Rajesh Jueppner, Harald TI Gain-of-Function Mutations in G alpha 11 Cause a Novel Form of Autosomal-Dominant Hypoparathyroidism SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Mannstadt, Michael] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Nesbit, M. Andrew; Howles, Sarah; Rogers, Angela; Thakker, Rajesh] Univ Oxford, Nuffield Dept Clin Med, Oxford OX1 2JD, England. [Jueppner, Harald] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SU0115 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035804181 ER PT J AU Mcnabb, B Vittinghoff, E Eastell, R Schwartz, A Bauer, D Ensrud, K Barrett-Connor, E Black, D AF Mcnabb, Brian Vittinghoff, Eric Eastell, Richard Schwartz, Ann Bauer, Douglas Ensrud, Kristine Barrett-Connor, Elizabeth Black, Dennis TI Post-Alendronate DXA Monitoring Strategy Based on 5-year Changes in BMD SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Mcnabb, Brian] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Vittinghoff, Eric; Schwartz, Ann; Bauer, Douglas; Black, Dennis] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Eastell, Richard] Univ Sheffield, Sheffield S10 2TN, S Yorkshire, England. [Ensrud, Kristine] Univ Minnesota, Minneapolis, MN 55455 USA. [Ensrud, Kristine] Minneapolis VA Hlth Care Syst, Minneapolis, MN USA. [Barrett-Connor, Elizabeth] Univ Calif San Diego, San Diego, CA 92103 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA LB-MO21 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035800222 ER PT J AU Medina-Gomez, C Heppe, DHM Estrada, K Oei, L Kruithof, CJ Hofman, A Jaddoe, VVW Uitterlinden, A Rivadeneira, F AF Medina-Gomez, Carolina Heppe, Denise H. M. Estrada, Karol Oei, Ling Kruithof, Claudia J. Hofman, Albert Jaddoe, Vincent V. W. Uitterlinden, Andre Rivadeneira, Fernando TI Bone Mineral Density Variation In Children Across Different Ethnic Backgrounds Is Partially Explained By Genetic Profiling. The Generation R Study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Medina-Gomez, Carolina] Erasmus MC, Rotterdam, Netherlands. [Heppe, Denise H. M.; Kruithof, Claudia J.; Jaddoe, Vincent V. W.] Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands. [Estrada, Karol] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Oei, Ling; Rivadeneira, Fernando] Erasmus Univ, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Hofman, Albert] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Uitterlinden, Andre] Genet Lab, Utrecht, Netherlands. RI Rivadeneira, Fernando/O-5385-2015; Oei, Ling/E-8163-2013 OI Rivadeneira, Fernando/0000-0001-9435-9441; Oei, Ling/0000-0003-3523-458X 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SA0026 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035802225 ER PT J AU Nielson, C Srikanth, P Zmuda, J Shen, J Klein, R Orwoll, E AF Nielson, Carrie Srikanth, Priya Zmuda, Joseph Shen, Jian Klein, Robert Orwoll, Eric TI Gene by genome-wide interactions on femoral neck BMD in MrOS and SOF: a synergistic effect of polymorphisms in the alkaline phosphatase (ALPL) and lecithin retinol acyltransferase (LRAT) genes SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Nielson, Carrie; Srikanth, Priya; Shen, Jian; Orwoll, Eric] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Zmuda, Joseph] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Klein, Robert] Portland VA Med Ctr, Portland, OR 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA MO0337 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035802070 ER PT J AU Nishimori, S Lai, F Wein, M Kozhemyakina, E Olson, E Lassar, A Kronenberg, H AF Nishimori, Shigeki Lai, Forest Wein, Marc Kozhemyakina, Elena Olson, Eric Lassar, Andrew Kronenberg, Henry TI Complete Suppression of PTHrP Signaling in Chondrocytes in the Histone Deacetylase 4 and 5 Double Knockout Mouse SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Nishimori, Shigeki; Lai, Forest; Wein, Marc; Kronenberg, Henry] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kozhemyakina, Elena; Lassar, Andrew] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Olson, Eric] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SA0082 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035803016 ER PT J AU Nistala, H Nistala, H Takeyama, K Chen, HH Boback, B Gori, F Baron, R AF Nistala, Harikiran Nistala, Harikiran Takeyama, Ken-ichi Chen, Hsu-Hsin Boback, Bernard Gori, Francesca Baron, Roland TI Zfp521 in conjunction with the NuRD complex and Tgm3 regulates mesenchymal stem cell lineage determination and induced pluripotency SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Nistala, Harikiran; Nistala, Harikiran; Chen, Hsu-Hsin] Harvard Univ, Cambridge, MA 02138 USA. [Takeyama, Ken-ichi; Boback, Bernard] Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA. [Gori, Francesca] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Baron, Roland] Harvard Univ, Sch Med & Dent Med, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA MO0105 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035801141 ER PT J AU Oei, L Reppe, S Ntzani, E Hibbs, M Choi, K Zheng, HF Estrada, K van de Peppel, J Nielson, C Styrkarsdottir, U Ridker, P Hsu, YH Garcia, M Aragaki, A Duncan, E Enneman, A Lehtimaki, T Esko, T Trompet, S Kaptoge, S Eriksson, J Amin, N Kung, A Medina-Gomez, C Tsilidis, K Thorleifsson, G Rose, L Zmuda, J Liu, CT Vernon-Smith, A Srikanth, P Wilson, S Clark, G Viikari, J Mihailov, E Moayyeri, A Li, G Kammerer, C Lorentzon, M Rivera, N Xiao, SM Yang, J Visscher, P Tranah, G Evans, D Karasik, D Siggeirsdottir, K Oei, E Stefansson, K Aalto, V Willner, D Wareham, N Minster, R Bis, J van Duijn, C Boyle, A Snyder, M Herrera, L Cupples, LA Aspelund, T Raitakari, O Leo, P Khaw, KT Robbins, J Liu, YM Breda, S Luben, R Cauley, J Arnold, A Stolk, L Pols, H Hofman, A Shen, J Van Meurs, J Sham, P Zillikens, M Ohlsson, C Psaty, B Harris, T Reeve, J Jukema, JW Metspalu, A Kahonen, M van der Velde, N Brown, M Gudnason, V Ioannidis, J Uitterlinden, A Cummings, S Spector, T Kiel, D Jackson, R Thorsteinsdottir, U Chasman, D Orwoll, E Yadav, V Van Leeuwen, J Evangelou, E Grundberg, E Richards, B Gautvik, K Rivadeneira, F Ackert-Bicknell, C AF Oei, Ling Reppe, Sjur Ntzani, Evangelia Hibbs, Matthew Choi, Kwangbom Zheng, Hou-Feng Estrada, Karol van de Peppel, Jeroen Nielson, Carrie Styrkarsdottir, Unnur Ridker, Paul Hsu, Yi-Hsiang Garcia, Melissa Aragaki, Aaron Duncan, Emma Enneman, Anke Lehtimaki, Terho Esko, Tonu Trompet, Stella Kaptoge, Stephen Eriksson, Joel Amin, Najaf Kung, Annie Medina-Gomez, Carolina Tsilidis, Konstantinos Thorleifsson, Gudmar Rose, Lynda Zmuda, Joseph Liu, Ching-Ti Vernon-Smith, Albert Srikanth, Priya Wilson, Scott Clark, Graeme Viikari, Jorma Mihailov, Evelin Moayyeri, Alireza Li, Guo Kammerer, Candace Lorentzon, Mattias Rivera, Natalia Xiao, Sumei Yang, Jian Visscher, Peter Tranah, Gregory Evans, Dan Karasik, David Siggeirsdottir, Kristin Oei, Edwin Stefansson, Kari Aalto, Ville Willner, Dana Wareham, Nicholas Minster, Ryan Bis, Joshua van Duijn, Cornelia Boyle, Alan Snyder, Michael Herrera, Lizbeth Cupples, L. Adrienne Aspelund, Thor Raitakari, Olli Leo, Paul Khaw, Kay-Tee Robbins, John Liu, Yongmei Breda, Stephan Luben, Robert Cauley, Jane Arnold, Alice Stolk, Lisette Pols, Huibert Hofman, Albert Shen, Jian Van Meurs, Joyce Sham, Pak Zillikens, Maria Ohlsson, Claes Psaty, Bruce Harris, Tamara Reeve, Jonathan Jukema, J. Wouter Metspalu, Andres Kahonen, Mika van der Velde, Nathalie Brown, Matthew Gudnason, Vilmundar Ioannidis, John Uitterlinden, Andre Cummings, Steven Spector, Timothy Kiel, Douglas Jackson, Rebecca Thorsteinsdottir, Unnur Chasman, Daniel Orwoll, Eric Yadav, Vijay Van Leeuwen, Johannes Evangelou, Evangelos Grundberg, Elin Richards, Brent Gautvik, Kaare Rivadeneira, Fernando Ackert-Bicknell, Cheryl CA GEFOS Consortium TI Functional characterization of GWAS loci associated with fracture risk SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Oei, Ling] Erasmus Univ, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Reppe, Sjur] Oslo Univ Hosp, Ullevaal, Norway. [Ntzani, Evangelia; Tsilidis, Konstantinos; Evangelou, Evangelos] Univ Ioannina, Sch Med, GR-45110 Ioannina, Greece. [Hibbs, Matthew; Choi, Kwangbom; Ackert-Bicknell, Cheryl] Jackson Lab, Bar Harbor, ME USA. [Zheng, Hou-Feng; Grundberg, Elin; Richards, Brent] McGill Univ, Montreal, PQ H3A 2T5, Canada. [Estrada, Karol] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [van de Peppel, Jeroen; Enneman, Anke; Amin, Najaf; Rivera, Natalia; Oei, Edwin; van Duijn, Cornelia; Herrera, Lizbeth; Breda, Stephan; Stolk, Lisette; Hofman, Albert; Zillikens, Maria; van der Velde, Nathalie] Erasmus MC, Rotterdam, Netherlands. [Nielson, Carrie; Srikanth, Priya; Shen, Jian; Orwoll, Eric] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Styrkarsdottir, Unnur; Thorleifsson, Gudmar; Stefansson, Kari; Thorsteinsdottir, Unnur] deCODE Genet, Reykjavik, Iceland. [Ridker, Paul; Rose, Lynda; Chasman, Daniel] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hsu, Yi-Hsiang] Hebrew SeniorLife Inst Aging Res, Roslindale, MA USA. [Hsu, Yi-Hsiang] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Garcia, Melissa] NIA, NIH, Bethesda, MD 20892 USA. [Aragaki, Aaron] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA USA. [Duncan, Emma] Royal Brisbane & Womens Hosp, Herston, Qld, Australia. [Lehtimaki, Terho; Kahonen, Mika] Univ Tampere, FIN-33101 Tampere, Finland. [Lehtimaki, Terho; Kahonen, Mika] Tampere Univ Hosp, Tampere, Finland. [Esko, Tonu; Mihailov, Evelin; Metspalu, Andres] Univ Tartu, Tartu, Estonia. [Trompet, Stella; Jukema, J. Wouter] Leiden Univ, Med Ctr, NL-2300 RA Leiden, Netherlands. [Kaptoge, Stephen] Univ Cambridge, Bone Res Grp, Cambridge CB2 1TN, England. [Eriksson, Joel] Ctr Bone & Arthrit Res, Gothenburg, Sweden. [Kung, Annie] Dr Kung Wai Chee Clin, Hong Kong, Hong Kong, Peoples R China. [Medina-Gomez, Carolina] Erasmus MC, Rotterdam, Netherlands. [Zmuda, Joseph] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Liu, Ching-Ti] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Vernon-Smith, Albert] Iceland Heart Assoc, Reykjavik, Iceland. [Vernon-Smith, Albert] Univ Iceland, IS-101 Reykjavik, Iceland. [Wilson, Scott] Univ Western Australia, Nedlands, WA 6009, Australia. [Clark, Graeme] Univ Queensland, Diamantina Inst, Brisbane, Qld 4072, Australia. [Viikari, Jorma] Univ Turku, SF-20500 Turku, Finland. [Viikari, Jorma] Turku Univ Hosp, Turku, Finland. [Moayyeri, Alireza] Kings Coll London, London WC2R 2LS, England. [Li, Guo] Univ Washington, Seattle, WA 98195 USA. [Kammerer, Candace] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Lorentzon, Mattias] Sahlgrens Acad, Ctr Bone Res, Gothenburg, Sweden. [Xiao, Sumei] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. [Yang, Jian; Visscher, Peter] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Tranah, Gregory; Evans, Dan] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Karasik, David] Bar Ilan Univ, Hebrew SeniorLife, Ramat Gan, Israel. [Siggeirsdottir, Kristin] Iceland Heart Assoc, Reykjavik, Iceland. [Aalto, Ville] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, SF-20500 Turku, Finland. [Willner, Dana] Univ Queensland, Diamantina Inst, Brisbane, Qld 4072, Australia. [Wareham, Nicholas] MRC, Epidemiol Unit, London W1N 4AL, England. [Minster, Ryan; Cauley, Jane] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Bis, Joshua; Arnold, Alice; Psaty, Bruce] Univ Washington, Seattle, WA 98195 USA. [Boyle, Alan; Snyder, Michael] Stanford Univ, Stanford, CA 94305 USA. [Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Aspelund, Thor; Gudnason, Vilmundar] Iceland Heart Assoc, Reykjavik, Iceland. [Aspelund, Thor; Gudnason, Vilmundar] Univ Iceland, IS-101 Reykjavik, Iceland. [Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, SF-20500 Turku, Finland. [Leo, Paul] Univ Queensland, Diamantina Inst, Brisbane, Qld 4072, Australia. [Khaw, Kay-Tee; Luben, Robert] Univ Cambridge, Cambridge CB2 1TN, England. [Robbins, John] Univ Calif, Davis Med Ctr, Davis, CA USA. [Liu, Yongmei] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. [Pols, Huibert; Van Meurs, Joyce] Erasmus Univ, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Sham, Pak] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. [Ohlsson, Claes] Sahlgrens Acad, Ctr Bone & Arthrit Res, Gothenburg, Sweden. [Harris, Tamara] NIA, Intramural Res Program, Bethesda, MD 20892 USA. [Reeve, Jonathan] Univ Oxford, Oxford OX1 2JD, England. [Brown, Matthew] Diamantina Inst Canc Immunol & Metab Med, Brisbane, Qld, Australia. [Ioannidis, John] Stanford Univ, Stanford, CA 94305 USA. [Uitterlinden, Andre] Genet Lab, Leiden, Netherlands. [Cummings, Steven] San Francisco Coordinating Ctr, San Francisco, CA USA. [Spector, Timothy] Kings Coll London, London WC2R 2LS, England. [Kiel, Douglas] Hebrew SeniorLife, Roslindale, MA USA. [Jackson, Rebecca] Ohio State Univ, Columbus, OH 43210 USA. [Yadav, Vijay] Sanger Welcome Trust Inst, Hinxton, Cambs, England. [Van Leeuwen, Johannes; Rivadeneira, Fernando] Erasmus Univ, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Gautvik, Kaare] Inst Basic Med Sci, Oslo, Norway. RI Leo, Paul/B-3470-2011; Moayyeri, Alireza/N-3332-2014; Gudnason, Vilmundur/K-6885-2015; Aspelund, Thor/C-5983-2008; Rivadeneira, Fernando/O-5385-2015; Oei, Ling/E-8163-2013 OI Leo, Paul/0000-0001-8325-4134; Moayyeri, Alireza/0000-0002-9143-2161; Gudnason, Vilmundur/0000-0001-5696-0084; Aspelund, Thor/0000-0002-7998-5433; Rivadeneira, Fernando/0000-0001-9435-9441; Oei, Ling/0000-0003-3523-458X 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SA0140 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035803064 ER PT J AU Oei, L Nordstrom, P Ntzani, E Zheng, HF Estrada, K Duncan, E Medina-Gomez, C Kaptoge, S Hsu, YH Yang, J Nielson, C Styrkarsdottir, U Ridker, P Garcia, M Aragaki, A Enneman, A Lehtimaki, T Esko, T Trompet, S Eriksson, J Amin, N Kung, A Tsilidis, K Thorleifsson, G Rose, L Zmuda, J Liu, CT Vernon-Smith, A Srikanth, P Wilson, S Clark, G Viikari, J Mihailov, E Moayyeri, A Li, G Kammerer, C Lorentzon, M Rivera, N Xiao, SM Tranah, G Evans, D Siggeirsdottir, K Oei, E Stefansson, K Aalto, V Willner, D Wareham, N Minster, R Bis, J van Duijn, C Boyle, A Snyder, M Herrera, L Cupples, LA Aspelund, T Raitakari, O Leo, P Khaw, KT Robbins, J Liu, YM Breda, S Luben, R Cauley, J Arnold, A Reppe, S Hibbs, M Stolk, L Pasco, J Grundberg, E Gautvik, K Ackert-Bicknell, C Yadav, V Choi, K van de Peppel, J Van Leeuwen, J Pols, H Hofman, A Shen, J van Meurs, J Atanasovska, B Sham, P Ohlsson, C Psaty, B Harris, T Reeve, J Jukema, JW Metspalu, A Kahonen, M van der Velde, N Brown, M Gudnason, V Ioannidis, J Uitterlinden, A Cummings, S Spector, T Kiel, D Jackson, R Thorsteinsdottir, U Chasman, D Orwoll, E Karasik, D Zillikens, M Evangelou, E Richards, B Visscher, P Michaelsson, K Rivadeneira, F AF Oei, Ling Nordstrom, Peter Ntzani, Evangelia Zheng, Hou-Feng Estrada, Karol Duncan, Emma Medina-Gomez, Carolina Kaptoge, Stephen Hsu, Yi-Hsiang Yang, Jian Nielson, Carrie Styrkarsdottir, Unnur Ridker, Paul Garcia, Melissa Aragaki, Aaron Enneman, Anke Lehtimaki, Terho Esko, Tonu Trompet, Stella Eriksson, Joel Amin, Najaf Kung, Annie Tsilidis, Konstantinos Thorleifsson, Gudmar Rose, Lynda Zmuda, Joseph Liu, Ching-Ti Vernon-Smith, Albert Srikanth, Priya Wilson, Scott Clark, Graeme Viikari, Jorma Mihailov, Evelin Moayyeri, Alireza Li, Guo Kammerer, Candace Lorentzon, Mattias Rivera, Natalia Xiao, Sumei Tranah, Gregory Evans, Dan Siggeirsdottir, Kristin Oei, Edwin Stefansson, Kari Aalto, Ville Willner, Dana Wareham, Nicholas Minster, Ryan Bis, Joshua van Duijn, Cornelia Boyle, Alan Snyder, Michael Herrera, Lizbeth Cupples, L. Adrienne Aspelund, Thor Raitakari, Olli Leo, Paul Khaw, Kay-Tee Robbins, John Liu, Yongmei Breda, Stephan Luben, Robert Cauley, Jane Arnold, Alice Reppe, Sjur Hibbs, Matthew Stolk, Lisette Pasco, Julie Grundberg, Elin Gautvik, Kaare Ackert-Bicknell, Cheryl Yadav, Vijay Choi, Kwangbom van de Peppel, Jeroen Van Leeuwen, Johannes Pols, Huibert Hofman, Albert Shen, Jian van Meurs, Joyce Atanasovska, Biljana Sham, Pak Ohlsson, Claes Psaty, Bruce Harris, Tamara Reeve, Jonathan Jukema, J. Wouter Metspalu, Andres Kahonen, Mika van der Velde, Nathalie Brown, Matthew Gudnason, Vilmundar Ioannidis, John Uitterlinden, Andre Cummings, Steven Spector, Tim Kiel, Douglas Jackson, Rebecca Thorsteinsdottir, Unnur Chasman, Daniel Orwoll, Eric Karasik, David Zillikens, Maria Evangelou, Evangelos Richards, Brent Visscher, Peter Michaelsson, Karl Rivadeneira, Fernando TI The genetic basis of cross-phenotype correlation with bone fracture risk: the GEFOS consortium SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Oei, Ling] Erasmus Univ, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Nordstrom, Peter] Umea Univ, S-90187 Umea, Sweden. [Ntzani, Evangelia] Univ Ioannina, Sch Med, GR-45110 Ioannina, Greece. [Zheng, Hou-Feng] McGill Univ, Montreal, PQ H3A 2T5, Canada. [Estrada, Karol] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Duncan, Emma] Royal Brisbane & Womens Hosp, Herston, Qld, Australia. [Medina-Gomez, Carolina] Erasmus MC, Rotterdam, Netherlands. [Kaptoge, Stephen] Univ Cambridge, Bone Res Grp, Cambridge CB2 1TN, England. [Hsu, Yi-Hsiang] Hebrew SeniorLife Inst Aging Res, Roslindale, MA USA. [Hsu, Yi-Hsiang] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Yang, Jian] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Nielson, Carrie] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Styrkarsdottir, Unnur] Decode Genet, Reykjavik, Iceland. [Ridker, Paul] Brigham & Womens Hosp, Boston, MA 02115 USA. [Garcia, Melissa] NIA, NIH, Bethesda, MD 20892 USA. [Aragaki, Aaron] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA USA. [Enneman, Anke] Erasmus MC, Rotterdam, Netherlands. [Lehtimaki, Terho] Univ Tampere, FIN-33101 Tampere, Finland. [Lehtimaki, Terho] Tampere Univ Hosp, Tampere, Finland. [Esko, Tonu] Univ Tartu, Tartu, Estonia. [Trompet, Stella] Leiden Univ, Med Ctr, NL-2300 RA Leiden, Netherlands. [Eriksson, Joel] Ctr Bone & Arthrit Res, Gothenburg, Sweden. [Amin, Najaf] Erasmus MC, Rotterdam, Netherlands. [Tsilidis, Konstantinos] Univ Ioannina, Sch Med, GR-45110 Ioannina, Greece. [Thorleifsson, Gudmar] deCODE Genet, Reykjavik, Iceland. [Rose, Lynda] Brigham & Womens Hosp, Boston, MA 02115 USA. [Zmuda, Joseph] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Liu, Ching-Ti] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Vernon-Smith, Albert] Iceland Heart Assoc, Kopavogur, Iceland. [Vernon-Smith, Albert] Univ Iceland, IS-101 Reykjavik, Iceland. [Srikanth, Priya] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Wilson, Scott] Univ Western Australia, Nedlands, WA, Australia. [Clark, Graeme] Univ Queensland, Diamantina Inst, Brisbane, Qld 4072, Australia. [Viikari, Jorma] Univ Turku, SF-20500 Turku, Finland. [Viikari, Jorma] Turku Univ Hosp, Turku, Finland. [Mihailov, Evelin] Univ Tartu, Tartu, Estonia. [Moayyeri, Alireza] Kings Coll London, London WC2R 2LS, England. [Li, Guo] Univ Washington, Seattle, WA 98195 USA. [Kammerer, Candace] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Lorentzon, Mattias] Sahlgrens Acad, Ctr Bone Res, Gothenburg, Sweden. [Rivera, Natalia; Oei, Edwin] Erasmus MC, Rotterdam, Netherlands. [Xiao, Sumei] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. [Tranah, Gregory; Evans, Dan] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Siggeirsdottir, Kristin] Iceland Heart Assoc, Kopavogur, Iceland. [Stefansson, Kari] deCODE Genet, Reykjavik, Iceland. [Aalto, Ville] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, SF-20500 Turku, Finland. [Willner, Dana] Univ Queensland, Diamantina Inst, Brisbane, Qld 4072, Australia. [Wareham, Nicholas] MRC, Epidemiol Unit, London W1N 4AL, England. [Minster, Ryan] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Bis, Joshua] Univ Washington, Seattle, WA 98195 USA. [van Duijn, Cornelia; Herrera, Lizbeth] Erasmus MC, Rotterdam, Netherlands. [Boyle, Alan; Snyder, Michael] Stanford Univ, Stanford, CA 94305 USA. [Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Aspelund, Thor] Iceland Heart Assoc, Kopavogur, Iceland. [Aspelund, Thor] Univ Iceland, IS-101 Reykjavik, Iceland. [Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, SF-20500 Turku, Finland. [Leo, Paul] Univ Queensland, Diamantina Inst, Brisbane, Qld 4072, Australia. [Khaw, Kay-Tee; Luben, Robert] Univ Cambridge, Cambridge CB2 1TN, England. [Liu, Yongmei] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. [Breda, Stephan; Stolk, Lisette] Erasmus MC, Rotterdam, Netherlands. [Cauley, Jane] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Arnold, Alice] Univ Washington, Seattle, WA 98195 USA. [Reppe, Sjur] Oslo Univ Hosp, Ullevaal, Norway. [Hibbs, Matthew; Ackert-Bicknell, Cheryl; Choi, Kwangbom] Jackson Lab, Bar Harbor, ME USA. [Pasco, Julie] Deakin Univ, Geelong, Vic 3217, Australia. [Grundberg, Elin] McGill Univ, Montreal, PQ H3A 2T5, Canada. [Gautvik, Kaare] Inst Basic Med Sci, Oslo, Norway. [Yadav, Vijay] Sanger Welcome Trust Inst, Hinxton, England. [van de Peppel, Jeroen; Hofman, Albert; van Meurs, Joyce; Atanasovska, Biljana] Erasmus MC, Rotterdam, Netherlands. [Van Leeuwen, Johannes; Pols, Huibert] Erasmus Univ, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Shen, Jian] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Sham, Pak] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. [Ohlsson, Claes] Sahlgrens Acad, Ctr Bone & Arthrit Res, Gothenburg, Sweden. [Psaty, Bruce] Univ Washington, Seattle, WA 98195 USA. [Harris, Tamara] NIA, Intramural Res Program, Bethesda, MD 20892 USA. [Reeve, Jonathan] Univ Oxford, Oxford OX1 2JD, England. [Jukema, J. Wouter] Leiden Univ, Med Ctr, NL-2300 RA Leiden, Netherlands. [Metspalu, Andres] Univ Tartu, Tartu, Estonia. [Kahonen, Mika] Univ Tampere, FIN-33101 Tampere, Finland. [Kahonen, Mika] Tampere Univ Hosp, Tampere, Finland. [van der Velde, Nathalie] Erasmus MC, Rotterdam, Netherlands. [Brown, Matthew] Diamantina Inst Canc Immunol & Metab Med, Brisbane, Qld, Australia. [Gudnason, Vilmundar] Iceland Heart Assoc, Kopavogur, Iceland. [Gudnason, Vilmundar] Univ Iceland, IS-101 Reykjavik, Iceland. [Ioannidis, John] Stanford Univ, Stanford, CA 94305 USA. [Uitterlinden, Andre] Genet Lab, Amsterdam, Netherlands. [Cummings, Steven] San Francisco Coordinating Ctr, San Francisco, CA USA. [Spector, Tim] Kings Coll London, London WC2R 2LS, England. [Kiel, Douglas] Hebrew SeniorLife, Roslindale, MA USA. [Jackson, Rebecca] Ohio State Univ, Columbus, OH 43210 USA. [Thorsteinsdottir, Unnur] deCODE Genet, Reykjavik, Iceland. [Chasman, Daniel] Brigham & Womens Hosp, Boston, MA 02115 USA. [Orwoll, Eric] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Karasik, David] Bar Ilan Univ, Hebrew SeniorLife, Roslindale, MA USA. [Zillikens, Maria] Erasmus Mc, Rotterdam, Netherlands. [Evangelou, Evangelos] Univ Ioannina, Sch Med, GR-45110 Ioannina, Greece. [Richards, Brent] McGill Univ, Montreal, PQ H3A 2T5, Canada. [Visscher, Peter] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Michaelsson, Karl] Uppsala Clin Res Ctr, Uppsala, Sweden. [Rivadeneira, Fernando] Erasmus Univ, Med Ctr, GEFOS Consortium, NL-3000 DR Rotterdam, Netherlands. RI Leo, Paul/B-3470-2011; Moayyeri, Alireza/N-3332-2014; Gudnason, Vilmundur/K-6885-2015; Aspelund, Thor/C-5983-2008; Rivadeneira, Fernando/O-5385-2015; Oei, Ling/E-8163-2013 OI Leo, Paul/0000-0001-8325-4134; Moayyeri, Alireza/0000-0002-9143-2161; Gudnason, Vilmundur/0000-0001-5696-0084; Aspelund, Thor/0000-0002-7998-5433; Rivadeneira, Fernando/0000-0001-9435-9441; Oei, Ling/0000-0003-3523-458X 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA MO0140 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035801175 ER PT J AU Ono, N Ono, W Kronenberg, H AF Ono, Noriaki Ono, Wanida Kronenberg, Henry TI Cells Expressing Type 2 Collagen Are Self-renewing Multipotent Mesenchymal Progenitors during Postnatal Bone Development SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Ono, Noriaki; Ono, Wanida; Kronenberg, Henry] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA 1104 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035800105 ER PT J AU Ovejero, D Lim, Y Juppner, H Gottschalk, M Tifft, C Gafni, R Boyce, A Cowen, E Bhattacharyya, N Guthrie, L Gahl, W Golas, G Choate, K Collins, M AF Ovejero, Diana Lim, Young Jueppner, Harald Gottschalk, Michael Tifft, Cynthia Gafni, Rachel Boyce, Alison Cowen, Edward Bhattacharyya, Nisan Guthrie, Lori Gahl, William Golas, Gretchen Choate, Keith Collins, Michael TI Cutaneous Skeletal Hypophosphatemic Syndrome: A new syndrome of FGF23 excess SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Ovejero, Diana; Guthrie, Lori] Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. [Lim, Young; Choate, Keith] Yale Univ, Dept Dermatol, Sch Med, New Haven, CT 06520 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Jueppner, Harald] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Gottschalk, Michael] Rady Childrens Hosp, San Diego, CA USA. [Gottschalk, Michael] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [Tifft, Cynthia; Gahl, William; Golas, Gretchen] NHGRI, Undiagnosed Dis Program, Common Fund, Off Clin Director,NIH, Bethesda, MD USA. [Gafni, Rachel; Collins, Michael] NIH, Bethesda, MD USA. [Boyce, Alison] Childrens Natl Med Ctr, Washington, DC USA. [Cowen, Edward] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Bhattacharyya, Nisan] Natl Inst Dent & Craniofacial Res, Clin Studies Unit 2Skeletal, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA LB-SA17 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035800253 ER PT J AU Papaioannou, G Ono, N Nedelcu, S Lees, JA Kronenberg, H Kobayashi, T AF Papaioannou, Garyfallia Ono, Noriaki Nedelcu, Simona Lees, Jacqueline A. Kronenberg, Henry Kobayashi, Tatsuya TI Ras Signaling Increases the Number of Osteoprogenitor Cells leading to Increased Bone Mass SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Papaioannou, Garyfallia; Ono, Noriaki; Kronenberg, Henry; Kobayashi, Tatsuya] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nedelcu, Simona; Lees, Jacqueline A.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA LB-MO19 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035800220 ER PT J AU Park, D Lin, C Scadden, D AF Park, Dongsu Lin, Charles Scadden, David TI Sequential in vivo tracking of osteogenic stem/progenitor cells during fracture repair SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Park, Dongsu] Baylor Coll Med, Houston, TX 77030 USA. [Lin, Charles] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Scadden, David] Massachusetts Gen Hosp, Ctr Regenerat 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA LB-SU08 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035801011 ER PT J AU Pereira, R Gales, B Tumber, N Jueppner, H Salusky, I Wesseling-Perry, K AF Pereira, Renata Gales, Barbara Tumber, Navdeep Jueppner, Harald Salusky, Isidro Wesseling-Perry, Katherine TI Primary osteoblasts from CKD patients retain abnormal gene expression ex vivo SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Pereira, Renata; Gales, Barbara; Tumber, Navdeep] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Salusky, Isidro] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. [Wesseling-Perry, Katherine] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SU0221 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035805009 ER PT J AU Putman, M Derrico, N Sicilian, L Uluer, A Lapey, A Gordon, C Bouxsein, M Finkelstein, J AF Putman, Melissa Derrico, Nicholas Sicilian, Leonard Uluer, Ahmet Lapey, Allen Gordon, Catherine Bouxsein, Mary Finkelstein, Joel TI Bone Microarchitecture in Young Adults with Cystic Fibrosis: Differential Mechanisms of Fragility in Weight Bearing and Non-Weight Bearing Bone SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Putman, Melissa] Childrens Hosp, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Derrico, Nicholas] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Sicilian, Leonard; Finkelstein, Joel] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Uluer, Ahmet] Boston Childrens Hosp, Div Pulm & Resp Dis, Boston, MA USA. [Lapey, Allen] Massachusetts Gen Hosp Children, Boston, MA USA. [Gordon, Catherine] Hasbro Childrens Hosp, Providence, RI USA. [Gordon, Catherine] Brown Univ, Providence, RI 02912 USA. [Bouxsein, Mary] Beth Israel Deaconess Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA MO0430 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035802163 ER PT J AU Saini, V Fulzele, K Liu, XL Dedic, C Saito, H Hesse, E Pajevic, PD AF Saini, Vaibhav Fulzele, Keertik Liu, Xiaolong Dedic, Christopher Saito, Hiroaki Hesse, Eric Pajevic, Paola Divieti TI PTH/PTHrP Receptor Signaling in Osteocytes Differentially Regulates Skeletal Homeostasis during Adulthood and Aging SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Saini, Vaibhav; Fulzele, Keertik] Harvard Univ, Sch Med, MGH, Cambridge, MA 02138 USA. [Liu, Xiaolong; Dedic, Christopher] Harvard Univ, Sch Med, MGH, Endocrine Unit, Cambridge, MA 02138 USA. [Saito, Hiroaki; Hesse, Eric] Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany. [Pajevic, Paola Divieti] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pajevic, Paola Divieti] Harvard Univ, Sch Med, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SA0286 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035803183 ER PT J AU Sato, K Idelevich, A Rowe, G Gori, F Baron, R AF Sato, Kazusa Idelevich, Anna Rowe, Glenn Gori, Francesca Baron, Roland TI Leptin-independent Regulation of Bone Homeostasis by Delta FosB in the Ventral Hypothalamus Contrasts with its Leptin-dependent Effects on Energy and Glucose Metabolism SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Sato, Kazusa] Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA. [Idelevich, Anna] Harvard Univ, Cambridge, MA 02138 USA. [Rowe, Glenn] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Gori, Francesca] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Baron, Roland] Harvard Univ, Sch Med & Dent Med, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA MO0125 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035801161 ER PT J AU Scheller, E Cawthorn, W Learman, B Mori, H Simon, B Parlee, S Ning, XM Miller, J Gallagher, K Fazeli, P Rosen, C Horowitz, M Klibanski, A MacDougald, O AF Scheller, Erica Cawthorn, William Learman, Brian Mori, Hiroyuki Simon, Becky Parlee, Sebastian Ning, Xiaomin Miller, Joshua Gallagher, Katherine Fazeli, Pouneh Rosen, Clifford Horowitz, Mark Klibanski, Anne MacDougald, Ormond TI The Metabolic Nature of Marrow Fat: insulin signaling, CREB phosphorylation and the 'adiponectin paradox' SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Scheller, Erica] Univ Michigan, Ann Arbor, MI 48109 USA. [Cawthorn, William; Learman, Brian; Mori, Hiroyuki; Simon, Becky; Parlee, Sebastian; Ning, Xiaomin; MacDougald, Ormond] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. [Miller, Joshua] Univ Michigan, Dept Orthoped, Ann Arbor, MI 48109 USA. [Gallagher, Katherine] Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. [Fazeli, Pouneh] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fazeli, Pouneh] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Rosen, Clifford] Maine Med Ctr, Portland, ME USA. [Horowitz, Mark] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Klibanski, Anne] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SU0155 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035804221 ER PT J AU Spolidorio, LC Coimbra, LS Rossa, C Kantarci, A Van Dyke, TE Steffens, JP AF Spolidorio, Luis Carlos Coimbra, Leila Santana Rossa, Carlos, Jr. Kantarci, Alpdogan Van Dyke, Thomas E. Steffens, Joao Paulo TI Testosterone Modulates Inflammation-Induced Periodontal Bone Loss SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Coimbra, Leila Santana; Rossa, Carlos, Jr.; Steffens, Joao Paulo] State Univ Sao Paulo UNESP, Dept Physiol & Pathol, Dent Sch Araraquara, Sao Paulo, Brazil. [Kantarci, Alpdogan; Van Dyke, Thomas E.] Forsyth Inst, Dept Appl Oral Sci, Boston, MA USA. RI Spolidorio, Luis Carlos/G-1857-2012; Rossa Jr, Carlos/D-8328-2012 OI Rossa Jr, Carlos/0000-0003-1705-5481 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SA0004 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035802207 ER PT J AU Takeyama, K Nistala, H Gygi, S Boback, B Gori, F Baron, R AF Takeyama, Ken-ichi Nistala, Harikiran Gygi, Steven Boback, Bernard Gori, Francesca Baron, Roland TI Zinc finger protein 521 recruits the NuRD complex together with transglutaminases and regulates mesenchymal stem cell differentiation SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Takeyama, Ken-ichi; Nistala, Harikiran; Boback, Bernard] Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA. [Gygi, Steven] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Gori, Francesca] Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Cambridge, MA 02138 USA. [Baron, Roland] Harvard Univ, Sch Med & Dent Med, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA MO0226 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035801259 ER PT J AU Tsai, J Uihlein, A Zhu, YL Foley, K Derrico, N Lee, H Burnett-Bowie, SA Neer, R Bouxsein, M Leder, B AF Tsai, Joy Uihlein, Alexander Zhu, Yuli Foley, Katelyn Derrico, Nicholas Lee, Hang Burnett-Bowie, Sherri-Ann Neer, Robert Bouxsein, Mary Leder, Benjamin TI Comparative Effects of Teriparatide, Denosumab, and Combination Therapy on Peripheral Compartmental Bone Density and Microarchitecture: the DATA-HRpQCT Study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Tsai, Joy; Zhu, Yuli; Foley, Katelyn; Derrico, Nicholas; Lee, Hang; Burnett-Bowie, Sherri-Ann; Neer, Robert] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Uihlein, Alexander] Northwestern Mem Fac Fdn, Chicago, IL USA. [Bouxsein, Mary] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Leder, Benjamin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SA0372 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035803259 ER PT J AU Turan, S Thiele, S Brix, B Atay, Z Abali, S Bastepe, M AF Turan, Serap Thiele, Susanne Brix, Bettina Atay, Zeynep Abali, Saygin Bastepe, Murat TI Subclinical PTH resistance in a patient with a novel heterozygous GNAS mutation: G alpha s haploinsufficiency as a plausible cause. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Turan, Serap] Marmara Univ Istanbul Turkey, Istanbul, Turkey. [Thiele, Susanne; Brix, Bettina] Univ Lubeck, Div Expt Paediat Endocrinol & Diabet, Lubeck, Germany. [Atay, Zeynep; Abali, Saygin] Marmara Univ, Istanbul, Turkey. [Bastepe, Murat] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SA0122 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035803049 ER PT J AU Wang, YM Menendez, A Fong, C Bikle, D AF Wang, Yongmei Menendez, Alicia Fong, Chak Bikle, Daniel TI EphrinB2/EphB4 Mediates the Actions of IGF-I Signaling in Regulating Vascularization during Endochondral Bone Formation SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Wang, Yongmei; Menendez, Alicia; Fong, Chak] Univ Calif San Francisco, Endocrine Unit, San Francisco VA Med Ctr, San Francisco, CA USA. [Bikle, Daniel] Div Endocrinol UCSF, Endocrine Res Unit, San Francisco, CA USA. [Bikle, Daniel] VAMC, Portland, OR 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SA0156 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035803078 ER PT J AU Wein, M Lai, F Kronenberg, H AF Wein, Marc Lai, Forest Kronenberg, Henry TI Visualization of Osteoblast-Derived Trabecular and Endosteal Bone Lining Cells SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Wein, Marc; Lai, Forest; Kronenberg, Henry] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA MO0246 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035801277 ER PT J AU Yamana, K Saito, H Nagano, K Kiviranta, R Gori, F Baron, R AF Yamana, Kei Saito, Hiroaki Nagano, Kenichi Kiviranta, Riku Gori, Francesca Baron, Roland TI R-spondin 3 Is a Negative Regulator of Bone Formation SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Yamana, Kei; Saito, Hiroaki; Nagano, Kenichi; Kiviranta, Riku] Harvard Univ, Sch Med, Sch Dent Med, Cambridge, MA 02138 USA. [Gori, Francesca] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Baron, Roland] Harvard Univ, Sch Med & Dent Med, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA 1077 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035800078 ER PT J AU Yu, E Putman, M Bouxsein, M Roy, A Derrico, N Finkelstein, J AF Yu, Elaine Putman, Melissa Bouxsein, Mary Roy, Adam Derrico, Nicolas Finkelstein, Joel TI Endosteal Resorption and Worsening Cortical Porosity after Roux-en-Y Gastric Bypass Surgery SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Yu, Elaine; Roy, Adam; Derrico, Nicolas; Finkelstein, Joel] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Putman, Melissa] Childrens Hosp Boston, Massachusetts Gen Hosp, Boston, MA USA. [Bouxsein, Mary] Beth Israel Deaconess Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SU0433 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035805218 ER PT J AU Yu, V Saez, B Lotinun, S Cook, C Yusuf, R Raajimakers, M Wu, J Kronenberg, H Baron, R Scadden, D AF Yu, Vionnie Saez, Borja Lotinun, Sutada Cook, Colleen Yusuf, Rushdia Raajimakers, Marc Wu, Joy Kronenberg, Henry Baron, Roland Scadden, David TI Bone cells govern T lymphopoiesis by regulating thymic emigrants from bone marrow SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Yu, Vionnie] Harvard Univ, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Saez, Borja; Cook, Colleen; Yusuf, Rushdia; Raajimakers, Marc; Kronenberg, Henry; Scadden, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lotinun, Sutada] Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA. [Wu, Joy] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Baron, Roland] Harvard Univ, Sch Med & Dent Med, Cambridge, MA 02138 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA MO0159 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035801193 ER PT J AU Zamarioli, A Maranho, D De Paula, FJ Morse, L Battaglino, R Volpon, J Shimano, A AF Zamarioli, Ariane Maranho, Daniel De Paula, Francisco Jose Morse, Leslie Battaglino, Ricardo Volpon, Jose Shimano, Antonio TI Passive Standing and Electrical Stimulation are Eligible Therapies for Preserving and Reverting the Loss of Bone Quality in Rats with Complete Spinal Cord Injury SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Zamarioli, Ariane; Maranho, Daniel; Volpon, Jose; Shimano, Antonio] Univ Sao Paulo, BR-05508 Sao Paulo, Brazil. [De Paula, Francisco Jose] Sch Med Ribeirao Preto USP, Ribeirao Preto, Brazil. [Morse, Leslie] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Battaglino, Ricardo] Forsyth Inst, Cambridge, MA USA. RI Zamarioli, Ariane/K-7001-2012; Maranho, Daniel Augusto/C-1337-2013 OI Zamarioli, Ariane/0000-0002-7939-0528; Maranho, Daniel Augusto/0000-0002-3893-0292 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA LB-SA05 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035800241 ER PT J AU Chung, HW Fragomeni, RAS Shacham, S Kauffman, M Cusack, JC AF Chung, Hye Won Fragomeni, Roberto A. Salas Shacham, Sharon Kauffman, Michael Cusack, James C. TI Use of selective inhibition of nuclear export (SINE) using a CRM1/XPO1 antagonist to overcome resistance to CPT-11 in colon cancer in preclinical models SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO) CY JAN 24-26, 2013 CL San Francisco, CA SP Amer Soc Clin Oncol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Boston, MA USA. Karyopharm Therapeut, Newton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2013 VL 31 IS 4 SU S MA 396 PG 1 WC Oncology SC Oncology GA AE0TL UT WOS:000333679000389 ER PT J AU Corcoran, RB Ebi, H Ryan, DP Meyerhardt, JA Engelman, JA AF Corcoran, Ryan Bruce Ebi, Hiromichi Ryan, David P. Meyerhardt, Jeffrey A. Engelman, Jeffrey A. TI Relationship of EGFR-independent activation of PI3K in KRAS wild-type colorectal cancers and cetuximab resistance SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO) CY JAN 24-26, 2013 CL San Francisco, CA SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2013 VL 31 IS 4 SU S MA 385 PG 1 WC Oncology SC Oncology GA AE0TL UT WOS:000333679000378 ER PT J AU Coveler, AL Von Hoff, DD Ko, AH Whiting, NC Zhao, BT Wolpin, BA AF Coveler, Andrew L. Von Hoff, Daniel D. Ko, Andrew H. Whiting, Nancy Cherry Zhao, Baiteng Wolpin, Brian A. TI A phase I study of ASG-5ME, a novel antibody-drug conjugate, in pancreatic ductal adenocarcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO) CY JAN 24-26, 2013 CL San Francisco, CA SP Amer Soc Clin Oncol C1 Univ Washington, Seattle, WA 98195 USA. Scottsdale Healthcare TGen, Virginia G Piper Canc Ctr, Scottsdale, AZ USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Seattle Genet Inc, Bothell, WA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 4 Z9 4 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 FEB 1 PY 2013 VL 31 IS 4 SU S MA 176 PG 1 WC Oncology SC Oncology GA AE0TL UT WOS:000333679000175 ER PT J AU Drakaki, A Hatziapostolou, M Polytarchou, C Iliopoulos, D AF Drakaki, Alexandra Hatziapostolou, Maria Polytarchou, Christos Iliopoulos, Dimitrios TI The role of microRNA-9 in hepatocellular oncogenesis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO) CY JAN 24-26, 2013 CL San Francisco, CA SP Amer Soc Clin Oncol C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2013 VL 31 IS 4 SU S MA 168 PG 1 WC Oncology SC Oncology GA AE0TL UT WOS:000333679000168 ER PT J AU Fuchs, CS Tomasek, J Cho, JY Dumitru, F Passalacqua, R Goswami, C Safran, H dos Santos, LV Aprile, G Ferry, DR Melichar, B Tehfe, M Topuzov, E Tabemero, J Zalcberg, JR Chau, I Koshiji, M Hsu, YZ Schwartz, JD Ajani, JA AF Fuchs, Charles S. Tomasek, Jiri Cho, Jae Yong Dumitru, Filip Passalacqua, Rodolfo Goswami, Chanchal Safran, Howard dos Santos, Lucas Vieira Aprile, Giuseppe Ferry, David R. Melichar, Bohuslav Tehfe, Mustapha Topuzov, Eldar Tabemero, Josep Zalcberg, John Raymond Chau, Ian Koshiji, Minori Hsu, Yanzhi Schwartz, Jonathan D. Ajani, Jaffer A. TI REGARD phase III, randon ed, double-blinded trial of mum ib and best supportive care (BSC) versus placebo and BSC in the Ireattneiti of metasta lie gastric or gastroesophageal junction (GEJ) adenocarcino u following disease progression on first-line platinum- and/or fluorop., midine-containing combination therapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO) CY JAN 24-26, 2013 CL San Francisco, CA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Masaryk Univ, Fac Med, Masaryk Mem Canc Inst, Brno, Czech Republic. Gangnam Severance Hosp, Seoul, South Korea. Spitalul Judetean Urgenta Constantin Opris, Baia Mare, Romania. Ist Ospitalieri Cremona, Cremona, Italy. BP Poddar Hosp & Med Res Ltd, Kolkata, W Bengal, India. Brown Univ, Sch Med, Providence, RI 02912 USA. Barretos Canc Hosp, Barretos, Brazil. Univ & Gen Hosp, Dept Oncol, Udine, Italy. New Cross Hosp, Wolverhampton, England. Fak Nemocnice Olomouc, Onkol Klin, Olomouc, Czech Republic. CHUM, Notre Dame Hosp, Montreal, PQ, Canada. Vail dHebron Univ Hosp, Vail dHebron Inst Oncol, Barcelona, Spain. Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. Univ Melbourne, Melbourne, Vic, Australia. Royal Marsden Hosp, Sutton, Surrey, England. ImClone Syst, Bridgewater, NJ USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RI Topuzov, Eldar/O-9523-2015 OI Topuzov, Eldar/0000-0002-1700-1128 NR 0 TC 2 Z9 3 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2013 VL 31 IS 4 SU S MA LBA5 PG 1 WC Oncology SC Oncology GA AE0TL UT WOS:000333679000004 ER PT J AU Goyal, L Wadlow, RC Blaszkowsky, LS Wolpin, BM Vasudev, E Sheehan, S Knowles, M Zhu, AX AF Goyal, Lipika Wadlow, Raymond Couric Blaszkowsky, Lawrence Scott Wolpin, Brian M. Vasudev, Eamala Sheehan, Susan Knowles, Michelle Zhu, Andrew X. TI A phase I study of ganetespib in advanced hepatocellular carcinoma (HCC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO) CY JAN 24-26, 2013 CL San Francisco, CA SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Virginia Canc Specialists, Fairfax, VA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2013 VL 31 IS 4 SU S MA 259 PG 1 WC Oncology SC Oncology GA AE0TL UT WOS:000333679000255 ER PT J AU Goyal, L Supko, JG Berlin, J Blaszkowsky, LS Carpenter, A Heuman, DM Stuart, KE Cotler, S Senzer, NN Berg, CL Clark, JW Hezel, AF Ryan, DP Zhu, AX AF Goyal, Lipika Supko, Jeffrey G. Berlin, Jordan Blaszkowsky, Lawrence Scott Carpenter, Amanda Heuman, Douglas M. Stuart, Keith E. Cotler, Scott Senzer, Neil N. Berg, Carl L. Clark, Jeffrey W. Hezel, Aram F. Ryan, David P. Zhu, Andrew X. TI A phase I study of DENSPM (N1, N11-diethylnorspermine) in patients with advanced hepatocellular carcinoma (HCC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO) CY JAN 24-26, 2013 CL San Francisco, CA SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Virginia Commonwealth Univ, Med Ctr, Div Hepatol, Richmond, VA USA. Tufts Univ, Sch Med, Lahey Clin Med Ctr, Burlington, MA USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Mary Crowley Canc Res Ctr, Dallas, TX USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2013 VL 31 IS 4 SU S MA 260 PG 1 WC Oncology SC Oncology GA AE0TL UT WOS:000333679000256 ER PT J AU Mahadevan, D Shapiro, G Kurtin, SE Cleary, JM Lyons, JF Rodriguez-Lopez, A Yule, M Ahanonu, V Choy, GS Noursalehi, M Azab, M AF Mahadevan, Daruka Shapiro, Geoffrey Kurtin, Sandra E. Cleary, James M. Lyons, John F. Rodriguez-Lopez, Ana Yule, Murray Ahanonu, Valerie Choy, Gavin S. Noursalehi, Mojtaba Azab, Mohammad TI Activity of AT13387, a novel, non-ansamycin inhibitor of heat shock protein 90, against gastrointestinal stromal tumors (GIST) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO) CY JAN 24-26, 2013 CL San Francisco, CA SP Amer Soc Clin Oncol C1 Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Astex Pharmaceut, Cambridge, England. Astex Pharmaceut, Dublin, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2013 VL 31 IS 4 SU S MA 105 PG 1 WC Oncology SC Oncology GA AE0TL UT WOS:000333679000107 ER PT J AU Miksad, RA Goyal, R Wei, J Shaikh, R Halpern, EF Gazelle, GS AF Miksad, Rebecca A. Goyal, Rohit Wei, Jesse Shaikh, Raja Halpern, Elkan F. Gazelle, G. Scott TI Hepatocellular cancer tumor growth and metabolic risk factors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO) CY JAN 24-26, 2013 CL San Francisco, CA SP Amer Soc Clin Oncol C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Childrens Hosp Boston, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2013 VL 31 IS 4 SU S MA 162 PG 1 WC Oncology SC Oncology GA AE0TL UT WOS:000333679000162 ER PT J AU Patel, SA Chen, YH Hornick, JL Catalano, PJ Nowak, J Zukerberg, LR Hong, TS Mamon, HJ AF Patel, Sagar A. Chen, Yu-Hui Hornick, Jason L. Catalano, Paul J. Nowak, Jonathan Zukerberg, Lawrence R. Hong, Theodore S. Mamon, Harvey J. TI Prognostic markers of time to local recurrence and overall survival in early-stage rectal cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO) CY JAN 24-26, 2013 CL San Francisco, CA SP Amer Soc Clin Oncol C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2013 VL 31 IS 4 SU S MA 473 PG 1 WC Oncology SC Oncology GA AE0TL UT WOS:000333679000464 ER PT J AU Russo, AL Ryan, DP Borger, DR Wo, JYL Szymonifka, J Kwak, EL Blaszkowsky, LS Clark, JW Allen, JN Zhu, AX Berger, DL Cusack, JC Haigis, KM Hong, TS AF Russo, Andrea Lyn Ryan, David P. Borger, Darrell R. Wo, Jennifer Yon-Li Szymonifka, Jackie Kwak, Eunice Lee Blaszkowsky, Lawrence Scott Clark, Jeffrey W. Allen, Jill N. Zhu, Andrew X. Berger, David L. Cusack, James C. Haigis, Kevin M. Hong, Theodore S. TI Mutational analysis of locally advanced rectal cancer and response to neoadjuvant chemoradiation SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO) CY JAN 24-26, 2013 CL San Francisco, CA SP Amer Soc Clin Oncol C1 Harvard Radiat Oncol Program, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Oncol, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Massachusetts Gen Hosp, Div Gen Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Boston, MA USA. Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2013 VL 31 IS 4 SU S MA 449 PG 1 WC Oncology SC Oncology GA AE0TL UT WOS:000333679000440 ER PT J AU Ryan, DP Reddy, SG Bahary, N Uronis, HE Sigal, D Cohn, AL Schelman, WR Stephenson, J Eng, C Borad, MJ AF Ryan, David P. Reddy, Shantan G. Bahary, Nathan Uronis, Hope Elizabeth Sigal, Darren Cohn, Allen Lee Schelman, William R. Stephenson, Joe Eng, Clarence Borad, Mitesh J. TI TH-302 plus gemcitabine (G plus T) versus gemcitabine (G) in patients with previously untreated advanced pancreatic cancer (PAC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO) CY JAN 24-26, 2013 CL San Francisco, CA SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Louisiana State Univ, Hlth Sci Ctr Shreveport, Shreveport, LA 71105 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Duke Univ, Med Ctr, Durham, NC USA. Scripps Clin, San Diego, CA USA. Rocky Mt Canc Ctr LLP, Denver, CO USA. Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. Inst Translat Oncol Res, Greenville, SC USA. Threshold Pharmaceut, Redwood City, CA USA. Mayo Clin, Scottsdale, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2013 VL 31 IS 4 SU S MA 325 PG 1 WC Oncology SC Oncology GA AE0TL UT WOS:000333679000320 ER PT J AU Schoenfeld, JD Wo, JYL Mamon, HJ Kwak, EL Mullen, JT Enzinger, PC Blaszkowsky, LS Ryan, DP Hong, TS AF Schoenfeld, Jonathan D. Wo, Jennifer Yon-Li Mamon, Harvey J. Kwak, Eunice Lee Mullen, John Thomas Enzinger, Peter C. Blaszkowsky, Lawrence Scott Ryan, David P. Hong, Theodore S. TI The impact of positive margins on outcome among patients with gastric cancer treated with radiation SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO) CY JAN 24-26, 2013 CL San Francisco, CA SP Amer Soc Clin Oncol C1 Harvard Radiat Oncol Program, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2013 VL 31 IS 4 SU S MA 81 PG 1 WC Oncology SC Oncology GA AE0TL UT WOS:000333679000083 ER PT J AU Sadik, C Kim, N Luster, A AF Sadik, C. Kim, N. Luster, A. TI Neutrophils orchestrate their own recruitment in murine arthritis through C5aR and Fc gamma R signaling SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract C1 [Sadik, C.; Kim, N.; Luster, A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Sadik, C.] UKSH, Klin Dermatol Allergol & Venerol, D-23538 Lubeck, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0028-1298 EI 1432-1912 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD FEB PY 2013 VL 386 SU 1 MA 280 BP S69 EP S69 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V40KB UT WOS:000209476400281 ER PT J AU Fazeli, PK Mendes, N Russell, M Herzog, DB Klibanski, A Misra, M AF Fazeli, Pouneh K. Mendes, Nara Russell, Melissa Herzog, David B. Klibanski, Anne Misra, Madhusmita TI Bone Density Characteristics and Major Depressive Disorder in Adolescents SO PSYCHOSOMATIC MEDICINE LA English DT Article DE bone mineral density; adolescents; depression ID BORDERLINE PERSONALITY-DISORDER; X-RAY ABSORPTIOMETRY; MINERAL DENSITY; RISK-FACTOR; FOLLOW-UP; WOMEN; ASSOCIATION; CHILDREN; OBESITY; GIRLS AB Objective: Major depressive disorder (MDD) is common during adolescence, a period characterized by rapid bone mineral accrual. MDD has recently been associated with lower bone mineral density (BMD) in adults. Our objective was to determine whether MDD is associated with BMD, bone turnover markers, vitamin D, and gonadal steroids in adolescents. Methods: Sixty-five adolescents 12 to 18 years of age (32 boys: 16 with MDD and 16 controls; 33 girls: 17 with MDD and 16 controls) were included in a cross-sectional study. BMD and body composition were obtained by dual-energy x-ray absorptiometry. Estradiol, testosterone, 25-hydroxy vitamin D levels, N-terminal propeptide of Type 1 procollagen (a marker of bone formation), and Type I collagen C-telopeptide (a marker of bone resorption) were measured. Results: Boys with MDD had a significantly lower BMD at the hip (mean [standard deviation] = 0.99 [0.17] g/cm(2) versus 1.04 [0.18] g/cm(2), body mass index [BMI] adjusted, p = .005) and femoral neck (0.92 [0.17] g/cm(2) versus 0.94 [0.17] g/cm(2); BMI adjusted, p = .024) compared with healthy controls after adjusting for BMI. This significant finding was maintained after also adjusting for lean mass and bone age (hip: p = .007; femoral neck: p = .020). In girls, there were no significant differences in BMD between the girls with MDD and the controls after adjusting for BMI (p > .17). Conclusions: Male adolescents with MDD have a significantly lower BMD as compared with healthy controls after adjusting for body mass and maturity. This association is not observed in girls. C1 [Fazeli, Pouneh K.; Mendes, Nara; Russell, Melissa; Klibanski, Anne; Misra, Madhusmita] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unit, Boston, MA USA. [Herzog, David B.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Misra, Madhusmita] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Endocrine Unit, Boston, MA 02115 USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457,55 Fruit St, Boston, MA 02114 USA. EM mmisra@partners.org RI Mendes Estella, Nara/A-1469-2015 FU Claflin Award, Harvard Clinical and Translational Science Center [UL1 RR02575803, M01RR01066]; National Center for Research Resources; National Institutes of Health [K23 DK094820] FX The project was supported by the Claflin Award (principal investigator: M. Misra), Grant Nos. UL1 RR02575803 and M01RR01066, Harvard Clinical and Translational Science Center, the National Center for Research Resources, and National Institutes of Health Grant K23 DK094820 (P.K.F.). 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. The authors have no conflicts of interest to disclose. The funding sources had no role in study design; the collection, analysis, or interpretation of the data; the writing of the report; or the decision to submit the manuscript for publication. NR 44 TC 5 Z9 5 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD FEB-MAR PY 2013 VL 75 IS 2 BP 117 EP 123 DI 10.1097/PSY.0b013e3182821e91 PG 7 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 300LW UT WOS:000330466400003 PM 23362498 ER PT J AU Ye, S Park, BH Song, KJ Kim, JR Jang, KY Park, HS Bae, JS Brochmann, EJ Wang, JC Murray, SS Lee, KB AF Ye, Shuai Park, Byung-Hyun Song, Kyung-Jin Kim, Jung-Ryul Jang, Kyu-Yun Park, Ho-Sung Bae, Jun Sang Brochmann, Elsa J. Wang, Jeffrey C. Murray, Samuel S. Lee, Kwang-Bok TI In Vivo Inhibition of Bone Morphogenetic Protein-2 on Breast Cancer Cell Growth SO SPINE LA English DT Article DE BMP2; breast cancer; cell line MDA-MB-231; cell cycle ID PROSTATE-CANCER; EXPRESSION; TUMORIGENICITY; ENHANCEMENT; ANTAGONISTS; MATRIGEL; PATHWAY; LESIONS; KINASE; BMP-2 AB Study Design. In vitro and in vivo study. Objective. To evaluate the role of recombinant human bone morphogenetic protein-2 (rhBMP2) on breast cancer cell (MDA-MB-231 cells) growth. Summary of Background Data. Bone morphogenetic proteins (BMPs) are expressed in a variety of human carcinoma cell lines and are known to promote tumor invasion and metastasis. However, their roles in tumor progression have not been fully clarified. In addition, there is no in vivo study regarding the inhibitory effect of BMP2 on breast cancer cell proliferation. Method. Cell proliferation was determined by BrdU incorporation assay and flow cytometry. BMP2 signal transduction pathways were estimated on Western blot. Fifteen animals were divided into 2 groups; 1 (control = 5) was breast cancer cells alone, while the other (experiment = 5) was rhBMP2 + breast cancer cells. Cancer cells were injected into 2 sites (subcutaneous and femur) of nude mice with or without BMP2. Tumor size was determined by direct measurements for subcutaneous tumor formation and by femur radiographs. Histological and immunohistochemical analyses were performed. Results. RhBMP2 inhibited the proliferation of MDA-MB-231 cells in vitro. Inhibition was associated with changes in both the Smad and Wnt signaling pathways and was ultimately mediated through effects on various cell cycle proteins. Furthermore, rhBMP2 inhibited the growth of MDA-MB-231 cells injected both subcutaneously and intrafemorally. Conclusion. In this model using human breast adenocarcinoma cell line, rhBMP2 has no stimulatory effect of tumor growth. Therefore, we can provide the basic science data to support the utilization in the management of patients with spine tumor in the future. C1 [Ye, Shuai; Song, Kyung-Jin; Kim, Jung-Ryul; Lee, Kwang-Bok] Chonbuk Natl Univ, Sch Med, Dept Orthopaed Surg, Jeonju 561756, Jeonbuk, South Korea. [Park, Byung-Hyun] Chonbuk Natl Univ, Sch Med, Dept Biochem, Jeonju 561756, Jeonbuk, South Korea. [Jang, Kyu-Yun; Park, Ho-Sung; Bae, Jun Sang] Chonbuk Natl Univ, Sch Med, Dept Pathol, Jeonju 561756, Jeonbuk, South Korea. [Lee, Kwang-Bok] Chonbuk Natl Univ, Sch Med, Res Inst Clin Med, Biomed Res Inst,Chonbuk Natl Univ Hosp, Jeonju 561756, Jeonbuk, South Korea. [Wang, Jeffrey C.] Univ Calif Los Angeles, Dept Orthopaed Surg, Los Angeles, CA USA. [Brochmann, Elsa J.; Murray, Samuel S.] VA Greater Los Angeles, Geriatr Res Educ & Clin Ctr, Hlth Care Syst, Sepulveda, CA USA. [Brochmann, Elsa J.; Murray, Samuel S.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Wang, Jeffrey C.; Murray, Samuel S.] Univ Calif Los Angeles, Biomed Engn Interdept Program, Los Angeles, CA USA. RP Lee, KB (reprint author), Chonbuk Natl Univ, Sch Med, Dept Orthopaed Surg, 567 Baekje Daero, Jeonju 561756, Jeonbuk, South Korea. EM osdr2815@naver.com FU Biomedical Research Institute, Chonbuk National University Hospital FX This article was supported by the Biomedical Research Institute, Chonbuk National University Hospital. NR 21 TC 8 Z9 10 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 EI 1528-1159 J9 SPINE JI SPINE PD FEB 1 PY 2013 VL 38 IS 3 BP E143 EP E150 DI 10.1097/BRS.0b013e31827db4c6 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA AD1WD UT WOS:000333023500004 PM 23169070 ER PT J AU Ali, SF Ruff, IM Feske, SK Rost, NS Cohen, AB Viswanathan, A Schwamm, LH AF Ali, Syed F. Ruff, Ilana M. Feske, Steven K. Rost, Natalia S. Cohen, Adam B. Viswanathan, Anand Schwamm, Lee H. TI Predictors of IV tPA Use among Acute Ischemic Stroke patients presenting to a Regional Telestroke Network: The Partners Telestroke Center Experience SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Thrombolysis; Healthcare delivery systems C1 [Ali, Syed F.; Ruff, Ilana M.; Rost, Natalia S.; Cohen, Adam B.; Viswanathan, Anand; Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Feske, Steven K.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200407 ER PT J AU Arnold, CW Love, A El-Saden, S Liebeskind, DS Andrada, L Saver, J Bui, AA AF Arnold, Corey W. Love, Alexa El-Saden, Suzie Liebeskind, David S. Andrada, Lewellyn Saver, Jeffery Bui, Alex A. TI A Bayesian Network for Reasoning on Acute Ischemic Stroke Intervention SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Computer C1 [Arnold, Corey W.; Love, Alexa; Liebeskind, David S.; Andrada, Lewellyn; Saver, Jeffery; Bui, Alex A.] Univ Calif Los Angeles, Los Angeles, CA USA. [El-Saden, Suzie] VA Greater Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201057 ER PT J AU Atochin, DN Schepetkin, IA Swanson, H Kirpotina, LN Patel, NB Quinn, MT Huang, PL AF Atochin, Dmitriy N. Schepetkin, Igor A. Swanson, Helen Kirpotina, Lilia N. Patel, Nikitaben B. Quinn, Mark T. Huang, Paul L. TI The Novel C-Jun N-terminal Kinase Inhibitor IQ-1S Protects Against Cerebral Ischemia-reperfusion Injury In Mice SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Research; Stroke; Ischemia reperfusion; Pharmacology; Research C1 [Atochin, Dmitriy N.; Swanson, Helen; Huang, Paul L.] Massachusetts Gen Hosp, Charlestown, MA USA. [Schepetkin, Igor A.; Kirpotina, Lilia N.; Patel, Nikitaben B.; Quinn, Mark T.] Montana State Univ, Bozeman, MT 59717 USA. RI Atochin, Dmitriy/Q-3150-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201475 ER PT J AU Auriel, E Martinez-Ramirez, S Gurol, ME Schwab, K Edlow, B Boulouis, G Dumas, A Greenberg, SM Viswanathan, A AF Auriel, Eitan Martinez-Ramirez, Sergi Gurol, Mahmut Edip Schwab, Kristin Edlow, Brian Boulouis, Gregoire Dumas, Andrew Greenberg, Steven M. Viswanathan, Anand TI Incidental Diffusion-weighted Imaging Lesions In Patients With Cognitive Decline SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Magnetic resonance imaging; Vascular disease; Infarction C1 [Auriel, Eitan; Martinez-Ramirez, Sergi; Gurol, Mahmut Edip; Schwab, Kristin; Edlow, Brian; Boulouis, Gregoire; Dumas, Andrew; Greenberg, Steven M.; Viswanathan, Anand] Massachusetts Gen Hosp, J Philip Kistler Stroke Rsch Cntr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201231 ER PT J AU Avery, R Caceres, JA Park, KY Lorenzano, S Neto, OP Siket, M Ay, I Buonanno, FS Bhat, R Kapetanovic, E Yastas, S Furie, KL Ay, H AF Avery, Ross Caceres, Juan A. Park, Kwang Yeol Lorenzano, Svetlana Neto, Octavio Pontes Siket, Matthew Ay, Ilknur Buonanno, Ferdinando S. Bhat, Ram Kapetanovic, Ernest Yastas, Samir Furie, Karen L. Ay, Hakan TI A New Biomarker for Diagnosis of Ischemic Stroke: Plasma Glycogen Phosphorylase-BB SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Biomarkers C1 [Avery, Ross; Caceres, Juan A.; Park, Kwang Yeol; Lorenzano, Svetlana; Neto, Octavio Pontes; Siket, Matthew; Ay, Ilknur; Buonanno, Ferdinando S.; Furie, Karen L.; Ay, Hakan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bhat, Ram] MRL Millenium Rsch Labs, Woburn, MA USA. [Kapetanovic, Ernest; Yastas, Samir] Diagen SE, Luxemburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200030 ER PT J AU Bettger, JP Magdon-Ismail, Z Hedeman, R Sicklick, A Schwamm, L Stein, J AF Bettger, Janet Prvu Magdon-Ismail, Zainab Hedeman, Robin Sicklick, Alyse Schwamm, Lee Stein, Joel TI Predictive Validity of Barthel Index Compared to NIHSS for Discharge Destination Following an Acute Stroke Hospitalization SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Rehabilitation C1 [Bettger, Janet Prvu] Duke Univ, Durham, NC USA. [Magdon-Ismail, Zainab] Amer Heart Assoc, Albany, NY USA. [Hedeman, Robin] Kessler Inst Rehabil, W Orange, NJ USA. [Sicklick, Alyse] Gaylord Specialty Healthcare, Wallingford, CT USA. [Schwamm, Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stein, Joel] Columbia Univ, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200119 ER PT J AU Bonaca, MP Alberts, MJ Mohr, JP Ameriso, SF Hankey, GJ Murphy, SA Scirica, BM Braunwald, E Morrow, DA AF Bonaca, Marc P. Alberts, Mark J. Mohr, Jay P. Ameriso, Sebastian F. Hankey, Graeme J. Murphy, Sabina A. Scirica, Benjamin M. Braunwald, Euegene Morrow, David A. TI Outcomes after Intracranial Hemorrhage in Patients with Atherosclerotic Vascular Disease: Observations from the TRA 2 degrees P-TIMI 50 Trial SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Antiplatelet drugs; Central nervous system; Stroke; Thrombin inhibitors C1 [Bonaca, Marc P.; Scirica, Benjamin M.; Braunwald, Euegene; Morrow, David A.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Alberts, Mark J.] Northwestern Univ, Feinberg Sch Med, Stroke Program, Chicago, IL 60611 USA. [Mohr, Jay P.] Columbia Univ, Neurol Inst New York, New York, NY USA. [Ameriso, Sebastian F.] FLENI, Inst Neurol Rsch, Buenos Aires, DF, Argentina. [Hankey, Graeme J.] Royal Perth Hosp, Dept Neurol, Stroke Unit, Perth, WA 6001, Australia. [Murphy, Sabina A.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. RI Hankey, Graeme /H-4968-2014 OI Hankey, Graeme /0000-0002-6044-7328 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201526 ER PT J AU Bonaca, MP Mohr, JP Alberts, MJ Ameriso, SF Hankey, GJ Murphy, SA Scirica, BM Braunwald, E Morrow, DA AF Bonaca, Marc P. Mohr, Jay P. Alberts, Mark J. Ameriso, Sebastian F. Hankey, Graeme J. Murphy, Sabina A. Scirica, Benjamin M. Braunwald, Euegene Morrow, David A. TI Predictors of Intracranial Hemorrhage in Patients with Atherosclerotic Vascular Disease: Observations from the TRA 2 degrees P-TIMI 50 Trial SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Antiplatelet drugs; Stroke C1 [Bonaca, Marc P.; Murphy, Sabina A.; Scirica, Benjamin M.; Braunwald, Euegene; Morrow, David A.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Mohr, Jay P.] Columbia Univ, Neurol Inst New York, New York, NY USA. [Alberts, Mark J.] Northwestern Univ, Feinberg Sch Med, Stroke Program, Chicago, IL 60611 USA. [Ameriso, Sebastian F.] FLENI, Inst Neurol Rsch, Buenos Aires, DF, Argentina. [Hankey, Graeme J.] Royal Perth Hosp, Stroke Unit, Dept Neurol, Perth, WA 6001, Australia. RI Hankey, Graeme /H-4968-2014 OI Hankey, Graeme /0000-0002-6044-7328 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200619 ER PT J AU Bonaca, MP Ameriso, SF Alberts, MJ Mohr, JP Hankey, GJ Murphy, SA Scirica, BM Braunwald, E Morrow, DA AF Bonaca, Marc P. Ameriso, Sebastian F. Alberts, Mark J. Mohr, Jay P. Hankey, Graeme J. Murphy, Sabina A. Scirica, Benjamin M. Braunwald, Euegene Morrow, David A. TI Predictors of Ischemic Stroke in Patients with Atherosclerotic Vascular Disease: Observations from the TRA 2 degrees P-TIMI 50 Trial SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Coronary artery disease; Cerebrovascular disorders C1 [Bonaca, Marc P.; Murphy, Sabina A.; Scirica, Benjamin M.; Braunwald, Euegene; Morrow, David A.] Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, Boston, MA 02115 USA. [Ameriso, Sebastian F.] FLENI, Inst Neurol Rsch, Buenos Aires, DF, Argentina. [Alberts, Mark J.] Northwestern Univ, Feinberg Sch Med, Stroke Program, Chicago, IL 60611 USA. [Mohr, Jay P.] Columbia Univ, Neurol Inst New York, New York, NY USA. [Hankey, Graeme J.] Royal Perth Hosp, Dept Neurol, Stroke Unit, Perth, WA 6001, Australia. RI Hankey, Graeme /H-4968-2014 OI Hankey, Graeme /0000-0002-6044-7328 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S MA TP121 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200453 ER PT J AU Brouwers, HB Raffeld, MR Falcone, GJ Ayres, AM Schwab, K Romero, JM Viswanathan, A Greenberg, SM Ogilvy, CS Goldstein, JN Rosand, J AF Brouwers, H. B. Raffeld, Miriam R. Falcone, Guido J. Ayres, Alison M. Schwab, Kristin Romero, Javier M. Viswanathan, Anand Greenberg, Steven M. Ogilvy, Christopher S. Goldstein, Joshua N. Rosand, Jonathan TI CT Angiography Spot Sign Predicts Perioperative Bleeding in Primary Intracerebral Hemorrhage SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Surgery; CT angiography; Stroke C1 [Brouwers, H. B.; Raffeld, Miriam R.; Falcone, Guido J.; Ayres, Alison M.; Schwab, Kristin; Romero, Javier M.; Viswanathan, Anand; Greenberg, Steven M.; Ogilvy, Christopher S.; Goldstein, Joshua N.; Rosand, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RI Goldstein, Joshua/H-8953-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201510 ER PT J AU Brouwers, HB Chang, YC Falcone, GJ Ayres, AM McNamara, KA Vashkevich, A Battey, TW Valant, V Schwab, K Rost, NS Romero, JM Viswanathan, A Greenberg, SM Rosand, J Goldstein, JN AF Brouwers, H. B. Chang, Yuchiao Falcone, Guido J. Ayres, Alison M. McNamara, Kristen A. Vashkevich, Anastasia Battey, Thomas W. Valant, Valerie Schwab, Kristin Rost, Natalia S. Romero, Javier M. Viswanathan, Anand Greenberg, Steven M. Rosand, Jonathan Goldstein, Joshua N. TI A Prediction Score for Hematoma Expansion Following Acute Intracerebral Hemorrhage SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; CT angiography; Anticoagulation; Risk factors; Intervention C1 [Brouwers, H. B.; Chang, Yuchiao; Falcone, Guido J.; Ayres, Alison M.; McNamara, Kristen A.; Vashkevich, Anastasia; Battey, Thomas W.; Valant, Valerie; Schwab, Kristin; Rost, Natalia S.; Romero, Javier M.; Viswanathan, Anand; Greenberg, Steven M.; Rosand, Jonathan; Goldstein, Joshua N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RI Goldstein, Joshua/H-8953-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200306 ER EF