FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Wang, ZX Liu, Y Hu, M Pan, XC Shi, J Chen, F He, KB Koutrakis, P Christiani, DC AF Wang, Zhaoxi Liu, Yang Hu, Mu Pan, Xiaochuan Shi, Jing Chen, Feng He, Kebin Koutrakis, Petros Christiani, David C. TI Acute health impacts of airborne particles estimated from satellite remote sensing SO ENVIRONMENT INTERNATIONAL LA English DT Article DE Absolute humidity; Aerosol optical depth; Environmental health; Particulate matter; Satellite remote sensing ID PARTICULATE AIR-POLLUTION; AEROSOL OPTICAL DEPTH; GROUND-LEVEL PM2.5; EASTERN UNITED-STATES; MYOCARDIAL-INFARCTION; HOSPITAL ADMISSIONS; SPATIAL-ANALYSIS; HEART-DISEASE; MORTALITY; QUALITY AB Satellite-based remote sensing provides a unique opportunity to monitor air quality from space at global, continental, national and regional scales. Most current research focused on developing empirical models using ground measurements of the ambient particulate. However, the application of satellite-based exposure assessment in environmental health is still limited, especially for acute effects, because the development of satellite PM2.5 model depends on the availability of ground measurements. We tested the hypothesis that MODIS AOD (aerosol optical depth) exposure estimates, obtained from NASA satellites, are directly associated with daily health outcomes. Three independent healthcare databases were used: unscheduled outpatient visits, hospital admissions, and mortality collected in Beijing metropolitan area, China during 2006. We use generalized linear models to compare the short-term effects of air pollution assessed by ground monitoring (PM10) with adjustment of absolute humidity (AH) and AH-calibrated AOD. Across all databases we found that both AH-calibrated AOD and PM10 (adjusted by AH) were consistently associated with elevated daily events on the current day and/or lag days for cardiovascular diseases, ischemic heart diseases, and COPD. The relative risks estimated by AH-calibrated AOD and PM10 (adjusted by AH) were similar. Additionally, compared to ground PM10, we found that AH-calibrated AOD had narrower confidence intervals for all models and was more robust in estimating the current day and lag day effects. Our preliminary findings suggested that, with proper adjustment of meteorological factors, satellite AOD can be used directly to estimate the acute health impacts of ambient particles without prior calibrating to the sparse ground monitoring networks. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Wang, Zhaoxi; Shi, Jing; Koutrakis, Petros; Christiani, David C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Sch Publ Hlth, Boston, MA 02115 USA. [Liu, Yang] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Hu, Mu; Pan, Xiaochuan] Peking Univ, Hlth Sci Ctr, Beijing 100191, Peoples R China. [Chen, Feng] Nanjing Med Univ, Sch Publ Hlth, Nanjing 210029, Jiangsu, Peoples R China. [He, Kebin] Tsinghua Univ, Dept Environm Engn & Sci, Beijing 100084, Peoples R China. RP Wang, ZX (reprint author), 665 Huntington Ave,I-1406C, Boston, MA 02115 USA. EM mikewang@hsph.harvard.edu FU National Institute of Environmental Health Sciences [ES000002]; Harvard University Center for the Environment; Harvard-NIEHS Center for Environmental Health FX This work was supported by grant ES000002 from National Institute of Environmental Health Sciences, by Research Project Awards from Harvard University Center for the Environment, and by pilot project from Harvard-NIEHS Center for Environmental Health. NR 44 TC 14 Z9 14 U1 9 U2 79 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0160-4120 EI 1873-6750 J9 ENVIRON INT JI Environ. Int. PD JAN PY 2013 VL 51 BP 150 EP 159 DI 10.1016/j.envint.2012.10.011 PG 10 WC Environmental Sciences SC Environmental Sciences & Ecology GA 085ME UT WOS:000314618100015 PM 23220016 ER PT J AU Weyman, AE AF Weyman, Arthur E. TI More May Not Always Be Better SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE contrast echocardiography; coronary artery disease; coronary flow reserve; dipyridamole; myocardial perfusion; prognosis; stress echocardiography ID STRESS; ECHOCARDIOGRAPHY; DOBUTAMINE C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Weyman, AE (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St,VBK 508, Boston, MA 02114 USA. EM aweyman@partners.org NR 8 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD JAN PY 2013 VL 6 IS 1 BP 13 EP 15 DI 10.1016/j.jcmg.2012.10.008 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 084ZY UT WOS:000314581600002 PM 23219413 ER PT J AU Ahmed, W Schlett, CL Uthamalingam, S Truong, QA Koenig, W Rogers, IS Blankstein, R Nagurney, JT Tawakol, A Januzzi, JL Hoffmann, U AF Ahmed, Waleed Schlett, Christopher L. Uthamalingam, Shanmugam Truong, Quynh A. Koenig, Wolfgang Rogers, Ian S. Blankstein, Ron Nagurney, John T. Tawakol, Ahmed Januzzi, James L. Hoffmann, Udo TI Single Resting hsTnT Level Predicts Abnormal Myocardial Stress Test in Acute Chest Pain Patients With Normal Initial Standard Troponin SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE coronary computed tomographic angiography; high-sensitivity troponin T; myocardial perfusion imaging; single-photon emission computed tomography ID ACUTE CORONARY SYNDROMES; COMPUTED-TOMOGRAPHY; ANGIOGRAPHY CHARACTERISTICS; ATHEROSCLEROTIC PLAQUE; CARDIOVASCULAR RISK; PROGNOSTIC VALUE; SENSITIVE ASSAY; EARLY-DIAGNOSIS; ARTERY-DISEASE; HEART-FAILURE AB OBJECTIVES The goal of this study was to determine the ability of a single, resting high-sensitivity troponin T (hsTnT) measurement to predict abnormal myocardial perfusion imaging (MPI) in patients presenting with acute chest pain to the emergency department (ED). BACKGROUND HsTnT assays precisely detect very low levels of troponin T, which may be a surrogate for the presence and extent of myocardial ischemia. METHODS We included all patients from the ROMICAT I (Rule Out Myocardial Infarction Using Computer Assisted Tomography) trial, an observational cohort study, who underwent both single-photon emission computed tomography (SPECT)-MPI stress testing and 64-slice computed tomography angiography (CTA) and in whom hsTnT measurements were available. We assessed the discriminatory value of hsTnT for abnormal SPECT-MPI and the association of reversible myocardial ischemia by SPECT-MPI and the extent of coronary atherosclerosis by CTA to hsTnT levels. RESULTS Of the 138 patients (mean age 54 +/- 11 years, 46% male), 19 (13.7%) had abnormal SPECT-MPI. Median hsTnT levels were significantly different between patients with normal and abnormal SPECT-MPI (9.41 pg/ml [interquartile range (IQR): 5.73 to 19.20 pg/ml] vs. 4.89 pg/ml [IQR: 2.34 to 7.68 pg/ml], p = 0.001). Sensitivity of 80% and 90% to detect abnormal SPECT-MPI was reached at hsTnT levels as low as 5.73 and 4.26 pg/ml, respectively. Corresponding specificity was 62% and 46%, and negative predictive value was 96% and 96%, respectively. HsTnT levels had good discriminatory ability for prediction of abnormal SPECT-MPI (area under the curve: 0.739, 95% confidence interval: 0.609 to 0.868). Both reversible myocardial ischemia and the extent of coronary atherosclerosis (combined model r(2) = 0.19 with partial of r(2) = 0.12 and r(2) = 0.05, respectively) independently and incrementally predicted the measured hsTnT levels. CONCLUSIONS In patients with acute chest pain, myocardial perfusion abnormalities and coronary artery disease are predicted by resting hsTnT levels. Prospective evaluations are warranted to confirm whether resting hsTnT could serve as a powerful triage tool in chest pain patients in the ED before diagnostic testing and improve the effectiveness of patient management. (J Am Coll Cardiol Img 2013;6:72-82) (C) 2013 by the American College of Cardiology Foundation C1 [Ahmed, Waleed; Schlett, Christopher L.; Uthamalingam, Shanmugam; Truong, Quynh A.; Rogers, Ian S.; Blankstein, Ron; Tawakol, Ahmed; Hoffmann, Udo] Harvard Univ, Cardiac MR PET CT Program, Dept Radiol, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. [Truong, Quynh A.; Januzzi, James L.; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Koenig, Wolfgang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. [Nagurney, John T.] Univ Ulm, Dept Cardiol, D-89069 Ulm, Germany. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM uhoffmann@partners.org FU Radiology Educational Media Services (REMS) of the Massachusetts General Hospital, Boston Massachusetts; NIH [R01 HL080053, T32HL076136, K23HL098370, L30HL093896]; Roche Diagnostics; Siemens Diagnostics; BRAHMS FX The authors thank the Radiology Educational Media Services (REMS) of the Massachusetts General Hospital, Boston Massachusetts, for their support in the artworks.; This work was supported by the NIH (R01 HL080053). The reagents for high-sensitivity troponin assays were provided free by Roche Diagnostics. Drs. Ahmed, Uthamalingam, and Rogers received support from NIH grant T32HL076136. Dr. Truong also received support from NIH grants K23HL098370 and L30HL093896. Dr. Januzzi has received grant support from Roche Diagnostics, Siemens Diagnostics, and BRAHMS. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 31 TC 16 Z9 16 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD JAN PY 2013 VL 6 IS 1 BP 72 EP 82 DI 10.1016/j.jcmg.2012.08.014 PG 11 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 084ZY UT WOS:000314581600011 PM 23328564 ER PT J AU Vina, ER Green, SL Trivedi, T Kwoh, CK Utset, TO AF Vina, Ernest R. Green, Stephanie L. Trivedi, Tarak Kwoh, C. Kent Utset, Tammy O. TI Correlates of Sleep Abnormalities in Systemic Lupus A Cross-Sectional Survey in an Urban, Academic Center SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article DE systemic lupus erythematosus; sleep quality; depression; anxiety ID QUALITY-OF-LIFE; TRAIT ANXIETY INVENTORY; DISEASE-ACTIVITY; RHEUMATOID-ARTHRITIS; PSYCHOMETRIC PROPERTIES; DAYTIME SLEEPINESS; MEDICAL OUTCOMES; REPORTED SLEEP; HEALTH-STATUS; ERYTHEMATOSUS AB Background: Systemic lupus erythematosus (SLE) is a complex autoimmune disease that is associated with poor health-related quality-of-life outcomes. Objectives: The objectives of this study were to identify correlates of the domains of the Medical Outcomes Study (MOS) Sleep Scale in SLE and to determine the factors most associated with overall sleep quality. Methods: Sleep in 118 SLE patients was assessed using the self-administered MOS Sleep Scale. Bivariate correlations were determined between each of 6 MOS Sleep subscale scores and each sociodemographic, clinical, or psychological predictor variable. Serial hierarchical multiple regression analyses were computed to identify the variables associated with the individual sleep domains and the overall Sleep Problems Index. Results: The MOS Sleep Scale scores of patients with SLE were poorer than the US general population. Depression moderately correlated with 5 (all P < 0.01) and anxiety with 4 subscale scores (all P < 0.05). The SLE Disease Activity Index did not significantly correlate with any of the subscale scores. Results of a multivariate regression model showed that sleep adequacy and sleep disturbance were independently associated with depression (beta = -0.84; 95% confidence interval [CI], -1.37 to -0.32; and beta = 0.80; 95% CI, 0.15-1.45; respectively). Daytime somnolence was significantly associated with daily prednisone dosage (beta = 0.54; 95% CI, 0.29-0.80) and anxiety trait (beta = 0.81; 95% CI, 0.41-1.21). Snoring independently correlated with anxiety (beta = 1.64; 95% CI, 0.80-2.29). When demographic, clinical, and psychological variables were simultaneously regressed on the Sleep Problems Index, pain trended toward association with overall sleep problems (beta = 0.17; 95% CI, -0.02 to 0.36). Conclusions: Patients with SLE have greater sleep problems relative to the general population. Psychosocial factors, particularly depression and anxiety, are important determinants that are significantly associated with sleep abnormalities in SLE. C1 [Vina, Ernest R.; Kwoh, C. Kent] Univ Pittsburgh, Div Rheumatol & Clin Immunol, Pittsburgh, PA USA. [Vina, Ernest R.; Kwoh, C. Kent] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Green, Stephanie L.; Utset, Tammy O.] Univ Chicago, Rheumatol Sect, Dept Internal Med, Chicago, IL 60637 USA. [Trivedi, Tarak] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. RP Vina, ER (reprint author), Arthrit Res Ctr, 3347 Forbes Ave,Ste 220, Pittsburgh, PA 15213 USA. EM evina1@pitt.edu OI Vina, Ernest/0000-0001-8135-1731 NR 50 TC 8 Z9 8 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-1608 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD JAN PY 2013 VL 19 IS 1 BP 7 EP 13 DI 10.1097/RHU.0b013e31827cd20d PG 7 WC Rheumatology SC Rheumatology GA 085LE UT WOS:000314615500002 PM 23319017 ER PT J AU Goldman, M Szucs-Reed, RP Jagannathan, K Ehrman, RN Wang, Z Li, Y Suh, JJ Kampman, K O'Brien, CP Childress, AR Franklin, TR AF Goldman, Marina Szucs-Reed, Regina P. Jagannathan, Kanchana Ehrman, Ronald N. Wang, Ze Li, Yin Suh, Jesse J. Kampman, Kyle O'Brien, Charles P. Childress, Anna Rose Franklin, Teresa R. TI Reward-related Brain Response and Craving Correlates of Marijuana Cue Exposure: A Preliminary Study in Treatment-seeking Marijuana-dependent Subjects SO JOURNAL OF ADDICTION MEDICINE LA English DT Article DE addiction; brain reward circuitry; cannabis; craving; marijuana cues; neuroimaging ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; LIMBIC ACTIVATION; CANNABIS WITHDRAWAL; CONTROLLED TRIAL; DRUG-ADDICTION; UNITED-STATES; DSM-IV; SMOKING; REACTIVITY; DOPAMINE AB Objective: Determining the brain substrates underlying the motivation to abuse addictive drugs is critical for understanding and treating addictive disorders. Laboratory neuroimaging studies have demonstrated differential activation of limbic and motivational circuitry (eg, amygdala, hippocampus, ventral striatum, insula, and orbitofrontal cortex) triggered by cocaine, heroin, nicotine, and alcohol cues. The literature on neural responses to marijuana cues is sparse. Thus, the goals of this study were to characterize the brain's response to marijuana cues, a major motivator underlying drug use and relapse, and determine whether these responses are linked to self-reported craving in a clinically relevant population of treatment-seeking marijuana-dependent subjects. Methods: Marijuana craving was assessed in 12 marijuana-dependent subjects using the Marijuana Craving Questionnaire-Short Form. Subsequently, blood oxygen level dependent functional magnetic resonance imaging data were acquired during exposure to alternating 20-second blocks of marijuana-related versus matched nondrug visual cues. Results: Brain activation during marijuana cue exposure was significantly greater in the bilateral amygdala and the hippocampus. Significant positive correlations between craving scores and brain activation were found in the ventral striatum and the medial and lateral orbitofrontal cortex (P < 0.0001). Conclusions: This study presents direct evidence for a link between reward-relevant brain responses to marijuana cues and craving and extends the current literature on marijuana cue reactivity. Furthermore, the correlative relationship between craving and brain activity in reward-related regions was observed in a clinically relevant sample (treatment-seeking marijuana-dependent subjects). Results are consistent with prior findings in cocaine, heroin, nicotine, and alcohol cue studies, indicating that the brain substrates of cue-triggered drug motivation are shared across abused substances. C1 [Goldman, Marina; Szucs-Reed, Regina P.; Jagannathan, Kanchana; Wang, Ze; Li, Yin; Suh, Jesse J.; Kampman, Kyle; O'Brien, Charles P.; Childress, Anna Rose; Franklin, Teresa R.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Ehrman, Ronald N.; Suh, Jesse J.; O'Brien, Charles P.; Childress, Anna Rose] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Ehrman, Ronald N.; Suh, Jesse J.; O'Brien, Charles P.; Childress, Anna Rose] VISN 4 Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. [Wang, Ze] Univ Penn, Dept Neurol, Ctr Funct Neuroimaging, Philadelphia, PA 19104 USA. RP Goldman, M (reprint author), Univ Penn, Dept Psychiat, 3900 Walnut St, Philadelphia, PA 19104 USA. EM marinag@mail.med.upenn.edu FU National Institute of Drug Abuse [5-P60-DA-05186, T32-DA-07241]; Philadelphia Veterans Affairs Medical Center and VISN 4 Mental Illness Research, Education & Clinical Center; Pennsylvania Department of Health; National Institute of Health/National Institute of NeurologicaI Disorders and Stroke [P30 NS045839] FX Supported by grants from the National Institute of Drug Abuse (Dr. O'Brien, principle investigator: 5-P60-DA-05186 and T32-DA-07241), the Philadelphia Veterans Affairs Medical Center and VISN 4 Mental Illness Research, Education & Clinical Center, the Pennsylvania Department of Health (Dr. Childress, principle investigator: CURE Center of Excellence: Brain Mechanisms of Relapse and Recovery), and imaging and infrastructure support for this work was kindly provided by the National Institute of Health/National Institute of NeurologicaI Disorders and Stroke (P30 NS045839). The funding agencies had no further role in the conduct of the research, preparation of the manuscript, study design, collection, analysis and interpretation of data, writing of the report, and the decision to submit the paper for publication. NR 56 TC 17 Z9 17 U1 3 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1932-0620 J9 J ADDICT MED JI J. Addict. Med. PD JAN-FEB PY 2013 VL 7 IS 1 BP 8 EP 16 DI 10.1097/ADM.0b013e318273863a PG 9 WC Substance Abuse SC Substance Abuse GA 088HP UT WOS:000314825100002 PM 23188041 ER PT J AU Kalapatapu, RK Campbell, A Aharonovich, E Hu, MC Levin, FR Nunes, EV AF Kalapatapu, Raj K. Campbell, Aimee Aharonovich, Efrat Hu, Mei-Chen Levin, Frances R. Nunes, Edward V. TI Demographic and Clinical Characteristics of Middle-aged Versus Younger Adults Enrolled in a Clinical Trial of a Web-delivered Psychosocial Treatment for Substance Use Disorders SO JOURNAL OF ADDICTION MEDICINE LA English DT Article DE addiction; aging; neurocognitive; Web-based treatment ID MILD COGNITIVE IMPAIRMENT; COCAINE-DEPENDENT PATIENTS; RANDOMIZED CONTROLLED-TRIAL; OLDER-ADULTS; LATE-LIFE; PSYCHOLOGICAL DISTRESS; NARCOTIC ADDICTION; ABUSE TREATMENT; DRUG-USE; ALCOHOL AB Objective: Evidence suggests that substance abuse is becoming more prevalent in middle-aged adults. The objective of this secondary analysis was to add to the growing empirical literature on the unique features of middle-aged substance abuse populations. Methods: We descriptively compared baseline demographic and clinical characteristics of middle-aged (age 45-62 years, n = 111) and younger (age 18-44 years, n = 395) substance abusers entering a Web-based psychosocial treatment study as part of the National Institute on Drug Abuse Clinical Trials Network. Results: A significantly greater percentage of middle-aged adults were nonwhite and had a marital status other than single/never married. There was a significant association between frequency of Internet use and the age group. Forty-six percent of middle-aged adults versus 21% of younger adults reported no Internet use in the prior 90 days. A significantly greater percentage of middle-aged adults used cocaine, and a significantly greater percentage of younger adults used marijuana and opioids. Clinically significant cognitive impairment (z < -1.0) was found for the average participant in both groups on logical association of familiar concepts. Conclusions: This secondary analysis of a National Institute on Drug Abuse Clinical Trials Network study provides additional information on the unique features of middle-aged substance abusers. Increasing knowledge of similarities and differences between younger and middle-aged substance abusers can help with potential age-specific substance abuse treatment planning. C1 [Kalapatapu, Raj K.] Univ Calif San Francisco, Dept Psychiat, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. [Campbell, Aimee; Aharonovich, Efrat; Hu, Mei-Chen; Levin, Frances R.; Nunes, Edward V.] Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, New York, NY 10032 USA. [Campbell, Aimee; Aharonovich, Efrat; Hu, Mei-Chen; Levin, Frances R.; Nunes, Edward V.] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. RP Kalapatapu, RK (reprint author), San Francisco VA Med Ctr, Bldg 8 Mental Hlth,Ground Floor,Room 4C,4150 Clem, San Francisco, CA 94121 USA. EM kalapatapu.raj.k@gmail.com FU NIDA [3U10DA013035-10S2, 5T32DA007294-19, R01DA020647, 5K24DA029647-02, 2K24DA022412-06]; Clinical/Research Fellowship in Psychiatry through the Veterans Affairs Medical Center FX Supported by the NIDA grant 3U10DA013035-10S2 (PI: Nunes). Dr. Kalapatapu was funded by the NIDA grant 5T32DA007294-19 (PI: Levin) while he was at Columbia University and is now funded by a Clinical/Research Fellowship in Psychiatry through the Veterans Affairs Medical Center. Dr. Aharonovich was funded by the NIDA grant R01DA020647 (PI: Aharonovich). Dr. Levin was funded by the NIDA grant 5K24DA029647-02 (PI: Levin). Dr. Nunes was funded by the NIDA grant 2K24DA022412-06 (PI: Nunes). NR 83 TC 3 Z9 3 U1 2 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1932-0620 J9 J ADDICT MED JI J. Addict. Med. PD JAN-FEB PY 2013 VL 7 IS 1 BP 66 EP 72 DI 10.1097/ADM.0b013e31827e2d04 PG 7 WC Substance Abuse SC Substance Abuse GA 088HP UT WOS:000314825100010 PM 23340711 ER PT J AU Hickman, SE El Khoury, J AF Hickman, Suzanne E. El Khoury, Joseph TI The NeuroImmune System in Alzheimer's Disease: The Glass is Half Full SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Review DE Alzheimer's disease; amyloid-beta; chemokines; microglia; mononuclear phagocytes; scavenger receptors ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; MARROW-DERIVED MICROGLIA; BETA-AMYLOID FIBRILS; PERIVASCULAR MACROPHAGES; SCAVENGER RECEPTOR; INTERFERON-GAMMA; TRANSGENIC MICE; CRYPTOCOCCUS-NEOFORMANS; REACTIVE MICROGLIA; SENILE PLAQUES AB It is well established that rnicroglia, the neuroimmune cells of the brain, are associated with amyloid-beta (A beta) deposits in Alzheimer's disease (AD). However, the roles of these cells and other mononuclear phagocytes such as monocytes and macrophages in AD pathogenesis and progression have been elusive. Clues to mononuclear phagocyte involvement came with the demonstration that A beta directly activates microglia and monocytes to produce neurotoxins, signifying that a receptor mediated interaction of A beta with these cells may be critical for neurodegeneration seen in AD. Also, in AD brain, mononuclear phagocyte distribution changes from a uniform pattern that covers the brain parenchyma to distinct clusters intimately associated with areas of A beta deposition, but the driving force behind this choreography was unclear. Here, we review our recent work identifying mononuclear phagocyte receptors for A beta and unraveling mechanisms of recruitment of these cells to areas of A beta deposition. While our findings and those of others have added significantly to our understanding of the role of the neuroimmune system in AD, the glass remains half full (or half empty) and a lot remains to be uncovered. C1 [Hickman, Suzanne E.; El Khoury, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA 02129 USA. [El Khoury, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02129 USA. RP El Khoury, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, CNY 149,Room 8301,149 13th St, Boston, MA 02129 USA. EM jelkhoury@partners.org FU NIH [NS059005, AG032349, AI082660]; Dana Foundation Neuroimmunology Program FX Work summarized in this manuscript was supported by NIH grants NS059005, AG032349, and AI082660 and a grant from the Dana Foundation Neuroimmunology Program. NR 54 TC 13 Z9 14 U1 1 U2 9 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2013 VL 33 SU 1 SI SI BP S295 EP S302 DI 10.3233/JAD-2012-129027 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 083FH UT WOS:000314447600029 PM 22751176 ER PT J AU Quinn, JF AF Quinn, Joseph F. TI Biomarkers for Alzheimer's Disease: Showing the Way or Leading Us Astray? SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Review DE Alzheimer's disease; biomarkers; clinical trials ID MILD COGNITIVE IMPAIRMENT; GAMMA-SECRETASE INHIBITOR; DECLINE; TRIAL; ACID AB The indolent nature of Alzheimer's disease, coupled with burgeoning interest in a "presymptomatic" stage of disease, has motivated efforts to identify, validate, and exploit surrogate disease markers for trials of disease-modifying or preventive strategies. Many of these efforts have been productive, and biomarkers are now routinely applied in selection of study subjects and evaluation of outcomes in clinical trials. On the other hand, biomarkers also have the capacity to lead to bad therapeutic outcomes when they determine "go- no go" decisions in early drug development. This paper reviews several reports of biomarker studies which illustrate the great potential, for both good and ill, of biomarkers of Alzheimer's disease. C1 [Quinn, Joseph F.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Quinn, Joseph F.] Portland VA Med Ctr, Portland, OR USA. RP Quinn, JF (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Mail Code CR-131,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM quinnj@ohsu.edu FU NIA NIH HHS [P30 AG008017] NR 15 TC 3 Z9 3 U1 0 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2013 VL 33 SU 1 SI SI BP S371 EP S376 DI 10.3233/JAD-2012-129022 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 083FH UT WOS:000314447600035 PM 22766735 ER PT J AU Tanzi, RE AF Tanzi, Rudolph E. TI A Brief History of Alzheimer's Disease Gene Discovery SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Review DE Amyloid-beta; amyloid-beta protein precursor; APOE; CD33; chromosome 21; down syndrome; genome-wide association study; presenilin ID AMYLOID BETA-PROTEIN; GENOME-WIDE ASSOCIATION; SYSTEMATIC METAANALYSES; IDENTIFIES VARIANTS; HUMAN CHROMOSOME-21; MISSENSE MUTATIONS; PRECURSOR PROTEIN; APOLIPOPROTEIN-E; COMMON VARIANTS; HYPOTHESIS AB The rich and colorful history of gene discovery in Alzheimer's disease (AD) over the past three decades is as complex and heterogeneous as the disease, itself. Twin and family studies indicate that genetic factors are estimated to play a role in at least 80% of AD cases. The inheritance of AD exhibits a dichotomous pattern. On one hand, rare mutations in APP, PSEN1, and PSEN2 are fully penetrant for early-onset (<60 years) familial AD, which represents <5% of AD. On the other hand, common gene polymorphisms, such as the epsilon 4 and epsilon 2 variants of the APOE gene, influence susceptibility for common (>95%) late-onset AD. These four genes account for 30-50% of the inheritability of AD. Genome-wide association studies have recently led to the identification of additional highly confirmed AD candidate genes. Here, I review the past, present, and future of attempts to elucidate the complex and heterogeneous genetic underpinnings of AD along with some of the unique events that made these discoveries possible. C1 [Tanzi, Rudolph E.] Harvard Univ, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Genet & Aging Res Unit,Dept Neurol,Med Sch, Boston, MA USA. RP Tanzi, RE (reprint author), Harvard Univ, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Genet & Aging Res Unit,Dept Neurol,Med Sch, 114 16th St, Charlestown, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu NR 46 TC 21 Z9 21 U1 2 U2 31 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2013 VL 33 SU 1 SI SI BP S5 EP S13 DI 10.3233/JAD-2012-129044 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 083FH UT WOS:000314447600002 PM 22986781 ER PT J AU Keane, TM Chaudhry, B Docherty, JP Jesse, RL Lee, J McNurlen, J Zeller, E AF Keane, Terence M. Chaudhry, Basit Docherty, John P. Jesse, Robert L. Lee, Jennifer McNurlen, Jessica Zeller, Eileen TI Caring for Returning Veterans: Meeting Mental Health Needs SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material C1 [Keane, Terence M.] US Dept Vet Affairs, Natl Ctr PTSD, Behav Sci Div, Washington, DC USA. [Keane, Terence M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Chaudhry, Basit] IBM Res, Washington, DC USA. [Docherty, John P.] Weill Cornell Med Coll, Dept Psychiat, New York, NY USA. [Docherty, John P.] New York Presbyterian Hosp, New York, NY USA. [Jesse, Robert L.; Lee, Jennifer] US Dept Vet Affairs, Washington, DC USA. [McNurlen, Jessica] Mental Hlth Assoc Montgomery Cty, Rockville, MD USA. [Zeller, Eileen] SAMHSA, Ctr Mental Hlth Serv, Suicide Prevent Branch, Rockville, MD USA. RP Keane, TM (reprint author), US Dept Vet Affairs, Natl Ctr PTSD, Behav Sci Div, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JAN PY 2013 VL 74 IS 1 BP 23 EP + DI 10.4088/JCP.12071co1c PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 083UN UT WOS:000314490800004 PM 23419222 ER PT J AU Cook, IA Hunter, AM Gilmer, WS Iosifescu, DV Zisook, S Burgoyne, KS Howland, RH Trivedi, MH Jain, R Greenwald, S Leuchter, AF AF Cook, Ian A. Hunter, Aimee M. Gilmer, William S. Iosifescu, Dan V. Zisook, Sidney Burgoyne, Karl S. Howland, Robert H. Trivedi, Madhukar H. Jain, Rakesh Greenwald, Scott Leuchter, Andrew F. TI Quantitative Electroencephalogram Biomarkers for Predicting Likelihood and Speed of Achieving Sustained Remission in Major Depression: A Report From the Biomarkers for Rapid Identification of Treatment Effectiveness in Major Depression (BRITE-MD) Trial SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; STAR-ASTERISK-D; DSM-IV; DISORDER; ANTIDEPRESSANTS; PREVALENCE; OUTCOMES; MINI AB Objective: Clinical trials in major depressive disorder (MDD) commonly assess remission at a single endpoint. Complementary, clinically relevant metrics include the likelihood and speed of achieving sustained remission. A neurophysiologic measure, the Antidepressant Treatment Response (ATR) index, previously predicted 8-week outcomes of pharmacotherapy. We retrospectively examined data from the Biomarkers for Rapid Identification of Treatment Effectiveness in Major Depression (BRITE-MD) trial to evaluate this biomarker's properties in predicting sustained remission and time to achieve sustained remission. Method: In the BRITE-MD trial, 67 adults with DSM-IV MDD received escitalopram continuously for 13 weeks. The 17-item Hamilton Depression Rating Scale (HDRS17) was used to define sustained remission as achieving remission (HDRS17 score <= 7) at a series of consecutive assessments, including week 13. The onset of sustained remission was defined as the earliest time from which all subsequent HDRS17 assessments were <= 7. The ATR was evaluated by using frontal quantitative electroencephalogram recordings at baseline and week 1. Subjects were stratified based on AIR status (ie, ATR+/ATR-). Kaplan-Meier survival analysis evaluated group differences in time to sustained remission. Higher AIR was hypothesized to predict sustained remission and time to sustained remission. Subjects participated between January 2006 and July 2007. Results: Of 67 subjects, 36 achieved remission by week 13, and ATR predicted this single endpoint in receiver operating characteristic analyses (P=.016; sensitivity, 52.8%; positive predictive value, 76.0%). Remitters had a higher mean (SD) ATR value than those who did not remit (57.9 [10.0] vs 51.9 [8.7], P=.012). Sixteen of the 31 individuals with sustained remission had ATR+ status, while 28 of the 36 who were not sustained remitters had ATR- status (P=.012). The mean time to reach sustained remission was significantly shorter among ATR+ subjects than AIR-individuals (38 vs 53 days, P=.038). Conclusions: The ATR index predicted remission at 13 weeks as well as the speed of achieving sustained remission with antidepressant monotherapy. This finding suggests that the ATR biomarker may predict stable longer-term outcomes. Trial Registration: ClinicalTrials.gov identifier: NCT00289523 J Clin Psychiatry 2013;74(1):51-56 (C) Copyright 2013 Physicians Postgraduate Press, Inc. C1 [Cook, Ian A.; Hunter, Aimee M.; Leuchter, Andrew F.] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Semel Inst Neurosci & Human Behav, Depress Res & Clin Program, Los Angeles, CA 90095 USA. [Cook, Ian A.; Hunter, Aimee M.; Leuchter, Andrew F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Burgoyne, Karl S.] Harbor UCLA Med Ctr, Dept Psychiat, Los Angeles, CA USA. [Zisook, Sidney] Univ Calif San Diego, Dept Psychiat, San Diego, CA USA. [Gilmer, William S.] Northwestern Univ, Dept Psychiat, Chicago, IL 60611 USA. [Iosifescu, Dan V.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Howland, Robert H.] Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. [Trivedi, Madhukar H.] Univ Texas Dallas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. [Jain, Rakesh] RD Clin Res, Houston, TX USA. [Greenwald, Scott] Covidien Inc, Norwood, MA USA. RP Cook, IA (reprint author), UCLA Depress Res & Clin Program, 760 Westwood Plaza, Los Angeles, CA 90095 USA. EM icook@ucla.edu RI Howland, Robert/K-6937-2015 OI Howland, Robert/0000-0002-6533-6010 FU National Institutes of Health; Sepracor; Neuronetics; Aspect Medical Systems/Covidien; Aspect Medical Systems; Forest; Janssen; PAMLAB; National Institute of Mental Health (NIMH); American Federation for Suicide Prevention; Abbott; Abdi Ibrahim; Akzo (Organon); AstraZeneca; Axon Advisors; Bristol-Myers Squibb; Cephalon; CME Institute of Physicians Postgraduate Press; Eli Lilly; Evotek; Fabre-Kramer; GlaxoSmithKline; Johnson Johnson; Lundbeck; Meade Johnson; MedAvante; Medtronic; Otsuka; Parke-Davis; Pfizer; PgxHealth; Rexahn; Shire; Takeda; VantagePoint; Wyeth-Ayerst; Agency for Healthcare Research and Quality; Corcept; Cyberonics; Merck; National Alliance for Research in Schizophrenia and Depression; NIMH; National Institute on Drug Abuse; Novartis; Pharmacia Upjohn; Predix (Epix); Solvay; Targacept; division of Covidien PLC FX Dr Cook has been a consultant to the US Departments of Justice and Defense, Neuronetics, and NeuroSigma; has received grant/research support from National Institutes of Health, Sepracor, and Neuronetics, and Aspect Medical Systems/Covidien; and has served on speakers or advisory boards of Neuronetics. Dr Iosifescu has received grant/research support from Aspect Medical Systems, Forest, and Janssen; and has served on speakers or advisory boards of Eli Lilly, Forest, Pfizer, and Reed Medical Education. Dr Zisook has received grant/research support from PAMLAB, National Institute of Mental Health (NIMH), and American Federation for Suicide Prevention. Dr Trivedi has received consulting fees from Abbott, Abdi Ibrahim, Akzo (Organon), AstraZeneca, Axon Advisors, Bristol-Myers Squibb, Cephalon, CME Institute of Physicians Postgraduate Press, Eli Lilly, Evotek, Fabre-Kramer, Forest, GlaxoSmithKline, Janssen, Johnson & Johnson, Lundbeck, Meade Johnson, MedAvante, Medtronic, Neuronetics, Otsuka, PAMLAB, Parke-Davis, Pfizer, PgxHealth, Rexahn, Sepracor, Shire, Takeda, VantagePoint, and Wyeth-Ayerst; and has received research support from Agency for Healthcare Research and Quality, Corcept, Cyberonics, Merck, National Alliance for Research in Schizophrenia and Depression, NIMH, National Institute on Drug Abuse, Novartis, Pharmacia & Upjohn, Predix (Epix), Solvay, and Targacept. Dr Greenwald is an employee of and stock shareholder in Aspect Medical Systems. Dr Leuchter has served on an advisory board of Aspect Medical Systems; has collaborated on research on placebo response, participated in 2 clinical trials on treatment of fibromyalgia and 1 on attention-deficit/hyperactivity disorder, advised on medication and technology development for and served on speakers bureau of Eli Lilly; and has discussed and planned new educational initiatives for Pfizer. Drs Hunter, Gilmer, Burgoyne, Howland, and Jain report no potential or other conflicts of interest.; Funding for the BRITE-MD trial was provided by Aspect Medical Systems, Inc (Norwood, Massachusetts), now a division of Covidien PLC. NR 32 TC 11 Z9 11 U1 0 U2 7 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JAN PY 2013 VL 74 IS 1 BP 53 EP 58 DI 10.4088/JCP.10m06813 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 083UN UT WOS:000314490800009 PM 23419226 ER PT J AU Westover, MB Cohen, AB AF Westover, M. Brandon Cohen, Adam B. TI Reversible Vasoconstriction Syndrome with Bilateral Basal Ganglia Hemorrhages SO JOURNAL OF NEUROIMAGING LA English DT Article DE Stroke; hemorrhage; vasoconstriction; RCVS; reversible; SSRI AB Reversible cerebral vasoconstriction syndrome (RCVS) is an increasingly recognized acute cerebrovascular condition that may produce myriad transient and sustained neurologic deficits as well as a host of radiologic features. We report the case of a woman with RCVS and a severe clinical syndrome with bilateral basal ganglia hemorrhages, cerebral infarctions, and marked vascular abnormalities. The patient made a near complete clinical recovery, representing an extreme and illustrative form of RCVS. C1 [Westover, M. Brandon; Cohen, Adam B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02118 USA. RP Cohen, AB (reprint author), Massachusetts Gen Hosp, Dept Neurol, 15 Parkman St,WACC7, Boston, MA 02118 USA. EM abcohen@partners.org NR 4 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1051-2284 J9 J NEUROIMAGING JI J. Neuroimaging PD JAN PY 2013 VL 23 IS 1 BP 122 EP 125 DI 10.1111/j.1552-6569.2011.00645.x PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 075IF UT WOS:000313877600027 PM 21899647 ER PT J AU Yeh, DD Hwabejire, JO Imam, A Mullen, JT Smink, D Velmahos, G DeMoya, M AF Yeh, Daniel Dante Hwabejire, John O. Imam, Ayesha Mullen, John T. Smink, Douglas Velmahos, George DeMoya, Marc TI A Survey of Study Habits of General Surgery Residents SO JOURNAL OF SURGICAL EDUCATION LA English DT Article DE study habits; general surgery; ABSITE; motivation ID IN-TRAINING EXAMINATION; AMERICAN-BOARD; EXAMINATION SCORES; ABSITE PERFORMANCE; ACQUISITION; KNOWLEDGE; IMPACT AB OBJECTIVE: To understand the study habits of general surgery residents as well as their motivating factors for study. DESIGN: A survey was mailed to general surgical residents. Performance on the American Board of Surgery In-Training Examination (ABSITE) was correlated with reported study habits using the Pearson's correlation coefficient. SETTING: Massachusetts General Hospital and Brigham and Women's Hospital, 2 urban tertiary referral academic training institutions in Boston, Massachusetts. PARTICIPANTS: Fifty-eight general surgical residents of all training levels (including research). RESULTS: On average, surgical residents studied for 3 1 days per week, the average duration of each study session being 1.3 +/- 0.6 hours. The average total number of study hours per week was 3.4 +/- 2.3. There were strong positive correlations between increased study frequency and high overall ABSITE score (Pearson's r = 0.339; p = 0.02) and between the total number of study hours per week and high overall ABSITE score (Pearson's r = 0.423; p < 0.005). Only 10% and 3% reported complete satisfaction with current study materials and routine, respectively. Most residents (96%) reported a willingness to try a new type of study method and 75% were willing to enroll in a trial comparing study methods. CONCLUSIONS: Increased study frequency and overall increased study duration are positively correlated with ABSITE performance. Dissatisfaction with current study materials and study routine is high, as is willingness to adopt new methods and enroll in investigational trials comparing study methods. (J Surg 70:15-23. (C) 2012 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.) C1 [Yeh, Daniel Dante; Hwabejire, John O.; Imam, Ayesha; Mullen, John T.; Velmahos, George; DeMoya, Marc] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Hwabejire, John O.; Imam, Ayesha; Velmahos, George] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA USA. [Mullen, John T.] Harvard Univ, Div Surg Oncol, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. [Smink, Douglas] Harvard Univ, Brigham & Womens Hosp, Dept Surg, Sch Med, Boston, MA 02115 USA. RP Yeh, DD (reprint author), Massachusetts Gen Hosp, Dept Surg, 165 Cambridge St 810, Boston, MA 02114 USA. EM dyeh2@partners.org NR 18 TC 8 Z9 8 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1931-7204 J9 J SURG EDUC JI J. Surg. Educ. PD JAN-FEB PY 2013 VL 70 IS 1 BP 15 EP 23 DI 10.1016/j.jsurg.2012.08.006 PG 9 WC Education, Scientific Disciplines; Surgery SC Education & Educational Research; Surgery GA 084SK UT WOS:000314559200004 PM 23337665 ER PT J AU Mananga, ES Reid, AE AF Mananga, Eugene S. Reid, Alicia E. TI Investigation of the effect of finite pulse errors on the BABA pulse sequence using the Floquet-Magnus expansion approach SO MOLECULAR PHYSICS LA English DT Article DE BABA pulse sequence; finite pulse widths; dipolar coupling; Floquet-Magnus expansion ID NUCLEAR-MAGNETIC-RESONANCE; AVERAGE HAMILTONIAN THEORY; NMR-SPECTROSCOPY; ROTATING SOLIDS; SYMMETRY PRINCIPLES; SPINNING SOLIDS; I=1; FREQUENCIES; PHASE; SPINS AB This paper presents a study of finite pulse widths for the BABA pulse sequence using the FloquetMagnus expansion (FME) approach. In the FME scheme, the first order is identical to its counterparts in average Hamiltonian theory (AHT) and Floquet theory (FT). However, the timing part in the FME approach is introduced via the Lambda 1(t) function not present in other schemes. This function provides an easy way for evaluating the spin evolution during the time in between through the Magnus expansion of the operator connected to the timing part of the evolution. The evaluation of Lambda 1(t) is particularly useful for the analysis of the non-stroboscopic evolution. Here, the importance of the boundary conditions, which provide a natural choice of Lambda 1(0), is ignored. This work uses the function to compare the efficiency of the BABA pulse sequence with delta-pulses and the BABA pulse sequence with finite pulses. Calculations of Lambda 1(t) and F1 are presented. C1 [Mananga, Eugene S.] Harvard Univ, Harvard Med Sch, Boston, MA 02114 USA. [Mananga, Eugene S.] Massachusetts Gen Hosp, Ctr Adv Radiol Sci, Div Nucl Med & Mol Imaging Phys, Dept Radiol, Boston, MA 02114 USA. [Reid, Alicia E.] CUNY Medgar Evers Coll, Brooklyn, NY 11225 USA. RP Mananga, ES (reprint author), Harvard Univ, Harvard Med Sch, 55 Fruit St, Boston, MA 02114 USA. EM emananga@pet.mgh.harvard.edu FU United States National Institute of Health at Harvard Medical School [T32 EB013180]; Massachusetts General Hospital FX Eugene S. Mananga acknowledges Professor Georges El Fakhri and the support from the United States National Institute of Health (T32 EB013180) at Harvard Medical School and Massachusetts General Hospital. This paper is dedicated to the memory of Emeritus University Distinguished Professor of Physics Herman Z. Cummins of The City University of New York who was a great mentor. NR 38 TC 8 Z9 8 U1 1 U2 14 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0026-8976 EI 1362-3028 J9 MOL PHYS JI Mol. Phys. PD JAN 1 PY 2013 VL 111 IS 2 BP 241 EP 255 DI 10.1080/00268976.2012.718379 PG 15 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 079JX UT WOS:000314167500008 PM 25792763 ER PT J AU Wang, HF Livingston, KA Fox, CS Meigs, JB Jacques, PF AF Wang, Huifen Livingston, Kara A. Fox, Caroline S. Meigs, James B. Jacques, Paul F. TI Yogurt consumption is associated with better diet quality and metabolic profile in American men and women SO NUTRITION RESEARCH LA English DT Article DE Yogurt; Milk; Diet; Nutrition status; Metabolic profile; Human ID FOOD FREQUENCY QUESTIONNAIRE; DAIRY CONSUMPTION; INSULIN-RESISTANCE; CONTINUING SURVEY; MAGNESIUM INTAKE; MILK-PRODUCTS; UNITED-STATES; ADULTS; RISK; PLASMA AB The evidence-based Dietary Guidelines for Americans recommends increasing the intake of fat-free or low-fat milk and milk products. However, yogurt, a nutrient-dense milk product, has been understudied. This cross-sectional study examined whether yogurt consumption was associated with better diet quality and metabolic profile among adults (n = 6526) participating in the Framingham Heart Study Offspring (1998-2001) and Third Generation (2002-2005) cohorts. A validated food frequency questionnaire was used to assess dietary intake, and the Dietary Guidelines Adherence Index (DGAI) was used to measure overall diet quality. Standardized clinical examinations and laboratory tests were conducted. Generalized estimating equations examined the associations of yogurt consumption with diet quality and levels of metabolic factors. Approximately 64% of women (vs 41% of men) were yogurt consumers (ie, consumed >0 servings/week). Yogurt consumers had a higher DGAI score (ie, better diet quality) than nonconsumers. Adjusted for demographic and lifestyle factors and DGAI, yogurt consumers, compared with nonconsumers, had higher potassium intakes (difference, 0.12 g/d) and were 47%, 55%, 48%, 38%, and 34% less likely to have inadequate intakes (based on Dietary Reference Intake) of vitamins B2 and B12, calcium, magnesium, and zinc, respectively (all P <= .001). In addition, yogurt consumption was associated with lower levels of circulating triglycerides, glucose, and lower systolic blood pressure and insulin resistance (all P < .05). Yogurt is a good source of several micronutrients and may help to improve diet quality and maintain metabolic well-being as part of a healthy, energy-balanced dietary pattern. (C) 2013 Elsevier Inc. All rights reserved. C1 [Wang, Huifen; Livingston, Kara A.; Jacques, Paul F.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr, Boston, MA 02111 USA. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Gen Internal Med Unit, Boston, MA 02114 USA. RP Jacques, PF (reprint author), Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr, Boston, MA 02111 USA. EM Paul.jacques@tufts.edu FU National Heart, Lung and Blood Institute of the National Institute of Health [NO1-HC-25195]; US Department of Agriculture [58-1950-7-707]; The Dannon Company, Inc. FX This work was supported by National Heart, Lung and Blood Institute of the National Institute of Health (contract number: NO1-HC-25195), US Department of Agriculture Agreement 58-1950-7-707, and a research grant from The Dannon Company, Inc. NR 40 TC 43 Z9 44 U1 7 U2 49 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD JAN PY 2013 VL 33 IS 1 BP 18 EP 26 DI 10.1016/j.nutres.2012.11.009 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 084TE UT WOS:000314561200003 PM 23351406 ER PT J AU Chabner, BA AF Chabner, Bruce A. TI Resolution: Refresh, Recharge, Renew SO ONCOLOGIST LA English DT Editorial Material C1 [Chabner, Bruce A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Chabner, Bruce A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Chabner, BA (reprint author), 10 N Grove St,LRH 214, Boston, MA 02114 USA. EM bchabner@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD JAN PY 2013 VL 18 IS 1 BP 1 EP 1 DI 10.1634/theoncologist.2012-0482 PG 1 WC Oncology SC Oncology GA 086RD UT WOS:000314703200004 ER PT J AU McCleary, NJ Wigler, D Berry, D Sato, K Abrams, T Chan, J Enzinger, P Ng, K Wolpin, B Schrag, D Fuchs, CS Hurria, A Meyerhardt, JA AF McCleary, Nadine J. Wigler, Devin Berry, Donna Sato, Kaori Abrams, Thomas Chan, Jennifer Enzinger, Peter Ng, Kimmie Wolpin, Brian Schrag, Deborah Fuchs, Charles S. Hurria, Arti Meyerhardt, Jeffrey A. TI Feasibility of Computer-Based Self-Administered Cancer-Specific Geriatric Assessment in Older Patients With Gastrointestinal Malignancy SO ONCOLOGIST LA English DT Article DE Gastrointestinal cancer; Geriatric oncology; Geriatric assessment; Clinical decision-making ID FUNCTIONAL STATUS; ELDERLY-PATIENTS; COLORECTAL-CANCER; COMORBIDITY; ADULTS; CARE; CHEMOTHERAPY; MANAGEMENT; ONCOLOGY; HEALTH AB Background. The Cancer-Specific Geriatric Assessment (CSGA) is a primarily self-administered paper survey of validated measures. Methods. We developed and tested the feasibility of a computer-based CSGA in patients >= 70 years of age who were receiving treatment for gastrointestinal malignancies at the Dana-Farber Cancer Institute. From December 2009 to June 2011, patients were invited to complete the CSGA at baseline (start of new treatment) and follow-up (at the first of 4 months later or within 4 weeks of completing treatment). Feasibility endpoints were proportion of eligible patients consented, proportion completing CSGA at baseline and follow-up, time to complete CSGA, and proportion of physicians reporting CSGA results that led to a change in clinical decision-making. Results. Of the 49 eligible patients, 38 consented (76% were treatment naive). Median age was 77 years (range: 70-89 years), and 48% were diagnosed with colorectal cancer. Mean physician-rated Karnofsky Performance Status was 87.5 at baseline (SD 8.4) and 83.5 at follow-up (SD 8). At baseline, 92% used a touchscreen computer; 97% completed the CSGA (51% independently). At follow-up, all patients used a touchscreen computer; 71% completed the CSGA (41% independently). Mean time to completion was 23 minutes at baseline (SD 8.4) and 20 minutes at follow-up (SD 5.1). The CSGA added information to clinical assessment for 75% at baseline (n = 27) and 65% at follow-up (n = 17), but it did not alter immediate clinical decision-making. Conclusion. The computer-based CSGA feasibility endpoints were met, although approximately half of patients required assistance. The CSGA added information to clinical assessment but did not affect clinical decision-making, possibly due to limited alternate treatment options in this subset of patients. The Oncologist 2013;18:64-72 C1 [McCleary, Nadine J.; Wigler, Devin; Sato, Kaori; Abrams, Thomas; Chan, Jennifer; Enzinger, Peter; Ng, Kimmie; Wolpin, Brian; Schrag, Deborah; Fuchs, Charles S.; Meyerhardt, Jeffrey A.] Dana Farber Canc Inst, Dept Med Oncol, Gastrointestinal Canc Ctr, Boston, MA 02215 USA. [Berry, Donna] Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02215 USA. [Hurria, Arti] City Hope Natl Med Ctr, Dept Med Oncol, Canc & Aging Res Program, Los Angeles, CA USA. RP McCleary, NJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM Nj_mccleary@dfci.harvard.edu FU American Society of Clinical Oncologists Young Investigator Award; National Institutes of Health Program in Cancer Outcomes Research Training [R25CA092203]; Dana-Farber Cancer Institute Gastrointestinal SPORE Career Development Award [5P50CA127003-05] FX This work was supported by the American Society of Clinical Oncologists Young Investigator Award and the National Institutes of Health Program in Cancer Outcomes Research Training (R25CA092203) and Dana-Farber Cancer Institute Gastrointestinal SPORE Career Development Award (5P50CA127003-05). We also acknowledge the assistance of the Survey and Data Management Core of the Dana-Farber Cancer Institute. NR 29 TC 15 Z9 15 U1 1 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD JAN PY 2013 VL 18 IS 1 BP 64 EP 72 DI 10.1634/theoncologist.2012-0241 PG 9 WC Oncology SC Oncology GA 086RD UT WOS:000314703200015 PM 23287880 ER PT J AU Riddle, DL Singh, JA Harmsen, WS Schleck, CD Lewallen, DG AF Riddle, D. L. Singh, J. A. Harmsen, W. S. Schleck, C. D. Lewallen, D. G. TI Clinically important body weight gain following total hip arthroplasty: a cohort study with 5-year follow-up SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE Hip; Arthroplasty; Obesity ID KNEE ARTHROPLASTY; MASS INDEX; NONOBESE PATIENTS; UNITED-STATES; OLDER-ADULTS; RISK-FACTORS; US ADULTS; OBESITY; REPLACEMENT; POPULATION AB Objective: Literature examining the effects of total hip arthroplasty (THA) on subsequent body weight gain is inconclusive. Determining the extent to which clinically relevant weight gain occurs following THA has important public health implications. Design: We used multi-variable logistic regression to compare data from one of the largest US-based THA registries to a population-based control sample from the same geographic region. We also identified factors that increased risk of clinically important weight gain specifically among persons undergoing THA. The outcome measure of interest was weight gain of >= 5% of body weight up to 5 years following surgery. Results: The multi-variable adjusted [age, sex, body mass index (BMI), education, comorbidity and presurgical weight change] odds ratio for important weight gain was 1.7 [95% confidence interval (CI), 1.06, 2.6] for a person with THA as compared to the control sample. Additional arthroplasty procedures during the 5-year follow-up further increased odds for important weight gain (OR = 2.0, 95% CI, 1.4, 2.7) relative to the control sample. A patient with THA had increased risk of important post-surgical weight gain of 12% (OR = 1.12, 95% CI, 1.08, 1.16) for every kilogram of pre-operative weight loss. Conclusions: While findings should be interpreted with caution because of missing follow-up weight data, patients with THA appear to be at increased risk of clinically important weight gain following surgery as compared to peers. Patients less than 60 years and who have lost a substantial amount of weight prior to surgery appear to be at particularly high risk of important post-surgical weight gain. (C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 [Riddle, D. L.] Virginia Commonwealth Univ, Dept Phys Therapy, Richmond, VA 23298 USA. [Riddle, D. L.] Virginia Commonwealth Univ, Dept Orthopaed Surg, Richmond, VA 23298 USA. [Singh, J. A.] Univ Alabama Birmingham, Mayo Clin, Birmingham Vet Affairs Med Ctr, Rochester, MN USA. [Harmsen, W. S.; Schleck, C. D.; Lewallen, D. G.] Mayo Clin, Rochester, MN USA. RP Riddle, DL (reprint author), Virginia Commonwealth Univ, Dept Phys Therapy, POB 980224, Richmond, VA 23298 USA. EM dlriddle@vcu.edu; jasvinder.md@gmail.com; william.harmsen@mayo.edu; schleck@mayo.edu; lewallen.david@mayo.edu OI singh, jasvinder/0000-0003-3485-0006 FU Virginia Commonwealth University Presidential Research Initiative Program; Allergan; Takeda; Savient; Zimmer; DePuy; Stryker FX The study was funded by a grant from the Virginia Commonwealth University Presidential Research Initiative Program. The funding source played no role in the design, data collection or reporting of the study.; Dr. Singh has received grants from Allergan, Takeda, Savient and is a consultant with Allergan, Takeda, Savient, URL, Regeneron, Ardea and Novartis. Dr. Lewallen has received royalties/speaker fees from Zimmer, has been a paid consultant to Zimmer and has received institutional research funds from DePuy, Stryker and Zimmer. NR 51 TC 5 Z9 5 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD JAN PY 2013 VL 21 IS 1 BP 35 EP 43 DI 10.1016/j.joca.2012.09.010 PG 9 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 083QL UT WOS:000314480200006 PM 23047011 ER PT J AU Ofman, P Rahilly-Tierney, C Djousse, L Peralta, A Hoffmeister, P Gaziano, JM Weiss, A Lotan, C Rosenheck, S AF Ofman, Peter Rahilly-Tierney, Catherine Djousse, Luc Peralta, Adelqui Hoffmeister, Peter Gaziano, J. Michael Weiss, Alexey Lotan, Chaim Rosenheck, Shimon TI Pacing System Malfunction is a Rare Cause of Hospital Admission for Syncope in Patients with a Permanent Pacemaker SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE clinical electrophysiology; permanent pacemaker; syncope AB Background: Few studies have examined the prevalence of permanent pacemaker (PPM) malfunction among patients with a previously implanted pacemaker admitted to the hospital with syncope. Objective: This study sought to examine causes of syncope in patients with a previously implanted pacemaker admitted to our hospital with syncope. Methods: We retrospectively reviewed our hospital admission database for patients who had both keywords "syncope" and "pacemaker" as their diagnoses from January 1, 1995 until June 1, 2012. One hundred and sixty-two patients who were admitted to the hospital because of syncope and had a PPM implanted prior to the index syncopal episode were included. All patients had pacemakers interrogated during the admission. Two independent physicians examined the discharge summary of each patient and determined the cause of syncope in each case. Results: Of the 162 patients studied, eight (4.9%) were found to have pacemaker system malfunction as a cause of syncope. In 96 patients (59.2%), the cause of syncope could not be determined prior to hospital discharge. Among the identifiable causes of syncope, orthostatic hypotension was most prevalent (16%) followed by vasovagal (6%), severe aortic stenosis (4.3%), atrial arrhythmia (3.1%), acute and subacute infection (3.1%), and other less prevalent causes (3.1%). Conclusion: In this study, PPM system malfunction was rarely a cause of syncope in patients admitted to the hospital with a previously implanted device. (PACE 2013; 36: 109-112) C1 [Ofman, Peter; Weiss, Alexey; Lotan, Chaim; Rosenheck, Shimon] Hadassah Hebrew Univ, Dept Cardiol, Med Ctr, Jerusalem, Israel. [Ofman, Peter; Rahilly-Tierney, Catherine; Djousse, Luc; Gaziano, J. Michael] Boston Vet Affairs Healthcare Syst, Massachusetts Vet Epidemiol & Res Informat Ctr MA, Boston, MA USA. [Ofman, Peter; Peralta, Adelqui; Hoffmeister, Peter; Gaziano, J. Michael] VA Boston Healthcare Syst, Dept Med, Div Cardiol, Boston, MA USA. [Ofman, Peter; Rahilly-Tierney, Catherine; Djousse, Luc; Peralta, Adelqui; Hoffmeister, Peter; Gaziano, J. Michael] Harvard Univ, Sch Med, Boston, MA USA. [Ofman, Peter; Rahilly-Tierney, Catherine; Djousse, Luc; Gaziano, J. Michael] Brigham & Women Hosp, Dept Med, Div Aging, Boston, MA USA. [Ofman, Peter; Gaziano, J. Michael] Brigham & Women Hosp, Div Prevent Med, Boston, MA USA. [Djousse, Luc; Gaziano, J. Michael] Boston Vet Affairs Healthcare Syst, Geriatr Res Educ & Clin Ctr GRECC, Boston, MA USA. RP Ofman, P (reprint author), VA Boston Healthcare Syst, Dept Med, Div Cardiol, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM Peter.Ofman@va.gov RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 NR 5 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD JAN PY 2013 VL 36 IS 1 BP 109 EP 112 DI 10.1111/pace.12041 PG 4 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 086BS UT WOS:000314658600025 PM 23121111 ER PT J AU Selimyan, R Gerstein, RM Ivanova, I Precht, P Subrahmanyam, R Perlot, T Alt, FW Sen, R AF Selimyan, Roza Gerstein, Rachel M. Ivanova, Irina Precht, Patricia Subrahmanyam, Ramesh Perlot, Thomas Alt, Frederick W. Sen, Ranjan TI Localized DNA Demethylation at Recombination Intermediates during Immunoglobulin Heavy Chain Gene Assembly SO PLOS BIOLOGY LA English DT Article ID V(D)J RECOMBINATION; INTRONIC ENHANCER; LYMPHOCYTE DEVELOPMENT; HISTONE MODIFICATIONS; TRANSGENIC SUBSTRATE; METHYLATION PATTERNS; IGH LOCUS; REARRANGEMENT; TRANSCRIPTION; MU AB Multiple epigenetic marks have been proposed to contribute to the regulation of antigen receptor gene assembly via V(D)J recombination. Here we provide a comprehensive view of DNA methylation at the immunoglobulin heavy chain (IgH) gene locus prior to and during V(D) J recombination. DNA methylation did not correlate with the histone modification state on unrearranged alleles, indicating that these epigenetic marks were regulated independently. Instead, pockets of tissue-specific demethylation were restricted to DNase I hypersensitive sites within this locus. Though unrearranged diversity (D-H) and joining (J(H)) gene segments were methylated, DJ(H) junctions created after the first recombination step were largely demethylated in pro-, pre-, and mature B cells. Junctional demethylation was highly localized, B-lineage-specific, and required an intact tissue-specific enhancer, E mu. We propose that demethylation occurs after the first recombination step and may mark the junction for secondary recombination. C1 [Selimyan, Roza; Ivanova, Irina; Precht, Patricia; Subrahmanyam, Ramesh; Sen, Ranjan] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. [Gerstein, Rachel M.] Univ Massachusetts, Sch Med, Dept Mol Genet & Microbiol, Worcester, MA 01655 USA. [Perlot, Thomas] Childrens Hosp, Howard Hughes Med Inst, Immune Dis Inst, Boston, MA 02115 USA. [Perlot, Thomas; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Selimyan, R (reprint author), NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. EM senranja@grc.nia.nih.gov FU NIH [AI 2047, AI 43534]; Intramural Research Program of the National Institute on Aging (Baltimore, MD); NIH NIDDK Diabetes Endocrinology Research Center [5 P30DK32520] FX This work was supported by NIH grant AI 2047 (to F. W. A.) and AI 43534 (to R. M. G.), and by the Intramural Research Program of the National Institute on Aging (Baltimore, MD). The U-Mass Medical School Flow Cytometry Core is supported by NIH NIDDK Diabetes Endocrinology Research Center grant 5 P30DK32520. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 7 Z9 7 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1545-7885 J9 PLOS BIOL JI PLoS. Biol. PD JAN PY 2013 VL 11 IS 1 AR e1001475 DI 10.1371/journal.pbio.1001475 PG 14 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 085XX UT WOS:000314648700015 PM 23382652 ER PT J AU Beck, AH Knoblauch, NW Hefti, MM Kaplan, J Schnitt, SJ Culhane, AC Schroeder, MS Risch, T Quackenbush, J Haibe-Kains, B AF Beck, Andrew H. Knoblauch, Nicholas W. Hefti, Marco M. Kaplan, Jennifer Schnitt, Stuart J. Culhane, Aedin C. Schroeder, Markus S. Risch, Thomas Quackenbush, John Haibe-Kains, Benjamin TI Significance Analysis of Prognostic Signatures SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID NEGATIVE BREAST-CANCER; SET ENRICHMENT ANALYSIS; GENE-EXPRESSION; MOLECULAR SUBTYPES; HISTOLOGIC GRADE; CHEMOTHERAPY; METAANALYSIS; PROFILES; REVEALS; HYPOXIA AB A major goal in translational cancer research is to identify biological signatures driving cancer progression and metastasis. A common technique applied in genomics research is to cluster patients using gene expression data from a candidate prognostic gene set, and if the resulting clusters show statistically significant outcome stratification, to associate the gene set with prognosis, suggesting its biological and clinical importance. Recent work has questioned the validity of this approach by showing in several breast cancer data sets that "random'' gene sets tend to cluster patients into prognostically variable subgroups. This work suggests that new rigorous statistical methods are needed to identify biologically informative prognostic gene sets. To address this problem, we developed Significance Analysis of Prognostic Signatures (SAPS) which integrates standard prognostic tests with a new prognostic significance test based on stratifying patients into prognostic subtypes with random gene sets. SAPS ensures that a significant gene set is not only able to stratify patients into prognostically variable groups, but is also enriched for genes showing strong univariate associations with patient prognosis, and performs significantly better than random gene sets. We use SAPS to perform a large meta-analysis (the largest completed to date) of prognostic pathways in breast and ovarian cancer and their molecular subtypes. Our analyses show that only a small subset of the gene sets found statistically significant using standard measures achieve significance by SAPS. We identify new prognostic signatures in breast and ovarian cancer and their corresponding molecular subtypes, and we show that prognostic signatures in ER negative breast cancer are more similar to prognostic signatures in ovarian cancer than to prognostic signatures in ER positive breast cancer. SAPS is a powerful new method for deriving robust prognostic biological signatures from clinically annotated genomic datasets. C1 [Beck, Andrew H.; Knoblauch, Nicholas W.; Hefti, Marco M.; Kaplan, Jennifer; Schnitt, Stuart J.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Beck, Andrew H.; Knoblauch, Nicholas W.; Hefti, Marco M.; Kaplan, Jennifer; Schnitt, Stuart J.] Harvard Univ, Sch Med, Boston, MA USA. [Culhane, Aedin C.; Schroeder, Markus S.; Risch, Thomas; Quackenbush, John] Dana Farber Canc Inst, Boston, MA 02115 USA. [Culhane, Aedin C.; Schroeder, Markus S.; Risch, Thomas; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Haibe-Kains, Benjamin] IRCM, Bioinformat & Computat Genom Lab, Montreal, PQ, Canada. RP Beck, AH (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA. EM abeck2@bidmc.harvard.edu; bhaibeka@ircm.qc.ca RI Haibe-Kains, Benjamin/D-3702-2011 OI Haibe-Kains, Benjamin/0000-0002-7684-0079 FU Klarman Family Foundation FX AHB was supported by an award from the Klarman Family Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 17 Z9 16 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD JAN PY 2013 VL 9 IS 1 AR e1002875 DI 10.1371/journal.pcbi.1002875 PG 17 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 085ED UT WOS:000314595600031 PM 23365551 ER PT J AU Koren, O Knights, D Gonzalez, A Waldron, L Segata, N Knight, R Huttenhower, C Ley, RE AF Koren, Omry Knights, Dan Gonzalez, Antonio Waldron, Levi Segata, Nicola Knight, Rob Huttenhower, Curtis Ley, Ruth E. TI A Guide to Enterotypes across the Human Body: Meta-Analysis of Microbial Community Structures in Human Microbiome Datasets SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID GUT MICROBIOTA; VALIDATION; HABITATS; DIET AB Recent analyses of human-associated bacterial diversity have categorized individuals into 'enterotypes' or clusters based on the abundances of key bacterial genera in the gut microbiota. There is a lack of consensus, however, on the analytical basis for enterotypes and on the interpretation of these results. We tested how the following factors influenced the detection of enterotypes: clustering methodology, distance metrics, OTU-picking approaches, sequencing depth, data type (whole genome shotgun (WGS) vs. 16S rRNA gene sequence data), and 16S rRNA region. We included 16S rRNA gene sequences from the Human Microbiome Project (HMP) and from 16 additional studies and WGS sequences from the HMP and MetaHIT. In most body sites, we observed smooth abundance gradients of key genera without discrete clustering of samples. Some body habitats displayed bimodal (e.g., gut) or multimodal (e.g., vagina) distributions of sample abundances, but not all clustering methods and workflows accurately highlight such clusters. Because identifying enterotypes in datasets depends not only on the structure of the data but is also sensitive to the methods applied to identifying clustering strength, we recommend that multiple approaches be used and compared when testing for enterotypes. C1 [Koren, Omry; Ley, Ruth E.] Cornell Univ, Dept Microbiol, Ithaca, NY 14853 USA. [Knights, Dan; Gonzalez, Antonio] Univ Colorado, Dept Comp Sci, Boulder, CO 80309 USA. [Waldron, Levi; Segata, Nicola; Huttenhower, Curtis] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Waldron, Levi] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Knight, Rob] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA. [Knight, Rob] Univ Colorado, Howard Hughes Med Inst, Boulder, CO 80309 USA. RP Koren, O (reprint author), Cornell Univ, Dept Microbiol, Ithaca, NY 14853 USA. EM rel222@cornell.edu RI Ley, Ruth/M-8542-2014; Knight, Rob/D-1299-2010; OI Ley, Ruth/0000-0002-9087-1672; Waldron, Levi/0000-0003-2725-0694; Koren, Omry/0000-0002-7738-1337; Huttenhower, Curtis/0000-0002-1110-0096; Segata, Nicola/0000-0002-1583-5794 FU HMP DACC [HG4866]; Hartwell Foundation; Arnold and Mabel Beckman Foundation; David and Lucile Packard Foundation; National Science Foundation [DBI-1053486]; National Institutes of Health [HG4872, 1R01HG005969]; Danone [PLF-5972-GD]; Crohns and Colitis Foundation of America; Howard Hughes Medical Institute FX This research was supported by the HMP DACC (HG4866), The Hartwell Foundation (REL), the Arnold and Mabel Beckman Foundation (REL), the David and Lucile Packard Foundation (REL), the National Science Foundation (DBI-1053486 to CH), the National Institutes of Health (HG4872 to RK and 1R01HG005969 to CH), Danone (PLF-5972-GD to CH), the Crohns and Colitis Foundation of America (RK), and the Howard Hughes Medical Institute (RK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 137 Z9 141 U1 7 U2 111 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD JAN PY 2013 VL 9 IS 1 AR e1002863 DI 10.1371/journal.pcbi.1002863 PG 16 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 085ED UT WOS:000314595600021 PM 23326225 ER PT J AU De, S Shaknovich, R Riester, M Elemento, O Geng, HM Kormaksson, M Jiang, YW Woolcock, B Johnson, N Polo, JM Cerchietti, L Gascoyne, RD Melnick, A Michor, F AF De, Subhajyoti Shaknovich, Rita Riester, Markus Elemento, Olivier Geng, Huimin Kormaksson, Matthias Jiang, Yanwen Woolcock, Bruce Johnson, Nathalie Polo, Jose M. Cerchietti, Leandro Gascoyne, Randy D. Melnick, Ari Michor, Franziska TI Aberration in DNA Methylation in B-Cell Lymphomas Has a Complex Origin and Increases with Disease Severity SO PLOS GENETICS LA English DT Article ID NON-HODGKINS-LYMPHOMA; CYTOSINE METHYLATION; FOLLICULAR LYMPHOMA; BINDING-SITES; GENOME-WIDE; EXPRESSION; GENE; BCL6; AID; DEMETHYLATION AB Despite mounting evidence that epigenetic abnormalities play a key role in cancer biology, their contributions to the malignant phenotype remain poorly understood. Here we studied genome-wide DNA methylation in normal B-cell populations and subtypes of B-cell non-Hodgkin lymphoma: follicular lymphoma and diffuse large B-cell lymphomas. These lymphomas display striking and progressive intra-tumor heterogeneity and also inter-patient heterogeneity in their cytosine methylation patterns. Epigenetic heterogeneity is initiated in normal germinal center B-cells, increases markedly with disease aggressiveness, and is associated with unfavorable clinical outcome. Moreover, patterns of abnormal methylation vary depending upon chromosomal regions, gene density and the status of neighboring genes. DNA methylation abnormalities arise via two distinct processes: i) lymphomagenic transcriptional regulators perturb promoter DNA methylation in a target gene-specific manner, and ii) aberrant epigenetic states tend to spread to neighboring promoters in the absence of CTCF insulator binding sites. C1 [De, Subhajyoti] Univ Colorado, Dept Med, Sch Med, Aurora, CO USA. [De, Subhajyoti] Univ Colorado, Mol Oncol Program, Ctr Canc, Aurora, CO USA. [Shaknovich, Rita; Geng, Huimin; Jiang, Yanwen; Melnick, Ari] Weill Cornell Med Coll, Div Hematol Oncol, Dept Med, New York, NY USA. [Shaknovich, Rita; Cerchietti, Leandro] Weill Cornell Med Coll, Div Immunopathol, Dept Pathol, New York, NY USA. [Riester, Markus; Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Riester, Markus; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Elemento, Olivier; Geng, Huimin] Weill Cornell Med Coll, Inst Computat Biomed, New York, NY USA. [Kormaksson, Matthias] Weill Cornell Med Coll, Div Biostat & Epidemiol, Dept Publ Hlth, New York, NY USA. [Woolcock, Bruce; Johnson, Nathalie; Gascoyne, Randy D.] British Columbia Canc Agcy, British Columbia Canc Res Ctr, Ctr Lymphoid Canc, Vancouver, BC V5Z 4E6, Canada. [Woolcock, Bruce; Johnson, Nathalie; Gascoyne, Randy D.] British Columbia Canc Agcy, Dept Pathol, British Columbia Canc Res Ctr, Vancouver, BC V5Z 4E6, Canada. [Woolcock, Bruce; Johnson, Nathalie; Gascoyne, Randy D.] British Columbia Canc Agcy, Dept Expt Therapeut, British Columbia Canc Res Ctr, Vancouver, BC V5Z 4E6, Canada. [Polo, Jose M.] Monash Univ, Monash Immunol & Stem Cell Labs, Clayton, Vic, Australia. RP De, S (reprint author), Univ Colorado, Dept Med, Sch Med, Aurora, CO USA. EM amm2014@med.cornell.edu; michor@jimmy.harvard.edu OI Cerchietti, Leandro/0000-0003-0608-1350; Riester, Markus/0000-0002-4759-8332 FU NCI/NIH FX This work was supported by the NCI/NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 52 Z9 52 U1 1 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2013 VL 9 IS 1 AR e1003137 DI 10.1371/journal.pgen.1003137 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 085YZ UT WOS:000314651500008 PM 23326238 ER PT J AU Vijai, J Kirchhoff, T Schrader, KA Brown, J Dutra-Clarke, AV Manschreck, C Hansen, N Rau-Murthy, R Sarrel, K Przybylo, J Shah, S Cheguri, S Stadler, Z Zhang, LY Paltiel, O Ben-Yehuda, D Viale, A Portlock, C Straus, D Lipkin, SM Lacher, M Robson, M Klein, RJ Zelenetz, A Offit, K AF Vijai, Joseph Kirchhoff, Tomas Schrader, Kasmintan A. Brown, Jennifer Dutra-Clarke, Ana Virginia Manschreck, Christopher Hansen, Nichole Rau-Murthy, Rohini Sarrel, Kara Przybylo, Jennifer Shah, Sohela Cheguri, Srujana Stadler, Zsofia Zhang, Liying Paltiel, Ora Ben-Yehuda, Dina Viale, Agnes Portlock, Carol Straus, David Lipkin, Steven M. Lacher, Mortimer Robson, Mark Klein, Robert J. Zelenetz, Andrew Offit, Kenneth TI Susceptibility Loci Associated with Specific and Shared Subtypes of Lymphoid Malignancies SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; LONG-TERM SURVIVORS; FOLLICULAR LYMPHOMA; HODGKINS-LYMPHOMA; VISUALIZATION; METAANALYSIS; GENES; RISK; VARIANTS; PAXILLIN AB The genetics of lymphoma susceptibility reflect the marked heterogeneity of diseases that comprise this broad phenotype. However, multiple subtypes of lymphoma are observed in some families, suggesting shared pathways of genetic predisposition to these pathologically distinct entities. Using a two-stage GWAS, we tested 530,583 SNPs in 944 cases of lymphoma, including 282 familial cases, and 4,044 public shared controls, followed by genotyping of 50 SNPs in 1,245 cases and 2,596 controls. A novel region on 11q12.1 showed association with combined lymphoma (LYM) subtypes. SNPs in this region included rs12289961 near LPXN, (P-LYM = 3.89x10(-8), OR = 1.29) and rs948562 (P-LYM = 5.85x10(-7), OR = 1.29). A SNP in a novel non-HLA region on 6p23 (rs707824, P-NHL = 5.72x10(-7)) was suggestive of an association conferring susceptibility to lymphoma. Four SNPs, all in a previously reported HLA region, 6p21.32, showed genome-wide significant associations with follicular lymphoma. The most significant association with follicular lymphoma was for rs4530903 (P-FL = 2.69x10(-12), OR = 1.93). Three novel SNPs near the HLA locus, rs9268853, rs2647046, and rs2621416, demonstrated additional variation contributing toward genetic susceptibility to FL associated with this region. Genes implicated by GWAS were also found to be cis-eQTLs in lymphoblastoid cell lines; candidate genes in these regions have been implicated in hematopoiesis and immune function. These results, showing novel susceptibility regions and allelic heterogeneity, point to the existence of pathways of susceptibility to both shared as well as specific subtypes of lymphoid malignancy. C1 [Vijai, Joseph; Schrader, Kasmintan A.; Dutra-Clarke, Ana Virginia; Manschreck, Christopher; Hansen, Nichole; Rau-Murthy, Rohini; Sarrel, Kara; Przybylo, Jennifer; Shah, Sohela; Cheguri, Srujana; Stadler, Zsofia; Robson, Mark; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10021 USA. [Vijai, Joseph; Schrader, Kasmintan A.; Shah, Sohela; Klein, Robert J.; Offit, Kenneth] Sloan Kettering Inst, Canc Biol & Genet Program, New York, NY USA. [Kirchhoff, Tomas] NYU, Sch Med, Inst Canc, New York, NY USA. [Brown, Jennifer] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zhang, Liying] Mem Sloan Kettering Canc Ctr, Dept Pathol, Diagnost Mol Genet Lab, New York, NY 10021 USA. [Paltiel, Ora; Ben-Yehuda, Dina] Hadassah Hebrew Univ, Med Ctr, Dept Hematol, Jerusalem, Israel. [Viale, Agnes] Mem Sloan Kettering Canc Ctr, Genom Core, New York, NY 10021 USA. [Portlock, Carol; Straus, David; Lacher, Mortimer; Zelenetz, Andrew; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Dept Med, Lymphoma Serv, New York, NY 10021 USA. [Lipkin, Steven M.] Weill Cornell Med Ctr, New York, NY USA. RP Vijai, J (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, 1275 York Ave, New York, NY 10021 USA. EM offitk@mskcc.org RI Joseph, Vijai/J-9158-2013; Klein, Robert/K-1888-2013; OI Joseph, Vijai/0000-0002-7933-151X; Klein, Robert/0000-0003-3539-5391; Zelenetz, Andrew/0000-0003-1403-6883; Robson, Mark/0000-0002-3109-1692; Kirchhoff, Tomas/0000-0002-9055-2364 FU Lymphoma Foundation [LF5541]; Barbara K. Lipman Lymphoma Research Fund [74419]; Robert and Kate Niehaus Clinical Cancer Genetics Research Initiative [57470]; Niehaus fellowship; Koodish Fellowship; Sabin Family Research Fund; Sharon Corzine Research Initiative; Israel Science Foundation; NIH [K23 CA115682, CA CA167824]; Melton Fund; Rosenbach Fund; Weill Cornell Clinical and Translational Science Award Pilot Grant; TRP grant from Leukemia and Lymphoma Society [TRP 6202-09] FX We are grateful to the Lymphoma Foundation (LF5541, http://www.lymphomafoundation.org/), the Barbara K. Lipman Lymphoma Research Fund (74419), the Robert and Kate Niehaus Clinical Cancer Genetics Research Initiative (57470), Niehaus fellowship (JV), the Koodish Fellowship (to SS, KS, 6773), the Sabin Family Research Fund, the Sharon Corzine Research Initiative, the Israel Science Foundation, and Arlene Reisman and Matthew Bell. JB was supported by NIH K23 CA115682 and by the Melton and Rosenbach Funds, and is a Scholar of the American Society of Hematology as well as a Scholar in Clinical Research of the Leukemia and Lymphoma Society. KO, SML, JV, and RJK were supported by NIH CA CA167824 and a Weill Cornell Clinical and Translational Science Award Pilot Grant. TK was supported by TRP grant from Leukemia and Lymphoma Society (TRP 6202-09). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 21 Z9 21 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2013 VL 9 IS 1 AR e1003220 DI 10.1371/journal.pgen.1003220 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 085YZ UT WOS:000314651500061 PM 23349640 ER PT J AU Xu, C Wang, P Liu, Y Zhang, YZ Fan, WH Upton, MP Lohavanichbutr, P Houck, JR Doody, DR Futran, ND Zhao, LP Schwartz, SM Chen, C Mendez, E AF Xu, Chang Wang, Pei Liu, Yan Zhang, Yuzheng Fan, Wenhong Upton, Melissa P. Lohavanichbutr, Pawadee Houck, John R. Doody, David R. Futran, Neal D. Zhao, Lue Ping Schwartz, Stephen M. Chen, Chu Mendez, Eduardo TI Integrative Genomics in Combination with RNA Interference Identifies Prognostic and Functionally Relevant Gene Targets for Oral Squamous Cell Carcinoma SO PLOS GENETICS LA English DT Article ID GTPASE-ACTIVATING PROTEIN; BREAST-CANCER METASTASIS; LYMPH-NODE METASTASIS; DNA COPY NUMBER; OROPHARYNGEAL CANCER; EXPRESSION PROFILES; BINDING-PROTEIN; NECK-CANCER; P53 NETWORK; HEAD AB In oral squamous cell carcinoma (OSCC), metastasis to lymph nodes is associated with a 50% reduction in 5-year survival. To identify a metastatic gene set based on DNA copy number abnormalities (CNAs) of differentially expressed genes, we compared DNA and RNA of OSCC cells laser-microdissected from non-metastatic primary tumors (n = 17) with those from lymph node metastases (n = 20), using Affymetrix 250K Nsp single-nucleotide polymorphism (SNP) arrays and U133 Plus 2.0 arrays, respectively. With a false discovery rate (FDR)<5%, 1988 transcripts were found to be differentially expressed between primary and metastatic OSCC. Of these, 114 were found to have a significant correlation between DNA copy number and gene expression (FDR<0.01). Among these 114 correlated transcripts, the corresponding genomic regions of each of 95 transcripts had CNAs differences between primary and metastatic OSCC (FDR<0.01). Using an independent dataset of 133 patients, multivariable analysis showed that the OSCC-specific and overall mortality hazards ratio (HR) for patients carrying the 95-transcript signature were 4.75 (95% CI: 2.03-11.11) and 3.45 (95% CI: 1.84-6.50), respectively. To determine the degree by which these genes impact cell survival, we compared the growth of five OSCC cell lines before and after knockdown of over-amplified transcripts via a high-throughput siRNA-mediated screen. The expression-knockdown of 18 of the 26 genes tested showed a growth suppression >= 30% in at least one cell line (P<0.01). In particular, cell lines derived from late-stage OSCC were more sensitive to the knockdown of G3BP1 than cell lines derived from early-stage OSCC, and the growth suppression was likely caused by increase in apoptosis. Further investigation is warranted to examine the biological role of these genes in OSCC progression and their therapeutic potentials. C1 [Xu, Chang; Futran, Neal D.; Chen, Chu; Mendez, Eduardo] Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. [Xu, Chang; Mendez, Eduardo] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Wang, Pei; Liu, Yan; Zhang, Yuzheng; Fan, Wenhong; Lohavanichbutr, Pawadee; Houck, John R.; Doody, David R.; Zhao, Lue Ping; Schwartz, Stephen M.; Chen, Chu] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Wang, Pei; Zhao, Lue Ping] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Upton, Melissa P.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Schwartz, Stephen M.; Chen, Chu] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Mendez, Eduardo] VA Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, Seattle, WA USA. RP Xu, C (reprint author), Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. EM edmendez@u.washington.edu OI Schwartz, Stephen/0000-0001-7499-8502 FU National Center for Research Resources, National Institutes of Health (NIH) [5KL2RR025015-03]; Robert Wood Johnson Foundation; Howard Hughes Medical Institute; National Cancer Institute, NIH [R01CA095419]; Institute of Translational Health Sciences, University of Washington; National Center for Research Resources, NIH [UL1RR025014]; Department of Otolaryngology-Head and Neck Surgery, University of Washington; VA Puget Sound Health Care System, Fred Hutchinson Cancer Research Center, University of Washington Medical Center; Harborview Medical Center, Seattle, Washington FX This work was supported in part by grants 5KL2RR025015-03 from National Center for Research Resources, National Institutes of Health (NIH); Amos Medical Faculty Development Program Award from The Robert Wood Johnson Foundation; Early Physician-Scientist Career Development Award from the Howard Hughes Medical Institute; R01CA095419 from the National Cancer Institute, NIH; Small Grants Translational Research Projects Award from the Institute of Translational Health Sciences, University of Washington, supported by grant UL1RR025014 from the National Center for Research Resources, NIH; center funds from the Department of Otolaryngology-Head and Neck Surgery, University of Washington; and by resources from and use of facilities at the VA Puget Sound Health Care System, Fred Hutchinson Cancer Research Center, University of Washington Medical Center and Harborview Medical Center, Seattle, Washington. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 5 Z9 5 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2013 VL 9 IS 1 AR e1003169 DI 10.1371/journal.pgen.1003169 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 085YZ UT WOS:000314651500022 PM 23341773 ER PT J AU Purohit, MP Wells, RE Zafonte, RD Davis, RB Phillips, RS AF Purohit, Maulik P. Wells, Rebecca Erwin Zafonte, Ross D. Davis, Roger B. Phillips, Russell S. TI Neuropsychiatric Symptoms and the Use of Complementary and Alternative Medicine SO PM&R LA English DT Article ID COMMON NEUROLOGICAL CONDITIONS; STRESS REDUCTION; UNITED-STATES; DEPRESSION; THERAPIES; ADULTS; SURVIVORS; PATTERNS; ANXIETY; STROKE AB Objectives: To assess the prevalence of complementary and alternative medicine (CAM) use by U.S. adults reporting neuropsychiatric symptoms and whether this prevalence changes based on the number of symptoms reported. Additional objectives include identifying patterns of CAM use, reasons for use, and disclosure of use with conventional providers in U.S. adults with neuropsychiatric symptoms. Design: Secondary database analysis of a prospective survey. Participants: A total of 23,393 U.S. adults from the 2007 National Health Interview Survey. Methods: We compared CAM use between adults with and without neuropsychiatric symptoms. Symptoms included self-reported anxiety, depression, insomnia, headaches, memory deficits, attention deficits, and excessive sleepiness. CAM use was defined as use of mind-body therapies (eg, meditation), biological therapies (eg, herbs), or manipulation therapies (eg, massage) or alternative medical systems (eg, Ayurveda). Statistical analysis included bivariable comparisons and multivariable logistical regression analyses. Main Outcome Measures: The prevalence of CAM use among adults with neuropsychiatric symptoms within the previous 12 months and the comparison of CAM use between those with and without neuropsychiatric symptoms. Results: Adults with neuropsychiatric symptoms had a greater prevalence of CAM use compared with adults who did not have neuropsychiatric symptoms (43.8% versus 29.7%, P < .001); this prevalence increased with an increasing number of symptoms (trend, P < .001). Differences in the likelihood of CAM use as determined by the number of symptoms persisted after we adjusted for covariates. Twenty percent of patients used CAM because standard treatments were either too expensive or ineffective, and 25% used CAM because it was recommended by a conventional provider. Adults with at least one neuropsychiatric symptom were more likely to disclose the use of CAM to a conventional provider (47.9% versus 39.0%, P < .001). Conclusion: More than 40% of adults with neuropsychiatric symptoms commonly observed in many diagnoses use CAM; an increasing number of symptoms was associated with an increased likelihood of CAM use. PM R 2013;5:24-31 C1 [Purohit, Maulik P.; Zafonte, Ross D.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Boston, MA 02114 USA. [Purohit, Maulik P.; Zafonte, Ross D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Purohit, Maulik P.; Davis, Roger B.; Phillips, Russell S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02114 USA. [Wells, Rebecca Erwin] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02114 USA. [Wells, Rebecca Erwin] Harvard Univ, Sch Med, Faulkner Hosp, Boston, MA 02114 USA. RP Purohit, MP (reprint author), Harvard Univ, Sch Med, Spaulding Rehabil Hosp, 125 Nashua St,720, Boston, MA 02114 USA. EM mpurohit1@partners.org FU institutional National Research Service Award from the National Center for Complementary & Alternative Medicine (NCCAM), NIH [T32AT000051]; American Headache Society; NIDR [5R24HD065688-02]; Department of Defense; U.S. Food and Drug Administration orphan drug program; Neurohealing; [K24AT000589] FX support, institutional National Research Service Award #T32AT000051 from the National Center for Complementary & Alternative Medicine (NCCAM), NIH; support, institutional National Research Service Award #T32AT000051 from the NCCAM, NIH; headache fellowship, American Headache Society; support, Investigator Award #5R24HD065688-02, NIDR, and the Department of Defense; royalties, demos, Brain Injury Medicare test; stipend, PM&R senior editor; principal investigator on a study funded by the U.S. Food and Drug Administration orphan drug program in collaboration with Neurohealing; nonfinancial, member of Neurohealing's scientific advisory board ACRM, J of Neurotrauma; Mid-Career Investigator Award #K24AT000589; Mid-Career Investigator Award K24AT000589 NR 28 TC 9 Z9 9 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD JAN PY 2013 VL 5 IS 1 BP 24 EP 31 DI 10.1016/j.pmrj.2012.06.012 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 085KW UT WOS:000314614700005 PM 23098832 ER PT J AU Adeyemo, BO Nesathurai, S AF Adeyemo, Bamidele O. Nesathurai, Shanker TI The Original Description of Anton Syndrome SO PM&R LA English DT Letter C1 [Adeyemo, Bamidele O.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA 02163 USA. [Adeyemo, Bamidele O.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Adeyemo, Bamidele O.] Spaulding Rehabil Hosp, Lab Neuromodulat, Boston, MA USA. [Adeyemo, Bamidele O.] Massachusetts Gen Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Nesathurai, Shanker] Harvard Univ, Sch Med, Boston, MA USA. [Nesathurai, Shanker] McMaster Univ, Hamilton, ON, Canada. [Nesathurai, Shanker] Hamilton Hlth Sci, Dept PM&R, Hamilton, ON, Canada. RP Adeyemo, BO (reprint author), Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA 02163 USA. NR 7 TC 1 Z9 1 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD JAN PY 2013 VL 5 IS 1 BP 74 EP 74 DI 10.1016/j.pmrj.2012.09.580 PG 1 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 085KW UT WOS:000314614700016 PM 23332914 ER PT J AU Burguete, SR Maselli, DJ Fernandez, JF Levine, SM AF Burguete, Sergio R. Maselli, Diego J. Fernandez, Juan F. Levine, Stephanie M. TI Lung transplant infection SO RESPIROLOGY LA English DT Review DE Aspergillus; bacterial pneumonia; cytomegalovirus; immunosuppression; lung transplantation ID BRONCHIOLITIS-OBLITERANS-SYNDROME; RESPIRATORY VIRAL-INFECTIONS; INVASIVE FUNGAL-INFECTIONS; PNEUMOCYSTIS-CARINII-PNEUMONIA; BURKHOLDERIA-CEPACIA-COMPLEX; AEROSOLIZED AMPHOTERICIN-B; ANTI-THYMOCYTE GLOBULIN; CELL-MEDIATED-IMMUNITY; CYSTIC-FIBROSIS; RISK-FACTORS AB Lung transplantation has become an accepted therapeutic procedure for the treatment of end-stage pulmonary parenchymal and vascular disease. Despite improved survival rates over the decades, lung transplant recipients have lower survival rates than other solid organ transplant recipients. The morbidity and mortality following lung transplantation is largely due to infection-and rejection-related complications. This article will review the common infections that develop in the lung transplant recipient, including the general risk factors for infection in this population, and the most frequent bacterial, viral, fungal and other less frequent opportunistic infections. The epidemiology, diagnosis, prophylaxis, treatment and outcomes for the different microbial pathogens will be reviewed. The effects of infection on lung transplant rejection will also be discussed. C1 [Levine, Stephanie M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Pulm Dis & Crit Care Med, San Antonio, TX 78229 USA. S Texas Vet Healthcare Syst, San Antonio, TX USA. RP Levine, SM (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Pulm Dis & Crit Care Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM levines@uthscsa.edu NR 161 TC 15 Z9 17 U1 1 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1323-7799 J9 RESPIROLOGY JI Respirology PD JAN PY 2013 VL 18 IS 1 BP 22 EP 38 DI 10.1111/j.1440-1843.2012.02196.x PG 17 WC Respiratory System SC Respiratory System GA 078RD UT WOS:000314116100005 PM 22591266 ER PT J AU Jung, M Viswanath, K AF Jung, Minsoo Viswanath, K. TI Does community capacity influence self-rated health? Multilevel contextual effects in Seoul, Korea SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE Contextual effect; Community capacity; Community mobilization; Social capital; Multilevel analysis; Seoul; South Korea ID DEVELOPING INDICATORS; SOCIAL-ORGANIZATION; NEIGHBORHOOD; PROMOTION; SENSE; PARTICIPATION; DETERMINANTS; EMPOWERMENT; DIMENSIONS; MORTALITY AB This study examined the relationship between community-level contextual effects and self-rated health (SRH) based on the perspective of community capacity rather than social capital. Community capacity for mobilization is broad cooperation for networking among indigenous social agents and grassroots organizations that may serve as potential resources. The idea of community capacity is rooted in the philosophy that a community not only faces problems but also possesses the necessary resources to solve its problems. We used nationally representative data from South Korea, 2010, drawing on 14,228 residents in 404 communities. Community capacity was measured at two levels: an individual-level indicator of community satisfaction, and community-level indicators of participation rate in community organizations, number of community-based organizations (CBOs), and number of volunteer work camps (VWCs). The outcome variable was SRH, which was categorized into two groups: the low-SRH and high-SRH groups. Confounders included gender, age, and income at the individual level, and aggregate length of residency, financial independence ratio, and aggregate income at the community level. We estimated the effects of community capacity on SRH using hierarchical generalized linear models. The likelihood of belonging to the group having low-SRH is significantly high among those respondents living in places with lower community capacity at the community level, that report lower community satisfaction, and that have lower income at the individual level. After controlling for socio-economic confounders, the odds ratios were attenuated but remained significant in the final model, which included the gender-specific model. This study revealed that SRH is related to the level of community capacity for mobilization. It is probably because CBOs and VWCs not only provide necessary information and complementary services but also play an active role in identifying and resolving health problems therein. Thus, community capacity building warrants serious consideration for a community-based health promotion. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Jung, Minsoo; Viswanath, K.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Community Based Res, Boston, MA 02215 USA. [Jung, Minsoo; Viswanath, K.] Harvard Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA USA. RP Jung, M (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 450 Brookline Ave, Boston, MA 02215 USA. EM minsoo_jung@dfci.harvard.edu OI Jung, Minsoo/0000-0003-3317-6507 FU National Research Foundation of Korea; Korean Government [NRF-2011-357-E00028] FX This work was supported by National Research Foundation of Korea Grant funded by the Korean Government to Dr. Minsoo Jung (NRF-2011-357-E00028). NR 68 TC 8 Z9 8 U1 3 U2 26 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD JAN PY 2013 VL 77 BP 60 EP 69 DI 10.1016/j.socscimed.2012.11.005 PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 083TB UT WOS:000314487000009 PM 23232024 ER PT J AU Silvestrini, MT Yin, DL Coppes, VG Mann, P Martin, AJ Larson, PS Starr, PA Gupta, N Panter, SS Desai, TA Lim, DA AF Silvestrini, Matthew T. Yin, Dali Coppes, Valerie G. Mann, Preeti Martin, Alastair J. Larson, Paul S. Starr, Philip A. Gupta, Nalin Panter, S. Scott Desai, Tejal A. Lim, Daniel A. TI Radially Branched Deployment for More Efficient Cell Transplantation at the Scale of the Human Brain SO STEREOTACTIC AND FUNCTIONAL NEUROSURGERY LA English DT Article DE Radially branched deployment; Neural stem cell; Cell transplantation; Stereotactic surgery ID INTRACEREBRAL MICROINJECTION INSTRUMENT; FETAL STRIATAL TRANSPLANTATION; PARKINSONS-DISEASE; HUNTINGTONS-DISEASE; TECHNICAL NOTE; STEM-CELLS; HEMORRHAGIC COMPLICATIONS; NEURAL TRANSPLANTATION; AUTOMATED DELIVERY; IMPLANTATION AB Background: In preclinical studies, cell transplantation into the brain has shown great promise for the treatment of a wide range of neurological diseases. However, the use of a straight cannula and syringe for cell delivery to the human brain does not approximate cell distribution achieved in animal studies. This technical deficiency may limit the successful clinical translation of cell transplantation. Objective: To develop a stereotactic device that effectively distributes viable cells to the human brain. Our primary aims were to (1) minimize the number of transcortical penetrations required for transplantation, (2) reduce variability in cell dosing and (3) increase cell survival. Methods: We developed a modular cannula system capable of radially branched deployment (RBD) of a cell delivery catheter at variable angles from the longitudinal device axis. We also developed an integrated catheter-plunger system, eliminating the need for a separate syringe delivery mechanism. The RBD prototype was evaluated in vitro and in vivo with subcortical injections into the swine brain. Performance was compared to a 20G straight cannula with dual side ports, a device used in current clinical trials. Results: RBD enabled therapeutic delivery in a precise 'tree-like' pattern branched from a single initial trajectory, thereby facilitating delivery to a volumetrically large target region. RBD could transplant materials in a radial pattern up to 2.0 cm from the initial penetration tract. The novel integrated catheter-plunger system facilitated manual delivery of small and precise volumes of injection (1.36 +/- 0.13 mu l per cm of plunger travel). Both dilute and highly concentrated neural precursor cell populations tolerated transit through the device with high viability and unaffected developmental potential. While reflux of infusate along the penetration tract was problematic with the use of the 20G cannula, RBD was resistant to this source of cell dose variability in agarose. RBD enabled radial injections to the swine brain when used with a modern clinical stereotactic system. Conclusions: By increasing the total delivery volume through a single transcortical penetration in agarose models, RBD strategy may provide a new approach for cell transplantation to the human brain. Incorporation of RBD or selected aspects of its design into future clinical trials may increase the likelihood of successful translation of cell-based therapy to the human patient. Copyright (c) 2013 S. Karger AG, Basel C1 [Silvestrini, Matthew T.; Yin, Dali; Coppes, Valerie G.; Mann, Preeti; Larson, Paul S.; Starr, Philip A.; Gupta, Nalin; Panter, S. Scott; Lim, Daniel A.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Desai, Tejal A.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. [Martin, Alastair J.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Coppes, Valerie G.; Mann, Preeti; Panter, S. Scott; Lim, Daniel A.] San Francisco VA Med Ctr, Dept Surg, San Francisco, CA USA. [Lim, Daniel A.] Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA USA. RP Lim, DA (reprint author), Univ Calif San Francisco, Dept Neurol Surg, Ray & Dagmar Dolby Regenerat Med Bldg,35 Med Ctr, San Francisco, CA 94143 USA. EM LimD@neurosurg.ucsf.edu OI Lim, Daniel/0000-0001-7221-3425 FU California Institute for Regeneration Medicine [CIRM RT2-01975]; NIH grant [DP2-OD006505-01] FX This work was supported by a grant from the California Institute for Regeneration Medicine (CIRM RT2-01975) and NIH grant DP2-OD006505-01 to D.A.L. In addition, some aspects of this work were supported with resources and the use of facilities at the San Francisco Veterans Affairs Medical Center. NR 46 TC 7 Z9 7 U1 0 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1011-6125 J9 STEREOT FUNCT NEUROS JI Stereotact. Funct. Neurosurg. PY 2013 VL 91 IS 2 BP 92 EP 103 DI 10.1159/000343213 PG 12 WC Neurosciences; Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 086SO UT WOS:000314707500003 PM 23343609 ER PT J AU Boudsocq, M Sheen, J AF Boudsocq, Marie Sheen, Jen TI CDPKs in immune and stress signaling SO TRENDS IN PLANT SCIENCE LA English DT Review ID DEPENDENT PROTEIN-KINASE; REGULATED GENE-EXPRESSION; CALMODULIN-LIKE DOMAIN; ABSCISIC-ACID; GUARD-CELL; ARABIDOPSIS-THALIANA; ANION CHANNEL; ENDOPLASMIC-RETICULUM; TRANSCRIPTION FACTORS; OVER-EXPRESSION AB Ca2+ has long been recognized as a conserved second messenger and principal mediator in plant immune and stress responses. How Ca2+ signals are sensed and relayed into diverse primary and global signaling events is still largely unknown. Comprehensive analyses of the plant-specific multigene family of Ca2+-dependent protein kinases (CDPKs) are unraveling the molecular, cellular and genetic mechanisms of Ca2+ signaling. CDPKs, which exhibit overlapping and distinct expression patterns, sub-cellular localizations, substrate specificities and Ca2+ sensitivities, play versatile roles in the activation and repression of enzymes, channels and transcription factors. Here, we review the recent advances on the multifaceted functions of CDPKs in the complex immune and stress signaling networks, including oxidative burst, stomatal movements, hormonal signaling and gene regulation. C1 [Boudsocq, Marie] CNRS ERL8196, INRA UEVE UMR1165, Unite Rech Genom Vegetale, F-91057 Evry, France. [Sheen, Jen] Harvard Univ, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. [Sheen, Jen] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol,Dept Genet, Boston, MA 02114 USA. RP Boudsocq, M (reprint author), CNRS ERL8196, INRA UEVE UMR1165, Unite Rech Genom Vegetale, 2 Rue Gaston Cremieux, F-91057 Evry, France. EM boudsocq@evry.inra.fr FU National Science Foundation; National Institutes of Health; Marie Curie International fellowship within the 6th European Community Framework Program FX The projects on CDPK signaling have been supported by the National Science Foundation and the National Institutes of Health (J.S.). M.B. was supported by a Marie Curie International fellowship within the 6th European Community Framework Program. NR 100 TC 96 Z9 107 U1 8 U2 100 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1360-1385 J9 TRENDS PLANT SCI JI Trends Plant Sci. PD JAN PY 2013 VL 18 IS 1 BP 30 EP 40 DI 10.1016/j.tplants.2012.08.008 PG 11 WC Plant Sciences SC Plant Sciences GA 077BF UT WOS:000314002200005 PM 22974587 ER PT J AU Fishman, JA AF Fishman, Jay A. TI Microbiological safety of xenotransplantation compared with allotransplantation SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Berlin Symposium on Xenotransplantation in association with the 24th International Congress of the Transplantation-Society (TTS) CY JUL 13-19, 2012 CL Robert Koch Inst, Berlin, GERMANY SP Transplantat Soc (TTS), Int Xenotransplantat Assoc (IXA) HO Robert Koch Inst ID INFECTIOUS RISK C1 [Fishman, Jay A.] Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, MGH Transplant Ctr, Boston, MA 02114 USA. [Fishman, Jay A.] Harvard Univ, Sch Med, Boston, MA USA. NR 2 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JAN-FEB PY 2013 VL 20 IS 1 BP 58 EP 59 DI 10.1111/xen.12014_15 PG 2 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 087PN UT WOS:000314774400020 ER PT J AU Sheldrick, RC Henson, BS Neger, EN Merchant, S Murphy, JM Perrin, EC AF Sheldrick, R. Christopher Henson, Brandi S. Neger, Emily N. Merchant, Shela Murphy, J. Michael Perrin, Ellen C. TI The Baby Pediatric Symptom Checklist: Development and Initial Validation of a New Social/Emotional Screening Instrument for Very Young Children SO ACADEMIC PEDIATRICS LA English DT Article DE social; emotional; behavioral; screening; pediatrics ID PRIMARY-CARE; INFANT TEMPERAMENT; EXTERNALIZING BEHAVIORS; PSYCHOSOCIAL PROBLEMS; MATERNAL-BEHAVIOR; CHILDHOOD; MODEL; PERSONALITY; DEPRESSION; COMMUNITY AB OBJECTIVE: To develop and validate the Baby Pediatric Symptom Checklist (BPSC), a brief social/emotional screening instrument for children less than 18 months. The BPSC is modeled after the Pediatric Symptom Checklist (PSC) and is part of the Survey of Wellbeing of Young Children, a comprehensive, freely available screening instrument designed for use in pediatric primary care. METHOD: BPSC items were developed by a team of experts who reviewed existing assessment instruments and relevant research literature. Scale construction and initial validation were conducted with 205 families from pediatric primary care sites and 54 families from referral clinics. A replication sample of 146 additional families were enrolled from an independent set of primary care practices. RESULTS: Exploratory factor analysis revealed 3 dimensions of the BPSC: irritability, inflexibility, and difficulty with routines. Factor structure was confirmed in the replication sample. Retest reliability and internal reliability were adequate (intraclass correlation coefficient >0.70) across subscales, with the exception of the "irritability" subscale's internal reliability in the replication sample. Construct validity of the "irritability" and the "difficulty with routines" subscales is supported by correlations with the Parenting Stress Index and the Ages & Stages Questionnaire: Social/Emotional, but the "inflexibility" subscale seems to be distinct from performance on these instruments. Tests of differential item functioning revealed no significant effects for race/ethnicity, child gender, parent education, or family income. Age-based normative data were calculated for each subscale. CONCLUSION: The BPSC assesses 3 domains of behavior for very young children and shows promise as a social/emotional screening instrument for pediatric primary care. C1 [Sheldrick, R. Christopher; Henson, Brandi S.; Neger, Emily N.; Merchant, Shela; Perrin, Ellen C.] Floating Hosp Children, Tufts Med Ctr, Div Dev Behav Pediat, Boston, MA USA. [Murphy, J. Michael] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Sheldrick, RC (reprint author), 800 Washington St,Box 854, Boston, MA 02111 USA. EM rsheldrick@tuftsmedicalcenter.org FU Commonwealth Fund; National Institutes of Health [KM1CA156726] FX Research support for the development and validation of the Baby Pediatric Symptom Checklist was provided by The Commonwealth Fund & National Institutes of Health grant KM1CA156726.; We are indebted to The Commonwealth Fund for its support of the larger project of which this is a part. In particular, Dr Ed Schor's vision and imagination motivated us to create a practical instrument to guide surveillance in pediatric primary care settings. Dr Michael Jellinek had the foresight long ago to create a tool to help pediatricians identify children who had unmet needs for mental health attention. We are grateful also for the assistance of Dr Robin Adair, Dr Liz McGowan, and a large number of pediatricians and other child health specialists,* who allowed us to enroll parents through their offices, to Kate Mattern and Robyn Della Giustina for help with data collection and management, and to the Tufts Medical Center CTSI for ongoing support. We acknowledge as well the wise suggestions of anonymous reviewers of an earlier version of this article. NR 48 TC 7 Z9 7 U1 5 U2 21 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 J9 ACAD PEDIATR JI Acad. Pediatr. PD JAN-FEB PY 2013 VL 13 IS 1 BP 72 EP 80 PG 9 WC Pediatrics SC Pediatrics GA 076CA UT WOS:000313932900012 PM 23092547 ER PT J AU Raschke, R Hazani, R Yaremchuk, MJ AF Raschke, Ralf Hazani, Ron Yaremchuk, Michael J. TI Identifying a Safe Zone for Midface Augmentation Using Anatomic Landmarks for the Infraorbital Foramen SO AESTHETIC SURGERY JOURNAL LA English DT Article DE midface augmentation; alloplastic facial implants; safe zone; infraorbital nerve; anatomic landmarks; nerve block; paresthesia ID ANTHROPOMETRIC ANALYSIS; MAXILLOFACIAL SURGERY; MENTAL FORAMINA; IMPLANTS; SKELETON AB Background: Midface augmentation is commonly used to improve the appearance of concave faces and to achieve balance in the facial contour. It can also be an adjunct to orthognathic or reconstructive surgery. However, an inherent risk of midface augmentation is injury to the infraorbital nerve where it exits the infraorbital foramen (IOF). This can result in significant morbidity, including loss of sensation to the midface, nasal sidewall, upper lip, and lower eyelid. Objectives: The authors identify a safe zone of dissection in the midface for subperiosteal placement of infraorbital, paranasal, malar, and submalar implants, which avoids injury to the infraorbital nerve. Methods: Given the popularity of transconjuctival and intraoral access to the midface skeleton, the authors identified relevant bony and dental landmarks from radiographic images and measured distances between the IOF and these landmarks. Forty-four computed tomography scans of adult hemifaces were used to accurately locate the OF in relation to the anatomic landmarks. Results: Most often, the IOF's location correlated with the second premolar on a vertical axis. The average distance between the IOF and the infraorbital rim, piriforrn aperture, tip of the second premolar cusps, and lateral orbital rim was approximately 8.61, 17.43, 41.81, and 25.93 mm (respectively) in men and 8.25, 15.69, 37.33, and 24.21 mm (respectively) in women. Conclusions: A safe zone of dissection for midface augmentation has been identified, which differs from previous findings. Awareness of this zone may help clinicians locate the IOF and avoid injury to the nerve. C1 [Raschke, Ralf; Hazani, Ron; Yaremchuk, Michael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Yaremchuk, MJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 15 Parkman St,WAC 435, Boston, MA 02114 USA. EM dr.y@dryaremchuk.com NR 31 TC 3 Z9 3 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-820X J9 AESTHET SURG J JI Aesthet. Surg. J. PD JAN PY 2013 VL 33 IS 1 BP 13 EP 18 DI 10.1177/1090820X12468752 PG 6 WC Surgery SC Surgery GA 068VS UT WOS:000313394900001 PM 23220876 ER PT J AU Kling, MA Trojanowski, JQ Wolk, DA Lee, VMY Arnold, SE AF Kling, Mitchel A. Trojanowski, John Q. Wolk, David A. Lee, Virginia M. Y. Arnold, Steven E. TI Vascular disease and dementias: Paradigm shifts to drive research in new directions SO ALZHEIMERS & DEMENTIA LA English DT Article DE Dementia; Vascular; Cerebrovascular; Pathophysiology; Risk factors; Metabolic syndrome; Magnetic resonance imaging; White matter hyperintensities; Obesity; Hypertension; Insulin resistance; Dyslipidemia ID MILD COGNITIVE IMPAIRMENT; CORONARY HEART-DISEASE; WHITE-MATTER LESIONS; CLINICAL DIAGNOSTIC-CRITERIA; CEREBRAL AMYLOID ANGIOPATHY; VISCERAL ADIPOSE-TISSUE; ALZHEIMERS-DISEASE; METABOLIC SYNDROME; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE AB Vascular disease was once considered the principal cause of aging-related dementia. More recently, however, research emphasis has shifted to studies of progressive neurodegenerative disease processes, such as those giving rise to neuritic plaques, neurofibrillary tangles, and Lewy bodies. Although these studies have led to critical insights and potential therapeutic strategies, interest in the role of systemic and cerebrovascular disease mechanisms waned and has received relatively less attention and research support. Recent studies suggest that vascular disease mechanisms play an important role in the risk for aging-related cognitive decline and disorders. Vascular disease frequently coexists with cognitive decline in aging individuals, shares many risk factors with dementias considered to be of the "Alzheimer type," and is observed more frequently than expected in postmortem material from individuals manifesting "specific" disease stigmata, such as abundant plaques and tangles. Considerable difficulties have emerged in attempting to classify dementias as being related to vascular versus neurodegenerative causes, and several systems of criteria have been used. Despite multiple attempts, a lack of consensus remains regarding the optimal means of incorporating vascular disease into clinical diagnostic, neurocognitive, or neuropathologic classification schemes for dementias. We propose here an integrative, rather than a strictly taxonomic, approach to the study and elucidation of how vascular disease mechanisms contribute to the development of dementias. We argue that, instead of discriminating between, for example, "Alzheimer's disease," "vascular dementia," and other diseases, there is a greater need to focus clinical and research efforts on elucidating specific pathophysiologic mechanisms that contribute to dementia phenotypes and neuropathologic outcomes. We outline a multitiered strategy, beginning with clinical and public health interventions that can be implemented immediately, enhancements to ongoing longitudinal studies to increase their informative value, and new initiatives to capitalize on recent advances in systems biology and network medicine. This strategy will require funding from multiple public and private sources to support collaborative and interdisciplinary research efforts to take full advantage of these opportunities and realize their societal benefits. (C) 2013 The Alzheimer's Association. All rights reserved. C1 [Kling, Mitchel A.; Arnold, Steven E.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kling, Mitchel A.] Philadelphia Vet Affairs Med Ctr, Behav Hlth Serv, Philadelphia, PA USA. [Trojanowski, John Q.; Lee, Virginia M. Y.] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USA. [Trojanowski, John Q.; Wolk, David A.; Lee, Virginia M. Y.; Arnold, Steven E.] Univ Penn, Inst Aging, Perelman Sch Med, Philadelphia, PA 19104 USA. [Wolk, David A.; Arnold, Steven E.] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Kling, MA (reprint author), Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. EM mitchel.kling@uphs.upenn.edu OI Kling, Mitchel/0000-0002-2232-1409 FU Alzheimer's Diseases Coordinating Center [NIH P30 AG010124]; Allen H. and Selma W. Berkman Charitable Trust FX This work was supported in part by funding from the Alzheimer's Diseases Coordinating Center (NIH P30 AG010124), and by a grant from the Allen H. and Selma W. Berkman Charitable Trust. NR 174 TC 45 Z9 48 U1 1 U2 31 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JAN PY 2013 VL 9 IS 1 BP 76 EP 92 DI 10.1016/j.jalz.2012.02.007 PG 17 WC Clinical Neurology SC Neurosciences & Neurology GA 078EO UT WOS:000314081400009 PM 23183137 ER PT J AU Han, HS Martin, JD Lee, J Harris, DK Fukumura, D Jain, RK Bawendi, M AF Han, Hee-Sun Martin, John D. Lee, Jungmin Harris, Daniel K. Fukumura, Dai Jain, Rakesh K. Bawendi, Moungi TI Spatial Charge Configuration Regulates Nanoparticle Transport and Binding Behavior In Vivo SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE cancer; ligand design; nanoparticles; quantum dots; zwitterions ID QUANTUM DOTS; PROTEIN ADSORPTION; CELL-SURFACE; DELIVERY; SIZE; NANOCRYSTALS; RESISTANCE; MONOLAYERS; VESSELS; CDSE C1 [Han, Hee-Sun; Lee, Jungmin; Bawendi, Moungi] MIT, Dept Chem, Cambridge, MA 02139 USA. [Martin, John D.; Fukumura, Dai; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. [Martin, John D.; Fukumura, Dai; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Martin, John D.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Harris, Daniel K.] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. RP Bawendi, M (reprint author), MIT, Dept Chem, Cambridge, MA 02139 USA. EM mgb@mit.edu RI Martin, John/L-6892-2016 OI Martin, John/0000-0002-9828-8203 FU U.S. National Institute of Health [P01-CA080124, R01-CA085140, R01-CA096915, R01-CA115767, R01-CA126642, U54-CA151884]; Federal Share Proton Beam Program Income; MIT DCIF [CHE-9808061, DBI-9729592]; ISN [W911NF-07-D-0004]; NSF-MRSEC program [DMR-0117795]; DoD Breast Cancer Research Innovator award [W81XWH-10-1-0016]; Samsung Scholarship; [T32-CA073479] FX The research work is supported by the U.S. National Institute of Health grants, P01-CA080124 (R.K.J and D. F.), R01-CA085140 (R.K.J.), R01-CA096915 (D. F.), R01-CA115767 (R.K.J.), R01-CA126642 (R.K.J.), U54-CA151884 (M. G. B.), R01-CA126642 (M. G. B.), Federal Share Proton Beam Program Income (R.K.J.), and T32-CA073479 (R.K.J.); by the MIT DCIF CHE-9808061, DBI-9729592; by the ISN W911NF-07-D-0004 (M. G. B); by the NSF-MRSEC program DMR-0117795 through the use of its shared user facilities; and by DoD Breast Cancer Research Innovator award (W81XWH-10-1-0016 (R.K.J.). H.-S.H. was supported by the Samsung Scholarship. We would like to thank Julia Kahn for technical assistance. NR 45 TC 41 Z9 41 U1 3 U2 91 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2013 VL 52 IS 5 BP 1414 EP 1419 DI 10.1002/anie.201208331 PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA 075UV UT WOS:000313913300010 PM 23255143 ER PT J AU Denzen, EM Majhail, NS Ferguson, SS Anasetti, C Bracey, A Burns, L Champlin, R Chell, J Leather, H Lill, M Maziarz, RT Medoff, E Neumann, J Schmit-Pokorny, K Snyder, EL Wiggins, L Raley, DSY Murphy, EA AF Denzen, Ellen M. Majhail, Navneet S. Ferguson, Stacy Stickney Anasetti, Claudio Bracey, Arthur Burns, Linda Champlin, Richard Chell, Jeffrey Leather, Helen Lill, Michael Maziarz, Richard T. Medoff, Erin Neumann, Joyce Schmit-Pokorny, Kim Snyder, Edward L. Wiggins, Laura Raley, Deborah S. Yolin Murphy, Elizabeth A. TI Hematopoietic Cell Transplantation in 2020: Summary of Year 2 Recommendations of the National Marrow Donor Program's System Capacity Initiative SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Allogeneic transplant; Care delivery model; Reimbursement; Healthcare disparities; Workforce AB The National Marrow Donor Program, in partnership with the American Society for Blood and Marrow Transplantation, sponsored and organized a series of symposia to identify complex issues affecting the delivery of hematopoietic cell transplantation (HCT) and to collaboratively develop options for solutions. "Hematopoietic Cell Transplantation in 2020: A System Capacity Initiative" used a deliberative process model to engage professional organizations, experts, transplant centers, and stakeholders in a national collaborative effort. Year 2 efforts emphasized data analysis and identification of innovative ideas to increase HCT system efficiency, address future capacity requirements, and ensure adequate reimbursement for HCT programs to meet the projected need for HCT. This report highlights the deliberations and recommendations of Year 2 and the associated symposium held in September 2011. (C) 2013 American Society for Blood and Marrow Transplantation. C1 [Denzen, Ellen M.] Natl Marrow Donor Program, Patient Serv, Minneapolis, MN 55413 USA. [Majhail, Navneet S.] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. [Anasetti, Claudio] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Anasetti, Claudio] Univ S Florida, Res Inst, Tampa, FL USA. [Bracey, Arthur] St Lukes Episcopal Hosp, Dept Pathol, Houston, TX 77030 USA. [Burns, Linda] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Champlin, Richard; Neumann, Joyce] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Leather, Helen] Univ Florida, Gainesville, FL USA. [Lill, Michael] Cedars Sinai Med Ctr, Stem Cell BMT Program, Los Angeles, CA 90048 USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Ctr Hematol Malignancies, Portland, OR 97201 USA. [Medoff, Erin] Yale New Haven Med Ctr, Yale Canc Ctr, New Haven, CT 06504 USA. [Schmit-Pokorny, Kim] Univ Nebraska Med Ctr, Blood & Marrow Transplantat Program, Hematol Oncol Sect, Omaha, NE USA. [Snyder, Edward L.] Yale Univ, Sch Med, Yale New Haven Hosp, New Haven, CT USA. [Wiggins, Laura] Univ Florida, Shands Hosp, Gainesville, FL USA. [Raley, Deborah S. Yolin] Dana Farber Canc Inst, Stem Cell Bone Marrow Transplant Program, Boston, MA 02115 USA. RP Denzen, EM (reprint author), Natl Marrow Donor Program, Patient Serv, 3001 Broadway St NE, Minneapolis, MN 55413 USA. EM edenzen@nmdp.org FU National Institutes of Health [1R13HL110705-01]; Yale School of Medicine, Yale University; National Marrow Donor Program FX Funding for this conference was made possible (in part) by grant 1R13HL110705-01 from the National Institutes of Health, Yale School of Medicine, Yale University and the National Marrow Donor Program. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services, nor does the mention of trade names, commercial practices, or organizations imply endorsement by the US Government. The authors have no conflicts of interest to disclose. NR 3 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2013 VL 19 IS 1 BP 4 EP 11 DI 10.1016/j.bbmt.2012.10.005 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 076ZP UT WOS:000313998000003 PM 23078785 ER PT J AU Duncan, CN Clark, JJ Silverman, LB AF Duncan, Christine N. Clark, Jennifer J. Silverman, Lewis B. TI Hematopoietic Stem Cell Transplantation in Unique Pediatric Populations: Adolescents, Infants, and Children with Down Syndrome SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; ADULT AYA ONCOLOGY; ACUTE LYMPHOCYTIC-LEUKEMIA; CLINICAL-TRIAL ENROLLMENT; MLL GENE REARRANGEMENTS; YOUNG-ADULTS; FERTILITY PRESERVATION; CHILDHOOD-CANCER; SURVIVORS C1 [Duncan, Christine N.; Silverman, Lewis B.] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. [Clark, Jennifer J.] Rocky Mt Pediat Hematol Oncol, Denver, CO USA. RP Duncan, CN (reprint author), 450 Brookline Ave, Boston, MA 02215 USA. EM Christine_duncan@dfci.harvard.edu NR 56 TC 1 Z9 2 U1 1 U2 7 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 JAN PY 2013 VL 19 IS 1 SU 1 BP S52 EP S57 DI 10.1016/j.bbmt.2012.10.018 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 076ZQ UT WOS:000313998100015 PM 23085602 ER PT J AU Huang, AY Haining, WN Barkauskas, DS Myers, JT Petrosiute, A Garrett, AP Singh, K Cooke, KR Kean, LS AF Huang, Alex Y. Haining, W. Nicholas Barkauskas, Deborah S. Myers, Jay T. Petrosiute, Agne Garrett, Aneesah P. Singh, Karnail Cooke, Kenneth R. Kean, Leslie S. TI Viewing Transplantation Immunology Through Today's Lens: New Models, New Imaging, and New Insights SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article ID HEMATOPOIETIC STEM-CELLS; CD8(+) T-CELLS; BONE-MARROW; ALLOGRAFT SURVIVAL; DENDRITIC CELLS; IMMUNE; NICHE; LYMPHOCYTES; TISSUES; MEMORY C1 [Huang, Alex Y.; Barkauskas, Deborah S.; Myers, Jay T.; Petrosiute, Agne; Cooke, Kenneth R.] Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA. [Haining, W. Nicholas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Broad Inst Harvard & Massachuse, Boston, MA 02115 USA. [Garrett, Aneesah P.; Singh, Karnail; Kean, Leslie S.] Emory Univ, Sch Med, Dept Surg, Emory Transplant Ctr, Atlanta, GA 30322 USA. [Kean, Leslie S.] Childrens Healthcare Atlanta, Aflac Canc & Blood Disorders Ctr, Atlanta, GA USA. [Kean, Leslie S.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA. RP Kean, LS (reprint author), Room 5203 WMB,101 Woodruff Circle NE, Atlanta, GA 30322 USA. EM Leslie.kean@emory.edu OI Barkauskas, Deborah S./0000-0002-1872-4109; Petrosiute, Agne/0000-0003-4010-9898; Huang, Alex/0000-0002-5701-4521 FU National Institute of Allergy and Infectious Diseases [2U19 AI051731, R21A1092299]; National Cancer Institute [R01 CA171523]; St Baldrick's Foundation; Hyundai; Gabrielle's Angel Foundation; Dana Foundation; Cancer Research Institute; National Institutes of Health [K12HD057581, AI082630, A1057266, AI090023]; Burroughs Welcome Fund; Leukemia and Lymphoma Society; National Center for Regenerative Medicine at Case Western Reserve University; National Heart, Lung and Blood Institute [1R01 HL095791, 2U24 RR018109]; Burroughs Wellcome Fund Career Award in the Biomedical Sciences FX Karnail Singh was supported by the National Institute of Allergy and Infectious Diseases (grant 2U19 AI051731).; Financial disclosure: Alex Y. Huang was supported by the National Cancer Institute (grant R01 CA171523), National Institute of Allergy and Infectious Diseases (grant R21A1092299), St Baldrick's Foundation, Hyundai "Hope-onWheels" Program, Alex's Lemonade Stand, Gabrielle's Angel Foundation, Dana Foundation, and Cancer Research Institute. Agne Petrosiute was supported by the National Institutes of Health (grant K12HD057581), St Baldrick's Foundation, and Hyundai "Hope-on-Wheels" Program. Deborah S. Barkauskas was supported by the National Institutes of Health (grant T32EB7509). W. Nicholas Haining was supported by the National Institutes of Health (grants AI082630, A1057266, and AI090023). Kenneth R. Cooke was supported by the Burroughs Welcome Fund, Leukemia and Lymphoma Society, and National Center for Regenerative Medicine at Case Western Reserve University. Leslie S. Kean was supported by the National Institute of Allergy and Infectious Diseases (grant 2U19 AI051731), National Heart, Lung and Blood Institute (grants 1R01 HL095791 and 2U24 RR018109), and a Burroughs Wellcome Fund Career Award in the Biomedical Sciences. NR 40 TC 2 Z9 2 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2013 VL 19 IS 1 SU 1 BP S44 EP S51 DI 10.1016/j.bbmt.2012.10.020 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 076ZQ UT WOS:000313998100014 PM 23092813 ER PT J AU Richardson, PG Ho, VT Cutler, C Glotzbecker, B Antin, JH Soiffer, R AF Richardson, P. G. Ho, V. T. Cutler, C. Glotzbecker, B. Antin, J. H. Soiffer, R. TI Hepatic Veno-Occlusive Disease after Hematopoietic Stem Cell Transplantation: Novel Insights to Pathogenesis, Current Status of Treatment, and Future Directions SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article ID BONE-MARROW-TRANSPLANTATION; COMPASSIONATE-USE; DEFIBROTIDE; LIVER; PROPHYLAXIS; PREVENTION; CHILDREN; UPDATE; PAI-1; VOD C1 [Richardson, P. G.; Ho, V. T.; Cutler, C.; Glotzbecker, B.; Antin, J. H.; Soiffer, R.] Dana Farber Canc Inst, Div Hematol Malignancy, Boston, MA 02115 USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, Div Hematol Malignancy, 44 Binney St, Boston, MA 02115 USA. EM Paul_Richardson@dfci.harvard.edu NR 28 TC 10 Z9 12 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2013 VL 19 IS 1 SU 1 BP S88 EP S90 DI 10.1016/j.bbmt.2012.10.023 PG 3 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 076ZQ UT WOS:000313998100022 PM 23089567 ER PT J AU Murphey, P McLean, DJ McMahan, CA Walter, CA McCarrey, JR AF Murphey, Patricia McLean, Derek J. McMahan, C. Alex Walter, Christi A. McCarrey, John R. TI Enhanced Genetic Integrity in Mouse Germ Cells SO BIOLOGY OF REPRODUCTION LA English DT Article DE mutations; oogenesis; spermatogenesis; spermatogonial stem cells ID EMBRYONIC STEM-CELLS; INDUCED SPECIFIC-LOCUS; EXCISION-REPAIR ACTIVITY; MUTATION FREQUENCY; TRANSGENIC MICE; OLD MICE; IN-VIVO; SPERMATOGENIC CELLS; MUTANT FREQUENCIES; HETEROZYGOUS MICE AB Genetically based diseases constitute a major human health burden, and de novo germline mutations represent a source of heritable genetic alterations that can cause such disorders in offspring. The availability of transgenic rodent systems with recoverable, mutation reporter genes has been used to assess the occurrence of spontaneous point mutations in germline cells. Previous studies using the lacI mutation reporter transgenic mouse system showed that the frequency of spontaneous mutations is significantly lower in advanced male germ cells than in somatic cell types from the same individuals. Here we used this same mutation reporter transgene system to show that female germ cells also display a mutation frequency that is lower than that in corresponding somatic cells and similar to that seen in male germ cells, indicating this is a common feature of germ cells in both sexes. In addition, we showed that statistically significant differences in mutation frequencies are evident between germ cells and somatic cells in both sexes as early as mid-fetal stages in the mouse. Finally, a comparison of the mutation frequency in a general population of early type A spermatogonia with that in a population enriched for Thy-1-positive spermatogonia suggests there is heterogeneity among the early spermatogonial population such that a subset of these cells are predestined to form true spermatogonial stem cells. Taken together, these results support the disposable soma theory, which posits that genetic integrity is normally maintained more stringently in the germ line than in the soma and suggests that this is achieved by minimizing the initial occurrence of mutations in early germline cells and their subsequent gametogenic progeny relative to that in somatic cells. C1 [Murphey, Patricia; McCarrey, John R.] Univ Texas San Antonio, Dept Biol, San Antonio, TX 78249 USA. [McLean, Derek J.] Washington State Univ, Dept Anim Sci, Pullman, WA 99164 USA. [McMahan, C. Alex] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Walter, Christi A.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP McCarrey, JR (reprint author), Univ Texas San Antonio, Dept Biol, 1 UTSA Circle, San Antonio, TX 78249 USA. EM john.mccarrey@utsa.edu FU National Institutes of Health [HD42772, HD046521] FX Supported in part by National Institutes of Health grant HD42772 to J.R.M. and grant HD046521 to D.J.M. NR 58 TC 11 Z9 11 U1 0 U2 3 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JAN PY 2013 VL 88 IS 1 AR 6 DI 10.1095/biolreprod.112.103481 PG 8 WC Reproductive Biology SC Reproductive Biology GA 081YD UT WOS:000314357700005 PM 23153565 ER PT J AU Wu, JN Roberts, CWM AF Wu, Jennifer N. Roberts, Charles W. M. TI ARID1A Mutations in Cancer: Another Epigenetic Tumor Suppressor? SO CANCER DISCOVERY LA English DT Review ID CHROMATIN-REMODELING COMPLEX; CLEAR-CELL CARCINOMA; IDENTIFIES FREQUENT MUTATION; SWI/SNF-RELATED COMPLEXES; SOMATIC MUTATIONS; BREAST-CANCER; CYCLE ARREST; GENE ARID1A; TRANSCRIPTIONAL ACTIVATION; HEPATOCELLULAR-CARCINOMA AB Although disordered chromatin organization has long been recognized as a feature of cancer, the molecular underpinnings of chromatin structure, epigenetic regulation, and their relationships to transcription are only beginning to be understood. Cancer genome sequencing studies have revealed a novel theme: frequent mutation of epigenetic regulators. Among these, the ARID1A/BAF250A subunit of the SWI/SNF (BRG1-associated factors) chromatin remodeling complex has emerged as recurrently mutated in a broad array of tumor types. We review the genomic and functional data supporting classification of ARID1A as a tumor suppressor. C1 [Wu, Jennifer N.; Roberts, Charles W. M.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Boston Childrens Hosp, Dept Pediat Oncol,Div Hematol Oncol,Dept Pediat, Boston, MA 02115 USA. RP Roberts, CWM (reprint author), 450 Brookline Ave,Mayer 657, Boston, MA 02215 USA. EM Charles_Roberts@dfci.harvard.edu FU PHS awards [R01CA113794, U01-1156106]; Stand Up To Cancer Innovative Research Grant; Program of the Entertainment Industry Foundation [SU2C-AACR-IRG0309]; Cure AT/RT Now Foundation; Garrett B. Smith Foundation; St. Baldrick's Foundation; Alex's Lemonade Stand Foundation; William Lawrence and Blanche Hughes Foundation; Boston Children's Hospital FX The work in Dr. Roberts' laboratory is partly supported by PHS awards R01CA113794 and U01-1156106; a Stand Up To Cancer Innovative Research Grant, a Program of the Entertainment Industry Foundation (SU2C-AACR-IRG0309); the Cure AT/RT Now Foundation; and the Garrett B. Smith Foundation. Dr. Wu is supported by St. Baldrick's Foundation, Alex's Lemonade Stand Foundation, William Lawrence and Blanche Hughes Foundation, and Boston Children's Hospital. NR 60 TC 72 Z9 76 U1 2 U2 22 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD JAN PY 2013 VL 3 IS 1 BP 35 EP 43 DI 10.1158/2159-8290.CD-12-0361 PG 9 WC Oncology SC Oncology GA 072BI UT WOS:000313642900022 PM 23208470 ER PT J AU Jia, SD Gao, XL Lee, SH Maira, SM Wu, XQ Stack, EC Signoretti, S Loda, M Zhao, JJ Roberts, TM AF Jia, Shidong Gao, Xueliang Lee, Sang Hyun Maira, Sauveur-Michel Wu, Xiaoqiu Stack, Edward C. Signoretti, Sabina Loda, Massimo Zhao, Jean J. Roberts, Thomas M. TI Opposing Effects of Androgen Deprivation and Targeted Therapy on Prostate Cancer Prevention SO CANCER DISCOVERY LA English DT Article ID INTRAEPITHELIAL NEOPLASIA; MOUSE MODEL; PTEN; PROGRESSION; CELL; EXPRESSION; DELETION; GROWTH; GENE; PI3K AB Prostate cancer is an ideal target for chemoprevention. To date, chemoprevention clinical trials with 5 alpha-reductase inhibitors have yielded encouraging yet ultimately confounding results. Using a preclinical mouse model of high-grade prostatic intraepithelial neoplasia (HG-PIN) induced by PTEN loss, we observed unprecedented deteriorating effects of androgen deprivation, in which surgical castration or MDV3100 treatment accelerated disease progression of the otherwise stable HG-PIN to invasive castration-resistant prostate cancer (CRPC). As an alternative, targeting the phosphoinositide 3-kinase (PI3K) signaling pathway via either genetic ablation of genes encoding PI3K components or pharmacologic inhibition of the PI3K pathway reversed the PTEN loss-induced HG-PIN phenotype. Finally, concurrent inhibition of the PI3K and mitogen-activated protein kinase (MAPK) pathways was effective in blocking the growth of PTEN-null CRPC. Together, these data have revealed the potential adverse effects of antiandrogen chemoprevention in certain genetic contexts (such as PTEN loss) while showing the promise of targeted therapy in the clinical management of this complex and prevalent disease. C1 [Jia, Shidong; Gao, Xueliang; Lee, Sang Hyun; Zhao, Jean J.; Roberts, Thomas M.] Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Wu, Xiaoqiu; Stack, Edward C.; Signoretti, Sabina; Loda, Massimo] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Gao, Xueliang; Zhao, Jean J.; Roberts, Thomas M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Jia, Shidong; Lee, Sang Hyun; Wu, Xiaoqiu; Stack, Edward C.; Signoretti, Sabina; Loda, Massimo] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Maira, Sauveur-Michel] Novartis Inst BioMed Res Inc, Oncol Dis Area, Basel, Switzerland. RP Roberts, TM (reprint author), Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM thomas_roberts@dfci.harvard.edu FU Novartis; Dana-Farber/Harvard Cancer Center Specialized Program of Research Excellence (P.A.R.T Investigatorship Award); NIH [CA030002, CA089021, CA134502, CA148164-01] FX T.M. Roberts has a commercial research grant and is a consultant/advisory board member of Novartis. J.J. Zhao has a commercial research grant from Novartis, receives honoraria for serving on the speakers' bureau for Sanofi, and is a consultant/advisory board member of the National Brain Tumor Society. No potential conflicts of interest were disclosed by the other authors.; This work was supported by grants from the Dana-Farber/Harvard Cancer Center Specialized Program of Research Excellence (P.A.R.T Investigatorship Award to S. Jia), the NIH (CA030002 and CA089021 to T. M. Roberts; CA089021 to M. Loda; CA134502 to J.J. Zhao; and CA148164-01 to T. M. Roberts and J.J. Zhao). NR 24 TC 26 Z9 26 U1 0 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD JAN PY 2013 VL 3 IS 1 BP 44 EP 51 DI 10.1158/2159-8290.CD-12-0262 PG 8 WC Oncology SC Oncology GA 072BI UT WOS:000313642900023 PM 23258246 ER PT J AU Tam, LM Fonarow, GC Bhatt, DL Grau-Sepulveda, MV Hernandez, AF Peterson, ED Schwamm, LH Giugliano, RP AF Tam, Lori M. Fonarow, Gregg C. Bhatt, Deepak L. Grau-Sepulveda, Maria V. Hernandez, Adrian F. Peterson, Eric D. Schwamm, Lee H. Giugliano, Robert P. CA GWTG Steering Comm Investigators TI Achievement of Guideline-Concordant Care and In-Hospital Outcomes in Patients With Coronary Artery Disease in Teaching and Nonteaching Hospitals Results From the Get With The Guidelines-Coronary Artery Disease Program SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE acute coronary syndromes; adherence; performance measures; quality improvement; secondary prevention ID ACUTE MYOCARDIAL-INFARCTION; QUALITY-OF-CARE; US HOSPITALS; ASSOCIATION; PERFORMANCE; IMPROVEMENT; ADHERENCE; MORTALITY AB Background-Secondary prevention therapies improve longitudinal outcomes in patients with coronary artery disease. Previous studies showed that teaching hospitals (THs) more consistently use evidence-based secondary prevention therapies than non-THs (NTHs). It is unclear whether these differences persist after initiation of a national quality improvement system. Methods and Results-We analyzed 270 902 patients across 361 hospitals in the Get With The Guidelines-Coronary Artery Disease program from June 2000 to September 2009. The primary outcome was guideline-concordant care, defined as compliance with all Get With The Guidelines-Coronary Artery Disease quality measures: (1) aspirin within 24 hours, (2) aspirin at discharge, (3) angiotensin-converting enzyme inhibitor/angiotensin receptor blockers for systolic dysfunction, (4) beta-blockers at discharge, (5) lipid therapy if low-density lipoprotein >100 mg/dL, and (6) smoking cessation. We used multivariate modeling to compare the relationship between TH and NTH status on quality measures, in-hospital mortality, and length of stay. Guideline-concordant care was higher at THs (78.4% versus 73.3%; P<0.01). The adjusted odds ratio between 2000 and 2009 for guideline-concordant care at THs compared with NTHs was 2.78 (confidence interval, 1.28-6.06; P=0.01). Guideline-concordant care increased from 2000 to 2009 at THs (n=176; 65.3%-> 88.3%; adjusted odds ratio for year increase, 1.24 [confidence interval, 1.16-1.30; P<0.01]) and NTHs (n=185; 61.0%-> 93.9%; adjusted odds ratio for year increase, 1.35 [confidence interval, 1.26-1.45]; P<0.01). THs had shorter length of stay (adjusted odds ratio, 0.74 for length of stay >4 days; confidence interval, 0.58-0.94) from 2000 to 2009. Lower in-hospital mortality was observed at THs (3.7% versus 4.4% at NTHs; P<0.01), but this was not significant after adjustment. Conclusions-Adherence to guideline-recommended therapies increased over time with participation in the Get With The Guidelines-Coronary Artery Disease program, regardless of the teaching status. Guideline-concordant care over the full decade was higher in THs; however, NTHs demonstrated greater incremental improvement over time. (Circ Cardiovasc Qual Outcomes. 2013; 6: 58-65.) C1 [Tam, Lori M.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.; Schwamm, Lee H.; Giugliano, Robert P.] Harvard Univ, Sch Med, Boston, MA USA. [Grau-Sepulveda, Maria V.; Hernandez, Adrian F.; Peterson, Eric D.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Giugliano, RP (reprint author), 350 Longwood Ave,1st Off Floor, Boston, MA 02115 USA. EM rgiugliano@partners.org RI Hernandez, Adrian F./A-7818-2016 OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616 FU American Heart Association Pharmaceutical Roundtable; Merck; Amarin; AstraZeneca; Bristol-Myers Squibb; Eisai; Ethicon; Medtronic; Sanofi Aventis; The Medicines Company; Johnson Johnson; Amylin; Portola; Lilly; Amgen; Daiichi-Sankyo FX The Get With the Guidelines-Coronary Artery Disease (GWTG-CAD) program was provided by the American Heart Association. The GWTG-CAD program was supported in part by the American Heart Association Pharmaceutical Roundtable and an unrestricted educational grant from Merck.; Dr Bhatt receives research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis and The Medicines Company. Advisory Board for: Medscape Cardiology; Board of Directors: Boston VA Research Institute, Society of Chest Pain Centers; Chair: American Heart Association Get With The Guidelines Science Subcommittee; Honoraria: American College of Cardiology (Editor, Clinical Trials, Cardiosource), Senior Associate Editor, Journal of Invasive Cardiology, Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), WebMD (continuing medical education steering committees). Unfunded Research: FlowCo, PLx Pharma, Takeda. Dr Hernandez receives research grants from Johnson & Johnson, Amylin, Portola and honorarium from AstraZeneca, Corthera, and Sanofi. Dr Peterson receives research grants from Lilly and Johnson & Johnson. Dr Schwamm is Chair of the GWTG steering committee (unpaid).; Dr Giugliano's research group receives research grants related to clinical trials he participates in from Amgen, Daiichi-Sankyo, and Merck. Dr Giugliano receives honoraria for CME lectures or is a consultant for Amgen, Daiichi-Sankyo, Merck, Regeneron, Sanofi-Aventis and Janssen. The other authors report no conflicts. NR 18 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JAN PY 2013 VL 6 IS 1 BP 58 EP 65 DI 10.1161/CIRCOUTCOMES.112.965525 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 071ZN UT WOS:000313637500012 PM 23233750 ER PT J AU Beard, AJ Hofer, TP Downs, JR Lucatorto, M Klamerus, ML Holleman, R Kerr, EA AF Beard, Ashley J. Hofer, Timothy P. Downs, John R. Lucatorto, Michelle Klamerus, Mandi L. Holleman, Rob Kerr, Eve A. CA Diabet Clinical Action Measures TI Assessing Appropriateness of Lipid Management Among Patients With Diabetes Mellitus Moving From Target to Treatment SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE cholesterol; performance measures; quality of care; diabetes mellitus; lipids ID CORONARY-HEART-DISEASE; INTENSIVE STATIN THERAPY; RANDOMIZED CONTROLLED-TRIALS; PLACEBO-CONTROLLED TRIAL; AVERAGE CHOLESTEROL LEVELS; RISK-FACTOR CONTROL; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; PERFORMANCE-MEASURES; LOWERING THERAPY AB Background-Performance measures that emphasize only a treat-to-target approach may motivate overtreatment with high-dose statins, potentially leading to adverse events and unnecessary costs. We developed a clinical action performance measure for lipid management in patients with diabetes mellitus that is designed to encourage appropriate treatment with moderate-dose statins while minimizing overtreatment. Methods and Results-We examined data from July 2010 to June 2011 for 964 818 active Veterans Affairs primary care patients >= 18 years of age with diabetes mellitus. We defined 3 conditions as successfully meeting the clinical action measure for patients 50 to 75 years old: (1) having a low-density lipoprotein (LDL) <100 mg/dL, (2) taking a moderate-dose statin regardless of LDL level or measurement, or (3) receiving appropriate clinical action (starting, switching, or intensifying statin therapy) if LDL is >= 100 mg/dL. We examined possible overtreatment for patients >= 18 years of age by examining the proportion of patients without ischemic heart disease who were on a high-dose statin. We then examined variability in measure attainment across 881 facilities using 2-level hierarchical multivariable logistic models. Of 668 209 patients with diabetes mellitus who were 50 to 75 years of age, 84.6% passed the clinical action measure: 67.2% with LDL <100 mg/dL, 13.0% with LDL >= 100 mg/dL and either on a moderate-dose statin (7.5%) or with appropriate clinical action (5.5%), and 4.4% with no index LDL on at least a moderate-dose statin. Of the entire cohort >= 18 years of age, 13.7% were potentially overtreated. Facilities with higher rates of meeting the current threshold measure (LDL <100 mg/dL) had higher rates of potential overtreatment (P<0.001). Conclusions-Use of a performance measure that credits appropriate clinical action indicates that almost 85% of diabetic veterans 50 to 75 years of age are receiving appropriate dyslipidemia management. However, many patients are potentially overtreated with high-dose statins. (Circ Cardiovasc Qual Outcomes. 2013; 6: 66-74.) C1 [Hofer, Timothy P.; Klamerus, Mandi L.; Holleman, Rob; Kerr, Eve A.] Dept Vet Affairs Ann Arbor Healthcare Syst, Ctr Clin Management Res, Ann Arbor, MI USA. [Beard, Ashley J.; Hofer, Timothy P.; Kerr, Eve A.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Hofer, Timothy P.; Kerr, Eve A.] Univ Michigan, Michigan Diabet Res & Training Ctr, Ann Arbor, MI 48109 USA. [Downs, John R.] S Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat Implementat Ctr, San Antonio, TX USA. [Downs, John R.] Univ Texas Hlth Sci Ctr, Div Hosp Med, Dept Med, San Antonio, TX USA. [Lucatorto, Michelle] Dept Vet Affairs, Off Nursing Serv, Washington, DC USA. RP Kerr, EA (reprint author), VA Ctr Clin Management Res 152, 2215 Fuller Rd,POB 130170, Ann Arbor, MI 48113 USA. EM ekerr@umich.edu RI Kerr, Eve/I-3330-2013 FU VA QUERI RRP [09-111]; Veteran Affairs Diabetes Quality Enhancement Research Initiative [DIB 98-001]; Measurement Core of the Michigan Diabetes Research and Training Center (National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health] [P60 DK-20572] FX This study was funded by VA QUERI RRP 09-111. Additional support was provided by the Veteran Affairs Diabetes Quality Enhancement Research Initiative (DIB 98-001) and the Measurement Core of the Michigan Diabetes Research and Training Center (National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [P60 DK-20572]). NR 59 TC 14 Z9 14 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JAN PY 2013 VL 6 IS 1 BP 66 EP 74 DI 10.1161/CIRCOUTCOMES.112.966697 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 071ZN UT WOS:000313637500013 PM 23233749 ER PT J AU Kreydin, EI Ko, DSC AF Kreydin, Evgeniy I. Ko, Dicken S. C. TI Immediate renal transplantation after radical prostatectomy for low-risk prostate cancer SO CLINICAL TRANSPLANTATION LA English DT Article DE cancer recurrence; cancer screening; predictive models; prostate cancer; waiting period ID KIDNEY-TRANSPLANTATION; BIOCHEMICAL RECURRENCE; PRETREATMENT NOMOGRAM; PREOPERATIVE NOMOGRAM; UNITED-STATES; RECIPIENTS; PROBABILITY; VALIDATION; GUIDELINES; EXPERIENCE AB Introduction For most cancers, a two- to five-yr period with no evidence of disease must be demonstrated before organ transplantation. The natural history of prostate cancer is unique both because of extensive pre-treatment screening and the ease of post-treatment monitoring for recurrence. Using available predictive models for prostate cancer recurrence, we examine whether current evidence supports a prolonged waiting period after radical prostatectomy and before renal transplantation. Materials and Methods A MedLine search was conducted to identify five series (published between 2000 and 2011), which examined biochemical recurrence (BCR) after prostatectomy for low-risk prostate cancer. The likelihood of BCR at one, two, and five yr after radical prostatectomy was identified for each series. Results Each of the analyzed series demonstrated that the likelihood of BCR after radical prostatectomy for low-risk prostate cancer was identical at one, two, and five yr and did not exceed 5%. Conclusions The likelihood of BCR does not increase during the first five yr after radical prostatectomy for low-risk prostate cancer. Additionally, the risk of recurrence approaches zero during this period. Therefore, current evidence does not support the mandated waiting period of five yr before organ transplantation. C1 [Kreydin, Evgeniy I.; Ko, Dicken S. C.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Ko, Dicken S. C.] Massachusetts Gen Hosp, Div Transplantat, Boston, MA 02114 USA. RP Kreydin, EI (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St, Boston, MA 02114 USA. EM ekreydin@partners.org NR 34 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0902-0063 J9 CLIN TRANSPLANT JI Clin. Transplant. PD JAN-FEB PY 2013 VL 27 IS 1 BP 162 EP 167 DI 10.1111/ctr.12023 PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 079YL UT WOS:000314208000032 PM 23004927 ER PT J AU Wong, LL Naugler, WE Schwartz, J Scott, DL Bhattacharya, R Reyes, J Orloff, SL AF Wong, Linda L. Naugler, Willscott E. Schwartz, Jonathan Scott, David L. Bhattacharya, Renuka Reyes, Jorge Orloff, Susan L. TI Impact of locoregional therapy and alpha-fetoprotein on outcomes in transplantation for liver cancer: a UNOS Region 6 pooled analysis SO CLINICAL TRANSPLANTATION LA English DT Article DE alpha-fetoprotein; chemoembolization; hepatocellular cancer; liver transplant; locoregional therapy ID HEPATOCELLULAR-CARCINOMA RECURRENCE; PROGNOSTIC-FACTORS; MICROVASCULAR INVASION; SELECTION CRITERIA; TUMOR RECURRENCE; RISK-FACTORS; SURVIVAL; LEVEL; HEPATECTOMY; PROGRESSION AB Liver transplantation (LT) provides optimal long-term disease-free survival for hepatocellular carcinoma (HCC). High pre-LT alpha-fetoprotein (AFP) has been associated with HCC recurrence, but it is unclear whether a drop in AFP or locoregional therapy impacts survival/recurrence after LT. LT-recipients transplanted for HCC in three centers (UNOS Region 6) were reviewed (20062009) for demographics, tumor characteristics, locoregional therapy, AFP, recurrence, and survival. Among 211 LT recipients (mean age 56.4 yr, 83% male, mean MELD 12.2), 94% met Milan criteria and 61% received locoregional therapy. Mean disease-free survival (DFS) was 1549.7 d, and 84% are currently alive. Factors affecting DFS included recurrence (RR, 0.074; 95% CI, 0.0380.14), normal peak AFP (29.6, 95% CI, 2.96296.3), peak AFP >400 (RR, 0.15; 95% CI, 0.030.73) and AFP at LT >400 (RR, 15.5; 95% CI, 2.4100.5). Twenty-one patients had recurrence and were more likely beyond Milan criteria (5/23(21%) vs. 8/220 (4%), p = 0.0038), with peak AFP >400 and AFP at LT >400 (p = 0.001). Locoregional therapy did not affect mean DFS (1458.0 vs. 1603.8 d, p = 0.05) or recurrence (12.5% vs. 6%). Predictors of recurrence were similar to previous studies, including high AFP and tumor outside Milan criteria. While locoregional therapy itself did not affect DFS/recurrence, a decrease in AFP pre-transplant appears to positively influence outcomes in those who received locoregional therapy. C1 [Wong, Linda L.] Hawaii Med Ctr E, Transplant Inst, Honolulu, HI USA. [Naugler, Willscott E.; Schwartz, Jonathan] Oregon Hlth & Sci Univ, Div Gastroenterol, Portland, OR 97201 USA. [Scott, David L.; Orloff, Susan L.] Oregon Hlth & Sci Univ, Div Abdominal Organ Transplantat, Portland, OR 97201 USA. [Scott, David L.; Orloff, Susan L.] Portland VA Med Ctr, Liver Transplant Program, Portland, OR USA. [Bhattacharya, Renuka; Reyes, Jorge] Univ Washington, Med Ctr, Transplant Serv, Seattle, WA 98195 USA. RP Wong, LL (reprint author), Queens Med Ctr, 550 S Beretania St,Suite 403, Honolulu, HI 96813 USA. EM hepatoma@aol.com NR 38 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0902-0063 J9 CLIN TRANSPLANT JI Clin. Transplant. PD JAN-FEB PY 2013 VL 27 IS 1 BP E72 EP E79 DI 10.1111/ctr.12056 PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 079YL UT WOS:000314208000019 PM 23278701 ER PT J AU Nigwekar, SU Strippoli, GFM Navaneethan, SD AF Nigwekar, Sagar U. Strippoli, Giovanni F. M. Navaneethan, Sankar D. TI Thyroid hormones for acute kidney injury SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID ACUTE-RENAL-FAILURE; ACUTE TUBULAR-NECROSIS; MERCURY-INDUCED LESIONS; CRITICALLY-ILL PATIENTS; L-THYROXINE; ENZYMATIC-ACTIVITY; RISK-FACTORS; MORTALITY; MULTICENTER; PROGNOSIS AB Background Acute kidney injury (AKI), which is common in hospitalised patients, is associated with significant morbidity and mortality. Despite recent advances in treatment, AKI outcomes have not changed substantially during the past four decades, and incidence is increasing. There is an urgent need to explore novel therapeutic agents and revisit some older drugs to review their roles in the management of AKI. Although thyroid hormone therapy has shown promise in experimental animal studies, clinical efficacy and safety have not been systematically assessed for the management of people with AKI. Objectives To evaluate the benefits and harms of thyroid hormones for the treatment of hospitalised adults with AKI of any aetiology. Search methods We searched the Cochrane Renal Group's Specialised Register, CENTRAL, MEDLINE, and EMBASE. We also checked the reference lists of retrieved studies and articles. Date of search: November 2012 Selection criteria Randomised controlled trials (RCTs) and quasi-RCTs (in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) that compared any dose or form of thyroid hormone therapy alone or in combination with other agents compared with placebo or supplemental treatment (such as furosemide, dopamine, or atrial natriuretic peptide) in adult AKI patients. Data collection and analysis Two authors independently assessed study quality and extracted data. The quality of included studies was assessed using the Cochrane Collaboration's risk of bias assessment tool. For dichotomous outcomes (death, need for renal replacement therapy (RRT), progression to end-stage kidney disease (ESKD)), we planned to express results as risk ratios (RR) with 95% confidence intervals (CI). Where continuous scales of measurement were used to assess the effects of treatment (length of hospital stay, durations of AKI and RRT), we planned to use the mean difference (MD). Main results Two studies, enrolling 97 participants, met our inclusion criteria. The studies differed significantly in terms of study populations, natural history of AKI (multifactorial AKI in patients with native kidneys versus delayed graft function associated with acute tubular necrosis in transplant recipients), and study interventions; hence, data were not meta-analysed. One study reported a significant increase in the risk of all-cause mortality associated with thyroid hormone interventions compared with placebo (59 participants, RR 3.32, 95% CI 1.21 to 9.12); no deaths were reported in the other study. Both studies reported no significant difference in the need for RRT associated with thyroid hormone therapy when compared to placebo. Neither study reported incidence of progression to ESKD. There was a significantly longer duration of AKI (MD 2.00 days, 95% CI 0.18 to 3.82) and RRT (5.00 days, 95% CI 2.05 to 7.95) associated with thyroid hormone therapy compared with placebo in one study; no differences in durations of AKI (MD 2.00 days, 95% CI -3.53 to 7.53) and RRT (MD 2.00 days, 95% CI -2.36 to 6.36) were noted in the other study. One study reported similar lengths of stay in the intensive care unit and hospital in both intervention and control arms (MD -0.20 days, 95% CI -8.17 to 7.77); the other did not report this outcome. No adverse events were noted to be associated with thyroid hormone therapy in either study. Adequate data were not available to assess changes in kidney function or numbers of RRT sessions. Both included studies were small and methodological quality was suboptimal. Authors' conclusions We found a paucity of large, high quality studies to inform analysis of thyroid hormone interventions for the treatment of people with AKI. Current evidence suggested that thyroid hormone therapy may be associated with worse outcomes for patients with established AKI; therefore, its use for these patients should be avoided. The role of thyroid hormone therapy in preventing AKI has not been adequately investigated and may be considered in future clinical studies. C1 [Nigwekar, Sagar U.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Strippoli, Giovanni F. M.] Childrens Hosp Westmead, Cochrane Renal Grp, Ctr Kidney Res, Westmead, NSW, Australia. [Strippoli, Giovanni F. M.] Mario Negri Sud Consortium, Dept Clin Pharmacol & Epidemiol, Santa Maria Imbaro, Italy. [Strippoli, Giovanni F. M.] Univ Sydney, Sydney Sch Publ Hlth, Sydney, NSW 2006, Australia. [Strippoli, Giovanni F. M.] Diaverum, Med Sci Off, Lund, Sweden. [Navaneethan, Sankar D.] Cleveland Clin, Dept Nephrol & Hypertens, Glickman Urol & Kidney Inst, Cleveland, OH 44106 USA. RP Nigwekar, SU (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. EM sagarnigs@gmail.com NR 41 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2013 IS 1 AR CD006740 DI 10.1002/14651858.CD006740.pub2 PG 25 WC Medicine, General & Internal SC General & Internal Medicine GA 081JL UT WOS:000314315200003 PM 23440810 ER PT J AU Blood, AJ AF Blood, Anne J. TI Imaging Studies in Focal Dystonias: A Systems Level Approach to Studying a Systems Level Disorder SO CURRENT NEUROPHARMACOLOGY LA English DT Article DE Dystonia; fMRI; DTI; PET; TMS; MEG; posture; basal ganglia; premotor; cerebellum; botulinum toxin; DBS ID TRANSCRANIAL MAGNETIC STIMULATION; PRIMARY SOMATOSENSORY CORTEX; ANTICIPATORY POSTURAL ADJUSTMENTS; IMPAIRED SENSORIMOTOR INTEGRATION; BOTULINUM TOXIN TREATMENT; SUPPLEMENTARY MOTOR AREA; HAND DYSTONIA; CERVICAL DYSTONIA; BASAL GANGLIA; WRITERS CRAMP AB Focal dystonias are dystonias that affect one part of the body, and are sometimes task-specific. Brain imaging and transcranial magnetic stimulation techniques have been valuable in defining the pathophysiology of dystonias in general, and are particularly amenable to studying focal dystonias. Over the past few years, several common themes have emerged in the imaging literature, and this review summarizes these findings and suggests some ways in which these distinct themes might all point to one common systems-level mechanism for dystonia. These themes include (1) the role of premotor regions in focal dystonia, (2) the role of the sensory system and sensorimotor integration in focal dystonia, (3) the role of decreased inhibition/increased excitation in focal dystonia, and (4) the role of brain imaging in evaluating and guiding treatment of focal dystonias. The data across these themes, together with the features of dystonia itself, are consistent with a hypothesis that all dystonias reflect excessive output of postural control/stabilization systems in the brain, and that the mechanisms for dystonia reflect amplification of an existing functional system, rather than recruitment of the wrong motor programs. Imaging is currently being used to test treatment effectiveness, and to visually guide treatment of dystonia, such as placement of deep brain stimulation electrodes. In the future, it is hoped that imaging may be used to individualize treatments across behavioral, pharmacologic, and surgical domains, thus optimizing both the speed and effectiveness of treatment for any given individual with focal dystonia. C1 [Blood, Anne J.] Athinoula A Martinos Ctr Biomed Imaging, Lab Neuroimaging & Genet, Mood & Motor Control Lab, Charlestown, MA USA. [Blood, Anne J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Blood, Anne J.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Blood, AJ (reprint author), 120 2nd Ave, Charlestown, MA 02129 USA. EM ablood@nmr.mgh.harvard.edu FU National Institute of Neurological Disorders and Stroke [R01NS052368]; Dystonia Medical Research Foundation FX The MGH Mood and Motor Control Laboratory is supported by a grant from the National Institute of Neurological Disorders and Stroke (grant number R01NS052368 to A.J.B.) and a grant from the Dystonia Medical Research Foundation to A.J.B. NR 125 TC 5 Z9 5 U1 1 U2 15 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-159X J9 CURR NEUROPHARMACOL JI Curr. Neuropharmacol. PD JAN PY 2013 VL 11 IS 1 BP 3 EP 15 PG 13 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 082AX UT WOS:000314365200003 PM 23814533 ER PT J AU Morasco, BJ Turk, DC Donovan, DM Dobscha, SK AF Morasco, Benjamin J. Turk, Dennis C. Donovan, Dennis M. Dobscha, Steven K. TI Risk for prescription opioid misuse among patients with a history of substance use disorder SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Prescription opioid misuse; Chronic pain; Substance use disorder; Aberrant medication-related behaviors; Quality of life ID CHRONIC NONCANCER PAIN; DRUG-RELATED BEHAVIORS; MEDICATION MISUSE; PRIMARY-CARE; HEPATITIS-C; ANXIETY DISORDERS; VALIDATION; ABUSE; PREVALENCE; VETERANS AB Background: History of substance use disorder (SUD) is associated with risk for prescription opioid misuse in chronic pain patients; however, little data are available regarding risk for prescription opioid misuse within the subgroup of patients with SUD histories. Methods: Participants with chronic pain, histories of SUD, and current opioid prescriptions were recruited from a single VA Medical Center. Participants (n = 80) completed measures of risk for prescription opioid misuse, pain severity, pain-related interference, pain catastrophizing, attitudes about managing pain, emotional functioning, and substance abuse. Results: Participants were divided into three groups based on risk for prescription opioid misuse, as assessed by the Pain Medication Questionnaire (PMQ). Participants in the High-PMQ group reported more pain severity, interference, catastrophizing, depressive symptoms, and lowest self-efficacy for managing pain, relative to the Low-PMQ group; the High-PMQ group and Moderate-PMQ group differed on measures of pain severity, catastrophizing, and psychiatric symptoms (all p-values <0.05). The High-PMQ group had the highest rates of current SUD (32% versus 20% and 0, p = 0.009). A regression analysis evaluated factors associated with PMQ scores: pain catastrophizing was the only variable significantly associated with risk for prescription opioid misuse. Conclusions: Among patients with SUD histories, those with higher risk for prescription opioid misuse reported more pain and impairment, symptoms of depression, and were more likely to have current SUD, relative to patients with lower risk for prescription opioid misuse. In adjusted analyses, pain catastrophizing was significantly associated with risk for prescription opioid misuse, but current SUD status was not a significant predictor. Published by Elsevier Ireland Ltd. C1 [Morasco, Benjamin J.; Dobscha, Steven K.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR USA. [Morasco, Benjamin J.; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Turk, Dennis C.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [Donovan, Dennis M.] Univ Washington, Alcohol & Drug Abuse Inst, Seattle, WA 98195 USA. [Dobscha, Steven K.] Portland VA Med Ctr, Ctr Study Chron Comorbid Med & Psychiat Disorders, Portland, OR USA. RP Morasco, BJ (reprint author), Portland VA Med Ctr R&D99, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM benjamin.morasco@va.gov FU National Institute on Drug Abuse (NIDA) [023467]; Endo; Johnson Johnson; Philips Respironics; National Institutes of Health; Eli Lilly; OrthoMcNeill-Janssen; Pfizer; SK LifeScience FX Funding for this study was provided in part by The National Institute on Drug Abuse (NIDA) grant 023467. NIDA had no further role in study design; in the collection, analysis or interpretation of data; in the writing of the manuscript; or in the decision to submit for publication.; Dr. Turk has received research support from Endo, Johnson & Johnson, Philips Respironics, and the National Institutes of Health, and consulting fees from Eli Lilly, OrthoMcNeill-Janssen, Pfizer, Philips Respironics, and SK LifeScience. He is also a Special Government Employee of the U.S. Food and Drug Administration. All other authors declare that they have no conflicts of interest. NR 49 TC 27 Z9 27 U1 4 U2 17 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 JAN 1 PY 2013 VL 127 IS 1-3 BP 193 EP 199 DI 10.1016/j.drugalcdep.2012.06.032 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 079VK UT WOS:000314200100028 PM 22818513 ER PT J AU van Eeghen, AM Nellist, M van Eeghen, EE Thiele, EA AF van Eeghen, Agnies M. Nellist, Mark van Eeghen, Elmer E. Thiele, Elizabeth A. TI Central TSC2 missense mutations are associated with a reduced risk of infantile spasms SO EPILEPSY RESEARCH LA English DT Article DE TSC; Epilepsy; Infantile spasms; Genetics; Phenotype ID TUBEROUS SCLEROSIS COMPLEX; AMINO-ACID CHANGES; PHENOTYPE; GENOTYPE; GENES AB Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome with a variable neurocognitive phenotype. Recently, different intelligence profiles were observed for distinct mutation types and locations, suggesting that individuals with missense mutations represent a subgroup with milder neurocognitive outcomes. We applied these recent insights to the analysis of the epilepsy phenotype in a large cohort of patients with TSC. Associations between genotype and a history of epilepsy and/or infantile spasms (IS) were explored retrospectively, using data from 478 TSC patients from the databases of the Tuberous Sclerosis Alliance and the Herscot Center at Massachusetts General Hospital. Absolute and relative risks for IS and other types of epilepsy were calculated for various mutation classes, selected according to type and location. As expected, TSC2 mutations were associated with a significantly higher occurrence of IS and other epilepsy types. However, missense mutations located in the central region of TSC2 (exons 23-33) were associated with a significantly reduced incidence of IS. Our study further delineates the epilepsy phenotype in TSC patients. Identifying distinct epilepsy phenotypes for specific mutation subgroups may help identify relevant biomarkers and assist clinicians in making treatment decisions. (c) 2012 Elsevier B.V. All rights reserved. C1 [van Eeghen, Agnies M.; van Eeghen, Elmer E.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Herscot Ctr Tuberous Sclerosis Complex, Boston, MA 02114 USA. [van Eeghen, Agnies M.] Erasmus MC, Dept Neurosci, Expertise Ctr Neurodev Disorders, ENCORE, NL-3000 CA Rotterdam, Netherlands. [Nellist, Mark] Erasmus MC, Dept Clin Genet, NL-3000 CA Rotterdam, Netherlands. RP Thiele, EA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Herscot Ctr Tuberous Sclerosis Complex, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM m.nellist@erasmusmc.nl; elmervaneeghen@gmail.com; ethiele@partners.org FU Carol and James Herscot Center for Tuberous Sclerosis Complex; NIH/NINDS [P01NS024279] FX We thank the TSC Database Natural History Consortium, especially Joanne Nakagawa, for data collection. The views expressed in this article are those of the authors and do not necessarily reflect the opinion of the Tuberous Sclerosis Alliance or the Tuberous Sclerosis Complex Natural History Database Consortium. This study was supported by the Carol and James Herscot Center for Tuberous Sclerosis Complex and NIH/NINDS P01NS024279. NR 19 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD JAN PY 2013 VL 103 IS 1 BP 83 EP 87 DI 10.1016/j.eplepsyres.2012.07.007 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 080SO UT WOS:000314263800008 PM 22867869 ER PT J AU Durant, RW Brown, QL Cherrington, AL Andreae, LJ Hardy, CM Scarinci, IC AF Durant, Raegan W. Brown, Qiana L. Cherrington, Andrea L. Andreae, Lynn J. Hardy, Claudia M. Scarinci, Isabel C. TI Social support among African Americans with heart failure: Is there a role for community health advisors? SO HEART & LUNG LA English DT Article DE African Americans; Community health advisors; Heart failure; Social support ID RANDOMIZED CONTROLLED-TRIAL; WORKER INTERVENTIONS; RACIAL-DIFFERENCES; BLOOD-PRESSURE; DIABETES CARE; SELF-CARE; DISPARITIES; OUTCOMES; POPULATION; HYPERTENSION AB Objective: The study had 2 objectives: (1) to gather the observations of community health advisors (CHAs) on the role of social support in the lives of African Americans; and (2) to develop a lay support intervention framework, on the basis of the existing literature and observations of CHAs, depicting how social support may address the needs of African American patients with heart failure. Methods: Qualitative data were collected in semistructured interviews among 15 CHAs working in African American communities in Birmingham, Alabama. Results: Prominent themes included the challenge of meeting clients' overlapping health care and general life needs, the variation in social support received from family and friends, and the opportunities for CHAs to provide multiple types of social support to clients. CHAs also believed that their, support activities could be implemented among populations with heart failure. Conclusion: The experience of CHAs with social support can inform a potential framework of a lay support intervention among African Americans with heart failure. Published by Elsevier Inc. C1 [Durant, Raegan W.; Cherrington, Andrea L.; Andreae, Lynn J.; Scarinci, Isabel C.] Univ Alabama Birmingham, Sch Med, Birmingham, AL 35294 USA. [Durant, Raegan W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Brown, Qiana L.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Hardy, Claudia M.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. RP Durant, RW (reprint author), Univ Alabama Birmingham, Sch Med, 1717 11th Ave S,MT 607, Birmingham, AL 35294 USA. EM rdurant@dopm.uab.edu FU National Institute on Aging (Deep Resource Center for Minority Aging Research) [P30AG031054]; National Cancer Institute (Deep South Network for Cancer Control [U01CA114619] FX This project was funded by grants from the National Institute on Aging (Deep Resource Center for Minority Aging Research, P30AG031054) and the National Cancer Institute (Deep South Network for Cancer Control, U01CA114619). NR 48 TC 2 Z9 2 U1 2 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0147-9563 J9 HEART LUNG JI Heart Lung PD JAN-FEB PY 2013 VL 42 IS 1 BP 19 EP 25 DI 10.1016/j.hrtlng.2012.06.007 PG 7 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA 083BB UT WOS:000314436600005 PM 22920609 ER PT J AU Taqueti, VR Jaffer, FA AF Taqueti, Viviany R. Jaffer, Farouc A. TI High-resolution molecular imaging via intravital microscopy: illuminating vascular biology in vivo SO INTEGRATIVE BIOLOGY LA English DT Review ID NEAR-INFRARED FLUORESCENCE; CORONARY ATHEROSCLEROTIC PLAQUES; SMOOTH-MUSCLE-CELLS; E-DEFICIENT MICE; APOLIPOPROTEIN-E; THROMBUS FORMATION; MULTIPHOTON MICROSCOPY; ENDOTHELIAL SELECTINS; CATHEPSIN-S; INFLAMMATION AB Complications of atherosclerosis and thrombosis are leading causes of death worldwide. While experimental investigations have yielded valuable insights into key molecular and cellular phenomena in these diseases of medium-and large-sized vessels, direct visualization of relevant in vivo biological processes has been limited. However, recent developments in molecular imaging technology, specifically fluorescence imaging agents coupled with high-resolution, high-speed intravital microscopy (IVM), are now enabling dynamic and longitudinal investigations into the mechanisms and progression of many vascular diseases. Here we review recent advances in IVM that have provided new in vivo biological insights into atherosclerosis and thrombosis. C1 [Taqueti, Viviany R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. [Jaffer, Farouc A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Jaffer, Farouc A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Taqueti, VR (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. EM fjaffer@mgh.harvard.edu OI Jaffer, Farouc/0000-0001-7980-384X FU National Institutes of Health [NIH HL 108229]; American Heart Association Scientist Development Grant [0830352N]; Howard Hughes Medical Institute Career Development Award; MGH SPARK Award FX Dr Jaffer's laboratory is funded by the National Institutes of Health (NIH HL 108229), American Heart Association Scientist Development Grant #0830352N, Howard Hughes Medical Institute Career Development Award, and MGH SPARK Award. NR 67 TC 7 Z9 7 U1 2 U2 24 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1757-9694 J9 INTEGR BIOL-UK JI Integr. Biol. PY 2013 VL 5 IS 2 BP 278 EP 290 DI 10.1039/c2ib20194a PG 13 WC Cell Biology SC Cell Biology GA 080TJ UT WOS:000314265900002 PM 23135362 ER PT J AU Jamil, Z Tearney, G Bruining, N Sihan, K van Soest, G Ligthart, J van Domburg, R Bouma, B Regar, E AF Jamil, Z. Tearney, G. Bruining, N. Sihan, K. van Soest, G. Ligthart, J. van Domburg, R. Bouma, B. Regar, E. TI Interstudy reproducibility of the second generation, Fourier domain optical coherence tomography in patients with coronary artery disease and comparison with intravascular ultrasound: a study applying automated contour detection SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Article DE Interstudy variability; Fourier domain; Optical coherence tomography; Intravascular; Ultrasound; Reproducibility ID IN-VIVO; QUANTITATIVE-ANALYSIS; STENT; QUANTIFICATION; VARIABILITY; VALIDATION; MICROSCOPY; NEOINTIMA; AGREEMENT; PLAQUES AB Recently, Fourier domain OCT (FD-OCT) has been introduced for clinical use. This approach allows in vivo, high resolution (15 micron) imaging with very fast data acquisition, however, it requires brief flushing of the lumen during imaging. The reproducibility of such fast data acquisition under intracoronary flush application is poorly understood. To assess the inter-study variability of FD-OCT and to compare lumen morphometry to the established invasive imaging method, IVUS. 18 consecutive patients with coronary artery disease scheduled for PCI were included. In each target vessel a FD-OCT pullback (MGH system, light source 1,310 nm, 105 fps, pullback speed 20 mm/s) was acquired during brief (3 s) injection of X-ray contrast (flow 3 ml/s) through the guiding catheter. A second pullback was repeated under the same conditions after re-introduction of the FD OCT catheter into the coronary artery. IVUS and OCT imaging was performed in random order. FD-OCT and IVUS pullback data were analyzed using a recently developed software employing semi automated lumen contour and stent strut detection algorithms. Corresponding ROI were matched based on anatomical landmarks such as side branches and/or stent edges. Inter-study variability is presented as the absolute difference between the two pullbacks. FD-OCT showed remarkably good reproducibility. Inter-study variability in native vessels (cohort A) was very low for mean and minimal luminal area (0.10 +/- A 0.38, 0.19 +/- A 0.57 mm(2), respectively). Likewise inter-study variability was very low in stented coronary segments (cohort B) for mean lumen, mean stent, minimal luminal and minimal stent area (0.06 +/- A 0.08, 0.07 +/- A 0.10, 0.04 +/- A 0.09, 0.04 +/- A 0.10 mm(2), respectively). Comparison to IVUS morphometry revealed no significant differences. The differences between both imaging methods, OCT and IVUS, were very low for mean lumen, mean stent, minimal luminal and minimal stent area (0.10 +/- A 0.45, 0.10 +/- A 0.36, 0.26 +/- A 0.54, 0.05 +/- A 0.47 mm(2), respectively). FD-OCT shows excellent reproducibility and very low inter-study variability in both, native and stented coronary segments. No significant differences in quantitative lumen morphometry were observed between FD-OCT and IVUS. Evaluating these results suggest that FD-OCT is a reliable imaging tool to apply in longitudinal coronary artery disease studies. C1 [Jamil, Z.; Bruining, N.; Sihan, K.; van Soest, G.; Ligthart, J.; van Domburg, R.; Regar, E.] Erasmus MC, Thoraxctr, NL-3015 GD Rotterdam, Netherlands. [Tearney, G.; Bouma, B.] Wellman Ctr Photomed, Boston, MA USA. [Tearney, G.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Tearney, G.; Bouma, B.] Harvard MIT Hlth Sci & Technol, Cambridge, MA USA. [Bouma, B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Regar, E (reprint author), Erasmus MC, Thoraxctr, Bd 585,Dr Molewaterpl 40, NL-3015 GD Rotterdam, Netherlands. EM e.regar@erasmusmc.nl RI van Soest, Gijs/B-4881-2008 NR 33 TC 9 Z9 11 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD JAN PY 2013 VL 29 IS 1 BP 39 EP 51 DI 10.1007/s10554-012-0067-8 PG 13 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 076QB UT WOS:000313971000007 PM 22639296 ER PT J AU Desjardins, B Dill, KE Flamm, SD Francois, CJ Gerhard-Herman, MD Kalva, SP Mansour, MA Mohler, ER Oliva, IB Schenker, MP Weiss, C Rybicki, FJ AF Desjardins, Benoit Dill, Karin E. Flamm, Scott D. Francois, Christopher J. Gerhard-Herman, Marie D. Kalva, Sanjeeva P. Mansour, M. Ashraf Mohler, Emile R., III Oliva, Isabel B. Schenker, Matthew P. Weiss, Clifford Rybicki, Frank J. TI ACR Appropriateness Criteria (R) pulsatile abdominal mass, suspected abdominal aortic aneurysm SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Review DE Appropriateness criteria; Aortic aneurysm; Ultrasonography; Computed tomography; Magnetic resonance angiography; Catheter arteriography ID MULTIDETECTOR ROW CT; COMPUTED-TOMOGRAPHY; ENDOVASCULAR REPAIR; WALL STRESS; INTEROBSERVER VARIABILITY; ULTRASOUND MEASUREMENTS; INTRALUMINAL THROMBUS; NATURAL-HISTORY; ANGIOGRAPHY; DIAMETER AB Clinical palpation of a pulsating abdominal mass alerts the clinician to the presence of a possible abdominal aortic aneurysm (AAA). Generally an arterial aneurysm is defined as a localized arterial dilatation a parts per thousand yen50 % greater than the normal diameter. Imaging studies are important in diagnosing the cause of a pulsatile abdominal mass and, if an AAA is found, in determining its size and involvement of abdominal branches. Ultrasound (US) is the initial imaging modality of choice when a pulsatile abdominal mass is present. Noncontrast computed tomography (CT) may be substituted in patients for whom US is not suitable. When aneurysms have reached the size threshold for intervention or are clinically symptomatic, contrast-enhanced multidetector CT angiography (CTA) is the best diagnostic and preintervention planning study, accurately delineating the location, size, and extent of aneurysm and the involvement of branch vessels. Magnetic resonance angiography (MRA) may be substituted if CT cannot be performed. Catheter arteriography has some utility in patients with significant contraindications to both CTA and MRA. The American College of Radiology Appropriateness Criteria(A (R)) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Desjardins, Benoit] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Dill, Karin E.] Univ Chicago, Chicago, IL 60637 USA. [Flamm, Scott D.] Cleveland Clin, Cleveland, OH 44106 USA. [Francois, Christopher J.] Univ Wisconsin, Madison, WI USA. [Gerhard-Herman, Marie D.] Brigham & Womens Hosp, Amer Coll Cardiol, Boston, MA 02115 USA. [Kalva, Sanjeeva P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mansour, M. Ashraf] Vasc Associates, Soc Vasc Surg, Grand Rapids, MI USA. [Mohler, Emile R., III] Univ Penn, Amer Coll Cardiol, Philadelphia, PA 19104 USA. [Oliva, Isabel B.] Yale Univ, Sch Med, New Haven, CT USA. [Schenker, Matthew P.; Rybicki, Frank J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Weiss, Clifford] Johns Hopkins Bayview Med Ctr, Baltimore, MD USA. RP Desjardins, B (reprint author), Univ Penn, Dept Radiol, 3400 Spruce St,1 Silverstein Bldg, Philadelphia, PA 19104 USA. EM bd_md_phd@me.com NR 65 TC 4 Z9 4 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD JAN PY 2013 VL 29 IS 1 BP 177 EP 183 DI 10.1007/s10554-012-0044-2 PG 7 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 076QB UT WOS:000313971000022 PM 22644671 ER PT J AU Amparo, F Sadrai, Z Jin, YP Alfonso-Bartolozzi, B Wang, HB Shikari, H Ciolino, JB Chodosh, J Jurkunas, U Schaumberg, DA Dana, R AF Amparo, Francisco Sadrai, Zahra Jin, Yiping Alfonso-Bartolozzi, Belen Wang, Haobing Shikari, Hasanain Ciolino, Joseph B. Chodosh, James Jurkunas, Ula Schaumberg, Debra A. Dana, Reza TI Safety and Efficacy of the Multitargeted Receptor Kinase Inhibitor Pazopanib in the Treatment of Corneal Neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; CHOROIDAL NEOVASCULARIZATION; PERICYTE RECRUITMENT; GRAFT-SURVIVAL; ANGIOGENESIS; THERAPY; TRANSPLANTATION; MATURATION; PDGF; LYMPHANGIOGENESIS AB PURPOSE. To evaluate the safety and efficacy of topical pazopanib in the treatment of corneal neovascularization (CNV). METHODS. Twenty eyes of 20 patients with stable CNV were enrolled in a prospective, open label, noncomparative study and treated with topical pazopanib 0.5% for 3 weeks, and followed for 12 weeks. The primary endpoint was to determine the tolerability and safety of topical pazopanib in the treatment of CNV defined by the occurrence of ocular and systemic adverse events during the study. The secondary endpoint was to evaluate the effect of topical pazopanib on the reduction of (1) neovascular area (NA), defined as the area of the corneal vessels themselves, (2) invasion area (IA), defined as the fraction of the total cornea into which the vessels extend, (3) vessel length (VL), defined as the mean measurement of the extent of vessels from end to end, and (4) vessel caliber (VC), defined as the mean diameter of the corneal vessels. RESULTS. There were no severe adverse events following the use of topical pazopanib. Compared with the baseline visit, NA and VL showed a statistically significant decrease at week 3 (P 0.02 and 0.01, respectively); and NA, IA, and VL statistically significantly decreased at week 12 (P = 0.03, 0.04, and <0.01, respectively). Visual acuity maintained without changes after the 12 week follow-up. CONCLUSIONS. This preliminary study suggests that topical treatment with pazopanib 0.5% is safe, well tolerated, and may have a role as an alternative for the treatment of CNV (ClinicalTrials.gov number, NCT01257750). (Invest Ophthalmol Vis Sci. 2013;54:537-544) DOI:10.1167/iovs.12-11032 C1 [Amparo, Francisco; Sadrai, Zahra; Jin, Yiping; Alfonso-Bartolozzi, Belen; Wang, Haobing; Shikari, Hasanain; Ciolino, Joseph B.; Chodosh, James; Jurkunas, Ula; Dana, Reza] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Schaumberg, Debra A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA. RP Dana, R (reprint author), Massachusetts Eye & Ear Infirm, Cornea Serv, 243 Charles St, Boston, MA 02114 USA. EM reza_dana@meei.harvard.edu FU National Institutes of Health [K24 EY019098]; GlaxoSmithKline Laboratories FX Supported by grants from the National Institutes of Health (K24 EY019098) and by GlaxoSmithKline Laboratories. NR 39 TC 7 Z9 9 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2013 VL 54 IS 1 BP 537 EP 544 DI 10.1167/iovs.12-11032 PG 8 WC Ophthalmology SC Ophthalmology GA 081QX UT WOS:000314338400070 PM 23233252 ER PT J AU Ferrari, G Hajrasouliha, AR Sadrai, Z Ueno, H Chauhan, SK Dana, R AF Ferrari, Giulio Hajrasouliha, Amir R. Sadrai, Zahra Ueno, Hiroki Chauhan, Sunil K. Dana, Reza TI Nerves and Neovessels Inhibit Each Other in the Cornea SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; EPITHELIUM-DERIVED FACTOR; IN-VIVO; ANTIANGIOGENIC ACTIVITY; VASCULAR DEVELOPMENT; AXON GUIDANCE; BLOOD-VESSEL; ANGIOGENESIS; NEOVASCULARIZATION; CELLS AB PURPOSE. To evaluate the regulatory cross-talk of the vascular and neural networks in the cornea. METHODS. b-FGF micropellets (80 ng) were implanted in the temporal side of the cornea of healthy C57Bl/6 mice. On day 7, blood vessels (hemangiogenesis) and nerves were observed by immunofluorescence staining of corneal flat mounts. The next group of mice underwent either trigeminal stereotactic electrolysis (TSE), or sham operation, to ablate the ophthalmic branch of the trigeminal nerve. Blood vessel growth was detected by immunohistochemistry for PECAM-1 (CD31) following surgery. In another set of mice following TSE or sham operation, corneas were harvested for ELISA (VEGFR3 and pigment epithelium-derived factor [PEDF]) and for quantitative RT-PCR (VEGFR3, PEDF, and CD45). PEDF, VEGFR3, beta-3 tubulin, CD45, CD11b, and F4/80 expression in the cornea were evaluated using immunostaining. RESULTS. No nerves were detected in the areas subject to corneal neovascularization, whereas they persisted in the areas that were neovessel-free. Conversely, 7 days after denervation, significant angiogenesis was detected in the cornea, and this was associated with a significant decrease in VEGFR3 (57.5% reduction, P = 0.001) and PEDF protein expression (64% reduction, P < 0.001). Immunostaining also showed reduced expression of VEGFR3 in the corneal epithelial layer. Finally, an inflammatory cell infiltrate, including macrophages, was observed. CONCLUSION. Our data suggest that sensory nerves and neovessels inhibit each other in the cornea. When vessel growth is stimulated, nerves disappear and, conversely, denervation induces angiogenesis. This phenomenon, here described in the eye, may have far-reaching implications in understanding angiogenesis. (Invest Ophthalmol Vis Sci. 2013;54:813-820) DOI:10.1167/iovs.11-8379 C1 [Ferrari, Giulio; Hajrasouliha, Amir R.; Sadrai, Zahra; Ueno, Hiroki; Chauhan, Sunil K.; Dana, Reza] Schepens Eye Res Inst, Boston, MA USA. [Ferrari, Giulio; Hajrasouliha, Amir R.; Sadrai, Zahra; Ueno, Hiroki; Chauhan, Sunil K.; Dana, Reza] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Sch Med, Boston, MA 02114 USA. [Ferrari, Giulio] Ist Sci San Raffaele, Cornea & Ocular Surface Unit, I-20132 Milan, Italy. RP Ferrari, G (reprint author), Ist Sci San Raffaele, Ophthalmol Cornea & Ocular Surface Unit, Via Olgettina 60, I-20132 Milan, Italy. EM giulio.ferrari@schepens.harvard.edu RI ferrari, giulio/J-9260-2016 OI ferrari, giulio/0000-0001-6474-9908 FU National Institutes of Health [EY-12963, EY-20889]; G.B. Bietti Eye Foundation, IRCCS, Rome, Italy FX Supported by National Institutes of Health Grants EY-12963 and EY-20889, and the G.B. Bietti Eye Foundation, IRCCS, Rome, Italy. NR 49 TC 14 Z9 14 U1 1 U2 8 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2013 VL 54 IS 1 BP 813 EP 820 DI 10.1167/iovs.11-8379 PG 8 WC Ophthalmology SC Ophthalmology GA 081QX UT WOS:000314338400107 PM 23307967 ER PT J AU Sun, Q Huang, Q Feng, AN Fan, XS Wu, HY Mashimo, H Zhou, Q Chen, J Lauwers, GY AF Sun, Qi Huang, Qin Feng, An Ning Fan, Xiang Shan Wu, Hong Yan Mashimo, Hiroshi Zhou, Qiang Chen, Jin Lauwers, Gregory Y. TI Columnar-lined esophagus in Chinese patients with proximal gastric carcinomas SO JOURNAL OF DIGESTIVE DISEASES LA English DT Article DE Chinese; columnar-lined esophagus; esophagus; gastroesophageal junction; superficial esophageal gland ID GASTROESOPHAGEAL-REFLUX DISEASE; HELICOBACTER-PYLORI INFECTION; BARRETTS-ESOPHAGUS; INTESTINAL METAPLASIA; PREVALENCE; CARDITIS; JUNCTION; ADENOCARCINOMA; DYSPLASIA; FEATURES AB OBJECTIVE: To investigate the clinicopathological features of columnar-lined esophagus (CLE) in Chinese patients. METHODS: Among 182 consecutive resections of proximal gastric cancer with residual esophageal tissue, 114 were eligible for the study. The maximal lengths of CLE and superficial esophageal glands (SEG) and the presence or absence of chronic inflammation (CI), lymphoid follicles (LF), Helicobacter pylori (H. pylori) infection, intestinal metaplasia (IM), pancreatic metaplasia (PM) and dysplasia were analyzed and compared with those in the adjacent proximal gastric mucosa. RESULTS: SEG were present in 110 cases with a mean length of 5.4 mm (range 1-16 mm, 90% equal to or under 10 mm and 10% between 11-16 mm). These glands were associated with CI (95%), LF (85%), H. pylori infection (42%), IM (25%), PM (36%) and dysplasia (10%). CLE was found in 65% of the cases and was associated with SEG (mean length of 4.0 mm, range 1-13 mm, 97% within 10 mm and 3% between 11-13 mm). The frequencies of CI (97%), LF (86%), H. pylori infection (65%) and PM (46%) in CLE were similar to those in the proximal stomach (CI 90%, LF 54%, H. pylori infection 58%, PM 39%). In contrast, the frequencies of IM (37%) and dysplasia (15%) in CLE were significantly lower than those in the proximal stomach (66% and 31%, respectively; P < 0.01). CONCLUSIONS: CLE in Chinese patients was within 10 mm in length in 97% of cases, and with SEG and H. pylori infection-related changes similar to those in the proximal stomach. C1 [Sun, Qi; Huang, Qin; Feng, An Ning; Fan, Xiang Shan; Wu, Hong Yan; Zhou, Qiang; Chen, Jin] Nanjing Univ, Sch Med, Affiliated Hosp, Dept Pathol,Nanjing Drum Tower Hosp, Nanjing 210008, Jiangsu, Peoples R China. [Huang, Qin] Vet Affairs Boston Healthcare Syst, Dept Pathol & Lab Med, W Roxbury, MA 02132 USA. [Mashimo, Hiroshi] Vet Affairs Boston Healthcare Syst, Dept Gastroenterol, W Roxbury, MA 02132 USA. [Huang, Qin; Mashimo, Hiroshi; Lauwers, Gregory Y.] Harvard Univ, Sch Med, Boston, MA USA. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Huang, Q (reprint author), Vet Affairs Boston Healthcare Syst, Dept Pathol & Lab Med, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM qinhuang0122@gmail.com FU Science and Technology Development Project of Nanjing [ZKX05013, ZKX07011, QYK11164]; Nanjing Drum Tower Hospital (Nanjing, Jiangsu Province, China) FX This research project was financed partially by grants from the Science and Technology Development Project of Nanjing (ZKX05013, ZKX07011 and QYK11164), and a special grant from the Nanjing Drum Tower Hospital (Nanjing, Jiangsu Province, China). NR 25 TC 3 Z9 6 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1751-2972 J9 J DIGEST DIS JI J. Dig. Dis. PD JAN PY 2013 VL 14 IS 1 BP 22 EP 28 DI 10.1111/1751-2980.12007 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 078VV UT WOS:000314129000004 PM 23134360 ER PT J AU Chiu, MW Modlin, RL AF Chiu, Melvin W. Modlin, Robert L. TI RESIDENT ROUNDS: PART I Program Spotlight: The UCLA Division of Dermatology Residency Training Program SO JOURNAL OF DRUGS IN DERMATOLOGY LA English DT Editorial Material C1 [Chiu, Melvin W.; Modlin, Robert L.] Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Los Angeles, CA 90095 USA. [Chiu, Melvin W.] Greater Los Angeles Vet Adm Hlth Care Syst, Dermatol Serv, Los Angeles, CA USA. RP Chiu, MW (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Los Angeles, CA 90095 USA. EM mchiu@mednet.ucla.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOURNAL OF DRUGS IN DERMATOLOGY PI NEW YORK PA 377 PARK AVE SOUTH, 6TH FLOOR, NEW YORK, NY 10016 USA SN 1545-9616 J9 J DRUGS DERMATOL JI J. Drugs Dermatol. PD JAN PY 2013 VL 12 IS 1 BP 109 EP 110 PG 2 WC Dermatology SC Dermatology GA 081KC UT WOS:000314319900020 ER PT J AU Abbo, ED Yuen, TC Buhrmester, L Geocadin, R Volandes, AE Siddique, J Edelson, DP AF Abbo, Elmer D. Yuen, Trevor C. Buhrmester, Luke Geocadin, Romergryko Volandes, Angelo E. Siddique, Juned Edelson, Dana P. TI Cardiopulmonary Resuscitation Outcomes in Hospitalized Community-Dwelling Individuals and Nursing Home Residents Based on Activities of Daily Living SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE CPR outcomes; functional status; nursing home ID FUNCTIONAL STATUS; CARDIAC-ARREST; ELDERLY PATIENTS; SURVIVAL; OLDER; MORTALITY; ASSOCIATION; PREFERENCES; PREDICTORS; ILLNESS AB Objectives To determine whether poor functional status is associated with worse outcomes after attempted cardiopulmonary resuscitation (CPR). Design Retrospective study of individuals who experienced cardiac arrest stratified according to dependence in activities of daily living (ADLs) and residential status (nursing home (NH) or community dwelling). Setting Two hundred thirty-five hospitals throughout North America. Participants Adult inpatients aged 65 and older who had experienced a cardiac arrest as reported to the Get with the GuidelinesResuscitation registry between 2000 and 2008. Measurements Primary outcomes were return of spontaneous circulation (ROSC) and survival to discharge. Results Twenty-six thousand three hundred twenty-nine individuals who experienced cardiac arrest met inclusion criteria. NH residents dependent in ADLs had a lower odds than community-dwelling independent participants of achieving ROSC (odds ratio (OR) = 0.73, 95% confidence interval (CI) = 0.630.85), whereas participants dependent in ADLs from either residential setting had lower odds of survival (community-dwelling: OR = 0.76, 95% CI = 0.630.92; NH: OR = 0.79, 95% CI = 0.640.96) after adjusting for participant and arrest characteristics. Duration of resuscitation and doses of epinephrine or vasopressin were similar between groups and had no significant effect on ROSC or survival, although participants dependent in ADLs were more likely to have a do-not-resuscitate (DNR) order placed after ROSC. Overall, median time to signing a DNR order after resuscitation was 10 hours (interquartile range 270). Conclusion Functional and residential status are important predictors of survival after in-hospital cardiac arrest. Contrary to the hypothesis but reassuring from a quality-of-care perspective, less-aggressive attempts at resuscitation do not appear to contribute to poorer outcomes in individuals dependent in ADL, regardless of residential status. J Am Geriatr Soc 61:34-39, 2013. C1 [Abbo, Elmer D.; Yuen, Trevor C.; Edelson, Dana P.] Univ Chicago, Sect Hosp Med, Dept Med, Chicago, IL 60637 USA. [Buhrmester, Luke] St Lukes Roosevelt Hosp, Dept Emergency Med, New York, NY USA. [Geocadin, Romergryko] Johns Hopkins Bayview Med Ctr, Dept Anesthesiol Crit Care Med, Div Neurosci Crit Care, Baltimore, MD USA. [Volandes, Angelo E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Siddique, Juned] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA. RP Abbo, ED (reprint author), Univ Chicago, Sect Hosp Med, Dept Med, 5841 S Maryland Ave,MC 5000, Chicago, IL 60637 USA. EM eabbo@medicine.bsd.uchicago.edu FU American Heart Association FX The American Heart Association Get with the Guidelines-Resuscitation provided the primary data for this investigation and assisted in review and preparation of the manuscript for publication. NR 24 TC 6 Z9 6 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2013 VL 61 IS 1 BP 34 EP 39 DI 10.1111/jgs.12068 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 073AM UT WOS:000313715600007 PM 23311551 ER PT J AU Peralta, CA Lee, A Odden, MC Lopez, L Al Hazzouri, AZ Neuhaus, J Haan, MN AF Peralta, Carmen A. Lee, Anne Odden, Michelle C. Lopez, Lenny Al Hazzouri, Adina Zeki Neuhaus, John Haan, Mary N. TI Association Between Chronic Kidney Disease Detected Using Creatinine and Cystatin C and Death and Cardiovascular Events in Elderly Mexican Americans: The Sacramento Area Latino Study on Aging SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE chronic kidney disease; Mexican Americans; elderly; creatinine; cystatin C; cardiovascular disease AB Objectives Creatinine, the current clinical standard to detect chronic kidney disease (CKD), is biased by muscle mass, age and race. The authors sought to determine whether cystatin C, an alternative marker of kidney function less biased by these factors, can identify elderly Mexican Americans with CKD who are at high risk for death and cardiovascular disease. Design Longitudinal, with mean follow-up of 6.8 years. Setting Sacramento Area Latino Study of Aging (SALSA). Participants One thousand four hundred and thirty five Mexican Americans aged 60 to 101. Measurements Estimated glomerular filtration rate (eGFR, mL/min per 1.73 m2) was determined according to creatinine (eGFRcreat) and cystatin C (eGFRcys), and participants were classified into four mutually exclusive categories: CKD neither (eGFRcreat =60 mL/min per 1.73 m2; eGFRcys =60 mL/min per 1.73 m2), CKD creatinine only (eGFRcreat <60 mL/min per 1.73 m2; eGFRcys =60 mL/min per 1.73 m2), CKD cystatin only (eGFRcreat =60 mL/min per 1.73 m2; eGFRcys <60), and CKD both (eGFRcreat <60 mL/min per 1.73 m2; GFRcys <60 mL/min per 1.73 m2). The associations between each CKD classification and all-cause death and cardiovascular (CV) death were studied using Cox regression. Results At baseline, mean age was 71 +/- 7; 481 (34%) had diabetes mellitus, and 980 (68%) had hypertension. Persons with CKD both had higher risk for all-cause (HR = 2.30, 95% confidence interval (CI) = 1.782.98) and CV disease (CVD) (HR = 2.75, 95% CI = 1.963.86) death than CKD neither after full adjustment. Persons with CKD cystatin C only were also at greater risk of all-cause (HR = 1.91, 95% CI = 1.372.67) and CV (HR = 2.56, 95% CI = 1.643.99) death than CKD neither. In contrast, persons with CKD creatinine only were not at greater risk for CV death (HR = 1.39, 95% CI = 0.712.72) but were at higher risk for all-cause death (HR = 1.95, 95% CI = 1.272.98). Conclusion Cystatin C may be a useful alternative to creatinine for detecting high risk of death and CVD in elderly Mexican Americans with CKD. C1 [Peralta, Carmen A.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Lee, Anne; Al Hazzouri, Adina Zeki; Neuhaus, John; Haan, Mary N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Odden, Michelle C.] Oregon State Univ, Coll Publ Hlth & Human Sci, Portland, OR USA. [Lopez, Lenny] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Lopez, Lenny] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Peralta, CA (reprint author), 4150 Clement St,111A1, San Francisco, CA 94121 USA. EM carmenalicia.peralta@ucsf.edu FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDKD) [1K23SK082793]; Robert Wood Johnson Harold Amos award; National Institute of Aging [R01012975]; NIDDKD [R01DK60753] FX CP is funded by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDKD) Grant 1K23SK082793 and a Robert Wood Johnson Harold Amos award. SALSA and Dr. Haan are funded by National Institute of Aging Grant R01012975 and NIDDKD Grant R01DK60753. These funding sources had no involvement in the design or execution of this study. NR 0 TC 5 Z9 5 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2013 VL 61 IS 1 BP 90 EP 95 DI 10.1111/jgs.12040 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 073AM UT WOS:000313715600016 PM 23252993 ER PT J AU Zarraga, IGE Kron, J AF Zarraga, Ignatius Gerardo E. Kron, Jack TI Oral Anticoagulation in Elderly Adults with Atrial Fibrillation: Integrating New Options with Old Concepts SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE anticoagulation; antithrombotic; atrial fibrillation; elderly ID WARFARIN-ASSOCIATED HEMORRHAGE; RANDOMIZED CONTROLLED-TRIAL; EURO HEART SURVEY; RE-LY TRIAL; PREDICTING STROKE; ANTITHROMBOTIC THERAPY; RISK STRATIFICATION; COST-EFFECTIVENESS; DABIGATRAN; ASPIRIN AB Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and the second most common cardiovascular condition in adults in the United States. It is prevalent in the elderly population and is an important risk factor for stroke. Oral anticoagulation offers significant protection against AF-related thromboembolic events, but several complex issues that contribute to its underuse in elderly adults surround it. To aid clinicians in their approach to these problems, a comprehensive PubMed-based search of the literature published in English from 1990 through July 2012 was conducted using the following terms or combination of terms: atrial fibrillation, elderly, antiplatelet, anticoagulation, stroke, bleeding, hemorrhage, and falls. Additional references were identified in a manual search of bibliographies in retrieved articles. The data were then synthesized to address the most relevant questions regarding anticoagulation in elderly adults, including fall risk, responsiveness to warfarin, physician perception of risks, and other barriers to the prescription of anticoagulants. Recently proposed risk-stratification schemes for stroke and hemorrhage that could refine the selection of antithrombotic therapy for AF are highlighted. Finally, available data on the use of antiplatelet therapy, warfarin, and new oral anticoagulants (direct thrombin inhibitor and factor Xa inhibitors) in AF are summarized. J Am Geriatr Soc 61:143-150, 2013. C1 [Zarraga, Ignatius Gerardo E.] Portland VA Med Ctr, Div Cardiol, Portland, OR 97239 USA. [Zarraga, Ignatius Gerardo E.; Kron, Jack] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Zarraga, IGE (reprint author), Portland VA Med Ctr, Div Cardiol, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM Ignatius.Zarraga@va.gov FU Boehringer-Ingelheim Pharmaceuticals, Inc.; Johnson Johnson FX This work was supported by Boehringer-Ingelheim Pharmaceuticals, Inc. The authors received no compensation related to the development of the manuscript. The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. JK received a consulting fee from Johnson & Johnson in March 2011 and was a speaker for Biotronik. NR 40 TC 18 Z9 19 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2013 VL 61 IS 1 BP 143 EP 150 DI 10.1111/jgs.12042 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 073AM UT WOS:000313715600025 PM 23252345 ER PT J AU Billings, JA AF Billings, J. Andrew TI Advance Care Planning Intervention SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter ID LIFE CARE; END C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge Hlth Alliance,Ctr Palliat Care, Boston, MA 02115 USA. RP Billings, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge Hlth Alliance,Ctr Palliat Care, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2013 VL 61 IS 1 BP 172 EP 173 DI 10.1111/jgs.12055 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 073AM UT WOS:000313715600037 PM 23311566 ER PT J AU Lipsky, BA Berendt, AR Cornia, PB Pile, JC Peters, EJG Armstrong, DG Deery, HG Embil, JM Joseph, WS Karchmer, AW Pinzur, MS Senneville, E AF Lipsky, Benjamin A. Berendt, Anthony R. Cornia, Paul B. Pile, James C. Peters, Edgar J. G. Armstrong, David G. Deery, H. Gunner Embil, John M. Joseph, Warren S. Karchmer, Adolf W. Pinzur, Michael S. Senneville, Eric TI 2012 Infectious Diseases Society of America Clinical Practice Guideline for the Diagnosis and Treatment of Diabetic Foot Infections (Reprinted from Clinical Infectious Diseases, vol 54, pg 132, 2012) SO JOURNAL OF THE AMERICAN PODIATRIC MEDICAL ASSOCIATION LA English DT Reprint AB Foot infections are a common and serious problem in persons with diabetes. Diabetic foot infections (DFIs) typically begin in a wound, most often a neuropathic ulceration. While all wounds are colonized with microorganisms, the presence of infection is defined by >= 2 classic findings of inflammation or purulence. Infections are then classified into mild (superficial and limited in size and depth), moderate (deeper or more extensive), or severe (accompanied by systemic signs or metabolic perturbations). This classification system, along with a vascular assessment, helps determine which patients should be hospitalized, which may require special imaging procedures or surgical interventions, and which will require amputation. Most DFIs are polymicrobial, with aerobic gram-positive cocci (GPC), and especially staphylococci, the most common causative organisms. Aerobic gram-negative bacilli are frequently copathogens in infections that are chronic or follow antibiotic treatment, and obligate anaerobes may be copathogens in ischemic or necrotic wounds. Wounds without evidence of soft tissue or bone infection do not require antibiotic therapy. For infected wounds, obtain a post-debridement specimen (preferably of tissue) for aerobic and anaerobic culture. Empiric antibiotic therapy can be narrowly targeted at GPC in many acutely infected patients, but those at risk for infection with antibiotic-resistant organisms or with chronic, previously treated, or severe infections usually require broader spectrum regimens. Imaging is helpful in most DFIs; plain radiographs may be sufficient, but magnetic resonance imaging is far more sensitive and specific. Osteomyelitis occurs in many diabetic patients with a foot wound and can be difficult to diagnose (optimally defined by bone culture and histology) and treat (often requiring surgical debridement or resection, and/or prolonged antibiotic therapy). Most DFIs require some surgical intervention, ranging from minor (debridement) to major (resection, amputation). Wounds must also be properly dressed and off-loaded of pressure, and patients need regular follow-up. An ischemic foot may require revascularization, and some nonresponding patients may benefit from selected adjunctive measures. Employing multidisciplinary foot teams improves outcomes. Clinicians and healthcare organizations should attempt to monitor, and thereby improve, their outcomes and processes in caring for DFIs. C1 [Lipsky, Benjamin A.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. [Berendt, Anthony R.] Oxford Univ Hosp NHS Trust, Nuffield Orthopaed Ctr, Bone Infect Unit, Oxford, England. [Cornia, Paul B.] Univ Washington, Veteran Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98195 USA. [Pile, James C.] MetroHlth Med Ctr, Div Hosp Med, Cleveland, OH USA. [Pile, James C.] Metrohlth Med Ctr, Div Infect Dis, Cleveland, OH USA. [Peters, Edgar J. G.] Vrije Univ Amsterdam, Med Ctr, Dept Internal Med, Amsterdam, Netherlands. [Armstrong, David G.] Univ Arizona, Dept Med, So Arizona Limb Salvage Alliance, Tucson, AZ USA. [Deery, H. Gunner] No Michigan Infect Dis, Petoskey, MI USA. [Embil, John M.] Univ Manitoba, Dept Med, Winnipeg, MB, Canada. [Joseph, Warren S.] Roxborough Mem Hosp, Dept Surg, Div Podiatr Surg, Philadelphia, PA USA. [Karchmer, Adolf W.] Harvard Univ, Sch Med, Dept Med,Div Infect Dis, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Pinzur, Michael S.] Loyola Univ, Med Ctr, Dept Orthopaed Surg & Rehabil, Maywood, IL 60153 USA. [Senneville, Eric] Dron Hosp, Dept Infect Dis, Tourcoing, France. RP Lipsky, BA (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM balipsky@uw.edu RI Peters, Edgar /B-7790-2014; OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 1 TC 21 Z9 22 U1 3 U2 30 PU AMER PODIATRIC MED ASSOC PI BETHESDA PA 9312 OLD GEORGETOWN ROAD, BETHESDA, MD 20814-1621 USA SN 8750-7315 J9 J AM PODIAT MED ASSN JI J. Am. Podiatr. Med. Assoc. PD JAN-FEB PY 2013 VL 103 IS 1 BP 2 EP 7 DI 10.1093/cid/cis346 PG 6 WC Orthopedics SC Orthopedics GA 081JU UT WOS:000314318600002 PM 23328846 ER PT J AU Nguyen, USDT Dufour, AB Positano, RG Dines, JS Dodson, CC Gagnon, DG Hillstrom, HJ Hannan, MT AF Nguyen, Uyen-Sa D. T. Dufour, Alyssa B. Positano, Rock G. Dines, Joshua S. Dodson, Christopher C. Gagnon, David G. Hillstrom, Howard J. Hannan, Marian T. TI The Occurrence of lpsilateral or Contra lateral Foot Disorders and Hand Dominance The Framingham Foot Study SO JOURNAL OF THE AMERICAN PODIATRIC MEDICAL ASSOCIATION LA English DT Article ID LEFT-HANDEDNESS; INJURY RISK; PREFERENCES; AGE; ADULTS; EYE AB Background: To our knowledge, hand dominance and side of foot disorders has not been described in the literature. We sought to evaluate whether hand dominance was associated with ipsilateral foot disorders in community-dwelling older men and women. Methods: Data were from the Framingham Foot Study (N = 2,089, examined 2002-2008). Hand preference for writing was used to classify hand dominance. Foot disorders and side of disorders were based on validated foot examination findings. Generalized linear models with generalized estimating equations were used to estimate odds ratios and 95% confidence intervals, accounting for intraperson variability. Results: Left-handed people were less likely to have foot pain or any foot disorders ipsilateral but were more likely to have hallux valgus ipsilateral to the left hand. Among right-handed people, the following statistically significant increased odds of having an ipsilateral versus contralateral foot disorder were seen: 30% for Morton's neuroma, 18% for hammer toes, 21% for lesser toe deformity, and a twofold increased odds of any foot disorder; there was a 17% decreased odds for Tailor's bunion and an 11% decreased odds for pes cavus. Conclusions: For the 2,089 study participants, certain forefoot disorders were shown to be ipsilateral and others were contralateral to the dominant hand. Future studies should examine whether the same biological mechanism that explains ipsilateral hand and foot preference may explain ipsilateral hand dominance and forefoot disorders. (J Am Podiatr Med Assoc 103(1): 16-23, 2013) C1 [Nguyen, Uyen-Sa D. T.] Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, Boston, MA 02118 USA. [Dufour, Alyssa B.; Hannan, Marian T.] Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA. [Dufour, Alyssa B.; Hannan, Marian T.] Harvard Univ, Sch Med, Boston, MA USA. [Positano, Rock G.] Hosp Special Surg, Nonsurg Foot & Ankle Serv, New York, NY 10021 USA. [Positano, Rock G.] Hosp Special Surg, Joe DiMaggio Sports Foot & Ankle Ctr, New York, NY 10021 USA. [Dines, Joshua S.] Hosp Special Surg, Sports Med & Shoulder Serv, New York, NY 10021 USA. [Dodson, Christopher C.] Thomas Jefferson Univ Hosp, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. [Gagnon, David G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Gagnon, David G.] US Dept Vet Affairs, Cooperat Studies Program, Boston, MA USA. [Hillstrom, Howard J.] Hosp Special Surg, MD Motion Anal Lab, New York, NY 10021 USA. RP Hannan, MT (reprint author), Hebrew SeniorLife, Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA. EM Hannan@hsl.harvard.edu FU Non-surgical Foot and Ankle Service at the Hospital for Special Surgery; National Institutes of Health [R01-AR047853]; National Heart Lung and Blood Institute of the National Institutes of Health [N01-HC-25195]; Boston University School of Medicine; National Institutes of Health-National Institute on Aging supplement [3R01AG026316-03S1] FX This work was funded by an unrestricted research grant from the Non-surgical Foot and Ankle Service at the Hospital for Special Surgery and from the National Institutes of Health (R01-AR047853). This work was derived from the Framingham Heart Study, supported by the National Heart Lung and Blood Institute of the National Institutes of Health (contract No. N01-HC-25195) and Boston University School of Medicine. Dr. Hannan was supported by the National Institutes of Health-National Institute on Aging supplement 3R01AG026316-03S1. The sponsors played no role in the design and conduct of the study. NR 14 TC 1 Z9 1 U1 1 U2 6 PU AMER PODIATRIC MED ASSOC PI BETHESDA PA 9312 OLD GEORGETOWN ROAD, BETHESDA, MD 20814-1621 USA SN 8750-7315 J9 J AM PODIAT MED ASSN JI J. Am. Podiatr. Med. Assoc. PD JAN-FEB PY 2013 VL 103 IS 1 BP 16 EP 23 PG 8 WC Orthopedics SC Orthopedics GA 081JU UT WOS:000314318600004 PM 23328848 ER PT J AU Williams, ME AF Williams, Mark E. TI Preface Diabetic Chronic Kidney Disease: When the Other Shoe Drops SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Williams, ME (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM mark.williams@joslin.harvard.edu NR 2 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 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD JAN PY 2013 VL 97 IS 1 BP XI EP XII DI 10.1016/j.mcna.2012.11.005 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 082DY UT WOS:000314373700001 PM 23290737 ER PT J AU Williams, ME AF Williams, Mark E. TI Diabetic Kidney Disease in Elderly Individuals SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Diabetes; Kidney disease; Elderly individuals ID STAGE RENAL-DISEASE; GLYCATION END-PRODUCTS; NUTRITION EXAMINATION SURVEY; GLOMERULAR-FILTRATION-RATE; BLOOD-GLUCOSE CONTROL; 3RD NATIONAL-HEALTH; CARDIOVASCULAR OUTCOMES; TYPE-2 DIABETES/; GLYCEMIC CONTROL; MORTALITY RISK AB Chronic kidney disease (CKD) complicates diabetes and also has an increased prevalence in elderly individuals. Particularly in those older than 60 years, the most common cause of CKD and end-stage renal disease in the United States is diabetic kidney disease. This growing population represents unique challenges in multidisciplinary medical management. Elderly diabetic patients with CKD may be underserved with regard to fundamental standards of care like the role of glucose control, hypertension management, and the use of renin-angiotensin blocking agents. Current management therefore needs to be reassessed in terms of the special needs of this growing population. C1 Joslin Diabet Ctr, Renal Unit, Boston, MA 02215 USA. RP Williams, ME (reprint author), Joslin Diabet Ctr, Renal Unit, 1 Joslin Pl, Boston, MA 02215 USA. EM mark.williams@joslin.harvard.edu NR 66 TC 7 Z9 7 U1 1 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD JAN PY 2013 VL 97 IS 1 BP 75 EP + DI 10.1016/j.mcna.2012.10.011 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 082DY UT WOS:000314373700007 PM 23290731 ER PT J AU Pezzolesi, MG Krolewski, AS AF Pezzolesi, Marcus G. Krolewski, Andrzej S. TI The Genetic Risk of Kidney Disease in Type 2 Diabetes SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Type 2 diabetes; Diabetic nephropathy; Kidney disease; Genetic risk ID STAGE RENAL-DISEASE; FOCAL SEGMENTAL GLOMERULOSCLEROSIS; URINARY ALBUMIN EXCRETION; GLOMERULAR-FILTRATION-RATE; GENOME-WIDE SCAN; AFRICAN-AMERICANS; NEPHROTIC SYNDROME; FAMILIAL PREDISPOSITION; SUSCEPTIBILITY GENES; EUROPEAN AMERICANS AB In this review, the authors discuss the major approaches being used to identify diabetic nephropathy (DN) susceptibility genes in type 2 diabetes (12D) and highlight the salient findings from studies whereby these approaches have been implemented. The recent advent of next-generation sequencing technology is beginning to impact DN gene mapping strategies. As the field moves forward, family based approaches should greatly facilitate efforts to identify variants in genes that have a major effect on the risk of DN in T2D. To be successful, the ascertainment and comprehensive study of families with multiple affected members is critical. C1 [Pezzolesi, Marcus G.; Krolewski, Andrzej S.] Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA. [Pezzolesi, Marcus G.; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Pezzolesi, MG (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Room 445C,1 Joslin Pl, Boston, MA 02215 USA. EM marcus.pezzolesi@joslin.harvard.edu FU National Institutes of Health [DK090125, DK58549, DK77532, DK53534] FX We acknowledge grant support from the National Institutes of Health (DK090125 to MGP and DK58549, DK77532 and DK53534 to ASK). NR 53 TC 15 Z9 16 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD JAN PY 2013 VL 97 IS 1 BP 91 EP + DI 10.1016/j.mcna.2012.10.005 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA 082DY UT WOS:000314373700008 PM 23290732 ER PT J AU Garg, R Williams, ME AF Garg, Rajesh Williams, Mark E. TI Diabetes Management in the Kidney Patient SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Hyperglycemia; Chronic kidney disease; Diabetes ID BLOOD-GLUCOSE CONTROL; CHRONIC-RENAL-FAILURE; CHRONIC-HEMODIALYSIS PATIENTS; ASSESSING GLYCEMIC CONTROL; INSULIN-RESISTANCE; GLYCATED ALBUMIN; HEMOGLOBIN A(1C); MAINTENANCE HEMODIALYSIS; GLYCOSYLATED HEMOGLOBIN; VASCULAR COMPLICATIONS AB Hyperglycemia management in chronic kidney disease (CKD) patients presents difficult challenges, partly due to the complexity involved in treating these patients, and partly due to lack of data supporting benefits of tight glycemic control. While hyperglycemia is central to the pathogenesis and management of diabetes, hypoglycemia and glucose variability also contribute to outcomes. Multiple agents with different mechanisms of action are now available; some can lower glucose levels without the risk of hypoglycemia. This article reviews metabolic changes present in kidney impairment/failure, current views about glycemic goals, and treatment options for the diabetic patient with CKD. C1 [Garg, Rajesh] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Williams, Mark E.] Joslin Diabet Ctr, Div Renal, Boston, MA 02215 USA. RP Williams, ME (reprint author), Joslin Diabet Ctr, Div Renal, 1 Joslin Pl, Boston, MA 02215 USA. EM mark.williams@joslin.harvard.edu NR 110 TC 15 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 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD JAN PY 2013 VL 97 IS 1 BP 135 EP + DI 10.1016/j.mcna.2012.11.001 PG 23 WC Medicine, General & Internal SC General & Internal Medicine GA 082DY UT WOS:000314373700011 PM 23290735 ER PT J AU Belkind-Gerson, J Carreon-Rodriguez, A Benedict, LA Steiger, C Pieretti, A Nagy, N Dietrich, J Goldstein, AM AF Belkind-Gerson, J. Carreon-Rodriguez, A. Benedict, L. Andrew Steiger, C. Pieretti, A. Nagy, N. Dietrich, J. Goldstein, A. M. TI Nestin-expressing cells in the gut give rise to enteric neurons and glial cells SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE enteric nervous system; Hirschsprung's disease; Nestin; neural stem cell; neurosphere ID CREST STEM-CELLS; INTERMEDIATE-FILAMENT NESTIN; PERIPHERAL NERVOUS-SYSTEM; PROGENITOR CELLS; INTESTINAL INFLAMMATION; INTRINSIC DIFFERENCES; PRECURSOR CELLS; TRANSGENIC MICE; POSITIVE CELLS; SELF-RENEWAL AB Background Neuronal stem cells (NSCs) are promising for neurointestinal disease therapy. Although NSCs have been isolated from intestinal musclularis, their presence in mucosa has not been well described. Mucosa-derived NSCs are accessible endoscopically and could be used autologously. Brain-derived Nestin-positive NSCs are important in endogenous repair and plasticity. The aim was to isolate and characterize mucosa-derived NSCs, determine their relationship to Nestin-expressing cells and to demonstrate their capacity to produce neuroglial networks in vitro and in vivo. Methods Neurospheres were generated from periventricular brain, colonic muscularis (Musc), and mucosa-submucosa (MSM) of mice expressing green fluorescent protein (GFP) controlled by the Nestin promoter (Nestin-GFP). Neuronal stem cells were also grown as adherent colonies from intestinal mucosal organoids. Their differentiation potential was assessed using immunohistochemistry using glial and neuronal markers. Brain and gut-derived neurospheres were transplanted into explants of chick embryonic aneural hindgut to determine their fate. Key Results Muscand MSM-derived neurospheres expressed Nestin and gave rise to cells of neuronal, glial, and mesenchymal lineage. Although Nestin expression in tissue was mostly limited to glia co-labelled with glial fibrillary acid protein (GFAP), neurosphere-derived neurons and glia both expressed Nestin in vitro, suggesting that Nestin+/GFAP+ glial cells may give rise to new neurons. Moreover, following transplantation into aneural colon, brain-and gut-derived NSCs were able to differentiate into neurons. Conclusions & Inferences Nestin-expressing intestinal NSCs cells give rise to neurospheres, differentiate into neuronal, glial, and mesenchymal lineages in vitro, generate neurons in vivo and can be isolated from mucosa. Further studies are needed for exploring their potential for treating neuropathies. C1 [Belkind-Gerson, J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Gastroenterol, Boston, MA 02114 USA. [Carreon-Rodriguez, A.; Benedict, L. Andrew; Steiger, C.; Pieretti, A.; Goldstein, A. M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. [Carreon-Rodriguez, A.] Inst Nacl Salud Publ, Cuernavaca, Morelos, Mexico. [Nagy, N.] Semmelweis Univ, Fac Med, Dept Human Morphol & Dev Biol, H-1094 Budapest, Hungary. [Dietrich, J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Canc Ctr, Boston, MA 02114 USA. [Dietrich, J.] Harvard Univ, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA. RP Belkind-Gerson, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp Children, Div Pediat GI Pediat Surg Res Labs, 175 Cambridge St,Room 575, Boston, MA 02114 USA. EM jbelkindgerson@partners.org FU American Academy of Neurology; Stephen E. and Catherine Pappas Foundation; Paul Calabresi Career Development Award for Clinical Oncology; Hungarian Academy of Sciences; NIH [DK080914] FX The authors gratefully acknowledge support from the American Academy of Neurology (JD) and the Stephen E. and Catherine Pappas Foundation (JD). JD is a recipient of a Paul Calabresi Career Development Award for Clinical Oncology. NN is supported be a Bolyai Fellowship of the Hungarian Academy of Sciences. AMG is supported by NIH grant DK080914. NR 50 TC 15 Z9 16 U1 1 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD JAN PY 2013 VL 25 IS 1 BP 61 EP E7 DI 10.1111/nmo.12015 PG 10 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 075ME UT WOS:000313890000017 PM 22998406 ER PT J AU Wang, GH Jiang, XY Pu, HJ Zhang, WT An, CR Hu, XM Liou, AKF Leak, RK Gao, YQ Chen, J AF Wang, Guohua Jiang, Xiaoyan Pu, Hongjian Zhang, Wenting An, Chengrui Hu, Xiaoming Liou, Anthony Kian-Fong Leak, Rehana K. Gao, Yanqin Chen, Jun TI Scriptaid, a Novel Histone Deacetylase Inhibitor, Protects Against Traumatic Brain Injury via Modulation of PTEN and AKT Pathway SO NEUROTHERAPEUTICS LA English DT Review DE TBI; Histone deacetylase inhibitor; CCI; Long-term protection; p-AKT; PTEN ID EXPERIMENTAL ANIMAL-MODELS; GLOBAL CEREBRAL-ISCHEMIA; ALZHEIMERS-DISEASE; TUMOR-SUPPRESSOR; H3 ACETYLATION; MOUSE MODEL; CELL-DEATH; RAT; NEURODEGENERATION; PHOSPHORYLATION AB Traumatic brain injury (TBI) is a leading cause of motor and cognitive deficits in young adults for which there is no effective therapy. The present study characterizes the protective effect of a new histone deacetylase inhibitor, Scriptaid (Sigma-Aldrich Corporation, St. Louis, MO), against injury from controlled cortical impact (CCI). Scriptaid elicited a dose-dependent decrease in lesion size at 1.5 to 5.5 mg/kg and a concomitant attenuation in motor and cognitive deficits when delivered 30 minutes postinjury in a model of moderate TBI. Comparable protection was achieved even when treatment was delayed to 12 h postinjury. Furthermore, the protection of motor and cognitive functions was long lasting, as similar improvements were detected 35 days postinjury. The efficacy of Scriptaid (Sigma-Aldrich Corporation) was manifested as an increase in surviving neurons, as well as the number/length of their processes within the CA3 region of the hippocampus and the pericontusional cortex. Consistent with other histone deacetylase inhibitors, Scriptaid treatment prevented the decrease in phospho-AKT (p-AKT) and phosphorylated phosphatase and tensin homolog deleted on chromosome 10 (p-PTEN) induced by TBI in cortical and CA3 hippocampal neurons. Notably, the p-AKT inhibitor LY294002 attenuated the impact of Scriptaid, providing mechanistic evidence that Scriptaid functions partly by modulating the prosurvival AKT signaling pathway. As Scriptaid offers long-lasting neuronal and behavioral protection, even when delivered 12 h after controlled cortical impact, it is an excellent new candidate for the effective clinical treatment of TBI. C1 [Wang, Guohua; Jiang, Xiaoyan; Pu, Hongjian; Zhang, Wenting; An, Chengrui; Gao, Yanqin; Chen, Jun] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China. [Wang, Guohua; Jiang, Xiaoyan; Pu, Hongjian; Zhang, Wenting; An, Chengrui; Gao, Yanqin; Chen, Jun] Fudan Univ, Inst Brain Sci, Shanghai 200032, Peoples R China. [Wang, Guohua; Hu, Xiaoming; Liou, Anthony Kian-Fong; Gao, Yanqin; Chen, Jun] Univ Pittsburgh, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. [Leak, Rehana K.] Duquesne Univ, Div Pharmaceut Sci, Mylan Sch Pharm, Pittsburgh, PA 15282 USA. [Wang, Guohua] Nantong Univ, Dept Neuropharmacol, Inst Naut Med, Nantong 226001, Jiangsu, Peoples R China. [Hu, Xiaoming; Liou, Anthony Kian-Fong; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15240 USA. [Gao, Yanqin; Chen, Jun] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. RP Gao, YQ (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. EM yqgao@shmu.edu.cn; ChenJ2@upmc.edu RI Gao, Yanqin/I-6790-2016 OI Gao, Yanqin/0000-0002-4915-9819 FU Chinese Ministry of Science and Technology; National Institutes of Health/National Institute of Neurological Disorders and Stroke [NS36736, NS43802, NS45048]; Veterans Administration Merit Review; Chinese Natural Science Foundation [30870794, 81020108021, 81171149, 81150110494, 81000497] FX This research is supported in part by the Special Research Funds from the Chinese Ministry of Science and Technology to State Key Laboratories (to G. H. W, Y.G, and J.C); the National Institutes of Health/National Institute of Neurological Disorders and Stroke (grants NS36736, NS43802 and NS45048 to J.C.); the Veterans Administration Merit Review (grant to J.C.); and the Chinese Natural Science Foundation (grants No. 30870794, No. 81020108021, No. 81171149, No. 81150110494 to Y.G., and No. 81000497 to G. W.) The authors declare no conflict of interest. Full conflict of interest disclosures is available in the electronic supplementary material for this article. NR 65 TC 30 Z9 31 U1 3 U2 26 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2013 VL 10 IS 1 BP 124 EP 142 DI 10.1007/s13311-012-0157-2 PG 19 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 080WM UT WOS:000314274800014 PM 23132328 ER PT J AU Rosas, HD Doros, G Gevorkian, S Malarick, K Reuter, M Matson, W Scherzer, C Ferrante, R Salat, D Hersch, S AF Rosas, H. D. Doros, G. Gevorkian, S. Malarick, K. Reuter, M. Matson, W. Scherzer, C. Ferrante, R. Salat, D. Hersch, S. TI PLATFORM PRESENTATION: Secondary prevention ofHuntington disease: a feasibility, safety, and biomarker study of high dose creatine in "at-risk" individuals SO NEUROTHERAPEUTICS LA English DT Meeting Abstract C1 [Rosas, H. D.; Gevorkian, S.; Malarick, K.; Reuter, M.; Scherzer, C.; Hersch, S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Rosas, H. D.; Gevorkian, S.; Malarick, K.; Reuter, M.; Salat, D.] Massachusetts Gen Hosp, Ctr Neuroimaging Aging & Neurodegenerat Dis, Boston, MA 02114 USA. [Rosas, H. D.; Gevorkian, S.; Malarick, K.; Reuter, M.; Salat, D.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Rosas, H. D.; Reuter, M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Scherzer, C.] Harvard Univ, Brigham & Womens Hosp, Ctr Neurol Dis, Sch Med, Boston, MA 02115 USA. [Doros, G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Matson, W.] Univ Pittsburgh, Vet Adm, Pittsburgh, PA USA. [Ferrante, R.] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15260 USA. [Ferrante, R.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Ferrante, R.] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA USA. [Ferrante, R.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2013 VL 10 IS 1 BP 170 EP 170 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 080WM UT WOS:000314274800022 ER PT J AU Cudkowicz, M McDermott, M Kieburtz, K McGarry, A de Blieck, E AF Cudkowicz, M. McDermott, M. Kieburtz, Karl McGarry, A. de Blieck, E. CA 2CARE Investigators Coordinators TI Recruitment and retention challenges in 2CARE, a long-term therapeutic clinical trial of coenzyme Q(10) in Huntington's disease SO NEUROTHERAPEUTICS LA English DT Meeting Abstract C1 [Cudkowicz, M.] Massachusetts Gen Hosp, Charlestown, MA USA. [McDermott, M.; Kieburtz, Karl; de Blieck, E.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [McGarry, A.] Cooper Univ Hosp, Camden, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2013 VL 10 IS 1 BP 177 EP 178 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 080WM UT WOS:000314274800039 ER PT J AU Lin, CX Perrault, SD Kwak, M Graf, F Shih, WM AF Lin, Chenxiang Perrault, Steven D. Kwak, Minseok Graf, Franziska Shih, William M. TI Purification of DNA-origami nanostructures by rate-zonal centrifugation SO NUCLEIC ACIDS RESEARCH LA English DT Article ID NANOSCALE SHAPES; FOLDING DNA; SEPARATION; ULTRACENTRIFUGATION; NANOPORES; DESIGN AB Most previously reported methods for purifying DNA-origami nanostructures rely on agarose-gel electrophoresis (AGE) for separation. Although AGE is routinely used to yield 0.1-1 mu g purified DNA nanostructures, obtaining >100 mu g of purified DNA-origami structure through AGE is typically laborious because of the post-electrophoresis extraction, desalting and concentration steps. Here, we present a readily scalable purification approach utilizing rate-zonal centrifugation, which provides comparable separation resolution as AGE. The DNA nanostructures remain in aqueous solution throughout the purification process. Therefore, the desired products are easily recovered with consistently high yield (40-80%) and without contaminants such as residual agarose gel or DNA intercalating dyes. Seven distinct three-dimensional DNA-origami constructs were purified at the scale of 0.1-100 mu g (final yield) per centrifuge tube, showing the versatility of this method. Given the commercially available equipment for gradient mixing and fraction collection, this method should be amenable to automation and further scale up for preparation of larger amounts (e.g. milligram quantities) of DNA nanostructures. C1 [Lin, Chenxiang; Perrault, Steven D.; Kwak, Minseok; Graf, Franziska; Shih, William M.] Harvard Univ, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Lin, Chenxiang; Perrault, Steven D.; Kwak, Minseok; Graf, Franziska; Shih, William M.] Harvard Univ, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Lin, Chenxiang; Perrault, Steven D.; Kwak, Minseok; Graf, Franziska; Shih, William M.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. RP Shih, WM (reprint author), Harvard Univ, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM William_Shih@dfci.harvard.edu RI Kwak, Minseok/G-6415-2010; Lin, Chenxiang/G-2303-2010; OI Lin, Chenxiang/0000-0001-7041-1946; Kwak, Minseok/0000-0002-0480-1804 FU National Institutes of Health (NIH) [1DP2OD004641, 1U54GM094608]; Office of Naval Research [N000141010241, N000014091118]; Wyss Institute for Biologically Inspired Engineering Faculty Award; Canadian Institutes for Health Research; Netherlands Organization for Scientific Research (NWO-Rubicon); NIH [1DP2OD004641] FX National Institutes of Health (NIH) [1DP2OD004641, 1U54GM094608]; Office of Naval Research [N000141010241, N000014091118]; Wyss Institute for Biologically Inspired Engineering Faculty Award (to W.M.S.); Canadian Institutes for Health Research (to S.D.P.); Netherlands Organization for Scientific Research (NWO-Rubicon) (to M. K.). Funding for open access charge: NIH [1DP2OD004641]. NR 30 TC 25 Z9 26 U1 5 U2 89 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2013 VL 41 IS 2 AR e40 DI 10.1093/nar/gks1070 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 078SZ UT WOS:000314121100007 PM 23155067 ER PT J AU Buckenmaier, CC Galloway, KT Polomano, RC McDuffie, M Kwon, N Gallagher, RM AF Buckenmaier, Chester C., III Galloway, Kevin T. Polomano, Rosemary C. McDuffie, Mary Kwon, Nancy Gallagher, Rollin M. TI Preliminary Validation of the Defense and Veterans Pain Rating Scale (DVPRS) in a Military Population SO PAIN MEDICINE LA English DT Article DE Validation Study; Pain Measurement; Pain Scales ID POLYTRAUMA CLINICAL TRIAD; RECEIVING PRIMARY-CARE; 5TH VITAL SIGN; IRAQI FREEDOM; CANCER PAIN; MANAGEMENT; INTERFERENCE; SEVERITY; VALIDITY; INJURY AB Background. The Army Surgeon General released the Pain Management Task Force final report in May 2010. Among military providers, concerns were raised that the standard numeric rating scale (NRS) for pain was inconsistently administered and of questionable clinical value. In response, the Defense and Veterans Pain Rating Scale (DVPRS) was developed. Methods. The instrument design integrates pain rating scale features to improve interpretability of incremental pain intensity levels, and to improve communication and documentation across all transitions of care. A convenience sample of 350 inpatient and outpatient active duty or retired military service members participated in the study at Walter Reed Army Medical Center. Participants completed the five-item DVPRSone pain intensity NRS with and without word descriptors presented in random order and four supplemental items measuring general activity, sleep, mood, and level of stress and the Brief Pain Inventory seven interference items. Using systematic sampling, a random sample was selected for a word descriptor validation procedure matching word phases to corresponding pain intensity on the NRS. Results. Parallel forms reliability and concurrent validity testing demonstrated a robust correlation. When the DVPRS was presented with the word descriptors first, the correlation between the two ratings was slightly higher, r?=?0.929 (N?=?171; P?3, >5, and >7 mm in size; and treat no patients. If nodal metastases or unsuspected stage T3 disease went untreated preoperatively, postoperative chemoradiation was needed, resulting in poorer outcomes. For each strategy, rates of acute and long-term chemoradiation toxicity and of 5-year local recurrence were computed. Effects of input parameter uncertainty were evaluated in sensitivity analysis. Results: The optimal strategy depended on the outcome prioritized. Acute and long-term chemoradiation toxicity rates were minimized by triaging only patients with nodes >7 mm to preoperative chemoradiation (18.9% and 10.8%, respectively). A treat-all strategy minimized the 5-year local recurrence rate (5.6%). A 7-mm nodal triage threshold increased the 5-year local recurrence rate to 8.0%; when no patients were treated preoperatively, the local recurrence rate was 10.1%. With improved primary tumor staging, all outcomes could be further optimized. Conclusions: Mesorectal nodal size thresholds for preoperative chemoradiation should depend on the outcome prioritized: higher size thresholds reduce chemoradiation toxicity but increase recurrence rates. Improvements in nodal staging will have greater impact if primary tumor staging can be improved. C1 [Hartman, Rebecca I.; Eisenberg, Jonathan D.; Gazelle, G. Scott; Pandharipande, Pari V.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Chang, Connie Y.; Harisinghani, Mukesh G.; Gazelle, G. Scott; Pandharipande, Pari V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Wo, Jennifer Y.; Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Hartman, Rebecca I.; Gazelle, G. Scott] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Pandharipande, PV (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM pari@mgh-ita.org FU National Cancer Institute (Bethesda, MD) [K07CA133097]; Medical Imaging and Technology Alliance (Arlington, VA) FX From the Massachusetts General Hospital Institute for Technology Assessment (R.I.H., J.D.E., G.S.G., P.V.P.), 101 Merrimac Street, 10th Floor, Boston, MA 02114; the Departments of Radiology (C.Y.C., M.G.H., G.S.G., P.V.P.) and Radiation Oncology (J.Y.W., T.S.H.), Massachusetts General Hospital, Boston, Massachusetts; and the Department of Health Policy and Management, Harvard School of Public Health (R.I.H., G.S.G.), Boston, Massachusetts. Received May 4, 2012; accepted July 20, 2012. This study was supported in part by Award Number K07CA133097 from the National Cancer Institute (Bethesda, MD; Dr. Pandharipande, principal investigator). The research content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. Dr. Gazelle is a consultant for GE (Milwaukee, WI). Dr. Pandharipande receives additional research funding from the Medical Imaging and Technology Alliance (Arlington, VA) for unrelated research. Address correspondence to: P.V.P. e-mail: pari@mgh-ita.org NR 34 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 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JAN PY 2013 VL 20 IS 1 BP 79 EP 89 DI 10.1016/j.acra.2012.07.010 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 063CL UT WOS:000312973600011 PM 22947271 ER PT J AU Lo Re, V Teal, V Localio, AR Amorosa, VK Kaplan, DE Gross, R AF Lo Re, Vincent, III Teal, Valerie Localio, A. Russell Amorosa, Valerianna K. Kaplan, David E. Gross, Robert TI Adherence to Hepatitis C Virus Therapy in HIV/Hepatitis C-Coinfected Patients SO AIDS AND BEHAVIOR LA English DT Article DE Adherence; Hepatitis C virus; HIV; Antiviral therapy; Pegylated interferon; Ribavirin ID HIV-INFECTED PATIENTS; ACTIVE ANTIRETROVIRAL THERAPY; ALPHA-2A PLUS RIBAVIRIN; PEGINTERFERON ALPHA-2A; VIROLOGICAL OUTCOMES; VIRAL LOAD; SUSTAINED RESPONSE; PHARMACY RECORDS; RECOMMENDATIONS; INTERFERON AB Adherence to hepatitis C virus (HCV) therapy has been incompletely examined among HIV-infected patients. We assessed changes in interferon and ribavirin adherence and evaluated the relationship between adherence and early (EVR) and sustained virologic response (SVR). We performed a cohort study among 333 HIV/HCV-coinfected patients who received pegylated interferon and ribavirin between 2001 and 2006 and had HCV RNA before and after treatment. Adherence was calculated over 12-week intervals using pharmacy refills. Mean interferon and ribavirin adherence declined 2.5 and 4.1 percentage points per 12-week interval, respectively. Among genotype 1/4 patients, EVR increased with higher ribavirin adherence, but this association was less strong for interferon. SVR among these patients was higher with increasing interferon and ribavirin adherence over the first, second, and third, but not fourth, 12-week intervals. Among HIV/HCV patients, EVR and SVR increased with higher interferon and ribavirin adherence. Adherence to both antivirals declined over time, but more so for ribavirin. C1 [Lo Re, Vincent, III; Amorosa, Valerianna K.; Gross, Robert] Univ Penn, Div Infect Dis, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Lo Re, Vincent, III; Teal, Valerie; Localio, A. Russell; Gross, Robert] Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Lo Re, Vincent, III; Amorosa, Valerianna K.; Kaplan, David E.; Gross, Robert] Philadelphia Vet Affairs Med Ctr, Med Serv, Philadelphia, PA USA. [Kaplan, David E.] Univ Penn, Div Gastroenterol, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Lo Re, V (reprint author), Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, 836 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM vincentl@mail.med.upenn.edu RI Lo Re, Vincent/N-7817-2015; OI Teal, Valerie/0000-0001-7116-5353; Kaplan, David E./0000-0002-3839-336X FU NIAID NIH HHS [K01 AI070001, K01-AI070001] NR 40 TC 2 Z9 2 U1 0 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 JAN PY 2013 VL 17 IS 1 BP 94 EP 103 DI 10.1007/s10461-012-0288-9 PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 073HL UT WOS:000313734000009 PM 22907288 ER PT J AU Liu, HH Wilson, IB Goggin, K Reynolds, N Simoni, JM Golin, CE Rosen, MI Gross, R Wagner, G Remien, RH Schneiderman, N Erlen, JA Arnsten, JH Bangsberg, DR AF Liu, Honghu Wilson, Ira B. Goggin, Kathy Reynolds, Nancy Simoni, Jane M. Golin, Carol E. Rosen, Marc I. Gross, Robert Wagner, Glenn Remien, Robert H. Schneiderman, Neil Erlen, Judith A. Arnsten, Julia H. Bangsberg, David R. TI MACH14: A Multi-Site Collaboration on ART Adherence Among 14 Institutions SO AIDS AND BEHAVIOR LA English DT Article DE HIV/AIDS; Adherence; MEMS; Multi-site; Antiretroviral medication; Individual participant data ID ACTIVE ANTIRETROVIRAL THERAPY; INDIVIDUAL PATIENT DATA; MISSING DATA; SELF-REPORT; PROTEASE INHIBITORS; DRUG-RESISTANCE; HIV-INFECTION; METAANALYSIS; TRIALS; POPULATION AB The integration of original data from multiple antiretroviral (ARV) adherence studies offers a promising, but little used method to generate evidence to advance the field. This paper provides an overview of the design and implementation of MACH14, a collaborative, multi-site study in which a large data system has been created for integrated analyses by pooling original data from 16 longitudinal ARV adherence studies. Studies selected met specific criteria including similar research design and data domains such as adherence measured with medication event monitoring system, psychosocial factors related to adherence behavior, and virologic and clinical outcomes. The data system created contains individual data (collected between 1997 and 2009) from 2,860 HIV patients. Collaboration helped resolve the challenges inherent in pooling data across multiple studies, yet produced a data system with strong statistical power and potentially greater capacity to address key scientific questions than possible with single-sample studies or even meta-analytic designs. C1 [Liu, Honghu] Univ Calif Los Angeles, Sch Dent, Div Publ Hlth & Community Dent, Los Angeles, CA 90024 USA. [Wilson, Ira B.] Brown Univ, Publ Hlth Program, Warren Alpert Sch Med, Providence, RI 02912 USA. [Goggin, Kathy] Univ Missouri, Dept Psychol, Kansas City, MO 64110 USA. [Reynolds, Nancy] Yale Univ, Sch Nursing, New Haven, CT 06536 USA. [Simoni, Jane M.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Golin, Carol E.] Univ N Carolina, Sch Med, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Rosen, Marc I.] Yale Univ, Sch Med, New Haven, CT USA. [Gross, Robert] Univ Penn, Sch Med, Epidemiol Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Wagner, Glenn] RAND Corp, Bethel, CT USA. [Remien, Robert H.] New York State Psychiat Inst & Hosp, HIV Ctr Clin & Behav Studies, New York, NY 10032 USA. [Remien, Robert H.] Columbia Univ, New York, NY USA. [Schneiderman, Neil] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. [Erlen, Judith A.] Univ Pittsburgh, Sch Nursing, Dept Hlth & Community Syst, Pittsburgh, PA 15261 USA. [Arnsten, Julia H.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Arnsten, Julia H.] Albert Einstein Coll Med, Dept Psychiat, Bronx, NY 10467 USA. [Arnsten, Julia H.] Albert Einstein Coll Med, Dept Epidemiol, Bronx, NY 10467 USA. [Arnsten, Julia H.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Bangsberg, David R.] Harvard Univ, Sch Med, Ragon Inst MGH MIT & Harvard, Massachusetts Gen Hosp,Ctr Global Hlth, Boston, MA USA. RP Liu, HH (reprint author), Univ Calif Los Angeles, Sch Dent, Div Publ Hlth & Community Dent, Los Angeles, CA 90024 USA. EM hhliu@ucla.edu RI Wilson, Ira/F-9190-2016; OI Wilson, Ira/0000-0002-0246-738X; Simoni, Jane/0000-0002-8711-1576 FU NCRR NIH HHS [K24 RR020300]; NIAID NIH HHS [AI069419, AI38858, P30 AI050410, R01AI41413, U01 AI069419, UM1 AI069419]; NIDA NIH HHS [R01 DA013826, K02 DA017277, K02DA017277, R01DA015679, R01DA11869, R01DA13826, R01DA15215]; NIMH NIH HHS [K23MH01862, K24 MH092242, P01MH49548, P30 MH043520, R01 MH054907, R01 MH058986, R01 MH061173, R01 MH061695, R01 MH068197, R01 MH078773, R01 MH61173, R01MH01584, R01MH078773, R01MH54907, R01MH58986, R01MH61695, R01MH68197]; NINR NIH HHS [2R01NR04749, R01 NR004749, R01NR04749] NR 28 TC 6 Z9 6 U1 2 U2 7 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 JAN PY 2013 VL 17 IS 1 BP 127 EP 141 DI 10.1007/s10461-012-0272-4 PG 15 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 073HL UT WOS:000313734000013 PM 22864921 ER PT J AU Rosen, MI Black, AC Arnsten, JH Goggin, K Remien, RH Simoni, JM Golin, CE Bangsberg, DR Liu, H AF Rosen, M. I. Black, A. C. Arnsten, J. H. Goggin, K. Remien, R. H. Simoni, J. M. Golin, C. E. Bangsberg, D. R. Liu, H. TI Association Between Use of Specific Drugs and Antiretroviral Adherence: Findings from MACH 14 SO AIDS AND BEHAVIOR LA English DT Article DE HIV; AIDS; Substance use; Adherence; Cannabis ID HIV-INFECTED PERSONS; MEDICATION ADHERENCE; VIRAL SUPPRESSION; INHIBITOR THERAPY; ABUSE; CARE; NONADHERENCE; PREDICTORS; DISORDERS; FAILURE AB To determine the association between individual substances of abuse and antiretroviral adherence, analyses require a large sample assessed using electronic data monitoring (EDM). In this analysis, EDM data from 1,636 participants in 12 US adherence-focused studies were analyzed to determine the associations between recent use of various substances and adherence during the preceding 4 weeks. In bivariate analyses comparing adherence among patients who had used a specific substance to those who had not, adherence was significantly lower among those who had recently used cocaine, other stimulants or heroin but not among those who had used cannabis or alcohol. In multivariate analyses controlling for sociodemographics, amount of alcohol use and recent use of any alcohol, cocaine, other stimulants and heroin each was significantly negatively associated with adherence. The significant associations of cocaine, other stimulants, heroin, and alcohol use with adherence suggest that these are important substances to target with adherence-focused interventions. C1 [Rosen, M. I.; Black, A. C.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. [Rosen, M. I.; Black, A. C.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Arnsten, J. H.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Arnsten, J. H.] Albert Einstein Coll Med, Dept Psychiat & Behav Sci, Bronx, NY 10467 USA. [Arnsten, J. H.] Montefiore Med Ctr, Einstein Montefiore Ctr AIDS Res, Bronx, NY 10467 USA. [Goggin, K.] Univ Missouri, Dept Psychol, Kansas City, MO 64110 USA. [Remien, R. H.] Columbia Univ, New York State Psychiat Inst, HIV Ctr Clin & Behav Studies, New York, NY USA. [Simoni, J. M.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Golin, C. E.] Cecil G Sheps Ctr Hlth Serv Res, UNC Dept Med, UNC Ctr AIDS Res, Chapel Hill, NC USA. [Golin, C. E.] Cecil G Sheps Ctr Hlth Serv Res, Dept Hlth Behav & Hlth Educ, UNC Ctr AIDS Res, Chapel Hill, NC USA. [Bangsberg, D. R.] Mbarara Univ Sci & Technol, Boston, MA USA. [Bangsberg, D. R.] Harvard Univ, Sch Med, Boston, MA USA. [Bangsberg, D. R.] Ragon Inst MGH Harvard & MIT, Boston, MA USA. [Bangsberg, D. R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Liu, H.] Univ Calif Los Angeles, Sch Med, Div Publ Hlth & Community Dent, Los Angeles, CA USA. RP Rosen, MI (reprint author), Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. EM Marc.Rosen@Yale.edu OI Simoni, Jane/0000-0002-8711-1576 FU NIAID NIH HHS [AI069419, AI38858, P30 AI050410, R01AI41413]; NIDA NIH HHS [K02DA017277, R01 DA015215, R01DA015679, R01DA11869, R01DA13826, R01DA15215]; NIMH NIH HHS [R01 MH61173, K23MH01862, P01MH49548, P30 MH043520, R01 MH054907, R01 MH068197, R01 MH078773, R01MH01584, R01MH078773, R01MH54907, R01MH58986, R01MH61695, R01MH68197]; NINR NIH HHS [R01NR04749]; ODCDC CDC HHS [CC02-SD-003, CC99-SD003] NR 36 TC 17 Z9 17 U1 2 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 JAN PY 2013 VL 17 IS 1 BP 142 EP 147 DI 10.1007/s10461-011-0124-7 PG 6 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 073HL UT WOS:000313734000014 PM 22246513 ER PT J AU Gonzalez, A Mimiaga, MJ Israel, J Bedoya, CA Safren, SA AF Gonzalez, Adam Mimiaga, Matthew J. Israel, Jared Bedoya, C. Andres Safren, Steven A. TI Substance Use Predictors of Poor Medication Adherence: The Role of Substance Use Coping Among HIV-Infected Patients in Opioid Dependence Treatment SO AIDS AND BEHAVIOR LA English DT Article DE HIV/AIDS; Medication adherence; Substance use; Coping; Cocaine ID ACTIVE ANTIRETROVIRAL THERAPY; COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; INJECTION-DRUG USERS; DEPRESSION CBT-AD; CRACK-COCAINE USE; VIRAL LOAD; HETEROSEXUAL TRANSMISSION; VIROLOGICAL RESPONSE; COHORT AB Many HIV-infected injection drug users (IDUs) continue to use illicit substances despite being in substance use treatment. Substance use is associated with non-adherence to HIV medications; however underlying mechanisms regarding this relation are understudied. The current investigation examined the role of substance use coping in terms of the relation between substance use and HIV medication adherence. Participants were 121 HIV-infected IDUs (41 % female, M age = 47, SD = 7.1) in opioid dependence treatment. Participants completed self-report questionnaires, were administered clinical interviews and oral toxicology screens, and used a medication-event-monitoring-system cap to assess 2 week HIV medication adherence. The use of cocaine and multiple substances were significantly related to decreased medication adherence. Substance use coping mediated these associations. Findings highlight the importance of assessing, monitoring, and targeting ongoing substance use, and ways to increase positive coping for HIV-infected IDUs in substance use treatment to aid in HIV medication adherence. C1 [Gonzalez, Adam; Mimiaga, Matthew J.; Bedoya, C. Andres; Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Gonzalez, Adam; Mimiaga, Matthew J.; Bedoya, C. Andres; Safren, Steven A.] Harvard Univ, Sch Med, Boston, MA USA. [Gonzalez, Adam] SUNY Stony Brook, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. [Mimiaga, Matthew J.; Safren, Steven A.] Fenway Inst, Boston, MA USA. [Israel, Jared] Univ Missouri, Dept Psychol, St Louis, MO 63121 USA. RP Gonzalez, A (reprint author), SUNY Stony Brook, Dept Psychiat & Behav Sci, Putnam Hall,South Campus, Stony Brook, NY 11794 USA. EM adam.gonzalez@stonybrook.edu FU NIDA NIH HHS [R-01 DA018603, R01 DA018603]; NIMH NIH HHS [K24 MH094214] NR 48 TC 19 Z9 20 U1 2 U2 15 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 JAN PY 2013 VL 17 IS 1 BP 168 EP 173 DI 10.1007/s10461-012-0319-6 PG 6 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 073HL UT WOS:000313734000017 PM 23008124 ER PT J AU Ohl, M Lund, B Belperio, PS Goetz, MB Rimland, D Richardson, K Justice, A Perencevich, E Vaughan-Sarrazin, M AF Ohl, Michael Lund, Brian Belperio, Pamela S. Goetz, Matthew Bidwell Rimland, David Richardson, Kelly Justice, Amy Perencevich, Eli Vaughan-Sarrazin, Mary TI Rural Residence and Adoption of a Novel HIV Therapy in a National, Equal-Access Healthcare System SO AIDS AND BEHAVIOR LA English DT Article DE HIV; Diffusion of innovation; Rural health ID ACTIVE ANTIRETROVIRAL THERAPY; UNITED-STATES; INFECTED ADULTS; HIV/AIDS; AREAS; URBAN; SPECIALIZATION; INDIVIDUALS; PREDICTORS; STRATEGIES AB Rural persons with HIV face barriers to care that may influence adoption of advances in therapy. We performed a retrospective cohort study to determine rural-urban variation in adoption of raltegravir-the first HIV integrase inhibitor-in national Veterans Afffairs (VA) healthcare. There were 1,222 veterans with clinical indication for raltegravir therapy at time of its FDA approval in October 2007, of whom 223 (19.1%) resided in rural areas. Urban persons were more likely than rural to initiate raltegravir within 180 days (17.3% vs. 11.2%, P = 0.02) and 360 days (27.5% vs. 19.7%, P = 0.02), but this gap narrowed slightly at 720 days (36.3% vs. 31.8%, P = 0.19). In multivariable analysis adjusting for patient characteristics, urban residence predicted raltegravir adoption within 180 days (odds ratio 1.72, 95% CI 1.09-2.70) and 360 days (OR 1.63, 95% CI 1.13-2.34), but not 720 days (OR 1.26, 95% CI 0.84-1.87). Efforts are needed to reduce geographic variation in adoption of advances in HIV therapy. C1 [Ohl, Michael; Lund, Brian; Richardson, Kelly; Perencevich, Eli; Vaughan-Sarrazin, Mary] Iowa City VAMC, VA Off Rural Hlth ORH, Vet Rural Hlth Resource Ctr Cent Reg, Iowa City, IA USA. [Ohl, Michael; Lund, Brian; Richardson, Kelly; Perencevich, Eli; Vaughan-Sarrazin, Mary] Iowa City VA Med Ctr, Ctr Comprehens Access & Delivery Res & Evaluat CA, Iowa City, IA 52246 USA. [Ohl, Michael; Perencevich, Eli; Vaughan-Sarrazin, Mary] Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA. [Belperio, Pamela S.] VA Ctr Qual Management Publ Hlth, Palo Alto, CA USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Rimland, David] Atlanta VAMC, Atlanta, GA USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA. [Justice, Amy] Yale Univ, Sch Med, VA Connecticut Healthcare Syst, New Haven, CT USA. [Justice, Amy] Yale Univ, Sch Publ Hlth, VA Connecticut Healthcare Syst, New Haven, CT USA. RP Ohl, M (reprint author), Iowa City VA Med Ctr, Ctr Comprehens Access & Delivery Res & Evaluat CA, Mailstop 152, Iowa City, IA 52246 USA. EM michael.ohl@va.gov OI Vaughan Sarrazin, Mary/0000-0001-8717-1061; Goetz, Matthew/0000-0003-4542-992X FU NIAAA NIH HHS [U10 AA013566, U24 AA020794, U01 AA020790] NR 31 TC 3 Z9 3 U1 1 U2 6 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 JAN PY 2013 VL 17 IS 1 BP 250 EP 259 DI 10.1007/s10461-011-0107-8 PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 073HL UT WOS:000313734000026 PM 22205324 ER PT J AU Horwitz, RH Tsai, AC Maling, S Bajunirwe, F Haberer, JE Emenyonu, N Muzoora, C Hunt, PW Martin, JN Bangsberg, DR AF Horwitz, Russell H. Tsai, Alexander C. Maling, Samuel Bajunirwe, Francis Haberer, Jessica E. Emenyonu, Nneka Muzoora, Conrad Hunt, Peter W. Martin, Jeffrey N. Bangsberg, David R. TI No Association Found Between Traditional Healer Use and Delayed Antiretroviral Initiation in Rural Uganda SO AIDS AND BEHAVIOR LA English DT Article DE HIV/AIDS; Traditional healer; Spiritual counselor; Late presentation; Uganda ID HOPKINS SYMPTOM CHECKLIST-25; SUB-SAHARAN AFRICA; QUALITY-OF-LIFE; HIV-INFECTION; MEDICAL OUTCOMES; SCREENING INSTRUMENT; LATE DIAGNOSIS; BREAST-CANCER; RISK-FACTORS; CARE AB Traditional healer and/or spiritual counselor (TH/SC) use has been associated with delays in HIV testing. We examined HIV-infected individuals in southwestern Uganda to test the hypothesis that TH/SC use was also associated with lower CD4 counts at antiretroviral therapy (ART) initiation. Approximately 450 individuals initiating ART through an HIV/AIDS clinic at the Mbarara University of Science and Technology (MUST) were recruited to participate. Patients were predominantly female, ranged in age from 18 to 75, and had a median CD4 count of 130. TH/SC use was not associated with lower CD4 cell count, but age and quality-of-life physical health summary score were associated with CD4 cell count at initiation while asset index was negatively associated with CD4 count at ART initiation. These findings suggest that TH/SC use does not delay initiation of ART. C1 [Horwitz, Russell H.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Horwitz, Russell H.; Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Horwitz, Russell H.] MGH Revere HealthCare Ctr, Dept Mental Hlth, Revere, MA 02151 USA. [Tsai, Alexander C.] Harvard Univ, Robert Wood Johnson Hlth & Soc Scholars Program, Cambridge, MA 02138 USA. [Maling, Samuel] Mbarara Univ Sci & Technol, Dept Psychiat, Mbarara, Uganda. [Bajunirwe, Francis] Mbarara Univ Sci & Technol, Dept Community Hlth, Mbarara, Uganda. [Bajunirwe, Francis] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Haberer, Jessica E.; Bangsberg, David R.] Harvard Initiat Global Hlth, Cambridge, MA USA. [Haberer, Jessica E.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Emenyonu, Nneka; Muzoora, Conrad; Bangsberg, David R.] Mbarara Univ Sci & Technol, Dept Med, Mbarara, Uganda. [Emenyonu, Nneka; Hunt, Peter W.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Hunt, Peter W.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. [Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Bangsberg, David R.] Harvard Univ, Phillip T & Susan M Ragon Inst, Massachusetts Gen Hosp, MIT, Charlestown, MA USA. RP Horwitz, RH (reprint author), MGH Revere HealthCare Ctr, Dept Mental Hlth, 300 Ocean Ave, Revere, MA 02151 USA. EM rhorwitz@partners.org OI Tsai, Alexander/0000-0001-6397-7917 FU NCRR NIH HHS [UL1RR024131, UL1 RR024131]; NIAAA NIH HHS [K24 AA015287]; NIAID NIH HHS [P30 AI027763, P30AI027763]; NIMH NIH HHS [K23 MH096620, K24 MH087227, K24MH87227, R01 MH054907, R01MH54907] NR 39 TC 3 Z9 3 U1 1 U2 6 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 JAN PY 2013 VL 17 IS 1 BP 260 EP 265 DI 10.1007/s10461-011-0132-7 PG 6 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 073HL UT WOS:000313734000027 PM 22246516 ER PT J AU Graham, JL Grimes, RM Slomka, J Ross, M Hwang, LY Giordano, TP AF Graham, James L. Grimes, Richard M. Slomka, Jacquelyn Ross, Michael Hwang, Lu-Yu Giordano, Thomas P. TI The Role of Trust in Delayed HIV Diagnosis in a Diverse, Urban Population SO AIDS AND BEHAVIOR LA English DT Article DE Trust; Physicians; Healthcare system; Delayed diagnosis; Race/ethnicity ID HEALTH-CARE-SYSTEM; EMERGENCY-DEPARTMENT; MEDICAL-CARE; ANTIRETROVIRAL THERAPY; INFECTION; PROVIDERS; SETTINGS; PREVENTION; ADHERENCE; ROUTINE AB Delayed diagnosis of HIV infection is a common problem. We hypothesized that persons with less trust in physicians and in the healthcare system would be diagnosed with lower CD4 cell counts than persons with more trust because they would delay seeking healthcare. From January 2006 to October 2007, 171 newly diagnosed HIV-infected persons, not yet in HIV primary care, were recruited from HIV testing sites in Houston, Texas, that primarily serve the under- and un-insured. The participants completed instruments measuring trust in physicians and trust in the healthcare system. Initial CD4 cell counts were obtained from medical record review. Mean trust scores for participants with CD4 cell counts a parts per thousand yen200 cells/mm(3) were compared with scores from participants with CD4 cell counts < 200 cells/mm(3). We found that 51% of the cohort was diagnosed with a CD4 cell count < 200 cells/mm(3). Neither trust in physicians nor trust in the healthcare system was an independent predictor of delayed diagnosis of HIV infection. In multivariate analysis, men who have sex with men and injection drug users were more likely to have early HIV diagnosis. Race/ethnicity was the only variable statistically significantly predictive of trust in physicians and in the healthcare system. Hispanics had the highest trust scores, followed by Blacks and Whites. Low trust is likely not a barrier to timely diagnosis of HIV infection. C1 [Graham, James L.] Legacy Community Hlth Serv, Houston, TX USA. [Grimes, Richard M.] Univ Texas Hlth Sci Ctr Houston, Sch Med, Houston, TX USA. [Slomka, Jacquelyn; Ross, Michael; Hwang, Lu-Yu] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Houston, TX USA. [Giordano, Thomas P.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Giordano, Thomas P.] Michael E DeBakey VA Med Ctr 152, Hlth Serv Res & Dev Ctr Excellence, Houston, TX 77030 USA. RP Giordano, TP (reprint author), Michael E DeBakey VA Med Ctr 152, Hlth Serv Res & Dev Ctr Excellence, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM tpg@bcm.edu FU AHRQ HHS [U18 HS016093, U18HS016093]; NIAID NIH HHS [P30 AI036211, P30AI036211]; NIMH NIH HHS [R34 MH074360, R34MH074360] NR 30 TC 7 Z9 7 U1 4 U2 11 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 JAN PY 2013 VL 17 IS 1 BP 266 EP 273 DI 10.1007/s10461-011-0114-9 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 073HL UT WOS:000313734000028 PM 22198316 ER PT J AU Tsai, AC Weiser, SD Steward, WT Mukiibi, NFB Kawuma, A Kembabazi, A Muzoora, C Hunt, PW Martin, JN Bangsberg, DR AF Tsai, Alexander C. Weiser, Sheri D. Steward, Wayne T. Mukiibi, Nozmo F. B. Kawuma, Annet Kembabazi, Annet Muzoora, Conrad Hunt, Peter W. Martin, Jeffrey N. Bangsberg, David R. TI Evidence for the Reliability and Validity of the Internalized AIDS-Related Stigma Scale in Rural Uganda SO AIDS AND BEHAVIOR LA English DT Article DE HIV; Social stigma; Uganda ID HIV-RELATED STIGMA; ANTIRETROVIRAL THERAPY; SOUTH-AFRICA; HIV/AIDS STIGMA; MEDICAL OUTCOMES; MENTAL-HEALTH; POSITIVE WOMEN; SOCIAL SUPPORT; CAPE-TOWN; BARRIERS AB HIV infection remains highly stigmatized throughout sub-Saharan Africa despite the increasing availability of treatment. HIV-related stigma is commonly described to be highly prevalent in East Africa, but none of these studies have employed validated scales for measurement. We used data from 456 people living with HIV/AIDS in rural Uganda to validate the six-item Internalized AIDS-Related Stigma Scale. The scale demonstrated acceptable internal consistency (Cronbach's alpha = 0.73) and time stability. Exploratory factor analysis indicated the presence of a single factor. Construct validity was supported by observations that the scale was correlated with related constructs such as depression and mental health-related quality of life. The scale was able to discriminate between groups of persons who were different in terms of treatment status and their experience of HIV-related self-blame. Taken together, these findings suggest that the Internalized AIDS-Related Stigma Scale may be a useful tool for socio-behavioral HIV research. C1 [Tsai, Alexander C.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, Chester M Pierce MD Div Global Psychiat, Dept Psychiat, Boston, MA 02114 USA. [Weiser, Sheri D.; Hunt, Peter W.] Univ Calif San Francisco, Div HIV AIDS, San Francisco, CA 94143 USA. [Weiser, Sheri D.; Hunt, Peter W.] Univ Calif San Francisco, Posit Hlth Program, San Francisco, CA 94143 USA. [Steward, Wayne T.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Mukiibi, Nozmo F. B.; Kawuma, Annet; Kembabazi, Annet; Muzoora, Conrad; Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. RP Tsai, AC (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, Room 1529-E3,100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM atsai@post.harvard.edu OI Tsai, Alexander/0000-0001-6397-7917 FU NIAAA NIH HHS [K24 AA015287]; NIAID NIH HHS [P30 AI027763, P30 AI060354, P30 AI27763]; NIMH NIH HHS [K23 MH079713, K23 MH-096620, K23 MH-79713, K23 MH096620, K24 MH-087227, K24 MH087227, R01 MH-054907, R01 MH054907] NR 63 TC 18 Z9 20 U1 0 U2 15 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 JAN PY 2013 VL 17 IS 1 BP 427 EP 433 DI 10.1007/s10461-012-0281-3 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 073HL UT WOS:000313734000043 PM 22869104 ER PT J AU Levy, DE Rigotti, NA Winickoff, JP AF Levy, Douglas E. Rigotti, Nancy A. Winickoff, Jonathan P. TI Tobacco Smoke Exposure in a Sample of Boston Public Housing Residents SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID COTININE LEVELS; UNITED-STATES; NONSMOKERS; CHILDREN; NICOTINE; BEHAVIOR; ASTHMA; SERUM AB Background: There is no safe level of tobacco smoke exposure. Nonsmoking residents of public housing are at particular risk of suffering the health consequences of tobacco smoke exposure. Purpose: To compare levels of tobacco smoke exposure among nonsmoking residents of the Boston Housing Authority (BHA) to previously published data from the National Health and Nutrition Examination Survey and identify factors associated with such exposure in the BHA. Methods: Nonsmoking adults and children from two BHA housing developments were invited to participate in a tobacco smoke exposure screening in which they completed a short survey and provided a saliva sample for cotinine analysis. Data were collected in 2011 and analyzed in 2012. Results: Of 51 eligible study participants, 88% (95% CI = 76%, 95%) had detectable cotinine levels (0.15 ng/mL lower limit of detection) compared to at most 56% of residents nationally (using a more sensitive 0.05 ng/mL lower limit of detection). Geometric mean cotinine levels among study participants were 0.52 ng/mL (95% CI = 0.37 ng/mL, 0.74 ng/mL) compared to at most 0.10 ng/mL nationally. Residents living in homes with strict no-smoking rules had lower cotinine levels than those without such rules (0.40 ng/mL vs 1.07 ng/mL, p = 0.006). Conclusions: Tobacco smoke exposure is substantially higher in this sample of nonsmoking BHA residents than among nonsmoking Americans nationally. A comprehensive prohibition on smoking in BHA housing units enacted in October 2012 will help protect this highly exposed group of residents and serve as a model for other housing authorities. (Am J Prev Med 2013;44(1):63-66) (C) 2013 American Journal of Preventive Medicine C1 [Levy, Douglas E.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Levy, Douglas E.; Rigotti, Nancy A.; Winickoff, Jonathan P.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Levy, Douglas E.; Rigotti, Nancy A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Winickoff, Jonathan P.] MassGen Hosp Children, Div Gen Pediat, MGH Ctr Child & Adolescent Hlth Res & Policy, Boston, MA USA. [Winickoff, Jonathan P.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Winickoff, Jonathan P.] Amer Acad Pediat, Julius B Richmond Ctr, Elk Grove Village, IL USA. RP Levy, DE (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM dlevy3@partners.org FU Flight Attendant Medical Research Institute FX The project described was supported by a Young Clinical Scholars Award to Dr. Levy from the Flight Attendant Medical Research Institute. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, and approval of the paper. The authors are grateful to the BHA residents and staff members who made this study possible. NR 17 TC 9 Z9 9 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JAN PY 2013 VL 44 IS 1 BP 63 EP 66 DI 10.1016/j.amepre.2012.09.048 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 071FQ UT WOS:000313574700009 PM 23253651 ER PT J AU Grande, D Barg, FK Johnson, S Cannuscio, CC AF Grande, David Barg, Frances K. Johnson, Sarah Cannuscio, Carolyn C. TI Life Disruptions for Midlife and Older Adults With High Out-of-Pocket Health Expenditures SO ANNALS OF FAMILY MEDICINE LA English DT Article DE insurance benefits; cost sharing; health care financing ID CARE; BURDEN; FAMILIES; ACCESS AB PURPOSE Out-of-pocket cost sharing for health care expenses is a growing burden. Prior research has emphasized the medical consequences of cost sharing. This study investigates the range of social, medical, financial, and sometimes legal disruptions from high out-of-pocket health expenses. METHODS We conducted open-ended, semistructured interviews with 33 insured patients (two-thirds covered by Medicare). All had chronic illnesses and sought philanthropic financial assistance. RESULTS We found that high levels of cost sharing precipitated considerable anxiety and substantial debt problems, as well as disruptions of medical care. Participants described various borrowing strategies (eg, credit cards), legal problems (eg, debt collections), and threats to their nonmedical household budgets (eg, food, housing). Participants described explicit and rank-ordered strategies for coping with new medical expenses. Participants understood their health benefits with exceptional detail but described considerable anxiety about changes to those benefits that could easily disrupt carefully managed household budgets. Benefit designs that resulted in large a variations in financial liability from month to month (eg, large deductibles or coverage gaps) imposed considerable financial challenges. CONCLUSIONS As health care cost sharing grows, policy makers will need to consider the consequences of high cost sharing for families facing strained household budgets. Although the generosity of health insurance is important, continuity of benefits and month-to-month stability of financial liability are also important and may be undervalued in policy discussions. Ann Fam Med 2013;11:37-42. doi:10.1370/afm.1444. C1 [Grande, David] Univ Penn, Div Internal Med, Dept Med, Philadelphia, PA 19104 USA. [Grande, David; Cannuscio, Carolyn C.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Barg, Frances K.; Cannuscio, Carolyn C.] Univ Penn, Dept Family & Community Hlth, Philadelphia, PA 19104 USA. [Johnson, Sarah] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Cannuscio, Carolyn C.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Grande, D (reprint author), Univ Penn, Div Internal Med, Dept Med, 3641 Locust Walk,Room 407, Philadelphia, PA 19104 USA. EM dgrande@wharton.upenn.edu FU HealthWell Foundation, Gaithersburg, Maryland FX This study was supported by the HealthWell Foundation, Gaithersburg, Maryland. NR 24 TC 6 Z9 6 U1 0 U2 12 PU ANNALS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672 USA SN 1544-1709 J9 ANN FAM MED JI Ann. Fam. Med. PD JAN-FEB PY 2013 VL 11 IS 1 BP 37 EP 42 DI 10.1370/afm.1444 PG 6 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 074VE UT WOS:000313841600009 PM 23319504 ER PT J AU Huber, RJ Catalano, A O'Day, DH AF Huber, Robert J. Catalano, Andrew O'Day, Danton H. TI Cyclin-dependent kinase 5 is a calmodulin-binding protein that associates with puromycin-sensitive aminopeptidase in the nucleus of Dictyostelium SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE Cyclin-dependent kinase 5; Calmodulin; Puromycin-sensitive aminopeptidase; Calmodulin-binding protein; Dictyostelium; Nucleus ID CONTRACTILE VACUOLE COMPLEX; EPIDERMAL-GROWTH-FACTOR; CELL MOTILITY; DNA-SYNTHESIS; DISCOIDEUM; CDK5; PHOSPHORYLATION; DIFFERENTIATION; LOCALIZATION; EXPRESSION AB Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase that has been implicated in a number of cellular processes. In Dictyostelium, Cdk5 localizes to the nucleus and cytoplasm, interacts with puromycin-sensitive aminopeptidase A (PsaA), and regulates endocytosis, secretion, growth, and multicellular development. Here we show that Cdk5 is a calmodulin (CaM)-binding protein (CaMBP) in Dictyostelium. Cdk5, PsaA, and CaM were all present in isolated nuclei and Cdk5 and PsaA co-immunoprecipitated with nuclear CaM. Although nuclear CaMBPs have previously been identified in Dictyostelium, the detection of CaM in purified nuclear fractions had not previously been shown. Putative CaM-binding domains (CaMBDs) were identified in Cdk5 and PsaA. Deletion of one of the two putative CaMBDs in Cdk5 ((132)LLINRKGELKLADFGLARAFGIP(154)) prevented CaM-binding indicating that this region encompasses a functional CaMBD. This deletion also increased the nuclear distribution of Cdk5 suggesting that CaM regulates the nucleocytoplasmic transport of Cdk5. A direct binding between CaM and PsaA could not be determined since deletion of the one putative CaMBD in PsaA prevented the nuclear localization of the deletion protein. Together, this study provides the first direct evidence for nuclear CaM in Dictyostelium and the first evidence in any system for Cdk5 being a CaMBP. (c) 2012 Elsevier B.V. All rights reserved. C1 [Huber, Robert J.; Catalano, Andrew; O'Day, Danton H.] Univ Toronto, Dept Cell & Syst Biol, Toronto, ON M5S 3G5, Canada. [O'Day, Danton H.] Univ Toronto, Dept Biol, Mississauga, ON L5L 1C6, Canada. RP Huber, RJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res,Richard B Simches Res Ctr, 185 Cambridge St, Boston, MA 02114 USA. EM rhuber@chgr.mgh.harvard.edu; andrew.catalano@utoronto.ca; danton.oday@utoronto.ca FU Discovery Grant [A6807]; Canada Graduate Scholarship; Natural Sciences and Engineering Research Council of Canada FX This study was supported by a Discovery Grant (D.H.O'D.; A6807) and a Canada Graduate Scholarship (R.J.H.) from the Natural Sciences and Engineering Research Council of Canada. NR 60 TC 4 Z9 5 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD JAN PY 2013 VL 1833 IS 1 BP 11 EP 20 DI 10.1016/j.bbamcr.2012.10.005 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 076BS UT WOS:000313932100002 PM 23063531 ER PT J AU Linnman, C Zeidan, MA Pitman, RK Milad, MR AF Linnman, Clas Zeidan, Mohamed A. Pitman, Roger K. Milad, Mohammed R. TI Reprint of: Resting cerebral metabolism correlates with skin conductance and functional brain activation during fear conditioning SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE PET; fMRI; Fear conditioning; Glucose metabolism; Electrodermal activity ID POSTTRAUMATIC-STRESS-DISORDER; VENTROMEDIAL PREFRONTAL CORTEX; ANTERIOR CINGULATE CORTEX; ANXIETY DISORDERS; PERIAQUEDUCTAL GRAY; EXTINCTION MEMORY; DEFAULT MODE; AMYGDALA; RESPONSES; HUMANS AB We investigated whether resting brain metabolism can be used to predict autonomic and neuronal responses during fear conditioning in 20 healthy humans. Regional cerebral metabolic rate for glucose was measured via positron emission tomography at rest. During conditioning, autonomic responses were measured via skin conductance, and blood oxygen level dependent signal was measured via functional magnetic resonance imaging. Resting dorsal anterior cingulate metabolism positively predicted differentially conditioned skin conductance responses. Midbrain and insula resting metabolism negatively predicted midbrain and insula functional reactivity, while dorsal anterior cingulate resting metabolism positively predicted midbrain functional reactivity. We conclude that resting metabolism in limbic areas can predict some aspects of psychophysiological and neuronal reactivity during fear learning. (C) 2011 Elsevier B.V. All rights reserved. C1 [Linnman, Clas] Harvard Univ, Sch Med, Dept Psychiat, Charlestown, MA USA. Massachusetts Gen Hosp, Charlestown, MA USA. RP Linnman, C (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Charlestown, MA USA. EM linnman@nmr.mgh.harvard.edu OI Linnman, Clas/0000-0001-8449-894X FU Institute of Mental Health [1R01MH081975-01] FX This work was supported by Institute of Mental Health grant 1R01MH081975-01 (MGH subcontract) to M.R.M. NR 56 TC 4 Z9 4 U1 5 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD JAN PY 2013 VL 92 IS 1 SI SI BP 26 EP 35 DI 10.1016/j.biopsycho.2012.03.002 PG 10 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 075WN UT WOS:000313918000005 ER PT J AU Kolappa, K Henderson, DC Kishore, SP AF Kolappa, Kavitha Henderson, David C. Kishore, Sandeep P. TI No physical health without mental health: lessons unlearned? SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Editorial Material C1 [Kolappa, Kavitha; Henderson, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kishore, Sandeep P.] Young Profess Chron Dis Network, New York, NY 10065 USA. RP Kishore, SP (reprint author), Young Profess Chron Dis Network, 1230 York Ave,Box 292, New York, NY 10065 USA. EM sunny.kishore@gmail.com FU NIGMS NIH HHS [T32 GM007739] NR 0 TC 17 Z9 17 U1 0 U2 7 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PD JAN PY 2013 VL 91 IS 1 BP 3 EP 3 DI 10.2471/BLT.12.115063 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 073QA UT WOS:000313756400002 PM 23397342 ER PT J AU Madan, RA Gulley, JL Kantoff, PW AF Madan, Ravi A. Gulley, James L. Kantoff, Philip W. TI Demystifying Immunotherapy in Prostate Cancer Understanding Current and Future Treatment Strategies SO CANCER JOURNAL LA English DT Article DE Immunotherapy; prostate cancer; therapeutic cancer vaccines; immune-checkpoint inhibitors; combination immunotherapy ID RECOMBINANT VACCINIA VIRUS; RE INTERDISCIPLINARY CRITIQUE; ANDROGEN-DEPRIVATION THERAPY; DOSE-ESCALATION TRIAL; PHASE-I TRIAL; SIPULEUCEL-T; CELLULAR IMMUNOTHERAPY; METASTATIC MELANOMA; TUMOR-CELLS; ACID-PHOSPHATASE AB Immunotherapy has emerged as a viable therapeutic option for patients with prostate cancer. There are multiple potential strategies that use the immune system, including therapeutic cancer vaccines that are designed to stimulate immune cells to target antigens expressed by cancer cells. Sipuleucel-T is a vaccine currently approved for the treatment of minimally symptomatic metastatic prostate cancer, whereas the vaccine PSA-TRICOM and the immune-checkpoint inhibitor ipilimumab are in phase III testing. Although there are no short-term changes in disease progression or available biomarkers to assess response, these agents appear to improve survival. One hypothesis suggests that this apparent paradox can be explained by the growth-moderating effects of these treatments, which do not cause tumor size to diminish, but rather stall or slow their growth rate over time. For this reason, the use of immunotherapy earlier in the disease process is being investigated. Another approach is to block immune-regulatory mechanisms mediated by the molecules cytotoxic T lymphocyte antigen 4 and programmed cell death protein 1. Additional future strategies will combine immunotherapy with other standard therapies, potentially enhancing the latter's clinical impact and thereby improving both time to progression and overall survival due to the combined effects of both treatments. Prospective trials are currently evaluating these hypotheses and will ultimately serve to optimize immunotherapy in the treatment of prostate cancer. C1 [Madan, Ravi A.; Gulley, James L.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kantoff, Philip W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gulley, JL (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,8B09 MSC 1750, Bethesda, MD 20892 USA. EM gulleyj@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU Intramural NIH HHS [ZIA BC010666-08] NR 84 TC 13 Z9 15 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD JAN-FEB PY 2013 VL 19 IS 1 BP 50 EP 58 DI 10.1097/PPO.0b013e31828160a9 PG 9 WC Oncology SC Oncology GA 075SN UT WOS:000313906900008 PM 23337757 ER PT J AU Lee, RJ Smith, MR AF Lee, Richard J. Smith, Matthew R. TI Targeting MET and Vascular Endothelial Growth Factor Receptor Signaling in Castration-Resistant Prostate Cancer SO CANCER JOURNAL LA English DT Article DE MET; VEGFR; cabozantinib; prostate cancer; bone metastasis ID LEUKEMIA GROUP-B; C-MET; PHASE-II; CLINICAL-TRIALS; DOUBLE-BLIND; END-POINTS; IN-VITRO; EXPRESSION; VEGF; METASTASIS AB Effective management of bone metastases in men with castration-resistant prostate cancer (CRPC) remains an important unmet medical need. MET and vascular endothelial growth factor receptor (VEGFR) are rational targets for intervention in CRPC. Clinical trials involving agents that inhibit one but not both pathways have reported modest activity and no improvement in overall survival. Cabozantinib is an oral multitargeted tyrosine kinase inhibitor that inhibits both MET and VEGFR-2. A phase II randomized discontinuation study involving subjects with CRPC demonstrated that cabozantinib therapy is associated with improvement in bone scans, bone turnover markers, and pain response, but with significant adverse events leading to dose reduction and treatment discontinuation. Lower doses of cabozantinib retain high levels of activity with less toxicity. Ongoing phase III clinical trials will define the role of cabozantinib in CRPC. We summarize the rationale for targeting MET and VEGFR pathways in CRPC and the clinical data available to date. C1 [Lee, Richard J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lee, RJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 7108, Boston, MA 02114 USA. EM rjlee@partners.org FU Department of Defense Prostate Cancer Research Program [W81XWH-09-1-0471]; Conquer Cancer Foundation Career Development Award; National Institutes of Health Midcareer Investigator Award [5K24CA121990]; Prostate Cancer Foundation; Exelixis, Inc, South San Francisco, CA FX This study was supported by the Department of Defense Prostate Cancer Research Program under Award W81XWH-09-1-0471 and a Conquer Cancer Foundation Career Development Award (to R.J.L.), by National Institutes of Health Midcareer Investigator Award (no. 5K24CA121990 to M.R.S.), and competitive research awards from the Prostate Cancer Foundation.; Conflicts of Interest and Source of Funding: R.J.L. has received sponsored research funding from Exelixis, Inc, South San Francisco, CA. M.R.S. is a paid consultant of, and has received sponsored research funding from, Exelixis, Inc, South San Francisco, CA. NR 49 TC 23 Z9 24 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1528-9117 EI 1540-336X J9 CANCER J JI Cancer J. PD JAN-FEB PY 2013 VL 19 IS 1 BP 90 EP 98 DI 10.1097/PPO.0b013e318281e280 PG 9 WC Oncology SC Oncology GA 075SN UT WOS:000313906900013 PM 23337762 ER PT J AU Jaffe, RJ Novakovic, V Peselow, ED AF Jaffe, Robert J. Novakovic, Vladan Peselow, Eric D. TI Scopolamine as an Antidepressant: A Systematic Review SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE scopolamine hydrobromide; depression; antidepressant ID DEPRESSED-PATIENTS; SLEEP; MOOD AB Objectives: The cholinergic-adrenergic hypothesis of mania and depression states that depression is characterized by an increase in central cholinergic activity relative to noradrenergic tone. Scopolamine is a centrally acting competitive inhibitor of the muscarinic cholinergic receptor site. This review seeks to find all available data investigating scopolamine as an antidepressant. Methods: A systematic review of all the published and unpublished or ongoing literature was conducted via Ovid MEDLINE. Keywords used for the search were "scopolamine hydrobromide'' in association with one of the following: "depression,'' "antidepressive agents,'' "depressive disorder,'' "depression, chemical,'' and "affect.'' PubMed was also searched using "scopolamine'' (all fields) and "antidepressant'' (all fields) or "depression'' (all fields). Results: A small study with elderly patients failed to show a statistically significant improvement in depression when measured at 120 minutes after infusion. A second small, well-controlled study using intramuscular scopolamine showed a small but statistically significant improvement in depression on the morning after the second dose was received. Two double-blind randomized placebo-controlled crossover trials with intravenous scopolamine 4.0 Kg/kg infusions showed a significant improvement in depressive symptoms seen as soon as 3 days after the first treatment. Further data analyses showed a greater antidepressant effect in women, significant improvements in bipolar depression, and 85% success rates predicting who will respond to treatment. Conclusions: Scopolamine is an effective and rapid antidepressant in both unipolar and bipolar depression, working as quickly as 3 days after initial infusion. Independent replication would greatly enhance the literature. C1 [Jaffe, Robert J.; Novakovic, Vladan] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Novakovic, Vladan] James J Peters VA Med Ctr, Dept Psychiat, Bronx, NY USA. [Peselow, Eric D.] New York Med Coll, Dept Psychiat, New York, NY USA. RP Jaffe, RJ (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM robert.jaffe@mountsinai.org NR 20 TC 15 Z9 15 U1 2 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD JAN-FEB PY 2013 VL 36 IS 1 BP 24 EP 26 DI 10.1097/WNF.0b013e318278b703 PG 3 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 074EV UT WOS:000313796600005 PM 23334071 ER PT J AU Foynes, MM Shipherd, JC Harrington, EF AF Foynes, Melissa Ming Shipherd, Jillian C. Harrington, Ellen F. TI Race and Gender Discrimination in the Marines SO CULTURAL DIVERSITY & ETHNIC MINORITY PSYCHOLOGY LA English DT Article DE race-based discrimination; gender-based discrimination; Marines; double jeopardy ID POSTTRAUMATIC STRESS SYMPTOMS; AFRICAN-AMERICAN WOMEN; SEXUAL-HARASSMENT; PERCEIVED DISCRIMINATION; RACIAL-DISCRIMINATION; DOUBLE JEOPARDY; WORKPLACE HARASSMENT; ASIAN-AMERICANS; PHYSICAL HEALTH; INVENTORY AB Although women of color have been hypothesized to experience double jeopardy in the form of chronic exposure to both race-based (RBD) and gender-based discrimination (GBD; Beal, 1970), few empirical investigations that examine both RBD and GBD in multiple comparison groups have been conducted. In addition to being one of the only simultaneous examinations of RBD and GBD in multiple comparison groups, the current study includes both self-report and objective behavioral data to examine the independent and interactive effects of both forms of discrimination. This study is also the first of its kind to examine these constructs in these ways and to explore their impact in a unique sample of ethnically diverse male and female Marine recruits (N = 1,516). As anticipated, both RBD and GBD had a strong and consistent negative impact on mental health symptoms (e.g., depression, anxiety), independent of the contributions of gender and race. Partial support was found for the hypothesis that people of color are able to maintain resiliency (as measured by physical fitness testing) in the face of low levels of RBD, but are less able to overcome the negative effects of discrimination at high levels. It is interesting to note that the interaction between race, gender, and levels of discrimination was only found with objective physical fitness test scores but not with self-report measures. These findings underscore the importance of including objective measures when assessing the impact of discrimination in order to understand these complex interrelationships. C1 [Foynes, Melissa Ming; Shipherd, Jillian C.] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Shipherd, Jillian C.] Boston Univ, Boston, MA 02215 USA. [Harrington, Ellen F.] Summa Hlth Syst, Ctr Treatment & Study Traumat Stress, Akron, OH USA. RP Foynes, MM (reprint author), VA Boston Healthcare Syst 116B, 150 S Huntington Ave, Boston, MA 02130 USA. EM melissa.foynes2@va.gov NR 52 TC 8 Z9 8 U1 2 U2 24 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1099-9809 J9 CULT DIVERS ETHN MIN JI Cult. Divers. Ethn. Minor. Psychol. PD JAN PY 2013 VL 19 IS 1 BP 111 EP 119 DI 10.1037/a0030567 PG 9 WC Ethnic Studies; Psychology, Social SC Ethnic Studies; Psychology GA 077PB UT WOS:000314038500012 PM 23148901 ER PT J AU Thorpe, CT Fahey, LE Johnson, H Deshpande, M Thorpe, JM Fisher, EB AF Thorpe, Carolyn T. Fahey, Lauren E. Johnson, Heather Deshpande, Maithili Thorpe, Joshua M. Fisher, Edwin B. TI Facilitating Healthy Coping in Patients With Diabetes A Systematic Review SO DIABETES EDUCATOR LA English DT Review ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; SUBCUTANEOUS INSULIN INFUSION; COGNITIVE-BEHAVIOR THERAPY; AFRICAN-AMERICAN WOMEN; TREATMENT SATISFACTION; SELF-MANAGEMENT; MULTISYSTEMIC THERAPY; DEPRESSION TREATMENT; GLYCEMIC CONTROL AB Purpose The purpose of this study is to summarize recent literature on approaches to supporting healthy coping in diabetes in 2 specific areas: (1) the impact of different approaches to diabetes treatment on healthy coping and (2) the effectiveness of interventions specifically designed to support healthy coping. Methods A PubMed search identified 129 articles published August 1, 2006, to April 30, 2011, addressing diabetes in relation to emotion, quality of life, depression, adjustment, anxiety, coping, family therapy, behavior therapy, psychotherapy, problem solving, couples therapy, or marital therapy. Results Evidence suggests that treatment choice may significantly influence quality of life, with treatment intensification in response to poor metabolic control often improving quality of life. The recent literature provides support for a variety of healthy coping interventions in diverse populations, including diabetes self-management education, support groups, problem-solving approaches, and coping skills interventions for improving a range of outcomes; cognitive behavior therapy and collaborative care for treating depression; and family therapy for improving coping in youths. Conclusions Healthy coping in diabetes has received substantial attention in the past 5 years. A variety of approaches show positive results. Research is needed to compare the effectiveness of different approaches in different populations and determine how to overcome barriers to intervention dissemination and implementation. C1 [Thorpe, Carolyn T.; Thorpe, Joshua M.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Thorpe, Carolyn T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Fahey, Lauren E.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA. [Johnson, Heather] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. [Deshpande, Maithili] Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA. [Fisher, Edwin B.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. RP Thorpe, CT (reprint author), Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, 919 Salk Hall,3501 Terrace St, Pittsburgh, PA 15261 USA. EM ctthorpe@pitt.edu RI Thorpe, Joshua/C-1188-2013 FU University of Wisconsin Institute for Clinical and Translational Research (UW ICTR); Clinical and Translational Science Award (CTSA) program of the National Center for Research Resources [1UL1RR025011]; National Institutes of Health; Peers for Progress of the American Academy of Family Physicians Foundation; UW School of Medicine and Public Health from the Wisconsin Partnership Program; UW School of Medicine and Public Health from the Centennial Scholars Program FX Support was provided by the Health Innovation Program and the Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research (UW ICTR), grant 1UL1RR025011 from the Clinical and Translational Science Award (CTSA) program of the National Center for Research Resources, the National Institutes of Health, and the Peers for Progress of the American Academy of Family Physicians Foundation (Dr Fisher). Additional funding for this project was provided by the UW School of Medicine and Public Health from the Wisconsin Partnership Program and the Centennial Scholars Program. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs, the United States government, the University of Pittsburgh, the University of Wisconsin, or the University of North Carolina. NR 99 TC 32 Z9 32 U1 5 U2 37 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD JAN-FEB PY 2013 VL 39 IS 1 BP 33 EP 52 DI 10.1177/0145721712464400 PG 20 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 073HE UT WOS:000313733300002 PM 23073967 ER PT J AU Kutyifa, V Zareba, W McNitt, S Singh, J Hall, WJ Polonsky, S Goldenberg, I Huang, DT Merkely, B Wang, PJ Moss, AJ Klein, H AF Kutyifa, Valentina Zareba, Wojciech McNitt, Scott Singh, Jagmeet Hall, William Jackson Polonsky, Slava Goldenberg, Ilan Huang, David T. Merkely, Bela Wang, Paul J. Moss, Arthur J. Klein, Helmut TI Left ventricular lead location and the risk of ventricular arrhythmias in the MADIT-CRT trial SO EUROPEAN HEART JOURNAL LA English DT Article DE Cardiac resynchronization therapy; Ventricular tachycardia; Ventricular fibrillation; Left ventricular lead position ID CARDIAC-RESYNCHRONIZATION THERAPY; CHRONIC HEART-FAILURE; TORSADE-DE-POINTES; TRANSMURAL DISPERSION; QT INTERVAL; DEFIBRILLATOR; REPOLARIZATION; MORTALITY; MODERATE; OUTCOMES AB We aimed to evaluate the influence of left ventricular (LV) lead position on the risk of ventricular tachyarrhythmias in cardiac resynchronization therapy (CRT) patients. Left ventricular (LV) lead position was evaluated by biplane coronary venograms and anterior/posterior, lateral chest X-rays in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial Cardiac Resynchronization Therapy (MADIT-CRT). The LV lead location could be defined in 797 of 1089 patients (73). The LV lead was placed at the LV apex in 110 (14) patients, in the anterior position in 146 (18), in the lateral position in 448 (56), and in the posterior position in 93 (12) patients. After adjustment for clinical covariates, lateral or posterior lead location was associated with significantly lower risk of ventricular tachycardia (VT)/ventricular fibrillation (VF) [hazard ratio (HR) 0.57, 95 confidence interval (CI): 0.380.85; P 0.006] when compared with an anterior lead location. Patients with anterior lead position had similar risk of VT/VF as patients with implantable cardioverter defibrillator (ICD)-only (HR 1.04, 95 CI: 0.721.81; P 0.837). There was no difference in the risk of mortality between posterior or lateral and anterior LV lead locations. Cardiac resynchronization therapy with posterior or lateral LV lead position is associated with decreased risk of arrhythmic events in comparison with anterior lead location and ICD-only patients. There is no evidence for increased risk of VT/VF episodes associated with CRT. C1 [Kutyifa, Valentina; Zareba, Wojciech; McNitt, Scott; Hall, William Jackson; Polonsky, Slava; Goldenberg, Ilan; Huang, David T.; Moss, Arthur J.; Klein, Helmut] Univ Rochester, Med Ctr, Heart Res Follow Up Program, Div Cardiol, Rochester, NY 14642 USA. [Kutyifa, Valentina; Merkely, Bela] Semmelweis Univ, Ctr Heart, Budapest, Hungary. [Singh, Jagmeet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Heart, Boston, MA USA. [Wang, Paul J.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Kutyifa, V (reprint author), Univ Rochester, Med Ctr, Heart Res Follow Up Program, Div Cardiol, 265 Crittenden Blvd,Box 653, Rochester, NY 14642 USA. EM valentina.kutyifa@heart.rochester.edu FU Boston Scientific, St Paul, MN, USA; Boston Scientific; Medtronic; St Jude Medical; Biotronik; Gilead; Medtronic St. Jude Medical; St. Jude FX The MADIT-CRT study was supported by a research grant from Boston Scientific, St Paul, MN, USA, to the University of Rochester School of Medicine and Dentistry.; V. K. has received research support from Boston Scientific and honoraria from BiotronikGmBH and Servier. J.S., A.J.M, and W.Z. have received research grant from Boston Scientific. D. T. H. has received research support from Boston Scientific, Medtronic, St Jude Medical, Biotronik, Gilead; fellowship education support from Boston Scientific, Medtronic St. Jude Medical, Biotronik; is a speaker for Biotronik and consultant for St Jude Medical. B. M. has received consultant fees/honoraria from Biotronik, Boston Scientific, Medtronic, and St Jude Medical, and serves in the speaker's bureau of BoehringerIngelheim. P.J.W. has received EP fellowship support from Medtronic, St. Jude, Boston Scientific, honoraria from Medtronic and Boston Scientific, research support from Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 28 TC 21 Z9 23 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD JAN PY 2013 VL 34 IS 3 BP 184 EP 190 DI 10.1093/eurheartj/ehs334 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 074RO UT WOS:000313831000009 PM 23053173 ER PT J AU Yao, YL Han, WZ Liang, JJ Ji, J Wang, JL Cantor, H Lu, LR AF Yao, Yunliang Han, Wenzheng Liang, Jingjing Ji, Jian Wang, Jianli Cantor, Harvey Lu, Linrong TI Glatiramer acetate ameliorates inflammatory bowel disease in mice through the induction of Qa-1-restricted CD8+regulatory cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CD8+Treg; Colitis; Inflammation; Qa-1 ID REGULATORY T-CELLS; INDUCED EXPERIMENTAL COLITIS; LAMINA PROPRIA; MULTIPLE-SCLEROSIS; CROHNS-DISEASE; SCID MICE; INTESTINAL INFLAMMATION; IMMUNODEFICIENT MICE; ULCERATIVE-COLITIS; LYMPHOCYTES AB Inflammatory bowel diseases (IBDs) are complex multifactorial immunological disorders characterized by dysregulated immune reactivity in the intestine. Here, we investigated the contribution of Qa-1-restricted CD8+ Treg cells in regulating experimental IBD in mice. We found that CD8+ T cells induced by T-cell vaccination ameliorated the pathological manifestations of dextran sulfate sodium induced IBD when adoptively transferred into IBD mice. In addition, CD8+ cell suppressive activity was induced by vaccination with glatiramer acetate (GA), an FDA-approved drug for multiple sclerosis (MS). We next showed that GA-induced CD8+ Treg cells worked in a Qa-1-dependent manner and their suppressive activity depends on perforin-mediated cytotoxicity. Finally, we confirmed the role of CD4+ T cells in dextran sulfate sodium induced colitis progression, and clarified that GA-induced CD8+ T cells exerted their therapeutic effects on colitis by targeting pathogenic CD4+ T cells. Our results reveal a new regulatory role of Qa-1-restricted CD8+ Treg cells in IBD and suggest their induction by GA vaccination as a potential therapeutic approach to IBD. C1 [Yao, Yunliang; Liang, Jingjing; Wang, Jianli; Lu, Linrong] Zhejiang Univ, Sch Med, Inst Immunol, Hangzhou 310003, Zhejiang, Peoples R China. [Yao, Yunliang; Liang, Jingjing; Lu, Linrong] Zhejiang Univ, Sch Med, Program Mol & Cellular Biol, Hangzhou 310003, Zhejiang, Peoples R China. [Yao, Yunliang] Huzhou Teachers Coll, Sch Med, Dept Microbiol & Immunol, Huzhou, Peoples R China. [Han, Wenzheng] Zhejiang Sci Tech Univ, Life Sci Coll, Xin Yuan Inst Med & Biotechnol, Hangzhou, Zhejiang, Peoples R China. [Ji, Jian] Zhejiang Univ, Coll Anim Sci, Key Lab Anim Mol Nutr, Minist Educ, Hangzhou 310003, Zhejiang, Peoples R China. [Cantor, Harvey] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Cantor, Harvey] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Lu, LR (reprint author), 866 Yuhang Tang Rd,Med Res Bldg B819, Hangzhou 310058, Zhejiang, Peoples R China. EM lu_linrong@zju.edu.cn FU National Natural Science Foundation of China [30972724, 31070782]; National Basic Research Program of China (973 Program) [2011CB944100, 2012CB945004]; Zhejiang Provincial Natural Science Foundation of China [R2090202] FX The authors thank Dr. D. Wang and H. Hu for their helpful discussion; Dr. I. Bruce for his critical reading. This work was supported by grants from the National Natural Science Foundation of China (30972724, 31070782 to L. L.), National Basic Research Program of China (973 Program) (2011CB944100 and 2012CB945004 to L. L.), and Zhejiang Provincial Natural Science Foundation of China (R2090202 to L.L.) NR 34 TC 10 Z9 10 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JAN PY 2013 VL 43 IS 1 BP 125 EP 136 DI 10.1002/eji.201242758 PG 12 WC Immunology SC Immunology GA 075KB UT WOS:000313883200020 PM 23002042 ER PT J AU Wang, F Man, JKM Lee, EKO Wu, TX Benson, H Fricchione, GL Wang, WD Yeung, A AF Wang, Fang Man, Jenny K. M. Lee, Eun-Kyoung Othelia Wu, Taixiang Benson, Herbert Fricchione, Gregory L. Wang, Weidong Yeung, Albert TI The Effects of Qigong on Anxiety, Depression, and Psychological Well-Being: A Systematic Review and Meta-Analysis SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; ESSENTIAL-HYPERTENSION; CLINICAL-TRIALS; BLOOD-PRESSURE; EXERCISE; THERAPY; COMBINATION; EFFICACY; PROGRAM; IMPACT AB Introduction. The effect of Qigong on psychological well-being is relatively unknown. This study systematically reviewed the effects of Qigong on anxiety, depression, and psychological well-being. Methods. sing fifteen studies published between 2001 and 2011, a systematic review was carried out and meta-analyses were performed on studies with appropriate homogeneity. The quality of the outcome measures was also assessed. Results. We categorized these studies into three groups based on the type of subjects involved as follows: (1) healthy subjects, (2) subjects with chronic illnesses, and (3) subjects with depression. Based on the heterogeneity assessment of available studies, meta-analyses were conducted in three studies of patients with type II diabetes in the second group, which suggested that Qigong was effective in reducing depression (ES = -0.29; 95% CI, -0.58-0.00) and anxiety (ES = -0.37; 95% CI, -0.66-0.08), as measured by Symptom Checklist 90, and in improving psychological well-being (ES = -0.58; 95% CI, -0.91-0.25) as measured by Diabetes Specific Quality of Life Scale. Overall, the quality of research methodology of existing studies was poor. Conclusions. Preliminary evidence suggests that Gigong may have positive effects on psychological well-being among patients with chronic illnesses. However the published studies generally had significant methodological limitations. More high-quality studies are needed. C1 [Wang, Fang; Wang, Weidong] Chinese Med Sci, China Acad, Guangan Men Hosp, Dept Psychol, Beijing 100053, Peoples R China. [Man, Jenny K. M.; Yeung, Albert] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Lee, Eun-Kyoung Othelia] Univ N Carolina, Dept Social Work, Charlotte, NC 28223 USA. [Wu, Taixiang] Sichuan Univ, W China Hosp, Chinese Cochrane Ctr, Chengdu 610041, Peoples R China. [Benson, Herbert; Fricchione, Gregory L.] Massachusetts Gen Hosp, Benson Henry Inst, Boston, MA 02114 USA. RP Wang, WD (reprint author), Chinese Med Sci, China Acad, Guangan Men Hosp, Dept Psychol, Beijing 100053, Peoples R China. EM vision_wf@126.com FU U.S. Centers for Disease Control and Prevention; Ministry of Science and Technology of the People' Republic of China; U.S. Centers for Disease Control and Prevention [5R01DP000339]; Ministry of Science and Technology of the People' Republic of China [2008DFA32010] FX . e authors declare that they have no competing interests and no financial benefits to the authors. Each author's contribution to this paper is as follows: H. Benson and G. Fricchione obtained funding from the U.S. Centers for Disease Control and Prevention for the study. W. Wang obtained funding from the Ministry of Science and Technology of the People' Republic of China for the study. A. S. Yeung designed the study. F. Wang, J. K. M. Man, and E. Lee conducted the research. F. Wang conducted the meta-analysis. E. Lee, F. Wang, J. K. M. Man, and A. S. Yeung wrote the first draft of the paper. F. Wang, J. K. M. Man, E. Lee, T. Wu, and A. S. Yeung participated in the revision of subsequent dra. s. All authors read and approved the final paper.; The research was partly funded by the following two projects: (1) U.S. Centers for Disease Control and Prevention: Grant no. 5R01DP000339. (2) The Ministry of Science and Technology of the People' Republic of China: Grant no. 2008DFA32010. F. Wang and J. K. M. Man are cofirst authors W. Wang and A. S. Yeung are cosenior authors. NR 45 TC 10 Z9 10 U1 3 U2 33 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1741-427X EI 1741-4288 J9 EVID-BASED COMPL ALT JI Evid.-based Complement Altern. Med. PY 2013 AR 152738 DI 10.1155/2013/152738 PG 16 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 079CQ UT WOS:000314148200001 ER PT J AU Largent, EA Miller, FG Joffe, S AF Largent, Emily A. Miller, Franklin G. Joffe, Steven TI A Prescription for Ethical Learning SO HASTINGS CENTER REPORT LA English DT Editorial Material ID CARE AB We argued last year in this journal that extensive integration of research and care is a worthy goal of health system design, and we second the call from Ruth Faden and colleagues to move toward learning health care systems. As they recognize, learning health care systems demand the coordination of research and medical ethicstwo sets of normative commitments that have long been considered distinct. In offering a novel ethics framework for such systems, Faden et al. advance the scholarly debate about how best to do this and challenge us to think more deeply about its practical implications. However, we believe that at least three issues they raise require additional attention. First, the research-care distinction has more normative bite than they are willing to concede. Second, the role for independent oversight requires clarification. Finally, they neglect the concept of stewardship as a guiding obligation of learning health care systems. C1 [Largent, Emily A.] Harvard Univ, Hlth Policy Program, Cambridge, MA 02138 USA. [Joffe, Steven] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Joffe, Steven] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Largent, EA (reprint author), Harvard Univ, Hlth Policy Program, Cambridge, MA 02138 USA. OI Joffe, Steven/0000-0002-0667-7384 NR 6 TC 5 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD JAN-FEB PY 2013 VL 43 SU 1 BP S28 EP S29 DI 10.1002/hast.135 PG 2 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 073AC UT WOS:000313714600004 ER PT J AU Youn, SJ Trinh, NH Shyu, I Chang, T Fava, M Kvedar, J Yeung, A AF Youn, Soo Jeong Nhi-Ha Trinh Shyu, Irene Chang, Trina Fava, Maurizio Kvedar, Joseph Yeung, Albert TI Using online social media, Facebook, in screening for major depressive disorder among college students SO INTERNATIONAL JOURNAL OF CLINICAL AND HEALTH PSYCHOLOGY LA English DT Article DE Screening for Major Depressive Disorder; Social networking media; College students; Internet; Survey descriptive study ID NETWORKING SITES; HEALTH; INTERNET; SUICIDE; ANXIETY; INTERVENTIONS; INFORMATION; UNIVERSITY; IDEATION; ILLNESS AB This study explored the feasibility of using Internet social networking media in an online program for Major Depressive Disorder (MDD) screening and psychoeducation targeting college students. A Facebook advertisement targeted students at five colleges in the United States to complete a mental health research survey that screened for MDD using the Patient Health Questionnaire-9 (PHQ-9). Students who screened positive for MDD were offered an eight-week follow-up survey. Of the 259 students who consented to participate in the study, 26.7% screened positive for MDD, while only 14.2% were receiving treatment. The use of Facebook to advertise for online screening for MDD required very little start-up time, and the average cost was $11.45 per subject recruited. It is feasible to use online, commercially available social networking media such as Facebook for online screening for MDD among college students. However, conducting online screening and offering treatment resources alone did not increase treatment rate in this population. (C) 2012 Asociacion Espanola de Psicologia Conductual. Published by Elsevier Espana, S.L. All rights reserved. C1 [Yeung, Albert] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Yeung, A (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM ayeung@partners.org NR 29 TC 4 Z9 4 U1 8 U2 59 PU ASOCIACION ESPANOLA PSICOLOGIA CONDUCTUAL PI GRANADA PA UNIVERSIDAD DE GRANADA, 18071 GRANADA, SPAIN SN 1697-2600 J9 INT J CLIN HLTH PSYC JI Int. J. Clin. Health Psychol. PD JAN PY 2013 VL 13 IS 1 BP 74 EP 80 PG 7 WC Psychology, Clinical SC Psychology GA 075CC UT WOS:000313860400011 ER PT J AU Foley, OW Rauh-Hain, JA del Carmen, MG AF Foley, Olivia W. Rauh-Hain, J. Alejandro del Carmen, Marcela G. TI The Role of Intraoperative Radiation Therapy in the Management of Recurrent and Locally Advanced Gynecologic Cancers SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Review DE Intraoperative; Surgery; Radiation ID ADVANCED CERVICAL-CANCER; ENDOMETRIAL CARCINOMA; HDR-IORT; RADIOTHERAPY; MALIGNANCIES; EXPERIENCE; TRIAL AB For patients with locally advanced primary or recurrent gynecologic cancers, prognosis is poor. Doses of external beam radiation therapy required to treat either gross or microscopic disease in patients previously irradiated or treated surgically exceed doses that are tolerated by normal anatomic structures. Intraoperative radiation therapy allows maximal tumor control achievable with radiation while minimizing radiation exposure of dose-limiting surrounding structures. Intraoperative radiation therapy is a unique treatment modality, allowing direct visualization of the target volume during a planned surgical procedure. Intraoperative radiation therapy has the potential to improve both long-term local control and overall survival especially in patients with para-aortic and/or pelvic sidewall recurrences. C1 [Foley, Olivia W.; Rauh-Hain, J. Alejandro; del Carmen, Marcela G.] Harvard Univ, Div Gynecol Oncol Vincent Obstet & Gynecol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP del Carmen, MG (reprint author), Harvard Univ, Div Gynecol Oncol Vincent Obstet & Gynecol, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,Yawkey 9 E, Boston, MA 02114 USA. EM mdelcarmen@partners.org NR 28 TC 3 Z9 3 U1 0 U2 5 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 JAN PY 2013 VL 23 IS 1 BP 9 EP 15 DI 10.1097/IGC.0b013e318275232f PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 077CH UT WOS:000314005000003 PM 23187790 ER PT J AU Worley, MJ Rauh-Hain, JA Sandberg, EM Muto, MG AF Worley, Michael J., Jr. Rauh-Hain, J. Alejandro Sandberg, Evelien M. Muto, Michael G. TI Venous Thromboembolism Prophylaxis for Laparoscopic Surgery A Survey of Members of the Society of Gynecologic Oncology SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE Venous thromboembolism; Laparoscopy; Prophylaxis; Surgery ID LOW-DOSE HEPARIN; PNEUMATIC CALF COMPRESSION; RANDOMIZED TRIAL; PREVENTION; COMPLICATIONS; THROMBOSIS; CANCER; TROCAR; RISK AB Objective: This study aimed to evaluate the use of venous thromboembolism (VTE) prophylaxis for laparoscopic surgery among members of the Society of Gynecologic Oncology (SGO). Methods: A 23-item questionnaire was sent to all working/eligible SGO member e-mail addresses (n = 1356). Data were collected and analyzed using descriptive statistics. chi(2) was used to determine differences in responses between groups. Results: Of the 287 (21.2%) responding SGO members, most (61.3%) estimated the risk of VTE for laparoscopic surgery between 1% and 2%. Most (51.2%) of respondents did not routinely use preoperative pharmacoprophylaxis, and most discontinued prophylaxis upon hospital discharge, regardless of benign (73.5%) or malignant (53.3%) pathology. Combination prophylaxis was preferred for procedures in the setting of intermediate- (50.2%) or high-complexity (78%), malignancy (70.7%), obesity (71.4%), multiple medical comorbidities (76%), or the elderly (64.5%). When compared with respondents of greater surgical volume, respondents who performed less than 5 laparoscopic cases per month were more likely to use sequential compression devices alone in the setting of malignancy (52.6%, P = 0.025). The omission of VTE prophylaxis was rare and varied depending on the patient scenario (0.7%-3.5%). When compared with younger respondents, those who were 61 to 70 years old more frequently omitted VTE prophylaxis in the setting of low-complexity procedures (22.2%, P = 0.003), obesity (11.1%, P = 0.021), multiple medical comorbidities (11.1%, P = 0.008), and the elderly (11.1%, P = 0.009). Conclusions: Among SGO members, the preferred method of VTE prophylaxis during laparoscopic surgery for several high-risk patient scenarios was combination prophylaxis. The use versus nonuse and the preferred method of VTE prophylaxis were influenced by respondent age and surgical volume. C1 [Worley, Michael J., Jr.; Sandberg, Evelien M.; Muto, Michael G.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Div Gynecol Oncol, Boston, MA 02115 USA. [Rauh-Hain, J. Alejandro] Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. RP Muto, MG (reprint author), 75 Francis St, Boston, MA 02115 USA. EM mmuto@partners.org NR 32 TC 5 Z9 5 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1048-891X EI 1525-1438 J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD JAN PY 2013 VL 23 IS 1 BP 208 EP 215 DI 10.1097/IGC.0b013e318275c266 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 077CH UT WOS:000314005000029 PM 23221603 ER PT J AU Mercado, N Cohen, DJ Spertus, JA Chan, PS House, J Kennedy, K Brindis, RG White, CJ Rosenfield, KA Marso, SP AF Mercado, Nestor Cohen, David J. Spertus, John A. Chan, Paul S. House, John Kennedy, Kevin Brindis, Ralph G. White, Christopher J. Rosenfield, Kenneth A. Marso, Steven P. TI Carotid Artery Stenting of a Contralateral Occlusion and In-Hospital Outcomes Results From the CARE (Carotid Artery Revascularization and Endarterectomy) Registry SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE myocardial infarction; revascularization; stenting; stroke ID STENOSIS; TRIAL; RISK AB Objectives The authors sought to study the characteristics and outcomes of patients with contralateral carotid artery occlusions (CCOs) undergoing elective carotid artery stenting (CAS). Background CCOs are associated with adverse neurological events following carotid endarterectomy. Methods In-hospital outcomes were examined in patients with and without CCO undergoing elective CAS in the Carotid Artery Revascularization and Endarterectomy (CARE) registry. A CCO was defined as a 100% occlusion of the contralateral internal carotid artery. To minimize differences in measured comorbidities, a 3: 1 propensity matching analysis was performed comparing 42 clinical and demographic variables between CCO and non-CCO patients from the CARE registry. The primary endpoint was a composite of in-hospital death, nonfatal myocardial infarction, and nonfatal stroke. Results Between April 2005 and January 2012, 13,993 eligible patients underwent elective CAS, of whom 1,450 (10%) had CCO. There were 5,500 CAS procedures (1,375 CCO and 4,125 non-CCO) identified in the propensity analysis. The primary composite endpoint occurred in 29 (2.1%) and 107 (2.6%) patients with and without CCO, respectively (adjusted odds ratio: 0.81, 95% confidence interval: 0.53 to 1.23, p = 0.316). Conclusions In the CARE registry, there was no evidence that the presence of a CCO was associated with an increased risk of in-hospital death, nonfatal myocardial infarction, or nonfatal stroke in patients undergoing elective CAS. These findings may have implications on the selection of carotid revascularization procedures for such patients. (J Am Coll Cardiol Intv 2013;6:59-64) (C) 2013 by the American College of Cardiology Foundation C1 [Marso, Steven P.] Univ Missouri, St Lukes Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Mercado, Nestor; Cohen, David J.; Spertus, John A.; Chan, Paul S.; Marso, Steven P.] Univ Missouri, Sch Med, Kansas City, MO 64111 USA. [Brindis, Ralph G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Brindis, Ralph G.] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA USA. [White, Christopher J.] John Ochsner Cardiovasc Inst, Div Cardiol, New Orleans, LA USA. [Rosenfield, Kenneth A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Marso, SP (reprint author), Univ Missouri, St Lukes Mid Amer Heart Inst, 4401 Wornall Rd, Kansas City, MO 64111 USA. EM smarso@saint-lukes.org RI White, Christopher/J-6686-2012 OI White, Christopher/0000-0001-8618-7539 FU Medtronic; Abbott Vascular; Boston Scientific; St. Jude Medical; Abbott; Cordis for the Angioguard RX Guidewire System; Medicines Company; Novo Nordisk; Amylin Pharmaceuticals; Volcano Corporation; Terumo Medical FX From the *Saint Luke's Mid America Heart Institute, Kansas City, Missouri; dagger School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri; double dagger Department of Medicine and the Philip R. Lee Institute for Health Policy Studies, University of California, San Francisco, San Francisco, California; Division of Cardiology, the John Ochsner Cardiovascular Institute, New Orleans, Louisiana; and the parallel to Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts. The CARE Registry is an initiative of the American College of Cardiology Foundation, the Society for Cardiovascular Angiography and Interventions, the Society of Interventional Radiology, the American Academy of Neurology, the American Association of Neurological Surgeons/Congress of Neurological Surgeons, the Society for Vascular Medicine, and the Society of Vascular and Interventional Neurology. Dr. Cohen receives consulting income from Medtronic and Abbott Vascular; and research grant support from Medtronic, Abbott Vascular, Boston Scientific, and St. Jude Medical. Dr. Spertus has a contract with the American College of Cardiology Foundation for the analysis of the CARE Registry. Dr. Rosenfield is a consultant for and receives research support from Abbott; and receives royalties from Cordis for the Angioguard RX Guidewire System. All compensation for Dr. Marso's research activities, including research grants and consulting fees from the Medicines Company, Novo Nordisk, Abbott Vascular, Amylin Pharmaceuticals, Boston Scientific, Volcano Corporation, and Terumo Medical, are paid directly to the Saint Luke's Hospital Foundation of Kansas City. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. William Gray, MD, served as Guest Editor of this paper. NR 23 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD JAN PY 2013 VL 6 IS 1 BP 59 EP 64 DI 10.1016/j.jcin.2012.09.009 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 078HW UT WOS:000314090400011 PM 23347862 ER PT J AU Wang, J Wright, HM Vempati, P Li, H Wangsa, J Dzhuan, A Habbu, K Knable, LA Ho, L Pasinetti, GM AF Wang, Jun Wright, Harold M. Vempati, Prashant Li, Henry Wangsa, Julie Dzhuan, Anastasiya Habbu, Karishma Knable, Lindsay A. Ho, Lap Pasinetti, Giulio M. TI Investigation of Nebivolol as a Novel Therapeutic Agent for the Treatment of Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Adrenergic receptor blocker; Alzheimer's disease; brain bioavailability; inflammatory response; plaque ID TRANSGENIC MOUSE MODEL; AMYLOID-BETA PROTEIN; OBJECT RECOGNITION; MEMORY; BRAIN; RATS; EXPRESSION; MICE AB Nebivolol is a selective beta 1 adrenergic receptor antagonist with nitric oxide-mediated vasodilatory properties utilized in the treatment of hypertension. Previously, nebivolol was shown to modulate amyloid-beta protein precursor processing in vitro. In this study, we investigated the in vivo effects of nebivolol on the modulation of amyloid neuropathology in the Tg2576 mouse model of Alzheimer's disease (AD). We found that nebivolol is brain bioavailable and can be readily detected in the brain following three weeks of treatment at a dose of 1 mg/kg/day. Moreover, this treatment regime resulted in a significant reduction of amyloid-beta neuropathology in the brain, and this reduction was inversely correlated with plasma levels of amyloid-beta. Chronic nebivolol treatment of Tg2576 mice with established amyloid neuropathology and cognitive impairments significantly reduced brain amyloid content but failed to improve cognitive function. Our study demonstrates that nebivolol is highly tolerable and safe and can significantly reduce amyloid neuropathology in the brain, which could be one of the most important parameters for primary prevention of AD. Our studies support the continued investigation of nebivolol for the treatment of AD at very early stages of the disease. C1 [Wang, Jun; Vempati, Prashant; Dzhuan, Anastasiya; Habbu, Karishma; Knable, Lindsay A.; Ho, Lap; Pasinetti, Giulio M.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Wright, Harold M.] Forest Res Inst, Dept Pharmacol, Jersey City, NJ USA. [Li, Henry; Wangsa, Julie] Forest Res Inst, Dept Bioanalyt & Drug Metab, Jersey City, NJ USA. [Wang, Jun; Pasinetti, Giulio M.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Dept Neurol, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu FU Forest Research Institute FX This work was supported by an investigator-initiated grant from Forest Research Institute and in part, by discretional funds to GMP. NR 26 TC 11 Z9 11 U1 0 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2013 VL 33 IS 4 BP 1147 EP 1156 DI 10.3233/JAD-2012-120904 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 076NV UT WOS:000313964200022 PM 23128558 ER PT J AU Clarridge, JE Harrington, AT Roberts, MC Soge, OO Maquelin, K AF Clarridge, Jill E., III Harrington, Amanda T. Roberts, Marilyn C. Soge, Olusegun O. Maquelin, Kees TI Impact of Strain Typing Methods on Assessment of Relationship between Paired Nares and Wound Isolates of Methicillin-Resistant Staphylococcus aureus SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID FIELD GEL-ELECTROPHORESIS; MULTILOCUS VARIABLE NUMBER; REPEAT ANALYSIS MLVA; BACTERIAL EPIDEMIOLOGY; NASAL COLONIZATION; UNITED-STATES; INFECTIONS; VETERANS; SYSTEM; GUIDELINES AB The anterior nares are the site of choice for the Veterans Administration methicillin-resistant Staphylococcus aureus (MRSA) surveillance program; however, a correlation between nares colonization and concomitant wound infections has not been well established. The purpose of this study was 3-fold: to determine the relatedness of MRSA isolates from 40 paired wound and nares specimens by four different strain typing methods, to determine concordance of typing methods, and to establish a baseline of MRSA types at this medical center. Isolates were typed by repetitive PCR (rep-PCR) (DiversiLab System; DL) and SpectraCell Raman analysis (SCRA) (commercially available methods that can be performed within a clinical lab), pulsed-field gel electrophoresis (PFGE), and an antibiotic susceptibility profile (AB). Whole-genome optical mapping (WGM) (OpGen, Inc.) was performed on selected isolates. All methods agreed that 26 pairs were indistinguishable and four pairs were different. Discrepant results were as follows: 4 where only SCRA was discordant, 3 where only AB was discordant, 2 where both DL and AB were discordant, and 1 where both DL and SCRA were discordant. All WGM agreed with PFGE. After discrepancy resolution, 80% of the pairs were indistinguishable and 20% were different. A total of 56% of nares results were nonpredictive if negative nares and positive wound cultures are included. Methods agreed 85 to 93% of the time; however, congruence of isolates to a clade was lower. Baseline analysis of types showed that 15 pairs were unique to single patients (30 strains, 38%; 47% of the matching pairs). Twenty-five strains (30%) represented a single clade identical by PFGE, SCRA, and DL, decreasing specificity. Typing method and institutional type frequency are important in assessing MRSA strain relatedness. C1 [Clarridge, Jill E., III; Harrington, Amanda T.] Vet Affairs Puget Sound Hlth Care Syst, Pathol & Lab Med Serv, Seattle, WA USA. [Clarridge, Jill E., III; Harrington, Amanda T.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Roberts, Marilyn C.; Soge, Olusegun O.] Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. [Maquelin, Kees] Erasmus MC, Dept Dermatol, Ctr Opt Diagnost & Therapy, Rotterdam, Netherlands. RP Clarridge, JE (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Pathol & Lab Med Serv, Seattle, WA USA. EM jill.clarridge@va.gov NR 34 TC 8 Z9 8 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 JAN PY 2013 VL 51 IS 1 BP 224 EP 231 DI 10.1128/JCM.02423-12 PG 8 WC Microbiology SC Microbiology GA 078NF UT WOS:000314105100037 PM 23135945 ER PT J AU Kahle, KT Walcott, BP Simard, JM AF Kahle, Kristopher T. Walcott, Brian P. Simard, J. Marc TI Continuous hyperosmolar therapy for traumatic brain injury-associated cerebral edema: As good as it gets, or an iatrogenic secondary insult? SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Edema; Hypernatremia; Hyperosmolar; Hypertonic; Trauma; Tumor; Vasogenic AB Cerebral edema is a heterogeneous condition that is present in almost every type of neurological disease process - ranging from tumor, to cerebrovascular disease, to infection, to trauma, among others. It is associated with a high rate of morbidity and mortality. The pathophysiologic mechanisms of edema formation are distinct for the different conditions, thereby defining the various classifications. A relatively new treatment practice for cerebral edema is known as induced, sustained hypernatremia. This practice is highly controversial, is in widespread use, and lacks robust evidence for efficacy. Herein, we review details of the controversy regarding this practice. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Kahle, Kristopher T.; Walcott, Brian P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Kahle, Kristopher T.; Walcott, Brian P.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Simard, J. Marc] Univ Maryland, Sch Med, Dept Neurosurg, Baltimore, MA USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White Bldg,Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu FU NHLBI NIH HHS [R01 HL082517]; NINDS NIH HHS [R01 NS061808] NR 10 TC 5 Z9 6 U1 2 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD JAN PY 2013 VL 20 IS 1 BP 30 EP 31 DI 10.1016/j.jocn.2012.10.004 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 072JR UT WOS:000313667700006 PM 23200533 ER PT J AU Singer, AJ Thode, HC Peacock, WF Hollander, JE Diercks, D Birkhahn, R Shapiro, N Glynn, T Nowack, R Safdar, B Miller, C Lewandrowski, E Nagurney, J AF Singer, Adam J. Thode, Henry C., Jr. Peacock, W. Frank Hollander, Judd E. Diercks, Deborah Birkhahn, Robert Shapiro, Nathan Glynn, Ted Nowack, Richard Safdar, Basmah Miller, Chadwick Lewandrowski, Elizabeth Nagurney, John CA MIDAS Investigators TI THE ASSOCIATION BETWEEN SELF-REPORTED EXERCISE INTENSITY AND ACUTE CORONARY SYNDROME IN EMERGENCY DEPARTMENT CHEST PAIN PATIENTS SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE chest pain diagnosis; acute coronary syndromes; physical exercise; emergency department ID AMERICAN-HEART-ASSOCIATION; PHYSICAL-ACTIVITY; CARDIOVASCULAR-DISEASE; CLINICAL CARDIOLOGY; RISK STRATIFICATION; SPORTS-MEDICINE; PUBLIC-HEALTH; PREVENTION; STATEMENT; REHABILITATION AB Background: Regular exercise is thought to be protective against coronary artery disease. As a result, some physicians believe that the likelihood of acute coronary syndrome (ACS) in patients with acute chest pain is reduced in those who exercise regularly. We studied the association between self-reported frequency of exercising and the likelihood of ACS in patients presenting to the Emergency Department (ED) with chest pain. Methods: A multi-center prospective, descriptive, cohort study design was used in ED patients to determine whether the risk of ACS was reduced in patients who self-reported regular exercise. Results: There were 1093 patients enrolled. Median (interquartile range) age was 57 (48-67) years; 506 (45.7%) were female. ACS was diagnosed in 248 (22.7%) patients. Patients who did not exercise at least monthly were more likely to be diagnosed with ACS than those who did (129/466 [27.7%] vs. 119/627 [19.0%]; odds ratio 1.63, 95% CI 1.23-2.17). After adjusting for age, gender, body mass index, smoking, and prior history, limited exercise was still associated with ACS (adjusted odds ratio 1.52, 95% CI 1.10-2.10). There was no apparent association between frequency and intensity of exercise and risk of ACS. Conclusion: Although self-reported frequency of exercise was significantly associated with a decrease in ACS in ED patients with chest pain, it should not be used to exclude ACS in symptomatic ED patients. (C) 2013 Elsevier Inc. C1 [Singer, Adam J.] SUNY Stony Brook, Dept Emergency Med, Stony Brook, NY 11794 USA. [Singer, Adam J.; Thode, Henry C., Jr.] Med Ctr, Stony Brook, NY USA. [Peacock, W. Frank] Cleveland Clin, Cleveland, OH 44106 USA. [Hollander, Judd E.] Univ Penn, Philadelphia, PA 19104 USA. [Diercks, Deborah] Univ Calif Davis, Sacramento, CA 95817 USA. [Birkhahn, Robert] New York Methodist Hosp, Brooklyn, NY USA. [Shapiro, Nathan] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Glynn, Ted] Ingham Reg Med Ctr, Lansing, MI USA. [Nowack, Richard] Henry Ford Med Ctr, Detroit, MI USA. [Safdar, Basmah] Yale Univ, New Haven, CT USA. [Miller, Chadwick] Wake Forest Univ, Hlth Sci Ctr, Winston Salem, NC 27109 USA. [Lewandrowski, Elizabeth; Nagurney, John] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Singer, AJ (reprint author), SUNY Stony Brook, Dept Emergency Med, HSC L4-080, Stony Brook, NY 11794 USA. RI Shapiro, Nathan/F-1718-2016; OI Hollander, Judd/0000-0002-1318-2785 FU Alere San Diego Inc., San Diego, CA FX This study was funded by Alere San Diego Inc., San Diego, CA. NR 21 TC 1 Z9 1 U1 0 U2 8 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 JAN PY 2013 VL 44 IS 1 BP 17 EP 22 DI 10.1016/j.jemermed.2012.02.088 PG 6 WC Emergency Medicine SC Emergency Medicine GA 073PO UT WOS:000313755200049 PM 23103065 ER PT J AU Gonen, L Wilcox, SR Brown, DFM Nadel, ES AF Gonen, Liza Wilcox, Susan R. Brown, David F. M. Nadel, Eric S. TI RESPIRATORY DISTRESS SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID OCCLUSION C1 [Gonen, Liza] Harvard Affiliated Emergency Med Residency, Boston, MA USA. [Wilcox, Susan R.; Brown, David F. M.; Nadel, Eric S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nadel, Eric S.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Nadel, ES (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD JAN PY 2013 VL 44 IS 1 BP 161 EP 163 PG 3 WC Emergency Medicine SC Emergency Medicine GA 073PO UT WOS:000313755200077 PM 23089205 ER PT J AU White, BA Biddinger, PD Chang, YC Grabowski, B Carignan, S Brown, DFM AF White, Benjamin A. Biddinger, Paul D. Chang, Yuchiao Grabowski, Beth Carignan, Sarah Brown, David F. M. TI BOARDING INPATIENTS IN THE EMERGENCY DEPARTMENT INCREASES DISCHARGED PATIENT LENGTH OF STAY SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE ED crowding; boarding; ED LOS; ED capacity; ED throughput ID COMMUNITY-ACQUIRED PNEUMONIA; CARE; IMPACT; PAIN; TIME; ANTIBIOTICS; ASSOCIATION; THROUGHPUT; MORTALITY; VARIABLES AB Background:Boarding of inpatients in the Emergency Department (ED) has been widely recognized as a major contributor to ED crowding and a cause of adverse outcomes. We hypothesize that these deleterious effects extend to those patients who are discharged from the ED by increasing their length of stay (LOS). Study Objectives: This study investigates the impact of boarding inpatients on the ED LOS of discharged patients. Methods: This retrospective, observational, cohort study investigated the association between ED boarder burden and discharged patient LOS over a 3-year period in an urban, academic tertiary care ED. Median ED LOS of 179,840 discharged patients was calculated for each quartile of the boarder burden at time of arrival, and Spearman correlation coefficients were used to summarize the relationship. Subgroup analyses were conducted, stratified by patient acuity defined by triage designation, and hour of arrival. Results:Overall median discharged patient ED LOS increased by boarder burden quartile (205 [95% confidence interval (CI) 203-207], 215 [95% CI 214-217], 221 [95% CI 219-223], and 221 [95% CI 219-223] min, respectively), with a Spearman correlation of 0.25 between daily total boarder burden hours and median LOS. When stratified by patient acuity and hour of arrival (11:00 a.m.-11:00 p.m.), LOS of medium-acuity patients increased significantly by boarder burden quartile (252 [95% CI 247-255], 271 [95% CI 267275], 285 [95% CI 95% CI 278-289], and 309 [95% CI 305-315] min, respectively) with a Spearman correlation of 0.18. Conclusion:In this retrospective study, increasing boarder burden was associated with increasing LOS of patients discharged from the ED, with the greatest effect between 11:00 a. m. and 11:00 p. m. on medium-acuity patients. This relationship between LOS and ED capacity limitation by inpatient boarders has important implications, as ED and hospital leadership increasingly focus on ED LOS as a measure of efficiency and throughput. (C) 2013 Elsevier Inc. C1 [White, Benjamin A.; Biddinger, Paul D.; Chang, Yuchiao; Grabowski, Beth; Carignan, Sarah; Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP White, BA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson Pl 3B, Boston, MA 02114 USA. NR 31 TC 14 Z9 14 U1 3 U2 17 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 JAN PY 2013 VL 44 IS 1 BP 230 EP 235 DI 10.1016/j.jemermed.2012.05.007 PG 6 WC Emergency Medicine SC Emergency Medicine GA 073PO UT WOS:000313755200101 PM 22766404 ER PT J AU Lu, ZY Zhang, XM Li, YC Jin, JF Huang, Y AF Lu, Zhongyang Zhang, Xiaoming Li, Yanchun Jin, Junfei Huang, Yan TI TLR4 antagonist reduces early-stage atherosclerosis in diabetic apolipoprotein E-deficient mice SO JOURNAL OF ENDOCRINOLOGY LA English DT Article DE toll-like receptor 4; atherosclerosis; inflammation; hyperlipidemia ID LOW-DENSITY-LIPOPROTEIN; DIPHOSPHORYL LIPID-A; RHODOPSEUDOMONAS-SPHAEROIDES; RECEPTOR 4; NONTOXIC LIPOPOLYSACCHARIDE; RHODOBACTER-SPHAEROIDES; INNATE IMMUNITY; KAPPA-B; INFLAMMATION; SECRETION AB Although it has been reported that deficiency of toll-like receptor 4 (TLR4) is associated with reduced atherosclerosis in atherosclerosis-prone mice and attenuated pro-inflammatory state in diabetic mice, it remains undetermined whether treatment with a TLR4 antagonist reduces atherosclerosis in nondiabetic or diabetic mice that have TLR4 expression. In this study, we determined the effect of Rhodobacter sphaeroides lipopolysaccharide (Rs-LPS), an established TLR4 antagonist, on early-stage atherosclerosis in nondiabetic and streptozotocin-induced diabetic apolipoprotein E-deficient (Apoe(-/-)) mice. Analysis of atherosclerotic lesions of both en face aortas and cross sections of aortic roots showed that administration of Rs-LPS in 14-week-old diabetic Apoe(-/-) mice for 10 weeks significantly reduced atherosclerotic lesions. Although atherosclerotic lesions in nondiabetic Apoe(-/-) mice appeared to be decreased by Rs-LPS treatment, the difference was not statistically significant. Metabolic study showed that Rs-LPS significantly lowered serum levels of cholesterol and triglycerides in nondiabetic mice but not in diabetic mice. Furthermore, immunohistochemistry studies showed that Rs-LPS inhibited the expression of interleukin 6 and matrix metalloproteinase-9 and reduced the content of monocytes and macrophages in atherosclerotic plaques. Taken together, this study demonstrated for the first time that TLR4 antagonist inhibited vascular inflammation and atherogenesis in diabetic Apoe(-/-) mice and lowered serum cholesterol and triglyceride levels in nondiabetic Apoe(-/-) mice. C1 [Huang, Yan] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Lu, Zhongyang; Zhang, Xiaoming; Li, Yanchun; Jin, Junfei; Huang, Yan] Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29403 USA. RP Huang, Y (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. EM huangyan@musc.edu FU Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs; NIH [RO1 DE016353] FX This work was supported by Merit Review Grant from the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs and by NIH grant RO1 DE016353 (to Y H). NR 31 TC 35 Z9 38 U1 1 U2 11 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD JAN PY 2013 VL 216 IS 1 BP 61 EP 71 DI 10.1530/JOE-12-0338 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 073BM UT WOS:000313718300011 PM 23060524 ER PT J AU Wang, DH Buckner, RL Liu, HS AF Wang, Danhong Buckner, Randy L. Liu, Hesheng TI Cerebellar asymmetry and its relation to cerebral asymmetry estimated by intrinsic functional connectivity SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE lateralization; cerebellum; functional magnetic resonance imaging; functional connectivity ID SURFACE-BASED ANALYSIS; HUMAN BRAIN; HEMISPHERIC ASYMMETRIES; COGNITIVE DEFICITS; CORTICAL SURFACE; GEOMETRICALLY ACCURATE; PREFRONTAL CORTEX; COORDINATE SYSTEM; BROCAS REGION; MOTOR CORTEX AB Wang D, Buckner RL, Liu H. Cerebellar asymmetry and its relation to cerebral asymmetry estimated by intrinsic functional connectivity. J Neurophysiol 109: 46-57, 2013. First published October 17, 2012; doi:10.1152/jn.00598.2012.-Asymmetry of the human cerebellum was investigated using intrinsic functional connectivity. Regions of functional asymmetry within the cerebellum were identified during resting-state functional MRI (n = 500 subjects) and replicated in an independent cohort (n = 500 subjects). The most strongly right lateralized cerebellar regions fell within the posterior lobe, including crus I and crus II, in regions estimated to link to the cerebral association cortex. The most strongly left lateralized cerebellar regions were located in lobules VI and VIII in regions linked to distinct cerebral association networks. Comparison of cerebellar asymmetry with independently estimated cerebral asymmetry revealed that the lateralized regions of the cerebellum belong to the same networks that are strongly lateralized in the cerebrum. The degree of functional asymmetry of the cerebellum across individuals was significantly correlated with cerebral asymmetry and varied with handedness. In addition, cerebellar asymmetry estimated at rest predicted cerebral lateralization during an active language task. These results demonstrate that functional lateralization is likely a unitary feature of large-scale cerebrocerebellar networks, consistent with the hypothesis that the cerebellum possesses a roughly homotopic map of the cerebral cortex including the prominent asymmetries of the association cortex. C1 [Wang, Danhong; Buckner, Randy L.; Liu, Hesheng] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Wang, Danhong; Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Buckner, Randy L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Buckner, Randy L.] Howard Hughes Med Inst, Cambridge, MA USA. RP Liu, HS (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM Hesheng@nmr.mgh.harvard.edu RI wang, danhong/C-8353-2014; wang, danhong/M-2699-2014; OI Liu, Hesheng/0000-0002-7233-1509 FU National Institutes of Health [K25-NS-069805, AG-021910, P41-RR-14074]; National Alliance for Research on Schizophrenia and Depression Young Investigator grant; Massachusetts General Hospital-University of California-Los Angeles Human Connectome Project [U54MH091665]; Simons Foundation; Howard Hughes Medical Institute FX This work was supported by National Institutes of Health Grants K25-NS-069805, AG-021910, and P41-RR-14074, a National Alliance for Research on Schizophrenia and Depression Young Investigator grant, Massachusetts General Hospital-University of California-Los Angeles Human Connectome Project U54MH091665, the Simons Foundation, and the Howard Hughes Medical Institute. NR 70 TC 32 Z9 33 U1 0 U2 21 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2013 VL 109 IS 1 BP 46 EP 57 DI 10.1152/jn.00598.2012 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 064EY UT WOS:000313056100005 PM 23076113 ER PT J AU Shim, WH Baek, K Kim, JK Chae, Y Suh, JY Rosen, BR Jeong, J Kim, YR AF Shim, Woo H. Baek, Kwangyeol Kim, Jeong Kon Chae, Yongwook Suh, Ji-Yeon Rosen, Bruce R. Jeong, Jaeseung Kim, Young R. TI Frequency distribution of causal connectivity in rat sensorimotor network: resting-state fMRI analyses SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE resting-state connectivity; sensorimotor system; partial directed coherence; postmortem; frequency-domain analysis ID PARTIAL DIRECTED COHERENCE; ECHO-PLANAR MRI; FUNCTIONAL CONNECTIVITY; GRANGER CAUSALITY; MOTOR CORTEX; HUMAN BRAIN; BOLD FMRI; FLUCTUATIONS; SIGNALS; IDENTIFICATION AB Shim WH, Baek K, Kim JK, Chae Y, Suh J-Y, Rosen BR, Jeong J, Kim YR. Frequency distribution of causal connectivity in rat sensorimotor network: resting-state fMRI analyses. J Neurophysiol 109: 238-248, 2013. First published September 26, 2012; doi:10.1152/jn.00332.2012.-Resting-state functional MRI (fMRI) has emerged as an important method for assessing neural networks, enabling extensive connectivity analyses between multiple brain regions. Among the analysis techniques proposed, partial directed coherence (PDC) provides a promising tool to unveil causal connectivity networks in the frequency domain. Using the MRI time series obtained from the rat sensorimotor system, we applied PDC analysis to determine the frequency-dependent causality networks. In particular, we compared in vivo and postmortem conditions to establish the statistical significance of directional PDC values. Our results demonstrate that two distinctive frequency populations drive the causality networks in rat; significant, high-frequency causal connections clustered in the range of 0.2-0.4 Hz, and the frequently documented low-frequency connections <0.15 Hz. Frequency-dependence and directionality of the causal connection are characteristic between sensorimotor regions, implying the functional role of frequency bands to transport specific resting-state signals. In particular, whereas both intra-and interhemispheric causal connections between heterologous sensorimotor regions are robust over all frequency levels, the bilaterally homologous regions are interhemispherically linked mostly via low-frequency components. We also discovered a significant, frequency-independent, unidirectional connection from motor cortex to thalamus, indicating dominant cortical inputs to the thalamus in the absence of external stimuli. Additionally, to address factors underlying the measurement error, we performed signal simulations and revealed that the interactive MRI system noise alone is a likely source of the inaccurate PDC values. This work demonstrates technical basis for the PDC analysis of resting-state fMRI time series and the presence of frequency-dependent causality networks in the sensorimotor system. C1 [Shim, Woo H.; Baek, Kwangyeol; Kim, Jeong Kon; Suh, Ji-Yeon; Rosen, Bruce R.; Kim, Young R.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Shim, Woo H.; Baek, Kwangyeol; Chae, Yongwook; Jeong, Jaeseung] Korea Adv Inst Sci & Technol, Dept Bio & Brain, Taejon 305701, South Korea. [Kim, Jeong Kon; Suh, Ji-Yeon] Univ Ulsan, Asan Med Ctr, Dept Radiol, Seoul, South Korea. [Kim, Jeong Kon] Korea Basic Sci Inst, Div Magnet Resonance Res, Cheongwon, Chungbuk, South Korea. [Kim, Young R.] Ulsan Natl Inst Sci & Technol, Ulsan, South Korea. RP Kim, YR (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, 149 13th St,Rm 2301, Charlestown, MA 02129 USA. EM spmn@nmr.mgh.harvard.edu RI Jeong, Jaeseung /C-1620-2011 FU Basic Science Research Program through the National Research Foundation of Korea; Ministry of Education, Science and Technology [2011-0028826, 2011-0030094]; Korea Basic Science Institute [T3222K] FX This research was supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (nos. 2011-0028826 and 2011-0030094) and by Korea Basic Science Institute Grant T3222K. NR 54 TC 7 Z9 8 U1 0 U2 16 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2013 VL 109 IS 1 BP 238 EP 248 DI 10.1152/jn.00332.2012 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 064EY UT WOS:000313056100023 PM 23019001 ER PT J AU Gow, KW Barnhart, DC Hamilton, TE Kandel, JJ Chen, MKS Ferrer, FA Price, MR Mullen, EA Geller, JI Gratias, EJ Rosen, N Khanna, G Naranjo, A Ritchey, ML Grundy, PE Dome, JS Ehrlich, PF AF Gow, Kenneth W. Barnhart, Douglas C. Hamilton, Thomas E. Kandel, Jessica J. Chen, Mike K. S. Ferrer, Fernando A. Price, Mitchell R. Mullen, Elizabeth A. Geller, James I. Gratias, Eric J. Rosen, Nancy Khanna, Geetika Naranjo, Arlene Ritchey, Michael L. Grundy, Paul E. Dome, Jeffrey S. Ehrlich, Peter F. TI Primary nephrectomy and intraoperative tumor spill: Report from the Children's Oncology Group (COG) renal tumors committee SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE Wilms' tumor; Nephroureterectomy; Rupture; Spill; Surgery ID NATIONAL WILMS-TUMOR; SURGICAL COMPLICATIONS; EXPERIENCE; 2ND AB Purpose: Initial Children's Oncology Group (COG) management for Wilms' tumor (WT) consists of primary nephroureterectomy with lymph node sampling. While this provides accurate staging to define further treatment, it may result in intraoperative spill (IOS), which is associated with higher recurrence rates and therefore requires more intensive therapy. The purpose of this study is to determine current rates and identify factors which may predispose a patient to IOS. Methods: The study population was drawn from the AREN03B2 renal tumor banking and classification study of the Children's Oncology Group. All children with a first time occurrence of a renal mass were eligible for the study. At the time of enrollment and prior to risk stratification, the institution is required to submit operative notes, pathology specimens, a chest computed tomography scan (CT), and a contrast-enhanced CT or magnetic resonance imaging (MRI) of the abdomen and pelvis for central imaging review. These data are then used to determine an initial risk classification and therapeutic protocol eligibility. Patients who had a unilateral nephroureterectomy for favorable histology WT underwent further review to assure data accuracy and to clarify details regarding the spill. Analyses were performed using chi square and logistic regression. Odd ratios (OR) are shown with 95% confidence intervals. Results: There were 1,131 primary nephrectomies for unilateral WT with an IOS rate of 9.7% with an additional 1.8% having possible tumor spill during renal vein or IVC tumor thrombectomy. IOS correlated with diameter (> 12cm, p<0.0001) and laterality (right, p=0.0414). Simple logistic regression indicated that IOS increased 2.7% [p=0.0240, OR 1.027 (1.004, 1.052)] with each 1 cm increase in diameter (3 - 21cm) and 4.7% [p=0.0147 OR 1.047 (1.009, 1.086)] with each 100 g increase in weight (80 - 1800 g). Multiple logistic regression indicated that laterality [right p=0.048, OR 1.46 (1.004, 2.110)] and weight (p=0.03, OR 1.039 (1.003, 1.075) were predictive of IOS when diameter was included as a continuous variable. Diameter as a binary variable was highly prognostic of IOS (p=0.0002), while laterality and weight were not significant. Conclusions: Intraoperative tumor spill occurs in about one out of every ten cases of primary nephroureterectomies for WT. Right-sided and larger tumors are at higher risk of IOS. (C) 2013 Elsevier Inc. All rights reserved. C1 [Gow, Kenneth W.] Seattle Childrens Hosp, Seattle, WA 98105 USA. [Gow, Kenneth W.] Univ Washington, Seattle, WA 98105 USA. [Barnhart, Douglas C.] Univ Utah, Salt Lake City, UT 84113 USA. [Hamilton, Thomas E.; Mullen, Elizabeth A.] Boston Childrens, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kandel, Jessica J.] Columbia Univ, Med Ctr, New York, NY 10032 USA. [Chen, Mike K. S.] Univ Alabama Birmingham, Birmingham, AL 35233 USA. [Ferrer, Fernando A.] Connecticut Childrens Med Ctr, Hartford, CT 06106 USA. [Price, Mitchell R.] Univ Illinois, Chicago, IL 60612 USA. [Geller, James I.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Gratias, Eric J.] TC Thompson Childrens Hosp, Chattanooga, TN 37403 USA. [Rosen, Nancy] Childrens Oncol Grp, Arcadia, CA 91006 USA. [Khanna, Geetika] Washington Univ, Sch Med, St Louis, MO 63110 USA. [Naranjo, Arlene] Childrens Oncol Grp, Gainesville, FL 32601 USA. [Ritchey, Michael L.] Phoenix Childrens Hosp, Phoenix, AZ 85006 USA. [Grundy, Paul E.] Univ Alberta Hosp, Edmonton, AB T5J 3H1, Canada. [Dome, Jeffrey S.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Ehrlich, Peter F.] Univ Michigan, CS Mott Childrens Hosp, Ann Arbor, MI 48109 USA. [Ehrlich, Peter F.] Univ Michigan, Ann Arbor, MI 48109 USA. RP Gow, KW (reprint author), Seattle Childrens Hosp, Seattle, WA 98105 USA. EM Kenneth.gow@seattlechildrens.org FU National Institutes of Health [CA-42326] FX Supported by National Institutes of Health Grant No. CA-42326. NR 19 TC 16 Z9 18 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD JAN PY 2013 VL 48 IS 1 BP 34 EP 38 DI 10.1016/j.jpedsurg.2012.10.015 PG 5 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 075IY UT WOS:000313879800018 PM 23331790 ER PT J AU Bruny, JL Hall, BL Barnhart, DC Billmire, DF Dias, MS Dillon, PW Fisher, C Heiss, KF Hennrikus, WL Ko, CY Moss, L Oldham, KT Richards, KE Shah, R Vinocur, CD Ziegler, MM AF Bruny, Jennifer L. Hall, Bruce L. Barnhart, Douglas C. Billmire, Deborah F. Dias, Mark S. Dillon, Peter W. Fisher, Charles Heiss, Kurt F. Hennrikus, William L. Ko, Clifford Y. Moss, Lawrence Oldham, Keith T. Richards, Karen E. Shah, Rahul Vinocur, Charles D. Ziegler, Moritz M. TI American College of Surgeons National Surgical Quality Improvement Program Pediatric: A beta phase report SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE ACS NSQIP; Pediatric surgery; Outcomes; Quality assessment ID PRIVATE-SECTOR; OUTCOMES; NSQIP; CARE AB Purpose: The American College of Surgeons (ACS) National Surgical Quality Improvement Program Pediatric (NSQIP-P) expanded to beta phase testing with the enrollment of 29 institutions. Data collection and analysis were aimed at program refinement and development of risk-adjusted models for inter-institutional comparisons. Methods: Data from the first full year of beta-phase NSQIP-P were analyzed. Patient accrual used ACS-NSQIP methodology tailored to pediatric specialties. Preliminary risk adjusted modeling for all pediatric and neonatal operations and pediatric (excluding neonatal) abdominal operations was performed for all cause morbidity (other than death) and surgical site infections (SSI) using hierarchical logistic regression methodology and eight predictor variables. Results were expressed as odds ratios with 95% confidence intervals. Results: During calendar year 2010, 29 institutions enrolled 37,141 patients. 1644 total CPT codes were entered, of which 456 accounted for 90% of the cases. 450 codes were entered only once (1.2% of cases). For all cases, overall mortality was 0.25%, overall morbidity 7.9%, and the SSI rate 1.8%. For neonatal cases, mortality was 2.39%, morbidity 18.7%, and the SSI rate 3%. For the all operations model, risk-adjusted morbidity institutional odds ratios ranged 0.48-2.63, with 9/29 hospitals categorized as low outliers and 9/29 high outliers, while risk-adjusted SSI institutional odds ratios ranged 0.36-2.04, with 2/29 hospitals low outliers and 7/29 high outliers. Conclusion: This report represents the first risk-adjusted hospital-level comparison of surgical outcomes in infants and children using NSQIP-P data. Programmatic and analytic modifications will improve the impact of this program as it moves into full implementation. These results indicate that NSQIP-P has the potential to serve as a model for determining risk-adjusted outcomes in the neonatal and pediatric population with the goal of developing quality improvement initiatives for the surgical care of children. (C) 2013 Elsevier Inc. All rights reserved. C1 [Bruny, Jennifer L.; Ziegler, Moritz M.] Univ Colorado, Sch Med, Childrens Hosp Colorado, Div Pediat Surg,Dept Surg, Aurora, CO USA. [Hall, Bruce L.; Fisher, Charles; Ko, Clifford Y.; Richards, Karen E.] ACS, Div Res & Optimal Patient Care, Chicago, IL USA. [Hall, Bruce L.] Washington Univ, Dept Surg, St Louis, MO USA. [Hall, Bruce L.] Barnes Jewish Hosp, Ctr Hlth Policy, St Louis, MO 63110 USA. [Hall, Bruce L.] Washington Univ, John M Olin Sch Business, St Louis Vet Affairs Med Ctr, St Louis, MO 63130 USA. [Barnhart, Douglas C.] Univ Utah, Div Pediat Surg, Salt Lake City, UT USA. [Billmire, Deborah F.] Riley Hosp Children, Div Pediat Surg, Indianapolis, IN USA. [Dias, Mark S.] Penn State Univ, Sch Med, Dept Neurosurg, Hershey, PA USA. [Dias, Mark S.] Penn State Univ, Sch Med, Dept Pediat, Hershey, PA USA. [Dillon, Peter W.] Penn State Univ, Sch Med, Dept Surg, Div Pediat Surg, Hershey, PA USA. [Heiss, Kurt F.] Emory Univ, Dept Surg, Div Pediat Surg, Atlanta, GA 30322 USA. [Hennrikus, William L.] Penn State Univ, Sch Med, Dept Orthoped Surg, Hershey, PA USA. [Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Moss, Lawrence] Ohio State Univ, Coll Med, Nationwide Childrens Hosp, Columbus, OH 43210 USA. [Oldham, Keith T.] Med Coll Wisconsin, Dept Surg, Milwaukee, WI 53226 USA. [Shah, Rahul] Childrens Natl Med Ctr, Div Otolaryngol, Washington, DC 20010 USA. [Vinocur, Charles D.] Thomas Jefferson Univ, AI DuPont Hosp Children, Div Pediat Surg, Wilmington, DE USA. RP Bruny, JL (reprint author), 13123 E 16th Ave B323, Aurora, CO 80045 USA. EM jennifer.bruny@childrenscolorado.org OI Vinocur, Charles/0000-0001-9650-1122 NR 11 TC 45 Z9 45 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD JAN PY 2013 VL 48 IS 1 BP 74 EP 80 DI 10.1016/j.jpedsurg.2012.10.019 PG 7 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 075IY UT WOS:000313879800024 PM 23331796 ER PT J AU Li, P Stratton, ZS Dao, M Ritz, J Huang, TJ AF Li, Peng Stratton, Zackary S. Dao, Ming Ritz, Jerome Huang, Tony Jun TI Probing circulating tumor cells in microfluidics SO LAB ON A CHIP LA English DT Editorial Material ID CANCER-CELLS; BREAST-CANCER; WHOLE-BLOOD; BIOMECHANICS; ENUMERATION; ENRICHMENT; CHIP AB Circulating tumor cells (CTCs) are important targets for study as we strive to better understand, diagnose, and treat cancers. However, CTCs are found in blood at extremely low concentrations; this makes isolation, enrichment, and characterization of CTCs technically challenging. Recently, the development of CTC separation devices has grown rapidly in both academia and industry. Part of this development effort centered on microfluidic platforms, exploiting the advantages of microfluidics to improve CTC separation performance and device integration. In this Focus article, we highlight some of the recent work in microfluidic CTC separation and detection systems and discuss our appraisal of what the field should do next. C1 [Li, Peng; Stratton, Zackary S.; Huang, Tony Jun] Penn State Univ, Dept Engn Sci & Mech, University Pk, PA 16802 USA. [Dao, Ming] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. [Ritz, Jerome] Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02215 USA. RP Huang, TJ (reprint author), Penn State Univ, Dept Engn Sci & Mech, 227 Hammond Bldg, University Pk, PA 16802 USA. EM junhuang@psu.edu RI Dao, Ming/B-1602-2008; Li, Peng/B-3054-2013; Huang, Tony/A-1546-2009 OI Li, Peng/0000-0002-8332-7142; FU NIH HHS [DP2 OD007209, 1DP2OD007209-01] NR 39 TC 75 Z9 78 U1 8 U2 131 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2013 VL 13 IS 4 BP 602 EP 609 DI 10.1039/c2lc90148j PG 8 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 076QE UT WOS:000313971300013 PM 23306378 ER PT J AU Kahn, JM Werner, RM David, G Ten Have, TR Benson, NM Asch, DA AF Kahn, Jeremy M. Werner, Rachel M. David, Guy Ten Have, Thomas R. Benson, Nicole M. Asch, David A. TI Effectiveness of Long-term Acute Care Hospitalization in Elderly Patients With Chronic Critical Illness SO MEDICAL CARE LA English DT Article DE mechanical ventilation; costs; Medicare; patient readmission; intensive care ID PROLONGED MECHANICAL VENTILATION; OUTCOMES; MEDICARE; REGRESSION; MORTALITY; PATTERNS; COHORT; BIAS AB Background: For patients recovering from severe acute illness, admission to a long-term acute care hospital (LTAC) is an increasingly common alternative to continued management in an intensive care unit (ICU). Objective: To examine the effectiveness of LTAC transfer in patients with chronic critical illness. Research Design: Retrospective cohort study in United States hospitals from 2002 to 2006. Subjects: Medicare beneficiaries with chronic critical illness, defined as mechanical ventilation and at least 14 days of intensive care. Measures: Survival, costs, and hospital readmissions. We used multivariate analyses and instrumental variables to account for differences in patient characteristics, the timing of LTAC transfer, and selection bias. Results: A total of 234,799 patients met our definition of chronic critical illness. Of these, 48,416 (20.6%) were transferred to an LTAC. In the instrumental variable analysis, patients transferred to an LTAC experienced similar survival compared with patients who remained in an ICU [adjusted hazard ratio = 0.99; 95% confidence interval (CI), 0.96 to 1.01; P = 0.27). Total hospital-related costs in the 180 days after admission were lower among patients transferred to LTACs (adjusted cost difference = -$13,422; 95% CI, -26,662 to -223, P = 0.046). This difference was attributable to a reduction in skilled nursing facility admissions (adjusted admission rate difference = -0.591; 95% CI, -0.728 to -0.454; P < 0.001). Total Medicare payments were higher (adjusted cost difference = $15,592; 95% CI, 6343 to 24,842; P = 0.001). Conclusions: Patients with chronic critical illness transferred to LTACs experience similar survival compared with patients who remain in ICUs, incur fewer health care costs driven by a reduction in postacute care utilization, however, invoke higher overall Medicare payments. C1 [Kahn, Jeremy M.] Univ Pittsburgh, Sch Med, Dept Crit Care Med, Clin Res Invest & Syst Modeling Acute Illness CRI, Pittsburgh, PA 15261 USA. [Kahn, Jeremy M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA 15261 USA. [Werner, Rachel M.; Asch, David A.] Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Werner, Rachel M.; Asch, David A.] Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Werner, Rachel M.; David, Guy; Ten Have, Thomas R.; Asch, David A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [David, Guy; Asch, David A.] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA. [Ten Have, Thomas R.; Benson, Nicole M.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Kahn, JM (reprint author), Univ Pittsburgh, Sch Med, Dept Crit Care Med, Clin Res Invest & Syst Modeling Acute Illness CRI, Scaife Hall,Rom 602-B,3550 Terrace St, Pittsburgh, PA 15261 USA. EM kahnjm@upmc.edu OI Asch, David/0000-0002-7970-286X FU National Institutes of Health [R01HL096651] FX Supported by a research grant from the National Institutes of Health (R01HL096651). NR 32 TC 23 Z9 25 U1 1 U2 18 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 JAN PY 2013 VL 51 IS 1 BP 4 EP 10 DI 10.1097/MLR.0b013e31826528a7 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 078LS UT WOS:000314101000003 PM 22874500 ER PT J AU Pizer, SD AF Pizer, Steven D. TI Should Hospital Readmissions be Reduced Through Payment Penalties? SO MEDICAL CARE LA English DT Editorial Material ID HEART-FAILURE; PROGRAM; CARE C1 [Pizer, Steven D.] VA Boston Hlth Care Syst, Boston, MA USA. RP Pizer, SD (reprint author), Boston Univ, Sch Med, 150 S Huntington Ave,Mail Stop 152H, Boston, MA 02130 USA. EM pizer@bu.edu NR 15 TC 6 Z9 6 U1 1 U2 3 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 JAN PY 2013 VL 51 IS 1 BP 20 EP 22 DI 10.1097/MLR.0b013e318277eb92 PG 3 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 078LS UT WOS:000314101000006 PM 23222467 ER PT J AU Rosen, AK Loveland, S Shin, M Shwartz, M Hanchate, A Chen, Q Kaafarani, HMA Borzecki, A AF Rosen, Amy K. Loveland, Susan Shin, Marlena Shwartz, Michael Hanchate, Amresh Chen, Qi Kaafarani, Haytham M. A. Borzecki, Ann TI Examining the Impact of the AHRQ Patient Safety Indicators (PSIs) on the Veterans Health Administration The Case of Readmissions SO MEDICAL CARE LA English DT Article DE patient safety; readmissions; adverse events; coordination of care ID POSTOPERATIVE HEMORRHAGE; CONTROLLED-TRIAL; CARE; QUALITY; EVENTS; HEMATOMA; OUTCOMES; PROGRAM AB Background: By focusing primarily on outcomes in the inpatient setting one may overlook serious adverse events that may occur after discharge (eg, readmissions, mortality) as well as opportunities for improving outpatient care. Objective: Our overall objective was to examine whether experiencing an Agency for Healthcare Research and Quality Patient Safety Indicator (PSI) event in an index medical or surgical hospitalization increased the likelihood of readmission. Methods: We applied the Agency for Healthcare Research and Quality PSI software (version 4.1.a) to 2003-2007 Veterans Health Administration inpatient discharge data to generate risk-adjusted PSI rates for 9 individual PSIs and 4 aggregate PSI measures: any PSI event and composite PSIs reflecting "Technical Care," "Continuity of Care," and both surgical and medical care (Mixed). We estimated separate logistic regression models to predict the likelihood of 30-day readmission for individual PSIs, any PSI event, and the 3 composites, adjusting for age, sex, comorbidities, and the occurrence of other PSI(s). Results: The odds of readmission were 23% higher for index hospitalizations with any PSI event compared with those with no event [confidence interval (CI), 1.19-1.26], and ranged from 22% higher for Iatrogenic Pneumothorax (CI, 1.03-1.45) to 61% higher for Postoperative Wound Dehiscence (CI, 1.27-2.05). For the composites, the odds of readmission ranged from 15% higher for the Technical Care composite (CI, 1.08-1.22) to 37% higher for the Continuity of Care composite (CI, 1.26-1.50). Conclusions: Our results suggest that interventions that focus on minimizing preventable inpatient safety events as well as improving coordination of care between and across settings may decrease the likelihood of readmission. C1 [Rosen, Amy K.; Loveland, Susan; Shin, Marlena; Shwartz, Michael; Hanchate, Amresh; Chen, Qi] VA Boston Healthcare Syst, Ctr Leadership Org & Management Res COLMR, Boston, MA 02130 USA. [Rosen, Amy K.; Hanchate, Amresh; Borzecki, Ann] Boston Univ, Sch Med, Boston, MA 02118 USA. [Shwartz, Michael] Boston Univ, Sch Management, Dept Operat & Technol Management, Boston, MA 02215 USA. [Chen, Qi; Borzecki, Ann] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Kaafarani, Haytham M. A.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Kaafarani, Haytham M. A.] Harvard Univ, Sch Med, Boston, MA USA. [Borzecki, Ann] Bedford VAMC, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. RP Rosen, AK (reprint author), VA Boston Healthcare Syst, Ctr Leadership Org & Management Res, Boston, MA 02130 USA. EM akrosen@bu.edu OI Hanchate, Amresh/0000-0002-7038-4463 FU VA grant HSRD [SDR-07-002] FX Supported by VA grant HSR&D SDR-07-002. NR 50 TC 22 Z9 22 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD JAN PY 2013 VL 51 IS 1 BP 37 EP 44 DI 10.1097/MLR.0b013e318270c0f7 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 078LS UT WOS:000314101000010 PM 23032358 ER PT J AU Mohr, DC Benzer, JK Young, GJ AF Mohr, David C. Benzer, Justin K. Young, Gary J. TI Provider Workload and Quality of Care in Primary Care Settings Moderating Role of Relational Climate SO MEDICAL CARE LA English DT Article DE patient satisfaction; Veterans Affairs (US); primary health care; climate; workload; patient care team ID PATIENT SATISFACTION; GENERAL-PRACTITIONERS; PHYSICIAN WORKFORCE; HOSPITAL-CARE; HEALTH; PERFORMANCE; OUTCOMES; SYSTEMS; TIME; ORGANIZATIONS AB Primary care providers are increasingly under pressure to do more with fewer resources. We examined the effect of workload on patients' experiences of quality of care, measured through approximately 44,000 patient experience surveys in a sample of 222 primary care clinics in the Veterans Health Administration. We tested the extent to which relational climate, a measure of teamwork, moderated the relationship between workload and patient ratings of quality of care. Our outcome measures included patient complaints, time spent with provider, and overall visit quality. Workload was negatively associated with patients' quality of care ratings and relational climate moderated the relation between workload and quality of care ratings. Patients seen in clinics with higher workload and greater relational climate reported better care compared with patients in clinics with higher workload but lower relational climate. Findings highlight the importance of relational climate as an important teamwork factor when managing and developing clinic policies, practices, and procedures in resource-constrained settings. C1 [Mohr, David C.; Benzer, Justin K.; Young, Gary J.] VA Boston Healthcare Syst, Dept Vet Affairs, Ctr Org Leadership & Management Res, Boston, MA USA. [Mohr, David C.; Benzer, Justin K.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Young, Gary J.] Northeastern Univ, Ctr Hlth Policy & Healthcare Res, Boston, MA 02115 USA. RP Mohr, DC (reprint author), VA Boston Healthcare Syst 152M, 150 S Huntington Ave, Boston, MA 02130 USA. EM david.mohr2@va.gov OI Benzer, Justin/0000-0001-5151-2127 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development [IIR 05-221] FX Supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development for IIR 05-221. NR 47 TC 11 Z9 12 U1 3 U2 16 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 JAN PY 2013 VL 51 IS 1 BP 108 EP 114 DI 10.1097/MLR.0b013e318277f1cb PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 078LS UT WOS:000314101000019 PM 23222471 ER PT J AU Frongillo, M Feibelmann, S Belkora, J Lee, C Sepucha, K AF Frongillo, Marissa Feibelmann, Sandra Belkora, Jeff Lee, Clara Sepucha, Karen TI Is there shared decision making when the provider makes a recommendation? SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Shared decision making; Decision quality; Patient involvement; Provider recommendation; Breast cancer treatment decisions ID PHYSICIAN-PATIENT RELATIONSHIP; STAGE BREAST-CANCER; MEDICAL-TREATMENT; INVOLVEMENT; MASTECTOMY; QUALITY AB Objective: To compare the amount of shared decision making in breast cancer surgery interactions when providers do and do not make a treatment recommendation. Methods: We surveyed breast cancer survivors who were eligible for mastectomy and lumpectomy. Patients reported whether the provider made a recommendation and the recommendation given. They completed items about their interaction including discussion of options, pros, cons, and treatment preference. A total involvement score was calculated with higher scores indicating more shared decision making. Results: Most patients (85%) reported that their provider made a recommendation. Patients who did not receive a recommendation had higher involvement scores compared to those who did (52% vs. 39.1%, p = 0.004). Type of recommendation was associated with involvement. Patients given different recommendations had the highest total involvement scores followed by those who received mastectomy and lumpectomy recommendations (65.5% vs. 42.5% vs. 33.2%, respectively, p < 0.001). Conclusion: Providers were less likely to present a balanced view of the options when they gave a recommendation for surgery. Patients who received a recommendation for lumpectomy had the lowest involvement score. Practice implications: Providers need to discuss both mastectomy and lumpectomy and elicit patients' goals and treatment preferences regardless of whether or not a recommendation is given. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Frongillo, Marissa] Massachusetts Gen Hosp, Hlth Decis Sci Ctr, Dept Gen Med, Boston, MA 02114 USA. [Belkora, Jeff] Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA USA. [Lee, Clara] Univ N Carolina, Lineberger Comprehens Canc Ctr, Div Plast & Reconstruct Surg, Sheps Ctr Hlth Serv Res, Chapel Hill, NC 27599 USA. RP Frongillo, M (reprint author), Massachusetts Gen Hosp, Hlth Decis Sci Ctr, Dept Gen Med, 326 Cambridge St,2nd Floor, Boston, MA 02114 USA. EM mfrongillo@partners.org FU Informed Medical Decisions Foundation; Foundation for Informed Medical Decision Making FX A portion of this work was presented at the annual meeting of the Society for Medical Decision Making in October 2011. This work was funded by the Informed Medical Decisions Foundation.; Drs. Sepucha, Belkora, and Lee receive research and salary support through for the Foundation for Informed Medical Decision Making, a not-for-profit (501(c)3) private foundation (http://www.informedmedicaldecisions.org). The Foundation develops content for patient education programs. The Foundation has an arrangement with a for profit company, Health Dialog, to co-produce these programs. The programs are used as part of the decision support and disease management services Health Dialog provides to consumers through health care organizations and employers. NR 27 TC 9 Z9 9 U1 2 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD JAN PY 2013 VL 90 IS 1 BP 69 EP 73 DI 10.1016/j.pec.2012.08.016 PG 5 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 077FA UT WOS:000314012100011 PM 22999786 ER PT J AU Arney, J Street, RL Naik, AD AF Arney, Jennifer Street, Richard L., Jr. Naik, Aanand D. TI Consumers' various and surprising responses to direct-to-consumer advertisements in magazine print SO PATIENT PREFERENCE AND ADHERENCE LA English DT Article DE communication; decision making; doctor-patient relationships; qualitative research ID DOCTOR-PATIENT-RELATIONSHIP; SHARED DECISION-MAKING; PRESCRIPTION DRUGS; INFORMATION-SEEKING; HIDDEN POPULATIONS; PHYSICIAN; COMMUNICATION; CARE; PERCEPTIONS; AWARENESS AB Direct-to-consumer advertising (DTCA) is ubiquitous in media outlets, but little is known about the ways in which consumers' values, needs, beliefs, and biases influence the perceived meaning and value of DTCA. This article aims to identify the taxonomy of readership categories that reflect the complexity of how health care consumers interact with DTCA, with particular focus on individuals' perceptions of print DTCA in popular magazines. Respondent-driven sampling was used to recruit 18 male and female magazine readers and 18 male and female prescription medication users aged 18-71 years. Semi-structured, in-depth interviews with consumers about their attentiveness, motivations, perceived value, and behavioral responses to DTCA were conducted. The analyses were guided by principles of grounded theory analysis; four categories that vary in consumers' attentiveness, motivations, perceived value, and behavioral responses to DTCA were identified. Two categories - the lay physician and the informed shopper - see value in information from DTCA and are likely to seek medical care based on the information. One category - the voyeur - reads DTCA, but is not likely to approach a clinician regarding advertised information. The fourth category - the evader - ignores DTCA and is not likely to approach a clinician with DTCA information. Responses to DTCA vary considerably among consumers, and physicians should view patients' understanding and response to DTCA within the context of their health-related needs. Patients' comments related to DTCA may be used as an opportunity to engage and understand patients' perspectives about illness and medication use. Clinicians may use information about these categories to facilitate shared understanding and improve communication within the doctor-patient relationship. C1 Univ Houston Clear Lake, Dept Sociol, Houston, TX 77058 USA. [Arney, Jennifer; Street, Richard L., Jr.; Naik, Aanand D.] VA Hlth Serv Res & Dev, Ctr Excellence, Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX USA. [Arney, Jennifer; Street, Richard L., Jr.; Naik, Aanand D.] Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Street, Richard L., Jr.] Texas A&M Univ, Dept Commun, College Stn, TX USA. RP Arney, J (reprint author), Univ Houston Clear Lake, Dept Sociol, 2700 Bay Area Blvd, Houston, TX 77058 USA. EM arney@uhcl.edu FU Division of Graduate Studies at Arizona State University; National Science Foundation's Division of Social, Behavioral, and Economic Sciences [0828582]; Houston VA HSR&D Center of Excellence [HFP900-20]; National Institute on Aging [K23AG027144] FX Dr Arney would like to thank Dr Cecilia Menjivar (Arizona State University), Dr Rose Weitz (Arizona State University), Dr Victor Agadjanian (Arizona State University), and Dr Adam Rafalovich (Pacific University) for their thoughtful review of prior versions of this work. This work was supported by the Division of Graduate Studies at Arizona State University and by the National Science Foundation's Division of Social, Behavioral, and Economic Sciences (Award ID 0828582, Dr Arney). Additional support was provided by the Houston VA HSR&D Center of Excellence (HFP900-20). Dr Naik received additional support from the National Institute on Aging (K23AG027144). NR 44 TC 2 Z9 2 U1 4 U2 19 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1177-889X J9 PATIENT PREFER ADHER JI Patient Prefer. Adherence PY 2013 VL 7 BP 95 EP 102 DI 10.2147/PPA.S38243 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 073KO UT WOS:000313742100003 PM 23378746 ER PT J AU Tamers, SL Okechukwu, C Allen, J Yang, M Stoddard, A Tucker-Seeley, R Sorensen, G AF Tamers, Sara L. Okechukwu, Cassandra Allen, Jennifer Yang, May Stoddard, Anne Tucker-Seeley, Reginald Sorensen, Glorian TI Are social relationships a healthy influence on obesogenic behaviors among racially/ethnically diverse and socio-economically disadvantaged residents? SO PREVENTIVE MEDICINE LA English DT Article DE Social support; Social ties; Diet; Physical activity; Low-income population ID PHYSICAL-ACTIVITY; VEGETABLE CONSUMPTION; PSYCHOSOCIAL FACTORS; HOST-RESISTANCE; SUPPORT; INCOME; MORTALITY; WOMEN; OBESE; BODY AB Objective. To examine associations between social support and ties (family, friend, and neighbors) individually and jointly with diet and physical activity among an ethnically-diverse, low-income population. Methods. The Health in Common study (2005-2009) was designed to examine risk factors among individuals residing in low-income housing in the Boston, MA area. Cross-sectional surveys (n=828) were administered in residents' homes. Linear/logistic multivariable analyses were employed with clustering of individuals within housing sites controlled as a random effect. Results. In multivariable analyses, total social support was significantly associated with higher red meat consumption per day (p=0.029). Having more friends was significantly associated with more daily fruit and vegetable intake (p=0.007) and higher levels of daily vigorous physical activity (p=0.011). Those who reported having a greater number of family ties also reported higher daily consumption of sugary drinks (p=0.013) and fast food (p=0.011). More neighbor social ties were associated with more fast food per day (p=0.024). Conclusions. Social relationships can have both positive and negative associations with health behaviors. Understanding these relationships could help to inform the design of interventions that promote healthy behavior change among vulnerable populations. (C) 2012 Elsevier Inc. All rights reserved. C1 [Tamers, Sara L.; Okechukwu, Cassandra; Tucker-Seeley, Reginald; Sorensen, Glorian] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Tamers, Sara L.; Allen, Jennifer; Tucker-Seeley, Reginald; Sorensen, Glorian] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Allen, Jennifer] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Yang, May; Stoddard, Anne] New England Res Inst Inc, Watertown, MA USA. RP Tamers, SL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 677 Huntington Ave, Boston, MA 02115 USA. EM sara_tamers@dfci.harvard.edu RI Allen, Jennifer/M-2113-2015 FU National Cancer Institute [R01 CA111310-01A1, K05 CA108663-05]; NIH/NCI Harvard Education Program in Cancer Prevention and Control [R25 CA057713]; NIH/NCI Reducing Social Disparities in Cancer Risk [K05 CA108663-05] FX This research was supported by the National Cancer Institute (grant numbers R01 CA111310-01A1; K05 CA108663-05), the NIH/NCI Harvard Education Program in Cancer Prevention and Control (R25 CA057713; PI: Glorian Sorensen, PhD), and the NIH/NCI Reducing Social Disparities in Cancer Risk (K05 CA108663-05 to GS). The authors would like to thank the 20 low-income housing sites that participated in this research, and the assistance from the Cambridge, Somerville and Chelsea Public Housing Authorities. The authors also acknowledge the administrative and field staff at the Harvard School of Public Health and Dana-Farber Cancer Institute, and the study participants for their contributions to this project. They also thank Marty Alvarez-Reeves, Linnea Benson-Whelan, Caitlin Caspi, Amy Harley, Ruth Lederman, Samuel Lipson, Carol Lowenstein, Gary Adamkiewicz, Brianna Wadler, and Lorraine Wallace for their contributions to the overall study design and implementation. NR 38 TC 7 Z9 8 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 EI 1096-0260 J9 PREV MED JI Prev. Med. PD JAN PY 2013 VL 56 IS 1 BP 70 EP 74 DI 10.1016/j.ypmed.2012.11.012 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 077AN UT WOS:000314000400013 PM 23200880 ER PT J AU Rutter, LA Weatherill, RP Krill, SC Orazem, R Taft, CT AF Rutter, Lauren A. Weatherill, Robin P. Krill, Sarah C. Orazem, Robert Taft, Casey T. TI Posttraumatic Stress Disorder Symptoms, Depressive Symptoms, Exercise, and Health in College Students SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE PTSD symptoms; depressive symptoms; college students; exercise; health ID SELF-REPORTED HEALTH; PHYSICAL-ACTIVITY; VIETNAM VETERANS; TRAUMA EXPOSURE; LIFE; PROGRAM; QUALITY; EVENTS; WOMEN AB Posttraumatic stress disorder (PTSD) symptoms have consistently been associated with poorer health in highly traumatized samples. However, less is known about the relationship between PTSD symptoms, depressive symptoms, and health in nonclinical groups. Because exercise contributes to health, we hypothesized that PTSD symptoms and depressive symptoms would be related to poorer health status, in part, through their association with lower exercise. We examined this in a sample of 200 undergraduates. Health status variables included functional health and negative health symptoms. Results indicated that greater PTSD symptoms and depressive symptoms were associated with poorer health status, and exercise mediated these relationships, in most cases. This study has implications for future research examining the effects of PTSD and depressive symptoms on health. C1 [Rutter, Lauren A.; Weatherill, Robin P.; Krill, Sarah C.; Taft, Casey T.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Weatherill, Robin P.; Taft, Casey T.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Orazem, Robert] Minneapolis VA Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. RP Taft, CT (reprint author), VA Boston Healthcare Syst 116B 4, 150 S Huntington Ave, Boston, MA 02130 USA. EM casey.taft@va.gov NR 33 TC 11 Z9 11 U1 2 U2 27 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD JAN PY 2013 VL 5 IS 1 BP 56 EP 61 DI 10.1037/a0021996 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 077BK UT WOS:000314002700008 ER PT J AU McLean, CP Handa, S Dickstein, BD Benson, TA Baker, MT Isler, WC Peterson, AL Litz, BT AF McLean, Carmen P. Handa, Sonia Dickstein, Benjamin D. Benson, Trisha A. Baker, Monty T. Isler, William C. Peterson, Alan L. Litz, Brett T. TI Posttraumatic Growth and Posttraumatic Stress Among Military Medical Personnel SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE military; posttraumatic growth; PTSD; medical personnel ID CONFIRMATORY FACTOR-ANALYSIS; HEALTH-CARE PROVIDERS; TRAUMATIC GROWTH; BREAST-CANCER; PTSD; INVENTORY; WAR; PREDICTORS; EXPERIENCE; DEPLOYMENT AB Military medical personnel deployed to war zones are dually burdened with stressors related to providing healthcare and combat and operational experiences. To better understand how different types and levels of stress exposure relate to positive and negative mental health outcomes among military medical personnel, the associations between combat and healthcare stress exposure and posttraumatic growth and posttraumatic stress disorder (PTSD) were examined among 253 Air Force medical personnel recently redeployed from Iraq. Both types of stress exposure were uniquely associated with increased PTSD symptomatology. However, combat exposure was linearly associated with PTSD, suggesting a dose-response relationship, whereas the relationship between healthcare stress and PTSD was curvilinear. Both forms of stress exposure showed an inverted U-shaped relationship with posttraumatic growth. C1 [McLean, Carmen P.; Handa, Sonia; Dickstein, Benjamin D.; Litz, Brett T.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Dickstein, Benjamin D.; Litz, Brett T.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Benson, Trisha A.; Peterson, Alan L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX USA. [Baker, Monty T.] Wilford Hall USAF Med Ctr, San Antonio, TX 78236 USA. [Isler, William C.] Columbus AFB, Columbus, MS USA. RP McLean, CP (reprint author), Univ Penn, Ctr Treatment & Study Anxiety, 3535 Market St,6th Floor, Philadelphia, PA 19104 USA. EM mcleanca@mail.med.upenn.edu NR 42 TC 4 Z9 5 U1 0 U2 16 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 EI 1942-969X J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD JAN PY 2013 VL 5 IS 1 BP 62 EP 68 DI 10.1037/a0022949 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 077BK UT WOS:000314002700009 ER PT J AU Price, M Gros, DF Strachan, M Ruggiero, KJ Acierno, R AF Price, Matthew Gros, Daniel F. Strachan, Martha Ruggiero, Kenneth J. Acierno, Ron TI The Role of Social Support in Exposure Therapy for Operation Iraqi Freedom/Operation Enduring Freedom Veterans: A Preliminary Investigation SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE PTSD; OEF/OIF; Veterans; social support; exposure therapy ID POSTTRAUMATIC-STRESS-DISORDER; CONFIRMATORY FACTOR-ANALYSIS; ADMINISTERED PTSD SCALE; MENTAL-HEALTH PROBLEMS; VIETNAM VETERANS; RISK-FACTORS; COMBAT VETERANS; WAR; SYMPTOMS; AFGHANISTAN AB The lack of social support has consistently been identified as a relevant factor in the development, maintenance, and treatment of posttraumatic stress disorder (PTSD). Prospective studies with combat veterans have supported the erosion model of social support in the development of PTSD. This model posits that increased PTSD symptoms lead to diminished social support over time. Additional epidemiological work that has investigated mental health and functional impairment in recently returning Operation Iraqi Freedom and Operation Enduring Freedom (OIF/OEF) veterans has suggested that interpersonal problems coincide with the onset of PTSD. Despite research that suggests OIF/OEF veterans experience high rates of PTSD and associated interpersonal problems, no studies have examined social support in relation to treatment response in this group. The current study examined the role of four theorized functional aspects of social support-emotional/informational support, positive social interactions, affectionate support, and tangible support on pretreatment PTSD symptom severity and treatment response in a sample of OIF/OEF veterans receiving exposure-based psychotherapy. Findings showed that positive social interactions were negatively correlated with pretreatment symptom severity, and emotional/informational support was positively related to increased treatment response. Together, these findings suggest that specific types of social support may have an important influence on the course of exposure treatment. C1 [Price, Matthew] Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv 116, Charleston, SC 29401 USA. [Price, Matthew; Gros, Daniel F.; Strachan, Martha; Ruggiero, Kenneth J.; Acierno, Ron] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. RP Price, M (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM prima@musc.edu FU NIDA NIH HHS [R01 DA030143] NR 59 TC 30 Z9 30 U1 2 U2 17 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD JAN PY 2013 VL 5 IS 1 BP 93 EP 100 DI 10.1037/a0026244 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 077BK UT WOS:000314002700013 PM 23869250 ER PT J AU El-Sherief, AH Wu, CC Schoenhagen, P Little, BP Cheng, A Abbara, S Roselli, EE AF El-Sherief, Ahmed H. Wu, Carol C. Schoenhagen, Paul Little, Brent P. Cheng, Allen Abbara, Suhny Roselli, Eric E. TI Basics of Cardiopulmonary Bypass: Normal and Abnormal Postoperative CT Appearances SO RADIOGRAPHICS LA English DT Article ID AORTIC DISSECTION; SURGICAL-TREATMENT; AXILLARY ARTERY; CARDIAC-SURGERY; PSEUDOANEURYSM; CANNULATION AB Cardiothoracic surgical procedures with and without cardiopulmonary bypass are becoming more commonly performed as surgical techniques improve and the population ages. Changes related to cardiopulmonary bypass are often depicted at routine postoperative computed tomographic (CT) studies performed for various reasons. The purpose of this article is to present knowledge critical to the accurate postoperative evaluation of the patient who has undergone cardiopulmonary bypass. This article will review the surgical technique for cardiopulmonary bypass, as well as the associated normal and abnormal postoperative imaging findings. Common cannulation sites used for cardiopulmonary bypass include the ascending aorta, axillary artery, right atrium, superior vena cava, and inferior vena cava. Normal postoperative findings related to cardiopulmonary bypass include (a) felt pledgets, which are used to reinforce cannulation sites; (b) oversewn side grafts; and (c) oversewn graft side branches. These normal postoperative findings can be mistaken for abnormalities. Abnormal postoperative findings related to cardiopulmonary bypass include pseudoaneurysm formation at cannulation sites, aortic dissection, and seroma formation. An awareness of normal and abnormal postoperative CT findings related to cardiopulmonary bypass is critical for all radiologists who interpret chest CT studies, to help prevent unnecessary further evaluation and to help direct prompt treatment when warranted. C1 [El-Sherief, Ahmed H.] Cleveland Clin, Div Thorac Imaging, Cleveland, OH 44195 USA. [Schoenhagen, Paul] Cleveland Clin, Div Cardiovasc Imaging, Cleveland, OH 44195 USA. [Roselli, Eric E.] Cleveland Clin, Div Thorac & Cardiovasc Surg, Cleveland, OH 44195 USA. [Wu, Carol C.] Massachusetts Gen Hosp, Div Thorac Imaging & Intervent, Boston, MA 02114 USA. [Abbara, Suhny] Massachusetts Gen Hosp, Div Cardiovasc Imaging, Boston, MA 02114 USA. [Cheng, Allen] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. [Little, Brent P.] Emory Univ Hosp, Div Cardiothorac Imaging, Atlanta, GA 30322 USA. RP El-Sherief, AH (reprint author), Cleveland Clin, Div Thorac Imaging, 9500 Euclid Ave,Hb6, Cleveland, OH 44195 USA. EM ahelsherief@gmail.com OI Schoenhagen, Paul/0000-0002-7751-5243 NR 16 TC 3 Z9 3 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD JAN-FEB PY 2013 VL 33 IS 1 BP 63 EP 72 DI 10.1148/rg.331115747 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 073NA UT WOS:000313748500007 PM 23322827 ER PT J AU Prescott-Focht, JA Martinez-Jimenez, S Hurwitz, LM Hoang, JK Christensen, JD Ghoshhajra, BB Abbara, S AF Prescott-Focht, Julia A. Martinez-Jimenez, Santiago Hurwitz, Lynne M. Hoang, Jenny K. Christensen, Jared D. Ghoshhajra, Brian B. Abbara, Suhny TI Ascending Thoracic Aorta: Postoperative Imaging Evaluation SO RADIOGRAPHICS LA English DT Article ID ELEPHANT TRUNK PROCEDURE; BILATERAL ANTERIOR THORACOTOMY; CORONARY OSTIAL ANASTOMOSES; MODIFIED BENTALL PROCEDURE; VALVE-SPARING OPERATIONS; SINGLE-STAGE REPAIR; ARCH-1ST TECHNIQUE; ROOT REPLACEMENT; CT ANGIOGRAPHY; ANEURYSMS AB Advances in computed tomography (CT) scanners and electrocardiographic gating techniques have resulted in superior image quality of the ascending aorta and increased the use of CT angiography for evaluating the postoperative ascending aorta. Several abnormalities of the ascending aorta and aortic arch often require surgery, and various open techniques may be used to reconstruct the aorta, such as the Wheat procedure, in which both an ascending aortic graft and an aortic valve prosthesis are implanted; the Cabrol and modified Bentall procedures, in which a composite synthetic ascending aorta and aortic valve graft are placed; the Ross procedure, in which the aortic valve and aortic root are replaced with the patient's native pulmonary valve and proximal pulmonary artery; valve-sparing procedures such as the T. David-V technique, which leaves the native aortic valve intact; and more extensive arch repair procedures such as the elephant trunk and arch-first techniques, in which interposition or inclusion grafts are implanted, with or without replacement of the aortic valve. Normal postoperative imaging findings, such as hyper-attenuating felt pledgets, prosthetic conduits, and reanastomosis sites, may mimic pathologic processes. Postoperative complications seen at CT angiography that require further intervention include pseudoaneurysms, anastomotic stenoses, dissections, and aneurysms. Radiologists must be familiar with these procedures and their imaging features to identify normal postoperative appearances and complications. C1 [Prescott-Focht, Julia A.] Sanford USD Med Ctr, Dept Radiol, Sioux Falls, SD USA. [Martinez-Jimenez, Santiago] St Lukes Hosp, Dept Radiol, Kansas City, MO 64111 USA. [Hurwitz, Lynne M.; Hoang, Jenny K.; Christensen, Jared D.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. [Ghoshhajra, Brian B.; Abbara, Suhny] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Martinez-Jimenez, S (reprint author), St Lukes Hosp, Dept Radiol, 4401 Wornall Rd, Kansas City, MO 64111 USA. EM smartinez-jimenez@saint-lukes.org RI Hurwitz Koweek, lynne/N-1351-2015; Christensen, Jared/A-2376-2016; Hoang, Jenny/B-7779-2016 OI Hurwitz Koweek, lynne/0000-0001-9990-3397; Christensen, Jared/0000-0001-9347-4720; Hoang, Jenny/0000-0002-6715-0922 NR 41 TC 9 Z9 9 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD JAN-FEB PY 2013 VL 33 IS 1 BP 73 EP 85 DI 10.1148/rg.331125090 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 073NA UT WOS:000313748500008 PM 23322828 ER PT J AU Woods, DC Tilly, JL AF Woods, Dori C. Tilly, Jonathan L. TI An Evolutionary Perspective on Adult Female Germline Stem Cell Function from Flies to Humans SO SEMINARS IN REPRODUCTIVE MEDICINE LA English DT Article DE germline stem cell; oogonial stem cell; oogenesis; oocyte; ovary; human ID DROSOPHILA OVARY; IN-VITRO; GERMINAL EPITHELIUM; RAINBOW-TROUT; POSTNATAL OOGENESIS; ONCORHYNCHUS-MYKISS; MAMMALIAN OVARY; EGGS FOREVER; REGENERATION; ZEBRAFISH AB The concept that oogenesis continues into reproductive life has been well established in nonmammalian species. Recent studies of mice and women indicate that oocyte formation is also not, as traditionally believed, restricted to the fetal or perinatal periods. Analogous to de novo oocyte formation in flies and fish, newly formed oocytes in adult mammalian ovaries arise from germline stem cells (GSCs) or, more specifically, oogonial stem cells (OSCs). Studies of mice have confirmed that isolated OSCs, once delivered back into adult ovaries, are capable of generating fully functional eggs that fertilize to produce healthy embryos and offspring. Parallel studies of OSCs recently purified from ovaries of reproductive-age women indicate that these cells closely resemble their mouse ovary-derived counterparts, although the fertilization competency of oocytes generated by human OSCs awaits clarification. Despite the ability of OSCs to produce new oocytes during adulthood, oogenesis will still ultimately cease with age, contributing to ovarian failure. The causal mechanisms behind these events in mammals are unknown, but studies of flies have revealed that GSC niche dysfunction plays a critical role in age-related oogenic failure. Such insights derived from evaluation of nonmammalian species, in which postnatal oogenesis has been studied in depth, may aid in development of new strategies to alleviate ovarian failure and infertility in mammals. C1 [Woods, Dori C.; Tilly, Jonathan L.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Woods, Dori C.; Tilly, Jonathan L.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Tilly, JL (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, THR 901,55 Fruit St, Boston, MA 02114 USA. EM jtilly@partners.org FU Method to Extend Research in Time (MERIT) Award from the National Institute on Aging [NIH R37-AG012279]; Ruth L. Kirschstein National Research Service Award [NIH F32-AG034809]; Henry and Vivian Rosenberg Philanthropic Fund; Sea Breeze Foundation; Vincent Memorial Hospital Research Funds FX Work conducted by the authors discussed herein was supported by a Method to Extend Research in Time (MERIT) Award from the National Institute on Aging (NIH R37-AG012279 to Jonathan Tilly), a Ruth L. Kirschstein National Research Service Award (NIH F32-AG034809 to Dori Woods), the Henry and Vivian Rosenberg Philanthropic Fund, the Sea Breeze Foundation, and Vincent Memorial Hospital Research Funds. NR 78 TC 14 Z9 15 U1 1 U2 22 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1526-8004 J9 SEMIN REPROD MED JI Semin. Reprod. Med. PD JAN PY 2013 VL 31 IS 1 BP 24 EP 32 DI 10.1055/s-0032-1331794 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 074EX UT WOS:000313796800005 PM 23329633 ER PT J AU Vita, S Coplin, H Feiereisel, KB Garten, S Mechaber, AJ Estrada, C AF Vita, Swaroop Coplin, Heidi Feiereisel, Kristen B. Garten, Sarajane Mechaber, Alex J. Estrada, Carlos TI Decreasing the Ceiling Effect in Assessing Meeting Quality at an Academic Professional Meeting SO TEACHING AND LEARNING IN MEDICINE LA English DT Article ID CONTINUING MEDICAL-EDUCATION; PSYCHOMETRIC PROPERTIES; SELECTING ABSTRACTS; STRUCTURED METHOD; OUTCOMES; CARE AB Background: The psychometric properties of evaluations at academic meetings have not been well studied. Purpose: To explore the ceiling effect in the evaluation of quality of a professional meeting and whether a change in the scale labels would decrease the ceiling effect. Methods: Cross-sectional study at two national meetings (2009-2010), attendees completed the evaluation on paper forms or online (5-point Likert scale). Results: Of 1,064 evaluations, the mean session ratings was higher among respondents to the paper version in 2009 (4.2; 95% confidence interval [CI], 4.1 to 4.3) as compared to online responders in 2009 (3.0; 95% CI, 2.9 to 3.1) or online responders in 2010 (3.0; 95% CI, 2.9 to 3.1)(p < 0.001). Conclusion: A ceiling effect was present in the evaluation of an academic meeting. A change in the evaluation scale labels decreased the ceiling effect and increased evaluation variability. C1 [Vita, Swaroop] Birmingham So Coll, Birmingham, AL USA. [Coplin, Heidi] Allina Med Clin, Minneapolis, MN USA. [Feiereisel, Kristen B.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Garten, Sarajane] Soc Gen Internal Med, Alexandria, VA USA. [Mechaber, Alex J.] Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33136 USA. [Estrada, Carlos] Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Div Gen Internal Med, Birmingham, AL 35294 USA. RP Estrada, C (reprint author), Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Div Gen Internal Med, FOT 732,510 20th St S, Birmingham, AL 35294 USA. EM cestrada@uab.edu NR 18 TC 3 Z9 3 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1040-1334 J9 TEACH LEARN MED JI Teach. Learn. Med. PD JAN 1 PY 2013 VL 25 IS 1 BP 47 EP 54 DI 10.1080/10401334.2012.741543 PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 072OB UT WOS:000313680600009 PM 23330894 ER PT J AU Ojikutu, B Nnaji, C Sithole, J Schneider, KL Higgins-Biddle, M Cranston, K Earls, F AF Ojikutu, Bisola Nnaji, Chioma Sithole, Juliet Schneider, Karen L. Higgins-Biddle, Molly Cranston, Kevin Earls, Felton TI All Black People Are Not Alike: Differences in HIV Testing Patterns, Knowledge, and Experience of Stigma Between U.S.-Born and Non-U.S.-Born Blacks in Massachusetts SO AIDS PATIENT CARE AND STDS LA English DT Article ID HIV/AIDS STIGMA; UNITED-STATES; AFRICAN MIGRANTS; PREGNANT-WOMEN; BARRIERS; SELF; PERCEPTIONS; IMMIGRANTS; INFECTION; COMMUNITY AB Non-U.S.-born black individuals comprise a significant proportion of the new diagnoses of HIV in the United States. Concurrent diagnosis (obtaining an AIDS diagnosis in close proximity to an initial diagnosis of HIV) is common in this subpopulation. Although efforts have been undertaken to increase HIV testing among African Americans, little is known about testing patterns among non-U.S.-born black people. A cross-sectional survey was self-administered by 1060 black individuals in Massachusetts (57% non-U.S.-born) to assess self-reported rates of HIV testing, risk factors, and potential barriers to testing, including stigma, knowledge, immigration status, and access to health care. Bivariate analysis comparing responses by birthplace and multivariate logistic regression assessing correlates of recent testing were completed. Non-U.S.-born individuals were less likely to report recent testing than U.S.-born (41.9% versus 55.6%, p < 0.0001). Of those who recently tested, the majority did so for immigration purposes, not because of perceived risk. Stigma was significantly higher and knowledge lower among non-U.S.-born individuals. In multivariate analysis, greater length of time since immigration was a significant predictor of nontesting among non-U.S.-born (adjusted odds ratio [AOR] 0.56, 95% confidence interval [CI] 0.36-0.87). Poor health care access and older age were correlated to nontesting in both U.S.- and non-U.S.-born individuals. Our findings indicate that differences in HIV testing patterns exist by nativity. Efforts addressing unique factors limiting testing in non-U.S.-born black individuals are warranted. C1 [Ojikutu, Bisola] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nnaji, Chioma] Multicultural AIDS Coalit, Jamaica Plain, MA USA. [Sithole, Juliet] Massachusetts Dept Hlth, Bur Infect Dis Preventiona & Serv, Refugee & Immigrant Hlth Program, Boston, MA USA. [Ojikutu, Bisola; Schneider, Karen L.; Higgins-Biddle, Molly] Johns Snow Res & Training Inst, Boston, MA USA. [Cranston, Kevin] Massachusetts Dept Hlth, Bur Infect Dis, Boston, MA USA. [Earls, Felton] Harvard Univ, Sch Med, Boston, MA USA. RP Ojikutu, B (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM bojikutu@partners.org FU NIAID NIH HHS [P30 AI060354] NR 40 TC 17 Z9 17 U1 1 U2 17 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD JAN PY 2013 VL 27 IS 1 BP 45 EP 54 DI 10.1089/apc.2012.0312 PG 10 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 071HX UT WOS:000313583400007 PM 23259482 ER PT J AU Bryant, A Madden, E AF Bryant, Allison Madden, Erin TI Short interpregnancy intervals: what is the effect of multiple gestations? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Bryant, Allison] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Madden, Erin] Vet Hlth Res Inst, NCIRE, San Francisco, CA 94121 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S292 EP S292 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500692 ER PT J AU Darney, B Cheng, Y Snowden, J Jacob, L Nicholson, J Kaimal, A Dublin, S Gethun, D Caughey, A AF Darney, Blair Cheng, Yvonne Snowden, Jonathan Jacob, Lorie Nicholson, James Kaimal, Anjali Dublin, Sascha Gethun, Darios Caughey, Aaron TI Effect of elective induction of labor at 37-40 weeks compared with expectant management on perinatal mortality in California SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Jacob, Lorie] Oregon Hlth & Sci Univ, Ctr Hlth Syst Effectiveness, Portland, OR 97201 USA. [Cheng, Yvonne] Univ Calif San Francisco, Sch Med, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA. [Dublin, Sascha] Grp Hlth Res Inst, Ctr Hlth Studies, Seattle, WA USA. [Nicholson, James] Univ Penn Hlth Syst, Dept Family Med & Community Hlth, Philadelphia, PA USA. [Kaimal, Anjali] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Gethun, Darios] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S294 EP S294 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500696 ER PT J AU Darney, B Cheng, Y Snowden, J Jacob, L Kaimal, A Nicholson, J Dublin, S Gethun, D Caughey, A AF Darney, Blair Cheng, Yvonne Snowden, Jonathan Jacob, Lorie Kaimal, Anjali Nicholson, James Dublin, Sascha Gethun, Darios Caughey, Aaron TI Effect of elective induction of labor at 37-40 weeks compared with expectant management on primary cesarean delivery in California SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Jacob, Lorie] Oregon Hlth & Sci Univ, Ctr Hlth Syst Effectiveness, Portland, OR 97201 USA. [Cheng, Yvonne] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Nicholson, James] Univ Penn, Sch Med, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. [Gethun, Darios] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA USA. [Kaimal, Anjali] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Dublin, Sascha] Grp Hlth Res Inst, Ctr Hlth Studies, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S293 EP S294 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500695 ER PT J AU Doss, A Allen, A Pilliod, R Little, S Kaimal, A Sparks, T Caughey, A AF Doss, Amy Allen, Allison Pilliod, Rachel Little, Sarah Kaimal, Anjali Sparks, Teresa Caughey, Aaron TI What is the optimal time to deliver dichorionic diamniotic twins when one twin has intrauterine growth restriction? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Doss, Amy; Allen, Allison; Caughey, Aaron] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Pilliod, Rachel; Little, Sarah; Sparks, Teresa] Brigham & Womens Mass Gen Hosp, Boston, MA USA. [Kaimal, Anjali] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S54 EP S55 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500097 ER PT J AU Easter, SR Lim, KH Parry, S McElrath, T AF Easter, Sarah Rae Lim, Kee-Hak Parry, Samuel McElrath, Thomas TI Relationship between urinary tract infection and circulating angiogenic factors in patients with preeclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Easter, Sarah Rae] Harvard Univ, Brigham & Womens Hosp, Sch Med, Massachusetts Gen Hosp,Dept Obstet & Gynecol, Boston, MA 02115 USA. [Lim, Kee-Hak] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Maternal Fetal Med, Boston, MA 02215 USA. [Parry, Samuel] Hosp Univ Penn, Div Maternal Fetal Med, Philadelphia, PA 19104 USA. [McElrath, Thomas] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Maternal Fetal Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S276 EP S277 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500653 ER PT J AU Goldfarb, I Madden, E Bryant, A AF Goldfarb, Ilona Madden, Erin Bryant, Allison TI Early hospital readmission after low risk cesarean delivery: evidence for racial and ethnic disparities SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Goldfarb, Ilona; Bryant, Allison] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Maternal Fetal Med, Boston, MA USA. [Madden, Erin] No Calif Inst Res & Educ, Dept Res, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S346 EP S346 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500825 ER PT J AU Jessel, R Thomas, A Lim, KH Parry, S McElrath, T AF Jessel, Rebecca Thomas, Ann Lim, Kee-Hak Parry, Samuel McElrath, Thomas TI Prospective evaluation of circulating angiogenic factors in the prediction of early- versus late-onset pre-eclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Thomas, Ann; McElrath, Thomas] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynecol,Div Maternal Fetal Med, Boston, MA 02115 USA. [Lim, Kee-Hak] Harvard Univ, Sch Med, Boston Maternal Fetal Med, Boston MFM,BIDMC, Boston, MA USA. [Parry, Samuel] Hosp Univ Penn, Div Maternal Fetal Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S275 EP S275 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500649 ER PT J AU Kaimal, A Norton, M Kovshilovskaya, B Pena, S Bishop, J Sit, A Nakagawa, S Kuppermann, M AF Kaimal, Anjali Norton, Mary Kovshilovskaya, Bogdana Pena, Sherri Bishop, Judith Sit, Anita Nakagawa, Sanae Kuppermann, Miriam TI Health literacy, genetic literacy, and numeracy in a diverse population of pregnant women: implications for prenatal counseling SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Kaimal, Anjali] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Norton, Mary] Stanford Univ, Stanford, CA 94305 USA. [Kovshilovskaya, Bogdana; Pena, Sherri; Bishop, Judith; Nakagawa, Sanae; Kuppermann, Miriam] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Sit, Anita] Santa Clara Valley Med Ctr, Santa Clara, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S242 EP S242 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500565 ER PT J AU Klein, A Keenan, H Mittendorf, R Hernandez-Diaz, S Pennell, P Llewellyn, N Smith, C Holmes, L McElrath, T AF Klein, Autumn Keenan, Hillary Mittendorf, Robert Hernandez-Diaz, Sonia Pennell, Page Llewellyn, Nichelle Smith, Caitlin Holmes, Lewis McElrath, Thomas TI Obstetrical outcomes in women with epilepsy enrolled in the North American Antiepileptic Drug Registry (NAAPR) SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Klein, Autumn] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Keenan, Hillary] Joslin Diabet Ctr, Boston, MA 02215 USA. [Mittendorf, Robert] Loyola Univ, Chicago, IL 60611 USA. [Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Pennell, Page; Llewellyn, Nichelle; Smith, Caitlin; Holmes, Lewis; McElrath, Thomas] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S56 EP S56 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500102 ER PT J AU Young, B Panda, B Stanic, A Panda, A Rueda, B AF Young, Brett Panda, Britta Stanic, Aleksandar Panda, Alexander Rueda, Bo TI Toll-like receptors 7, 9 are differentially expressed on dendritic cells in uncomplicated pregnancies and postpartum compared to non-pregnant controls SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Young, Brett; Stanic, Aleksandar; Rueda, Bo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Panda, Britta] Tufts Med Ctr, Boston, MA USA. [Panda, Alexander] Yale Univ, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S279 EP S279 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500659 ER PT J AU Young, B Stanic, A Panda, B Panda, A Rueda, B AF Young, Brett Stanic, Aleksandar Panda, Britta Panda, Alexander Rueda, Bo TI Postpartum elevation of Toll-like receptor 1: innate immune system activation persists beyond the prototypical postpartum period SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Young, Brett; Stanic, Aleksandar; Rueda, Bo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Panda, Britta] Tufts Med Ctr, Boston, MA USA. [Panda, Alexander] Yale Univ, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S57 EP S58 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500105 ER PT J AU Young, B Nadel, A Panda, B Kaimal, A AF Young, Brett Nadel, Allan Panda, Britta Kaimal, Anjali TI Does placenta previa location matter? Surgical morbidity associated with previa location SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Young, Brett; Nadel, Allan; Panda, Britta; Kaimal, Anjali] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S57 EP S57 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500104 ER PT J AU Ichikawa, A Kuba, K Morita, M Chida, S Tezuka, H Hara, H Sasaki, T Ohteki, T Ranieri, VM dos Santos, CC Kawaoka, Y Akira, S Luster, AD Lu, B Penninger, JM Uhlig, S Slutsky, AS Imai, Y AF Ichikawa, Akihiko Kuba, Keiji Morita, Masayuki Chida, Shinsuke Tezuka, Hiroyuki Hara, Hiromitsu Sasaki, Takehiko Ohteki, Toshiaki Ranieri, V. Marco dos Santos, Claudia C. Kawaoka, Yoshihiro Akira, Shizuo Luster, Andrew D. Lu, Bao Penninger, Josef M. Uhlig, Stefan Slutsky, Arthur S. Imai, Yumiko TI CXCL10-CXCR3 Enhances the Development of Neutrophil-mediated Fulminant Lung Injury of Viral and Nonviral Origin SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE CXCL10; CXCR3; ARDS ID RESPIRATORY-DISTRESS-SYNDROME; CHEMOKINE RECEPTOR CXCR3; ACUTE ALLOGRAFT-REJECTION; PULMONARY-FIBROSIS; EPITHELIAL-CELLS; HUMAN ALVEOLAR; IP-10; MICE; EXPRESSION; AIRWAY AB Rationale: Patients who developed acute respiratory distress syndrome (ARDS) after infection with severe respiratory viruses (e.g., severe acute respiratory syndrome coronavirus, H5N1 avian influenza virus), exhibited unusually high levels of CXCL10, which belongs to the non-ELR (glutamic-leucine-arginine) CXC chemokine superfamily. CXCL10 may not be a bystander to the severe virus infection but may directly contribute to the pathogenesis of neutrophil-mediated, excessive pulmonary inflammation. Objectives: We investigated the contribution of CXCL10 and its receptor CXCR3 axis to the pathogenesis of ARDS with nonviral and viral origins. Methods: We induced nonviral ARDS by acid aspiration and viral ARDS by intratracheal influenza virus infection in wild-type mice and mice deficient in CXCL10, CXCR3, IFNAR1 (IFN-alpha/beta receptor 1), or TIR domain-containing adaptor inducing IFN-beta (TRIF). Measurements and Main Results: We found that the mice lacking CXCL10 or CXCR3 demonstrated improved severity and survival of nonviral and viral ARDS, whereas mice that lack IFNAR1 did not control the severity of ARDS in vivo. The increased levels of CXCL10 in lungs with ARDS originate to a large extent from infiltrated pulmonary neutrophils, which express a unique CXCR3 receptor via TRIF. CXCL10-CXCR3 acts in an autocrine fashion on the oxidative burst and chemotaxis in the inflamed neutrophils,leading to fulminant pulmonary inflammation. Conclusions: CXCL10-CXCR3 signaling appears to be a critical factor for the exacerbation of the pathology of ARDS. Thus, the CXCL10-CXCR3 axis could represent a prime therapeutic target in the treatment of the acute phase of ARDS of nonviral and viral origins. C1 [Ichikawa, Akihiko; Kuba, Keiji; Morita, Masayuki; Imai, Yumiko] Akita Univ, Dept Biol Informat & Expt Therapeut, Grad Sch Med, Akita 0108543, Japan. [Chida, Shinsuke; Sasaki, Takehiko] Akita Univ, Dept Med Biol, Grad Sch Med, Akita 0108543, Japan. [Tezuka, Hiroyuki; Ohteki, Toshiaki] Tokyo Med & Dent Univ, Dept Biodef Res, Med Res Inst, Tokyo, Japan. [Tezuka, Hiroyuki; Ohteki, Toshiaki] Japan Sci & Technol Agcy, CREST, Tokyo, Japan. [Hara, Hiromitsu] Saga Univ, Div Mol & Cellular Immunosci, Dept Biomol Sci, Saga 840, Japan. [Ranieri, V. Marco] Univ Turin, Dipartimento Anestesia, Osped S Giovanni Battista, Turin, Italy. [dos Santos, Claudia C.; Slutsky, Arthur S.] St Michaels Hosp, Keenan Res Ctr, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada. [dos Santos, Claudia C.; Slutsky, Arthur S.] Univ Toronto, Interdept Div Crit Care Med, Toronto, ON, Canada. [Kawaoka, Yoshihiro] Univ Wisconsin, Influenza Res Inst, Madison, WI USA. [Kawaoka, Yoshihiro] Univ Tokyo, Inst Med Sci, Div Virol, Dept Microbiol & Immunol, Tokyo, Japan. [Kawaoka, Yoshihiro] Univ Tokyo, Inst Med Sci, Int Res Ctr Infect Dis, Tokyo, Japan. [Kawaoka, Yoshihiro] Japan Sci & Technol Agcy, ERATO Infect Induced Host Responses Project, Saitama, Japan. [Akira, Shizuo] Osaka Univ, Dept Host Def, Microbial Dis Res Inst, Osaka, Japan. [Luster, Andrew D.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. [Lu, Bao] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. [Penninger, Josef M.] Austrian Acad Sci, Inst Mol Biotechnol, A-1010 Vienna, Austria. [Uhlig, Stefan] Rhein Westfal TH Aachen, Inst Pharmacol & Toxicol, Aachen, Germany. RP Imai, Y (reprint author), Akita Univ, Dept Biol Informat & Expt Therapeut, Grad Sch Med, Akita 0108543, Japan. EM imai@med.akita-u.ac.jp RI Akira, Shizuo/C-3134-2009; Penninger, Josef/I-6860-2013; Uhlig, Stefan/A-7290-2014 OI Penninger, Josef/0000-0002-8194-3777; Uhlig, Stefan/0000-0003-2332-1280 FU Funding Program for Next Generation World-Leading Researchers (NEXT Program, JSPS); Center of Education and Research for the Advanced Genome-Based Medicine for Personalized Medicine and the Control of Worldwide Infectious Diseases; Japan Initiative for Global Research Network on Infectious Diseases from the Ministry of Education, Culture, Sports, Science, and Technology; ERATO (Japan Science and Technology Agency); Public Health Service research grants from the National Institute of Allergy and Infectious Diseases; IMBA; Austrian National Bank; Austrian Ministry of Science and Education; Canadian Institutes of Health Research (CIHR); Canada Foundation for Innovation (CFI); Deutsche Forschungsgemeinschaft (DFG, Bonn, Germany) [SFB542 (TPC16)]; NIH [CA069212] FX Y.I. and K.K. are supported by Funding Program for Next Generation World-Leading Researchers (NEXT Program, JSPS), grants-in-aid for Specially Promoted Research and for Scientific Research, and the Global COE Program. Y.K. is supported by Center of Education and Research for the Advanced Genome-Based Medicine for Personalized Medicine and the Control of Worldwide Infectious Diseases and by a Grant-in-Aid for Specially Promoted Research and by Japan Initiative for Global Research Network on Infectious Diseases from the Ministry of Education, Culture, Sports, Science, and Technology, by ERATO (Japan Science and Technology Agency), and by Public Health Service research grants from the National Institute of Allergy and Infectious Diseases. J.M.P. is supported by IMBA, the Austrian National Bank and the Austrian Ministry of Science and Education. A.S.S. is supported by the Canadian Institutes of Health Research (CIHR) and the Canada Foundation for Innovation (CFI). S.U. was supported by the SFB542 (TPC16) of the Deutsche Forschungsgemeinschaft (DFG, Bonn, Germany). A.D.L. was supported by NIH grant CA069212. NR 42 TC 54 Z9 54 U1 0 U2 16 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN 1 PY 2013 VL 187 IS 1 BP 65 EP 77 DI 10.1164/rccm.201203-0508OC PG 13 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 071PM UT WOS:000313606700013 PM 23144331 ER PT J AU Maldonado, NG Takhar, SS AF Maldonado, Nicholas G. Takhar, Sukhjit S. TI Update on Emerging Infections: News From the Centers for Disease Control and Prevention SO ANNALS OF EMERGENCY MEDICINE LA English DT Editorial Material ID SEXUALLY-TRANSMITTED-DISEASES; GONOCOCCAL INFECTIONS; NEISSERIA-GONORRHOEAE; CEFTRIAXONE; CEFIXIME AB Editor's note: This article is part of a regular series on emerging infection from the Centers for Disease Control and Prevention (CDC) and the EMERGEncy ID NET, an emergency department based and CDC-collaborative surveillance network. Important infectious disease public health information with relevance to emergency physicians is reported. The goal of this series is to advance knowledge about communicable diseases in emergency medicine and foster cooperation between the front line of clinical medicine and public health agencies. C1 [Maldonado, Nicholas G.] Harvard Affiliated Emergency Med Residency, Brigham & Womens Hosp, Massachusetts Gen Hosp, Boston, MA USA. [Takhar, Sukhjit S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Emergency Med,Div Emergency Med, Boston, MA 02115 USA. RP Maldonado, NG (reprint author), Harvard Affiliated Emergency Med Residency, Brigham & Womens Hosp, Massachusetts Gen Hosp, Boston, MA USA. NR 11 TC 3 Z9 4 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD JAN PY 2013 VL 61 IS 1 BP 91 EP 93 DI 10.1016/j.annemergmed.2012.10.014 PG 3 WC Emergency Medicine SC Emergency Medicine GA 069WY UT WOS:000313469000018 PM 23260686 ER PT J AU Cheng, G AF Cheng, Gang TI Using a cut-off SUV level to define bone marrow lesions on FDG PET is not appropriate SO ANNALS OF HEMATOLOGY LA English DT Letter ID POSITRON-EMISSION-TOMOGRAPHY; WHOLE-BODY MRI; LYMPHOMA; INFILTRATION; INVOLVEMENT C1 Philadelphia VA Med Ctr, Dept Radiol, Philadelphia, PA 19104 USA. RP Cheng, G (reprint author), Philadelphia VA Med Ctr, Dept Radiol, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM gangcheng99@yahoo.com NR 13 TC 2 Z9 3 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-5555 J9 ANN HEMATOL JI Ann. Hematol. PD JAN PY 2013 VL 92 IS 2 BP 283 EP 284 DI 10.1007/s00277-012-1549-4 PG 2 WC Hematology SC Hematology GA 069OE UT WOS:000313445100024 PM 22885991 ER PT J AU Carr, CE Rowedder, H Vafadari, C Lui, CS Cascio, E Zuber, MT Ruvkun, G AF Carr, Christopher E. Rowedder, Holli Vafadari, Cyrus Lui, Clarissa S. Cascio, Ethan Zuber, Maria T. Ruvkun, Gary TI Radiation Resistance of Biological Reagents for In Situ Life Detection SO ASTROBIOLOGY LA English DT Article DE Laboratory simulation experiments; Life detection instruments; Nucleic acids; Mars; Panspermia ID MURCHISON METEORITE; EXTRATERRESTRIAL NUCLEOBASES; ASTROBIOLOGICAL APPLICATIONS; CARBONACEOUS METEORITES; SUBSURFACE OCEAN; MARS; SIMULATION; PLANETS; SURFACE; GENOME AB Life on Mars, if it exists, may share a common ancestry with life on Earth derived from meteoritic transfer of microbes between the planets. One means to test this hypothesis is to isolate, detect, and sequence nucleic acids in situ on Mars, then search for similarities to known common features of life on Earth. Such an instrument would require biological and chemical components, such as polymerase and fluorescent dye molecules. We show that reagents necessary for detection and sequencing of DNA survive several analogues of the radiation expected during a 2-year mission to Mars, including proton (H-1), heavy ion (Fe-56, O-18), and neutron bombardment. Some reagents have reduced performance or fail at higher doses. Overall, our findings suggest it is feasible to utilize space instruments with biological components, particularly for mission durations of up to several years in environments without large accumulations of charged particles, such as the surface of Mars, and have implications for the meteoritic transfer of microbes between planets. C1 [Carr, Christopher E.; Lui, Clarissa S.; Zuber, Maria T.] MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA. [Carr, Christopher E.; Rowedder, Holli; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Vafadari, Cyrus] MIT, Dept Nucl Engn, Cambridge, MA 02139 USA. [Cascio, Ethan] Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. [Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Ruvkun, G (reprint author), MGH Dept Mol Biol, Simches Res Bldg,185 Cambridge St,CPZN 7250, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu OI Carr, Christopher/0000-0002-7946-5622 FU NASA's ASTID program [NNX08AX15G] FX We thank Thomas Bork and William McCarthy for assistance with exposures at the MIT NRL, and Peter Guida, Adam Rusek, Michael Sivertz, and the rest of the NSRL-associated staff for assistance with heavy ion exposures. This work was funded by NASA's ASTID program (NNX08AX15G). NR 45 TC 5 Z9 5 U1 3 U2 24 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1531-1074 J9 ASTROBIOLOGY JI Astrobiology PD JAN PY 2013 VL 13 IS 1 BP 68 EP 78 DI 10.1089/ast.2012.0869 PG 11 WC Astronomy & Astrophysics; Biology; Geosciences, Multidisciplinary SC Astronomy & Astrophysics; Life Sciences & Biomedicine - Other Topics; Geology GA 072MP UT WOS:000313676000005 PM 23330963 ER PT J AU Eckhouse, SR Jones, JA Spinale, FG AF Eckhouse, Shaina R. Jones, Jeffrey A. Spinale, Francis G. TI Gene targeting in ischemic heart disease and failure: Translational and clinical studies SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE Gene therapy; Myocardial infarction; Ischemia; Plasmid; Adenovirus; Adeno-associated virus ID ENDOTHELIAL GROWTH-FACTOR; CHRONIC MYOCARDIAL-ISCHEMIA; CORONARY-ARTERY-DISEASE; RECOMBINANT ADENOASSOCIATED VIRUS; PRESSURE-REGULATED RETROINFUSION; SLEEPING-BEAUTY TRANSPOSON; LEFT-VENTRICULAR FUNCTION; CALCIUM UP-REGULATION; INTRAMYOCARDIAL INJECTION; ANGINA-PECTORIS AB Alternative and innovative targeted strategies hold relevance in improving the current treatments for ischemic heart disease (IHD). One potential treatment modality, gene targeting, may provide a unique alternative to current IHD therapies. The principal function of gene targeting in IHD is to augment the expression of an endogenous gene through amplification of an exogenous gene, delivered by a plasmid or a viral vector to enhance myocardial perfusion, and limit the long-term sequelae. The initial clinical studies of gene targeting in IHD were focused upon induction of angiogenic factors and the outcomes were equivocal. Nevertheless, significant advancements have been made in viral vectors, mode of delivery, and potentially relevant targets for IHD. Several of these advancements, particularly with a focus on translational large animal studies, are the focus of this review. The development of novel vectors with prolonged transduction efficiency and minimal inflammation, coupled with hybrid perfusion-mapping delivery devices, and improving the safety of vector use and efficacy of gene systems are but a few of the exciting progresses that are likely to proceed to clinical studies in the near future. Published by Elsevier Inc. C1 [Eckhouse, Shaina R.; Jones, Jeffrey A.; Spinale, Francis G.] Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC USA. [Eckhouse, Shaina R.; Jones, Jeffrey A.; Spinale, Francis G.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Spinale, Francis G.] Univ S Carolina, Sch Med, CBA, Cardiovasc Translat Res Ctr,Div Cell Biol & Anat, Columbia, SC 29208 USA. [Spinale, Francis G.] Wm Jennings Bryan Dorn Vet Affairs Med Ctr, Columbia, SC USA. RP Spinale, FG (reprint author), Univ S Carolina, Sch Med, CBA, Cardiovasc Translat Res Ctr,Div Cell Biol & Anat, 6439 Garners Ferry Rd, Columbia, SC 29208 USA. EM cvctrc@uscmed.sc.edu FU National Institute of Health [HL057952, HL059165, HL095608, T32 HL007260]; Merit Award from the Veterans' Affairs Health Administration FX This work was supported by National Institute of Health grants HL057952, HL059165, HL095608, and a Merit Award from the Veterans' Affairs Health Administration. SRE was supported by National Institute of Health grant T32 HL007260. The authors wish to thank Dr. Roger Hajjar for the images in Fig. 2 and Ashley Sapp for editorial assistance. NR 94 TC 3 Z9 3 U1 1 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JAN 1 PY 2013 VL 85 IS 1 BP 1 EP 11 DI 10.1016/j.bcp.2012.08.018 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 071RF UT WOS:000313611200001 PM 22935384 ER PT J AU Le Gall, JB Milone, MC Waxman, IM Shaw, LM Harrison, L Duffy, D van de Ven, C Militano, O Geyer, MB Morris, E Bhatia, M Satwani, P George, D Garvin, JH Bradley, MB Schwartz, J Baxter-Lowe, LA Cairo, MS AF Le Gall, J. B. Milone, M. C. Waxman, I. M. Shaw, L. M. Harrison, L. Duffy, D. van de Ven, C. Militano, O. Geyer, M. B. Morris, E. Bhatia, M. Satwani, P. George, D. Garvin, J. H. Bradley, M. B. Schwartz, J. Baxter-Lowe, L. A. Cairo, M. S. TI The pharmacokinetics and safety of twice daily i.v. BU during conditioning in pediatric allo-SCT recipients SO BONE MARROW TRANSPLANTATION LA English DT Article DE intravenous busulfan; pediatrics; allogeneic stem cell transplantation; pharmacokinetics; children ID STEM-CELL TRANSPLANTATION; UNDER-THE-CURVE; INTRAVENOUS BUSULFAN; HOST-DISEASE; MYCOPHENOLATE-MOFETIL; VENOOCCLUSIVE DISEASE; CHILDREN; PROPHYLAXIS; INFECTIONS; GRAFT AB Intravenous BU divided four times daily (q6 h) has been shown to be safe and effective in pediatric allo-SCT recipients. Though less frequent dosing is desirable, pharmacokinetic (PK) data on twice daily (q12 h) i.v. BU administration in pediatric allo-SCT recipients is limited. We prospectively examined the PK results in a cohort of pediatric allo-SCT recipients receiving i.v. BU q12 h as part of conditioning before allo-SCT. BU levels were obtained after the first dose of conditioning. PK parameter analysis (n = 49) yielded the following 95% confidence intervals (CI95): weight-normalized volume of distribution: 0.65-0.73 L/kg; t(1/2): 122-147 min; weight-normalized clearance (CLn): 3.4-4.3 mL/min/kg; and area under the curve: 1835-2180 mmol x min/L. From these results, a steady state concentration was calculated with CI95 between 628-746 ng/mL. Comparison between recipients <= 4 vs >44 years old revealed significant differences in t(1/2) (mean: 115 vs 146 min, P = 0.008) and CLn (mean: 4.4 vs 3.5 mL/min/kg, P = 0.038). Intravenous BU q12 h had a comparable PK to i.v. BU q6 h PK seen in the literature, and in pediatric allo-SCT recipients, is a feasible, attractive alternative to i.v. q6h dosing. Bone Marrow Transplantation (2013) 48, 19-25; doi:10.1038/bmt.2012.105; published online 11 June 2012 C1 [Le Gall, J. B.; Militano, O.; Bhatia, M.; Satwani, P.; George, D.; Garvin, J. H.] Columbia Univ, Dept Pediat, New York, NY 10027 USA. [Milone, M. C.; Shaw, L. M.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA. [Waxman, I. M.; Bradley, M. B.] Bristol Myers Squibb, Princeton, NJ USA. [Harrison, L.; Duffy, D.; van de Ven, C.; Morris, E.; Cairo, M. S.] New York Med Coll, Maria Fareri Childrens Hosp, Westchester Med Ctr, Dept Pediat, Valhalla, NY 10595 USA. [Geyer, M. B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Schwartz, J.] Columbia Univ, Dept Pathol & Cell Biol, New York, NY USA. [Baxter-Lowe, L. A.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Cairo, M. S.] New York Med Coll, Dept Med, Valhalla, NY 10595 USA. [Cairo, M. S.] New York Med Coll, Dept Pathol, Valhalla, NY 10595 USA. [Cairo, M. S.] New York Med Coll, Dept Microbiol & Immunol, Valhalla, NY 10595 USA. [Cairo, M. S.] New York Med Coll, Dept Cell Biol & Anat, Valhalla, NY 10595 USA. RP Cairo, MS (reprint author), New York Med Coll, Maria Fareri Childrens Hosp, Westchester Med Ctr, Dept Pediat, Munger Pavil,RM 110A, Valhalla, NY 10595 USA. EM mitchell_cairo@nymc.edu OI Geyer, Mark/0000-0001-5248-9117 FU Pediatric Cancer Research Foundation; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R21 AR49330]; Marisa Fund; Sonia Scaramella Fund; Paul Luisi Foundation; Brittany Barron Fund; Doris Duke Charitable Foundation FX This work was supported in part by grants from the Pediatric Cancer Research Foundation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (R21 AR49330; MSC), Marisa Fund, Sonia Scaramella Fund, Paul Luisi Foundation, Brittany Barron Fund and the Doris Duke Charitable Foundation. NR 29 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JAN PY 2013 VL 48 IS 1 BP 19 EP 25 DI 10.1038/bmt.2012.105 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 070OO UT WOS:000313519100005 PM 22684047 ER PT J AU van Walraven, SM Straathof, LM Switzer, GE Lankester, A Korthof, ET Brand, A Ball, LM AF van Walraven, S. M. Straathof, L. M. Switzer, G. E. Lankester, A. Korthof, E. T. Brand, A. Ball, L. M. TI Immediate and long-term somatic effects, and health-related quality of life of BM donation during early childhood. A single-center report in 210 pediatric donors SO BONE MARROW TRANSPLANTATION LA English DT Article DE BM donation; pediatrics; child donor; side effects; long-term follow-up ID LIVING KIDNEY DONORS; BONE-MARROW DONATION; CELL TRANSPLANTATION CENTERS; BLOOD STEM-CELLS; SIBLING DONORS; 20 KG; CHILDREN; COLLECTION; EXPERIENCE; CARE AB Since 1968, when Leiden undertook the first successful European pediatric BM transplantation with a 7-year-old sibling donor, more than 300 young children have donated BM in our unit. We first retrospectively studied a cohort of 210 donors, younger than 13 years at donation, to survey procedures of donor eligibility and study immediate effects of BM donation. We then performed a long-term follow-up (FU) and health-related quality of life (HRQoL) study. Despite documentation of previous medical conditions, no child was declared unfit to donate. We found that iron deficiency anemia or low-iron stores in BM did not result in treatment or extended FU. Harvest volumes exceeded 15 mL/kg in 65% of donors, with more than half requiring allogeneic blood transfusions. Donors had no structured FU after their first post-donation control. In this study, 25% of donors reported at least one somatic complaint at long-term FU. Finally long-term HRQoL revealed high scores in most subdomains (representing a higher QoL), compared to norm groups. These results indicate the need for development of (inter) national guidelines for pediatric stem cell donor care management. Bone Marrow Transplantation (2013) 48, 40-45; doi:10.1038/bmt.2012.102; published online 18 June 2012 C1 [van Walraven, S. M.; Straathof, L. M.; Lankester, A.; Brand, A.; Ball, L. M.] Leiden Univ, Med Ctr, Dept Pediat SCT, Leiden, Netherlands. [van Walraven, S. M.; Korthof, E. T.; Brand, A.] Europdonor Fdn, Transplant Ctr Coordinat Unit, NL-2333 BZ Leiden, Netherlands. [Switzer, G. E.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Switzer, G. E.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Switzer, G. E.] Univ Pittsburgh, Dept Clin & Translat Sci, Pittsburgh, PA USA. [Switzer, G. E.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Ctr Hlth Equ & Promot, Pittsburgh, PA USA. [Brand, A.] Sanquin Blood Bank, Leiden, Netherlands. RP van Walraven, SM (reprint author), Europdonor Fdn, Transplant Ctr Coordinat Unit, Plesmanlaan 1B, NL-2333 BZ Leiden, Netherlands. EM walraven@europdonor.nl NR 47 TC 6 Z9 6 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JAN PY 2013 VL 48 IS 1 BP 40 EP 45 DI 10.1038/bmt.2012.102 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 070OO UT WOS:000313519100009 PM 22705802 ER PT J AU Armand, P Sainvil, MM Kim, HT Rhodes, J Cutler, C Ho, VT Koreth, J Alyea, EP Neufeld, EJ Kwong, RY Soiffer, RJ Antin, JH AF Armand, P. Sainvil, M-M Kim, H. T. Rhodes, J. Cutler, C. Ho, V. T. Koreth, J. Alyea, E. P. Neufeld, E. J. Kwong, R. Y. Soiffer, R. J. Antin, J. H. TI Pre-transplantation iron chelation in patients with MDS or acute leukemia and iron overload undergoing myeloablative allo-SCT SO BONE MARROW TRANSPLANTATION LA English DT Letter ID STEM-CELL TRANSPLANTATION; FERRITIN C1 [Armand, P.; Sainvil, M-M; Cutler, C.; Ho, V. T.; Koreth, J.; Alyea, E. P.; Soiffer, R. J.; Antin, J. H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kim, H. T.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Rhodes, J.] SUNY Stony Brook, Sch Med, Dept Med, Stony Brook, NY 11794 USA. [Neufeld, E. J.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Kwong, R. Y.] Brigham & Womens Hosp, Dept Cardiovasc Med, Boston, MA 02115 USA. RP Armand, P (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM parmand@partners.org FU NCI NIH HHS [CA142106-06, P01 CA142106]; NHLBI NIH HHS [R01 HL091157] NR 10 TC 14 Z9 14 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JAN PY 2013 VL 48 IS 1 BP 146 EP 147 DI 10.1038/bmt.2012.94 PG 2 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 070OO UT WOS:000313519100027 PM 22609885 ER PT J AU Zelefsky, MJ Cohen, GN Bosch, WR Morikawa, L Khalid, N Crozier, CL Lee, WR Zietman, A Owen, J Wilson, JF Devlin, PM AF Zelefsky, Michael J. Cohen, Gil'ad N. Bosch, Walter R. Morikawa, Lisa Khalid, Najma Crozier, Cheryl L. Lee, W. Robert Zietman, Anthony Owen, Jean Wilson, J. Frank Devlin, Phillip M. TI Results from the Quality Research in Radiation Oncology (QRRO) survey: Evaluation of dosimetric outcomes for low-dose-rate prostate brachytherapy SO BRACHYTHERAPY LA English DT Article DE Prostate cancer; Brachytherapy; Quality assurance; Dosimetric outcomes ID MULTIINSTITUTIONAL DATABASE; BIOCHEMICAL CONTROL; PRO-QURA; CANCER; IMPLANTATION; PARAMETERS; EXPERIENCE AB PURPOSE: We report on quality of dose delivery to target and normal tissues from low-dose-rate prostate brachytherapy using postimplantation dosimetric evaluations from a random sample of U.S. patients. METHODS AND MATERIALS: Nonmetastatic prostate cancer patients treated with external beam radiotherapy or brachytherapy in 2007 were randomly sampled from radiation oncology facilities nationwide. Of 414 prostate cancer cases from 45 institutions, 86 received low-dose-rate brachytherapy. We collected the 30-day postimplantation CT images of these patients and 10 test cases from two other institutions. Scans were downloaded into a treatment planning system and prostate/rectal contours were redrawn. Dosimetric outcomes were reanalyzed and compared with calculated outcomes from treating institutions. RESULTS: Median prostate volume was 33.4 cm(3). Reevaluated median V-100, D-90, and V-150 were 91.1% (range, 45.5-99.8%), 101.7% (range, 59.6-145.9%), and 53.9% (range, 15.7-88.4%), respectively. Low gland coverage included 27 patients (39%) with a D-90 lower than 100% of the prescription dose (PD), 12 of whom (17% of the entire group) had a D-90 lower than 80% of PD. There was no correlation between D-90 coverage and prostate volume, number of seeds, or implanted activity. The median V-100 for the rectum was 0.3 cm(3) (range, 0-4.3 cm(3)). No outcome differences were observed according to the institutional strata. Concordance between reported and reevaluated D-90 values (defined as within +/- 10%) was observed in 44 of 69 cases. CONCLUSIONS: Central review of postimplantation CT scans to assess the quality of prostate brachytherapy is feasible. Most patients achieved excellent dosimetric outcomes, yet 17% had less than optimal target coverage by the PD. There was concordance between submitted target-coverage parameters and central dosimetric review in 64% of implants. These findings will require further validation in a larger cohort of patients. (C) 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Zelefsky, Michael J.; Cohen, Gil'ad N.; Morikawa, Lisa] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10065 USA. [Bosch, Walter R.] Washington Univ, Image Guided Therapy Ctr, St Louis, MO USA. [Khalid, Najma; Crozier, Cheryl L.; Owen, Jean] Amer Coll Radiol, Qual Res Radiat Oncol, Philadelphia, PA USA. [Lee, W. Robert] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA. [Zietman, Anthony] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Wilson, J. Frank] Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53226 USA. [Devlin, Phillip M.] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Zelefsky, MJ (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, 1275 York Ave, New York, NY 10065 USA. EM zelefskm@mskcc.org OI Cohen, Gilad/0000-0003-4252-6855 FU NCI NIH HHS [R01 CA065435] NR 23 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 J9 BRACHYTHERAPY JI Brachytherapy PD JAN-FEB PY 2013 VL 12 IS 1 BP 19 EP 24 DI 10.1016/j.brachy.2012.04.001 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 073RD UT WOS:000313759300004 PM 22819388 ER PT J AU Nguyen, PL Devlin, PM Beard, CJ Orio, PF O'Leary, MP Wolfsberger, LD O'Farrell, DA Sweeney, CM Hadaschik, BA Hohenfellner, M Hatiboglu, G AF Nguyen, Paul L. Devlin, Phillip M. Beard, Clair J. Orio, Peter F., III O'Leary, Michael P. Wolfsberger, Luciant D. O'Farrell, Desmond A. Sweeney, Christopher M. Hadaschik, Boris A. Hohenfellner, Markus Hatiboglu, Gencay TI High-dose-rate brachytherapy for prostate cancer in a previously radiated patient with polyethylene glycol hydrogel spacing to reduce rectal dose: Case report and review of the literature SO BRACHYTHERAPY LA English DT Review DE Prostate cancer; Salvage radiotherapy; Hydrogel; Spacer ID ANDROGEN DEPRIVATION THERAPY; LOW ALPHA/BETA-RATIO; SALVAGE CRYOTHERAPY; HDR BRACHYTHERAPY; CRYOSURGICAL ABLATION; PHASE-II; RADIOTHERAPY; MONOTHERAPY; OUTCOMES; COMPLICATIONS AB PURPOSE: To describe the use of a temporary spacer to reduce rectal dose prior to prostate radiation in a man with prior pelvic radiotherapy and review the relevant literature. METHODS AND MATERIALS: A healthy 57-year-old man presented with high-risk prostate cancer (Gleason score of 8, prostate-specific antigen level [PSA] 12.6 ng/mL, T3a by magnetic resonance imaging [MRI]), only 2.5 years after a low anterior resection followed by pelvic chemo-radiotherapy to 50.4 Gy for a locally advanced rectal cancer. Due to the prior radiation, he was not felt to be a candidate for surgery or external beam radiation, so he chose long-term androgen deprivation therapy (ADT) plus high-dose-rate brachytherapy to 36 Gy in 6 fractions. To reduce the radiation dose to the anterior rectal wall, 10 mL of a polyethylene glycol hydrogel spacer was injected between the prostate and rectum and created between 1.4 and 1.5 cm of separation along the length of the prostate. RESULTS: Two randomized trials demonstrating that local therapy plus ADT improves overall survival compared to ADT alone provided the rationale for additional prostate radiotherapy in this otherwise healthy patient. Salvage brachytherapy is associated with a 3.4% rate of rectal fistula among the 251 cases reported in the literature from 2000-2007, with rates as high as 12% in one series. The spacer allowed the rectal dose constraint goals to be easily met. CONCLUSIONS: Injecting an absorbable polyethylene glycol hydrogel to separate the prostate and rectum appears to be associated with decreased maximum and mean rectal doses, and may have particular utility in previously irradiated patients. (C) 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Nguyen, Paul L.; Devlin, Phillip M.; Beard, Clair J.; Orio, Peter F., III; Wolfsberger, Luciant D.; O'Farrell, Desmond A.] Harvard Univ, Dept Radiat Oncol, Dana Farber Canc Inst, Brigham & Womens Canc Ctr,Med Sch, Boston, MA 02115 USA. [O'Leary, Michael P.] Harvard Univ, Dept Urol, Dana Farber Canc Inst, Brigham & Womens Canc Ctr,Med Sch, Boston, MA 02115 USA. [Sweeney, Christopher M.] Harvard Univ, Dept Med Oncol, Dana Farber Canc Inst, Brigham & Womens Canc Ctr,Med Sch, Boston, MA 02115 USA. [Hadaschik, Boris A.; Hohenfellner, Markus; Hatiboglu, Gencay] Univ Heidelberg Hosp, Dept Urol, Heidelberg, Germany. RP Nguyen, PL (reprint author), Harvard Univ, Dept Radiat Oncol, Dana Farber Canc Inst, Brigham & Womens Canc Ctr,Med Sch, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@lroc.harvard.edu FU Prostate Cancer Foundation Young Investigator Award; anonymous Family Foundation; David and Cynthia Chapin FX This work was supported by a grant from an anonymous Family Foundation, David and Cynthia Chapin, and a Prostate Cancer Foundation Young Investigator Award. NR 36 TC 10 Z9 10 U1 3 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 EI 1873-1449 J9 BRACHYTHERAPY JI Brachytherapy PD JAN-FEB PY 2013 VL 12 IS 1 BP 77 EP 83 DI 10.1016/j.brachy.2012.03.005 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 073RD UT WOS:000313759300012 PM 22543116 ER PT J AU Owen, RG Kyle, RA Stone, MJ Rawstron, AC Leblond, V Merlini, G Garcia-Sanz, R Ocio, EM Morra, E Morel, P Anderson, KC Patterson, CJ Munshi, NC Tedeschi, A Joshua, DE Kastritis, E Terpos, E Ghobrial, IM Leleu, X Gertz, MA Ansell, SM Morice, WG Kimby, E Treon, SP AF Owen, Roger G. Kyle, Robert A. Stone, Marvin J. Rawstron, Andy C. Leblond, Veronique Merlini, Giampaolo Garcia-Sanz, Ramon Ocio, Enrique M. Morra, Enrica Morel, Pierre Anderson, Kenneth C. Patterson, Christopher J. Munshi, Nikhil C. Tedeschi, Alessandra Joshua, Douglas E. Kastritis, Efstathios Terpos, Evangelos Ghobrial, Irene M. Leleu, Xavier Gertz, Morie A. Ansell, Stephen M. Morice, William G. Kimby, Eva Treon, Steven P. TI Response assessment in Waldenstrom macroglobulinaemia: update from the VIth International Workshop SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Waldenstrom macroglobulinaemia; trials; residual disease ID FREE LIGHT-CHAIN; CONSENSUS PANEL RECOMMENDATIONS; CHRONIC LYMPHOCYTIC-LEUKEMIA; NATIONAL-CANCER-INSTITUTE; MULTIPLE-MYELOMA; RESIDUAL DISEASE; PROGRESSION-FREE; CLINICAL-TRIAL; PLASMA-CELLS; THERAPY AB This report represents a further update of the consensus panel criteria for the assessment of clinical response in patients with Waldenstrom macroglobulinaemia (WM). These criteria have been updated in light of further data demonstrating an improvement in categorical responses with new drug regimens as well as acknowledgement of the fact that such responses are predictive of overall outcome. A number of key changes are proposed but challenges do however remain and these include the variability in kinetics of immunoglobulin M (IgM) reduction with different treatment modalities and the apparent discrepancy between IgM and bone marrow/tissue response noted with some regimens. Planned sequential bone marrow assessments are encouraged in clinical trials. C1 [Owen, Roger G.] St James Univ Hosp, HMDS Lab, Leeds LS9 7TF, W Yorkshire, England. [Kyle, Robert A.; Gertz, Morie A.; Ansell, Stephen M.; Morice, William G.] Mayo Clin & Mayo Fdn, Mayo Med Sch, Rochester, MN 55905 USA. [Stone, Marvin J.] Baylor Sammons Canc Ctr, Dallas, TX USA. [Leblond, Veronique] Hop La Pitie Salpetriere, Paris, France. [Merlini, Giampaolo] IRCCS Policlin San Matteo, Pavia, Italy. [Merlini, Giampaolo] Univ Pavia, I-27100 Pavia, Italy. [Garcia-Sanz, Ramon; Ocio, Enrique M.] Hosp Univ Salamanca, Salamanca, Spain. [Morra, Enrica; Tedeschi, Alessandra] Osped Niguarda Ca Granda, Milan, Italy. [Morel, Pierre] Hosp Schaffner, Lens, France. [Anderson, Kenneth C.; Patterson, Christopher J.; Munshi, Nikhil C.; Ghobrial, Irene M.; Treon, Steven P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Joshua, Douglas E.] Royal Prince Alfred Hosp, Sydney, NSW, Australia. [Kastritis, Efstathios; Terpos, Evangelos] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Leleu, Xavier] Ctr Hosp Reg & Univ Lille, Hop Huriez, F-59037 Lille, France. [Kimby, Eva] Karolinska Inst, Stockholm, Sweden. [Kimby, Eva] Karolinska Univ Hosp, Stockholm, Sweden. RP Owen, RG (reprint author), St James Univ Hosp, HMDS Lab, Level 3,Bexley Wing,Beckett St, Leeds LS9 7TF, W Yorkshire, England. EM rogerowen@nhs.net RI Garcia-Sanz, Ramon/B-7986-2017; OI Garcia-Sanz, Ramon/0000-0003-4120-2787; Merlini, Giampaolo/0000-0001-7680-3254; Rawstron, Andy/0000-0003-0798-9790 NR 35 TC 50 Z9 52 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2013 VL 160 IS 2 BP 171 EP 176 DI 10.1111/bjh.12102 PG 6 WC Hematology SC Hematology GA 070OZ UT WOS:000313520300007 PM 23150997 ER PT J AU Pitman, MB Yaeger, KA Brugge, WR Mino-Kenudson, M AF Pitman, Martha B. Yaeger, Kurt A. Brugge, William R. Mino-Kenudson, Mari TI Prospective analysis of atypical epithelial cells as a high-risk cytologic feature for malignancy in pancreatic cysts SO CANCER CYTOPATHOLOGY LA English DT Article DE pancreas; mucinous cysts; cytology; atypical epithelial cells; endoscopic ultrasound; fine-needle aspiration biopsy; intraductal papillary mucinous neoplasm ID PAPILLARY MUCINOUS NEOPLASMS; INTERNATIONAL CONSENSUS GUIDELINES; ENDOSCOPIC ULTRASOUND; ADDS VALUE; MANAGEMENT; LESIONS; DIAGNOSIS; CYTOMORPHOLOGY; PREDICTORS; SOCIETY AB BACKGROUND: Pancreatic cysts are aspirated to assess whether a cyst is mucinous on one hand and malignant on the other. The authors' retrospective data have indicated that high-grade atypical epithelial cells (AECs) identified on cytology are a high-risk feature and a better threshold than positive for detecting malignancy. The objective of the current study was to assess the accuracy of AECs in predicting malignancy in pancreatic cysts. METHODS: Cysts aspirated by endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS-FNAs) obtained between January 2006 and June 2011 were evaluated. Cytologic, histologic, imaging, and cyst fluid analysis data were recorded. AECs were defined as cells that had an increased nuclear-to-cytoplasmic ratio and nuclear hyperchromasia with or without membrane abnormalities and with or without cytoplasmic vacuoles, but of insufficient quality and quantity for a positive interpretation. Malignancy included mucinous cysts with high-grade dysplasia and invasive carcinoma. Performance characteristics of cytology with AECs or worse (high-grade atypia [HGA]) for predicting malignancy were assessed. RESULTS: There were 70 FNAs that had histologic confirmation from 404 EUS-FNAs in 352 patients. Excluding 4 nondiagnostic FNAs, the study cohort consisted of 66 FNAs for analysis. There were 24 malignant cysts with 20 true-positive, 4 false-negative, 36 true-negative, and 6 false-positive results. For the detection of malignancy, HGA had 83% sensitivity, 86% specificity, a positive predictive value of 77%, a negative predictive value of 90%, and 85% overall accuracy. The lower threshold for malignancy with AECs resulted in a 12% increase in the detection of malignancy. CONCLUSIONS: A finding of AECs on cytology is a high-risk feature for malignancy and is an accurate triage threshold for resection. Cancer (Cancer Cytopathol) 2013;121:2936 (C) 2012 American Cancer Society. C1 [Pitman, Martha B.; Yaeger, Kurt A.; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 01907 USA. [Pitman, Martha B.; Yaeger, Kurt A.; Brugge, William R.; Mino-Kenudson, Mari] Harvard Univ, Sch Med, Boston, MA USA. [Brugge, William R.] Massachusetts Gen Hosp, Dept Med, Boston, MA 01907 USA. RP Pitman, MB (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 01907 USA. EM mpitman@partners.org NR 24 TC 16 Z9 16 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD JAN PY 2013 VL 121 IS 1 BP 29 EP 36 DI 10.1002/cncy.21242 PG 8 WC Oncology; Pathology SC Oncology; Pathology GA 073BZ UT WOS:000313719700007 PM 23132817 ER PT J AU Kwan, ML Chen, WDY Flatt, SW Weltzien, EK Nechuta, SJ Poole, EM Holmes, MD Patterson, RE Shu, XO Pierce, JP Caan, BJ AF Kwan, Marilyn L. Chen, Wendy Y. Flatt, Shirley W. Weltzien, Erin K. Nechuta, Sarah J. Poole, Elizabeth M. Holmes, Michelle D. Patterson, Ruth E. Shu, Xiao Ou Pierce, John P. Caan, Bette J. TI Postdiagnosis Alcohol Consumption and Breast Cancer Prognosis in the After Breast Cancer Pooling Project SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; PROGESTERONE-RECEPTOR STATUS; LONG-TERM TAMOXIFEN; POSTMENOPAUSAL WOMEN; HORMONE CONCENTRATIONS; ADJUVANT CHEMOTHERAPY; PREMENOPAUSAL WOMEN; PROSPECTIVE COHORT; PHYSICAL-ACTIVITY; DIETARY FACTORS AB Background: Alcohol consumption is an established risk factor for incident breast cancer. However, its role in breast cancer prognosis remains unclear. Methods: We conducted an investigation of postdiagnosis alcohol consumption with recurrence and mortality among 9,329 breast cancer patients in the After Breast Cancer Pooling Project. Women were diagnosed from 1990 to 2006 with AJCC Stage I-III breast tumors from three prospective US cohorts. Alcohol intake was assessed at cohort entry (mean 2.1 years postdiagnosis) using a food frequency questionnaire. HR and 95% confidence intervals (CI) were estimated using delayed entry Cox proportional hazards models with adjustment for known prognostic factors. Results: After a mean follow-up of 10.3 years, 1,646 recurrences and 1,543 deaths were ascertained. 5,422 women (58%) were considered drinkers (>= 0.36 g/day of alcohol, >= 0.25 drinks/week) with a median of 5.3 g/day. Overall, compared with nondrinking, regular alcohol intake (>= 6.0 g/day) was not associated with risk of recurrence (HR for 6 to less than 12 g/day, 1.03; 95% CI, 0.86-1.24; HR for 12 to less than 24 g/day, 1.12; 95% CI, 0.93-1.34; HR for >= 24 g/day, 1.04; 95% CI, 0.84-1.31). However, risk varied significantly by menopausal status (P for interaction <0.05). Postmenopausal women who regularly consumed alcohol (>= 6.0 g/day) had increased risk of recurrence (HR, 1.19; 95% CI, 1.01-1.40). Alcohol intake was not associated with mortality. Conclusions: Regular alcohol consumption was not associated with breast cancer recurrence and total mortality overall, yet recurrence risk was only elevated in postmenopausal women. Impact: The association between alcohol intake and recurrence may depend on menopausal status at breast cancer diagnosis. Cancer Epidemiol Biomarkers Prev; 22(1); 32-41. (c) 2012 AACR. C1 [Kwan, Marilyn L.; Weltzien, Erin K.; Caan, Bette J.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Flatt, Shirley W.; Patterson, Ruth E.; Pierce, John P.] Univ Calif San Diego, Canc Prevent & Control Program, Moores UCSD Canc Ctr, San Diego, CA 92103 USA. [Chen, Wendy Y.; Poole, Elizabeth M.; Holmes, Michelle D.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Chen, Wendy Y.; Poole, Elizabeth M.; Holmes, Michelle D.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Wendy Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Nechuta, Sarah J.; Shu, Xiao Ou] Vanderbilt Univ, Sch Med, Dept Med, Div Epidemiol, Nashville, TN 37212 USA. RP Kwan, ML (reprint author), 2000 Broadway, Oakland, CA 94612 USA. EM Marilyn.L.Kwan@kp.org FU National Cancer Institute [3R01CA118229-03S1, R01 CA118229, R01 CA129059, P01 CA87969, T32 CA009001]; Department of Defense [DAMD 17-02-1-0607]; Susan G. Komen Foundation [KG100988] FX This work was supported by the National Cancer Institute (3R01CA118229-03S1). Funding for each individual cohort participating in the After Breast Cancer Pooling Project is as follows: The SBCSS was supported by the Department of Defense (DAMD 17-02-1-0607); and the National Cancer Institute (R01 CA118229). The WHEL Study was supported by the Susan G. Komen Foundation (#KG100988). The LACE Study was supported by the National Cancer Institute (R01 CA129059). The NHS was supported by the National Cancer Institute (P01 CA87969, T32 CA009001). NR 62 TC 11 Z9 11 U1 2 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2013 VL 22 IS 1 BP 32 EP 41 DI 10.1158/1055-9965.EPI-12-1022 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 070SS UT WOS:000313531900005 PM 23150063 ER PT J AU Ozanne, EM Drohan, B Bosinoff, P Semine, A Jellinek, M Cronin, C Millham, F Dowd, D Rourke, T Block, C Hughes, KS AF Ozanne, Elissa M. Drohan, Brian Bosinoff, Phil Semine, Alan Jellinek, Michael Cronin, Claire Millham, Frederick Dowd, Dana Rourke, Taryn Block, Caroline Hughes, Kevin S. TI Which Risk Model to Use? Clinical Implications of the ACS MRI Screening Guidelines SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CANCER-SOCIETY GUIDELINES; BREAST-CANCER; FAMILY-HISTORY; PREDICTION; WOMEN AB The American Cancer Society (ACS) guidelines define the appropriate use of MRI as an adjunct to mammography for breast cancer screening. Three risk assessment models are recommended to determine if women are at sufficient risk to warrant the use of this expensive screening tool, however, the real-world application of these models has not been explored. We sought to understand how these models behave in a community setting for women undergoing mammography screening. We conducted a retrospective analysis of 5,894 women, who received mammography screening at a community hospital and assessed their eligibility for MRI according to the ACS guidelines. Of the 5,894 women, 342 (5.8%) were eligible for MRI, but we found significant differences in the number of eligible women identified by each model. Our results indicate that these models identify very different populations, implying that the ACS guidelines deserve further development and consideration. Cancer Epidemiol Biomarkers Prev; 22(1); 146-9. (C) 2012 AACR. C1 [Ozanne, Elissa M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Drohan, Brian; Bosinoff, Phil; Hughes, Kevin S.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Semine, Alan; Jellinek, Michael; Cronin, Claire; Millham, Frederick; Hughes, Kevin S.] Harvard Univ, Sch Med, Boston, MA USA. [Block, Caroline] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Semine, Alan; Jellinek, Michael; Cronin, Claire; Millham, Frederick; Dowd, Dana; Rourke, Taryn; Hughes, Kevin S.] Newton Wellesley Hosp, Newton, MA USA. RP Hughes, KS (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, 55 Fruit St,YAW 7, Boston, MA 02114 USA. EM kshughes@partners.org OI Hughes, Kevin/0000-0003-4084-6484 FU Myriad; Massachusetts General Hospital; Newton-Wellesley Hospital; American Cancer Society [MRSG112037] FX K.S. Hughes has commercial research grant from Myriad, honoraria from Speakers Bureau of Myriad, and has ownership interest (including patents) in HughesRiskApps.Net. No potential conflicts of interest were disclosed by the other authors.; This work was supported by Philanthropic Funds from Massachusetts General Hospital and Newton-Wellesley Hospital. E. Ozanne's work on this project was supported in part by grant number MRSG112037 from the American Cancer Society. NR 11 TC 17 Z9 17 U1 1 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2013 VL 22 IS 1 BP 146 EP 149 DI 10.1158/1055-9965.EPI-12-0570 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 070SS UT WOS:000313531900018 PM 23093547 ER PT J AU Tan, ASL Moldovan-Johnson, M Gray, SW Hornik, RC Armstrong, K AF Tan, Andy S. L. Moldovan-Johnson, Mihaela Gray, Stacy W. Hornik, Robert C. Armstrong, Katrina TI An Analysis of the Association Between Cancer-Related Information Seeking and Adherence to Breast Cancer Surveillance Procedures SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOLLOW-UP; AMERICAN-SOCIETY; SELF-REPORTS; MAMMOGRAPHY; SURVIVORS; CARE; GUIDELINES; PATTERNS; UPDATE; WOMEN AB Background: Breast cancer surveillance is important for women with a known history of breast cancer. However, relatively little is known about the prevalence and determinants of adherence to surveillance procedures, including associations with seeking of cancer-related information from medical and nonmedical sources. Methods: We conducted a longitudinal cohort study of breast cancer patients diagnosed in Pennsylvania in 2005. Our main analyses included 352 women who were eligible for surveillance and participated in both baseline (similar to 1 year after cancer diagnosis) and follow-up surveys. Outcomes were self-reported doctor visits and physical examination, mammography, and breast self-examination (BSE) at 1-year follow-up. Results: Most women underwent two or more physical examinations according to recommended guidelines (85%). For mammography, 56% of women were adherent (one mammogram in a year) while 39% reported possible overuse (two or more mammograms). Approximately 60% of respondents reported regular BSE (>= 5 times in a year). Controlling for potential confounders, higher levels of cancer-related information seeking from nonmedical sources at baseline was associated with regular BSE (OR, 1.52; 95% CI, 1.01-2.29; P, 0.046). There was no significant association between information-seeking behaviors from medical or nonmedical sources and surveillance with physical examination or mammography. Conclusions: Seeking cancer-related information from nonmedical sources is associated with regular BSE, a surveillance behavior that is not consistently recommended by professional organizations. Impact: Findings from this study will inform clinicians on the contribution of active information seeking toward breast cancer survivors' adherence to different surveillance behaviors. Cancer Epidemiol Biomarkers Prev; 22(1); 167-74. (C) 2012 AACR. C1 [Tan, Andy S. L.; Hornik, Robert C.; Armstrong, Katrina] Univ Penn, Ctr Excellence Canc Commun Res, Annenberg Sch Commun, Philadelphia, PA 19104 USA. [Armstrong, Katrina] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Armstrong, Katrina] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Armstrong, Katrina] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Moldovan-Johnson, Mihaela] Nebraska Dept Hlth & Human Serv, Off Hlth Promot, Div Publ Hlth, Lincoln, NE USA. [Gray, Stacy W.] Dana Farber Canc Inst, Ctr Community Based Res, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. RP Tan, ASL (reprint author), Univ Penn, Ctr Excellence Canc Commun Res, Annenberg Sch Commun, 3620 Walnut St, Philadelphia, PA 19104 USA. EM atan@asc.upenn.edu OI Tan, Andy/0000-0001-6459-6171; Hornik, Robert/0000-0002-2148-8805 FU National Cancer Institute's Center of Excellence in Cancer Communication (CECCR) located at the Annenberg School for Communication, University of Pennsylvania [P20CA095856, P50CA095856] FX Financial support for this work was provided by the National Cancer Institute's Center of Excellence in Cancer Communication (CECCR) located at the Annenberg School for Communication, University of Pennsylvania (P20CA095856 and P50CA095856). NR 51 TC 4 Z9 4 U1 5 U2 18 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2013 VL 22 IS 1 BP 167 EP 174 DI 10.1158/1055-9965.EPI-12-0781 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 070SS UT WOS:000313531900021 PM 23118144 ER PT J AU Hariri, LP Applegate, MB Mino-Kenudson, M Mark, EJ Medoff, BD Luster, AD Bouma, BE Tearney, GJ Suter, MJ AF Hariri, Lida P. Applegate, Matthew B. Mino-Kenudson, Mari Mark, Eugene J. Medoff, Benjamin D. Luster, Andrew D. Bouma, Brett E. Tearney, Guillermo J. Suter, Melissa J. TI Volumetric Optical Frequency Domain Imaging of Pulmonary Pathology With Precise Correlation to Histopathology SO CHEST LA English DT Article ID CELL LUNG-CANCER; COHERENCE TOMOGRAPHY; IN-VIVO; AIRWAYS MICROSTRUCTURE; COMPUTED-TOMOGRAPHY; BARRETTS-ESOPHAGUS; BRONCHIAL LESIONS; BIOPSY SPECIMENS; SWEPT SOURCE; BRONCHOSCOPY AB Background: Lung cancer is the leading cause of cancer-related mortality. Radiology and bronchoscopy techniques do not have the necessary resolution to evaluate lung lesions on the microscopic scale, which is critical for diagnosis. Bronchial biopsy specimens can be limited by sampling error and small size. Optical frequency domain imaging (OFDI) provides volumetric views of tissue microstructure at near-histologic resolution and may be useful for evaluating pulmonary lesions to increase diagnostic accuracy. Bronchoscopic OFDI has been evaluated in vivo, but a lack of correlated histopathology has limited the ability to develop accurate image interpretation criteria. Methods: We performed OFDI through two approaches (airway-centered and parenchymal imaging) in 22 ex vivo lung specimens, using tissue dye to precisely correlate imaging and histology. Results: OFDI of normal airway allowed visualization of epithelium, lamina propria, cartilage, and alveolar attachments. Carcinomas exhibited architectural disarray, loss of normal airway and alveolar structure, and rapid light attenuation. Squamous cell carcinomas showed nested architecture. Atypical glandular formation was appreciated in adenocarcinomas, and uniform trabecular gland formation was seen in salivary gland carcinomas. Mucinous adenocarcinomas showed alveolar wall thickening with intraalveolar mucin. Interstitial fibrosis was visualized as signal-dense tissue, with an interstitial distribution in mild interstitial fibrotic disease and a diffuse subpleural pattern with cystic space formation in usual interstitial pneumonitis. Conclusions: To our knowledge, this study is the first demonstration of volumetric OFDI with precise correlation to histopathology in lung pathology. We anticipate that OFDI may play a role in assessing airway and parenchymal pathology, providing fresh insights into the volumetric features of pulmonary disease. CHEST 2013; 143(1):64-74 C1 [Hariri, Lida P.; Mino-Kenudson, Mari; Mark, Eugene J.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Applegate, Matthew B.; Medoff, Benjamin D.; Suter, Melissa J.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Hariri, Lida P.; Applegate, Matthew B.; Bouma, Brett E.; Tearney, Guillermo J.; Suter, Melissa J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Luster, Andrew D.] Massachusetts Gen Hosp, Rheumatol Allergy & Immunol Div, Boston, MA 02114 USA. [Hariri, Lida P.; Mino-Kenudson, Mari; Mark, Eugene J.; Medoff, Benjamin D.; Luster, Andrew D.; Bouma, Brett E.; Tearney, Guillermo J.; Suter, Melissa J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Bouma, Brett E.; Tearney, Guillermo J.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. RP Suter, MJ (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, 55 Fruit St,Warren Bldg,Room 408D, Boston, MA 02114 USA. EM msuter@partners.org FU National Institutes of Health [R00CAI34920, R37AI040618, U19AI095261, P4IEB01590]; American Lung Association [RG-194681-N]; NinePoint Medical, Inc.; NinePoint Medical, Inc FX This work was funded in part by the National Institutes of Health [Grants R00CAI34920, R37AI040618, U19AI095261, P4IEB01590] and the American Lung Association [Grant RG-194681-N].; The authors have reported to CHEST the following conflicts of interest: Drs Bouma and Tearney receive consulting income from NinePoint Medical, Inc. Dr Suter receives clinical research support from NinePoint Medical, Inc. NinePoint Medical, Inc has a licensing arrangement with Massachusetts General Hospital. Drs Tearney, Bouma, and Suter have the right to receive royalty payments from NinePoint Medical, Inc. Drs Hariri, Mino-Kenuclson, Mark, Medoff, and Luster and Mr Applegate have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. NR 57 TC 16 Z9 16 U1 0 U2 12 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2013 VL 143 IS 1 BP 64 EP 74 DI 10.1378/chest.11-2797 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 070SL UT WOS:000313531200014 PM 22459781 ER PT J AU See, KC Christiani, DC AF See, Kay Choong Christiani, David C. TI Normal Values and Thresholds for the Clinical Interpretation of Exhaled Nitric Oxide Levels in the US General Population Results from the National Health and Nutrition Examination Survey 2007-2010 SO CHEST LA English DT Article ID BODY-MASS INDEX; AIRWAY INFLAMMATION; EPITHELIAL-CELLS; REFERENCE RANGES; CYSTIC-FIBROSIS; CIGARETTE-SMOKE; PASSIVE SMOKE; ASTHMA; CHILDREN; ADULTS AB Background: Elevated fractional excretion of exhaled nitric oxide (FENO) reflects airway inflammation, but few studies have established its normal values. This study aims to establish the normal values and thresholds for the clinical interpretation of FENO in the US general population. Methods: Thirteen thousand two hundred seventy-five subjects aged 6 to 80 years sampled for the National Health and Nutrition Examination Survey (NHANES) 2007-2010 underwent interviews, physical examination, and FENO analysis at 50 mL/s using an online chemiluminescence device according to American Thoracic Society/European Respiratory Society guidelines. After excluding subjects with self-reported asthma and subjects with wheeze in the prior 12 months, prediction equations for the natural logarithm (ln) of FENO were constructed using age, sex, ethnicity, height, BMI, active/passive smoke exposure, and hay fever episodes as covariates. Results: The fifth to 95th percentile values of FENO were 3.5 to 36.5 parts per billion (ppb) for children <12 years of age and 3.5 to 39 ppb for subjects 12 to 80 years of age. Using multiple linear regression, prediction equations explained only 10.3% to 15.7% of the variation in the general population. In the general population, 39% to 45% had ln(FENO) levels > 2 SD of the predicted means. When applied to the general population inclusive of subjects who reported asthma but who did not have attacks within the past year, nearly identical results were obtained. Conclusions: Assuming 95% of the healthy US general population had no clinically significant airway inflammation as assessed by FENO, values exceeding the 95th percentiles indicated abnormality and a high risk of airway inflammation. A large variation of normal FENO values existed in the general population, which was poorly predicted by multiple linear regression models. CHEST 2013; 143(1):107-116 C1 [See, Kay Choong] Natl Univ Singapore Hosp, Dept Med, Div Resp & Crit Care Med, Singapore 119228, Singapore. [See, Kay Choong; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Christiani, David C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Christiani, David C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP See, KC (reprint author), Natl Univ Singapore Hosp, Dept Med, Div Resp & Crit Care Med, 1E Kent Ridge Rd,NUHS Tower Block Level 10, Singapore 119228, Singapore. EM kay_choong_see@nuhs.edu.sg NR 49 TC 33 Z9 34 U1 0 U2 4 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2013 VL 143 IS 1 BP 107 EP 116 DI 10.1378/chest.12-0416 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 070SL UT WOS:000313531200019 PM 22628492 ER PT J AU Mackenzie, DC Liteplo, AS Noble, VE AF Mackenzie, David C. Liteplo, Andrew S. Noble, Vicki E. TI Sensitivity of Point-of-Care Ultrasonography for Common Thoracic Injuries SO CHEST LA English DT Letter ID TRAUMA; ULTRASOUND C1 [Mackenzie, David C.; Liteplo, Andrew S.; Noble, Vicki E.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Mackenzie, DC (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St,0 Emerson Pl,Ste 3B, Boston, MA 02114 USA. EM dcmackenzie@partners.org OI Mackenzie, David/0000-0002-5535-9964 NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2013 VL 143 IS 1 BP 269 EP 269 DI 10.1378/chest.12-1988 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 070SL UT WOS:000313531200042 PM 23401874 ER PT J AU Guinan, EC Agarwal, S AF Guinan, Eva C. Agarwal, Suneet TI A Young Adult with Aplastic Anemia and Gray Hair SO CLINICAL CHEMISTRY LA English DT Editorial Material ID DYSKERATOSIS-CONGENITA; MUTATIONS; LENGTH C1 [Guinan, Eva C.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. [Guinan, Eva C.; Agarwal, Suneet] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Guinan, Eva C.; Agarwal, Suneet] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Guinan, Eva C.; Agarwal, Suneet] Harvard Univ, Sch Med, Boston, MA USA. [Agarwal, Suneet] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Guinan, EC (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM eva_guinan@dfci.harvard.edu NR 10 TC 0 Z9 0 U1 3 U2 4 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2013 VL 59 IS 1 BP 47 EP 50 DI 10.1373/clinchem.2012.187237 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 070TV UT WOS:000313535100012 PM 23284013 ER PT J AU Weisbord, SD Mor, MK Green, JA Sevick, MA Shields, AM Zhao, XH Rollman, BL Palevsky, PM Arnold, RM Fine, MJ AF Weisbord, Steven D. Mor, Maria K. Green, Jamie A. Sevick, Mary Ann Shields, Anne Marie Zhao, Xinhua Rollman, Bruce L. Palevsky, Paul M. Arnold, Robert M. Fine, Michael J. TI Comparison of Symptom Management Strategies for Pain, Erectile Dysfunction, and Depression in Patients Receiving Chronic Hemodialysis: A Cluster Randomized Effectiveness Trial SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID QUALITY-OF-LIFE; STAGE RENAL-DISEASE; DIALYSIS PATIENTS; PSYCHOSOCIAL FACTORS; COLLABORATIVE CARE; PREVALENCE; VALIDATION; SILDENAFIL; FLUOXETINE; SEVERITY AB Background and objectives Pain, erectile dysfunction (ED), and depression are common yet frequently untreated in chronic hemodialysis patients. This study compared two management strategies for these symptoms in this patient population. Design, setting, participants, & measurements Pain, ED, and depression were assessed monthly during an observation usual care phase. Patients were then randomized to 12-month participation in either a feedback arm in which these symptoms were assessed monthly, renal providers were informed of patients' symptoms, and treatment was left treatment at their discretion; or a nurse management arm in which symptoms were assessed monthly and trained nurses were used to evaluate patients and generate and facilitate the implementation of treatment recommendations. Results Of 288 patients enrolled into observation between January 1, 2009 and March 30, 2010, 220 (76%) were randomized. Compared with the feedback approach, the results (shown as Delta symptom score [95% confidence interval]) indicated that nurse management was not associated with improved pain (0.49 [-0.56, 1.54]), ED (0.20 [-0.55, 0.95]), or depression (0.32 [-0.94, 1.58]). Relative to their symptoms during observation, feedback patients experienced small, statistically significant improvements in pain (-0.98 [-1.67, -0.28]), ED (-0.98 [-1.54, -0.41]), and depression (-1.36 [-2.19, -0.54]), whereas nurse management patients experienced small, statistically significant improvements in ED (-0.78 [-1.41, -0.15]) and depression (-1.04 [-2.04, -0.04]). Conclusions Compared with informing renal providers of their patients' pain, ED, and depression and leaving management at their discretion, a nurse-implemented management strategy does not improve these symptoms. Both approaches modestly reduced symptoms relative to usual care. Clin J Am Soc Nephrol 8: 90-99, 2013. doi: 10.2215/CJN.04450512 C1 [Weisbord, Steven D.; Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Renal Sect, Med Specialty Serv Line, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.; Mor, Maria K.; Sevick, Mary Ann; Shields, Anne Marie; Zhao, Xinhua; Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.; Green, Jamie A.; Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. [Mor, Maria K.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Sevick, Mary Ann; Rollman, Bruce L.; Arnold, Robert M.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. [Arnold, Robert M.] Univ Pittsburgh, Div Palliat Care, Sch Med, Pittsburgh, PA USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Med Specialty Serv Line, 7E Room 120,111F-U, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu OI Palevsky, Paul/0000-0002-7334-5400 FU Department of Veterans Affairs Health Services Research and Development Merit Review award [IIR 07-190] FX This work was supported by a Department of Veterans Affairs Health Services Research and Development Merit Review award (IIR 07-190). The opinions expressed in this article are those of the authors and do not represent the views of the Department of Veterans Affairs or the US Government. NR 37 TC 24 Z9 24 U1 2 U2 9 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JAN PY 2013 VL 8 IS 1 BP 90 EP 99 DI 10.2215/CJN.04450512 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 066LE UT WOS:000313221500014 PM 23024159 ER PT J AU Rodgers, RF Melioli, T Laconi, S Bui, E Chabrol, H AF Rodgers, Rachel F. Melioli, Tiffany Laconi, Stephanie Bui, Eric Chabrol, Henri TI Internet Addiction Symptoms, Disordered Eating, and Body Image Avoidance SO CYBERPSYCHOLOGY BEHAVIOR AND SOCIAL NETWORKING LA English DT Article ID ATTITUDES TEST; LONELINESS; VALIDATION AB Internet addiction is an increasing concern among young adults. Self-presentational theory posits that the Internet offers a context in which individuals are able to control their image. Little is known about body image and eating concerns among pathological Internet users. The aim of this study was to explore the association between Internet addiction symptoms, body image esteem, body image avoidance, and disordered eating. A sample of 392 French young adults (68 percent women) completed an online questionnaire assessing time spent online, Internet addiction symptoms, disordered eating, and body image avoidance. Fourteen men (11 percent) and 26 women (9.7 percent) reported Internet addiction. Body image avoidance was associated with Internet addiction symptoms among both genders. Controlling for body-mass index, Internet addiction symptoms, and body image avoidance were both significant predictors of disordered eating among women. These findings support the self-presentational theory of Internet addiction and suggest that body image avoidance is an important factor. C1 [Rodgers, Rachel F.; Melioli, Tiffany; Laconi, Stephanie; Chabrol, Henri] Toulouse Univ Le Mirail, Ctr Res Psychopathol, Toulouse, France. [Rodgers, Rachel F.; Bui, Eric] Univ Toulouse 3, Lab Traumat Stress, F-31062 Toulouse, France. [Rodgers, Rachel F.] Northeastern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. [Bui, Eric] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bui, Eric] Harvard Univ, Sch Med, Boston, MA USA. RP Rodgers, RF (reprint author), Northeastern Univ, Dept Counseling & Appl Educ Psychol, 360 Huntington Ave, Boston, MA 02115 USA. EM rodgers.rachel@gmail.com RI Bui, Eric/J-8347-2015; OI Bui, Eric/0000-0002-1413-6473; LACONI, Stephanie/0000-0002-0906-5631 NR 29 TC 18 Z9 18 U1 2 U2 36 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2152-2715 J9 CYBERPSYCH BEH SOC N JI Cyberpsychology Behav. Soc. Netw. PD JAN PY 2013 VL 16 IS 1 BP 56 EP 60 DI 10.1089/cyber.2012.1570 PG 5 WC Psychology, Social SC Psychology GA 071DG UT WOS:000313565500011 PM 23320871 ER PT J AU Alam, M Helenowksi, IB Cohen, JL Levy, R Liegeois, N Mafong, EA Mooney, MA Nehal, KS Nguyen, TH Ratner, D Rohrer, T Schmults, CD Tan, S Yoon, J Kakar, R Rademaker, AW White, LE Yoo, S AF Alam, Murad Helenowksi, Irene B. Cohen, Joel L. Levy, Ross Liegeois, Nanette Mafong, Erick A. Mooney, Maureen A. Nehal, Kishwer S. Nguyen, Tri H. Ratner, Desiree Rohrer, Tom Schmults, Chrysalyne D. Tan, Stephen Yoon, Jaeyoung Kakar, Rohit Rademaker, Alfred W. White, Lucile E. Yoo, Simon TI Association Between Type of Reconstruction After Mohs Micrographic Surgery and Surgeon-, Patient-, and Tumor-Specific Features: A Cross-Sectional Study SO DERMATOLOGIC SURGERY LA English DT Article AB Background There are few data to indicate whether the type of final wound defect is associated with the type of post-Mohs repair. Objective To determine the methods of reconstruction that Mohs surgeons typically select and, secondarily, to assess the association between the method and the number of stages, tumor type, anatomic location, and patient and surgeon characteristics. Methods Statistical analysis of procedure logs of 20 representative young to mid-career Mohs surgeons. Results The number of stages associated with various repairs were different (analysis of variance, p<.001.). Linear repairs, associated with the fewest stages (1.5), were used most commonly (4355% of defects). Primary repairs were used for 20.2% to 35.3% of defects of the nose, eyelids, ears, and lips. Local flaps were performed typically after two stages of Mohs surgery (range 1.982.06). Referral for repair and skin grafts were associated with cases with more stages (2.16 and 2.17 stages, respectively). Experienced surgeons were nominally more likely perform flaps than grafts. Regression analyses did not indicate any association between patient sex and closure type (p=.99) or practice location and closure type (p=.99). Conclusions Most post-Mohs closures are linear repairs, with more bilayered linear repairs more likely at certain anatomic sites and after a larger number of stages. C1 [Alam, Murad; Kakar, Rohit; White, Lucile E.; Yoo, Simon] Northwestern Univ, Feinberg Sch Med, Dept Dermatol, Chicago, IL 60611 USA. [Helenowksi, Irene B.; Rademaker, Alfred W.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Cohen, Joel L.] AboutSkin Dermatol & DermSurg, Englewood, CO USA. [Levy, Ross] NorthShore Univ HealthSystem, Div Dermatol, Dermatol Surg Unit, Skokie, IL USA. [Liegeois, Nanette] Johns Hopkins Univ, Dept Plast Surg & Oncol, Baltimore, MD USA. [Mafong, Erick A.] Dermatol & Laser Ctr San Diego, Chula Vista, CA USA. [Mooney, Maureen A.] Cascade Eye Ctr, Washington, DC USA. [Mooney, Maureen A.] Cascade Skin Ctr, Washington, DC USA. [Nehal, Kishwer S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Nguyen, Tri H.] Mohs & Dermatol Associates, NW Diagnost Clin PA, Houston, TX USA. [Ratner, Desiree] Columbia Univ, Dept Dermatol, Med Ctr, New York, NY 10027 USA. [Rohrer, Tom] SkinCare Phys Chestnut Hill, Chestnut Hill, MA USA. [Schmults, Chrysalyne D.] Harvard Univ, Dana Farber Canc Ctr, Ctr Cutaneous Oncol, Boston, MA 02115 USA. [Tan, Stephen] Hlth Partners Specialty Ctr, St Paul, MN USA. [Yoon, Jaeyoung] St Louis Dermatol & Surg Ctr, St Louis, MO USA. RP Alam, M (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Dermatol, 676 N St Clair St,Ste 1600, Chicago, IL 60611 USA. EM m-alam@northwestern.edu NR 5 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD JAN PY 2013 VL 39 IS 1 BP 51 EP 55 DI 10.1111/dsu.12045 PN 1 PG 5 WC Dermatology; Surgery SC Dermatology; Surgery GA 071KJ UT WOS:000313591100006 PM 23199073 ER PT J AU McDermott, S Oliveira, G Ergul, E Brazeau, N Wicky, S Oklu, R AF McDermott, Shaunagh Oliveira, George Erguel, Emel Brazeau, Nicholas Wicky, Stephan Oklu, Rahmi TI May-Thurner syndrome: can it be diagnosed by a single MR venography study? SO DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY LA English DT Article ID ILIAC VEIN COMPRESSION; THROMBOSIS AB PURPOSE We aimed to evaluate the longitudinal stability of left common iliac vein (LCIV) compression by the right common iliac artery on magnetic resonance venography (MRV). MATERIALS AND METHODS This retrospective study included 214 patients diagnosed with May-Thurner syndrome by MRV. We identified a subset of patients who underwent contrast-enhanced cross-sectional imaging of the pelvis six months before or anytime after the MRV and did not undergo any interventional venous procedures between the two studies; 36 patients met these criteria. The degree of venous compression was calculated in both the index and comparison study. RESULTS On the index MRV, the mean compression of the LCIV was 62%. However, on the comparison study in the same patients, the mean compression was 39%. The mean change in degree of compression between the two studies was 23% (P < 0.0001), ranging from a 12% increase to 69% decrease in degree of compression on the comparison study. CONCLUSION The compressed LCIV on a single MRV study was not stable over time and thus may be insufficient to diagnose May-Thurner syndrome. C1 [Oklu, Rahmi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent,Dept Imaging, Boston, MA 02115 USA. RP Oklu, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent,Dept Imaging, Boston, MA 02115 USA. EM rahmioklu@gmail.com NR 19 TC 17 Z9 19 U1 0 U2 5 PU TURKISH SOC RADIOLOGY PI ANKARA PA HOSDERE CAD, GUZELKENT SOK, CANKAYA EVLERI, F-2, ANKARA, 06540, TURKEY SN 1305-3825 J9 DIAGN INTERV RADIOL JI Diagn. Interv. Radiol. PD JAN-FEB PY 2013 VL 19 IS 1 BP 44 EP 48 DI 10.4261/1305-3825.DIR.5939-12.1 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 069UP UT WOS:000313462900008 PM 22801870 ER PT J AU Lee, HH Lee, HJ Cho, JI Stampfer, MJ Willett, WC Kim, CI Cho, E AF Lee, H. H. Lee, H. J. Cho, J. I. Stampfer, M. J. Willett, W. C. Kim, C. I. Cho, E. TI Overall and abdominal adiposity and hypertriglyceridemia among Korean adults: the Korea National Health and Nutrition Examination Survey 2007-2008 SO EUROPEAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE hypertriglyceridemia; Asian; epidemiology; abdominal obesity; body mass index ID BODY-MASS INDEX; SIMPLE ANTHROPOMETRIC INDEXES; CARDIOVASCULAR RISK-FACTORS; WAIST-CIRCUMFERENCE; METABOLIC SYNDROME; CUTOFF POINT; OBESITY; PREVALENCE; CHINESE; BMI AB BACKGROUND/OBJECTIVES: Obesity is associated with increased triglyceride levels. We examined whether overall obesity (body mass index (BMI)) and abdominal obesity (waist circumference (WC)) are independently associated with hypertriglyceridemia among the Korean population. SUBJECTS/METHODS: A national sample of 5036 Koreans aged 19-64 was examined with cross-sectional surveys, the Korea National Health and Nutrition Examination Survey, in 2007 and 2008. BMI, WC and other lifestyle information were assessed. RESULTS: We documented 1344 cases (26.7%) of hypertriglyceridemia (fasting triglycerides of >150 mg/dl). Both BMI and WC were each independently associated with hypertriglyceridemia. Multivariate odds ratios (ORs) of increasing categories of BMI (<18.5, 18.5 <=-<23, 23 <=-<25, 25 <=-<28, >= 28 kg/m(2)), were 0.49, 1.00 (reference), 1.26, 1.63 and 1.84, respectively (P=0.0007) adjusting for WC. There was a positive association between WC and hypertriglyceridemia across increasing quintiles of WC (multivariate-adjusted ORs: 1.00 (reference), 1.54, 2.54, 2.21 and 2.36; P<0.0001), adjusting for BMI. WC was positively related to hypertriglyceridemia in both gender. However, only women's BM! was independently associated with hypertriglyceridemia after adjusting for WC. The joint relation between BMI and WC and hypertriglyceridemia showed that within each BMI category, higher WC predicted a greater prevalence of hypertriglyceridemia and vice versa. The receiver operating characteristic curves indicated that BMI (0.69) and WC (0.72) were similar in predicting hypertriglyceridemia. CONCLUSIONS: Both BMI and WC were strongly independently associated with hypertriglyceridemia among the population. Both measurements should be considered for use in assessing health risk at clinical settings and epidemiologic research among Asian population. European Journal of Clinical Nutrition (2013) 67, 83-90; doi:10.1038/ejcn.2012.181; published online 21 November 2012 C1 [Lee, H. H.; Stampfer, M. J.; Willett, W. C.; Cho, E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Div Network Med,Dept Med, Boston, MA 02115 USA. [Lee, H. J.; Kim, C. I.] Korea Hlth Ind Dev Inst KHIDI, Dept Hlth Ind & Policy, Osan, South Korea. [Cho, J. I.] Dept Med, Cardiovasc Div, TIMI Study Grp, Boston, MA USA. [Stampfer, M. J.; Willett, W. C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Stampfer, M. J.; Willett, W. C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Cho, E (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Div Network Med,Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM eunyoung.cho@channing.harvard.edu NR 36 TC 2 Z9 4 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0954-3007 J9 EUR J CLIN NUTR JI Eur. J. Clin. Nutr. PD JAN PY 2013 VL 67 IS 1 BP 83 EP 90 DI 10.1038/ejcn.2012.181 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 070RD UT WOS:000313527300016 PM 23169471 ER PT J AU Schrems-Hoesl, LM Schrems, WA Cruzat, A Shahatit, BM Bayhan, HA Jurkunas, UV Hamrah, P AF Schrems-Hoesl, L. M. Schrems, W. A. Cruzat, A. Shahatit, B. M. Bayhan, H. A. Jurkunas, U. V. Hamrah, P. TI Cellular and subbasal nerve alterations in early stage Fuchs' endothelial corneal dystrophy: an in vivo confocal microscopy study SO EYE LA English DT Article DE in vivo confocal microscopy; Fuchs' endothelial corneal dystrophy; cornea; corneal nerves; epithelium; keratocytes ID SPECULAR MICROSCOPY; MORPHOLOGY; PLEXUS; VIP AB Purpose To analyze the morphology and density of corneal epithelial cells, keratocytes, and subbasal nerves, in patients with early stage Fuchs' endothelial corneal dystrophy (FECD) by in vivo confocal microscopy (IVCM). Methods IVCM (Confoscan 4, Nidek, Inc.) of the central cornea was performed in 30 corneas of 30 patients with early stage FECD and 13 corneas of 13 normal controls. Images were analyzed for morphology and density of the superficial and basal epithelial cells, keratocyte density, endothelial cell density (ECD), as well as subbasal corneal nerve parameters. Central corneal thickness (CCT) was measured in all patients and normals by ultrasound pachymetry. Results The ECD was significantly lower (-45.5%, P<0.001) in FECD patients as compared with controls. Total number of nerves and main nerve trunks were significantly reduced (-46.3%, P<0.001; -39.7%, P<0.001) in patients with FECD. Posterior keratocyte density was significantly higher in FECD patients (P<0.001). Significant inverse correlations were found between CCT and total number of nerves (r = -0.69, P<0.001), CCT and main nerve trunks (-0.47, P = 0.016), as well as CCT and total nerve length (r = -0.62, P = 0.006). Significant correlation was found between ECD and total number of nerves (r = 0.44, P = 0.012) as well as between ECD and main nerve trunks (r = 0.65, P<0.001). Conclusions IVCM demonstrates alterations in corneal innervation in patients with early stage FECD, suggesting a potential role of corneal nerves in the pathogenesis of FECD. Additional studies are required to investigate whether subbasal nerve alterations are caused by nonspecific corneal edema, from FECD-induced decrease in ECD, or potentially leading to loss of endothelial cells. Eye (2013) 27, 42-49; doi:10.1038/eye.2012.220; published online 16 November 2012 C1 [Hamrah, P.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med,Dept Ophthalmol, Ocular Surface Imaging Ctr,Cornea Serv, Boston, MA 02114 USA. RP Hamrah, P (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med,Dept Ophthalmol, Ocular Surface Imaging Ctr,Cornea Serv, 243 Charles St, Boston, MA 02114 USA. EM pedram_hamrah@meei.harvard.edu OI Cruzat, Andrea/0000-0002-3724-7037 FU NIH [K12-EY016335, K08-EY020575]; New England Corneal Transplant Research Fund; Falk Medical Research Foundation FX This work was supported by the NIH K12-EY016335, NIH K08-EY020575, New England Corneal Transplant Research Fund, Falk Medical Research Foundation, and an unrestricted grant to the Department of Ophthalmology, Harvard Medical School. The funding organisations had no role in the design or conduct of this research. NR 24 TC 17 Z9 18 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X J9 EYE JI Eye PD JAN PY 2013 VL 27 IS 1 BP 42 EP 49 DI 10.1038/eye.2012.220 PG 8 WC Ophthalmology SC Ophthalmology GA 071AJ UT WOS:000313557200006 PM 23154490 ER PT J AU Johnson, MD Apesoa-Varano, C Hay, J Unutzer, J Hinton, L AF Johnson, Megan Dwight Apesoa-Varano, Carolina Hay, Joel Unutzer, Juergen Hinton, Ladson TI Depression treatment preferences of older white and Mexican origin men SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Older men; Depression; Treatment preferences; Conjoint analysis; Latino ID PRIMARY-CARE PATIENTS; RANDOMIZED CONTROLLED-TRIAL; LATE-LIFE DEPRESSION; LOW-INCOME LATINOS; HEALTH-CARE; COLLABORATIVE CARE; CONJOINT-ANALYSIS; UNITED-STATES; ADULTS; PSYCHOTHERAPY AB Objective: Among older white and Mexican origin male primary care patients, we examined preferences for features of depression care programs that would encourage depressed older men to enter and remain in treatment. Method: Sixty-three (45 white, 18 Mexican origin) older men were recruited in six primary care clinics. All had clinical depression in the past year and/or were receiving depression treatment. Participants completed a conjoint analysis preference survey regarding depression treatments, providers and treatment enhancements. Results: The data suggest that white men preferred medication over counseling [odds ratio (OR): 1.64 95% confidence interval (CI): 1.12-2.41], while Mexican origin men preferred counseling (OR: medication over counseling: 0.28, 95% CI: 0.12-0.66). Both white and Mexican origin men preferred treatment that included family involvement (vs. none) (white: OR: 1.60, 95% CI 1.12-2.30; Mexican origin: OR: 3.31 95% CI 1.44-7.62) and treatment for insomnia (vs. treatment for alcohol use) (white: OR: 1.72, 95% CI 1.01-2.91; Mexican origin: OR: 3.93 95% CI 1.35-11.42). White men also preferred treatment by telephone (OR: 1.80, 95% CI 1.12-2.87). Conclusions: Findings could inform development of patient-centered depression treatment programs for older men and suggest strategies, such as attention to sleep problems, which providers may employ to tailor treatment to preferences of older men. Published by Elsevier Inc. C1 [Johnson, Megan Dwight] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. [Johnson, Megan Dwight] RAND Corp, Santa Monica, CA 90401 USA. [Johnson, Megan Dwight] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA. [Apesoa-Varano, Carolina] Univ Calif Davis, Betty Irene Sch Nursing, Davis, CA USA. [Hay, Joel] Univ So Calif, Sch Pharm, Los Angeles, CA 90089 USA. [Unutzer, Juergen] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. [Hinton, Ladson] Univ Calif Davis, Sch Med, Dept Psychiat & Behav Sci, Davis, CA USA. RP Johnson, MD (reprint author), RAND Corp, 1776 Main St, Santa Monica, CA 90401 USA. EM meganj@rand.org FU National Institute of Mental Health [MHR01080067]; National Institute of Mental Health (NIMH) [R01MH080067] FX National Institute of Mental Health, MHR01080067 "Reducing disparities in depression care for diverse older men".; This study was supported by Award Number R01MH080067 from the National Institute of Mental Health (NIMH). NR 50 TC 7 Z9 7 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JAN-FEB PY 2013 VL 35 IS 1 BP 59 EP 65 DI 10.1016/j.genhosppsych.2012.08.003 PG 7 WC Psychiatry SC Psychiatry GA 072BJ UT WOS:000313643000013 ER PT J AU Gros, DF Magruder, KM Frueh, BC AF Gros, Daniel F. Magruder, Kathryn M. Frueh, B. Christopher TI Obsessive compulsive disorder in veterans in primary care: prevalence and impairment SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Obsessive compulsive disorder; Veterans; Primary care; Comorbidity; Prevalence; Impairment; Quality of life ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMATIC LIFE EVENTS; COMORBIDITY; INTERVIEW AB Objective: Obsessive compulsive disorder (OCD) is a severely impairing psychiatric disorder with an estimated 12-month prevalence of 0.39% to 1.20% in community settings. However, there has been little research on the prevalence of OCD in primary care settings and veteran samples. Thus, the present study investigated prevalence, comorbidity, and physical and mental health impairment of veterans with OCD. Method: A total of 854 veterans participated in a cross-sectional investigation in primary care clinics in four Veteran Affairs Medical Centers. Participants completed the Mini International Neuropsychiatric Interview, Clinician-Administered PTSD Scale and Short-Form Health Survey. Results: A total of 1.9% of participants met the diagnostic criteria for OCD based on the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition. Participants with OCD were significantly younger and demonstrated greater psychiatric comorbidity than participants without OCD. Participants with OCD also reported significantly more severe physical health impairment (role limitation, pain, general health), mental health impairment (emotional well-being, role limitations, energy/fatigue) and impairment in social functioning than participants without OCD. Conclusions: These findings demonstrate moderately high prevalence and severe impairment associated with OCD in veterans, thus highlighting the need for improved recognition, assessment and specialized treatments for OCD in primary care settings and with veteran patients. Published by Elsevier Inc. C1 [Gros, Daniel F.] Ralph H Johnson VAMC, Mental Hlth Serv 116, Charleston, SC 29401 USA. [Gros, Daniel F.; Magruder, Kathryn M.] Med Univ S Carolina, Charleston, SC 29425 USA. [Frueh, B. Christopher] Univ Hawaii, Dept Psychol, Hilo, HI 96720 USA. [Frueh, B. Christopher] Menninger Clin, Houston, TX USA. RP Gros, DF (reprint author), Ralph H Johnson VAMC, Mental Hlth Serv 116, Charleston, SC 29401 USA. EM grosd@musc.edu FU Veterans Affairs Health Services Research and Development [VCR-99-010-2] FX This work was partially supported by a grant from Veterans Affairs Health Services Research and Development (VCR-99-010-2). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. There are no conflicts of interest to disclose. NR 24 TC 7 Z9 7 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JAN-FEB PY 2013 VL 35 IS 1 BP 71 EP 73 DI 10.1016/j.genhosppsych.2012.09.004 PG 3 WC Psychiatry SC Psychiatry GA 072BJ UT WOS:000313643000015 PM 23044243 ER PT J AU Berkowitz, RS Goldstein, DP AF Berkowitz, Ross S. Goldstein, Donald Peter TI Current advances in the management of gestational trophoblastic disease SO GYNECOLOGIC ONCOLOGY LA English DT Editorial Material ID AGENT METHOTREXATE CHEMOTHERAPY; RECURRENT HYDATIDIFORM MOLE; UNDETECTABLE HCG LEVELS; QUALITY-OF-LIFE; LOW-RISK; MATRIX METALLOPROTEINASES; CLINICAL PRESENTATION; NLRP7 MUTATIONS; NORMAL PLACENTA; NEOPLASIA C1 [Berkowitz, Ross S.; Goldstein, Donald Peter] Harvard Univ, Div Gynecol Oncol,Sch Med,Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Obstet & Gynecol, New England Trophoblast Dis Ctr,Donald P Goldstei, Boston, MA 02115 USA. RP Berkowitz, RS (reprint author), Harvard Univ, Div Gynecol Oncol,Sch Med,Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Obstet & Gynecol, New England Trophoblast Dis Ctr,Donald P Goldstei, 75 Francis St, Boston, MA 02115 USA. EM rberkowitz@partners.org NR 62 TC 12 Z9 16 U1 0 U2 17 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 JAN PY 2013 VL 128 IS 1 BP 3 EP 5 DI 10.1016/j.ygyno.2012.07.116 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 068SQ UT WOS:000313386900002 PM 22846466 ER PT J AU Zaino, RJ Abendroth, C Yemelyanova, A Oliva, E Lim, D Soslow, R DeLair, D Hagemann, IS Montone, K Zhu, JJ AF Zaino, Richard J. Abendroth, Catherine Yemelyanova, Anna Oliva, Esther Lim, Diana Soslow, Robert DeLair, Deborah Hagemann, Ian S. Montone, Kathleen Zhu, Junjia TI Endocervical involvement in endometrial adenocarcinoma is not prognostically significant and the pathologic assessment of the pattern of involvement is not reproducible SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Endometrium; Carcinoma; FIGO stage; Cervix; Reproducibility; Pathology ID GYNECOLOGIC-ONCOLOGY-GROUP; CERVICAL STROMAL INVASION; STAGE-II CARCINOMA; SURGICAL STAGE; CLINICAL STAGE; ADJUVANT RADIATION; CANCER; WOMEN; SURVIVAL; CORPUS AB Objectives. Since 1988, cervical gland involvement and stromal invasion defined stage IIA and stage IIB endometrial carcinoma. In 2009, FIGO changed the criteria for stage II disease to include only those with cervical stromal invasion. We wished to: 1) assess the reproducibility of pathologists to distinguish patterns of cervical spread, and 2) determine the prognostic significance of cervical involvement. Methods. Slides from 46 women with cervical involvement by endometrial adenocarcinoma were scored for 5 patterns of involvement by 6 experienced pathologists to determine reproducibility. To assess prognostic significance, 206 patients with FIGO 1988 stage II adenocarcinoma formed the study population with matched FIGO stage I controls. Results. At least 5 of the 6 pathologists agreed that the cervix was involved in the 46 cases. The reproducibility for cervical gland involvement and endocervical stromal invasion was slight (kappas of 0.15 and 0.28). The survival with any type of cervical involvement was not significantly different from that of matched stage I controls (p = 0.18). The 5 year recurrence-free survival rates were 84% for FIGO 1988 stage I, 73% for stage IIA, and 82% for stage BB (FIGO 2009 stage II). Conclusions. Pathologists reliably recognize cervical involvement by endometrial carcinoma. However, reproducibility for the determination of pattern of cervical spread by experienced pathologists is too low to be of clinical utility. Women with spread of carcinoma to the cervix do not have a significantly lower survival than matched stage I controls. Cervical spread should not be the basis for determination of stage II disease. (C) 2012 Elsevier Inc. All rights reserved. C1 [Zaino, Richard J.; Abendroth, Catherine] Penn State Univ, Dept Pathol, Hershey, PA USA. [Zaino, Richard J.; Abendroth, Catherine] Penn State Univ, Milton S Hershey Med Ctr, Inst Canc, Hershey, PA 17033 USA. [Yemelyanova, Anna] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. [Oliva, Esther; Lim, Diana] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Soslow, Robert; DeLair, Deborah] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Hagemann, Ian S.; Montone, Kathleen] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Zhu, Junjia] Penn State Univ, Milton S Hershey Med Ctr, Dept Publ Hlth Sci, Hershey, PA 17033 USA. RP Zaino, RJ (reprint author), Penn State MS Hershey Med Ctr, Dept Pathol, H179,500 Univ Dr,POB 850, Hershey, PA 17033 USA. EM rzaino@hmc.psu.edu OI Soslow, Robert/0000-0002-7269-5898 NR 25 TC 3 Z9 4 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2013 VL 128 IS 1 BP 83 EP 87 DI 10.1016/j.ygyno.2012.09.035 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 068SQ UT WOS:000313386900016 PM 23063759 ER PT J AU Boruta, DM Bradford, LS AF Boruta, David M., II Bradford, Leslie S. TI Laparoendoscopic single-site extraperitoneal paraaortic lymphadenectomy for endometrial cancer staging SO GYNECOLOGIC ONCOLOGY LA English DT Editorial Material DE Laparoendoscopic single-site surgery; endometrial cancer; surgical staging; lymphadenectomy; obesity; extraperitoneal C1 [Boruta, David M., II] Massachusetts Gen Hosp, Yawkey Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA. RP Boruta, DM (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Suite 9E,55 Fruit St, Boston, MA 02114 USA. EM dboruta@partners.org NR 6 TC 2 Z9 2 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 JAN PY 2013 VL 128 IS 1 BP 132 EP 132 DI 10.1016/j.ygyno.2012.10.011 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 068SQ UT WOS:000313386900024 ER PT J AU Young, RH Scully, RE AF Young, Robert H. Scully, Robert E. TI Dr. Robert E. Scully, MD (1921-2012) Memoriam SO GYNECOLOGIC ONCOLOGY LA English DT Biographical-Item C1 [Young, Robert H.; Scully, Robert E.] 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 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 JAN PY 2013 VL 128 IS 1 BP 144 EP 145 DI 10.1016/j.ygyno.2012.12.001 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 068SQ UT WOS:000313386900027 ER PT J AU Manchanda, R Drapkin, R Menon, U AF Manchanda, Ranjit Drapkin, Ronny Menon, Usha TI There is a need for routine peritoneal cytology at RRSO SO GYNECOLOGIC ONCOLOGY LA English DT Letter ID FALLOPIAN-TUBE CARCINOMA; SUSPECTED BRCA-1; FOLLOW-UP; MUTATIONS; PROVEN; WOMEN; RISK C1 [Manchanda, Ranjit; Menon, Usha] UCL, EGA Inst Womens Hlth, Gynaecol Canc Res Ctr, Dept Gynaecol Oncol, London W1T 7DN, England. [Drapkin, Ronny] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. RP Manchanda, R (reprint author), EGA Inst Womens Hlth, Gynaecol Canc Res Ctr, 1st Floor,Maple House,149 Tottenham Court Rd, London W1T 7NF, England. EM u.menon@ucl.ac.uk RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 NR 4 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2013 VL 128 IS 1 BP 149 EP 150 DI 10.1016/j.ygyno.2012.09.031 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 068SQ UT WOS:000313386900032 PM 23063757 ER PT J AU Savard, C Tartaglione, EV Kuver, R Haigh, WG Farrell, GC Subramanian, S Chait, A Yeh, MM Quinn, LS Ioannou, GN AF Savard, Christopher Tartaglione, Erica V. Kuver, Rahul Haigh, W. Geoffrey Farrell, Geoffrey C. Subramanian, Savitha Chait, Alan Yeh, Matthew M. Quinn, LeBris S. Ioannou, George N. TI Synergistic interaction of dietary cholesterol and dietary fat in inducing experimental steatohepatitis SO HEPATOLOGY LA English DT Article ID LIVER-DISEASE; NONALCOHOLIC STEATOHEPATITIS; HEPATIC STEATOSIS; ATHEROGENIC DIET; ADIPOSE-TISSUE; UNITED-STATES; MICE; INFLAMMATION; EZETIMIBE; OBESE AB The majority of patients with nonalcoholic fatty liver disease (NAFLD) have simple steatosis, which is defined by hepatic steatosis in the absence of substantial inflammation or fibrosis and is considered to be benign. However, 10%-30% of patients with NAFLD progress to fibrosing nonalcoholic steatohepatitis (NASH), which is characterized by varying degrees of hepatic inflammation and fibrosis, in addition to hepatic steatosis, and can lead to cirrhosis. The cause(s) of progression to fibrosing steatohepatitis are unclear. We aimed to test the relative contributions of dietary fat and dietary cholesterol and their interaction on the development of NASH. We assigned C57BL/6J mice to four diets for 30 weeks: control (4% fat and 0% cholesterol); high cholesterol (HC; 4% fat and 1% cholesterol); high fat (HF; 15% fat and 0% cholesterol); and high fat, high cholesterol (HFHC; 15% fat and 1% cholesterol). The HF and HC diets led to increased hepatic fat deposition with little inflammation and no fibrosis (i.e., simple hepatic steatosis). However, the HFHC diet led to significantly more profound hepatic steatosis, substantial inflammation, and perisinusoidal fibrosis (i.e., steatohepatitis), associated with adipose tissue inflammation and a reduction in plasma adiponectin levels. In addition, the HFHC diet led to other features of human NASH, including hypercholesterolemia and obesity. Hepatic and metabolic effects induced by dietary fat and cholesterol together were more than twice as great as the sum of the separate effects of each dietary component alone, demonstrating significant positive interaction. Conclusion: Dietary fat and dietary cholesterol interact synergistically to induce the metabolic and hepatic features of NASH, whereas neither factor alone is sufficient to cause NASH in mice. (HEPATOLOGY 2013; 57:81-92) C1 [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Res Enhancement Award Program, Seattle, WA 98108 USA. [Savard, Christopher; Kuver, Rahul; Ioannou, George N.] Univ Washington, Div Gastroenterol, Seattle, WA 98195 USA. [Farrell, Geoffrey C.] Austrailian Natl Univ, Canberra Hosp, Sch Med, Liver Res Grp, Garran, ACT, Australia. [Subramanian, Savitha; Chait, Alan] Univ Washington, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Subramanian, Savitha; Chait, Alan] Univ Washington, Diabet Obes Ctr Excellence, Seattle, WA 98195 USA. [Yeh, Matthew M.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Quinn, LeBris S.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Res Enhancement Award Program, S-111 Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu FU Office of Research and Development, Veterans Affairs FX This work was supported by the Research Enhancement Award Program (to G.N.I.), Office of Research and Development, Veterans Affairs. NR 30 TC 55 Z9 58 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2013 VL 57 IS 1 BP 81 EP 92 DI 10.1002/hep.25789 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 070XO UT WOS:000313547700011 PM 22508243 ER PT J AU Sun, XF Han, LH Seth, P Bian, S Li, LL Csizmadia, E Junger, WG Schmelzle, M Usheva, A Tapper, EB Baffy, G Sukhatme, VP Wu, Y Robson, SC AF Sun, Xiaofeng Han, Lihui Seth, Pankaj Bian, Shu Li, Linglin Csizmadia, Eva Junger, Wolfgang G. Schmelzle, Moritz Usheva, Anny Tapper, Elliot B. Baffy, Gyorgy Sukhatme, Vikas P. Wu, Yan Robson, Simon C. TI Disordered purinergic signaling and abnormal cellular metabolism are associated with development of liver cancer in Cd39/Entpd1 null Mice SO HEPATOLOGY LA English DT Article ID VASCULAR CD39/ENTPD1; EXTRACELLULAR ATP; TUMOR-GROWTH; INHIBITION; HEPATOCYTES; MOUSE; CD39; ANGIOGENESIS; TRIPHOSPHATE; DISRUPTION AB Liver cancer is associated with chronic inflammation, which is linked to immune dysregulation, disordered metabolism, and aberrant cell proliferation. Nucleoside triphosphate diphosphohydrolase-1; (CD39/ENTPD1) is an ectonucleotidase that regulates extracellular nucleotide/nucleoside concentrations by scavenging nucleotides to ultimately generate adenosine. These properties inhibit antitumor immune responses and promote angiogenesis, being permissive for the growth of transplanted tumors. Here we show that Cd39 deletion promotes development of both induced and spontaneous autochthonous liver cancer in mice. Loss of Cd39 results in higher concentrations of extracellular nucleotides, which stimulate proliferation of hepatocytes, abrogate autophagy, and disrupt glycolytic metabolism. Constitutive activation of Ras-mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR)-S6K1 pathways occurs in both quiescent Cd39 null hepatocytes in vitro and liver tissues in vivo. Exogenous adenosine 5'-triphosphate (ATP) boosts these signaling pathways, whereas rapamycin inhibits such aberrant responses in hepatocytes. Conclusion: Deletion of Cd39 and resulting changes in disordered purinergic signaling perturb hepatocellular metabolic/proliferative responses, paradoxically resulting in malignant transformation. These findings might impact adjunctive therapies for cancer. Our studies indicate that the biology of autochthonous and transplanted tumors is quite distinct. (HEPATOLOGY 2013; 57:205-216)2013) C1 [Seth, Pankaj; Sukhatme, Vikas P.; Wu, Yan] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Interdisciplinary Med & Biotechnol, Boston, MA 02215 USA. [Li, Linglin; Junger, Wolfgang G.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. [Usheva, Anny] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol,Dept Med & Surg, Boston, MA 02215 USA. [Baffy, Gyorgy] Harvard Univ, VA Boston Healthcare Syst, Dept Med, Boston, MA USA. [Baffy, Gyorgy] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02215 USA. RP Wu, Y (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Interdisciplinary Med & Biotechnol, 330 Brookline Ave,E CLS 614, Boston, MA 02215 USA. EM ywu@bidmc.harvard.edu; srobson@bidmc.harvard.edu FU National Institutes of Health [NHLBI P01-HL076540, R01-HL094400] FX Supported by National Institutes of Health (NHLBI P01-HL076540 and R01-HL094400). NR 34 TC 16 Z9 16 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2013 VL 57 IS 1 BP 205 EP 216 DI 10.1002/hep.25989 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 070XO UT WOS:000313547700023 PM 22859060 ER PT J AU Ioannou, GN Bryson, CL Weiss, NS Miller, R Scott, JD Boyko, EJ AF Ioannou, George N. Bryson, Christopher L. Weiss, Noel S. Miller, Richard Scott, John D. Boyko, Edward J. TI The prevalence of cirrhosis and hepatocellular carcinoma in patients with human immunodeficiency virus infection SO HEPATOLOGY LA English DT Article ID HEPATITIS-C VIRUS; CHRONIC LIVER-DISEASE; UNITED-STATES; HIV; PREDICTORS; VETERANS; FIBROSIS; ASSOCIATION; COINFECTION; PROGRESSION AB Cirrhosis is a leading cause of death among patients infected with human immunodeficiency virus (HIV). We sought to determine risk factors for and time trends in the prevalence of cirrhosis, decompensated cirrhosis, and hepatocellular carcinoma (HCC) among patients diagnosed with HIV who received care in the Veterans Affairs (VA) health care system nationally between 1996 and 2009 (n = 24,040 in 2009). Among patients coinfected with HIV and hepatitis C virus (HCV), there was a dramatic increase in the prevalence of cirrhosis (3.5%-13.2%), decompensated cirrhosis (1.9%-5.8%), and HCC (0.07%-1.6%). Little increase was observed among patients without HCV coinfection in the prevalence of cirrhosis (1.7%-2.2%), decompensated cirrhosis (1.1%-1.2%), and HCC (0.03%-0.13%). In 2009, HCV infection was present in the majority of patients with HIV who had cirrhosis (66%), decompensated cirrhosis (62%), and HCC (80%). Independent risk factors for cirrhosis included HCV infection (adjusted odds ratio [AOR], 5.82; 95% confidence interval [CI], 5.0-6.7), hepatitis B virus (HBV) infection (AOR, 2.40; 95% CI, 2.0-2.9), age (AOR, 1.03; 95% CI, 1.02-1.04), Hispanic ethnicity (AOR, 1.76; 95% CI, 1.4-2.2), diabetes (AOR, 1.79; 95% CI, 1.6-2.1), and alcohol abuse (AOR, 1.78; 95% CI, 1.5-2.1), whereas black race (AOR, 0.56; 95% CI, 0.48-0.64) and successful eradication of HCV (AOR, 0.61; 95% CI, 0.4-0.9) were protective. Independent risk factors for HCC included HCV infection (AOR, 10.0; 95% CI, 6.1-16.4), HBV infection (AOR, 2.82; 95% CI, 1.7-4.7), age (AOR, 1.05; 95% CI, 1.03-1.08), and low CD4+ cell count (AOR, 2.36; 95% CI, 1.3-4.2). Among 5999 HIV/HCV-coinfected patients, 994 (18%) had ever received HCV antiviral treatment, of whom 165 (17%) achieved sustained virologic response. Conclusion: The prevalence of cirrhosis and HCC has increased dramatically among HIV-infected patients driven primarily by the HCV epidemic. Potentially modifiable risk factors include HCV infection, HBV infection, diabetes, alcohol abuse, and low CD4+ cell count. (HEPATOLOGY 2013;57:249-257) C1 [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Seattle, WA 98108 USA. [Bryson, Christopher L.; Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Div Internal Med, Seattle, WA 98108 USA. [Miller, Richard] Vet Affairs Puget Sound Hlth Care Syst, Div Infect Dis, Seattle, WA 98108 USA. [Weiss, Noel S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Scott, John D.] Univ Washington, Div Infect Dis, Seattle, WA 98195 USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, S-111 Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu FU Investigator Initiated Research grant, Clinical Science Research and Development, Office of Research and Development, Veterans Affairs [EPID-007-10S] FX Supported by Investigator Initiated Research grant EPID-007-10S, Clinical Science Research and Development, Office of Research and Development, Veterans Affairs (to G. N. I.). NR 29 TC 60 Z9 60 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2013 VL 57 IS 1 BP 249 EP 257 DI 10.1002/hep.25800 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 070XO UT WOS:000313547700027 PM 22532055 ER PT J AU Shanechi, MM Wornell, GW Williams, ZM Brown, EN AF Shanechi, Maryam M. Wornell, Gregory W. Williams, Ziv M. Brown, Emery N. TI Feedback-Controlled Parallel Point Process Filter for Estimation of Goal-Directed Movements From Neural Signals SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Article DE Brain-machine interfaces (BMIs); motor control; neural decoding; optimal feedback control; point processes ID POSTERIOR PARIETAL CORTEX; MOTOR CORTICAL REPRESENTATION; BRAIN-COMPUTER INTERFACE; MACHINE INTERFACE; SPIKING ACTIVITY; ARM MOVEMENTS; STATE; NEURONS; SPACE; TETRAPLEGIA AB Real-time brain-machine interfaces have estimated either the target of a movement, or its kinematics. However, both are encoded in the brain. Moreover, movements are often goal-directed and made to reach a target. Hence, modeling the goal-directed nature of movements and incorporating the target information in the kinematic decoder can increase its accuracy. Using an optimal feedback control design, we develop a recursive Bayesian kinematic decoder that models goal-directed movements and combines the target information with the neural spiking activity during movement. To do so, we build a prior goal-directed state-space model for the movement using an optimal feedback control model of the sensorimotor system that aims to emulate the processes underlying actual motor control and takes into account the sensory feedback. Most goal-directed models, however, depend on the movement duration, not known a priori to the decoder. This has prevented their real-time implementation. To resolve this duration uncertainty, the decoder discretizes the duration and consists of a bank of parallel point process filters, each combining the prior model of a discretized duration with the neural activity. The kinematics are computed by optimally combining these filter estimates. Using the feedback-controlled model and even a coarse discretization, the decoder significantly reduces the root mean square error in estimation of reaching movements performed by a monkey. C1 [Shanechi, Maryam M.] MIT, Dept Elect Engn & Comp Sci EECS, Cambridge, MA 02139 USA. [Wornell, Gregory W.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Williams, Ziv M.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Brown, Emery N.] MIT, Inst Med Engn & Sci, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Brown, Emery N.] MIT, Harvard Hlth Sci & Technol Program, Cambridge, MA 02139 USA. [Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Brown, Emery N.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Shanechi, MM (reprint author), Univ Calif Berkeley, Dept EECS, Berkeley, CA 94720 USA. EM shanechi@cornell.edu; gww@mit.edu; zwilliams1@partners.org; enb@neurostat.mit.edu NR 47 TC 17 Z9 17 U1 2 U2 16 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1534-4320 J9 IEEE T NEUR SYS REH JI IEEE Trans. Neural Syst. Rehabil. Eng. PD JAN PY 2013 VL 21 IS 1 BP 129 EP 140 DI 10.1109/TNSRE.2012.2221743 PG 12 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA 069GL UT WOS:000313423200016 PM 23047892 ER PT J AU Braunwald, E AF Braunwald, Eugene TI Cardiovascular science: opportunities for translating research into improved care introduction SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID KINASE-C-ALPHA; HEART-FAILURE; DILATED CARDIOMYOPATHY; STEM-CELLS; MYOCARDIAL-INFARCTION; THERAPEUTIC APPROACH; CARDIAC-DISEASE; S-NITROSYLATION; GENE-TRANSFER; NITRIC-OXIDE AB Cardiovascular research is progressing on many fronts, as highlighted in the collection of Reviews in this issue of the JCI. MicroRNAs that regulate cardiac function have been implicated in cardiac disorders, and efforts to develop therapeutic antagomirs are underway. The genetic bases of several cardiac disorders, including cardiomyopathies that cause heart failure and channelopathies that underlie cardiac arrhythmias, have been elucidated. Genetic testing can identify asymptomatic individuals at risk, potentially leading to effective preventative measures. Growing evidence supports the role of chronic inflammation in atherosclerosis, providing new opportunities for therapeutic intervention. For heart failure, recent work suggests that cardiac regeneration using stem/progenitor cells, gene transfer, new drugs that restore normal Ca2+ cycling, and agents that reduce reperfitsion injury following myocardial infarction are all viable new approaches to managing disease. Cumulatively, it seems likely that the clinical advances emerging from ongoing research will, in the foreseeable future, reduce the number of deaths in the industrialized world from cardiovascular disease. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Cardiovasc Div,TIMI Study Grp,Dept Med, Boston, MA 02115 USA. RP Braunwald, E (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Cardiovasc Div,TIMI Study Grp,Dept Med, 350 Longwood Ave, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 68 TC 9 Z9 9 U1 0 U2 8 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 JAN PY 2013 VL 123 IS 1 BP 6 EP 10 DI 10.1172/JCI67541 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 071MV UT WOS:000313598500003 PM 23281404 ER PT J AU Stanford, KI Middelbeek, RJW Townsend, KL An, D Nygaard, EB Hitchcox, KM Markan, KR Nakano, K Hirshman, MF Tseng, YH Goodyear, LJ AF Stanford, Kristin I. Middelbeek, Roeland J. W. Townsend, Kristy L. An, Ding Nygaard, Eva B. Hitchcox, Kristen M. Markan, Kathleen R. Nakano, Kazuhiro Hirshman, Michael F. Tseng, Yu-Hua Goodyear, Laurie J. TI Brown adipose tissue regulates glucose homeostasis and insulin sensitivity SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SKELETAL-MUSCLE; INTERLEUKIN-6-DEFICIENT MICE; SYMPATHETIC INNERVATION; TRANSCRIPTIONAL CONTROL; ENERGY-EXPENDITURE; ADULT HUMANS; BODY-WEIGHT; OBESITY; FAT; ADIPOCYTES AB Brown adipose tissue (BAT) is known to function in the dissipation of chemical energy in response to cold or excess feeding, and also has the capacity to modulate energy balance. To test the hypothesis that BAT is fundamental to the regulation of glucose homeostasis, we transplanted BAT from male donor mice into the visceral cavity of age- and sex-matched recipient mice. By 8-12 weeks following transplantation, recipient mice had improved glucose tolerance, increased insulin sensitivity, lower body weight, decreased fat mass, and a complete reversal of high-fat diet-induced insulin resistance. Increasing the quantity of BAT transplanted into recipient mice further improved the metabolic effects of transplantation. BAT transplantation increased insulin-stimulated glucose uptake in vivo into endogenous BAT, white adipose tissue (WAT), and heart muscle but, surprisingly, not skeletal muscle. The improved metabolic profile was lost when the BAT used for transplantation was obtained from Il6-knockout mice, demonstrating that BAT-derived IL-6 is required for the profound effects of BAT transplantation on glucose homeostasis and insulin sensitivity. These findings reveal a previously under-appreciated role for BAT in glucose metabolism. C1 [Stanford, Kristin I.; Middelbeek, Roeland J. W.; Townsend, Kristy L.; An, Ding; Nygaard, Eva B.; Hitchcox, Kristen M.; Markan, Kathleen R.; Nakano, Kazuhiro; Hirshman, Michael F.; Tseng, Yu-Hua; Goodyear, Laurie J.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA. RP Goodyear, LJ (reprint author), 1 Joslin Pl, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu FU NIH [R01-DK068626, R01-AR45670, F32-DK091048-01, T32 DK07260-33, 5P30 DK36836]; American Diabetes Association FX The authors thank Margarette Adelman, Allen Clermont, Alevtina Pinkhasov, and Geetha Sankaranarayan of the Joslin Diabetes Center DERC Physiology, Histology, and Complex Assay cores for technical assistance; Julie A. Ripley for editorial contributions; and Aaron Cypess and Hans Lauritzen for critical discussions. This work was supported by NIH grants R01-DK068626 and R01-AR45670 (to L.J. Goodyear), F32-DK091048-01 and T32 DK07260-33 (to K.I. Stanford), and 5P30 DK36836 (Joslin Diabetes Center DERC). R.J.W. Middelbeek was supported by a mentor-based fellowship awarded to U. Goodyear from the American Diabetes Association. NR 44 TC 245 Z9 254 U1 13 U2 83 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 JAN PY 2013 VL 123 IS 1 BP 215 EP 223 DI 10.1172/JCI62308 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 071MV UT WOS:000313598500027 PM 23221344 ER PT J AU Faber, K Bullinger, L Ragu, C Garding, A Mertens, D Miller, C Martin, D Walcher, D Dohner, K Dohner, H Claus, R Plass, C Sykes, SM Lane, SW Scholl, C Frohling, S AF Faber, Katrin Bullinger, Lars Ragu, Christine Garding, Angela Mertens, Daniel Miller, Christina Martin, Daniela Walcher, Daniel Doehner, Konstanze Doehner, Hartmut Claus, Rainer Plass, Christoph Sykes, Stephen M. Lane, Steven W. Scholl, Claudia Froehling, Stefan TI CDX2-driven leukemogenesis involves KLF4 repression and deregulated PPAR gamma signaling SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACTIVATED RECEPTOR-GAMMA; HOMEOBOX GENE CDX2; CANCER CELL-LINES; TUMOR-SUPPRESSOR; COLON-CANCER; INTESTINAL METAPLASIA; TRANSCRIPTION FACTORS; COLORECTAL-CANCER; ECTOPIC EXPRESSION AB Aberrant expression of the homeodomain transcription factor CDX2 occurs in most cases of acute myeloid leukemia (AML) and promotes leukemogenesis, making CDX2, in principle, an attractive therapeutic target. Conversely, CDX2 acts as a tumor suppressor in colonic epithelium. The effectors mediating the leukemogenic activity of CDX2 and the mechanism underlying its context-dependent properties are poorly characterized, and strategies for interfering with CDX2 function in AML remain elusive. We report data implicating repression of the transcription factor KLF4 as important for the oncogenic activity of CDX2, and demonstrate that CDX2 differentially regulates KLF4 in AML versus colon cancer cells through a mechanism that involves tissue-specific patterns of promoter binding and epigenetic modifications. Furthermore, we identified deregulation of the PPAR gamma signaling pathway as a feature of CDX2-associated AML and observed that PPAR gamma agonists derepressed KLF4 and were preferentially toxic to CDX2(+) leukemic cells. These data delineate transcriptional programs associated with CDX2 expression in hematopoietic cells, provide insight into the antagonistic duality of CDX2 function in AML versus colon cancer, and suggest reactivation of KLF4 expression, through modulation of PPAR gamma signaling, as a therapeutic modality in a large proportion of AML patients. C1 [Faber, Katrin; Bullinger, Lars; Garding, Angela; Mertens, Daniel; Miller, Christina; Martin, Daniela; Doehner, Konstanze; Doehner, Hartmut; Scholl, Claudia; Froehling, Stefan] Univ Ulm, Dept Internal Med 3, D-89081 Ulm, Germany. [Bullinger, Lars; Sykes, Stephen M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA USA. [Mertens, Daniel] Univ Ulm, Dept Internal Med 2, D-89069 Ulm, Germany. [Claus, Rainer; Plass, Christoph] German Canc Res Ctr, Div Epigen & Canc Risk Factors, Heidelberg, Germany. [Lane, Steven W.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. RP Frohling, S (reprint author), Natl Ctr Tumor Dis, Dept Translat Oncol, Neuenheimer Feld 460, D-69120 Heidelberg, Germany. EM daudia.scholl@uni-ulm.de; stefan.froehling@nct-heidelberg.de RI Plass, Christoph/H-7192-2014; Lane, Steven/C-3215-2012; Mertens, Daniel/F-4681-2011; OI Lane, Steven/0000-0002-8050-6209; Mertens, Daniel/0000-0003-0227-7188; Ragu, Christine/0000-0002-1150-1105 FU Deutsche Jose Carreras Leukamie-Stiftung [DJCLS R 09/12]; German Research Foundation; Leukaemia Foundation of Australia; Emmy Noether Fellowship from the German Research Foundation; European Hematology Association-Jose Carreras Foundation Young Investigator Fellowship FX We thank Gary Gilliland for advice and critical review of the manuscript. We thank Ursula Botzenhardt for technical assistance. This work was supported by grant DJCLS R 09/12 from the Deutsche Jose Carreras Leukamie-Stiftung. L. Bullinger is the recipient of a Heisenberg Fellowship from the German Research Foundation. S.W. Lane is supported by the Leukaemia Foundation of Australia. C. Scholl is the recipient of an Emmy Noether Fellowship from the German Research Foundation. S. Frohling is the recipient of a European Hematology Association-Jose Carreras Foundation Young Investigator Fellowship. NR 68 TC 17 Z9 19 U1 0 U2 13 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 JAN PY 2013 VL 123 IS 1 BP 299 EP 314 DI 10.1172/JCI64745 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 071MV UT WOS:000313598500034 PM 23202735 ER PT J AU Muller, TD Lee, SJ Jastroch, M Kabra, D Stemmer, K Aichler, M Abplanalp, B Ananthakrishnan, G Bhardwaj, N Collins, S Divanovic, S Endele, M Finan, B Gao, YQ Habegger, KM Hembree, J Heppner, KM Hofmann, S Holland, J Kuchler, D Kutschke, M Krishna, R Lehti, M Oelkrug, R Ottaway, N Perez-Tilve, D Raver, C Walch, AK Schriever, SC Speakman, J Tseng, YH Diaz-Meco, M Pfluger, PT Moscat, J Tschop, MH AF Mueller, Timo D. Lee, Sang Jun Jastroch, Martin Kabra, Dhiraj Stemmer, Kerstin Aichler, Michaela Abplanalp, Bill Ananthakrishnan, Gayathri Bhardwaj, Nakul Collins, Sheila Divanovic, Senad Endele, Max Finan, Brian Gao, Yuanqing Habegger, Kirk M. Hembree, Jazzmin Heppner, Kristy M. Hofmann, Susanna Holland, Jenna Kuechler, Daniela Kutschke, Maria Krishna, Radha Lehti, Maarit Oelkrug, Rebecca Ottaway, Nickki Perez-Tilve, Diego Raver, Christine Walch, Axel K. Schriever, Sonja C. Speakman, John Tseng, Yu-Hua Diaz-Meco, Maria Pfluger, Paul T. Moscat, Jorge Tschoep, Matthias H. TI p62 Links beta-adrenergic input to mitochondrial function and thermogenesis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BROWN ADIPOSE-TISSUE; P38 MAP KINASE; ACTIVATED PROTEIN-KINASE; TRANSCRIPTIONAL CONTROL; ADAPTIVE THERMOGENESIS; INSULIN-RESISTANCE; CRE RECOMBINASE; ADULT HUMANS; P62/SQSTM1; FAT AB The scaffold protein p62 (sequestosome 1; SQSTM1) is an emerging key molecular link among the metabolic, immune, and proliferative processes of the cell. Here, we report that adipocyte-specific, but not CNS-, liver-, muscle-, or myeloid-specific p62-deficient mice are obese and exhibit a decreased metabolic rate caused by impaired nonshivering thermogenesis. Our results show that p62 regulates energy metabolism via control of mitochondrial function in brown adipose tissue (BAT). Accordingly, adipocyte-specific p62 deficiency led to impaired mitochondrial function, causing BAT to become unresponsive to beta-adrenergic stimuli. Ablation of p62 leads to decreased activation of p38 targets, affecting signaling molecules that control mitochondrial function, such as ATF2, CREB, PGC1 alpha, DIO2, NRF1, CYTC, COX2, ATP5 beta, and UCP1.p62 ablation in HIB1B and BAT primary cells demonstrated that p62 controls thermogenesis in a cell-autonomous manner, independently of brown adipocyte development or differentiation. Together, our data identify p62 as a novel regulator of mitochondrial function and brown fat thermogenesis. C1 [Mueller, Timo D.; Jastroch, Martin; Kabra, Dhiraj; Stemmer, Kerstin; Finan, Brian; Kuechler, Daniela; Kutschke, Maria; Schriever, Sonja C.; Pfluger, Paul T.; Tschoep, Matthias H.] Tech Univ Munich, Inst Diabet & Obes, Helmholtz Zentrum Muenchen, D-85764 Munich, Germany. [Mueller, Timo D.; Jastroch, Martin; Kabra, Dhiraj; Stemmer, Kerstin; Finan, Brian; Kuechler, Daniela; Kutschke, Maria; Schriever, Sonja C.; Pfluger, Paul T.; Tschoep, Matthias H.] Tech Univ Munich, Dept Med, D-85764 Munich, Germany. [Lee, Sang Jun; Diaz-Meco, Maria; Moscat, Jorge] Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA. [Aichler, Michaela; Walch, Axel K.] Helmholtz Ctr Munich, Inst Pathol, Res Unit Analyt Pathol, Munich, Germany. [Abplanalp, Bill; Ananthakrishnan, Gayathri; Bhardwaj, Nakul; Gao, Yuanqing; Habegger, Kirk M.; Hembree, Jazzmin; Heppner, Kristy M.; Holland, Jenna; Krishna, Radha; Lehti, Maarit; Ottaway, Nickki; Perez-Tilve, Diego; Raver, Christine; Pfluger, Paul T.; Tschoep, Matthias H.] Univ Cincinnati, Dept Internal Med, Metabol Dis Inst, Cincinnati, OH USA. [Collins, Sheila] Sanford Burnham Med Res Inst, Diabetes & Obes Res Ctr, Orlando, FL USA. [Divanovic, Senad] Cincinnati Childrens Hosp Res Fdn, Div Mol Immunol, Cincinnati, OH USA. [Divanovic, Senad] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Endele, Max] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Res Unit Stem Cell Dynam, Neuherberg, Germany. [Hofmann, Susanna] Helmholtz Ctr Munich, Inst Expt Genet, Munich, Germany. [Oelkrug, Rebecca] Univ Marburg, Dept Anim Physiol, Marburg, Germany. [Speakman, John] Inst Genet & Dev Biol, Beijing, Peoples R China. [Speakman, John] Univ Aberdeen, Inst Biol & Environm Sci, Aberdeen, Scotland. [Tseng, Yu-Hua] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Tschop, MH (reprint author), Tech Univ Munich, Inst Diabet & Obes, Helmholtz Zentrum Muenchen, D-85764 Munich, Germany. EM jmoscat@sanfordburnham.org; tschoep@helmholtz-muenchen.de RI John, Speakman/A-9494-2008; Aichler, Michaela/B-5356-2014; Hofmann, Susanna/F-2654-2014; Tschoep, Matthias/I-5443-2014; Walch, Axel/B-4554-2012; OI John, Speakman/0000-0002-2457-1823; Walch, Axel/0000-0001-5578-4023; Lehti, Maarit/0000-0002-9063-6541 FU AstraZeneca; Pfizer; Chugai Pharmaceutical Co. FX John Speakman holds stock in Swedish Orphan Biovitrum, has received grants from AstraZeneca and Pfizer, and is a founder shareholder in Cambridge Biotechnology. Yu-Hua Tseng receives grant support from Chugai Pharmaceutical Co. D. Perez-Tilve has a collaborative association with F. Hoffmann-La Roche Ltd. pertaining to peptide-based therapeutics in metabolism. NR 43 TC 28 Z9 30 U1 1 U2 20 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 JAN PY 2013 VL 123 IS 1 BP 469 EP 478 DI 10.1172/JCI64209 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 071MV UT WOS:000313598500048 PM 23257354 ER PT J AU Verhaak, RGW Tamayo, P Yang, JY Hubbard, D Zhang, HL Creighton, CJ Fereday, S Lawrence, M Carter, SL Mermel, CH Kostic, AD Etemadmoghadam, D Saksena, G Cibulskis, K Duraisamy, S Levanon, K Sougnez, C Tsherniak, A Gomez, S Onofrio, R Gabriel, S Chin, L Zhang, NX Spellman, PT Zhang, YQ Akbani, R Hoadley, KA Kahn, A Kobel, M Huntsman, D Soslow, RA Defazio, A Birrer, MJ Gray, JW Weinstein, JN Bowtell, DD Drapkin, R Mesirov, JP Getz, G Levine, DA Meyerson, M AF Verhaak, Roel G. W. Tamayo, Pablo Yang, Ji-Yeon Hubbard, Diana Zhang, Hailei Creighton, Chad J. Fereday, Sian Lawrence, Michael Carter, Scott L. Mermel, Craig H. Kostic, Aleksandar D. Etemadmoghadam, Dariush Saksena, Gordon Cibulskis, Kristian Duraisamy, Sekhar Levanon, Keren Sougnez, Carrie Tsherniak, Aviad Gomez, Sebastian Onofrio, Robert Gabriel, Stacey Chin, Lynda Zhang, Nianxiang Spellman, Paul T. Zhang, Yiqun Akbani, Rehan Hoadley, Katherine A. Kahn, Ari Koebel, Martin Huntsman, David Soslow, Robert A. Defazio, Anna Birrer, Michael J. Gray, Joe W. Weinstein, John N. Bowtell, David D. Drapkin, Ronny Mesirov, Jill P. Getz, Gad Levine, Douglas A. Meyerson, Matthew CA Canc Genome Atlas Res Network TI Prognostically relevant gene signatures of high-grade serous ovarian carcinoma SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BREAST-CANCER; EXPRESSION PROFILES; BRCA2 MUTATIONS; FALLOPIAN-TUBE; COPY-NUMBER; CHEMOTHERAPY; SURVIVAL; PLATINUM; ASSOCIATION; SUBTYPES AB Because of the high risk of recurrence in high-grade serous ovarian carcinoma (HGS-OvCa), the development of outcome predictors could be valuable for patient stratification. Using the catalog of The Cancer Genome Atlas (TCGA), we developed subtype and survival gene expression signatures, which, when combined, provide a prognostic model of HGS-OvCa classification, named "Classification of Ovarian Cancer" (CLOVAR). We validated CLOVAR on an independent dataset consisting of 879 HGS-OvCa expression profiles. The worst outcome group, accounting for 23% of all cases, was associated with a median survival of 23 months and a platinum resistance rate of 63%, versus a median survival of 46 months and platinum resistance rate of 23% in other cases. Associating the outcome prediction model with BRCA1/BRCA2 mutation status, residual disease after surgery, and disease stage further optimized outcome classification. Ovarian cancer is a disease in urgent need of more effective therapies. The spectrum of outcomes observed here and their association with CLOVAR signatures suggests variations in underlying tumor biology. Prospective validation of the CLOVAR model in the context of additional prognostic variables may provide a rationale for optimal combination of patient and treatment regimens. C1 [Verhaak, Roel G. W.; Yang, Ji-Yeon; Zhang, Nianxiang; Akbani, Rehan; Weinstein, John N.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. [Tamayo, Pablo; Hubbard, Diana; Lawrence, Michael; Carter, Scott L.; Mermel, Craig H.; Kostic, Aleksandar D.; Saksena, Gordon; Cibulskis, Kristian; Sougnez, Carrie; Tsherniak, Aviad; Gomez, Sebastian; Onofrio, Robert; Gabriel, Stacey; Chin, Lynda; Mesirov, Jill P.; Getz, Gad; Meyerson, Matthew] MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02139 USA. [Tamayo, Pablo; Hubbard, Diana; Lawrence, Michael; Carter, Scott L.; Mermel, Craig H.; Kostic, Aleksandar D.; Saksena, Gordon; Cibulskis, Kristian; Sougnez, Carrie; Tsherniak, Aviad; Gomez, Sebastian; Onofrio, Robert; Gabriel, Stacey; Chin, Lynda; Mesirov, Jill P.; Getz, Gad; Meyerson, Matthew] Harvard Univ, Cambridge, MA 02138 USA. [Hubbard, Diana; Zhang, Hailei; Carter, Scott L.; Mermel, Craig H.; Kostic, Aleksandar D.; Duraisamy, Sekhar; Levanon, Keren; Chin, Lynda; Drapkin, Ronny; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Creighton, Chad J.; Zhang, Yiqun] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Fereday, Sian; Etemadmoghadam, Dariush; Bowtell, David D.] Peter MacCallum Canc Ctr, Canc Genet & Genom Lab, Melbourne, Vic, Australia. [Levanon, Keren] Chaim Sheba Med Ctr, Sheba Canc Res Ctr, Ramat Gan, Israel. [Spellman, Paul T.; Gray, Joe W.] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. [Hoadley, Katherine A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Kahn, Ari] SRA Int, Fairfax, VA USA. [Koebel, Martin] Univ Calgary, Calgary Lab Serv, Dept Pathol & Lab Med, Calgary, AB, Canada. [Huntsman, David] British Columbia Canc Agcy, Ctr Translat & Appl Genom, Vancouver, BC V5Z 4E6, Canada. [Soslow, Robert A.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Defazio, Anna] Univ Sydney, Dept Gynaecol Oncol, Westmead, NSW 2145, Australia. [Defazio, Anna] Univ Sydney, Westmead Inst Canc Res, Westmead, NSW 2145, Australia. [Defazio, Anna] Westmead Millennium Inst, Westmead, NSW, Australia. [Birrer, Michael J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10021 USA. RP Verhaak, RGW (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, 1400 Pressler St,Unit 1410, Houston, TX 77030 USA. EM rverhaak@mdanderson.org RI deFazio, Anna/D-3939-2013; Drapkin, Ronny/E-9944-2016; Bowtell, David/H-1007-2016; OI deFazio, Anna/0000-0003-0057-4744; Drapkin, Ronny/0000-0002-6912-6977; Bowtell, David/0000-0001-9089-7525; Soslow, Robert/0000-0002-7269-5898; Kostic, Aleksandar/0000-0002-0837-4360; Kobel, Martin/0000-0002-6615-2037 FU Foundation Medicine; Novartis; NIH [U24CA143867, U24CA143883]; Chapman Foundation; National Health and Medical Research Council of Australia FX Matthew Meyerson is an equity holder of and has received consulting fees from Foundation Medicine and has received consulting fees and research support from Novartis.; We thank the members of TCGA Research Network for their collaboration and comments. This work was supported by NIH grants U24CA143867 (to M. Meyerson) and U24CA143883 (to J.N. Weinstein); by the Chapman Foundation (to J.N. Weinstein); and by the National Health and Medical Research Council of Australia (to D.D. Bowtell and A. Defazio). No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 51 TC 137 Z9 144 U1 0 U2 23 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 JAN PY 2013 VL 123 IS 1 BP 517 EP 525 DI 10.1172/JCI65833 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 071MV UT WOS:000313598500052 PM 23257362 ER PT J AU Sharma, A Lanuti, M He, W Palmer, EL Shepard, JAO Digumarthy, SR AF Sharma, Amita Lanuti, Michael He, Wei Palmer, Edwin L. Shepard, Jo-Anne O. Digumarthy, Subba R. TI Increase in Fluorodeoxyglucose Positron Emission Tomography Activity Following Complete Radiofrequency Ablation of Lung Tumors SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE ablation; radiofrequency; percutaneous CT-guided; technique; interventional radiology; lung cancer; treatment; lung tumors; radiology; follow-up; FDG-PET; CT ID COLORECTAL-CANCER; LIVER METASTASES; FDG-PET/CT; CT; CANDIDATES; MIDTERM; LESIONS; MRI AB Objective: The objective of this study was to evaluate the F-18-fluorodeoxyglucose positron emission tomography (F-18-FDG-PET) findings following complete radiofrequency ablation (RFA) treatment of malignant lung tumors. Methods: Follow-up PET and computed tomography examinations in 18 patients (mean age, 67 +/- 16 years [range, 30-91 years]; 10 males, 8 females) who underwent 19 RFA sessions for the treatment of primary (n = 14) and metastatic (n = 5) lung tumors with mean follow-up of 18 months (range, 12-24 months) were retrospectively reviewed by 2 thoracic radiologists. All tumors were completely ablated. The maximum standardized uptake value (SUV) of the tumor and surrounding lung at baseline and at 1, 6, 12 and 24 months after RFA was measured. In addition, the size, histology, location of the tumor, presence of underlying emphysema, electrode type, and complications from RFA were recorded. Data were analyzed using Fisher exact test. Results: Baseline tumor SUV was variable (mean, 1.8 +/- 1.5 [range, 0.7-7]). The post-RFA F-18-FDG-PET appearances could be divided into 2 groups. A ring of peripheral activity and central photopenia was seen following 13 (68%) of 19 of ablations, and no ring was noted following 6 (32%) of 19 of ablations. The ring of F-18-FDG-PET activity was present at 1 month in 62%, at 6 months in 69% and at both 1 and 6 months in 31%. In all cases, central photopenia at 1 or 6 months was replaced by increased activity as the ring resolved at 6 or 12 months, mimicking local tumor progression. The presence of a ring of activity was associated with the use of a cluster electrode (P = 0.01). Lesion size, histology, location, baseline SUV, electrode type, or development of cavitation following RFA were not significantly associated with a post-RFA ring (P > 0.05) on PET scans. At 12 or 24 months, the SUV in the center of the lesion was equal to or greater than the SUV at baseline in 9 (47%) of 19 cases. Conclusions: Recognition of the normal FDG-PET appearances after RFA is important to prevent misdiagnosis of local tumor progression. C1 [Sharma, Amita; He, Wei; Palmer, Edwin L.; Shepard, Jo-Anne O.; Digumarthy, Subba R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Lanuti, Michael] Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA. RP Sharma, A (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Founders 202, Boston, MA 02114 USA. EM asharma2@partners.org NR 25 TC 7 Z9 7 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JAN-FEB PY 2013 VL 37 IS 1 BP 9 EP 14 DI 10.1097/RCT.0b013e3182732341 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 071TO UT WOS:000313617600002 PM 23321827 ER PT J AU Kulkarni, NM Eisner, BH Pinho, DF Joshi, MC Kambadakone, AR Sahani, DV AF Kulkarni, Naveen M. Eisner, Brian H. Pinho, Daniella F. Joshi, Mukta C. Kambadakone, Avinash R. Sahani, Dushyant V. TI Determination of Renal Stone Composition in Phantom and Patients Using Single-Source Dual-Energy Computed Tomography SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE single-source dual-energy CT; effective atomic number; material density image; uric acid stone; non-uric acid stone ID ACUTE FLANK PAIN; URINARY CALCULI; KIDNEY-STONES; IN-VITRO; CT; MANAGEMENT; UROLITHIASIS; DIAGNOSIS; DIFFERENTIATION; EXPERIENCE AB Purpose: This study aimed to characterize the urinary tract stones in phantom and patients using single-source dual-energy computed tomography. Materials and Methods: Twenty stones of pure crystalline composition (uric acid [UA], struvite, cystine, and calcium oxalate monohydrate) were assessed in a phantom and 11 patients (age 39-67 years) with urinary tract stones were evaluated. An initial low-dose unenhanced CT (tube potential, 120 kilovolts [peak]; milliampere range, 150-450; noise index, 26; section thickness, 5 mm) followed by a targeted dual-energy computed tomography acquisition on a single-source dual-energy computed tomography (Discovery CT 750 HDCT, GE) was performed. Uric acid and non-UA stones were defined using a 2-material decomposition (material density-iodine/water) algorithm. The stone effective atomic number (Zeff) was used to subclassify non-UA stones. The stone attenuation (Hounsfield unit) was also studied to determine its performance in predicting the composition. Ex vivo chemical analysis of the stone served as a criterion standard. Results: Of the 59 verified stones (phantom, 20; patients, 39; mean size, 6 mm), there were 16 UA and 43 non-UA type. The material density images were 100% sensitive and accurate in detecting UA and non-UA stones. The Zeff accurately stratified struvite, cystine, and calcium (calcium oxalate monohydrate) stones in the phantom. In patients, Zeff identified 83% of calcium stones (n = 24), and in stones of mixed type, it resembled dominant composition. The Hounsfield unit measurements alone were 71% sensitive and 69% accurate in detecting the UA stones. Conclusions: Single-source dual-energy computed tomography can accurately predict UA and non-UA stone composition in vitro and in vivo. Substratification of non-UA stones of pure composition can be made in vitro and in vivo. In stones of mixed composition, the Zeff values reflect the dominant composition. C1 [Sahani, Dushyant V.] Harvard Univ, Sch Med, Div Abdominal Imaging & Intervent, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Harvard Univ, Sch Med, Div Abdominal Imaging & Intervent, Massachusetts Gen Hosp, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org FU GE Healthcare FX Dr Dushyant Sahani received funding support from GE Healthcare. NR 29 TC 29 Z9 32 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JAN-FEB PY 2013 VL 37 IS 1 BP 37 EP 45 DI 10.1097/RCT.0b013e3182720f66 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 071TO UT WOS:000313617600006 PM 23321831 ER PT J AU Hammert, WC Ring, D Kozin, S AF Hammert, Warren C. Ring, David Kozin, Scott TI Evidence-Based Hand and Upper Extremity Surgery SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Editorial Material C1 [Hammert, Warren C.] Univ Rochester, Med Ctr, Dept Orthopaed Surg, Rochester, NY 14642 USA. [Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Kozin, Scott] Temple Univ, Dept Orthopaed Surg, Shriners Hosp Children, Philadelphia, PA 19122 USA. RP Hammert, WC (reprint author), Univ Rochester, Med Ctr, Dept Orthopaed Surg, Rochester, NY 14642 USA. NR 0 TC 2 Z9 2 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 JAN PY 2013 VL 38A IS 1 BP 1 EP 1 DI 10.1016/j.jhsa.2012.11.003 PG 1 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 071MP UT WOS:000313597800001 PM 23261187 ER PT J AU Ring, D AF Ring, David TI Commentary: A Good Question SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Editorial Material C1 Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. NR 1 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JAN PY 2013 VL 38A IS 1 BP 34 EP 34 DI 10.1016/j.jhsa.2012.10.014 PG 1 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 071MP UT WOS:000313597800006 PM 23261188 ER PT J AU Brenner, LA Homaifar, BY Olson-Madden, JH Nagamoto, HT Huggins, J Schneider, AL Forster, JE Matarazzo, B Corrigan, JD AF Brenner, Lisa A. Homaifar, Beeta Y. Olson-Madden, Jennifer H. Nagamoto, Herbert T. Huggins, Joe Schneider, Alexandra L. Forster, Jeri E. Matarazzo, Bridget Corrigan, John D. TI Prevalence and Screening of Traumatic Brain Injury Among Veterans Seeking Mental Health Services SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE mental health; screening; sensitivity; specificity; traumatic brain injury; Veterans ID SUBSTANCE-ABUSE TREATMENT; TBI IDENTIFICATION METHOD; RELIABILITY; VALIDITY; INDIVIDUALS AB Objectives: To assess the prevalence of traumatic brain injury (TBI) among Veterans seeking mental health services using a 4-item tool, the Traumatic Brain Injury-4 (TBI-4), and to establish the classification accuracy of the TBI-4 using the Ohio State University TBI-Identification Method as the criterion standard. Study Design: Archival and observational data collected from individuals seeking care at a Mountain State VA Medical Center. Participants: The sample for the archival study was 1810. Three hundred sixteen Veterans completed observational study measures. Main Measures: For the archival study, TBI-4 and demographic data extracted from electronic medical records. For the observational study, the Ohio State University TBI-Identification Method and a demographic questionnaire were used. TBI-4 data were also obtained from electronic medical records. Results: The prevalence of probable TBI among those seeking VA MH treatment was 45%. Sensitivity and specificity of the TBI-4 were 0.74 and 0.56, respectively. Veterans with all levels of TBI severity sought care within this VA mental health setting. Conclusions: The prevalence of TBI in this VA mental health treatment population was higher than expected. Additional research is required to assess the clinical utility of screening for TBI among this population of Veterans. C1 [Brenner, Lisa A.; Homaifar, Beeta Y.; Olson-Madden, Jennifer H.; Nagamoto, Herbert T.; Huggins, Joe; Schneider, Alexandra L.; Forster, Jeri E.; Matarazzo, Bridget] VA VISN 19 Mental Illness Res Educ & Clin Ctr MIR, Denver, CO USA. [Brenner, Lisa A.; Olson-Madden, Jennifer H.; Nagamoto, Herbert T.; Matarazzo, Bridget] Univ Colorado Denver, Sch Med, Dept Psychiat, Aurora, CO USA. [Brenner, Lisa A.] Univ Colorado Denver, Sch Med, Dept Neurol, Aurora, CO USA. [Brenner, Lisa A.] Univ Colorado Denver, Sch Med, Dept Phys Med & Rehabil, Aurora, CO USA. [Forster, Jeri E.] Univ Colorado Denver, Sch Med, Dept Pediat, Aurora, CO USA. [Homaifar, Beeta Y.] VA Boston Healthcare Syst, Boston, MA USA. [Homaifar, Beeta Y.] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. [Nagamoto, Herbert T.] Eastern Colorado Hlth Care Syst, Vet Affairs Med Ctr, Denver, CO USA. [Forster, Jeri E.] Univ Colorado Denver, Colorado Sch Publ Hlth, Dept Biostat & Informat, Aurora, CO USA. [Corrigan, John D.] Ohio State Univ, Dept Phys Med & Rehabil, Columbus, OH 43210 USA. RP Brenner, LA (reprint author), VISN 19 Mental Illness Res Educ & Clin Ctr MIRECC, 1055 Clermont St, Denver, CO 80220 USA. EM lisa.brenner@va.gov OI Huggins, Joe/0000-0001-8151-5062 FU Colorado Traumatic Brain Injury Trust Fund Program FX Support for this project was provided by the Colorado Traumatic Brain Injury Trust Fund Program. NR 31 TC 11 Z9 11 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-9701 J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD JAN-FEB PY 2013 VL 28 IS 1 BP 21 EP 30 DI 10.1097/HTR.0b013e31827df0b5 PG 10 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 070ZW UT WOS:000313555400003 PM 23288308 ER PT J AU Horgan, SJ Margey, R Brennan, DJ O'Herlihy, C Mahon, NG AF Horgan, Stephen J. Margey, Ronan Brennan, Donal J. O'Herlihy, Colm Mahon, Niall G. TI Natural history, management, and outcomes of peripartum cardiomyopathy: an Irish single-center cohort study SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Cardiac transplantation; ejection fraction; left ventricular failure; maternal mortality; puerperium ID HEART-FAILURE; UNITED-STATES; PREGNANCY; PROGNOSIS; MORTALITY; ETIOLOGY; WOMEN; RISK AB Aim: To describe the natural history, management and outcomes of peripartum cardiomyopathy (PPCM) in an unselected Northern European population. Methods: A retrospective single-center observational study was performed at a tertiary referral heart failure and transplantation unit. Outcomes measured were baseline demographics, clinical presentation, course, and treatment. Echocardiographic findings were compared at baseline, 2 months, and 6 months. Results: Twelve cases of PPCM were identified between 2002 and 2008. Mean age was 34.7 years. Nine patients were multiparous and nine had preeclampsia. Ten patients presented in the first week postpartum. Two patients required inotropic support. Mean ejection fraction (EF) at presentation was 27% (SD = 8%) which improved to 47% (SD = 13%) at 6 months. At this time, 10 patients were asymptomatic and 6 had recovered normal cardiac function. Left ventricular (LV) function improved but did not reach normal limits in five cases. One case with persistent severe LV dysfunction required cardiac transplantation. One patient suffered an arrhythmic death several years after the 6 months follow-up period. Conclusions: PPCM is a rare condition. With appropriate therapy, a good clinical outcome is common but not universal. Continued deterioration requiring ventricular support and cardiac transplantation can occur. In our cohort, older maternal age, multiparity, and preeclampsia appeared to be risk factors. C1 [Horgan, Stephen J.; Margey, Ronan; Mahon, Niall G.] Mater Misericordiae Univ Hosp, Dept Cardiol, Dublin 7, Ireland. [Horgan, Stephen J.] Univ Coll Dublin, Conway Inst Biomol & Biomed Res, UCD Sch Med & Med Sci, Dublin 2, Ireland. [Margey, Ronan] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Margey, Ronan] Harvard Univ, Sch Med, Boston, MA USA. [Brennan, Donal J.; O'Herlihy, Colm] Natl Matern Hosp, UCD Sch Med & Med Sci, Dublin 2, Ireland. RP Mahon, NG (reprint author), Mater Misericordiae Univ Hosp, Dept Cardiol, Eccles St, Dublin 7, Ireland. EM niallgmahon@me.com OI Mahon, Niall/0000-0002-2872-2297 NR 29 TC 3 Z9 3 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD JAN PY 2013 VL 26 IS 2 BP 161 EP 165 DI 10.3109/14767058.2012.726299 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 072NH UT WOS:000313678100012 PM 22978474 ER PT J AU Hingtgen, S Figueiredo, JL Farrar, C Duebgen, M Martinez-Quintanilla, J Bhere, D Shah, K AF Hingtgen, Shawn Figueiredo, Jose-Luiz Farrar, Christian Duebgen, Matthias Martinez-Quintanilla, Jordi Bhere, Deepak Shah, Khalid TI Real-time multi-modality imaging of glioblastoma tumor resection and recurrence SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Glioma; Image-Guided resection; In vivo imaging; Recurrence ID STEM-CELLS; MALIGNANT GLIOMA; MULTIFORME; SURGERY; MODEL; VECTORS; EXTENT AB The lack of relevant pre-clinical animal models incorporating the clinical scenario of Glioblastoma multiforme (GBM) resection and recurrence has contributed significantly to the inability to successfully treat GBM. A multi-modality imaging approach that allows real-time assessment of tumor resection during surgery and non-invasive detection of post-operative tumor volumes is urgently needed. In this study, we report the development and implementation of an optical imaging and magnetic resonance imaging (MRI) approach to guide GBM resection during surgery and track tumor recurrence at multiple resolutions in mice. Intra-operative fluorescence-guided surgery allowed real-time monitoring of intracranial tumor removal and led to greater than 90 % removal of established intracranial human GBM. The fluorescent signal clearly delineated tumor margins, residual tumor, and correlated closely with the clinically utilized fluorescence surgical marker 5-aminolevulinic acid/porphyrin. Post-operative non-invasive optical imaging and MRI confirmed near-complete tumor removal, which was further validated by immunohistochemistry (IHC). Longitudinal non-invasive imaging and IHC showed rapid recurrence of multi-focal tumors that exhibited a faster growth rate and altered blood-vessel density compared to non-resected tumors. Surgical tumor resection significantly extended long-term survival, however mice ultimately succumbed to the recurrent GBM. This multi-modality imaging approach to GBM resection and recurrence in mice should provide an important platform for investigating multiple aspects of GBM and ultimately evaluating novel therapeutics. C1 [Hingtgen, Shawn; Figueiredo, Jose-Luiz; Duebgen, Matthias; Martinez-Quintanilla, Jordi; Bhere, Deepak; Shah, Khalid] Harvard Univ, Sch Med, Mol Neurotherapy & Imaging Lab, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Farrar, Christian] Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. [Shah, Khalid] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shah, Khalid] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Shah, K (reprint author), Harvard Univ, Sch Med, Mol Neurotherapy & Imaging Lab, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM kshah@mgh.harvard.edu FU Alliance for Cancer Cell and Gene Therapy; American Cancer Society; James McDonald Foundation; National Institute of Health [R01-NSO71197] FX This work was supported by Alliance for Cancer Cell and Gene Therapy (KS), American Cancer Society (KS), James McDonald Foundation (KS) and National Institute of Health, R01-NSO71197 (KS). NR 31 TC 15 Z9 16 U1 2 U2 14 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 JAN PY 2013 VL 111 IS 2 BP 153 EP 161 DI 10.1007/s11060-012-1008-z PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 072HG UT WOS:000313660000007 PM 23242736 ER PT J AU Smith, BN Wang, JM Vogt, D Vickers, K King, DW King, LA AF Smith, Brian N. Wang, Joyce M. Vogt, Dawne Vickers, Kristin King, Daniel W. King, Lynda A. TI Gulf War Illness Symptomatology Among Veterans 10 Years After Deployment SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID CHRONIC MULTISYMPTOM ILLNESS; CHRONIC-FATIGUE-SYNDROME; PERSIAN-GULF; VETERANS; SYMPTOMS; PREVALENCE; HEALTH; ASSOCIATION; DEFICITS; LESSONS AB Objective: To further elucidate the nature of illness in veterans of the 1990 to 1991 Gulf War (GW) by examining the GW Illness (GWI) definition advanced by the Centers for Disease Control and Prevention, which specified caseness as having at least one symptom from two of the three factors: fatigue, mood-cognition, and musculoskeletal. Methods: A total of 311 male and female GW veterans drawn from across the nation were assessed in a survey-based study approximately 10 years after deployment. Results: A total of 33.8% of the probability-weighted sample met GWI criteria. Multiple symptom profiles were found, with more than half of GWI cases endorsing a symptom on all the three factors, and almost all cases endorsing at least one mood-cognition symptom. Conclusion: Although the Centers for Disease Control and Prevention definition has some limitations that should be considered, it remains a useful tool for assessing the presence of illness in GW veterans. C1 [Smith, Brian N.; Wang, Joyce M.; Vogt, Dawne; King, Lynda A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. [King, Daniel W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA 02130 USA. [Smith, Brian N.; Vogt, Dawne] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Vickers, Kristin] Ryerson Univ, Dept Psychol, Toronto, ON, Canada. [King, Daniel W.; King, Lynda A.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Smith, BN (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, 150 S Huntington Ave,116B-3, Boston, MA 02130 USA. EM Brian.Smith12@va.gov FU Department of Defense/Department of Veterans Affairs [DoD-87]; National Center for PTSD; Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System FX This study was supported by a Department of Defense/Department of Veterans Affairs grant PG Project DoD-87.; The authors thank the National Center for PTSD for ongoing support. The authors also express their appreciation to colleagues of the Stress, Health, and Aging Research Program (SHARP), VA Boston Healthcare System; SHARP is supported by the National Center for PTSD and the Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System. NR 31 TC 9 Z9 9 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD JAN PY 2013 VL 55 IS 1 BP 116 EP 122 DI 10.1097/JOM.0b013e318270d709 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 068TL UT WOS:000313389000016 PM 23235463 ER PT J AU Jacobsen, J Thomas, JD Jackson, VA AF Jacobsen, Juliet Thomas, Jane deLima Jackson, Vicki A. TI Misunderstandings about Prognosis: An Approach for Palliative Care Consultants When the Patient Does Not Seem To Understand What Was Said SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID CANCER-PATIENTS; TERMINALLY-ILL; COMMUNICATION; HOPE; PERCEPTIONS; INFORMATION; PHYSICIANS; CLINICIAN; DIAGNOSIS; DELIRIUM AB Called in after discussions about prognosis between referring clinicians and patients, palliative care consultants sometimes find that the patient does not seem to understand what the referring clinician believes he or she explained. However, holding a more explicit discussion about prognosis may compromise the palliative care clinician's rapport with both the patient and the referring clinician. We therefore propose a two-part approach to explore apparent prognostic misunderstandings: first, generate a differential diagnosis for why the patient and referring clinician have different reports of what was said, and second, cultivate a partnership with the referring clinician to provide a unified patient care plan. C1 [Jacobsen, Juliet; Jackson, Vicki A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Thomas, Jane deLima] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Jacobsen, Juliet; Thomas, Jane deLima; Jackson, Vicki A.] Harvard Univ, Sch Med, Boston, MA USA. RP Jacobsen, J (reprint author), Massachusetts Gen Hosp, Founders 600,55 Fruit St, Boston, MA 02114 USA. EM jjacobsen@partners.org NR 29 TC 5 Z9 5 U1 1 U2 7 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 JAN PY 2013 VL 16 IS 1 BP 91 EP 95 DI 10.1089/jpm.2012.0142 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 071AZ UT WOS:000313559000017 PM 23234301 ER PT J AU Villamar, MF Contreras, VS Kuntz, RE Fregni, F AF Villamar, Mauricio F. Contreras, Vanessa Suarez Kuntz, Richard E. Fregni, Felipe TI THE REPORTING OF BLINDING IN PHYSICAL MEDICINE AND REHABILITATION RANDOMIZED CONTROLLED TRIALS: A SYSTEMATIC REVIEW SO JOURNAL OF REHABILITATION MEDICINE LA English DT Review DE blinding; clinical research; physical medicine; rehabilitation; randomized controlled trials as topic ID CLINICAL-TRIALS; EMPIRICAL-EVIDENCE; CONSORT STATEMENT; QUALITY; BIAS; OSTEOARTHRITIS; INTERVENTION; METAANALYSES; STIMULATION; MAINTAIN AB Objective: To conduct a systematic review evaluating the reporting of blinding in randomized controlled trials published in the field of Physical Medicine and Rehabilitation over two time periods. Data sources: We searched MEDLINE via PubMed for all randomized controlled trials published in American Journal of Physical Medicine and Rehabilitation, Archives of Physical Medicine and Rehabilitation, Clinical Rehabilitation, Disability and Rehabilitation and (Scandinavian) Journal of Rehabilitation Medicine in the years 2000 and 2010. Study selection: We initially identified 222 articles, and 139 (62.6%) met our selection criteria. Data extraction: Two independent investigators collected data regarding study characteristics and blinding from each article. Consistency of data extraction was evaluated. Data synthesis: When comparing articles from 2010 and 2000, the former showed significantly higher rates for reporting of blinding, explicitly describing key persons' blinding status, and discussing the absence of blinding as a study limitation. There was a trend for lower reporting among trials with positive outcomes. No improvement was observed in other CONSORT-enforced parameters. Conclusions: Although the reporting of blinding in Physical Medicine and Rehabilitation randomized controlled trials shows some improvement over the past decade, it still does not fulfill current recommendations. Given its critical role in determining internal validity, stricter enforcement of CONSORT guidelines is needed. C1 [Villamar, Mauricio F.; Contreras, Vanessa Suarez; Fregni, Felipe] Spaulding Rehabil Hosp, Lab Neuromodulat, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Villamar, Mauricio F.; Contreras, Vanessa Suarez; Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Villamar, Mauricio F.] Pontifical Catholic Univ Ecuador, Sch Med, Quito, Ecuador. [Kuntz, Richard E.] Medtronic Inc, Minneapolis, MN USA. RP Fregni, F (reprint author), Spaulding Rehabil Hosp, Lab Neuromodulat, Dept Phys Med & Rehabil, 125 Nashua St 726, Boston, MA 02114 USA. EM Fregni.Felipe@mgh.harvard.edu NR 37 TC 7 Z9 8 U1 0 U2 1 PU FOUNDATION REHABILITATION INFORMATION PI UPPSALA PA TRADGARDSGATAN 14, UPPSALA, SE-753 09, SWEDEN SN 1650-1977 J9 J REHABIL MED JI J. Rehabil. Med. PD JAN PY 2013 VL 45 IS 1 BP 6 EP 13 DI 10.2340/16501977-1071 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 071OF UT WOS:000313603400002 PM 23150143 ER PT J AU Wallace, ZS Stone, JH AF Wallace, Zachary S. Stone, John H. TI Refractory Relapsing Polychondritis Treated with Serial Success with Interleukin 6 Receptor Blockade SO JOURNAL OF RHEUMATOLOGY LA English DT Letter ID RHEUMATOID-ARTHRITIS; TOCILIZUMAB; ANTIBODY; DISEASE; IL-6 C1 [Wallace, Zachary S.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Stone, John H.] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. [Stone, John H.] Harvard Univ, Sch Med, Boston, MA USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, 55 Fruit St,Yawkey 2, Boston, MA 02114 USA. EM jhstone@partners.org NR 7 TC 9 Z9 10 U1 0 U2 2 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JAN PY 2013 VL 40 IS 1 BP 100 EP 102 DI 10.3899/jrheum.120381 PG 3 WC Rheumatology SC Rheumatology GA 068UN UT WOS:000313391800031 PM 23280172 ER PT J AU Krishnaraj, A Weinreb, JC Ellenbogen, PH Patti, JA Hillman, BJ AF Krishnaraj, Arun Weinreb, Jeffrey C. Ellenbogen, Paul H. Patti, John A. Hillman, Bruce J. TI Radiology in 2022: Challenges and Opportunities in the Coming Decade-Proceedings of the 12th Annual ACR Forum SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE ACR Forum; future payment models; research; innovation; precision medicine; patient-centered radiology; information management ID MEDICINE; FUTURE AB The 2012 ACR Forum focused on the anticipated challenges and opportunities facing radiology in the next 10 years, centered on the themes of health care reform, future payment models, research and innovation, patient-centered radiology, and information management. The recommendations generated from the forum seek to inform ACR leadership on the best strategies to pursue to ensure the continued success of the profession in the coming decade. C1 [Krishnaraj, Arun; Patti, John A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Weinreb, Jeffrey C.] Yale Univ, New Haven, CT USA. [Ellenbogen, Paul H.] Presbyterian Med Ctr, Radiol Associates N Texas, Dallas, TX USA. [Hillman, Bruce J.] Univ Virginia, Charlottesville, VA USA. RP Krishnaraj, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM akrishnaraj@partners.org NR 9 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JAN PY 2013 VL 10 IS 1 BP 15 EP 20 DI 10.1016/j.jacr.2012.09.022 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 070AN UT WOS:000313478300007 PM 23290668 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Caring for Breast Cancer Survivors SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material C1 [Burstein, Harold J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Burstein, Harold J.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JAN PY 2013 VL 11 IS 1 BP 1 EP 2 PG 2 WC Oncology SC Oncology GA 071FU UT WOS:000313575200001 PM 23307974 ER PT J AU Anderson, KC Alsina, M Bensinger, W Biermann, JS Cohen, AD Devine, S Djulbegovic, B Faber, EA Gasparetto, C Hernandez-Illizaliturri, F Huff, CA Kassim, A Krishnan, AY Liedtke, M Meredith, R Raje, N Schriber, J Singhal, S Somlo, G Stockerl-Goldstein, K Treon, SP Weber, D Yahalom, J Yunus, F Shead, DA Kumar, R AF Anderson, Kenneth C. Alsina, Melissa Bensinger, William Biermann, J. Sybil Cohen, Adam D. Devine, Steven Djulbegovic, Benjamin Faber, Edward A., Jr. Gasparetto, Cristina Hernandez-Illizaliturri, Francisco Huff, Carol Ann Kassim, Adetola Krishnan, Amrita Y. Liedtke, Michael Meredith, Ruby Raje, Noopur Schriber, Jeffrey Singhal, Seema Somlo, George Stockerl-Goldstein, Keith Treon, Steven P. Weber, Donna Yahalom, Joachim Yunus, Furhan Shead, Dorothy A. Kumar, Rashmi TI Multiple Myeloma, Version 1.2013 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID SINGLE-AGENT CARFILZOMIB; RANDOMIZED PHASE-III; PERIPHERAL NEUROPATHY; OPEN-LABEL; BORTEZOMIB; DEXAMETHASONE; COMBINATION; MANAGEMENT; ARM AB These NCCN Guidelines Insights highlight the important updates/changes specific to the management of relapsed or progressive disease in the 2013 version of the NCCN Clinical Practice Guidelines in Oncology for Multiple Myeloma. These changes include the addition of new regimens as options for salvage therapy and strategies to mitigate the adverse effects and risks associated with newer regimens for the treatment of multiple myeloma. (JNCCN 2013;11:11-17) C1 [Anderson, Kenneth C.; Treon, Steven P.] Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Milford, MA USA. [Alsina, Melissa; Djulbegovic, Benjamin] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Bensinger, William] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Biermann, J. Sybil] Univ Michigan, Comprehens Canc Ctr, Ann Arbor, MI 48109 USA. [Cohen, Adam D.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Devine, Steven] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Faber, Edward A., Jr.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Gasparetto, Cristina] Duke Canc Inst, Durham, NC USA. [Hernandez-Illizaliturri, Francisco] Roswell Pk Canc Inst, Buffalo, NY USA. [Kassim, Adetola] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Liedtke, Michael] Stanford Canc Inst, Stanford, CA USA. [Meredith, Ruby] Univ Alabama, Birmingham Comprehens Canc Ctr, Tuscaloosa, AL 35487 USA. [Raje, Noopur] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Schriber, Jeffrey; Weber, Donna] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Singhal, Seema] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Stockerl-Goldstein, Keith] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Stockerl-Goldstein, Keith] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Yahalom, Joachim] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Yunus, Furhan] Univ Tennessee, St Jude Childrens Res Hosp, Inst Canc, Knoxville, TN 37996 USA. RP Anderson, KC (reprint author), Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Milford, MA USA. RI Djulbegovic, Benjamin/I-3661-2012 OI Djulbegovic, Benjamin/0000-0003-0671-1447 FU Celgene Corporation; Millennium Pharmaceuticals, Inc.; AstraZeneca; Pharmaceuticals LP; Bristol-Myers Squibb Company; Genentech, Inc.; Genzyme Corporation; Novartis Pharmaceuticals Corporation; Onyx Pharmaceuticals, Inc.; Amgen Inc.; Eli Lilly and Company; Acetylon; Eisai, Inc.; Millennium: The Takeda Oncology Company; Teva Pharmaceuticals; Bayer HealthCare Pharmaceuticals Inc.; Endo Pharmaceuticals and HealthTronics FX Dr. Alsina: Clinical research support from Celgene Corporation and Millennium Pharmaceuticals, Inc. Consultant for Celgene Corporation. Advisory board member for Millennium Pharmaceuticals, Inc. Speaker bureau member for Ortho Biotech Products, L.P.; Dr. Bensinger: Clinical research support from AstraZeneca Pharmaceuticals LP; Bristol-Myers Squibb Company; Celgene Corporation; Genentech, Inc.; Genzyme Corporation; Millennium Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; and Speaker bureau member for Celgene Corporation. Advisory board member for Genzyme Corporation; Millennium Pharmaceuticals, Inc.; and Onyx Pharmaceuticals, Inc.; Dr. Raje: Research funding from Amgen Inc. and Eli Lilly and Company. Research grant from Acetylon. Consultant for Celgene Corporation; Millennium Pharmaceuticals, Inc.; Onyx Pharmaceuticals, Inc.; Supported by educational grants from Eisai, Inc.; Millennium: The Takeda Oncology Company; Teva Pharmaceuticals; Bayer HealthCare Pharmaceuticals Inc.; Celgene Corporation; and Endo Pharmaceuticals and HealthTronics. NR 20 TC 40 Z9 49 U1 0 U2 7 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JAN PY 2013 VL 11 IS 1 BP 11 EP 17 PG 7 WC Oncology SC Oncology GA 071FU UT WOS:000313575200004 PM 23307977 ER PT J AU Kalemkerian, GP Akerley, W Bogner, P Borghaei, H Chow, LQM Downey, RJ Gandhi, L Ganti, AKP Govindan, R Grecula, JC Hayman, J Heist, RS Horn, L Jahan, T Koczywas, M Loo, BW Merritt, RE Moran, CA Niell, HB O'Malley, J Patel, JD Ready, N Rudin, CM Williams, CC Gregory, K Hughes, M AF Kalemkerian, Gregory P. Akerley, Wallace Bogner, Paul Borghaei, Hossein Chow, Laura Q. M. Downey, Robert J. Gandhi, Leena Ganti, Apar Kishor P. Govindan, Ramaswamy Grecula, John C. Hayman, James Heist, Rebecca Suk Horn, Leora Jahan, Thierry Koczywas, Marianna Loo, Billy W., Jr. Merritt, Robert E. Moran, Cesar A. Niell, Harvey B. O'Malley, Janis Patel, Jyoti D. Ready, Neal Rudin, Charles M. Williams, Charles C., Jr. Gregory, Kristina Hughes, Miranda TI Small Cell Lung Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID PHASE-III TRIAL; PROPHYLACTIC CRANIAL IRRADIATION; COOPERATIVE-ONCOLOGY-GROUP; COLONY-STIMULATING FACTOR; CISPLATIN PLUS ETOPOSIDE; QUALITY-OF-LIFE; POSITRON-EMISSION-TOMOGRAPHY; MULTICENTER RANDOMIZED-TRIAL; EATON MYASTHENIC SYNDROME; FORTHCOMING 7TH EDITION AB Neuroendocrine tumors account for approximately 20% of lung cancers; most (approximate to 15%) are small cell lung cancer (SCLC). These NCCN Clinical Practice Guidelines in Oncology for SCLC focus on extensive-stage SCLC because it occurs more frequently than limited-stage disease. SCLC is highly sensitive to initial therapy; however, most patients eventually die of recurrent disease. In patients with extensive-stage disease, chemotherapy alone can palliate symptoms and prolong survival in most patients; however, long-term survival is rare. Most cases of SCLC are attributable to cigarette smoking; therefore, smoking cessation should be strongly promoted. (JNCCN 2013;11:78-98) C1 [Kalemkerian, Gregory P.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Akerley, Wallace] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Bogner, Paul] Roswell Pk Canc Inst, Buffalo, NY USA. [Borghaei, Hossein] Fox Chase Canc Ctr, Philadelphia, PA USA. [Chow, Laura Q. M.] Seattle Canc Ctr Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Downey, Robert J.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Ganti, Apar Kishor P.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Govindan, Ramaswamy] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Govindan, Ramaswamy] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Grecula, John C.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Hayman, James] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Heist, Rebecca Suk] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Horn, Leora] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Jahan, Thierry] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Loo, Billy W., Jr.; Merritt, Robert E.] Stanford Canc Inst, Stanford, CA USA. [Moran, Cesar A.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Niell, Harvey B.] Univ Tennessee, St Jude Childrens Res Hosp, Inst Canc, Knoxville, TN 37996 USA. [O'Malley, Janis] Univ Alabama, Birmingham Comprehens Canc Ctr, Tuscaloosa, AL 35487 USA. [Patel, Jyoti D.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Ready, Neal] Duke Canc Inst, Durham, NC USA. RP Kalemkerian, GP (reprint author), Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. RI Grecula, John/E-3149-2011 FU NCI NIH HHS [P30 CA006973] NR 143 TC 77 Z9 93 U1 4 U2 18 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JAN PY 2013 VL 11 IS 1 BP 78 EP 98 PG 21 WC Oncology SC Oncology GA 071FU UT WOS:000313575200011 PM 23307984 ER PT J AU van der Wilden, GM Albers, CE Haefeli, PC Zimmermann, H Exadaktylos, A Levy, P Birkhan, O Michaildou, M Sideris, A Velmahos, GC Alam, HB King, DR Fagenholz, PJ Yeh, DD de Moya, MA AF van der Wilden, Gwendolyn M. Albers, Christoph E. Haefeli, Pascal C. Zimmermann, Heinz Exadaktylos, Aristomenis Levy, Phillip Birkhan, Oscar Michaildou, Maria Sideris, Antonios Velmahos, George C. Alam, Hasan B. King, David R. Fagenholz, Peter J. Yeh, D. Dante de Moya, Marc A. TI Using micropower impulse radar technology to screen for pneumothorax: An international bi-institutional study (vol 73, pg 1046, 2012) SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Correction C1 [van der Wilden, Gwendolyn M.; Birkhan, Oscar; Michaildou, Maria; Sideris, Antonios; Velmahos, George C.; Alam, Hasan B.; King, David R.; Fagenholz, Peter J.; Yeh, D. Dante; de Moya, Marc A.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [van der Wilden, Gwendolyn M.; Birkhan, Oscar; Michaildou, Maria; Sideris, Antonios; Velmahos, George C.; Alam, Hasan B.; King, David R.; Fagenholz, Peter J.; Yeh, D. Dante; de Moya, Marc A.] Harvard Univ, Sch Med, Boston, MA USA. [Albers, Christoph E.; Haefeli, Pascal C.; Zimmermann, Heinz; Exadaktylos, Aristomenis] Univ Bern, Inselspital, Univ Hosp Bern, Dept Emergency Med, CH-3010 Bern, Switzerland. RP van der Wilden, GM (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD JAN PY 2013 VL 74 IS 1 BP 347 EP 347 DI 10.1097/01.ta.0000426021.38942.9d PG 1 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 071VI UT WOS:000313623300076 ER PT J AU Patel, NH Krishnamurthy, VN Kim, S Saad, WE Ganguli, S Walker, TG Nikolic, B AF Patel, Nilesh H. Krishnamurthy, Venkataramu N. Kim, Stanley Saad, Wael E. Ganguli, Suvranu Walker, T. Gregory Nikolic, Boris CA CIRSE Stand Practice Comm SIR Stand Practice Comm TI Quality Improvement Guidelines for Percutaneous Management of Acute Lower-extremity Ischemia SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID TISSUE-PLASMINOGEN-ACTIVATOR; DIRECTED THROMBOLYTIC THERAPY; ACUTE PERIPHERAL ARTERIAL; LOWER-LIMB ISCHEMIA; PROSPECTIVE RANDOMIZED TRIAL; ULTRASOUND-ENHANCED THROMBOLYSIS; TRELLIS THROMBECTOMY SYSTEM; HIGH-DOSE UROKINASE; BYPASS GRAFTS; INTRAARTERIAL THROMBOLYSIS C1 [Patel, Nilesh H.; Kim, Stanley] Cent DuPage Hosp, Vasc & Intervent Program, Winfield, IL 60190 USA. [Krishnamurthy, Venkataramu N.] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. Ann Arbor Vet Affairs Hlth Syst, Ann Arbor, MI USA. [Saad, Wael E.] Univ Virginia Hlth Syst, Dept Radiol, Charlottesville, VA USA. [Ganguli, Suvranu; Walker, T. Gregory] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Nikolic, Boris] Albert Einstein Med Ctr, Dept Radiol, Philadelphia, PA 19141 USA. RP Patel, NH (reprint author), Cent DuPage Hosp, Vasc & Intervent Program, 25 N Winfield Rd, Winfield, IL 60190 USA. EM nilesh.patel@cadencehealth.org NR 119 TC 5 Z9 5 U1 1 U2 3 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 JAN PY 2013 VL 24 IS 1 BP 3 EP 15 DI 10.1016/j.jvir.2012.09.026 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 071MT UT WOS:000313598300002 PM 23273693 ER PT J AU Etchin, J Sun, Q Kentsis, A Farmer, A Zhang, ZC Sanda, T Mansour, MR Barcelo, C McCauley, D Kauffman, M Shacham, S Christie, AL Kung, AL Rodig, SJ Chook, YM Look, AT AF Etchin, J. Sun, Q. Kentsis, A. Farmer, A. Zhang, Z. C. Sanda, T. Mansour, M. R. Barcelo, C. McCauley, D. Kauffman, M. Shacham, S. Christie, A. L. Kung, A. L. Rodig, S. J. Chook, Y. M. Look, A. T. TI Antileukemic activity of nuclear export inhibitors that spare normal hematopoietic cells SO LEUKEMIA LA English DT Article DE CRM1; nuclear export inhibitors; AML ID LEPTOMYCIN-B; NUCLEOCYTOPLASMIC TRANSPORT; STRUCTURAL BASIS; CRM1; SIGNALS; COMPLEX; ENTRAPMENT; RESISTANCE; MECHANISM; APOPTOSIS AB Drugs that target the chief mediator of nuclear export, chromosome region maintenance 1 protein (CRM1) have potential as therapeutics for leukemia, but existing CRM1 inhibitors show variable potencies and a broad range of cytotoxic effects. Here, we report the structural analysis and antileukemic activity of a new generation of small-molecule inhibitors of CRM1. Designated selective inhibitors of nuclear export (SINE), these compounds were developed using molecular modeling to screen a small virtual library of compounds against the nuclear export signal (NES) groove of CRM1. The 2.2-angstrom crystal structure of the CRM1-Ran-RanBP1 complex bound to KPT-251, a representative molecule of this class of inhibitors, shows that the drug occupies part of the groove in CRM1 that is usually occupied by the NES, but penetrates much deeper into the groove and blocks CRM1-directed protein export. SINE inhibitors exhibit potent antileukemic activity, inducing apoptosis at nanomolar concentrations in a panel of 14 human acute myeloid leukemia (AML) cell lines representing different molecular subtypes of the disease. When administered orally to immunodeficient mice engrafted with human AML cells, KPT-251 had potent antileukemic activity with negligible toxicity to normal hematopoietic cells. Thus, KPT-SINE CRM1 antagonists represent a novel class of drugs that warrant further testing in AML patients. Leukemia (2013) 27, 66-74; doi:10.1038/leu.2012.219 C1 [Etchin, J.; Kentsis, A.; Sanda, T.; Mansour, M. R.; Barcelo, C.; Christie, A. L.; Kung, A. L.; Look, A. T.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Div Hematol Oncol,Childrens Hos, Boston, MA 02115 USA. [Sun, Q.; Farmer, A.; Zhang, Z. C.; Chook, Y. M.] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA. [McCauley, D.; Kauffman, M.; Shacham, S.] Karyopharm Therapeut, Natick, MA USA. [Rodig, S. J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Chook, YM (reprint author), Univ Texas SW Med Ctr Dallas, Dept Pharmacol, 6001 Forest Pk,ND8-120C, Dallas, TX 75390 USA. EM yuhminchook@utsouthwestern.edu; thomas_look@dfci.harvard.edu RI ZHANG, ZICHAO/C-1764-2014; OI ZHANG, ZICHAO/0000-0003-3402-7757; Kentsis, Alex/0000-0002-8063-9191; Kung, Andrew/0000-0002-9091-488X FU William Lawrence and Hughes Blanche Foundation; V Foundation; National Institutes of Health [R01-GM069909]; Welch Foundation [I-1532]; Leukemia and Lymphoma Society; CPRIT [RP120352, PR-101496]; UT Southwestern Endowed Scholars Program; U.S. Department of Energy, Office of Biological and Environmental Research [DE-AC02-06CH11357]; [NIH-T32HL007623]; [NIH-K08CA160660] FX The research was supported by NIH-T32HL007623 (JE), William Lawrence and Hughes Blanche Foundation (JE), NIH-K08CA160660 (AK) and the V Foundation (ATL). This work is also funded by the National Institutes of Health R01-GM069909 (YMC), Welch Foundation (I-1532; YMC), Leukemia and Lymphoma Society Scholar award (YMC), CPRIT (RP120352; YMC), UT Southwestern Endowed Scholars Program (YMC) and CPRIT (PR-101496; QS). Results shown in this report are derived from work performed at Argonne National Laboratory, Structural Biology Center at the Advanced Photon Source. Argonne is operated by UChicago Argonne, LLC, for the U.S. Department of Energy, Office of Biological and Environmental Research under contract DE-AC02-06CH11357. We thank John Gilbert for his editorial review and critical comments. NR 37 TC 77 Z9 77 U1 6 U2 22 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JAN PY 2013 VL 27 IS 1 BP 66 EP 74 DI 10.1038/leu.2012.219 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 070MP UT WOS:000313511400010 PM 22847027 ER PT J AU Pemberton, JD Miller, J Commander, J Michalos, P Fay, A AF Pemberton, John D. Miller, John Commander, Jason Michalos, Peter Fay, Aaron TI Electronically Assisted Nasolacrimal Duct Silicone Intubation SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID LACRIMAL SYSTEM; GROOVE DIRECTOR; OBSTRUCTION; CHILDREN AB Purpose: Nasolacrimal duct intubation (NLDI) with silicone stents is a common procedure used by general ophthalmologists, oculoplastic surgeons, and otolaryngologists, among others. The procedure can be difficult to teach and to master. The authors investigated the usefulness and safety of an electronic device to aid endonasal retrieval of the lacrimal stent used in NLDI. Methods: A prospective interventional surgical technique case series was designed and executed with institutional review board approval. Twelve adult patients who were scheduled to undergo NLDI were enrolled. The audible alarm device was used during endonasal retrieval of the probe in each patient. Each patient underwent intraoperative rigid nasal endoscopy at the conclusion of the case. Results: The electronic device successfully localized the endonasal probe in each patient. Nasal endoscopy revealed healthy mucosa with no evidence of thermal or electrical injury. Conclusions: Electronically assisted NLDI with audible feedback is a small technological advance with potential to improve the safety and efficacy of NLDI. The technique is safe and effective in localizing the intranasal portion of a metal lacrimal probe. Further testing will assess its usefulness in complex cases and as a teaching tool. (Ophthal Plast Reconstr Surg 2013;29:18-20) C1 [Pemberton, John D.] Univ Arkansas Med Sci, Dept Ophthalmol, Little Rock, AR 72205 USA. [Pemberton, John D.] Jones Eye Inst, Little Rock, AR USA. [Miller, John; Commander, Jason; Fay, Aaron] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Michalos, Peter] Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA. [Fay, Aaron] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Fay, A (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM aaron_fay@meei.harvard.edu OI Pemberton, John/0000-0001-6305-4653 NR 18 TC 2 Z9 5 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD JAN-FEB PY 2013 VL 29 IS 1 BP 18 EP 20 DI 10.1097/IOP.0b013e31826e4bed PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 070XM UT WOS:000313547400022 PM 23128537 ER PT J AU Corey, KC Cheng, CE Irwin, B Kimball, AB AF Corey, Kristen C. Cheng, Carol E. Irwin, Blair Kimball, Alexandra B. TI Self-Reported Help-Seeking Behaviors and Treatment Choices of Adolescents Regarding Acne SO PEDIATRIC DERMATOLOGY LA English DT Article ID PREVALENCE; VULGARIS; PERCEPTIONS; SEVERITY; ADHERENCE; BELIEFS AB Acne vulgaris is a common condition affecting adolescents that they often choose to treat on their own rather than seek out and follow medical advice. Using data from an anonymous survey administered to 1,214 students in public middle and high schools in New Jersey, we compared the self-reported acne frequency, severity, and beliefs of students based on their help-seeking behaviors, treatment choices, and treatment adherence. Chi-square analyses were performed for data comparison. A large proportion of students in this sample (57%) treated their own acne, and a much smaller proportion (17%) have sought medical care. Students who saw a health professional reported acne of higher frequency and severity than those who did not (p = 0.01). Severity also appeared to affect treatment adherence, with students who adhered to recommended treatments reporting more frequent (p < 0.001) and more severe (p = 0.02) acne than those who chose to self-treat. Beliefs and knowledge varied most significantly according to treatment adherence. In conclusion, most adolescent students treat their own acne. Self-assessment of acne severity plays a significant role in the tendency to seek out and adhere to medical treatment. Beliefs and knowledge may also affect adherence, suggesting a role for physicians to influence adherence rates through patient education. Because the majority of students are getting information from nonphysician sources, there may be a need to evaluate the resources they are using to make sure they are receiving appropriate, helpful information. C1 [Corey, Kristen C.] Univ Massachusetts Med Sch, Worcester, MA USA. [Irwin, Blair] Duke Univ Med Ctr, Durham, NC USA. [Kimball, Alexandra B.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kimball, Alexandra B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. EM harvardskinstudies@partners.org NR 16 TC 6 Z9 7 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-8046 J9 PEDIATR DERMATOL JI Pediatr. Dermatol. PD JAN-FEB PY 2013 VL 30 IS 1 BP 36 EP 41 DI 10.1111/j.1525-1470.2012.01807.x PG 6 WC Dermatology; Pediatrics SC Dermatology; Pediatrics GA 073FA UT WOS:000313727700006 PM 22888857 ER PT J AU Beach, SR Celano, CM Noseworthy, PA Januzzi, JL Huffman, JC AF Beach, Scott R. Celano, Christopher M. Noseworthy, Peter A. Januzzi, James L. Huffman, Jeff C. TI QTc Prolongation, Torsades de Pointes, and Psychotropic Medications SO PSYCHOSOMATICS LA English DT Review ID PLACEBO-CONTROLLED TRIAL; SUDDEN CARDIAC DEATH; INTERVAL PROLONGATION; DOUBLE-BLIND; ANTIPSYCHOTIC-DRUGS; ANTIDEPRESSANT DRUGS; CITALOPRAM OVERDOSE; MAJOR DEPRESSION; TRICYCLIC ANTIDEPRESSANTS; INTRAMUSCULAR OLANZAPINE AB Background: Prolongation of the corrected QT (QTc) interval is a key issue for patients who receive psychotropic medications. Such patients may have baseline clinical risk factors for QTc prolongation, and many psychotropic medications may further prolong this interval. This has great clinical relevance, as QTc prolongation is linked with dangerous arrhythmias, especially torsades de pointes (TdP). Methods: We summarize current literature regarding appropriate methods of calculating the QTc interval, the association of the QTc interval with TdP, and risk factors for QTc prolongation. We then review connections between psychiatric medications and QTc prolongation, with a specific focus on antidepressants and antipsychotics. Results: QTc interval prolongation is an established, though imperfect, risk marker for TdP. There are no well-controlled studies that assess the risk of TdP associated with psychotropic agents. There are limited data that selective serotonin reuptake inhibitors (SSRIs) as a class are linked to QTc prolongation; citalopram appears more likely than others to induce this phenomenon. Among antipsychotics, thioridazine remains the agent most associated with QTc prolongation; intravenous haloperidol also appears to carry an increased risk Of the atypical antipsychotics, ziprasidone appears most likely to prolong the QTc interval. Conclusions: The majority of patients in need of psychotropic medications display few risk factors for QTc prolongation and should be considered to be at low risk for TdP. The frequency of cardiac monitoring for patients receiving psychiatric medications should be individually determined, based on the prescribed agent(s) and additional risk factors for TdP. (Psychosomatics 2013; 54:1-13) C1 [Celano, Christopher M.; Noseworthy, Peter A.; Januzzi, James L.; Huffman, Jeff C.] Harvard Univ, Sch Med, Boston, MA USA. [Celano, Christopher M.; Huffman, Jeff C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Noseworthy, Peter A.; Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Beach, SR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Warren 605, Boston, MA 02114 USA. EM sbeach1@partners.org NR 108 TC 68 Z9 72 U1 1 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 2013 VL 54 IS 1 BP 1 EP 13 PG 13 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 071QS UT WOS:000313609900001 PM 23295003 ER PT J AU Bauer, LK Baggett, TP Stern, TA O'Connell, JJ Shtasel, D AF Bauer, Leah K. Baggett, Travis P. Stern, Theodore A. O'Connell, Jim J. Shtasel, Derri TI Caring for Homeless Persons with Serious Mental Illness in General Hospitals SO PSYCHOSOMATICS LA English DT Review ID ASSERTIVE COMMUNITY TREATMENT; CRITICAL TIME INTERVENTION; HEALTH-CARE; RANDOMIZED-TRIAL; ACCESS PROGRAM; SERVICE USE; TRAUMA; PEOPLE; ADULTS; MORTALITY AB Background: The care of homeless persons with serious mental illness remains a common and challenging problem in general hospital settings. Objective: This article aims to review data on homelessness and its psychiatric comorbidities, and to expand the skills of providers who encounter homeless individuals in general hospital settings. Results: Literature review reveals patient, provider, and systems factors that contribute to suboptimal health outcomes in homeless individuals. Conclusions: Diagnostic rigor, integrated medical and psychiatric care, trauma-informed interventions, special considerations in capacity evaluations, and health care reform initiatives can improve the treatment of homeless persons with serious mental illness. (Psychosomatics 2013; 54:14-21) C1 [Stern, Theodore A.; Shtasel, Derri] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bauer, Leah K.] McLean Hosp, Belmont, MA 02478 USA. [Baggett, Travis P.; O'Connell, Jim J.] Boston Hlth Care Homeless Program, Boston, MA USA. RP Bauer, LK (reprint author), McLean Hosp, Mail Stop 109, Belmont, MA 02478 USA. EM lbauer@partners.org FU National Institute on Drug Abuse of the National Institutes of Health [K23DA034008] FX Travis P. Baggett is supported by award number K23DA034008 from the National Institute on Drug Abuse of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 43 TC 6 Z9 6 U1 1 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 2013 VL 54 IS 1 BP 14 EP 21 PG 8 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 071QS UT WOS:000313609900002 PM 23295004 ER PT J AU Wiechers, IR Freudenreich, O AF Wiechers, Ilse R. Freudenreich, Oliver TI The Role of Consultation-Liaison Psychiatrists in Improving Health Care of Patients with Schizophrenia SO PSYCHOSOMATICS LA English DT Article ID RANDOMIZED-CONTROLLED-TRIAL; SERIOUS MENTAL-ILLNESS; INDUCED WEIGHT-GAIN; COLLABORATIVE CARE; METABOLIC SYNDROME; MEDICAL-CARE; ANTIPSYCHOTIC POLYPHARMACY; CONSENSUS STATEMENT; COST-EFFECTIVENESS; HEPATITIS-C AB One key challenge for care of the next generation of patients with schizophrenia is reducing and preventing medical morbidity. To improve their healthcare, we suggest that consultation-liaison (C-L) psychiatrists should be leaders in an effort to close the gap between psychiatric and medical care for patients with schizophrenia. We contend that C-L psychiatrists are well equipped to help manage the care of these patients because of their expertise in caring for complex patients, working in teams, and collaborating with medical and surgical colleagues. We provide specific examples (antipsychotic-induced metabolic monitoring; smoking cessation; infectious disease screening) of how C-L psychiatrists can rise to the challenge now and moving forward. (Psychosomatics 2013; 54:22-27) C1 [Wiechers, Ilse R.] Yale Univ, Sch Med, Robert Wood Johnson Fdn Clin Scholars Program, New Haven, CT 06520 USA. [Wiechers, Ilse R.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Freudenreich, Oliver] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Wiechers, IR (reprint author), Yale Univ, Sch Med, Robert Wood Johnson Fdn Clin Scholars Program, 333 Cedar St,POB 208088, New Haven, CT 06520 USA. EM ilse.wiechers@yale.edu FU Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment; VA Connecticut Healthcare System; National Center for PTSD; Pfizer; Psychogenics FX Dr. Wiechers discloses research support from the Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment, the VA Connecticut Healthcare System, and the National Center for PTSD. Dr. Freudenreich discloses research grant support from Pfizer and Psychogenics; consultant, for Beacon Health Strategies and Optimal Medicine; honoraria for lectures from MGH Psychiatry Academy and General Medical Education. NR 57 TC 3 Z9 3 U1 4 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 2013 VL 54 IS 1 BP 22 EP 27 PG 6 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 071QS UT WOS:000313609900003 PM 23194936 ER PT J AU Kroll, DS Smallwood, J Chang, G AF Kroll, David S. Smallwood, Jennifer Chang, Grace TI Drug Screens for Psychiatric Patients in the Emergency Department: Evaluation and Recommendations SO PSYCHOSOMATICS LA English DT Article ID SUBSTANCE USE; MANAGEMENT; INTOXICATION; DISORDERS; OVERDOSE; ALCOHOL AB Objective: To better understand how toxicology screening for psychiatric patients in the emergency department (ED) setting affects diagnostic decisions. Methods: Retrospective chart review of 439 ED visits of adult patients receiving psychiatry consultations at two hospitals, one an academic medical center (n =224) and the other a community hospital (n = 220), between July 2008 and February 2009. Clinical, demographic, and ED length of stay (LOS) information was abstracted from the psychiatry consultation notes and the medical records. Results: Positive urine toxicology results, when combined with a basic substance abuse history, were not associated independently with a patient's receiving a substance-related diagnosis as part of the psychiatric assessment. By contrast, a positive blood alcohol level was associated independently with a patient's receiving one of these diagnoses while a positive alcohol use history was not. Conclusions: Urine toxicology screens do not add significant diagnostic value to all ED psychiatric evaluations when combined with standard substance use histories. (Psychosomatics 2013; 54:60-66) C1 [Chang, Grace] Brigham & Womens Hosp, Dept Psychiat, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Smallwood, Jennifer] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Kroll, DS (reprint author), 221 Longwood Ave,BLI 4th Floor, Boston, MA 02115 USA. EM dskroll@partners.org FU Psychiatry and Mental Health Division of Health Services Research; NIAAA [AA K24 000289] FX This study was supported in part by the Partners Psychiatry and Mental Health Division of Health Services Research (Jennifer Smallwood, Grace Chang) and NIAAA AA K24 000289 (Grace Chang). NR 18 TC 3 Z9 3 U1 3 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 2013 VL 54 IS 1 BP 60 EP 66 PG 7 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 071QS UT WOS:000313609900008 PM 23194932 ER PT J AU Branson McCoy Mangus, MW Lewarski, JS Pierson, DJ Kallet Criner Hess, DR Ward, J AF Branson McCoy Mangus, Mark W., Sr. Lewarski, Joseph S. Pierson, David J. Kallet Criner Hess, Dean R. Ward, Jeff TI Options for Home Oxygen Therapy Equipment: Storage and Metering of Oxygen in the Home Discussion SO RESPIRATORY CARE LA English DT Editorial Material C1 [Mangus, Mark W., Sr.] Inova Labs, Austin, TX USA. [Lewarski, Joseph S.] Invacare, Elyria, OH USA. [Pierson, David J.] Univ Washington, Harborview Med Ctr, Div Pulm & Crit Care Med, Seattle, WA 98104 USA. [Hess, Dean R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Resp Care, Boston, MA USA. NR 4 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2013 VL 58 IS 1 SI SI BP 81 EP 85 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 071PG UT WOS:000313606100009 ER PT J AU Owens Branson Kallet McCoy Hess, DR Lewarski, JS Criner Pierson, DJ Ward, K Treggiari AF Owens Branson Kallet McCoy Hess, Dean R. Lewarski, Joseph S. Criner Pierson, David J. Ward, Kevin Treggiari TI Pre-Hospital Oxygen Therapy Discussion SO RESPIRATORY CARE LA English DT Editorial Material ID OBSTRUCTIVE PULMONARY-DISEASE; EXERCISE; BREATHLESSNESS; HYPOXEMIA; DYSPNEA; TRIAL C1 [Hess, Dean R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Resp Care, Boston, MA USA. [Lewarski, Joseph S.] Invacare, Elyria, OH USA. [Pierson, David J.] Univ Washington, Harborview Med Ctr, Div Pulm & Crit Care Med, Seattle, WA 98104 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2013 VL 58 IS 1 SI SI BP 95 EP 97 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 071PG UT WOS:000313606100011 ER PT J AU Hess, DR Ward, K Ward, J Branson Kallet AF Hess, Dean R. Ward, Kevin Ward, Jeff Branson Kallet TI Chemical Oxygen Generation Discussion SO RESPIRATORY CARE LA English DT Editorial Material C1 [Hess, Dean R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Resp Care, Boston, MA 02115 USA. RP Hess, DR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Resp Care, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 1 U2 1 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 JAN PY 2013 VL 58 IS 1 SI SI BP 194 EP 195 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 071PG UT WOS:000313606100025 ER PT J AU Goldman, DR Freund, KB McCannel, CA Sarraf, D AF Goldman, Darin R. Freund, K. Bailey McCannel, Colin A. Sarraf, David TI PERIPHERAL POLYPOIDAL CHOROIDAL VASCULOPATHY AS A CAUSE OF PERIPHERAL EXUDATIVE HEMORRHAGIC CHORIORETINOPATHY A Report of 10 Eyes SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE age-related macular degeneration; anti-vascular endothelial growth factor; choroidal neovascular membrane; fluorescein angiography; indocyanine green angiography; optical coherence tomography; peripheral exudative hemorrhagic chorioretinopathy; peripheral retina; polypoidal choroidal vasculopathy; type 1 neovascularization AB Purpose: Polypoidal choroidal vasculopathy (PCV) is characterized by polyp-like subretinal pigment epithelium vascular abnormalities predominantly found in the macula and peripapillary region. Less commonly, PCV can be found peripherally and be a cause of peripheral exudative hemorrhagic chorioretinopathy (PEHCR). We sought to further describe the clinical spectrum of this ill-defined subgroup of PEHCR. Methods: A retrospective observational case series, of 10 eyes of 8 patients diagnosed with PEHCR caused by peripheral PCV, was conducted. In all cases, the presence of PCV was confirmed with indocyanine green angiography and/or fluorescein angiography and optical coherence tomography. The clinical presentation, natural history, and clinical outcomes with or without intervention were studied. Results: Patients with PEHCR caused by peripheral PCV were most commonly men, white, asymptomatic, and had a concomitant diagnosis of age-related macular degeneration. The mean age was 70 years (range, 59-82 years) with a mean follow-up of 32.5 months (range, 4-91 months). Four patients had unilateral involvement with minimal subretinal hemorrhage that resolved spontaneously, one patient had unilateral involvement outside the macula that responded to anti-vascular endothelial growth factor therapy, one patient had unilateral involvement with subretinal hemorrhage threatening the macula that responded to anti-vascular endothelial growth factor therapy, and two patients had extensive bilateral subretinal hemorrhage requiring surgical intervention. Both patients with multiple lesions in one eye had bilateral lesions (two of eight patients). Lesions were most commonly located in the temporal periphery (8 of 10 eyes). Conclusion: A new subclassification is proposed that includes both eyes with polyps and those without polyps within the spectrum of disease described previously as PEHCR. Within the spectrum of disease described previously as PEHCR exists a subgroup of lesions caused by peripheral PCV, which has not been well defined before this report. The largest case series to date of eyes with PEHCR due to peripheral PCV, a unique form of type 1 neovascularization, is further classified and described. These eyes have a spectrum of disease, including small, medium-sized, and large lesions. Although most eyes with PEHCR from peripheral PCV experience a benign course with spontaneous resolution, a subset of eyes may experience macula-threatening hemorrhage, requiring treatment with laser-based therapies, anti-vascular endothelial growth factor injections, or surgical intervention. RETINA 33:48-55, 2013 C1 [Sarraf, David] Univ Calif Los Angeles, Geffen Sch Med, Retinal Disorders & Ophthalm Genet Div, Dept Ophthalmol,Jules Stein Eye Inst, Los Angeles, CA 90095 USA. [Freund, K. Bailey] NYU, Dept Ophthalmol, Sch Med, New York, NY 10016 USA. [Freund, K. Bailey] Vitreous Retina Macula Consultants New York, New York, NY USA. [Sarraf, David] Greater Los Angeles VA Healthcare Ctr, Dept Ophthalmol, Los Angeles, CA USA. RP Sarraf, D (reprint author), Univ Calif Los Angeles, Geffen Sch Med, Retinal Disorders & Ophthalm Genet Div, Dept Ophthalmol,Jules Stein Eye Inst, Los Angeles, CA 90095 USA. EM dsarraf@ucla.edu OI McCannel, Colin/0000-0003-0774-6414; Freund, K. Bailey/0000-0002-7888-9773 FU Macula Foundation, Inc., New York, New York; Karl Kirchgessner Foundation FX This study was partly funded by a grant from the Macula Foundation, Inc., New York, New York, and partly funded by a grant from the Karl Kirchgessner Foundation. NR 11 TC 8 Z9 8 U1 0 U2 1 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 JAN PY 2013 VL 33 IS 1 BP 48 EP 55 DI 10.1097/IAE.0b013e31825df12a PG 8 WC Ophthalmology SC Ophthalmology GA 069GE UT WOS:000313422500006 PM 22836900 ER PT J AU Worley, MJ Tate, SR McQuaid, JR Granholm, EL Brown, SA AF Worley, Matthew J. Tate, Susan R. McQuaid, John R. Granholm, Eric L. Brown, Sandra A. TI 12-Step Affiliation and Attendance Following Treatment for Comorbid Substance Dependence and Depression: A Latent Growth Curve Mediation Model SO SUBSTANCE ABUSE LA English DT Article DE Comorbidity; mediation; 12-step involvement ID USE DISORDERS; MAJOR DEPRESSION; BEHAVIORAL TREATMENT; PROJECT MATCH; USE OUTCOMES; ALCOHOL; FACILITATION; INVOLVEMENT; MECHANISMS; RELAPSE AB Among substance-dependent individuals, comorbid major depressive disorder (MDD) is associated with greater severity and poorer treatment outcomes, but little research has examined mediators of posttreatment substance use outcomes within this population. Using latent growth curve models, the authors tested relationships between individual rates of change in 12-step involvement and substance use, utilizing posttreatment follow-up data from a trial of group Twelve-Step Facilitation (TSF) and integrated cognitive-behavioral therapy (ICBT) for veterans with substance dependence and MDD. Although TSF patients were higher on 12-step affiliation and meeting attendance at end-of-treatment as compared with ICBT, they also experienced significantly greater reductions in these variables during the year following treatment, ending at similar levels as ICBT. Veterans in TSF also had significantly greater increases in drinking frequency during follow-up, and this group difference was mediated by their greater reductions in 12-step affiliation and meeting attendance. Patients with comorbid depression appear to have difficulty sustaining high levels of 12-step involvement after the conclusion of formal 12-step interventions, which predicts poorer drinking outcomes over time. Modifications to TSF and other formal 12-step protocols or continued therapeutic contact may be necessary to sustain 12-step involvement and reduced drinking for patients with substance dependence and MDD. C1 [Worley, Matthew J.] San Diego State Univ Univ Calif Joint Doctoral Pr, San Diego, CA USA. [Tate, Susan R.; Granholm, Eric L.] San Diego Vet Affairs Healthcare Syst, San Diego, CA USA. [McQuaid, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. [Granholm, Eric L.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Brown, Sandra A.] Univ Calif San Diego, Dept Psychol, La Jolla, CA 92093 USA. RP Brown, SA (reprint author), Univ Calif San Diego, Dept Psychol, La Jolla, CA 92093 USA. EM sandrabrown@ucsd.edu RI Granholm, Eric/P-7680-2014 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research & Development Merit Review Awards; National Institute on Drug Abuse [F31DA030861] FX This research was funded by Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research & Development Merit Review Awards to Dr. Sandra A. Brown and Dr. Susan R. Tate, and by National Institute on Drug Abuse fellowship grant (F31DA030861) awarded to Matthew J. Worley. NR 35 TC 2 Z9 2 U1 2 U2 9 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 J9 SUBST ABUS JI Subst. Abus. PD JAN 1 PY 2013 VL 34 IS 1 SI SI BP 43 EP 50 DI 10.1080/08897077.2012.691451 PG 8 WC Substance Abuse SC Substance Abuse GA 072KL UT WOS:000313669700006 PM 23327503 ER PT J AU Feng, WW Bowden, MG Kautz, S AF Feng, Wuwei (Wayne) Bowden, Mark G. Kautz, Steven TI Review of Transcranial Direct Current Stimulation in Poststroke Recovery SO TOPICS IN STROKE REHABILITATION LA English DT Review DE aphasia; dysphagia; motor deficit; neurorehabilitation; stroke; transcranial direct current stimulation; visual impairment ID SUBACUTE STROKE PATIENTS; HUMAN MOTOR CORTEX; NONINVASIVE CORTICAL STIMULATION; INDUCED MOVEMENT THERAPY; ACUTE ISCHEMIC-STROKE; MAGNETIC STIMULATION; ELECTRICAL-STIMULATION; BRAIN-STIMULATION; DC-STIMULATION; INTERHEMISPHERIC INHIBITION AB Motor impairment, dysphagia, aphasia, and visual impairment are common disabling residual deficits experienced by stroke survivors. Recently, many novel rehabilitative modalities have been investigated for their potential to ameliorate such deficits and to improve functional outcomes. Noninvasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS), have emerged as a promising tool to facilitate stroke recovery. tDCS can alter cortical excitability to induce brain plasticity by modulating the lesioned, contralesional, or bilateral hemispheres with various stimulation modalities. Along with peripheral therapies, tDCS can lead to subsequent sustained behavioral and clinical gains in patients with stroke. In this review, we summarize characteristics of tDCS (method of stimulation, safety profile, and mechanism) and its application in the treatment of various stroke-related deficits, and we highlight future directions for tDCS in this capacity. C1 [Feng, Wuwei (Wayne)] Med Univ S Carolina, Coll Med, Dept Neurosci, Charleston, SC 29425 USA. [Feng, Wuwei (Wayne); Bowden, Mark G.; Kautz, Steven] Med Univ S Carolina, Coll Hlth Profess, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Bowden, Mark G.; Kautz, Steven] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Feng, WW (reprint author), Med Univ S Carolina, Coll Med, Dept Neurosci, Charleston, SC 29425 USA. FU RRD VA [IK2 RX000787] NR 68 TC 15 Z9 20 U1 2 U2 45 PU THOMAS LAND PUBLISHERS, INC PI ST LOUIS PA 255 JEFFERSON RD, ST LOUIS, MO 63119-3627 USA SN 1074-9357 J9 TOP STROKE REHABIL JI Top. Stroke Rehabil. PD JAN-FEB PY 2013 VL 20 IS 1 BP 68 EP 77 DI 10.1310/tsr2001-68 PG 10 WC Rehabilitation SC Rehabilitation GA 073UJ UT WOS:000313768200009 PM 23340073 ER PT J AU Iqbal, SI Elmi, A Hedgire, S Yeddula, K Ganguli, S Walker, TG Salazar, GM Wicky, S Kalva, SP AF Iqbal, Shams I. Elmi, Azadeh Hedgire, Sandeep Yeddula, Kalpana Ganguli, Suvranu Walker, T. Gregory Salazar, Gloria M. Wicky, Stephan Kalva, Sanjeeva P. TI Preliminary Experience With Option Inferior Vena Cava Filter SO VASCULAR AND ENDOVASCULAR SURGERY LA English DT Article DE venous thrombosis; filter; inferior vena cava; pulmonary embolism ID VENOUS THROMBOEMBOLISM; LONG-TERM; PREVENTION; PLACEMENT; RETRIEVAL; SAFETY AB Objectives: To evaluate the safety and efficacy of Option inferior vena cava (IVC) filter during placement and short-term follow-up. Methods: A total of 165 patients (mean age: 60-years) who received Option IVC filter from June 2009 to July 2011 were included. In all, 42 patients presented with deep vein thrombosis (DVT), 26 with pulmonary embolism (PE), and 17 with both. All outcomes were examined until April 30, 2012. Results: The filters were successfully deployed in 161 patients. During follow-up (mean, 9.5 +/- 0.68months), 10 patients were diagnosed with post-filter PE and 13 patients with DVT. There were no instances of fatal PE. Follow-up abdominal computed tomography was available in 60 patients and demonstrated filter-related problems in 8 patients (2: penetration of filter legs, 5: asymptomatic nonocclusive thrombus, and 1: caval occlusion). There were no instances of filter migration or fracture. In total, 27 filters were successfully retrieved after a mean of 5.27 +/- 0.76 months. Conclusion: The Option filter was effective and safe during implantation and short-term follow-up and associated with high technical success at retrieval. C1 [Iqbal, Shams I.] Lahey Clin Fdn, Dept Radiol, Burlington, MA USA. [Elmi, Azadeh; Hedgire, Sandeep; Ganguli, Suvranu; Walker, T. Gregory; Salazar, Gloria M.; Wicky, Stephan; Kalva, Sanjeeva P.] Massachusetts Gen Hosp, Dept Imaging, Boston, MA 02114 USA. [Yeddula, Kalpana] St Joseph Hosp, Dept Med, Chicago, IL USA. [Ganguli, Suvranu; Walker, T. Gregory; Salazar, Gloria M.; Wicky, Stephan; Kalva, Sanjeeva P.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Kalva, SP (reprint author), Massachusetts Gen Hosp, Dept Imaging, GRB 297,55 Fruit St, Boston, MA 02114 USA. EM skalva@partners.org FU National Institutes of Health; National Institutes of Health and Angiodynamics FX The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: TGW received honoraria and royalties from Amirsys for writing book chapters. SW received research grant from the National Institutes of Health and royalties from Amirsys for writing book chapters. SPK received research grant from the National Institutes of Health and Angiodynamics, and royalties from Amirsys and Elsevier for book chapters. NR 22 TC 2 Z9 3 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1538-5744 J9 VASC ENDOVASC SURG JI Vasc. Endovasc. Surg. PD JAN PY 2013 VL 47 IS 1 BP 24 EP 29 DI 10.1177/1538574412465971 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 072IM UT WOS:000313663600004 PM 23143226 ER PT J AU Kassis, C Kalva, SP AF Kassis, Christine Kalva, Sanjeeva P. TI Inferior Vena Cava Filter Penetration Resulting in Renal Pelvis Rupture With Urinoma Formation SO VASCULAR AND ENDOVASCULAR SURGERY LA English DT Article DE inferior vena cava filter; penetration; complication ID GREENFIELD FILTER; MANAGEMENT; DESIGN AB Inferior vena cava (IVC) filter penetration is common and most often asymptomatic. However, penetration may potentially result in a variety of complications, including aortic trauma and small bowel perforation. Described is a case of IVC filter penetration resulting in renal pelvis perforation with urinoma formation. C1 [Kassis, Christine] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Kassis, C (reprint author), Massachusetts Gen Hosp, Dept Radiol, FND 216, Boston, MA 02114 USA. EM ckassis@partners.org NR 13 TC 2 Z9 2 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1538-5744 J9 VASC ENDOVASC SURG JI Vasc. Endovasc. Surg. PD JAN PY 2013 VL 47 IS 1 BP 70 EP 72 DI 10.1177/1538574412465477 PG 3 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 072IM UT WOS:000313663600014 PM 23129578 ER PT J AU Bogoch, II Andrews, JR Zachary, KC Hohmann, EL AF Bogoch, Isaac I. Andrews, Jason R. Zachary, Kimon C. Hohmann, Elizabeth L. TI Diagnosis of influenza from lower respiratory tract sampling after negative upper respiratory tract sampling SO VIRULENCE LA English DT Article DE influenza; human; H1N1 virus; bronchoalveolar lavage; polymerase chain reaction ID 2009 A(H1N1) INFLUENZA; SWINE; INFECTION; CHILDREN; ADULTS; VIRUS AB In this retrospective cohort study, we demonstrate that PCR-confirmed diagnoses of influenza were made solely by lower respiratory sampling in 6.9% of cases, as traditional upper respiratory tract tests were negative, indeterminate or not performed. Clinical features of these cases are presented. Clinicians should consider lower respiratory tract sampling in select cases of influenza-like illness for diagnosis. C1 [Bogoch, Isaac I.] Toronto Gen Hosp, Div Internal Med, Toronto, ON, Canada. [Bogoch, Isaac I.] Toronto Gen Hosp, Div Infect Dis, Toronto, ON, Canada. [Bogoch, Isaac I.; Andrews, Jason R.; Zachary, Kimon C.; Hohmann, Elizabeth L.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Bogoch, Isaac I.; Andrews, Jason R.; Zachary, Kimon C.; Hohmann, Elizabeth L.] Harvard Univ, Sch Med, Boston, MA USA. RP Bogoch, II (reprint author), Toronto Gen Hosp, Div Internal Med, Toronto, ON, Canada. EM Isaac.Bogoch@uhn.ca OI Andrews, Jason/0000-0002-5967-251X NR 13 TC 3 Z9 3 U1 1 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2150-5594 EI 2150-5608 J9 VIRULENCE JI Virulence PD JAN PY 2013 VL 4 IS 1 BP 82 EP 84 DI 10.4161/viru.22466 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 071DL UT WOS:000313566000005 PM 23135351 ER PT J AU Palevsky, PM AF Palevsky, Paul M. TI Renal Replacement Therapy in Acute Kidney Injury SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE Acute kidney injury; Hemodialysis; Hemofiltration; Continuous renal replacement therapy; Critical illness ID CRITICALLY-ILL PATIENTS; CONTINUOUS VENOVENOUS HEMOFILTRATION; INTENSIVE-CARE-UNIT; FAILURE REQUIRING DIALYSIS; ULTRAFILTRATION FLOW-RATES; VOLUME PERITONEAL-DIALYSIS; RANDOMIZED CLINICAL-TRIAL; DAILY HEMODIALYSIS; INTERMITTENT HEMODIALYSIS; INTRACRANIAL-PRESSURE AB Although the use of renal replacement therapy (RRT) to support critically ill patients with acute kidney injury (AKI) has become routine, many of the fundamental questions regarding optimal management of RRT remain. This review summarizes current evidence regarding the timing of initiation of RRT, the selection of the specific modality of RRT, and prescription of the intensity of therapy. Although absolute indications for initiating RRT-such as hyperkalemia and overt uremic symptoms are well recognized, the optimal timing of therapy in patients without these indications continues to be a subject of debate. There does not appear to be a difference in either mortality or recovery of kidney function associated with the various modalities of RRT. Finally, providing higher doses of RRT is not associated with improved clinical outcomes. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. C1 [Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Room 7E123,111F-U,Univ Dr, Pittsburgh, PA 15240 USA. EM palevsky@pitt.edu OI Palevsky, Paul/0000-0002-7334-5400 FU Spectral Diagnostics FX P.M.P is a consultant for the medical advisory boards of Sanofi-Aventis and Cytopherx and has received research support front Spectral Diagnostics. NR 84 TC 14 Z9 21 U1 0 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 1548-5595 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD JAN PY 2013 VL 20 IS 1 BP 76 EP 84 DI 10.1053/j.ackd.2012.09.004 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 068VO UT WOS:000313394500011 PM 23265599 ER PT J AU Miller, JW AF Miller, Joan W. TI Age-Related Macular Degeneration Revisited - Piecing the Puzzle: The LXIX Edward Jackson Memorial Lecture SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID COMPLEMENT FACTOR-H; RETINAL-PIGMENT EPITHELIUM; ORPHAN RECEPTOR-ALPHA; POLYPOIDAL CHOROIDAL VASCULOPATHY; DENSITY LIPOPROTEIN RECEPTOR; NUTRITION EXAMINATION SURVEY; GENOME-WIDE ASSOCIATION; BRUCHS MEMBRANE; RISK-FACTORS; MOUSE MODEL AB PURPOSE: To present the current understanding of age-related macular degeneration (AMD) pathogenesis, based on clinical evidence, epidemiologic data, histopathologic examination, and genetic data; to provide an update on current and emerging therapies; and to propose an integrated model of the pathogenesis of AMD. DESIGN: Review of published clinical and experimental studies. METHODS: Analysis and synthesis of clinical and experimental data. RESULTS: We are closer to a complete understanding of the pathogenesis of AMD, having progressed from clinical observations to epidemiologic observations and clinical pathologic correlation. More recently, modern genetic and genomic studies have facilitated the exploration of molecular pathways. It seems that AMD is a complex disease that results from the interaction of genetic susceptibility with aging and environmental factors. Disease progression also seems to be driven by a combination of genetic and environmental factors. CONCLUSIONS: Therapies based on pathophysiologic features have changed the paradigm for treating neovascular AMD. With improved understanding of the underlying genetic susceptibility, we can identify targets to halt early disease and to prevent progression and vision loss. (Am J Ophthalmol 2013;155:1-35. (c) 2013 by Elsevier Inc. All rights reserved.) C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Massachusetts Eye & Ear Infirm,Dept Ophthalmol, Boston, MA 02114 USA. RP Miller, JW (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Massachusetts Eye & Ear Infirm,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM joan_miller@meei.harvard.edu FU Neovascular Research Fund; Yeatts Retina Fund (Massachusetts Eye and Ear Foundation, Boston, Massachusetts) FX THE AUTHOR COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST AND the following were reported. The Massachusetts Eye and Ear Infirmary has an ownership interest in 3 United States patents directed to the use of verteporfin. In addition, the Massachusetts Eye and Ear Infirmary has ownership interest in certain patent applications directed to the selective destruction of subretinal choroidal neovasculature for the treatment of macular degeneration and other disorders. The Massachusetts Eye and Ear Infirmary receives royalties as a result of these patents and patent applications, and Dr Miller receives a share of the same in accordance with the Massachusetts Eye and Ear Infirmary's institutional Patent Policy and Procedures, which includes royalty-sharing provisions. Publication of this article was supported by the Neovascular Research Fund and Yeatts Retina Fund (Massachusetts Eye and Ear Foundation, Boston, Massachusetts). The author was involved in Design of study; Data collection; Analysis and interpretation of data; Provision of materials, patients, or resources; Obtaining funding; Literature search; Writing article and critical revision; and Final approval of article. Given the editorial perspective nature of this manuscript, there are no issues related to institutional review board approval, Clinical Trials registration, or Institutional Animal Care and Use Committee guidelines. Clinical images are used with proper informed consent and Health Insurance Portability and Accountability Act compliance. The author thanks the following individuals (all from the Department of Ophthalmology, Massachusetts Eye and Ear Infirmary and Harvard Medical School, unless otherwise noted): Wendy Chao for her unflagging support in data acquisition, critical review, and creative/technical input; Kimberley Fechtel for her critical input and review; Alexander Coster Scott (Boston, Massachusetts) for creative and technical help with figures; her mentors, Evangelos Gragoudas, Judah Folkman, (Department of Surgery, Boston Children's Hospital and Harvard Medical School, deceased), Simmons Lessell, and Ephraim Friedman (deceased), for their career-long advice and support; her colleagues Patricia D'Amore and Anthony Adamis (Genentech), for their collaboration and friendship; and her mentees, particularly Ivana Kim, Margaret DeAngelis, (Department of Ophthalmology and Visual Sciences, University of Utah School of Medicine, John A. Moran Eye Center), and Demetrios Vavvas, for their insight and critical review, and who are the generation who will lead the field forward. NR 278 TC 66 Z9 66 U1 0 U2 31 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 JAN PY 2013 VL 155 IS 1 BP 1 EP 35 DI 10.1016/j.ajo.2012.10.018 PG 35 WC Ophthalmology SC Ophthalmology GA 066ML UT WOS:000313224800001 PM 23245386 ER PT J AU Brenner, GJ Nemark, JL Raemer, D AF Brenner, Gary J. Nemark, Jordan L. Raemer, Daniel TI Curriculum and Cases for Pain Medicine Crisis Resource Management Education SO ANESTHESIA AND ANALGESIA LA English DT Article ID SIMULATION; ANESTHESIA; ENVIRONMENT; CARE AB Medical crises that may occur in the setting of a pain medicine service are rare events that require skillful action and teamwork to ensure safe patient outcome. A simulated environment is an ideal venue for both acquisition and reinforcement of this knowledge and skill set. Here, we present an educational curriculum in pain medicine crisis resource management for both pain medicine fellows and attending physicians as well as the results of a successful pilot program. (Anesth Analg 2013;116:107-10) C1 [Brenner, Gary J.] Massachusetts Gen Hosp, Ctr Pain Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Brenner, Gary J.; Raemer, Daniel] Ctr Med Simulat, Cambridge, MA USA. [Brenner, Gary J.; Raemer, Daniel] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Brenner, GJ (reprint author), Massachusetts Gen Hosp, Ctr Pain Med, Dept Anesthesia Crit Care & Pain Med, WAC 330,15 Parkman St, Boston, MA 02114 USA. EM gjbrenner@partners.org NR 20 TC 3 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JAN PY 2013 VL 116 IS 1 BP 107 EP 110 DI 10.1213/ANE.0b013e31826f0ae0 PG 4 WC Anesthesiology SC Anesthesiology GA 065JT UT WOS:000313145300013 PM 23223099 ER PT J AU Chitsaz, S Wenk, JF Ge, L Wisneski, A Mookhoek, A Ratcliffe, MB Guccione, JM Tseng, EE AF Chitsaz, Sam Wenk, Jonathan F. Ge, Liang Wisneski, Andrew Mookhoek, Aart Ratcliffe, Mark B. Guccione, Julius M. Tseng, Elaine E. TI Material Properties of CorCap Passive Cardiac Support Device SO ANNALS OF THORACIC SURGERY LA English DT Article ID VENTRICULAR RESTRAINT THERAPY; HEART-FAILURE; DILATED CARDIOMYOPATHY; MYOCARDIAL-INFARCTION; MODEL; CONSTRAINT; GEOMETRY; TRIAL AB Background. Myocardial function deteriorates during ventricular remodeling in patients with congestive heart failure (HF). Ventricular restraint therapy using a cardiac support device (CSD) is designed to reduce the amount of stress inside the dilated ventricles, which in turn halts remodeling. However, as an open mesh surrounding the heart, it is unknown what the mechanical properties of the CSD are in different fiber orientations. Methods. Composite specimens of CorCap (Acorn Cardiovascular, Inc, St. Paul, MN) CSD fabric and silicone were constructed in different fiber orientations and tested on a custom-built biaxial stretcher. Silicone controls were made and stretched to detect the parameters of the matrix. CSD coefficients were calculated using the composite and silicone matrix stress-strain data. Stiffness in different fiber orientations was determined. Results. Silicone specimens exerted a linear behavior, with stiffness of 2.57 MPa. For the composites with 1 fiber set aligned with respect to the stretch axes, stiffness in the direction of the aligned fiber set was higher than that in the cross-fiber direction (14.39 MPa versus 5.66 MPa), indicating greater compliance in the cross-fiber direction. When the orientation of the fiber sets in the composite were matched to the expected clinical orientation of the implanted CorCap, the stiffness in the circumferential axis (with respect to the heart) was greater than in the longitudinal axis (10.55 MPa versus 9.70 MPa). Conclusions. The mechanical properties of the CorCap demonstrate directionality with greater stiffness circumferentially than longitudinally. Implantation of the CorCap clinically should take into account the directionality of the biomechanics to optimize ventricular restraint. (Ann Thorac Surg 2013;95:148-54) (C) 2013 by The Society of Thoracic Surgeons C1 [Tseng, Elaine E.] Univ Calif San Francisco, Med Ctr, Div Cardiothorac Surg, Dept Surg, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Univ Kentucky, Dept Mech Engn, Lexington, KY 40506 USA. Univ Kentucky, Dept Surg, Lexington, KY USA. Erasmus Univ, Med Ctr, Dept Cardiothorac Surg, Rotterdam, Netherlands. RP Tseng, EE (reprint author), Univ Calif San Francisco, Med Ctr, Div Cardiothorac Surg, Dept Surg, 500 Parnassus Ave,Ste 405W,Box 0118, San Francisco, CA 94143 USA. EM elaine.tseng@ucstmedctr.org RI Chitsaz, Sam/C-4586-2008 FU National Institutes of Health (NIH) [R01HL077921] FX This work by supported by the National Institutes of Health (NIH) grant number R01HL077921. NR 29 TC 2 Z9 2 U1 1 U2 6 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 JAN PY 2013 VL 95 IS 1 BP 148 EP 154 DI 10.1016/j.athoracsur.2012.07.036 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 068DC UT WOS:000313343700031 PM 22981255 ER PT J AU Auchincloss, HG Morse, CR AF Auchincloss, Hugh G. Morse, Christopher R. TI Tracheal Disruption From Invasive Pretracheal Lymphadenopathy SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 [Auchincloss, Hugh G.] Massachusetts Gen Hosp, Codman Ctr Clin Effectiveness Surg, Div Cardiothorac Surg, Boston, MA 02114 USA. RP Auchincloss, HG (reprint author), Massachusetts Gen Hosp, Codman Ctr Clin Effectiveness Surg, Div Cardiothorac Surg, Charles River Plaza,Ste 403, Boston, MA 02114 USA. EM hauchincloss1@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JAN PY 2013 VL 95 IS 1 BP E23 EP E23 DI 10.1016/j.athoracsur.2012.07.070 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 068DC UT WOS:000313343700009 PM 23272888 ER PT J AU Bettger, JAP Kaltenbach, L Reeves, MJ Smith, EE Fonarow, GC Schwamm, LH Peterson, ED AF Bettger, Janet A. Prvu Kaltenbach, Lisa Reeves, Mathew J. Smith, Eric E. Fonarow, Gregg C. Schwamm, Lee H. Peterson, Eric D. TI Assessing Stroke Patients for Rehabilitation During the Acute Hospitalization: Findings From the Get With The Guidelines-Stroke Program SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Quality of health care; Rehabilitation; Stroke ID AMERICAN-HEART-ASSOCIATION; TRANSIENT ISCHEMIC ATTACK; MEDICARE BENEFICIARIES; SCIENTIFIC STATEMENT; PERFORMANCE-MEASURES; UNIT CARE; OUTCOMES; REGISTRY AB Objective: To examine the frequency and determinants of an assessment for rehabilitation during the hospitalization for acute stroke. Design: Prospective cohort of patients admitted with acute stroke in the Get With The Guidelines Stroke (GWTG-Stroke) program from January 8, 2008, to March 31, 2011. Setting: Acute hospitals (n=1532) in the United States participating in the GWTG-Stroke program. Participants: Adults with a stroke diagnosis (N=616,982) from a GWTG-Stroke participating acute hospital. Interventions: Not applicable. Main Outcome Measure: Documentation of an assessment for rehabilitation services during the acute hospitalization. Results: Overall, almost 90% of stroke patients had documentation of an acute assessment for rehabilitation. In multivariable analysis, patients significantly more likely to be assessed for rehabilitation were younger, male, black or of other nonwhite races (Asian, American Indian, Alaska Native, Native Hawaiian, or Pacific Islander) when compared with white, independently ambulating before admission, and admitted from the community. Patients who received a stroke consult, cared for in a stroke unit, and treated in the northeast region of the United States were also more likely to be assessed. Conclusions: There is evidence that rehabilitation was considered for 90% of acute stroke patients in this sample. Future research is needed to examine what assessments are conducted and by whom, and how these are used to determine the appropriate level of rehabilitation care for their needs. Archives of Physical Medicine and Rehabilitation 2013;94:38-45 (C) 2013 by the American Congress of Rehabilitation Medicine C1 [Bettger, Janet A. Prvu] Duke Univ, Sch Nursing, Durham, NC 27710 USA. [Bettger, Janet A. Prvu; Kaltenbach, Lisa; Peterson, Eric D.] Duke Univ, Duke Clin Res Inst, Durham, NC 27710 USA. [Reeves, Mathew J.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary, AB T2N 1N4, Canada. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Div Neurol, Boston, MA 02114 USA. RP Bettger, JAP (reprint author), Duke Univ, Sch Nursing, 311 Trent Dr,DUMC 3322, Durham, NC 27710 USA. EM janet.bettger@duke.edu RI Smith, Eric/C-5443-2012; OI Smith, Eric/0000-0003-3956-1668; Schwamm, Lee/0000-0003-0592-9145 FU Agency for Healthcare Research and Quality Mentored Scholar in Comparative Effectiveness Research training grant [K12HS019479]; Boehringer-Ingelheim; Merck; Bristol-Myers Squibb/Sanofi Pharmaceutical; AHA Pharmaceutical; Janssen Pharmaceutical Companies of Johnson Johnson FX Supported in part by an Agency for Healthcare Research and Quality Mentored Scholar in Comparative Effectiveness Research training grant awarded to Duke University (grant no. K12HS019479). The Get With The Guidelines Stroke (GWTG-Stroke) program is currently supported in part by a charitable contribution from Janssen Pharmaceutical Companies of Johnson & Johnson. GWTG-Stroke has been funded in the past through support from Boehringer-Ingelheim, Merck, Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership, and the AHA Pharmaceutical Roundtable. These organizations did not and do not participate in the design, analysis, manuscript preparation, or approval. NR 25 TC 7 Z9 7 U1 0 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JAN PY 2013 VL 94 IS 1 BP 38 EP 45 DI 10.1016/j.apmr.2012.06.029 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 067PV UT WOS:000313308500006 ER PT J AU Ullrich, PM Smith, BM Poggensee, L Evans, CT Stroupe, KT Weaver, FM Burns, SP AF Ullrich, Philip M. Smith, Bridget M. Poggensee, Linda Evans, Charlesnika T. Stroupe, Kevin T. Weaver, Frances M. Burns, Stephen P. TI Pain and Post-Traumatic Stress Disorder Symptoms During Inpatient Rehabilitation Among Operation Enduring Freedom/Operation Iraqi Freedom Veterans With Spinal Cord Injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Pain; PTSD; Rehabilitation; Spinal cord injuries; Veterans ID MENTAL-HEALTH DISORDERS; POST TRAUMATIC DISTRESS; COMORBID CHRONIC PAIN; EMOTIONAL DISTRESS; US VETERANS; PREVALENCE; AFGHANISTAN; CARE; IMPACT; PTSD AB Objective: To examine the frequency of post-traumatic stress disorder (PTSD) symptoms and pain, and how PTSD symptoms were associated with pain severity ratings and the longitudinal course of pain during inpatient rehabilitation for spinal cord injury (SCI) among veterans of the Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) conflicts. Design: Longitudinal analysis of data gathered from electronic medical records. Setting: SCI specialty care centers within the Department of Veterans Affairs. Participants: Veterans of the OEF/OIF conflicts (N=87) who received inpatient rehabilitation for SCI and disorders at Department of Veterans Affairs SCI centers between May 2003 and October 2009. Interventions: Not applicable. Main Outcome Measure(s): PTSD screening at start of rehabilitation and pain numeric rating scale measurements completed throughout rehabilitation. Cut-scores were used to categorize participants into 1 of 4 groups on the basis of scores at the start of rehabilitation: Pain and PTSD, Pain Alone, PTSD Alone, Neither Condition. Results: Comorbid pain and PTSD symptoms were more common than either condition alone, and nearly as common as not having either condition. Participants with pain at the start of rehabilitation (Pain and PTSD, Pain-Alone groups) showed declines in pain ratings over the course of rehabilitation. In contrast, participants in the PTSD-Alone group showed increasing pain over the course of rehabilitation. Conclusions: Pain and PTSD symptoms may be more likely to manifest as comorbidities than as isolated conditions during inpatient rehabilitation. Assessment routines and care plans should be prepared with comorbidities as a foremost concern. It is advisable to screen for pain and PTSD at multiple time points during inpatient rehabilitation to detect new or emerging concerns. Archives of Physical Medicine and Rehabilitation 2013;94:80-5 (C) 2013 by the American Congress of Rehabilitation Medicine C1 [Ullrich, Philip M.; Burns, Stephen P.] VA Puget Sound Healthcare Syst, Dept Vet Affairs, Spinal Cord Injury Serv, Seattle, WA USA. [Ullrich, Philip M.; Burns, Stephen P.] VA Puget Sound Healthcare Syst, Dept Vet Affairs, Spinal Cord Disorders Serv, Seattle, WA USA. [Ullrich, Philip M.; Burns, Stephen P.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Smith, Bridget M.; Poggensee, Linda; Evans, Charlesnika T.; Stroupe, Kevin T.; Weaver, Frances M.] Edward Hines Jr VA Hosp, Dept Vet Affairs, Spinal Cord Injury Qual Enhancement Res Initiat, Hines, IL USA. [Smith, Bridget M.; Poggensee, Linda; Evans, Charlesnika T.; Stroupe, Kevin T.; Weaver, Frances M.] Edward Hines Jr VA Hosp, Ctr Management Complex Chron Care, Hines, IL USA. [Smith, Bridget M.; Stroupe, Kevin T.; Weaver, Frances M.] Loyola Univ Chicago, Stritch Sch Med, Program Hlth Serv Res, Maywood, IL USA. [Evans, Charlesnika T.] Northwestern Univ, Feinberg Sch Med, Inst Healthcare Studies, Chicago, IL 60611 USA. RP Ullrich, PM (reprint author), 128 NAT,1660 S Columbian Wy, Seattle, WA 98108 USA. EM philip.ullrich@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [IIR 07-188-3]; Spinal Cord Injury Quality Enhancement Research Initiative [QLP 42-002] FX Supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (grant no. IIR 07-188-3) and Spinal Cord Injury Quality Enhancement Research Initiative (grant no. QLP 42-002). NR 32 TC 8 Z9 8 U1 1 U2 15 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JAN PY 2013 VL 94 IS 1 BP 80 EP 85 DI 10.1016/j.apmr.2012.07.018 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 067PV UT WOS:000313308500012 PM 22864017 ER PT J AU Ehde, DM Wegener, ST Williams, RM Ephraim, PL Stevenson, JE Isenberg, PJ MacKenzie, EJ AF Ehde, Dawn M. Wegener, Stephen T. Williams, Rhonda M. Ephraim, Patti L. Stevenson, Jennifer E. Isenberg, Patricia J. MacKenzie, Ellen J. TI Developing, Testing, and Sustaining Rehabilitation Interventions Via Participatory Action Research SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Clinical trials as topic; Community-based participatory research; Rehabilitation; Research design ID ACTION RESEARCH-PROJECT; LIMB LOSS; COMMUNITY; HEALTH; DISABILITY; PEOPLE; CARE; DISSEMINATION; INDIVIDUALS; MANAGEMENT AB Few published intervention studies in the rehabilitation literature have included consumers in the research process other than as study participants. This lack of consumer involvement in intervention research may contribute to the challenges encountered developing, translating, disseminating, and sustaining evidence-based rehabilitation interventions in clinical practice. The overall objective of this article is to promote the integration of participatory action research (PAR) into rehabilitation intervention research as a mechanism for addressing these gaps. First, we outline essential components of a PAR model across 5 key phases of intervention research, specifically: agenda setting, methods, implementation, diffusion/dissemination, and sustainability. Second, we describe the use of PAR in rehabilitation intervention research within each of these phases by reviewing relevant literature and by providing an illustrative research example from a randomized controlled trial that integrated PAR throughout the research process. Finally, we conclude with a discussion of 5 specific recommendations for promoting the integration of PAR into rehabilitation intervention research. Archives of Physical Medicine and Rehabilitation 2013;94(1 Suppl 1):S30-42 (C) 2013 by the American Congress of Rehabilitation Medicine C1 [Ehde, Dawn M.; Williams, Rhonda M.] Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98119 USA. [Wegener, Stephen T.; Stevenson, Jennifer E.] Johns Hopkins Univ, Sch Med, Dept Phys Med & Rehabil, Baltimore, MD USA. [Williams, Rhonda M.] VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA USA. [Ephraim, Patti L.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Isenberg, Patricia J.] Amputee Coalit Amer, Knoxville, TN USA. [MacKenzie, Ellen J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. RP Ehde, DM (reprint author), Univ Washington, Sch Med, Dept Rehabil Med, 325 9th Ave,Box 359612, Seattle, WA 98119 USA. EM ehde@uw.edu FU Centers for Disease Control and Prevention [R04/CCU322981, R01DD000153]; Department of Education, National Institute on Disability and Rehabilitation Research [H133B080024, H13313080025] FX Supported by the Centers for Disease Control and Prevention (grant nos. R04/CCU322981 and R01DD000153) and the Department of Education, National Institute on Disability and Rehabilitation Research (grant nos. H133B080024 and H13313080025). NR 67 TC 11 Z9 11 U1 4 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 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JAN PY 2013 VL 94 IS 1 SU 1 BP S30 EP S42 DI 10.1016/j.apmr.2012.10.025 PG 13 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 067PU UT WOS:000313308400005 PM 23260776 ER PT J AU Khoo, XJ Simons, EJ Chiang, HH Hickey, JM Sabharwal, V Pelton, SI Rosowski, JJ Langer, R Kohane, DS AF Khoo, Xiaojuan Simons, Emmanuel J. Chiang, Homer H. Hickey, Julia M. Sabharwal, Vishakha Pelton, Stephen I. Rosowski, John J. Langer, Robert Kohane, Daniel S. TI Formulations for trans-tympanic antibiotic delivery SO BIOMATERIALS LA English DT Article DE Infection; Drug delivery; Hydrogels; Controlled drug release ID TRANSDERMAL DRUG-DELIVERY; PLURONIC F-127 GELS; EXCISED HUMAN SKIN; PENETRATION ENHANCERS; OTITIS-MEDIA; IN-VITRO; PERMEATION ENHANCER; CHEMICAL ENHANCERS; SUSTAINED-RELEASE; POLOXAMER GELS AB We have developed a drug delivery system for prolonged trans-tympanic antibiotic delivery from a single dose administration. Increased permeability to ciprofloxacin of the intact tympanic membrane (TM) was achieved by chemical permeation enhancers (CPEs - bupivacaine, limonene, sodium dodecyl sulfate); this was also seen by CPEs contained within a hydrogel (poloxamer 407) to maintain the formulation at the TM. The CPE-hydrogel formulation had minimal effects on auditory thresholds and tissue response in vivo. CPE-hydrogel formulations have potential for ototopical delivery of ciprofloxacin for the treatment of acute otitis media (AOM) and other middle ear diseases. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Simons, Emmanuel J.; Rosowski, John J.; Langer, Robert; Kohane, Daniel S.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Dept Otol & Laryngol, Boston, MA 02114 USA. [Khoo, Xiaojuan; Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Khoo, Xiaojuan; Simons, Emmanuel J.; Chiang, Homer H.; Hickey, Julia M.; Kohane, Daniel S.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Crit Care Med,Dept Anesthiol,Lab Biomat & Dru, Boston, MA 02115 USA. [Sabharwal, Vishakha; Pelton, Stephen I.] Boston Med Ctr, Maxwell Finland Lab Infect Dis, Div Pediat Infect Dis, Boston, MA 02118 USA. RP Kohane, DS (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Div Crit Care Med,Dept Anesthiol,Lab Biomat & Dru, 300 Longwood Ave, Boston, MA 02115 USA. EM Daniel.Kohane@childrens.harvard.edu OI Sabharwal, Vishakha/0000-0002-5092-4442; Pelton, Stephen/0000-0003-4862-5344 FU National Institute of Deafness and Communicative Disorders (NIDCD) [R21DC009986] FX This work was financially supported by Grant Number R21DC009986 from the National Institute of Deafness and Communicative Disorders (NIDCD). NR 61 TC 13 Z9 13 U1 1 U2 50 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD JAN PY 2013 VL 34 IS 4 BP 1281 EP 1288 DI 10.1016/j.biomaterials.2012.10.025 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 065NS UT WOS:000313155800041 PM 23146430 ER PT J AU Luptakova, K Rosenblatt, J Glotzbecker, B Mills, H Stroopinsky, D Kufe, T Vasir, B Arnason, J Tzachanis, D Zwicker, JI Joyce, RM Levine, JD Anderson, KC Kufe, D Avigan, D AF Luptakova, Katarina Rosenblatt, Jacalyn Glotzbecker, Brett Mills, Heidi Stroopinsky, Dina Kufe, Turner Vasir, Baldev Arnason, Jon Tzachanis, Dimitri Zwicker, Jeffrey I. Joyce, Robin M. Levine, James D. Anderson, Kenneth C. Kufe, Donald Avigan, David TI Lenalidomide enhances anti-myeloma cellular immunity SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Lenalidomide; Multiple myeloma; Dendritic cell vaccine; PD-1 ID CHRONIC LYMPHOCYTIC-LEUKEMIA; REFRACTORY MULTIPLE-MYELOMA; NATURAL-KILLER-CELL; REGULATORY T-CELLS; DENDRITIC CELLS; PLUS DEXAMETHASONE; ANTI-PD-1 ANTIBODY; CARCINOMA-CELLS; THALIDOMIDE; TUMOR AB Lenalidomide is an effective therapeutic agent for multiple myeloma that exhibits immunomodulatory properties including the activation of T and NK cells. The use of lenalidomide to reverse tumor-mediated immune suppression and amplify myeloma-specific immunity is currently being explored. In the present study, we examined the effect of lenalidomide on T-cell activation and its ability to amplify responses to a dendritic cell-based myeloma vaccine. We demonstrate that exposure to lenalidomide in the context of T-cell expansion with direct ligation of CD3/CD28 complex results in polarization toward a Th1 phenotype characterized by increased IFN-gamma, but not IL-10 expression. In vitro exposure to lenalidomide resulted in decreased levels of regulatory T cells and a decrease in T-cell expression of the inhibitory marker, PD-1. Lenalidomide also enhanced T-cell proliferative responses to allogeneic DCs. Most significantly, lenalidomide treatment potentiated responses to the dendritic cell/myeloma fusion vaccine, which were characterized by increased production of inflammatory cytokines and increased cytotoxic lymphocyte-mediated lysis of autologous myeloma targets. These findings indicate that lenalidomide enhances the immunologic milieu in patients with myeloma by promoting T-cell proliferation and suppressing inhibitory factors, and thereby augmenting responses to a myeloma-specific tumor vaccine. C1 [Luptakova, Katarina; Rosenblatt, Jacalyn; Mills, Heidi; Stroopinsky, Dina; Kufe, Turner; Arnason, Jon; Tzachanis, Dimitri; Zwicker, Jeffrey I.; Joyce, Robin M.; Levine, James D.; Avigan, David] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Glotzbecker, Brett; Vasir, Baldev; Anderson, Kenneth C.; Kufe, Donald] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Luptakova, K (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol Oncol, 330 Brookline Ave, Boston, MA 02215 USA. EM kluptako@bidmc.harvard.edu OI Zwicker, Jeffrey/0000-0001-5810-6893 FU Celgene FX This study was supported by research funding from Celgene to J.R. NR 44 TC 38 Z9 42 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD JAN PY 2013 VL 62 IS 1 BP 39 EP 49 DI 10.1007/s00262-012-1308-3 PG 11 WC Oncology; Immunology SC Oncology; Immunology GA 068JP UT WOS:000313363300005 PM 22733396 ER PT J AU Sheikh, NA Petrylak, D Kantoff, PW dela Rosa, C Stewart, FP Kuan, LY Whitmore, JB Trager, JB Poehlein, CH Frohlich, MW Urdal, DL AF Sheikh, Nadeem A. Petrylak, Daniel Kantoff, Philip W. dela Rosa, Corazon Stewart, Frances P. Kuan, Ling-Yu Whitmore, James B. Trager, James B. Poehlein, Christian H. Frohlich, Mark W. Urdal, David L. TI Sipuleucel-T immune parameters correlate with survival: an analysis of the randomized phase 3 clinical trials in men with castration-resistant prostate cancer SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Prostate cancer; Cellular; Humoral; Immunotherapy; Survival ID COLONY-STIMULATING FACTOR; CELL RESPONSES; ACID-PHOSPHATASE; DENDRITIC CELLS; DOUBLE-BLIND; IMMUNOTHERAPY; LYMPHOCYTES; ANTIGENS; INTERLEUKIN-1; ACTIVATION AB Sipuleucel-T, the first FDA-approved autologous cellular immunotherapy for treatment of advanced prostate cancer, is manufactured by activating peripheral blood mononuclear cells, including antigen presenting cells (APCs), with a fusion protein containing prostatic acid phosphatase. Analysis of data from three phase 3 trials was performed to immunologically characterize this therapy during the course of the three doses, and to relate the immunological responses to overall survival (OS). Sipuleucel-T product characteristics [APC numbers, APC activation (CD54 upregulation), and total nucleated cell (TNC) numbers] were assessed in three randomized, controlled phase 3 studies (N = 737). Antigen-specific cellular and humoral responses were assessed in a subset of subjects. The relationships between these parameters and OS were assessed. APC activation occurred in the first dose preparation [6.2-fold, (4.65, 7.70); median (25th, 75th percentile)] and increased in the second [10.6-fold (7.83, 13.65)] and third [10.5-fold (7.89, 13.65)] dose preparations. Cytokines and chemokines associated with activated APCs were produced during the manufacture of each dose; T-cell activation-associated cytokines were detected in the second and third dose preparations. Antigen-specific T cells were detectable after administration of the first sipuleucel-T dose. Cumulative APC activation, APC number, and TNC number correlated with OS (P < 0.05). Antigen-specific immune responses were observed in 78.8 % of monitored subjects and their presence correlated with OS (P = 0.003). Sipuleucel-T broadly engages the immune system by activating APCs ex vivo and inducing long-lived immune responses in vivo. These data indicate antigen-specific immune activation as a mechanism by which sipuleucel-T prolongs OS. C1 [Sheikh, Nadeem A.; dela Rosa, Corazon; Stewart, Frances P.; Kuan, Ling-Yu; Whitmore, James B.; Trager, James B.; Poehlein, Christian H.; Frohlich, Mark W.; Urdal, David L.] Dendreon Corp, Seattle, WA 98102 USA. [Petrylak, Daniel] Columbia Univ, Dept Med, New York, NY 10032 USA. [Kantoff, Philip W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Sheikh, NA (reprint author), Dendreon Corp, 1208 Eastlake Ave E, Seattle, WA 98102 USA. EM nsheikh@dendreon.com FU Celgene; Dendreon; Sanofi; Pfizer; AstraZeneca; Glaxo Smith Kline; Rogosin Institute; Boehringer Ingelheim; Amgen; Ferring Pharmaceuticals; Millennium; Novartis; Johnson and Johnson FX NA Sheikh, C dela Rosa, FP Stewart, LY Kuan, JB Whitmore, JB Trager, CH Poehlein, MW Frohlich, and DL Urdal are employees and stockholders of Dendreon. D Petrylak has received grant support from Celgene, Dendreon, Sanofi, Pfizer, AstraZeneca, Glaxo Smith Kline, Rogosin Institute, Boehringer Ingelheim; acted as a paid consultant from Amgen, Pfizer, Ferring Pharmaceuticals, Millennium, Novartis, Dendreon, Johnson and Johnson, and Galaxo Smith Kline; and participated on scientific advisory boards for Bellicum and Egenix. PW Kantoff has acted as a consultant for Dendreon, Progenics, Amgen, Tokai, BN Immunotherapeutics, Janssen, Genentech, Johnson and Johnson, and Bellicum. NR 36 TC 89 Z9 92 U1 2 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD JAN PY 2013 VL 62 IS 1 BP 137 EP 147 DI 10.1007/s00262-012-1317-2 PG 11 WC Oncology; Immunology SC Oncology; Immunology GA 068JP UT WOS:000313363300013 PM 22865266 ER PT J AU Bourge, RC Tapson, VF Safdar, Z Benza, RL Channick, RN Rosenzweig, EB Shapiro, S White, RJ McSwain, CS Gotzkowsky, SK Nelsen, AC Rubin, LJ AF Bourge, Robert C. Tapson, Victor F. Safdar, Zeenat Benza, Raymond L. Channick, Richard N. Rosenzweig, Erika B. Shapiro, Shelley White, Richard James McSwain, Christopher Shane Gotzkowsky, Stephen Karl Nelsen, Andrew C. Rubin, Lewis J. TI Rapid Transition from Inhaled Iloprost to Inhaled Treprostinil in Patients with Pulmonary Arterial Hypertension SO CARDIOVASCULAR THERAPEUTICS LA English DT Article DE Iloprost; Inhaled; Pulmonary arterial hypertension; Quality of life; Treprostinil ID QUALITY-OF-LIFE; THERAPY; PROSTACYCLIN; TRIAL; INFUSION; CAMPHOR AB Background Inhaled treprostinil is a prostacyclin analog approved for the treatment of pulmonary arterial hypertension (PAH) that may provide a more convenient treatment option for patients receiving inhaled iloprost while maintaining the clinical benefit of inhaled prostacyclin therapy. Aims In this open-label safety study, 73 PAH patients were enrolled with primarily World Health Organization Class II (56%) or III (42%) symptoms. At baseline, most patients (93%) were receiving 5 mu g of iloprost per dose but 38% of patients reported a dosing frequency below the labeled rate of 69 times daily. Patients initiated inhaled treprostinil at 3 breaths four times daily (qid) at the immediate next scheduled iloprost dose. The primary objective was to assess the safety of rapid transition from iloprost to inhaled treprostinil; clinical status and quality of life were also assessed. Results Most patients (84%) achieved the target treprostinil dose of 9 breaths qid and remained on study until transition to commercial therapy (89%). The most frequent adverse events (AEs) were cough (74%), headache (44%), and nausea (30%), and five patients prematurely discontinued study drug due to AE (n = 3), disease progression (n = 1), or death (n = 1). At week 12, the time spent on daily treatment activities was reduced compared to baseline, with a mean total savings of 1.4 h per day. Improvements were also observed at week 12 for 6-min walk distance (+16.0; P < 0.001), N-terminal pro-B-type natriuretic peptide (-74 pg/mL; P = 0.001), and the Cambridge Pulmonary Hypertension Outcome Review (all domains P < 0.001). Conclusions Pulmonary arterial hypertension patients can be safely transitioned from inhaled iloprost to inhaled treprostinil while maintaining clinical status. C1 [Bourge, Robert C.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Tapson, Victor F.] Duke Univ, Med Ctr, Durham, NC USA. [Safdar, Zeenat] Baylor Coll Med, Houston, TX 77030 USA. [Benza, Raymond L.] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. [Channick, Richard N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rosenzweig, Erika B.] Columbia Presbyterian Med Ctr, New York, NY 10032 USA. [Shapiro, Shelley] Greater Los Angeles VA Healthcare Syst, David Geffen UCLA Sch Med, Los Angeles, CA USA. [White, Richard James] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [McSwain, Christopher Shane; Gotzkowsky, Stephen Karl; Nelsen, Andrew C.] United Therapeut Corp, Res Triangle Pk, NC USA. [Rubin, Lewis J.] UCSD Med Ctr, San Diego, CA USA. RP Bourge, RC (reprint author), Univ Alabama Birmingham, 311 THT,1900 Univ Blvd, Birmingham, AL 35294 USA. EM bbourge@uab.edu FU Actelion; Bayer; CardioMEMS; Gilead Sciences; Medtronic; Novartis; Pfizer; United Therapeutics; GlaxoSmithKline; Lung Rx; Medtronics; Lilly/ICOS; Gilead FX R.C.B. serves on the Scientific Advisory Board and Speaker's Bureau for United Therapeutics and has received research grant support from Actelion, Bayer, CardioMEMS, Gilead Sciences, Medtronic, Novartis, Pfizer, and United Therapeutics. V. F. T. serves on the Scientific Advisory Board and provides consulting and lecturing services for Actelion, Bayer, Gilead Sciences, GlaxoSmithKline, Pfizer, United Therapeutics, and Novartis and has received research grants from Actelion, Bayer, Gilead Sciences, GlaxoSmithKline, United Therapeutics, and Novartis. Z.S. has served on the Advisory Board and Speaker's Bureau for United Therapeutics, Actelion and Gilead Sciences and is a consultant for United Therapeutics, Actelion and Gilead Sciences. R. L. B. has received grant support from United Therapeutics, Gilead Sciences, Lung Rx, Bayer, and Novartis and has received honorarium from Actelion, Gilead Sciences, United Therapeutics, and GlaxoSmithKline. R.N.C. is a consultant for Actelion Pharmaceuticals and United Therapeutics and has received research funding from Actelion and Bayer. E. B. R. has received honoraria for consultation at Scientific Advisory Board meetings from United Therapeutics and Actelion and has also received support for research from United Therapeutics and Actelion. S. S. has received grant support from Gilead Sciences, United Therapeutics, Bayer, Actelion, Medtronics, and Novartis and has provided consulting and Speaker's Bureau services for Gilead Sciences, United Therapeutics, Actelion, and Novartis. R.J.W. has served as a paid consultant to the sponsor and has received research funding to participate in multicenter clinical trials with this study's sponsor (United Therapeutics), Lilly/ICOS, Gilead Sciences, and Actelion. R.J.W. also has investigator-initiated research support from United Therapeutics and Gilead. R.J.W. does not have equity interest in any pharmaceutical company, and his paid consulting activities are employees of the sponsor, United Therapeutics. L.J.R. has been a consultant and investigator for Actelion and United Therapeutics and serves on the Scientific Advisory Board for United Therapeutics. NR 28 TC 12 Z9 13 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-5914 J9 CARDIOVASC THER JI Cardiovasc. Ther. PY 2013 VL 31 IS 1 BP 38 EP 44 DI 10.1111/1755-5922.12008 PG 7 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 070EX UT WOS:000313490000007 PM 22970909 ER PT J AU Ademi, Z Liew, D Hollingsworth, B Steg, PG Bhatt, DL Reid, CM AF Ademi, Zanfina Liew, Danny Hollingsworth, Bruce Steg, Ph. Gabriel Bhatt, Deepak L. Reid, Christopher M. CA REACH Registry Investigators TI Is It Cost-Effective To Increase Aspirin Use in Outpatient Settings for Primary or Secondary Prevention? Simulation Data from the REACH Registry Australian Cohort SO CARDIOVASCULAR THERAPEUTICS LA English DT Article DE Aspirin; Coronary heart disease; Cost-effectiveness analysis; Registries ID CARDIOVASCULAR RISK-FACTORS; UNITED-STATES; STABLE OUTPATIENTS; VASCULAR-DISEASE; EVENT RATES; ATHEROTHROMBOSIS; RESISTANCE; DISABILITY; UPDATE; LIFE AB Aims: To describe aspirin use in primary and secondary prevention and to determine the incremental costs effectiveness ratio (ICER) per life year gain (LYG) of aspirin use among subjects with, or at high risk of atherothrombotic disease. Design and Subjects: To project the cost-effectiveness of aspirin over 5 years of follow-up, a Markov state transition model was developed with yearly cycles and the following health states: Alive (post-CAD) and Dead. The model compared current coverage observed among 2361 subjects using the prospective Australian subset of Reduction of Atherothrombosis for continued Health (REACH) registry, and hypothetical situation whereby all subjects assumed to be treated. Costs were calculated based on the Australian government reimbursed data for 2010. Main outcome measures: ICER per LYG for increased use of aspirin. Results: The use of aspirin in current group varied from 67% to 70%. The base-case analysis showed that increasing aspirin use among subjects with existing CAD in outpatient settings was cost saving, while increasing use of aspirin in primary prevention equated to an ICER of AUD 7126 per LYG. Conclusion: Among subjects with existing CAD aspirin use was shown to be a dominant choice of treatment. However, among patients without existing cardiovascular disease (primary prevention), increased uptake of aspirin was cost effective but with uncertain benefit, with two hemorrhagic bleeding events occurring for every life saved. C1 [Ademi, Zanfina; Liew, Danny] Univ Melbourne, Melbourne EpiCtr, Royal Melbourne Hosp, Dept Med, Parkville, Vic 3050, Australia. [Ademi, Zanfina; Reid, Christopher M.] Monash Univ, Dept Epidemiol & Prevent Med, Clayton, Vic 3800, Australia. [Hollingsworth, Bruce] Monash Univ, Ctr Hlth Econ, Clayton, Vic 3800, Australia. [Steg, Ph. Gabriel] Univ Paris 07, INSERM U 698, Paris, France. [Steg, Ph. Gabriel] AP HP, Paris, France. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Ademi, Z (reprint author), Univ Melbourne, Melbourne EpiCtr, Royal Melbourne Hosp, Dept Med, 7 East,Main Bldg,Grattan St, Parkville, Vic 3050, Australia. EM zademi@unimelb.edu.au OI Hollingsworth, Bruce/0000-0002-4314-6523; Liew, Danny/0000-0002-0131-623X FU Monash University; Australian Research Council (ARC) [LP077532]; sanofi-aventis; Bristol-Myers Squibb; Waksman Foundation (Tokyo, Japan); MSD; Servier; AstraZeneca; Pfizer; Eisai; Medicines Company FX This work was supported by Monash University. In addition, this work was supported in part by the Australian Research Council (ARC) Linkage Project LP077532. The global REACH Registry is sponsored by sanofi-aventis, Bristol-Myers Squibb and the Waksman Foundation (Tokyo, Japan), and is endorsed by the World Heart Federation. The REACH Registry enforces a no-ghost-writing policy. A complete list of the REACH Registry Investigators appears in JAMA. 2006; 295(2):180-189.; Zanfina Ademi and Bruce Hollingsworth declare no conflict of interest. Christopher Reid has received research funding and honoraria from sanofi-aventis, MSD, Servier and AstraZeneca. Danny Liew has received research grants and honoraria from sanofi-aventis and Pfizer (sponsor of atorvastatin). Ph Gabriel Steg has the following disclosures: Research Grant (to institution): Servier (2009-2014), Consulting/advisory board: Astellas, C. Bayer, Boehringer-Ingelheim, BMS, Daiichi-Sankyo-Lilly, GSK, Medtronic, MSD, Otsuka, Pfizer, Roche, sanofi-aventis, Servier, The Medicines Company. Stockholding: Aterovax. Deepak L. Bhatt has received research grants from sanofi-aventis and Bristol-Myers Squibb who have funded the REACH Registry. He has also received institutional research support from AstraZeneca, Eisai, and The Medicines Company. NR 49 TC 3 Z9 3 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-5914 J9 CARDIOVASC THER JI Cardiovasc. Ther. PY 2013 VL 31 IS 1 BP 45 EP 52 DI 10.1111/j.1755-5922.2011.00291.x PG 8 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 070EX UT WOS:000313490000008 PM 21884025 ER PT J AU Borcar, A Menze, MA Toner, M Hand, SC AF Borcar, Apurva Menze, Michael A. Toner, Mehmet Hand, Steven C. TI Metabolic preconditioning of mammalian cells: mimetic agents for hypoxia lack fidelity in promoting phosphorylation of pyruvate dehydrogenase SO CELL AND TISSUE RESEARCH LA English DT Article DE Metabolic preconditioning; Hypoxia inducible factor 1; Cobalt chloride; Desferrioxamine; Pyruvate dehydrogenase; Cell Culture (human, mouse) ID INDUCIBLE FACTOR-I; ERYTHROPOIETIN GENE; MITOCHONDRIAL RESPIRATION; REPERFUSION INJURY; HIF-ALPHA; ADAPTATION; COMPLEX; EXPRESSION; FACTOR-1; CARDIOPROTECTION AB Induction of HIF-1 alpha by oxygen limitation promotes increased phosphorylation and catalytic depression of mitochondrial pyruvate dehydrogenase (PDH) and an enhanced glycolytic poise in cells. Cobalt chloride and desferrioxamine are widely used as mimics for hypoxia because they increase the levels of HIF-1 alpha. We evaluated the ability of these agents to elicit selected physiological responses to hypoxia as a means to metabolically precondition mammalian cells, but without the detrimental effects of hypoxia. We show that, while CoCl2 does increase HIF-1 alpha in a dose-dependent manner, it unexpectedly and strikingly decreases PDH phosphorylation at E1 alpha sites 1, 2, and 3 (Ser(293), Ser(300), and Ser(232), respectively) in HepG2 cells. This same effect is also observed for site 1 in mouse NIH/3T3 fibroblasts and J774 macrophages. CoCl2 unexpectedly decreases the mRNA expression for PDH kinase-2 in HepG2 cells, which likely explains the dephosphorylation of PDH observed. And nor does desferrioxamine promote the expected increase in PDH phosphorylation. Dimethyloxaloylglycine (a prolyl hydroxylase inhibitor) performs better in this regard, but failed to promote the stronger effects seen with hypoxia. Consequently, CoCl2 and desferrioxamine are unreliable mimics of hypoxia for physiological events downstream of HIF-1 alpha stabilization. Our study demonstrates that mimetic chemicals must be chosen with caution and evaluated thoroughly if bona fide cellular outcomes are to be promoted with fidelity. C1 [Borcar, Apurva; Hand, Steven C.] Louisiana State Univ, Dept Biol Sci, Div Cellular Dev & Integrat Biol, Baton Rouge, LA 70803 USA. [Menze, Michael A.] Eastern Illinois Univ, Dept Biol Sci, Charleston, IL 61920 USA. [Toner, Mehmet] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. [Toner, Mehmet] Harvard Univ, Sch Med, Massachusetts Gen Hosp, BioMEMS Resource Ctr, Boston, MA 02114 USA. [Toner, Mehmet] Shriners Burn Hosp, Boston, MA 02114 USA. RP Borcar, A (reprint author), Louisiana State Univ, Dept Biol Sci, Div Cellular Dev & Integrat Biol, Baton Rouge, LA 70803 USA. EM aborca2@tigers.lsu.edu OI Menze, Michael/0000-0003-1072-5462 FU National Institutes of Health [2-RO1-DK046270-14A1] FX This study was supported by National Institutes of Health (2-RO1-DK046270-14A1) NR 38 TC 3 Z9 3 U1 0 U2 17 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD JAN PY 2013 VL 351 IS 1 BP 99 EP 106 DI 10.1007/s00441-012-1517-2 PG 8 WC Cell Biology SC Cell Biology GA 064JA UT WOS:000313069800009 PM 23138570 ER PT J AU Lipnick, MS Braun, AB Cheung, JTW Gibbons, FK Christopher, KB AF Lipnick, Michael S. Braun, Andrea B. Cheung, Joyce Ting-Wai Gibbons, Fiona K. Christopher, Kenneth B. TI The Difference Between Critical Care Initiation Anion Gap and Prehospital Admission Anion Gap is Predictive of Mortality in Critical Illness SO CRITICAL CARE MEDICINE LA English DT Article DE anion gap; intensive care; mortality ID ACUTE KIDNEY INJURY; STRONG-ION-GAP; CHARLSON COMORBIDITY INDEX; ACUTE-RENAL-FAILURE; ACID-BASE CHEMISTRY; ILL PATIENTS; METABOLIC-ACIDOSIS; UNMEASURED ANIONS; RIFLE CRITERIA; ADMINISTRATIVE DATABASES AB Objective: We hypothesized that the delta anion gap defined as difference between critical care initiation standard anion gap and prehospital admission standard anion gap is associated with all cause mortality in the critically ill. Design: Observational cohort study. Setting: Two hundred nine medical and surgical intensive care beds in two hospitals in Boston, MA. Patients: Eighteen thousand nine hundred eighty-five patients, age >= 8 yrs, who received critical care between 1997 and 2007. Measurements: The exposure of interest was delta anion gap and categorized a priori as <0, 0-5, 5-10, and >10 mEq/L. Logistic regression examined death by days 30, 90, and 365 postcritical care initiation and in-hospital mortality. Adjusted odds ratios were estimated by multivariable logistic regression models. The discrimination of delta anion gap for 30-day mortality was evaluated using receiver operator characteristic curves performed for a subset of patients with all laboratory data required to analyze the data via physical chemical principles (n = 664). Interventions: None. Results: Delta anion gap was a particularly strong predictor of 30-day mortality with a significant risk gradient across delta anion gap quartiles following multivariable adjustment: delta anion gap <0 mEq/L odds ratio 0.75 (95% confidence interval 0.67-0.81; p < 0.0001); delta anion gap 5-10 mEq/L odds ratio 1.56 (95% confidence interval 1.35-1.81; p < 0.0001); delta anion gap >10 mEq/L odds ratio 2.18 (95% confidence interval 1.76-2.71; p < 0.0001); and all relative to patients with delta anion gap 0-5 mEq/L. Similar significant robust associations post nnultivariable adjustments are seen with death by days 90 and 365 as well as in-hospital mortality. Correcting for albumin or limiting the cohort to patients with standard anion gap at critical care initiation of 10-18 mEq/L did not materially change the delta anion gap-mortality association. Delta anion gap has similarly moderate discriminative ability for 30-day mortality in comparison to standard base excess and strong ion gap. Conclusion: An increase in standard anion gap at critical care initiation relative to prehospital admission standard anion gap is a predictor of the risk of all cause patient mortality in the critically ill. (Crit Care Med 2013; 41:49-59) C1 [Lipnick, Michael S.] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. [Cheung, Joyce Ting-Wai] Univ Western Ontario, Schulich Sch Med & Dent, London, ON N6A 3K7, Canada. [Gibbons, Fiona K.] Massachusetts Gen Hosp, Div Pulm, Boston, MA 02114 USA. [Christopher, Kenneth B.] Brigham & Womens Hosp, Div Renal, Nathan E Hellman Mem Lab, Boston, MA 02115 USA. RP Christopher, KB (reprint author), Brigham & Womens Hosp, Div Renal, Nathan E Hellman Mem Lab, Boston, MA 02115 USA. EM kbchristopher@partners.org FU NIH [K08Al060881] FX Dr. Christopher received grant support from the NIH grant (K08Al060881). NR 72 TC 7 Z9 8 U1 1 U2 3 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 JAN PY 2013 VL 41 IS 1 BP 49 EP 59 DI 10.1097/CCM.0b013e31826764cd PG 11 WC Critical Care Medicine SC General & Internal Medicine GA 065LR UT WOS:000313150300007 PM 23190721 ER PT J AU Villar, J Kacmarek, RM AF Villar, Jestuis Kacmarek, Robert M. TI Modern Critical Care Medicine From China: An Ancient Civilization SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE acute respiratory distress syndrome; critical illness; ICU; outcome; sepsis ID MULTICENTER C1 [Villar, Jestuis] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Villar, Jestuis] Hosp Univ Dr Negrin, Res Unit, Las Palmas Gran Canaria, Spain. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Kacmarek, Robert M.] Harvard Univ, Dept Anesthesia, Boston, MA 02115 USA. RP Villar, J (reprint author), Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. NR 18 TC 2 Z9 2 U1 0 U2 3 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 JAN PY 2013 VL 41 IS 1 BP 343 EP 345 DI 10.1097/CCM.0b013e318270e6dc PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 065LR UT WOS:000313150300042 PM 23269142 ER PT J AU Bronshteyn, YS Alston, TA AF Bronshteyn, Yuriy S. Alston, Theodore A. TI To Breathe or Not to Breathe? SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE cardiac arrest; compression:ventilation ratio; inspiratory impedance threshold device; lung protection; resuscitation ID STANDARD CARDIOPULMONARY-RESUSCITATION; HOSPITAL CARDIAC-ARREST; BASIC-LIFE-SUPPORT; VENTILATION; MASSAGE C1 [Bronshteyn, Yuriy S.; Alston, Theodore A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02163 USA. RP Bronshteyn, YS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02163 USA. OI Bronshteyn, Yuriy/0000-0002-9250-9490 NR 14 TC 0 Z9 0 U1 1 U2 4 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 JAN PY 2013 VL 41 IS 1 BP 346 EP 348 DI 10.1097/CCM.0b013e31826a4687 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 065LR UT WOS:000313150300044 PM 23269144 ER PT J AU Krause, DS Scadden, DT Preffer, FI AF Krause, Daniela S. Scadden, David T. Preffer, Frederic I. TI The hematopoietic stem cell niche-home for friend and foe? SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Review DE hematopoietic stem cell; bone marrow microenvironment; leukemia stem cell; flow cytometry ID ACUTE MYELOID-LEUKEMIA; BONE-MARROW MICROENVIRONMENT; ACUTE MYELOGENOUS LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; RECEPTOR-ALPHA CHAIN; E-SELECTIN LIGAND; PROGENITOR CELLS; IN-VIVO; MOUSE MODEL; OSTEOBLASTIC CELLS AB The hematopoietic stem cell (HSC) niche is involved in the maintainance and regulation of quiescence, self-renewal and differentiation of hematopoietic stem cells and the fate of their progeny in mammals dealing with the daily stresses to the hematopoietic system. From the discovery that perturbations of the HSC niche can lead to hematopoietic disorders, we have now arrived at the prospect that the HSC niche may play a role in hematological malignancies and that this HSC niche may be a target for therapy. This review attempts to capture the discoveries of the last few years regarding the normal and malignant hematopoietic stem cell niche and possible ways to target this niche. (c) 2012 International Clinical Cytometry Society C1 [Krause, Daniela S.; Preffer, Frederic I.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Krause, Daniela S.; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Krause, Daniela S.; Scadden, David T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Krause, Daniela S.; Scadden, David T.] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Boston, MA 02114 USA. RP Krause, DS (reprint author), 185 Cambridge St, Boston, MA 02114 USA. EM dkrause1@partners.org FU The Ellison Foundation; [5KO8CA138916-02]; [T32 CA009216]; [2-R01HL044851-21]; [1S10RR020936-01] FX We thank Mitchell Preffer for artistically drawing the figures and on-line animations. This work was supported by grants 5KO8CA138916-02 and T32 CA009216 to D.S.K., grant 2-R01HL044851-21 and The Ellison Foundation to D. T. S. and grant 1S10RR020936-01 to F.I.P. D.T.S. is a consultant for Genzyme and Bone Therapeutics, a stockholder at Fate Therapeutics and a member of the scientific advisory board at Fate Therapeutics and Hospira. The other authors have no relevant conflicts of interest. NR 113 TC 37 Z9 38 U1 1 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD JAN-FEB PY 2013 VL 84B IS 1 BP 7 EP 20 DI 10.1002/cyto.b.21066 PG 14 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 066UK UT WOS:000313246100003 PM 23281119 ER PT J AU Singh, T Prasad, R Katiyar, SK AF Singh, Tripti Prasad, Ram Katiyar, Santosh K. TI Inhibition of class I histone deacetylases in non-small cell lung cancer by honokiol leads to suppression of cancer cell growth and induction of cell death in vitro and in vivo SO EPIGENETICS LA English DT Article DE apoptotic index; cell cycle; histone; histone deacetylase; histone acetyl transferase; honokiol; non-small cell lung cancer ID SUBEROYLANILIDE HYDROXAMIC ACID; CLINICAL DEVELOPMENT; NATURAL-PRODUCT; CYCLE CONTROL; APOPTOSIS; ARREST; GENES; ANGIOGENESIS; ACETYLATION; MECHANISMS AB Non-small-cell lung cancer (NSCLC) represents approximately 80% of all types of lung cancer. Here, we report the chemotherapeutic effect of honokiol, a phytochemical from Magnolia grandiflora, on NSCLC cells and the molecular mechanisms underlying these effects using in vitro and in vivo models. Treatment of NSCLC cells (A549, H1299, H460 and H226) with honokiol (20, 40 and 60 mu M) inhibited histone deacetylase (HDAC) activity, reduced the levels of class I HDAC proteins and enhanced histone acetyltransferase activity in a dose-dependent manner. These effects of honokiol were associated with a significant reduction in the viability of NSCLC cells. Concomitant treatment of cells with a proteasome inhibitor, MG132, prevented honokiol-induced degradation of class I HDACs, suggesting that honokiol reduced the levels of HDACs in NSCLC cells through proteasomal degradation. Valproic acid, an inhibitor of HDACs, exhibited a similar pattern of reduced viability and induction of death of NSCLC cells. Treatment of A549 and H1299 cells with honokiol resulted in an increase in G(1) phase arrest, and a decrease in the levels of cyclin D1, D2 and cyclin dependent kinases. Further, administration of honokiol by oral gavage significantly inhibited the growth of subcutaneous A549 and H1299 tumor xenografts in athymic nude mice, which was associated with the induction of apoptotic cell death and marked inhibition of class I HDACs proteins and HDAC activity in the tumor xenograft tissues. Together, our study provides new insights into the role of class I HDACs in the chemotherapeutic effects of honokiol on lung cancer cells. C1 [Singh, Tripti; Prasad, Ram; Katiyar, Santosh K.] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Katiyar, SK (reprint author), Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU Veterans Administration Merit Review Award [1I01BX001059] FX This work was supported by the Veterans Administration Merit Review Award, 1I01BX001059 (S.K.K.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Dr Fiona Hunter for her assistance in editing the manuscript. NR 45 TC 27 Z9 30 U1 0 U2 9 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1559-2294 J9 EPIGENETICS-US JI Epigenetics PD JAN PY 2013 VL 8 IS 1 BP 54 EP 65 DI 10.4161/epi.23078 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 067GT UT WOS:000313282900008 PM 23221619 ER PT J AU Ladabaum, U Brill, JV Sonnenberg, A Shaheen, NJ Inadomi, J Wilcox, CM Park, WG Hur, C Pasricha, PJ AF Ladabaum, Uri Brill, Joel V. Sonnenberg, Amnon Shaheen, Nicholas J. Inadomi, John Wilcox, C. Mel Park, Walter G. Hur, Chin Pasricha, Pankaj J. TI How to Value Technological Innovation: A Proposal for Determining Relative Clinical Value SO GASTROENTEROLOGY LA English DT Editorial Material ID CONJOINT-ANALYSIS; COST-EFFECTIVENESS; HEALTH-CARE; MEDICARE COVERAGE; PREFERENCES; RECOMMENDATIONS; RELIABILITY; MEDICINE C1 [Ladabaum, Uri; Park, Walter G.] Stanford Univ, Stanford, CA 94305 USA. [Brill, Joel V.] Predict Hlth LLC, Phoenix, AZ USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Shaheen, Nicholas J.] Univ N Carolina, Chapel Hill, NC USA. [Inadomi, John] Univ Washington, Seattle, WA 98195 USA. [Wilcox, C. Mel] Univ Alabama Birmingham, Birmingham, AL USA. [Hur, Chin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pasricha, Pankaj J.] Johns Hopkins Univ, Baltimore, MD USA. RP Ladabaum, U (reprint author), Stanford Univ, Stanford, CA 94305 USA. RI Inadomi, John/A-6221-2014; OI Inadomi, John/0000-0001-6776-8661; Hur, Chin/0000-0002-2819-7576 NR 20 TC 1 Z9 1 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2013 VL 144 IS 1 BP 5 EP 8 DI 10.1053/j.gastro.2012.11.006 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 062ZY UT WOS:000312965100010 PM 23153872 ER PT J AU Gukovsky, I Gukovskaya, A AF Gukovsky, Ilya Gukovskaya, Anna TI Nuclear Factor-kappa B in Pancreatitis: Jack-of-All-Trades, But Which One Is More Important? SO GASTROENTEROLOGY LA English DT Editorial Material ID ACINAR-CELL DEATH; TRYPSINOGEN ACTIVATION; CERULEIN PANCREATITIS; IKK-BETA; INFLAMMATION; PATHOGENESIS; NEUTROPHILS; INHIBITION; RELA/P65; NECROSIS C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Gukovsky, I (reprint author), W Los Angeles VA Healthcare Ctr, Pancreat Res Grp, 11301 Wilshire Blvd,Blg 258,Rm 340, Los Angeles, CA 90073 USA. EM igukovsk@ucla.edu NR 36 TC 16 Z9 16 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2013 VL 144 IS 1 BP 26 EP 29 DI 10.1053/j.gastro.2012.11.016 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 062ZY UT WOS:000312965100016 PM 23164573 ER PT J AU Alemi, F Poole, DP Chiu, J Schoonjans, K Cattaruzza, F Grider, JR Bunnett, NW Corvera, CU AF Alemi, Farzad Poole, Daniel P. Chiu, Jonathan Schoonjans, Kristina Cattaruzza, Fiore Grider, John R. Bunnett, Nigel W. Corvera, Carlos U. TI The Receptor TGR5 Mediates the Prokinetic Actions of Intestinal Bile Acids and Is Required for Normal Defecation in Mice SO GASTROENTEROLOGY LA English DT Article DE Digestion; Mouse Model; Intestine; Diarrhea ID ENTERIC NERVOUS-SYSTEM; PERISTALTIC REFLEX; RABBIT COLON; POSTPRANDIAL CONCENTRATIONS; GASTROINTESTINAL MOTILITY; DEOXYCHOLIC-ACID; GPBAR1 TGR5; ACTIVATION; SECRETION; RELEASE AB BACKGROUND & AIMS: Abnormal delivery of bile acids (BAs) to the colon as a result of disease or therapy causes constipation or diarrhea by unknown mechanisms. The G protein-coupled BA receptor TGR5 (or GPBAR1) is expressed by enteric neurons and endocrine cells, which regulate motility and secretion. METHODS: We analyzed gastrointestinal and colon transit, as well as defecation frequency and water content, in wild-type, knockout, and transgenic mice (trg5-wt, tgr5-ko, and tgr5-tg, respectively). We analyzed colon tissues for contractility, peristalsis, and transmitter release. RESULTS: Deoxycholic acid inhibited contractility of colonic longitudinal muscle from tgr5-wt but not tgr5-ko mice. Application of deoxycholic acid, lithocholic acid, or oleanolic acid (a selective agonist of TGR5) to the mucosa of tgr5-wt mice caused oral contraction and caudal relaxation, indicating peristalsis. BAs stimulated release of the peristaltic transmitters 5-hydroxytryptamine and calcitonin gene-related peptide; antagonists of these transmitters suppressed BA-induced peristalsis, consistent with localization of TGR5 to enterochromaffin cells and intrinsic primary afferent neurons. tgr5-ko mice did not undergo peristalsis or transmitter release in response to BAs. Mechanically induced peristalsis and transmitter release were not affected by deletion of tgr5. Whole-gut transit was 1.4-fold slower in tgr5-ko than tgr5-wt or tgr5-tg mice, whereas colonic transit was 2.2-fold faster in tgr5-tg mice. Defecation frequency was reduced 2.6-fold in tgr5-ko and increased 1.4-fold in tgr5-tg mice compared with tgr5-wt mice. Water content in stool was lower (37%) in tgr5-ko than tgr5-tg (58%) or tgr5-wt mice (62%). CONCLUSIONS: The receptor TGR5 mediates the effects of BAs on colonic motility, and deficiency of TGR5 causes constipation in mice. These findings might mediate the long-known laxative properties of BAs, and TGR5 might be a therapeutic target for digestive diseases. C1 [Alemi, Farzad; Chiu, Jonathan; Cattaruzza, Fiore; Corvera, Carlos U.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94121 USA. [Poole, Daniel P.] Univ Melbourne, Dept Anat & Neurosci, Parkville, Vic 3052, Australia. [Schoonjans, Kristina] Ecole Polytech Fed Lausanne, Sch Life Sci, Inst Bioengn, Lab Integrat & Syst Physiol, Lausanne, Switzerland. [Grider, John R.] Virginia Commonwealth Univ, Dept Physiol, Richmond, VA USA. [Bunnett, Nigel W.] Monash Inst Pharmaceut Sci, Parkville, Vic 3052, Australia. [Corvera, Carlos U.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Bunnett, NW (reprint author), Monash Inst Pharmaceut Sci, 381 Royal Parade, Parkville, Vic 3052, Australia. EM carlos.corvera@ucsfmedctr.org FU Northern California Institute for Research and Education, Veterans Health Administration; National Health and Medical Research Council [63303, 103188, 454858]; National Institutes of Health [DK39957, DK43207, DK57840, DK34153]; Monash University; Ecole Polytechnique Federale de Lausanne, Swiss National Science Foundation [SNF 31003A_125487] FX Supported by the Northern California Institute for Research and Education, Veterans Health Administration (C.U.C.); National Health and Medical Research Council grants 63303, 103188 (to N.W.B.), and 454858 (to D.P.P.); National Institutes of Health grants DK39957, DK43207, DK57840 (to N.W.B.), and DK34153 (to J.R.G.); Monash University (N.W.B.); and Ecole Polytechnique Federale de Lausanne, Swiss National Science Foundation (SNF 31003A_125487) (K.S.). NR 44 TC 55 Z9 55 U1 0 U2 15 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2013 VL 144 IS 1 BP 145 EP 154 DI 10.1053/j.gastro.2012.09.055 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 062ZY UT WOS:000312965100035 PM 23041323 ER PT J AU Rutherford, A King, LY Lee, WM Chung, RT AF Rutherford, Anna King, Lindsay Y. Lee, William M. Chung, Raymond T. TI Accuracy of the ALFSG Index as a Triage Marker in Acute Liver Failure Reply SO GASTROENTEROLOGY LA English DT Letter C1 [Rutherford, Anna] Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA. [King, Lindsay Y.; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. RP Rutherford, A (reprint author), Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, 75 Francis St, Boston, MA 02115 USA. NR 2 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2013 VL 144 IS 1 BP E26 EP E26 DI 10.1053/j.gastro.2012.11.026 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 062ZY UT WOS:000312965100009 PM 23177160 ER PT J AU Spadea, MF Verburg, J Baroni, G Seco, J AF Spadea, Maria F. Verburg, Joost Baroni, Guido Seco, Joao TI Dosimetric assessment of a novel metal artifact reduction method in CT images SO JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS LA English DT Article DE CT; metal artifact reduction; dose inaccuracies; IMRT ID HIP PROSTHESES; MONTE-CARLO; SUPPRESSION; IMPLANTS AB The aim of this study was to assess the ability of metal artifact reduction (MAR) algorithm in restoring the CT image quality while correcting the tissue density information for the accurate estimation of the absorbed dose. A phantom filled with titanium (low-Z metal) and Cerrobend (high-Z metal) inserts was used for this purpose. The MAR algorithm was applied to phantom's CT dataset. Static intensity-modulated radiation therapy (IMRT) plans, including five beam angles, were designed and optimized on the uncorrected images to deliver 10 Gy on the simulated target. Monte Carlo dose calculation was computed on uncorrected, corrected, and ground truth image datasets. It was firstly verified that MAR methodology was able to correct HU errors due to the metal presence. In the worst situation (high-Z phantom), the image difference, uncorrected ground truth and corrected ground truth, went from -4.4 +/- 118.8 HU to 0.4 +/- 10.8 HU, respectively. Secondly, it was observed that the impact of dose errors estimation depends on the atomic number of the metal: low-Z inserts do not produce significant dose inaccuracies, while high-Z implants substantially influence the computation of the absorbed dose. In this latter case, dose errors in the PTV region were up to 23.56% (9.72% mean value) when comparing the uncorrected vs. the ground truth dataset. After MAR correction, errors dropped to 0.11% (0.10% mean value). In conclusion, it was assessed that the new MAR algorithm is able to restore image quality without distorting mass density information, thus producing a more accurate dose estimation. C1 [Spadea, Maria F.] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, I-88100 Catanzaro, Italy. [Verburg, Joost; Seco, Joao] Harvard Univ, Sch Med, Dept Radiat Oncol, Cambridge, MA 02138 USA. [Verburg, Joost; Seco, Joao] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Baroni, Guido] Politecn Milano Univ, Dept Bioengn, Milan, Italy. [Baroni, Guido] Fdn CNAO, Bioengn Unit, Pavia, Italy. RP Spadea, MF (reprint author), Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, Viale Europa, I-88100 Catanzaro, Italy. EM mfspadea@unicz.it FU Fulbright fellowship; U.S.-Italy Fulbright Commission FX This work was partly supported by a Fulbright fellowship awarded by the U.S.-Italy Fulbright Commission. NR 12 TC 5 Z9 5 U1 0 U2 3 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 1526-9914 J9 J APPL CLIN MED PHYS JI J. Appl. Clin. Med. Phys PY 2013 VL 14 IS 1 BP 299 EP 304 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 064BW UT WOS:000313046900024 ER PT J AU Bao, YC Dai, HS Wang, T Chuang, SK AF Bao, Yanchun Dai, Hongsheng Wang, Tao Chuang, Sung-Kiang TI A joint modelling approach for clustered recurrent events and death events SO JOURNAL OF APPLIED STATISTICS LA English DT Article DE Bayesian analysis; censoring; clustered events; joint modelling; recurrent events ID FAILURE TIME DATA; DENTAL IMPLANT SURVIVAL; COX REGRESSION-MODEL; TERMINATING EVENT; CLINICAL-TRIALS; FRAILTY MODEL; STRATEGY; HAZARDS AB In dental implant research studies, events such as implant complications including pain or infection may be observed recurrently before failure events, i.e. the death of implants. It is natural to assume that recurrent events and failure events are correlated to each other, since they happen on the same implant (subject) and complication times have strong effects on the implant survival time. On the other hand, each patient may have more than one implant. Therefore these recurrent events or failure events are clustered since implant complication times or failure times within the same patient (cluster) are likely to be correlated. The overall implant survival times and recurrent complication times are both interesting to us. In this paper, a joint modelling approach is proposed for modelling complication events and dental implant survival times simultaneously. The proposed method uses a frailty process to model the correlation within cluster and the correlation within subjects. We use Bayesian methods to obtain estimates of the parameters. Performance of the joint models are shown via simulation studies and data analysis. C1 [Bao, Yanchun; Wang, Tao] Yunnan Normal Univ, Sch Math, Kunming, Yunnan, Peoples R China. [Dai, Hongsheng] Univ Brighton, Dept Math, Brighton BN2 4GJ, E Sussex, England. [Chuang, Sung-Kiang] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Chuang, Sung-Kiang] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Bao, YC (reprint author), Yunnan Normal Univ, Sch Math, Kunming, Yunnan, Peoples R China. EM yanchun.bao@brunel.ac.uk OI Dai, Hongsheng/0000-0003-1734-2026 FU Chun Hui Plan Scientific Research Project of the Ministry of Education of the People's Republic of China [Z2006-1-65010] FX Tao Wang was supported by the grant Z2006-1-65010 from Chun Hui Plan Scientific Research Project of the Ministry of Education of the People's Republic of China. NR 32 TC 1 Z9 1 U1 1 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0266-4763 EI 1360-0532 J9 J APPL STAT JI J. Appl. Stat. PD JAN 1 PY 2013 VL 40 IS 1 BP 123 EP 140 DI 10.1080/02664763.2012.735225 PG 18 WC Statistics & Probability SC Mathematics GA 063VE UT WOS:000313029300010 ER PT J AU Singh, JA Jensen, MR Harmsen, SW Lewallen, DG AF Singh, Jasvinder A. Jensen, Matthew R. Harmsen, Scott W. Lewallen, David G. TI Are Gender, Comorbidity, and Obesity Risk Factors for Postoperative Periprosthetic Fractures After Primary Total Hip Arthroplasty? SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total hip arthroplasty; periprosthetic fracture; predictors; risk factors; comorbidity; gender; primary THA ID KNEE ARTHROPLASTY; FEMORAL FRACTURES; UNITED-STATES; FEMUR; REPLACEMENT; MORTALITY; MORBIDITY; REGISTER; OUTCOMES; INDEX AB We studied the frequency and patient risk factors for postoperative periprosthetic fractures after primary total hip arthroplasty (THA). With a mean follow-up of 6.3 years, 305 postoperative periprosthetic fractures occurred in 14 065 primary THAs. In multivariable-adjusted Cox regression analyses, female gender (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.17-1.88), Deyo-Charlson comorbidity score of 2 (HR, 1.74 for score of 2; 95% CI, 1.25-2.43) or 3 or higher (HR, 1.71; 95% CI, 1.26-2.32), and American Society of Anesthesiologist class of 2 (HR, 1.84; 95% CI, 0.90-3.76) or 3 (HR, 2.45; 95% CI, 1.18-5.1) or 4 or higher (HR, 2.68; 95% CI, 0.70-10.28) were significantly associated with higher risk/hazard, and cemented implant, with lower hazard (HR, 0.68; 95% CI, 0.54-0.87) of postoperative periprosthetic fractures. Interventions targeted at optimizing comorbidity management may decrease postoperative fractures after THA. C1 [Singh, Jasvinder A.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Div Epidemiol, Sch Publ Hlth, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit CSMART, Birmingham, AL USA. [Singh, Jasvinder A.; Lewallen, David G.] Mayo Clin, Sch Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Dept Med, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. OI singh, jasvinder/0000-0003-3485-0006 FU NCRR NIH HHS [KL2 RR024151, KL2 RR024151-01] NR 32 TC 18 Z9 20 U1 0 U2 6 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD JAN PY 2013 VL 28 IS 1 BP 126 EP 131 DI 10.1016/j.arth.2012.03.010 PG 6 WC Orthopedics SC Orthopedics GA 065HH UT WOS:000313138900020 PM 22552223 ER PT J AU Friedstat, JS Moore, ME Weber, JM Fagan, SP Goverman, J AF Friedstat, Jonathan S. Moore, Molly E. Weber, Joan M. Fagan, Shawn P. Goverman, Jeremy TI Selection of Appropriate Empiric Gram-Negative Coverage in a Multinational Pediatric Burn Hospital SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID SEVERE SEPSIS; POLYMYXIN-B; COLISTIN; INFECTIONS; EPIDEMIOLOGY; SURVEILLANCE; MORTALITY; UNIT AB The choice of appropriate empiric antimicrobial therapy for burn patients with suspected multidrug-resistant organisms remains a challenge. Burn patients transferred from outside the United States seem to be at particularly high risk. Given this perceived risk of multidrug resistance among our international patient population, we set out to determine which empiric antimicrobial therapy should be used at admission. A retrospective analysis was conducted of all burn patients admitted to a pediatric burn specialty hospital between 2006 and 2010. Patients with burns >10% TBSA were included. Demographics, burn data, and routine/nonroutine culture data were collected. Of the 385 total patients, 133 (34.5%) were international. International patients had significantly larger burns (39.73 vs 22.80% TBSA; P < .001) and more inhalational injuries (27.1 vs 16.3%; P < .03) than their U. S. counterparts. International patients presented with a higher incidence of infection in general (66.9 vs 2%; P < .001) as well as a higher prevalence of infection caused by multidrug-resistant bacteria (51.2 vs 1%; P < .001) and pan-multidrug-resistant bacteria (13.5 vs 1.1%; P < .001). Bacterial resistance was not related to the length of time after burn injury or to a delay in transfer. In conclusion, multidrug-resistant and pan-resistant organisms seem to be more prevalent among the international pediatric burn population when compared with the U. S. pediatric burn population. Given the relatively high incidence of pan-resistant gram-negative organisms among international transfers, colistin seems to be a reasonable choice for empiric antimicrobial coverage for presumed infections. (J Burn Care Res 2013;34:203-210) C1 [Friedstat, Jonathan S.; Moore, Molly E.; Fagan, Shawn P.; Goverman, Jeremy] Massachusetts Gen Hosp, Dept Surg, Div Burns, Boston, MA 02114 USA. [Friedstat, Jonathan S.; Moore, Molly E.; Weber, Joan M.; Fagan, Shawn P.; Goverman, Jeremy] Shriners Hosp Children, Dept Surg, Div Burns, Boston, MA USA. RP Goverman, J (reprint author), 55 Fruit St,GRB 1303, Boston, MA 02114 USA. NR 29 TC 5 Z9 5 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD JAN-FEB PY 2013 VL 34 IS 1 BP 203 EP 210 DI 10.1097/BCR.0b013e3182781829 PG 8 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 068IH UT WOS:000313359400039 PM 23292590 ER PT J AU Portilla, AS Bravo, GL Miraval, FK Villamar, MF Schneider, JC Ryan, CM Fregni, F AF Portilla, Andrea Santos Bravo, Gabriela L. Miraval, Fiorella K. Villamar, Mauricio F. Schneider, Jeffrey C. Ryan, Colleen M. Fregni, Felipe TI A Feasibility Study Assessing Cortical Plasticity in Chronic Neuropathic Pain Following Burn Injury SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID DIRECT-CURRENT STIMULATION; BRAIN-STIMULATION; MOTOR CORTEX; DISINHIBITION; FIBROMYALGIA AB The aim of this article is to evaluate the neuroplastic changes associated with chronic neuropathic pain following burn injury and modulation feasibility using transcranial direct current stimulation (tDCS). This is a crossover, double-blinded case series involving three patients with chronic neuropathic pain following burn injury. Participants were randomly assigned to undergo single sessions of both sham and active anodal tDCS over the primary motor cortex, contralateral to the most painful site. Excitability of the motor cortex was assessed before and after each stimulation session with the use of transcranial magnetic stimulation. An overall decrease in cortical excitability was seen after active tDCS only, as characterized by a decrease in intracortical facilitation and amplitude of motor evoked potentials and an increase in intracortical inhibition. Clinical outcomes did not change after a single session of tDCS. Results are consistent with previous studies showing that patients with chronic neuropathic pain have defective intracortical inhibition. This case series shows early evidence that chronic pain following burn injury may share similar central neural mechanisms, which could be modulated using tDCS. (J Burn Care Res 2013;34:e48-e52) C1 [Portilla, Andrea Santos; Bravo, Gabriela L.; Miraval, Fiorella K.; Villamar, Mauricio F.; Fregni, Felipe] Spaulding Rehabil Hosp, Lab Neuromodulat, Dept Phys Med & Rehabil, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Ryan, Colleen M.] Massachusetts Gen Hosp, Dept Surg, Sumner Redstone Ctr, Shriners Hosp Children, Boston, MA 02114 USA. RP Fregni, F (reprint author), Spaulding Rehabil Hosp, Lab Neuromodulat, Dept Phys Med & Rehabil, 125 Nashua St 726, Boston, MA 02114 USA. EM Fregni.Felipe@mgh.harvard.edu OI Villamar, Mauricio F./0000-0003-4503-8152 NR 18 TC 8 Z9 9 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD JAN-FEB PY 2013 VL 34 IS 1 BP E48 EP E52 DI 10.1097/BCR.0b013e3182700675 PG 5 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 068IH UT WOS:000313359400008 PM 23292595 ER PT J AU Stetler, RA Leak, RK Gao, YQ Chen, J AF Stetler, R. Anne Leak, Rehana K. Gao, Yanqin Chen, Jun TI The dynamics of the mitochondrial organelle as a potential therapeutic target SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE Biogenesis; cerebral ischemia; mitochondrial dynamics; mitophagy; neurodegeneration ID TRANSIENT CEREBRAL-ISCHEMIA; POLYUNSATURATED FATTY-ACIDS; DELAYED NEURONAL DEATH; RESPIRATORY FACTOR-I; MARIE-TOOTH-DISEASE; PARKINSONS-DISEASE; TRANSCRIPTIONAL CONTROL; FLUORESCENT PROTEIN; AXONAL-TRANSPORT; OXIDATIVE STRESS AB Mitochondria play a central role in cell fate after stressors such as ischemic brain injury. The convergence of intracellular signaling pathways on mitochondria and their release of critical factors are now recognized as a default conduit to cell death or survival. Besides the individual processes that converge on or emanate from mitochondria, a mitochondrial organellar response to changes in the cellular environment has recently been described. Whereas mitochondria have previously been perceived as a major center for cellular signaling, one can postulate that the organelle's dynamics themselves affect cell survival. This brief perspective review puts forward the concept that disruptions in mitochondrial dynamics-biogenesis, clearance, and fission/fusion events-may underlie neural diseases and thus could be targeted as neuroprotective strategies in the context of ischemic injury. To do so, we present a general overview of the current understanding of mitochondrial dynamics and regulation. We then review emerging studies that correlate mitochondrial biogenesis, mitophagy, and fission/fusion events with neurologic disease and recovery. An overview of the system as it is currently understood is presented, and current assessment strategies and their limitations are discussed. Journal of Cerebral Blood Flow & Metabolism (2013) 33, 22-32; doi:10.1038/jcbfm.2012.158; published online 24 October 2012 C1 [Stetler, R. Anne; Gao, Yanqin; Chen, Jun] Fudan Univ, State Key Lab Med Neurobiol, Shanghai Med Coll, Shanghai 200032, Peoples R China. [Stetler, R. Anne; Gao, Yanqin; Chen, Jun] Fudan Univ, Inst Brain Sci, Shanghai Med Coll, Shanghai 200032, Peoples R China. [Stetler, R. Anne] Univ Pittsburgh, Sch Med, Dept Neurol, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. [Stetler, R. Anne; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Leak, Rehana K.] Duquesne Univ, Div Pharmaceut Sci, Mylan Sch Pharm, Pittsburgh, PA 15219 USA. RP Stetler, RA (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. EM stetlerra@upmc.edu; chenj2@upmc.edu RI Gao, Yanqin/I-6790-2016; OI Gao, Yanqin/0000-0002-4915-9819; Leak, Rehana/0000-0003-2817-7417 FU National Institutes of Health/NINDS [NS36736, NS43802, NS56118, NS45048]; VA Merit Review Grant; Chinese Natural Science Foundation [30670642, 30870794, 81020108021]; VA Career Scientist Award; RK Mellon Endowed Chair from the University of Pittsburgh Medical Center; Changjiang Chair Professorship from the Chinese Ministry of Education FX This work was supported by National Institutes of Health/NINDS grants NS36736, NS43802, NS56118, and NS45048, the VA Merit Review Grant, and Chinese Natural Science Foundation grants 30670642, 30870794, and 81020108021. JC is a recipient of the VA Career Scientist Award, the RK Mellon Endowed Chair from the University of Pittsburgh Medical Center, and the Changjiang Chair Professorship from the Chinese Ministry of Education. NR 124 TC 11 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 JAN PY 2013 VL 33 IS 1 BP 22 EP 32 DI 10.1038/jcbfm.2012.158 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 066MJ UT WOS:000313224600003 ER PT J AU Zhang, MJ Li, WJ Niu, GM Leak, RK Chen, J Zhang, F AF Zhang, Meijuan Li, Wenjin Niu, Guangming Leak, Rehana K. Chen, Jun Zhang, Feng TI ATP induces mild hypothermia in rats but has a strikingly detrimental impact on focal cerebral ischemia SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE acidosis; ATP; brain ischemia; hyperglycemia; hypothermia AB The purpose of this study was to test if ATP induces mild hypothermia in rats and reduces ischemic brain injury. We found that ATP (2 g/kg) injection induced mild hypothermia in rats. When ATP induced hypothermia was applied to stroke, however, the infarct volume was larger than control rats. Monitoring of physiological parameters revealed that ATP caused cardiosuppression, hyperglycemia and acidosis. ATP also decreased Akt levels in the cortex. Our results reveal that despite inducing hypothermia, ATP is not appropriate for protecting the brain against stroke. Journal of Cerebral Blood Flow & Metabolism (2013) 33, 157-158; doi:10.1038/jcbfm.2012.146 C1 [Zhang, Meijuan; Li, Wenjin; Chen, Jun; Zhang, Feng] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Zhang, Meijuan; Li, Wenjin; Chen, Jun; Zhang, Feng] Univ Pittsburgh, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. [Zhang, Meijuan; Chen, Jun; Zhang, Feng] Fudan Univ, State Key Lab Med Neurobiol, Shanghai, Peoples R China. [Zhang, Meijuan; Chen, Jun; Zhang, Feng] Fudan Univ, Inst Brain Sci, Shanghai, Peoples R China. [Zhang, Meijuan] Nanjing Univ, Sch Med, Affiliated Drum Tower Hosp, Dept Neurol, Nanjing 210008, Jiangsu, Peoples R China. [Niu, Guangming] Zhengzhou Univ, Affiliated Hosp 2, Dept Neurosurg, Zhengzhou, Henan, Peoples R China. [Leak, Rehana K.] Duquesne Univ, Mylan Sch Pharm, Div Pharmaceut Sci, Pittsburgh, PA 15219 USA. [Chen, Jun; Zhang, Feng] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Zhang, F (reprint author), Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. EM zhanfx2@upmc.edu OI Leak, Rehana/0000-0003-2817-7417; Zhang, Meijuan/0000-0002-5375-5349 FU NIH [NS36736, NS43802, NS45048]; VA Merit Review Grant; American Heart Association [10SDG2560122] FX This work was supported by NIH grants (NS36736, NS43802 and NS45048 to JC), the VA Merit Review Grant (to JC) and the American Heart Association (10SDG2560122 to FZ). NR 4 TC 4 Z9 5 U1 0 U2 4 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 JAN PY 2013 VL 33 IS 1 BP 157 EP 158 DI 10.1038/jcbfm.2012.146 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 066MJ UT WOS:000313224600020 ER PT J AU Koenig, CJ Maguen, S Daley, A Cohen, G Seal, KH AF Koenig, Christopher J. Maguen, Shira Daley, Aaron Cohen, Greg Seal, Karen H. TI Passing the Baton: A Grounded Practical Theory of Handoff Communication Between Multidisciplinary Providers in Two Department of Veterans Affairs Outpatient Settings SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE handoff; communication; outpatient care; decision making; coordination of care; continuity of care; patient-centeredness; clinic efficiency ID HEALTH-CARE-SYSTEM; MENTAL-HEALTH; CURBSIDE CONSULTATION; SPECIALTY CARE; SIGN-OUT; REFERRALS; MEDICINE; OPPORTUNITIES; AFGHANISTAN; EXPERIENCES AB Handoffs are communication processes that enact the transfer of responsibility between providers across clinical settings. Prior research on handoff communication has focused on inpatient settings between provider teams and has emphasized patient safety. This study examines handoff communication within multidisciplinary provider teams in two outpatient settings. To conduct an exploratory study that describes handoff communication among multidisciplinary providers, to develop a theory-driven descriptive framework for outpatient handoffs, and to evaluate the strengths and weaknesses of different handoff types. Qualitative, in-depth, semi-structured interviews with 31 primary care, mental health, and social work providers in two Department of Veterans Affairs (VA) Medical Center outpatient clinics. Audio-recorded interviews were transcribed and analyzed using Grounded Practical Theory to develop a theoretical model of and a descriptive framework for handoff communication among multidisciplinary providers. Multidisciplinary providers reported that handoff decisions across settings were made spontaneously and without clear guidelines. Two situated values, clinic efficiency and patient-centeredness, shaped multidisciplinary providers' handoff decisions. Providers reported three handoff techniques along a continuum: the electronic handoff, which was the most clinically efficient; the provider-to-provider handoff, which balanced clinic efficiency and patient-centeredness; and the collaborative handoff, which was the most patient-centered. Providers described handoff choice as a practical response to manage constituent features of clinic efficiency (time, space, medium of communication) and patient-centeredness (information continuity, management continuity, relational continuity, and social interaction). We present a theoretical and descriptive framework to help providers evaluate differential handoff use, reflect on situated values guiding clinic communication, and guide future research. Handoff communication reflected multidisciplinary providers' efforts to balance clinic efficiency with patient-centeredness within the constraints of day-to-day clinical practice. Evaluating the strengths and weaknesses among alternative handoff options may enhance multidisciplinary provider handoff decision-making and may contribute to increased coordination and continuity of care across outpatient settings. C1 [Koenig, Christopher J.; Seal, Karen H.] Univ Calif San Francisco, Dept Med, San Francisco Vet Adm Med Ctr, San Francisco, CA 94121 USA. [Maguen, Shira; Seal, Karen H.] Univ Calif San Francisco, Dept Psychiat, San Francisco Vet Adm Med Ctr, San Francisco, CA 94121 USA. [Daley, Aaron] San Francisco Gen Hosp, Dept Surg, San Francisco, CA 94110 USA. [Cohen, Greg] Columbia Univ, Dept Epidemiol, New York, NY USA. RP Koenig, CJ (reprint author), Univ Calif San Francisco, Dept Med, San Francisco Vet Adm Med Ctr, 4150 Clement St,116P, San Francisco, CA 94121 USA. EM christopher.koenig@ucsf.edu OI Koenig, Christopher J./0000-0003-0884-4120 FU Department of Defense [W81XWH-08-2-0072, W81XWH-08-2-0106] FX Department of Defense awards W81XWH-08-2-0072 and W81XWH-08-2-0106 funded this study. The funders had no role in the design, data analysis, writing or approval of the manuscript. NR 60 TC 9 Z9 9 U1 3 U2 23 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 JAN PY 2013 VL 28 IS 1 BP 41 EP 50 DI 10.1007/s11606-012-2167-5 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 066GL UT WOS:000313208500009 PM 22868947 ER PT J AU Wenger, NS Citko, J O'Malley, K Diamant, A Lorenz, K Gonzalez, V Tarn, DM AF Wenger, Neil S. Citko, Judy O'Malley, Kate Diamant, Allison Lorenz, Karl Gonzalez, Victor Tarn, Derjung M. TI Implementation of Physician Orders for Life Sustaining Treatment in Nursing Homes in California: Evaluation of a Novel Statewide Dissemination Mechanism SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE nursing home; POLST; end-of-life care; community intervention ID TREATMENT PROGRAM; POLST; CARE; PREFERENCES; FACILITIES; PARADIGM AB Implementing Physician Orders for Life Sustaining Treatment (POLST) forms aims to improve communication of life-sustaining treatment preferences across care venues. California enabled this clinical tool in 2009, and a novel intervention of community coalitions was undertaken to advance POLST in localities around the state. Coalitions engaged facilities, including nursing homes (NHs), to foster POLST adoption. Eighteen months after introduction of POLST, we studied POLST implementation in California NHs. NHs randomly selected in coalition and non-coalition areas were mailed surveys about POLST preparation and use in 2010. Coalitions identified which NHs they worked with. Of 546 NHs surveyed, 143 (52 %) in coalition areas and 141 (52 %) in non-coalition areas responded. In 82 % of responding NHs, staff received POLST education and 59 % of NHs reported having a formal policy on handling POLST. Two-thirds of NHs had admitted a resident with a POLST, and 15 % of newly admitted residents over the past month had a POLST (range 0-100 %). Eighty-one percent of NHs had completed a POLST with a resident. Fifty-four percent of residents were estimated to have a POLST (range 0-100 %) (coalition area NHs 60 % vs. non- coalition area NHs 48 %, p = 0.02). Within coalition areas, NHs that had worked with coalitions were more likely to have completed a POLST with a resident after admission than NHs that had not worked with coalitions. Few NHs (7 %) reported difficulty following POLST orders, but 38 % noted difficulty involving physicians in POLST completion. Less than 2 years after introduction, many California nursing homes report using POLST, although some NHs reported no experience. A novel community coalition intervention facilitated POLST implementation. C1 [Wenger, Neil S.; Diamant, Allison; Gonzalez, Victor] Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90024 USA. [Citko, Judy] Coalit Compassionate Care Calif, Sacramento, CA USA. [O'Malley, Kate] Calif HealthCare Fdn, Oakland, CA USA. [Lorenz, Karl] Greater Los Angeles VA Med Ctr, Los Angeles, CA USA. [Tarn, Derjung M.] Univ Calif Los Angeles, Dept Family Med, Los Angeles, CA 90024 USA. RP Wenger, NS (reprint author), Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, 911 Broxton Plaza 309, Los Angeles, CA 90024 USA. EM nwenger@mednet.ucla.edu FU California HealthCare Foundation FX The authors describe the following conflicts of interest concerning this research: Neil S. Wenger received funding from the California HealthCare Foundation for this project. Judy Citko received funding from the California HealthCare Foundation. Kate O'Malley was employed by the California HealthCare Foundation. Allison Diamant, Karl Lorenz, Victor Gonzalez, Mimi Tarn declare that they have no conflicts of interest. NR 15 TC 13 Z9 13 U1 2 U2 10 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 JAN PY 2013 VL 28 IS 1 BP 51 EP 57 DI 10.1007/s11606-012-2178-2 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 066GL UT WOS:000313208500010 PM 22878851 ER PT J AU Morone, NE Belnap, BH He, FY Mazumdar, S Weiner, DK Rollman, BL AF Morone, Natalia E. Belnap, Bea Herbeck He, Fanyin Mazumdar, Sati Weiner, Debra K. Rollman, Bruce L. TI Pain Adversely Affects Outcomes to a Collaborative Care Intervention for Anxiety in Primary Care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE panic disorder; generalized anxiety disorder; pain; collaborative care; clinical trial ID NATIONAL-COMORBIDITY-SURVEY; DISORDER SEVERITY SCALE; QUALITY-OF-LIFE; GENERALIZED ANXIETY; MENTAL-DISORDERS; PANIC DISORDER; UNITED-STATES; PREVALENCE; DEPRESSION; TRIAL AB Primary care patients with Panic Disorder (PD) and Generalized Anxiety Disorder (GAD) experience poorer than expected clinical outcomes, despite the availability of efficacious pharmacologic and non-pharmacologic treatments. A barrier to recovery from PD/GAD may be the co-occurrence of pain. To evaluate whether pain intensity interfered with treatment response for PD and/or GAD in primary care patients who had received collaborative care for anxiety disorders. A secondary data analysis of a randomized, controlled effectiveness trial comparing a telephone-delivered collaborative care intervention for primary care patients with severe PD and/or GAD to their doctor's "usual" care. Patients had to have a diagnosis of PD and/or GAD and a severe level of anxiety symptoms. The 124 patients randomized at baseline to the collaborative care intervention were analyzed. Participants were divided into two pain intensity groups based on their response to the SF-36 Bodily Pain scale (none or mild pain vs. at least moderate pain). Pain was assessed using the Bodily Pain scale of the SF-36. Anxiety symptoms were measured with the Hamilton Anxiety Rating Scale (HRS-A), Panic Disorder Severity Scale (PDSS) and Generalized Anxiety Disorder Severity Scale (GADSS). Measures were collected over 12 months. At baseline, patients with at least moderate pain were significantly more likely to endorse more anxiety symptoms on the HRS-A than patients with no pain or mild pain (P < .001). Among patients with severe anxiety symptoms, 65 % (80/124) endorsed experiencing at least moderate pain in the previous month. A significantly lesser number of patients achieved a 50 % improvement at 12 months on the HRS-A and GADSS if they had at least moderate pain as compared to patients with little or no pain (P = 0.01 and P = 0.04, respectively). Coexisting pain was common in a sample of primary care patients with severe PD/GAD, and appeared to negatively affect response to anxiety treatment. C1 [Morone, Natalia E.; Belnap, Bea Herbeck; Rollman, Bruce L.] Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Morone, Natalia E.; Weiner, Debra K.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [He, Fanyin; Mazumdar, Sati] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15213 USA. [Weiner, Debra K.] Univ Pittsburgh, Sch Med, Div Geriatr, Pittsburgh, PA 15213 USA. [Weiner, Debra K.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. [Weiner, Debra K.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15213 USA. [Morone, Natalia E.; Belnap, Bea Herbeck; Weiner, Debra K.; Rollman, Bruce L.] Univ Pittsburgh, Sch Med, Clin & Translat Sci Inst, Pittsburgh, PA 15213 USA. RP Morone, NE (reprint author), Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Div Gen Internal Med, 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM moronene@upmc.edu FU National Institute of Mental Health [R01 MH59395] FX All work described was supported by a grant from the National Institute of Mental Health (R01 MH59395). The funding source had no role in the design, conduct, or reporting of our study, or in the preparation, review, or decision to submit this manuscript for publication. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. NR 48 TC 3 Z9 3 U1 4 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 JAN PY 2013 VL 28 IS 1 BP 58 EP 66 DI 10.1007/s11606-012-2186-2 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 066GL UT WOS:000313208500011 PM 22878857 ER PT J AU Edelman, EJ Gordon, K Becker, WC Goulet, JL Skanderson, M Gaither, JR Braden, JB Gordon, AJ Kerns, RD Justice, AC Fiellin, DA AF Edelman, E. Jennifer Gordon, Kirsha Becker, William C. Goulet, Joseph L. Skanderson, Melissa Gaither, Julie R. Braden, Jennifer Brennan Gordon, Adam J. Kerns, Robert D. Justice, Amy C. Fiellin, David A. TI Receipt of Opioid Analgesics by HIV-Infected and Uninfected Patients SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE opioid; pain; HIV; narcotics; veterans ID CHRONIC NONCANCER PAIN; SUBSTANCE USE DISORDERS; CORONARY-HEART-DISEASE; UNITED-STATES; OLDER-ADULTS; PRESCRIBING PATTERNS; COMPARATIVE SAFETY; PRIMARY-CARE; HEPATITIS-C; TROUP AB Opioids are increasingly prescribed, but there are limited data on opioid receipt by HIV status. To describe patterns of opioid receipt by HIV status and the relationship between HIV status and receiving any, high-dose, and long-term opioids. Cross-sectional analysis of the Veterans Aging Cohort Study. HIV-infected (HIV+) patients receiving Veterans Health Administration care, and uninfected matched controls. Pain-related diagnoses were determined using ICD-9 codes. Any opioid receipt was defined as at least one opioid prescription; high-dose was defined as an average daily dose a parts per thousand yen120 mg of morphine equivalents; long-term opioids was defined as a parts per thousand yen90 consecutive days, allowing a 30 day refill gap. Multivariable models were used to assess the relationship between HIV infection and the three outcomes. Among the HIV+ (n = 23,651) and uninfected (n = 55,097) patients, 31 % of HIV+ and 28 % of uninfected (p < 0.001) received opioids. Among patients receiving opioids, HIV+ patients were more likely to have an acute pain diagnosis (7 % vs. 4 %), but less likely to have a chronic pain diagnosis (53 % vs. 69 %). HIV+ patients received a higher mean daily morphine equivalent dose than uninfected patients (41 mg vs. 37 mg, p = 0.001) and were more likely to receive high-dose opioids (6 % vs. 5 %, p < 0.001). HIV+ patients received fewer days of opioids than uninfected patients (median 44 vs. 60, p < 0.001), and were less likely to receive long-term opioids (31 % vs. 34 %, p < 0.001). In multivariable analysis, HIV+ status was associated with receipt of any opioids (AOR 1.40, 95 % CI 1.35, 1.46) and high-dose opioids (AOR 1.22, 95 % CI 1.07, 1.39), but not long-term opioids (AOR 0.94, 95 % CI 0.88, 1.01). Patients with HIV infection are more likely to be prescribed opioids than uninfected individuals, and there is a variable association with pain diagnoses. Efforts to standardize approaches to pain management may be warranted in this highly complex and vulnerable patient population. C1 [Edelman, E. Jennifer; Becker, William C.; Justice, Amy C.; Fiellin, David A.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA. [Edelman, E. Jennifer; Justice, Amy C.; Fiellin, David A.] Yale Univ, Sch Publ Hlth, Ctr Interdisciplinary Res AIDS, New Haven, CT 06520 USA. [Gordon, Kirsha; Becker, William C.; Goulet, Joseph L.; Skanderson, Melissa; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Goulet, Joseph L.; Kerns, Robert D.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. [Braden, Jennifer Brennan] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. [Gordon, Adam J.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Skanderson, Melissa; Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Goulet, Joseph L.; Kerns, Robert D.; Justice, Amy C.] Ctr VA Connecticut Healthcare Syst, Pain Res Informat Med Comorbid & Educ PRIME, West Haven, CT USA. [Kerns, Robert D.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06520 USA. [Kerns, Robert D.] Yale Univ, Sch Med, Dept Psychol, New Haven, CT 06520 USA. RP Edelman, EJ (reprint author), Yale Univ, Sch Med, Dept Internal Med, POB 208093, New Haven, CT 06520 USA. EM ejennifer.edelman@yale.edu OI Becker, William/0000-0002-0788-1467; Fiellin, David/0000-0002-4006-010X; Goulet, Joseph/0000-0002-0842-804X FU Society of General Internal Medicine's Lawrence Linn Award; Robert Wood Johnson Foundation Clinical Scholars Program; Department of Veterans Affairs; Veterans Aging Cohort study; National Institute on Alcohol Abuse and Alcoholism [U10 AA 13566] FX This work was generously supported by the Society of General Internal Medicine's Lawrence Linn Award, the Robert Wood Johnson Foundation Clinical Scholars Program, the Department of Veterans Affairs and the Veterans Aging Cohort study, funded by the National Institute on Alcohol Abuse and Alcoholism (U10 AA 13566). NR 50 TC 19 Z9 19 U1 2 U2 6 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 JAN PY 2013 VL 28 IS 1 BP 82 EP 90 DI 10.1007/s11606-012-2189-z PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 066GL UT WOS:000313208500014 PM 22895747 ER PT J AU Weiser, SD Hatcher, A Frongillo, EA Guzman, D Riley, ED Bangsberg, DR Kushel, MB AF Weiser, Sheri D. Hatcher, Abigail Frongillo, Edward A. Guzman, David Riley, Elise D. Bangsberg, David R. Kushel, Margot B. TI Food Insecurity Is Associated with Greater Acute Care Utilization among HIV-Infected Homeless and Marginally Housed Individuals in San Francisco SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE food security; HIV/AIDS; acute care utilization ID SUPPLEMENTAL NUTRITION PROGRAM; ACTIVE ANTIRETROVIRAL THERAPY; HEALTH-SERVICES UTILIZATION; MEDICAL-CARE; UNITED-STATES; DRUG-USERS; HOUSING INSTABILITY; GENDER DISPARITIES; SUBSISTENCE NEEDS; BEHAVIORAL-MODEL AB Food insecurity, or the uncertain availability of nutritionally adequate, safe foods, has been associated with poor HIV outcomes. There are few data on the extent to which food insecurity impacts patterns of health-care utilization among HIV-infected individuals. We examined whether food insecurity was associated with hospitalizations, Emergency Department (ED) visits, and non-ED outpatient visits. HIV-infected, homeless and marginally housed individuals participating in the San Francisco Research on Access to Care in the Homeless (REACH) cohort underwent quarterly structured interviews and blood draws. We measured food insecurity with the validated Household Food Insecurity Access Scale, and categorized participants as food secure, mild/moderately food insecure, and severely food insecure. Primary outcomes were: (1) any hospitalizations, (2) any ED visits, and (3) any non-ED outpatient visits. Generalized estimating equations were used to estimate model parameters, adjusting for socio-demographic (age, sex, ethnicity, education, income, housing status, health insurance) and clinical variables (CD4 nadir, time on antiretroviral therapy, depression, and illicit drug use). Beginning in November 2007, 347 persons were followed for a median of 2 years. Fifty-six percent of participants were food insecure at enrollment. Compared with food-secure persons, those with severe food insecurity had increased odds of hospitalizations [adjusted odds ratio (AOR) = 2.16, 95 % confidence interval (CI) = 1.50-3.09] and ED visits (AOR = 1.71, 95 % CI = 1.06-2.30). While the odds of an outpatient visit were 41 % higher for severely food insecure individuals, the effect was not statistically significant (AOR = 1.41, 95 % CI = 0.99-2.01). Mild/moderate food insecurity was also associated with increased hospitalizations (AOR = 1.56, 95 % CI = 1.06-2.30), ED visits (AOR = 1.57, 95 % CI = 1.22-2.03), and outpatient visits (AOR = 1.68, 95 % CI = 1.20-2.17). Food insecurity is associated with increased health services utilization among homeless and marginally housed HIV-infected individuals in San Francisco. Increased ED visits and hospitalizations are not related to fewer ambulatory care visits among food-insecure individuals. Addressing food insecurity should be a critical component of HIV treatment programs and may reduce reliance on acute care utilization. C1 [Weiser, Sheri D.; Hatcher, Abigail; Riley, Elise D.] Univ Calif San Francisco UCSF, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA 94143 USA. [Weiser, Sheri D.] Univ Calif San Francisco UCSF, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA. [Frongillo, Edward A.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Hlth Promot Educ & Behav, Columbia, SC 29208 USA. [Guzman, David; Kushel, Margot B.] Univ Calif San Francisco UCSF, San Francisco Gen Hosp, Div Gen Internal Med, San Francisco, CA 94143 USA. [Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Global Hlth,Ragon Inst MGH MIT & Harvard, Boston, MA USA. RP Weiser, SD (reprint author), Univ Calif San Francisco UCSF, San Francisco Gen Hosp, Div HIV AIDS, POB 0874, San Francisco, CA 94143 USA. EM Sheri.Weiser@ucsf.edu RI Nguyen, Giang/D-9027-2016; Hatcher, Abigail/G-9128-2011 OI Hatcher, Abigail/0000-0002-4150-1405 FU NIMH [54907, 79713-01]; CHRP [ID08-SF-054]; UCSF Academic Senate; Hurlbut-Johnson funds from AIDS Research Institute award, UCSF [557858-8-148]; Burke Family Foundation; Hellman Family Foundation [K24 MH-87227]; National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [UL1 RR024131]; NIH Roadmap for Medical Research FX NIMH 54907, 79713-01; CHRP ID08-SF-054; UCSF Academic Senate; Hurlbut-Johnson funds from AIDS Research Institute award, UCSF, no. 557858-8-148. The authors acknowledge the following additional sources of salary support: the Burke Family Foundation and the Hellman Family Foundation (to Dr. Weiser), and K24 MH-87227 (to Dr. Bangsberg).; This publication was made possible by grant no. UL1 RR024131 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the NCRR or the NIH. Information on NCRR is available at http:///www.ncrr.nih.gov. NR 87 TC 22 Z9 22 U1 3 U2 15 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 JAN PY 2013 VL 28 IS 1 BP 91 EP 98 DI 10.1007/s11606-012-2176-4 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 066GL UT WOS:000313208500015 PM 22903407 ER PT J AU Castiglioni, A Aagaard, E Spencer, A Nicholson, L Karani, R Bates, CK Willett, LL Chheda, SG AF Castiglioni, Analia Aagaard, Eva Spencer, Abby Nicholson, Laura Karani, Reena Bates, Carol K. Willett, Lisa L. Chheda, Shobhina G. TI Succeeding as a Clinician Educator: Useful Tips and Resources SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article ID ACADEMIC MEDICINE; FACULTY-DEVELOPMENT; SUCCESS; GUIDE; SCHOLARSHIP; WORK AB Clinician Educators (CEs) play an essential role in the education and patient care missions of academic medical centers. Despite their crucial role, academic advancement is slower for CEs than for other faculty. Increased clinical productivity demands and financial stressors at academic medical centers add to the existing challenges faced by CEs. This perspective seeks to provide a framework for junior CEs to consider with the goal of maximizing their chance of academic success. We discuss six action areas that we consider central to flourishing at academic medical centers: 1. Clarify what success means and define goals; 2. Seek mentorship and be a responsible mentee; 3. Develop a niche and engage in relevant professional development; 4. Network; 5. Transform educational activities into scholarship; and 6. Seek funding and other resources. C1 [Castiglioni, Analia] Univ Alabama Birmingham, Div Gen Internal Med, Birmingham VA Med Ctr, Birmingham, AL USA. [Aagaard, Eva] Univ Colorado, Sch Med, Div Gen Internal Med, Aurora, CO USA. [Spencer, Abby] Temple Univ, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. [Nicholson, Laura] Scripps Clin, La Jolla, CA USA. [Nicholson, Laura] Green Hosp, La Jolla, CA USA. [Nicholson, Laura] Univ Calif San Diego, San Diego, CA 92103 USA. [Karani, Reena] Mt Sinai Sch Med, New York, NY USA. [Bates, Carol K.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Willett, Lisa L.] Univ Alabama Birmingham, Sch Med, Internal Med Residency Program, Birmingham, AL USA. [Chheda, Shobhina G.] Univ Wisconsin, Sch Med & Publ Hlth, Div Gen Internal Med, Madison, WI USA. RP Castiglioni, A (reprint author), Univ Alabama Birmingham, Div Gen Internal Med, Birmingham VA Med Ctr, Birmingham, AL USA. EM ANALIA.CASTIGLIONI@GMAIL.COM NR 32 TC 2 Z9 2 U1 0 U2 6 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 JAN PY 2013 VL 28 IS 1 BP 136 EP 140 DI 10.1007/s11606-012-2156-8 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 066GL UT WOS:000313208500021 PM 22836953 ER PT J AU Lobo, LJ Aris, RM Schmitz, J Neuringer, IP AF Lobo, Leonard J. Aris, Robert M. Schmitz, John Neuringer, Isabel. P. TI Donor-specific antibodies are associated with antibody-mediated rejection, acute cellular rejection, bronchiolitis obliterans syndrome, and cystic fibrosis after lung transplantation SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article DE lung transplant; donor-specific antibodies; antibody-mediated rejection; cystic fibrosis; lung allograft dysfunction ID HLA ANTIBODIES; C4D DEPOSITION; 2 PARTS; ALLOGRAFT; RECIPIENTS; ANTIGENS; SENSITIZATION; LYMPHOCYTES; PHENOTYPE; INFECTION AB BACKGROUND: Lung transplantation is limited by chronic lung allograft dysfunction. Acute cellular rejection (ACR) is a risk factor for allograft dysfunction; however, the role of antibody-mediated rejection (AMR) is not well characterized. METHODS: This was a retrospective review from 2007 to 2011 of lung transplant recipients with human leukocyte antigen (HLA) antibody testing using Luminex (Luininex Corp, Austin, TX) single-antigen beads. Statistics included Fisher's exact test for significance. RESULTS: Donor-specific antibodies (DSA) developed in 13 of 44 patients. Of the 13 with DSA, 12 had cystic fibrosis compared with 18 of 31 in the non-DSA group (p = 0.035). Of those with DSAs, 23.1% occurred within the first year, and 69.2% occurred between 1 and 3 years. Twelve of 13 DSA patients had anti-HLA DQ specificity compared with 2 of 31 non-DSA patients (p = 0.0007). AMR developed in 10 of the 13 DSA patients compared with 1 of 31 non-DSA patients (p = 0.0001). The DSA group experienced 2.6 episodes/patient of cellular rejection vs 1.7 episodes/patient in the non-DSA group (p = 0.059). Bronchiolitis obliterans syndrome developed in 11 of 13 in the DSA group vs 10 of 31 in the non-DSA group (p = 0.0024). In the DSA group, 11.5% HLAs matched compared with 20.4% in the non-DSA group (p = 0.093). AMR developed in 11 of 22 patients in the non-DSA HLA group compared with 0 of 22 in the group without non-DSA HLA antibodies (p = 0.002). Survival at 1 and 3 years was 92% and 36% in the DSA group, respectively, and 97% and 65% in the non-DSA group. CONCLUSIONS: DSAs and non-DSAs occur frequently after lung transplantation. DSAs are prevalent in the cystic fibrosis population and are associated with AMR, bronchiolitis obliterans syndrome, and possibly, ACR. J Heart Lung Transplant 2013;32:70-77 (C) 2013 International Society for Heart and Lung Transplantation. All rights reserved. C1 [Lobo, Leonard J.; Aris, Robert M.] Univ N Carolina, Div Pulm & Crit Care Med, Chapel Hill, NC 27599 USA. [Neuringer, Isabel. P.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Lobo, LJ (reprint author), Univ N Carolina, Div Pulm & Crit Care Med, 130 Mason Farm Rd,Campus Box 7020, Chapel Hill, NC 27599 USA. EM leonardlobo@gmail.com NR 50 TC 53 Z9 53 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD JAN PY 2013 VL 32 IS 1 BP 70 EP 77 DI 10.1016/j.healun.2012.10.007 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 066LT UT WOS:000313223000012 PM 23260706 ER PT J AU Jiang, T Zhu, AX Sahani, DV AF Jiang, Tao Zhu, Andrew X. Sahani, Dushyant V. TI Established and novel imaging biomarkers for assessing response to therapy in hepatocellular carcinoma SO JOURNAL OF HEPATOLOGY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; DIFFUSION-WEIGHTED MRI; TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION; TUMOR RESPONSE; COMPUTED-TOMOGRAPHY; SOLID TUMORS; EVALUATION CRITERIA; TARGETED THERAPIES; MODIFIED RECIST; TRANSARTERIAL CHEMOEMBOLIZATION AB The management of hepatocellular carcinoma (HCC) is evolving because of recently introduced novel therapeutic approaches. There is growing recognition that optimal outcome requires choosing treatment tailored to suit each individual patient, necessitating an early and accurate assessment of tumor response to therapy. The established and adapted image biomarkers based on size for tumor burden measurement continues to be applied to HCC as size measurement can easily be used in any clinical practice. However, in the setting of novel targeted therapies and liver directed treatments, simple tumor anatomical changes can be less informative and usually appear later than biological changes. Therefore the importance of image biomarkers such as tumor viability measurement, functional perfusion and diffusion imaging for response assessment is increasingly being recognized. Although promising, these imaging biomarkers have not gone through all the required steps of standardization and validation. In this review, we discuss various established, evolving and emerging imaging biomarkers and the criteria of response evaluation and their challenges in HCC. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 [Jiang, Tao; Sahani, Dushyant V.] Harvard Univ, Sch Med, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Jiang, Tao] Second Mil Med Univ, ChangZheng Hosp, Dept Radiol, Shanghai 200003, Peoples R China. [Zhu, Andrew X.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Zhu, AX (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,LH POB 232, Boston, MA 02114 USA. EM azhu@partners.org; dsahani@partners.org FU National Natural Science Foundation of China [81101044]; Shanghai Rising-Star Program; Special program of military medicine of second military medical university FX Tao Jiang, M.D. received partial financial support from the National Natural Science Foundation of China (No. 81101044), Shanghai Rising-Star Program, Special program of military medicine of second military medical university. The other authors declared no conflicts of interest. NR 75 TC 15 Z9 17 U1 0 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD JAN PY 2013 VL 58 IS 1 BP 169 EP 177 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 066NJ UT WOS:000313227200027 PM 22944253 ER PT J AU Baxi, S Platts-Mills, J Dhruva, S Huang, L Hanks, D Dhaliwal, G AF Baxi, Sanjiv Platts-Mills, James Dhruva, Sanket Huang, Laurence Hanks, Doug Dhaliwal, Gurpreet TI A double-edged sword SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID RECONSTITUTION INFLAMMATORY SYNDROME; HIV-INFECTED PATIENTS; NON-HODGKIN-LYMPHOMA; KAPOSI-SARCOMA; ANTIRETROVIRAL THERAPY; AIDS; FEATURES C1 [Baxi, Sanjiv] Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA 94110 USA. [Platts-Mills, James] Univ Virginia, Dept Internal Med, Div Infect Dis, Charlottesville, VA USA. [Dhruva, Sanket] Univ Calif Davis, Dept Internal Med, Div Cardiovasc Med, Sacramento, CA 95817 USA. [Huang, Laurence] Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco Gen Hosp, San Francisco, CA 94110 USA. [Hanks, Doug] Univ Calif San Francisco, Dept Pathol, San Francisco Gen Hosp, San Francisco, CA 94110 USA. [Dhaliwal, Gurpreet] Univ Calif San Francisco, Med Serv, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94110 USA. RP Baxi, S (reprint author), Univ Calif San Francisco, Dept Med, Div Infect Dis, 505 Parnassus St,M987, San Francisco, CA 94110 USA. EM sanjiv.baxi@ucsf.edu OI Huang, Laurence/0000-0003-3888-2195 NR 20 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD JAN PY 2013 VL 8 IS 1 BP 47 EP 51 DI 10.1002/jhm.1999 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 065BK UT WOS:000313121800009 PM 23293015 ER PT J AU Susarla, SM Dodson, TB AF Susarla, Srinivas M. Dodson, Thomas B. TI Predicting Third Molar Surgery Operative Time: A Validated Model SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID DIFFICULTY AB Purpose: The purpose of the present study was to develop and validate a statistical model to predict third molar (M3) operative time. Materials and Methods: This was a prospective cohort study consisting of a sample of subjects presenting for M3 removal. The demographic, anatomic, and operative variables were recorded for each subject. Using an index sample of randomly selected subjects, a multiple linear regression model was generated to predict the operating time. A nonoverlapping group of randomly selected subjects (validation sample) was used to assess model accuracy. P <= .05 was considered significant. Results: The sample was composed of 150 subjects (n) who had 450 (k) M3s removed. The index sample (n = 100 subjects, k = 313 M3s extracted) had a mean age of 25.4 +/- 10.0 years. The mean extraction time was 6.4 +/- 7.0 minutes. The multiple linear regression model included M3 location, Winter's classification, tooth morphology, number of teeth extracted, procedure type, and surgical experience (R-2 = 0.58). No statistically significant differences were seen between the index sample and the validation sample (n = 50, k = 137) for any of the study variables. Compared with the index model, the beta-coefficients of the validation model were similar in direction and magnitude for most variables. Compared with the observed extraction time for all teeth in the sample, the predicted extraction time was not significantly different (P = .16). Conclusions: Fair agreement was seen between the beta-coefficients for our multiple models in the index and validation populations, with no significant difference in the predicted and observed operating times. (C) 2013 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 71: 5-13, 2013 C1 [Susarla, Srinivas M.; Dodson, Thomas B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, Boston, MA 02114 USA. [Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. RP Susarla, SM (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, WACC230, Boston, MA 02114 USA. EM SSUSARLA1@partners.org OI Susarla, Srinivas/0000-0003-0155-8260 FU Harvard Medical School Office of Enrichment Programs Student Research Award; Oral and Maxillofacial Surgery Research Foundation; National Institutes of Dental and Craniofacial Research [K24-DE000448]; Oral and Maxillofacial Surgery Foundation; Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Center for Applied Clinical Investigation and Education and Research Fund FX This work was supported by the Harvard Medical School Office of Enrichment Programs Student Research Award (S.M.S.), Oral and Maxillofacial Surgery Research Foundation Student Training Award (S.M.S.), National Institutes of Dental and Craniofacial Research Mid-Career Award in Patient-Oriented Research (grant K24-DE000448; T.B.D.), Oral and Maxillofacial Surgery Foundation Fellowship Award in Clinical Investigation (S.M.S.), and Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Center for Applied Clinical Investigation and Education and Research Fund (S.M.S., T.B.D.). NR 11 TC 3 Z9 3 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JAN PY 2013 VL 71 IS 1 BP 5 EP 13 DI 10.1016/j.joms.2012.08.004 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 068EH UT WOS:000313347400013 PM 23010375 ER PT J AU Abramowicz, S Goldwaser, BR Troulis, MJ Padwa, BL Kaban, LB AF Abramowicz, Shelly Goldwaser, Batya R. Troulis, Maria J. Padwa, Bonnie L. Kaban, Leonard B. TI Primary Jaw Tumors in Children SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID GIANT-CELL GRANULOMA; CRANIOFACIAL FIBROUS DYSPLASIA; CALCITONIN THERAPY; ANTIANGIOGENIC THERAPY; INTERFERON-ALPHA; LESIONS; MANAGEMENT; MAXILLA; BONE AB Purpose: To document tumor type, biological/clinical behavior, management, and outcomes in children with primary jaw tumors. Materials and Methods: A retrospective analysis of children with primary benign jaw tumors evaluated at Massachusetts General Hospital and Children's Hospital Boston from 1991 to 2009 was conducted. Patients were included if they were aged 16 years or younger and had adequate records and follow-up. Patient charts, radiographs, and pathology reports were reviewed. Demographic data; clinical, radiographic, and histopathologic findings; treatment; and outcomes were recorded. Predictor variables were tumor type, clinical behavior (nonaggressive/aggressive), and treatment. Outcome variables included presence or absence of recurrence and complications. Descriptive statistics were computed. Results: There were 102 patients (44 male and 58 female patients) with a mean age of 8.3 years (range, 6 months to 16 years). Tumors were grouped by tumor type: mesenchymal (n = 96), neurogenic (n = 5), vascular (n = 5), or hematopoietic (n = 3); in addition, when appropriate, they were classified as nonaggressive (n = 54) or aggressive (n = 27). Treatment was based on the tumor's clinical/biological behavior and radiographic features and whether it was solitary or multifocal. Patients with nonaggressive tumors were treated by enucleation, debulking/contouring, or observation, and the recurrence rate was 0%. Aggressive tumors underwent en bloc resection or enucleation with systemic adjuvant therapy, and the recurrence rate was 7.1%. Mean follow-up was 2.4 years. Conclusions: The results of this study indicate that primary jaw tumors in children exhibit variable biological/clinical behavior, often not predicted by descriptive histologic findings. Management of these tumors should therefore be guided by clinical/biological behavior. (C) 2013 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 71: 47-52, 2013 C1 [Abramowicz, Shelly; Troulis, Maria J.; Padwa, Bonnie L.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Abramowicz, Shelly; Padwa, Bonnie L.] Childrens Hosp, Dept Plast & Oral Surg, Boston, MA 02445 USA. [Goldwaser, Batya R.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Abramowicz, S (reprint author), Childrens Hosp, Dept Plast & Oral Surg, 300 Longwood Ave, Boston, MA 02445 USA. EM shelly.abramowicz@childrens.harvard.edu FU Oral and Maxillofacial Surgery Foundation/American Association of Oral and Maxillofacial Surgeons Faculty Educator Development Award; Massachusetts General Hospital Oral and Maxillofacial Surgery Education and Research Fund; Hanson Foundation (Boston, MA) FX Supported in part by Oral and Maxillofacial Surgery Foundation/American Association of Oral and Maxillofacial Surgeons Faculty Educator Development Award (S.A.), Massachusetts General Hospital Oral and Maxillofacial Surgery Education and Research Fund (B.R.G.), and the Hanson Foundation (Boston, MA) (M.J.T.). NR 35 TC 3 Z9 3 U1 1 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JAN PY 2013 VL 71 IS 1 BP 47 EP 52 DI 10.1016/j.joms.2012.04.045 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 068EH UT WOS:000313347400019 PM 22766384 ER PT J AU Abramson, ZR Susarla, SM Lawler, ME Peacock, ZS Troulis, MJ Kaban, LB AF Abramson, Zachary R. Susarla, Srinivas M. Lawler, Matthew E. Peacock, Zachary S. Troulis, Maria J. Kaban, Leonard B. TI Effects of Mandibular Distraction Osteogenesis on Three-Dimensional Airway Anatomy in Children With Congenital Micrognathia SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID OBSTRUCTIVE SLEEP-APNEA; COMPUTED TOMOGRAPHIC ANALYSIS; MAXILLOMANDIBULAR ADVANCEMENT; LENGTH AB Purpose: To assess the 3-dimensional (3D) computed tomography (CT) changes in airway size and shape in children with congenital micrognathia treated by mandibular distraction osteogenesis (DO). Patients and Methods: This was a retrospective study of patients with congenital micrognathia, treated by mandibular DO, who had pre- and postoperative 3D maxillofacial CT scans from the hard palate to the hyoid bone. Digital 3D-CT reconstructions were made before and after distraction. Demographic (age, gender, and diagnosis) and anatomic (airway size and shape) variables were recorded and analyzed. The pre-distraction measures of size and shape were compared with the post-distraction measures. P <= .05 was considered significant. Results: During the study period (1999 to 2010), 17 children with congenital micrognathia underwent mandibular DO. Of these patients, 11 (3 females) met the inclusion criteria. The mean age was 6.8 years (range 1.3 to 20.6). All subjects had first and second pharyngeal arch deformities. Nine were tracheostomy dependent before distraction. Postdistraction increases in the anteroposterior diameter (153%), lateral airway diameter (70%), airway volume (76%), minimal retroglossal (162%) and retropalatal (77%), and minimal cross-sectional areas (282%) were obtained. The mean airway length decreased after distraction by 4 mm DO also affected the airway shape: the airway surface area and airway compactness increased after distraction. Six subjects were decannulated or had their tracheostomies capped. Three subjects remained tracheostomy dependent after distraction. The reasons for continued tracheostomy included copious secretions, muscle hypotonia, hypopharnygeal stenosis, and mandibular hypomobility. Conclusions: DO for congenital micrognathia increases airway size, decreases airway length, and alters the shape as measured using 3D-CT. (C) 2013 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 71: 90-97, 2013J Oral Maxillofac Surg 71: 90-97, 2013 C1 [Abramson, Zachary R.; Susarla, Srinivas M.; Peacock, Zachary S.; Kaban, Leonard B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Peacock, Zachary S.; Troulis, Maria J.; Kaban, Leonard B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. RP Kaban, LB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,WRN 1201, Boston, MA 02114 USA. EM lkaban@partners.org OI Susarla, Srinivas/0000-0003-0155-8260 FU MGH Department of Oral and Maxillofacial Surgery Education and Research Fund; MGH/AO/Synthes Fellowship in Pediatric Craniomaxillofacial Surgery FX The study was funded by the MGH Department of Oral and Maxillofacial Surgery Education and Research Fund and the MGH/AO/Synthes Fellowship in Pediatric Craniomaxillofacial Surgery. NR 22 TC 8 Z9 8 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JAN PY 2013 VL 71 IS 1 BP 90 EP 97 DI 10.1016/j.joms.2012.03.014 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 068EH UT WOS:000313347400027 PM 22632931 ER PT J AU Loftis, JM Patterson, AL Wilhelm, CJ McNett, H Morasco, BJ Huckans, M Morgan, T Saperstein, S Asghar, A Hauser, P AF Loftis, Jennifer M. Patterson, Alexander L. Wilhelm, Clare J. McNett, Henry Morasco, Benjamin J. Huckans, Marilyn Morgan, Timothy Saperstein, Shira Asghar, Aliya Hauser, Peter TI Vulnerability to somatic symptoms of depression during interferon-alpha therapy for hepatitis C: A 16-week prospective study SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE Cytokines; Depression; Fatigue; Hepatitis C; Interferon-alpha; Pain; Serotonin ID QUALITY-OF-LIFE; NECROSIS-FACTOR-ALPHA; INDOLEAMINE 2,3-DIOXYGENASE; SEROTONIN TRANSPORTER; ANTIVIRAL THERAPY; CANCER-PATIENTS; INVENTORY-II; RISK-FACTOR; POLYMORPHISM; ACTIVATION AB Objective: This study evaluated the distinctive clinical and biological manifestations of depressive symptom sub-types (i.e., cognitive-affective and somatic) in Veterans with hepatitis C viral infection (HCV) before and during interferon-alpha (IFN) based antiviral therapy. Methods: Thirty-two Veterans with HCV and no prior history of IFN therapy were followed prospectively during the first 16 weeks of therapy to evaluate depressive symptoms and to determine if baseline cytokine and serotonin levels predicted subsequent changes in depressive scores. Results: IFN therapy resulted in a significant increase in total depressive symptoms from baseline (week 0) to week 16, with neurovegetative and somatic symptoms of depression including loss of appetite, fatigue and irritability increasing within the first two weeks of therapy and continuing to increase throughout IFN therapy. When depressive symptoms were evaluated using a two-factor (i.e., Cognitive-Affective and Somatic) model; the Cognitive-Affective factor score did not change significantly following IFN therapy initiation, while the Somatic factor score showed a significant increase from week 0 to week.16. Veterans with the largest increases in somatic symptoms from week 0 to week 2 had significantly higher levels of tumor necrosis factor-alpha. (TNF-alpha) and lower levels of serotonin at baseline, as compared to Veterans with minimal or no increase in somatic symptoms. Conclusion: Somatic symptoms of depression can be significantly exacerbated during IFN therapy and may be predicted by higher TNF-alpha levels and lower serotonin levels at baseline. Published by Elsevier Inc. C1 [Loftis, Jennifer M.; Wilhelm, Clare J.; McNett, Henry; Huckans, Marilyn] Portland VA Med Ctr, Res & Dev Serv, Portland, OR 97239 USA. [Loftis, Jennifer M.; Wilhelm, Clare J.; McNett, Henry; Morasco, Benjamin J.; Huckans, Marilyn] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Patterson, Alexander L.; Morasco, Benjamin J.; Huckans, Marilyn] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR 97239 USA. [Morgan, Timothy; Saperstein, Shira; Asghar, Aliya] VA Long Beach Healthcare Syst, Long Beach, CA USA. [Hauser, Peter] VISN 22 Network Off, Long Beach, CA 90802 USA. RP Loftis, JM (reprint author), Portland VA Med Ctr, Res & Dev Serv, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM Jennifer.loftis2@va.gov; Peter.hauser2@va.gov FU Department of Veterans Affairs (VA), Veterans Health Administration, Office of Research and Development, Clinical Sciences Research and Development FX This material is based upon work supported by a Merit Review grant (P.H.) and Career Development Awards (J.M.L. and M.H.) from the Department of Veterans Affairs (VA), Veterans Health Administration, Office of Research and Development, Clinical Sciences Research and Development. This material is the result of work supported with resources and the use of facilities at the Portland VA Medical Center, Portland, Oregon and the VA Long Beach Health Care System. The authors would like to thank Matthew McQuesten and Elizabeth Grimaldi for their help with patient recruitment, data collection/ entry, and study coordination; Starr DeGennaro for administrative and programmatic support; and, Anna Sasaki, Betsy Zucker, Patricia Taylor-Young, Michael Chang, and Frank Lotrich for their continued collaboration and support of this research program. NR 57 TC 17 Z9 18 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD JAN PY 2013 VL 74 IS 1 BP 57 EP 63 DI 10.1016/j.jpsychores.2012.10.012 PG 7 WC Psychiatry SC Psychiatry GA 068TW UT WOS:000313390100011 PM 23272989 ER PT J AU Strong, R Miller, RA Astle, CM Baur, JA de Cabo, R Fernandez, E Guo, W Javors, M Kirkland, JL Nelson, JF Sinclair, DA Teter, B Williams, D Zaveri, N Nadon, NL Harrison, DE AF Strong, Randy Miller, Richard A. Astle, Clinton M. Baur, Joseph A. de Cabo, Rafael Fernandez, Elizabeth Guo, Wen Javors, Martin Kirkland, James L. Nelson, James F. Sinclair, David A. Teter, Bruce Williams, David Zaveri, Nurulain Nadon, Nancy L. Harrison, David E. TI Evaluation of Resveratrol, Green Tea Extract, Curcumin, Oxaloacetic Acid, and Medium-Chain Triglyceride Oil on Life Span of Genetically Heterogeneous Mice SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Longevity; Aging; Mice; Diet; Interventions ID INTERVENTIONS TESTING PROGRAM; CAENORHABDITIS-ELEGANS; EXTENDING LIFE; RATS; ANTIOXIDANT; LONGEVITY; RESTRICTION; RAPAMYCIN; SURVIVAL; CATECHIN AB The National Institute on Aging Interventions Testing Program (ITP) was established to evaluate agents that are hypothesized to increase life span and/or health span in genetically heterogeneous mice. Each compound is tested in parallel at three test sites. It is the goal of the ITP to publish all results, negative or positive. We report here on the results of lifelong treatment of mice, beginning at 4 months of age, with each of five agents, that is, green tea extract (GTE), curcumin. oxaloacetic acid, medium-chain triglyceride oil, and resveratrol, on the life span of genetically heterogeneous mice. Each agent was administered beginning at 4 months of age. None of these five agents had a statistically significant effect on life span of male or female mice, by log-rank test, at the concentrations tested, although a secondary analysis suggested that GTE might diminish the risk of midlife deaths in females only. C1 [Strong, Randy; Fernandez, Elizabeth] Univ Texas Hlth Sci Ctr San Antonio, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78245 USA. [Strong, Randy; Fernandez, Elizabeth] Univ Texas Hlth Sci Ctr San Antonio, Res Serv, S Texas Vet Hlth Care Syst, San Antonio, TX 78245 USA. [Strong, Randy; Fernandez, Elizabeth; Javors, Martin] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78245 USA. [Strong, Randy; Fernandez, Elizabeth; Nelson, James F.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Miller, Richard A.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Miller, Richard A.] Univ Michigan, Geriatr Ctr, Ann Arbor, MI 48109 USA. [Astle, Clinton M.; Harrison, David E.] Jackson Lab, Bar Harbor, ME 04609 USA. [Baur, Joseph A.] Univ Penn, Dept Physiol, Philadelphia, PA 19104 USA. [Baur, Joseph A.] Univ Penn, Inst Diabet Obes & Metab, Perelman Sch Med, Philadelphia, PA 19104 USA. [de Cabo, Rafael] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. [Guo, Wen] Boston Univ, Dept Med, Evans Biomed Res Ctr, Boston, MA 02215 USA. [Javors, Martin] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78245 USA. [Kirkland, James L.] Mayo Clin, Robert & Arlene Kogod Ctr Aging, Sw Rochester, MN USA. [Nelson, James F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78245 USA. [Sinclair, David A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Teter, Bruce] VA Greater Angeles Healthcare Syst, Dept Med, Sepulveda, CA USA. [Williams, David] Univ Calif Los Angeles, Sch Med, Dept Ophthalmol, Los Angeles, CA 90024 USA. [Williams, David] Univ Calif Los Angeles, Sch Med, Dept Neurobiol, Los Angeles, CA 90024 USA. [Zaveri, Nurulain] Astraea Therapeut LLC, Mountain View, CA USA. [Nadon, Nancy L.] NIA, Div Aging Biol, Bethesda, MD 20892 USA. RP Strong, R (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM strong@uthscsa.edu RI Kirkland, James/F-9159-2016; de Cabo, Rafael/J-5230-2016; OI , rafael/0000-0003-2830-5693; de Cabo, Rafael/0000-0002-3354-2442; Baur, Joseph/0000-0001-8262-6549; Sinclair, David/0000-0002-9936-436X FU National Institute on Aging at the National Institutes of Health [U01-AG022303, U01-AG025707, U01-AG022308, AG13925, U01-AG022307, P30-AG13319]; Department of Veterans Affairs; Intramural Research Program of the National Institute on Aging FX This work was supported by the National Institute on Aging at the National Institutes of Health (U01-AG022303 to RAM., U01-AG025707 and U01-AG022308 to D.E.H., AG13925 to J.L.K., and U01-AG022307 and P30-AG13319 to R.S.) and the Department of Veterans Affairs (R.S.). R.d.C. is supported by the Intramural Research Program of the National Institute on Aging. NR 44 TC 48 Z9 48 U1 3 U2 30 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 JAN PY 2013 VL 68 IS 1 BP 6 EP 16 DI 10.1093/gerona/gls070 PG 11 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 065MU UT WOS:000313153400002 PM 22451473 ER PT J AU Wieland, D Kinosian, B Stallard, E Boland, R AF Wieland, Darryl Kinosian, Bruce Stallard, Eric Boland, Rebecca TI Does Medicaid Pay More to a Program of All-Inclusive Care for the Elderly (PACE) Than for Fee-for-Service Long-term Care? SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Long-term care financing; Grade-of-membership analysis; Medicare/Medicaid dual eligibles; Managed long-term care; Latent structure models ID ALZHEIMERS-DISEASE; MEMBERSHIP; GRADE; HOME; MODELS AB Background. In rebalancing from nursing homes (NHs), states are increasing access of NH-certified dually eligible (Medicare/Medicaid) patients to community waiver programs and Programs of All-Inclusive Care for the Elderly (PACE). Prior evaluations suggest Medicaid's PACE capitation exceeds its spending for comparable admissions in alternative care, although the latter may be underestimated. We test whether Medicaid payments to PACE are lower than predicted fee-for-service outlays in a long-term care admission cohort. Methods. Using grade-of-membership methods, we model health deficits for dual eligibles aged 55 or more entering waiver, PACE, and NH in South Carolina (n = 3,988). Clinical types, membership vectors, and program type prevalences are estimated. We calculate a blend, fitting PACE between fee-for-service cohorts, whose postadmission 1-year utilization was converted to attrition-adjusted outlays. PACE's capitation is compared with blend-based expenditure predictions. Results. Four clinical types describe population health deficits/service needs. The waiver cohort is most represented in the least impaired type (1: 47.1%), NH entrants in the most disabled (4: 38.5%). Most prevalent in PACE was a dementia type, 3 (32.7%). PACE's blend was waiver: 0.5602 (95% CI: 0.5472, 0.5732) and NH: 0.4398 (0.4268.0.4528). Average Medicaid attrition adjusted 1-year payments for waiver and NH were $4,177 and $77,945. The mean predicted cost for PACE patients in alternative long-term care was $36,620 ($35,662 and $37,580). PACE's Medicaid capitation was $27,648-28% below the lower limit of predicted fee-for-service payments. Conclusions. PACE's capitation was well under outlays for equivalent patients in alternative care-a substantial savings for Medicaid. Our methods provide a rate-setting element for PACE and other managed long-term care. C1 [Wieland, Darryl; Boland, Rebecca] Univ S Carolina, Palmetto Hlth Richland, Div Geriatr Serv, Sch Med, Columbia, SC 29203 USA. [Wieland, Darryl] Univ S Carolina, Div Geriatr, Sch Med, Columbia, SC 29203 USA. [Kinosian, Bruce] Univ Penn, Ctr Hlth Equ Res & Promot, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Kinosian, Bruce] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Stallard, Eric] Duke Univ, Ctr Populat Hlth & Aging, Duke Populat Res Inst, Durham, NC USA. [Stallard, Eric] Duke Univ, Social Sci Res Inst, Durham, NC USA. RP Wieland, D (reprint author), Univ S Carolina, Palmetto Hlth Richland, Div Geriatr Serv, Sch Med, 3010 Farrow Rd,300A, Columbia, SC 29203 USA. EM darryl.wieland@palmettohealth.org FU South Carolina Department of Health and Human Services; Palmetto Health Richland, Columbia SC FX Earlier versions of the work reported here were supported under contract from the South Carolina Department of Health and Human Services with Palmetto Health Richland, Columbia SC. NR 31 TC 6 Z9 6 U1 0 U2 28 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 JAN PY 2013 VL 68 IS 1 BP 47 EP 55 DI 10.1093/gerona/gls137 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 065MU UT WOS:000313153400006 PM 22565242 ER PT J AU Metti, AL Cauley, JA Newman, AB Ayonayon, HN Barry, LC Kuller, LM Satterfield, S Simonsick, EM Yaffe, K AF Metti, Andrea L. Cauley, Jane A. Newman, Anne B. Ayonayon, Hilsa N. Barry, Lisa C. Kuller, Lewis M. Satterfield, Suzanne Simonsick, Eleanor M. Yaffe, Kristine TI Plasma Beta Amyloid Level and Depression in Older Adults SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Depression; Epidemiology; Plasma beta amyloid ID MILD COGNITIVE IMPAIRMENT; ALZHEIMER-DISEASE; APOLIPOPROTEIN-E; CES-D; RISK; SYMPTOMS; DEMENTIA; ASSOCIATION; HISTORY; DECLINE AB Background. Older adults with depression have an increased risk of developing dementia. Low plasma beta-amyloid 42 (A beta 42) and A beta 42/A beta 40 have emerged as promising biomarkers of dementia. The association between depression and plasma A beta is unclear. Methods. In this longitudinal study of 988 community-dwelling elders from the Health Aging and Body Composition study, depression was assessed with the Center for Epidemiologic Studies-Depression Scale 10-item version. We determined the association between A beta 42 and A beta 42/A beta 40 tertile and depression at baseline and over 9 years. We also stratified the models to determine if apolipoprotein E e4 allele status modified the associations. Results. Mean baseline age was 74.0 +/- 3.0 years, 51(5.2%) participants had depression, 545 (55.2%) were women, 531 (53.7%) were black, and 286(30.7%) had one or more apolipoprotein E e4 allele. At baseline, there was no association between A beta 42/A beta 40 or A beta 42 and depression. Over 9 years, 220 (23.5%) participants developed depression. In adjusted Cox proportional hazards models, among those with one or more e4 allele, low A beta 42/A beta 40 was associated with an increased risk of developing depression over time (low 10.8% vs high 3.2%, hazard ratio = 2.38, 95% confidence interval: 1.15-4.92). Among those with no e4 allele, there was no association between A beta 42/A beta 40 and risk of depression over time (13.3% vs 17.5%, hazard ratio = 0.80, 95% confidence interval: 0.52-1.23; p value for interaction = .003). Conclusions. The association between low plasma A beta 42/A beta 40 and increased risk of incident depression among those with one or more apolipoprotein E e4 allele implies a synergistic relationship similar to that found with dementia. Future work should investigate the interrelationships among plasma A beta 42/A beta 40, depression, and dementia. C1 [Metti, Andrea L.] Univ Pittsburgh, Ctr Aging & Populat Hlth, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Ayonayon, Hilsa N.; Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Barry, Lisa C.] Univ Connecticut, Ctr Hlth, Ctr Aging, Farmington, CT USA. [Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Memphis, TN USA. [Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. RP Metti, AL (reprint author), Univ Pittsburgh, Ctr Aging & Populat Hlth, Dept Epidemiol, Grad Sch Publ Hlth, 130 N Bellefield,Room 434, Pittsburgh, PA 15213 USA. EM alw111@pitt.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Cauley, Jane A/0000-0003-0752-4408 FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIA [R01-AG028050]; National Institute of Nursing Research [R01-NR012459]; Intramural Research Program on the National Institutes of Health (NIH), NIA FX This work was supported by National Institute on Aging (NIA) Contracts N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA grant R01-AG028050, and National Institute of Nursing Research grant R01-NR012459. This research was supported in part by the Intramural Research Program on the National Institutes of Health (NIH), NIA. NR 31 TC 15 Z9 15 U1 2 U2 10 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 JAN PY 2013 VL 68 IS 1 BP 74 EP 79 DI 10.1093/gerona/gls093 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 065MU UT WOS:000313153400010 PM 22499763 ER PT J AU Wang, H Chen, YL Fernandez-Del Castillo, C Yilmaz, O Deshpande, V AF Wang, He Chen, Yili Fernandez-Del Castillo, Carlos Yilmaz, Omer Deshpande, Vikram TI Heterogeneity in signaling pathways of gastroenteropancreatic neuroendocrine tumors: a critical look at notch signaling pathway SO MODERN PATHOLOGY LA English DT Article DE carcinoid tumor; neuroendocrine tumor; notch ID CARCINOID-TUMORS; CELL-CARCINOMA; EXPRESSION; DIFFERENTIATION; INHIBITOR; SYSTEM AB The molecular pathogenesis of gastroenteropancreatic neuroendocrine tumors is largely unknown. We hypothesize that gastroenteropancreatic neuroendocrine tumors are heterogeneous with regard to these signaling pathways and these differences could have a significant impact on the outcome of clinical trials. We selected 120 well-differentiated neuroendocrine tumors including tumors originating in pancreas (n=74), ileum (n=31), and rectum (n=15). Immunohistochemistry was performed on tissue microarrays using the following antibodies: NOTCH1, HES1, HEY1, pIGF1R, and FGF2. Gene profiling study was performed by using human genome U133A 2.0 array and data were analyzed. The gene profiling results were selectively confirmed by using quantitative reverse-transcription PCR. Initial immunohistochemical analysis showed NOTCH1 was uniformly expressed in rectal neuroendocrine tumors (100%), a subset of pancreatic neuroendocrine tumors (34%), and negative in Heal neuroendocrine tumors. Similarly, a downstream target of NOTCH1, HES1 was preferentially expressed in rectal neuroendocrine tumors (64%), a subset of pancreatic neuroendocrine tumors (10%), and uniformly negative in Heal neuroendocrine tumors. Messenger RNAs for NOTCH1, HES1, and HEY1 were 2.32-, 2.44-, and 2.39-folds, respectively, higher in rectal neuroendocrine tumors as compared with ileal neuroendocrine tumors. Global gene expression profiling showed 95 genes were differentially expressed in small intestinal vs rectal neuroendocrine tumors, with changes as high as 50-fold. These genes were concentrated in several signal transduction pathways including cancer endocrine pathway and cell growth/proliferation pathway. The differential expression of selected genes including ISL LIM homeobox 1, cathepsin B, glucagon, and tryptophan hydroxylase 1 were confirmed by qPCR and immunohistochemistry. Our results confirm the heterogeneity in signaling pathways of gastroenteropancreatic neuroendocrine tumors. NOTCH1 inhibitors are unlikely to provide benefit in Heal neuroendocrine tumors; conversely, their efficacy in rectal neuroendocrine tumors needs further study. Further analysis of signaling pathways is critical for designing clinical trials in gastroenteropancreatic neuroendocrine tumors. Modern Pathology (2013) 26, 139-147; doi:10.1038/nnodpathol.2012.143; published online 24 August 2012 C1 [Wang, He; Chen, Yili; Yilmaz, Omer; Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Fernandez-Del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 3,55 Fruit St, Boston, MA 02114 USA. EM vdeshpande@partners.org NR 24 TC 11 Z9 11 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 JAN PY 2013 VL 26 IS 1 BP 139 EP 147 DI 10.1038/nnodpathol.2012.143 PG 9 WC Pathology SC Pathology GA 067PF UT WOS:000313306900016 PM 22918166 ER PT J AU Harris, NL AF Harris, Nancy L. TI Shades of gray between large B-cell lymphomas and Hodgkin lymphomas: differential diagnosis and biological implications SO MODERN PATHOLOGY LA English DT Article DE classification; immunophenotype; lymphoma ID CD23 EXPRESSION; LIMITED-STAGE; ZONE LYMPHOMA; MARKER; DISTINGUISHES; SIGNATURE; CHILDREN; FEATURES; TUMOR AB Hodgkin lymphomas (HLs) are neoplasms of large B cells. Two types are recognized: nodular lymphocyte predominant HL (NLPHL) and classical HL (CHL). In both types, there may be morphological and possibly biological overlap with large B-cell lymphomas (LBCLs) of non-HL types. These include nodular sclerosis CHL and primary mediastinal large B-cell lymphoma; CHL rich in lymphocytes and NLPHL; and NLPHL and T-cell/histiocyte-rich LBCL. This review covers the defining features of each of these diseases, the borderlines between them, and strategies for differential diagnosis. Modern Pathology (2013) 26, S57-S70; doi:10.1038/modpathol.2012.182 C1 [Harris, Nancy L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Harris, Nancy L.] Harvard Univ, Sch Med, Boston, MA USA. RP Harris, NL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,32 Fruit St, Boston, MA 02114 USA. EM nlharris@partners.org NR 32 TC 26 Z9 27 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 JAN PY 2013 VL 26 SU 1 BP S57 EP S70 DI 10.1038/modpathol.2012.182 PG 14 WC Pathology SC Pathology GA 067PH UT WOS:000313307100005 PM 23281436 ER PT J AU Sperling, RA Karlawish, J Johnson, KA AF Sperling, Reisa A. Karlawish, Jason Johnson, Keith A. TI OPINION Preclinical Alzheimer disease-the challenges ahead SO NATURE REVIEWS NEUROLOGY LA English DT Article ID AMYLOID-BETA; CLINICAL DECLINE; RISK; ASSOCIATION; COGNITION; ADULTS; RECOMMENDATIONS; ABNORMALITIES; PREDICTION; BIOMARKERS AB There is growing recognition that the pathophysiological process of Alzheimer disease (AD) begins many years prior to clinically obvious symptoms, and the concept of a presymptomatic or preclinical stage of AD is becoming more widely accepted. Advances in biomarker studies have enabled detection of AD pathology in vivo in clinically normal older individuals. The predictive value of these biomarkers at the individual patient level, however, remains to be elucidated. The ultimate goal of identifying individuals in the preclinical stages of AD is to facilitate early intervention to delay and perhaps even prevent emergence of the clinical syndrome. A number of challenges remain to be overcome before this concept can be validated and translated into clinical practice. Sperling, R. A. et al. Nat. Rev. Neurol. 9, 54-58 (2013); published online 27 November 2012; doi:10.1038/nrneurol.2012.241 C1 [Sperling, Reisa A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment,Dept Neurol, Boston, MA 02115 USA. [Karlawish, Jason] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Karlawish, Jason] Univ Penn, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. [Johnson, Keith A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Johnson, Keith A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Sperling, RA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment,Dept Neurol, 221 Longwood Ave, Boston, MA 02115 USA. EM reisa@rics.bwh.harvard.edu FU National Institute on Aging [P01 AG036694, P50 AG005134, R01 AG027435, R01 AG037497]; American Health Assistance Foundation; Alzheimer's Association; Robert Wood Johnson Investigator Award in Health Policy Research FX The work of R. A. Sperling and K. A. Johnson is supported in part by the National Institute on Aging (P01 AG036694; P50 AG005134; R01 AG027435; R01 AG037497), the American Health Assistance Foundation, and the Alzheimer's Association. J. Karlawish's work is supported by a Robert Wood Johnson Investigator Award in Health Policy Research. The authors thank N. Arzoumanian for her assistance with preparation of this manuscript before submission. NR 33 TC 60 Z9 60 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4758 J9 NAT REV NEUROL JI Nat. Rev. Neurol. PD JAN PY 2013 VL 9 IS 1 BP 54 EP 58 DI 10.1038/nrneurol.2012.241 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 062ZE UT WOS:000312962600008 PM 23183885 ER PT J AU Schwamm, LH Starkman, S AF Schwamm, Lee H. Starkman, Sidney TI Have CT-will travel To boldly go where no scan has gone before SO NEUROLOGY LA English DT Editorial Material ID ACUTE STROKE; GUIDELINES; ATTACK; CARE C1 [Schwamm, Lee H.] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, TeleStroke & Acute Stroke Serv, Boston, MA 02115 USA. [Starkman, Sidney] Univ Calif Los Angeles, Los Angeles, CA USA. RP Schwamm, LH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, TeleStroke & Acute Stroke Serv, Boston, MA 02115 USA. EM lschwamm@partners.org OI Schwamm, Lee/0000-0003-0592-9145 NR 11 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN PY 2013 VL 80 IS 2 BP 130 EP 131 DI 10.1212/WNL.0b013e31827d44ca PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 068DM UT WOS:000313344700007 PM 23223538 ER PT J AU Weintraub, D Papay, K Siderowf, A AF Weintraub, Daniel Papay, Kimberly Siderowf, Andrew CA Parkinson's Progression Markers TI Screening for impulse control symptoms in patients with de novo Parkinson disease A case-control study SO NEUROLOGY LA English DT Article ID CONTROL DISORDERS; COGNITIVE IMPAIRMENT; DOPAMINE AGONISTS; BEHAVIORS; DYSREGULATION; PROGRESSION; PREVALENCE; ONSET; MOCA AB Objective: To determine the frequency and correlates of impulse control and related behavior symptoms in patients with de novo, untreated Parkinson disease (PD) and healthy controls (HCs). Methods: The Parkinson's Progression Markers Initiative is an international, multisite, case-control clinical study conducted at 21 academic movement disorders centers. Participants were recently diagnosed, untreated PD patients (n = 168) and HCs (n = 143). The outcome measures were presence of current impulse control and related behavior symptoms based on recommended cutoff points for the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP)-Short Form. Results: There were 311 participants with complete QUIP data. Frequencies of impulse control and related behavior symptoms for patients with PD vs HCs were as follows: gambling (1.2% vs 0.7%), buying (3.0% vs 2.1%), sexual behavior (4.2% vs 3.5%), eating (7.1% vs 10.5%), punding (4.8% vs 2.1%), hobbyism (5.4% vs 11.9%), walkabout (0.6% vs 0.7%), and any impulse control or related behavior (18.5% vs 20.3%). In multivariable models, a diagnosis of PD was not associated with symptoms of any impulse control or related behavior (p >= 0.10 in all cases). Conclusions: PD itself does not seem to confer an increased risk for development of impulse control or related behavior symptoms, which further reinforces the reported association between PD medications and impulse control disorders in PD. Given that approximately 20% of patients with newly diagnosed PD report some impulse control or related behavior symptoms, long-term follow-up is needed to determine whether such patients are at increased risk for impulse control disorder development once PD medications are initiated. Neurology (R) 2013;80:176-180 C1 [Weintraub, Daniel; Papay, Kimberly; Siderowf, Andrew] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis & Mental Illness Res, Educ Ctr, Philadelphia, PA USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis & Mental Illness Res, Clin Ctr, Philadelphia, PA USA. RP Weintraub, D (reprint author), Univ Penn, Sch Med, Philadelphia, PA 19104 USA. EM daniel.weintraub@uphs.upenn.edu FU NIH [NS-053488]; Michael J. Fox Foundation for Parkinson's Research; Novartis Pharmaceuticals; Morris K. Udall Parkinson's Disease Research Center of Excellence grant from NINDS [NS-053488]; NINDS [NS0444451]; National Parkinson Foundation; Michael J. Fox Foundation; Teva Neuroscience; Ipsen pharmaceuticals; Schering-Plough; Merck Serono; General Electric; PPMI; Abbott; Biogen Idec; F. Hoffman-La Roche Ltd.; GE Healthcare; Genentech; Pfizer Inc. FX D. Weintraub receives grant support from the NIH (NS-053488), The Michael J. Fox Foundation for Parkinson's Research, and Novartis Pharmaceuticals; consulting or advisory board membership with honoraria from Teva Pharmaceuticals, Eli Lilly and Company, Lundbeck Inc., Biogen, Pfizer, and Avanir Pharmaceuticals, Merck & Co. K. Papay reports no disclosures. A. Siderowf is supported by a Morris K. Udall Parkinson's Disease Research Center of Excellence grant from NINDS (NS-053488), a U01 from the NINDS (NS0444451), the National Parkinson Foundation and The Michael J. Fox Foundation. He is an employee of Avid Radiopharmaceuticals. He has received consulting fees and honoraria from Teva Neuroscience, Ipsen pharmaceuticals, Schering-Plough and Merck Serono, and General Electric. Go to Neurology.org for full disclosures.; The study was sponsored by the PPMI.; PPMI, a public-private partnership, is funded by The Michael J. Fox Foundation for Parkinson's Research and funding partners, including Abbott, Biogen Idec, F. Hoffman-La Roche Ltd., GE Healthcare, Genentech, and Pfizer Inc. A list of the Executive Steering Committee contributors is available online. NR 27 TC 54 Z9 55 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 JAN PY 2013 VL 80 IS 2 BP 176 EP 180 DI 10.1212/WNL.0b013e31827b915c PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 068DM UT WOS:000313344700014 PM 23296128 ER PT J AU Pulicken, MJ Hsieh, DT Hoch, DB Cole, AJ AF Pulicken, Mathew J. Hsieh, David T. Hoch, Daniel B. Cole, Andrew J. TI Journal Club: Randomized phase III study 306 Adjunctive perampanel for refractory partial-onset seizures SO NEUROLOGY LA English DT Editorial Material ID EPILEPSY C1 [Pulicken, Mathew J.; Hsieh, David T.; Hoch, Daniel B.; Cole, Andrew J.] Massachusetts Gen Hosp, Epilepsy Serv, Boston, MA 02114 USA. RP Cole, AJ (reprint author), Massachusetts Gen Hosp, Epilepsy Serv, Boston, MA 02114 USA. EM cole.andrew@mgh.harvard.edu OI Hoch, Daniel/0000-0002-4294-024X NR 6 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN PY 2013 VL 80 IS 2 BP E17 EP E19 DI 10.1212/WNL.0b013e31827b92e4 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 068DM UT WOS:000313344700002 ER PT J AU Caffee, MW Nishiizumi, K Sisterson, JM Ullmann, J Welten, KC AF Caffee, M. W. Nishiizumi, K. Sisterson, J. M. Ullmann, J. Welten, K. C. TI Cross section measurements at neutron energies 71 and 112 MeV and energy integrated cross section measurements (0.1 < E-n < 750 MeV) for the neutron induced reactions O(n,x)Be-10, Si(n,x)Be-10, and Si(n,x)Al-26 SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS LA English DT Article; Proceedings Paper CT 12th International Conference on Accelerator Mass Spectrometry (AMS) CY MAR 20-25, 2011 CL GNS Sci, Wellington, NEW ZEALAND SP GNS Sci, Natl Isotope Ctr, Australian Nucl Sci & Technol Org, High Voltage Engn, Natl Electrostat Corp HO GNS Sci DE Neutron induced reaction; Cross sections; Cosmogenic nuclides; Long-lived nuclides; Accelerator mass spectrometry ID COSMOGENIC-NUCLIDE PRODUCTION; ACCELERATOR MASS-SPECTROMETRY; PRODUCTION-RATES; AMS STANDARDS; AL-26; BE-10; SOLAR; SIMULATIONS; CL-36 AB The cross sections for the reactions O(n,x)Be-10, Si(n,x)Be-10, and Si(n,x)Al-26 were measured at neutron energies 71 and 112 MeV. The neutron cross sections for O(n,x)10Be are higher than the corresponding proton cross sections at 70-110 MeV and the neutron induced cross section for Si(n,x)Be-10 at 112 MeV is slightly higher than the corresponding proton cross section. Cross sections for the production of Al-26 from Si are similar to those from protons at low energies (<40 MeV) while at higher energies the measured neutron cross sections for Si(n,x)Al-26 are lower than the corresponding proton cross sections. Energy integrated (average) cross sections for these reactions were measured using 'white' neutron beams (0.1 < E-n < 750 MeV). The Al-26/Be-10 production rate ratio from SiO2 measured using 'white' neutrons is considerably lower than that observed in terrestrial quartz (SiO2). (C) 2012 Elsevier B.V. All rights reserved. C1 [Caffee, M. W.] Purdue Univ, Dept Phys, W Lafayette, IN 47907 USA. [Nishiizumi, K.; Welten, K. C.] Univ Calif Berkeley, Space Sci Lab, Berkeley, CA 94720 USA. [Sisterson, J. M.] Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. [Ullmann, J.] Los Alamos Natl Lab, LANSCE, Los Alamos, NM 87545 USA. RP Caffee, MW (reprint author), Purdue Univ, Dept Phys, W Lafayette, IN 47907 USA. EM mcaffee@purdue.edu RI Caffee, Marc/K-7025-2015 OI Caffee, Marc/0000-0002-6846-8967 NR 21 TC 5 Z9 5 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-583X J9 NUCL INSTRUM METH B JI Nucl. Instrum. Methods Phys. Res. Sect. B-Beam Interact. Mater. Atoms PD JAN PY 2013 VL 294 BP 479 EP 483 DI 10.1016/j.nimb.2012.07.011 PG 5 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Atomic, Molecular & Chemical; Physics, Nuclear SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA 066QC UT WOS:000313234300093 ER PT J AU Rosen, CS Tiet, QQ Harris, AHS Julian, TF McKay, JR Moore, WM Owen, RR Rogers, S Rosito, O Smith, DE Smith, MW Schnurr, PP AF Rosen, Craig S. Tiet, Quyen Q. Harris, Alex H. S. Julian, Terri F. McKay, James R. Moore, William Mark Owen, Richard R. Rogers, Susan Rosito, Olga Smith, Dale E. Smith, Mark W. Schnurr, Paula P. TI Telephone Monitoring and Support After Discharge From Residential PTSD Treatment: A Randomized Controlled Trial SO PSYCHIATRIC SERVICES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; ADDICTION SEVERITY INDEX; MENTAL-HEALTH TREATMENT; OF-VETERANS-AFFAIRS; CLINICAL EFFECTIVENESS; PSYCHIATRIC-TREATMENT; MEDICATION ADHERENCE; TREATMENT ENGAGEMENT; CARE MANAGEMENT; CONTINUING CARE AB Objective: This study assessed whether adding a telephone care management protocol to usual aftercare improved the outcomes of veterans in the year after they were discharged from residential treatment for post-traumatic stress disorder (PTSD). Methods: In a multisite randomized controlled trial, 837 veterans entering residential PTSD treatment were assigned to receive either standard outpatient aftercare (N=425) or standard aftercare plus biweekly telephone monitoring and support (N=412) for three months after discharge. Symptoms of PTSD and depression, violence, substance use, and quality of life were assessed by self-report questionnaires at intake, discharge, and four and 12 months postdischarge. Treatment utilization was determined from the Department of Veterans Affairs administrative data. Results: Telephone case monitors reached 355 participants (86%) by phone at least once and provided an average of 4.5 of the six calls planned. Participants in the telephone care and treatment-as-usual groups showed similar outcomes on all clinical measures. Time to rehospitalization did not differ by condition. In contrast with prior studies reporting poor treatment attendance among veterans, participants in both telephone monitoring and treatment as usual completed a mental health visit an average of once every ten days in the year after discharge. Many participants had continuing problems despite high utilization of outpatient care. Conclusions: Telephone care management had little incremental value for patients who were already high utilizers of mental health services. Telephone care management could potentially be beneficial in settings where patients experience greater barriers to engaging with outpatient mental health care after discharge from inpatient treatment. (Psychiatric Services 64:13-20, 2013; doi: 10.1176/appi.ps.201200142) C1 [Rosen, Craig S.; Tiet, Quyen Q.] Vet Affairs VA Palo Alto Hlth Care Syst, Natl Ctr Posttraumat Stress Disorder PTSD, Disseminat & Training Div, Menlo Pk, CA 94025 USA. [Harris, Alex H. S.] Vet Affairs VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA 94025 USA. [Rosen, Craig S.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. [Tiet, Quyen Q.] Alliant Int Univ, Calif Sch Profess Psychol, San Francisco, CA USA. [Julian, Terri F.] VA Western New York Hlth Care Syst, Behav Hlth Care Line, Batavia, IL USA. [McKay, James R.] Philadelphia VA Med Ctr, Philadelphia VA Ctr Excellence Subst Abuse Treatm, Philadelphia, PA USA. [McKay, James R.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Moore, William Mark] Cent Arkansas Vet Healthcare Syst, PTSD Outpatient Program, N Little Rock, AR USA. [Owen, Richard R.] Cent Arkansas Vet Healthcare Syst, Ctr Mental Healthcare & Outcomes Res, N Little Rock, AR USA. [Owen, Richard R.] Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. [Owen, Richard R.] Univ Arkansas Med Sci, Dept Epidemiol, Little Rock, AR 72205 USA. [Rogers, Susan] Coatesville VA Med Ctr, PTSD Domiciliary, Coatesville, PA USA. [Rosito, Olga] Palo Alto Univ, Pacific Grad Sch Psychol, Palo Alto, CA USA. [Smith, Dale E.] VA Puget Sound Hlth Care Syst, PTSD Domiciliary, Amer Lake, Washington, DC USA. [Smith, Mark W.] Truven Hlth Analyt, Washington, DC USA. [Schnurr, Paula P.] White River Junct VA Med Ctr, Natl Ctr PTSD Execut Div, White River Jct, VT USA. [Schnurr, Paula P.] Geisel Sch Med Dartmouth, Dept Psychiat, Hanover, NH USA. RP Rosen, CS (reprint author), Vet Affairs VA Palo Alto Hlth Care Syst, Natl Ctr Posttraumat Stress Disorder PTSD, Disseminat & Training Div, 795 Willow Rd, Menlo Pk, CA 94025 USA. EM craig.rosen@va.gov RI Smith, Mark/G-1522-2012 OI Smith, Mark/0000-0002-4582-9088 FU Office of Research and Development, U.S. Department of Veterans Affairs (VA) Veterans Health Administration [TEL-03-135]; VA Center for Health Care Evaluation; VA Palo Alto Health Care System FX This work was partially supported by grant TEL-03-135 awarded to Dr. Rosen by the Office of Research and Development, U.S. Department of Veterans Affairs (VA) Veterans Health Administration. It was also supported by the VA Center for Health Care Evaluation and the VA Palo Alto Health Care System. The authors thank the veterans whoparticipated in this trial as well as Eric Crawford, Ph.D., and Carolyn Greene, Ph.D., for clinical and administrative supervision; Julie Fitt, B.A., B.S., and Kathryn Kalaf, B.S., for study coordination; Douglas Anderson, M.A., Debra Boyd, M.Ed., Emerald Katz, B.A., Leslie McCulloch, Ph.D., Skye Sellars, B.A., and Samantha Tidd, B.S., for subject recruitment; and Brad Belsher, Ph.D., Allison Broennimann, Ph.D., Zeno Franco, Ph.D., Megan Goodwin, Psy.D., Erin Joyce, Psy.D., Candy Katoa, Psy.D., David Scott Klajic, Ph.D., Megan McElheran, Psy.D., Kate Marino, Psy.D., Jennifer Sweeton, Psy.D., and Seth Tuengel, M.S.W., for delivery of the telephone care intervention. The opinions expressed in this article are those of the authors and do not necessarily represent the position of the VA. NR 53 TC 10 Z9 10 U1 1 U2 18 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JAN PY 2013 VL 64 IS 1 BP 13 EP 20 DI 10.1176/appi.ps.201200142 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 067MV UT WOS:000313299500005 PM 23117443 ER PT J AU Sousa, SA Corriveau, D Lee, AF Bianco, LG Sousa, GM AF Sousa, Sharon Ann Corriveau, Donald Lee, Austin Fong Bianco, Louis G. Sousa, George M. TI The LORS-Enabled Dialogue: A Collaborative Intervention to Promote Recovery From Psychotic Disorders SO PSYCHIATRIC SERVICES LA English DT Article ID BIPOLAR DISORDER; CHRONIC-SCHIZOPHRENIA; TREATMENT ADHERENCE; LONG-TERM; INSIGHT; MEDICATION; ATTITUDES; ILLNESS; RELAPSE AB Objective: This study examined the effectiveness of the LORS-Enabled Dialogue (LED) in reducing the discrepancy between clinicians' and patients' ratings of the severity of symptoms of psychotic disorders, improving adherence to medication, and improving functioning. Methods: The LED intervention addresses the discrepancy between a clinician's severity rating of 13 symptoms measured by the Levels of Recovery From Psychotic Disorders Scale (LORS-clinician) and a patient's severity rating (LORS-patient). A discrepancy in ratings (LORS-discrepancy), which is conceptualized as a patient's lack of awareness of his or her symptoms, is used by the clinician as the focus of a brief motivational interviewing technique, the LED, to enhance recovery. Ninety adult inpatients or outpatients with psychotic disorders were randomly assigned to the LED intervention (N=50) or a control group (N=40). They were assessed on measures of symptom awareness (LORS-discrepancy), psychopathology (LORS-clinician, LORS-patient, and the Positive and Negative Syndrome Scale [PANSS]), adherence to medication (Kemp Compliance Tool), and functioning at baseline and at four postbaseline monthly assessments. The LED intervention was provided weekly for inpatients and monthly for outpatients. Results: Among LED intervention participants, a decrease in psychopathology, as measured by the PANSS and LORS-clinician scores, and an improvement in functioning were noted, along with a decrease in LORS-discrepancy scores. Conclusions: The LED intervention appears to be an efficient and effective treatment to reduce the severity of psychotic symptoms and improve functioning among persons with psychotic disorders. Further study of this intervention in various populations and clinical settings is needed. (Psychiatric Services 64:58-64, 2013; doi: 10.1176/appi.ps.201100421) C1 [Sousa, Sharon Ann] Univ Massachusetts Dartmouth, Coll Nursing, N Dartmouth, MA 02747 USA. [Corriveau, Donald] Univ Massachusetts Dartmouth, Dept Psychol, N Dartmouth, MA 02747 USA. [Lee, Austin Fong] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Bianco, Louis G.] Univ Massachusetts Dartmouth, Dept Math, N Dartmouth, MA 02747 USA. [Sousa, George M.] Bentley Univ, Dept Nat & Appl Sci, Waltham, MA USA. RP Sousa, SA (reprint author), Univ Massachusetts Dartmouth, Coll Nursing, 285 Old Westport Rd,Dion 201D, N Dartmouth, MA 02747 USA. EM ssousa@umassd.edu FU Eli Lilly and Company [FID-US-X301] FX This research was supported by grant FID-US-X301 from Eli Lilly and Company. The authors thank patients, clinicians, students, colleagues, and mentors for their efforts and support over multiple years. They also thank the National Alliance on Mental Illness for the original inspiration for the LORS and the need to have improved interventions to increase patient awareness of and recovery from psychotic symptoms. NR 29 TC 1 Z9 1 U1 0 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JAN PY 2013 VL 64 IS 1 BP 58 EP 64 DI 10.1176/appi.ps.201100421 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 067MV UT WOS:000313299500011 PM 23117253 ER PT J AU Lindquist, KA Siegel, EH Quigley, KS Barrett, LF AF Lindquist, Kristen A. Siegel, Erika H. Quigley, Karen S. Barrett, Lisa Feldman TI The Hundred-Year Emotion War: Are Emotions Natural Kinds or Psychological Constructions? Comment on Lench, Flores, and Bench (2011) SO PSYCHOLOGICAL BULLETIN LA English DT Editorial Material DE emotion; natural kinds; psychological construction; construct validity; meta-analysis ID BASIC EMOTIONS; CHALLENGE APPRAISAL; FACIAL EXPRESSIONS; CORE AFFECT; BRAIN; EXPERIENCE; FEAR; ANGER; METAANALYSIS; SPECIFICITY AB For the last century, there has been a continuing debate about the nature of emotion. In the most recent offering in this scientific dialogue, Lench, Flores, and Bench (2011) reported a meta-analysis of emotion induction research and claimed support for the natural kind hypothesis that discrete emotions (e.g., happiness, sadness, anger, and anxiety) elicit specific changes in cognition, judgment, behavior, experience, and physiology. In this article, we point out that Lench et al. (2011) is not the final word on the emotion debate. First, we point out that Lench et al.'s findings do not support their claim that discrete emotions organize cognition, judgment, experience, and physiology because they did not demonstrate emotion-consistent and emotion-specific directional changes in these measurement domains. Second, we point out that Lench et al.'s findings are in fact consistent with the alternative (a psychological constructionist approach to emotion). We close by appealing for a construct validity approach to emotion research, which we hope will lead to greater consensus on the operationalization of the natural kind and psychological construction approaches, as well as the criteria required to finally resolve the emotion debate. C1 [Lindquist, Kristen A.] Univ N Carolina, Dept Psychol, Chapel Hill, NC 27599 USA. [Siegel, Erika H.; Quigley, Karen S.; Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Bedford, MA USA. [Quigley, Karen S.] Edith Nourse Rogers Mem Vet Adm Hosp, Bedford, MA 01730 USA. [Barrett, Lisa Feldman] Harvard Univ, Massachusetts Gen Hosp, Med School, Cambridge, MA 02138 USA. RP Lindquist, KA (reprint author), Univ N Carolina, Dept Psychol, Davie Hall, Chapel Hill, NC 27599 USA. EM kristen.lindquist@unc.edu FU NIH HHS [DP1OD003312, DP1 OD003312] NR 90 TC 22 Z9 23 U1 14 U2 74 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0033-2909 J9 PSYCHOL BULL JI Psychol. Bull. PD JAN PY 2013 VL 139 IS 1 BP 255 EP 263 DI 10.1037/a0029038 PG 9 WC Psychology; Psychology, Multidisciplinary SC Psychology GA 066OR UT WOS:000313230600014 PM 23294094 ER PT J AU Kim, Y Ripke, S Kirov, G Sklar, P Purcell, SM Owen, MJ O'Donovan, MC Sullivan, PF AF Kim, Yunjung Ripke, Stephan Kirov, George Sklar, Pamela Purcell, Shaun M. Owen, Michael J. O'Donovan, Michael C. Sullivan, Patrick F. TI Non-random mating, parent-of-origin, and maternal-fetal incompatibility effects in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Human leukocyte antigens; Non-random mating; Maternal-fetal incompatibility ID RISK; ASSOCIATION; HISTOCOMPATIBILITY; COMMON AB Although the association of common genetic variation in the extended MHC region with schizophrenia is the most significant yet discovered, the MHC region is one of the more complex regions of the human genome, with unusually high gene density and long-range linkage disequilibrium. The statistical test on which the MHC association is based is a relatively simple, additive model which uses logistic regression of SNP genotypes to predict case-control status. However, it is plausible that more complex models underlie this association. Using a well-characterized sample of trios, we evaluated more complex models by looking for evidence for: (a) non-random mating for HLA alleles, schizophrenia risk profiles, and ancestry; (b) parent- of-origin effects for HLA alleles; and (c) maternal-fetal genotype incompatibility in the HLA. We found no evidence for non-random mating in the parents of individuals with schizophrenia in terms of MHC genotypes or schizophrenia risk profile scores. However, there was evidence of non-random mating that appeared mostly to be driven by ancestry. We did not detect over-transmission of HLA alleles to affected offspring via the general TDT test (without regard to parent of origin) or preferential transmission via paternal or maternal inheritance. We evaluated the hypothesis that maternal-fetal HLA incompatibility may increase risk for schizophrenia using eight classical HLA loci. The most significant alleles were in HLA-B, HLA-C, HLA-DQB1, and HLA-DRB1 but none was significant after accounting for multiple comparisons. We did not find evidence to support more complex models of gene action, but statistical power may have been limiting. (C) 2012 Elsevier B.V. All rights reserved. C1 [Kim, Yunjung; Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Ripke, Stephan; Purcell, Shaun M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kirov, George; Owen, Michael J.; O'Donovan, Michael C.] Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF10 3AX, S Glam, Wales. [Sullivan, Patrick F.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. [Sklar, Pamela; Purcell, Shaun M.] Mt Sinai Sch Med, Div Psychiat Genom, New York, NY USA. [Purcell, Shaun M.] Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Purcell, Shaun M.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Purcell, Shaun M.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Purcell, Shaun M.] Harvard Univ, Sch Med, Boston, MA USA. RP Sullivan, PF (reprint author), Univ N Carolina, Dept Genet, CB 7264,5097 Genom Med, Chapel Hill, NC 27599 USA. EM pfsulliv@med.unc.edu OI O'Donovan, Michael/0000-0001-7073-2379 FU Medical Research Council FX Funding for recruitment was provided by the Janssen Research Foundation. Genotyping was funded by multiple grants to the Stanley Center for Psychiatric Research at the Broad Institute from the Stanley Medical Research Institute, The Merck Genome Research Foundation, and the Herman Foundation. Work at Cardiff University was funded by Medical Research Council Programme and Centre Grants. The funding bodies had no role in dictating the design of the study, the analysis, or any conclusions derived. NR 32 TC 1 Z9 1 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2013 VL 143 IS 1 BP 11 EP 17 DI 10.1016/j.schres.2012.11.002 PG 7 WC Psychiatry SC Psychiatry GA 065AL UT WOS:000313118700003 PM 23177929 ER PT J AU Linnman, C Coombs, G Goff, DC Holt, DJ AF Linnman, Clas Coombs, Garth, III Goff, Donald C. Holt, Daphne J. TI Lack of insula reactivity to aversive stimuli in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Classical conditioning; Unconditioned response; Pain; Insula ID CORTEX ABNORMALITIES; PAIN; BRAIN; EXTINCTION; AWARENESS; CONNECTIVITY; MECHANISMS; REVEALS; NETWORK; MRI AB Patients with schizophrenia may have altered pain perception, as suggested by clinical reports of pain insensitivity, and recent neuroimaging findings. Here, we examined neural responses to an aversive electrical stimulus and the immediate anticipation of such a stimulus using fMRI and a classical conditioning paradigm, which involved pairing an electrical shock with a neutral photograph. Fifteen men with schizophrenia and 13 healthy men, matched for demographic characteristics, electrical stimulation level and scan movement, were studied. The shock induced robust responses in midbrain, thalamus, cingulate gyrus, insula and somatosensory cortex in both groups. However, compared to controls, the schizophrenic patients displayed significantly lower activation of the middle insula (p(FWE)=0.002, T=5.72, cluster size=24 voxels). Moreover, the lack of insula reactivity in the schizophrenia group was predicted by the magnitude of positive symptoms (r=-0.46, p=0.04). In contrast, there were no significant differences between the two groups in the magnitude of neural responses during anticipation of the shock. These findings provide support for the existence of a basic deficit in interoceptive perception in schizophrenia, which could play a role in the generation and/or maintenance of psychotic states. (C) 2012 Elsevier B.V. All rights reserved. C1 [Linnman, Clas] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA USA. [Linnman, Clas; Coombs, Garth, III; Holt, Daphne J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Coombs, Garth, III; Holt, Daphne J.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Goff, Donald C.] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. [Goff, Donald C.] NYU, Dept Psychiat, Langone Med Ctr, New York, NY 10003 USA. RP Linnman, C (reprint author), 7 Grove St 9, Boston, MA 02114 USA. EM linnman@nmr.mgh.harvard.edu OI Linnman, Clas/0000-0001-8449-894X FU National Institute of Mental Health [K23MH076054, RO1MH095904]; National Alliance for Research on Depression and Schizophrenia; Sidney R. Baer, Jr Foundation; Swedish Society for Medical Research (SSMF); Janssen; Pfizer; GSK; PamLab; Novartis FX This study was supported by the National Institute of Mental Health K23MH076054 and RO1MH095904 (Dr. Holt) and the National Alliance for Research on Depression and Schizophrenia with the Sidney R. Baer, Jr Foundation (Dr. Holt). Dr. Linnman received support from the Swedish Society for Medical Research (SSMF).; Over the past 3 years, Dr. Goff has served as a consultant to Eli Lilly, Bristol-Meyer-Squibb, Roche, Endo Pharmaceuticals, Genentech, Cypress Bioscience, Dianippon Sumitomo, Solvay, Biovail, and Takeda Pharmaceuticals. He served on a DMC for Otsuka. He received research funding from Janssen, Pfizer, GSK, PamLab and Novartis and he has applied for patents regarding genetic predictors of response to glutamatergic agents and folate. NR 54 TC 11 Z9 11 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2013 VL 143 IS 1 BP 150 EP 157 DI 10.1016/j.schres.2012.10.038 PG 8 WC Psychiatry SC Psychiatry GA 065AL UT WOS:000313118700026 PM 23201307 ER PT J AU Gilman, SE Bruce, ML Ten Have, T Alexopoulos, GS Mulsant, BH Reynolds, CF Cohen, A AF Gilman, Stephen E. Bruce, Martha L. Ten Have, Thomas Alexopoulos, George S. Mulsant, Benoit H. Reynolds, Charles F., III Cohen, Alex TI Social inequalities in depression and suicidal ideation among older primary care patients SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY LA English DT Article DE Depression; Suicide; Older adulthood; Inequalities; Primary care ID LATE-LIFE DEPRESSION; RANDOMIZED CONTROLLED-TRIAL; SOCIOECONOMIC-STATUS; MAJOR DEPRESSION; FINANCIAL STRAIN; ANTIDEPRESSANT TREATMENT; PSYCHIATRIC OUTPATIENTS; PSYCHOLOGICAL DISTRESS; MEDICAL COMORBIDITY; NATURAL-HISTORY AB Depression and suicide are major public health concerns, and are often unrecognized among the elderly. This study investigated social inequalities in depressive symptoms and suicidal ideation among older adults. Data come from 1,226 participants in PROSPECT (Prevention of Suicide in Primary Care Elderly: Collaborative Trial), a large primary care-based intervention trial for late-life depression. Linear and logistic regressions were used to analyze depressive symptoms and suicidal ideation over the 2-year follow-up period. Mean Hamilton Depression Rating Scale (HDRS) scores were significantly higher among participants in financial strain [regression coefficient (b) = 1.78, 95 % confidence interval (CI) = 0.67-2.89] and with annual incomes below $20,000 (b = 1.67, CI = 0.34-3.00). Financial strain was also associated with a higher risk of suicidal ideation (odds ratio = 2.35, CI = 1.38-3.98). There exist marked social inequalities in depressive symptoms and suicidal ideation among older adults attending primary care practices, the setting in which depression is most commonly treated. Our results justify continued efforts to understand the mechanisms generating such inequalities and to recognize and provide effective treatments for depression among high-risk populations. C1 [Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Gilman, Stephen E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Bruce, Martha L.; Alexopoulos, George S.] Weill Cornell Med Coll, Dept Psychiat, White Plains, NY 10605 USA. [Ten Have, Thomas] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Mulsant, Benoit H.] Univ Toronto, Ctr Addict & Mental Hlth, Dept Psychiat, Toronto, ON M6J 1H4, Canada. [Reynolds, Charles F., III] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. [Cohen, Alex] Univ London London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, London WC1E 7HT, England. 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; Alexopoulos, George/0000-0001-5677-7001 FU National Institutes of Health [MH83335, MH085944, MH059366]; Forest; US National Institute of Mental Health; Canadian Institutes for Health Research; Bristol-Myers Squibb; Wyeth; Astra-Zeneca; Eli Lilly; Forest Laboratories; GlaxoSmithKline; Janssen; Lundbeck; Pfizer; Medispin, Inc.; NIH FX This work was supported by the National Institutes of Health grants MH83335, MH085944, and MH059366. Forest Pharmaceuticals provided free citalopram for the PROSPECT study. The authors sincerely appreciate the contributions of Ms. Kathleen McGaffigan for data management and statistical programming, and Ms. Rebecca Hawrusik for conducting literature reviews.; George S. Alexopoulos, M. D., receives research support from Forest; he serves on the speakers' bureau for Forest, Lilly, Bristol Meyers Squibb, Astra Zeneca, Merck; and is a stockholder in Johnson & Johnson. Martha L. Bruce, Ph.D., M. P. H., has received financial compensation for consulting to Medispin, Inc., a medical education company. Benoit H. Mulsant, M. D., currently receives research support from the US National Institute of Mental Health, the Canadian Institutes for Health Research, Bristol-Myers Squibb, and Wyeth. During the past five years, he has also received research support or honoraria from Astra-Zeneca, Bristol-Myers Squibb, Eli Lilly, Forest Laboratories, GlaxoSmithKline, Janssen, Lundbeck, Pfizer and Wyeth; he previously directly held stocks (all less than $10,000) of Akzo-Nobel, Alkermes, AstraZeneca, Biogen, Celsion, Elan, Eli Lilly, Forest, Orchestra Therapeutics, and Pfizer. Charles F. Reynolds III, M. D., receives pharmaceutical supplies from Forest Laboratories, BMS, Pfizer, and Lilly for his NIH sponsored research. NR 61 TC 10 Z9 10 U1 1 U2 29 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0933-7954 J9 SOC PSYCH PSYCH EPID JI Soc. Psychiatry Psychiatr. Epidemiol. PD JAN PY 2013 VL 48 IS 1 BP 59 EP 69 DI 10.1007/s00127-012-0575-9 PG 11 WC Psychiatry SC Psychiatry GA 069BD UT WOS:000313409000007 PM 22948560 ER PT J AU Margolis, DJ Gupta, J Thom, SR Townsend, RR Kanetsky, PA Hoffstad, O Papdopoulos, M Fischer, M Schelling, JR Mitra, N AF Margolis, David J. Gupta, Jayanta Thom, Stephen R. Townsend, Raymond R. Kanetsky, Peter A. Hoffstad, Ole Papdopoulos, Maryte Fischer, Michael Schelling, Jeffrey R. Mitra, Nandita TI Diabetes, lower extremity amputation, loss of protective sensation, and neuronal nitric oxide synthase associated protein in the Chronic Renal Insufficiency Cohort study SO WOUND REPAIR AND REGENERATION LA English DT Article ID MESENCHYMAL STEM-CELLS; ENGINEERED SKIN SUBSTITUTES; FIBROBLAST-GROWTH-FACTOR; EXTRACELLULAR-MATRIX; WOUND REPAIR; ANTIBACTERIAL PROPERTIES; REGENERATIVE MEDICINE; ELECTROSPUN SCAFFOLDS; POLYURETHANE MEMBRANE; TISSUE REGENERATION AB Lower extremity amputation (LEA) is a life-altering complication of diabetes. The goal of our study was to investigate the possibility that genetic variation in neuronal nitric oxide synthase associated protein (NOS1AP) is associated with LEA and diabetic peripheral neuropathy (DPN). Our work used data from the Chronic Renal Insufficiency Cohort (CRIC) study. CRIC is a multicenter investigation undertaken to pursue the relationship between chronic renal insufficiency and cardiovascular disease. We evaluated 3,040 CRIC study subjects; 1,490 individuals were African Americans and 1,550 were whites. LEA occurred in 162 (5.3%) subjects, 93 (6.2%) of African Americans and 69 (4.4%) of whites. In whites, NOS1AP single nucleotide polymorphism rs1963645 was most strongly associated with LEA (1.73 [1.23, 2.44]). In African Americans three NOS1AP single nucleotide polymorphisms were associated with LEA: rs6659759 (1.65 [1.21, 2.24]); rs16849113 (1.58 [1.16, 2.14]); rs880296 (1.54 [1.14, 2.10]). We tested a subset of 100 CRIC participants for DPN using Semmes-Weinstein filaments. DPN in those with diabetes was associated with rs1963645 (16.97 [2.38, 120.97]) in whites and rs16849113 and rs6659759 (3.62 [1.11, 11.83] and 3.02 [0.82, 11.12], respectively) in African Americans. In conclusion, this is one of the first studies to show that NOS1AP gene variants are associated with DPN and LEA. C1 [Margolis, David J.] Univ Penn, Perelman Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. [Margolis, David J.; Gupta, Jayanta; Kanetsky, Peter A.; Hoffstad, Ole; Papdopoulos, Maryte; Mitra, Nandita] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Thom, Stephen R.] Univ Penn, Perelman Sch Med, Dept Emergency Med, Philadelphia, PA 19104 USA. [Townsend, Raymond R.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Fischer, Michael] Jesse Brown VA Med Ctr, Dept Med, Chicago, IL USA. [Fischer, Michael] Univ Hosp & Hlth Sci Syst, Chicago, IL USA. [Fischer, Michael] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA. [Schelling, Jeffrey R.] Case Western Reserve Univ, Cincinnati, OH USA. [Schelling, Jeffrey R.] MetroHlth Med Ctr, Cincinnati, OH USA. RP Margolis, DJ (reprint author), Univ Penn, Perelman Sch Med, Dept Dermatol, 901 Blockely Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM margo@mail.med.upenn.edu FU CRIC [U01-DK060990, U01-DK060984]; Career Development Award Department of Veterans; University of Pennsylvania CTRC CTSA [UL1 RR-024134]; Case Western Reserve [M01RR00080]; [K24-AR002212]; [UL1RR024989] FX This project was supported in part by grants; U01-DK060990 and U01-DK060984 (CRIC), K24-AR002212 (Margolis); Career Development Award Department of Veterans (Fischer), UL1 RR-024134 (University of Pennsylvania CTRC CTSA), M01RR00080 (Case Western Reserve), and UL1RR024989 (Schelling). NR 92 TC 5 Z9 6 U1 0 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD JAN-FEB PY 2013 VL 21 IS 1 BP 17 EP 24 DI 10.1111/j.1524-475X.2012.00866.x PG 8 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 068EQ UT WOS:000313348500041 PM 23228162 ER PT J AU Bohr, S Patel, SJ Sarin, D Irimia, D Yarmush, ML Berthiaume, F AF Bohr, Stefan Patel, Suraj J. Sarin, Dhruv Irimia, Daniel Yarmush, Martin L. Berthiaume, Francois TI Resolvin D2 prevents secondary thrombosis and necrosis in a mouse burn wound model SO WOUND REPAIR AND REGENERATION LA English DT Article ID LOWER-EXTREMITY AMPUTATION; CHRONIC KIDNEY-DISEASE; IMPAIRED GLUCOSE-TOLERANCE; DIABETIC-NEUROPATHY; FOOT ULCERS; NITRIC-OXIDE; RISK-FACTORS; ASSOCIATION; PROTEIN; NOS1AP AB Deep partial thickness burns are subject to delayed necrosis of initially viable tissues surrounding the primary zone of thermally induced coagulation, which results in an expansion of the burn wound, both in area and depth, within 48 hours postburn. Neutrophil sequestration and activation leading to microvascular damage is thought to mediate this secondary tissue damage. Resolvins, a class of endogenous mediators derived from omega-3 polyunsaturated fatty acids, have been shown to regulate the resolution of inflammation. We hypothesized that exogenous resolvins could mitigate the deleterious impact of the inflammatory response in burn wounds. Using two different mouse burn injury models involving significant partial thickness injuries, we found that a systemically administered single dose of resolvin D2 (RvD2) as low as 25 pg/g bw given within an interval of up to 4 hours postburn effectively prevented thrombosis of the deep dermal vascular network and subsequent dermal necrosis. By preserving the microvascular network, RvD2 enhanced neutrophil access to the dermis, but prevented neutrophil-mediated damage through other anti-inflammatory actions, including inhibition of tumor necrosis factor-alpha, interleukin-1 beta, and neutrophil platelet-endothelial cell adhesion molecule-1. In a clinical context, RvD2 may be therapeutically useful by reducing the need for surgical debridement and the area requiring skin grafting. C1 [Bohr, Stefan; Patel, Suraj J.; Sarin, Dhruv; Irimia, Daniel; Yarmush, Martin L.; Berthiaume, Francois] Massachusetts Gen Hosp, Dept Surg, Ctr Engn Med, Boston, MA 02114 USA. [Bohr, Stefan; Patel, Suraj J.; Sarin, Dhruv; Irimia, Daniel; Yarmush, Martin L.; Berthiaume, Francois] Shriners Bruns Hosp, Boston, MA USA. [Yarmush, Martin L.; Berthiaume, Francois] Rutgers State Univ, Dept Biomed Engn, New Brunswick, NJ 08903 USA. RP Berthiaume, F (reprint author), Rutgers State Univ, Dept Biomed Engn, 599 Taylor Rd, Piscataway, NJ 08854 USA. EM fberthia@rci.rutgers.edu OI Irimia, Daniel/0000-0001-7347-2082 FU Shriners Hospitals for Children; Deutsche Forschungs Gemeinschaft (DFG, Germany) [GZ:BO3468/2-1] FX This work was funded by the Shriners Hospitals for Children. S. Bohr is a receipt of a Deutsche Forschungs Gemeinschaft (DFG, Germany) postdoctoral fellowship award (GZ:BO3468/2-1). S. J. Patel was supported by a Shriners Hospitals for Children postdoctoral fellowship. NR 43 TC 34 Z9 35 U1 1 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD JAN-FEB PY 2013 VL 21 IS 1 BP 35 EP 43 DI 10.1111/j.1524-475X.2012.00853.x PG 9 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 068EQ UT WOS:000313348500043 PM 23110665 ER PT J AU Ackerly, DC Parekh, A Stein, D AF Ackerly, D. Clay Parekh, Ami Stein, Daniel TI Perspective: A Framework for Career Paths in Health Systems Improvement SO ACADEMIC MEDICINE LA English DT Editorial Material ID MEDICAL-STUDENTS; IMPLEMENTATION; LEADERSHIP; EDUCATION; SCIENCE AB The difference between the U.S. health care system's potential and the outcomes it delivers is vast and well documented. Fortunately, many medical trainees recognize this challenge and aspire to careers that will enable them to help close this gap by improving the systems of care around them. However, the career paths in health systems improvement are not well defined, and interested trainees are frequently left without clear direction. The circuitous and often serendipitous routes that many current leaders in health systems improvement-including medical researchers, health system managers, and policy experts-have navigated to reach their positions of influence do not provide consistent road maps for the trainees who wish to follow in their footsteps. The authors of this Perspective propose a framework to guide career development in health systems improvement. The framework is designed to help medical trainees and their mentors critically analyze various career options in three core focus areas (research, policy, management) and the intersections where those areas overlap (policy advising, implementation science, policy translation).The authors provide examples of the types of work done in each focus area and each intersection to help trainees make explicit decisions concerning skill development and to select opportunities that best fit their interests and strengths. In all, the authors intend the framework to support the development of a generation of physician leaders equipped to drive the improvement that the U.S. heath care system requires. C1 [Stein, Daniel] Harvard Univ, Sch Med, Dept Internal Med, Boston, MA USA. [Stein, Daniel] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Parekh, Ami] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Ackerly, D. Clay] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ackerly, D. Clay] Massachusetts Gen Phys Org, Boston, MA USA. RP Ackerly, DC (reprint author), 165 Cambridge St,Suite 500, Boston, MA 02114 USA. EM dackerly@partners.org NR 18 TC 9 Z9 9 U1 0 U2 7 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 JAN PY 2013 VL 88 IS 1 BP 56 EP 60 DI 10.1097/ACM.0b013e318276cef1 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 060RN UT WOS:000312795900019 PM 23165276 ER PT J AU Schacht, JP Anton, RF Myrick, H AF Schacht, Joseph P. Anton, Raymond F. Myrick, Hugh TI Functional neuroimaging studies of alcohol cue reactivity: a quantitative meta-analysis and systematic review SO ADDICTION BIOLOGY LA English DT Article DE Activation likelihood estimation; addiction; alcoholism; fMRI; PET ID COMPULSIVE DRINKING SCALE; INDUCED BRAIN ACTIVATION; ABSTINENT ALCOHOLICS; NUCLEUS-ACCUMBENS; RETROSPLENIAL CORTEX; VENTRAL STRIATUM; DECISION-MAKING; FAMILY-HISTORY; RISK DRINKERS; ADDICTION AB A comprehensive understanding of the neurobiology of alcohol cue reactivity is critical in identifying the neuropathology of alcohol use disorders (AUD) and developing treatments that may attenuate alcohol craving and reduce relapse risk. Functional neuroimaging studies have identified many brain areas in which alcohol cues elicit activation. However, extant studies have included relatively small numbers of cases, with AUD of varying severity, and have employed many different cue paradigms. We used activation likelihood estimation, a quantitative, coordinate-based meta-analytic method, to analyze the brain areas activated by alcohol-related cues across studies, and to examine whether these areas were differentially activated between cases and controls. Secondarily, we reviewed correlations between behavioral measures and cue-elicited activation, as well as treatment effects on such activation. Data analyzed were from 28 studies of 679 cases and 174 controls. Among cases, alcohol cues elicited robust activation of limbic and prefrontal regions, including ventral striatum, anterior cingulate and ventromedial prefrontal cortex. As compared to controls, cases demonstrated greater activation of parietal and temporal regions, including posterior cingulate, precuneus and superior temporal gyrus. Cue-elicited activation of ventral striatum was most frequently correlated with behavioral measures and most frequently reduced by treatment, but these results were often derived from region-of-interest analyses that interrogated only limbic regions. These findings support long-standing theories of mesolimbic involvement in alcohol cue processing, but suggest that cue-elicited activation of other brain areas may more clearly differentiate cases from controls. Prevention and treatment for AUD should consider interventions that may reduce cue-elicited activation of these areas. C1 [Schacht, Joseph P.; Anton, Raymond F.; Myrick, Hugh] Med Univ S Carolina, Dept Psychiat & Behav Sci, Ctr Drug & Alcohol Programs, Charleston, SC 29425 USA. [Myrick, Hugh] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Schacht, JP (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Ctr Drug & Alcohol Programs, 171 Ashley Ave, Charleston, SC 29425 USA. EM schacht@musc.edu FU National Institute of Alcohol Abuse and Alcoholism (NIAAA); Alcohol Research Center [P50 AA010761]; [T32 AA007474]; [K05 AA017435] FX This work was supported by grants from the National Institute of Alcohol Abuse and Alcoholism (NIAAA). Dr. Schacht was supported by T32 AA007474, Dr. Anton by K05 AA017435 and Dr. Myrick by the Charleston Alcohol Research Center (P50 AA010761). Portions of this work were presented at the 2011 NIAAA Training Directors Meeting, Providence, RI. NR 75 TC 90 Z9 94 U1 5 U2 36 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1355-6215 J9 ADDICT BIOL JI Addict. Biol. PD JAN PY 2013 VL 18 IS 1 BP 121 EP 133 DI 10.1111/j.1369-1600.2012.00464.x PG 13 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA 059YB UT WOS:000312740500013 PM 22574861 ER PT J AU Narasimhan, M Rathinam, M Riar, A Patel, D Mummidi, S Yang, HS Colburn, NH Henderson, GI Mahimainathan, L AF Narasimhan, Madhusudhanan Rathinam, Marylatha Riar, Amanjot Patel, Dhyanesh Mummidi, Srinivas Yang, Hsin-Shen Colburn, Nancy H. Henderson, George I. Mahimainathan, Lenin TI Programmed Cell Death 4 (PDCD4): A Novel Player in Ethanol-Mediated Suppression of Protein Translation in Primary Cortical Neurons and Developing Cerebral Cortex SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE EtOH; Protein Synthesis; PDCD4; Primary Cortical Neurons; eIF4A; Cerebral Cortex ID PRENATAL ALCOHOL EXPOSURE; INITIATION-FACTOR 4A; EUKARYOTIC TRANSLATION; SYNAPTIC PLASTICITY; ELONGATION-FACTORS; OXIDATIVE STRESS; APOPTOTIC DEATH; BINDING-PROTEIN; SKELETAL-MUSCLE; GENE-EXPRESSION AB Background Prenatal exposure to ethanol (EtOH) elicits a range of neuro-developmental abnormalities, microcephaly to behavioral deficits. Impaired protein synthesis has been connected to pathogenesis of EtOH-induced brain damage and abnormal neuron development. However, mechanisms underlying these impairments of protein synthesis are not known. In this study, we illustrate the effects of EtOH on programmed cell death protein 4 (PDCD4), a tumor and translation repressor. Methods Primary cortical neurons (PCNs) were treated with 2.5 and 4 mg/ml EtOH for different time points (4 to 24 hours), and PDCD4 expression was detected by Western blotting. Protein synthesis was determined using [35S] methionine incorporation assay. Methyl cap pull-down assay was performed to establish the effect of EtOH on association of eukaryotic initiation factor 4A (eIF4A) with capped mRNA. Luciferase assay was performed to determine the in vivo translation. A 2-day acute 5-dose binge model with EtOH (4 g/kg body wt, 25% v/v) was performed in SpragueDawley rats at 12-hour intervals and analyzed for PDCD4, eIF4A, and eIF4Amethyl cap association. Results EtOH increased PDCD4 expression in a time- and dose-dependent manner in PCNs, which inhibited the association of eIF4A with methyl cap. EtOH and ectopic PDCD4 expression suppressed in vivo translation in PCNs and RNAi targeting of PDCD4 blocked the inhibitory effect of EtOH on protein synthesis. In utero exposure of pregnant rats to EtOH resulted in a significant increase in PDCD4 in fetal cerebral cortex along with the inhibition of methyl capassociated eIF4A, compared with isocaloric controls. Increased PDCD4 also occurred in pooled fractions of remaining brain regions. Conclusions Our data, for the first time, illustrate that PDCD4 mediates inhibitory effects of EtOH on protein synthesis in PCNs and developing brain. C1 [Narasimhan, Madhusudhanan; Rathinam, Marylatha; Riar, Amanjot; Patel, Dhyanesh; Henderson, George I.; Mahimainathan, Lenin] Texas Tech Univ, Dept Pharmacol & Neurosci, Hlth Sci Ctr, Lubbock, TX 79430 USA. [Narasimhan, Madhusudhanan; Henderson, George I.; Mahimainathan, Lenin] Texas Tech Univ, S Plains Alcohol & Addict Res Ctr, Hlth Sci Ctr, Lubbock, TX 79430 USA. [Mummidi, Srinivas] S Texas Vet Hlth Care Syst, Ctr Personalized Med, San Antonio, TX USA. [Mummidi, Srinivas] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, San Antonio, TX 78229 USA. [Yang, Hsin-Shen] Univ Kentucky, Grad Ctr Toxicol, Lexington, KY 40536 USA. [Yang, Hsin-Shen] Univ Kentucky, Lucille P Markey Canc Ctr, Lexington, KY USA. [Colburn, Nancy H.] NCI, Lab Canc Prevent, Frederick, MD 21701 USA. RP Mahimainathan, L (reprint author), Texas Tech Univ, Dept Pharmacol & Neurosci, Hlth Sci Ctr, 3601 4th St,STOP 6592, Lubbock, TX 79430 USA. EM lenin.mahimainathan@ttuhsc.edu OI /0000-0001-5077-3552 FU Biomedical Laboratory Research and Development Service of the Veterans Affairs Office of Research and Development [1I01BX000975]; NIH [RO1AI043279]; [RO1 AA010114] FX This work was supported by RO1 AA010114 (to GIH). SM is supported by grants awarded by the Biomedical Laboratory Research and Development Service of the Veterans Affairs Office of Research and Development (1I01BX000975) and by NIH (RO1AI043279). We thank Dr. Michele Pagano, NYUMC, New York, for PDCD4 plasmid. NR 61 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JAN PY 2013 VL 37 IS 1 BP 96 EP 109 DI 10.1111/j.1530-0277.2012.01850.x PG 14 WC Substance Abuse SC Substance Abuse GA 064ZN UT WOS:000313115200013 PM 22757755 ER PT J AU Ruiz, SM Oscar-Berman, M Sawyer, KS Valmas, MM Urban, T Harris, GJ AF Ruiz, Susan Mosher Oscar-Berman, Marlene Sawyer, Kayle S. Valmas, Mary M. Urban, Trinity Harris, Gordon J. TI Drinking History Associations with Regional White Matter Volumes in Alcoholic Men and Women SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE White Matter; Volumetric MRI; Gender; Corpus Callosum; Abstinence ID MAGNETIC-RESONANCE; DEPENDENT INDIVIDUALS; ABSTINENT ALCOHOLICS; GENDER-DIFFERENCES; CORPUS-CALLOSUM; CEREBRAL-CORTEX; BRAIN CHANGES; RECOVERY; SYSTEM; GRAY AB Background Alcoholism has been repeatedly associated with gray and white matter pathology. Although neuroimaging has shown alcoholism-related brain volume reductions and axonal compromise, the integrity of white matter volumes in chronic alcoholism has been challenging to measure on a regional level. Methods We first examined the effects of alcoholism on cerebral white matter volumes by lobar and gyral subdivisions in 42 abstinent alcoholics and 42 control participants (split evenly by gender). We also examined cerebellar white matter and regions of the corpus callosum, as well as ventricular volumes. Next, relationships between white matter and ventricular volumes with measures of drinking patterns were assessed. Finally, an examination of early versus late abstinence was conducted. Within each examination, gender effects were explored. Results Differences in regional white matter volumes between alcoholics and controls were observed primarily in the corpus callosum, with a stronger group difference among men than women. Years of heavy drinking had a strong negative impact on frontal and temporal white matter among alcoholic women, and on the corpus callosum among alcoholic men. Quantity of alcohol consumption was associated with smaller corpus callosum and larger ventricular volumes among alcoholic women, whereas abstinence duration was associated with larger corpus callosum volume among alcoholic men. Preliminary data indicated that alcoholic women showed stronger positive associations between sobriety duration and white matter volume than men within the first year of abstinence, whereas men showed this association more so than women after 1 year of abstinence. Conclusions Effects of drinking history on white matter and ventricular volumes vary by gender, with alcoholic women showing greatest sensitivity in frontal, temporal, ventricular, and corpus callosum regions, and alcoholic men showing effects mainly in the corpus callosum. Preliminary results indicate that recovery of white matter volume may occur sooner for women than for men. C1 [Ruiz, Susan Mosher] Boston Univ, Grad Program Neurosci, Boston, MA 02118 USA. [Ruiz, Susan Mosher; Oscar-Berman, Marlene; Sawyer, Kayle S.; Valmas, Mary M.] VA Healthcare Syst, Psychol Res Serv, Boston, MA USA. [Oscar-Berman, Marlene; Valmas, Mary M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Oscar-Berman, Marlene; Sawyer, Kayle S.] Boston Univ, Sch Med, Program Behav Neurosci, Boston, MA 02118 USA. [Oscar-Berman, Marlene; Urban, Trinity; Harris, Gordon J.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Urban, Trinity; Harris, Gordon J.] Massachusetts Gen Hosp, Radiol Comp Aided Diagnost Lab, Boston, MA 02114 USA. RP Oscar-Berman, M (reprint author), Boston Univ, Sch Med, Dept Psychiat, L-815,72 E Concord St, Boston, MA 02118 USA. EM oscar@bu.edu OI Ruiz, Susan Mosher/0000-0002-5237-2389; Sawyer, Kayle/0000-0001-7767-5688 FU National Institute on Alcohol Abuse and Alcoholism (NIAAA) [R01-AA07112, K05-AA00219]; Medical Research Service of the US Department of Veterans Affairs; Center for Functional Neuroimaging Technologies [P41RR14075] FX This work was supported by funds from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) grants R01-AA07112 and K05-AA00219, and the Medical Research Service of the US Department of Veterans Affairs to MOB, as well as the Center for Functional Neuroimaging Technologies, P41RR14075. The authors thank Diane Merritt for recruitment assistance and neuropsychological testing. NR 49 TC 14 Z9 14 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JAN PY 2013 VL 37 IS 1 BP 110 EP 122 DI 10.1111/j.1530-0277.2012.01862.x PG 13 WC Substance Abuse SC Substance Abuse GA 064ZN UT WOS:000313115200014 PM 22725728 ER PT J AU Imamura, T Brown, CA Ofuchi, H Yamagami, H Branch, J Hagiwara, Y Brown, DFM Hasegawa, K AF Imamura, Taichi Brown, Calvin A., III Ofuchi, Hisashi Yamagami, Hiroshi Branch, Joel Hagiwara, Yusuke Brown, David F. M. Hasegawa, Kohei CA Japanese Emergency Med Res TI Emergency airway management in geriatric and younger patients: analysis of a multicenter prospective observational study SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID RAPID-SEQUENCE INTUBATION; ELDERLY-PATIENTS; TRACHEAL INTUBATION; ANESTHESIA; REMIFENTANIL; RESIDENTS; LANDIOLOL; INDUCTION; RESPONSES; CARE AB Objectives: There is little information on geriatric emergency airway management. We sought to describe intubation practices and outcomes for emergency department (ED) geriatric and younger patients in Japan. Method: We formed the Japanese Emergency Airway Network, a consortium of 11 medical centers, and prospectively collected data on ED intubations between 2010 and 2011. All patients 18 years or older who underwent emergent airway management were included in our study. Patients were divided to into 2 groups: 18 to 64-year olds and 65 years or older. We present descriptive data as proportions with 95% confidence intervals (CI). Results: The database recorded 3277 patients (capture rate 96%), and 3178 met the inclusion criteria. Of 3178 patients, 1844 (58%) were 65 years or older, 1334 (42%) were 18 to 64 years old, 809 (25%) were 80 years or older, and 407 (50%) of them were in the state of cardiac arrest. The geriatric group, compared to the younger group, had a higher success rate on the initial attempt (71% vs 64%; difference 7%; 95% CI 4%-10%;) and in 2 attempts (90% vs 88%; difference 3%; 95% CI 1%-5%) or less. There was no significant difference in the adverse event rates by age group (difference 0%; 95% CI -2% to 3%). Conclusion: In our multicenter study involving a large geriatric population, we found that geriatric patients were intubated with a higher success rate, compared to younger patients. These data provide implications for the geriatric ED airway practice that may lead to better patient-centered emergency care. (C) 2013 Elsevier Inc. All rights reserved. C1 [Imamura, Taichi; Ofuchi, Hisashi; Yamagami, Hiroshi; Branch, Joel] Shonan Kamakura Gen Hosp, Dept Emergency Med, Kamakura, Kanagawa 2478533, Japan. [Brown, Calvin A., III; Hasegawa, Kohei] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Hagiwara, Yusuke] Tokyo Metropolitan Childrens Med Ctr, Dept Emergency Med, Fuchu, Tokyo 1838561, Japan. [Brown, David F. M.; Hasegawa, Kohei] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Imamura, T (reprint author), Shonan Kamakura Gen Hosp, Dept Emergency Med, Okamoto 1370-1, Kamakura, Kanagawa 2478533, Japan. EM imamurata1@yahoo.co.jp FU Harvard Affiliated Emergency Medicine Residency; St. Luke's Life Science Institute FX This study was supported by a grant for emergency medicine research from Harvard Affiliated Emergency Medicine Residency and a grant from St. Luke's Life Science Institute. The study sponsors have no involvement in the study design; in the collection, analysis or interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. NR 23 TC 7 Z9 7 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD JAN PY 2013 VL 31 IS 1 BP 190 EP 196 DI 10.1016/j.ajem.2012.07.008 PG 7 WC Emergency Medicine SC Emergency Medicine GA 062WM UT WOS:000312954600029 PM 23083883 ER PT J AU Teekakirikul, P Milewicz, DM Miller, DT Lacro, RV Regalado, ES Rosales, AM Ryan, DP Toler, TL Lin, AE AF Teekakirikul, Polakit Milewicz, Dianna M. Miller, David T. Lacro, Ronald V. Regalado, Ellen S. Rosales, Ana Maria Ryan, Daniel P. Toler, Tomi L. Lin, Angela E. TI Thoracic aortic disease in two patients with juvenile polyposis syndrome and SMAD4 mutations SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE aortic dilation; hereditary hemorrhagic telangiectasia; juvenile polyposis syndrome; SMAD4; TGF-beta signaling; thoracic aortic aneurysm and dissection ID HEREDITARY HEMORRHAGIC TELANGIECTASIA; MARFAN-SYNDROME; TGFBR2 MUTATIONS; BMPR1A MUTATIONS; MYHRE-SYNDROME; BETA RECEPTOR; ANEURYSMS; DISSECTIONS; GENE; PHENOTYPE AB Dilation or aneurysm of the ascending aorta can progress to acute aortic dissection (Thoracic Aortic Aneurysms and Aortic Dissections, TAAD). Mutations in genes encoding TGF-beta-related proteins (TGFBR1, TGFBR2, FBN1, and SMAD3) cause syndromic and inherited TAAD. SMAD4 mutations are associated with juvenile polyposis syndrome (JPS) and a combined JPShereditary hemorrhagic telangiectasia (HHT) known as JPSHHT. A family with JPSHHT was reported to have aortic root dilation and mitral valve abnormalities. We report on two patients with JPSHHT with SMAD4 mutations associated with thoracic aortic disease. The first patient, an 11-year-old boy without Marfan syndrome features, had JPS and an apparently de novo SMAD4 mutation (c.1340_1367dup28). Echocardiography showed mild dilation of the aortic annulus and aortic root, and mild dilation of the sinotubular junction and ascending aorta. Computed tomography confirmed aortic dilation and showed small pulmonary arteriovenous malformations (PAVM). The second patient, a 34-year-old woman with colonic polyposis, HHT, and features of Marfan syndrome, had a SMAD4 mutation (c.1245_1248delCAGA). Echocardiography showed mild aortic root dilation. She also had PAVM and hepatic focal nodular hyperplasia. Her family history was significant for polyposis, HHT, thoracic aortic aneurysm, and dissection and skeletal features of Marfan syndrome in her father. These two cases confirm the association of thoracic aortic disease with JPSHHT resulting from SMAD4 mutations. We propose that the thoracic aorta should be screened in patients with SMAD4 mutations to prevent untimely death from dissection. This report also confirms that SMAD4 mutations predispose to TAAD. (c) 2012 Wiley Periodicals, Inc. C1 [Teekakirikul, Polakit; Toler, Tomi L.; Lin, Angela E.] MassGen Hosp Children, Genet Unit, Boston, MA 02114 USA. [Teekakirikul, Polakit] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Teekakirikul, Polakit] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Milewicz, Dianna M.; Regalado, Ellen S.] Univ Texas Hlth Sci Ctr Houston, Dept Internal Med, Div Med Genet, Houston, TX USA. [Miller, David T.] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Miller, David T.] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Lacro, Ronald V.] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Rosales, Ana Maria] MassGen Hosp Children, Pediat Cardiol Unit, Boston, MA 02114 USA. [Ryan, Daniel P.] MassGen Hosp Children, Dept Pediat Surg, Boston, MA 02114 USA. RP Lin, AE (reprint author), MassGen Hosp Children, Genet Unit, 185 Cambridge St,CPZN 2222, Boston, MA 02114 USA. EM lin.angela@mgh.harvard.edu OI Toler, Tomi/0000-0002-1637-8310 FU [P50HL083794-01]; [RO1 HL62594] FX Grant numbers: P50HL083794-01, RO1 HL62594. NR 37 TC 15 Z9 17 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JAN PY 2013 VL 161A IS 1 BP 185 EP 191 DI 10.1002/ajmg.a.35659 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 062RO UT WOS:000312939200030 PM 23239472 ER PT J AU Soto-Gomez, N Anzueto, A Waterer, GW Restrepo, MI Mortensen, EM AF Soto-Gomez, Natalia Anzueto, Antonio Waterer, Grant W. Restrepo, Marcos I. Mortensen, Eric M. TI Pneumonia: An Arrhythmogenic Disease? SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Cardiac arrhythmia; Mortality; Pneumonia ID COMMUNITY-ACQUIRED PNEUMONIA; RECENT RESPIRATORY-INFECTION; ACUTE MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; COMORBIDITY INDEX; RISK; INFLUENZA; COMPLICATION; VALIDATION AB BACKGROUND: Recent studies suggest that there is an increase in cardiovascular disease after pneumonia; however, there is little information on cardiac arrhythmias after pneumonia. The aims of this study were to assess the incidence of, and examine risk factors for, cardiac arrhythmias after hospitalization for pneumonia. METHODS: We conducted a national cohort study using Department of Veterans Affairs administrative data including patients aged >= 65 years hospitalized with pneumonia in fiscal years 2002-2007, receiving antibiotics within 48 hours of admission, having no prior diagnosis of a cardiac arrhythmia, and having at least 1 year of Veterans Affairs care. We included only the first pneumonia-related hospitalization, and follow-up was for the 90 days after admission. Cardiac arrhythmias included atrial fibrillation, ventricular tachycardia/fibrillation, cardiac arrest, and symptomatic bradycardia. We used a multilevel regression model, adjusting for hospital of admission, to examine risk factors for cardiac arrhythmias. RESULTS: We identified 32,689 patients who met the inclusion criteria. Of these, 3919 (12%) had a new diagnosis of cardiac arrhythmia within 90 days of admission. Variables significantly associated with increased risk of cardiac arrhythmia included increasing age, history of congestive heart failure, and a need for mechanical ventilation or vasopressors. Beta-blocker use was associated with a decreased incidence of events. CONCLUSION: An important number of patients have new cardiac arrhythmia during and after hospitalization for pneumonia. Additional research is needed to determine whether use of cardioprotective medications will improve outcomes for patients hospitalized with pneumonia. At-risk patients hospitalized with pneumonia should be monitored for cardiac arrhythmias during the hospitalization. Published by Elsevier Inc. The American Journal of Medicine (2013) 126, 43-48 C1 [Mortensen, Eric M.] VA N Texas Hlth Care Syst, Gen Internal Med 111E, Dallas, TX 75216 USA. [Mortensen, Eric M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Soto-Gomez, Natalia; Anzueto, Antonio; Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Waterer, Grant W.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia. [Waterer, Grant W.] Northwestern Univ, Sch Med, Chicago, IL USA. [Restrepo, Marcos I.] VERDICT S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Mortensen, EM (reprint author), VA N Texas Hlth Care Syst, Gen Internal Med 111E, 4500 S Lancaster, Dallas, TX 75216 USA. EM eric.mortensen@UTSouthwestern.edu RI Restrepo, Marcos/H-4442-2014; OI Mortensen, Eric/0000-0002-3880-5563 FU National Institute of Nursing Research [R01NR010828] FX The project described was supported by Grant Number R01NR010828 from the National Institute of Nursing Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Nursing Research or the National Institutes of Health. This material is the result of work supported with resources and the use of facilities at the VA North Texas Health Care System. The funding agencies had no role in conducting the study, or role in the preparation, review, or approval of the manuscript. NR 25 TC 11 Z9 11 U1 0 U2 7 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 JAN PY 2013 VL 126 IS 1 BP 43 EP 48 DI 10.1016/j.amjmed.2012.08.005 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 060VC UT WOS:000312805300024 PM 23177550 ER PT J AU Kumbhani, DJ Fonarow, GC Cannon, CP Hernandez, AF Peterson, ED Peacock, WF Laskey, WK Pan, WQ Schwamm, LH Bhatt, DL AF Kumbhani, Dharam J. Fonarow, Gregg C. Cannon, Christopher P. Hernandez, Adrian F. Peterson, Eric D. Peacock, W. Frank Laskey, Warren K. Pan, Wenqin Schwamm, Lee H. Bhatt, Deepak L. CA Get Guidelines Steering Comm Inves TI Predictors of Adherence to Performance Measures in Patients with Acute Myocardial Infarction SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Arteriosclerosis; Myocardial infarction; Risk factors; Sex; Statins ID ACUTE CORONARY SYNDROMES; QUALITY-OF-CARE; LEFT-VENTRICULAR FUNCTION; ASSOCIATION TASK-FORCE; SECONDARY PREVENTION; HEART-ASSOCIATION; AMERICAN-COLLEGE; RENAL-INSUFFICIENCY; GUIDELINES PROGRAM; HOSPITAL QUALITY AB BACKGROUND: There have been substantial improvements in the use of evidence-based, guideline-recommended therapies for patients with acute myocardial infarction. Nevertheless, some gaps, disparities, and variations in use remain. To understand how such gaps in recommended care may be narrowed further, it may be useful to determine those factors associated with lessened adherence to guideline-based care. METHODS: The Get with the Guidelines-Coronary Artery Disease registry measured adherence with 6 performance measures (aspirin within 24 hours, discharge on aspirin and beta-blockers, patients with low ejection fraction discharged on angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, smoking cessation counseling, use of lipid-lowering medications) in 148,654 patients with acute myocardial infarction between 2002 and 2009. Logistic multivariable regression models using generalized estimating equations were utilized to identify patient and hospital characteristics associated with adherence to each of 6 measures, and to a summary score of performance for all measures, in eligible patients. RESULTS: We identified 10 variables that were associated significantly with either greater adherence (hypertension, hyperlipidemia, hospital with full interventional capabilities, calendar year) or worse adherence (age, female sex, congestive heart failure, chronic renal insufficiency, atrial fibrillation, chronic dialysis) in at least 4 of the 6 treatment adherence models, as well as the summary score adherence model. Age, sex, and calendar year were significant in all models. CONCLUSIONS: Use of evidence-based acute myocardial infarction treatments remains less than ideal for certain high-risk populations. The close correlations among factors associated with underperformance highlights the potential for specifically targeting and tailoring quality improvement interventions. (C) 2013 Elsevier Inc. All rights reserved. . The American Journal of Medicine (2013) 126, 74. e1-74.e9 C1 [Kumbhani, Dharam J.; Cannon, Christopher P.; Bhatt, Deepak L.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Kumbhani, Dharam J.; Cannon, Christopher P.; Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA. [Hernandez, Adrian F.; Peterson, Eric D.; Pan, Wenqin] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Peacock, W. Frank] Baylor Coll Med, Dept Emergency Med, Houston, TX 77030 USA. [Laskey, Warren K.] Univ New Mexico, Dept Med, Div Cardiol, Albuquerque, NM 87131 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Div Cardiol, Boston, MA USA. RP Bhatt, DL (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. EM dlbhattmd@post.harvard.edu RI Hernandez, Adrian F./A-7818-2016 OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616 FU Council on Clinical Cardiology of the American Heart Association; Merck/Schering-Plough Pharmaceutical; Accumetrics; AstraZeneca; Essentialis; GlaxoSmithKline; Merck; Regeneron; Sanofi; Takeda; Advisory Board; Alnylam; Bristol-Myers Squibb; Pfizer; Johnson and Johnson; BMS Sanofi; Eli Lilly; Ortho McNeil Pharmaceutical; Abbott; Alere; Brahms; Corthera; EKR; Nanosphere; Medicine's Company FX This study is supported by a Young Investigator grant from the Council on Clinical Cardiology of the American Heart Association to Dr Dharam Kumbhani. GWTG-CAD is a program of the American Heart Association and is supported by an unrestricted educational grant from Merck/Schering-Plough Pharmaceutical. Data collection and management were performed by Outcome, Inc. (Cambridge, Mass). The analysis of registry data was performed at Duke Clinical Research Institute (Durham, NC), which also receives funding from the American Heart Association. The sponsor was not involved in the management, analysis, or interpretation of data or the preparation of the manuscript.; DJ Kumbhani: None; GC Fonarow: None; CP Cannon: Research grants/support from: Accumetrics, AstraZeneca, Essentialis, GlaxoSmithKline, Merck, Regeneron, Sanofi, Takeda. Advisory Board (but funds donated to charity): Alnylam, Bristol-Myers Squibb, Pfizer. Clinical Advisor, equity: Automedics Medical Systems; AF Hernandez: Research grants/support from: Accumetrics, AstraZeneca, Essentialis, GlaxoSmithKline, Merck, Regeneron, Sanofi, Takeda. Advisory Board (but funds donated to charity): Alnylam, Bristol-Myers Squibb, Pfizer. Clinical Advisor, equity: Automedics Medical Systems. AF Hernandez: Research Grants from Johnson and Johnson; ED Peterson: Research Grants from BMS Sanofi, Merck, Eli Lilly, and Ortho McNeil Pharmaceutical; WF Peacock: Research Grants (Significant) from Abbott, Alere, Brahms, Corthera, EKR, Nanosphere, The Medicine's Company; Consultant (Modest) for Abbott, Alere, Beckman Coulter, Electrocore, The Medicine's Company; Speaker's Bureau (Modest) for Abbott, Alere; Ownership Interest (Modest) in Comprehensive Research Associates LLC, Vital Sensors, Emergencies in Medicine LLC; WK Laskey: None; W Pan: None; LH Schwamm: None; DL Bhatt: Advisory Board: Medscape Cardiology; Board of Directors: Boston VA Research Institute, Society of Chest Pain Centers; Chair: American Heart Association Get With The Guidelines Science Subcommittee; Honoraria: American College of Cardiology (Editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), WebMD (CME steering committees); Research Grants: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, The Medicines Company; Unfunded Research: FlowCo, PLx Pharma, Takeda. NR 46 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD JAN PY 2013 VL 126 IS 1 DI 10.1016/j.amjmed.2012.02.025 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 060VC UT WOS:000312805300028 ER PT J AU Saint-Geniez, M Jiang, AH Abend, S Liu, L Sweigard, H Connor, KM Arany, Z AF Saint-Geniez, Magali Jiang, Aihua Abend, Stephanie Liu, Laura Sweigard, Harry Connor, Kip M. Arany, Zoltan TI PGC-1 alpha Regulates Normal and Pathological Angiogenesis in the Retina SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID OXYGEN-INDUCED RETINOPATHY; TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA; SKELETAL-MUSCLE; MOUSE MODEL; VEGF; VASCULATURE; PREMATURITY; RECEPTOR; EXPRESSION; DISEASE AB Neovascular diseases of the eye are the most common causes of blindness worldwide. The mechanisms underlying pathological neovascularization in the retina remain incompletely understood. PGC-1 alpha is a transcriptional coactivator that plays a central role in the regulation of cellular metabolism. In skeletal muscle, PGC-1 alpha induces VEGFA expression and powerfully promotes angiogenesis, suggesting a similar rote in other tissues. This study investigates the role of PGC-1 alpha during normal and pathological vascularization in the retina. We show that PGC-1 alpha induces the expression of VEGFA in numerous retinal cells, and that PGC-1 alpha expression is strongly induced during postnatal retinal development, coincident with VEGFA expression and angiogenesis. PGC-1 alpha(-/-) mice have a significant reduction of early retinal vascular outgrowth, and reduced density of capillaries and number of main arteries and veins as adults. In the oxygen-induced retinopathy model of retinopathy of prematurity, PGC-1 alpha expression is dramatically induced in the inner nuclear layer of the retina, suggesting that PGC-1 alpha drives pathological neovascularization. In support of this, PGC-1 alpha(-/-) mice subjected to oxygen-induced retinopathy had decreased expression of VEGFA and were protected against pathological neovascularization. These results demonstrate that PGC-1 alpha regulates VEGFA in the retina and is required for normal vessel development and for pathological neovascularization. The data highlight PGC-1 alpha as a novel target in the treatment of neovascular diseases of the eye. (Am 3 Pathol 2013, 182: 255-265; http://dx.doiorg/10.1016/j.ajpath.2012.09.003) C1 [Saint-Geniez, Magali; Abend, Stephanie] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. [Sweigard, Harry; Connor, Kip M.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Jiang, Aihua; Liu, Laura; Arany, Zoltan] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Jiang, Aihua; Liu, Laura; Arany, Zoltan] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA. RP Arany, Z (reprint author), Beth Israel Deaconess Med Ctr, Cardiovasc Inst, ECLS906,330 Brookline Ave, Boston, MA 02215 USA. EM zarany@bidmc.harvard.edu FU March of Dimes; Harvard Catalyst; Harvard Clinical and Translational Science Center; National Heart, Lung, and Blood Institute; American Heart Association; American Diabetes Association; Ellison Foundation; National Eye Institute Training Grant; Core Grant for Vision Research; Research to Prevent Blindness; NIH [R01EY022084]; Harvard University FX Supported by the March of Dimes (Z.A.), the Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (Z.A. and M.S.-G.), the National Heart, Lung, and Blood Institute (Z.A.), the American Heart Association (A.J.), the American Diabetes Association (Z.A.), the Ellison Foundation (Z.A.), the National Eye Institute Training Grant (H.S.) and Core Grant for Vision Research (K.M.C.), Research to Prevent Blindness unrestricted grant to Harvard Department of Ophthalmology (K.M.C.), the NIH R01EY022084 (K.M.C.), and financial contributions from Harvard University and its affiliated academic health care centers. NR 39 TC 18 Z9 20 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 2013 VL 182 IS 1 BP 255 EP 265 DI 10.1016/j.ajpath.2012.09.003 PG 11 WC Pathology SC Pathology GA 065JG UT WOS:000313144000026 PM 23141926 ER PT J AU Yui, N Lu, HAJ Chen, Y Nomura, N Bouley, R Brown, D AF Yui, Naofumi Lu, Hua A. J. Chen, Ying Nomura, Naohiro Bouley, Richard Brown, Dennis TI Basolateral targeting and microtubule-dependent transcytosis of the aquaporin-2 water channel SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE clathrin; endocytosis; Rab5; Rab11; MDCK cells ID POLARIZED MDCK CELLS; RENAL PRINCIPAL CELLS; COLLECTING DUCT; EPITHELIAL-CELLS; PLASMA-MEMBRANE; RAT-KIDNEY; APICAL MEMBRANE; ANCHORED PROTEINS; EARLY ENDOSOMES; PHOSPHORYLATION AB Yui N, Lu HA, Chen Y, Nomura N, Bouley R, Brown D. Basolateral targeting and microtubule-dependent transcytosis of the aquaporin-2 water channel. Am J Physiol Cell Physiol 304: C38-C48, 2013. First published September 26, 2012; doi:10.1152/ajpcell.00109.2012.-The aquaporin-2 (AQP2) water channel relocates mainly to the apical plasma membrane of collecting duct principal cells after vasopressin (VP) stimulation. AQP2 transport to this membrane domain is assumed to be a direct route involving recycling of intracellular vesicles. However, basolateral plasma membrane expression of AQP2 is observed in vivo in principal cells. Here, we asked whether there is a transcytotic pathway of AQP2 trafficking between apical and basolateral membranes. We used MDCK cells in which AQP2 normally accumulates apically after VP exposure. In contrast, both site-specific biotinylation and immunofluorescence showed that AQP2 is strongly accumulated in the basolateral membrane, along with the endocytic protein clathrin, after a brief cold shock (4 degrees C). This suggests that AQP2 may be constitutively targeted to basolateral membranes and then retrieved by clathrin-mediated endocytosis at physiological temperatures. Rab11 does not accumulate in basolateral membranes after cold shock, suggesting that the AQP2 in this location is not associated with Rab11-positive vesicles. After rewarming (37 degrees C), basolateral AQP2 staining is diminished and it subsequently accumulates at the apical membrane in the presence of VP/forskolin, suggesting that transcytosis can be followed by apical insertion of AQP2. This process is inhibited by treatment with colchicine. Our data suggest that the cold shock procedure reveals the presence of microtubule-dependent AQP2 transcytosis, which represents an indirect pathway of apical AQP2 delivery in these cells. Furthermore, our data indicate that protein polarity data obtained from biotinylation assays, which require cells to be cooled to 4 degrees C during the labeling procedure, should be interpreted with caution. C1 [Brown, Dennis] Massachusetts Gen Hosp, MGH Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Simches Res Ctr, Div Nephrol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Brown, D (reprint author), Massachusetts Gen Hosp, MGH Ctr Syst Biol, Program Membrane Biol, Simches Res Bldg,185 Cambridge St,CPZN 8202, Boston, MA 02114 USA. EM brown.dennis@mgh.harvard.edu FU NIH [DK-38452, DK-96586]; Gottschalk research grant (American Society of Nephrology); Boston Area Diabetes and Endocrinology Research Center [DK-57521]; MGH Center for the Study of Inflammatory Bowel Disease [DK-43351]; Japan Society for the Promotion of Science; [DK-75940] FX This work was supported by NIH Grants DK-38452 and DK-96586 (to D. Brown), DK-75940 and a Gottschalk research grant (American Society of Nephrology) to H. A. J. Lu. Additional support for the Program in Membrane Biology Microscopy Core comes from the Boston Area Diabetes and Endocrinology Research Center (DK-57521) and the MGH Center for the Study of Inflammatory Bowel Disease (DK-43351). N. Yui and N. Nomura were also supported by a grant for "Strategic young researcher overseas visits program for accelerating brain circulation" from the Japan Society for the Promotion of Science. NR 55 TC 21 Z9 22 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JAN PY 2013 VL 304 IS 1 BP C38 EP C48 DI 10.1152/ajpcell.00109.2012 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 064AA UT WOS:000313042100005 PM 23015545 ER PT J AU Raj, S Scott, DR Nguyen, T Sachs, G Kraut, JA AF Raj, Suraja Scott, David R. Thomas Nguyen Sachs, George Kraut, Jeffrey A. TI Acid stress increases gene expression of proinflammatory cytokines in Madin-Darby canine kidney cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE metabolic acidosis; lubricin; CCL7; MDCK cells; intracellular pH; proinflammatory cytokines ID DAVID BIOINFORMATICS RESOURCES; ENDOPLASMIC-RETICULUM STRESS; METABOLIC-ACIDOSIS; INDUCED APOPTOSIS; INTRACELLULAR PH; NDRG2; DISEASE; INFLAMMATION; ENDOTHELIN; LUBRICIN AB Raj S, Scott DR, Nguyen T, Sachs G, Kraut JA. Acid stress increases gene expression of proinflammatory cytokines in Madin-Darby canine kidney cells. Am J Physiol Renal Physiol 304: F41-F48, 2013. First published October 17, 2012; doi:10.1152/ajprenal.00128.2012.Metabolic acidosis is thought to exacerbate chronic kidney disease in part by stimulating the release of potentially injurious substances. To define the genes whose expression is affected by exposure to an acidic milieus, we examined the effect of exposure of MDCK cells to pH 7.4 and pH 7.0 for 24 h on gene expression using a canine derived microarray. Exposure to this pH stress for 24 h led to increased expression of 278 genes (2.2% of the transcriptome) by at least 2-fold and 60 of these (21%) were upregulated by >3-fold. On the other hand, 186 genes (1.5% of the transcriptome) were downregulated by at least 2-fold and 16 of these (9%) were downregulated by 3-fold or more. Ten percent of the genes upregulated by at least threefold encode proinflammatory cytokine proteins, including colony stimulating factor 2, chemokine ligand 7, chemokine ligand 20, chemokine ligand 8, and interleukin-1 alpha. Two others encode metallopeptidases. The most highly upregulated gene encodes a protein, lubricin, shown to be important in preventing cartilage damage and in tissue injury or repair. Upregulation of four genes was confirmed by quantitative PCR. Housekeeping genes were not increased. To examine the effect of decreasing medium pH, we measured intracellular pH (pH(i)) using 2,7-bis (2-carboxyethyl)5-carboxyfluorescein. With extracellular pH (pH(o)) of 7.0, pHi fell and remained depressed. These findings suggest that a pH stress alone can increase renal expression of proinflammatory and other genes that contribute to renal injury. C1 [Raj, Suraja; Thomas Nguyen; Sachs, George; Kraut, Jeffrey A.] Vet Affairs Greater Los Angeles Healthcare Syst, Med Serv, Los Angeles, CA USA. [Raj, Suraja; Scott, David R.; Thomas Nguyen; Sachs, George; Kraut, Jeffrey A.] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. [Scott, David R.; Sachs, George] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. [Sachs, George; Kraut, Jeffrey A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Thomas Nguyen; Kraut, Jeffrey A.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Nephrol, Los Angeles, CA USA. RP Kraut, JA (reprint author), VHAGLA Healthcare Syst, Div Nephrol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jkraut@ucla.edu FU Veterans Administration; University of California, Los Angeles, Academic Senate FX These studies were supported by funds from the Veterans Administration and a grant from the University of California, Los Angeles, Academic Senate. Brad Sherman is a Bioinformatics Analyst of the Laboratory of Immunopathogenesis and Bioinformatics at the National Institute of Allergy and Infectious Diseases and assisted in performance of the GO analysis. NR 35 TC 7 Z9 7 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN PY 2013 VL 304 IS 1 BP F41 EP F48 DI 10.1152/ajprenal.00128.2012 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 064FV UT WOS:000313059100006 PM 23077097 ER PT J AU Nierenberg, AA Friedman, ES Bowden, CL Sylvia, LG Thase, ME Ketter, T Ostacher, MJ Leon, AC Reilly-Harrington, N Iosifescu, DV Pencina, M Severe, JB Calabrese, JR AF Nierenberg, Andrew A. Friedman, Edward S. Bowden, Charles L. Sylvia, Louisa G. Thase, Michael E. Ketter, Terence Ostacher, Michael J. Leon, Andrew C. Reilly-Harrington, Noreen Iosifescu, Dan V. Pencina, Michael Severe, Joanne B. Calabrese, Joseph R. TI Lithium Treatment Moderate-Dose Use Study (LiTMUS) for Bipolar Disorder: A Randomized Comparative Effectiveness Trial of Optimized Personalized Treatment With and Without Lithium SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; PSYCHOTROPIC-DRUG PRESCRIPTION; COMORBIDITY SURVEY REPLICATION; PATTERN-MIXTURE MODELS; LOW SERUM LEVELS; DOUBLE-BLIND; I-DISORDER; MAINTENANCE TREATMENT; MOOD DISORDERS; DSM-IV AB Objective: Lithium salts, once the mainstay of therapy for bipolar disorder, have tolerability issues at a higher dosage that often limit adherence. The authors investigated the comparative effectiveness of more tolerable dosages of lithium as part of optimized personalized treatment (OPT). Method: The authors randomly assigned 283 bipolar disorder outpatients to 6 months of open, flexible, moderate dosages of lithium plus OPT or to 6 months of OPT alone. The primary outcome measures were the Clinical Global Impression Scale for Bipolar Disorder-Severity (CGI-BP-S) and "necessary clinical adjustments" (medication adjustments per month). Secondary outcome measures included mood symptoms and functioning. The authors also assessed sustained remission (defined as a CGI-BPS score <= 2 for 2 months) and treatment with second-generation antipsychotics. The authors hypothesized that lithium plus OPT would result in greater clinical improvement and fewer necessary clinical adjustments. Results: The authors observed no statistically significant advantage of lithium plus OPT on CGI-BP-S scores, necessary clinical adjustments, or proportion with sustained remission. Both groups had similar outcomes across secondary clinical and functional measures. Fewer patients in the lithium-plus-OPT group received second-generation antipsychotics compared with the OPT-only group (48.3% and 62.5%, respectively). Conclusions: In this pragmatic comparative effectiveness study, a moderate but tolerated dosage of lithium plus OPT conferred no symptomatic advantage when compared with OPT alone, but the lithium-plus-OPT group had less exposure to second-generation antipsychotics. Only about one-quarter of patients in both groups achieved sustained remission of symptoms. These findings highlight the persistent and chronic nature of bipolar disorder as well as the magnitude of unmet needs in its treatment. (Am J Psychiatry 2013; 170:102-110) C1 [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Stanford Univ, Stanford, CA 94305 USA. Weill Cornell Med Coll, New York, NY USA. Mt Sinai Sch Med, New York, NY USA. Harvard Clin Res Inst, Boston, MA USA. NIMH, Rockville, MD 20857 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM anierenberg@partners.org OI Ostacher, Michael/0000-0003-0353-7535 FU American Drug Utilization Review; American Professional Society of ADHD and Related Disorders; American Psychiatric Association; American Society for Clinical Psychopharmacology; Appliance Computing (Mindsite); AstraZeneca; Basliea; Baystate Medical Center; Belvoir Publishing; Brain Cells; Brandeis University; Bristol-Myers Squibb; Columbia University; Corcept; Dainippon Sumitomo; Eli Lilly; EpiQ; Forest Pharmaceuticals, Hillside Hospital; IMEDEX; International Society for Bipolar Disorders; Johnson Johnson; MJ Consulting; Medscape; MBL Publishing, New York State; NIMH; Novartis; PamLabs; Pfizer; PGx Health; Physicians Postgraduate Press; Ridge Diagnostics; Schering-Plough; SciMed; ShireSUNY Buffalo; Takeda/Lundbeck; Targacept; Teva Pharmaceuticals; University of Texas Southwestern Dallas; University of Wisconsin; University of Pisa; GlaxoSmithKline; Wyeth; Solvay; Schering-Plough,; Sanofi-Aventis; Merck FX Dr. Nierenberg has received consulting fees, advisory board fees, research support, or speakers honoraria from American Drug Utilization Review, American Professional Society of ADHD and Related Disorders, American Psychiatric Association, American Society for Clinical Psychopharmacology, Appliance Computing (Mindsite), AstraZeneca, Basliea, Baystate Medical Center, Belvoir Publishing, Brain Cells, Brandeis University, Bristol-Myers Squibb, Columbia University, Corcept, Dainippon Sumitomo, Eli Lilly, EpiQ, Forest Pharmaceuticals, Hillside Hospital, IMEDEX, International Society for Bipolar Disorders, Johnson & Johnson, MJ Consulting, Medscape, MBL Publishing, New York State, NIMH, Novartis, PamLabs, Pfizer, PGx Health, Physicians Postgraduate Press, Ridge Diagnostics, Schering-Plough, SciMed, Shire, SUNY Buffalo, Takeda/Lundbeck, Targacept, Teva Pharmaceuticals, University of Texas Southwestern Dallas, University of Wisconsin, and University of Pisa; has consulted through the MGH Clinical Trials Network and Institute for Brain Cells, Dianippon Sumitomo/Sepracor, Johnson & Johnson, Labopharm, Merck, Methylation Science, Novartis, PGx Health, Schering-Plough, Shire, Targacept, and Takeda/Lundbeck Pharmaceuticals; and owns stock options in Appliance Computing and Brain Cells. Through Massachusetts General Hospital, Dr. Nierenberg is named for copyrights to the Clinical Positive Affect Scale and the MGH Structured Clinical Interview for the Montgomery-Asberg Depression Scale exclusively licensed to the MGH Clinical Trials Network and Institute. Dr. Nierenberg is a presenter for the Massachusetts General Hospital Psychiatry Academy (MGHPA). The education programs conducted by the MGHPA were supported through Independent Medical Education grants from Astra Zeneca, Bristol-Myers Squibb, Eli Lilly, and Janssen Pharmaceuticals. Dr. Friedman has received consulting fees, advisory board fees, research support, royalties, or speakers honoraria from Aspect Medical Systems, AstraZeneca, Bristol-Myers Squibb, Cyberonics, Indevus, Medtronics, the NIMH Agency for Healthcare Research and Quality, NorthStar/St. Jude Medical, Novartis, Respironics, Sanofi-Aventis, Springer, and Wyeth-Ayerst. Dr. Bowden has received consulting fees, advisory board fees, research support, or speakers honoraria from Bristol-Myers Squibb, Johnson & Johnson, Merck Pfizer, NIMH, Repligen, and Sanofi-Aventis. Dr. Sylvia has received consulting fees from Bracket Global and Clintara, was a shareholder for Concordant Rater Systems, has received royalties from New Harbinger Publisher, and has presented for the MGHPA. Dr. Thase has received consulting fees, advisory board fees, research support, or speakers honoraria from AstraZeneca, Bristol-Myers Squibb, Dey Pharma, Eli Lilly, Forest Pharmaceuticals, Gerson Lehman Group, GlaxoSmithKline, Guidepoint Global, H. Lundbeck A/S, MedAvante, Merck, Neuronetics, the NIMH Agency for Healthcare Research Quality, Novartis, Ortho-McNeil Pharmaceuticals, Otsuka, PamLab, Pfizer, Schering-Plough, Sepracor, Shire, Supernus Pharmaceuticals, Takeda (Lundbeck), and Transcept Pharmaceuticals; has equity holdings in MedAvante; and has received royalty income from American Psychiatric Foundation, Guilford Publications, Herald House, Oxford University Press, and W.W. Norton. Dr. Thase's spouse is employed by Embryon (formerly Advogent). Dr.; Ketter has received consulting fees, advisory board fees, research support, royalties, or speakers honoraria from American Psychiatric Publishing, AstraZeneca, Astellas Pharmaceuticals, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutica, Merck, the NIMH Agency for Healthcare Research and Quality, Hoven Pharmaceuticals, Pfizer, Sunovion, and XenoPort. Dr. Ketter's spouse is an employee with and holds stock in Johnson & Johnson. Dr. Ostacher has served as a consultant to Sunovion. Dr. Leon has served on independent data and safety monitoring boards for AstraZeneca, Pfizer, and Sunovion; has received consulting fees from the Food and Drug Administration, MedAvante, NIMH, and Roche; and held equity in MedAvante. Dr. Reilly-Harrington has received royalties from the American Psychological Association and Oxford University Press, was a shareholder in Concordant Rater Systems, and has received consulting fees from Bracket Global. Dr. losifescu has received consulting or advisory board fees from Aspect Medical, Forest Pharmaceuticals, Ortho-McNeil, and Reed Medical (sponsor of the Massachusetts General Hospital Psychiatry Academy). Dr. Pencina consults for Pamlab and RCT Logic. Ms. Severe is a former employee of NIMH. Dr. Calabrese has received consulting fees, advisory board fees, research support, or speakers honoraria from Abbott, Astra-Zeneca, Bristol-Myers Squibb, Cephalon, Cleveland Foundation, Dainippon Sumitomo, Eli Lilly, EPI-Q, Forest Pharmaceuticals, France Foundation, GlaxoSmithKline, Health Resources Services Administration. Janssen, Johnson SE Johnson, Lundbeck, Merck, NARSAD, Neurosearch, NIMH, Ortho-McNeil, Otsuka, Pfizer, Rep ligen, Schering-Plough, Servier, Solvay, Stanley Medical Research Institute, Supernus, Synosia, Takeda, the US Department of Defense, and Wyeth, and has provided CME lectures supported by AstraZeneca, Bristol-Myers Squibb, France Foundation, GlaxoSmithKline, Janssen, Johnson bz Johnson, Merck, Pfizer, Sanofi-Aventis, Schering-Plough, Solvay, and Wyeth. NR 40 TC 31 Z9 31 U1 6 U2 30 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 JAN PY 2013 VL 170 IS 1 BP 102 EP 110 DI 10.1176/appi.ajp.2012.12060751 PG 9 WC Psychiatry SC Psychiatry GA 064OZ UT WOS:000313086200013 PM 23288387 ER PT J AU Lewiecki, EM Miller, SA AF Lewiecki, E. Michael Miller, Sara A. TI Suicide, Guns, and Public Policy SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID OF-THE-LITERATURE; UNITED-STATES; FIREARM SUICIDE; EUROPEAN-UNION; RATES; PREVENTION; MORTALITY; LETHALITY; ASSOCIATION; IMPULSIVITY AB Suicide is a serious public health concern that is responsible for almost 1 million deaths each year worldwide. It is commonly an impulsive act by a vulnerable individual. The impulsivity of suicide provides opportunities to reduce the risk of suicide by restricting access to lethal means. In the United States, firearms, particularly handguns, are the most common means of suicide. Despite strong empirical evidence that restriction of access to firearms reduces suicides, access to firearms in the United States is generally subject to few restrictions. Implementation and evaluation of measures such as waiting periods and permit requirements that restrict access to handguns should be a top priority for reducing deaths from impulsive suicide in the United States. (Am J Public Health. 2013;103:27-31. doi:10.2105/AJPH.2012.300964) C1 [Lewiecki, E. Michael] Univ New Mexico, Sch Med, Dept Internal Med, Albuquerque, NM 87131 USA. [Lewiecki, E. Michael] New Mexico Clin Res & Osteoporosis Ctr, Albuquerque, NM 87106 USA. [Miller, Sara A.] Harvard Univ, Massachusetts Gen Hosp, Richard B Simches Res Ctr, Boston, MA 02115 USA. RP Lewiecki, EM (reprint author), New Mexico Clin Res & Osteoporosis Ctr, 300 Oak St NE, Albuquerque, NM 87106 USA. EM elewiecki@salud.unm.edu NR 62 TC 15 Z9 15 U1 1 U2 23 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 2013 VL 103 IS 1 BP 27 EP 31 DI 10.2105/AJPH.2012.300964 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 062NZ UT WOS:000312927900008 PM 23153127 ER PT J AU Chatterjee, NA He, YL Keating, NL AF Chatterjee, Neal A. He, Yulei Keating, Nancy L. TI Racial Differences in Breast Cancer Stage at Diagnosis in the Mammography Era SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID SERVICES TASK-FORCE; SCREENING MAMMOGRAPHY; RACIAL/ETHNIC DISPARITIES; HORMONE-THERAPY; INCIDENCE RATES; DISEASE STAGE; UNITED-STATES; SELF-REPORTS; WHITE WOMEN; BLACK-WOMEN AB Objectives. We assessed racial differences in breast cancer mortality by stage at diagnosis, since mammography became available. Methods. We calculated adjusted odds of distant (versus local or regional) tumors for 143 249 White and 13 571 Black women aged 50 to 69 years, diagnosed with breast cancer between 1982 and 2007 and living in a Surveillance, Epidemiology, and End Results region. We compared linear trends in stage at diagnosis before and after 1998. Results. Distant-stage cancer was diagnosed in 5.8% of White and 10.2% of Black participants. The Black-White disparity in distant tumors narrowed until 1998 (1998 adjusted difference = 0.65%), before increasing. Between 1982 and 1997, the proportion of distant tumors decreased for Blacks (adjusted odds ratio [AOR]/y = 0.973; 95% confidence interval [CI] = 0.960, 0.987) and Whites (AOR/y = 0.978; 95% CI = 0.973, 0.983), with no racial differences (P = .47). From 1998 to 2007, the odds of distant versus local or regional tumors increased for Blacks (AOR/y = 1.036; 95% CI = 1.013, 1.060) and Whites (AOR/y = 1.011; 95% CI = 1.002, 1.021); the rate of increase was greater for Blacks than Whites (P = .04). Conclusions. In the mammography era, racial disparities remain in stage at diagnosis. (Am J Public Health. 2013;103:170-176. doi:10.2105/AJPH.2011.300550) C1 [Chatterjee, Neal A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [He, Yulei; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Diuis Gen Internal Med, Boston, MA 02115 USA. RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM keating@hcp.med.harvard.edu FU Susan G. Komen for the Cure Foundation FX This work was supported by the Susan G. Komen for the Cure Foundation. NR 60 TC 13 Z9 13 U1 0 U2 10 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 2013 VL 103 IS 1 BP 170 EP 176 DI 10.2105/AJPH.2011.300550 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 062NZ UT WOS:000312927900032 PM 22698058 ER PT J AU Rajesh, A Cloud, G Harisinghani, MG AF Rajesh, Arumugam Cloud, Gretchen Harisinghani, Mukesh G. TI Improving the Quality of Manuscript Reviews: Impact of Introducing a Structured Electronic Template to Submit Reviews SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE manuscript; quality; review ID PERFORMANCE AB OBJECTIVE. The purpose of this study is to evaluate the impact of structured electronic templates on the quality of manuscript reviews. MATERIALS AND METHODS. Twenty-five gastrointestinal and genitourinary reviewers for the American Journal of Roentgenology were included in this investigation. Reviewers were selected and anonymized on the basis of having reviewed one or more manuscripts during period 1 (January 2008 through December 2009). All manuscript reviews were given a review quality score. Reviewers with at least one suboptimal review (i.e., a quality review score of < 3 on a scale of 1 to 4, with 1 being poor and 4 being an excellent review) were selected for further follow-up. During period 1, the reviewers received minimal guidance regarding the expectations of a high-quality review. During period 2 (August 2010 through August 2011), the reviewers meeting the criteria selected for follow-up received a structured electronic template outlining the review process. Reviews were again scored for review quality and were compared with a paired Student t test. RESULTS. The mean (+/- SD) and median review quality scores were 2.07 +/- 0.44 and 2.0, respectively, for period 1 and 3.02 +/- 0.89 and 3.0, respectively, for period 2. There was a 1-point improvement during period 2 after the introduction of the structured electronic template. Most of the reviews (19/25 [76%; 95% CI, 55%-91%]) improved after introduction of the structured electronic template, whereas only two of 19 worsened. Review scores significantly increased after introduction of the structured electronic templates (mean increase, 0.95 +/- 0.92; t = 5.13; p < 0.0001). By specialty, the 13 gastrointestinal reviewers increased their score by 0.39 (p = 0.03), and the 12 genitourinary reviewers increased their score by 1.55 points (p < 0.0001). CONCLUSION. The introduction of a structured electronic template significantly improved the quality of manuscript reviews submitted. C1 [Rajesh, Arumugam] Univ Hosp Leicester NHS Trust, Leicester Gen Hosp, Dept Radiol, Leicester LE5 4PW, Leics, England. [Cloud, Gretchen] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Rajesh, A (reprint author), Univ Hosp Leicester NHS Trust, Leicester Gen Hosp, Dept Radiol, Gwendolen Rd, Leicester LE5 4PW, Leics, England. EM arajesh27@hotmail.com NR 7 TC 4 Z9 4 U1 1 U2 5 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 JAN PY 2013 VL 200 IS 1 BP 20 EP 23 DI 10.2214/AJR.11.8299 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 060JF UT WOS:000312772200019 PM 23255737 ER PT J AU Kang, HC Tan, KS Keefe, SM Heitjan, DF Siegelman, ES Flaherty, KT O'Dwyer, PJ Rosen, MA AF Kang, Hyunseon Christine Tan, Kay-See Keefe, Stephen M. Heitjan, Daniel F. Siegelman, Evan S. Flaherty, Keith T. O'Dwyer, Peter J. Rosen, Mark A. TI MRI Assessment of Early Tumor Response in Metastatic Renal Cell Carcinoma Patients Treated With Sorafenib SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE MRI; renal cell carcinoma; sorafenib; tyrosine kinase inhibitors ID RECEPTOR TYROSINE KINASES; TARGETED THERAPY; PHASE-II; CANCER; CRITERIA; ANGIOGENESIS; PROGRESSION; RECIST; SIZE; ATTENUATION AB OBJECTIVE. The purpose of this study was to examine early MRI changes in renal cell carcinoma (RCC) treated with the antiangiogenic agent sorafenib and to identify MRI biomarkers of RCC response to sorafenib. MATERIALS AND METHODS. Sixteen patients with RCC were evaluated by MRI before and 3-12 weeks after commencing treatment with sorafenib. Two experienced MR radiologists, blinded to treatment status, independently graded tumor appearance on T1-weighted, T2-weighted, and gadolinium-enhanced images. The proportional odds mixed model was used to compare qualitative appearance of tumors before and after therapy. Time-to-progression was correlated with Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 and MR-modified Choi criteria, incorporating changes in both tumor enhancement and size. RESULTS. After sorafenib therapy, there was a significant increase in T1 signal intensity of tumors (p < 0.0001) and a significant decrease in degree of tumor enhancement (p < 0.0001). The sum of unidimensional tumor diameters decreased significantly after therapy (p = 0.005). However, the average decrease in size at early follow-up was 13%, and all patients except one had stable disease by RECIST 1.0. Early responders defined by MR-modified Choi criteria had increased time-to-progression compared with nonresponders, whereas early RECIST evaluation did not predict clinical outcome. CONCLUSION. Decreased enhancement and T1 shortening of tumors on MRI may be useful biomarkers of RCC response to angiogenesis inhibitors. Response criteria combining early changes in size and enhancement lead to better correlation with clinical outcome compared with size decrease alone. C1 [Kang, Hyunseon Christine; Siegelman, Evan S.; Rosen, Mark A.] Hosp Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Tan, Kay-See; Heitjan, Daniel F.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Keefe, Stephen M.; O'Dwyer, Peter J.] Univ Penn, Div Hematol & Oncol, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Oncol, Boston, MA USA. RP Kang, HC (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Unit 1473, POB 301402, Houston, TX 77030 USA. EM hkang2@mdanderson.org OI Kang, Hyunseon/0000-0001-5313-3526 FU National Institutes of Health [NIH T32 04311-05] FX Supported by a departmental grant from the National Institutes of Health (NIH T32 04311-05) NR 27 TC 6 Z9 6 U1 1 U2 3 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 JAN PY 2013 VL 200 IS 1 BP 120 EP 126 DI 10.2214/AJR.12.8536 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 060JF UT WOS:000312772200032 PM 23255750 ER PT J AU Sainani, NI Gervais, DA Mueller, PR Arellano, RS AF Sainani, Nisha I. Gervais, Debra A. Mueller, Peter R. Arellano, Ronald S. TI Imaging After Percutaneous Radiofrequency Ablation of Hepatic Tumors: Part 1, Normal Findings SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE ablation; CT; hepatic tumors; MRI; PET/CT; radiofrequency ablation ID THERMAL ABLATION; HEPATOCELLULAR-CARCINOMA; FOLLOW-UP; CT; SPECTRUM; RECURRENCE; FREQUENCY; MRI AB OBJECTIVE. The purpose of this article is to review the spectrum of early and delayed normal cross-sectional imaging findings after percutaneous radiofrequency ablation of hepatic tumors. CONCLUSION. Knowledge of postablation imaging changes is vital not only for the interventionalist who performs the procedure but also for the diagnostician who interprets the postablation imaging. Recognition of normal postprocedural changes and differentiation from abnormal imaging findings prevent overcalling benign changes as abnormal and can thus avoid needless treatment. C1 [Sainani, Nisha I.] Brigham & Womens Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02115 USA. [Gervais, Debra A.; Mueller, Peter R.; Arellano, Ronald S.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Sainani, NI (reprint author), Brigham & Womens Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 15 Francis St, Boston, MA 02115 USA. EM nsainani@partners.org NR 22 TC 23 Z9 24 U1 0 U2 10 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 JAN PY 2013 VL 200 IS 1 BP 184 EP 193 DI 10.2214/AJR.12.8478 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 060JF UT WOS:000312772200043 PM 23255761 ER PT J AU Sainani, NI Gervais, DA Mueller, PR Arellano, RS AF Sainani, Nisha I. Gervais, Debra A. Mueller, Peter R. Arellano, Ronald S. TI Imaging After Percutaneous Radiofrequency Ablation of Hepatic Tumors: Part 2, Abnormal Findings SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE ablation; CT; hepatic tumors; MRI; PET/CT; radiofrequency ablation ID HEPATOCELLULAR-CARCINOMA; LIVER-TUMORS; FOLLOW-UP; CT; COMPLICATIONS; FREQUENCY; LESIONS; RECURRENCE; METASTASES; SECONDARY AB OBJECTIVE. The purpose of this article is to review the spectrum of early and delayed abnormal cross-sectional imaging findings after radiofrequency ablation (RFA) of hepatic tumors. CONCLUSION. Recognition of abnormal post-RFA imaging findings and differentiation of abnormal findings from normal postprocedural changes are important for diagnostic and interventional radiologists. Early identification of residual or recurrent disease and complications can facilitate timely retreatment, management, and follow-up care. C1 [Sainani, Nisha I.] Brigham & Womens Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02115 USA. [Gervais, Debra A.; Mueller, Peter R.; Arellano, Ronald S.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Sainani, NI (reprint author), Brigham & Womens Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 15 Francis St, Boston, MA 02115 USA. EM nsainani@partners.org NR 27 TC 15 Z9 19 U1 0 U2 10 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 JAN PY 2013 VL 200 IS 1 BP 194 EP 204 DI 10.2214/AJR.12.8479 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 060JF UT WOS:000312772200044 PM 23255762 ER PT J AU Hedegard, W Niell, B Specht, M Winograd, J Rafferty, E AF Hedegard, Wade Niell, Bethany Specht, Michelle Winograd, Jonathan Rafferty, Elizabeth TI Breast Reconstruction With a Deep Inferior Epigastric Perforator Flap: Imaging Appearances of the Normal Flap and Common Complications SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE breast reconstruction; deep inferior epigastric perforator flap; DIEP flap ID ABDOMINIS MYOCUTANEOUS FLAP; TUMOR RECURRENCE; FAT NECROSIS; PART 2; DIEP; TRAM; MRI AB OBJECTIVE. The purpose of this essay is to illustrate the normal imaging appearance of deep inferior epigastric perforator (DIEP) flap breast reconstruction and common postoperative complications. CONCLUSION. Familiarity with the anatomy and normal imaging appearance of a DIEP flap reconstruction will help the breast imager recognize normal postsurgical findings and common postoperative complications. C1 [Hedegard, Wade; Niell, Bethany; Specht, Michelle; Rafferty, Elizabeth] Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA. [Winograd, Jonathan] Massachusetts Gen Hosp, Wang Ambulatory Care Ctr, Dept Plast Surg, Boston, MA 02114 USA. RP Niell, B (reprint author), Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Wang Bldg Ste 240, Boston, MA 02114 USA. EM bniell@partners.org NR 15 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 JAN PY 2013 VL 200 IS 1 BP W75 EP W84 DI 10.2214/AJR.12.9270 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 060JF UT WOS:000312772200008 PM 23255774 ER PT J AU Ho, ML Moonis, G Ginat, DT Eisenberg, RL AF Ho, Mai-Lan Moonis, Gul Ginat, Daniel T. Eisenberg, Ronald L. TI Lesions of the Corpus Callosum SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE brain; corpus callosum ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; DIFFUSE AXONAL INJURY; MULTIPLE-SCLEROSIS; MR-IMAGES; STROKE; BRAIN C1 [Ho, Mai-Lan; Moonis, Gul; Eisenberg, Ronald L.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02115 USA. [Ho, Mai-Lan; Moonis, Gul; Eisenberg, Ronald L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ginat, Daniel T.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Eisenberg, RL (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, 330 Brookline Ave, Boston, MA 02115 USA. EM rleisenb@bidmc.harvard.edu NR 23 TC 5 Z9 5 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 JAN PY 2013 VL 200 IS 1 BP W1 EP W16 DI 10.2214/AJR.11.8080 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 060JF UT WOS:000312772200001 PM 23255767 ER PT J AU Isakova, T Xie, H Messinger, S Cortazar, F Scialla, JJ Guerra, G Contreras, G Roth, D Burke, GW Molnar, MZ Mucsi, I Wolf, M AF Isakova, T. Xie, H. Messinger, S. Cortazar, F. Scialla, J. J. Guerra, G. Contreras, G. Roth, D. Burke, G. W., III Molnar, M. Z. Mucsi, I. Wolf, M. TI Inhibitors of mTOR and Risks of Allograft Failure and Mortality in Kidney Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Allograft failure; kidney transplantation; mortality; mTOR inhibitors ID RENAL-TRANSPLANTATION; CALCINEURIN INHIBITORS; IMMUNOSUPPRESSIVE REGIMENS; SIROLIMUS CONVERSION; MAMMALIAN TARGET; RANDOMIZED-TRIAL; ACUTE REJECTION; RECIPIENTS; CYCLOSPORINE; RAPAMYCIN AB Data on long-term outcomes of users of inhibitors of the mammalian target of rapamycin (mTORI) are lacking in kidney transplantation. In an analysis of 139 370 US kidney transplant recipients between 1999 through 2010, we compared clinical outcomes among users of mTORIs versus calcineurin inhibitors (CNI) in their primary immunosuppresive regimen. During the first 2 years posttransplantation, primary use of mTORIs without CNIs (N = 3237) was associated with greater risks of allograft failure and death compared with a CNI-based regimen (N = 125 623); the hazard ratio (HR) of the composite outcome ranged from 3.67 (95% confidence interval [CI], 3.124.32) after discharge to 1.40 (95% CI 1.261.57) by year 2. During years 28, primary use of mTORIs without CNIs was independently associated with greater risks of death (HR 1.25; 95% CI, 1.111.41) and the composite (HR 1.17; 95%CI, 1.081.27) in fully adjusted analyses. The results were qualitatively unchanged in subgroups defined by medical history, immunological risk and clinical course during the index transplant hospitalization. In a propensity-score matched cohort, use of mTORIs was associated with significantly worse outcomes during the first 2 years and greater risks of death (HR 1.21; 95% CI, 1.051.39) and the composite (HR 1.18; 95% CI, 1.081.30) in years 28. Compared with CNI-based regimens, use of an mTORI-based regimen for primary immunosuppression in kidney transplantation was associated with inferior recipient survival. C1 [Isakova, T.; Scialla, J. J.; Guerra, G.; Contreras, G.; Roth, D.; Wolf, M.] Univ Miami, Miller Sch Med, Dept Med, Div Nephrol & Hypertens, Miami, FL 33136 USA. [Xie, H.; Messinger, S.] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. [Cortazar, F.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Burke, G. W., III] Univ Miami, Miller Sch Med, Dept Surg, Miami, FL 33136 USA. [Molnar, M. Z.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Harold Simmons Ctr Chron Dis Res & Epidemiol, Torrance, CA 90509 USA. [Molnar, M. Z.] Univ Toronto, Dept Med, Div Nephrol, Univ Hlth Network, Toronto, ON, Canada. [Molnar, M. Z.; Mucsi, I.] Semmelweis Univ, Inst Pathophysiol, H-1085 Budapest, Hungary. [Mucsi, I.] Semmelweis Univ, Inst Behav Sci, H-1085 Budapest, Hungary. [Mucsi, I.] McGill Univ, Dept Med, Div Nephrol, Ctr Hlth, Montreal, PQ, Canada. RP Wolf, M (reprint author), Univ Miami, Miller Sch Med, Dept Med, Div Nephrol & Hypertens, Miami, FL 33136 USA. EM mwolf2@med.miami.edu OI Molnar, Miklos Z/0000-0002-9665-330X FU NIH [K23DK087858, R01DK076116, R01DK081374]; Health Resources and Services Administration [234-2005-37011C] FX TI was supported by NIH grant K23DK087858. MW was supported by NIH grants R01DK076116 and R01DK081374.; This work was supported in part by Health Resources and Services Administration contract 234-2005-37011C. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 38 TC 19 Z9 21 U1 0 U2 8 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 JAN PY 2013 VL 13 IS 1 BP 100 EP 110 DI 10.1111/j.1600-6143.2012.04281.x PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA 062SD UT WOS:000312941200014 PM 23025566 ER PT J AU Shaw, AT Varghese, AM Solomon, BJ Costa, DB Novello, S Mino-Kenudson, M Awad, MM Engelman, JA Riely, GJ Monica, V Yeap, BY Scagliotti, GV AF Shaw, A. T. Varghese, A. M. Solomon, B. J. Costa, D. B. Novello, S. Mino-Kenudson, M. Awad, M. M. Engelman, J. A. Riely, G. J. Monica, V. Yeap, B. Y. Scagliotti, G. V. TI Pemetrexed-based chemotherapy in patients with advanced, ALK-positive non-small cell lung cancer SO ANNALS OF ONCOLOGY LA English DT Article DE ALK; lung cancer; pemetrexed ID EML4-ALK FUSION GENE; THYMIDYLATE SYNTHASE; 1ST-LINE TREATMENT; CLINICAL-FEATURES; OPEN-LABEL; PHASE-III; EGFR; MULTICENTER; MUTATIONS; GEFITINIB AB Anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) is highly responsive to crizotinib. To determine whether ALK-positive NSCLC is also sensitive to pemetrexed, we retrospectively evaluated progression-free survival (PFS) of ALK-positive versus ALK-negative patients who had been treated with pemetrexed-based chemotherapy for advanced NSCLC. We identified 121 patients with advanced, ALK-positive NSCLC in the USA, Australia, and Italy. For comparison, we evaluated 266 patients with advanced, ALK-negative, epidermal growth factor receptor (EGFR)-wild-type NSCLC, including 79 with KRAS mutations and 187 with wild-type KRAS (WT/WT/WT). We determined PFS on different pemetrexed regimens. Among 70 ALK-positive patients treated with a platinum/pemetrexed regimen, the median PFS (mPFS) was 7.3 months (95% confidence interval (CI) 5.5-9.5). The mPFS of 51 ALK-positive patients treated with single-agent pemetrexed or nonplatinum/pemetrexed combinations was 5.5 months (2.8-9.0). For ALK-negative patients, PFS on all pemetrexed-based regimens was similar to that of ALK-positive patients, except in the specific setting of first-line platinum/pemetrexed where the mPFS was only 4.2 and 5.4 months in KRAS and WT/WT/WT patients, respectively. However, among patients with a never/light-smoking history (0-10 pack-year smoking history) treated with first-line platinum/pemetrexed, there was no difference in PFS between ALK-positive and ALK-negative patients. PFS on pemetrexed or nonplatinum/pemetrexed combinations was similar in ALK-positive and ALK-negative patients. PFS on first-line platinum/pemetrexed may be prolonged in never/light-smoking patients regardless of ALK status. C1 [Shaw, A. T.; Awad, M. M.; Engelman, J. A.; Yeap, B. Y.] Massachusetts Gen Hosp, Ctr Canc, Dept Med Hematol Oncol, Boston, MA 02114 USA. [Varghese, A. M.; Riely, G. J.] Mem Sloan Kettering Canc Ctr, Dept Thorac Oncol, New York, NY 10021 USA. [Solomon, B. J.] Peter MacCallum Canc Ctr, Dept Med Oncol, Melbourne, Vic, Australia. [Costa, D. B.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Novello, S.; Monica, V.; Scagliotti, G. V.] Univ Turin, Dept Clin & Biol Sci, Turin, Italy. [Mino-Kenudson, M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Shaw, AT (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Med Hematol Oncol, Yawkey 7B-7508,32 Fruit St, Boston, MA 02114 USA. EM ashaw1@partners.org OI Varghese, Anna/0000-0001-5426-0885; Costa, Daniel/0000-0002-0689-395X FU V Foundation for Cancer Research; Sig Adler Lung Cancer Research Fund; National Cancer Institute [P50-CA090578]; American Cancer Society [RSG 11-186]; MGH Cancer Center; MGH Pathology Department; Pfizer; Novartis; Chugai; Ariad; Daiichi-Sankyo; AstraZeneca; Lilly Oncology; Roche; Sanofi-Aventis; Abbott Molecular; Foundation Medicine FX This study was supported in part by the V Foundation for Cancer Research (ATS and JAE), the Sig Adler Lung Cancer Research Fund (ATS), the National Cancer Institute P50-CA090578 (BYY), an American Cancer Society grant RSG 11-186 (DBC), and by internal funds from the MGH Cancer Center and MGH Pathology Department. ATS is the Charles W. and Jennifer C. Johnson MIT Koch Institute Clinical Investigator.; ATS received consulting fees from Pfizer, Novartis, Chugai, Ariad, and Daiichi-Sankyo, and received research funding from Novartis and AstraZeneca. BJS received consulting fees from Pfizer and Lilly Oncology. DBC received consulting fees from Pfizer, Roche, and AstraZeneca. JAE received consulting fees from Novartis, Ariad, Chugai, and Sanofi-Aventis, and received research funding from Novartis and AstraZeneca. GJR received consulting fees from Abbott Molecular, Ariad, Chugai, and Foundation Medicine. GVS received consulting fees from Pfizer, Lilly Oncology, Roche, and AstraZeneca. The remaining authors (AV, SN, MMK, MA, VM, and BY) have declared no conflicts of interest. NR 25 TC 47 Z9 52 U1 3 U2 12 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 JAN PY 2013 VL 24 IS 1 BP 59 EP 66 DI 10.1093/annonc/mds242 PG 8 WC Oncology SC Oncology GA 058SI UT WOS:000312653900009 PM 22887466 ER PT J AU Khimani, N Chen, YH Mauch, PM Recklitis, C Diller, L Silver, B Ng, AK AF Khimani, N. Chen, Y. -H. Mauch, P. M. Recklitis, C. Diller, L. Silver, B. Ng, A. K. TI Influence of new late effects on quality of life over time in Hodgkin lymphoma Survivors: a longitudinal survey study SO ANNALS OF ONCOLOGY LA English DT Article DE fatigue; Hodgkin lymphoma; quality of life; survivorship ID LONG-TERM SURVIVORS; DISEASE SURVIVORS; PSYCHOLOGICAL DISTRESS; FATIGUE; CANCER; CHEMOTHERAPY AB Long-term Hodgkin lymphoma (HL) survivors are known to have diminished quality of life (QoL). However, limited data are available on temporal changes in QoL and factors associated with the changes. In 2010, we conducted a follow-up questionnaire study on 273 HL survivors who participated in a 2003 questionnaire study on late effects after HL. The questionnaire items were limited to new late complications and reassessment of QoL and fatigue level, using the Short Form 36 (SF-36) and the Functional Assessment of Chronic Illness Therapy-Fatigue instruments, respectively. We compared the results from the 2003 and the 2010 questionnaires, and QoL score changes between survivors with and without new late complications during the 7-year period. There was a significant decline in the SF-36 Physical Component Summary score (median change, -1.8; P < 0.0001) over the time period. The decline was significantly greater among survivors with a new cardiac (P = 0.005) or pulmonary (P < 0.0001) complication, compared with those without any new complications. The survivors reporting new cardiac complications also experienced significantly greater worsening of fatigue scores (P = 0.004). The significant association between the development of new cardiopulmonary complications and decline in QoL and energy level of HL survivors provides further support for current efforts to reduce treatment to limit late effects. C1 [Khimani, N.; Chen, Y. -H.; Mauch, P. M.; Recklitis, C.; Diller, L.; Silver, B.; Ng, A. K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Khimani, N.; Chen, Y. -H.; Mauch, P. M.; Recklitis, C.; Diller, L.; Silver, B.; Ng, A. K.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Khimani, N.; Chen, Y. -H.; Mauch, P. M.; Recklitis, C.; Diller, L.; Silver, B.; Ng, A. K.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Ng, AK (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St,ASBI L2, Boston, MA 02115 USA. EM ang@lroc.harvard.edu FU Murphy Family Fund; American Society for Therapeutic Radiology and Oncology (ASTRO) Junior Faculty Award FX Supported by the Murphy Family Fund and the American Society for Therapeutic Radiology and Oncology (ASTRO) Junior Faculty Award. NR 27 TC 9 Z9 9 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 2013 VL 24 IS 1 BP 226 EP 230 DI 10.1093/annonc/mds243 PG 5 WC Oncology SC Oncology GA 058SI UT WOS:000312653900033 PM 22875834 ER PT J AU Nagarkatti, SS Faquin, WC Lubitz, CC Garcia, DM Barbesino, G Ross, DS Hodin, RA Daniels, GH Parangi, S AF Nagarkatti, Sushruta S. Faquin, William C. Lubitz, Carrie C. Garcia, Dieter Morales Barbesino, Giuseppe Ross, Douglas S. Hodin, Richard A. Daniels, Gilbert H. Parangi, Sareh TI Management of Thyroid Nodules with Atypical Cytology on Fine-needle Aspiration Biopsy SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID SCIENCE CONFERENCE; UNDETERMINED SIGNIFICANCE; FOLLICULAR LESION; DIAGNOSIS; STATE; MALIGNANCY; SYNOPSIS AB Fine-needle aspiration biopsy (FNAB) of the thyroid categorized as atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is a newly defined category according to the recent Bethesda guidelines. We sought to assess the characteristics and treatment of patients with an AUS/FLUS FNAB at our institution. Additionally, we evaluated the utility of the recommended 3-month timing of repeat FNAB. A retrospective study of all patients with an FNAB categorized as AUS/FLUS at an academic tertiary-care center. Clinical, cytological, and ultrasound variables were compared among management groups. Differences in patients receiving repeat FNAB before or after a 3-month interval were compared. A total of 203 patients of the 5,391 FNABs performed at our institution met the Bethesda criteria for AUS/FLUS; 62 % were sent directly to surgery, 25 % had a repeat FNAB, and 13 % were observed. Younger (p = 0.006) and male patients (p = 0.04) were more likely to go directly to surgery. Microcalcifications, irregular margins, and marked hypoechogenicity on ultrasound did not appear to influence the decision to repeat the FNAB, observe the patient, or refer the patient for surgery. Timing of repeat FNAB (< 3 months or a parts per thousand yen3 months) did not alter the diagnostic results of the second FNAB (p = 0.73). The overall rate of malignancy in patients undergoing surgery was 15.7 %. Gender and age, not ultrasound characteristics, appear to influence the decision for surgery in AUS/FLUS patients. Timing of repeat biopsy did not alter management, repeat FNAB diagnosis, or rate of malignancy in our cohort. C1 [Nagarkatti, Sushruta S.; Lubitz, Carrie C.; Garcia, Dieter Morales; Hodin, Richard A.; Parangi, Sareh] Harvard Univ, Sch Med, Dept Surg, Thyroid Canc Lab,Endocrine Surg Unit,Massachusett, Boston, MA 02115 USA. [Faquin, William C.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Barbesino, Giuseppe; Ross, Douglas S.; Daniels, Gilbert H.] Harvard Univ, Sch Med, Dept Med, Thyroid Unit,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Nagarkatti, SS (reprint author), Harvard Univ, Sch Med, Dept Surg, Thyroid Canc Lab,Endocrine Surg Unit,Massachusett, Boston, MA 02115 USA. EM sparangi@partners.org FU NCI NIH HHS [R01 CA149738] NR 16 TC 27 Z9 28 U1 0 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 2013 VL 20 IS 1 BP 60 EP 65 DI 10.1245/s10434-012-2601-2 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA 059MK UT WOS:000312709400011 PM 22941160 ER PT J AU Hong, NJL Hornicek, FJ Raskin, KA Yoon, SS Szymonifka, J Yeap, B Chen, YL DeLaney, TF Nielsen, GP Mullen, JT AF Hong, Nicole J. Look Hornicek, Francis J. Raskin, Kevin A. Yoon, Sam S. Szymonifka, Jackie Yeap, Beow Chen, Yen-Lin DeLaney, Thomas F. Nielsen, G. Petur Mullen, John T. TI Prognostic Factors and Outcomes of Patients with Myxofibrosarcoma SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID LOW-GRADE MYXOFIBROSARCOMA; SOFT-TISSUE SARCOMA; SINGLE INSTITUTION; RADIATION-THERAPY; LOCAL-CONTROL; SURGERY; SURVIVAL; MRI; EXTREMITY; PATTERN AB Myxofibrosarcomas (MFS) are a historically heterogeneous group of tumors that exhibit a propensity for local recurrence. The objectives of this study were to analyze the prognostic factors and outcomes of patients with MFS treated at a single institution. We retrospectively reviewed the records of 69 consecutive patients with pathologically confirmed MFS of the extremities or superficial trunk who underwent surgery from August 1995 to November 2010. Clinicopathologic features, treatments, and patient outcomes were reviewed. Sixty-nine patients were identified, of whom 38 were men (55 %). The median age was 62 years. Sixty-four patients (93 %) presented with primary tumors, and 5 patients (7 %) presented with locally recurrent tumors. Median tumor size was 6.0 cm, and 44 patients (64 %) had grade 3 tumors (FNCLCC [F,d,ration Nationale des Centres de Lutte Contre le Cancer] classification). Margins were microscopically positive in 14 patients (20 %) and negative in 55 patients (80 %), including close margins (< 1 mm) in 14 patients (20 %). Fifty-three patients (77 %) received radiotherapy. At a median follow-up of 41 months, there were 11 local (16 %) and 11 distant (16 %) recurrences. The local and distant 5-year recurrence-free survival rates were 72 % and 82 %, and the 5-year overall survival was 61 %. Increased age (scaled by 0.1; hazard ratio [HR] 1.80, P = 0.002) and tumor size (HR 1.12, P = 0.004) were negatively correlated with overall survival. Positive/close (< 1 mm) margin status (HR 4.34, P = 0.030) predicted worsened local recurrence-free survival. MFS exhibit a propensity for local recurrence, which is predicted by resection with positive or close margins. Aggressive surgery combined with radiotherapy may contribute to more effective local control. C1 [Hong, Nicole J. Look; Yoon, Sam S.; Mullen, John T.] Harvard Univ, Sch Med, Dept Surg, Div Surg Oncol,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Hornicek, Francis J.; Raskin, Kevin A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Oncol, Boston, MA 02115 USA. [Szymonifka, Jackie; Yeap, Beow] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biostat, Boston, MA 02115 USA. [Chen, Yen-Lin; DeLaney, Thomas F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. [Nielsen, G. Petur] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Hong, NJL (reprint author), Harvard Univ, Sch Med, Dept Surg, Div Surg Oncol,Massachusetts Gen Hosp, Boston, MA 02115 USA. EM n.lookhong@utoronto.ca; jmullen@partners.org FU Biostatistics Core of Dana-Farber/Harvard Cancer Center; NCI Cancer Center Support Grant [NIH 5 P30 CA06516] FX Supported in part by Biostatistics Core of Dana-Farber/Harvard Cancer Center, supported by NCI Cancer Center Support Grant NIH 5 P30 CA06516. NR 20 TC 14 Z9 14 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 2013 VL 20 IS 1 BP 80 EP 86 DI 10.1245/s10434-012-2572-3 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 059MK UT WOS:000312709400014 ER PT J AU Malek, JY Kwolek, CJ Conrad, MF Patel, VI Watkins, MT Lancaster, RT LaMuraglia, GM AF Malek, Junaid Y. Kwolek, Christopher J. Conrad, Mark F. Patel, Virendra I. Watkins, Michael T. Lancaster, R. Todd LaMuraglia, Glenn M. TI Presentation and Treatment Outcomes of Patients With Symptomatic Inferior Vena Cava Filters SO ANNALS OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 22nd Annual Winter Meeting of the Peripheral-Vascular-Surgery-Society CY JAN 27-29, 2012 CL Vail, CO SP Peripheral Vasc Surg Soc ID DUODENAL PERFORATION; LATE COMPLICATION; EXPERIENCE; PREDICTORS; RETRIEVAL; STRUT; PAIN AB Background: Use of inferior vena cava filters (IVCFs) has become more prevalent for the prevention of venous thromboembolism in part due to their ease of deployment and retrieval. Nonthrombotic complications of IVCFs are unusual but have been described. This study characterizes this cohort of patients and elucidates their clinical outcome. Methods: Between January 1, 2006 and December 31, 2011, six patients were identified with nonthrombotic symptoms attributed to their IVCF. Symptoms included abdominal/back pain, hypertension from renal artery compression, and hydroureter from ureteral compression. Results: The average age of the patients was 38.8 years (range 21 to 71 years) and all were female. Indication for IVCF placement included deep vein thrombosis (n = 2), deep vein thrombosis with pulmonary embolism (n = 1), and perioperative prophylaxis (n = 3). Filter types included the Ninitol Bard G2 (n = 3), Cook Celect (n = 1), Gunther Tulip (n = 1), and ALN (n = 1). The median time from IVCF placement to retrieval was 285 days (range 20 to 2091 days). At presentation, all IVCFs were tilted and had struts penetrating through the vena cava wall. Every IVCF was successfully removed: four by endovascular approach and two by open surgery. All patients had complete resolution of symptoms and there were no procedural complications. Conclusions: Symptomatic IVCFs occur in female patients, and are always associated with device strut erosion outside the inferior vena cava. Successful retrieval can be safely achieved by an endovascular or open surgical technique, resulting in symptom resolution. C1 [Malek, Junaid Y.; Kwolek, Christopher J.; Conrad, Mark F.; Patel, Virendra I.; Watkins, Michael T.; Lancaster, R. Todd; LaMuraglia, Glenn M.] Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. RP LaMuraglia, GM (reprint author), Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Wang Ambulatory Care 440,15 Parkman St, Boston, MA 02114 USA. EM glamuraglia@partners.org 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 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD JAN PY 2013 VL 27 IS 1 BP 84 EP 88 DI 10.1016/j.avsg.2012.06.005 PG 5 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 056ZH UT WOS:000312530800012 PM 23084735 ER PT J AU Breen, P Joseph, N Thompson, K Kraveka, JM Gudz, TI Li, L Rahmaniyan, M Bielawski, J Pierce, JS Van Buren, E Bhatti, G Separovic, D AF Breen, Paul Joseph, Nicholas Thompson, Kyle Kraveka, Jacqueline M. Gudz, Tatyana I. Li, Li Rahmaniyan, Mehrdad Bielawski, Jacek Pierce, Jason S. Van Buren, Eric Bhatti, Gaurav Separovic, Duska TI Dihydroceramide Desaturase Knockdown Impacts Sphingolipids and Apoptosis after Photodamage in Human Head and Neck Squamous Carcinoma Cells SO ANTICANCER RESEARCH LA English DT Article DE Apoptosis; ceramide; dihydroceramide desaturase; dihydroceramide; PDT; sphingolipids; UM-SCC-22A cells; HNSCC ID THERAPY-INDUCED APOPTOSIS; DE-NOVO SPHINGOLIPIDS; PHOTODYNAMIC THERAPY; PHOTOSENSITIZED CELLS; CERAMIDE ACCUMULATION; IN-VITRO; MEMBRANE; CANCER; DEATH AB Background: Dihydroceramide desaturase 1 (DES) is the enzyme responsible for converting dihydroceramide into ceramide in the de novo sphingolipid biosynthesis pathway. Dihydroceramide can inhibit ceramide channel formation to interfere with apoptosis. We have shown that following ceramide synthase knockdown, photodynamic therapy (PDT), a cancer treatment modality, is associated with decreased levels of ceramides and dihydroceramides in cells that are resistant to apoptosis. Aim: Here we investigated the effect of DES knockdown on the sphingolipid profile and apoptosis in human head and neck squamous carcinoma cells after PDT with the silicon phthalocyanine Pc 4. Materials and Methods: Following siRNA transfection and PDT treatment, quantitative real-time polymerase chain reaction for quantification of DES mRNA, immunoblotting for protein expression, mass spectrometry for sphingolipid analysis, spectrofluorometry for caspase 3-like (DEVDase) activity, flow cytometry for apoptosis detection, and trypan blue assay for cell viability evaluation, were performed. Results: Down-regulation of DES led to a substantial increase in levels of dihydroceramides without affecting ceramide levels. PDT-induced accumulation of individual dihydroceramides and global ceramides was increased by DES knockdown. Concomitantly, mitochondrial depolarization, DEVDase activation, late-apoptosis and cell death were attenuated by DES knockdown. Early apoptosis, however, was enhanced. Conclusion: Our findings support the following: (i) dihydroceramide reduces pro-apoptotic effects of ceramide; (ii) cells adapt to DES knockdown to become more sensitive to ceramide and early-apoptosis; (iii) DES is a potential molecular target for regulating apoptotic resistance to PDT. C1 [Breen, Paul; Joseph, Nicholas; Thompson, Kyle; Separovic, Duska] Wayne State Univ, Dept Pharmaceut Sci, Eugene Applebaum Coll Pharm & Hlth Sci, Detroit, MI 48201 USA. [Van Buren, Eric; Separovic, Duska] Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48201 USA. [Bhatti, Gaurav] Wayne State Univ, Dept Biomed Engn, Sch Engn, Detroit, MI 48201 USA. [Kraveka, Jacqueline M.; Li, Li; Rahmaniyan, Mehrdad] Med Univ S Carolina, Dept Pediat, Div Hematol Oncol, Charleston, SC 29425 USA. [Gudz, Tatyana I.] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. [Gudz, Tatyana I.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Bielawski, Jacek; Pierce, Jason S.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. RP Separovic, D (reprint author), Wayne State Univ, Dept Pharmaceut Sci, Eugene Applebaum Coll Pharm & Hlth Sci, 259 Mack Ave, Detroit, MI 48201 USA. EM dseparovic@wayne.edu FU U.S. Public Health Service, National Institutes of Health [R01 CA77475, P20-RR17677]; Rally Foundation for Childhood Cancer Research; Hyundai Hope on Wheels; Monica Kreber Golf Tournament; Chase after a Cure Foundation; Veterans Administration Merit Awards from RRD program; Veterans Administration Merit Awards from BLRD program; NCI [IPO1CA097132, P30 CA 138313]; NIH/NCRR SC COBRE [P20 RR017677]; NIH, National Center for Research Resources [C06 RR018823] FX This work was supported by: U.S. Public Health Service Grants from the National Institutes of Health R01 CA77475 (DS), and P20-RR17677 (JMK); grants from the Rally Foundation for Childhood Cancer Research, Hyundai Hope on Wheels, Monica Kreber Golf Tournament, and Chase after a Cure Foundation (JMK); the Veterans Administration Merit Awards from RR&D and BLRD programs (TIG). The MS-related work was performed by the Lipidomics Shared Resource (Medical University of South Carolina), supported by NCI grants: IPO1CA097132 and P30 CA 138313 and NIH/NCRR SC COBRE Grant P20 RR017677. Laboratory space for the Lipidomics Shared Resource was supported by the NIH, grant C06 RR018823 from the Extramural Research Facilities Program of the National Center for Research Resources. NR 27 TC 10 Z9 10 U1 0 U2 3 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JAN PY 2013 VL 33 IS 1 BP 77 EP 84 PG 8 WC Oncology SC Oncology GA 063SR UT WOS:000313021600009 PM 23267130 ER PT J AU Hao, BH Cheng, SJ Clancy, CJ Nguyen, MH AF Hao, Binghua Cheng, Shaoji Clancy, Cornelius J. Nguyen, M. Hong TI Caspofungin Kills Candida albicans by Causing both Cellular Apoptosis and Necrosis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID AMPHOTERICIN-B; DNA FRAGMENTATION; HUMAN LACTOFERRIN; OXIDATIVE STRESS; IN-SITU; DEATH; YEAST; PATHWAYS; SUSCEPTIBILITY; METABOLISM AB Caspofungin exerts candidacidal activity by inhibiting cell wall (1,3)-beta-D-glucan synthesis. We investigated the physiologic mechanisms of caspofungin-induced Candida albicans cell death. Apoptosis (programmed cell death) and necrosis were studied after C. albicans SC5314 cells were exposed to caspofungin at 0.06, 0.125, and 0.5 mu g/ml (0.5x, 1x, and 4x the MIC, respectively) for 3 h. Caspofungin at 0.125 and 0.5 mu g/ml reduced cellular viability by > 50%, as measured by colony counts and methylene blue exclusion. Apoptosis and necrosis were demonstrated by annexin V and propidium iodide staining for phosphatidylserine externalization and loss of membrane integrity, respectively. At all concentrations of caspofungin, 20 to 25% and 5 to 7% of C. albicans cells exhibited early apoptosis and late apoptosis/necrosis, respectively (P value was not significant [NS]). Necrosis, on the other hand, was significantly greater at 0.125 (43%) and 0.5 (48%) mu g/ml than at 0.06 mu g/ml (26%) (P values of 0.003 and 0.003, respectively). The induction of apoptosis at concentrations less than or equal to the MIC was corroborated by dihydrorhodamine 123 (DHR-123) and dihydroethidium (DHE) staining (reactive oxygen species production), JC-1 staining (mitochondrial membrane potential dissipation), and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and 4', 6-diamidino-2-phenylindole dihydrochloride (DAPI) staining (DNA damage and nuclear fragmentation). Moreover, electron microscopy of cells exposed to 0.125 mu g/ml of caspofungin showed hallmark apoptotic features like chromatin margination and condensation and nuclear blebs. Apoptosis was associated with metacaspase 1 activation, as demonstrated by D2R staining. Caspofungin exerts activity against C. albicans by directly killing cells (resulting in necrosis) and causing others to undergo programmed cell death (apoptosis). Apoptosis is initiated at subinhibitory concentrations, suggesting that strategies to target this process may augment the benefits of antifungal agents. C1 [Clancy, Cornelius J.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. RP Clancy, CJ (reprint author), Univ Pittsburgh, Pittsburgh, PA 15260 USA. EM CJC76@pitt.edu NR 40 TC 38 Z9 40 U1 1 U2 23 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 JAN PY 2013 VL 57 IS 1 BP 326 EP 332 DI 10.1128/AAC.01366-12 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 062XS UT WOS:000312958400042 PM 23114781 ER PT J AU Kato, IT Prates, RA Sabino, CP Fuchs, BB Tegos, GP Mylonakis, E Hamblin, MR Ribeiro, MS AF Kato, Ilka Tiemy Prates, Renato Araujo Sabino, Caetano Padial Fuchs, Beth Burgwyn Tegos, George P. Mylonakis, Eleftherios Hamblin, Michael R. Ribeiro, Martha Simoes TI Antimicrobial Photodynamic Inactivation Inhibits Candida albicans Virulence Factors and Reduces In Vivo Pathogenicity SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID GERM TUBE FORMATION; CHEMOTHERAPY PACT; METHYLENE-BLUE; TRANSCRIPTIONAL RESPONSE; SACCHAROMYCES-CEREVISIAE; FUNGAL PATHOGENS; TOLUIDINE BLUE; MOUSE MODEL; CELL-DEATH; YEAST AB The objective of this study was to evaluate whether Candida albicans exhibits altered pathogenicity characteristics following sublethal antimicrobial photodynamic inactivation (APDI) and if such alterations are maintained in the daughter cells. C. albicans was exposed to sublethal APDI by using methylene blue (MB) as a photosensitizer (0.05 mM) combined with a GaAlAs diode laser (lambda 660 nm, 75 mW/cm(2), 9 to 27 J/cm(2)). In vitro, we evaluated APDI effects on C. albicans growth, germ tube formation, sensitivity to oxidative and osmotic stress, cell wall integrity, and fluconazole susceptibility. In vivo, we evaluated C. albicans pathogenicity with a mouse model of systemic infection. Animal survival was evaluated daily. Sublethal MB-mediated APDI reduced the growth rate and the ability of C. albicans to form germ tubes compared to untreated cells (P < 0.05). Survival of mice systemically infected with C. albicans pretreated with APDI was significantly increased compared to mice infected with untreated yeast (P < 0.05). APDI increased C. albicans sensitivity to sodium dodecyl sulfate, caffeine, and hydrogen peroxide. The MIC for fluconazole for C. albicans was also reduced following sublethal MB-mediated APDI. However, none of those pathogenic parameters was altered in daughter cells of C. albicans submitted to APDI. These data suggest that APDI may inhibit virulence factors and reduce in vivo pathogenicity of C. albicans. The absence of alterations in daughter cells indicates that APDI effects are transitory. The MIC reduction for fluconazole following APDI suggests that this antifungal could be combined with APDI to treat C. albicans infections. C1 [Kato, Ilka Tiemy; Prates, Renato Araujo; Sabino, Caetano Padial; Ribeiro, Martha Simoes] IPEN CNEN SP, Ctr Lasers & Applicat, Sao Paulo, Brazil. [Prates, Renato Araujo] UNINOVE, Hlth Div, Sch Dent, Sao Paulo, Brazil. [Prates, Renato Araujo] UNINOVE, Biophoton Program, Sao Paulo, Brazil. [Fuchs, Beth Burgwyn; Mylonakis, Eleftherios] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. [Tegos, George P.] Univ New Mexico, Sch Med, Dept Pathol, Hlth Sci Ctr, Albuquerque, NM 87131 USA. [Tegos, George P.] Univ New Mexico, Hlth Sci Ctr, Ctr Mol Discovery, Albuquerque, NM 87131 USA. [Tegos, George P.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tegos, George P.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Kato, IT (reprint author), IPEN CNEN SP, Ctr Lasers & Applicat, Sao Paulo, Brazil. EM itkato@usp.br; pratesra@uninove.br RI Kato, Ilka/G-7644-2012; FotonicaUFPE, Inct/J-8388-2013; Sabino, Caetano/K-8356-2013; Prates, Renato/F-8235-2014; Ribeiro, Martha/G-3517-2012; Sabino, Caetano/D-4196-2016; OI Ribeiro, Martha/0000-0002-4203-1134; Sabino, Caetano/0000-0002-2048-2823; Hamblin, Michael/0000-0001-6431-4605 FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [2010/13313-9]; Conselho Nacional de Pesquisa e Desenvolvimento; U.S. NIH [R01AI050875]; NIH [5U54MH084690-02] FX This work was supported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (grant 2010/13313-9) and Conselho Nacional de Pesquisa e Desenvolvimento. M. R. Hamblin was supported by U.S. NIH grant R01AI050875. G. Tegos was supported by the NIH (grant 5U54MH084690-02). NR 53 TC 16 Z9 19 U1 2 U2 11 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 JAN PY 2013 VL 57 IS 1 BP 445 EP 451 DI 10.1128/AAC.01451-12 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 062XS UT WOS:000312958400057 PM 23129051 ER PT J AU Weinstein, EA Liu, L Ordonez, AA Wang, H Hooker, JM Tonge, PJ Jain, SK AF Weinstein, E. A. Liu, L. Ordonez, A. A. Wang, H. Hooker, J. M. Tonge, P. J. Jain, S. K. TI Noninvasive Determination of 2-[F-18]-Fluoroisonicotinic Acid Hydrazide Pharmacokinetics by Positron Emission Tomography in Mycobacterium tuberculosis-Infected Mice (vol 56, pg 6284, 2012) SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Correction C1 [Weinstein, E. A.] Johns Hopkins Univ, Sch Med, Dept Med, Ctr Infect & Inflammat Imaging,Ctr TB Res, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. SUNY Stony Brook, Dept Chem, Inst Chem Biol & Drug Discovery, Stony Brook, NY 11794 USA. Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Weinstein, EA (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Ctr Infect & Inflammat Imaging,Ctr TB Res, Baltimore, MD 21205 USA. NR 1 TC 0 Z9 0 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 JAN PY 2013 VL 57 IS 1 BP 678 EP 678 DI 10.1128/AAC.02274-12 PG 1 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 062XS UT WOS:000312958400101 ER PT J AU Jennette, JC Falk, RJ Bacon, PA Basu, N Cid, MC Ferrario, F Flores-Suarez, LF Gross, WL Guillevin, L Hagen, EC Hoffman, GS Jayne, DR Kallenberg, CGM Lamprecht, P Langford, CA Luqmani, RA Mahr, AD Matteson, EL Merkel, PA Ozen, S Pusey, CD Rasmussen, N Rees, AJ Scott, DGI Specks, U Stone, JH Takahashi, K Watts, RA AF Jennette, J. C. Falk, R. J. Bacon, P. A. Basu, N. Cid, M. C. Ferrario, F. Flores-Suarez, L. F. Gross, W. L. Guillevin, L. Hagen, E. C. Hoffman, G. S. Jayne, D. R. Kallenberg, C. G. M. Lamprecht, P. Langford, C. A. Luqmani, R. A. Mahr, A. D. Matteson, E. L. Merkel, P. A. Ozen, S. Pusey, C. D. Rasmussen, N. Rees, A. J. Scott, D. G. I. Specks, U. Stone, J. H. Takahashi, K. Watts, R. A. TI 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides SO ARTHRITIS AND RHEUMATISM LA English DT Article ID GIANT-CELL ARTERITIS; RHEUMATOLOGY 1990 CRITERIA; NERVOUS-SYSTEM VASCULITIS; CHURG-STRAUSS-SYNDROME; WEGENERS-GRANULOMATOSIS; POLYANGIITIS WEGENERS; ALTERNATIVE NAME; IGA NEPHROPATHY; CLASSIFICATION; MANIFESTATIONS C1 [Jennette, J. C.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. [Bacon, P. A.] Univ Birmingham, Birmingham, W Midlands, England. [Basu, N.] Univ Aberdeen, Aberdeen, Scotland. [Cid, M. C.] Univ Barcelona Hosp Clin, Barcelona, Spain. [Ferrario, F.] Univ Milan Biocca, Milan, Italy. [Flores-Suarez, L. F.] Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico. [Gross, W. L.] Klinikum Bad Bramstedt, Bad Bramstedt, Germany. [Guillevin, L.; Mahr, A. D.] Hop Cochin, AP HP, F-75674 Paris, France. [Hagen, E. C.] Meander Med Ctr, Utrecht, Netherlands. [Hoffman, G. S.; Langford, C. A.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Jayne, D. R.] Univ Cambridge, Cambridge, England. [Jayne, D. R.] Addenbrookes Hosp, Cambridge, England. [Kallenberg, C. G. M.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Lamprecht, P.] Med Univ Lubeck, D-23538 Lubeck, Germany. [Luqmani, R. A.] Univ Oxford, Oxford, England. [Luqmani, R. A.] Nuffield Orthopaed Ctr, Oxford OX3 7LD, England. [Mahr, A. D.] Univ Paris 05, Paris, France. [Matteson, E. L.; Specks, U.] Mayo Clin, Rochester, MN USA. [Merkel, P. A.] Boston Univ, Boston, MA 02215 USA. [Ozen, S.] Hacettepe Univ, Ankara, Turkey. [Pusey, C. D.] Univ London Imperial Coll Sci Technol & Med, London, England. [Rasmussen, N.] Statens Serum Inst, DK-2300 Copenhagen, Denmark. [Rees, A. J.] Med Univ Vienna, Vienna, Austria. [Scott, D. G. I.] Norfolk & Norwich Univ Hosp, Norwich, Norfolk, England. [Stone, J. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Takahashi, K.] Toho Univ, Ohashi Med Ctr, Tokyo, Japan. [Watts, R. A.] Ipswich Hosp, Ipswich, Suffolk, England. [Watts, R. A.] Univ E Anglia, Norwich NR4 7TJ, Norfolk, England. RP Jennette, JC (reprint author), Univ N Carolina, Dept Pathol & Lab Med, 308 Brinkhous Bullitt Bldg,CB 7525, Chapel Hill, NC 27599 USA. EM jcj@med.unc.edu RI Lamprecht, Peter/F-1063-2013; Gross, Wolfgang Ludwig/C-8733-2011; OI Lamprecht, Peter/0000-0001-5929-868X; Luqmani, Raashid/0000-0002-4446-5841; Cid Xutgla, Maria Cinta/0000-0002-4730-0938 FU Roche; GlaxoSmithKline; Actelion Pharma; Genentech; Sanofi-Aventis; Human Genome Sciences; Nordic Pharma; ChemoCentryx; Novartis Turkey; Swedish Orphan Biovitrum; Baxter Innovations Vienna; Proximagen FX Dr. Guillevin has received consulting fees from Roche, GlaxoSmithKline, and Actelion Pharma (less than $10,000 each). Dr. Hoffman has received consulting fees, speaking fees, and/or honoraria from Genentech and Sanofi-Aventis (less than $10,000 each). Dr. Luqmani has received consulting fees, speaking fees, and/or honoraria from Human Genome Sciences (less than $10,000) and from Nordic Pharma and ChemoCentryx (more than $10,000 each). Dr. Ozen has received consulting fees from Novartis Turkey (less than $10,000) and speaking fees from Swedish Orphan Biovitrum (less than $10,000). Dr. Rees has received consulting fees, speaking fees, and/or honoraria from Baxter Innovations Vienna, and Proximagen (less than $10,000 each). Dr. Scott has received speaking fees and honoraria for advisory committee/board service from Roche (less than $10,000). NR 22 TC 798 Z9 888 U1 2 U2 34 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD JAN PY 2013 VL 65 IS 1 BP 1 EP 11 DI 10.1002/art.37715 PG 11 WC Rheumatology SC Rheumatology GA 062RD UT WOS:000312938100001 PM 23045170 ER PT J AU White, DK Tudor-Locke, C Felson, DT Gross, KD Niu, JB Nevitt, M Lewis, CE Torner, J Neogi, T AF White, Daniel K. Tudor-Locke, Catrine Felson, David T. Gross, K. Douglas Niu, Jingbo Nevitt, Michael Lewis, Cora E. Torner, James Neogi, Tuhina TI Do radiographic disease and pain account for why people with or at high risk of knee osteoarthritis do not meet physical activity guidelines? SO ARTHRITIS AND RHEUMATISM LA English DT Article ID OLDER-ADULTS; HEALTHY-ADULTS; UNITED-STATES; WALKING SPEED; US ADULTS; ARTHRITIS; EXERCISE; ACCELEROMETER; POPULATION; TIME AB Objective Knee osteoarthritis (OA) and pain are assumed to be barriers to meeting physical activity guidelines, but this has not been formally evaluated. The purpose of this study was to determine the proportions of people with and those without knee OA and knee pain who meet recommended physical activity levels through walking. Methods We performed a cross-sectional analysis of community-dwelling adults from the Multicenter Osteoarthritis Study who had or who were at high risk of knee OA. Participants wore a StepWatch activity monitor to record steps per day for 7 days. The proportion of participants who met the recommended physical activity levels was defined as those accumulating =150 minutes per week at =100 steps per minute in bouts lasting =10 minutes. These proportions were also determined for those with and those without knee OA, as classified by radiography and by severity of knee pain. Results Of the 1,788 study participants (mean +/- SD age 67.2 +/- 7.7 years, mean +/- SD body mass index 30.7 +/- 6.0 kg/m2, 60% women), lower overall percentages of participants with radiographic knee OA and knee pain met recommended physical activity levels. However, these differences were not statistically significant between those with and those without knee OA; 7.3% and 10.1% of men (P = 0.34) and 6.3% and 7.8% of women (P = 0.51), respectively, met recommended physical activity levels. Similarly, for those with moderate/severe knee pain and those with no knee pain, 12.9% and 10.9% of men (P = 0.74) and 6.7% and 11.0% of women (P = 0.40), respectively, met recommended physical activity levels. Conclusion Disease and pain have little impact on achieving recommended physical activity levels among people with or at high risk of knee OA. C1 [White, Daniel K.] Boston Univ, Clin Epidemiol Res & Training Unit, Boston, MA 02118 USA. [Tudor-Locke, Catrine] Pennington Biomed Res Ctr, Baton Rouge, LA USA. [Gross, K. Douglas] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. [Nevitt, Michael] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Lewis, Cora E.] Univ Alabama Birmingham, Birmingham, AL USA. [Torner, James] Univ Iowa, Iowa City, IA USA. RP White, DK (reprint author), Boston Univ, Clin Epidemiol Res & Training Unit, 650 Albany St,10 Bldg,Suite 200, Boston, MA 02118 USA. EM dwtbn@bu.edu OI Felson, David/0000-0002-2668-2447; Neogi, Tuhina/0000-0002-9515-1711 FU NIH [AG-18820, AG-18832, AG-18947, AG-19069, AR-007598, AR-47885, P30-AG-031679]; NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases) [K23-AR-055127]; Rheumatology Research Foundation of the American College of Rheumatology; Arthritis Foundation; Boston Claude D. Pepper Older Americans Independence Center; Foundation for Physical Therapy FX Supported by the NIH (grants AG-18820, AG-18832, AG-18947, AG-19069, AR-007598, AR-47885, and National Institute of Arthritis and Musculoskeletal and Skin Diseases grant K23-AR-055127), the Rheumatology Research Foundation of the American College of Rheumatology (Rheumatology Investigator Award to Dr. White), the Arthritis Foundation (Arthritis Investigator Award to Dr. Neogi), the Boston Claude D. Pepper Older Americans Independence Center (funded by NIH grant P30-AG-031679), and the Foundation for Physical Therapy. NR 51 TC 21 Z9 22 U1 2 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD JAN PY 2013 VL 65 IS 1 BP 139 EP 147 DI 10.1002/art.37748 PG 9 WC Rheumatology SC Rheumatology GA 062RD UT WOS:000312938100016 PM 23124774 ER PT J AU Drouin, EE Seward, RJ Strle, K McHugh, G Katchar, K Londono, D Yao, CX Costello, CE Steere, AC AF Drouin, Elise E. Seward, Robert J. Strle, Klemen McHugh, Gail Katchar, Kianoosh Londono, Diana Yao, Chunxiang Costello, Catherine E. Steere, Allen C. TI A novel human autoantigen, endothelial cell growth factor, is a target of T and B cell responses in patients with Lyme disease SO ARTHRITIS AND RHEUMATISM LA English DT Article ID ANTIBIOTIC-REFRACTORY ARTHRITIS; CENTRAL-NERVOUS-SYSTEM; DR-BOUND PEPTIDES; SURFACE PROTEIN-A; BORRELIA-BURGDORFERI; HLA-DR; RHEUMATOID-ARTHRITIS; CEREBROSPINAL-FLUID; IMMUNE-RESPONSES; MOLECULES AB Objective Autoantigen presentation by HLADR molecules is thought to be a central component of many autoimmune diseases, but identifying disease-relevant autoantigens has been a difficult challenge. In this study we aimed to identify autoantigens in patients with antibiotic-refractory Lyme arthritis, in which infection-induced autoimmunity is thought to play an important role. Methods Using tandem mass spectrometry, naturally presented HLADR self peptides from a patient's synovium were identified, synthesized, and reacted with his peripheral blood mononuclear cells (PBMCs). Immunoreactive peptides and their source proteins were then tested for T and B cell responses using large numbers of patient cells or sera. Results Of 120 HLADRpresented self peptides identified from one patient, one peptide derived from endothelial cell growth factor (ECGF) caused his PBMCs to proliferate. T and B cell responses to ECGF occurred systemically in similar to 1030% of patients with early or late manifestations of Lyme disease, primarily in those with refractory arthritisassociated HLADR alleles, such as DRB1*0101 and 0401. Compared with patients with antibiotic-responsive arthritis, those with antibiotic-refractory arthritis had significantly higher concentrations of ECGF in synovial fluid (P < 0.0001) and more often had ECGF antibody reactivity. Among nonantibiotic-treated historical patients who developed arthritis, 26% had ECGF reactivity, which often developed before the onset of arthritis and was associated with significantly longer courses of arthritis. Conclusion T and B cell responses to ECGF occur in a subset of patients with Lyme disease, particularly in those with antibiotic-refractory arthritis, providing the first direct evidence of autoimmune T and B cell responses in this illness. C1 [Drouin, Elise E.; Seward, Robert J.; Strle, Klemen; McHugh, Gail; Katchar, Kianoosh; Londono, Diana; Steere, Allen C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Drouin, Elise E.; Seward, Robert J.; Strle, Klemen; McHugh, Gail; Katchar, Kianoosh; Londono, Diana; Steere, Allen C.] Harvard Univ, Sch Med, Boston, MA USA. [Yao, Chunxiang; Costello, Catherine E.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Drouin, EE (reprint author), Massachusetts Gen Hosp, CNY 149-8301,55 Fruit St, Boston, MA 02114 USA. EM edrouin@partners.org OI Costello, Catherine/0000-0003-1594-5122 FU NIH [AR-20358, P41-GM-104603/RR-10888, S10-RR-15942, S10-RR-20946, N01-HV-28178, N01-HV-00239]; Dana Foundation; Mathers Foundation; English, Bonter, Mitchell Foundation; Eshe Fund; Lyme/Arthritis Research Fund at Massachusetts General Hospital; Arthritis Foundation; Walter J. and Lille A. Berbecker Foundation; Lillian B. Davey Foundation; Merck; Alere FX Supported by the NIH (grants AR-20358 [to Dr. Steere], P41-GM-104603/RR-10888, S10-RR-15942, and S10-RR-20946, and contracts N01-HV-28178 and N01-HV-00239 [to Dr. Costello]); the Dana Foundation (grants to Drs. Costello and Steere); the Mathers Foundation; the English, Bonter, Mitchell Foundation; the Eshe Fund; and the Lyme/Arthritis Research Fund at Massachusetts General Hospital (grant to Dr. Steere). Dr. Strle is recipient of postdoctoral fellowships from the Arthritis Foundation and the Walter J. and Lille A. Berbecker Foundation. Dr. Katchar is recipient of a scholarship for the study of Lyme disease from the Lillian B. Davey Foundation.; Drs. Drouin, Seward, Costello, and Steere have a patent application pending for endothelial cell growth factor antibody testing. Dr. Steere has received consulting fees, speaking fees, and/or honoraria from Merck and Alere (less than $10,000 each). NR 49 TC 24 Z9 24 U1 1 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD JAN PY 2013 VL 65 IS 1 BP 186 EP 196 DI 10.1002/art.37732 PG 11 WC Rheumatology SC Rheumatology GA 062RD UT WOS:000312938100021 PM 23044924 ER PT J AU Caplan, L Davis, LA Bright, CM Kerr, GS Lazaro, DM Khan, NA Richards, JS Johnson, DS Cannon, GW Reimold, AM Mikuls, TR AF Caplan, Liron Davis, Lisa A. Bright, Christina M. Kerr, Gail S. Lazaro, Deana M. Khan, Nasim A. Richards, J. Steuart Johnson, Dannette S. Cannon, Grant W. Reimold, Andreas M. Mikuls, Ted R. TI Body mass index and the rheumatoid arthritis swollen joint count: An observational study SO ARTHRITIS CARE & RESEARCH LA English DT Article ID OBESITY; ADIPONECTIN; RESISTIN; CRITERIA; TRENDS AB Objective Obesity is a prevalent condition and a serious health concern. The relationship between obesity and rheumatoid arthritis (RA) disease activity and severity has not been adequately examined, and there are concerns that periarticular adipose tissue may reduce the utility of the joint examination. Methods We used a cross-sectional study to compare the performance of swollen joint count (SJC) in subjects with RA across body mass index (BMI) strata. Specifically, regression techniques tested for associations of SJC and 7 RA disease activity/severity measures (including high-sensitivity C-reactive protein level, radiographic changes, and Multidimensional Health Assessment Questionnaire scores) within BMI quartiles. We also evaluated the association of BMI with radiographic evidence of RA in multivariate analyses and the association of BMI with SJC. Clinical and laboratory data from 980 Veterans Affairs Rheumatoid Arthritis registry participants were analyzed using linear and logistic regression. Results Associations were evident between SJC and 6 of the 7 examined RA disease activity/severity measures. SJC predicts RA disease activity/severity in more obese subjects at least as well as in subjects with lower BMIs, and there was a trend toward better performance in individuals with higher BMIs. Subjects with higher BMIs were marginally less likely to be characterized by radiographic changes (odds ratio 0.98, P = 0.051). We found no association between BMI and SJC. Conclusion BMI does not obscure the relationship of SJC and objective disease activity measures. There is a borderline association of higher BMI and the likelihood of radiographic changes characteristic of RA after controlling for clinical characteristics. C1 [Caplan, Liron; Davis, Lisa A.; Bright, Christina M.] Denver VAMC, Denver, CO USA. [Caplan, Liron; Davis, Lisa A.; Bright, Christina M.] Univ Colorado, Sch Med, Denver, CO 80045 USA. [Kerr, Gail S.; Richards, J. Steuart] Georgetown Univ, DC VAMC, Washington, DC USA. [Kerr, Gail S.; Richards, J. Steuart] Howard Univ, Washington, DC 20059 USA. [Lazaro, Deana M.] Brooklyn VAMC, Brooklyn, NY USA. [Lazaro, Deana M.] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. [Khan, Nasim A.] Little Rock VAMC, Little Rock, AR USA. [Khan, Nasim A.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Johnson, Dannette S.] Univ Mississippi, Jackson, MS USA. [Cannon, Grant W.] George E Wahlen VAMC, Salt Lake City, UT USA. [Cannon, Grant W.] Univ Utah, Salt Lake City, UT USA. [Reimold, Andreas M.] Dallas VAMC, Dallas, TX USA. [Reimold, Andreas M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Mikuls, Ted R.] Omaha VAMC, Omaha, NE USA. [Mikuls, Ted R.] Univ Nebraska Med Ctr, Omaha, NE USA. RP Caplan, L (reprint author), Univ Colorado, Sch Med, POB 6511,B115, Denver, CO 80045 USA. EM liron.caplan@ucdenver.edu FU Veterans Affairs Health Services Research and Development grant [SHP 08-172]; Clinical Science Research and Development Merit Review; Veterans Affairs Health Services Research and Development Career Development Award [07-221]; NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases [T32-AR007534-24]; Veterans Affairs Graduate Medical Education Enhancement Award FX Supported by a Veterans Affairs Health Services Research and Development grant (SHP 08-172) and a Clinical Science Research and Development Merit Review. Dr. Caplan's work was supported by a Veterans Affairs Health Services Research and Development Career Development Award (07-221). Dr. Davis's work was supported by the NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant T32-AR007534-24) and a Veterans Affairs Graduate Medical Education Enhancement Award. NR 17 TC 9 Z9 9 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD JAN PY 2013 VL 65 IS 1 BP 101 EP 106 DI 10.1002/acr.21734 PG 6 WC Rheumatology SC Rheumatology GA 062RR UT WOS:000312939700014 PM 22623288 ER PT J AU Bacci, S Prudente, S Copetti, M Spoto, B Rizza, S Baratta, R Di Pietro, N Morini, E Di Paola, R Testa, A Mallamaci, F Tripepi, G Zhang, YY Mercuri, L Di Silvestre, S Lauro, R Malatino, L Consoli, A Pellegrini, F Pandolfi, A Frittitta, L Zoccali, C Federici, M Doria, A Trischitta, V AF Bacci, Simonetta Prudente, Sabrina Copetti, Massimiliano Spoto, Belinda Rizza, Stefano Baratta, Roberto Di Pietro, Natalia Morini, Eleonora Di Paola, Rosa Testa, Alessandra Mallamaci, Francesca Tripepi, Giovanni Zhang, Yuan-Yuan Mercuri, Luana Di Silvestre, Sara Lauro, Renato Malatino, Lorenzo Consoli, Agostino Pellegrini, Fabio Pandolfi, Assunta Frittitta, Lucia Zoccali, Carmine Federici, Massimo Doria, Alessandro Trischitta, Vincenzo TI Joint effect of insulin signaling genes on cardiovascular events and on whole body and endothelial insulin resistance SO ATHEROSCLEROSIS LA English DT Article DE Genetic susceptibility; Nonsynonymous polymorphism; Insulin sensitivity; Insulin dependent endothelial function ID CORONARY-ARTERY-DISEASE; ENPP1 K121Q POLYMORPHISM; RECEPTOR SUBSTRATE-1; VARIANT; ATHEROSCLEROSIS; SUSCEPTIBILITY; OBESITY; CELLS; RISK; ASSOCIATION AB Objective: Insulin resistance (IR) and cardiovascular disease (CVD) share a common soil. We investigated the combined role of single nucleotide polymorphisms (SNPs) affecting insulin signaling (ENPP1 K121Q, rs1044498; IRS1 G972R, rs1801278; TRIB3 Q84R, rs2295490) on CVD, age at myocardial infarction (MI), in vivo insulin sensitivity and in vitro insulin-stimulated nitric oxide synthase (NOS) activity. Design and setting: 1. We first studied, incident cardiovascular events (a composite endpoint comprising myocardial infarction-MI, stroke and cardiovascular death) in 733 patients (2186 person-years, 175 events). 2. In a replication attempt, age at MI was tested in 331 individuals. 3. OGTT-derived insulin sensitivity index (ISI) was assessed in 829 individuals with fasting glucose <126 mg/dl. 4. NOS activity was measured in 40 strains of human vein endothelial cells (HUVECs). Results: 1. Risk variants jointly predicted cardiovascular events (HR = 1.181; p = 0.0009) and, when added to clinical risk factors, significantly improved survival C-statistics; they also allowed a significantly correct reclassification (by net reclassification index) in the whole sample (135/733 individuals) and, even more, in obese patients (116/204 individuals). 2. Risk variants were jointly associated with age at MI (p = 0.006). 3. A significant association was also observed with ISI (p = 0.02). 4. Finally, risk variants were jointly associated with insulin-stimulated NOS activity in HUVECs (p = 0.009). Conclusions: Insulin signaling genes variants jointly affect cardiovascular disease, very likely by promoting whole body and endothelium-specific insulin resistance. Further studies are needed to address whether their genotyping help identify very high-risk patients who need specific and/or more aggressive preventive strategies. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Bacci, Simonetta] IRCCS Casa Sollievo Sofferenza, Clin Unit Endocrinol, San Giovanni Rotondo, Italy. [Prudente, Sabrina; Mercuri, Luana; Trischitta, Vincenzo] IRCCS Casa Sollievo Sofferenza Mendel Lab, San Giovanni Rotondo, Italy. [Copetti, Massimiliano; Pellegrini, Fabio] IRCCS Casa Sollievo Sofferenza, Unit Biostat, San Giovanni Rotondo, Italy. [Spoto, Belinda; Testa, Alessandra; Mallamaci, Francesca; Tripepi, Giovanni; Zoccali, Carmine] CNR IBIM, Res Unit Clin Epidemiol & Physiopathol Renal Dis, Reggio Di Calabria, Italy. [Rizza, Stefano; Lauro, Renato; Federici, Massimo] Univ Roma Tor Vergata, Dept Internal Med, Rome, Italy. [Baratta, Roberto; Frittitta, Lucia] Univ Catania, Sch Med, Garibaldi Hosp, Dept Clin & Mol Biomed,Unit Internal Med, Catania, Italy. [Di Pietro, Natalia; Di Silvestre, Sara; Pandolfi, Assunta] Univ G DAnnunzio, Dept Biomed Sci, Aging Res Ctr, G dAnnunzio Univ Fdn,CeSI, Chieti, Italy. [Morini, Eleonora; Trischitta, Vincenzo] Univ Roma La Sapienza, Dept Expt Med, Rome, Italy. [Di Paola, Rosa; Trischitta, Vincenzo] IRCCS Casa Sollievo Sofferenza, Res Unit Diabet & Endocrine Dis, San Giovanni, Rotondo, Italy. [Zhang, Yuan-Yuan; Doria, Alessandro] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Malatino, Lorenzo] Univ Catania, Dept Med, Catania, Italy. [Consoli, Agostino] Univ G DAnnunzio, Dept Med & Aging Sci, Aging Res Ctr, G dAnnunzio Univ Fdn,CeSI, Chieti, Italy. [Pellegrini, Fabio] Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Lab Clin Epidemiol Diabet & Chron Dis, I-66030 Santa Maria Imbaro, Italy. RP Trischitta, V (reprint author), Ist CSS Mendel, Viale Regina Margherita 261, I-00198 Rome, Italy. EM vincenzo.trischitta@uniroma1.it RI Di Paola, Rosa/G-7813-2011; Prudente, Sabrina/H-2886-2016; Trischitta, Vincenzo/K-1487-2016; Di Pietro, Natalia/K-1604-2016; Copetti, Massimiliano/K-3186-2016; Federici, Massimo/G-9940-2012; pandolfi, assunta/K-4595-2016; OI Di Paola, Rosa/0000-0001-5837-9111; Prudente, Sabrina/0000-0001-9220-8981; Trischitta, Vincenzo/0000-0003-1174-127X; Di Pietro, Natalia/0000-0001-9720-2116; Copetti, Massimiliano/0000-0002-7960-5947; Federici, Massimo/0000-0003-4989-5194; pandolfi, assunta/0000-0003-4135-7631; TESTA, ALESSANDRA/0000-0002-0529-6571; Zoccali, Carmine/0000-0002-6616-1996 FU Italian Ministry of Health; Fondazione Roma; EFSD; SYSKID; European union; Regione Calabria; NIH [R01 HL073168, DK36836] FX This study was partly supported by the Italian Ministry of Health ("Ricerca Corrente 2011 and 2012" to S. Prudente, V. Trischitta and F. Pellegrini), by the "5x1000" voluntary contribution (to S. Prudente, V. Trischitta and F. Pellegrini), by the Fondazione Roma ("Sostegno alla ricerca scientifica biomedica 2008" to V. T), by EFSD Clinical Grant 2008 (to M. Federici), by SYSKID (a project funded by the European union - FP7 - and Regione Calabria, to C. Zoccali), and by the NIH grants R01 HL073168 (to A. Doria) and DK36836 (to the Genetics Core of the Diabetes & Endocrinology Research Center at the Joslin Diabetes Center). NR 33 TC 8 Z9 8 U1 1 U2 16 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JAN PY 2013 VL 226 IS 1 BP 140 EP 145 DI 10.1016/j.atherosclerosis.2012.10.035 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 060WA UT WOS:000312807700023 PM 23107043 ER PT J AU Ioannou, GN Boyko, EJ AF Ioannou, George N. Boyko, Edward J. TI Effects of menopause and hormone replacement therapy on the associations of hyperuricemia with mortality SO ATHEROSCLEROSIS LA English DT Article DE Serum uric acid; Mortality; Cardiovascular mortality; Cohort study; Population-based ID SERUM URIC-ACID; CORONARY-HEART-DISEASE; NUTRITION EXAMINATION SURVEY; GLOMERULAR-FILTRATION-RATE; 3RD NATIONAL-HEALTH; MIDDLE-AGED MEN; CARDIOVASCULAR MORTALITY; INDEPENDENT PREDICTOR; POSTMENOPAUSAL WOMEN; ALL-CAUSE AB Objective: Serum uric acid (SUA) levels have been associated with cardiovascular and all-cause mortality. It remains unclear whether these associations differ by gender, menopausal status and hormone replacement therapy (HRT) and whether they persist after adjustment for known cardiovascular risk factors. Methods: We determined the associations between fasting SUA level and death certificate-based mortality among 5856 participants of the third US National Health and Nutrition Examination Survey aged >= 20 years recruited between 1988 and 1994 and followed for mortality until December 2006 (mean follow-up: 13.5 years; maximum follow-up: 18 years). Cox proportional hazards regression analysis was used to adjust for demographic characteristics, cardiovascular risk factors and other variables potentially associated with SUA levels. Results: Among women, SUA level was associated with all-cause and cardiovascular mortality (adjusted hazard ratio [AHR] 1.17, 95% CI 1.03-1.32 and AHR 1.23 (1.01-1.51) respectively per unit increase in SUA. These associations persisted among postmenopausal but not premenopausal women. Furthermore, among postmenopausal women, significant associations were identified between SUA and all-cause (AHR 1.30 [1.11-1.51]) or cardiovascular (AHR 1.61 [1.33-1.94]) mortality only among women not taking HRT, but not among women on HRT. We did not identify associations between SUA levels and all-cause or cardiovascular mortality in men, either under or over 51 years of age, in unadjusted or adjusted analyses. Conclusions: SUA level predicts cardiovascular and all-cause mortality independently of major predictors and risk factors in postmenopausal women not taking HRT but not in premenopausal women, postmenopausal women on HRT, or men. Published by Elsevier Ireland Ltd. C1 [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Gastroenterol, Dept Med, Div Gastroenterol, Seattle, WA 98108 USA. [Ioannou, George N.; Boyko, Edward J.] Univ Washington, Seattle, WA 98195 USA. [Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Gastroenterol, Dept Med, Div Gastroenterol, S-111 Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu FU Veterans Affairs Research Enhancement Award Program; VA Puget Sound Health Care System FX There are no relevant financial disclosures or conflicts of interest. Dr. Ioannou is supported by the Veterans Affairs Research Enhancement Award Program. VA Puget Sound Health Care System provided support for Dr. Boyko's involvement in this research. NR 31 TC 7 Z9 12 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JAN PY 2013 VL 226 IS 1 BP 220 EP 227 DI 10.1016/j.atherosclerosis.2012.10.044 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 060WA UT WOS:000312807700038 PM 23141471 ER PT J AU Nierenberg, AA Kansky, C Brennan, BP Shelton, RC Perlis, R Iosifescu, DV AF Nierenberg, Andrew A. Kansky, Christine Brennan, Brian P. Shelton, Richard C. Perlis, Roy Iosifescu, Dan V. TI Mitochondrial modulators for bipolar disorder: A pathophysiologically informed paradigm for new drug development SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Review DE Bipolar disorder; mitochondria; modulators ID ACETYL-L-CARNITINE; ALPHA-LIPOIC ACID; PLACEBO-CONTROLLED TRIAL; MAGNETIC-RESONANCE-SPECTROSCOPY; RANDOMIZED DOUBLE-BLIND; SYMPTOMATIC DIABETIC POLYNEUROPATHY; CONTROLLED PILOT TRIAL; ANTIRETROVIRAL TOXIC NEUROPATHY; SEROTONIN REUPTAKE INHIBITORS; AMYOTROPHIC-LATERAL-SCLEROSIS AB Objectives: Bipolar patients frequently relapse within 12 months of their previous mood episode, even in the context of adequate treatment, suggesting that better continuation and maintenance treatments are needed. Based on recent research of the pathophysiology of bipolar disorder, we review the evidence for mitochondrial dysregulation and selected mitochondrial modulators (MM) as potential treatments. Methods: We reviewed the literature about mitochondrial dysfunction and potential MMs worthy of study that could improve the course of bipolar disorder, reduce subsyndromal symptoms, and prevent subsequent mood episodes. Results: MM treatment targets mitochondrial dysfunction, oxidative stress, altered brain energy metabolism and the dysregulation of multiple mitochondrial genes in patients with bipolar disorder. Several tolerable and readily available candidates include N-acetyl-cysteine (NAC), acetyl-L-carnitine (ALCAR), S-adenosylmethionine (SAMe), coenzyme Q(10) (CoQ10), alpha-lipoic acid (ALA), creatine monohydrate (CM), and melatonin. The specific metabolic pathways by which these MMs may improve the symptoms of bipolar disorder are discussed and combinations of selected MMs could be of interest as well. Conclusions: Convergent data implicate mitochondrial dysfunction as an important component of the pathophysiology of bipolar disorder. Clinical trials of individual MMs as well as combinations are warranted. C1 [Nierenberg, Andrew A.; Kansky, Christine; Brennan, Brian P.; Shelton, Richard C.; Perlis, Roy; Iosifescu, Dan V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Suite 580,50 Staniford St, Boston, MA 02114 USA. EM anierenberg@partners.org NR 207 TC 25 Z9 27 U1 0 U2 19 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD JAN PY 2013 VL 47 IS 1 BP 26 EP 42 DI 10.1177/0004867412449303 PG 17 WC Psychiatry SC Psychiatry GA 064FD UT WOS:000313056700008 PM 22711881 ER PT J AU Thomes, PG Ehlers, RA Trambly, CS Clemens, DL Fox, HS Tuma, DJ Donohue, TM AF Thomes, Paul G. Ehlers, Rebecca A. Trambly, Casey S. Clemens, Dahn L. Fox, Howard S. Tuma, Dean J. Donohue, Terrence M., Jr. TI Multilevel regulation of autophagosome content by ethanol oxidation in HepG2 cells SO AUTOPHAGY LA English DT Article DE acetaldehyde; autophagy; lysosome; oxidant stress; cytochrome P450 2E1; alcohol dehydrogenase ID PROTEIN HYPERACETYLATION; HEPATIC LYSOSOMES; LIVER-INJURY; RAT-LIVER; ACETALDEHYDE; BINDING; METABOLISM; ADDUCTS; ALTERS AB Acute and chronic ethanol administration increase autophagic vacuole (i.e., autophagosome; AV) content in liver cells. This enhancement depends on ethanol oxidation. Here, we used parental (nonmetabolizing) and recombinant (ethanol-metabolizing) Hep G2 cells to identify the ethanol metabolite that causes AV enhancement by quantifying AVs or their marker protein, microtubule-associated protein 1 light chain 3-II (LC3-II). The ethanol-elicited rise in LC3-II was dependent on ethanol dose, was seen only in cells that expressed alcohol dehydrogenase (ADH) and was augmented in cells that coexpressed cytochrome CYP2E1 (P450 2E1). Furthermore, the rise in LC3-II was inversely related to a decline in proteasome activity. AV flux measurements and colocalization of AVs with lysosomes or their marker protein Lysosomal-Associated Membrane Protein 1 (LAMP1) in ethanol-metabolizing VL-17A cells (ADH(+)/CYP2E1(+)) revealed that ethanol exposure not only enhanced LC3-II synthesis but also decreased its degradation. Ethanol-induced accumulation of LC3-II in these cells was similar to that induced by the microtubule inhibitor, nocodazole. After we treated cells with either 4-methylpyrazole to block ethanol oxidation or GSH-EE to scavenge reactive species, there was no enhancement of LC3-II by ethanol. Furthermore, regardless of their ethanol-metabolizing capacity, direct exposure of cells to acetaldehyde enhanced LC3-II content. We conclude that both ADH-generated acetaldehyde and CYP2E1-generated primary and secondary oxidants caused LC3-II accumulation, which rose not only from enhanced AV biogenesis, but also from decreased LC3 degradation by the proteasome and by lysosomes. C1 [Thomes, Paul G.; Ehlers, Rebecca A.; Trambly, Casey S.; Clemens, Dahn L.; Tuma, Dean J.; Donohue, Terrence M., Jr.] US Dept Vet Affairs, Liver Study Unit, VA Nebraska Western Iowa Hlth Care Syst NWIHCS, Omaha, NE USA. [Thomes, Paul G.; Ehlers, Rebecca A.; Trambly, Casey S.; Clemens, Dahn L.; Tuma, Dean J.; Donohue, Terrence M., Jr.] Univ Nebraska Med Ctr, Dept Internal Med, Coll Med, Omaha, NE USA. [Tuma, Dean J.; Donohue, Terrence M., Jr.] Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Coll Med, Omaha, NE USA. [Clemens, Dahn L.; Donohue, Terrence M., Jr.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Coll Med, Omaha, NE USA. [Fox, Howard S.] Univ Nebraska Med Ctr, Dept Pharmacol & Expt Neurosci, Coll Med, Omaha, NE USA. [Donohue, Terrence M., Jr.] Univ Nebraska Med Ctr, Ctr Environm Toxicol, Coll Publ Hlth, Omaha, NE USA. RP Thomes, PG (reprint author), US Dept Vet Affairs, Liver Study Unit, VA Nebraska Western Iowa Hlth Care Syst NWIHCS, Omaha, NE USA. EM pthomes@unmc.edu OI Fox, Howard/0000-0003-2032-374X FU Section of Gastroenterology and Hepatology, Department of Internal Medicine; University of Nebraska Medical Center FX Resources, Facilities and Grant Support: Financial support for this project was provided by institutional funds from the Section of Gastroenterology and Hepatology, Department of Internal Medicine, and a Dean's Reviewed Research Grant from the University of Nebraska Medical Center. The data presented are results of work supported with resources and use of facilities at the Nebraska-Western Iowa Health Care System of the Department of Veterans Affairs Veterans Health Administration, Office of Research and Development. NR 37 TC 24 Z9 24 U1 1 U2 11 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 EI 1554-8635 J9 AUTOPHAGY JI Autophagy PD JAN PY 2013 VL 9 IS 1 BP 63 EP 73 DI 10.4161/auto.22490 PG 11 WC Cell Biology SC Cell Biology GA 064LY UT WOS:000313077900005 PM 23090141 ER PT J AU Huang, HL Tata, S Prill, RJ AF Huang, Hailiang Tata, Sandeep Prill, Robert J. TI BlueSNP: R package for highly scalable genome-wide association studies using Hadoop clusters SO BIOINFORMATICS LA English DT Article AB Computational workloads for genome-wide association studies (GWAS) are growing in scale and complexity outpacing the capabilities of single-threaded software designed for personal computers. The BlueSNP R package implements GWAS statistical tests in the R programming language and executes the calculations across computer clusters configured with Apache Hadoop, a de facto standard framework for distributed data processing using the MapReduce formalism. BlueSNP makes computationally intensive analyses, such as estimating empirical p-values via data permutation, and searching for expression quantitative trait loci over thousands of genes, feasible for large genotype-phenotype datasets. C1 [Huang, Hailiang; Prill, Robert J.] IBM Almaden Res Ctr, Healthcare Informat, San Jose, CA 95120 USA. [Huang, Hailiang] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Tata, Sandeep] IBM Almaden Res Ctr, Informat Management, San Jose, CA 95120 USA. RP Prill, RJ (reprint author), IBM Almaden Res Ctr, Healthcare Informat, San Jose, CA 95120 USA. EM rjprill@us.ibm.com OI Huang, Hailiang/0000-0003-1461-5762 FU IBM Research FX H.H., S.T. and R.J.P. funded by IBM Research. NR 6 TC 10 Z9 11 U1 1 U2 31 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 EI 1460-2059 J9 BIOINFORMATICS JI Bioinformatics PD JAN PY 2013 VL 29 IS 1 BP 135 EP 136 DI 10.1093/bioinformatics/bts647 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 058SP UT WOS:000312654600024 PM 23202745 ER PT J AU Singer, SJ Vogus, TJ AF Singer, Sara J. Vogus, Timothy J. TI Safety climate research: taking stock and looking forward SO BMJ QUALITY & SAFETY LA English DT Editorial Material ID HEALTH-CARE ORGANIZATIONS; PATIENT SAFETY; QUALITY IMPROVEMENT; HOSPITALS; ATTITUDES; BEHAVIOR; CULTURE; CONTEXT; TEAMWORK; OUTCOMES C1 [Singer, Sara J.] Harvard Univ, Sch Publ Hlth, Dept Healthcare Policy & Management, Boston, MA 02115 USA. [Singer, Sara J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mongan Inst Hlth Policy,Dept Med, Boston, MA 02115 USA. [Vogus, Timothy J.] Vanderbilt Owen Grad Sch Management, Nashville, TN 37203 USA. RP Singer, SJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Healthcare Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. EM ssinger@hsph.harvard.edu RI Vogus, Tim/N-3820-2016 NR 48 TC 18 Z9 19 U1 3 U2 22 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 JAN PY 2013 VL 22 IS 1 BP 1 EP 4 DI 10.1136/bmjqs-2012-001572 PG 4 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 062ES UT WOS:000312902600001 PM 23112287 ER PT J AU Franklin, TR Wang, Z Shin, J Jagannathan, K Suh, JJ Detre, JA O'Brien, CP Childress, AR AF Franklin, Teresa R. Wang, Ze Shin, Joshua Jagannathan, Kanchana Suh, Jesse J. Detre, John A. O'Brien, Charles P. Childress, Anna Rose TI A VBM study demonstrating 'apparent' effects of a single dose of medication on T1-weighted MRIs SO BRAIN STRUCTURE & FUNCTION LA English DT Article DE Voxel-based morphometry; T1-weighted structural scan; Perfusion fMRI; Cerebral blood flow; Gray matter; Neurogenesis ID DENTATE GYRUS; HIPPOCAMPAL VOLUME; LIMBIC ACTIVATION; PERFUSION FMRI; LITHIUM; BRAIN; PROLIFERATION; RAT; NEUROGENESIS; WATER AB Voxel-based morphometry (VBM) studies have interpreted longitudinal medication- or behaviorally induced changes observed on T1-weighted magnetic resonance images (MRIs) as changes in neuronal structure. Although neurogenesis or atrophy certainly occurs, the use of T1-weighted scans to identify change in brain structure in vivo in humans has vulnerability: the T1 relaxation time for arterial blood and gray matter are not clearly distinguishable and therefore, apparent reported structural findings might be at least partially related to changes in blood flow or other physiological signals. To examine the hypothesis that apparent structural modifications may reflect changes introduced by additional mechanisms irrespective of potential neuronal growth/atrophy, we acquired a high-resolution T1-weighted structural scan and a 5-min perfusion fMRI scan (a measurement of blood flow), before and after administration of an acute pharmacological manipulation. In a within-subject design, 15 subjects were either un-medicated or were administered a 20 mg dose of baclofen (an FDA-approved anti-spastic) approximately 110 min before acquiring a T1-weighted scan and a pseudo continuous arterial spin labeled perfusion fMRI scan. Using diffeomorphic anatomical registration through exponentiated lie algebra within SPM7, we observed macroscopic, and therefore implausible, baclofen-induced decreases in VBM 'gray matter' signal in the dorsal rostral anterior cingulate (family wise error corrected at p < 0.04, T = 6.54, extent: 1,460 voxels) that overlapped with changes in blood flow. Given that gray matter reductions are unlikely following a single dose of medication these findings suggest that changes in blood flow are masquerading as reductions in gray matter on the T1-weighted scan irrespective of the temporal interval between baseline measures and longitudinal manipulations. These results underscore the crucial and immediate need to develop in vivo neuroimaging biomarkers for humans that can uniquely capture changes in neuronal structure dissociable from those related to blood flow or other physiological signals. C1 [Franklin, Teresa R.; Wang, Ze; Shin, Joshua; Jagannathan, Kanchana; Suh, Jesse J.; O'Brien, Charles P.; Childress, Anna Rose] Univ Penn, Dept Psychiat, Ctr Studies Addict, Sch Med, Philadelphia, PA 19104 USA. [Suh, Jesse J.; O'Brien, Charles P.; Childress, Anna Rose] Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Detre, John A.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Detre, John A.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. RP Franklin, TR (reprint author), Univ Penn, Dept Psychiat, Ctr Studies Addict, Sch Med, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM franklin_t@mail.trc.upenn.edu RI Wang, Ze/A-1043-2007 FU NIH [5-P60-DA-005186-18, 1R21DA025882-01A1, MH080729] FX The work was supported by NIH Grants 5-P60-DA-005186-18, 1R21DA025882-01A1, MH080729. The authors wish to acknowledge the nursing staff and Dr. Marina Goldman at the University of Pennsylvania Center for the Studies of Addiction, for conducting physical evaluations and medication monitoring; our clinicians Anita Hole PhD, and Kathleen Marquez, M.S. for conducting psychological evaluations; the MRI technicians at the Hospital of the University of Pennsylvania for conducting the scanning sessions and Daniel Willard B.A, and Robert Fabiansky, B.S. for assisting in conducting scanning sessions. NR 39 TC 18 Z9 18 U1 2 U2 20 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2653 J9 BRAIN STRUCT FUNCT JI Brain Struct. Funct. PD JAN PY 2013 VL 218 IS 1 BP 97 EP 104 DI 10.1007/s00429-012-0385-6 PG 8 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA 063SB UT WOS:000313019200008 PM 22302433 ER PT J AU Dusetzina, SB Alexander, GC Freedman, RA Huskamp, HA Keating, NL AF Dusetzina, Stacie B. Alexander, G. Caleb Freedman, Rachel A. Huskamp, Haiden A. Keating, Nancy L. TI Trends in co-prescribing of antidepressants and tamoxifen among women with breast cancer, 2004-2010 SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Tamoxifen; CYP2D6; Drug interaction; FDA advisories; Drug utilization ID RE CYP2D6 GENOTYPE; GROUP 1-98 TRIAL; ADJUVANT ENDOCRINE THERAPY; POSTMENOPAUSAL WOMEN; AMERICAN-SOCIETY; UGT2B7 GENOTYPE; HOT FLASHES; METABOLISM; DEPRESSION; RECURRENCE AB Nearly a decade ago, researchers identified a potential interaction between tamoxifen and strong CYP2D6 inhibitors, including several frequently used antidepressants. Based on evidence available at that time, a United States Food and Drug Administration advisory committee recommended tamoxifen's label be changed in October 2006, noting that postmenopausal women with estrogen receptor-positive breast cancer who are poor CYP2D6 metabolizers by genotype or drug interactions may be at increased risk of cancer recurrence. The impact of accumulating drug risk information on antidepressant use is unknown. We conducted a retrospective, longitudinal cohort study of 13,205 women aged 50-95 with breast cancer initiating tamoxifen between July 2004 and December 2009. We evaluated trends in strong, moderate, and weak CYP2D6-inhibitor antidepressants and tamoxifen co-prescribing and factors associated with ongoing strong inhibitor use. A propensity score matched control group (aromatase inhibitor initiators) was used to estimate changes in co-prescribing, accounting for secular trends. In each month, approximately 24 % of tamoxifen and aromatase inhibitor users were prescribed antidepressants. Among women using tamoxifen and antidepressants, 34 % used strong inhibitors between 2004 and 2006 versus 15 % in 2010. Strong inhibitor use decreased more among tamoxifen users than aromatase inhibitor users (difference-in-differences [DD] -0.09; 95 % confidence interval [CI] -0.15, -0.03). Weak inhibitor use increased among tamoxifen users from 32 % between 2004 and 2006 to 52 % in 2010, more rapidly than among aromatase inhibitor users (DD 0.15; CI 0.08, 0.23). The factor most strongly associated with strong inhibitor and tamoxifen co-prescribing after 2006 was prior strong inhibitor use (RR 4.73; CI 3.62-6.18). In conclusion, there were substantial declines in strong CYP2D6-inhibitor use among tamoxifen users following dissemination of information suggesting a potential for increased risk with co-prescribing. Whether patients and providers will continue to avoid strong inhibitor antidepressants is yet to be seen, but clinicians appear to be responsive to drug interaction risk information in this setting. C1 [Dusetzina, Stacie B.] Univ N Carolina, Div Gen Med & Clin Epidemiol, Chapel Hill, NC 27599 USA. [Dusetzina, Stacie B.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, Chapel Hill, NC 27599 USA. [Alexander, G. Caleb] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Alexander, G. Caleb] Johns Hopkins Univ, Sch Med, Dept Gen Internal Med, Baltimore, MD USA. [Freedman, Rachel A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Huskamp, Haiden A.; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. RP Dusetzina, SB (reprint author), Univ N Carolina, Div Gen Med & Clin Epidemiol, 5034 Old Clin Bldg,CB 7110, Chapel Hill, NC 27599 USA. EM Dusetzina@unc.edu FU Agency for Healthcare Research and Quality [RO1 HS0189960]; Ruth L. Kirschstein-National Research Service Award Post-Doctoral Traineeship; NIMH; Harvard Medical School, Department of Health Care Policy [T32MH019733-17]; Susan G. Komen for the Cure Foundation FX This study was supported by the Agency for Healthcare Research and Quality (RO1 HS0189960). The funding sources had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; and preparation, review, or approval of the manuscript for publication. Dr. Dusetzina currently receives funding through a Ruth L. Kirschstein-National Research Service Award Post-Doctoral Traineeship sponsored by NIMH and Harvard Medical School, Department of Health Care Policy, Grant No. T32MH019733-17. Dr. Freedman's effort was supported by the Susan G. Komen for the Cure Foundation. Dr. Keating's effort was supported by the Susan G. Komen for the Cure Foundation. Dr. Alexander has served as an ad hoc member of the FDA Drug Safety and Risk Management (DSaRM) Advisory Committee and is a consultant for IMS Health. Dr. Huskamp serves as an uncompensated steering committee member of the IMS Health Services Research Network. NR 43 TC 15 Z9 15 U1 4 U2 33 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 JAN PY 2013 VL 137 IS 1 BP 285 EP 296 DI 10.1007/s10549-012-2330-z PG 12 WC Oncology SC Oncology GA 059MV UT WOS:000312710500026 PM 23149465 ER PT J AU Mazzola, E Cheng, SC Parmigiani, G AF Mazzola, Emanuele Cheng, Su-Chun Parmigiani, Giovanni TI The penetrance of ductal carcinoma in situ among BRCA1 and BRCA2 mutation carriers SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Ductal carcinoma in situ; Penetrance function; BRCA1; BRCA2; Mutation carrier; Age-specific risk; Lifetime risk ID BREAST-CANCER; OVARIAN-CANCER; RISK; SUSCEPTIBILITY; GENES; MODEL AB Ductal carcinoma in situ (DCIS) is a precancerous lesion of the female breast and is strongly suspected to be a precursor of invasive breast cancer (IBC). Our goal is the estimation of the age-specific and lifetime penetrances of DCIS among carriers of either a BRCA1 or BRCA2 deleterious mutation. We jointly re-analyze the SEER9 database and a previous study by Claus et al. (JAMA 293:964-969, 2005). Estimation is performed via Bayes theorem after the evaluation of the ratio of age-specific DCIS incidences, and extrapolation to the general population of the study-specific penetrance obtained from Claus et al. From the SEER9 database, we estimate the lifetime risk of DCIS to be 0.98 %, in contrast to value of 12.5 % usually reported for IBC. By extending the result in Claus et al. to the general population, we obtain a lifetime risk for carriers of a deleterious mutation of either BRCA1 or BRCA2 of 6.21 % (95 % CI 6.09-6.33 %). The increase in lifetime risk of DCIS for a BRCA mutation carrier compared to a non-carrier is therefore about six-fold. Our quantification is directly relevant to the identification and genetic counseling of BRCA mutation carriers, and emphasizes the potential importance of including information on diagnoses of DCIS in counseling of individuals who are at familial risk for breast cancer. All these factors can contribute to a more specific and targeted prevention, potentially reducing the impact of IBC among BRCA mutation carriers. C1 [Mazzola, Emanuele; Cheng, Su-Chun; Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. RP Mazzola, E (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02215 USA. EM mazzola@jimmy.harvard.edu FU Susan G Komen Breast Cancer Foundation [KG081303]; NCI comprehensive cancer center core grant [5P30 CA006516-46] FX This work was supported by the Susan G Komen Breast Cancer Foundation (KG081303) and by the NCI comprehensive cancer center core grant 5P30 CA006516-46. NR 15 TC 3 Z9 3 U1 0 U2 9 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 JAN PY 2013 VL 137 IS 1 BP 315 EP 318 DI 10.1007/s10549-012-2345-5 PG 4 WC Oncology SC Oncology GA 059MV UT WOS:000312710500029 PM 23184082 ER PT J AU Elena, JW Steplowski, E Yu, K Hartge, P Tobias, GS Brotzman, MJ Chanock, SJ Stolzenberg-Solomon, RZ Arslan, AA Bueno-de-Mesquita, HB Helzlsouer, K Jacobs, EJ LaCroix, A Petersen, G Zheng, W Albanes, D Allen, NE Amundadottir, L Bao, Y Boeing, H Boutron-Ruault, MC Buring, JE Gaziano, JM Giovannucci, EL Duell, EJ Hallmans, G Howard, BV Hunter, DJ Hutchinson, A Jacobs, KB Kooperberg, C Kraft, P Mendelsohn, JB Michaud, DS Palli, D Phillips, LS Overvad, K Patel, AV Sansbury, L Shu, XO Simon, MS Slimani, N Trichopoulos, D Visvanathan, K Virtamo, J Wolpin, BM Zeleniuch-Jacquotte, A Fuchs, CS Hoover, RN Gross, M AF Elena, Joanne W. Steplowski, Emily Yu, Kai Hartge, Patricia Tobias, Geoffrey S. Brotzman, Michelle J. Chanock, Stephen J. Stolzenberg-Solomon, Rachael Z. Arslan, Alan A. Bueno-de-Mesquita, H. Bas Helzlsouer, Kathy Jacobs, Eric J. LaCroix, Andrea Petersen, Gloria Zheng, Wei Albanes, Demetrius Allen, Naomi E. Amundadottir, Laufey Bao, Ying Boeing, Heiner Boutron-Ruault, Marie-Christine Buring, Julie E. Gaziano, J. Michael Giovannucci, Edward L. Duell, Eric J. Hallmans, Goran Howard, Barbara V. Hunter, David J. Hutchinson, Amy Jacobs, Kevin B. Kooperberg, Charles Kraft, Peter Mendelsohn, Julie B. Michaud, Dominique S. Palli, Domenico Phillips, Lawrence S. Overvad, Kim Patel, Alpa V. Sansbury, Leah Shu, Xiao-Ou Simon, Michael S. Slimani, Nadia Trichopoulos, Dimitrios Visvanathan, Kala Virtamo, Jarmo Wolpin, Brian M. Zeleniuch-Jacquotte, Anne Fuchs, Charles S. Hoover, Robert N. Gross, Myron TI Diabetes and risk of pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium SO CANCER CAUSES & CONTROL LA English DT Article DE Diabetes; Risk factor; Cohort consortium; Pancreatic cancer ID BASE-LINE CHARACTERISTICS; BLOOD-GROUP ALLELES; BODY-MASS INDEX; CIGARETTE-SMOKING; WOMENS HEALTH; ORIGINAL WHITEHALL; INSULIN-RESISTANCE; MELLITUS; NUTRITION; MORTALITY AB Diabetes is a suspected risk factor for pancreatic cancer, but questions remain about whether it is a risk factor or a result of the disease. This study prospectively examined the association between diabetes and the risk of pancreatic adenocarcinoma in pooled data from the NCI pancreatic cancer cohort consortium (PanScan). The pooled data included 1,621 pancreatic adenocarcinoma cases and 1,719 matched controls from twelve cohorts using a nested case-control study design. Subjects who were diagnosed with diabetes near the time (< 2 years) of pancreatic cancer diagnosis were excluded from all analyses. All analyses were adjusted for age, race, gender, study, alcohol use, smoking, BMI, and family history of pancreatic cancer. Self-reported diabetes was associated with a forty percent increased risk of pancreatic cancer (OR = 1.40, 95 % CI: 1.07, 1.84). The association differed by duration of diabetes; risk was highest for those with a duration of 2-8 years (OR = 1.79, 95 % CI: 1.25, 2.55); there was no association for those with 9+ years of diabetes (OR = 1.02, 95 % CI: 0.68, 1.52). These findings provide support for a relationship between diabetes and pancreatic cancer risk. The absence of association in those with the longest duration of diabetes may reflect hypoinsulinemia and warrants further investigation. C1 [Elena, Joanne W.; Sansbury, Leah] NCI, DCCPS, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Steplowski, Emily] Informat Management Serv Inc, Silver Spring, MD USA. [Chanock, Stephen J.; Amundadottir, Laufey; Hutchinson, Amy] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Bethesda, MD 20892 USA. [Brotzman, Michelle J.] Westat Corp, Rockville, MD USA. [Arslan, Alan A.] NYU, Sch Med, Dept Obstet & Gynecol, New York, NY USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Environm Med, New York, NY USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Inst Canc, New York, NY USA. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands. [Bueno-de-Mesquita, H. Bas] Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, Utrecht, Netherlands. [Helzlsouer, Kathy] Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD USA. [Visvanathan, Kala] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Visvanathan, Kala] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Jacobs, Eric J.; Patel, Alpa V.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [LaCroix, Andrea; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Petersen, Gloria] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Dept Med, Div Epidemiol, Vanderbilt Epidemiol Ctr, Nashville, TN USA. [Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Allen, Naomi E.] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England. [Bao, Ying; Wolpin, Brian M.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Boeing, Heiner] German Inst Human Nutr Potsdam Rehbrucke, Nuthetal, Germany. [Boutron-Ruault, Marie-Christine] INSERM, Villejuif, France. [Boutron-Ruault, Marie-Christine] Inst Gustave Roussy, Villejuif, France. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Phys Hlth Study, Boston, MA 02115 USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Aging, Phys Hlth Study, Boston, MA 02115 USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Phys Hlth Study, Boston, MA 02115 USA. [Gaziano, J. Michael] Vet Affairs Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Giovannucci, Edward L.; Hunter, David J.; Kraft, Peter; Trichopoulos, Dimitrios] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward L.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Duell, Eric J.] Catalan Inst Oncol ICO IDIBELL, Unit Nutr Environm & Canc, Barcelona, Spain. [Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Howard, Barbara V.] Georgetown Univ, MedStar Hlth Res Inst, Hyattsville, MD USA. [Hutchinson, Amy] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA. [Michaud, Dominique S.] Brown Univ, Div Biol & Med, Providence, RI 02912 USA. [Michaud, Dominique S.] Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, London, England. [Palli, Domenico] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy. [Phillips, Lawrence S.] Emory Univ, Div Endocrinol, Atlanta, GA 30322 USA. [Phillips, Lawrence S.] Atlanta VA Med Ctr, Decatur, GA USA. [Overvad, Kim] Aarhus Univ, Sch Publ Hlth, Dept Epidemiol, Aalborg, Denmark. [Simon, Michael S.] Wayne State Univ, Dept Oncol, Karmanos Canc Inst, Detroit, MI USA. [Slimani, Nadia] Int Agcy Res Canc, F-69372 Lyon, France. [Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Wolpin, Brian M.; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Gross, Myron] Univ Minnesota, Sch Med, Dept Lab Med Pathol, Minneapolis, MN 55455 USA. RP Elena, JW (reprint author), NCI, DCCPS, NIH, US Dept HHS, Bethesda, MD 20892 USA. EM elenajw@mail.nih.gov RI Boutron, Marie-Christine/K-8168-2013; Michaud, Dominique/I-5231-2014; Albanes, Demetrius/B-9749-2015; Boutron-Ruault, Marie-Christine/H-3936-2014; Amundadottir, Laufey/L-7656-2016; Tobias, Geoffrey/M-4135-2016; OI Amundadottir, Laufey/0000-0003-1859-8971; Tobias, Geoffrey/0000-0002-2878-8253; Duell, Eric J/0000-0001-5256-0163; PALLI, Domenico/0000-0002-5558-2437; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Intramural Research Program of the National Cancer Institute; U.S. Public Health Service [N01-CN-45165, N01-RC-45035, N01-RC-37004]; National Institute of Aging [5U01AG018033]; National Cancer Institute [CA105069, CA73790, P01CA087969, R01CA124908]; European Commission: Public Health and Consumer Protection Directorate; Ligue contre le Cancer; Societe 3 M; Mutuelle Generale de l'Education Nationale; Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center, Federal Ministry of Education and Research (Germany); Danish Cancer Society (Denmark); Health Research Fund (FIS) of the Spanish Ministry of Health (Spain); Cancer Research UK; Medical Research Council; Stroke Association; British Heart Foundation; Department of Health, Food Standards Agency; Wellcome Trust (United Kingdom); Greek Ministry of Health and Social Solidarity; Hellenic Health Foundation; Stavros Niarchos Foundation (Greece); Italian Association for Research on Cancer (AIRC) (Italy); Dutch Ministry of Public Health, Welfare and Sports; Dutch Prevention Funds; LK Research Funds; Dutch ZON (Zorg Onderzoek Nederland) (the Netherlands); Swedish Cancer Society; Swedish Scientific Council; Regional Government of Skane and Vasterbotten (Sweden); World Cancer Research Fund (WCRF); National Institute of Environmental Health Sciences Center [ES000260]; Intramural Research Program of National Cancer Institute (Division of Cancer Epidemiology and Genetics); National Heart, Lung, and Blood Institute [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; National Cancer Institute, National Institutes of Health; [P01CA055075] FX The authors thank the investigators from the PanScan Cohort Consortium centers and the study participants, without whom this study would have not been possible. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Trial was supported by funding provided by the Intramural Research Program of the National Cancer Institute, and the U.S. Public Health Service contracts [(N01-CN-45165, N01-RC-45035, N01-RC-37004]. CLUE II was supported by National Institute of Aging [5U01AG018033] and National Cancer Institute [CA105069, CA73790]. European Prospective Investigation into Cancer and Nutrition was supported by the European Commission: Public Health and Consumer Protection Directorate 1993-2004; Research Directorate-General 2005; Ligue contre le Cancer; Societe 3 M; Mutuelle Generale de l'Education Nationale; Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center, Federal Ministry of Education and Research (Germany); Danish Cancer Society (Denmark); Health Research Fund (FIS) of the Spanish Ministry of Health, The participating regional governments and institutions (Spain); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, the Wellcome Trust (United Kingdom); Greek Ministry of Health and Social Solidarity, Hellenic Health Foundation and Stavros Niarchos Foundation (Greece); Italian Association for Research on Cancer (AIRC) (Italy); Dutch Ministry of Public Health, Welfare and Sports, Dutch Prevention Funds, LK Research Funds, Dutch ZON (Zorg Onderzoek Nederland) (the Netherlands); Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skane and Vasterbotten (Sweden); World Cancer Research Fund (WCRF). The New York University Women's Health Study is supported by the National Cancer Institute research grants [R01CA034588, R01CA098661, P30CA016087] and the National Institute of Environmental Health Sciences Center grant [ES000260]. The Nurses' Health Study is supported by the National Cancer Institute research grants P01CA087969 and R01CA124908. The Health Professional's Follow-up Study is supported by P01CA055075 and R01CA124908. The Physician's Health Study by R01CA097193 and R01CA124908. The Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial was supported by contracts from the National Cancer Institute [University of Colorado Denver, NO1-CN-25514, Georgetown University NO1-CN-25522, Pacific Health Research Institute NO1-CN-25515, Henry Ford Health System NO1-CN-25512, University of Minnesota, NO1-CN-25513, Washington University NO1-CN-25516, University of Pittsburgh NO1-CN-25511, University of Utah NO1-CN-25524 Marshfield Clinic Research Foundation NO1-CN-25518, University of Alabama at Birmingham NO1-CN-75022, Westat, Inc. NO1-CN-25476, University of California, Los Angeles NO1-CN-25404]. The PLCO Study is sponsored by National Cancer Institute's Division of Cancer Prevention, in collaboration with the Division of Cancer Epidemiology and Genetics.; The Shanghai Men's and Women's Health Studies were supported by the National Cancer Institute extramural research grants [R01CA82729, R01CA70867, R01CA124908] and by the Intramural Research Program of National Cancer Institute (Division of Cancer Epidemiology and Genetics). The Women's Health Initiative is funded by the National Heart, Lung, and Blood Institute through contracts [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221]. Role of the Sponsors: This project has been funded with federal funds from the National Cancer Institute, National Institutes of Health. The funding agency had no role in the conduct of the study, the interpretation of the data, or the decision to submit the manuscript for publication. NR 51 TC 47 Z9 48 U1 1 U2 14 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JAN PY 2013 VL 24 IS 1 BP 13 EP 25 DI 10.1007/s10552-012-0078-8 PG 13 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 060KZ UT WOS:000312778000002 PM 23112111 ER PT J AU Ott, PA Chang, J Madden, K Kannan, R Muren, C Escano, C Cheng, X Shao, YZ Mendoza, S Gandhi, A Liebes, L Pavlick, AC AF Ott, Patrick A. Chang, Jason Madden, Kathleen Kannan, Rajni Muren, Caroline Escano, Crystal Cheng, Xin Shao, Yongzhao Mendoza, Sandra Gandhi, Alex Liebes, Leonard Pavlick, Anna C. TI Oblimersen in combination with temozolomide and albumin-bound paclitaxel in patients with advanced melanoma: a phase I trial SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Albumin-bound paclitaxel; Melanoma; Neoplasm metastasis; Oblimersen; Temozolomide ID METASTATIC MELANOMA; MALIGNANT-MELANOMA; ANTISENSE THERAPY; PLUS DACARBAZINE; ONCOLOGY-GROUP; SURVIVAL; CANCER; BRAF; VEMURAFENIB; PROGRESSION AB The combination of oblimersen, a bcl-2 antisense oligonucleotide, and dacarbazine lead to superior progression-free survival in advanced melanoma patients. Albumin-bound paclitaxel (nab-paclitaxel) has single-agent activity in melanoma. In a phase I trial, chemotherapy-na < ve patients with metastatic melanoma and normal LDH levels were enrolled on 3 cohorts. The treatment regimen consisted of 56-day cycles of oblimersen (7 mg/kg/day continuous IV infusion on day 1-7 and 22-28 in cohort 1 and 2; 900 mg fixed dose, twice weekly in weeks 1-2, 4-5 for cohort 3), temozolomide (75 mg/m(2), days 1-42), and nab-paclitaxel (175 mg/m(2) in cohort 1 and 3, 260 mg/m(2) in cohort 2 on day 7 and 28). Apoptosis markers were tested in pre- and post-treatment specimens of a subset of patients. Six grade 3 events (neutropenia, renal insufficiency, hyponatremia, elevated creatinine, allergic reaction, and neuropathy) and 2 grade 4 events (neutropenia and thrombocytopenia) were seen in 32 patients. The objective response rate was 40.6 % (2 complete responses and 11 partial responses) and 11 patients had stable disease, for a disease control rate of 75 %. The combination of oblimersen, temozolomide, and nab-paclitaxel was well tolerated and demonstrated encouraging activity in patients with advanced melanoma. C1 [Ott, Patrick A.; Chang, Jason; Madden, Kathleen; Kannan, Rajni; Muren, Caroline; Escano, Crystal; Mendoza, Sandra; Gandhi, Alex; Liebes, Leonard; Pavlick, Anna C.] NYU, Sch Med, Inst Canc, Div Med Oncol, New York, NY 10016 USA. [Cheng, Xin; Shao, Yongzhao] NYU, Sch Med, Div Biostat, New York, NY 10016 USA. [Ott, Patrick A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Melanoma Dis Ctr, Boston, MA 02215 USA. RP Ott, PA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Melanoma Dis Ctr, 450 Brookline Ave, Boston, MA 02215 USA. EM Patrick_Ott@DFCI.harvard.edu FU Genta, Inc.; Abraxis BioScience, LLC. FX We thank all participating patients at the New York University Cancer Institute. This work was supported by Genta, Inc.; Abraxis BioScience, LLC. NR 28 TC 23 Z9 24 U1 1 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JAN PY 2013 VL 71 IS 1 BP 183 EP 191 DI 10.1007/s00280-012-1995-7 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 063MW UT WOS:000313004900020 PM 23064957 ER PT J AU Passer, BJ Cheema, T Wu, S Wu, CI Rabkin, SD Martuza, RL AF Passer, B. J. Cheema, T. Wu, S. Wu, C-I Rabkin, S. D. Martuza, R. L. TI Combination of vinblastine and oncolytic herpes simplex virus vector expressing IL-12 therapy increases antitumor and antiangiogenic effects in prostate cancer models SO CANCER GENE THERAPY LA English DT Article DE oncolytic HSV-1; prostate cancer; IL-12; angiogenesis; microtubule disrupting agents; combination therapy ID TRANSGENIC MICE; ANGIOGENESIS; CELLS; INTERLEUKIN-12; DRUGS; INHIBITION; DOCETAXEL; BEVACIZUMAB; VIROTHERAPY; PACLITAXEL AB Oncolytic herpes simplex virus (oHSV)-1-based vectors selectively replicate in tumor cells causing direct killing, that is, oncolysis, while sparing normal cells. The oHSVs are promising anticancer agents, but their efficacy, when used as single agents, leaves room for improvement. We hypothesized that combining the direct oncolytic and antiangiogenic activities of the interleukin (IL)-12-secreting NV1042 oHSV with microtubule disrupting agents (MDAs) would be an effective means to enhance antitumor efficacy. Vinblastine (VB) was identified among several MDAs screened, which displayed consistent and potent cytotoxic killing of both prostate cancer and endothelial cell lines. In matrigel tube-forming assays, VB was found to be highly effective at inhibiting tube formation of human umbilical vein endothelial cells. The combination of VB with NV1023 (the parental virus lacking IL-12) or NV1042 showed additive or synergistic activity against prostate cancer cell lines, and was not due to increased oHSV replication by VB. In athymic mice bearing CWR22 prostate tumors, VB in combination with NV1042 was superior to the combination of VB plus NV1023 in reducing tumor burden, appeared to be nontoxic and resulted in a statistically significant diminution in the number of CD31(+) cells as compared with other treatment groups. In human organotypic cultures using surgical samples from radical prostatectomies, both NV1023 and NV1042 were localized specifically to the epithelial cells of prostatic glands but not to the surrounding stroma. These data highlight the therapeutic advantage of combining the dual-acting antitumor and antiangiogenic activities of oHSVs and MDAs. Cancer Gene Therapy (2013) 20, 17-24; doi:10.1038/cgt.2012.75; published online 9 November 2012 C1 [Passer, B. J.; Cheema, T.; Rabkin, S. D.; Martuza, R. L.] Massachusetts Gen Hosp, Brain Tumor Res Ctr, Dept Neurosurg, Boston, MA 02114 USA. [Passer, B. J.; Cheema, T.; Wu, S.; Wu, C-I; Rabkin, S. D.; Martuza, R. L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Wu, S.; Wu, C-I] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Passer, BJ (reprint author), Massachusetts Gen Hosp, Brain Tumor Res Ctr, Dept Neurosurg, Simches Res Bldg,CRPZN 3800,185 Cambridge St, Boston, MA 02114 USA. EM bpasser@partners.org FU [R01CA102139] FX This study was supported in part by a grant to RLM (R01CA102139). We thank Melissa Marinelli for laboratory assistance. We also thank Dr K Pienta (University of Michigan) for the bone marrow-derived HBME-1 endothelial cells. NR 41 TC 10 Z9 13 U1 0 U2 21 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD JAN PY 2013 VL 20 IS 1 BP 17 EP 24 DI 10.1038/cgt.2012.75 PG 8 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 062BX UT WOS:000312895200003 PM 23138870 ER PT J AU Gomperts, BN Walser, TC Spira, A Dubinett, SM AF Gomperts, Brigitte N. Walser, Tonya C. Spira, Avrum Dubinett, Steven M. TI Enriching the Molecular Definition of the Airway "Field of Cancerization:" Establishing New Paradigms for the Patient at Risk for Lung Cancer SO CANCER PREVENTION RESEARCH LA English DT Article ID GENE-EXPRESSION CHANGES; RESPIRATORY EPITHELIUM; CARCINOGENESIS; TISSUE; MUTATIONS; SMOKERS AB The "field of cancerization" refers to histologically normal-appearing tissue adjacent to neoplastic tissue that displays molecular abnormalities, some of which are the same as those of the tumor. Improving our understanding of these molecular events is likely to increase our understanding of carcinogenesis. Kadara and colleagues attempt to characterize the molecular events occurring temporally and spatially within the field of cancerization of patients with early-stage non-small cell lung cancer (NSCLC) following definitive surgery. They followed patients with bronchoscopies annually after tumor resection and extracted RNA from the serial brushings from different endobronchial sites. They then conducted microarray analysis to identify gene expression differences over time and in different sites in the airway. Candidate genes were found that may have biologic relevance to the field of cancerization. For example, expression of phosphorylated AKT and ERK1/2 was found to increase in the airway epithelium with time. Although there are limitations in the study design, this investigation demonstrates the utility of identifying molecular changes in histologically normal airway epithelium in lung cancer. In addition to increasing our understanding of lung cancer biology, studying the field of cancerization has the potential to identify biomarkers from samples obtained in a minimally invasive manner. Cancer Prev Res; 6(1); 4-7. (C) 2012 AACR. C1 [Gomperts, Brigitte N.] Univ Calif Los Angeles, Mattel Childrens Hosp, Div Hematol Oncol, Dept Pediat,Los Angeles UCLA, Los Angeles, CA 90095 USA. [Gomperts, Brigitte N.; Walser, Tonya C.; Dubinett, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. [Dubinett, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Dubinett, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med & Mol Pharmacol, Los Angeles, CA 90095 USA. [Gomperts, Brigitte N.] Univ Calif Los Angeles, Broad Stem Cell Res Ctr, Los Angeles, CA 90095 USA. [Gomperts, Brigitte N.; Walser, Tonya C.; Dubinett, Steven M.] Jonsson Comprehens Canc Ctr, Lung Canc Res Program, Los Angeles, CA 90034 USA. [Spira, Avrum] Boston Univ, Med Ctr, Ctr Pulm, Boston, MA USA. [Spira, Avrum] Boston Univ, Bioinformat Program, Boston, MA USA. [Spira, Avrum] Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02118 USA. [Dubinett, Steven M.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Pulm & Crit Care Med, 37-131 Ctr Hlth Sci,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM sdubinett@mednet.ucla.edu FU Department of Defense [W81XWH-10 1 1006]; Veterans Administration [51016X000359]; UCLA Clinical and Translational Science Institute [UL1TR000124]; National Cancer Institute [U01CA152751] FX The authors' work is supported in part by funding from the National Cancer Institute (#U01CA152751), Department of Defense (#W81XWH-10 1 1006), Veterans Administration (Merit Review #51016X000359), and the UCLA Clinical and Translational Science Institute (#UL1TR000124). NR 22 TC 11 Z9 11 U1 0 U2 5 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 JAN PY 2013 VL 6 IS 1 BP 4 EP 7 DI 10.1158/1940-6207.CAPR-12-0470 PG 4 WC Oncology SC Oncology GA 062XQ UT WOS:000312958200002 PM 23233734 ER PT J AU Li, GM Rivas, P Bedolla, R Thapa, D Reddick, RL Ghosh, R Kumar, AP AF Li, Guiming Rivas, Paul Bedolla, Roble Thapa, Dinesh Reddick, Robert L. Ghosh, Rita Kumar, Addanki P. TI Dietary Resveratrol Prevents Development of High-Grade Prostatic Intraepithelial Neoplastic Lesions: Involvement of SIRT1/S6K Axis SO CANCER PREVENTION RESEARCH LA English DT Article ID GENETICALLY-ENGINEERED MICE; POOR-PROGNOSIS; MOUSE MODELS; CANCER-CELLS; AUTOPHAGY; MECHANISMS; EXPRESSION; ADENOCARCINOMA; INHIBITION; LONGEVITY AB SIRT1 (mammalian ortholog of the yeast silent information regulator 2) is a NAD-dependent histone deacetylase belonging to the multigene family of sirtuins. Anecdotal and epidemiologic observations provide evidence for beneficial effects of the calorie restriction mimetic resveratrol (RES), a SIRT1 activator in preventing cardiovascular diseases and cancer. Although SIRT1 possesses both tumorigenic and antitumorigenic potential, the molecular mechanisms underlying SIRT1-mediated tumor progression or inhibition are poorly understood. In this study, we investigated the role of SIRT1 in multiple human prostate cancer cell lines and prostate-specific PTEN knockout mouse model using resveratrol. Androgen-independent prostate cancer cell lines (C42B, PC3, and DU145) express higher levels of SIRT1 than androgen-responsive (LNCaP) and nontumorigenic prostate cells (RWPE-1). Resveratrol enhanced this expression without any significant effect on SIRT1 enzymatic activity. Inhibition of SIRT1 expression using shRNA enhanced cell proliferation and inhibited autophagy by repressing phosphorylation of S6K and 4E-BP1. These biologic correlates were reversed in the presence of resveratrol. Analysis of prostates from dietary intervention with resveratrol showed a significant reduction in prostate weight and reduction in the incidence of high-grade prostatic intraepithelial neoplastic (HGPIN) lesions by approximately 54% with no significant change in body weight. Consistent with the in vitro findings, resveratrol intervention in the PTEN knockout mouse model was associated with reduction in the prostatic levels of mTOR complex 1 (mTORC1) activity and increased expression of SIRT1. These data suggest that SIRT1/S6K-mediated inhibition of autophagy drives prostate tumorigenesis. Therefore, modulation of SIRT1/S6K signaling represents an effective strategy for prostate cancer prevention. Cancer Prev Res; 6(1); 27-39. (C) 2012 AACR. C1 [Li, Guiming; Rivas, Paul; Bedolla, Roble; Thapa, Dinesh; Ghosh, Rita; Kumar, Addanki P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Reddick, Robert L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Ghosh, Rita; Kumar, Addanki P.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. [Kumar, Addanki P.] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Kumar, AP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM kumara3@uthscsa.edu RI Thapa, Dinesh/A-6109-2013 FU National Cancer Institute [R21 CA 137578]; Veterans Affairs-Merit Award [1 I01 BX 000766-01, 1RO1 CA 135451]; Cancer Therapy and Research Center at University of Texas Health Science Center San Antonio through the National Cancer Institute [2P30 CA 054174-17]; [RO1 CA 149516] FX This work was supported in part by the funds from National Cancer Institute R21 CA 137578; Veterans Affairs-Merit Award 1 I01 BX 000766-01 and 1RO1 CA 135451 (APK); RO1 CA 149516 (to R. Ghosh). The authors were also supported by the Cancer Therapy and Research Center at University of Texas Health Science Center San Antonio through the National Cancer Institute support grant #2P30 CA 054174-17 (to A.P. Kumar and R. Ghosh). NR 48 TC 22 Z9 23 U1 1 U2 24 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 JAN PY 2013 VL 6 IS 1 BP 27 EP 39 DI 10.1158/1940-6207.CAPR-12-0349 PG 13 WC Oncology SC Oncology GA 062XQ UT WOS:000312958200005 PM 23248098 ER PT J AU Laderach, DJ Gentilini, LD Giribaldi, L Delgado, VC Nugnes, L Croci, DO Al Nakouzi, N Sacca, P Casas, G Mazza, O Shipp, MA Vazquez, E Chauchereau, A Kutok, JL Rodig, SJ Elola, MT Compagno, D Rabinovich, GA AF Laderach, Diego J. Gentilini, Lucas D. Giribaldi, Laura Delgado, Victor Cardenas Nugnes, Lorena Croci, Diego O. Al Nakouzi, Nader Sacca, Paula Casas, Gabriel Mazza, Osvaldo Shipp, Margaret A. Vazquez, Elba Chauchereau, Anne Kutok, Jeffery L. Rodig, Scott J. Elola, Maria T. Compagno, Daniel Rabinovich, Gabriel A. TI A Unique Galectin Signature in Human Prostate Cancer Progression Suggests Galectin-1 as a Key Target for Treatment of Advanced Disease SO CANCER RESEARCH LA English DT Article ID TUMOR-IMMUNE PRIVILEGE; ENDOTHELIAL-CELLS; EXPRESSION; ANGIOGENESIS; MIGRATION; HYPOXIA; LECTIN; GROWTH; GENE; INVOLVEMENT AB Galectins, a family of glycan-binding proteins, influence tumor progression by modulating interactions between tumor, endothelial, stromal, and immune cells. Despite considerable progress in identifying the roles of individual galectins in tumor biology, an integrated portrait of the galectin network in different tumor microenvironments is still missing. We undertook this study to analyze the "galectin signature" of the human prostate cancer microenvironment with the overarching goal of selecting novel-molecular targets for prognostic and therapeutic purposes. In examining androgen-responsive and castration-resistant prostate cancer cells and primary tumors representing different stages of the disease, we found that galectin-1 (Gal-1) was the most abundantly expressed galectin in prostate cancer tissue and was markedly upregulated during disease progression. In contrast, all other galectins were expressed at lower levels: Gal-3, -4, -9, and -12 were downregulated during disease evolution, whereas expression of Gal-8 was unchanged. Given the prominent regulation of Gal-1 during prostate cancer progression and its predominant localization at the tumor-vascular interface, we analyzed the potential role of this endogenous lectin in prostate cancer angiogenesis. In human prostate cancer tissue arrays, Gal-1 expression correlated with the presence of blood vessels, particularly in advanced stages of the disease. Silencing Gal-1 in prostate cancer cells reduced tumor vascularization without altering expression of other angiogenesis-related genes. Collectively, our findings identify a dynamically regulated "galectin-specific signature" that accompanies disease evolution in prostate cancer, and they highlight a major role for Gal-1 as a tractable target for antiangiogenic therapy in advanced stages of the disease. Cancer Res; 73(1); 86-96. (C) 2012 AACR. C1 [Croci, Diego O.; Rabinovich, Gabriel A.] Inst Biol & Med Expt IBYME CONICET, Lab Inmunopatol, Buenos Aires, DF, Argentina. [Laderach, Diego J.; Gentilini, Lucas D.; Giribaldi, Laura; Compagno, Daniel; Rabinovich, Gabriel A.] Univ Buenos Aires, Lab Glicomica Estruct & Func, Buenos Aires, DF, Argentina. [Sacca, Paula; Vazquez, Elba] Univ Buenos Aires, Fac Ciencias Exactas & Nat, Dept Quim Biol, IQUIBICEN CONICET, Buenos Aires, DF, Argentina. [Delgado, Victor Cardenas; Nugnes, Lorena; Elola, Maria T.] Univ Buenos Aires, Fac Farm & Bioquim, CONICET, Inst Quim & Fiscoquim Biol IQUIFIB, Buenos Aires, DF, Argentina. [Casas, Gabriel; Mazza, Osvaldo] Hosp Aleman, Div Anat Patol, Buenos Aires, DF, Argentina. [Mazza, Osvaldo] Hosp Nacl Clin Jose de San Martin, Div Urol, Buenos Aires, DF, Argentina. [Al Nakouzi, Nader; Chauchereau, Anne] Inst Gustave Roussy, INSERMU981, Villejuif, France. [Shipp, Margaret A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shipp, Margaret A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kutok, Jeffery L.; Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Rabinovich, GA (reprint author), Inst Biol & Med Expt IBYME CONICET, Lab Inmunopatol, Vuelta Obligado 2490, Buenos Aires, DF, Argentina. EM diegoladerach@qb.fcen.uba.ar; danielcompagno@qb.fcen.uba.ar; gabyrabi@gmail.com RI CHAUCHEREAU, Anne/N-8880-2016 OI CHAUCHEREAU, Anne/0000-0001-9447-3797 FU Prostate Action (UK); Agencia Nacional de Promocion Cientifica y Tecnica Argentina (ANPCyT) [PICT 2008-134, PICT 2010-870]; Programa de Cooperacion Franco-Argentino ECOS-Sud [A10S03]; Fundacion Sales; University of Buenos Aires; Association pour la Recherche sur les Tumeurs de la Prostate (ARTP), France FX This study was supported by grants from Prostate Action (UK) to G. A. Rabinovich, D.J. Laderach, and D. Compagno, Agencia Nacional de Promocion Cientifica y Tecnica Argentina (ANPCyT; PICT 2008-134 to D.J. Laderach; PICT 2010-870 to G. A. Rabinovich), Programa de Cooperacion Franco-Argentino ECOS-Sud (A10S03 to G. A. Rabinovich, A. Chauchereau, D.J. Laderach, and D. Compagno), Fundacion Sales to G. A. Rabinovich, University of Buenos Aires to G. A. Rabinovich, and Association pour la Recherche sur les Tumeurs de la Prostate (ARTP), France, to D. Compagno. NR 47 TC 53 Z9 54 U1 1 U2 18 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 JAN 1 PY 2013 VL 73 IS 1 BP 86 EP 96 DI 10.1158/0008-5472.CAN-12-1260 PG 11 WC Oncology SC Oncology GA 063SF UT WOS:000313019800010 PM 23108139 ER PT J AU Lu, FX Fernandes, SM Davis, AE AF Lu, Fengxin Fernandes, Stacey M. Davis, Alvin E., III TI The effect of C1 inhibitor on myocardial ischemia and reperfusion injury SO CARDIOVASCULAR PATHOLOGY LA English DT Article DE Myocardial ischemia and reperfusion; Complement inhibition; Leukocyte transmigration ID ALTERNATIVE COMPLEMENT PATHWAY; ESTERASE INHIBITOR; ISCHEMIA/REPERFUSION INJURY; C1-ESTERASE INHIBITOR; HEREDITARY ANGIOEDEMA; REACTIVE PROTEIN; P-SELECTIN; NEUTROPHILS; INFARCTION; RECEPTOR AB Background: Activation of the complement system has been demonstrated to be an important mechanism in the mediation of myocardial ischemia and reperfusion (MIR) injury. C1 inhibitor (C1INH) has been shown to be beneficial in experimental MIR models. The underlying mechanism of this effect has been assumed to result primarily from inhibition of complement system activation. We recently demonstrated that C1INH plays a direct role in suppression of leukocyte transmigration in the mouse intestinal ischemia and reperfusion model. The purpose of this study was to investigate the mechanism of the beneficial effect of C1INH in mouse MIR model. Methods: C57BL/6, C1INH-deficient (C1INH(-/-)), and C3-deficient mice (C3(-/-)) were subjected to 30-min (C57BL/6 and C1INH(-/-)) or 60-min (C3(-/-)) occlusion of the left anterior descending branch of the coronary artery followed by 4-h reperfusion. C1INH or reactive center cleaved inactive C1INH (iC1INH) was injected intravenously 5 min before reperfusion. Results: Myocardial infarct size relative to the area at risk or relative to left ventricular area was significantly reduced in C1INH-treated wild-type, C1INH(-/-), and C3(-/-) mice compared with vehicle-treated mice. MIR induced an increase in myocardial polymorphonuclear neutrophil accumulation and plasma cardiac specific troponin I levels in vehicle-treated MIR mice, while C1INH treatment significantly attenuated these effects. iC1INH had a similar protective effect. Conclusions: These results suggested that C1INH prevented MIR injury in mice and that this cardioprotective effect may not solely result from complement inhibition, but might be also contributed by inhibiting leukocyte recruitment into ischemic tissue, an effect that is not mediated via protease inhibition. (c) 2013 Elsevier Inc. All rights reserved. C1 [Lu, Fengxin; Fernandes, Stacey M.; Davis, Alvin E., III] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. RP Lu, FX (reprint author), 97 Gerry Rd, Chestnut Hill, MA 02467 USA. EM fengxinlu@gmail.com FU National Institute of Health [RO1-AI057366, R37-HD22082] FX This study was supported by National Institute of Health Grants RO1-AI057366 and R37-HD22082.; This study was supported by National Institute of Health Grants RO1-AI057366 and R37-HD22082. We would like to thank Dr. Roderick Bronson and Harry Leung for their excellent assistance. NR 52 TC 12 Z9 12 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-8807 J9 CARDIOVASC PATHOL JI Cardiovasc. Pathol. PD JAN-FEB PY 2013 VL 22 IS 1 BP 75 EP 80 DI 10.1016/j.carpath.2012.05.003 PG 6 WC Cardiac & Cardiovascular Systems; Pathology SC Cardiovascular System & Cardiology; Pathology GA 060FH UT WOS:000312761400014 PM 22705194 ER PT J AU Konieczkowski, DJ Garraway, LA AF Konieczkowski, David J. Garraway, Levi A. TI Resistance to EGFR blockade in colorectal cancer: liquid biopsies and latent subclones SO CELL RESEARCH LA English DT Editorial Material ID ACQUIRED-RESISTANCE; MUTATIONS; CETUXIMAB; KRAS AB Two recent papers identify KRAS activation as a mechanism of acquired resistance to EGFR blockade in colorectal cancer. In doing so, they suggest that resistance to single-agent EGFR blockade will be unavoidable because these alterations exist as latent subclones within the tumor even prior to the initiation of therapy. C1 [Konieczkowski, David J.; Garraway, Levi A.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Konieczkowski, David J.; Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Garraway, Levi A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Garraway, LA (reprint author), Broad Inst Harvard & Massachusetts Inst Technol, Cambridge Ctr 7, Cambridge, MA 02142 USA. EM levi_garraway@dfci.harvard.edu FU NIGMS NIH HHS [T32 GM007753] NR 6 TC 3 Z9 3 U1 0 U2 3 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD JAN PY 2013 VL 23 IS 1 SI SI BP 13 EP 14 DI 10.1038/cr.2012.115 PG 2 WC Cell Biology SC Cell Biology GA 066BL UT WOS:000313194700005 PM 22847744 ER PT J AU Morris, SA Daley, GQ AF Morris, Samantha A. Daley, George Q. TI A blueprint for engineering cell fate: current technologies to reprogram cell identity SO CELL RESEARCH LA English DT Review DE reprogramming; direct fate conversion; directed differentiation ID PLURIPOTENT STEM-CELLS; GENE REGULATORY NETWORKS; EARLY MOUSE EMBRYOS; HUMAN FIBROBLASTS; DIRECT CONVERSION; REGENERATIVE MEDICINE; TRANSCRIPTION FACTORS; FUNCTIONAL-NEURONS; NUCLEAR TRANSFER; B-CELLS AB Human diseases such as heart failure, diabetes, neurodegenerative disorders, and many others result from the deficiency or dysfunction of critical cell types. Strategies for therapeutic tissue repair or regeneration require the in vitro manufacture of clinically relevant quantities of defined cell types. In addition to transplantation therapy, the generation of otherwise inaccessible cells also permits disease modeling, toxicology testing and drug discovery in vitro. In this review, we discuss current strategies to manipulate the identity of abundant and accessible cells by differentiation from an induced pluripotent state or direct conversion between differentiated states. We contrast these approaches with recent advances employing partial reprogramming to facilitate lineage switching, and discuss the mechanisms underlying the engineering of cell fate. Finally, we address the current limitations of the field and how the resulting cell types can be assessed to ensure the production of medically relevant populations. C1 [Morris, Samantha A.; Daley, George Q.] Childrens Hosp, Howard Hughes Med Inst, Stem Cell Transplantat Program, Manton Ctr Orphan Dis Res,Div Pediat Hematol & On, Boston, MA 02115 USA. [Morris, Samantha A.; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Morris, Samantha A.; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Morris, Samantha A.; Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Daley, GQ (reprint author), Childrens Hosp, Howard Hughes Med Inst, Stem Cell Transplantat Program, Manton Ctr Orphan Dis Res,Div Pediat Hematol & On, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu FU NIH (Progenitor Cell Biology Consortium) [UO1-HL100001, RC4-DK090913, R24DK092760]; Ellison Medical Foundation; Doris Duke Medical Foundation; Harvard Stem Cell Institute FX GQD is supported by grants from the NIH (Progenitor Cell Biology Consortium UO1-HL100001, RC4-DK090913, and R24DK092760), the Ellison Medical Foundation, Doris Duke Medical Foundation, and the Harvard Stem Cell Institute. GQD is an affiliate member of the Broad Institute, and an investigator of the Howard Hughes Medical Institute and the Manton Center for Orphan Disease Research. NR 139 TC 41 Z9 43 U1 0 U2 34 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD JAN PY 2013 VL 23 IS 1 SI SI BP 33 EP 48 DI 10.1038/cr.2013.1 PG 16 WC Cell Biology SC Cell Biology GA 066BL UT WOS:000313194700009 PM 23277278 ER PT J AU Liang, GY Zhang, Y AF Liang, Gaoyang Zhang, Yi TI Embryonic stem cell and induced pluripotent stem cell: an epigenetic perspective SO CELL RESEARCH LA English DT Review DE epigenetics; pluripotency; iPS cell; reprogramming ID CHROMATIN-REMODELING COMPLEX; NOVO DNA METHYLATION; CORE TRANSCRIPTIONAL NETWORK; SMALL-MOLECULE COMPOUNDS; GROUP PROTEINS RING1A/B; HUMAN SOMATIC-CELLS; H3 LYSINE 27; SELF-RENEWAL; GENE-EXPRESSION; DEVELOPMENTAL REGULATORS AB Pluripotent stem cells, like embryonic stem cells (ESCs), have specialized epigenetic landscapes, which are important for pluripotency maintenance. Transcription factor-mediated generation of induced pluripotent stem cells (iPSCs) requires global change of somatic cell epigenetic status into an ESC-like state. Accumulating evidence indicates that epigenetic mechanisms not only play important roles in the iPSC generation process, but also affect the properties of reprogrammed iPSCs. Understanding the roles of various epigenetic factors in iPSC generation contributes to our knowledge of the reprogramming mechanisms. C1 [Liang, Gaoyang; Zhang, Yi] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Liang, Gaoyang; Zhang, Yi] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Liang, Gaoyang; Zhang, Yi] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Zhang, Yi] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Zhang, Yi] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Zhang, Y (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, WAB 149G,200 Longwood Ave, Boston, MA 02115 USA. EM yzhang@genetics.med.harvard.edu RI Liang, Gaoyang/L-2087-2013 OI Liang, Gaoyang/0000-0002-2157-974X FU NIH [U01DK089565]; HHMI FX We would like to thank Shinpei Yamaguchi and Gustavo German for critical reading of this manuscript. We apologize to the people whose work cannot be cited due to space limitation. Stem cell and related work in our lab is supported by NIH (U01DK089565) and HHMI. YZ is an Investigator of the HHMI. NR 206 TC 52 Z9 54 U1 11 U2 105 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD JAN PY 2013 VL 23 IS 1 SI SI BP 49 EP 69 DI 10.1038/cr.2012.175 PG 21 WC Cell Biology SC Cell Biology GA 066BL UT WOS:000313194700010 PM 23247625 ER PT J AU Patterson, B Holt, P Nienaber, C Cambria, R Fairman, R Thompson, M AF Patterson, Benjamin Holt, Peter Nienaber, Chrisoph Cambria, Richard Fairman, Ronald Thompson, Matt TI Aortic Pathology Determines Midterm Outcome After Endovascular Repair of the Thoracic Aorta Report From the Medtronic Thoracic Endovascular Registry (MOTHER) Database SO CIRCULATION LA English DT Article DE acute aortic syndrome; aneurysm; aortic dissection; endovascular surgery; pathology ID STENT-GRAFT PLACEMENT; ANEURYSM-REPAIR; INTERNATIONAL REGISTRY; RISK-FACTORS; DISSECTION; COMPLICATIONS; DISEASE; SURGERY; TRIAL; METAANALYSIS AB Background-Endovascular repair of the thoracic aorta has become an increasingly utilized therapy. Although the short-term mortality advantage over open surgery is well documented, late mortality and the impact of presenting pathology on long-term outcomes remain poorly reported. Methods and Results-A database was built from 5 prospective studies and a single institutional series. Rates of perioperative adverse events were calculated, as were midterm death and reintervention rates. Multivariate analysis was performed with the use of logistic regression modeling. Kaplan-Meier survival curves were drawn for midterm outcomes. The database contained 1010 patients: 670 patients with thoracic aortic aneurysm, 195 with chronic type B aortic dissection, and 114 with acute type B aortic dissection. Lower elective mortality was observed in patients with chronic dissections (3%) compared with patients with aneurysms (5%). Multivariate analysis identified age, mode of admission, American Society of Anesthesiologists grade, and pathology as independent predictors of 30-day death (P < 0.05). In the midterm, the all-cause mortality rate was 8, 4.9, and 3.2 deaths per 100 patient-years for thoracic aortic aneurysm, acute type B aortic dissection, and chronic type B aortic dissection, respectively. The rates of aortic-related death were 0.6, 1.2, and 0.4 deaths per 100 patient-years for thoracic aortic aneurysm, acute type B aortic dissection, and chronic type B aortic dissection, respectively. Conclusions-This study indicated that the midterm outcomes of endovascular repair of the thoracic aorta are defined by presenting pathology, associated comorbidities, and mode of admission. Nonaortic mortality is high in the midterm for patients with thoracic aortic aneurysm, and managing modifiable risk factors appears vital. Endovascular repair of the thoracic aorta results in excellent midterm protection from aortic-related mortality, regardless of presenting pathology. (Circulation. 2013;127:24-32.) C1 [Patterson, Benjamin; Holt, Peter; Thompson, Matt] St Georges Hosp Natl Hlth Serv Trust, St Georges Vasc Inst, London SW17 0QT, England. [Nienaber, Chrisoph] Univ Rostock, Rostock, Germany. [Cambria, Richard] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fairman, Ronald] Hosp Univ Penn, Philadelphia, PA 19104 USA. RP Thompson, M (reprint author), St Georges Hosp Natl Hlth Serv Trust, St Georges Vasc Inst, 4th Floor,St James Wing, London SW17 0QT, England. EM matt.thompson@stgeorges.nhs.uk RI Holt, Peter/B-2003-2013 OI Holt, Peter/0000-0002-5739-2813 FU Boston Scientific; Cook Medical; Medtronic FX Drs Patterson, Holt, and Fairman have no disclosures. Dr Nienaber has received speaker's bureau honoraria from Medtronic (<$10 vertical bar 000) and Cook Medical (<$10 vertical bar 000) and has been paid consultancy fees by and acted as a medical advisor to Boston Scientific (<$10 vertical bar 000 in total). Dr Cambria has received clinical trial support from Medtronic, which was >$10 vertical bar 000 in total. Dr Thompson has received research grants from both Cook Medical and Medtronic, which amounts to >$10 vertical bar 000 in total. He also has received speaker's bureau honoraria from Medtronic, Cook, Endologix, and GE (<$10 vertical bar 000 in total). NR 33 TC 62 Z9 65 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 1 PY 2013 VL 127 IS 1 BP 24 EP + DI 10.1161/CIRCULATIONAHA.112.110056 PG 13 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 064EA UT WOS:000313052900019 PM 23283856 ER PT J AU Khan, AM Lubitz, SA Sullivan, LM Sun, JX Levy, D Vasan, RS Magnani, JW Ellinor, PT Benjamin, EJ Wang, TJ AF Khan, Abigail May Lubitz, Steven A. Sullivan, Lisa M. Sun, Jenny X. Levy, Daniel Vasan, Ramachandran S. Magnani, Jared W. Ellinor, Patrick T. Benjamin, Emelia J. Wang, Thomas J. TI Low Serum Magnesium and the Development of Atrial Fibrillation in the Community The Framingham Heart Study SO CIRCULATION LA English DT Article DE arrhythmias, cardiac; epidemiology; atrial fibrillation; magnesium ID ARTERY-BYPASS SURGERY; INTRAVENOUS MAGNESIUM; CORONARY-ARTERY; CARDIAC-SURGERY; METAANALYSIS; ARRHYTHMIAS; POTASSIUM; HYPOMAGNESEMIA; DISEASE; ASSOCIATION AB Background-Low serum magnesium has been linked to increased risk of atrial fibrillation (AF) after cardiac surgery. It is unknown whether hypomagnesemia predisposes to AF in the community. Methods and Results-We studied 3530 participants (mean age, 44 years; 52% women) from the Framingham Offspring Study who attended a routine examination and were free of AF and cardiovascular disease. We used Cox proportional hazard regression analysis to examine the association between serum magnesium at baseline and risk of incident AF. Analyses were adjusted for conventional AF risk factors, use of antihypertensive medications, and serum potassium. During up to 20 years of follow-up, 228 participants developed AF. Mean serum magnesium was 1.88 mg/dL. The age- and sex-adjusted incidence rate of AF was 9.4 per 1000 person-years (95% confidence interval, 6.7-11.9) in the lowest quartile of serum magnesium (<= 1.77 mg/dL) compared with 6.3 per 1000 person-years (95% confidence interval, 4.1-8.4) in the highest quartile (>= 1.99 mg/dL). In multivariable-adjusted models, individuals in the lowest quartile of serum magnesium were similar to 50% more likely to develop AF (adjusted hazard ratio, 1.52; 95% confidence interval, 1.00-2.31; P=0.05) compared with those in the upper quartiles. Results were similar after the exclusion of individuals on diuretics. Conclusions-Low serum magnesium is moderately associated with the development of AF in individuals without cardiovascular disease. Because hypomagnesemia is common in the general population, a link with AF may have potential clinical implications. Further studies are warranted to confirm our findings and to elucidate the underlying mechanisms. (Circulation. 2013;127:33-38.) C1 [Sullivan, Lisa M.; Levy, Daniel; Vasan, Ramachandran S.; Benjamin, Emelia J.; Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Khan, Abigail May] Univ Penn, Div Cardiol, Philadelphia, PA 19104 USA. [Lubitz, Steven A.; Ellinor, Patrick T.; Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Sullivan, Lisa M.; Sun, Jenny X.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Vasan, Ramachandran S.; Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Div Cardiol, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Div Prevent Med, Boston, MA 02118 USA. RP Benjamin, EJ (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA. EM Emelia@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970; Sullivan, Lisa/0000-0003-0726-7149; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; National Institutes of Health [N01-HC-25195, 6R01-NS17950, 1R01HL092577, 1RC1HL101056, 1R01HL102214]; Evans Center for Interdisciplinary Biomedical Research ARC on Atrial Fibrillation at Boston University FX This work was supported in part by the National Heart, Lung and Blood Institute's Framingham Heart Study (contract No. N01-HC-25195); National Institutes of Health grants and contracts N01-HC-25195, 6R01-NS17950, 1R01HL092577, 1RC1HL101056, and 1R01HL102214; and the Evans Center for Interdisciplinary Biomedical Research ARC on Atrial Fibrillation at Boston University (http://www.bumc.bu.edu/evanscenteribr/). NR 37 TC 38 Z9 39 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 1 PY 2013 VL 127 IS 1 BP 33 EP 38 DI 10.1161/CIRCULATIONAHA.111.082511 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 064EA UT WOS:000313052900020 PM 23172839 ER PT J AU Fujimoto, N Borlaug, BA Lewis, GD Hastings, JL Shafer, KM Bhella, PS Carrick-Ranson, G Levine, BD AF Fujimoto, Naoki Borlaug, Barry A. Lewis, Gregory D. Hastings, Jeffrey L. Shafer, Keri M. Bhella, Paul S. Carrick-Ranson, Graeme Levine, Benjamin D. TI Hemodynamic Responses to Rapid Saline Loading The Impact of Age, Sex, and Heart Failure SO CIRCULATION LA English DT Article DE age and sex difference; filling pressure; heart failure; stroke volume; volume loading ID PRESERVED EJECTION FRACTION; PULMONARY ARTERIAL-HYPERTENSION; VENTRICULAR DIASTOLIC PRESSURE; CARDIAC-OUTPUT; BLOOD-VOLUME; DIAGNOSIS; GENDER; CAPACITANCE; CONSTRAINT; INFUSION AB Background-Hemodynamic assessment after volume challenge has been proposed as a way to identify heart failure with preserved ejection fraction. However, the normal hemodynamic response to a volume challenge and how age and sex affect this relationship remain unknown. Methods and Results-Sixty healthy subjects underwent right heart catheterization to measure age- and sex-related normative responses of pulmonary capillary wedge pressure and mean pulmonary arterial pressure to volume loading with rapid saline infusion (100-200 mL/min). Hemodynamic responses to saline infusion in heart failure with preserved ejection fraction (n=11) were then compared with those of healthy young (<50 years of age) and older (>= 50 years of age) subjects. In healthy subjects, pulmonary capillary wedge pressure increased from 10 +/- 2 to 16 +/- 3 mm Hg after similar to 1 L and to 20 +/- 3 mm Hg after similar to 2 L of saline infusion. Older women displayed a steeper increase in pulmonary capillary wedge pressure relative to volume infused (16 +/- 4 mm Hg.L-1.m(2)) than the other 3 groups (P <= 0.019). Saline infusion resulted in a greater increase in mean pulmonary arterial pressure relative to cardiac output in women compared with men regardless of age. Subjects with heart failure with preserved ejection fraction exhibited a steeper increase in pulmonary capillary wedge pressure relative to infused volume (25 +/- 12 mm Hg.L-1.m(2)) than healthy young and older subjects (P <= 0.005). Conclusions-Filling pressures rise significantly with volume loading, even in healthy volunteers. Older women and patients with heart failure with preserved ejection fraction exhibit the largest increases in pulmonary capillary wedge pressure and mean pulmonary arterial pressure. (Circulation. 2013;127:55-62.) C1 [Fujimoto, Naoki; Hastings, Jeffrey L.; Shafer, Keri M.; Bhella, Paul S.; Carrick-Ranson, Graeme; Levine, Benjamin D.] Texas Hlth Presbyterian Hosp, Inst Exercise & Environm Med, Dallas, TX 75231 USA. [Fujimoto, Naoki; Hastings, Jeffrey L.; Shafer, Keri M.; Bhella, Paul S.; Carrick-Ranson, Graeme; Levine, Benjamin D.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Borlaug, Barry A.] Mayo Clin Rochester, Div Cardiovasc Dis, Dept Med, Rochester, MN USA. [Lewis, Gregory D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Levine, BD (reprint author), Texas Hlth Presbyterian Hosp, Inst Exercise & Environm Med, 7232 Greenville Ave,Ste 435, Dallas, TX 75231 USA. EM BenjaminLevine@TexasHealth.org FU National Institutes of Health [AG17479] FX This study was supported by National Institutes of Health grant AG17479. NR 36 TC 50 Z9 51 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 1 PY 2013 VL 127 IS 1 BP 55 EP + DI 10.1161/CIRCULATIONAHA.112.111302 PG 16 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 064EA UT WOS:000313052900023 PM 23172838 ER PT J AU Alam, MM Arifuzzaman, M Ahmad, SM Hosen, MI Rahman, MA Rashu, R Sheikh, A Ryan, ET Calderwood, SB Qadri, F AF Alam, Mohammad Murshid Arifuzzaman, Mohammad Ahmad, Shaikh Meshbahuddin Hosen, M. Ismail Rahman, Mohammad Arif Rashu, Rasheduzzaman Sheikh, Alaullah Ryan, Edward T. Calderwood, Stephen B. Qadri, Firdausi TI Study of Avidity of Antigen-Specific Antibody as a Means of Understanding Development of Long-Term Immunological Memory after Vibrio cholerae O1 Infection SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID IMMUNOGLOBULIN-G AVIDITY; B-CELL RESPONSES; IMMUNE-RESPONSES; DENDRITIC CELLS; BANGLADESH; VACCINATION; IGG; PROTECTION; DYNAMICS; VACCINES AB The avidity of antibodies to specific antigens and the relationship of avidity to memory B cell responses to these antigens have not been studied in patients with cholera or those receiving oral cholera vaccines. We measured the avidity of antibodies to cholera toxin B subunit (CTB) and Vibrio cholerae O1 lipopolysaccharide (LPS) in Bangladeshi adult cholera patients (n = 30), as well as vaccinees (n = 30) after administration of two doses of a killed oral cholera vaccine. We assessed antibody and memory B cell responses at the acute stage in patients or prior to vaccination in vaccinees and then in follow-up over a year. Both patients and vaccinees mounted CTB-specific IgG and IgA antibodies of high avidity. Patients showed longer persistence of these antibodies than vaccinees, with persistence lasting in patients up to day 270 to 360. The avidity of LPS-specific IgG and IgA antibodies in patients remained elevated up to 180 days of follow-up. Vaccinees mounted highly avid LPS-specific antibodies at day 17 (3 days after the second dose of vaccine), but the avidity waned rapidly to baseline by 30 days. We examined the correlation between antigen-specific memory B cell responses and avidity indices for both antigens. We found that numbers of CTB- and LPS-specific memory B cells significantly correlated with the avidity indices of the corresponding antibodies (P < 0.05; Spearman's rho = 0.28 to 0.45). These findings suggest that antibody avidity after infection and immunization is a good correlate of the development and maintenance of memory B cell responses to Vibrio cholerae O1 antigens. C1 [Alam, Mohammad Murshid; Arifuzzaman, Mohammad; Ahmad, Shaikh Meshbahuddin; Hosen, M. Ismail; Rahman, Mohammad Arif; Rashu, Rasheduzzaman; Sheikh, Alaullah; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Ctr Vaccine Sci, Dhaka 1000, Bangladesh. [Ryan, Edward T.; Calderwood, Stephen B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Ryan, Edward T.; Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. RP Qadri, F (reprint author), Int Ctr Diarrhoeal Dis Res, Ctr Vaccine Sci, GPO Box 128, Dhaka 1000, Bangladesh. EM fqadri@icddrb.org FU ICDDR,B; National Institutes of Health; National Institute of Allergy and Infectious Diseases [AI058935, AI077883]; Fogarty International Center [TW005572, K01, TW007409]; Swedish Sida grant [INT-ICDDR, B-HN-01-AV] FX This work was supported by the ICDDR,B, and by grants from the National Institutes of Health, including grants from the National Institute of Allergy and Infectious Diseases (AI058935 [S. B. C., E. T. R., and F. Q.], AI077883 [E. T. R. and F. Q.]), a Training Grant in Vaccine Development from the Fogarty International Center (TW005572 [M. M. A. and F. Q.]), and a Career Development Award (K01) from the Fogarty International Center (TW007409 [J.B.H.]). This study was also supported by Swedish Sida grant INT-ICDDR,B-HN-01-AV (F.Q.). NR 42 TC 7 Z9 7 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD JAN PY 2013 VL 20 IS 1 BP 17 EP 23 DI 10.1128/CVI.00521-12 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 064HI UT WOS:000313064400003 PM 23114701 ER PT J AU Ananthakrishnan, AN Khalili, H Pan, A Higuchi, LM de Silva, P Richter, JM Fuchs, CS Chan, AT AF Ananthakrishnan, Ashwin N. Khalili, Hamed Pan, An Higuchi, Leslie M. de Silva, Punyanganie Richter, James M. Fuchs, Charles S. Chan, Andrew T. TI Association Between Depressive Symptoms and Incidence of Crohn's Disease and Ulcerative Colitis: Results From the Nurses' Health Study SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Inflammatory Bowel Disease; Stress; Epidemiology; Intestinal Inflammation ID INFLAMMATORY-BOWEL-DISEASE; PSYCHOLOGICAL STRESS; DIABETES-MELLITUS; NATURAL-HISTORY; RISK-FACTORS; WOMEN; ANXIETY; MODEL; IBD AB BACKGROUND & AIMS: Depression and psychosocial stress are believed to contribute to the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). Although many mechanisms have been proposed to link these disorders, few prospective studies have examined the relationship between depressed mood and incidence of CD or UC. METHODS: We analyzed data from 152,461 women (aged 29-72 years) enrolled since 1992-1993 in the Nurses' Health Study cohorts I and II. Self-reported depressive symptoms were assessed by using the Mental Health Index (MHI)-5, a validated 5-item subscale of the 36-item Short-Form health survey, which is designed to estimate psychological distress on the basis of scores that range from 0 to 100. Self-reported CD and UC were confirmed through blinded record review by 2 gastroenterologists. Cox proportional hazards models were used to associate recent (within 4 years) and baseline MHI-5 scores with risk for CD or UC, adjusting for other risk factors. RESULTS: During 1,787,070 person-years of follow-up, we documented 170 cases of CD and 203 cases of UC. Compared with women with recent MHI-5 scores of 86-100, women with recent depressive symptoms (MHI-5 scores <52) had an increased risk of CD (multivariate-adjusted hazard ratio [HR], 2.39; 95% confidence interval [CI], 1.40-3.98; P trend = .001). Baseline depressive symptoms, assessed from the baseline MHI-5 score, were also associated with CD, although with a lower HR (1.62; 95% CI, 0.94-2.77). Recent (HR, 1.14; 95% CI, 0.68-1.92) and baseline depressive symptoms were not associated with increased risk of UC (HR, 1.07; 95% CI, 0.63-1.83). CONCLUSIONS: On the basis of data from the Nurses' Health Study, depressive symptoms increase the risk for CD, but not UC, among women. Psychological factors might therefore contribute to development of CD. Further studies are needed to determine the mechanisms of this association. C1 [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Crohns & Colitis Ctr, Div Gastroenterol, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.; Khalili, Hamed; Higuchi, Leslie M.; de Silva, Punyanganie; Richter, James M.; Fuchs, Charles S.; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Higuchi, Leslie M.] Childrens Hosp, Div Gastroenterol & Nutr, Boston, MA 02115 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fuchs, Charles S.; Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 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 RI Pan, An/C-5572-2011 OI Pan, An/0000-0002-1089-7945 FU American Gastroenterological Association; Crohn's and Colitis Foundation of America; Broad Foundation; National Institutes of Health [R01 CA137178, P01 CA87969, P30 DK043351, K08 DK064256] FX Supported by a Research Scholars Award of the American Gastroenterological Association (A.N.A.), Crohn's and Colitis Foundation of America (H.K.), the Broad Medical Research Program of the Broad Foundation (A.T.C), and the National Institutes of Health R01 CA137178, P01 CA87969, P30 DK043351, and K08 DK064256. NR 38 TC 25 Z9 26 U1 0 U2 19 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 JAN PY 2013 VL 11 IS 1 BP 57 EP 62 DI 10.1016/j.cgh.2012.08.032 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 064YU UT WOS:000313112900014 PM 22944733 ER PT J AU Wang, YB Kalra, M Scott, J AF Wang, Yingbing Kalra, Mannudeep Scott, James TI Compensatory Asymmetric Hemidiaphragmatic Uptake Secondary to Contralateral Hemidiaphragmatic Paresis SO CLINICAL NUCLEAR MEDICINE LA English DT Editorial Material DE FDG PET/CT; pitfalls; diaphragmatic uptake; physiological uptake ID FDG UPTAKE; MUSCLES C1 [Wang, Yingbing; Kalra, Mannudeep; Scott, James] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Wang, YB (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 216, Boston, MA 02114 USA. EM ywang34@partners.org NR 9 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD JAN PY 2013 VL 38 IS 1 BP 53 EP 55 DI 10.1097/RLU.0b013e318270855f PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 056PL UT WOS:000312503100027 PM 23242049 ER PT J AU Stoner, K Jerabek, SA Tow, S Wright, TM Padgett, DE AF Stoner, Kirsten Jerabek, Seth A. Tow, Stephanie Wright, Timothy M. Padgett, Douglas E. TI Rotating-platform Has No Surface Damage Advantage Over Fixed-bearing TKA SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TOTAL KNEE ARTHROPLASTY; POLYETHYLENE TIBIAL COMPONENTS; POST WEAR; REPLACEMENT; CONFORMITY; DESIGN; MOBILE; PROSTHESES; IMPLANTS; INSERTS AB Rotating-platform TKA, although purported to have superior kinematics, has shown no clinical advantages over those of fixed-bearing TKA. Our design-matched retrieval study aimed to investigate if differences in bearing wear damage exist between fixed- and mobile-bearing TKAs with similar condylar geometry. We asked whether (1) the rotating platform's more conforming tibiofemoral articulation would be associated with less severe damage; (2) the location of damage and wear would be similar on the tibiofemoral or backside surfaces of two contemporary designs with similar condylar geometry; and (3) the combined damage and deformation measured as thickness would differ between the two designs. We performed damage grading and damage mapping on 25 rotating-platform and 17 fixed-bearing inserts. The patient demographic data from each of these cohorts were comparable. Inserts were also laser-scanned from which we obtained thicknesses, and inferior surface three-dimensional scans, from which we determined dimensional changes. Rotating-platform and fixed-bearing inserts had similar tibiofemoral damage scores. However, the scores on the inferior surface of rotating platforms were greater, often as a result of third-body debris scratching observed on both damage mapping and three-dimensional scans. The extent of damage as a function of surface area was greater for rotating platforms, consistent with the greater tibiofemoral conformity. Dimensional changes on the inferior surfaces of the fixed bearing followed loading areas of the knee. However, no differences were seen in the thicknesses between fixed- and rotating-platform bearings. The increased total damage score on the rotating platform, coupled with increased surface area damaged and the propensity for third-body debris, indicates no damage advantage to this mobile-bearing design. C1 [Stoner, Kirsten; Wright, Timothy M.; Padgett, Douglas E.] Hosp Special Surg, New York, NY 10021 USA. [Jerabek, Seth A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tow, Stephanie] Univ Med & Dent New Jersey, Newark, NJ 07103 USA. RP Wright, TM (reprint author), Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA. EM wrightt@hss.edu NR 29 TC 8 Z9 9 U1 2 U2 8 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 JAN PY 2013 VL 471 IS 1 BP 76 EP 85 DI 10.1007/s11999-012-2530-1 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 059PB UT WOS:000312716400013 PM 22948523 ER PT J AU Bozic, KJ Bashyal, RK Anthony, SG Chiu, V Shulman, B Rubash, HE AF Bozic, Kevin J. Bashyal, Ravi K. Anthony, Shawn G. Chiu, Vanessa Shulman, Brandon Rubash, Harry E. TI Is Administratively Coded Comorbidity and Complication Data in Total Joint Arthroplasty Valid? SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TOTAL HIP-ARTHROPLASTY; POSTOPERATIVE MORTALITY; MEDICARE PATIENTS; RISK-FACTORS; INFECTION; ACCURACY AB Administrative claims data are increasingly being used in public reporting of provider performance and health services research. However, the concordance between administrative claims data and the clinical record in lower extremity total joint arthroplasty (TJA) is unknown. We evaluated the concordance between administrative claims and the clinical record for 13 commonly reported comorbidities and complications in patients undergoing TJA. We compared 13 administratively coded comorbidities and complications derived from hospital billing records with clinical documentation from a consecutive series of 1350 primary and revision TJAs performed at three high-volume institutions during 2009. Concordance between administrative claims and the clinical record varied across comorbidities and complications. Concordance between diabetes and postoperative myocardial infarction was reflected by a kappa value > 0.80; chronic lung disease, coronary artery disease, and postoperative venous thromboembolic events by kappa values between 0.60 and 0.79; and for congestive heart failure, obesity, prior myocardial infarction, peripheral arterial disease, bleeding complications, history of venous thromboembolism, prosthetic-related complications, and postoperative renal failure by kappa values between 0.40 and 0.59. All comorbidities and complications had a high degree of specificity (> 92%) but lower sensitivity (29%-100%). The data suggest administratively coded comorbidities and complications correlate reasonably well with the clinical record. However, the specificity of administrative claims is much higher than the sensitivity, indicating that comorbidities and complications coded in the administrative record were accurate but often incomplete. Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence. C1 [Bozic, Kevin J.; Chiu, Vanessa] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. [Bozic, Kevin J.; Chiu, Vanessa] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94143 USA. [Anthony, Shawn G.; Rubash, Harry E.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Bashyal, Ravi K.] NorthShore Univ HealthSyst, Dept Orthopaed Surg, Evanston, IL USA. [Shulman, Brandon] Univ Penn, Perlman Sch Med, Philadelphia, PA 19104 USA. RP Bozic, KJ (reprint author), Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. EM kevin.bozic@ucsf.edu FU Orthopaedic Research and Education Foundation FX Financial support was received from the Orthopaedic Research and Education Foundation. One author (HER) receives royalties from Zimmer, Inc. (Warsaw, IN, USA). NR 11 TC 42 Z9 42 U1 0 U2 5 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 JAN PY 2013 VL 471 IS 1 BP 201 EP 205 DI 10.1007/s11999-012-2352-1 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 059PB UT WOS:000312716400030 PM 22528384 ER PT J AU Motiwala, SR Januzzi, JL AF Motiwala, S. R. Januzzi, J. L., Jr. TI The Role of Natriuretic Peptides as Biomarkers for Guiding the Management of Chronic Heart Failure SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID CONVERTING ENZYME-INHIBITOR; LEFT-VENTRICULAR HYPERTROPHY; BNP GENE-EXPRESSION; NT-PROBNP LEVELS; GUIDED THERAPY; BETA-BLOCKER; VAL-HEFT; CARDIOVASCULAR EVENTS; CLEARANCE RECEPTORS; HYPERTENSIVE-RATS AB The current standard treatment of chronic heart failure (HF) is based on clinical judgment, with the goal of achieving the maximally tolerated therapeutic program. The complexity of this approach may contribute to the well-established treatment gaps that exist in HF management; consequently, the risks for morbidity and mortality in this population remain extremely high. Alternative means are needed to improve the outcomes of patients with HF. Natriuretic peptides are biological markers for HF disease its presence, severity, and prognosis and show unique interactions with therapeutics known to have benefit in HF. Accordingly, interest has recently developed in "biomarker-guided"care for HF. This approach involves applying these assays to identify patients in need of therapy intensification and to provide an objective "monitor" of disease status. This review examines the biology of natriuretic peptides, discusses the rationale for their use in HF, and details the aggregate experience gained thus far in biomarker-guided care. C1 [Motiwala, S. R.; Januzzi, J. L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. EM JJanuzzi@partners.org FU Roche Diagnostics; Siemens; Critical Diagnostics; BRAHMS GmBH FX J.L.J. has received grants from Roche Diagnostics, Siemens, Critical Diagnostics, and BRAHMS GmBH. S.R.M. declared no conflict of interest. NR 75 TC 19 Z9 19 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 2013 VL 93 IS 1 BP 57 EP 67 DI 10.1038/clpt.2012.187 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 058EZ UT WOS:000312618200025 PM 23187878 ER PT J AU Cheney, ML AF Cheney, Mack L. TI Cross-Specialty Discussion Enables Educational Enlightenment Foreword SO CLINICS IN PLASTIC SURGERY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02215 USA. RP Cheney, ML (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02215 USA. EM Mack_Cheney@meei.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0094-1298 J9 CLIN PLAST SURG JI Clin. Plast. Surg. PD JAN PY 2013 VL 40 IS 1 BP XV EP XV DI 10.1016/j.cps.2012.11.002 PG 1 WC Surgery SC Surgery GA 065KC UT WOS:000313146200002 PM 23186775 ER PT J AU Dalziel, PJ Noble, VE AF Dalziel, Peregrine James Noble, Vicki Elizabeth TI Bedside ultrasound and the assessment of renal colic: a review SO EMERGENCY MEDICINE JOURNAL LA English DT Review ID UNENHANCED HELICAL CT; ACUTE FLANK PAIN; EMERGENCY-DEPARTMENT; URETERAL CALCULI; US; RADIOGRAPHY; SONOGRAPHY; VALIDATION; PHYSICIANS; DIAGNOSIS AB Renal colic is a common emergency department (ED) presentation. The use of CT in the diagnosis of renal colic has increased over the past two decades and is now the most common imaging modality used in many institutions. However, with growing concerns about cumulative radiation exposure, increasing healthcare costs and patient flow in EDs, alternative approaches may need to be considered. Point-of-care ultrasound may offer a radiation-free, rapid and cost-effective alternative. The authors reviewed the literature and synthesised some of the data comparing point-of-care ultrasound with CT scanning as well as some of the evidence for how it might be incorporated into a renal colic management strategy. It is concluded that there is enough evidence to define a rational algorithm for renal colic management. A prospectively validated algorithm would greatly assist primary care and emergency practitioners while reducing costs and radiation dose. C1 [Dalziel, Peregrine James; Noble, Vicki Elizabeth] Massachusetts Gen Hosp, Emergency Med Ultrasound Div, Boston, MA 02114 USA. RP Dalziel, PJ (reprint author), Massachusetts Gen Hosp, Emergency Med Ultrasound Div, Suite 140,5 Emerson Pl, Boston, MA 02114 USA. EM drpjdalziel@gmail.com NR 39 TC 21 Z9 21 U1 0 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1472-0205 EI 1472-0213 J9 EMERG MED J JI Emerg. Med. J. PD JAN PY 2013 VL 30 IS 1 BP 3 EP 8 DI 10.1136/emermed-2012-201375 PG 6 WC Emergency Medicine SC Emergency Medicine GA 062CN UT WOS:000312896800007 PM 22685250 ER PT J AU Luderer, HF Nazarian, RM Zhu, ED Demay, MB AF Luderer, Hilary F. Nazarian, Rosalynn M. Zhu, Eric D. Demay, Marie B. TI Ligand-Dependent Actions of the Vitamin D Receptor Are Required for Activation of TGF-beta Signaling during the Inflammatory Response to Cutaneous Injury SO ENDOCRINOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; KNOCKOUT MICE; KERATINOCYTE PROLIFERATION; 1,25-DIHYDROXYVITAMIN D-3; EPIDERMAL DIFFERENTIATION; PROTEIN-1 MCP-1; GENE-EXPRESSION; IMMUNE-SYSTEM; COACTIVATORS; ALOPECIA AB The vitamin D receptor (VDR) has both 1,25-dihydroxyvitamin D-dependent and -independent actions in the epidermis. Ligand-dependent actions of the VDR have been shown to promote keratinocyte differentiation and to regulate formation of the epidermal barrier. In contrast, the actions of the VDR that regulate postmorphogenic hair cycling do not require 1,25-dihydroxyvitamin D. The VDR also has immunomodulatory actions that are dependent on its ligand, 1,25-dihydroxyvitamin D. To determine whether the ligand-dependent or -independent actions of the VDR regulate the inflammatory response to cutaneous injury, studies were performed in control, VDR knockout, and vitamin D-deficient mice. These investigations demonstrate that absence of receptor or ligand impairs the dermal response to cutaneous injury. Although neutrophil recruitment is not affected, the absence of VDR signaling leads to defects in macrophage recruitment and granulation tissue formation. Studies performed to identify the molecular basis for this phenotype demonstrate that absence of the VDR, or its ligand, impairs TGF-beta signaling in the dermis, characterized by decreased expression of monocyte chemotactic protein-1 and reduced phosphorylation of phosphorylated Smad-3 as well as attenuated phosphorylated Smad-3 phosphorylation in response to TGF-beta in primary dermal fibroblasts lacking the VDR. Thus, these data demonstrate that the liganded VDR interacts with the TGF-beta signaling pathway to promote the normal inflammatory response to cutaneous injury. (Endocrinology 154: 16-24, 2013) C1 [Demay, Marie B.] Massachusetts Gen Hosp, Pathol Serv, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pathol Serv, Dermatopathol Unit, Boston, MA 02114 USA. [Demay, Marie B.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Demay, MB (reprint author), Massachusetts Gen Hosp, Pathol Serv, Endocrine Unit, Thier 1101,50 Blossom St, Boston, MA 02114 USA. EM demay@helix.mgh.harvard.edu FU National Institutes of Health [R01 DK-46974] FX This work was supported by Grant R01 DK-46974 (to M.B.D.) from the National Institutes of Health. NR 46 TC 15 Z9 17 U1 0 U2 4 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 JAN PY 2013 VL 154 IS 1 BP 16 EP 24 DI 10.1210/en.2012-1579 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 061SO UT WOS:000312868500004 PM 23132743 ER PT J AU Quinn, LS Anderson, BG Conner, JD Wolden-Hanson, T AF Quinn, LeBris S. Anderson, Barbara G. Conner, Jennifer D. Wolden-Hanson, Tami TI IL-15 Overexpression Promotes Endurance, Oxidative Energy Metabolism, and Muscle PPAR delta, SIRT1, PGC-1 alpha, and PGC-1 beta Expression in Male Mice SO ENDOCRINOLOGY LA English DT Article ID HUMAN SKELETAL-MUSCLE; INTERLEUKIN-15 RECEPTOR; GENE-EXPRESSION; ADIPOSE-TISSUE; EXERCISE; DRIVES; FAT; THERMOGENESIS; ACTIVATION; ADIPOCYTES AB Endurance exercise initiates a pattern of gene expression that promotes fat oxidation, which in turn improves endurance, body composition, and insulin sensitivity. The signals from exercise that initiate these pathways have not been completely characterized. IL-15 is a cytokine that is up-regulated in skeletal muscle after exercise and correlates with leanness and insulin sensitivity. To determine whether IL-15 can induce any of the metabolic adaptations associated with exercise, substrate metabolism, endurance, and molecular expression patterns were examined in male transgenic mice with constitutively elevated muscle and circulating IL-15 levels. IL-15 transgenic mice ran twice as long as littermate control mice in a run-to-exhaustion trial and preferentially used fat for energy metabolism. Fast muscles in IL-15 transgenic mice exhibited high expression of intracellular mediators of oxidative metabolism that are induced by exercise, including sirtuin 1, peroxisome proliferator-activated receptor (PPAR)-delta, PPAR-gamma coactivator-1 alpha, and PPAR-gamma coactivator-1 beta. Muscle tissue in IL-15 transgenic mice exhibited myosin heavy chain and troponin I mRNA isoform expression patterns indicative of a more oxidative phenotype than controls. These findings support a role for IL-15 in induction of exercise endurance, oxidative metabolism, and skeletal muscle molecular adaptations induced by physical training. (Endocrinology 154: 232-245, 2013) C1 [Quinn, LeBris S.; Anderson, Barbara G.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Quinn, LeBris S.; Conner, Jennifer D.; Wolden-Hanson, Tami] VA Puget Sound Hlth Care Syst, Res Serv, Seattle, WA 98108 USA. [Quinn, LeBris S.; Conner, Jennifer D.] Seattle Inst Biomed & Clin Res, Seattle, WA 98108 USA. [Quinn, LeBris S.; Anderson, Barbara G.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. RP Quinn, LS (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr S182, 1660 S Columbian Way, Seattle, WA 98108 USA. EM quinnL@uw.edu FU Merit Review from the Department of Veterans Affairs [BX001026]; National Institutes of Health (NIH) from the National Institute on Aging (NIA) [RO1AG024136]; Seattle Institute for Biomedical and Clinical Research; Transgenic Resource Core at the University of Washington Nathan Shock Center of Excellence in the Basic Biology of Aging (NIA) [5P30AG-013280]; University of Washington Diabetes Endocrinology Research Center (NIH) [P30 DK-17047] FX This work was supported by Merit Review BX001026 from the Department of Veterans Affairs (to L. S. Q.), National Institutes of Health (NIH) Grant RO1AG024136 from the National Institute on Aging (NIA) (to L. S. Q.), Seattle Institute for Biomedical and Clinical Research, and use of resources and facilities including the Rodent Metabolic and Behavioral Phenotyping Core at VA Puget Sound Health Care System, the Transgenic Resource Core at the University of Washington Nathan Shock Center of Excellence in the Basic Biology of Aging (NIA Grant 5P30AG-013280), and the University of Washington Diabetes Endocrinology Research Center (NIH Grant P30 DK-17047). NR 43 TC 25 Z9 28 U1 0 U2 16 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 JAN PY 2013 VL 154 IS 1 BP 232 EP 245 DI 10.1210/en.2012-1773 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 061SO UT WOS:000312868500024 PM 23161867 ER PT J AU Li, QX Kannan, A Das, A DeMayo, FJ Hornsby, PJ Young, SL Taylor, RN Bagchi, MK Bagchi, IC AF Li, Quanxi Kannan, Athilakshmi Das, Amrita DeMayo, Franco J. Hornsby, Peter J. Young, Steven L. Taylor, Robert N. Bagchi, Milan K. Bagchi, Indrani C. TI WNT4 Acts Downstream of BMP2 and Functions via beta-Catenin Signaling Pathway to Regulate Human Endometrial Stromal Cell Differentiation SO ENDOCRINOLOGY LA English DT Article ID FORKHEAD TRANSCRIPTION FACTOR; IN-VITRO; DECIDUALIZATION; PROGESTERONE; IMPLANTATION; MECHANISMS; EXPRESSION; INDUCTION; PROLIFERATION; PRIMATE AB Differentiation of endometrial stromal cells into decidual cells is a prerequisite for successful embryo implantation. Our previous studies in the mouse have shown that bone morphogenetic protein 2 (BMP2), a morphogen belonging to the TGF beta superfamily, is essential for this differentiation process. BMP2 is markedly induced in human primary endometrial stromal cells (HESCs) as they undergo differentiation in response to steroid hormones and cAMP. The present study was undertaken to identify the BMP2-mediated molecular pathways in primary cultures of HESCs during decidualization. Using gene expression profiling, we identified wingless-related murine mammary tumor virus integration site 4 (WNT4) as a target of BMP2 regulation during decidualization. Attenuation of WNT4 expression in HESCs by small interfering RNA administration greatly reduced BMP2-induced stromal differentiation. Additionally, adenovirus-mediated overexpression of WNT4 in HESCs markedly advanced the differentiation program, indicating that it is a key regulator of decidualization. The stimulatory effect of WNT4 was accompanied by the accumulation of active beta-catenin in the nuclei of decidualizing stromal cells, indicating the involvement of the canonical WNT signaling pathway. Functional inhibition of WNT4/beta-catenin pathway by Dickkopf-1, an inhibitor of the canonical WNT signaling, or small interfering RNA-mediated silencing of beta-catenin expression, greatly reduced the BMP2- and WNT4-induced decidualization. Gene expression profiling revealed that Forkhead box protein O1, a forkhead family transcription factor and previously reported regulator of HESC differentiation, is a common downstream mediator of both BMP2 and WNT4signaling. Taken together, these studies uncovered a linear pathway involving BMP2, WNT4/beta-catenin, and Forkhead box protein O1 that operates in human endometrium to critically control decidualization. (Endocrinology 154: 446-457, 2013) C1 [Li, Quanxi; Kannan, Athilakshmi; Das, Amrita; Bagchi, Indrani C.] Univ Illinois, Dept Comparat Biosci, Urbana, IL 61802 USA. [Taylor, Robert N.] Wake Forest Sch Med, Dept Obstet & Gynecol, Winston Salem, NC 27157 USA. [Young, Steven L.] Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC 27599 USA. [DeMayo, Franco J.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Hornsby, Peter J.] S Texas Vet Hlth Care Syst, San Antonio, TX 78245 USA. [Hornsby, Peter J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78245 USA. RP Bagchi, IC (reprint author), Univ Illinois, Dept Comparat Biosci, Urbana, IL 61802 USA. EM mbagchi@life.illinois.edu; ibagchi@illinois.edu FU National Institutes of Health (NIH) as part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH Centers Program in Reproduction and Infertility Research [U54 HD055787] FX This work was supported by National Institutes of Health (NIH) Grants U54 HD055787 as part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH Centers Program in Reproduction and Infertility Research. NR 42 TC 29 Z9 31 U1 0 U2 7 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2013 VL 154 IS 1 BP 446 EP 457 DI 10.1210/en.2012-1585 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 061SO UT WOS:000312868500043 PM 23142810 ER PT J AU Gilman, SE Fitzmaurice, GM Bruce, ML Ten Have, T Glymour, MM Carliner, H Alexopoulos, GS Mulsant, BH Reynolds, CF Cohen, A AF Gilman, Stephen E. Fitzmaurice, Garrett M. Bruce, Martha L. Ten Have, Thomas Glymour, M. Maria Carliner, Hannah Alexopoulos, George S. Mulsant, Benoit H. Reynolds, Charles F., III Cohen, Alex TI Economic Inequalities in the Effectiveness of a Primary Care Intervention for Depression and Suicidal Ideation SO EPIDEMIOLOGY LA English DT Article ID COMORBIDITY SURVEY REPLICATION; OLDER-ADULTS; SOCIOECONOMIC-STATUS; ANTIDEPRESSANT TREATMENT; MINORITY PATIENTS; CLINICAL-TRIALS; UNITED-STATES; SOCIAL INEQUALITIES; RANDOMIZED-TRIALS; SUBGROUP ANALYSES AB Background: Economic disadvantage is associated with depression and suicide. We sought to determine whether economic disadvantage reduces the effectiveness of depression treatments received in primary care. Methods: We conducted differential-effects analyses of the Prevention of Suicide in Primary Care Elderly: Collaborative Trial, a primary-care-based randomized, controlled trial for late-life depression and suicidal ideation conducted between 1999 and 2001, which included 514 patients with major depression or clinically significant minor depression. Results: The intervention effect, defined as change in depressive symptoms from baseline, was stronger among persons reporting financial strain at baseline (differential effect size = -4.5 Hamilton Depression Rating Scale points across the study period [95% confidence interval = -8.6 to -0.3]). We found similar evidence for effect modification by neighborhood poverty, although the intervention effect weakened after the initial 4 months of the trial for participants residing in poor neighborhoods. There was no evidence of substantial differences in the effectiveness of the intervention on suicidal ideation and depression remission by economic disadvantage. Conclusions: Economic conditions moderated the effectiveness of primary-care-based treatment for late-life depression. Financially strained individuals benefited more from the intervention; we speculate this was because of the enhanced treatment management protocol, which led to a greater improvement in the care received by these persons. People living in poor neighborhoods experienced only temporary benefit from the intervention. Thus, multiple aspects of economic disadvantage affect depression treatment outcomes; additional work is needed to understand the underlying mechanisms. (Epidemiology 2013;24: 14-22) C1 [Gilman, Stephen E.; Glymour, M. Maria; Carliner, Hannah] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Gilman, Stephen E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Fitzmaurice, Garrett M.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Fitzmaurice, Garrett M.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Bruce, Martha L.; Alexopoulos, George S.] Weill Cornell Med Coll, Dept Psychiat, White Plains, NY USA. [Ten Have, Thomas] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Mulsant, Benoit H.] Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON, Canada. [Mulsant, Benoit H.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Reynolds, Charles F., III] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Cohen, Alex] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, London WC1, England. 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; Alexopoulos, George/0000-0001-5677-7001 FU National Institute of Mental Health [MH83335, MH085943, MH059366]; Forest; Medispin, Inc., a medical education company; U.S. National Institute of Mental Health; Canadian Institutes for Health Research; NIH FX Supported by National Institute of Mental Health grants MH83335, MH085943, and MH059366. Forest Pharmaceuticals provided free citalopram for the PROSPECT study. The funders had no role in the design or conduct of the present study.; G.S.A. has received a research support from Forest; he serves on the speakers' bureau for Forest, Lilly, Bristol Meyers Squibb, Astra Zeneca, Merck, and is a stockholder in Johnson & Johnson. M.L.B. has received financial compensation for consulting to Medispin, Inc., a medical education company. B.H.M. has received financial support during the past 36 months from the U.S. National Institute of Mental Health and the Canadian Institutes for Health Research and pharmaceutical supplies from Bristol-Myers Squibb, Eli Lilly, and Pfizer for his NIH-sponsored research. He has also received reimbursement for travel expenses from Roche. B.H.M. has received pharmaceutical supplies from Bristol-Myers Squibb, Eli Lilly, and Pfizer for his NIH-sponsored research. He has also received reimbursement for travel expenses from Roche. C.F.R. III receives pharmaceutical supplies from Forest Laboratories, BMS, Pfizer, and Lilly for his NIH-sponsored research. NR 54 TC 4 Z9 4 U1 3 U2 34 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2013 VL 24 IS 1 BP 14 EP 22 DI 10.1097/EDE.0b013e3182762403 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 056NZ UT WOS:000312498600003 PM 23232609 ER PT J AU Erdmann, E Semigran, MJ Nieminen, MS Gheorghiade, M Agrawal, R Mitrovic, V Mebazaa, A AF Erdmann, Erland Semigran, Marc J. Nieminen, Markku S. Gheorghiade, Mihai Agrawal, Rahul Mitrovic, Veselin Mebazaa, Alexandre TI Cinaciguat, a soluble guanylate cyclase activator, unloads the heart but also causes hypotension in acute decompensated heart failure SO EUROPEAN HEART JOURNAL LA English DT Article DE Cinaciguat; Soluble guanylyl cyclase; Heart failure; Clinical trial; phase 2; Haemodynamics; Vasodilation ID BAY 58-2667; CARDIAC TROPONIN; DIAGNOSIS; GUIDELINES; NESIRITIDE; OUTCOMES; TRIAL AB Cinaciguat (BAY 58-2667) is a novel soluble guanylate cyclase activator. This study evaluated the haemodynamic effect and safety of cinaciguat added to standard therapy in patients with acute decompensated heart failure (ADHF). In this placebo-controlled, phase IIb study (NCT00559650), 139 patients admitted with ADHF, pulmonary capillary wedge pressure (PCWP)epsilon 18 mmHg, left ventricular ejection fraction 40, and a pre-existing need for invasive haemodynamic monitoring were randomized 2:1 to cinaciguat:placebo (continuous i.v. infusion). The dose was titrated for 8 h and maintained for 1640 h (starting dose: 100 g/h). At 8 h, mean PCWP changed from 25.7 5.0 mmHg by 7.7 mmHg with cinaciguat and from 25.0 5.3 mmHg by 3.7 mmHg with placebo (P 0.0001). The mean right atrial pressure changed from 12.4 5.3 mmHg by 2.7 mmHg with cinaciguat and from 11.8 4.9 mmHg by 0.6 mmHg with placebo (P 0.0019). Cinaciguat also decreased the pulmonary and systemic vascular resistance and the mean arterial pressure, and increased the cardiac index (all P 0.0001 vs. placebo). Systolic blood pressure changed by 21.6 17.0 mmHg with cinaciguat and 5.0 14.5 mmHg with placebo. Adverse events were experienced by 71 and 45 of patients receiving cinaciguat and placebo, respectively. No adverse effects on the 30-day mortality were seen; however, the trial was stopped prematurely due to an increased occurrence of hypotension at cinaciguat doses epsilon 200 g/h. Cinaciguat unloaded the heart in patients with ADHF. However, high doses were associated with hypotension. C1 [Erdmann, Erland] Univ Cologne, Herzzentrum, D-50931 Cologne, Germany. [Semigran, Marc J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Heart Failure & Transplant Program,Cardiol Div, Boston, MA USA. [Nieminen, Markku S.] Univ Helsinki, Cent Hosp, Div Cardiol, Helsinki, Finland. [Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Agrawal, Rahul] Bayer HealthCare, Global Clin Dev, Elberfeld, Germany. [Mitrovic, Veselin] Kerckhoff Clin Nauheim, Bad Nauheim, Germany. [Mebazaa, Alexandre] Hop Lariboisiere, AP HP, Dept Anesthesiol & Crit Care Med, F-75475 Paris, France. [Mebazaa, Alexandre] Univ Paris Diderot, PRES Sorbonne Paris Cite, Paris, France. [Mebazaa, Alexandre] INSERM, U942, Paris, France. RP Erdmann, E (reprint author), Univ Cologne, Herzzentrum, D-50931 Cologne, Germany. EM erland.erdmann@uni-koeln.de FU Bayer HealthCare AG; CardioPep Pharma GmbH FX E.E. has received consulting fees, and research and travel support from Bayer HealthCare AG. M.J.S. has received research support from Bayer HealthCare AG. M.S.N. has received consultation fees from Bayer HealthCare AG. M. G. has been a consultant for Abbott Laboratories, Astellas, AstraZeneca, Bayer HealthCare AG, CorThera, Cytokinetics, DebioPharm S.A., Errekappa Terapeutici, GlaxoSmithKline, Ikaria, Johnson & Johnson, Medtronic, Merck, Novartis Pharma AG, Otsuka Pharmaceuticals, Palatin Technologies, Pericor Therapeutics, Protein Design Laboratories, Sanofi-Aventis, Sigma Tau, Solvay Pharmaceuticals, Takeda Pharmaceutical, and Trevena Therapeutics. R. A. is an employee of Bayer HealthCare AG. V. M. has received consultation fees, speaking fees, and honoraria from Bayer HealthCare AG and CardioPep Pharma GmbH. A. M. has received consultation fees from Bayer HealthCare AG and honoraria from Alere, Edwards, Brahms, and Orion. NR 27 TC 39 Z9 41 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD JAN PY 2013 VL 34 IS 1 BP 57 EP 67 DI 10.1093/eurheartj/ehs196 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 065EO UT WOS:000313131200014 PM 22778174 ER PT J AU Matulonis, UA Lee, J Lasonde, B Tew, WP Yehwalashet, A Matei, D Behbakht, K Grothusen, J Fleming, G Lee, NK Arnott, J Bray, MR Fletcher, G Brokx, RD Castonguay, V Mackay, H Sidor, CF Oza, AM AF Matulonis, Ursula A. Lee, Julie Lasonde, Brian Tew, William P. Yehwalashet, Afra Matei, Daniela Behbakht, Kian Grothusen, Jill Fleming, Gini Lee, Nita K. Arnott, Jamie Bray, Mark R. Fletcher, Graham Brokx, Richard D. Castonguay, Vincent Mackay, Helen Sidor, Carolyn F. Oza, Amit M. TI ENMD-2076, an oral inhibitor of angiogenic and proliferation kinases, has activity in recurrent, platinum resistant ovarian cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE ENMD-2076; Recurrent ovarian cancer; Phase II ID GYNECOLOGIC-ONCOLOGY-GROUP; PHASE-II TRIAL; RENAL-CELL CARCINOMA; EPITHELIAL OVARIAN; PRIMARY PERITONEAL; BEVACIZUMAB; HYPERTENSION; PERSISTENT; TOXICITY; INTERVAL AB Purpose: The purpose was to assess the activity and side effect profile of ENMD-2076, an oral anti-angiogenic and anti-proliferative kinase inhibitor, in platinum-resistant recurrent epithelial ovarian cancer (EOC), fallopian tube or peritoneal cancer. Archival tumour tissue was obtained for correlative analyses. Experimental design: This was an open-label single-arm Phase II study of single agent ENMD-2076 taken daily orally (PO). The primary objective was to determine the progression free survival (PFS) rate at 6 months of ENMD-2076 in platinum-resistant cancer based on RECIST v1.1. Secondary objectives included response rate (RR), duration of response, overall survival (OS) and safety. An exploratory analysis of archival tissue for mitotic index and angiogenesis was conducted in an attempt to identify a sensitive or resistant patient phenotype. Results: 64 patients were enrolled, and the PFS rate at 6 months was 22% with a median time to progression of 3.6 months. The median number of prior regimens was 2. The most common adverse events were fatigue, hypertension and diarrhoea with the most common Grade 3/4 events being hypertension and fatigue. None of the markers of mitotic index or angiogenesis evaluated in the archival tissue samples were predictive of greater benefit or resistance to ENMD-2076 treatment. Conclusions: ENMD-2076 has activity in platinum-resistant ovarian cancer, and observed toxicities were similar to other PO kinase inhibitors. Additional studies with ENMD-2076 are warranted, especially in combination with active chemotherapeutic agents in platinum-resistant patients. Further work to determine appropriate biomarkers for ENMD-2076 should be incorporated into new clinical studies. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Matulonis, Ursula A.] Dana Farber Canc Inst, Yawkey Ctr Canc Care, Boston, MA 02215 USA. [Matulonis, Ursula A.; Lee, Julie; Lasonde, Brian] Harvard Univ, Sch Med, Boston, MA USA. [Tew, William P.; Yehwalashet, Afra] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Matei, Daniela] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. [Behbakht, Kian; Grothusen, Jill] Univ Colorado, Aurora, CO USA. [Fleming, Gini; Lee, Nita K.] Univ Chicago, Chicago, IL 60637 USA. [Arnott, Jamie; Bray, Mark R.; Sidor, Carolyn F.] EntreMed Inc, Durham, NC USA. [Arnott, Jamie; Bray, Mark R.; Sidor, Carolyn F.] EntreMed Inc, Toronto, ON, Canada. [Castonguay, Vincent; Mackay, Helen; Oza, Amit M.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Fletcher, Graham; Brokx, Richard D.] Ampbell Family Inst Canc Res, Toronto, ON, Canada. RP Matulonis, UA (reprint author), Dana Farber Canc Inst, Yawkey Ctr Canc Care, 450 Brookline Ave,14th Floor, Boston, MA 02215 USA. EM Ursula_matulonis@dfci.harvard.edu OI Behbakht, Kian/0000-0003-4793-9958 FU EntreMed, Inc. FX We thank the patients and their families for their participation. We also thank the physicians, nurses and clinical research coordinators for their assistance, Synteract, Inc. for data abstraction and statistics and Leigh Feigenbaum (EntreMed, Inc.) for editorial input. Grant Support: Supported by EntreMed, Inc. NR 30 TC 16 Z9 16 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 2013 VL 49 IS 1 BP 121 EP 131 DI 10.1016/j.ejca.2012.07.020 PG 11 WC Oncology SC Oncology GA 062CM UT WOS:000312896700016 PM 22921155 ER PT J AU Richardson, PG Corbacioglu, S Ho, VTV Kernan, NA Lehmann, L Maguire, C Maglio, M Hoyle, M Sardella, M Giralt, S Holler, E Carreras, E Niederwieser, D Soiffer, R AF Richardson, Paul G. Corbacioglu, Selim Ho, Vincent Trien-Vinh Kernan, Nancy A. Lehmann, Leslie Maguire, Craig Maglio, Michelle Hoyle, Margaret Sardella, Marco Giralt, Sergio Holler, Ernst Carreras, Enric Niederwieser, Dietger Soiffer, Robert TI Drug safety evaluation of defibrotide SO EXPERT OPINION ON DRUG SAFETY LA English DT Review DE anti-inflammatory; antithrombotic; defibrotide; endothelial protective; prevention; profibrinolytic; prophylaxis; safety; sinusoidal obstruction syndrome; treatment; veno-occlusive disease ID STEM-CELL TRANSPLANTATION; HEPATIC VENOOCCLUSIVE DISEASE; THROMBOTIC THROMBOCYTOPENIC PURPURA; ACUTE MYOCARDIAL-INFARCTION; DEEP VENOUS THROMBOSIS; CONTROLLED CLINICAL-TRIAL; ACUTE-RENAL-FAILURE; BONE-MARROW TRANSPLANTATION; RANDOMIZED CONTROLLED-TRIAL; HIGH-RISK POPULATION AB Introduction: Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of chemotherapeutic conditioning used in preparation for hematopoietic stem-cell transplantation (SCT). Defibrotide (DF) has been shown in Phase II and III trials to improve complete response in patients with severe VOD (sVOD). None of the articles, to date, provide a comprehensive review of the safety of DF in VOD and/or a range of other conditions. Areas covered: This article reviews current clinical findings on DF, primarily in terms of safety for use in treatment and prophylaxis of VOD, and relevant safety data for its use in other diseases. The literature review was conducted using a PubMed search with the fixed term 'defibrotide' in combination with >= 1 of 'safety', 'veno-occlusive disease' (with and without 'treatment', 'prevention'), 'oncology', 'myeloma', 'microangiopathy', 'anti-thrombotic' and 'peripheral vascular disorder'. Related articles from the EBMT and ASH conference websites were also included. Expert opinion: DF was well tolerated in majority of the studies. The safety profile of DF is largely favourable with toxicities comparable to control populations in the setting of SCT complicated by sVOD. C1 [Richardson, Paul G.; Ho, Vincent Trien-Vinh; Lehmann, Leslie; Maguire, Craig; Maglio, Michelle; Soiffer, Robert] Dana Farber Canc Inst, Boston, MA 02215 USA. [Corbacioglu, Selim] Univ Regensburg, Childrens Hosp Regensburg, D-93053 Regensburg, Germany. [Kernan, Nancy A.; Giralt, Sergio] Mem Sloan Kettering Canc Ctr, New York, NY 10023 USA. [Hoyle, Margaret; Sardella, Marco] Gentium SpA, I-22079 Villa Guardia, Italy. [Holler, Ernst] Univ Regensburg, Univ Med Ctr, D-93053 Regensburg, Germany. [Carreras, Enric] Josep Carreras Fdn, Barcelona 08021, Spain. [Niederwieser, Dietger] Univ Leipzig, Div Hematol & Med Oncol, D-04103 Leipzig, Germany. RP Richardson, PG (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Mayer 232, Boston, MA 02215 USA. EM paul_richardson@dfci.harvard.edu OI Kernan, Nancy/0000-0003-1417-1823 FU Gentium SpA; Gentium FX Writing assistance was provided by S Aggarwal of ApotheCom ScopeMedical Ltd, sponsored by an unrestricted grant from Gentium SpA.; MH and MS are employees of Gentium SpA. EC has been Chairman and speaker for Gentium in several meetings and received a grant from Gentium for a fellowship in his Endothelial Lab. DN has served on a Gentium advisory board. The remaining authors declare no conflict of interest. NR 93 TC 17 Z9 18 U1 0 U2 8 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1474-0338 J9 EXPERT OPIN DRUG SAF JI Expert Opin. Drug Saf. PD JAN PY 2013 VL 12 IS 1 BP 123 EP 136 DI 10.1517/14740338.2012.749855 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 059JT UT WOS:000312702000013 PM 23228043 ER PT J AU Roth, MY Lin, K Bay, K Amory, JK Anawalt, BD Matsumoto, AM Marck, BT Bremner, WJ Page, ST AF Roth, Mara Y. Lin, Kat Bay, Katrine Amory, John K. Anawalt, Bradley D. Matsumoto, Alvin M. Marck, Brett T. Bremner, William J. Page, Stephanie T. TI Serum insulin-like factor 3 is highly correlated with intratesticular testosterone in normal men with acute, experimental gonadotropin deficiency stimulated with low-dose human chorionic gonadotropin: a randomized, controlled trial SO FERTILITY AND STERILITY LA English DT Article DE Androgens; INSL3; male infertility; gonadotropins; intratesticular testosterone ID ANTI-MULLERIAN HORMONE; INHIBIN-B; STEROID-LEVELS; REPRODUCTIVE HORMONES; LUTEINIZING-HORMONE; ESTROGEN-TREATMENT; PROSTATIC-CANCER; ADULT MEN; YOUNG MEN; SPERMATOGENESIS AB Objective: To study the potential role for using serum biomarkers, including insulin-like factor 3 (INSL3), 17 alpha-hydroxyprogesterone, antimullerian hormone, and inhibin B, as correlates of intratesticular T (IT-T) concentrations in men. Design: Prospective, randomized, controlled trial. Setting: University-based medical center. Patient(s): Thirty-seven healthy men aged 18-50 years. Intervention(s): All men received the GnRH antagonist acyline, plus very low doses of hCG (0 IU, 15 IU, 60 IU, or 125 IU) SC every other day or 7.5 g T gel daily (75 mg delivered). The IT-T concentrations obtained by percutaneous testicular aspiration with simultaneous serum protein and steroid concentrations were measured at baseline and after 10 days of treatment. Main Outcome Measure(s): Intratesticular and serum hormone and gonadotropin concentrations. Result(s): After 10 days of gonadotropin suppression, serum INSL3 decreased by more than 90% and correlated highly with IT-T concentrations. In contrast, serum inhibin B, antimullerian hormone, and 17 alpha-hydroxyprogesterone did not correlate with IT-T. Serum INSL3 increased with the dose of hCG administered and returned to baseline after treatment. Conclusion(s): Serum INSL3 correlates highly with IT-T and serum T concentrations during acute gonadotropin suppression in men. Human chorionic gonadotropin stimulates dose-dependent increases in INSL3 and IT-T in healthy men and might be a useful biomarker of IT-T concentration in some clinical settings. Clinical Trial Registration Number: NCT# 00839319. (Fertil Steril (R) 2013;99:132-9. (C) 2013 by American Society for Reproductive Medicine.) C1 [Roth, Mara Y.; Amory, John K.; Anawalt, Bradley D.; Matsumoto, Alvin M.; Bremner, William J.; Page, Stephanie T.] Univ Washington, Dept Med, Ctr Res Reprod & Contracept, Seattle, WA 98195 USA. [Lin, Kat] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Bay, Katrine] Rigshosp, Univ Dept Growth & Reprod, DK-2100 Copenhagen, Denmark. [Matsumoto, Alvin M.; Marck, Brett T.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. RP Roth, MY (reprint author), Univ Washington, Dept Med, Ctr Res Reprod & Contracept, 1959 NE Pacific St,Box 357138, Seattle, WA 98195 USA. EM mylang@u.washington.edu FU Clarus Pharmaceuticals; Eunice Kennedy Shriver National Institute of Child Health and Human Development [U54 HD-42454, K12 HD053984]; US Department of Veterans Affairs FX M.Y.R. has nothing to disclose. K.L. has nothing to disclose. K.B. has nothing to disclose. J.K.A. receives research funds as a site in a phase III trial from Clarus Pharmaceuticals (unrelated to this work). B.D.A. has nothing to disclose. A.M.M. has nothing to disclose. B.T.M. has nothing to disclose. W.J.B. has nothing to disclose. S.T.P. has nothing to disclose.; The Eunice Kennedy Shriver National Institute of Child Health and Human Development supported this work through cooperative agreement U54 HD-42454 as part of the Cooperative Contraceptive Research Centers Program. M.Y.R. is supported, in part, by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant K12 HD053984). A.M.M. is supported by the US Department of Veterans Affairs. NR 39 TC 12 Z9 12 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD JAN PY 2013 VL 99 IS 1 BP 132 EP 139 DI 10.1016/j.fertnstert.2012.09.009 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 064AX UT WOS:000313044400026 PM 23040523 ER PT J AU Imudia, AN Awonuga, AO Kaimal, AJ Wright, DL Styer, AK Toth, TL AF Imudia, Anthony N. Awonuga, Awoniyi O. Kaimal, Anjali J. Wright, Diane L. Styer, Aaron K. Toth, Thomas L. TI Elective cryopreservation of all embryos with subsequent cryothaw embryo transfer in patients at risk for ovarian hyperstimulation syndrome reduces the risk of adverse obstetric outcomes: a preliminary study SO FERTILITY AND STERILITY LA English DT Article DE Cryothaw; fresh embryo transfer; IVF; preeclampsia; serum estradiol; small for gestational age ID IN-VITRO FERTILIZATION; ASSISTED REPRODUCTIVE TECHNOLOGY; INTRACYTOPLASMIC SPERM INJECTION; LOW-BIRTH-WEIGHT; EARLY BABOON PREGNANCY; CHILDREN BORN; PERINATAL OUTCOMES; SINGLE; FROZEN; FRESH AB Objective: To test the hypothesis that patients who undergo elective cryopreservation of all embryos, due to risk of ovarian hyperstimulation syndrome and elevated peak serum estradiol (E-2), previously defined as level > 3,450 pg/mL (90th percentile) during in vitro fertilization (IVF), will be less likely to have small for gestational age (SGA) infants and preeclampsia as compared with patients with elevated peak serum E-2 who undergo fresh embryo transfer (ET). Design: Cohort study. Setting: Tertiary care academic medical center. Patient(s): Twenty women who underwent elective cryopreservation of all embryos with subsequent cryothaw ET and 32 similar women with elevated peak E-2 during controlled ovarian hyperstimulation for IVF who underwent a fresh ET. Intervention(s): None. Main Outcome Measure(s): Prevalence of SGA infants and development of preeclampsia in patients with cryothaw ET or fresh ET in the setting of elevated peak E-2. Result(s): After adjusting for confounders (body mass index, antral follicle count, peak serum E-2 level) using forward stepwise logistic regression, the patients who elected cryopreservation of all embryos and subsequent cryothaw ET were statistically significantly less likely to deliver SGA infants as compared with the patients who had fresh ET in the setting of elevated peak E-2. In the entire cohort, a total of seven women had preeclampsia, all of whom had had fresh ET in the setting of elevated peak serum E-2: 7 (21.9%) in the fresh ET group versus 0 women in the elective cryopreservation group. Conclusion(s): This preliminary study suggests that elective cryopreservation of all embryos in patients with elevated peak serum E-2 for subsequent cryothaw ET in cycles with a better physiologic hormonal milieu may reduce the odds of SGA and preeclampsia in IVF singleton deliveries. (Fertil Steril (R) 2013;99:168-73. (C) 2013 by American Society for Reproductive Medicine.) C1 [Imudia, Anthony N.; Wright, Diane L.; Styer, Aaron K.; Toth, Thomas L.] Harvard Univ, Massachusetts Gen Hosp, Massachusetts Gen Hosp Fertil Ctr, Vincent Dept Obstet & Gynecol,Med Sch, Boston, MA 02114 USA. [Awonuga, Awoniyi O.] Wayne State Univ, Sch Med, Div Reprod Endocrinol & Infertil, Detroit, MI USA. [Kaimal, Anjali J.] Harvard Univ, Massachusetts Gen Hosp, Div Maternal Fetal Med, Vincent Dept Obstet & Gynecol,Med Sch, Boston, MA 02114 USA. RP Imudia, AN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Massachusetts Gen Hosp Fertil Ctr, Vincent Dept Obstet & Gynecol,Med Sch, 55 Fruit St,Yawkey 10A, Boston, MA 02114 USA. EM aimudia@partners.org NR 38 TC 17 Z9 19 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JAN PY 2013 VL 99 IS 1 BP 168 EP 173 DI 10.1016/j.fertnstert.2012.08.060 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 064AX UT WOS:000313044400031 PM 23025881 ER PT J AU Wang, HS Pisegna, J Modi, R Liang, LJ Atia, M Nguyen, M Cohen, H Ohning, G van Oijen, M Spiegel, BMR AF Wang, Hank S. Pisegna, Joseph Modi, Rusha Liang, Li-Jung Atia, Mary Minh Nguyen Cohen, Hartley Ohning, Gordon van Oijen, Martijn Spiegel, Brennan M. R. TI Adenoma detection rate is necessary but insufficient for distinguishing high versus low endoscopist performance SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID COLORECTAL-CANCER; COLONOSCOPY; SURVEILLANCE; GUIDELINES; QUALITY; POLYP; RISK AB Background: Endoscopist quality is benchmarked by the adenoma detection rate (ADR)-the proportion of cases with 1 or more adenomas removed. However, the ADR rewards the same credit for 1 versus more than 1 adenoma. Objective: We evaluated whether 2 endoscopist groups could have a similar ADR but detect significantly different total adenomas. Design: We retrospectively measured the ADR and multiple measures of total adenoma yield, including a metric called ADR-Plus, the mean number of incremental adenomas after the first. We plotted ADR versus ADR-Plus to create 4 adenoma detection patterns: (1) optimal (up arrow ADR/up arrow ADR-Plus); (2) one and done (up arrow ADR/down arrow ADR-Plus); (3) all or none (down arrow ADR/up arrow ADR-Plus); (4) none and done (down arrow ADR/down arrow ADR-Plus). Setting: Tertiary-care teaching hospital and 3 nonteaching facilities servicing the same patient pool. Patients: A total of 3318 VA patients who underwent screening between 2005 and 2009. Main Outcome Measurements: ADR, mean total adenomas detected, advanced adenomas detected, ADR-Plus. Results: The ADR was 28.8% and 25.7% in the teaching (n = 1218) and nonteaching groups (n = 2100), respectively (P = .052). Although ADRs were relatively similar, the teaching site achieved 23.5%, 28.7%, and 29.5% higher mean total adenomas, advanced adenomas, and ADR-Plus versus nonteaching sites (P < .001). By coupling ADR with ADR-Plus, we identified more teaching endoscopists as optimal (57.1% vs 8.3%; P = .02), and more nonteaching endoscopists in the none and done category (42% vs 0%; P = .047). Limitations: External generalizability, nonrandomized study. Conclusion: We found minimal ADR differences between the 2 endoscopist groups, but substantial differences in total adenomas; the ADR missed this difference. Coupling the ADR with other total adenoma metrics (eg, ADR-Plus) provides a more comprehensive assessment of adenoma clearance; implementing both would better distinguish high-from low-performing endoscopists. (Gastrointest Endosc 2013;77:71-8.) C1 [Spiegel, Brennan M. R.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, VA Ctr Outcomes Res & Educ CORE,Dept Med,Div Gast, Los Angeles, CA 90073 USA. [Wang, Hank S.; Pisegna, Joseph; Ohning, Gordon; van Oijen, Martijn; Spiegel, Brennan M. R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA 90073 USA. [Liang, Li-Jung] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90073 USA. [Wang, Hank S.; Spiegel, Brennan M. R.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90073 USA. [Wang, Hank S.; Pisegna, Joseph; Ohning, Gordon; Spiegel, Brennan M. R.] CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. [Modi, Rusha; Atia, Mary; Minh Nguyen] Cedars Sinai Med Ctr, Div Gen Internal Med, Los Angeles, CA 90048 USA. RP Spiegel, BMR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, VA Ctr Outcomes Res & Educ CORE,Dept Med,Div Gast, 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. FU Veterans Affairs Merit Award [IIR 08-310]; NIH [T32DK07180-34] FX All authors disclosed no financial relationships relevant to this publication. This research was supported by a Veterans Affairs Merit Award (IIR 08-310) to Dr Spiegel and an NIH training grant (T32DK07180-34) to Dr Wang. NR 14 TC 34 Z9 34 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JAN PY 2013 VL 77 IS 1 BP 71 EP 78 DI 10.1016/j.gie.2012.08.038 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 063QE UT WOS:000313014000009 PM 23261096 ER PT J AU Pabona, JMP Dave, B Su, Y Montales, MTE de Lumen, B de Mejia, EG Rahal, OM Simmen, RCM AF Pabona, John Mark P. Dave, Bhuvanesh Su, Ying Montales, Maria Theresa E. de Lumen, Ben O. de Mejia, Elvira G. Rahal, Omar M. Simmen, Rosalia C. M. TI The soybean peptide lunasin promotes apoptosis of mammary epithelial cells via induction of tumor suppressor PTEN: similarities and distinct actions from soy isoflavone genistein SO GENES AND NUTRITION LA English DT Article DE Lunasin; Genistein; Soy; Apoptosis; PTEN; Mammary epithelial; Breast cancer ID BREAST-CANCER; MAMMALIAN-CELLS; LEUKEMIA-CELLS; WOMENS HEALTH; IN-VITRO; INHIBITION; PROTEIN; RISK; ACETYLATION; GROWTH AB Breast cancer is the leading cause of cancer deaths in women. Diet and lifestyle are major contributing factors to increased breast cancer risk. While mechanisms underlying dietary protection of mammary tumor formation are increasingly elucidated, there remains a dearth of knowledge on the nature and precise actions of specific bioactive components present in foods with purported health effects. The 43-amino acid peptide lunasin (LUN) is found in soybeans, is bioavailable similar to the isoflavone genistein (GEN), and thus may mediate the beneficial effects of soy food consumption. Here, we evaluated whether LUN displays common and distinct actions from those of GEN in non-malignant (mouse HC11) and malignant (human MCF-7) mammary epithelial cells. In MCF-7 cells, LUN up-regulated tumor suppressor phosphatase and tensin homolog deleted in chromosome ten (PTEN) promoter activity, increased PTEN transcript and protein levels and enhanced nuclear PTEN localization, similar to that shown for GEN in mammary epithelial cells. LUN-induced cellular apoptosis, akin to GEN, was mediated by PTEN, but unlike that for GEN, was p53-independent. LUN promoted E-cadherin and beta-catenin non-nuclear localization similar to GEN, but unlike GEN, did not influence the proliferative effects of oncogene Wnt1 on HC11 cells. Further, LUN did not recapitulate GEN inhibitory effects on expansion of the cancer stem-like/progenitor population in MCF-7 cells. Results suggest the concerted actions of GEN and LUN on cellular apoptosis for potential mammary tumor preventive effects and highlight whole food consumption rather than intake of specific dietary supplements with limited biological effects for greater health benefits. C1 [Pabona, John Mark P.; Dave, Bhuvanesh; Su, Ying; Montales, Maria Theresa E.; Rahal, Omar M.; Simmen, Rosalia C. M.] Arkansas Childrens Nutr Ctr, Little Rock, AR 72202 USA. [Pabona, John Mark P.; Montales, Maria Theresa E.; Rahal, Omar M.; Simmen, Rosalia C. M.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Dave, Bhuvanesh] Methodist Hosp, Res Inst, Houston, TX 77030 USA. [Su, Ying] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [de Lumen, Ben O.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [de Mejia, Elvira G.] Univ Illinois, Urbana, IL 61801 USA. RP Simmen, RCM (reprint author), Arkansas Childrens Nutr Ctr, 15 Childrens Way, Little Rock, AR 72202 USA. EM simmenrosalia@uams.edu FU United States Department of Agriculture [CRIS 6251-5100002-06S]; Department of Defense Breast Cancer Research Program [W81XWH-08-1-0548] FX This work was supported by the United States Department of Agriculture [CRIS 6251-5100002-06S, Arkansas Children's Nutrition Center] and the Department of Defense Breast Cancer Research Program (W81XWH-08-1-0548) grants to R.C.M.S. NR 49 TC 10 Z9 10 U1 4 U2 30 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1555-8932 J9 GENES NUTR JI Genes Nutr. PD JAN PY 2013 VL 8 IS 1 BP 79 EP 90 DI 10.1007/s12263-012-0307-5 PG 12 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 063SA UT WOS:000313019100008 PM 22864686 ER PT J AU McKenna, K Leykum, LK McDaniel, RR AF McKenna, Kalin Leykum, Luci K. McDaniel, Reuben R., Jr. TI The role of improvising in patient care SO HEALTH CARE MANAGEMENT REVIEW LA English DT Article DE improvising; managing uncertainty; patient safety; quality care delivery ID COMPLEXITY; VIEW AB Background: Uncertainty is inherent in health care systems. This uncertainty is related to the complexity of the system itself, as well as the potentially unpredictable trajectory of each patient's disease. One implication of uncertainty is that patient outcomes may be dependent on providers' ability to perform effectively in uncertain situations. Improvising is a critical activity that helps physicians act when the course of action is unclear or not routine. Purposes: The objective of this study was to describe the phenomenon and role of improvising in health care settings. Methodology/Approach: We observed 7 inpatient physician teams, analyzed a written case, and interviewed 7 physicians across specialties. We identified examples and themes related to improvising in each of these data sources. Findings: We observed improvising in 2 of the 7 observed inpatient teams. We also identified improvising in the written case. Examples of improvising in health care were reported in 6 of the 7 physician interviews. In these examples, improvising was manifested in different ways, ranging from specific treatment regimens to interactions with patients and their families. However, the description of social interactions leading to a change from the usual course of action was a common theme. Practice Implications: Improvising frequently occurs in health care, enabling physicians to adjust to the inherent uncertainty of patient care activities. Improvising is contingent on a foundation of medical knowledge from which providers can act in creative, novel ways. In addition, improvising is a social activity requiring a supportive relationship infrastructure. Enabling improvising may be an important approach for improving patient outcomes. Improving relationships will be an important component of these strategies. C1 [McKenna, Kalin; Leykum, Luci K.] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, San Antonio, TX USA. [McDaniel, Reuben R., Jr.] Univ Texas Austin, Dept Management Sci & Informat Syst, Austin, TX 78712 USA. RP McKenna, K (reprint author), Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, San Antonio, TX USA. EM Kalinmckenna@gmail.com; Leykum@uthscsa.edu; Reuben.McDaniel@mccombs.utexas.edu NR 18 TC 4 Z9 4 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0361-6274 J9 HEALTH CARE MANAGE R JI Health Care Manage. Rev. PD JAN-MAR PY 2013 VL 38 IS 1 BP 1 EP 8 DI 10.1097/HMR.0b013e31823ea9c7 PG 8 WC Health Policy & Services SC Health Care Sciences & Services GA 050QZ UT WOS:000312070400001 PM 22261668 ER PT J AU Noel, PH Lanham, HJ Palmer, RF Leykum, LK Parchman, ML AF Noel, Polly Hitchcock Lanham, Holly J. Palmer, Ray F. Leykum, Luci K. Parchman, Michael L. TI The importance of relational coordination and reciprocal learning for chronic illness care within primary care teams SO HEALTH CARE MANAGEMENT REVIEW LA English DT Article DE Chronic Care Model; diabetes; primary care; reciprocal learning; relational coordination ID CHRONIC DISEASES; MODEL; ORGANIZATIONS; SENSEMAKING; MODERATOR; SETTINGS; MEDIATOR; RISK; TIME AB Background: Recent research from a complexity theory perspective suggests that implementation of complex models of care, such as the Chronic Care Model (CCM), requires strong relationships and learning capacities among primary care teams. Purposes: Our primary aim was to assess the extent to which practice member perceptions of relational coordination and reciprocal learning were associated with the presence of CCM elements in community-based primary care practices. Methodology/Approach: We used baseline measures from a cluster randomized controlled trial testing a practice facilitation intervention to implement the CCM and improve risk factor control for patients with Type 2 diabetes in small primary care practices. Practice members (i.e., physicians, nonphysician providers, and staff) completed baseline assessments, which included the Relational Coordination Scale, Reciprocal Learning Scale, and the Assessment of Chronic Illness Care (ACIC) survey, along with items assessing individual and clinic characteristics. To assess the association between Relational Coordination, Reciprocal Learning, and ACIC, we used a series of hierarchical linear regression models accounting for clustering of individual practice members within clinics and controlling for individual- and practice-level characteristics and tested for mediation effects. Findings: A total of 283 practice members from 39 clinics completed baseline measures. Relational Coordination scores were significantly and positively associated with ACIC scores (Model 1). When Reciprocal Learning was added, Relational Coordination remained a significant yet notably attenuated predictor of ACIC (Model 2). The mediation effect was significant (z = 9.3, p < .01); 24% of the association between Relational Coordination and ACIC scores was explained by Reciprocal Learning. Of the individual- and practice-level covariates included in Model 3, only the presence of an electronic medical record was significant; Relational Coordination and Reciprocal Learning remained significant independent predictors of ACIC. Practice Implications: Efforts to implement complex models of care should incorporate strategies to strengthen relational coordination and reciprocal learning among team members. C1 [Noel, Polly Hitchcock; Lanham, Holly J.; Leykum, Luci K.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Noel, Polly Hitchcock; Lanham, Holly J.; Palmer, Ray F.; Leykum, Luci K.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. [Parchman, Michael L.] Agcy Healthcare Res & Qual, Rockville, MD USA. RP Noel, PH (reprint author), S Texas Vet Hlth Care Syst, San Antonio, TX USA. EM noelp@uthscsa.edu OI Parchman, Michael/0000-0001-7129-2889 FU NIDDK NIH HHS [R18 DK075692, R18 DK 075692, R18 DK075692-05] NR 39 TC 16 Z9 16 U1 0 U2 26 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0361-6274 J9 HEALTH CARE MANAGE R JI Health Care Manage. Rev. PD JAN-MAR PY 2013 VL 38 IS 1 BP 20 EP 28 DI 10.1097/HMR.0b013e3182497262 PG 9 WC Health Policy & Services SC Health Care Sciences & Services GA 050QZ UT WOS:000312070400003 PM 22310483 ER PT J AU Rivard, PE Parker, VA Rosen, AK AF Rivard, Peter E. Parker, Victoria A. Rosen, Amy K. TI Quality improvement for patient safety: Project-level versus program-level learning SO HEALTH CARE MANAGEMENT REVIEW LA English DT Article DE organizational learning; patient safety; Patient Safety Indicators; quality improvement; quality improvement implementation ID MANAGEMENT-PRACTICES; HEALTH-CARE; HOSPITALS; IMPLEMENTATION; PERFORMANCE; INDICATORS; TQM; ORGANIZATIONS; PERSPECTIVE; LEADERSHIP AB Background: Improving quality and patient safety is of increasing strategic importance to health care organizations. However, simply increasing the volume of quality improvement (QI) activity does not necessarily improve patient outcomes. There is a need for greater understanding of QI success factors. Purpose: This study looked for differences in QI implementation across hospitals with a range of performance on Patient Safety Indicators. Methods: We conducted an exploratory comparative case study of 4 Veterans Health Administration hospitals including site visits and interviews with leaders and staff. Findings: Two themes emerged. Project-level QI learning is assessing and modifying specific QI projects relative to expectations. Program-level QI learning is assessing and modifying the overall QI endeavor. The nature of project-level QI learning was similar across sites, whereas we identified qualitative differences across organizations in program-level QI learning. The highest performing organization was evaluating and refining its overall approach to QI, whereas the others were learning how to build and control QI programs. Practice Implications: Program-level QI learning may be key if a QI program is to succeed in improving patient outcomes. This type of organizational learning entails a big-picture, organization-wide view of QI. It also entails second-order organizational learning based on assessment not only of whether QI is being done correctly but also whether the right QI activities are being done, for the right reasons. The organization is "learning to learn.'' In addition to gaining mastery and control of QI, leaders regularly engage with staff in rethinking QI and experimenting with new approaches. Leaders also assess how QI activity fits in the organization's developmental journey and how it supports realization of strategy. C1 [Rivard, Peter E.] Suffolk Univ, Sawyer Business Sch, Boston, MA 02114 USA. [Parker, Victoria A.; Rosen, Amy K.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Rosen, Amy K.] VA Boston Healthcare Syst, COLMR, Boston, MA USA. RP Rivard, PE (reprint author), Suffolk Univ, Sawyer Business Sch, Boston, MA 02114 USA. EM privard@suffolk.edu; vaparker@bu.edu; akrosen@bu.edu OI Parker, Victoria/0000-0002-7632-9174 NR 34 TC 3 Z9 3 U1 3 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0361-6274 J9 HEALTH CARE MANAGE R JI Health Care Manage. Rev. PD JAN-MAR PY 2013 VL 38 IS 1 BP 40 EP 50 DI 10.1097/HMR.0b013e318245019f PG 11 WC Health Policy & Services SC Health Care Sciences & Services GA 050QZ UT WOS:000312070400005 PM 22269781 ER PT J AU Laghi, F Fernandez, R AF Laghi, Franco Fernandez, Rafael TI Noninvasive ventilation for weaning in hypoxemic respiratory failure: not ready for prime time (vol 38, pg 1583, 2012) SO INTENSIVE CARE MEDICINE LA English DT Correction C1 [Laghi, Franco] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. [Laghi, Franco] Loyola Univ, Stritch Sch Med, Vet Affairs Edward Hines Jr Hosp, Maywood, IL 60153 USA. [Fernandez, Rafael] Deu Fundacio Althaia, Hosp St Joan de, Intens Care Unit, Manresa, Spain. [Fernandez, Rafael] Univ Int Catalunya, Sant Cugat Del Valles, Spain. [Fernandez, Rafael] CIBERES Grp 33, Sabadell, Spain. RP Laghi, F (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, 111N,5th Ave & Roosevelt Rd, Hines, IL 60141 USA. EM flaghi@lumc.edu RI Fernandez, Rafael/A-9586-2010 OI Fernandez, Rafael/0000-0001-5711-5317 NR 1 TC 0 Z9 0 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD JAN PY 2013 VL 39 IS 1 BP 162 EP 162 DI 10.1007/s00134-012-2741-7 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 052JK UT WOS:000312193700026 ER PT J AU Lau, T Weinstein, M Wakamatsu, M Macklin, EA Pulliam, S AF Lau, Trevin Weinstein, Milena Wakamatsu, May Macklin, Eric A. Pulliam, Samantha TI Low back pain does not improve with surgical treatment of pelvic organ prolapse SO INTERNATIONAL UROGYNECOLOGY JOURNAL LA English DT Article DE Low back pain; Pelvic organ prolapse; Outcomes of surgical management AB Our goal was to determine if there is a correlation between low back pain (LBP) and pelvic organ prolapse (POP) by assessing for change in LBP after surgical correction of prolapse. Patients undergoing POP surgery were recruited to participate. They completed the Oswestry Disability Index (ODI), a validated back pain questionnaire, at their preoperative and postoperative visits at 1, 3, and 6 months. A higher ODI score (0-100) represents more severe disability. A 9-point change represents a minimal clinically important difference (MCID). The primary outcome was the change in ODI scores from preoperative to 3 months postoperative. We analyzed ODI scores with repeated measures analysis of variance (ANOVA). Power analysis showed that a sample size of 50 was needed for 88 % power to resolve a MCID on ODI. A total of 51 patients were recruited and 43 (84 %), 34 (67 %), and 36 (71 %) completed the 1-, 3-, and 6-month follow-up, respectively. The mean ODI scores at the preoperative and the 1-, 3-, and 6-month postoperative visits were 15, 19, 9, and 9. The mean ODI score from preoperative to 3 months postoperative improved by 5 points [confidence interval (CI) -9.2 to -0.5, p = 0.03]. Of the participants 7 (20.6 %, CI 11-35 %) experienced a MCID improvement, 24 (70.6 %, CI 56-83 %) reported no substantial change, and 3 (8.8 %, CI 3-20 %) experienced a MCID worsening. Our study found a statistically significant but not clinically significant improvement of LBP after surgical repair of prolapse. C1 [Lau, Trevin; Macklin, Eric A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Lau, T (reprint author), Massachusetts Gen Hosp, Ctr Biostat, 55 Fruit St,Founders 444, Boston, MA 02114 USA. EM tlau1@partners.org RI Macklin, Eric/E-2955-2013 OI Macklin, Eric/0000-0003-1618-3502 NR 8 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-3462 J9 INT UROGYNECOL J JI Int. Urogynecol. J. PD JAN PY 2013 VL 24 IS 1 BP 147 EP 153 DI 10.1007/s00192-012-1797-9 PG 7 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA 064JX UT WOS:000313072300020 PM 22618206 ER PT J AU Ford, LS Bloom, KA Nowak-Wegrzyn, AH Shreffler, WG Masilamani, M Sampson, HA AF Ford, Lara S. Bloom, Katherine A. Nowak-Wegrzyn, Anna H. Shreffler, Wayne G. Masilamani, Madhan Sampson, Hugh A. TI Basophil reactivity, wheal size, and immunoglobulin levels distinguish degrees of cow's milk tolerance SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Cow's milk allergy; tolerance; extensively heated; baked; immunotherapy; immunomodulation; biomarker; basophil activation ID FOOD CHALLENGES; SERUM IGE; CHILDREN; ALLERGY; HYPERSENSITIVITY; HISTAMINE; RELEASE; TESTS AB Background: In our previous study about 75% of children with cow's milk allergy tolerated baked milk products, which improved their prognosis and quality of life. Objective: We sought to identify biomarkers of varying degrees of clinical tolerance among a cohort of children with cow's milk allergy. Methods: One hundred thirty-two subjects were initially classified as baked milk-reactive, baked milk-tolerant, or having "outgrown milk allergy'' based on the results of oral food challenges. The baked milk-tolerant group was then divided into 3 groups based on the amount and degree of heat-denatured milk protein that they could tolerate. Serum was analyzed for allergen-specific IgE and IgG(4) levels, basophil reactivity was assessed in whole blood stimulated with serial 10-fold dilutions of milk protein, and skin prick tests (SPTs) were performed to commercial milk extract. Activated basophils were defined by using flow cytometry as CD63(bright)CD203c(+)CD123(+)HLA-DR(dim/-)CD41a(-)lineage(-). Data were analyzed by using the Jonckheere-Terpstra test. Results: Significant differences across the 5 clinical groups were seen for median casein-and milk-specific IgE levels, casein-specific IgG(4) levels, and casein IgE/IgG(4) ratios; milk-specific to nonspecific basophil activation ratio, median basophil reactivity, and spontaneous basophil activation (CD203c expression after stimulation with RPMI); and milk SPT wheal diameters. Casein-and milk-specific IgE level, milk-specific basophil reactivity, and milk SPT wheal diameter are all significantly greater among patients with milk allergy who react to baked milk than among those who tolerate it. Conclusions: The majority of patients with milk allergy are able to tolerate some forms of baked milk in their diets. Different phenotypes of children with cow's milk allergy can be distinguished by casein-and milk-specific IgE levels, milk-specific basophil reactivity, and milk SPT mean wheal diameters. Spontaneous basophil activation is greater among patients with more severe clinical milk reactivity. (J Allergy Clin Immunol 2013;131:180-6.) C1 [Sampson, Hugh A.] Mt Sinai Sch Med, Dept Pediat, Jaffe Food Allergy Inst, New York, NY 10029 USA. [Shreffler, Wayne G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sampson, HA (reprint author), Mt Sinai Sch Med, Dept Pediat, Jaffe Food Allergy Inst, 1 Gustave L Levy Pl,Box 1198, New York, NY 10029 USA. EM Hugh.Sampson@mssm.edu OI Masilamani, Madhan/0000-0001-8181-8848 FU National Institutes of Health/National Institute of Allergy and Infectious Diseases [AI44236, AI066738]; National Center for Research Resources [RR026134]; AAAAI/Elliot; Roslyn Jaffe Third-Year Fellowship Food Allergy Research Award at Mount Sinai School of Medicine; American Academy of Allergy, Asthma & Immunology (AAAAI) Jaffe Third-Year Fellowship Food Allergy Research Award; chair of the AAAAI Fellow-in-Training Committee; Food Allergy Initiative (FAI); National Institute of Allergy and Infectious Diseases (NIAID)/National Institutes of Health (NIH) FX H.A.S. is funded in part by grants from the National Institutes of Health/National Institute of Allergy and Infectious Diseases (AI44236 and AI066738) and the National Center for Research Resources (RR026134). L.S.F. is funded by the AAAAI/Elliot and Roslyn Jaffe Third-Year Fellowship Food Allergy Research Award at Mount Sinai School of Medicine.; Disclosure of potential conflict of interest: L. S. Ford has received research support from the American Academy of Allergy, Asthma & Immunology (AAAAI) Jaffe Third-Year Fellowship Food Allergy Research Award and is chair of the AAAAI Fellow-in-Training Committee. H. A. Sampson is a consultant for Allertein Therapeutics, LLC; is on the advisory board for Immusan T and Novartis; has received research support from the Food Allergy Initiative (FAI) and the National Institute of Allergy and Infectious Diseases (NIAID)/National Institutes of Health (NIH); is a consultant and scientific advisor for the FAI; is a medical advisor for the Food Allergy & Anaphylaxis Network; is a scientific advisor for the University of Nebraska-FARRP; and is 45% owner of Herb Springs, LLC. The rest of the authors declare that they have no relevant conflicts of interest. NR 25 TC 47 Z9 49 U1 1 U2 17 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2013 VL 131 IS 1 BP 180 EP U261 DI 10.1016/j.jaci.2012.06.003 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA 062YR UT WOS:000312961200023 PM 22819512 ER PT J AU Julian, L Serafin, D Charvet, L Ackerson, J Benedict, R Braaten, E Brown, T O'Donnell, E Parrish, J Preston, T Zaccariello, M Belman, A Chitnis, T Gorman, M Ness, J Patterson, M Rodriguez, M Waubant, E Weinstock-Guttman, B Yeh, A Krupp, LB AF Julian, Laura Serafin, Dana Charvet, Leigh Ackerson, Joseph Benedict, Ralph Braaten, Ellen Brown, Tanya O'Donnell, Ellen Parrish, Joy Preston, Thomas Zaccariello, Michael Belman, Anita Chitnis, Tanuja Gorman, Mark Ness, Jayne Patterson, Marc Rodriguez, Moses Waubant, Emmanuelle Weinstock-Guttman, Bianca Yeh, Ann Krupp, Lauren B. CA Network Pediat MS Ctr Excellence TI Cognitive Impairment Occurs in Children and Adolescents With Multiple Sclerosis: Results From a United States Network SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE multiple sclerosis; cognition; clinically isolated syndrome; demyelination ID PSYCHOSOCIAL FEATURES; JUVENILE MS; FOLLOW-UP; CHILDHOOD; PERFORMANCE AB In the largest sample studied to date, we measured cognitive functioning in children and adolescents with pediatric multiple sclerosis (n = 187) as well as those with clinically isolated syndrome (n = 44). Participants were consecutively enrolled from six United States PediatricMultiple Sclerosis Centers of Excellence. Participants had a mean of 14.8 +/- 2.6 years of age and an average disease duration of 1.9 +/- 2.2 years. A total of 65 (35%) children with multiple sclerosis and 8 (18%) with clinically isolated syndrome met criteria for cognitive impairment. The most frequent areas involved were fine motor coordination (54%), visuomotor integration (50%), and speeded information processing (35%). A diagnosis of multiple sclerosis (odds ratio = 3.60, confidence interval = 1.07, 12.36, P=.04) and overall neurologic disability (odds ratio = 1.47, confidence interval = 1.10, 2.10, P=.03) were the only independent predictors of cognitive impairment. Cognitive impairment may occur early in these patients, and prompt recognition is critical for their care. C1 [Serafin, Dana; Charvet, Leigh; Preston, Thomas; Belman, Anita; Krupp, Lauren B.] SUNY Stony Brook, Dept Neurol, Med Ctr, Stony Brook, NY 11794 USA. [Julian, Laura] Univ Calif San Francisco, Dept Neuropsychol, San Francisco, CA 94143 USA. [Ackerson, Joseph] Univ Alabama Birmingham, Dept Psychiat & Behav Neurobiol, Birmingham, AL 35294 USA. [Benedict, Ralph; Weinstock-Guttman, Bianca; Yeh, Ann] SUNY Buffalo, Dept Neurol, Jacobs Neurol Inst, Buffalo, NY 14260 USA. [Braaten, Ellen; O'Donnell, Ellen] Massachusetts Gen Hosp, Dept Psychol, Boston, MA 02114 USA. [Brown, Tanya; Zaccariello, Michael] Mayo Clin, Dept Psychiat & Psychol, Rochester, MN USA. [Parrish, Joy] SUNY Buffalo, Dept Neuropsychol, Jacobs Neurol Inst, Buffalo, NY 14260 USA. [Chitnis, Tanuja; Gorman, Mark] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Ness, Jayne] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Patterson, Marc; Rodriguez, Moses] Mayo Clin, Dept Neurol, Rochester, MN USA. [Waubant, Emmanuelle] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. RP Krupp, LB (reprint author), SUNY Stony Brook, Dept Neurol, Med Ctr, HSC Level 12,Room 020, Stony Brook, NY 11794 USA. EM Lauren.krupp@stonybrook.edu OI Rodriguez, Moses/0000-0001-6328-6497; Charvet, Leigh/0000-0003-4429-9713; Patterson, Marc/0000-0002-1116-126X FU Accorda; Biogen Idec; Shire; Psychological Assessment Resources; Merck-Serono; NIH; Actelion; Roche; Sanofi-Aventis; Teva Neurosciences; EMD Serono; Pfizer; Novartis; Genzyme; Acorda; ITN; Questcor; Zymogenetics; Ortho-McNeill Pharmaceutical; ER Squibb Sons; Genentech; BiogenIdec; Celgene Corporation; Garnett McKeen Laboratory Incorporated; Slomo and Cindy Silvian Foundation; MS Foundation; Lourie Foundation; National Multiple Sclerosis Society FX The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: LJ is currently employed by Genentech. RHBB has served as a consultant for Actelion, Biogen Idec, Bayer, and Novartis; received grant/research support from Accorda, Biogen Idec, and Shire; and also receives royalties from Psychological Assessment Resources. TC has served as a consultant for Biogen-Idec, Sanofi Aventis, Novartis, EMD-Serono, and Teva Neurosciences, and has received grant support from Merck-Serono for unrelated activities. MG has research funding from NIH and Actelion. He has done consulting for Actelion, Shire HGT and Orphazyme and DMSB for Stem cells, Inc; Amicus and Shire HGT. EW has acted as an advisor/consultant/advisory board member or speaker for Actelion, Roche, Sanofi Aventis, and Teva, and has received research support from Biogen Idec, Roche, and Sanofi-Aventis. BWG has participated in speakers bureaus and served as a consultant for Biogen Idec, Teva Neurosciences, EMD Serono, Pfizer, Novartis, Genzyme, and Acorda; excluding Genzyme, she also has received grant/research support from the agencies listed above as well as ITN, Questcor, and Shire. LBK serves as a consultant and/or on the speakers' bureau for Teva Neurosciences, Biogen Idec, EMD Serono, MEDA Corp, Acorda, Betaseron/Bayer Healthcare Pharmaceuticals, Gerson Lehrman Group, Guidepoint Global, Adler, Cohen, Harvey, Wakeman & Guekguezian, and Daniel J. Edelman; receives royalties from Genzyme, Zymogenetics, Ortho-McNeill Pharmaceutical, and ER Squibb & Sons; and receives research support from Genentech, BiogenIdec, Teva Neurosciences, Celgene Corporation, Garnett McKeen Laboratory Incorporated, NIH, Slomo and Cindy Silvian Foundation, MS Foundation, and the Lourie Foundation. Rest of the authors report no disclosures.; The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported in part by the National Multiple Sclerosis Society. NR 32 TC 36 Z9 36 U1 3 U2 22 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD JAN PY 2013 VL 28 IS 1 BP 102 EP 107 DI 10.1177/0883073812464816 PG 6 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 059GX UT WOS:000312693500016 PM 23155206 ER PT J AU Basile, JN Bloch, MJ AF Basile, Jan N. Bloch, Michael J. TI Analysis of Recent Papers in Hypertension Nighttime Administration of At Least One Antihypertensive Medication is Associated With Better Blood Pressure Control and Cardiovascular Outcomes in Patients With Type 2 Diabetes or Chronic Kidney Disease SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article ID RISK C1 [Bloch, Michael J.] Univ Nevada, Sch Med, Dept Internal Med, Reno, NV 89557 USA. [Basile, Jan N.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Div Gen Internal Med Geriatr, Seinsheimer Cardiovasc Hlth Program, Charleston, SC 29425 USA. RP Bloch, MJ (reprint author), Univ Hlth Syst, 1500 E 2nd St,Suite 302, Reno, NV 89502 USA. EM mbloch@aol.com NR 2 TC 2 Z9 3 U1 0 U2 1 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 JAN PY 2013 VL 15 IS 1 BP 2 EP 4 DI 10.1111/jch.12028 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 063JN UT WOS:000312993600002 PM 23282118 ER PT J AU Rosendorff, C Jogendra, MRD AF Rosendorff, Clive Jogendra, Mather R. D. TI Uric Acid: Where Are We? SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Editorial Material ID CHRONIC HEART-FAILURE; XANTHINE-OXIDASE INHIBITION; ENDOTHELIAL DYSFUNCTION; BLOOD-PRESSURE; RENAL-DISEASE; RISK-FACTOR; ALLOPURINOL; MORTALITY; HYPERURICEMIA; HYPERTENSION C1 [Rosendorff, Clive; Jogendra, Mather R. D.] James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Rosendorff, Clive; Jogendra, Mather R. D.] Mt Sinai Sch Med, Dept Med Cardiol, New York, NY USA. RP Rosendorff, C (reprint author), James J Peters VA Med Ctr, Med 111,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM clive.rosendorff@va.gov NR 24 TC 2 Z9 2 U1 0 U2 6 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 JAN PY 2013 VL 15 IS 1 BP 5 EP 6 DI 10.1111/jch.12034 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 063JN UT WOS:000312993600003 PM 23282119 ER PT J AU Khrizman, P Niland, JC ter Veer, A Milne, D Dunn, KB Carson, WE Engstrom, PF Shibata, S Skibber, JM Weiser, MR Schrag, D Benson, AB AF Khrizman, Polina Niland, Joyce C. ter Veer, Anna Milne, Dana Dunn, Kelli Bullard Carson, William E., III Engstrom, Paul F. Shibata, Stephen Skibber, John M. Weiser, Martin R. Schrag, Deborah Benson, Al B., III TI Postoperative Adjuvant Chemotherapy Use in Patients With Stage II/III Rectal Cancer Treated With Neoadjuvant Therapy: A National Comprehensive Cancer Network Analysis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID III COLON-CANCER; FEE-FOR-SERVICE; HEALTH MAINTENANCE ORGANIZATION; POPULATION-BASED COHORT; COLORECTAL-CANCER; PREOPERATIVE CHEMORADIATION; ELDERLY-PATIENTS; CLINICAL DOCUMENTATION; MEDICAL OUTCOMES; CARE AB Purpose Practice guidelines recommend that patients who receive neoadjuvant chemotherapy and radiation for locally advanced rectal cancer complete postoperative adjuvant systemic chemotherapy, irrespective of tumor downstaging. Patients and Methods The National Comprehensive Cancer Network (NCCN) Colorectal Cancer Database tracks longitudinal care for patients treated at eight specialty cancer centers across the United States and was used to evaluate how frequently patients with rectal cancer who were treated with neoadjuvant chemotherapy also received postoperative systemic chemotherapy. Patient and tumor characteristics were examined in a multivariable logistic regression model. Results Between September 2005 and December 2010, 2,073 patients with stage II/III rectal cancer were enrolled in the database. Of these, 1,193 patients receiving neoadjuvant chemoradiotherapy were in the analysis, including 203 patients not receiving any adjuvant chemotherapy. For those seen by a medical oncologist, the most frequent reason chemotherapy was not recommended was comorbid illness (25 of 50, 50%); the most frequent reason chemotherapy was not received even though it was recommended or discussed was patient refusal (54 of 74, 73%). After controlling for NCCN Cancer Center and clinical TNM stage in a multivariable logistic model, factors significantly associated with not receiving adjuvant chemotherapy were age, Eastern Cooperative Oncology Group performance status >= 1, on Medicaid or indigent compared with private insurance, complete pathologic response, presence of re-operation/wound infection, and no closure of ileostomy/colostomy. Conclusion Even at specialty cancer centers, a sizeable minority of patients with rectal cancer treated with curative-intent neoadjuvant chemoradiotherapy do not complete postoperative chemotherapy. Strategies to facilitate the ability to complete this third and final component of curative intent treatment are necessary. J Clin Oncol 31:30-38. (c) 2012 by American Society of Clinical Oncology C1 [Benson, Al B., III] Northwestern Univ, Div Hematol Oncol, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 66011 USA. [Niland, Joyce C.; ter Veer, Anna; Shibata, Stephen] City Hope Comprehens Canc Ctr, Los Angeles, CA USA. [Milne, Dana; Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dunn, Kelli Bullard] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Weiser, Martin R.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Carson, William E., III] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Carson, William E., III] Solove Res Inst, Columbus, OH 43210 USA. [Engstrom, Paul F.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Skibber, John M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Benson, AB (reprint author), Northwestern Univ, Div Hematol Oncol, Robert H Lurie Comprehens Canc Ctr, 676 N St Clair,Ste 850, Chicago, IL 66011 USA. EM a-benson@northwestern.edu RI Carson, William/E-2846-2011 NR 52 TC 28 Z9 29 U1 1 U2 12 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 JAN 1 PY 2013 VL 31 IS 1 BP 30 EP 38 DI 10.1200/JCO.2011.40.3188 PG 9 WC Oncology SC Oncology GA 062IE UT WOS:000312911900014 PM 23169502 ER PT J AU Rosenthal, AN Fraser, L Manchanda, R Badman, P Philpott, S Mozersky, J Hadwin, R Cafferty, FH Benjamin, E Singh, N Evans, DG Eccles, DM Skates, SJ Mackay, J Menon, U Jacobs, IJ AF Rosenthal, Adam N. Fraser, Lindsay Manchanda, Ranjit Badman, Philip Philpott, Susan Mozersky, Jessica Hadwin, Richard Cafferty, Fay H. Benjamin, Elizabeth Singh, Naveena Evans, D. Gareth Eccles, Diana M. Skates, Steven J. Mackay, James Menon, Usha Jacobs, Ian J. TI Results of Annual Screening in Phase I of the United Kingdom Familial Ovarian Cancer Screening Study Highlight the Need for Strict Adherence to Screening Schedule SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID REDUCING SALPINGO-OOPHORECTOMY; RANDOMIZED CONTROLLED-TRIAL; MUTATION CARRIERS; BRCA2 MUTATIONS; LYNCH-SYNDROME; HIGH-RISK; WOMEN; BREAST; POPULATION; PENETRANCE AB Purpose To establish the performance characteristics of annual transvaginal ultrasound and serum CA125 screening for women at high risk of ovarian/fallopian tube cancer (OC/FTC) and to investigate the impact of delayed screening interval and surgical intervention. Patients and Methods Between May 6, 2002, and January 5, 2008, 3,563 women at an estimated >= 10% lifetime risk of OC/FTC were recruited and screened by 37 centers in the United Kingdom. Participants were observed prospectively by centers, questionnaire, and national cancer registries. Results Sensitivity for detection of incident OC/FTC at 1 year after last annual screen was 81.3% (95% CI, 54.3% to 96.0%) if occult cancers were classified as false negatives and 87.5% (95% CI, 61.7% to 98.5%) if they were classified as true positives. Positive and negative predictive values of incident screening were 25.5% (95% CI, 14.3 to 40.0) and 99.9% (95% CI, 99.8 to 100) respectively. Four (30.8%) of 13 incident screen-detected OC/FTCs were stage I or II. Compared with women screened in the year before diagnosis, those not screened in the year before diagnosis were more likely to have >= stage IIIc disease (85.7% v 26.1%; P = .009). Screening interval was delayed by a median of 88 days before detection of incident OC/FTC. Median interval from detection screen to surgical intervention was 79 days in prevalent and incident OC/FTC. Conclusion These results in the high-risk population highlight the need for strict adherence to screening schedule. Screening more frequently than annually with prompt surgical intervention seems to offer a better chance of early-stage detection. J Clin Oncol 31:49-57. (c) 2012 by American Society of Clinical Oncology C1 [Rosenthal, Adam N.] Queen Mary Univ London, Ctr Mol Oncol, Barts & London Sch Med & Dent, John Vane Sci Ctr,Barts Canc Inst, London EC1M 6BQ, England. [Rosenthal, Adam N.; Fraser, Lindsay; Manchanda, Ranjit; Badman, Philip; Philpott, Susan; Mozersky, Jessica; Hadwin, Richard; Mackay, James; Menon, Usha; Jacobs, Ian J.] UCL, London WC1E 6BT, England. [Singh, Naveena] Barts & London Natl Hlth Serv Trust, London, England. [Evans, D. Gareth] St Marys Hosp Manchester, Manchester, Lancs, England. [Eccles, Diana M.] Southampton Gen Hosp, Southampton SO9 4XY, Hants, England. [Skates, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Skates, Steven J.] Harvard Univ, Sch Med, Boston, MA USA. RP Rosenthal, AN (reprint author), Queen Mary Univ London, Ctr Mol Oncol, Barts & London Sch Med & Dent, John Vane Sci Ctr,Barts Canc Inst, Charterhouse Sq, London EC1M 6BQ, England. EM a.rosenthal@qmul.ac.uk OI Rosenthal, Adam/0000-0001-6924-0721; Evans, Gareth/0000-0002-8482-5784 FU Cancer Research UK [C315/A2621, C1005/A6383]; UK Department of Health; Eve Appeal; National Cancer Institute Early Detection Research Network [CA152990, CA086381]; National Institute for Health Research University College London (UCL) Hospitals/UCL Comprehensive Biomedical Research Centre; Bupa Foundation; Cancer Research UK; Fujirebio Diagnostics; Medical Research Council; National Institute for Health Research; National Institutes of Health FX Supported by Cancer Research UK (Grants No. C315/A2621 and C1005/A6383), the UK Department of Health, and the Eve Appeal and in part by the National Cancer Institute Early Detection Research Network (Grants No. CA152990 and CA086381) and the National Institute for Health Research University College London (UCL) Hospitals/UCL Comprehensive Biomedical Research Centre (research team at UCL coordinating center).; Adam N. Rosenthal, Cancer Research UK, Eve Appeal, UK Department of Health, Bupa Foundation; Lindsay Fraser, Cancer Research UK; Steven J. Skates, Fujirebio Diagnostics; Usha Menon, Medical Research Council, Cancer Research UK, National Institute for Health Research, National Institutes of Health; Ian J. Jacobs, Medical Research Council, Cancer Research UK, Beckton Dickinson NR 43 TC 37 Z9 38 U1 0 U2 4 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 JAN 1 PY 2013 VL 31 IS 1 BP 49 EP 57 DI 10.1200/JCO.2011.39.7638 PG 9 WC Oncology SC Oncology GA 062IE UT WOS:000312911900016 PM 23213100 ER PT J AU Azim, HA Kroman, N Paesmans, M Gelber, S Rotmensz, N Ameye, L De Mattos-Arruda, L Pistilli, B Pinto, A Jensen, MB Cordoba, O de Azambuja, E Goldhirsch, A Piccart, MJ Peccatori, FA AF Azim, Hatem A., Jr. Kroman, Niels Paesmans, Marianne Gelber, Shari Rotmensz, Nicole Ameye, Lieveke De Mattos-Arruda, Leticia Pistilli, Barbara Pinto, Alvaro Jensen, Maj-Britt Cordoba, Octavi de Azambuja, Evandro Goldhirsch, Aron Piccart, Martine J. Peccatori, Fedro A. TI Prognostic Impact of Pregnancy After Breast Cancer According to Estrogen Receptor Status: A Multicenter Retrospective Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FERTILITY PRESERVATION; SURVIVORS; DIAGNOSIS; BEHAVIOR; SAFETY; YOUNG; WOMEN AB Purpose We questioned the impact of pregnancy on disease-free survival (DFS) in women with history of breast cancer (BC) according to estrogen receptor (ER) status. Patients and Methods A multicenter, retrospective cohort study in which patients who became pregnant any time after BC were matched (1:3) to patients with BC with similar ER, nodal status, adjuvant therapy, age, and year of diagnosis. To adjust for guaranteed time bias, each nonpregnant patient had to have a disease-free interval at least equal to the time elapsing between BC diagnosis and date of conception of the matched pregnant one. The primary objective was DFS in patients with ER-positive BC. DFS in the ER-negative cohort, whole population, and overall survival (OS) were secondary objectives. Subgroup analyses included DFS according to pregnancy outcome and BC-pregnancy interval. With a two-sided alpha = 5% and beta = 20%, 645 ER-positive patients were required to detect a hazard ratio (HR) = 0.65. Results A total of 333 pregnant patients and 874 matched nonpregnant patients were analyzed, of whom 686 patients had an ER-positive disease. No difference in DFS was observed between pregnant and nonpregnant patients in the ER-positive (HR = 0.91; 95% CI, 0.67 to 1.24, P = .55) or the ER-negative (HR = 0.75; 95% CI, 0.51 to 1.08, P = .12) cohorts. However, the pregnant group had better OS (HR = 0.72; 95% CI, 0.54 to 0.97, P = .03), with no interaction according to ER status (P = .11). Pregnancy outcome and BC-pregnancy interval did not seem to impact the risk of relapse. Conclusion Pregnancy after ER-positive BC does not seem to reduce the risk of BC recurrence. J Clin Oncol 31:73-79. (c) 2012 by American Society of Clinical Oncology C1 [Azim, Hatem A., Jr.] Univ Libre Brussels, Inst Jules Bordet, BrEAST Data Ctr, B-1000 Brussels, Belgium. [Kroman, Niels; Jensen, Maj-Britt] Rigshosp, Danish Breast Canc Cooperat Grp, DK-2100 Copenhagen, Denmark. [Gelber, Shari] Dana Farber Canc Inst, Int Breast Canc Study Grp, Ctr Stat, Boston, MA 02115 USA. [Rotmensz, Nicole; Goldhirsch, Aron; Peccatori, Fedro A.] European Inst Oncol, Milan, Italy. [Pistilli, Barbara] Macerata Hosp, Macerata, Italy. [De Mattos-Arruda, Leticia; Cordoba, Octavi] Vall DHebron Univ Hosp, Barcelona, Spain. [Pinto, Alvaro] La Paz Univ Hosp, Madrid, Spain. RP Azim, HA (reprint author), Univ Libre Brussels, Inst Jules Bordet, BrEAST Data Ctr, Blvd Waterloo 121, B-1000 Brussels, Belgium. EM hatem.azim@bordet.be OI Cordoba, Octavi/0000-0002-9591-7430 FU Les Amis de l'Institut Bordet [2012-09]; European School of Oncology; European Society for Medical Oncology; National Institutes of Health [CA-753562] FX Supported by grants from Les Amis de l'Institut Bordet (Grant No. 2012-09) and the European School of Oncology. H.A.A. Jr and L.D.M.-A. are supported by fellowship grants from the European Society for Medical Oncology. The International Breast Cancer Study Group trial, which provided patient information for this study, was partially funded by the National Institutes of Health (Grant No. CA-753562). NR 22 TC 63 Z9 64 U1 0 U2 10 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 JAN 1 PY 2013 VL 31 IS 1 BP 73 EP 79 DI 10.1200/JCO.2012.44.2285 PG 7 WC Oncology SC Oncology GA 062IE UT WOS:000312911900019 PM 23169515 ER PT J AU Roth, BJ Krilov, L Adams, S Aghajanian, CA Bach, P Braiteh, F Brose, MS Ellis, LM Erba, H George, DJ Gilbert, MR Jacobson, JO Larsen, EC Lichtman, SM Partridge, AH Patel, JD Quinn, DI Robison, LL von Roenn, JH Samlowski, W Schwartz, GK Vogelzang, NJ AF Roth, Bruce J. Krilov, Lada Adams, Sylvia Aghajanian, Carol A. Bach, Peter Braiteh, Fadi Brose, Marcia S. Ellis, Lee M. Erba, Harry George, Daniel J. Gilbert, Mark R. Jacobson, Joseph O. Larsen, Eric C. Lichtman, Stuart M. Partridge, Ann H. Patel, Jyoti D. Quinn, David I. Robison, Leslie L. von Roenn, Jamie H. Samlowski, Wolfram Schwartz, Gary K. Vogelzang, Nicholas J. TI Clinical Cancer Advances 2012: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID EPITHELIAL OVARIAN-CANCER; COLORECTAL-CANCER; RANDOMIZED-TRIAL; PHASE-3 TRIAL; BREAST-CANCER; OPEN-LABEL; MULTIPLE-MYELOMA; DRUG-SENSITIVITY; COLON-CANCER; LUNG-CANCER C1 [Krilov, Lada] Amer Soc Clin Oncol, Alexandria, VA 22314 USA. [Roth, Bruce J.] Washington Univ, St Louis, MO USA. [Adams, Sylvia] NYU, New York, NY USA. [Aghajanian, Carol A.; Bach, Peter; Lichtman, Stuart M.; Schwartz, Gary K.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Braiteh, Fadi; Vogelzang, Nicholas J.] Comprehens Canc Ctr Nevada, US Oncol Res, Las Vegas, NV USA. [Samlowski, Wolfram] Nevada Canc Inst, US Oncol Res, Las Vegas, NV USA. [Brose, Marcia S.] Univ Penn, Philadelphia, PA 19104 USA. [Ellis, Lee M.; Gilbert, Mark R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Erba, Harry] Univ Alabama Birmingham, Birmingham, AL USA. [George, Daniel J.] Duke Univ, Med Ctr, Durham, NC USA. [Jacobson, Joseph O.; Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Larsen, Eric C.] Maine Med Ctr, Portland, ME 04102 USA. [Patel, Jyoti D.] Northwestern Univ, Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [von Roenn, Jamie H.] NW Mem Hosp, Chicago, IL 60611 USA. [Quinn, David I.] Univ So Calif, Los Angeles, CA USA. [Robison, Leslie L.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. RP Krilov, L (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA. EM lada.krilov@asco.org RI Quinn, David/F-4343-2015; Gilbert, Mark/J-7494-2016 OI Quinn, David/0000-0002-1411-0417; Samlowski, Wolfram/0000-0002-0713-914X; Gilbert, Mark/0000-0003-2556-9722 FU Eli Lilly; Pfizer; Genentech; Merrimack; Medimmune; GlaxoSmithKline; Foundation Medicine; Exelixis; Ambit; Ascenta; Chroma; Genzyme; Millennium Pharmaceuticals; Novartis; sanofi-aventis; Sunesis; Janssen Pharmaceuticals; Merck; UCB Pharma; Bristol-Myers Squibb; Bayer HealthCare Pharmaceuticals; Takeda Pharmaceuticals; Astella Pharma FX Fadi Braiteh, Eli Lilly, Pfizer, Genentech, Merrimack, Medimmune, GlaxoSmithKline, Foundation Medicine; Marcia S. Brose, Exelixis; Harry Erba, Ambit, Ascenta, Chroma, Eli Lilly, Genzyme, Millennium Pharmaceuticals, Novartis, sanofi-aventis, Sunesis; Daniel J. George, Pfizer, Novartis, GlaxoSmithKline, Janssen Pharmaceuticals, Genentech, Exelixis, Millennium Pharmaceuticals; Mark R. Gilbert, Genentech, Merck, UCB Pharma; Jyoti D. Patel, Eli Lilly; Wolfram Samlowski, Bristol-Myers Squibb; Nicholas J. Vogelzang, Bayer HealthCare Pharmaceuticals, Takeda Pharmaceuticals, Astella Pharma NR 111 TC 25 Z9 27 U1 0 U2 18 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 JAN 1 PY 2013 VL 31 IS 1 BP 131 EP 161 DI 10.1200/JCO.2012.47.1938 PG 31 WC Oncology SC Oncology GA 062IE UT WOS:000312911900027 PM 23213095 ER PT J AU York, J Lamis, DA Friedman, L Berman, AL Joiner, TE Mcintosh, JL Silverman, MM Konick, L Gutierrez, PM Pearson, J AF York, Janet Lamis, Dorian A. Friedman, Lee Berman, Alan L. Joiner, Thomas E. Mcintosh, John L. Silverman, Morton M. Konick, Lisa Gutierrez, Peter M. Pearson, Jane TI A SYSTEMATIC REVIEW PROCESS TO EVALUATE SUICIDE PREVENTION PROGRAMS: A SAMPLE CASE OF COMMUNITY-BASED PROGRAMS SO JOURNAL OF COMMUNITY PSYCHOLOGY LA English DT Article ID CHILDHOOD HOME VISITATION; TOWER-OF-BABEL; REVISED NOMENCLATURE; ADOLESCENT SUICIDE; YOUTH; INTERVENTIONS; CURRICULUM; SERVICES; PERSPECTIVE; EXPERIENCE AB The Guide to Community Preventive Services (Guide), one of the most rigorous methods of systematic reviews, was adopted to evaluate the effectiveness of 16 community, primarily youth, suicide prevention interventions, through a multisectoral collaboration. The Guide steps for obtaining and evaluating evidence on effectiveness include: forming a multidisciplinary team; developing a conceptual approach to organizing, grouping, selecting, and evaluating the interventions; selecting the interventions; searching for and retrieving evidence; assessing the quality of and summarizing the body of evidence; translating the evidence of effectiveness into recommendations; considering additional evidence; and identifying and summarizing research gaps. The intervention effects were calculated using Hedge's g-type (standardized mean differences) effect sizes. The strength of the body of evidence was characterized on the basis of suitability of the study design for assessing effectiveness and quality of study execution. Results indicated that student curriculum, combined curriculum and gatekeeper training, and competence programs have a positive effect on adolescent's knowledge and attitudes about suicide, but only a negligible effect on suicidal behaviors. Five of 7 studies with moderate to large effect sizes on outcomes were also those with both good quality of execution and the greatest suitability of the design. Policy recommendations are offered for the improved evaluation of the effectiveness of suicide prevention programs in youth. C1 [York, Janet] Med Univ S Carolina, Charleston, SC USA. [Lamis, Dorian A.] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Friedman, Lee] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Joiner, Thomas E.] Florida State Univ, Tallahassee, FL 32306 USA. [Mcintosh, John L.] Indiana Univ S Bend, South Bend, IN 46615 USA. [Silverman, Morton M.] Univ Chicago, Chicago, IL 60637 USA. [Gutierrez, Peter M.] Univ Colorado, Sch Med, Boulder, CO 80309 USA. RP York, J (reprint author), Ralph H Johnson VAMC, VA Nursing Acad, 109 Bee St, Charleston, SC 29401 USA. EM Grossmja@musc.edu NR 61 TC 5 Z9 5 U1 2 U2 32 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0090-4392 J9 J COMMUNITY PSYCHOL JI J. Community Psychol. PD JAN PY 2013 VL 41 IS 1 BP 35 EP 51 DI 10.1002/jcop.21509 PG 17 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Social Work SC Public, Environmental & Occupational Health; Psychology; Social Work GA 057DI UT WOS:000312541900003 ER PT J AU Seshadri, C Turner, MT Lewinsohn, DM Moody, DB Van Rhijn, I AF Seshadri, Chetan Turner, Marie T. Lewinsohn, David M. Moody, D. Branch Van Rhijn, Ildiko TI Lipoproteins Are Major Targets of the Polyclonal Human T Cell Response to Mycobacterium tuberculosis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DENDRITIC CELLS; LIPID ANTIGENS; INFECTION; LIPOPEPTIDES; RECOGNITION; INHIBITION; EPITOPES; VACCINES; ANTIBODY; ACIDS AB Most vaccines and basic studies of T cell epitopes in Mycobacterium tuberculosis emphasize water-soluble proteins that are secreted into the extracellular space and presented in the context of MHC class II. Much less is known about the role of Ags retained within the cell wall. We used polyclonal T cells from infected humans to probe for responses to immunodominant Ags in the M. tuberculosis cell wall. We found that the magnitude of response to secreted or cell wall intrinsic compounds was similar among healthy controls, patients with latent tuberculosis, and patients with active tuberculosis. Individual responses to secreted Ags and cell wall extract were strongly correlated (r(2) = 0.495, p = 0.001), suggesting that T cells responding to cell wall and secreted Ags are present at similar frequency. Surprisingly, T cell stimulatory factors intrinsic to the cell wall partition into organic solvents; however, these responses are not explained by CD1-mediated presentation of lipids. Instead, we find that molecules soluble in organic solvents are dependent upon MHC class II and recognized by IFN-gamma-secreting CD4(+) T cells. We reasoned that MHC class II-dependent Ags extracting into lipid mixtures might be found among triacylated lipoproteins present in mycobacteria. We used M. tuberculosis lacking prolipoprotein signal peptidase A (lspA), an enzyme required for lipoprotein synthesis, to demonstrate loss of polyclonal T cell responses. Our results demonstrate the use of bacterial genetics to identify lipoproteins as an unexpected and immunodominant class of cell wall-associated Ags targeted by the polyclonal human T cell response to M. tuberculosis. The Journal of Immunology, 2013, 190: 278-284. C1 [Seshadri, Chetan; Moody, D. Branch; Van Rhijn, Ildiko] Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Turner, Marie T.] Lemuel Shattuck Hosp, TB Treatment Unit, Jamaica Plain, MA 02130 USA. [Lewinsohn, David M.] Portland VA Med Ctr, Dept Med, Div Pulm & Crit Care Med, Portland, OR 97239 USA. [Van Rhijn, Ildiko] Univ Utrecht, Fac Vet Med, Dept Infect Dis & Immunol, NL-3584 CL Utrecht, Netherlands. RP Seshadri, C (reprint author), Univ Washington, Dept Med, Div Allergy & Infect Dis, Seattle, WA 98195 USA. EM seshadri@u.washington.edu; I.vanRhijn@uu.nl RI Lewinsohn, David/I-4936-2013 OI Lewinsohn, David/0000-0001-9906-9494 FU National Institutes of Health [T32-AI007061, R01 AI 049313]; Irvington Institute Fellowship Program of the Cancer Research Institute; Nederlands Wetenschappelijk Onderzoek Meervoud Grant [836.08.001] FX This work was supported by National Institutes of Health Grants T32-AI007061 (to C.S.) and R01 AI 049313 (to D.B.M.), the Irvington Institute Fellowship Program of the Cancer Research Institute (to C.S.), and Nederlands Wetenschappelijk Onderzoek Meervoud Grant 836.08.001 (to I.V.R.). NR 33 TC 9 Z9 11 U1 0 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2013 VL 190 IS 1 BP 278 EP 284 DI 10.4049/jimmunol.1201667 PG 7 WC Immunology SC Immunology GA 061FB UT WOS:000312832500031 PM 23197260 ER PT J AU Tai, TS Pai, SY Ho, IC AF Tai, Tzong-Shyuan Pai, Sung-Yun Ho, I-Cheng TI GATA-3 Regulates the Homeostasis and Activation of CD8(+) T Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TRANSCRIPTION FACTOR GATA-3; DOWN-REGULATION; NKT CELLS; DIFFERENTIATION; EXPRESSION; LINEAGE; CD4; GENE; THYMUS; PROLIFERATION AB GATA-3, a C2C2-type zinc finger transcription factor, regulates many steps of T cell development and differentiation. It is also required for optimal production of type 2 cytokines by CD8(+) T cells. However, its role in the development and function of this subset of T cells is still poorly characterized. In this paper, we report that GATA-3 is required for MHC-mediated positive selection and final maturation of CD8 single-positive thymocytes. Deficiency of GATA-3 mediated by a CD4cre transgene led to age-dependent lymphadenopathy partly because of abnormal expansion of CD8(+) T cells driven by a cell-extrinsic mechanism. Paradoxically, GATA-3-deficient CD8(+) T cells were hyporesponsive to Ag stimulation due to a defect in the maintenance/progression, but not initiation, of activation signals. More importantly, GATA-3-deficient CD8(+) T cells were less efficient in killing Ag-bearing tumor cells in vivo. Taken together, our data further expand the role of GATA-3 in T cells. The Journal of Immunology, 2013, 190: 428-437. C1 [Tai, Tzong-Shyuan; Ho, I-Cheng] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Pai, Sung-Yun] Boston Childrens Hosp, Dept Pediat, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Pai, Sung-Yun] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Ho, I-Cheng] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ho, IC (reprint author), Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, 1 Jimmy Fund Way,Smith Bldg,Room 526, Boston, MA 02115 USA. EM iho@partners.org FU National Institutes of Health [AI054451, AI097724, AI50601] FX This work was supported by National Institutes of Health Grants AI054451 (to I-C.H.), AI097724 (to I-C.H.), and AI50601 (to S.-Y.P.). NR 34 TC 15 Z9 16 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2013 VL 190 IS 1 BP 428 EP 437 DI 10.4049/jimmunol.1201361 PG 10 WC Immunology SC Immunology GA 061FB UT WOS:000312832500048 PM 23225883 ER PT J AU Miller, M Knaub, L Olivera, L Reusch, JE AF Miller, M. Knaub, L. Olivera, L. Reusch, J. E. TI NITRIC OXIDE-MEDIATED CONTROL OF VASCULAR MITOCHONDRIAL DYNAMICS IN VIVO SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 24-26, 2013 CL Carmel, CA SP Amer Federat Med Res, Western Reg C1 [Miller, M.; Knaub, L.; Reusch, J. E.] Univ Colorado, Sch Med, Aurora, CO USA. [Reusch, J. E.] Denver VA Med Ctr, Denver, CO USA. [Olivera, L.] Univ Puerto Rico, Bayamon, PR 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 JAN PY 2013 VL 61 IS 1 MA 9 BP 113 EP 113 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 058TT UT WOS:000312657900017 ER PT J AU Heinze, E Chan, G Li, E Farmani, N Rubell, A Nishimura, RN Colburn, K Weisbart, RH AF Heinze, E. Chan, G. Li, E. Farmani, N. Rubell, A. Nishimura, R. N. Colburn, K. Weisbart, R. H. TI ONCOGENIC ACTIVATION OF MAPK IN RHEUMATOID ARTHRITIS SYNOVIAL FIBROBLASTS SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 24-26, 2013 CL Carmel, CA SP Amer Federat Med Res, Western Reg C1 [Heinze, E.; Farmani, N.] Olive View UCLA Med Ctr, Sylmar, CA 91342 USA. [Chan, G.; Li, E.; Rubell, A.; Weisbart, R. H.] Vet Affairs Greater Los Angeles Hlth Care Syst, Sepulveda, CA USA. [Nishimura, R. N.] Univ Calif Los Angeles, Los Angeles, CA USA. [Colburn, K.] Loma Linda Univ, Loma Linda, CA 92350 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 JAN PY 2013 VL 61 IS 1 MA 30 BP 119 EP 119 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 058TT UT WOS:000312657900038 ER PT J AU Mazumder, R Cameron, M AF Mazumder, R. Cameron, M. TI FATIGUE IN MULTIPLE SCLEROSIS: RELATED TO FEAR OF FALLING AND PRIOR FALLS BUT NOT TO FUTURE FALLS SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 24-26, 2013 CL Carmel, CA SP Amer Federat Med Res, Western Reg C1 [Mazumder, R.; Cameron, M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Cameron, M.] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 7 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 JAN PY 2013 VL 61 IS 1 MA 131 BP 148 EP 148 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 058TT UT WOS:000312657900139 ER PT J AU Miller, M Knaub, L Olivera, L Reusch, JE AF Miller, M. Knaub, L. Olivera, L. Reusch, J. E. TI NITRIC OXIDE-MEDIATED CONTROL OF VASCULAR MITOCHONDRIAL DYNAMICS IN VIVO SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 24-26, 2013 CL Carmel, CA SP Amer Federat Med Res, Western Reg C1 [Miller, M.; Knaub, L.; Reusch, J. E.] Univ Colorado, Sch Med, Aurora, CO USA. [Reusch, J. E.] Denver VA Med Ctr, Denver, CO USA. [Olivera, L.] Univ Puerto Rico, Bayamon, PR USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2013 VL 61 IS 1 MA 155 BP 155 EP 155 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 058TT UT WOS:000312657900163 ER PT J AU Salehi, A Noerholm, M Balaj, L Zhu, LD Skog, J Breakefield, XO Carter, B AF Salehi, A. Noerholm, M. Balaj, L. Zhu, L. D. Skog, J. Breakefield, X. O. Carter, B. TI RNA EXPRESSION PATTERNS IN SERUM MICROVESICLES FROM PATIENTS WITH GLIOBLASTOMA MULTIFORME AND CONTROLS SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 24-26, 2013 CL Carmel, CA SP Amer Federat Med Res, Western Reg C1 [Salehi, A.; Carter, B.] UCSD Sch Med, San Diego, CA USA. [Salehi, A.; Noerholm, M.; Balaj, L.; Zhu, L. D.; Skog, J.; Breakefield, X. O.; Carter, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2013 VL 61 IS 1 MA 159 BP 156 EP 156 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 058TT UT WOS:000312657900167 ER PT J AU Shin, BS Arom, GA Nazemi, AN Yeranosian, M Petrigliano, FA Wu, BM Zuk, PA McAllister, DR AF Shin, B. S. Arom, G. A. Nazemi, A. N. Yeranosian, M. Petrigliano, F. A. Wu, B. M. Zuk, P. A. McAllister, D. R. TI LIGAMENTOGENIC PROPERTIES OF BONE MARROW STROMA CELL SEEDED POLYCAPROLACTONE SCAFFOLDS IN VIVO SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 24-26, 2013 CL Carmel, CA SP Amer Federat Med Res, Western Reg C1 [Shin, B. S.; Arom, G. A.; Yeranosian, M.; Petrigliano, F. A.; Zuk, P. A.; McAllister, D. R.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Hlth Sci, Los Angeles, CA 90095 USA. [Arom, G. A.; Nazemi, A. N.; Wu, B. M.] Univ Calif Los Angeles, Henry Samueli Sch Engn & Appl Sci, Los Angeles, CA USA. [Arom, G. A.; Petrigliano, F. A.; McAllister, D. R.] W Los Angeles Healthcare Ctr, VA Greater Angeles Healthcare Syst, Tissue Engn Lab, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2013 VL 61 IS 1 MA 368 BP 215 EP 216 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 058TT UT WOS:000312657900375 ER PT J AU Salehi, A Noerholm, M Balaj, L Zhu, LD Skog, J Breakefield, XO Carter, B AF Salehi, A. Noerholm, M. Balaj, L. Zhu, L. D. Skog, J. Breakefield, X. O. Carter, B. TI RNA EXPRESSION PATTERNS IN SERUM MICROVESICLES FROM PATIENTS WITH GLIOBLASTOMA MULTIFORME AND CONTROLS SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 24-26, 2013 CL Carmel, CA SP Amer Federat Med Res, Western Reg C1 [Salehi, A.; Carter, B.] UCSD Sch Med, San Diego, CA USA. [Salehi, A.; Noerholm, M.; Balaj, L.; Zhu, L. D.; Skog, J.; Breakefield, X. O.; Carter, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2013 VL 61 IS 1 MA 417 BP 230 EP 230 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 058TT UT WOS:000312657900424 ER PT J AU Alexander, BM Wang, MH Yung, WKA Fine, HA Donahue, BA Tremont, IW Richards, RS Kerlin, KJ Hartford, AC Curran, WJ Mehta, MP AF Alexander, Brian M. Wang, Meihua Yung, W. K. Alfred Fine, Howard A. Donahue, Bernadine A. Tremont, Ivo W. Richards, Ray S. Kerlin, Kevin J. Hartford, Alan C. Curran, Walter J. Mehta, Minesh P. TI A phase II study of conventional radiation therapy and thalidomide for supratentorial, newly-diagnosed glioblastoma (RTOG 9806) SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Glioblastoma; Clinical trial; Controlled; Radiation therapy; Thalidomide; Angiogenesis inhibitor ID ENDOTHELIAL GROWTH-FACTOR; HIGH-GRADE GLIOMAS; RECURRENT GLIOBLASTOMA; TRIAL DESIGN; MULTIFORME; TEMOZOLOMIDE; ANGIOGENESIS; ADULTS; IRINOTECAN; EXPRESSION AB The Radiation Therapy Oncology Group (RTOG) initiated the single-arm, phase II study 9806 to determine the safety and efficacy of daily thalidomide with radiation therapy in patients with newly diagnosed glioblastoma. Patients were treated with thalidomide (200 mg daily) from day one of radiation therapy, increasing by 100-200 to 1,200 mg every 1-2 weeks until tumor progression or unacceptable toxicity. The median survival time (MST) of all 89 evaluable patients was 10 months. When compared with the historical database stratified by recursive partitioning analysis (RPA) class, this end point was not different [hazard ratio (HR) = 1.18; 95 % CI: 0.95-1.46; P = 0.93]. The MST of RPA class III and IV patients was 13.9 versus 12.5 months in controls (HR = 0.99; 95 % CI: 0.73-1.36; P = 0.48), and 4.3 versus 8.6 months in RPA class V controls (HR = 1.63, 95 % CI: 1.17-2.27; P = 0.99). In all, 34 % of patients discontinued thalidomide because of adverse events or refusal. The most common grade 3-4 toxicities were venous thrombosis, fatigue, skin reactions, encephalopathy, and neuropathy. In conclusion, thalidomide given simultaneously with radiation therapy was safe, but did not improve survival in patients with newly diagnosed glioblastoma. C1 [Alexander, Brian M.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. [Wang, Meihua] RTOG Stat Ctr, Philadelphia, PA USA. [Yung, W. K. Alfred; Tremont, Ivo W.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Fine, Howard A.] NCI, Neurooncol Branch, Bethesda, MD 20892 USA. [Donahue, Bernadine A.] Maimonides Hosp, Brooklyn, NY 11219 USA. [Richards, Ray S.] Intermt Med Ctr, St George, UT USA. [Kerlin, Kevin J.] SE Canc Control Consortium Inc, CCOP, Winston Salem, NC USA. [Hartford, Alan C.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Curran, Walter J.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Mehta, Minesh P.] NW Mem Hosp, Chicago, IL 60611 USA. RP Alexander, BM (reprint author), Dana Farber Brigham & Womens Canc Ctr, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM bmalexander@lroc.harvard.edu OI mehta, minesh/0000-0002-4812-5713 FU RTOG grant from the National Cancer Institute (NCI) [U10 CA21661]; CCOP grant from the National Cancer Institute (NCI) [U10 CA37422] FX This trial was conducted by the Radiation Therapy Oncology Group (RTOG), and was supported by RTOG grant U10 CA21661 and CCOP grant U10 CA37422 from the National Cancer Institute (NCI). This manuscript's contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 36 TC 8 Z9 8 U1 0 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 JAN PY 2013 VL 111 IS 1 BP 33 EP 39 DI 10.1007/s11060-012-0987-0 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 059RS UT WOS:000312723500005 PM 23086432 ER PT J AU Narayanan, S Hurst, RW Abruzzo, TA Albuguergue, FC Blackham, KA Bulsara, KR Derdeyn, CP Gandhi, CD Hirsch, JA Hsu, DP Hussain, MS Jayaraman, MV Meyers, PM Patsalides, A Prestigiacomo, CJ AF Narayanan, Sandra Hurst, Robert W. Abruzzo, Todd A. Albuguergue, Felipe C. Blackham, Kristine A. Bulsara, Ketan R. Derdeyn, Colin P. Gandhi, Chirag D. Hirsch, Joshua A. Hsu, Daniel P. Hussain, Muhammad Shazam Jayaraman, Mahesh V. Meyers, Philip M. Patsalides, Athos Prestigiacomo, Charles J. TI Standard of practice: embolization of spinal arteriovenous fistulae, spinal arteriovenous malformations, and tumors of the spinal axis SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article ID VENOUS DRAINAGE; CORD; MANIFESTATIONS; PARAPLEGIA; PARTICLES AB Spinal vascular malformations include a heterogeneous group of pathological/anatomical entities with congenital and acquired etiologies that induce spinal cord dysfunction, primarily through intradural extramedullary drainage and enlargement of the coronal venous plexus, resulting in venous hypertension and/or a direct mass effect. These lesions are rare, comprising approximately 5% of neurovascular disorders. Clinical manifestations are pain or venous congestive myelopathy, usually in the thoracolumbar spine. This may progress to hemorrhage from vascular thrombosis and necrotizing myelopathy (Foix-Alajouanine syndrome).(1) Due to the differing hemodynamics, pathophysiology, and treatment considerations, a thorough knowledge of the various types of spinal dural arteriovenous fistulas (dAVEs) and arteriovenous malformations (AVMs) is essential. C1 [Narayanan, Sandra] Wayne State Univ, Sch Med, Dept Neurosurg & Neurol, Detroit, MI 48201 USA. [Hurst, Robert W.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Abruzzo, Todd A.] Univ Cincinnati, Dept Radiol, Cincinnati, OH USA. [Albuguergue, Felipe C.] Barrow Neurol Inst, Div Neurol Surg, Phoenix, AZ 85013 USA. [Blackham, Kristine A.] Case Western Reserve Univ, Univ Hosp Dept Radiol, Cleveland, OH 44106 USA. [Bulsara, Ketan R.] Yale Univ, Dept Neurosurg, New Haven, CT USA. [Derdeyn, Colin P.] Washington Univ, Dept Radiol, St Louis, MO USA. [Gandhi, Chirag D.] Univ Med & Dent New Jersey, New Jersey Med Sch, Neurol Inst New Jersey, Newark, NJ 07103 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hsu, Daniel P.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Hussain, Muhammad Shazam] Cleveland Clin, Cleveland Clin Stroke Program, Cleveland, OH 44106 USA. [Jayaraman, Mahesh V.] Brown Univ, Warren Alpert Sch Med, Providence, RI 02912 USA. [Meyers, Philip M.] Columbia Univ, Dept Radiol & Neurol Surg, New York, NY USA. [Patsalides, Athos] New York Presbyterian Hosp, Weill Cornell Med Coll New York, Dept Neurol Surg, New York, NY USA. [Prestigiacomo, Charles J.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol Surg, Newark, NJ 07103 USA. RP Narayanan, S (reprint author), Wayne State Univ, Sch Med, Dept Neurosurg & Neurol, 4160 John R,930, Detroit, MI 48201 USA. EM snarayanan@med.wayne.edu RI Hurst, Robert/E-8420-2015; OI Derdeyn, Colin/0000-0002-5932-2683 NR 24 TC 1 Z9 1 U1 0 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JAN PY 2013 VL 5 IS 1 BP 3 EP 5 DI 10.1136/neurintsurg-2012-010551 PG 3 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 065FJ UT WOS:000313133600002 PM 23112254 ER PT J AU Walcott, BP Smith, ER Scott, RM Orbach, DB AF Walcott, Brian P. Smith, Edward R. Scott, R. Michael Orbach, Darren B. TI Dural arteriovenous fistulae in pediatric patients: associated conditions and treatment outcomes SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article ID MALFORMATIONS; CLASSIFICATION; MANAGEMENT; CHILDREN; SINUS; ONYX AB Objective Dural arteriovenous fistulae (dAVF) are rare vascular lesions of the CNS with potentially significant morbidity and mortality. Our experience in the treatment of children with dAVF is reported. Design Our neurosurgical and neurointerventional pediatric database was retrospectively reviewed for patients with dAVF. Brain arteriovenous malformations, pial fistulae, vein of Galen malformations and extracranial fistulae were excluded. Angiography was used to assess radiographic outcome in all cases. Clinical outcome was assessed by the pediatric Functional Status Scale (6=normal, maximal incapacity=30). Results Between July 2003 and June 2011, seven patients with dAVF were treated, with a mean age at presentation of 4.8 years. Presenting symptoms included facial venous prominence, headache, macrocephaly and symptoms of elevated intracranial pressure; one patient (14%) had asymptomatic dAVF discovered on imaging follow-up after craniotomy for cavernous malformation. Two cases (28%) were associated with vascular anomaly syndromes, PHACE association and PTEN associated syndrome. Venous sinus thrombosis was identified in four patients (57%) and was associated with a systemic hypercoagulable state or trauma. Complete obliteration was achieved in six of seven patients. Treatment was exclusively endovascular in six patients and by combined surgical/endovascular means in the remaining patient. No treatment complications were experienced. Functional Status Scale scores at an average of 2 years of follow-up were 6 in all patients. Conclusion Treatment is effective in the obliteration of dAVF in children and is well tolerated, with patients having excellent prognoses. Genetic screening and hypercoagulable workup are indicated, particularly when other anomalies or sinus thrombosis coexist. C1 [Walcott, Brian P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Smith, Edward R.; Scott, R. Michael] Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Orbach, Darren B.] Childrens Hosp, Dept Neurointervent Radiol, Boston, MA 02115 USA. RP Orbach, DB (reprint author), Childrens Hosp, Dept Neurointervent Radiol, Boston, MA 02115 USA. EM darren.orbach@childrens.harvard.edu RI Orbach, Darren/M-5773-2013 OI Orbach, Darren/0000-0002-1793-3398 NR 21 TC 7 Z9 7 U1 1 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JAN PY 2013 VL 5 IS 1 BP 6 EP 9 DI 10.1136/neurintsurg-2011-010169 PG 4 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 065FJ UT WOS:000313133600003 PM 22213835 ER PT J AU Walcott, BP Smith, ER Scott, RM Orbach, DB AF Walcott, Brian P. Smith, Edward R. Scott, R. Michael Orbach, Darren B. TI Pial arteriovenous fistulae in pediatric patients: associated syndromes and treatment outcome SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article ID HEREDITARY HEMORRHAGIC TELANGIECTASIA; ENDOVASCULAR TREATMENT; SPONTANEOUS REGRESSION; RASA1 MUTATIONS; MALFORMATION; CHILDREN; SPECIFICATION; MANAGEMENT; SECONDARY; KINASE AB Objective Pediatric pial arteriovenous fistulae (pAVF) are rare vascular lesions of the CNS, reported to have up to a 25% association with hereditary hemorrhagic telangiectasia. The presentation, treatment and syndromes associated with pAVF in children are reported here. Design A pediatric database for pAVF was retrospectively reviewed. Patients with carotid cavernous fistulae, dural arteriovenous fistulae, brain arteriovenous malformations and vein of Galen malformations were excluded. Radiographic outcome was assessed using digital subtraction angiography, and clinical outcome by the Functional Status Scale (6=normal, maximal incapacity=30). Results Between July 2003 and June 2011, seven patients with pAVF (six intracranial and one spinal) were treated. Mean age was 4.2 years. The most common clinical presentation was high output cardiac failure (43%). Two patients (29%) harbored a known mutation in the RASA1 gene, associated with a hereditary vascular syndrome: capillary malformation arteriovenous malformation. No patient had hereditary hemorrhagic telangiectasia. Treatment resulted in complete lesional obliteration in six of seven patients, with treatment ongoing in the seventh. Five of seven patients had combined endovascular and surgical treatment while two underwent endovascular embolization alone. Functional Status Scale scores at the most recent follow-up were 6 in all but one patient who had presented with a pretreatment hemianopsia. Conclusion Treatment is effective in obliterating pAVF in children, with an excellent prognosis seen in our cohort. Genetic screening is indicated, with capillary malformation arteriovenous malformation being the most frequently seen syndrome. No patients had hemorrhagic hereditary telangiectasia. C1 [Walcott, Brian P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Smith, Edward R.; Scott, R. Michael] Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Orbach, Darren B.] Childrens Hosp, Dept Neurointervent Radiol, Boston, MA 02115 USA. RP Orbach, DB (reprint author), Childrens Hosp, Dept Neurointervent Radiol, 300 Longwood Ave, Boston, MA 02115 USA. EM darren.orbach@childrens.harvard.edu RI Orbach, Darren/M-5773-2013 OI Orbach, Darren/0000-0002-1793-3398 NR 27 TC 13 Z9 13 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JAN PY 2013 VL 5 IS 1 BP 10 EP 14 DI 10.1136/neurintsurg-2011-010168 PG 5 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 065FJ UT WOS:000313133600004 PM 22213836 ER PT J AU Manchikanti, L Falco, FJE Hirsch, JA AF Manchikanti, Laxmaiah Falco, Frank J. E. Hirsch, Joshua A. TI Ready or not! Here comes ICD-10 SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Review ID INTERVENTIONAL PAIN MANAGEMENT; CLINICAL-PRACTICE GUIDELINES; HEALTH-CARE; PERFECT STORM; FALLACIES; FACTS; CHALLENGES; POLITICS; DECADE AB The International Classification of Diseases-10 (ICD-10) is a new system that is a federally mandated change affecting all payers and providers, and is expected to exceed both the Health Insurance Portability and Accountability Act (HIPAA) and Y2K in terms of costs and risks. In 2003, HIPAA named ICD-9 as the code set for supporting diagnoses and procedures in electronic administrative transactions. However, on 16 January 2009, the Department of Health and Human Services published a regulation requiring the replacement of ICD-9 with ICD-10 as of 1 October 2013. While ICD-9 and ICD-10 have a similar type of hierarchy in their structures, ICD-10 is more complex and incorporates numerous changes. Overall, ICD-10 contains more than 141 000 codes, a whopping 712% increase over the <20 000 codes in ICD-9, creating enormous complexities, confusion and expense. Published statistics illustrate that there are instances where a single ICD-9 code can map to more than 50 distinct ICD-10 codes. Also, there are multiple instances where a single ICD-10 code can map to more than one ICD-9 code. Proponents of the new ICD-10 system argue that the granularity should lead to improvements in the quality of healthcare whereas detractors of the system see the same granularity as burdensome. The estimated cost per physician is projected to range from $25 000 to $50 000. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY 42003 USA. [Falco, Frank J. E.] Mid Atlantic Spine & Pain Phys, Newark, DC USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept NeuroIntervent Radiol, Boston, MA 02114 USA. RP Manchikanti, L (reprint author), Pain Management Ctr Paducah, 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 28 TC 12 Z9 12 U1 0 U2 11 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 EI 1759-8486 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JAN PY 2013 VL 5 IS 1 BP 86 EP 91 DI 10.1136/neurintsurg-2011-010155 PG 6 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 065FJ UT WOS:000313133600017 PM 22025181 ER PT J AU Dunn, GP Spiliopoulos, K Plotkin, SR Hornicek, FJ Harmon, DC Delaney, TF Williams, Z AF Dunn, Gavin P. Spiliopoulos, Konstantinos Plotkin, Scott R. Hornicek, Francis J. Harmon, David C. Delaney, Thomas F. Williams, Ziv TI Malignant nerve sheath tumors Response SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material ID SOFT-TISSUE SARCOMAS; ONCOLOGY GROUP; HIGH-GRADE; RHABDOMYOSARCOMA; RADIOTHERAPY; EXPERIENCE; CHILDREN; WALL C1 [Dunn, Gavin P.; Spiliopoulos, Konstantinos; Williams, Ziv] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02163 USA. [Plotkin, Scott R.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Hornicek, Francis J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Oncol, Boston, MA 02115 USA. [Plotkin, Scott R.; Harmon, David C.; Delaney, Thomas F.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Delaney, Thomas F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Dunn, GP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02163 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 JAN PY 2013 VL 118 IS 1 BP 141 EP 141 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 062UQ UT WOS:000312948800027 ER PT J AU Dunn, GP Spiliopoulos, K Plotkin, SR Hornicek, FJ Harmon, DC Delaney, TF Williams, Z AF Dunn, Gavin P. Spiliopoulos, Konstantinos Plotkin, Scott R. Hornicek, Francis J. Harmon, David C. Delaney, Thomas F. Williams, Ziv TI Role of resection of malignant peripheral nerve sheath tumors in patients with neurofibromatosis Type 1 Clinical article SO JOURNAL OF NEUROSURGERY LA English DT Article DE malignancy; peripheral nerve; neurofibromatosis; peripheral nerve sheath tumor ID SOFT-TISSUE SARCOMAS; NEOADJUVANT CHEMOTHERAPY; ADJUVANT CHEMOTHERAPY; RADIATION-THERAPY; RANDOMIZED-TRIAL; MANAGEMENT; RADIOTHERAPY; EXTREMITY; SURVIVAL; METAANALYSIS AB Object. Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that often arise from major peripheral nerves. Approximately half of MPNSTs arise in patients with neurofibromatosis Type 1 (NF1) who, in comparison with patients without NF1, present at younger ages and with larger tumors that are commonly associated with extensive plexiform neurofibromas. These tumors therefore pose a particularly difficult treatment challenge because of the morbidity often associated with attempted gross-total resection (GTR). Here, the authors aim to examine what role the extent of resection and other covariates play in the long-term survival of patients with NF1 in the setting of MPNST. Methods. The authors retrospectively reviewed the records of 23 adult patients with NF1 who underwent surgery for MPNSTs at their institution between 1991 and 2008. The primary end points of the study were mortality, local recurrence, and metastasis. Kaplan-Meier survival curves were evaluated for all patients. Differences for each of the primary end points were evaluated based on cause-specific covariates, which included tiered tumor size, tumor location, grade, resection margin status, postoperative weakness, and use of chemotherapy and radiation therapy. Multivariate analysis was performed using Cox proportional hazards models. Results. Gross-total resection (p = 0.01) and surgical margin status (p = 0.034) had a statistically important role in prolonging overall survival in patients with NF1 by univariate analysis. When tumor size, location, grade, postoperative weakness, and radiation therapy were also taken into account using multivariate analysis, GTR continued to be a significant prognostic factor (p = 0.035). Conclusions. These findings suggest that GTR offers significant long-term benefit on survival in patients with NF1. Benefit on survival occurred independently of all other covariates, suggesting that complete resection should be the principal goal of treatment in this patient population. (http://thejns.org/doi/abs/10.3171/2012.9.JNS101610) C1 [Dunn, Gavin P.; Spiliopoulos, Konstantinos; Williams, Ziv] Harvard Univ, Massachusetts Gen Hosp, Dept Neurosurg, Sch Med, Boston, MA 02114 USA. [Plotkin, Scott R.] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Sch Med, Boston, MA 02114 USA. [Hornicek, Francis J.] Harvard Univ, Massachusetts Gen Hosp, Dept Orthoped Oncol, Sch Med, Boston, MA 02114 USA. [Plotkin, Scott R.; Harmon, David C.; Delaney, Thomas F.] Harvard Univ, Massachusetts Gen Hosp, Canc Ctr, Sch Med, Boston, MA 02114 USA. RP Williams, Z (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Neurosurg, Sch Med, 55 Fruit St,WAC 745K, Boston, MA 02114 USA. EM zwilliams@partners.org FU Stryker; Zimmer FX Dr. Hornicek is a consultant for Stryker and received clinical or research support for the study described from Stryker and Zimmer. The other authors report no potential conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. NR 29 TC 12 Z9 13 U1 1 U2 9 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 JAN PY 2013 VL 118 IS 1 BP 142 EP 148 DI 10.3171/2012.9.JNS101610 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 062UQ UT WOS:000312948800028 PM 23101443 ER PT J AU Thompson, EM Whitney, NL Wu, YJ Neuwelt, EA AF Thompson, Eric M. Whitney, Nathaniel L. Wu, Y. Jeffrey Neuwelt, Edward A. TI The effect of alpha-v integrin inhibition on the malignant characteristics of medulloblastoma Laboratory investigation SO JOURNAL OF NEUROSURGERY-PEDIATRICS LA English DT Article DE medulloblastoma; intetumumab; alpha(v) integrin; hypoxia; c-Myc; hypoxia-inducible factor-1 alpha; oncology ID HUMAN MONOCLONAL-ANTIBODY; C-MYC; DOWN-REGULATION; BRAIN-TUMORS; HYPOXIA; PROLIFERATION; EXPRESSION; CANCER; CELLS; LEPTOMENINGEAL AB Object. Hypoxia induces an aggressive phenotype in some brain tumors in part due to hypoxia-inducible factor-1 alpha (HIF-1 alpha) and integrin expression. The importance of hypoxia in medulloblastoma is unclear and the interaction of HIF-1 alpha and c-Myc in medulloblastoma has not been explored. The objective of this study was to determine if hypoxia induces an aggressive phenotype in human medulloblastoma cells that constitutively express high (D283 Med) or low (DAOY) levels of c-Myc and to determine if blocking alpha(v) integrins with the monoclonal antibody intetumumab inhibits hypoxia-induced cellular stress responses. Methods. Cells were grown at 21% and 1% O-2 and in the presence or absence of intetumumab. Measures of malignancy evaluated included cell proliferation, cell migration, and expression of vascular endothelial growth factor (VEGF), alpha(v) integrins, HIF-1 alpha, and c-Myc. Results. Both cell lines robustly expressed alpha(v) integrins. Hypoxic DAOY cells showed significantly increased proliferation compared with normoxic controls (p < 0.05), whereas D283 Med cells did not. Both cell lines exhibited a dose-dependent decrease in proliferation when treated with intetumumab (p < 0.05). Hypoxia did not increase DAOY migration, but intetumumab significantly inhibited migration at both oxygen conditions (p < 0.05). Intetumumab significantly decreased VEGF levels in DAOY cells at both oxygen conditions (p < 0.05) and in normoxic D283 cells (p < 0.01). Neither cell line demonstrated increased HIF-1 alpha expression in response to hypoxia. However, hypoxic D283 Med cells grown in the presence of intetumumab demonstrated significantly decreased c-Myc expression (p < 0.05). Conclusions. Hypoxia did not clearly induce a more aggressive phenotype in medulloblastoma cells. Despite this result, intetumumab decreased medulloblastoma cell proliferation and migration and variably decreased VEGF and c-Myc expression in hypoxic conditions. Targeting alpha(v) integrins represents a promising potential adjuvant modality in the treatment of medulloblastoma, particularly subtypes that metastasize and overexpress VEGF and c-Myc. (http://thejns.org/doi/abs/10.3171/2012.9.PEDS12268) C1 [Thompson, Eric M.; Whitney, Nathaniel L.; Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurol Surg, Portland, OR 97239 USA. [Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurol, Blood Brain Barrier Program, Portland, OR 97239 USA. [Neuwelt, Edward A.] Portland VA Med Ctr, Portland, OR USA. RP Neuwelt, EA (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Blood Brain Barrier Program, 3181 Sam Jackson Pk Rd,L603, Portland, OR 97239 USA. EM neuwelte@ohsu.edu FU NIH [NS053468, CA137488, NS44687]; Medical Research Foundation of Oregon FX This study was supported by NIH grants NS053468, CA137488, and NS44687 to Dr. Neuwelt and a Medical Research Foundation of Oregon Early Clinical Investigator grant to Dr. Thompson. NR 35 TC 2 Z9 2 U1 0 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1933-0707 J9 J NEUROSURG-PEDIATR JI J. Neurosurg.-Pediatr. PD JAN PY 2013 VL 11 IS 1 BP 60 EP 67 DI 10.3171/2012.9.PEDS12268 PG 8 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 062VP UT WOS:000312951700010 PM 23082872 ER PT J AU MacLennan, MB Clarke, SE Perez, K Wood, GA Muller, WJ Kang, JX Ma, DWL AF MacLennan, Mira B. Clarke, Shannon E. Perez, Kate Wood, Geoffrey A. Muller, William J. Kang, Jing X. Ma, David W. L. TI Mammary tumor development is directly inhibited by lifelong n-3 polyunsaturated fatty acids SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE Breast cancer; Mammary tumorigenesis; n-3 PUFA; fat-1 mice; MMTV-neu(ndl)-YD5 mice; maternal nutrition ID BREAST-CANCER RISK; GLAND DEVELOPMENT; TRANSGENIC MICE; DIETARY N-3; FAT-1 MICE; HEALTH; TUMORIGENESIS; FISH; PREVENTION; DISEASE AB Introduction: Despite the advocacy that diet may be a significant contributor to cancer prevention, there is a lack of direct evidence from epidemiological and experimental studies to substantiate such claims. Experimental studies suggest that n-3 polyunsaturated fatty acids (n-3 PUFA) from marine oils may reduce breast cancer risk, however, findings are equivocal. Thus, in this study, novel transgenic mouse models were employed to provide, for the first time, direct evidence for an anti-cancer role of n-3 PUFA in mammary tumorigenesis. Methods: fat-1 Mice, which are capable of endogenous n-3 PUFA synthesis, were bred with mouse mammary tumor virus (MMTV)MMTV(Methods: fat-1 Mice, which are capable of endogenous n-3 PUFA synthesis, were bred with mouse mammary tumor virus (MMTV)MMTV(ndl)-YD5 mice, an)-YD5 mice, an aggressive breast cancer model. The resultant offspring, including novel hybrid progeny, were assessed for tumor onset, size and multiplicity as well as n-3 PUFA composition in mammary gland and tumor tissue. A complementary group of MMTV-neu(ndl)-YD5 mice were fed n-3 PUFA in the diet. Results: Mice expressing MMTV-neu(ndl)-YD5 and fat-1 displayed significant (P<.05) reductions in tumor volume (similar to 30%) and multiplicity (similar to 33%), as well as reduced n-6 PUFA and enriched n-3 PUFA in tumor phospholipids relative to MMTV-neu(ndI)-YD5 control mice. The effect observed in hybrid progeny was similarly observed in n-3 PUFA diet fed mice. Conclusion: Using complementary genetic and conventional dietary approaches we provide, for the first time, unequivocal experimental evidence that n-3 PUFA is causally linked to tumor prevention. (C) 2013 Elsevier Inc. All rights reserved. C1 [Ma, David W. L.] Univ Guelph, Coll Biol Sci, Dept Human Hlth & Nutr Sci, Guelph, ON N1G 2W1, Canada. [Wood, Geoffrey A.] Univ Guelph, Dept Pathobiol, Guelph, ON N1G 2W1, Canada. [Muller, William J.] McGill Univ, Royal Victoria Hosp, Mol Oncol Labs, Montreal, PQ H3A 1A1, Canada. [Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA USA. [Kang, Jing X.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ma, DWL (reprint author), Univ Guelph, Coll Biol Sci, Dept Human Hlth & Nutr Sci, Anim Sci Nutr Bldg,Rm 342,491 Gordon St, Guelph, ON N1G 2W1, Canada. EM davidma@uoguelph.ca FU Canadian Breast Cancer Research Alliance/Canadian Institutes of Health Research operating grant [MOP-89971]; Canada Foundation for Innovation Leaders Opportunity Fund with matching from the Ontario Research Fund; Canadian Institutes of Health Research Frederick Banting and Charles Best Canada Graduate Scholarship; Ontario Graduate Scholarships in Science and Technology; CIBC Health and Science Scholarship FX Sources of Funding: D.W.L. Ma is funded by the Canadian Breast Cancer Research Alliance/Canadian Institutes of Health Research operating grant (MOP-89971) and the Canada Foundation for Innovation Leaders Opportunity Fund with matching from the Ontario Research Fund. M.B. MacLennan is funded by a Canadian Institutes of Health Research Frederick Banting and Charles Best Canada Graduate Scholarship. S.E. Clarke is funded by the Ontario Graduate Scholarships in Science and Technology. K. Perez is funded by the CIBC Health and Science Scholarship. NR 43 TC 28 Z9 28 U1 0 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD JAN PY 2013 VL 24 IS 1 BP 388 EP 395 DI 10.1016/j.jnutbio.2012.08.002 PG 8 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 056HT UT WOS:000312479700047 PM 23026490 ER PT J AU Hammerness, P Joshi, G Doyle, R Georgiopoulos, A Geller, D Spencer, T Petty, CR Faraone, SV Biederman, J AF Hammerness, Paul Joshi, Gagan Doyle, Robert Georgiopoulos, Anna Geller, Daniel Spencer, Thomas Petty, Carter R. Faraone, Stephen V. Biederman, Joseph TI Do Stimulants Reduce the Risk for Cigarette Smoking in Youth with Attention-Deficit Hyperactivity Disorder? A Prospective, Long-Term, Open-Label Study of Extended-Release Methylphenidate SO JOURNAL OF PEDIATRICS LA English DT Article ID SUBSTANCE USE DISORDERS; DEFICIT/HYPERACTIVITY DISORDER; NICOTINE DEPENDENCE; FOLLOW-UP; PSYCHIATRIC-DISORDERS; ADHD; ADOLESCENTS; ASSOCIATION; SYMPTOMS; SMOKERS AB Objective Although attention-deficit hyperactivity disorder (ADHD) is a well-known risk factor for cigarette smoking, prospective studies aimed at reducing smoking risk in this population are critically needed. Study design This was a 2-year, prospective, open-label clinical trial of extended-release methylphenidate for smoking prevention in adolescents with ADHD (n = 154). Smoking outcomes were assessed with the Fagerstrom Tolerance Questionnaire. Comparisons were made using data from a historical, naturalistic sample of ADHD (n = 103) and non-ADHD comparators (n = 188) of similar age and sex assessed with the same assessment battery as that used in subjects participating in the clinical trial. Results The smoking rate at endpoint (mean, 10 months of methylphenidate treatment) was low in the clinical trial subjects and not significantly different from that in the non-ADHD comparators or the ADHD comparators receiving stimulants naturalistically (7.1% vs 8.0% vs 10.9%; P>.20). In contrast, the smoking rate was significantly lower in the clinical trial subjects than in the naturalistic sample of ADHD comparators who were not receiving stimulant treatment (7.1% vs 19.6%; P=.009 [not significant], adjusting for comorbid conduct disorder and alcohol and drug abuse). Conclusion Although considered preliminary until replicated in future randomized clinical trials, the findings from this single-site, open-label study suggest that stimulant treatment may contribute to a decreased risk for smoking in adolescents with ADHD. If confirmed, this finding would have significant clinical and public health impacts. (J Pediatr 2013;162:22-7). C1 [Hammerness, Paul; Joshi, Gagan; Doyle, Robert; Georgiopoulos, Anna; Geller, Daniel; Spencer, Thomas; Petty, Carter R.; Biederman, Joseph] Clin & Res Program Pediat Psychopharmacol & Adult, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hammerness, Paul; Joshi, Gagan; Doyle, Robert; Georgiopoulos, Anna; Geller, Daniel; Spencer, Thomas; Petty, Carter R.; Biederman, Joseph] Harvard Univ, Sch Med, Boston, MA USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. RP Hammerness, P (reprint author), Clin & Res Program Pediat Psychopharmacol, 185 Alewife Brook Pkwy,Suite 2000, Cambridge, MA 02138 USA. EM phammerness@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU Janssen Scientific Affairs FX Supported by Janssen Scientific Affairs (investigator-initiated trial). Conflict of interest and funding information is available at www.jpeds.com (Appendix). NR 27 TC 9 Z9 9 U1 1 U2 9 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 JAN PY 2013 VL 162 IS 1 BP 22 EP U287 DI 10.1016/j.jpeds.2012.06.046 PG 8 WC Pediatrics SC Pediatrics GA 062JK UT WOS:000312915900007 PM 22878114 ER PT J AU Hsieh, DT Thiele, EA AF Hsieh, David T. Thiele, Elizabeth A. TI Vigabatrin-Related Magnetic Resonance Imaging Abnormalities in an Infant with Tuberous Sclerosis Complex and Infantile Spasms SO JOURNAL OF PEDIATRICS LA English DT Editorial Material C1 [Hsieh, David T.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Pediat Epilepsy Program, Boston, MA 02114 USA. RP Hsieh, DT (reprint author), Massachusetts Gen Hosp, Pediat Epilepsy Program, Boston, MA 02114 USA. NR 2 TC 2 Z9 2 U1 0 U2 3 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 JAN PY 2013 VL 162 IS 1 BP 215 EP 215 DI 10.1016/j.jpeds.2012.07.061 PG 1 WC Pediatrics SC Pediatrics GA 062JK UT WOS:000312915900049 PM 22979977 ER PT J AU Kivisto, AJ Swan, SA AF Kivisto, Aaron J. Swan, Scott A. TI Rorschach Measures of Aggression: A Laboratory-Based Validity Study SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID PERSONALITY-ASSESSMENT; TRAUMA CONTENT; VARIABLES; VIOLENT; SAMPLE; RELIABILITY; PARADIGMS; OFFENDERS; BEHAVIOR; INDEXES AB This study sought to complement the archival research designs that have established the empirical foundations of Rorschach aggression scores, including Exner's () Aggressive Movement (AG) score and Meloy and Gacono's () Aggressive Content (AgC), Aggressive Past (AgPast), and Aggressive Potential (AgPot) variables. Utilizing a highly controlled laboratory-based aggression paradigm and self-report measures of violence history in a sample of 35 undergraduate males with an average age of 19.38 (SD = 2.11), this study found that only AgC was positively associated with in vivo aggression (r = .40, p = .02). None of the Rorschach measures of aggression were significantly associated with self-reported violence history, although there were several trends approaching significance. Theoretical and methodological implications are discussed. C1 [Kivisto, Aaron J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kivisto, Aaron J.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Swan, Scott A.] Univ Tennessee, Dept Psychol, Knoxville, TN 37996 USA. [Swan, Scott A.] Penn Hosp, Philadelphia, PA 19107 USA. RP Kivisto, AJ (reprint author), Univ Indianapolis, Sch Psychol Sci, 1400 E Hanna Ave, Indianapolis, IN 46227 USA. EM AaronKivistoPhD@gmail.com RI Kivisto, Aaron/O-6860-2015 OI Kivisto, Aaron/0000-0002-2243-1384 NR 54 TC 2 Z9 2 U1 2 U2 15 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD JAN 1 PY 2013 VL 95 IS 1 BP 38 EP 45 DI 10.1080/00223891.2012.713882 PG 8 WC Psychology, Clinical; Psychology, Social SC Psychology GA 059JB UT WOS:000312699600004 PM 22906090 ER PT J AU Satoh, H Amagase, K Ebara, S Akiba, Y Takeuchi, K AF Satoh, Hiroshi Amagase, Kikuko Ebara, Satomi Akiba, Yasutada Takeuchi, Koji TI Cyclooxygenase (COX)-1 and COX-2 Both Play an Important Role in the Protection of the Duodenal Mucosa in Cats SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUG; RANDOMIZED CONTROLLED-TRIAL; INDUCED INTESTINAL DAMAGE; MUCUS GEL THICKNESS; RHEUMATOID-ARTHRITIS; GASTROINTESTINAL TOXICITY; GENE DISRUPTION; GASTRIC DAMAGE; UP-REGULATION; RAT DUODENUM AB Although nonsteroidal anti-inflammatory drugs often cause ulcers in the duodenum in humans, the role of cyclooxygenase (COX) isoforms in the pathogenesis of duodenal ulcers has not been fully elucidated. We examined in cats the 1) ulcerogenic effects of selective COX-1 (SC-560, ketorolac) and COX-2 (celecoxib, meloxicam) inhibitors on the gastrointestinal mucosa, 2) effect of feeding and cimetidine on the expression of COX isoforms and prostaglandin E-2 (PGE(2)) level in the duodenum, and 3) localization of COX isoforms in the duodenum. COX inhibitors were administered after the morning meal in cats once daily for 3 days. Gastrointestinal lesions were examined on day 4. Localization and expression of COX isoforms (by immunohistochemistry, Western blot) and PGE(2) level (by enzyme immunoassay) were examined. Results were as follows. First, selective COX-1 or COX-2 inhibitors alone produced marked ulcers in the duodenum but did not cause obvious lesions in the small intestine. Coadministration of SC-560 and celecoxib produced marked lesions in the small intestine. Second, feeding increased both the expression of COX isoforms and PGE(2) level in the duodenum, and the effects were markedly inhibited by pretreatment with cimetidine. Third, COX-1 was localized in goblet and Brunner's gland cells, Meissner's and Auerbach's plexus, smooth muscle cells, and arterioles; and COX-2 was observed in capillaries, venules, and basal granulated cells. The expression of COX isoforms in the duodenum is up-regulated by feeding, and inhibition of either COX-1 or COX-2 causes ulcers in the duodenum, suggesting that both isoforms play an important role in the protection of the duodenal mucosa. C1 [Satoh, Hiroshi; Amagase, Kikuko; Takeuchi, Koji] Kyoto Pharmaceut Univ, Div Pathol Sci, Dept Pharmacol & Expt Therapeut, Kyoto 6078414, Japan. [Ebara, Satomi] Meiji Univ Integrat Med, Med Educ & Res Ctr, Dept Anat, Kyoto, Japan. [Akiba, Yasutada] Univ Calif Los Angeles, Ctr Ulcer Res & Educ, Greater Los Angeles Vet Affair Healthcare Syst, Brentwood Biomed Res Inst,Med Sch, Los Angeles, CA 90024 USA. RP Satoh, H (reprint author), Kyoto Pharmaceut Univ, Div Pathologial Sci, Dept Pharmacol & Expt Therapeut, Yamashina Ku, Kyoto 6078414, Japan. EM h_satoh@mb.kyoto-phu.ac.jp NR 34 TC 6 Z9 6 U1 0 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2013 VL 344 IS 1 BP 189 EP 195 DI 10.1124/jpet.112.199182 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 060VE UT WOS:000312805500021 PM 23008503 ER PT J AU Wang, ML Walls, CE Peterson, KE Richmond, TK Spadano-Gasbarro, J Greaney, ML Blood, E Mezgebu, S McCormick, MC Subramanian, SV Austin, SB AF Wang, Monica L. Walls, Courtney E. Peterson, Karen E. Richmond, Tracy K. Spadano-Gasbarro, Jennifer Greaney, Mary L. Blood, Emily Mezgebu, Solomon McCormick, Marie C. Subramanian, S. V. Austin, S. Bryn TI Dietary and Physical Activity Factors Related to Eating Disorder Symptoms Among Middle School Youth SO JOURNAL OF SCHOOL HEALTH LA English DT Article DE disordered weight control; youth; diet; physical activity ID WEIGHT-CONTROL BEHAVIORS; EARLY ADOLESCENT GIRLS; BODY SHAPE IDEALS; PROTECTIVE FACTORS; SHARED RISK; OVERWEIGHT ADOLESCENTS; MULTIPLE IMPUTATION; FOLLOW-UP; PREVENTION; OBESITY AB BACKGROUND: Dietary and physical activity (PA) behaviors can predict disordered weight control behaviors (DWCB) among youth. This study examines dietary and PA correlates of DWCB and differences by race/ethnicity and weight status in a diverse sample of youth. METHODS: Self-reported data on dietary weight management behaviors, strengthening/toning exercises, moderate-to-vigorous physical activity, and DWCB (vomiting, taking laxatives, and/or taking diet pills without a prescription) were obtained from 15,260 sixth to eighth graders in 47 middle schools participating in the Massachusetts Healthy Choices Study at baseline (2005). Generalized estimating equations were used to estimate odds of DWCB associated with dietary and PA behaviors and to examine for differences by race/ethnicity and weight status, adjusting for covariates and clustering of individuals within schools. RESULTS: Disordered weight control behaviors were reported by 3.6% of girls and 3.1% of boys. Youth who engaged in strengthening/toning exercises 7 days per week versus 0-3 days per week had increased odds of DWCB (girls odds ratio [OR] = 1.9; 95% confidence interval [CI] = 1.3 - 3.0; boys OR = 1.5; 95% CI = 1.0 - 2.2). Dietary weight management behaviors were associated with increased odds of DWCB (girls OR = 1.2; 95% CI = 1.1 - 1.3; boys OR = 1.3; 95% CI = 1.2 - 1.4) for each additional behavior. These associations did not differ by race/ethnicity or weight status. CONCLUSIONS: Persons promoting healthy dietary and PA behaviors among youth should consider the co-occurrence of strengthening/toning and dietary weight management behaviors with DWCB and the consistency in these associations across racial/ethnic and weight status groups. C1 [Wang, Monica L.] Univ Massachusetts, Sch Med, Div Prevent & Behav Med, Worcester, MA 01655 USA. [Walls, Courtney E.; Blood, Emily] Childrens Hosp, Clin Res Program, Boston, MA 02115 USA. [Peterson, Karen E.] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Spadano-Gasbarro, Jennifer; McCormick, Marie C.; Subramanian, S. V.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Greaney, Mary L.] Dana Farber Canc Inst, Medford, MA 02155 USA. [Mezgebu, Solomon] Massachusetts Dept Publ Hlth, Off Integrated Surveillance & Informat Serv, Bur Infect & Communicable Dis, Boston, MA 02108 USA. RP Wang, ML (reprint author), Univ Massachusetts, Sch Med, Div Prevent & Behav Med, 55 Lake Ave N, Worcester, MA 01655 USA. EM Monica.Wang@umassmed.edu; Courtney.walls@childrens.harvard.edu; karenep@umich.edu; Tracy.richmond@childrens.harvard.edu; jlsg1023@hotmail.com; Mary_Greaney@dfci.harvard.edu; emily.blood@childrens.harvard.edu; solomon.mezgebu@state.ma.us; mmccormi@hsph.harvard.edu; svsubram@hsph.harvard.edu; Bryn.austin@childrens.harvard.edu OI McCormmick, Marie/0000-0002-3938-1707 NR 40 TC 5 Z9 5 U1 3 U2 24 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4391 J9 J SCHOOL HEALTH JI J. Sch. Health PD JAN PY 2013 VL 83 IS 1 BP 14 EP 20 DI 10.1111/j.1746-1561.2012.00742.x PG 7 WC Education & Educational Research; Education, Scientific Disciplines; Health Care Sciences & Services; Public, Environmental & Occupational Health SC Education & Educational Research; Health Care Sciences & Services; Public, Environmental & Occupational Health GA 058TE UT WOS:000312656200003 PM 23253286 ER PT J AU Berkson, SS Espinola, J Corso, KA Cabral, H McGowan, R Chomitz, VR AF Berkson, Stephanie S. Espinola, Janice Corso, Katherine A. Cabral, Howard McGowan, Robert Chomitz, Virginia R. TI Reliability of Height and Weight Measurements Collected by Physical Education Teachers for a School-Based Body Mass Index Surveillance and Screening System SO JOURNAL OF SCHOOL HEALTH LA English DT Article DE growth and development; obesity; school health services; public health; child and adolescent health AB BACKGROUND: To address the obesity epidemic among children and youth, school-based body mass index (BMI) screening and surveillance is proposed or mandated in 30 states. In Cambridge, MA, physical education (PE) teachers are responsible for these measurements. This research reports the reliability of height and weight measures collected by these PE teachers. METHODS: Using Bland-Altman plots, mean absolute differences, and intraclass correlation coefficients (ICC), we estimated intra- and inter-rater reliability among PE teachers in a controlled setting and PE teacher-vs-expert inter-rater reliability in a natural classroom setting. We also qualitatively assessed barriers to reliability. RESULTS: For the controlled setting, of 150 measurements, 3 height (2.0%) and 2 weight (1.33%) measurement outliers were detected; intra-rater mean absolute differences for height/weight were 0.52 inches (SD 1.61) and 0.8 lbs (SD 3.2); intra- and inter-rater height/weight ICCs were =0.96. For the natural setting, of 105 measurements, 1 weight measurement outlier (0.9%) was detected; PE teacher-vs-expert-rater mean absolute differences for height/weight were 0.22 inches (SD 0.21) and 0.7 lbs (SD 0.8), and ICCs were both 0.99. Equipment deficiencies, data recording issues, and lack of students' preparation were identified as challenges to collecting reliable measurements. CONCLUSION: According to ICC criteria, reliability of PE teachers' measurements was excellent. However, the criteria for mean absolute differences were not consistently met. Results highlight the importance of staff training and data cleaning. C1 [Berkson, Stephanie S.] Univ Illinois, Sch Publ Hlth, Inst Community Hlth, Boston, MA 02118 USA. [Espinola, Janice] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Corso, Katherine A.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Dept Surg, Boston, MA 02115 USA. [Cabral, Howard] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02118 USA. [McGowan, Robert] Cambridge Publ Sch, Cambridge, MA 02141 USA. [Chomitz, Virginia R.] Tufts Univ, Sch Med, Dept Publ Hlth & Community Med, Inst Community Hlth, Boston, MA 02111 USA. RP Berkson, SS (reprint author), Univ Illinois, Sch Publ Hlth, Inst Community Hlth, 70 E Brookline St 3, Boston, MA 02118 USA. EM sshapi5@uic.edu; espinola@helix.mgh.harvard.edu; katherine_corso@rocketmail.com; hjcab@bu.edu; rmcgowan@cpsd.us; vchomitz@challiance.org OI Cabral, Howard/0000-0002-1185-8331 NR 11 TC 5 Z9 5 U1 1 U2 47 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4391 J9 J SCHOOL HEALTH JI J. Sch. Health PD JAN PY 2013 VL 83 IS 1 BP 21 EP 27 DI 10.1111/j.1746-1561.2012.00743.x PG 7 WC Education & Educational Research; Education, Scientific Disciplines; Health Care Sciences & Services; Public, Environmental & Occupational Health SC Education & Educational Research; Health Care Sciences & Services; Public, Environmental & Occupational Health GA 058TE UT WOS:000312656200004 PM 23253287 ER PT J AU Manning, DK Sergeev, M van Heesbeen, RG Wong, MD Oh, JH Liu, Y Henkelman, RM Drummond, I Shah, JV Beier, DR AF Manning, Danielle K. Sergeev, Mikhail van Heesbeen, Roy G. Wong, Michael D. Oh, Jin-Hee Liu, Yan Henkelman, R. Mark Drummond, Iain Shah, Jagesh V. Beier, David R. TI Loss of the Ciliary Kinase Nek8 Causes Left-Right Asymmetry Defects SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID POLYCYSTIC KIDNEY-DISEASE; RIGHT AXIS DETERMINATION; SITUS-INVERSUS; CAUSE NEPHRONOPHTHISIS; NODAL EXPRESSION; NEURAL ACTIVITY; CATION CHANNEL; PROTEIN-KINASE; MOUSE MODEL; MICE AB A missense mutation in mouse Nek8, which encodes a ciliary kinase, produces the juvenile cystic kidneys (jck) model of polycystic kidney disease, but the functions of Nek8 are incompletely understood. Here, we generated a Nek8-null allele and found that homozygous mutant mice die at birth and exhibit randomization of left-right asymmetry, cardiac anomalies, and glomerular kidney cysts. The requirement for Nek8 in left-right patterning is conserved, as knockdown of the zebrafish ortholog caused randomized heart looping. Ciliogenesis was intact in Nek8-deficient embryos and cells, but we observed misexpression of left-sided marker genes early in development, suggesting that nodal ciliary signaling was perturbed. We also generated jck/Nek8 compound heterozygotes; these mutants developed less severe cystic disease than jck homozygotes and provided genetic evidence that the jck allele may encode a gain-of-function protein. Notably, NEK8 and polycystin-2 (PC2) proteins interact, and we found that Nek8(-/-) and Pkd2(-/-) embryonic phenotypes are strikingly similar. Nek8-deficient embryos and cells did express PC2 normally, which localized properly to the cilia. However, similar to cells lacking PC2, NEK8-depleted inner medullary collecting duct cells exhibited a defective response to fluid shear, suggesting that NEK8 may play a role in mediating PC2-dependent signaling. J Am Soc Nephrol 24: 100-112, 2013. doi: 10.1681/ASN.2012050490 C1 [Manning, Danielle K.; Beier, David R.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Sergeev, Mikhail; van Heesbeen, Roy G.; Shah, Jagesh V.] Brigham & Womens Hosp, Div Renal Med, Boston, MA 02115 USA. [Sergeev, Mikhail; van Heesbeen, Roy G.; Shah, Jagesh V.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Wong, Michael D.; Henkelman, R. Mark] Hosp Sick Children, Mouse Imaging Ctr MICe, Toronto, ON M5G 1X8, Canada. [Oh, Jin-Hee] Catholic Univ Korea, Dept Pediat, Seoul, South Korea. [Liu, Yan; Drummond, Iain] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA USA. RP Beier, DR (reprint author), Brigham & Womens Hosp, Div Genet, 77 Ave Louis Pasteur,NRB Room 458H, Boston, MA 02115 USA. EM beier@receptor.med.harvard.edu RI Henkelman, Mark/F-3662-2011 FU National Institutes of Health [NIH P50 DK074030, NIH R01 DK053093, NIH R01 DK66370]; PKD Foundation; Harvard Center for PKD Research [NIH P50 DK074030] FX Support for this work was provided by grants from the National Institutes of Health to J.V.S. (NIH P50 DK074030 and Genzyme GRIP), I.D. (NIH R01 DK053093), and D.R.B. (NIH R01 DK66370), as well as grants from the PKD Foundation and the Harvard Center for PKD Research (NIH P50 DK074030). NR 73 TC 19 Z9 19 U1 0 U2 14 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 2013 VL 24 IS 1 BP 100 EP 112 DI 10.1681/ASN.2012050490 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 061CA UT WOS:000312823500015 PM 23274954 ER PT J AU Verfaellie, M Lafleche, G Spiro, A Tun, C Bousquet, K AF Verfaellie, Mieke Lafleche, Ginette Spiro, Avron, III Tun, Carlos Bousquet, Kathryn TI Chronic Postconcussion Symptoms and Functional Outcomes in OEF/OIF Veterans with Self-Report of Blast Exposure SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE TBI; Blast-injuries; PTSD; Depression; Postconcussion symptoms; Quality of life ID TRAUMATIC BRAIN-INJURY; POSTTRAUMATIC-STRESS-DISORDER; MILD HEAD-INJURY; NEUROPSYCHOLOGICAL PERFORMANCE; SOCIAL SUPPORT; IRAQI FREEDOM; CONCUSSION; DEPRESSION; DEPLOYMENT; COMPLAINTS AB Postconcussion symptoms (PCS) and functional outcomes were evaluated in 91 OEF/OIF outpatient veterans with reported histories of blast-exposure, with the goal of evaluating (1) the association between these outcomes and a clinical diagnosis of mild traumatic brain injury (mTBI) with or without loss of consciousness (LOC); and (2) the influence of post-traumatic stress disorder (PTSD) and depression on PCS reporting and perceived functional limitations. Individuals who reported mTBI with LOC had greater PCS complaints than individuals who reported mTBI without LOC or individuals without mTBI. However, after adjusting for severity of PTSD and depression symptoms, this group difference disappeared. Functional limitations were particularly prominent in the psychosocial domain. Again, PTSD was significantly associated with functional outcomes, but the mTBI with LOC group had greater psychosocial limitations than the other two groups, even when PTSD and depression symptoms were taken into account. These findings highlight the role of mental health in both outcomes, but additionally point to the impact of mTBI with LOC on long-term psychosocial adjustment. (JINS, 2013, 19, 1-10) C1 [Verfaellie, Mieke; Lafleche, Ginette; Bousquet, Kathryn] VA Boston Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02130 USA. [Verfaellie, Mieke; Lafleche, Ginette; Spiro, Avron, III; Bousquet, Kathryn] Boston Univ, Sch Med, Boston, MA 02118 USA. [Spiro, Avron, III] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA 02130 USA. [Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Tun, Carlos] VA Boston Healthcare Syst, Polytrauma Network Site, Boston, MA 02130 USA. [Tun, Carlos] Harvard Univ, Sch Med, Boston, MA USA. RP Verfaellie, M (reprint author), VA Boston Healthcare Syst, Memory Disorders Res Ctr 151A, 150 S Huntington Ave, Boston, MA 02130 USA. EM verf@bu.edu OI Spiro III, Avron/0000-0003-4080-8621; Verfaellie, Mieke/0000-0001-5535-4584 FU Clinical Science Research and Development; Rehabilitation Research and Development Services of the Department of Veterans Affairs FX This research was supported by the Clinical Science Research and Development and the Rehabilitation Research and Development Services of the Department of Veterans Affairs. The authors thank Laura Grande, Ph.D. and Susan McGlynn, Ph.D. for facilitating participant recruitment. The authors have no conflict of interest affecting this manuscript. NR 60 TC 17 Z9 18 U1 6 U2 12 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD JAN PY 2013 VL 19 IS 1 BP 1 EP U32 DI 10.1017/S1355617712000902 PG 21 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 063NB UT WOS:000313005400001 PM 23095177 ER PT J AU Wright, CD AF Wright, Cameron D. TI Historical perspectives of The American Association for Thoracic Surgery: John W. Strieder (1901-1993) SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material ID PATENT DUCTUS-ARTERIOSUS; LIGATION C1 Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA. RP Wright, CD (reprint author), Massachusetts Gen Hosp, Dept Thorac Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM wright.cameron@mgh.harvard.edu NR 7 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JAN PY 2013 VL 145 IS 1 BP 2 EP 4 DI 10.1016/j.jtcvs.2012.09.075 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 055AE UT WOS:000312386300009 PM 23111015 ER PT J AU Fann, JI Sullivan, ME Skeff, KM Stratos, GA Walker, JD Grossi, EA Verrier, ED Hicks, GL Feins, RH AF Fann, James I. Sullivan, Maura E. Skeff, Kelley M. Stratos, Georgette A. Walker, Jennifer D. Grossi, Eugene A. Verrier, Edward D. Hicks, George L., Jr. Feins, Richard H. TI Teaching behaviors in the cardiac surgery simulation environment SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID EDUCATIONAL FRAMEWORK; FACTORIAL VALIDATION; CLINICAL TEACHERS; MEDICAL-STUDENTS AB Objective: To understand how teaching behaviors contribute to simulation-based learning, we used a 7-category educational framework to assess the teaching behaviors used in basic skills training. Methods: Twenty-four first-year cardiothoracic surgery residents and 20 faculty participated in the Boot Camp vessel anastomosis sessions. A portable chest model with synthetic graft and target vessels and a tissue-based porcine model simulated coronary artery anastomosis. After each 2-hour session on days 1 and 2, residents assessed teaching behaviors of faculty using a 20-item questionnaire based on the 5-point Likert scale. After session on day 1, faculty completed a self-assessment questionnaire. At 3 months, faculty completed self-assessment questionnaires regarding teaching behaviors in simulation and clinical settings. Each questionnaire item represents 1 or more teaching categories: "learning climate,'' "control of session,'' "communication of goals,'' "promoting understanding and retention,'' "evaluation,'' "feedback,'' and "self-directed learning.'' Results: Generally, resident ratings indicated that faculty showed positive teaching behaviors. Faculty self-assessment ratings were all lower (P<.025) than those assigned to them by the residents except for 1 component representative of "feedback,'' which approached significance (P=.04); 2 items, representative of "promoting understanding and retention'' and "evaluation'', had mean scores of less than 3. At 3 months, compared with self-assessment at Boot Camp, faculty ratings suggested improved teaching behaviors in their simulation settings in the following: "learning climate,'' "control of session,'' "communication of goals,'' "promoting understanding and retention,'' and "evaluation.'' The simulation environment was perceived as more positive for technical skills training in certain aspects compared with clinical setting: instructor reviewed function and operation of equipment with learner before session (representative of "promoting understanding and retention'') and instructor allowed the learner ample time to practice (representative of "control of session'' and "promoting understanding and retention'') (P<.025). Conclusions: Simulation-based skills training is perceived by residents to be associated with positive teaching behaviors. Faculty self-ratings indicate that they do not always use many of these teaching behaviors and that their performance can be improved. The simulation setting may provide greater opportunity for positive teaching behaviors compared with the clinical environment. (J Thorac Cardiovasc Surg 2013;145:45-53) C1 [Fann, James I.] Stanford Univ, Dept Cardiothorac Surg, Stanford, CA 94305 USA. [Sullivan, Maura E.] Univ So Calif, Los Angeles, CA USA. [Walker, Jennifer D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Grossi, Eugene A.] NYU, New York, NY USA. [Verrier, Edward D.] Univ Washington, Seattle, WA 98195 USA. [Hicks, George L., Jr.] Univ Rochester, Rochester, NY USA. [Feins, Richard H.] Univ N Carolina, Chapel Hill, NC USA. RP Fann, JI (reprint author), Stanford Univ, Dept Cardiothorac Surg, 300 Pasteur Dr, Stanford, CA 94305 USA. EM jfann@stanford.edu OI GROSSI, eugene/0000-0002-2066-7035 FU Thoracic Surgery Directors Association; Joint Council for Thoracic Surgery Education; Thoracic Surgery Foundation for Research and Education; Western Thoracic Surgical Association Doty Award; Stanford Center for Immersive and Simulation-Based Learning FX This study was supported by the Thoracic Surgery Directors Association and the Joint Council for Thoracic Surgery Education and grant support from the Thoracic Surgery Foundation for Research and Education (to J.I.F. and R.H.F.), Western Thoracic Surgical Association Doty Award (to J.I.F.), and Stanford Center for Immersive and Simulation-Based Learning (to J.I.F.). Corporate sponsors of this session included the Chamberlain Group, Sorin Group, Cryolife, Inc, and Teleflex Medical. NR 24 TC 4 Z9 4 U1 0 U2 6 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 JAN PY 2013 VL 145 IS 1 BP 45 EP 53 DI 10.1016/j.jtcvs.2012.07.111 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 055AE UT WOS:000312386300017 PM 23098747 ER PT J AU Eckhouse, SR Akerman, AW Logdon, CB Oelsen, JM O'Quinn, EC Nadeau, EK Stroud, RE Mukherjee, R Jones, JA Spinale, FG AF Eckhouse, Shaina R. Akerman, Adam W. Logdon, Christina B. Oelsen, J. Marshall O'Quinn, Elizabeth C. Nadeau, Elizabeth K. Stroud, Robert E. Mukherjee, Rupak Jones, Jeffrey A. Spinale, Francis G. TI Differential membrane type 1 matrix metalloproteinase substrate processing with ischemia-reperfusion: Relationship to interstitial microRNA dynamics and myocardial function SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID 1-MATRIX METALLOPROTEINASE; EXTRACELLULAR-MATRIX; CARDIAC FIBROBLASTS; HEART-DISEASE; ACTIVATION; INFARCTION; FIBROSIS; BETA; INDUCTION; TARGETS AB Objectives: Membrane type 1 matrix metalloproteinase (MT1-MMP) is critical to a number of proteolytic and profibrotic events. However, upstream regulation of MT1-MMP with myocardial ischemia-reperfusion remains poorly understood. MicroRNAs regulate post-transcriptional events, and in silico mapping has identified a conserved sequence in MT1-MMP for microRNA-133a. This study tested the hypothesis that changes in microRNA-133a regulation occur with myocardial ischemia-reperfusion, which contributes to time- and region-dependent changes in MT1-MMP activity and processing of MT1-MMP substrates. Methods: Yorkshire pigs (n = 12) underwent ischemia-reperfusion (90 minutes ischemia and 120 minutes reperfusion), where regional preload recruitable stroke work (sonomicrometry), interstitial MT1-MMP activity (microdialysis), Smad2 abundance (immunoblotting), and interstitial microRNA-133a (polymerase chain reaction) were determined within the ischemia-reperfusion and remote regions. Human left ventricular fibroblasts were transduced with microRNA-133a and anti-microRNA-133a (lentivirus) to determine the effects on MT1-MMP protein abundance. Results: With ischemia-reperfusion, regional preload recruitable stroke work decreased from steady state (139 +/- 20 mm Hg to 44 +/- 11 mm Hg, P < .05) within the ischemia-reperfusion region. MT1-MMP activity increased in both regions. Phosphorylated Smad2 increased within the ischemia-reperfusion region. Both in vitro and in vivo interstitial levels of microRNA-133a decreased with ischemia and returned to steady-state levels with reperfusion. In vitro transduction of microRNA-133a in left ventricular fibroblasts decreased MT1-MMP levels. Conclusions: Modulation of MT1-MMP activity and microRNA-133a exportation into the myocardial interstitium occurred in the setting of acute myocardial ischemia-reperfusion. In addition, changes in microRNA-133a expression in left ventricular fibroblasts resulted in an inverse modulation of MT1-MMP abundance. Therefore, targeting of microRNA-133a represents a potentially novel means for regulating the cascade of profibrotic events after ischemia- reperfusion. (J Thorac Cardiovasc Surg 2013;145:267-77) C1 [Eckhouse, Shaina R.; Akerman, Adam W.; Logdon, Christina B.; Oelsen, J. Marshall; O'Quinn, Elizabeth C.; Nadeau, Elizabeth K.; Stroud, Robert E.; Mukherjee, Rupak; Jones, Jeffrey A.; Spinale, Francis G.] Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA. [Eckhouse, Shaina R.; Akerman, Adam W.; Logdon, Christina B.; Oelsen, J. Marshall; O'Quinn, Elizabeth C.; Nadeau, Elizabeth K.; Stroud, Robert E.; Mukherjee, Rupak; Jones, Jeffrey A.; Spinale, Francis G.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Spinale, Francis G.] Univ S Carolina, Sch Med, Div Cell Biol & Anat, Columbia, SC USA. RP Jones, JA (reprint author), Strom Thurmond Res Ctr, Cardiothorac Surg Res, 114 Doughty St,Suite 326, Charleston, SC 29425 USA. EM jonesja@musc.edu FU National Institute of Health [HL057952, HL059165, HL095608, T32 HL007260]; Veterans' Affairs Health Administration FX This work was supported by National Institute of Health Grants HL057952, HL059165, and HL095608, and a Merit Award from the Veterans' Affairs Health Administration. S.R.E. was supported by National Institute of Health Grant T32 HL007260. NR 43 TC 4 Z9 4 U1 0 U2 4 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 JAN PY 2013 VL 145 IS 1 BP 267 EP + DI 10.1016/j.jtcvs.2012.09.071 PG 15 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 055AE UT WOS:000312386300046 PM 23102905 ER PT J AU Reynolds, M Thompson, A Duhay, F AF Reynolds, Matthew Thompson, Ann Duhay, Francis TI CORRECTION OF FAULTY ASSUMPTIONS IN COST-EFFECTIVENESS ANALYSIS SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Letter ID AORTIC-VALVE-REPLACEMENT; TRANSCATHETER C1 [Reynolds, Matthew] Boston VA Healthcare Syst, Harvard Clin Res Inst, Boston, MA USA. [Thompson, Ann; Duhay, Francis] Edwards Lifesci LLC, Irvine, CA USA. RP Reynolds, M (reprint author), Boston VA Healthcare Syst, Harvard Clin Res Inst, Boston, MA USA. NR 5 TC 2 Z9 2 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JAN PY 2013 VL 145 IS 1 BP 308 EP 309 DI 10.1016/j.jtcvs.2012.09.038 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 055AE UT WOS:000312386300058 PM 23244261 ER PT J AU Podgaetz, E Deschamps, C AF Podgaetz, Eitan Deschamps, Claude TI Esophageal complications of catheter ablation for atrial fibrillation: A case report SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material ID PULMONARY-VEIN ABLATION; RADIOFREQUENCY ABLATION; ATRIOESOPHAGEAL FISTULA; RISK; PERFORATION; INJURY; PREVALENCE; MANAGEMENT C1 [Podgaetz, Eitan] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. [Deschamps, Claude] Mayo Clin, Div Thorac Surg, Rochester, MN USA. RP Podgaetz, E (reprint author), 7 Emerson Pl 702, Boston, MA 02114 USA. EM epodgaetz@partners.org NR 37 TC 2 Z9 2 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JAN PY 2013 VL 145 IS 1 BP E9 EP E13 DI 10.1016/j.jtcvs.2012.10.022 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 055AE UT WOS:000312386300005 PM 23142115 ER PT J AU Conrad, MF Fairman, RM Cambria, RP Farber, M Matsumoto, A Williams, D Criado, FJ Kwolek, CJ AF Conrad, Mark F. Fairman, Ronald M. Cambria, Richard P. Farber, Mark Matsumoto, Alan Williams, David Criado, Frank J. Kwolek, Christopher J. TI One-Year Safety and Efficacy of Thoracic Aortic Stent Grafting (TEVAR) in Patients Who Are Poor Open Surgical Candidates: Results of the High-Risk Arm of the Valor Trial SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT 41st Annual Symposium of the Society-for-Clinical-Vascular-Surgery CY MAR 12-16, 2013 CL Miami Beach, FL SP Soc Clin Vasc Surg C1 [Conrad, Mark F.; Cambria, Richard P.; Kwolek, Christopher J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fairman, Ronald M.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Farber, Mark] Univ N Carolina, Chapel Hill, NC USA. [Matsumoto, Alan] Univ Virginia, Charlottesville, VA USA. [Williams, David] Univ Michigan, Ann Arbor, MI 48109 USA. [Criado, Frank J.] Union Mem Hosp, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JAN PY 2013 VL 57 IS 1 BP 287 EP 287 PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 061FN UT WOS:000312833800065 ER PT J AU Lo, RC Lu, B Conrad, MF Fillinger, MF Matyal, R Hamdan, AD Schermerhorn, ML AF Lo, Ruby C. Lu, Bing Conrad, Mark F. Fillinger, Mark F. Matyal, Robina Hamdan, Allen D. Schermerhorn, Marc L. TI Relative Importance of Aneurysm Diameter and Body Size for Predicting AAA Rupture in Men and Women SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT 41st Annual Symposium of the Society-for-Clinical-Vascular-Surgery CY MAR 12-16, 2013 CL Miami Beach, FL SP Soc Clin Vasc Surg C1 [Lo, Ruby C.; Matyal, Robina; Hamdan, Allen D.; Schermerhorn, Marc L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Lu, Bing] Brigham & Womens Hosp, Boston, MA 02115 USA. [Conrad, Mark F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fillinger, Mark F.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JAN PY 2013 VL 57 IS 1 BP 287 EP 288 PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 061FN UT WOS:000312833800066 ER PT J AU Baril, DT Patel, VI Judelson, DR Goodney, PP McPhee, JT Prushik, SG Hevelone, N Cronenwett, JL Schanzer, A AF Baril, Donald T. Patel, Virendra I. Judelson, Dejah R. Goodney, Philip P. McPhee, James T. Prushik, Scott G. Hevelone, Nathanael Cronenwett, Jack L. Schanzer, Andres TI Outcomes of Lower Extremity Bypass Performed for Acute Limb Ischemia SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT 41st Annual Symposium of the Society-for-Clinical-Vascular-Surgery CY MAR 12-16, 2013 CL Miami Beach, FL SP Soc Clin Vasc Surg C1 [Baril, Donald T.; Judelson, Dejah R.; Schanzer, Andres] Univ Massachusetts, Med Ctr, Worcester, MA USA. [Patel, Virendra I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goodney, Philip P.; Cronenwett, Jack L.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [McPhee, James T.] Boston Med Ctr, Boston, MA USA. [Prushik, Scott G.] St Elizabeths Med Ctr, Boston, MA USA. [Hevelone, Nathanael] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JAN PY 2013 VL 57 IS 1 BP 296 EP 297 PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 061FN UT WOS:000312833800092 ER PT J AU Patel, VI Mukhopadhyay, S Ergul, E Conrad, MF Cambria, RP AF Patel, Virendra I. Mukhopadhyay, Shankha Ergul, Emel Conrad, Mark F. Cambria, Richard P. TI Extracorporeal Bypass Use Improves Outcomes of Open Thoracic and Thoracoabdominal Aneurysm Repair SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT 41st Annual Symposium of the Society-for-Clinical-Vascular-Surgery CY MAR 12-16, 2013 CL Miami Beach, FL SP Soc Clin Vasc Surg C1 [Patel, Virendra I.; Mukhopadhyay, Shankha; Ergul, Emel; Conrad, Mark F.; Cambria, Richard P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JAN PY 2013 VL 57 IS 1 BP 296 EP 296 PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 061FN UT WOS:000312833800090 ER PT J AU Dolle, JP Morrison, B Schloss, RS Yarmush, ML AF Dolle, Jean-Pierre Morrison, Barclay, III Schloss, Rene S. Yarmush, Martin L. TI An organotypic uniaxial strain model using microfluidics SO LAB ON A CHIP LA English DT Article ID TRAUMATIC BRAIN-INJURY; HIPPOCAMPAL SLICE CULTURES; DIFFUSE AXONAL INJURY; IN-VITRO MODEL; DYNAMIC STRETCH INJURY; HEAD-INJURY; MECHANICAL STRETCH; SODIUM-CHANNELS; NEURAL TRAUMA; OPTIC-NERVE AB Traumatic brain injuries are the leading cause of disability each year in the US. The most common and devastating consequence is the stretching of axons caused by shear deformation that occurs during rotational acceleration of the brain during injury. The injury effects on axonal molecular and functional events are not fully characterized. We have developed a strain injury model that maintains the three dimensional cell architecture and neuronal networks found in vivo with the ability to visualize individual axons and their response to a mechanical injury. The advantage of this model is that it can apply uniaxial strains to axons that make functional connections between two organotypic slices and injury responses can be observed in real-time and over long term. This uniaxial strain model was designed to be capable of applying an array of mechanical strains at various rates of strain, thus replicating a range of modes of axonal injury. Long term culture, preservation of slice and cell orientation, and slice-slice connection on the device was demonstrated. The device has the ability to strain either individual axons or bundles of axons through the control of microchannel dimensions. The fidelity of the model was verified by observing characteristic responses to various strain injuries which included axonal beading, delayed elastic effects and breakdown in microtubules. Microtubule breakdown was shown to be dependent on the degree of the applied strain field, where maximal breakdown was observed at peak strain and minimal breakdown is observed at low strain. This strain injury model could be a powerful tool in assessing strain injury effects on functional axonal connections. C1 [Dolle, Jean-Pierre; Schloss, Rene S.; Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. [Morrison, Barclay, III] Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA. [Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Rutgers State Univ, Dept Biomed Engn, 599 Taylor Rd, Piscataway, NJ 08854 USA. EM jpdolle@rutgers.edu; bm2119@columbia.edu; schloss@soemail.rutgers.edu; yarmush@rci.rutgers.edu RI Morrison, Barclay/B-7132-2008 OI Morrison, Barclay/0000-0001-7676-0864 FU New Jersey Commission for Brain Injury Research [BIR-1.08.016]; National Institute of Biomedical Imaging and Bioengineering [NIH P41 EB002503]; National Institute of General Medical Sciences (Rutgers-UMDNJ Biotechnology Training Program) [T32 GM 008339] FX This work was supported by grants from the New Jersey Commission for Brain Injury Research (BIR-1.08.016), the National Institute of Biomedical Imaging and Bioengineering (NIH P41 EB002503), and the National Institute of General Medical Sciences (Rutgers-UMDNJ Biotechnology Training Program: T32 GM 008339). NR 49 TC 6 Z9 6 U1 1 U2 36 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2013 VL 13 IS 3 BP 432 EP 442 DI 10.1039/c2lc41063j PG 11 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 062UE UT WOS:000312947300015 PM 23233120 ER PT J AU Kharfan-Dabaja, MA Boeckh, M Wilck, MB Langston, AA Chu, AH Wloch, MK Smith, LR Rolland, AP Kenney, RT AF Kharfan-Dabaja, Mohamed A. Boeckh, Michael Wilck, Marissa B. Langston, Amelia A. Chu, Alice H. Wloch, Mary K. Smith, Larry R. Rolland, Alain P. Kenney, Richard T. TI Reanalysis of TransVax immunogenicity SO LANCET INFECTIOUS DISEASES LA English DT Letter C1 [Kharfan-Dabaja, Mohamed A.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL 33612 USA. [Kharfan-Dabaja, Mohamed A.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Oncol Sci, Tampa, FL 33612 USA. [Kharfan-Dabaja, Mohamed A.] American Univ, Beirut Med Ctr, Div Hematol Oncol & Bone Marrow Transplantat, Beirut, Lebanon. [Boeckh, Michael] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA. [Wilck, Marissa B.] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Infect Dis, Boston, MA 02115 USA. [Wilck, Marissa B.] Hosp Univ Penn, Div Infect Dis, Philadelphia, PA 19104 USA. [Langston, Amelia A.] Emory Univ, Sch Med, Winship Canc Inst, Bone Marrow & Stem Cell Transplant Ctr, Atlanta, GA USA. [Chu, Alice H.] Vical, Dept Clin Dev, San Diego, CA USA. [Wloch, Mary K.; Smith, Larry R.] Vical, Dept Vaccinol, San Diego, CA USA. [Rolland, Alain P.] Vical, Dept Prod Dev, San Diego, CA USA. [Kenney, Richard T.] Crucell Holland BV, Leiden, Netherlands. RP Kharfan-Dabaja, MA (reprint author), Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL 33612 USA. NR 1 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1473-3099 EI 1474-4457 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD JAN PY 2013 VL 13 IS 1 BP 18 EP 18 DI 10.1016/S1473-3099(12)70296-7 PG 1 WC Infectious Diseases SC Infectious Diseases GA 060FO UT WOS:000312762100019 PM 23257230 ER PT J AU Janne, PA Shaw, AT Pereira, JR Jeannin, G Vansteenkiste, J Barrios, C Franke, FA Grinsted, L Zazulina, V Smith, P Smith, I Crino, L AF Jaenne, Pasi A. Shaw, Alice T. Pereira, Jose Rodrigues Jeannin, Gaelle Vansteenkiste, Johan Barrios, Carlos Franke, Fabio Andre Grinsted, Lynda Zazulina, Victoria Smith, Paul Smith, Ian Crino, Lucio TI Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study SO LANCET ONCOLOGY LA English DT Article ID INHIBITOR AZD6244 ARRY-142886; KINASE KINASE-1/2 INHIBITOR; GROWTH-FACTOR RECEPTOR; OPEN-LABEL; MEK1/2 INHIBITOR; RAS ONCOGENE; III TRIAL; CHEMOTHERAPY; COMBINATION; MUTATIONS AB Background No targeted therapies are available for KRAS-mutant non-small-cell lung cancer (NSCLC). Selumetinib is an inhibitor of MEK1/MEK2, downstream of KRAS, with preclinical evidence of synergistic activity with docetaxel in KRAS-mutant cancers. We did a prospective, randomised, phase 2 trial to assess selumetinib plus docetaxel in previously treated patients with advanced KRAS-mutant NSCLC. Methods Eligible patients were older than 18 years of age; had histologically or cytologically confirmed stage IIIB-IV KRAS-mutant NSCLC; had failed first-line therapy for advanced NSCLC; had WHO performance status of 0-1; had not received previous therapy with either a MEK inhibitor or docetaxel; and had adequate bone marrow, renal, and liver function. Patients were randomly assigned (in a 1:1 ratio) to either oral selumetinib (75 mg twice daily in a 21 day cycle) or placebo; all patients received intravenous docetaxel (75 mg/m(2) on day 1 of a 21 day cycle). Randomisation was done with an interactive voice response system and investigators, patients, data analysts, and the trial sponsor were masked to treatment assignment. The primary endpoint was overall survival, analysed for all patients with confirmed KRAS mutations. This study is registered with ClinicalTrials.gov, number NCT00890825. Findings Between April 20, 2009, and June 30, 2010, we randomly assigned 44 patients to receive selumetinib and docetaxel (selumetinib group) and 43 to receive placebo and docetaxel (placebo group). Of these, one patient in the selumetinib group and three in the placebo group were excluded from efficacy analyses because their tumours were not confirmed to be KRAS-mutation positive. Median overall survival was 9.4 months (6.8-13.6) in the selumetinib group and 5.2 months (95% CI 3.8-non-calculable) in the placebo group (hazard ratio [HR] for death 0.80, 80% CI 0.56-1.14; one-sided p=0.21). Median progression-free survival was 5.3 months (4.6-6.4) in the selumetinib group and 2.1 months (95% CI 1.4-3.7) in the placebo group (HR for progression 0.58, 80% CI 0.42-0.79; one-sided p=0.014). 16 (37%) patients in the selumetinib group and none in the placebo group had an objective response (p<0.0001). Adverse events of grade 3 or higher occurred in 36 (82%) patients in the selumetinib group and 28 (67%) patients in the placebo group. The most common grade 3-4 adverse events were neutropenia (29 [67%] of 43 patients in the selumetinib group vs 23 [55%] of 42 patients in the placebo group), febrile neutropenia (eight [18%] of 44 patients in the selumetinib group vs none in the placebo group), dyspnoea (one [2%] of 44 patients in the selumetinib group vs five [12%] of 42 in the placebo group), and asthenia (four [9%] of 44 patients in the selumetinib group vs none in the placebo group). Interpretation Selumetinib plus docetaxel has promising efficacy, albeit with a higher number of adverse events than with docetaxel alone, in previously treated advanced KRAS-mutant NSCLC. These findings warrant further clinical investigation of selumetinib plus docetaxel in KRAS-mutant NSCLC. Funding AstraZeneca. C1 [Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02215 USA. [Shaw, Alice T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Pereira, Jose Rodrigues] Inst Brasileiro Cancerol Torac, Sao Paulo, Brazil. [Jeannin, Gaelle] Hop Gabriel Montpied, Serv Pneumol, Clermont Ferrand, France. [Vansteenkiste, Johan] Univ Hosp Gasthuisberg, Dept Pneumol, Resp Oncol Unit, B-3000 Louvain, Belgium. [Vansteenkiste, Johan] Univ Hosp Gasthuisberg, Dept Pneumol, Trial Unit, B-3000 Louvain, Belgium. [Barrios, Carlos] Ctr Pesquisa Oncol, PUCRS Sch Med, Porto Alegre, RS, Brazil. [Franke, Fabio Andre] Hosp Caridade Ijui, CACON, Ijui, Brazil. [Grinsted, Lynda; Zazulina, Victoria; Smith, Paul; Smith, Ian] AstraZeneca UK, Macclesfield, Cheshire, England. [Crino, Lucio] Hosp S Maria Misericordia, Div Med Oncol, Perugia, Italy. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA. EM pjanne@partners.org RI Vansteenkiste, Johan/B-8191-2014; Barrios, Carlos/G-8525-2015 OI Vansteenkiste, Johan/0000-0002-6721-2775; FU AstraZeneca; Roche; Genentech; Pfizer; Boehringer Ingelheim; Sanofi; Novartis; Ariad; Chugi; Daiichi-Sankyo; GlaxoSmithKline FX PAJ has received consultancy fees from AstraZeneca, Roche, Genentech, Pfizer, Boehringer Ingelheim, and Sanofi, and other remuneration from Lab Corp. ATS has received consultancy fees from Pfizer, Ariad, Novartis, Chugi, and Daiichi-Sankyo, and received research funding from AstraZeneca and Novartis. JV's institute has received research funding from AstraZeneca. CB has received consultancy fees from Pfizer, Roche, and GlaxoSmithKline and has received research funding from AstraZeneca. LG is an employee of AstraZeneca. IS, PS, and LG are employees and stockholders of AstraZeneca. VZ is a former employee of AstraZeneca. JRP, GJ, FAF, and LC declare that they have no conflicts of interest. NR 32 TC 284 Z9 295 U1 7 U2 59 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD JAN PY 2013 VL 14 IS 1 BP 38 EP 47 DI 10.1016/S1470-2045(12)70489-8 PG 10 WC Oncology SC Oncology GA 064BM UT WOS:000313045900039 PM 23200175 ER PT J AU Schutz, FAB Pomerantz, MM Gray, KP Atkins, MB Rosenberg, JE Hirsch, MS McDermott, DF Lampron, ME Lee, GSM Signoretti, S Kantoff, PW Freedman, ML Choueiri, TK AF Schutz, Fabio A. B. Pomerantz, Mark M. Gray, Kathryn P. Atkins, Michael B. Rosenberg, Jonathan E. Hirsch, Michelle S. McDermott, David F. Lampron, Megan E. Lee, Gwo-Shu Mary Signoretti, Sabina Kantoff, Philip W. Freedman, Matthew L. Choueiri, Toni K. TI Single nucleotide polymorphisms and risk of recurrence of renal-cell carcinoma: a cohort study SO LANCET ONCOLOGY LA English DT Article ID MET SIGNALING PATHWAY; PREDICTIVE ACCURACY; CANCER PROGNOSIS; ASSOCIATION; SUSCEPTIBILITY; VARIANTS; MODELS; EXPRESSION; GERMLINE; SURVIVAL AB Background Germline genetic polymorphisms might affect the risk of recurrence in patients with localised renal-cell carcinoma. We investigated the association between genetic polymorphisms and recurrence of renal-cell carcinoma. Methods We analysed germline DNA samples extracted from patients with localised renal-cell carcinoma treated at the Dana-Farber/Harvard Cancer Center (Boston, MA, USA). We selected a discovery cohort from a prospective database at the Dana-Farber/Harvard Cancer Center and selected a validation cohort from department records at the Brigham and Women's Hospital (Boston, MA, USA). We validated the findings from the discovery cohort in the validation cohort. We genotyped 70 genes involved in the pathogenesis of renal-cell carcinoma (including the VHL/HIF/VEGF and PI3K/AKT/mTOR pathways, and genes involved in immune regulation and metabolism) for single nucleotide polymorphisms. We assessed the association between genotype and recurrence-free survival, adjusted for baseline characteristics, with the Cox proportional hazards model, the Kaplan-Meier method, and the log-rank test. We used a false discovery rate q value to adjust for multiple comparisons. Findings We included 554 patients (403 in the discovery cohort and 151 in the validation cohort). We successfully genotyped 290 single nucleotide polymorphisms in the discovery cohort, but excluded five because they did not have a variant group for comparison. The polymorphism rs11762213, which causes a synonymous aminoacid change in MET (144G -> A, located in exon 2), was associated with recurrence-free survival. Patients with one or two copies of the minor (risk) allele had an increased risk of recurrence or death (hazard ratio [HR] 1.86, 95% CI 1.17-2.95; p=0.0084) in multivariate analysis. Median recurrence-free survival for carriers of the risk allele was 19 months (95% CI 9-not reached) versus 50 months (95% CI 37-75) for patients without the risk allele. In the validation cohort the HR was 2.45 (95% CI 1.01-5.95; p=0.048). Interpretation Patients with localised renal-cell carcinoma and the MET polymorphism rs11762213 might have an increased risk of recurrence after nephrectomy. If these results are further validated in a similar population, they could be incorporated into future prognostic instruments, potentially aiding the design of adjuvant clinical trials of MET inhibitors and management of renal-cell carcinoma. C1 [Schutz, Fabio A. B.; Pomerantz, Mark M.; Gray, Kathryn P.; Rosenberg, Jonathan E.; Lee, Gwo-Shu Mary; Kantoff, Philip W.; Freedman, Matthew L.; Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pomerantz, Mark M.; Rosenberg, Jonathan E.; Hirsch, Michelle S.; Signoretti, Sabina; Kantoff, Philip W.; Choueiri, Toni K.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Atkins, Michael B.; McDermott, David F.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Atkins, Michael B.; McDermott, David F.; Lampron, Megan E.; Signoretti, Sabina; Choueiri, Toni K.] Dana Farber Harvard Canc Ctr, Kidney Canc Program, Boston, MA USA. [Schutz, Fabio A. B.; Pomerantz, Mark M.; Atkins, Michael B.; Rosenberg, Jonathan E.; Hirsch, Michelle S.; McDermott, David F.; Lee, Gwo-Shu Mary; Signoretti, Sabina; Kantoff, Philip W.; Freedman, Matthew L.; Choueiri, Toni K.] Harvard Univ, Sch Med, Boston, MA USA. [Gray, Kathryn P.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Choueiri, TK (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM toni_choueiri@DFCI.harvard.edu FU Conquer Cancer Foundation; American Society of Clinical Oncology (Career Development Award); The Trust Family Research Fund for Kidney Cancer; US National Institutes of Health, National Cancer Institute Kidney Cancer Specialized Program of Research Excellence; Pfizer; GlaxoSmithKline; Sanofi-Aventis; Novartis FX Conquer Cancer Foundation and American Society of Clinical Oncology (Career Development Award); The Trust Family Research Fund for Kidney Cancer; US National Institutes of Health, National Cancer Institute Kidney Cancer Specialized Program of Research Excellence.; TKC has received research funding from Pfizer and has served on advisory boards for Novartis, Pfizer, Aveo, and GlaxoSmithKline. MBA has served on advisory boards for Genentech, Bristol-Myers Squibb, Novartis, Prometheus, Amgen, Merck, and Aveo. JER has served on advisory boards or has been a consultant for Genentech, Abbott, and Novartis and has taken part in a speakers bureau for Novartis. He has also received research funding from GlaxoSmithKline, Sanofi-Aventis, and Novartis. The other authors declare that they have no conflicts of interest. NR 31 TC 27 Z9 28 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 JAN PY 2013 VL 14 IS 1 BP 81 EP 87 DI 10.1016/S1470-2045(12)70517-X PG 7 WC Oncology SC Oncology GA 064BM UT WOS:000313045900044 PM 23219378 ER PT J AU Goss, PE Smith, IE O'Shaughnessy, J Ejlertsen, B Kaufmann, M Boyle, F Buzdar, AU Fumoleau, P Gradishar, W Martin, M Moy, B Piccart-Gebhart, M Pritchard, KI Lindquist, D Chavarri-Guerra, Y Aktan, G Rappold, E Williams, LS Finkelstein, DM AF Goss, Paul E. Smith, Ian E. O'Shaughnessy, Joyce Ejlertsen, Bent Kaufmann, Manfred Boyle, Frances Buzdar, Aman U. Fumoleau, Pierre Gradishar, William Martin, Miguel Moy, Beverly Piccart-Gebhart, Martine Pritchard, Kathleen I. Lindquist, Deborah Chavarri-Guerra, Yanin Aktan, Gursel Rappold, Erica Williams, Lisa S. Finkelstein, Dianne M. CA TEACH Investigators TI Adjuvant lapatinib for women with early-stage HER2-positive breast cancer: a randomised, controlled, phase 3 trial SO LANCET ONCOLOGY LA English DT Article ID TRASTUZUMAB; CHEMOTHERAPY; RECEPTOR; THERAPY; N9831 AB Background Worldwide, many patients with HER2-positive early stage breast cancer do not receive trastuzumab-the standard adjuvant treatment. We investigated the efficacy and safety of adjuvant lapatinib for patients with trastuzumab-naive HER2-positive early-stage breast cancer, started at any time after diagnosis. Methods This study was a placebo-controlled, multicentre, randomised phase 3 trial. Women outpatients from 33 centres with HER2-positive early-breast cancer who had previously received adjuvant chemotherapy but not trastuzumab were randomly assigned (1:1) to receive daily lapatinib (1500 mg) or daily placebo for 12 months. Randomisation was done with a computer-generated sequence, stratified by time since diagnosis, lymph node involvement at diagnosis, and tumour hormone-receptor status. Investigators, site staff, and patients were masked to treatment assignment. The primary endpoint was disease-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00374322. Findings Between August, 2006, and May, 2008, 3161 women were enrolled and 3147 were assigned to lapatinib (n=1571) or placebo (n=1576). After a median follow-up of 47.4 months (range 0.4-60.0) in the lapatinib group and 48.3 (0.7-61.3) in the placebo group, 210 (13%) disease-free survival events had occurred in the lapatinib group versus 264 (17%) in the placebo group (hazard ratio [HR] 0.83, 95% CI 0.70-1.00; p=0.053). Central review of HER2 status showed that only 2490 (79%) of the randomised women were HER2-positive. 157 (13%) of 1230 confirmed HER2-positive patients in the lapatinib group and in 208 (17%) of 1260 in the placebo group had a disease-free survival event (HR 0.82, 95% 0.67-1.00; p=0.04). Serious adverse events occurred in 99 (6%) of 1573 patients taking lapatinib and 77 (5%) of 1574 patients taking placebo, with higher incidences of grade 3-4 diarrhoea (97 [6%] vs nine [<1%]), rash (72 [5%] vs three [<1%]), and hepatobiliary disorders (36 [2%] vs one [<1%]). Interpretation Our data show that there was no significant difference in disease-free survival between groups when analysed in the intention-to-treat population. However, exploratory analyses restricted to patients who had HER2-positive disease confirmed by central fluorescence in-situ hybridisation review suggested marginal benefit with lapatinib in terms of disease-free survival. Thus lapatinib might be an option for women with HER2-positive breast cancer who do not or cannot receive adjuvant trastuzumab. C1 [Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Smith, Ian E.] Royal Marsden Hosp, London SW3 6JJ, England. [O'Shaughnessy, Joyce] Baylor Sammons Canc Ctr, Dallas, TX USA. [Ejlertsen, Bent] Rigshosp, DBCG Secretariat, DK-2100 Copenhagen, Denmark. [Kaufmann, Manfred] Goethe Univ Frankfurt, Frankfurt, Germany. [Boyle, Frances] Mater Hosp, Sydney, NSW, Australia. [Buzdar, Aman U.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Fumoleau, Pierre] Ctr GF Leclerc, Dijon, France. [Gradishar, William] Northwestern Univ, Chicago, IL 60611 USA. [Martin, Miguel] Univ Complutense, Hosp Univ Gregorio Maranon, E-28040 Madrid, Spain. [Piccart-Gebhart, Martine] Univ Libre Brussels, Inst Jules Bordet, Brussels, Belgium. [Pritchard, Kathleen I.] Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Lindquist, Deborah] US Oncol, Arizona Oncol, Sedona, AZ USA. [Aktan, Gursel] GlaxoSmithKline, Collegeville, PA USA. [Williams, Lisa S.] GlaxoSmithKline, Uxbridge, Middx, England. 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 OI MARTIN, MIGUEL/0000-0001-9237-3231; Brunet, Joan/0000-0003-1945-3512 FU GlaxoSmithKline; Avon Foundation (New York, NY, USA); Roche FX GlaxoSmithKline.; PEG has received speaker's honoraria from GlaxoSmithKline and Pfizer and is supported by the Avon Foundation (New York, NY, USA). MP-G's institution has received grants from GlaxoSmithKline and Roche; MP-G has received consultancy fees and honoraria from Roche. BE has received fees from GlaxoSmithKline for participating in advisory boards. KIP and IES have received honoraria and consulting fees from Roche and GlaxoSmithKline. GA and ER are employees of GlaxoSmithKline and own stocks and shares of GlaxoSmithKline. JO'S is a consultant to GlaxoSmithKline. FB is consultant to GlaxoSmithKline and has received fees from GlaxoSmithKline for participating in advisory boards. LSW is employee of GlaxoSmithKline. MK, AUB, PF, WG, MM, BM, DL, YC-G, and DMF declare that they have no conflicts of interest.; The study drug and funding support were provided by GlaxoSmithKline. We thank the women who agreed to participate in this study. We also thank the trial committee; the many hundreds of investigators, pharmacists, and clinical research associates and centres involved in the trial; the members of the TEACH data safety monitoring committee; and GlaxoSmithKline for their financial and study conduct support, and for the provision of lapatinib and placebo. Editorial and figure support was provided by Sarah White and Susan Casson at Fishawack Scientific Communications. NR 24 TC 52 Z9 54 U1 0 U2 12 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 JAN PY 2013 VL 14 IS 1 BP 88 EP 96 DI 10.1016/S1470-2045(12)70508-9 PG 9 WC Oncology SC Oncology GA 064BM UT WOS:000313045900045 PM 23234763 ER PT J AU Shargorodsky, J Bhattacharyya, N AF Shargorodsky, Josef Bhattacharyya, Neil TI What is the Role of Nasal Endoscopy in the Diagnosis of Chronic Rhinosinusitis? SO LARYNGOSCOPE LA English DT Article C1 [Shargorodsky, Josef] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Bhattacharyya, Neil] Brigham & Womens Hosp, Div Otolaryngol, Boston, MA 02115 USA. [Shargorodsky, Josef; Bhattacharyya, Neil] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Bhattacharyya, N (reprint author), Brigham & Womens Hosp, Div Otolaryngol, 45 Francis St, Boston, MA 02115 USA. EM neiloy@massmed.org NR 5 TC 6 Z9 7 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JAN PY 2013 VL 123 IS 1 BP 4 EP 6 DI 10.1002/lary.23385 PG 3 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 062TW UT WOS:000312946400003 PM 23280937 ER PT J AU Sedaghat, AR Busaba, NY Cunningham, MJ Kieff, DA AF Sedaghat, Ahmad R. Busaba, Nicolas Y. Cunningham, Michael J. Kieff, David A. TI Clinical Assessment is an Accurate Predictor of Which Patients Will Need Septoplasty SO LARYNGOSCOPE LA English DT Article DE Septoplasty; deviated nasal septum; intranasal corticosteroids; medical therapy; practice guidelines; medical therapy requirement ID NASAL OBSTRUCTION; OUTCOMES; NOSE; SURGERY; ADULT AB Objectives/Hypothesis: Septoplasty is a frequently performed surgical procedure with the most common indication being nasal airway obstruction. Almost universally, health insurance companies mandate a trial of medical therapy consisting of intranasal corticosteroids prior to performance of septoplasty regardless of clinical assessment. Evidence for this requirement is lacking. We sought to evaluate the initial clinical assessment as a predictor of response to this mandated trial of medical treatment. Study Design: Retrospective review of prospectively collected data on 137 consecutive patients who presented with symptoms of nasal obstruction and a deviated nasal septum on physical examination. Methods: Patients were placed into one of three cohorts based on prediction of 1) failure of medical therapy with subsequent septoplasty, 2) success of medical therapy without subsequent septoplasty, or 3) unable to make a prediction. Patients from each cohort were assessed for subsequent response to medical therapy and ultimate need for septoplasty. Results: Overall clinical assessment had a sensitivity of 86.9%, specificity of 91.8%, positive predictive value of 93.6%, and negative predictive value of 96.4% for detecting/predicting need for septoplasty. The accuracy of the overall clinical assessment is considerably better than severe deviation at any one septal anatomical site. Of patients whose response to medical therapy could not be predicted, 61.3% failed medical therapy and needed surgery; this is statistically equivalent to a 50/50 distribution between either needing septoplasty or not. Conclusions: Clinical assessment at initial presentation of patients with nasal obstruction and deviated septum is highly accurate in predicting which patients will need septoplasty. Laryngoscope, 2013 C1 [Sedaghat, Ahmad R.; Busaba, Nicolas Y.; Kieff, David A.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Cunningham, Michael J.] Childrens Hosp, Dept Otolaryngol & Commun Enhancement, Boston, MA 02115 USA. [Sedaghat, Ahmad R.; Busaba, Nicolas Y.; Cunningham, Michael J.; Kieff, David A.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Sedaghat, AR (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM ahmad_sedaghat@meei.harvard.edu NR 14 TC 11 Z9 11 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JAN PY 2013 VL 123 IS 1 BP 48 EP 52 DI 10.1002/lary.23683 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 062TW UT WOS:000312946400012 PM 23169536 ER PT J AU Mehta, V Johnson, P Tassler, A Kim, S Ferris, RL Nance, M Johnson, JT Duvvuri, U AF Mehta, Vikas Johnson, Paul Tassler, Andrew Kim, Seungwon Ferris, Robert L. Nance, Melonie Johnson, Jonas T. Duvvuri, Umamaheswar TI A new paradigm for the diagnosis and management of unknown primary tumors of the head and neck: A role for transoral robotic surgery SO LARYNGOSCOPE LA English DT Article DE Unknown primary; transoral robotic surgery; base of tongue; diagnostic; Level of Evidence: 4 ID SQUAMOUS-CELL CARCINOMA; LYMPH-NODE METASTASES; CANCER; TONSILLECTOMY; SURVIVAL; ORIGIN; IMPACT AB Objectives/Hypothesis: In 2% to 3% of patients with cancer metastatic to cervical lymph nodes, a primary tumor will not be found despite exhaustive diagnostic efforts. The treatment for these patients includes cervical lymphadenectomy followed by radiation to areas with increased risk of harboring a mucosal primary. Wide-field radiation therapy increases the incidence of xerostomia and dysphagia. Localizing a primary tumor has thus both therapeutic and quality-of-life implications, allowing possible complete surgical excision, concentrated radiation therapy, and potential deintensification of adjuvant therapy. With improved visualization and freedom of motion, transoral robotic surgery (TORS) is an innovative surgical modality that allows resection of oropharyngeal subsites with minimal morbidity. Study Design: Retrospective chart review. Methods: Ten patients with unknown primary tumors of the head and neck were identified. All patients underwent a cervical biopsy, positron-emission tomography/computed tomography, formal endoscopy, and bilateral tonsillectomy. When the initial endoscopy and biopsies did not localize a primary tumor, all patients underwent transoral robotic base of tongue resection. Results: Evaluation of the patients' oropharyngeal mucosa using the robot did not reveal an obvious lesion and no palpable tumors were appreciated in the resected specimens. In 9/10 (90%) patients, pathologic examination revealed invasive squamous cell carcinoma (SCCA) with a mean diameter of 0.9 cm. Conclusions: Unknown primary SCCA presents a diagnostic challenge to the head and neck surgeon. We present a small series of tumors that would have been treated as unknown primaries under traditional diagnostic and therapeutic algorithms. TORS base of tongue resection identified primary tumors in 90% patients with minimal morbidity. Laryngoscope, 2013 C1 [Mehta, Vikas; Johnson, Paul; Tassler, Andrew; Kim, Seungwon; Ferris, Robert L.; Nance, Melonie; Johnson, Jonas T.; Duvvuri, Umamaheswar] Univ Pittsburgh, Inst Eye & Ear, Dept Otolaryngol Head & Neck Surg, Med Ctr, Pittsburgh, PA 15213 USA. [Nance, Melonie; Duvvuri, Umamaheswar] VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. RP Duvvuri, U (reprint author), Univ Pittsburgh, Inst Eye & Ear, Dept Otolaryngol Head & Neck Surg, Med Ctr, Suite 500,200 Lothrop St, Pittsburgh, PA 15213 USA. EM duvvuriu@upmc.edu OI Ferris, Robert/0000-0001-6605-2071 NR 26 TC 46 Z9 47 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JAN PY 2013 VL 123 IS 1 BP 146 EP 151 DI 10.1002/lary.23562 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 062TW UT WOS:000312946400028 PM 23154813 ER PT J AU Niesten, MEF McKenna, MJ Herrmann, BS Grolman, W Lee, DJ AF Niesten, Marlien E. F. McKenna, Michael J. Herrmann, Barbara S. Grolman, Wilko Lee, Daniel J. TI Utility of cVEMPs in bilateral superior canal dehiscence syndrome SO LARYNGOSCOPE LA English DT Article DE Superior canal dehiscence; canal plugging; middle fossa craniotomy; transmastoid approach; hearing outcomes; cervical vestibular evoked myogenic potentials; Level of Evidence: 4 ID EVOKED MYOGENIC POTENTIALS; PRESSURE-INDUCED VERTIGO; BONE DEHISCENCE; SURGERY; SOUND AB Objectives/Hypothesis: To determine the utility of cervical vestibular evoked myogenic potential (cVEMP) thresholds in the surgical management of bilateral superior canal dehiscence syndrome (SCDS). Study design: Retrospective review. Methods: We identified patients who underwent surgical treatment for SCDS from our database of 147 patients diagnosed with superior canal dehiscence (SCD) between 2000 and 2011 at our institution. The diagnosis of SCDS was based on clinical signs and symptoms, audiometric and cVEMP testing, and high-resolution computed tomography. Results: We identified 38 patients who underwent SCD surgery in 40 ears (2 bilateral). In seven patients with bilateral SCD, the more symptomatic ear had lower cVEMP thresholds, a larger air bone gap and a lateralizing tuning fork. In 13 patients with perioperative cVEMP testing, thresholds increased in 12 patients following primary repair, and no threshold shift was seen in one patient with persistence of symptoms after revision surgery. Audiometric data showed a significant mean decrease of the low-frequency air-bone gap and a mild (high-frequency) bone conduction loss after surgical repair. Conclusions: We found that, 1) preoperative cVEMP thresholds, the magnitude of the air-bone gap and tuning-fork testing are important to confirm the worse ear in patients with bilateral SCD, 2) elevation of cVEMP thresholds following surgery correlates with improvement of symptoms and underscores the importance of postoperative testing in patients with bilateral disease or recurrence of symptoms and, 3) SCD plugging is associated with a partial closure of the air-bone gap and a mild (high-frequency) sensorineural hearing loss. Laryngoscope, 2013 C1 [Niesten, Marlien E. F.; Grolman, Wilko] Univ Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, Utrecht, Netherlands. [Niesten, Marlien E. F.; Grolman, Wilko] Rudolf Magnus Inst Neurosci, NL-3508 TA Utrecht, Netherlands. [Niesten, Marlien E. F.; McKenna, Michael J.; Herrmann, Barbara S.; Lee, Daniel J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA USA. [Niesten, Marlien E. F.; McKenna, Michael J.; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Herrmann, Barbara S.] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. RP Lee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM daniel_lee@meei.harvard.edu OI Grolman, Wilko/0000-0002-3524-3526 NR 30 TC 9 Z9 9 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JAN PY 2013 VL 123 IS 1 BP 226 EP 232 DI 10.1002/lary.23550 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 062TW UT WOS:000312946400041 PM 22991076 ER PT J AU Lundell, H Barthelemy, D Biering-Sorensen, F Cohen-Adad, J Nielsen, JB Dyrby, TB AF Lundell, Henrik Barthelemy, Dorothy Biering-Sorensen, Fin Cohen-Adad, Julien Nielsen, Jens Bo Dyrby, Tim B. TI Fast diffusion tensor imaging and tractography of the whole cervical spinal cord using point spread function corrected echo planar imaging SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE spinal cord; diffusion tensor imaging; tractography; point spread function ID DISTORTION CORRECTION; IN-VIVO; TRACKING; BRAIN; DTI; INDIVIDUALS; DISABILITY; ATROPHY; INJURY; MOTION AB Diffusion tensor imaging has been used in a number of spinal cord studies, but severe distortions caused by susceptibility induced field inhomogeneities limit its applicability to investigate small volumes within acceptable acquisition times. A way to evaluate image distortions is to map the point spread function of the voxel intensity in a reference scan. In this study, the point spread function was mapped for an echo-planar imaging sequence in the human cervical spinal cord with isotropic resolution and large field of view. Correction with the point spread function map improved anatomical consistency, and full cervical tractography was thereby possible from a C1 seed region in healthy controls and one individual with spinal cord injury. It is suggested that point spread function mapping of the spinal cord can be used in combination with sequence-based methods for reduction of susceptibility artifacts or in high-field imaging settings where off-resonance effects are pronounced. Magn Reson Med, 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Lundell, Henrik; Barthelemy, Dorothy; Nielsen, Jens Bo] Copenhagen Univ Hosp, DRCMR, DK-2650 Hvidovre, Denmark. [Lundell, Henrik; Barthelemy, Dorothy; Nielsen, Jens Bo] Univ Copenhagen, Dept Exercise & Sport Sci, Copenhagen, Denmark. [Lundell, Henrik; Barthelemy, Dorothy; Nielsen, Jens Bo] Univ Copenhagen, Dept Neurosci & Pharmacol, Copenhagen, Denmark. [Barthelemy, Dorothy] Univ Montreal, Fac Med, Sch Rehabil, Montreal, PQ H3C 3J7, Canada. [Biering-Sorensen, Fin] Univ Copenhagen, Fac Hlth Sci, DK-1168 Copenhagen, Denmark. [Biering-Sorensen, Fin] Univ Copenhagen, Rigshosp, Clin Spinal Cord Injuries, DK-1168 Copenhagen, Denmark. [Cohen-Adad, Julien] Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Lundell, H (reprint author), Copenhagen Univ Hosp, DRCMR, 340B,Kettegaards Alle 30, DK-2650 Hvidovre, Denmark. EM lundell@drcmr.dk RI Dyrby, Tim/M-4823-2015; Lundell, Henrik/B-1270-2017; OI Dyrby, Tim/0000-0003-3361-9734; Nielsen, Jens Bo/0000-0001-5568-2916 FU Elsass Foundation, Denmark; Canadian Institutes of Health Research (CIHR); Lundbeck Foundation; Future and Emerging Technologies of the EU; CONNECT consortium project; Future and Emerging Technologies (FET open) of the EU FX Grant sponsors: Elsass Foundation, Denmark, Canadian Institutes of Health Research (CIHR), Lundbeck Foundation, The Future and Emerging Technologies of the EU FP7; The authors thank Maxim Zaitsev at MRDAC, Freiburg, Germany for providing the PSF-EPI sequences. Tim B. Dyrby has been supported by the Lundbeck Foundation. Tim B. Dyrby and Henrik Lundell are partly supported by the CONNECT consortium project supported by The Future and Emerging Technologies (FET open) of the EU FP7. NR 40 TC 4 Z9 4 U1 2 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD JAN PY 2013 VL 69 IS 1 BP 144 EP 149 DI 10.1002/mrm.24235 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 059SL UT WOS:000312725500016 PM 22396180 ER PT J AU Li, X Priest, RA Woodward, WJ Tagge, IJ Siddiqui, F Huang, W Rooney, WD Beer, TM Garzotto, MG Springer, CS AF Li, Xin Priest, Ryan A. Woodward, William J. Tagge, Ian J. Siddiqui, Faisal Huang, Wei Rooney, William D. Beer, Tomasz M. Garzotto, Mark G. Springer, Charles S., Jr. TI Feasibility of shutter-speed DCE-MRI for improved prostate cancer detection SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE shutter-speed; DCE-MRI; prostate ID CONTRAST-ENHANCED-MRI; CR BOLUS-TRACKING; WATER EXCHANGE; BLOOD-VOLUME; GD-DTPA; IN-VIVO; BREAST; BENIGN; DIFFERENTIATION; ACCURACY AB The feasibility of shutter-speed model dynamic-contrast-enhanced MRI pharmacokinetic analyses for prostate cancer detection was investigated in a prebiopsy patient cohort. Differences of results from the fast-exchange-regime-allowed (FXR-a) shutter-speed model version and the fast-exchange-limit-constrained (FXL-c) standard model are demonstrated. Although the spatial information is more limited, postdynamic-contrast-enhanced MRI biopsy specimens were also examined. The MRI results were correlated with the biopsy pathology findings. Of all the model parameters, region-of-interest-averaged Ktrans difference [?Ktrans = Ktrans(FXR-a) - Ktrans(FXL-c)] or two-dimensional Ktrans(FXR-a) vs. kep(FXR-a) values were found to provide the most useful biomarkers for malignant/benign prostate tissue discrimination (at 100% sensitivity for a population of 13, the specificity is 88%) and disease burden determination. (The best specificity for the fast-exchange-limit-constrained analysis is 63%, with the two-dimensional plot.) Ktrans and kep are each measures of passive transcapillary contrast reagent transfer rate constants. Parameter value increases with shutter-speed model (relative to standard model) analysis are larger in malignant foci than in normal-appearing glandular tissue. Pathology analyses verify the shutter-speed model (FXR-a) promise for prostate cancer detection. Parametric mapping may further improve pharmacokinetic biomarker performance. Magn Reson Med, 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Li, Xin] Oregon Hlth & Sci Univ, Adv Imaging Res Ctr, WM Keck Fdn, High Field MRI Lab, Portland, OR 97239 USA. [Priest, Ryan A.] Oregon Hlth & Sci Univ, Dept Radiol, Portland, OR 97239 USA. [Beer, Tomasz M.] Oregon Hlth & Sci Univ, Dept Hematol Oncol, Portland, OR 97239 USA. [Beer, Tomasz M.; Springer, Charles S., Jr.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA. [Garzotto, Mark G.] Oregon Hlth & Sci Univ, Dept Urol, Portland, OR 97239 USA. [Siddiqui, Faisal; Garzotto, Mark G.] Oregon Hlth & Sci Univ, Dept Radiat Med, Portland, OR 97239 USA. [Garzotto, Mark G.] Portland VA Med Ctr, Portland, OR USA. RP Li, X (reprint author), Oregon Hlth & Sci Univ, Adv Imaging Res Ctr, WM Keck Fdn, High Field MRI Lab, Mail Code L452, Portland, OR 97239 USA. EM lxin@ohsu.edu OI Springer, Charles/0000-0002-5966-2135; Tagge, Ian/0000-0002-5260-7117 FU NIH [R01-EB00422, R01-NS40801, R01-CA120861, U01-CA154602]; RSNA Research and Education Foundation (Research Medical Student Grant) [RMS0801]; Medical Research Foundation of Oregon FX Grant sponsor: NIH; Grant numbers: R01-EB00422, R01-NS40801, R01-CA120861, U01-CA154602; Grant sponsor: RSNA Research and Education Foundation (Research Medical Student Grant); Grant number: RMS0801; Grant sponsor: Medical Research Foundation of Oregon. NR 37 TC 14 Z9 15 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD JAN PY 2013 VL 69 IS 1 BP 171 EP 178 DI 10.1002/mrm.24211 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 059SL UT WOS:000312725500020 PM 22457233 ER PT J AU Muir, ER De La Garza, B Duong, TQ AF Muir, Eric R. De La Garza, Bryan Duong, Timothy Q. TI Blood flow and anatomical MRI in a mouse model of retinitis pigmentosa SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE retinal degeneration; retinitis pigmentosa; arterial spin labeling; blood flow; retina; choroid ID HEREDITARY RETINAL DEGENERATION; MANGANESE-ENHANCED MRI; PHOTORECEPTOR DEGENERATION; OXYGEN-METABOLISM; ABYSSINIAN CATS; BETA-SUBUNIT; RD10 MOUSE; GENE; RAT; PHOSPHODIESTERASE AB This study tested the sensitivity of an arterial spin labeling MRI method to image changes in retinal and choroidal blood flow (BF) and anatomical thickness of the retina in the rd10 mouse model of retinitis pigmentosa. High-resolution (42 x 42 mu m) MRI was performed on rd10 mice and age-matched controls at 25, 35, and 60 days of age (n = 6 each group) on a 7-T scanner. Anatomical MRI was acquired, and quantitative BF was imaged using arterial spin labeling MRI with a separate cardiac labeling coil. Histology was obtained to confirm thickness changes in the retina. In control mice, the retinal and choroidal vascular layers were quantitatively resolved. In rd10 mice, retinal BF decreased progressively over time, while choroidal BF was unchanged. The rd10 retina became progressively thinner at later time points compared with age-matched controls by anatomical MRI and histology (P < 0.01). BF and anatomical MRI were capable of detecting decreased BF and thickness in the rd10 mouse retina. Because BF is tightly coupled to metabolic function, BF MRI has the potential to noninvasively assess retinal diseases in which metabolism and function are perturbed and to evaluate novel treatments, complementing existing retinal imaging techniques. Magn Reson Med, 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Muir, Eric R.; De La Garza, Bryan; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Duong, Timothy Q.] SW Natl Primate Res Ctr, San Antonio, TX USA. RP Duong, TQ (reprint author), UTHSCSA, Res Imaging Ctr, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008; Muir, Eric/H-8830-2013 FU NIH/NEI [R01 EY014211, EY018855]; Clinical Translational Science Award Supplement [UL1RR025767]; NIH [5T32HL007446-29]; MERIT Award from the Department of Veterans Affairs FX Grant sponsor: NIH/NEI; Grant numbers: R01 EY014211, EY018855; Grant sponsor: Clinical Translational Science Award Supplement; Grant number: UL1RR025767; Grant sponsor: NIH; Grant number: 5T32HL007446-29 (to ERM); Grant sponsor: MERIT Award from the Department of Veterans Affairs NR 46 TC 8 Z9 8 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD JAN PY 2013 VL 69 IS 1 BP 221 EP 228 DI 10.1002/mrm.24232 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 059SL UT WOS:000312725500025 PM 22392583 ER PT J AU Shampo, MA Kyle, RA Steensma, DP AF Shampo, Marc A. Kyle, Robert A. Steensma, David P. TI Elias James Corey-Nobel Prize for Retrosynthetic Analysis SO MAYO CLINIC PROCEEDINGS LA English DT Biographical-Item C1 [Shampo, Marc A.; Kyle, Robert A.] Mayo Clin, Rochester, MN 55905 USA. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Shampo, MA (reprint author), Mayo Clin, Rochester, MN 55905 USA. OI Steensma, David/0000-0001-5130-9284 NR 1 TC 0 Z9 0 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JAN PY 2013 VL 88 IS 1 BP E7 EP E7 DI 10.1016/j.mayocp.2012.01.024 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 060VT UT WOS:000312807000002 PM 23274030 ER PT J AU Penson, RT AF Penson, Richard T. TI Complexions of compliance SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID BREAST-CANCER; TAMOXIFEN; NONADHERENCE; WOMEN C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Penson, RT (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. NR 12 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 JAN PY 2013 VL 20 IS 1 BP 3 EP 4 DI 10.1097/gme.0b013e31827e8295 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 060QP UT WOS:000312793400002 PM 23266837 ER PT J AU Tamura, K Wakimoto-, H Agarwal, AS Rabkin, SD Bhere, D Martuza, RL Kuroda, T Kasmieh, R Shah, K AF Tamura, Kaoru Wakimoto-, Hiroaki Agarwal, Aayush S. Rabkin, Samuel D. Bhere, Deepak Martuza, Robert L. Kuroda, Toshihiko Kasmieh, Randa Shah, Khalid TI Multimechanistic Tumor Targeted Oncolytic Virus Overcomes Resistance in Brain Tumors SO MOLECULAR THERAPY LA English DT Article ID BACTERIAL ARTIFICIAL CHROMOSOME; PROGRAMMED CELL-DEATH; STEM-CELLS; IN-VIVO; S-TRAIL; ADJUVANT TEMOZOLOMIDE; MALIGNANT GLIOMAS; CANCER-THERAPY; SIMPLEX; APOPTOSIS AB Only a subset of cancer patients inoculated with oncolytic herpes simplex virus (oHSV) type-1 has shown objective response in phase 1 and 2 clinical trials. This has raised speculations whether resistance of tumor cells to oHSV therapy may be a limiting factor. In this study, we have identified established and patient derived primary glioblastoma multiforme (GBM) stem cell lines (GSC) resistant to oHSV and also to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) that has recently shown promise in preclinical and initial clinical studies. We created a recombinant oHSV bearing a secretable TRAIL (oHSV-TRAIL) and hypothesized that oHSV-TRAIL could be used as a cancer therapeutic to target a broad spectrum of resistant tumors in a mechanism-based manner. Using the identified resistant GBM lines, we show that oHSV-TRAIL downregulates extracellular signal-regulated protein kinase (ERK)-mitogen-activated protein kinase (MAPK) and upregulates c-Jun N-terminal kinase (JNK) and p38-MAPK signaling, which primes resistant GBM cells to apoptosis via activation of caspase-8, -9, and -3. We further show that oHSV-TRAIL inhibits tumor growth and invasiveness and increases survival of mice bearing resistant intracerebral tumors without affecting the normal tissues. This study sheds new light on the mechanism by which oHSV and TRAIL function in concert to overcome therapeutic-resistance, and provides an oncolytic virus based platform to target a broad spectrum of different cancer types. C1 [Tamura, Kaoru; Wakimoto-, Hiroaki; Agarwal, Aayush S.; Bhere, Deepak; Kasmieh, Randa; Shah, Khalid] Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. [Tamura, Kaoru; Wakimoto-, Hiroaki; Agarwal, Aayush S.; Bhere, Deepak; Kasmieh, Randa; Shah, Khalid] Harvard Univ, Mol Neurotherapy & Imaging Lab, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. [Wakimoto-, Hiroaki; Rabkin, Samuel D.; Martuza, Robert L.] Harvard Univ, Dept Neurosurg, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. [Kuroda, Toshihiko] Harvard Univ, Dept Surg Oncol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. [Shah, Khalid] Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. RP Shah, K (reprint author), Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Sch Med, 149 13th St, Boston, MA 02129 USA. EM kshah@mgh.harvard.edu OI Kuroda, Toshihiko/0000-0001-6660-8930 FU Alliance for Cancer Gene Therapy; National Institutes of Health [NS03677, CA138922-01, NS076873]; American Cancer Society; James McDonnell Foundation FX We thank Dr Howard Chen for his help with Annexin-V staining and FACS analysis; Dr Andrew Kung for providing pico2-Fluc-mCherry lentiviral vector. This work was supported in part by Alliance for Cancer Gene Therapy (K. S.) National Institutes of Health (NS03677; R. L. M. and CA138922-01; NS076873; K. S.) American Cancer Society (K. S.) and James McDonnell Foundation (K. S.). The authors declared no conflict of interest. NR 50 TC 15 Z9 16 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JAN PY 2013 VL 21 IS 1 BP 68 EP 77 DI 10.1038/mt.2012.175 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 063XI UT WOS:000313035000009 PM 22929661 ER PT J AU Mizrak, A Bolukbasi, MF Ozdener, GB Brenner, GJ Madlener, S Erkan, EP Strobel, T Breakefield, XO Saydam, O AF Mizrak, Arda Bolukbasi, Mehmet Fatih Ozdener, Gokhan Baris Brenner, Gary J. Madlener, Sibylle Erkan, Erdogan Pekcan Stroebel, Thomas Breakefield, Xandra O. Saydam, Okay TI Genetically Engineered Microvesicles Carrying Suicide mRNA/Protein Inhibit Schwannoma Tumor Growth SO MOLECULAR THERAPY LA English DT Article ID GENE-THERAPY; CYTOSINE DEAMINASE; MEDIATED TRANSFER; IMMUNE-RESPONSES; PROTEIN-KINASE; T-CELLS; IN-VIVO; EXOSOMES; DELIVERY; MICRORNAS AB Microvesicles (MVs) play an important role in intercellular communication by carrying mRNAs, microRNAs (miRNAs), non-coding RNAs, proteins, and DNA from cell to cell. To our knowledge, this is the first report of delivery of a therapeutic mRNA/protein via MVs for treatment of cancer. We first generated genetically engineered MVs by expressing high levels of the suicide gene mRNA and protein-cytosine deaminase (CD) fused to uracil phosphoribosyltransferase (UPRT) in MV donor cells. MVs were isolated from these cells and used to treat pre-established nerve sheath tumors (schwannomas) in an orthotopic mouse model. We demonstrated that MV-mediated delivery of CD-UPRT mRNA/protein by direct injection into schwannomas led to regression of these tumors upon systemic treatment with the prodrug (5-fluorocytosine (5-FC)), which is converted within tumor cells to 5-fluorouracil (5-FU)-an anticancer agent. Taken together, these studies suggest that MVs can serve as novel cell-derived "liposomes" to effectively deliver therapeutic mRNA/proteins to treatment of diseases. C1 [Madlener, Sibylle; Erkan, Erdogan Pekcan; Saydam, Okay] Med Univ Vienna, Mol Neurooncol Res Unit, Dept Pediat, A-1090 Vienna, Austria. [Mizrak, Arda; Bolukbasi, Mehmet Fatih; Ozdener, Gokhan Baris; Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Neurol & Radiol, Boston, MA 02114 USA. [Mizrak, Arda; Bolukbasi, Mehmet Fatih; Ozdener, Gokhan Baris; Breakefield, Xandra O.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Brenner, Gary J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. [Stroebel, Thomas] Med Univ Vienna, Inst Neurol, A-1090 Vienna, Austria. RP Saydam, O (reprint author), Med Univ Vienna, Mol Neurooncol Res Unit, Dept Pediat, A-1090 Vienna, Austria. EM okay.saydam@meduniwien.ac.at OI Madlener, Sibylle/0000-0001-7099-9997 FU NIH NCI [CA141150]; NIH NINDS [NS037409]; Forschungsgesellschaft for Brain Tumors; EU-FP7-PEOPLE-2011-CIG; Association for conduct of scientific research in the field of neonatology and pediatric intensive care: "Unser Kind" FX We thank Suzanne McDavitt for skilled editorial assistance and Shilpa Prabhakar for technical help. Support for this work was provided by NIH NCI grant CA141150 (X.O.B.), NIH NINDS grant NS037409 (X.O.B., O.S.), Forschungsgesellschaft for Brain Tumors (O.S.), EU-FP7-PEOPLE-2011-CIG (O.S.), and Association for conduct of scientific research in the field of neonatology and pediatric intensive care: "Unser Kind" (O.S.). The authors declared no conflict of interest. NR 50 TC 53 Z9 58 U1 1 U2 27 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JAN PY 2013 VL 21 IS 1 BP 101 EP 108 DI 10.1038/mt.2012.161 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 063XI UT WOS:000313035000012 PM 22910294 ER PT J AU Gold, MC Eid, T Smyk-Pearson, S Eberling, Y Swarbrick, GM Langley, SM Streeter, PR Lewinsohn, DA Lewinsohn, DM AF Gold, M. C. Eid, T. Smyk-Pearson, S. Eberling, Y. Swarbrick, G. M. Langley, S. M. Streeter, P. R. Lewinsohn, D. A. Lewinsohn, D. M. TI Human thymic MR1-restricted MAIT cells are innate pathogen-reactive effectors that adapt following thymic egress SO MUCOSAL IMMUNOLOGY LA English DT Article ID CD8(+) T-CELLS; MYCOBACTERIUM-TUBERCULOSIS INFECTION; CD45 ISOFORM EXPRESSION; MHC-RELATED PROTEIN-1; PERIPHERAL-BLOOD; NKT CELLS; MR1; SELECTION; EMIGRANTS; GENE AB Human mucosal-associated invariant T (MAIT) cells express the semi-invariant T-cell receptor (TCR) V alpha 7.2 and are restricted by the major histocompatibility complex-Ib molecule MR1. While MAIT cells share similarities with other innate T cells, the extent to which MAIT cells are innate and their capacity to adapt is unknown. We evaluated the function of V alpha 7.2(+) T cells from the thymus, cord blood, and peripheral blood. Although antigen-inexperienced MAIT cells displayed a naive phenotype, these had intrinsic effector capacity in response to Mycobacterium tuberculosis (Mtb)-infected cells. V alpha 7.2(+) effector thymocytes contained signal joint TCR gene excision circles (sjTRECs) suggesting limited replication and thymic origin. In evaluating the capacity of Mtb-reactive MAIT cells to adapt, we found that those from the peripheral blood demonstrated a memory phenotype and had undergone substantial expansion, suggesting that they responded to antigenic stimulation. MAIT cells, an evolutionarily conserved T-cell subset that detects a variety of intracellular infections, share features of innate and adaptive immunity. C1 [Gold, M. C.; Eid, T.; Smyk-Pearson, S.; Eberling, Y.; Swarbrick, G. M.; Streeter, P. R.; Lewinsohn, D. A.; Lewinsohn, D. M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Gold, M. C.; Lewinsohn, D. M.] Portland VA Med Ctr, Portland, OR USA. [Langley, S. M.] Doernbecher Childrens Hosp, Portland, OR USA. RP Gold, MC (reprint author), Oregon Hlth & Sci Univ, Portland, OR 97201 USA. EM goldm@ohsu.edu; lewinsod@ohsu.edu RI Lewinsohn, David/I-4936-2013 OI Lewinsohn, David/0000-0001-9906-9494 FU Department of Veterans Affairs; Portland VA Medical Center, National Institutes of Health (NIH) [AI078965, AI48090]; NIH [HHSN266200400081C] FX We thank Dr Lewis for kindly providing us with plasmids and protocols to perform sjTREC analyses, Dr Hansen for his generous gift of the anti-MR1 antibody, members of the Operating Room Team at Doernbecher's Children's Hospital for their collaboration in collecting thymus for our studies, Dr Segel and the members of the Labor and Delivery Ward at OHSU for their collaboration in collecting cord blood for our studies, and Erin Merrifield for her expert assistance with human subjects protocols. Funding was provided in part by the Department of Veterans Affairs and with resources and the use of facilities at the Portland VA Medical Center, National Institutes of Health (NIH) grants AI078965 and AI48090, and NIH contract HHSN266200400081C. NR 47 TC 46 Z9 46 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD JAN PY 2013 VL 6 IS 1 BP 35 EP 44 DI 10.1038/mi.2012.45 PG 10 WC Immunology SC Immunology GA 062CA UT WOS:000312895500005 PM 22692454 ER PT J AU Salameh, J Goyal, N Choudry, R Camelo-Piragua, S Chong, PST AF Salameh, Johnny Goyal, Namita Choudry, Rabia Camelo-Piragua, Sandra Chong, Peter Siao Tick TI Phosphoglycerate mutase deficiency with tubular aggregates in a patient from panama SO MUSCLE & NERVE LA English DT Article DE CK elevation; glycogen-storage disease type X; PGAM; phosphoglycerate mutase; tubular aggregates AB Introduction: Phosphoglycerate mutase deficiency (PGAM) is a rare metabolic myopathy that results in terminal block in glycogenolysis. Clinically, patients with PGAM deficiency are asymptomatic, except when they engage in brief, strenuous efforts, which may trigger myalgias, cramps, muscle necrosis, and myoglobinuria. An unusual pathologic feature of PGAM deficiency is the association with tubular aggregates. Methods: We report an African-American patient from Panama with partial deficiency of PGAM who presented with asymptomatic elevation of creatine kinase levels and tubular aggregates on muscle biopsy. Results: Muscle biopsies showed subsarcolemmal and sarcolemmal tubular aggregates in type 2 fibers. Muscle PGAM enzymatic activity was decreased and gene sequencing revealed a heterozygous mutation in codon 78 of exon 1 of the PGAM2 gene, which is located on the short arm of chromosome 7. Conclusions: PGAM deficiency has been reported in 14 patients, 9 of whom were of African-American ethnicity, and in 5 (36%) tubular aggregates were seen on muscle biopsy. Contrary to previously reported cases, our patient was initially asymptomatic. This further expands the PGAM deficiency phenotype. Muscle Nerve, 2013 C1 [Salameh, Johnny] Univ Massachusetts, Med Ctr, Dept Neurol, Worcester, MA 01605 USA. [Goyal, Namita] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Choudry, Rabia] Albert Einstein Med Ctr, Dept Neurosensory Sci, Philadelphia, PA 19141 USA. [Camelo-Piragua, Sandra] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Chong, Peter Siao Tick] Boston Med Ctr, Dept Neurol, Boston, MA USA. RP Salameh, J (reprint author), Univ Massachusetts, Med Ctr, Dept Neurol, 55 Lake Ave N S5-751, Worcester, MA 01605 USA. EM johnnysalameh@hotmail.com NR 9 TC 6 Z9 7 U1 0 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 JAN PY 2013 VL 47 IS 1 BP 138 EP 140 DI 10.1002/mus.23527 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 058TN UT WOS:000312657200023 PM 23169535 ER PT J AU Ngwa, W Korideck, H Kassis, AI Kumar, R Sridhar, S Makrigiorgos, GM Cormack, RA AF Ngwa, Wilfred Korideck, Houari Kassis, Amin I. Kumar, Rajiv Sridhar, Srinivas Makrigiorgos, G. Mike Cormack, Robert A. TI In vitro radiosensitization by gold nanoparticles during continuous low-dose-rate gamma irradiation with I-125 brachytherapy seeds SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Article DE Gold nanoparticles; Radiosensitizers; Brachytherapy; Radiotherapy; In vitro ID RADIATION-THERAPY; CANCER-THERAPY; CELL-SURVIVAL; ENHANCEMENT; DNA; DOSIMETRY; APOPTOSIS; ENERGY; FOCI AB This communication reports the first experimental evidence of gold nanoparticle (AuNP) radiosensitization during continuous low-dose-rate (LDR) gamma irradiation with low-energy brachytherapy sources. HeLa cell cultures incubated with and without AuNP were irradiated with an I-125 seed plaque designed to produce a relatively homogeneous dose distribution in the plane of the cell culture slide. Four sets of irradiation experiments were conducted at low-dose rates ranging from 2.1 to 4.5 cGy/h. Residual gamma H2AX was measured 24 h after irradiation and used to compare radiation damage to the cells with and without AuNP. The data demonstrate that the biological effect when irradiating in the presence of 0.2mg/ml concentration of AuNP is about 70%-130% greater than without AuNP. Meanwhile, without radiation, the AuNP showed minimal effect on the cancer cells. These findings provide in vitro evidence that AuNP may be employed as radiosensitizers during continuous LDR brachytherapy. From the Clinical Editor: In this basic science paper, the application of gold nanoparticles as radiosensitizing agents for low dose rate gamma radiation therapy is discussed, demonstrating efficacy in cell culture models. (C) 2013 Elsevier Inc. All rights reserved. C1 [Ngwa, Wilfred; Korideck, Houari; Makrigiorgos, G. Mike; Cormack, Robert A.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Kassis, Amin I.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Ngwa, Wilfred; Sridhar, Srinivas; Makrigiorgos, G. Mike; Cormack, Robert A.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Kumar, Rajiv; Sridhar, Srinivas] Northeastern Univ, Elect Mat Res Inst, Boston, MA 02115 USA. [Kumar, Rajiv; Sridhar, Srinivas] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. RP Ngwa, W (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. EM wngwa@lroc.harvard.edu OI Cormack, Robert/0000-0001-5553-9984 FU NCI NIH HHS [1U54CA151881, U54 CA151881] NR 20 TC 38 Z9 43 U1 1 U2 40 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD JAN PY 2013 VL 9 IS 1 BP 25 EP 27 DI 10.1016/j.nano.2012.09.001 PG 3 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 064CA UT WOS:000313047300004 PM 23041410 ER PT J AU Deloukas, P Kanoni, S Willenborg, C Farrall, M Assimes, TL Thompson, JR Ingelsson, E Saleheen, D Erdmann, J Goldstein, BA Stirrups, K Konig, IR Cazier, JB Johansson, A Hall, AS Lee, JY Willer, CJ Chambers, JC Esko, T Folkersen, L Goel, A Grundberg, E Havulinna, AS Ho, WK Hopewell, JC Eriksson, N Kleber, ME Kristiansson, K Lundmark, P Lyytikainen, LP Rafelt, S Shungin, D Strawbridge, RJ Thorleifsson, G Tikkanen, E Van Zuydam, N Voight, BF Waite, LL Zhang, WH Ziegler, A Absher, D Altshuler, D Balmforth, AJ Barroso, I Braund, PS Burgdorf, C Claudi-Boehm, S Cox, D Dimitriou, M Do, R Doney, ASF El Mokhtari, N Eriksson, P Fischer, K Fontanillas, P Franco-Cereceda, A Gigante, B Groop, L Gustafsson, S Hager, J Hallmans, G Han, BG Hunt, SE Kang, HM Illig, T Kessler, T Knowles, JW Kolovou, G Kuusisto, J Langenberg, C Langford, C Leander, K Lokki, ML Lundmark, A McCarthy, MI Meisinger, C Melander, O Mihailov, E Maouche, S Morris, AD Muller-Nurasyid, M Nikus, K Peden, JF Rayner, NW Rasheed, A Rosinger, S Rubin, D Rumpf, MP Schafer, A Sivananthan, M Song, C Stewart, AFR Tan, ST Thorgeirsson, G van der Schoot, CE Wagner, PJ Wells, GA Wild, PS Yang, TP Amouyel, P Arveiler, D Basart, H Boehnke, M Boerwinkle, E Brambilla, P Cambien, F Cupples, AL de Faire, U Dehghan, A Diemert, P Epstein, SE Evans, A Ferrario, MM Ferrieres, J Gauguier, D Go, AS Goodall, AH Gudnason, V Hazen, SL Holm, H Iribarren, C Jang, Y Kahonen, M Kee, F Kim, HS Klopp, N Koenig, W Kratzer, W Kuulasmaa, K Laakso, M Laaksonen, R Lee, JY Lind, L Ouwehand, WH Parish, S Park, JE Pedersen, NL Peters, A Quertermous, T Rader, DJ Salomaa, V Schadt, E Shah, SH Sinisalo, J Stark, K Stefansson, K Tregouet, DA Virtamo, J Wallentin, L Wareham, N Zimmermann, ME Nieminen, MS Hengstenberg, C Sandhu, MS Pastinen, T Syvanen, AC Hovingh, GK Dedoussis, G Franks, PW Lehtimaki, T Metspalu, A Zalloua, PA Siegbahn, A Schreiber, S Ripatti, S Blankenberg, SS Perola, M Clarke, R Boehm, BO O'Donnell, C Reilly, MP Marz, W Collins, R Kathiresan, S Hamsten, A Kooner, JS Thorsteinsdottir, U Danesh, J Palmer, CNA Roberts, R Watkins, H Schunkert, H Samani, NJ AF Deloukas, Panos Kanoni, Stavroula Willenborg, Christina Farrall, Martin Assimes, Themistocles L. Thompson, John R. Ingelsson, Erik Saleheen, Danish Erdmann, Jeanette Goldstein, Benjamin A. Stirrups, Kathleen Koenig, Inke R. Cazier, Jean-Baptiste Johansson, Asa Hall, Alistair S. Lee, Jong-Young Willer, Cristen J. Chambers, John C. Esko, Tonu Folkersen, Lasse Goel, Anuj Grundberg, Elin Havulinna, Aki S. Ho, Weang K. Hopewell, Jemma C. Eriksson, Niclas Kleber, Marcus E. Kristiansson, Kati Lundmark, Per Lyytikainen, Leo-Pekka Rafelt, Suzanne Shungin, Dmitry Strawbridge, Rona J. Thorleifsson, Gudmar Tikkanen, Emmi Van Zuydam, Natalie Voight, Benjamin F. Waite, Lindsay L. Zhang, Weihua Ziegler, Andreas Absher, Devin Altshuler, David Balmforth, Anthony J. Barroso, Ines Braund, Peter S. Burgdorf, Christof Claudi-Boehm, Simone Cox, David Dimitriou, Maria Do, Ron Doney, Alex S. F. El Mokhtari, NourEddine Eriksson, Per Fischer, Krista Fontanillas, Pierre Franco-Cereceda, Anders Gigante, Bruna Groop, Leif Gustafsson, Stefan Hager, Joerg Hallmans, Goran Han, Bok-Ghee Hunt, Sarah E. Kang, Hyun M. Illig, Thomas Kessler, Thorsten Knowles, Joshua W. Kolovou, Genovefa Kuusisto, Johanna Langenberg, Claudia Langford, Cordelia Leander, Karin Lokki, Marja-Liisa Lundmark, Anders McCarthy, Mark I. Meisinger, Christa Melander, Olle Mihailov, Evelin Maouche, Seraya Morris, Andrew D. Mueller-Nurasyid, Martina Nikus, Kjell Peden, John F. Rayner, N. William Rasheed, Asif Rosinger, Silke Rubin, Diana Rumpf, Moritz P. Schaefer, Arne Sivananthan, Mohan Song, Ci Stewart, Alexandre F. R. Tan, Sian-Tsung Thorgeirsson, Gudmundur van der Schoot, C. Ellen Wagner, Peter J. Wells, George A. Wild, Philipp S. Yang, Tsun-Po Amouyel, Philippe Arveiler, Dominique Basart, Hanneke Boehnke, Michael Boerwinkle, Eric Brambilla, Paolo Cambien, Francois Cupples, Adrienne L. de Faire, Ulf Dehghan, Abbas Diemert, Patrick Epstein, Stephen E. Evans, Alun Ferrario, Marco M. Ferrieres, Jean Gauguier, Dominique Go, Alan S. Goodall, Alison H. Gudnason, Villi Hazen, Stanley L. Holm, Hilma Iribarren, Carlos Jang, Yangsoo Kahonen, Mika Kee, Frank Kim, Hyo-Soo Klopp, Norman Koenig, Wolfgang Kratzer, Wolfgang Kuulasmaa, Kari Laakso, Markku Laaksonen, Reijo Lee, Ji-Young Lind, Lars Ouwehand, Willem H. Parish, Sarah Park, Jeong E. Pedersen, Nancy L. Peters, Annette Quertermous, Thomas Rader, Daniel J. Salomaa, Veikko Schadt, Eric Shah, Svati H. Sinisalo, Juha Stark, Klaus Stefansson, Kari Tregouet, David-Alexandre Virtamo, Jarmo Wallentin, Lars Wareham, Nicholas Zimmermann, Martina E. Nieminen, Markku S. Hengstenberg, Christian Sandhu, Manjinder S. Pastinen, Tomi Syvanen, Ann-Christine Hovingh, G. Kees Dedoussis, George Franks, Paul W. Lehtimaki, Terho Metspalu, Andres Zalloua, Pierre A. Siegbahn, Agneta Schreiber, Stefan Ripatti, Samuli Blankenberg, Stefan S. Perola, Markus Clarke, Robert Boehm, Bernhard O. O'Donnell, Christopher Reilly, Muredach P. Maerz, Winfried Collins, Rory Kathiresan, Sekar Hamsten, Anders Kooner, Jaspal S. Thorsteinsdottir, Unnur Danesh, John Palmer, Colin N. A. Roberts, Robert Watkins, Hugh Schunkert, Heribert Samani, Nilesh J. CA CARDIoGRAMplusC4D Consortium DIAGRAM Consortium CARDIOGENENICS Consortium MuTHER Consortium Wellcome Trust Case Control TI Large-scale association analysis identifies new risk loci for coronary artery disease SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; CARDIOVASCULAR-DISEASE; FASTING GLUCOSE; MYOCARDIAL-INFARCTION; SUSCEPTIBILITY LOCUS; GENETIC-VARIANTS; COMPLEX TRAITS; ATHEROSCLEROSIS; POPULATION; EXPRESSION AB Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways. C1 [Deloukas, Panos; Kanoni, Stavroula; Stirrups, Kathleen; Barroso, Ines; Hunt, Sarah E.; Langford, Cordelia; Yang, Tsun-Po; Ouwehand, Willem H.; Sandhu, Manjinder S.; Ripatti, Samuli] Wellcome Trust Sanger Inst, Cambridge, England. [Willenborg, Christina; Erdmann, Jeanette] Univ Lubeck, Inst Integrat & Expt, Lubeck, Germany. [Farrall, Martin; Goel, Anuj; McCarthy, Mark I.; Peden, John F.; Rayner, N. William; Gauguier, Dominique; Watkins, Hugh] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Farrall, Martin; Cazier, Jean-Baptiste; Goel, Anuj; Watkins, Hugh] Univ Oxford, Radcliffe Dept Med, Oxford, England. [Assimes, Themistocles L.; Goldstein, Benjamin A.; Knowles, Joshua W.; Quertermous, Thomas] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [Thompson, John R.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England. [Ingelsson, Erik; Gustafsson, Stefan; Song, Ci; Pedersen, Nancy L.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Saleheen, Danish] Ctr Noncommunicable Dis, Karachi, Pakistan. [Saleheen, Danish; Rasheed, Asif; Danesh, John] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Saleheen, Danish; Ho, Weang K.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Koenig, Inke R.; Ziegler, Andreas] Univ Lubeck, Inst Med Biometrie & Stat, Lubeck, Germany. [Saleheen, Danish; Johansson, Asa; Eriksson, Niclas; Wallentin, Lars; Siegbahn, Agneta] Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden. [Hall, Alistair S.] Univ Leeds, Div Cardiovasc & Neuronal Remodelling, Multidisciplinary Cardiovasc Res Ctr, Leeds Inst Genet Hlth & Therapeut, Leeds, W Yorkshire, England. [Lee, Jong-Young; Han, Bok-Ghee; Lee, Ji-Young] Korea Ctr Dis Control & Prevent, Korea Natl Inst Hlth, Ctr Genome Sci, Yeonje Ri, Chungwon Gun, South Korea. [Willer, Cristen J.] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. [Willer, Cristen J.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. [Chambers, John C.; Zhang, Weihua] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England. [Esko, Tonu; Fischer, Krista; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Esko, Tonu; Mihailov, Evelin; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia. [Folkersen, Lasse; Strawbridge, Rona J.; Eriksson, Per; Hamsten, Anders] Karolinska Inst, Atherosclerosis Res Ctr, Dept Med, Stockholm, Sweden. [Folkersen, Lasse; Strawbridge, Rona J.; Eriksson, Per; Hamsten, Anders] Karolinska Univ Hosp, Ctr Mol Med, Stockholm, Sweden. [Grundberg, Elin] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Havulinna, Aki S.; Kristiansson, Kati; Kuulasmaa, Kari; Salomaa, Veikko; Virtamo, Jarmo; Perola, Markus] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Hopewell, Jemma C.; Parish, Sarah; Clarke, Robert; Collins, Rory] Univ Oxford, Clin Trial Serv Unit, Oxford, England. [Hopewell, Jemma C.; Parish, Sarah; Clarke, Robert; Collins, Rory] Univ Oxford, Epidemiol Studies Unit, Oxford, England. [Kleber, Marcus E.; Maerz, Winfried] Heidelberg Univ, Mannheim Inst Publ Hlth Social & Prevent Med, Med Fac Mannheim, D-6800 Mannheim, Germany. [Kleber, Marcus E.] Ludwigshafen Risk & Cardiovasc Hlth LURIC, Freiburg, Germany. [Lundmark, Per; Lundmark, Anders; Lind, Lars; Syvanen, Ann-Christine] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Tampere Univ Hosp, Dept Clin Chem, Fimlab Labs, FIN-33521 Tampere, Finland. [Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Univ Tampere, Dept Clin Sci, Sch Med, SF-33520 Tampere, Finland. [Rafelt, Suzanne; Braund, Peter S.; Goodall, Alison H.; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Glenfield Hosp, Leicester, Leics, England. [Shungin, Dmitry; Franks, Paul W.] Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Skane Univ Hosp,Diabet Ctr, Malmo, Sweden. [Shungin, Dmitry; Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Genet Epidemiol & Clin Res Grp, Med Sect, Umea, Sweden. [Shungin, Dmitry; Franks, Paul W.] Umea Univ, Dept Odontol, Umea, Sweden. [Thorleifsson, Gudmar; Holm, Hilma; Stefansson, Kari; Thorsteinsdottir, Unnur] deCODE Genet, Reykjavik, Iceland. [Tikkanen, Emmi; Wagner, Peter J.] Univ Helsinki, Inst Mol Med FIMM, Helsinki, Finland. [Tikkanen, Emmi; Wagner, Peter J.; Ripatti, Samuli] Natl Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki, Finland. [Van Zuydam, Natalie; Doney, Alex S. F.; Morris, Andrew D.; Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee DD1 9SY, Scotland. [Voight, Benjamin F.] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA. [Waite, Lindsay L.; Absher, Devin] HudsonAlpha Inst Biotechnol, Huntsville, AL USA. [Altshuler, David; Do, Ron; Fontanillas, Pierre; Kathiresan, Sekar] Broad Inst Harvard & MIT, Cambridge, MA USA. [Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Altshuler, David; Do, Ron] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Balmforth, Anthony J.] Univ Leeds, Div Cardiovasc & Diabet Res, Multidisciplinary Cardiovasc Res Ctr, Leeds Inst Genet Hlth & Therapeut, Leeds, W Yorkshire, England. [Barroso, Ines] Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Cambridge CB2 2QQ, England. [Braund, Peter S.; Goodall, Alison H.; Samani, Nilesh J.] Glenfield Hosp, NIHR, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England. [Burgdorf, Christof; Kessler, Thorsten; Rumpf, Moritz P.; Schunkert, Heribert] Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany. [Claudi-Boehm, Simone] Univ Ulm, Med Ctr, Ulm, Germany. [Cox, David] Pfizer, Biotherapeut & Bioinnovat Ctr, San Francisco, CA USA. [Dimitriou, Maria; Dedoussis, George] Harokopio Univ, Dept Dietet Nutr, Athens, Greece. [El Mokhtari, NourEddine; Rubin, Diana] Kreiskrankenhaus Rendsburg, Innere Med Klin, Rendsburg, Germany. [Franco-Cereceda, Anders] Karolinska Inst, Dept Mol Med & Surg, Cardiothorac Surg Unit, Stockholm, Sweden. [Gigante, Bruna; Leander, Karin; de Faire, Ulf] Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, S-10401 Stockholm, Sweden. [Groop, Leif; Melander, Olle] Lund Univ, Dept Clin Sci Diabet & Endocrinol, Malmo Univ Hosp, Malmo, Sweden. [Hager, Joerg] CEA, Genom Inst, Natl Genotyping Ctr, Paris, France. [Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med, Sect Nutr Res, Umea, Sweden. [Kang, Hyun M.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Illig, Thomas; Klopp, Norman] Hannover Med Sch, Hannover Unified Biobank, D-3000 Hannover, Germany. [Kolovou, Genovefa] Onassis Cardiac Surg Ctr 356, Cardiol Dept 1, Athens, Greece. [Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio, Finland. [Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Langenberg, Claudia; Wareham, Nicholas; Sandhu, Manjinder S.] Addenbrookes Hosp, MRC, Epidemiol Unit, Inst Metab Sci, Cambridge, England. [Lokki, Marja-Liisa] Univ Helsinki, Transplantat Lab, Haartman Inst, Helsinki, Finland. [McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [McCarthy, Mark I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England. [Meisinger, Christa; Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. [Maouche, Seraya; Cambien, Francois; Tregouet, David-Alexandre] Univ Paris 06, INSERM, Unite Mixte Rech UMR S937, ICAN, Paris, France. [Mueller-Nurasyid, Martina] Univ Munich, Dept Med 1, Univ Hosp Grosshadern, Munich, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Chair Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Genet Epidemiol, Munich, Germany. [Mueller-Nurasyid, Martina] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany. [Nikus, Kjell] Tampere Univ Hosp, Dept Cardiol, Ctr Heart, Tampere, Finland. [Rosinger, Silke; Boehm, Bernhard O.] Univ Ulm, Dept Internal Med, Div Endocrinol & Diabet, Med Ctr, D-7900 Ulm, Germany. [Schaefer, Arne; Schreiber, Stefan] Univ Kiel, Inst Klin Mol Biol, Kiel, Germany. [Sivananthan, Mohan] Univ Leeds, Div Epidemiol, Multidisciplinary Cardiovascular Res Ctr MCRC, Leeds, W Yorkshire, England. [Sivananthan, Mohan] Univ Leeds, Leeds Inst Genet Hlth & Therapeut, Leeds, W Yorkshire, England. [Stewart, Alexandre F. R.; Wells, George A.; Roberts, Robert] Univ Ottawa, Inst Heart, Cardiovasc Res Methods Ctr Ontario, Ottawa, ON, Canada. [Stewart, Alexandre F. R.; Wells, George A.; Roberts, Robert] Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada. [Tan, Sian-Tsung; Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, NHLI, Hammersmith Hosp, London, England. [Thorgeirsson, Gudmundur; Gudnason, Villi; Stefansson, Kari; Thorsteinsdottir, Unnur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Thorgeirsson, Gudmundur] Landspitali Univ Hosp, Dept Med, Reykjavik, Iceland. [van der Schoot, C. Ellen] Sanquin, Dept Expt Immunohematol, Amsterdam, Netherlands. [Wild, Philipp S.] Johannes Gutenberg Univ Mainz, Ctr Thrombosis & Hemostasis, Univ Med Ctr Mainz, Mainz, Germany. [Wild, Philipp S.] Johannes Gutenberg Univ Mainz, Dept Med 2, Univ Med Ctr Mainz, Mainz, Germany. [Amouyel, Philippe] Univ Lille Nord France, Inst Pasteur Lille, INSERM U744, Lille, France. [Arveiler, Dominique] Univ Strasbourg, Dept Epidemiol & Publ Hlth, EA3430, Strasbourg, France. [Basart, Hanneke; Hovingh, G. Kees] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Brambilla, Paolo] Univ Milano Bicocca, Dept Expt Med, Monza, Italy. [Cupples, Adrienne L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Cupples, Adrienne L.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Dehghan, Abbas; O'Donnell, Christopher] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Diemert, Patrick; Blankenberg, Stefan S.] Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, Hamburg, Germany. [Epstein, Stephen E.] Washington Hosp Ctr, Cardiovasc Res Inst, Washington, DC 20010 USA. [Evans, Alun] Queens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland. [Ferrario, Marco M.] Univ Insubria, Res Ctr Epidemiol & Prevent Med EPIMED, Dept Clin & Expt Med, Varese, Italy. [Ferrieres, Jean] Toulouse Univ, Sch Med, Rangueil Hosp, Dept Cardiol, Toulouse, France. [Gauguier, Dominique] INSERM, UMR S872, Cordeliers Res Ctr, Paris, France. [Go, Alan S.; Iribarren, Carlos] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Gudnason, Villi] Iceland Heart Assoc, Kopavogur, Iceland. [Hazen, Stanley L.] Cleveland Clin, Lerner Res Inst, Cleveland, OH 44106 USA. [Jang, Yangsoo] Yonsei Univ, Div Cardiol, Dept Internal Med, Cardiovascu Genome Ctr, Seoul 120749, South Korea. [Kahonen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland. [Kee, Frank] Queens Univ Belfast, UK Clin Res Collaborat UKCRC, Ctr Excellence Publ Hlth No Ireland, Belfast, Antrim, North Ireland. [Kim, Hyo-Soo] Seoul Natl Univ Hosp, Dept Internal Med, Ctr Cardiovasc, Seoul 110744, South Korea. [Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med 2, Ulm, Germany. [Kratzer, Wolfgang; Laaksonen, Reijo] Tampere Univ Hosp, Ctr Sci, Tampere, Finland. [Ouwehand, Willem H.] Univ Cambridge, Dept Haematol, Cambridge, England. [Ouwehand, Willem H.] Natl Hlth Serv NHS Blood & Transplant, Cambridge, England. [Park, Jeong E.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Cardiol, Seoul, South Korea. [Peters, Annette] Munich Heart Alliance, Munich, Germany. [Rader, Daniel J.] Univ Penn, Dept Med, Div Translat Med & Human Genet, Perelman Sch Med, Philadelphia, PA 19104 USA. [Schadt, Eric] Mt Sinai Sch Med, Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY USA. [Shah, Svati H.] Duke Univ, Med Ctr, Dept Med, Ctr Human Genet, Durham, NC 27710 USA. [Shah, Svati H.] Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA. [Sinisalo, Juha; Nieminen, Markku S.] Helsinki Univ Cent Hosp, Div Cardiol, Dept Med, Helsinki, Finland. [Stark, Klaus; Zimmermann, Martina E.; Hengstenberg, Christian] Klin & Poliklin Innere Med II, Regensburg, Germany. [Pastinen, Tomi] McGill Univ, Dept Human Genet, Montreal, PQ, Canada. [Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Zalloua, Pierre A.] Lebanese Amer Univ, Beirut, Lebanon. [Reilly, Muredach P.] Univ Penn, Cardiovasc Inst, Perelman Sch Med, Philadelphia, PA 19104 USA. [Maerz, Winfried] Synlab Acad, Mannheim, Germany. [Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Ctr Human Genet Res, Boston, MA 02114 USA. [Kathiresan, Sekar; CARDIOGENENICS Consortium] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Deloukas, P (reprint author), Wellcome Trust Sanger Inst, Cambridge, England. EM panos@sanger.ac.uk; njs@leicester.ac.uk RI Erdmann, Jeanette/P-7513-2014; Kessler, Thorsten/O-7426-2015; Peters, Annette/A-6117-2011; Lyytikainen, Leo-Pekka/C-8544-2016; Tregouet, David-Alexandre/E-3961-2016; Study, GoDARTS/K-9448-2016; Konig, Inke/A-4544-2009; Leander, Karin/C-7261-2017; Deloukas, Panos/B-2922-2013; Palmer, Colin/C-7053-2008; Knowles, Josh/C-9241-2013; Willenborg, Christina/D-2668-2012; Johansson, Asa/G-5270-2011; Strawbridge, Rona/H-5422-2012; Boehm, Bernhard/F-8750-2015; Gudnason, Vilmundur/K-6885-2015; Ripatti, Samuli/H-9446-2014; Altshuler, David/A-4476-2009; Meisinger, Christine/B-5358-2014; Schreiber, Stefan/B-6748-2008; Laaksonen, Reijo/D-6323-2014; OI Kleber, Marcus/0000-0003-0663-7275; Dehghan, Abbas/0000-0001-6403-016X; Yang, Tsun-Po/0000-0002-9077-4434; Lee, Ji-Young/0000-0002-7784-1401; HO, WEANG KEE/0000-0002-8269-7344; Hunt, Sarah/0000-0002-8350-1235; Stewart, Alexandre/0000-0003-2673-9164; Erdmann, Jeanette/0000-0002-4486-6231; Ferrario, Marco M/0000-0003-2741-7124; Gigante, Bruna/0000-0003-4508-7990; Folkersen, Lasse/0000-0003-0708-9530; Ziegler, Andreas/0000-0002-8386-5397; Lyytikainen, Leo-Pekka/0000-0002-7200-5455; Leander, Karin/0000-0002-1404-9222; Song, Ci/0000-0002-0947-9068; Shungin, Dmitry/0000-0001-7900-5856; Esko, Tonu/0000-0003-1982-6569; Kristiansson, Kati/0000-0003-4688-107X; Willer, Cristen/0000-0001-5645-4966; Deloukas, Panos/0000-0001-9251-070X; Palmer, Colin/0000-0002-6415-6560; Willenborg, Christina/0000-0001-5217-6882; Johansson, Asa/0000-0002-2915-4498; Strawbridge, Rona/0000-0001-8506-3585; Gudnason, Vilmundur/0000-0001-5696-0084; Ripatti, Samuli/0000-0002-0504-1202; Altshuler, David/0000-0002-7250-4107; Schreiber, Stefan/0000-0003-2254-7771; Franks, Paul/0000-0002-0520-7604; Meisinger, Christa/0000-0002-9026-6544; zalloua, pierre/0000-0002-8494-5081; Kuulasmaa, Kari/0000-0003-2165-1411; Watkins, Hugh/0000-0002-5287-9016; Ouwehand, Willem/0000-0002-7744-1790; Sinisalo, Juha/0000-0002-0169-5137 FU Merck; British Heart Foundation (BHF) Centre of Research Excellence FX The study was designed and conducted by the Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU) at the University of Oxford. Genotyping was supported by a grant to Oxford University and Centre National de Genotypage (CNG) from Merck. The funders had no role in the design of the study or in the data collection or analysis. We especially acknowledge the participants in the study, the Steering Committee and our collaborators. J.C.H. acknowledges support from the British Heart Foundation (BHF) Centre of Research Excellence. NR 34 TC 435 Z9 443 U1 16 U2 110 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 JAN PY 2013 VL 45 IS 1 BP 25 EP U52 DI 10.1038/ng.2480 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 061HJ UT WOS:000312838800009 ER PT J AU Fuchs, T Saunders-Pullman, R Masuho, I Luciano, MS Raymond, D Factor, S Lang, AE Liang, TW Trosch, RM White, S Ainehsazan, E Herve, D Sharma, N Ehrlich, ME Martemyanov, KA Bressman, SB Ozelius, LJ AF Fuchs, Tania Saunders-Pullman, Rachel Masuho, Ikuo Luciano, Marta San Raymond, Deborah Factor, Stewart Lang, Anthony E. Liang, Tsao-Wei Trosch, Richard M. White, Sierra Ainehsazan, Edmond Herve, Denis Sharma, Nutan Ehrlich, Michelle E. Martemyanov, Kirill A. Bressman, Susan B. Ozelius, Laurie J. TI Mutations in GNAL cause primary torsion dystonia SO NATURE GENETICS LA English DT Article ID AUTOSOMAL-DOMINANT INHERITANCE; CERVICAL DYSTONIA; ADENYLYL-CYCLASE; ADULT-ONSET; MYOCLONUS-DYSTONIA; GENETIC-ANALYSIS; ASHKENAZI JEWS; DYT1 DYSTONIA; BASAL GANGLIA; MOUSE MODEL AB Dystonia is a movement disorder characterized by repetitive twisting muscle contractions and postures(1,2). Its molecular pathophysiology is poorly understood, in part owing to limited knowledge of the genetic basis of the disorder. Only three genes for primary torsion dystonia (PTD), TOR1A (DYT1)(3), THAP1 (DYT6)(4) and CIZ1 (ref. 5), have been identified. Using exome sequencing in two families with PTD, we identified a new causative gene, GNAL, with a nonsense mutation encoding p.Ser293* resulting in a premature stop codon in one family and a missense mutation encoding p.Val137Met in the other. Screening of GNAL in 39 families with PTD identified 6 additional new mutations in this gene. Impaired function of several of the mutants was shown by bioluminescence resonance energy transfer (BRET) assays. C1 [Fuchs, Tania; White, Sierra; Ainehsazan, Edmond; Ozelius, Laurie J.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA. [Saunders-Pullman, Rachel; Raymond, Deborah; Bressman, Susan B.] Beth Israel Deaconess Med Ctr, Dept Neurol, New York, NY 10003 USA. [Saunders-Pullman, Rachel; Bressman, Susan B.] Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10467 USA. [Masuho, Ikuo; Martemyanov, Kirill A.] Scripps Res Inst, Dept Neurosci, Jupiter, FL USA. [Luciano, Marta San] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Factor, Stewart] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Lang, Anthony E.] Toronto Western Hosp, Dept Neurol, Toronto, ON M5T 2S8, Canada. [Liang, Tsao-Wei] Jefferson Hosp Neurosci, Dept Neurol, Philadelphia, PA USA. [Trosch, Richard M.] Parkinsons & Movement Disorders Ctr, Southfield, MI USA. [Herve, Denis] INSERM, Unite Mixte Rech UMR S839, Paris, France. [Herve, Denis] Inst Fer Moulin, Paris, France. [Herve, Denis] Univ Paris 06, Paris, France. [Sharma, Nutan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Ehrlich, Michelle E.; Ozelius, Laurie J.] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. [Ehrlich, Michelle E.] Mt Sinai Sch Med, Dept Pediat, New York, NY USA. RP Ozelius, LJ (reprint author), Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA. EM laurie.ozelius@mssm.edu RI Masuho, Ikuo/J-6115-2014; HERVE, Denis/E-2929-2017 OI HERVE, Denis/0000-0003-1376-1522 FU Dystonia Medical Research Foundation; Bachmann-Strauss Dystonia and Parkinson Foundation; Lockwood Family Foundation; National Institute of Neurological Disorders and Stroke [NS26656, NS037409, K02-NS073836]; National Institute on Drug Abuse [DA021743, DA026405]; Agence Nationale de la Recherche [ANR09-MNPS-014]; Lung GO Sequencing Project [HL-102923]; Women's Health Initiative (WHI) Sequencing Project [HL-102924]; Broad GO Sequencing Project [HL-102925]; Seattle GO Sequencing Project [HL-102926]; Heart GO Sequencing Project [HL-103010] FX We wish to thank all individuals with dystonia and their family members who participated in this study. We are indebted to the following physicians for referring families with dystonia included in this manuscript: S. Reich, J. Hammerstadt, D. Hobson, D. Truong, F. Danisi, M. Hutchinson, S. O'Riordan, T. Lynch and J. Rogers. We would also like to thank the following physicians who examined study subjects during their movement disorder fellowships: R. Tabamo, E. Chai, K. Blatt, P. Kavanagh, P. Kapoor and G. Petzinger. We thank R. Sachidanandam for the bioinformatics analysis related to the splice-site mutation; H. Lederman for technical help; N.A. Lambert (Georgia Health Sciences University) for sharing Venus155-239-G beta1 and Venus1-155-G gamma2; and B. Malnic (Universidade de Sao Paulo) for the gift of the Ric-8B construct. This work was supported by research grants from the Dystonia Medical Research Foundation (T. F.), the Bachmann-Strauss Dystonia and Parkinson Foundation (L. J. O.), the Lockwood Family Foundation (N. S. and L. J. O.), the National Institute of Neurological Disorders and Stroke (NS26656, S. B. B., R. S.-P. and L. J. O.; NS037409, N. S. and L. J. O.; K02-NS073836, R. S.-P.) the National Institute on Drug Abuse (DA021743 and DA026405, K. A. M.) and Agence Nationale de la Recherche (ANR09-MNPS-014, D. H.). The authors would like to thank the NHLBI GO Exome Sequencing Project and its ongoing studies, which produced and provided exome variant calls for comparison, including the Lung GO Sequencing Project (HL-102923), the Women's Health Initiative (WHI) Sequencing Project (HL-102924), the Broad GO Sequencing Project (HL-102925), the Seattle GO Sequencing Project (HL-102926) and the Heart GO Sequencing Project (HL-103010). NR 66 TC 103 Z9 103 U1 0 U2 12 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 JAN PY 2013 VL 45 IS 1 BP 88 EP U128 DI 10.1038/ng.2496 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 061HJ UT WOS:000312838800018 PM 23222958 ER PT J AU Gillette, MA Carr, SA AF Gillette, Michael A. Carr, Steven A. TI METHOD OF THE YEAR Quantitative analysis of peptides and proteins in biomedicine by targeted mass spectrometry SO NATURE METHODS LA English DT Article ID CARDIOVASCULAR-DISEASE; BIOMARKER DISCOVERY; ASSAY DEVELOPMENT; ISOTOPE-DILUTION; QUANTIFICATION; PLASMA; VERIFICATION; CANCER; PIPELINE; SERUM AB Targeted mass spectrometry (MS) is becoming widely used in academia and in pharmaceutical and biotechnology industries for sensitive and quantitative detection of proteins, peptides and post-translational modifications. Here we describe the increasing importance of targeted MS technologies in clinical proteomics and the potential key roles these techniques will have in bridging biomedical discovery and clinical implementation. C1 [Gillette, Michael A.; Carr, Steven A.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA. [Gillette, Michael A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Carr, SA (reprint author), Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA. EM scarr@broadinstitute.org FU Broad Institute of MIT and Harvard; US National Cancer Institute part of the Clinical Proteomics Tumor Analysis Consortium initiative [U24CA160034]; National Heart, Lung, and Blood Institute [HHSN268201000033C, R01HL096738]; Entertainment Industry Foundation; Komen Foundation FX We thank L. Gaffney for her help with graphics. This work was supported in part by the Broad Institute of MIT and Harvard, and by grants from the US National Cancer Institute (U24CA160034, part of the Clinical Proteomics Tumor Analysis Consortium initiative, to S. A. C.) and National Heart, Lung, and Blood Institute (HHSN268201000033C and R01HL096738 to S. A. C.). S. A. C. and M. A. G. acknowledge the financial support of the Women's Cancer Research Fund of the Entertainment Industry Foundation and the Komen Foundation for funding portions of this work. NR 42 TC 138 Z9 140 U1 12 U2 126 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD JAN PY 2013 VL 10 IS 1 BP 28 EP 34 DI 10.1038/nmeth.2309 PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 060WW UT WOS:000312810100022 PM 23269374 ER PT J AU von Boehmer, H Daniel, C AF von Boehmer, Harald Daniel, Carolin TI Therapeutic opportunities for manipulating T-Reg cells in autoimmunity and cancer SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID VERSUS-HOST-DISEASE; LIGASE CBL-B; NF-KAPPA-B; IN-VIVO; FOXP3 EXPRESSION; REGULATORY CELLS; IMMUNE-RESPONSE; NOD MICE; ANTITUMOR IMMUNITY; PERIPHERAL-BLOOD AB Forkhead box P3 (FOXP3)-expressing regulatory T (T-Reg) cells have a pivotal role in the regulation of immune responses and in the maintenance of immunological self-tolerance. These cells have emerged as attractive targets for strategies that allow the steering of immune responses in desired directions-arming the immune system to destroy infected cells and cancer cells or downregulating it to limit tissue destruction in autoimmunity. Efforts to understand the generation, activation and function of T-Reg cells should permit the development of therapeutics for reprogramming the immune system. In this Review, we discuss insights into the generation of T-Reg cells, their involvement in disease and the molecular basis of the dominant tolerance exerted by FOXP3(+) T-Reg cells that could permit their safe and specific manipulation in humans. C1 [von Boehmer, Harald; Daniel, Carolin] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Lab Lymphocyte Biol, Boston, MA 02115 USA. [von Boehmer, Harald] Harvard Univ, Harvard Fac Arts & Sci, Cambridge, MA 02138 USA. [Daniel, Carolin] Helmholtz Zentrum Muenchen German Ctr Environm Hl, Inst Diabet Res 1, D-85764 Munich, Germany. RP von Boehmer, H (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Lab Lymphocyte Biol, 450 Brookline Ave,Smith 736, Boston, MA 02115 USA. EM harald_von_boehmer@dfci.harvard.edu; carolin.daniel@helmholtz-muenchen.de RI Daniel, Carolin/M-4624-2014 OI Daniel, Carolin/0000-0003-4698-7069 FU US National Institutes of Health Grant [NIH-AI-53102]; Leopoldina research fellowship [BMBF-LPD 9901/8-184]; Junior Research Group at Helmholtz Zentrum Munchen, Germany FX The studies were supported by the US National Institutes of Health Grant NIH-AI-53102 (to H.V.B.). C.D. was supported by a Leopoldina research fellowship (BMBF-LPD 9901/8-184) and is now supported by a Junior Research Group at Helmholtz Zentrum Munchen, Germany. NR 187 TC 68 Z9 68 U1 4 U2 49 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD JAN PY 2013 VL 12 IS 1 BP 51 EP 63 DI 10.1038/nrd3683 PG 13 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 063HN UT WOS:000312987000015 PM 23274471 ER PT J AU Obermayr, F Hotta, R Enomoto, H Young, HM AF Obermayr, Florian Hotta, Ryo Enomoto, Hideki Young, Heather M. TI Development and developmental disorders of the enteric nervous system SO NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY LA English DT Review ID NEURAL CREST CELLS; ENDOTHELIN RECEPTOR-B; TOTAL COLONIC AGANGLIONOSIS; SYNDROMIC HIRSCHSPRUNG DISEASE; HYPERTROPHIC PYLORIC-STENOSIS; INTESTINAL NEURONAL DYSPLASIA; GOLDBERG-SHPRINTZEN SYNDROME; MOWAT-WILSON-SYNDROME; ADHESION MOLECULE L1; HOMEOBOX GENE PHOX2B AB The enteric nervous system (ENS) arises from neural crest-derived cells that migrate into and along the gut, leading to the formation of a complex network of neurons and glial cells that regulates motility, secretion and blood flow. This Review summarizes the progress made in the past 5 years in our understanding of ENS development, including the migratory pathways of neural crest-derived cells as they colonize the gut. The importance of interactions between neural crest-derived cells, between signalling pathways and between developmental processes (such as proliferation and migration) in ensuring the correct development of the ENS is also presented. The signalling pathways involved in ENS development that were determined using animal models are also described, as is the evidence for the involvement of the genes encoding these molecules in Hirschsprung disease-the best characterized paediatric enteric neuropathy. Finally, the aetiology and treatment of Hirschsprung disease in the clinic and the potential involvement of defects in ENS development in other paediatric motility disorders are outlined. Obermayr, F. et al. Nat. Rev. Gastroenterol. Hepatol. 10, 43-57 (2013); published online 11 December 2012; doi:10.1038/nrgastro.2012.234 C1 [Young, Heather M.] Univ Melbourne, Dept Anat & Neurosci, Parkville, Vic 3010, Australia. [Obermayr, Florian] Univ Tubingen, Dept Pediat Surg, Univ Childrens Hosp, D-72076 Tubingen, Germany. [Hotta, Ryo] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hotta, Ryo] Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. [Enomoto, Hideki] RIKEN Ctr Dev Biol, Chuo Ku, Kobe, Hyogo 6500047, Japan. RP Young, HM (reprint author), Univ Melbourne, Dept Anat & Neurosci, Parkville, Vic 3010, Australia. EM h.young@unimelb.edu.au OI Young, Heather/0000-0002-0457-8710 NR 218 TC 66 Z9 70 U1 2 U2 46 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5045 EI 1759-5053 J9 NAT REV GASTRO HEPAT JI Nat. Rev. Gastroenterol. Hepatol. PD JAN PY 2013 VL 10 IS 1 BP 43 EP 57 DI 10.1038/nrgastro.2012.234 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 063GJ UT WOS:000312983900008 PM 23229326 ER PT J AU Gold, MC Lewinsohn, DM AF Gold, Marielle C. Lewinsohn, David M. TI Co-dependents: MR1-restricted MAIT cells and their antimicrobial function SO NATURE REVIEWS MICROBIOLOGY LA English DT Article ID INVARIANT T-CELLS; MHC-RELATED PROTEIN-1; ADAPTIVE IMMUNITY; ALPHA-CHAIN; RECEPTOR; MR1; EVOLUTION; GENES; RECOGNITION; EXPRESSION AB Mucosal-associated invariant T (MAIT) cells are a unique T cell subset in mammals. They are present at high frequencies at mucosal tissue sites and have an intrinsic capacity to respond to microbial infections. The semi-invariant antigen recognition receptor of MAIT cells detects the non-polymorphic antigen-presenting molecule major histocompatibility complex class I-related protein 1 (MR1), which can bind microorganism-derived riboflavin metabolites. The striking evolutionary conservation in both the MR1 molecule and the MAIT T cell receptor suggests that strong selective pressures maintain this T cell pattern recognition system which detects microbial infection. C1 [Gold, Marielle C.; Lewinsohn, David M.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Pulm & Crit Care Med, Portland, OR 97239 USA. RP Gold, MC (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Pulm & Crit Care Med, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM goldm@ohsu.edu; lewinsod@ohsu.edu RI Lewinsohn, David/I-4936-2013; OI Lewinsohn, David/0000-0001-9906-9494; Gold, Marielle/0000-0003-2505-3291 FU NIAID NIH HHS [R01 AI078965, R01 AI048090, U01 AI095776] NR 48 TC 56 Z9 56 U1 2 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 EI 1740-1534 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD JAN PY 2013 VL 11 IS 1 BP 14 EP 19 DI 10.1038/nrmicro2918 PG 6 WC Microbiology SC Microbiology GA 056OG UT WOS:000312499500010 PM 23178389 ER PT J AU Qu, XD Xu, CS Wang, H Xu, J Liu, WR Wang, Y Jia, XY Xie, ZC Xu, ZP Ji, C Wu, AS Yue, Y AF Qu, Xiangdong Xu, Chengshi Wang, Hui Xu, Jie Liu, Weiran Wang, Yun Jia, Xingyuan Xie, Zhongcong Xu, Zhipeng Ji, Chao Wu, Anshi Yue, Yun TI Hippocampal Glutamate Level and Glutamate Aspartate Transporter (GLAST) are Up-Regulated in Senior Rat Associated with Isoflurane-Induced Spatial Learning/Memory Impairment SO NEUROCHEMICAL RESEARCH LA English DT Article DE Glutamate; Isoflurane; Learning/memory impairment; Glutamate transporter; Glutamate receptor ID POSTOPERATIVE COGNITIVE DYSFUNCTION; AMYLOID-BETA-PEPTIDE; CLINICALLY RELEVANT CONCENTRATIONS; NITROUS OXIDE ANESTHESIA; TRANSGENIC MOUSE MODEL; CENTRAL-NERVOUS-SYSTEM; IN-SITU HYBRIDIZATION; ALZHEIMERS-DISEASE; GLIAL GLUTAMATE; AGED RATS AB Postoperative cognitive decline is a clinical concern especially for senior patients. It is generally recognized that glutamatergic system plays a crucial role in the physiopathologic process of neurocognitive deterioration. However, alterations of glutamatergic system in prolonged isoflurane-induced learning/memory decline are still unclear. This study investigates the question whether glutamate concentration and corresponding transporters or receptors display any alternations in aged rat suffering from isoflurane-induced learning/memory impairment. 111 male Sprague-Dawley rats (> 18 months) were randomly divided into two main groups: hippocampal microdialysis group (n = 38) and western blotting group (n = 73). Each group was subdivided into three subgroups including (1) control subgroup (n = 6 and 10, receiving no behavioral trial, anesthesia or air exposure); (2) air-exposed subgroup (n = 7 and 15, receiving behavioral trial and air exposure but not anesthesia); (3) isoflurane anesthesia subgroup (n = 25 and 48, receiving both behavioral trial and anesthesia). The isoflurane-exposed rats were further divided into a learning/memory-impaired subgroup and a non-learning/memory-impaired subgroup according to their behavioral performance, which was measured using Morris water maze. Hippocampal glutamate concentrations in microdialysates were determined by high-performance liquid chromatography. Expression levels of GLAST, GLT-1, NMDAR1, NMDAR2A/B, AMPAR and tau in hippocampus were assessed via quantitative Western blotting. The incidences of learning/memory impairment of isoflurane-exposed rats in hippocampal microdialysis group and western blotting group were 12.0 (3/25) and 10.4 % (5/48) respectively. The intra-anesthesia hippocampal glutamate levels were significantly lower than those of non-anesthesized rats. The learning/memory-impaired rats showed a long-lasting increased glutamate level from 24 h after isoflurane exposure to the end of the study, but the other 22 isoflurane-exposed rats did not. The learning/memory-impaired subgroup displayed a significantly higher GLAST level than the other three subgroups (p = 0.026, 0.02 and 0.032 respectively). The expression levels of GLT-1, NMDAR1, NMDAR2A/B and AMPAR of every subgroup were comparable. We found a continuous raised hippocampal glutamate and an up-regulation of GLAST rather than GLT-1, NMDAR1, NMDAR2A/B, AMPAR or tau in hippocampus of aged rats associated with isoflurane-induced learning/memory impairment. C1 [Xu, Chengshi; Wang, Hui; Xu, Jie; Wang, Yun; Wu, Anshi; Yue, Yun] Capital Med Univ, Dept Anesthesia, Beijing Chao Yang Hosp, Beijing, Peoples R China. [Qu, Xiangdong] Beijing Jishuitan Hosp, Dept Anesthesia, Beijing, Peoples R China. [Liu, Weiran] Tianjin Med Univ, Dept Anesthesiol, Canc Inst & Hosp, Tianjin, Peoples R China. [Jia, Xingyuan] Capital Med Univ, Basic Med Res Ctr, Affiliated Beijing Chaoyang Hosp, Beijing, Peoples R China. [Xie, Zhongcong; Xu, Zhipeng] Massachusetts Gen Hosp, Geriatr Anesthesia Res Unit, Dept Anesthesia, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Xie, Zhongcong; Xu, Zhipeng] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Ji, Chao] PUMC, Dept Pharmacol, Inst Basic Med Sci, Sch Basic Med, Beijing, Peoples R China. [Ji, Chao] CAMS, Beijing, Peoples R China. RP Wu, AS (reprint author), Capital Med Univ, Dept Anesthesia, Beijing Chao Yang Hosp, Beijing, Peoples R China. EM wuanshi8@sina.com; yueyun@hotmail.com FU National Natural Science Foundation of China [30872425] FX Our study was supported by National Natural Science Foundation of China (grant no. 30872425). NR 90 TC 14 Z9 16 U1 3 U2 23 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD JAN PY 2013 VL 38 IS 1 BP 59 EP 73 DI 10.1007/s11064-012-0889-8 PG 15 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 058WB UT WOS:000312664400006 PM 23070469 ER PT J AU Augustinack, JC Huber, KE Stevens, AA Roy, M Frosch, MP van der Kouwe, AJW Wald, LL Van Leemput, K McKee, AC Fischl, B AF Augustinack, Jean C. Huber, Kristen E. Stevens, Allison A. Roy, Michelle Frosch, Matthew P. van der Kouwe, Andre J. W. Wald, Lawrence L. Van Leemput, Koen McKee, Ann C. Fischl, Bruce CA Alzheimers Dis Neuroimaging Initia TI Predicting the location of human perirhinal cortex, Brodmann's area 35, from MRI SO NEUROIMAGE LA English DT Article DE Morphometry; Mesocortex; Alzheimer's disease; Localization ID MEDIAL TEMPORAL-LOBE; HUMAN ENTORHINAL CORTEX; HUMAN CEREBRAL-CORTEX; NEUROIMAGING INITIATIVE ADNI; LAMINA-SPECIFIC PATHOLOGY; MILD ALZHEIMERS-DISEASE; SURFACE-BASED ANALYSIS; HIGH-FIELD MRI; PARAHIPPOCAMPAL CORTICES; HUMAN-BRAIN AB The perirhinal cortex (Brodmann's area 35) is a multimodal area that is important for normal memory function. Specifically, perirhinal cortex is involved in the detection of novel objects and manifests neurofibrillary tangles in Alzheimer's disease very early in disease progression. We scanned ex vivo brain hemispheres at standard resolution (1 mm x 1 mm x 1 mm) to construct pial/white matter surfaces in FreeSurfer and scanned again at high resolution (120 mu m x 120 mu m x 120 mu m) to determine cortical architectural boundaries. After labeling perirhinal area 35 in the high resolution images, we mapped the high resolution labels to the surface models to localize area 35 in fourteen cases. We validated the area boundaries determined using histological Nissl staining. To test the accuracy of the probabilistic mapping, we measured the Hausdorff distance between the predicted and true labels and found that the median Hausdorff distance was 4.0 mm for the left hemispheres (n = 7) and 3.2 mm for the right hemispheres (n = 7) across subjects. To show the utility of perirhinal localization, we mapped our labels to a subset of the Alzheimer's Disease Neuroimaging Initiative dataset and found decreased cortical thickness measures in mild cognitive impairment and Alzheimer's disease compared to controls in the predicted perirhinal area 35. Our ex vivo probabilistic mapping of the perirhinal cortex provides histologically validated, automated and accurate labeling of architectonic regions in the medial temporal lobe, and facilitates the analysis of atrophic changes in a large dataset for earlier detection and diagnosis. (C) 2012 Elsevier Inc. All rights reserved. C1 [Augustinack, Jean C.; Huber, Kristen E.; Stevens, Allison A.; Roy, Michelle; van der Kouwe, Andre J. W.; Wald, Lawrence L.; Van Leemput, Koen; Fischl, Bruce] MGH, Dept Radiol, Athinoula A Martinos Ctr, Charlestown, MA 02129 USA. [Frosch, Matthew P.] CS Kubik Lab Neuropathol, Pathol Serv, Boston, MA 02115 USA. [McKee, Ann C.] Boston Univ, Dept Pathol, Sch Med, Bedford Vet Adm Med Ctr, Bedford, MA 01730 USA. [Fischl, Bruce] MIT Comp Sci & AI Lab, Cambridge, MA 02139 USA. [Fischl, Bruce] MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Van Leemput, Koen] Tech Univ Denmark, Dept Informat & Math Modeling, Copenhagen, Denmark. RP Augustinack, JC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM jean@nmr.mgh.harvard.edu RI Van Leemput, Koen/A-9197-2009; Kowall, Neil/G-6364-2012; Preda, Adrian /K-8889-2013; Saykin, Andrew/A-1318-2007; Wald, Lawrence/D-4151-2009 OI Van Leemput, Koen/0000-0001-6466-5309; Kowall, Neil/0000-0002-6624-0213; Preda, Adrian /0000-0003-3373-2438; Saykin, Andrew/0000-0002-1376-8532; FU National Center for Research Resources [P41-RR14075, BIRN002, U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering [R01EB006758]; National Institute on Aging [AG022381, AG028521]; Massachusetts (MGH) Alzheimer's Disease Resource Center [5P50AG005134-28]; Boston University Alzheimer's Disease Center and Framingham Heart Study [P30-AG13846, R01 AG1649]; National Center for Alternative Medicine [RC1AT005728-01]; National Institute for Neurological Disorders and Stroke [R01 NS052585-01, 1R21NS072652-01, 1R01NS070963]; Shared Instrumentation Grants [1S10RR023401, 1S10RR019307, 1S10RR023043]; Autism & Dyslexia Project; Ellison Medical Foundation; NIH Blueprint for Neuro-science Research [U01-MH093765]; Alzheimer's Disease Neuro-imaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering; Canadian Institutes of Health Research; NIH [P30 AG010129, K01 AG030514]; Dana Foundation FX We would like to thank those who donated tissue; their generous donation made this work possible. We extend special thanks to Brad Dickerson for reading this manuscript and helpful comments. Support for this research was provided in part by the National Center for Research Resources (P41-RR14075, and the NCRR BIRN Morphometric Project BIRN002, U24 RR021382), the National Institute for Biomedical Imaging and Bioengineering (R01EB006758), the National Institute on Aging (AG022381) and (AG028521), the Massachusetts (MGH) Alzheimer's Disease Resource Center (5P50AG005134-28), Boston University Alzheimer's Disease Center and Framingham Heart Study (P30-AG13846 and R01 AG1649), the National Center for Alternative Medicine (RC1AT005728-01), the National Institute for Neurological Disorders and Stroke (R01 NS052585-01, 1R21NS072652-01, 1R01NS070963), and was made possible by the resources provided by Shared Instrumentation Grants 1S10RR023401, 1S10RR019307, and 1S10RR023043. Additional support was provided by The Autism & Dyslexia Project funded by the Ellison Medical Foundation and by the NIH Blueprint for Neuro-science Research (U01-MH093765, part of the multi-institutional Human Connectome Project). Data collection and sharing for this project was funded by the Alzheimer's Disease Neuro-imaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129, K01 AG030514, and the Dana Foundation. NR 88 TC 23 Z9 23 U1 0 U2 22 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN 1 PY 2013 VL 64 BP 32 EP 42 DI 10.1016/j.neuroimage.2012.08.071 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 056PU UT WOS:000312504200004 PM 22960087 ER PT J AU Larson, E Lee, AKC AF Larson, Eric Lee, Adrian K. C. TI The cortical dynamics underlying effective switching of auditory spatial attention SO NEUROIMAGE LA English DT Article DE Auditory attention; Frontal eye fields; Temporoparietal junction; Magnetoencephalography ID FUNCTIONAL NEUROANATOMY; SURFACE RECONSTRUCTION; VISUOSPATIAL ATTENTION; DORSAL FRONTOPARIETAL; EXECUTIVE CONTROL; TARGET DETECTION; PARIETAL CORTEX; BRAIN; DRIVEN; SEGMENTATION AB Successful rapid deployment of attention to relevant sensory stimuli is critical for survival. In a complex environment, attention can be captured by salient events or be deployed volitionally. Furthermore, when multiple events are of interest concurrently, effective interaction with one's surroundings hinges on efficient top-down control of shifting attention. It has been hypothesized that two separate cortical networks coordinate attention shifts across multiple modalities. However, the cortical dynamics of these networks and their behavioral relevance to switching of auditory attention are unknown. Here we show that the strength of each subject's right temporoparietal junction (RTPJ, part of the ventral network) activation was highly correlated with their behavioral performance in an auditory task. We also provide evidence that the recruitment of the RTPJ likely precedes the right frontal eye fields (FEF; participating in both the dorsal and ventral networks) and middle frontal gyrus (MFG) by around 100 ms when subjects switch their auditory spatial attention. (C) 2012 Elsevier Inc. All rights reserved. C1 [Larson, Eric; Lee, Adrian K. C.] Univ Washington, Dept Speech & Hearing Sci, Seattle, WA 98195 USA. [Larson, Eric; Lee, Adrian K. C.] Univ Washington, Inst Learning & Brain Sci, Seattle, WA 98195 USA. [Lee, Adrian K. C.] Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Lee, AKC (reprint author), Univ Washington, Dept Speech & Hearing Sci, 1715 NE Columbia Rd,Box 357988, Seattle, WA 98195 USA. EM larsoner@uw.edu; akclee@uw.edu OI Larson, Eric/0000-0003-4782-5360; Lee, Adrian KC/0000-0002-7611-0500 FU National Institute on Deafness and Other Communication Disorders [R00DC010196, T32DC000018] FX Thanks to Nick Kurkjy and Inyong Choi for help with analysis, and Ross K. Maddox and Geoffrey M. Boynton for suggestions. This work was supported by National Institute on Deafness and Other Communication Disorders grant R00DC010196 (AKCL) and training grant T32DC000018 (EL). NR 53 TC 15 Z9 15 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN 1 PY 2013 VL 64 BP 365 EP 370 DI 10.1016/j.neuroimage.2012.09.006 PG 6 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 056PU UT WOS:000312504200034 PM 22974974 ER PT J AU Lague-Beauvais, M Brunet, J Gagnon, L Lesage, F Bherer, L AF Lague-Beauvais, Maude Brunet, Julie Gagnon, Louis Lesage, Frederic Bherer, Louis TI A fNIRS investigation of switching and inhibition during the modified Stroop task in younger and older adults SO NEUROIMAGE LA English DT Article DE Prefrontal cortex; Executive functions; Attention; Aging; Neuroimaging; fNIRS ID NEAR-INFRARED SPECTROSCOPY; EVENT-RELATED FMRI; COGNITIVE CONTROL; ATTENTIONAL CONTROL; PREFRONTAL CORTEX; EXECUTIVE CONTROL; FRONTAL-CORTEX; AGING MIND; HEMODYNAMIC-RESPONSE; ANTERIOR CINGULATE AB Brain imaging studies have reported age-related differences in brain activation for attentional control functions, such as inhibition and task-switching. However, age-related differences in brain activation patterns in more than one attentional control task have rarely been studied in the same group of participants. In this study, younger and older adults completed a modified Stroop task with interference and switching conditions, using functional near infra-red spectroscopy. While interference did not reveal any significant activation of the prefrontal cortex in younger adults, switching produced an increased activation bilaterally in both the anterior dorsolateral prefrontal cortex (DLPFC) and the anterior ventrolateral prefrontal cortex (VLPFC). In older adults, an isolated right and left anterior DLPFC activation was observed even in the non-executive conditions of the Stroop task (color denomination) and the interference condition revealed activation mostly in the posterior left DLPFC and bilateral VLPFC with a small right anterior DLPFC component. Specific to older adults, switching induced an increased activation spread out bilaterally over the prefrontal cortex in the bilateral anterior DLPFC, the posterior left DLPFC and bilateral VLPFC. These results suggest that for both older and younger adults, inhibition and switching are associated with distinct patterns of prefrontal activation and that age-related differences exist in these patterns such that prefrontal activation seems to be more spread out at different sites in older adults. (C) 2012 Elsevier Inc. All rights reserved. C1 [Lague-Beauvais, Maude; Bherer, Louis] Univ Quebec Montreal, Dept Psychol, Montreal, PQ H3C 3P8, Canada. [Lague-Beauvais, Maude; Brunet, Julie; Bherer, Louis] Inst Univ Geriatr Montreal, Res Ctr, Montreal, PQ H3W 1W4, Canada. [Brunet, Julie] Univ Montreal, Dept Psychol, Montreal, PQ H3C 3J7, Canada. [Gagnon, Louis] Massachusetts Gen Hosp, Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Lesage, Frederic] Ecole Polytech Montreal, Montreal, PQ H3T 1J4, Canada. RP Bherer, L (reprint author), Univ Quebec Montreal UQAM, Dept Psychol, CP 8888,Succursale Ctr Ville, Montreal, PQ H3C 3P8, Canada. EM bherer.louis@uqam.ca OI Lague-Beauvais, Maude/0000-0002-0773-0343 FU Natural Sciences and Engineering Research Council of Canada [298918-2009]; Canadian Institutes of Health Research [200610SIA-170467-162735] FX This work was supported by the Natural Sciences and Engineering Research Council of Canada (grant number 298918-2009) and the Canadian Institutes of Health Research (grant number 200610SIA-170467-162735). NR 80 TC 12 Z9 12 U1 4 U2 35 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN 1 PY 2013 VL 64 BP 485 EP 495 DI 10.1016/j.neuroimage.2012.09.042 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 056PU UT WOS:000312504200047 PM 23000257 ER PT J AU Wilkenfeld, AJL Frank, SA McCarthy, DC AF Wilkenfeld, Ari J. L. Frank, Samuel A. McCarthy, David C., Jr. TI Botulinum Toxin for Painful Spasms From Focal Seizures Theoretical Considerations and Case Report SO NEUROLOGIST LA English DT Article DE botulinum toxins; muscle spasm; seizures ID DYSTONIA AB Introduction: Botulinum toxin (BTX) has been used to treat muscle overactivity and can reduce pain from muscle spasm. There are no previous reports to our knowledge of using BTX to treat the pain from intractable focal motor seizures. Case Report: We present a case of chronic, focal, muscle pain, and spasm secondary to intractable focal motor seizures treated with BTX. The patient experienced significant relief in muscle pain despite continued seizures. Conclusions: On the basis of the case presented, BTX may have a limited role in the treatment of pain from muscle spasm in intractable focal seizures. Further study is necessary to see if this use of BTX is generally applicable. C1 [Wilkenfeld, Ari J. L.] Cleveland Clin, Dept Neurol, Cleveland, OH 44195 USA. [Frank, Samuel A.; McCarthy, David C., Jr.] VA Boston Healthcare Syst, Dept Neurol, Boston, MA USA. [Frank, Samuel A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Frank, Samuel A.; McCarthy, David C., Jr.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Wilkenfeld, AJL (reprint author), Cleveland Clin, Dept Neurol, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM awilkenfeld@alum.mit.edu OI Frank, Samuel/0000-0002-1866-162X NR 9 TC 1 Z9 1 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1074-7931 J9 NEUROLOGIST JI Neurologist PD JAN PY 2013 VL 19 IS 1 BP 15 EP 16 DI 10.1097/NRL.0b013e31827aa7ab PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 063FL UT WOS:000312981500004 PM 23269101 ER PT J AU Gomperts, SN Locascio, JJ Rentz, D Santarlasci, A Marquie, M Johnson, KA Growdon, JH AF Gomperts, Stephen N. Locascio, Joseph J. Rentz, Dorene Santarlasci, Andrea Marquie, Marta Johnson, Keith A. Growdon, John H. TI Amyloid is linked to cognitive decline in patients with Parkinson disease without dementia SO NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; LEWY BODIES; IMPAIRMENT; PET; A-BETA(42); PATHOLOGY; DEFICITS; BURDEN; LOAD AB Objective: To determine whether amyloid burden, as indexed by Pittsburgh compound B (PiB) retention, identifies patients with Parkinson disease with mild cognitive impairment (PD-MCI) compared to those with normal cognition (PD-nl). A related aim is to determine whether amyloid burden predicts cognitive decline in a cohort of subjects with PD without dementia. Methods: In this prospective cohort study, we examined 46 subjects with PD without dementia, of whom 35 had normal cognition and 11 met criteria for PD-MCI at study baseline. All subjects underwent standardized neurologic and neuropsychological examinations and PiB PET at baseline, and clinical examinations were conducted annually for up to 5 years. Results: At baseline, precuneus PiB retention did not distinguish PD-MCI from PD-nl. Subjects with PD-MCI declined more rapidly than PD-nl subjects on cognitive tests of memory, executive function, and activation retrieval. Of the 35 PD-nl subjects, 8 progressed to PD-MCI and 1 to dementia; of the 11 PD-MCI subjects, 5 converted to dementia. Both higher PiB retention and a diagnosis of PD-MCI predicted a greater hazard of conversion to a more severe diagnosis. Baseline PiB retention predicted worsening in executive function over time. The APOE epsilon 4 allele also related to worsening in executive function, as well as visuospatial function, activation retrieval, and performance on the Mini-Mental State Examination. In contrast to its relation to cognitive decline, PiB retention did not affect progression of motor impairment. Conclusions: At baseline measurements, amyloid burden does not distinguish between cognitively impaired and unimpaired subjects with PD without dementia, but our data suggest that amyloid contributes to cognitive, but not motor, decline over time. Neurology (R) 2013;80:85-91 C1 [Gomperts, Stephen N.; Locascio, Joseph J.; Rentz, Dorene; Santarlasci, Andrea; Marquie, Marta; Johnson, Keith A.; Growdon, John H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Johnson, Keith A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Marquie, Marta] Autonomous Univ Barcelona Med Doctoral Studies, Barcelona, Spain. RP Growdon, JH (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM jgrowdon@partners.org OI Marquie, Marta/0000-0002-0660-0950 FU Michael J. Fox Foundation for Parkinson's Research; National Institute of Neurological Disorders and Stroke; National Institute on Aging; Alzheimer's Disease Association; Caja Madrid Foundation scholarship FX Supported by the Michael J. Fox Foundation for Parkinson's Research (to S.N.G. and J.H.G.), the National Institute of Neurological Disorders and Stroke (to K.A.J.), the National Institute on Aging (to K.A.J.), the Alzheimer's Disease Association (to K.A.J.), and the Caja Madrid Foundation scholarship for postgraduate studies (to M.M.). This study is not industry- sponsored. NR 40 TC 52 Z9 55 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN PY 2013 VL 80 IS 1 BP 85 EP 91 DI 10.1212/WNL.0b013e31827b1a07 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 061ZT UT WOS:000312889600018 PM 23243071 ER PT J AU Dunn, GP Spiliopoulos, K Plotkin, SR Hornicek, FJ Harmon, DC Delaney, TF Williams, Z AF Dunn, Gavin P. Spiliopoulos, Konstantinos Plotkin, Scott R. Hornicek, Francis J. Harmon, David C. Delaney, Thomas F. Williams, Ziv TI Malignant nerve sheath tumors Response SO NEUROSURGICAL FOCUS LA English DT Editorial Material ID SOFT-TISSUE SARCOMAS; ONCOLOGY GROUP; HIGH-GRADE; RHABDOMYOSARCOMA; RADIOTHERAPY; EXPERIENCE; CHILDREN; WALL C1 [Dunn, Gavin P.; Spiliopoulos, Konstantinos; Williams, Ziv] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. [Plotkin, Scott R.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Hornicek, Francis J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Oncol, Boston, MA USA. [Plotkin, Scott R.; Harmon, David C.; Delaney, Thomas F.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Delaney, Thomas F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Dunn, GP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 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 1092-0684 J9 NEUROSURG FOCUS JI Neurosurg. Focus PD JAN PY 2013 VL 34 IS 1 BP 141 EP 141 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 062VU UT WOS:000312952400028 ER PT J AU Dunn, GP Spiliopoulos, K Plotkin, SR Hornicek, FJ Harmon, DC Delaney, TF Williams, Z AF Dunn, Gavin P. Spiliopoulos, Konstantinos Plotkin, Scott R. Hornicek, Francis J. Harmon, David C. Delaney, Thomas F. Williams, Ziv TI Role of resection of malignant peripheral nerve sheath tumors in patients with neurofibromatosis Type 1 Clinical article SO NEUROSURGICAL FOCUS LA English DT Article DE malignancy; peripheral nerve; neurofibromatosis; peripheral nerve sheath tumor ID SOFT-TISSUE SARCOMAS; NEOADJUVANT CHEMOTHERAPY; ADJUVANT CHEMOTHERAPY; RADIATION-THERAPY; RANDOMIZED-TRIAL; MANAGEMENT; RADIOTHERAPY; EXTREMITY; SURVIVAL; METAANALYSIS AB Object. Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that often arise from major peripheral nerves. Approximately half of MPNSTs arise in patients with neurofibromatosis Type 1 (NF1) who, in comparison with patients without NF1, present at younger ages and with larger tumors that are commonly associated with extensive plexiform neurofibromas. These tumors therefore pose a particularly difficult treatment challenge because of the morbidity often associated with attempted gross-total resection (GTR). Here, the authors aim to examine what role the extent of resection and other covariates play in the long-term survival of patients with NF1 in the setting of MPNST. Methods. The authors retrospectively reviewed the records of 23 adult patients with NF1 who underwent surgery for MPNSTs at their institution between 1991 and 2008. The primary end points of the study were mortality, local recurrence, and metastasis. Kaplan-Meier survival curves were evaluated for all patients. Differences for each of the primary end points were evaluated based on cause-specific covariates, which included tiered tumor size, tumor location, grade, resection margin status, postoperative weakness, and use of chemotherapy and radiation therapy. Multivariate analysis was performed using Cox proportional hazards models. Results. Gross-total resection (p = 0.01) and surgical margin status (p = 0.034) had a statistically important role in prolonging overall survival in patients with NF1 by univariate analysis. When tumor size, location, grade, postoperative weakness, and radiation therapy were also taken into account using multivariate analysis, GTR continued to be a significant prognostic factor (p = 0.035). Conclusions. These findings suggest that GTR offers significant long-term benefit on survival in patients with NF1. Benefit on survival occurred independently of all other covariates, suggesting that complete resection should be the principal goal of treatment in this patient population. (http://thejns. org/doi/abs/10.3171/2012.9.JNS101610) C1 [Dunn, Gavin P.; Spiliopoulos, Konstantinos; Williams, Ziv] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. [Plotkin, Scott R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Hornicek, Francis J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Oncol, Boston, MA 02114 USA. [Plotkin, Scott R.; Harmon, David C.; Delaney, Thomas F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. [Delaney, Thomas F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Williams, Z (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, 55 Fruit St,WAC 745K, Boston, MA 02114 USA. EM zwilliams@partners.org FU Stryker; Zimmer FX Dr. Hornicek is a consultant for Stryker and received clinical or research support for the study described from Stryker and Zimmer. The other authors report no potential conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. NR 29 TC 0 Z9 0 U1 0 U2 3 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 JAN PY 2013 VL 34 IS 1 BP 142 EP 148 DI 10.3171/2012.9.JNS101610 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 062VU UT WOS:000312952400029 ER PT J AU Primack, BA Shensa, A Kim, KH Carroll, MV Hoban, MT Leino, EV Eissenberg, T Dachille, KH Fine, MJ AF Primack, Brian A. Shensa, Ariel Kim, Kevin H. Carroll, Mary V. Hoban, Mary T. Leino, E. Victor Eissenberg, Thomas Dachille, Kathleen H. Fine, Michael J. TI Waterpipe Smoking Among US University Students SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; HIGH-SCHOOL-STUDENTS; TOBACCO SMOKING; NICOTINE EXPOSURE; COLLEGE-STUDENTS; PREVALENCE; SMOKERS; PIPE; USERS AB While cigarette use is declining, smoking tobacco with a waterpipe is an emerging trend. We aimed to determine the prevalence of waterpipe use in a large diverse sample of U.S. university students and to assess the association of waterpipe use with individual and institution-related characteristics. We assessed students from 152 U.S. universities participating in the National College Health Assessment during 2008-2009. We used multivariable regression models to determine independent associations between individual and institutional characteristics and waterpipe tobacco use in the past 30 days and ever. Of 105,012 respondents included in the analysis, most were female (65.7%), White (71.2%), and attending public (59.7%) nonreligious (83.1%) institutions. Mean age was 22.1 years. A total of 32,013 (30.5%) reported ever using a waterpipe to smoke tobacco. Rates for current tobacco use were 8.4% for waterpipes, 16.8% for cigarettes, 7.4% for cigars (including cigarillos), and 3.5% for smokeless tobacco. Of current waterpipe users, 51.4% were not current cigarette smokers. Although current waterpipe use was reported across all individual and institutional characteristics, fully adjusted multivariable models showed that it was most strongly associated with younger age, male gender, White race, fraternity/sorority membership, and nonreligious institutions in large cities in the western United States. After cigarettes, waterpipe use was the most common form of tobacco use among university students. Because waterpipe use affects groups with a wide variety of individual and institutional characteristics, it should be included with other forms of tobacco in efforts related to tobacco surveillance and intervention. C1 [Primack, Brian A.; Shensa, Ariel; Carroll, Mary V.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. [Primack, Brian A.; Shensa, Ariel; Carroll, Mary V.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Pittsburgh, PA USA. [Primack, Brian A.] Univ Pittsburgh, Sch Med, Dept Pediat, Div Adolescent Med, Pittsburgh, PA 15261 USA. [Kim, Kevin H.] Univ Pittsburgh, Sch Educ, Dept Educ Psychol, Pittsburgh, PA 15260 USA. [Hoban, Mary T.; Leino, E. Victor] Amer Coll Hlth Assoc, Baltimore, MD USA. [Eissenberg, Thomas] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA. [Eissenberg, Thomas] Virginia Commonwealth Univ, Inst Drug & Alcohol Studies, Richmond, VA USA. [Dachille, Kathleen H.] Univ Maryland, Francis King Carey Sch Law, Legal Resource Ctr Tobacco Regulat Litigat & Advo, Baltimore, MD 21201 USA. [Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Primack, BA (reprint author), 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM bprimack@pitt.edu FU National Cancer Institute (NCI) [K07-CA114315, R01-CA140150]; Steven Manners Memorial Fund; NCI [R01-CA140150, R01-CA120142] FX Dr. Primack is supported by grants K07-CA114315 and R01-CA140150 from the National Cancer Institute (NCI) and an additional grant from the Steven Manners Memorial Fund. Dr. Eissenberg is supported by grants R01-CA140150 and R01-CA120142 from the NCI. The funding sources had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript. NR 35 TC 68 Z9 68 U1 1 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD JAN PY 2013 VL 15 IS 1 BP 29 EP 35 DI 10.1093/ntr/nts076 PG 7 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 061WM UT WOS:000312880900004 PM 22641433 ER PT J AU Etter, JF Schneider, NG AF Etter, Jean-Francois Schneider, Nina G. TI An Internet Survey of Use, Opinions and Preferences for Smoking Cessation Medications: Nicotine, Varenicline, and Bupropion SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID SUSTAINED-RELEASE BUPROPION; RANDOMIZED CONTROLLED-TRIAL; RECEPTOR PARTIAL AGONIST; REPLACEMENT THERAPY; CLINICAL PHARMACOKINETICS; CIGARETTE CONSUMPTION; TOBACCO DEPENDENCE; NASAL SPRAY; EX-SMOKERS; OPEN-LABEL AB We assessed use, compliance and preferences among smoking cessation medications in a "real world" sample of current and former smokers. Internet survey on a smoking cessation website (French/English, 2008-2010) to assess use of nicotine replacement therapies (NRT), varenicline, and bupropion. There were 885 participants (39% current smokers, 61% former smokers), the majority of the sample (70%) was female. The most frequently used medications were, in order: patches (40%), varenicline (23%), nicotine gum (16%), nicotine lozenge/tablet (10%), bupropion (8%), and inhaler (3%). Satisfaction, perceived relief of craving/withdrawal and effectiveness were best for varenicline and lowest for gum. In current users, duration of use was longest for gum (121 days), lozenge/tablet (152 days) and shortest for patch (25 days). Daily use was good for lozenge (9 pieces/day) but less than recommended for gum (6 pieces/day) and inhaler (2 plugs/day). People who tried more than 1 medication found varenicline more effective and satisfactory than NRT or bupropion; and users preferred patch to gum. By smoking status, former smokers had more education, reported greater use of medications (daily, over time) and reported more satisfaction with medications than current smokers. An Internet survey showed smoking cessation medications differed significantly in perceived effectiveness, satisfaction, and smoking status (former vs. current smoking). Except for lozenge/tablet, insufficient daily use remained a problem with acute NRTs. For all medications, improving outcome may require better instruction for proper use, approval of new indications (precessation) or development of new medications that bypass compliance issues that undermine success. C1 [Etter, Jean-Francois] Univ Geneva, Inst Social & Prevent Med, CMU, Fac Med, CH-1211 Geneva 4, Switzerland. [Schneider, Nina G.] Greater Los Angeles Vet Affairs Healthcare Serv, Nicotine Dependence Res Unit, Los Angeles, CA USA. [Schneider, Nina G.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Etter, JF (reprint author), Univ Geneva, Inst Social & Prevent Med, CMU, Fac Med, CH-1211 Geneva 4, Switzerland. EM jean-francois.etter@unige.ch OI ETTER, Jean-Francois/0000-0002-1426-3157 NR 47 TC 15 Z9 15 U1 0 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD JAN PY 2013 VL 15 IS 1 BP 59 EP 68 DI 10.1093/ntr/nts084 PG 10 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 061WM UT WOS:000312880900008 PM 22529220 ER PT J AU Tidey, JW Rohsenow, DJ Kaplan, GB Swift, RM AhnAllen, CG AF Tidey, Jennifer W. Rohsenow, Damaris J. Kaplan, Gary B. Swift, Robert M. AhnAllen, Christopher G. TI Separate and Combined Effects of Very Low Nicotine Cigarettes and Nicotine Replacement in Smokers with Schizophrenia and Controls SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID SMOKING-CESSATION; DENICOTINIZED CIGARETTES; TOBACCO SMOKING; WITHDRAWAL; ABSTINENCE; EXPOSURE; SCALE; REINFORCEMENT; ASSOCIATION; DEPENDENCE AB The prevalence of smoking among people with schizophrenia in the United States is about 3 times that of the general population. Novel approaches are needed to reduce rates of smoking-related morbidity and mortality among these smokers. This study used a within-subjects design to investigate the separate and combined effects of sensorimotor replacement for smoking (very low nicotine content [VLNC] cigarettes vs. no cigarettes) and transdermal nicotine replacement (42 mg nicotine [NIC] vs. placebo [PLA] patches) in smokers with schizophrenia (SS; n = 30) and control smokers without psychiatric illness (CS; n = 26). Each session contained a 5-hr controlled administration period in which participants underwent the following conditions, in counterbalanced order: VLNC + NIC, VLNC + PLA, no cigarettes + NIC, no cigarettes + PLA, usual-brand cigarettes + no patches. Next, participants completed measures of cigarette craving, nicotine withdrawal, smoking habit withdrawal, and cigarette subjective effects, followed by a 90-min period of ad libitum usual-brand smoking. Smoking VLNC cigarettes during the controlled administration periods reduced cigarette craving, nicotine withdrawal symptoms, habit withdrawal symptoms, and usual-brand smoking in SS and CS relative to the no cigarette conditions. VLNC cigarettes were well accepted by both groups and did not affect psychiatric symptom levels in SS. Transdermal nicotine significantly reduced cigarette craving but did not affect usual-brand smoking. These findings suggest that reducing the nicotine content of cigarettes to nonaddictive levels may be a promising approach for reducing nicotine dependence among people with schizophrenia. C1 [Tidey, Jennifer W.; Rohsenow, Damaris J.; Swift, Robert M.] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Rohsenow, Damaris J.; Swift, Robert M.] Providence VA Med Ctr, Providence, RI USA. [Kaplan, Gary B.; AhnAllen, Christopher G.] VA Boston Healthcare Syst, Brockton, MA USA. [Kaplan, Gary B.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [AhnAllen, Christopher G.] Harvard Univ, Sch Med, Boston, MA USA. RP Tidey, JW (reprint author), Brown Univ, Ctr Alcohol & Addict Studies, Box S121-5, Providence, RI 02912 USA. EM jennifer_tidey@brown.edu FU National Institutes of Health [R01DA14002, P50DA031659]; Department of Veterans Affairs FX This work was supported by National Institutes of Health grants R01DA14002 and P50DA031659 (JWT) and a Senior Research Career Scientist Award from the Department of Veterans Affairs (DJR). NR 46 TC 19 Z9 20 U1 2 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD JAN PY 2013 VL 15 IS 1 BP 121 EP 129 DI 10.1093/ntr/nts098 PG 9 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 061WM UT WOS:000312880900016 PM 22517190 ER PT J AU Corliss, HL Wadler, BM Jun, HJ Rosario, M Wypij, D Frazier, AL Austin, SB AF Corliss, Heather L. Wadler, Brianna M. Jun, Hee-Jin Rosario, Margaret Wypij, David Frazier, A. Lindsay Austin, S. Bryn TI Sexual-Orientation Disparities in Cigarette Smoking in a Longitudinal Cohort Study of Adolescents SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID BISEXUAL YOUNG-ADULTS; SUBSTANCE USE; NICOTINE DEPENDENCE; TOBACCO USE; GAY; HEALTH; INITIATION; YOUTHS; RISK; AGE AB Youths with a minority sexual orientation (i.e., gay, lesbian, bisexual, and mostly heterosexual) are at high risk for cigarette smoking. We examined sexual-orientation disparities in smoking during adolescence and emerging adulthood and investigated the role of age at first smoking in contributing to smoking disparities. We used data from the Growing Up Today Study, a large longitudinal cohort of adolescents followed from ages 12 to 24 years (N = 13,913). Self-administered questionnaires filled out annually or biennially assessed age at first smoking, current smoking, frequency of smoking, number of cigarettes smoked daily, and nicotine dependence. Proportional hazards survival analysis and repeated measures regression estimated sexual-orientation differences in smoking. Compared with completely heterosexuals, lesbian/gay, bisexual, and mostly heterosexual youths smoked their first cigarette at younger ages, were more likely to be current smokers, and had higher frequency of smoking. Among past-year smokers, sexual-minority females smoked more cigarettes daily and scored higher on nicotine dependence than completely heterosexual females. In some instances, gender and age modified relationships between sexual orientation and smoking, with relative risk accentuated in female sexual minorities and in sexual minorities during younger ages. Younger age of smoking onset contributed to elevated smoking in mostly heterosexuals and bisexuals, and to a lesser extent in lesbians, but not in gay males. Sexual-orientation minorities are at greater risk for smoking during adolescence and emerging adulthood than heterosexuals. Disparities are larger in females and evident in early adolescence. Prevention and cessation efforts should target this population, preferably beginning in early adolescence. C1 [Corliss, Heather L.; Austin, S. Bryn] Childrens Hosp, Div Adolescent & Young Adult Med, Boston, MA 02115 USA. [Corliss, Heather L.; Wypij, David; Austin, S. Bryn] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Corliss, Heather L.; Jun, Hee-Jin; Frazier, A. Lindsay; Austin, S. Bryn] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Wadler, Brianna M.; Austin, S. Bryn] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Rosario, Margaret] CUNY City Coll, Dept Psychol, New York, NY 10031 USA. [Rosario, Margaret] CUNY, Grad Ctr, New York, NY USA. [Wypij, David] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Wypij, David] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Frazier, A. Lindsay] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Corliss, HL (reprint author), Childrens Hosp, Div Adolescent & Young Adult Med, 300 Longwood Ave, Boston, MA 02115 USA. EM heather.corliss@childrens.harvard.edu FU Robert Wood Johnson Foundation; National Institutes of Health [HD45763, DK46834, HL03533]; American Cancer Society [RSGPB-04-009-01-CPPB]; National Institute on Drug Abuse [DA23610]; Leadership Education in Adolescent Health Project, Maternal and Child Health Bureau, Health Resources and Services Administration [6T71-MC00009] FX The GUTS cohort has been funded by the Robert Wood Johnson Foundation; grants HD45763, DK46834, and HL03533 from the National Institutes of Health; and grant RSGPB-04-009-01-CPPB from the American Cancer Society. Dr. Corliss is supported by career development award DA23610 from the National Institute on Drug Abuse. Drs. Corliss and Austin are also supported by the Leadership Education in Adolescent Health Project, Maternal and Child Health Bureau, Health Resources and Services Administration grant 6T71-MC00009 NR 39 TC 36 Z9 36 U1 2 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD JAN PY 2013 VL 15 IS 1 BP 213 EP 222 DI 10.1093/ntr/nts114 PG 10 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 061WM UT WOS:000312880900027 PM 22581940 ER PT J AU Cheng, G Alavi, A AF Cheng, Gang Alavi, Abass TI Value of F-18-FDG PET versus iliac biopsy in the initial evaluation of bone marrow infiltration in the case of Hodgkin's disease: a meta-analysis SO NUCLEAR MEDICINE COMMUNICATIONS LA English DT Article DE biopsy; bone marrow infiltration; F-18-FDG PET; Hodgkin's disease ID POSITRON-EMISSION-TOMOGRAPHY; B-CELL LYMPHOMA; FDG-PET/CT; MALIGNANT-LYMPHOMA; STANDARD PROCEDURES; CLINICAL UTILITY; INVOLVEMENT; MANAGEMENT; THERAPY; IMPACT AB Objective We carried out a meta-analysis to evaluate the performance of 2-deoxy-2-[F-18]fluoro-D-glucose (F-18-FDG) PET and PET/CT against bone marrow biopsy (BM B) in the initial diagnosis of bone marrow infiltration (BMI) in patients with Hodgkin's disease (HD). Materials and methods Retrospective and prospective studies with direct comparison of F-18-FDG PET with BMB in the initial evaluation of BMI in HD were included. Seven eligible studies were included in the meta-analysis comprising a total of 687 patients. Results Both F-18-FDG PET and BMB had excellent specificity in detecting BMI. However, F-18-FDG PET had excellent pooled sensitivity (94.5%; 95% confidence interval: 89.0-97.8%) in detecting BMI in the initial staging of HD patients, whereas the pooled sensitivity of iliac BMB was very poor (39.4%; 95% confidence interval: 30.8-48.4%). The diagnostic odds ratio, a measure of the overall diagnostic power of the test, was much higher for PET (pooled value of 1591) than for iliac BMB (pooled value of 137). Conclusion F-18-FDG PET significantly outperforms iliac BMB in the detection of BMI in the initial staging of HD patients and therefore should be used as a first-line study. Iliac BMB has low sensitivity and a high rate of false-negative findings. Thus, a negative BMB finding cannot rule out marrow involvement in HD patients on initial staging. Nucl Med Commun 34:25-31 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. Nuclear Medicine Communications 2013, 34:25-31 C1 [Cheng, Gang] Philadelphia VA Med Ctr, Dept Radiol, Philadelphia, PA 19104 USA. [Alavi, Abass] Hosp Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. RP Cheng, G (reprint author), Philadelphia VA Med Ctr, Dept Radiol, 3400 Spruce St, Philadelphia, PA 19104 USA. EM gangcheng99@yahoo.com NR 49 TC 0 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0143-3636 J9 NUCL MED COMMUN JI Nucl. Med. Commun. PD JAN PY 2013 VL 34 IS 1 BP 25 EP 31 DI 10.1097/MNM.0b013e32835afc19 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 056SS UT WOS:000312512300005 PM 23111383 ER PT J AU Yang, WJ Soares, J Greninger, P Edelman, EJ Lightfoot, H Forbes, S Bindal, N Beare, D Smith, JA Thompson, IR Ramaswamy, S Futreal, PA Haber, DA Stratton, MR Benes, C McDermott, U Garnett, MJ AF Yang, Wanjuan Soares, Jorge Greninger, Patricia Edelman, Elena J. Lightfoot, Howard Forbes, Simon Bindal, Nidhi Beare, Dave Smith, James A. Thompson, I. Richard Ramaswamy, Sridhar Futreal, P. Andrew Haber, Daniel A. Stratton, Michael R. Benes, Cyril McDermott, Ultan Garnett, Mathew J. TI Genomics of Drug Sensitivity in Cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells SO NUCLEIC ACIDS RESEARCH LA English DT Article ID IDENTIFICATION AB Alterations in cancer genomes strongly influence clinical responses to treatment and in many instances are potent biomarkers for response to drugs. The Genomics of Drug Sensitivity in Cancer (GDSC) database(www.cancerRxgene.org) is the largest public resource for information on drug sensitivity in cancer cells and molecular markers of drug response. Data are freely available without restriction. GDSC currently contains drug sensitivity data for almost 75 000 experiments, describing response to 138 anticancer drugs across almost 700 cancer cell lines. To identify molecular markers of drug response, cell line drug sensitivity data are integrated with large genomic datasets obtained from the Catalogue of Somatic Mutations in Cancer database, including information on somatic mutations in cancer genes, gene amplification and deletion, tissue type and transcriptional data. Analysis of GDSC data is through a web portal focused on identifying molecular biomarkers of drug sensitivity based on queries of specific anticancer drugs or cancer genes. Graphical representations of the data are used throughout with links to related resources and all datasets are fully downloadable. GDSC provides a unique resource incorporating large drug sensitivity and genomic datasets to facilitate the discovery of new therapeutic biomarkers for cancer therapies. C1 [Yang, Wanjuan; Soares, Jorge; Lightfoot, Howard; Forbes, Simon; Bindal, Nidhi; Beare, Dave; Thompson, I. Richard; Futreal, P. Andrew; Stratton, Michael R.; McDermott, Ultan; Garnett, Mathew J.] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England. [Greninger, Patricia; Edelman, Elena J.; Ramaswamy, Sridhar; Haber, Daniel A.; Benes, Cyril] Harvard Univ, Massachusetts Gen Hosp, Ctr Mol Therapeut, Canc Ctr,Med Sch, Charlestown, MA 02129 USA. [Smith, James A.] Wellcome Trust Sanger Inst, Core Software Serv, Hinxton CB10 1SA, England. [Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Garnett, MJ (reprint author), Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England. EM um1@sanger.ac.uk; mg12@sanger.ac.uk RI Thompson, Ian/J-9900-2016; OI McDermott, Ultan/0000-0001-9032-4700; Smith, James/0000-0002-0445-8305 FU Wellcome Trust [086357]; Royal College of Physicians and Surgeons of Glasgow/Cancer Research UK Clinician Scientist Fellowship FX The Wellcome Trust [086357 to M.R.S., P.A.F., D.A.H.]; Royal College of Physicians and Surgeons of Glasgow/Cancer Research UK Clinician Scientist Fellowship (to U.M.). Funding for open access charge: Wellcome Trust. NR 11 TC 156 Z9 158 U1 2 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2013 VL 41 IS D1 BP D955 EP D961 DI 10.1093/nar/gks1111 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 062BE UT WOS:000312893300135 PM 23180760 ER PT J AU Hamrah, P Cruzat, A Dastjerdi, MH Pruss, H Zheng, LX Shahatit, BM Bayhan, HA Dana, R Pavan-Langston, D AF Hamrah, Pedram Cruzat, Andrea Dastjerdi, Mohammad H. Pruess, Harald Zheng, Lixin Shahatit, Bashar M. Bayhan, Hasan A. Dana, Reza Pavan-Langston, Deborah TI Unilateral Herpes Zoster Ophthalmicus Results in Bilateral Corneal Nerve Alteration An In Vivo Confocal Microscopy Study SO OPHTHALMOLOGY LA English DT Article ID POSTHERPETIC NEURALGIA; SAPHENOUS NERVE; NATURAL-HISTORY; INJURY; INNERVATION; SENSITIVITY; RAT; PAIN; SENSATION; KERATITIS AB Purpose: Herpes zoster ophthalmicus (HZO), thought to be a unilateral disease, results in loss of corneal sensation, leading to neurotrophic keratopathy. This study aimed to analyze bilateral corneal nerve changes in patients with HZO by in vivo confocal microscopy (IVCM) and their correlation with corneal sensation as a measure of nerve function. Design: Prospective, cross-sectional, controlled, single-center study. Participants: Twenty-seven eyes with the diagnosis of HZO and their contralateral clinically unaffected eyes were studied and compared with normal controls (n = 15). Methods: In vivo confocal microscopy (Confoscan 4; Nidek Technologies, Gamagori, Japan) and corneal esthesiometry (Cochet-Bonnet; Luneau Ophthalmologie, Chartres, France) of the central cornea were performed bilaterally in all patients and controls. Patients were grouped into normal (>5.5 cm), mild (>2.5-5.5 cm), and severe (<2.5 cm) loss of sensation. Main Outcome Measures: Changes in corneal nerve density, total nerve number, main nerve trunks, branching, and tortuosity were evaluated after IVCM and were correlated to corneal sensation, disease duration, and number of recurrences. Results: Eyes with herpes zoster ophthalmicus had a significant (P<0.001) decrease in total nerve length (595.8 +/- 358.1 vs. 2258.4 +/- 989.0 mu m/frame), total number of nerves (5.4 +/- 2.8 vs. 13.1 +/- 3.8), number of main nerve trunks (2.3 +/- 1.1 vs. 4.7 +/- 1.2), and number of nerve branches (3.2 +/- 2.3 vs. 8.4 +/- 3.7) as compared with controls. In the contralateral clinically unaffected eyes, total nerve length (1053.1 +/- 441.4 mu m/frame), total number of nerves (8.3 +/- 2.9), and main nerve trunks (3.1 +/- 1.0) also were decreased significantly as compared with controls (P<0.01). Reduced nerve density, total nerve count, main trunks, and tortuosity was correlated significantly with corneal sensation across all subgroups (P<0.001). Conclusions: Patients with unilateral HZO demonstrated a profound and significant bilateral loss of the corneal nerve plexus as compared with controls, demonstrating bilateral changes in a clinically unilateral disease. Loss of corneal sensation strongly correlated with subbasal nerve plexus alterations as shown by IVCM. C1 [Hamrah, Pedram] Harvard Univ, Massachusetts Eye & Ear Infirm, Cornea Serv, Sch Med,Dept Ophthalmol,Ocular Surface Imaging Ct, Boston, MA 02114 USA. [Hamrah, Pedram; Cruzat, Andrea; Dastjerdi, Mohammad H.; Zheng, Lixin; Shahatit, Bashar M.; Bayhan, Hasan A.; Dana, Reza; Pavan-Langston, Deborah] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea & Refract Surg Serv,Dept Ophthalmol, Boston, MA 02114 USA. [Pruess, Harald] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Hamrah, P (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Cornea Serv, Sch Med,Dept Ophthalmol,Ocular Surface Imaging Ct, 243 Charles St, Boston, MA 02114 USA. EM pedram_hamrah@meei.harvard.edu OI Cruzat, Andrea/0000-0002-3724-7037 FU National Institutes of Health, Bethesda, Maryland [K08-EY020575, K12-EY016335, K24-EY019098]; Research to Prevent Blindness, New York, New York; New England Corneal Transplant Research Fund; Dr. Ralph and Marian Falk Medical Research Trust, Chicago, IL; Johnstone Research Fund, Boston, Massachusetts; Stevens Research Fund, Boston, Massachusetts FX Support by the National Institutes of Health, Bethesda, Maryland (grant nos.: K08-EY020575 [PH], K12-EY016335 [P. H.], and K24-EY019098 [R. D.]; a Career Development Award by Research to Prevent Blindness, New York, New York (P. H.); the New England Corneal Transplant Research Fund (P. H.); Dr. Ralph and Marian Falk Medical Research Trust, Chicago, IL (P. H.); the Johnstone Research Fund, Boston, Massachusetts (D. P-L.); and the Stevens Research Fund, Boston, Massachusetts (D. P-L.). The funding organizations had no role in the design or conduct of this research. NR 36 TC 39 Z9 41 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JAN PY 2013 VL 120 IS 1 BP 40 EP 47 DI 10.1016/j.ophtha.2012.07.036 PG 8 WC Ophthalmology SC Ophthalmology GA 063PI UT WOS:000313011700008 PM 22999636 ER PT J AU Miller, JW Le Couter, J Strauss, EC Ferrara, N AF Miller, Joan W. Le Couter, Jennifer Strauss, Erich C. Ferrara, Napoleone TI Vascular Endothelial Growth Factor A in Intraocular Vascular Disease SO OPHTHALMOLOGY LA English DT Article ID RETINAL VEIN OCCLUSION; DIABETIC-RETINOPATHY; MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION; VEGF-A; OCULAR NEOVASCULARIZATION; IRIS NEOVASCULARIZATION; PERMEABILITY FACTOR; NONHUMAN PRIMATE; AQUEOUS-HUMOR AB The vascular beds supplying the retina may sustain injury as a result of underlying disease such as diabetes, and/or the interaction of genetic predisposition, environmental insults, and age. The vascular pathologic features observed in different intraocular vascular diseases can be categorized broadly as proliferation, exemplified by proliferative diabetic retinopathy, leakage such as macular edema secondary to retinal vein occlusion, or a combination of proliferation and leakage, as seen in neovascular age-related macular degeneration (AMD). The World Health Organization has identified diabetic retinopathy and AMD as priority eye diseases for the prevention of vision loss in developed countries. The pathologic transformations of the retinal vasculature seen in intraocular vascular disease are associated with increased expression of vascular endothelial growth factor A (VEGF), a potent endothelial-specific mitogen. Furthermore, in model systems, VEGF alone is sufficient to trigger intraocular neovascularization, and its inhibition is associated with functional and anatomic improvements in the affected eye. Therapeutic interventions with effect on VEGF include intraocular capture and neutralization by engineered antibodies or chimeric receptors, downregulation of its expression with steroids, or alleviation of retinal ischemia, a major stimulus for VEGF expression, with retinal ablation by laser treatment. Data from prospective randomized clinical trials indicate that VEGF inhibition is a potent therapeutic strategy for intraocular vascular disease. These findings are changing clinical practice and are stimuli for further study of the basic mechanisms controlling intraocular angiogenesis. C1 [Miller, Joan W.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Le Couter, Jennifer; Strauss, Erich C.; Ferrara, Napoleone] Genentech Inc, San Francisco, CA 94080 USA. RP Miller, JW (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Joan_Miller@meei.harvard.edu FU Genentech, Inc., South San Francisco, California FX Support for third-party writing and formatting assistance for this manuscript was provided by Ivo Stoilov, MD, CMPP, and was funded by Genentech, Inc., South San Francisco, California. NR 60 TC 114 Z9 119 U1 2 U2 34 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JAN PY 2013 VL 120 IS 1 BP 106 EP 114 DI 10.1016/j.ophtha.2012.07.038 PG 9 WC Ophthalmology SC Ophthalmology GA 063PI UT WOS:000313011700017 PM 23031671 ER PT J AU Gregory, AC Kempen, JH Daniel, E Kacmaz, RO Foster, CS Jabs, DA Levy-Clarke, GA Nussenblatt, RB Rosenbaum, JT Suhler, EB Thorne, JE AF Gregory, Anthony C., II Kempen, John H. Daniel, Ebenezer Kacmaz, R. Oktay Foster, C. Stephen Jabs, Douglas A. Levy-Clarke, Grace A. Nussenblatt, Robert B. Rosenbaum, James T. Suhler, Eric B. Thorne, Jennifer E. CA Systemic Immunosuppressive Therapy TI Risk Factors for Loss of Visual Acuity among Patients with Uveitis Associated with Juvenile Idiopathic Arthritis: The Systemic Immunosuppressive Therapy for Eye Diseases Study SO OPHTHALMOLOGY LA English DT Article ID OCULAR INFLAMMATORY DISEASES; RHEUMATOID-ARTHRITIS; OPHTHALMOLOGIC EXAMINATIONS; PEDIATRIC UVEITIS; COMPLICATIONS; CHILDHOOD; OUTCOMES; PROGNOSTICATORS; EPIDEMIOLOGY; PREVALENCE AB Purpose: To describe the incidence of and risk factors for visual acuity (VA) loss and ocular complications in patients with juvenile idiopathic arthritis (JIA)-associated uveitis. Design: Multicenter retrospective cohort study. Participants: A total of 327 patients (596 affected eyes) with JIA-associated uveitis managed at 5 tertiary uveitis clinics in the United States. Methods: Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) cohort study. Demographic and clinical characteristics were obtained for every eye of every patient at every visit via medical record review by trained expert reviewers. Main Outcome Measures: Loss of VA to 20/50 or to 20/200 or worse thresholds and the development of ocular complications. Results: At presentation, 240 eyes (40.3%) had a VA of <= 20/50, 144 eyes (24.2%) had a VA of <= 20/200, and 359 eyes (60.2%) had at least 1 ocular complication. The incidences of VA loss to the <= 20/50 and <= 20/200 thresholds were 0.18 and 0.09 per eye-year (EY), respectively; the incidence of developing at least 1 new ocular complication over follow-up was 0.15/EY (95% confidence interval [CI], 0.13-0.17). However, among eyes with uveitis that had no complications at presentation, the rate of developing at least 1 ocular complication during follow-up was lower (0.04/EY; 95% CI, 0.02-0.06). Posterior synechiae, active uveitis, and prior intraocular surgery were statistically significantly associated with VA to the <= 20/50 and <= 20/200 thresholds both at presentation and during follow-up. Increasing (time-updated) anterior chamber cell grade was associated with increased rates of visual loss in a dose-dependent fashion. Use of immunosuppressive drugs was associated with a reduced risk of visual loss, particularly for the <= 20/50 outcome (hazard ratio, 0.40; 95% CI, 0.21-0.75; P < 0.01). Conclusions: Ocular complications and vision loss were common in our cohort. Increasing uveitis activity was associated with increased risk of vision loss, and use of immunosuppressive drugs was associated with reduced risk of vision loss, suggesting that control of inflammation and use of immunosuppression may be critical aspects in improving the outcomes of patients with JIA-related uveitis. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2013; 120:186-192 (C) 2013 by the American Academy of Ophthalmology. C1 [Gregory, Anthony C., II; Thorne, Jennifer E.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Dept Ophthalmol, Baltimore, MD 21287 USA. [Kempen, John H.; Daniel, Ebenezer] Univ Penn, Sch Med, Dept Ophthalmol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kempen, John H.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Kacmaz, R. Oktay] Allergan Pharmaceut Inc, Irvine, CA 92715 USA. [Kacmaz, R. Oktay; Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA. [Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Jabs, Douglas A.; Thorne, Jennifer E.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Ctr Clin Trials, Dept Epidemiol, Baltimore, MD 21287 USA. [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA. [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Levy-Clarke, Grace A.; Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD 20892 USA. [Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. RP Thorne, JE (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Dept Ophthalmol, 600 N Wolfe St,Woods Bldg,Room 476, Baltimore, MD 21287 USA. EM jthorne@jhmi.edu OI Daniel, Ebenezer/0000-0002-2027-2316 FU National Eye Institute, National Institutes of Health, Bethesda, Maryland [ey014943]; Paul and Evanina Mackall Foundation, Philadelphia, Pennsylvania; Research to Prevent Blindness Inc, New York, New York; Research to Prevent Blindness; National Eye Institute FX Supported primarily by Grant ey014943 from the National Eye Institute, National Institutes of Health, Bethesda, Maryland (Dr. Kempen). Additional support was provided by the Paul and Evanina Mackall Foundation, Philadelphia, Pennsylvania, and Research to Prevent Blindness Inc, New York, New York. Dr. Kempen is a Research to Prevent Blindness James S. Adams Special Scholar Award recipient. Dr. Thorne is a Research to Prevent Blindness Harrington Special Scholar Award recipient. Drs. Jabs and Rosenbaum are Research to Prevent Blindness Senior Scientific Investigator Award recipients. Dr. Levy-Clarke was previously and Dr. Nussenblatt continues to be supported by intramural funds of the National Eye Institute. NR 39 TC 51 Z9 53 U1 0 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JAN PY 2013 VL 120 IS 1 BP 186 EP 192 DI 10.1016/j.ophtha.2012.07.052 PG 7 WC Ophthalmology SC Ophthalmology GA 063PI UT WOS:000313011700027 PM 23062650 ER PT J AU Ring, D AF Ring, David TI Monteggia Fractures SO ORTHOPEDIC CLINICS OF NORTH AMERICA LA English DT Article DE Monteggia fractures; Proximal ulna; Anterior dislocation; Radial head; Radioulnar; Radiocapitellar ID SURGICAL-TREATMENT; PROXIMAL ULNA; ELBOW; DISLOCATION; INSTABILITY; MANAGEMENT; OLECRANON; FIXATION; ADULTS; RADIUS AB Monteggia described a fracture of the proximal third of the ulna with anterior dislocation of the radial head from both the proximal radioulnar and radiocapitellar joints. Application of this eponym to all injuries with radiocapitellar subluxation or dislocation has led to some confusion. In addition, there are substantial differences between Monteggia injuries in children and adults. With careful definition, specific subsets of patients may benefit from consideration as a separate type of Monteggia injury. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 27 TC 9 Z9 10 U1 0 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 0030-5898 J9 ORTHOP CLIN N AM JI Orthop. Clin. North Am. PD JAN PY 2013 VL 44 IS 1 BP 59 EP + DI 10.1016/j.ocl.2012.08.007 PG 9 WC Orthopedics SC Orthopedics GA 065FY UT WOS:000313135100007 PM 23174326 ER PT J AU Loggia, ML Kim, J Gollub, RL Vangel, MG Kirsch, I Kong, J Wasan, AD Napadow, V AF Loggia, Marco L. Kim, Jieun Gollub, Randy L. Vangel, Mark G. Kirsch, Irving Kong, Jian Wasan, Ajay D. Napadow, Vitaly TI Default mode network connectivity encodes clinical pain: An arterial spin labeling study SO PAIN LA English DT Article DE Resting state networks; Chronic low back pain; Functional magnetic resonance imaging; Psychophysics; Human ID INTRINSIC BRAIN CONNECTIVITY; RESTING-STATE CONNECTIVITY; CEREBRAL-BLOOD-FLOW; CHRONIC BACK-PAIN; FUNCTIONAL CONNECTIVITY; PERFUSION MRI; NEURAL ACTIVITY; PERCEPTION; DISEASE; FMRI AB Neuroimaging studies have suggested the presence of alterations in the anatomo-functional properties of the brain of patients with chronic pain. However, investigation of the brain circuitry supporting the perception of clinical pain presents significant challenges, particularly when using traditional neuroimaging approaches. While potential neuroimaging markers for clinical pain have included resting brain connectivity, these cross-sectional studies have not examined sensitivity to within-subject exacerbation of pain. We used the dual regression probabilistic Independent Component Analysis approach to investigate resting-state connectivity on arterial spin labeling data. Brain connectivity was compared between patients with chronic low back pain (cLBP) and healthy controls, before and after the performance of maneuvers aimed at exacerbating clinical pain levels in the patients. Our analyses identified multiple resting state networks, including the default mode network (DMN). At baseline, patients demonstrated stronger DMN connectivity to the pregenual anterior cingulate cortex (pgACC), left inferior parietal lobule, and right insula (rINS). Patients' baseline clinical pain correlated positively with connectivity strength between the DMN and right insula (DMN-rINS). The performance of calibrated physical maneuvers induced changes in pain, which were paralleled by changes in DMN-rINS connectivity. Maneuvers also disrupted the DMN-pgACC connectivity, which at baseline was anticorrelated with pain. Finally, baseline DMN connectivity predicted maneuver-induced changes in both pain and DMN-rINS connectivity. Our results support the use of arterial spin labeling to evaluate clinical pain, and the use of resting DMN connectivity as a potential neuroimaging biomarker for chronic pain perception. (C) 2012 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved. C1 [Loggia, Marco L.; Kim, Jieun; Gollub, Randy L.; Vangel, Mark G.; Kong, Jian; Napadow, Vitaly] Massachusetts Gen Hosp, MIT, HMS, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Loggia, Marco L.; Wasan, Ajay D.; Napadow, Vitaly] Harvard Univ, Brigham & Womens Hosp, Med Sch HMS, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Loggia, Marco L.; Gollub, Randy L.; Kong, Jian] Massachusetts Gen Hosp, Dept Psychiat, HMS, Boston, MA 02114 USA. [Kirsch, Irving] Beth Israel Deaconess Med Ctr, Program Placebo Studies & Therapeut Encounter, HMS, Boston, MA 02215 USA. [Wasan, Ajay D.] Brigham & Womens Hosp, Dept Psychiat, HMS, Boston, MA 02115 USA. RP Loggia, ML (reprint author), Massachusetts Gen Hosp, MIT, HMS, Athinoula A Martinos Ctr Biomed Imaging, Bldg 75,2132-A, Boston, MA 02129 USA. EM marco@nmr.mgh.harvard.edu OI Gollub, Randy L./0000-0002-9434-4044 FU National Institutes of Health [K23-DA020681, R01-AT004714, P01-AT002048, R01-AT 005280, R01-AT006146, P01-AT006663] FX We would like to thank Bruce Rosen, Randy Buckner, and Karin Jensen for their helpful comments. We also thank Helen Chen and Amanda Cook for their help during the preparation of the manuscript. This study was supported in part by Grants from the National Institutes of Health: K23-DA020681, R01-AT004714, P01-AT002048, R01-AT 005280, R01-AT006146, P01-AT006663. NR 58 TC 59 Z9 62 U1 0 U2 21 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JAN PY 2013 VL 154 IS 1 BP 24 EP 33 DI 10.1016/j.pain.2012.07.029 PG 10 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 061AF UT WOS:000312818800008 PM 23111164 ER PT J AU Hausmann, LRM Gao, SS Lee, ES Kwoh, CK AF Hausmann, Leslie R. M. Gao, Shasha Lee, Edward S. Kwoh, C. Kent TI Racial disparities in the monitoring of patients on chronic opioid therapy SO PAIN LA English DT Article DE Opioid monitoring; Pain management; Race disparities; Veterans ID CLINICAL COMORBIDITY INDEX; RISK REDUCTION STRATEGIES; CHRONIC PAIN; ETHNIC DISPARITIES; PRIMARY-CARE; EMERGENCY-DEPARTMENT; ADMINISTRATIVE DATA; WHITE AMERICANS; UNITED-STATES; HEALTH-CARE AB Despite well-documented racial disparities in prescribing opioid medications for pain, little is known about whether there are disparities in the monitoring and follow-up treatment of patients who are prescribed opioid medications. We conducted a retrospective cohort study to examine whether there are racial differences in the use of recommended opioid monitoring and follow-up treatment practices. Our sample included 1646 white and 253 black patients who filled opioid prescriptions for noncancer pain for >= 90 consecutive days at the Veterans Affairs Pittsburgh Healthcare System pharmacy in fiscal years 2007 and 2008. Several opioid monitoring and follow-up treatment practices were extracted from electronic health records for a 12-month follow-up period. Findings indicated that 26.3% of patients had opioid agreements on file, pain was documented in 71.7% of primary care follow-up visits, urine drug tests were administered to 49.3% of patients, and 21.2% and 4.2% of patients were referred to pain and substance abuse specialists, respectively. Racial differences were observed in several of these practices. In adjusted comparisons, pain was documented less frequently for black patients than for white patients. Among those who had at least 1 urine drug test, black patients were subjected to more tests, especially if they were on higher doses of opioids. Compared with white patients, black patients were less likely to be referred to a pain specialist and more likely to be referred for substance abuse assessment. Addressing disparities in opioid monitoring and follow-up treatment practices may be a previously neglected route to reducing racial disparities in pain management. Published by Elsevier B. V. on behalf of International Association for the Study of Pain. C1 [Hausmann, Leslie R. M.; Gao, Shasha; Lee, Edward S.; Kwoh, C. Kent] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. [Hausmann, Leslie R. M.; Kwoh, C. Kent] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Hausmann, LRM (reprint author), VA Pittsburgh Healthcare Syst, 7180 Highland Dr,151C-H, Pittsburgh, PA 15206 USA. EM leslie.hausmann@gmail.com FU VISN 4 Center for Health Equity Research and Promotion Competitive Pilot Research Program; Veterans Affairs Health Services Research and Development Career Development Program [RCD 06-287] FX This study was funded by the VISN 4 Center for Health Equity Research and Promotion Competitive Pilot Research Program (L. R. M. Hausmann). Dr. Hausmann's effort on the project was supported by the Veterans Affairs Health Services Research and Development Career Development Program (RCD 06-287). The views expressed here are those of the authors and do not represent those of the Department of Veterans Affairs or the United States Government. NR 38 TC 18 Z9 18 U1 4 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JAN PY 2013 VL 154 IS 1 BP 46 EP 52 DI 10.1016/j.pain.2012.07.034 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 061AF UT WOS:000312818800010 PM 23273103 ER PT J AU Puli, SR Bechtold, ML Buxbaum, JL Eloubeidi, MA AF Puli, Srinivas R. Bechtold, Matthew L. Buxbaum, James L. Eloubeidi, Mohamad A. TI How Good Is Endoscopic Ultrasound-Guided Fine-Needle Aspiration in Diagnosing the Correct Etiology for a Solid Pancreatic Mass? A Meta-Analysis and Systematic Review SO PANCREAS LA English DT Review DE meta-analysis; endoscopic ultrasound; systematic review; pancreatic mass ID TRUCUT NEEDLE; MULTICENTER EXPERIENCE; CLINICAL UTILITY; EUS; BIOPSY; FNA; CANCER; LESIONS; ACCURACY; METAANALYSIS AB Objectives: The objective of this study was to evaluate the accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in diagnosing the correct etiology for a solid pancreatic mass. Method: Data extracted from EUS-FNA studies with a criterion standard (either confirmed by surgery or appropriate follow-up) were selected. Articles were searched in MEDLINE, CINAHL, and Cochrane Central Register of Controlled Trials & Database of Systematic Reviews. Pooling was conducted by both fixed- and random-effects models. Results: Initial search identified 3610 reference articles, of these 360 relevant articles were selected and reviewed. Data were extracted from 41 studies (N = 4766) which met the inclusion criteria. Pooled sensitivity of EUS-FNA in diagnosing the correct etiology for solid pancreatic mass was 86.8% (95% confidence interval [CI], 85.5-87.9). Endoscopic ultrasound-guided FNA had a pooled specificity of 95.8% (95% CI, 94.6-96.7). Positive likelihood ratio of EUS was 15.2 (95% CI, 8.5-27.3), and the negative likelihood ratio was 0.17 (95% CI, 0.13-0.21). Conclusions: Endoscopic ultrasound-guided FNA is an excellent diagnostic tool to detect the correct etiology for solid pancreatic masses. When available, EUS-FNA should be strongly considered as the first diagnostic tool for sampling these lesions to optimize patient management. C1 [Puli, Srinivas R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol & Hepatol, Boston, MA USA. [Puli, Srinivas R.] Harvard Univ, Brigham Womens Hosp, Sch Med, Boston, MA USA. [Bechtold, Matthew L.] Univ Missouri Columbia, Div Gastroenterol & Hepatol, Columbia, MO USA. [Buxbaum, James L.] Univ So Calif, Keck Sch Med, Div Gastroenterol & Hepatol, Los Angeles, CA 90033 USA. [Eloubeidi, Mohamad A.] Univ Alabama Birmingham, Dept Med, Div Gastroenterol & Hepatol, Birmingham, AL 35294 USA. [Eloubeidi, Mohamad A.] Univ Alabama Birmingham, Pancreaticobiliary Ctr, Birmingham, AL USA. EM srinivaspuli@yahoo.com NR 57 TC 69 Z9 72 U1 1 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD JAN PY 2013 VL 42 IS 1 BP 20 EP 26 DI 10.1097/MPA.0b013e3182546e79 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 057JU UT WOS:000312560200004 PM 23254913 ER PT J AU Sheldon, LK Kazmi, M Klein, C Berry, DL AF Sheldon, Lisa Kennedy Kazmi, Maryum Klein, Cynthia Berry, Donna L. TI Concerns of stem cell transplant patients during routine ambulatory assessment SO PATIENT PREFERENCE AND ADHERENCE LA English DT Article DE self-report; electronic self-report assessment - cancer; cancer; patient concerns ID QUALITY-OF-LIFE; LONG-TERM SURVIVORS; BONE-MARROW; CANCER CARE; PHYSICIAN COMMUNICATION; PSYCHOLOGICAL DISTRESS; LATE MORTALITY; POCKET COSTS; BARRIERS AB Background: Stem cell transplant (SCT) is a treatment choice for many hematological malignancies. There is currently a lack of evidence regarding the self-reported concerns of SCT patients before and after SCT. Aim and design: This exploratory study performed a secondary analysis of self-reported, written concerns of SCT patients before and after transplant to determine patients' concerns. Methods: Content analysis of text box entries of SCT patients collected between 2005 and 2007 at the Seattle Cancer Care Alliance. Text box entries were collected as part of symptom assessment using the Electronic Self-Report Assessment - Cancer instrument. The assessment was presented to 137 patients undergoing SCT at two time points: prior to ambulatory visits before any therapy had begun (T1) and at the first visit after hospital discharge following SCT (T2). Results: Text box entries were made before (n = 52) and after (n = 87) the transplant, resulting in 139 text box entries made by 137 patients representing 133 concerns. Using content analysis, the entries were categorized and ranked according to frequency. After symptom concerns, patients ranked work and financial issues the most frequent concerns prior to SCT. After SCT, symptoms remained the most frequently entered area of concern, followed by survival. Conclusion: Oncology providers need to assess SCT patients for work and financial concerns before and after transplant. Appropriate and timely referrals may ease the burden of these concerns for patients. Thus, assessment of financial and work concerns by the oncology team should be an integral part of quality health care for patients undergoing SCT. C1 [Sheldon, Lisa Kennedy; Kazmi, Maryum] Univ Massachusetts, Boston, MA 02125 USA. [Klein, Cynthia] Seattle Canc Care Alliance, Seattle, WA USA. [Berry, Donna L.] Dana Farber Canc Inst, Phyllis Cantor Ctr Res Nursing & Patient Care Ser, Boston, MA 02115 USA. RP Sheldon, LK (reprint author), Univ Massachusetts, 100 Morrissey Blvd, Boston, MA 02125 USA. EM lisa.kennedysheldon@umb.edu NR 34 TC 1 Z9 1 U1 0 U2 6 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1177-889X J9 PATIENT PREFER ADHER JI Patient Prefer. Adherence PY 2013 VL 7 BP 15 EP 20 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 065SU UT WOS:000313170200002 PM 23319854 ER PT J AU Collett, BR Gray, KE Starr, JR Heike, CL Cunningham, ML Speltz, ML AF Collett, Brent R. Gray, Kristen E. Starr, Jacqueline R. Heike, Carrie L. Cunningham, Michael L. Speltz, Matthew L. TI Development at Age 36 Months in Children With Deformational Plagiocephaly SO PEDIATRICS LA English DT Article DE plagiocephaly; developmental assessment; preschool age; Back to Sleep ID HEAD SHAPE; INFANTS; NEURODEVELOPMENT; INCREASE AB OBJECTIVES: Infants and toddlers with deformational plagiocephaly (DP) have been shown to score lower on developmental measures than unaffected children. To determine whether these differences persist, we examined development in 36-month-old children with and without a history of DP. METHODS: Participants included 224 children with DP and 231 children without diagnosed DP, all of who had been followed in a longitudinal study since infancy. To confirm the presence or absence of DP, pediatricians blinded to children's case status rated 3-dimensional cranial images taken when children were 7 months old on average. The Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) was administered as a measure of child development. RESULTS: Children with DP scored lower on all scales of the BSID-III than children without DP. Differences were largest in cognition, language, and parent-reported adaptive behavior (adjusted differences = -2.9 to -4.4 standard score points) and smallest in motor development (adjusted difference = -2.7). Children in the control group who did not have previously diagnosed DP but who were later rated by pediatricians to have at least mild cranial deformation also scored lower on the BSID-III than unaffected controls. CONCLUSIONS: Preschool-aged children with a history of DP continue to receive lower developmental scores than unaffected controls. These findings do not imply that DP causes developmental problems, but DP may nonetheless serve as a marker of developmental risk. We encourage clinicians to screen children with DP for developmental concerns to facilitate early identification and intervention. Pediatrics 2013;131:e109-e115 C1 [Collett, Brent R.; Speltz, Matthew L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Gray, Kristen E.; Starr, Jacqueline R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Heike, Carrie L.; Cunningham, Michael L.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Collett, Brent R.; Speltz, Matthew L.] Seattle Childrens Hosp, Dept Psychiat & Behav Med, Seattle, WA USA. [Heike, Carrie L.; Cunningham, Michael L.] Seattle Childrens Hosp, Seattle Childrens Craniofacial Ctr, Seattle, WA USA. [Starr, Jacqueline R.] Forsyth Inst, Dept Clin & Translat Res, Cambridge, MA USA. [Starr, Jacqueline R.] Harvard Univ, Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, Boston, MA 02115 USA. RP Collett, BR (reprint author), Seattle Childrens Res Inst, 2001 8th Ave,Suite 600,Mailstop CW8-6, Seattle, WA 98121 USA. EM bcollett@u.washington.edu OI Starr, Jacqueline/0000-0002-3039-2311 FU National Institute of Child Health and Human Development (NICHHD) [1 R01 HD046565]; National Center for Research Resources (NCRR), components of the National Institutes of Health (NIH) [1 UL1 RR025014]; National Institutes of Health (NIH) FX This publication was made possible in part by grant 1 R01 HD046565 from the National Institute of Child Health and Human Development (NICHHD) to Dr Speltz and grant 1 UL1 RR025014 from the National Center for Research Resources (NCRR), components of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NICHHD, NCRR, or NIH. Funded by the National Institutes of Health (NIH). NR 19 TC 20 Z9 20 U1 1 U2 13 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2013 VL 131 IS 1 BP E109 EP E115 DI 10.1542/peds.2012-1779 PG 7 WC Pediatrics SC Pediatrics GA 063PO UT WOS:000313012400014 PM 23266929 ER PT J AU St Denis, TG Dai, TH Hamblin, MR AF St Denis, Tyler G. Dai, Tianhong Hamblin, Michael R. TI Killing Bacterial Spores with Blue Light: When Innate Resistance Meets the Power of Light SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID ANTIMICROBIAL PHOTODYNAMIC THERAPY; BACILLUS-ANTHRACIS SPORES; VISIBLE-LIGHT; HELICOBACTER-PYLORI; PROPIONIBACTERIUM-ACNES; GRUINARD ISLAND; HIGH-INTENSITY; INACTIVATION; THURINGIENSIS; PHOTOTHERAPY AB This article is a highlight of the study by Maclean et al. in this issue of Photochemistry and Photobiology describing the sporicidal effects 405 nm visible light alone on endospores of the Clostridium and Bacillus genera. 1.73 kJ cm(-2) was capable of reducing endospore colony-forming units by up to 4-log(10). These findings have never been previously demonstrated and may be incorporated into decontamination methods that span medical, military and food preparatory applications. C1 [St Denis, Tyler G.; Dai, Tianhong; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [St Denis, Tyler G.] Columbia Univ, Dept Chem, New York, NY 10027 USA. [Dai, Tianhong; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [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 OI Hamblin, Michael/0000-0001-6431-4605 FU Columbia University I. I. Rabi Science Research Fellowship; Airlift Research Foundation Extremity Trauma Research grant [109421]; Orthopaedic Trauma Association Basic Research grant [16]; NIH [RO1AI050875] FX T. G. St Denis was supported by the Columbia University I. I. Rabi Science Research Fellowship. T. Dai was supported by an Airlift Research Foundation Extremity Trauma Research grant #109421, and an Orthopaedic Trauma Association Basic Research grant 2012 #16. M. R. Hamblin was supported by NIH grant RO1AI050875. NR 40 TC 2 Z9 2 U1 0 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0031-8655 EI 1751-1097 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JAN-FEB PY 2013 VL 89 IS 1 BP 2 EP 4 DI 10.1111/j.1751-1097.2012.01233.x PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 063IP UT WOS:000312990200002 PM 22946878 ER PT J AU Lev, MH AF Lev, Michael H. TI Perfusion Imaging of Acute Stroke: Its Role in Current and Future Clinical Practice SO RADIOLOGY LA English DT Article ID ACUTE ISCHEMIC-STROKE; ANEURYSMAL SUBARACHNOID HEMORRHAGE; COMPUTED-TOMOGRAPHY PERFUSION; ADMISSION CT PERFUSION; CEREBRAL-BLOOD-FLOW; UNKNOWN ONSET TIME; SYMPTOM ONSET; INFARCT CORE; INTRAVENOUS THROMBOLYSIS; COST-EFFECTIVENESS C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Lev, MH (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 60 TC 16 Z9 17 U1 0 U2 6 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2013 VL 266 IS 1 BP 22 EP 27 DI 10.1148/radiol.12121355 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 061JQ UT WOS:000312844700007 PM 23264524 ER PT J AU Sahani, DV Bonaffini, PA Fernandez-Del Castillo, C Blake, MA AF Sahani, Dushyant V. Bonaffini, Pietro A. Fernandez-Del Castillo, Carlos Blake, Michael A. TI Gastroenteropancreatic Neuroendocrine Tumors: Role of Imaging in Diagnosis and Management SO RADIOLOGY LA English DT Review ID SOMATOSTATIN RECEPTOR SCINTIGRAPHY; PANCREATIC ENDOCRINE TUMORS; POSITRON-EMISSION-TOMOGRAPHY; SMALL-BOWEL NEOPLASMS; CARCINOID-TUMORS; ENDOSCOPIC ULTRASONOGRAPHY; FOLLOW-UP; PREOPERATIVE LOCALIZATION; GASTROINTESTINAL-TRACT; CONSENSUS GUIDELINES AB Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of neoplasms that arise from cells of the diffuse neuroendocrine system and are characterized by a wide spectrum of clinical manifestations. All NETs are potentially malignant but differ in their biologic characteristics and the probability of metastatic disease. The pathologic classification of these tumors relies on their proliferation and differentiation. In the past decades, several nomenclatures have been proposed to stratify neuroendocrine tumors, but the World Health Organization classification is the one that is most widely accepted and used. The diagnosis of neuroendocrine tumor relies on clinical manifestation, laboratory parameters, imaging features, and tissue biomarkers in a biopsy specimen. With improved understanding of the natural history and lesion biology, management of GEP-NETs has also evolved. Although surgery remains the only potentially curative therapy for patients with primary GEP-NETs, other available treatments include chemotherapy, interferon, somatostatin analogs, and targeted therapies. Recent improvements in both morphologic and functional imaging methods have contributed immensely to patient care. Morphologic imaging with contrast agent-enhanced multidetector computed tomography and magnetic resonance imaging is most widely used for initial evaluation and staging of disease in these patients, whereas functional imaging techniques are useful both for detection and prognostic evaluation and can change treatment planning. (C) RSNA, 2013 C1 [Sahani, Dushyant V.; Blake, Michael A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal Imaging & Intervent Rad, Boston, MA 02114 USA. [Fernandez-Del Castillo, Carlos] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Bonaffini, Pietro A.] Univ Milano Bicocca, Sch Med, San Gerardo Hosp, Dept Diagnost Radiol, Monza, Italy. RP Sahani, DV (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal Imaging & Intervent Rad, 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 FU GE Healthcare FX D.V.S. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: institution has grants or grants pending from GE Healthcare; author receives royalties from Elsevier. Other relationships: none to disclose. P. A. B. No relevant conflicts of interest to disclose. C. F. No relevant conflicts of interest to disclose. M. A. B. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: receives royalties from Springer. Other relationships: none to disclose. NR 150 TC 25 Z9 27 U1 0 U2 11 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2013 VL 266 IS 1 BP 38 EP 61 DI 10.1148/radiol.12112512 PG 24 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 061JQ UT WOS:000312844700009 PM 23264526 ER PT J AU Rafferty, EA Park, JM Philpotts, LE Poplack, SP Sumkin, JH Halpern, EF Niklason, LT AF Rafferty, Elizabeth A. Park, Jeong Mi Philpotts, Liane E. Poplack, Steven P. Sumkin, Jules H. Halpern, Elkan F. Niklason, Loren T. TI Assessing Radiologist Performance Using Combined Digital Mammography and Breast Tomosynthesis Compared with Digital Mammography Alone: Results of a Multicenter, Multireader Trial SO RADIOLOGY LA English DT Article ID SCREENING MAMMOGRAPHY; CANCER MORTALITY; CLASSIFICATION; RECOMMENDATION; POPULATION AB Purpose: To compare radiologists' diagnostic accuracy and recall rates for breast tomosynthesis combined with digital mammography versus digital mammography alone. Materials and Methods: Institutional review board approval was obtained at each accruing institution. Participating women gave written informed consent. Mediolateral oblique and craniocaudal digital mammographic and tomosynthesis images of both breasts were obtained from 1192 subjects. Two enriched reader studies were performed to compare digital mammography with tomosynthesis against digital mammography alone. Study 1 comprised 312 cases (48 cancer cases) with images read by 12 radiologists; study 2, 312 cases (51 cancer cases) with 15 radiologists. Study 1 readers recorded only that an abnormality requiring recall was present; study 2 readers had additional training and recorded both lesion type and location. Diagnostic accuracy was compared with receiver operating characteristic analysis. Recall rates of noncancer cases, sensitivity, specificity, and positive and negative predictive values determined by analyzing Breast Imaging Reporting and Data System scores were compared for the two methods. Results: Diagnostic accuracy for combined tomosynthesis and digital mammography was superior to that of digital mammography alone. Average difference in area under the curve in study 1 was 7.2% (95% confidence interval [CI]: 3.7%, 10.8%; P < .001) and in study 2 was 6.8% (95% CI: 4.1%, 9.5%; P < .001). All 27 radiologists increased diagnostic accuracy with addition of tomosynthesis. Recall rates for noncancer cases for all readers significantly decreased with addition of tomosynthesis (range, 6%-67%; P < .001 for 25 readers, P < .03 for all readers). Increased sensitivity was largest for invasive cancers: 15% and 22% in studies 1 and 2 versus 3% for in situ cancers in both studies. Conclusion: Addition of tomosynthesis to digital mammography offers the dual benefit of significantly increased diagnostic accuracy and significantly reduced recall rates for noncancer cases. (C) RSNA, 2012 C1 [Rafferty, Elizabeth A.; Halpern, Elkan F.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Park, Jeong Mi] Univ Iowa Hosp, Dept Radiol, Iowa City, IA USA. [Philpotts, Liane E.] Yale Univ, Sch Med, Dept Radiol, Yale New Haven Hosp, New Haven, CT 06510 USA. [Poplack, Steven P.] Dartmouth Hitchcock Med Ctr, Dept Radiol, Lebanon, NH 03766 USA. [Sumkin, Jules H.] Magee Womens Hosp, Dept Radiol, Pittsburgh, PA USA. [Niklason, Loren T.] Hologic, Bedford, MA USA. RP Rafferty, EA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM erafferty@partners.org FU NIH; Komen FX E.A.R. No relevant conflict of interest to disclose. J.M.P. No relevant conflict of interest to disclose. L. E. P. No relevant conflict of interest to disclose. S. P. P. No relevant conflict of interest to disclose. J.H.S. Financial activities related to the present article: grants to institution from NIH and Komen. Financial activities not related to the present article: consultancy for Guidepoint Global, Morgan Stanley, MEDACorp; expert testimony in malpractice cases, Steven J. Forrey, Stege & Michelson Co., L. P. A., Moscarino & Treu LLP; payment for lectures including service on speakers bureaus, Educational Symposia (review course), Postgraduate Institute for Medicne (webinar), Innova Health System (breast seminar), and University of Florida (visiting professor); travel/accommodations/meeting expenses, Suros (scientific advisory board). Other relationships: none to disclose. E. F. H. Financial activities related to the present article: consultant and statistician for Hologic. Financial activities not related to the present article: expert testimony for Ameritox. Other relationships: none to disclose. L.T.N. Financial activities related to the present article: employee of Hologic. Financial activities not related to the present article: patent on breast tomosyntheses issued by Massachusetts General Hospital; stock in Hologic. Other relationships: none to disclose. NR 22 TC 141 Z9 145 U1 1 U2 32 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2013 VL 266 IS 1 BP 104 EP 113 DI 10.1148/radiol.12120674 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 061JQ UT WOS:000312844700015 PM 23169790 ER PT J AU Stewart, RC Bansal, PN Entezari, V Lusic, H Nazarian, RM Snyder, BD Grinstaff, MW AF Stewart, Rachel C. Bansal, Prashant N. Entezari, Vahid Lusic, Hrvoje Nazarian, Rosalynn M. Snyder, Brian D. Grinstaff, Mark W. TI Contrast-enhanced CT with a High-Affinity Cationic Contrast Agent for Imaging ex Vivo Bovine, Intact ex Vivo Rabbit, and in Vivo Rabbit Cartilage SO RADIOLOGY LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; ARTICULAR-CARTILAGE; COMPUTED-TOMOGRAPHY; EXTRACELLULAR-MATRIX; MU-CT; OSTEOARTHRITIS; MORPHOLOGY; KNEE; PROTEOGLYCAN; DEGRADATION AB Purpose: To quantify the affinity of a cationic computed tomography (CT) contrast agent (CA(4+)) and that of an anionic contrast agent (ioxaglate) to glycosaminoglycans (GAGs) in ex vivo cartilage tissue explants and to characterize the in vivo diffusion kinetics of CA(4+) and ioxaglate in a rabbit model. Materials and Methods: All in vivo procedures were approved by the institutional animal care and use committee. The affinities of ioxaglate and CA(4+) to GAGs in cartilage (six bovine osteochondral plugs) were quantified by means of a modified binding assay using micro-CT after plug equilibration in serial dilutions of each agent. The contrast agents were administered intraarticularly to the knee joints of five New Zealand white rabbits to determine the in vivo diffusion kinetics and cartilage tissue imaging capabilities. Kinetics of diffusion into the femoral groove cartilage and relative contrast agent uptake into bovine plugs were characterized by means of nonlinear mixed-effects models. Diffusion time constants (tau) were compared by using a Student t test. Results: The uptake of CA(4+) in cartilage was consistently over 100% of the reservoir concentration, whereas it was only 59% for ioxaglate. In vivo, the contrast material-enhanced cartilage reached a steady CT attenuation for both CA(4+) and ioxaglate, with t values of 13.8 and 6.5 minutes, respectively (P = .04). The cartilage was easily distinguishable from the surrounding tissues for CA(4+) (12 mg of iodine per milliliter); comparatively, the anionic contrast agent provided less favorable imaging results, even when a higher concentration was used (80 mg of iodine per milliliter). Conclusion: The affinity of the cationic contrast agent CA(4+) to GAGs enables high-quality imaging and segmentation of ex vivo bovine and rabbit cartilage, as well as in vivo rabbit cartilage. (C) RSNA, 2012 C1 [Stewart, Rachel C.; Bansal, Prashant N.; Lusic, Hrvoje; Grinstaff, Mark W.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Stewart, Rachel C.; Bansal, Prashant N.; Lusic, Hrvoje; Grinstaff, Mark W.] Boston Univ, Dept Chem, Boston, MA 02215 USA. [Entezari, Vahid; Snyder, Brian D.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Adv Orthoped Studies, Boston, MA 02215 USA. [Nazarian, Rosalynn M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pathol Serv, Boston, MA 02215 USA. RP Grinstaff, MW (reprint author), Boston Univ, Dept Biomed Engn, 590 Commonwealth Ave, Boston, MA 02215 USA. EM mgrin@bu.edu RI Entezari , Vahid/B-5459-2013; OI Nazarian, Rosalynn/0000-0003-4003-7193; Grinstaff, Mark/0000-0002-5453-3668 FU Coulter Foundation; Boston University; Henry Luce Foundation; National Institutes of Health [R01GM098361] FX Supported by the Coulter Foundation and Boston University. R.C.S. supported by the Henry Luce Foundation.; This research was supported by the National Institutes of Health (grant R01GM098361). NR 44 TC 15 Z9 16 U1 2 U2 19 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2013 VL 266 IS 1 BP 141 EP 150 DI 10.1148/radiol.12112246 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 061JQ UT WOS:000312844700019 PM 23192774 ER PT J AU Cheng, EM Bravata, DM El-Saden, S Vassar, SD Ofner, S Williams, LS Keyhani, S AF Cheng, Eric M. Bravata, Dawn M. El-Saden, Suzie Vassar, Stefanie D. Ofner, Susan Williams, Linda S. Keyhani, Salomeh TI Carotid Artery Stenosis: Wide Variability in Reporting Formats-A Review of 127 Veterans Affairs Medical Centers SO RADIOLOGY LA English DT Article ID VELOCITY CRITERIA; ENDARTERECTOMY; ANGIOGRAPHY; DIAGNOSIS; US AB Purpose: To determine whether radiology reports describe clinically significant carotid arterial stenosis in a consistent format that is actionable by ordering clinicians. Materials and Methods: This study was HIPAA compliant. Informed consent was waived. Institutional review board approval was obtained for this retrospective chart review, which included radiology reports of carotid artery imaging for patients hospitalized with ischemic stroke at 127 Veterans Affairs medical centers in 2006-2007. "Clinically significant results" were defined as results with at least 50% stenosis or at least moderate stenosis, excluding complete occlusion. How often clinically significant results were reported as an exact percentage stenosis (such as 60%), range (such as 50%-69%), or category (such as moderate) was determined. Among results reported as a range, how often the range bracketed clinical thresholds of 50% and 70% (typically used to determine appropriateness of carotid arterial revascularization) was determined. Results: Among 2675 patients, there were 6618 carotid imaging results, of which 1015 (15%) were considered clinically significant. Among 695 clinically significant results at ultrasonography (US), 348 (50%) were described as a range, and another 314 (45%) were reported as an exact percentage stenosis. Among the 348 clinically significant US results reported as a range, 259 (74%) bracketed the thresholds of 50% or 70%. For magnetic resonance angiographic results, 48% (106 of 221) qualitatively described clinically significant results as a category, 38% (84 of 221) as an exact percentage stenosis, and 14% (31 of 221) as a range. Conclusion: In this national health care system, the manner in which clinically significant carotid arterial stenosis was reported varied widely. (C)RSNA, 2012 C1 [Cheng, Eric M.; Vassar, Stefanie D.] VA Greater Los Angeles Healthcare Syst, Dept Neurol, Los Angeles, CA 90073 USA. [El-Saden, Suzie] VA Greater Los Angeles Healthcare Syst, Dept Radiol, Los Angeles, CA 90073 USA. [Cheng, Eric M.; Vassar, Stefanie D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Bravata, Dawn M.] Richard L Roudebush VA Med Ctr, HSR&D Ctr Implementing Evidence Based Practice, Indianapolis, IN USA. [Williams, Linda S.] Richard L Roudebush VA Med Ctr, Dept Neurol, Indianapolis, IN USA. [Bravata, Dawn M.] Indiana Univ Sch Med, Dept Internal Med, Indianapolis, IN USA. [Ofner, Susan] Indiana Univ Sch Med, Dept Biostat, Indianapolis, IN USA. [Williams, Linda S.] Indiana Univ Sch Med, Dept Neurol, Indianapolis, IN USA. RP Cheng, EM (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Neurol, 11301 Wilshire Blvd,ML 127, Los Angeles, CA 90073 USA. EM eric.cheng@va.gov FU Veterans Administration [RRP 09-184, RRP 09-185]; VHA HSR&D Center of Excellence on Implementing Evidence-Based Practice, Richard L. Roudebush VA Medical Center, Indianapolis, Indiana; VHA HSR&D Stroke Quality Enhancement Research Initiative Program, Indianapolis, Indiana; University of California, Los Angeles, Outcomes Research Center; American Heart Association Pharmaceutical Roundtable; Career Development Award from the VA; Research and Development, VA Medical Center, Indianapolis, Indiana FX From the Departments of Neurology (E. M. C., S. D. V.) and Radiology (S. E.), VA Greater Los Angeles Healthcare System, 11301 Wilshire Blvd, ML 127, Los Angeles, CA 90073; Department of Neurology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, Calif (E. M. C., S. D. V.); HSR&D Center for Implementing Evidence Based Practice (D. M. B.) and Department of Neurology (L. S. W.), Richard L. Roudebush VA Medical Center, Indianapolis, Ind; Departments of Internal Medicine (D. M. B.), Biostatistics (S.O.), and Neurology (L. S. W.), Indiana University School of Medicine, Indianapolis, Ind; The Research Enhancement Award Program, San Francisco VA Medical Center, San Francisco, Calif (S. K.); and Department of Medicine, Division of General Internal Medicine, University of California-San Francisco, San Francisco, Calif (S. K.). Received March 7, 2012; revision requested April 9; revision received May 31; accepted June 15; final version accepted July 24. Supported by Veterans Administration RRP 09-184 (primary investigator, D. M. B.) and RRP 09-185 (primary investigator, S. K.); the VHA HSR&D Center of Excellence on Implementing Evidence-Based Practice, Richard L. Roudebush VA Medical Center, Indianapolis, Indiana; and the VHA HSR&D Stroke Quality Enhancement Research Initiative Program, Indianapolis, Indiana. E. M. C. supported by the University of California, Los Angeles, Outcomes Research Center, funded through the American Heart Association Pharmaceutical Roundtable and David and Stevie Spina. S. K. supported by a Career Development Award from the VA. Address correspondence to E. M. C. (e-mail: eric.cheng@va.gov).; E. M. C. No relevant conflicts of interest to disclose. D. M. B. No relevant conflicts of interest to disclose. S. E. No relevant conflicts of interest to disclose. S. D. V. No relevant conflicts of interest to disclose. S.O. Financial activities related to the present article: institution receives fees for participation in review activities and payment for writing or reviewing manuscript from Research and Development, VA Medical Center, Indianapolis, Indiana. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. L. S. W. No relevant conflicts of interest to disclose. S. K. No relevant conflicts of interest to disclose. NR 21 TC 2 Z9 2 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2013 VL 266 IS 1 BP 289 EP 294 DI 10.1148/radiol.12120453 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 061JQ UT WOS:000312844700035 PM 23143022 ER PT J AU Pomerantz, SR Kamalian, S Zhang, D Gupta, R Rapalino, O Sahani, DV Lev, MH AF Pomerantz, Stuart R. Kamalian, Shervin Zhang, Da Gupta, Rajiv Rapalino, Otto Sahani, Dushyant V. Lev, Michael H. TI Virtual Monochromatic Reconstruction of Dual-Energy Unenhanced Head CT at 65-75 keV Maximizes Image Quality Compared with Conventional Polychromatic CT SO RADIOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY; ARTIFACTS; NOISE; REDUCTION; SYSTEM AB Purpose: To determine the virtual monochromatic imaging (VMI) energy levels that maximize brain parenchymal image quality in dual-energy unenhanced head computed tomography (CT) and to assess the improvement with this technique compared with conventional polychromatic scanning. Materials and Methods: Institutional review board approval was obtained with no informed consent required for this HIPAA-compliant retrospective analysis. Twenty-five consecutive unenhanced head CT scans were acquired with a 64-section dual-energy scanner with fast tube voltage switching (80-140 kVp). Scans were retrospectively reconstructed at VMI energy levels from 40 to 140 keV in 5-keV increments and were analyzed by using four quality indexes: gray matter (GM) signal-to-noise ratio (SNR), white matter (WM) SNR, GM-WM contrast-to-noise ratio (CNR), and posterior fossa artifact index (PFAI). Optimal mean values for each parameter were compared with those from 50 consecutive scans obtained with the same scanner in 120-kVp single-energy mode. Repeated-measures analysis of variance and Dunnett post hoc t test were then used to determine significance. Results: Maximal GM SNR, WM SNR, and GM-WM CNR values were observed at 65 keV, and minimal PFAI was observed at 75 keV. These values were significantly better than those of conventional polychromatic CT (P < .01); quality index improvement ratios (corrected for radiation dose) ranged from 17% to 50%. Conclusion: Virtual monochromatic reconstruction of dual-energy unenhanced head CT scans at 65-75 keV (optimal energy levels) maximizes image quality compared with scans obtained with conventional polychromatic CT. (C)RSNA, 2012 C1 [Pomerantz, Stuart R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Pomerantz, SR (reprint author), Massachusetts Gen Hosp, Dept Radiol, GRB 273A,55 Fruit St, Boston, MA 02114 USA. EM spomerantz@partners.org RI Kamalian, Shervin/D-7667-2013 OI Kamalian, Shervin/0000-0001-8962-4773 FU abdomen CT protocol optimization from GE Healthcare; textbook of abdomen imaging from Elsevier Publishing; Advanced image analysis work-station (AW), from GE Healthcare FX S.R.P. Financial activities related to the present article: institution received research fellow salary support and an image analysis workstation with relevant software for the defined duration of the study from GE Healthcare. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. S. K. Financial activities related to the present article: institution received equipment, Advanced image analysis workstation (AW), from GE Healthcare. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. D.Z. No relevant conflicts of interest to disclose. R. G. No relevant conflicts of interest to disclose. O.R. No relevant conflicts of interest to disclose. D. V. S. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: institution received grant for abdomen CT protocol optimization from GE Healthcare and author received royalties for textbook of abdomen imaging from Elsevier Publishing. Other relationships: none to disclose. M. H. L. Financial activities related to the present article: institution received salary support for research assistant and equipment, Advanced image analysis work-station (AW), from GE Healthcare. Financial activities not related to the present article: received stock or stock options for common stock ownership less than $10K from GE Healthcare. Other relationships: none to disclose. NR 19 TC 16 Z9 20 U1 0 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2013 VL 266 IS 1 BP 318 EP 325 DI 10.1148/radiol.12111604 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 061JQ UT WOS:000312844700038 PM 23074259 ER PT J AU Schlett, CL Nance, JW Schoepf, UJ Bamberg, F AF Schlett, Christopher L. Nance, John W., Jr. Schoepf, U. Joseph Bamberg, Fabian TI Incremental Prognostic Value of Cardiac CT Angiography in Patients with Acute Chest Pain Response SO RADIOLOGY LA English DT Letter ID PLAQUE C1 [Schlett, Christopher L.; Bamberg, Fabian] Harvard Univ, Sch Med, Dept Radiol, Cardiac MR PET CT Program,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Nance, John W., Jr.; Schoepf, U. Joseph] Med Univ S Carolina, Dept Radiol & Radiol Sci, Charleston, SC 29425 USA. [Nance, John W., Jr.] Johns Hopkins Univ Hosp, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. [Bamberg, Fabian] Univ Munich, Dept Radiol, Munich, Germany. [Bamberg, Fabian] Munich Heart Alliance, Munich, Germany. RP Schlett, CL (reprint author), Harvard Univ, Sch Med, Dept Radiol, Cardiac MR PET CT Program,Massachusetts Gen Hosp, Boston, MA 02115 USA. EM schoepf@musc.edu NR 4 TC 0 Z9 0 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2013 VL 266 IS 1 BP 364 EP 364 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 061JQ UT WOS:000312844700047 PM 23390627 ER PT J AU Blanco-Centurion, C Liu, M Konadhode, R Pelluru, D Shiromani, PJ AF Blanco-Centurion, Carlos Liu, Meng Konadhode, RodaRani Pelluru, Dheeraj Shiromani, Priyattam J. TI Effects of Orexin Gene Transfer in the Dorsolateral Pons in Orexin Knockout Mice SO SLEEP LA English DT Article DE Narcolepsy; hypocretin; orexin; recombinant adenoassociated virus; gene transfer; cataplexy; sleep; REM sleep ID LOCUS-COERULEUS NEURONS; HUMAN NARCOLEPSY; MEDIAL MEDULLA; LIVING CELLS; REM-SLEEP; CATAPLEXY; HYPOTHALAMUS; PEPTIDES; AMYGDALA; WAKING AB Study Objectives: Narcolepsy is a sleep disorder characterized by loss of orexin neurons. Previously, our group demonstrated that transfer of the orexin gene into surrogate neurons in the lateral hypothalamus and the zona incerta significantly reduced cataplexy bouts in the orexin-ataxin-3 mice model of narcolepsy. The current study determined the effects of orexin gene transfer into the dorsolateral pontine neurons in the orexin knockout (KO) mice model of narcolepsy. The dorsolateral pons was chosen because it plays a critical role in regulating muscle tone and thus it is conceivable to be involved in cataplexy as well. Cataplexy is the pathognomonic symptom in narcolepsy. Design: Independent groups of orexin KO mice were given bilateral microinjections (0.75 mu L each side) of either recombinant adenoassociated virus-orexin (rAAV-orexin; n = 7), or rAAV-green fluorescent protein (rAAV-GFP; n = 7) into the dorsolateral pons. A group of orexin KO mice that did not receive rAAV (n = 7) and a group of wild-type mice (C57BL/J6; n = 5) were used as controls. Three weeks after rAAV-mediated gene transfer narcolepsy symptoms were examined using sleep and behavioral recordings. Number, location of the orexin-immunoreactive neurons, and relative density of orexin immunoreactive fibers were determined. Measurements and Results: Orexin gene transfer into the dorsolateral pons significantly decreased cataplexy and modestly improved wake maintenance compared to the orexin KO mice that did not receive rAAV. In contrast, GFP gene transfer worsened narcoleptic symptoms compared to the no-rAAV orexin KO group. Conclusion: Orexin gene transfer into the dorsolateral pontine neurons can control cataplexy attacks and modestly improve wake maintenance. C1 [Shiromani, Priyattam J.] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. [Blanco-Centurion, Carlos; Liu, Meng; Konadhode, RodaRani; Pelluru, Dheeraj; Shiromani, Priyattam J.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. RP Shiromani, PJ (reprint author), Ralph H Johnson VA Med Ctr, 109 Bee St,Res Serv 151, Charleston, SC 29401 USA. EM shiroman@musc.edu FU Medical Research Service of the Department of Veterans Affairs [1I01BX000798-01]; NIH [HL091363, MH055772, NS030140, NS052287]; Sleep Research Foundation FX Supported by Medical Research Service of the Department of Veterans Affairs grant number 1I01BX000798-01 and NIH grants HL091363, MH055772, NS030140, NS052287 (Dr. Shiromani), and J. Christian Gillin research grant from the Sleep Research Foundation (Dr. Blanco-Centurion). NR 42 TC 17 Z9 17 U1 1 U2 4 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD JAN 1 PY 2013 VL 36 IS 1 BP 31 EP 40 DI 10.5665/sleep.2296 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063LT UT WOS:000313001200008 PM 23288969 ER PT J AU Fan, X Ning, MM Lo, EH Wang, XY AF Fan, Xiang Ning, MingMing Lo, Eng H. Wang, Xiaoying TI Early Insulin Glycemic Control Combined With tPA Thrombolysis Reduces Acute Brain Tissue Damages in a Focal Embolic Stroke Model of Diabetic Rats SO STROKE LA English DT Article DE focal embolic stroke; hyperglycemia; insulin glycemic control; rats; thrombolysis; tPA; Type I diabetes ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; ACUTE ISCHEMIC-STROKE; POSTSTROKE HYPERGLYCEMIA; INTRAVENOUS THROMBOLYSIS; TRIAL; PREDICTS; GLUCOSE AB Background and Purpose-Therapeutic effects of early insulin glycemic control for poststroke hyperglycemia in combination with tissue-type plasminogen activator (tPA) thrombolytic therapy have not yet been studied but are of great clinical interest. In this study, we tested the effects of insulin plus tPA combination in a model of focal embolic stroke in Type I diabetic rats. Methods-Streptozotocin was used to produce Type I diabetes in male Wistar rats for 6 weeks and then embolic focal strokes were induced. All rats were treated with insulin or saline at 1 hour followed by tPA or saline at 1.5 hour after stroke. Mortality, infarction, hemispheric swelling, hemorrhagic transformation, and perfusion defects were examined at 24 hours after stroke. Total plasma plasminogen activator inhibitor-1 antigen and activity levels were measured before stroke and 1.5, 3, and 6 hours after stroke by ELISA. Results-Early insulin glycemic control alone or tPA thrombolysis alone had no significant effects on ischemic infarction. However, early insulin glycemic control combined with tPA significantly reduced brain infarction and swelling, ameliorated tPA-associated hemorrhagic transformation, and improved plasma perfusion at 24 hours after stroke. We also found that the combination significantly decreased plasma plasminogen activator inhibitor-1 antigen level at 6 hours and plasminogen activator inhibitor-1 activity at 1.5 and 6 hours after stroke. Conclusions-Early insulin glycemic control may be beneficial in combination with tPA thrombolysis for ischemic stroke with diabetes mellitus or poststroke hyperglycemia. (Stroke. 2013;44:255-259.) C1 [Wang, Xiaoying] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Neurol,Neurosci Program, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Radiol,Neurosci Program, Charlestown, MA 02129 USA. RP Wang, XY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Neurol,Neurosci Program, 149 13th St,Room 2411A, Charlestown, MA 02129 USA. EM wangxi@helix.mgh.harvard.edu FU National Institute of Health [R01-NS065998, UO1-NS072324] FX This work was supported in part by National Institute of Health grants R01-NS065998 and UO1-NS072324 (to Xiaoying Wang). NR 15 TC 10 Z9 12 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2013 VL 44 IS 1 BP 255 EP 259 DI 10.1161/STROKEAHA.112.663476 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 061XP UT WOS:000312883800047 PM 23117722 ER PT J AU Omata, J Pierre, JF Heneghan, AF Tsao, FHC Sano, Y Jonker, MA Kudsk, KA AF Omata, Jiro Pierre, Joseph F. Heneghan, Aaron F. Tsao, Francis H. C. Sano, Yoshifumi Jonker, Mark A. Kudsk, Kenneth A. TI Parenteral nutrition suppresses the bactericidal response of the small intestine SO SURGERY LA English DT Article ID PHOSPHOLIPASE A(2); PANETH CELLS; LYMPHOID-TISSUE; DEFENSINS; SECRETION; MOUSE AB Background. Parenteral nutrition (PN) increases infectious risk in critically ill patients compared with enteral feeding. Previously, we demonstrated that PN feeding suppresses the concentration of the Paneth cell antimicrobial protein secretory phospholipase A2 (sPLA(2)) in the gut lumen. sPLA2 and other Paneth cell proteins are released in response to bacterial components, such as lipopolysaccharide (LPS), and they modulate the intestinal microbiome. Because the Paneth cell protein sPLA(2) was suppressed with PN feeding, we hypothesized PN would diminish the responsiveness of the small bowel to LPS through reduced secretions and as a result exhibit less bactericidal activity. Methods. The distal ileum was harvested from Institute of Cancer Research mice, washed, and randomized for incubation with LPS (0; 1, or 10 mu g/mL). Culture supernatant was collected and sPLA(2) activity was measured. Bactericidal activity of the ileum segment secretions was assessed against Pseudomonas aeruginosa with and without an sPLA(2) inhibitor at 2 concentrations, 100 nmol/L and 1 mu mol/L. Institute of Cancer Research mice were randomized to chow or PN for 5 days. Tissue was collected for immunohistochemistry (IHC) and ileal segments were incubated with LPS (0 or 10 mu g/mL). sPLA(2) activity and bactericidal activity were measured in secretions from ileal segments. Results. Real segments responded to 10 mu g/mL LPS with significantly greater sPLA(2) activity and bactericidal activity. The bactericidal activity of secretions from LPS stimulated tissue was suppressed 50% and 70%, respectively, with the addition of the sPLA(2)-inhibitor. Chow displayed greater sPLA(2) in the Paneth cell granules and secreted higher levels of sPLA(2) than PN before and after LPS. Accordingly, media collected from chow was more bactericidal than PN. IHC confirmed a reduction in Paneth cell granules after PN. Conclusion. This work demonstrates that ileal segments secrete bactericidal secretions after LPS exposure and the inhibition of the Paneth cell antimicrobial protein sPLA(2) significantly diminishes this. PN feeding resulted in suppressed secretion of the sPLA(2) and resulted in increased bacterial survival. This demonstrates that PN significantly impairs the innate immune response by suppressing Paneth cell function. (Surgery 2013;153:17-24.) C1 [Omata, Jiro; Pierre, Joseph F.; Heneghan, Aaron F.; Sano, Yoshifumi; Jonker, Mark A.; Kudsk, Kenneth A.] Univ Wisconsin, Dept Surg, Madison Sch Med & Publ Hlth, Madison, WI USA. [Omata, Jiro] Natl Def Med Coll, Dept Surg, Tokorozawa, Saitama 359, Japan. [Tsao, Francis H. C.] Univ Wisconsin, Madison Sch Med & Publ Hlth, Div Allergy Pulm & Crit Care Med, Dept Med, Madison, WI USA. [Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. RP Kudsk, KA (reprint author), 600 Highland Ave,H4-736, Madison, WI 53792 USA. EM Kudsk@surgery.wisc.edu FU National Institute of Health (NIH) [R01 GM53439]; Department of Veteran Affairs, Veteran Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development Service FX Supported by National Institute of Health (NIH) Grant R01 GM53439.; Based on work supported in part by the Department of Veteran Affairs, Veteran Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development Service. The contents of this article do not represent the views of the Veterans Affairs or the United States Government. NR 20 TC 16 Z9 19 U1 0 U2 11 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD JAN PY 2013 VL 153 IS 1 BP 17 EP 24 DI 10.1016/j.surg.2012.04.001 PG 8 WC Surgery SC Surgery GA 060EU UT WOS:000312760100003 PM 22698933 ER PT J AU Babrowski, T Romanowski, K Fink, D Kim, M Gopalakrishnan, V Zaborina, O Alverdy, JC AF Babrowski, Trissa Romanowski, Kathleen Fink, David Kim, Moses Gopalakrishnan, Vissagan Zaborina, Olga Alverdy, John C. TI The intestinal environment of surgical injury transforms Pseudomonas aeruginosa into a discrete hypervirulent morphotype capable of causing lethal peritonitis SO SURGERY LA English DT Article ID INTENSIVE-CARE-UNIT; PHASE VARIATION; CONTROLS EXPRESSION; GENE-EXPRESSION; VIRULENCE; ACTIVATION; RIBOSWITCH; INFECTION AB Background. Secondary peritonitis continues to carry a high mortality rate despite the aggressive use of imaging, drainage, and antibiotics. Although host factors and microbial burden contribute to the outcome of peritonitis, we propose a role for bacterial virulence as a determinant of outcome from peritonitis. Bacterial virulence is an inducible trait that is activated in response to specific local "cues" that we have previously shown to be present in the mouse gut exposed to surgical stress and injury. Methods. Pseudomonas aeruginosa was harvested after its intestinal inoculation into the cecum of mice subjected to surgical injury (30% hepatectomy) or sham surgery (controls). Harvested strains were then injected into the peritoneum of noninjured (naive) mice and mortality determined. Results. P aeruginosa harvested from the intestines of surgically injured mice caused 100% mortality, whereas strains harvested from control mice caused no mortality. Among recovered strains, a distinct aeruginosa morphotype (wrinkled shape) was shown to cause lethal peritonitis compared to smooth-shaped strains, which were nonlethal. Wrinkled strains were associated with a tendency to elicit a more proinflammatory response in mice compared to smooth-shaped strains. Conclusion. Surgical injury transforms the morphotype of intestinal P aeruginosa to express a hypervirulent response in the peritoneum of mice. Enhanced virulence of intestinal pathogens in response to surgical injury may play an important role in predicting the outcome of peritonitis. (Surgery 2013;153:36-43.) C1 [Babrowski, Trissa; Romanowski, Kathleen; Kim, Moses; Zaborina, Olga; Alverdy, John C.] Univ Chicago, Pritzker Sch Med, Ctr Surg Infect Res & Therapeut, Chicago, IL 60637 USA. [Fink, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Gopalakrishnan, Vissagan] Johns Hopkins Univ, Baltimore, MD USA. RP Alverdy, JC (reprint author), Univ Chicago, Med Ctr, 5841 S Maryland Ave,MC 6090, Chicago, IL 60637 USA. EM jalverdy@surgery.bsd.uchicago.edu FU NIGMS NIH HHS [R01 GM062344] NR 23 TC 15 Z9 15 U1 1 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD JAN PY 2013 VL 153 IS 1 BP 36 EP 43 DI 10.1016/j.surg.2012.06.022 PG 8 WC Surgery SC Surgery GA 060EU UT WOS:000312760100005 PM 22862900 ER PT J AU Telem, DA Han, KS Kim, MC Ajari, I Sohn, DK Woods, K Kapur, V Sbeih, MA Perretta, S Rattner, DW Sylla, P AF Telem, Dana A. Han, Kyung Su Kim, Min-Chan Ajari, Ifode Sohn, Dae Kyung Woods, Kevin Kapur, Varun Sbeih, Mohammad A. Perretta, Silvana Rattner, David W. Sylla, Patricia TI Transanal rectosigmoid resection via natural orifice translumenal endoscopic surgery (NOTES) with total mesorectal excision in a large human cadaver series SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article; Proceedings Paper CT Honored with a Gerald Marks Rectal Cancer Award at the Annual Meeting of the Society-of-American-Gastrointestinal-and-Endoscopic-Surgeons (SAGES) / 15th World Congress of Endoscopic Surgery / Foregut Session CY MAR 07-10, 2012 CL San Diego, CA SP Soc Amer Gastrointestinal & Endoscop Surg (SAGES) DE Human cadaver model; NOTES; Rectosigmoid resection; Total mesorectal excision; Transanal; Transanal endoscopic microsurgery ID MICROSURGERY; SWINE AB The authors' group has previously described successful transanal rectosigmoid resection via natural orifice translumenal endoscopic surgery (NOTES) in both porcine and cadaveric models using the transanal endoscopic microsurgery platform. This report describes the largest cadaveric series to date as optimization of this approach for clinical application continues. Between December 2008 and September 2011, NOTES transanal rectosigmoid resection with total mesorectal excision (TME) was successfully performed in 32 fresh human cadavers using transanal dissection alone (n = 19), with transgastric endoscopic assistance (n = 5), or with laparoscopic assistance (n = 8). The variables recorded were gender, body mass index (BMI), operative time, length of the mobilized specimen, integrity of the mesorectum and the resected specimen, and complications. Univariate statistical analysis was performed. Of the 32 cadavers, 22 were male with a mean BMI of 24 kg/m(2) (range 16.3-37 kg/m(2)). The mean operative time was 5.1 h (range 3-8 h), and the mean specimen length was 53 cm (range 15-91.5 cm). After the first five cadavers, specimen length significantly improved, and a trend toward decreased operative time was demonstrated. The mesorectum was intact in 100 % of the specimens. In nine cadavers, endoscopic dissection was complicated by organ injury. Evaluation by the operative approach demonstrated a significantly longer specimen with laparoscopic assistance (67.7 cm) than with transgastric assistance (45.4 cm) or transanal dissection alone (49.2 cm) (p = 0.013). Comparison of the technique used for inferior mesenteric pedicle division demonstrated both significantly decreased operative time (4.8 vs 6 h; p = 0.024) and increased specimen length (57.7 vs 39.6 cm; p = 0.025) when a stapler was used in lieu of a bipolar cautery device. Transanal NOTES rectosigmoid resection with TME is feasible and demonstrates improvement in specimen length and operative time with experience. Transitioning to clinical application requires laparoscopic assistance to overcome limitations related to NOTES instrumentation, as well as procedural training with fresh human cadavers. C1 [Telem, Dana A.; Ajari, Ifode; Kapur, Varun; Sbeih, Mohammad A.; Rattner, David W.; Sylla, Patricia] Massachusetts Gen Hosp, Div Gastrointestinal Surg, Boston, MA 02114 USA. [Han, Kyung Su] Natl Canc Ctr, Ctr Colorectal Canc, Goyang, South Korea. [Kim, Min-Chan] Seoul Natl Univ, Bundang Hosp, Dept Surg, Gyeonggi Do, South Korea. [Sohn, Dae Kyung] Natl Canc Ctr, Res Inst & Hosp, Goyang, South Korea. [Woods, Kevin] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Perretta, Silvana] IRCAD, Strasbourg, France. RP Telem, DA (reprint author), Massachusetts Gen Hosp, Div Gastrointestinal Surg, 15 Parkman St,Wang 460, Boston, MA 02114 USA. EM dtelem@partners.org; psylla@partners.org NR 14 TC 27 Z9 34 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD JAN PY 2013 VL 27 IS 1 BP 74 EP 80 DI 10.1007/s00464-012-2409-y PG 7 WC Surgery SC Surgery GA 061XV UT WOS:000312884500010 PM 22752277 ER PT J AU Lacy, AM Adelsdorfer, C Delgado, S Sylla, P Rattner, DW AF Lacy, Antonio M. Adelsdorfer, Cedric Delgado, Salvadora Sylla, Patricia Rattner, David W. TI Minilaparoscopy-assisted transrectal low anterior resection (LAR): a preliminary study SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE NOTES; MA-NOS; Minimally invasive surgery; Transrectal; Rectal cancer ID TRANSANAL ENDOSCOPIC MICROSURGERY; INTRACORPOREAL RECTAL TRANSECTION; RANDOMIZED CLINICAL-TRIAL; TOTAL MESORECTAL EXCISION; DOUBLE-STAPLING TECHNIQUE; LONG-TERM OUTCOMES; ANASTOMOTIC LEAKAGE; RISK-FACTORS; COLON-CANCER; OPEN COLECTOMY AB Natural orifice translumenal endoscopic surgery (NOTES) represents the evolution of surgery towards less invasive procedures. The feasibility of NOTES transrectal approach has increased its clinical applicability. This report describes a first series of minilaparoscopy-assisted transrectal low anterior resection with double purse-string end-to-end circular stapler anastomoses. Between March and April 2012 three selected patients underwent transrectal minilaparoscopy-assisted natural orifice surgery total mesorectal excision for rectal cancer. All the oncologic principles of open/laparoscopic low anterior resection for rectal cancer were strictly fulfilled. Two patients underwent neoadjuvant treatment. Laparoscopic visualization and assistance was provided through one 10-mm umbilical port and two ports, one of which was used as stoma site (5 mm) and the other as a drain site (2 mm needle port). The specimen was transected transanally followed by the confection of double purse-string lateral/end-to-end anastomoses. There were no intraoperative complications. Mean operative time was 143 min. Oral intake was initiated on the second postoperative day. Patients were discharged home by day 5. The pathology unit confirmed that distal and circumferential margins were free of tumor invasion, and quality of mesorectum resection was reported satisfactory. One patient had to be readmitted because of severe dehydration due to increased ileostomy output. The patient was discharged at the third day after the readmission without renal failure. In this preliminary report, transrectal minilaparoscopy-assisted low anterior resection was feasible and safe. Lateral/end-to-end anastomoses can be considered an interesting alternative to the double-stapling technique. However, it is necessary to further study and develop these procedures, along with careful patient selection, before transrectal low anterior resection may be considered for routine clinical use. C1 [Lacy, Antonio M.; Adelsdorfer, Cedric; Delgado, Salvadora] Univ Barcelona, Dept Gastrointestinal Surg, Inst Digest & Metab Dis ICMDM, Hosp Clin,IDIBAPS,CIBERehd,Ctr Esther Koplowitz, Barcelona, Spain. [Sylla, Patricia; Rattner, David W.] Massachusetts Gen Hosp, Div Gastrointestinal Surg, Boston, MA 02114 USA. RP Lacy, AM (reprint author), Univ Barcelona, Dept Gastrointestinal Surg, Inst Digest & Metab Dis ICMDM, Hosp Clin,IDIBAPS,CIBERehd,Ctr Esther Koplowitz, Barcelona, Spain. EM alacy@clinic.ub.es NR 36 TC 47 Z9 51 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD JAN PY 2013 VL 27 IS 1 BP 339 EP 346 DI 10.1007/s00464-012-2443-9 PG 8 WC Surgery SC Surgery GA 061XV UT WOS:000312884500046 PM 22806513 ER PT J AU Parekh, A Chen, MH Hoffman, KE Choueiri, TK Hu, JC Bennett, CL Kattan, MW Sartor, O Stein, K Graham, PL D'Amico, AV Nguyen, PL AF Parekh, Arti Chen, Ming-Hui Hoffman, Karen E. Choueiri, Toni K. Hu, Jim C. Bennett, Charles L. Kattan, Michael W. Sartor, Oliver Stein, Karen Graham, Powell L. D'Amico, Anthony V. Nguyen, Paul L. TI Reduced Penile Size and Treatment Regret in Men With Recurrent Prostate Cancer After Surgery, Radiotherapy Plus Androgen Deprivation, or Radiotherapy Alone SO UROLOGY LA English DT Article ID LENGTH; THERAPY AB OBJECTIVE To report the relative incidence of the perceived reduction in penile size across prostate cancer treatment modalities and to describe its effect on quality of life and treatment regret. MATERIALS AND METHODS The incidence of patient complaints about reduced penile size was calculated for 948 men in the Comprehensive, Observational, Multicenter, Prostate Adenocarcinoma (COMPARE) registry who experienced biochemical failure (per registry definition) and were assessed a median of 5.53 years after prostatectomy or radiotherapy (RT) consisting of either external beam RT or brachytherapy, with or without androgen deprivation therapy (ADT). Multivariate logistic regression analysis was used to determine the factors associated with treatment regret and interference with emotional relationships. RESULTS Of 948 men, 25 (2.63%) complained of a reduced penile size. The incidence of reduced penile size stratified by treatment was 3.73% for surgery (19 of 510), 2.67% for RT plus ADT (6 of 225), and 0% for RT without ADT (0 of 213). The surgery (P = .004) and RT plus ADT (P = .016) groups had significantly more shortened penis complaints than the RT alone group. The rate of a shortened penis after surgery and after RT plus ADT was similar (P = .47). On multivariate analysis adjusting for age, treatment type, and baseline comorbidity, a perceived reduction in penile size was associated with interference with close emotional relationships (odds ratio 2.36, 95% confidence interval 1.02-8.26; P = .04) and increased treatment regret (odds ratio 3.37, 95% confidence interval 1.37-8.26; P = .0079). CONCLUSION Complaints about a reduced penile size were more common with RT plus ADT or surgery than RT alone and were associated with greater interference with close emotional relationships and increased treatment regret. Physicians should discuss the possibility of this rarely mentioned side effect with their patients to help them make more informed treatment choices. UROLOGY 81: 130-135, 2013. (c) 2013 Elsevier Inc. C1 [Nguyen, Paul L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. Harvard Univ, Lank Ctr Genitourinary Oncol, Dana Farber Canc Inst, Brigham & Womens Hosp,Med Sch, Boston, MA 02115 USA. Univ Calif Los Angeles, Med Ctr, Dept Urol Surg, Los Angeles, CA USA. S Carolina Coll Pharm, Charleston, SC USA. Hollings Canc Ctr, Charleston, SC USA. Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA. Tulane Univ, Dept Med, New Orleans, LA 70118 USA. Tulane Univ, Dept Urol, New Orleans, LA 70118 USA. Novartis, E Hanover, NJ USA. RP Nguyen, PL (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu FU Doris Duke Charitable Foundation Clinical Research Fellowship at Harvard Medical School; Heritage Medical Research Institute/Prostate Cancer Foundation Young Investigator Award FX This work was supported by an anonymous family foundation, the Doris Duke Charitable Foundation Clinical Research Fellowship at Harvard Medical School, David and Cynthia Chapin, Fitz's Cancer Warriors, and a Heritage Medical Research Institute/Prostate Cancer Foundation Young Investigator Award. NR 11 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD JAN PY 2013 VL 81 IS 1 BP 130 EP 134 DI 10.1016/j.urology.2012.08.090 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 062YJ UT WOS:000312960300041 PM 23273077 ER PT J AU Parekh, A Graham, PL D'Amico, AV Nguyen, PL Chen, MH Hoffman, KE Choueiri, TK Hu, JC Bennett, CL Kattan, MW Sartor, O Stein, K AF Parekh, Arti Graham, Powell L. D'Amico, Anthony V. Nguyen, Paul L. Chen, Ming-Hui Hoffman, Karen E. Choueiri, Toni K. Hu, Jim C. Bennett, Charles L. Kattan, Michael W. Sartor, Oliver Stein, Karen TI Reduced Penile Size and Treatment Regret in Men With Recurrent Prostate Cancer After Surgery, Radiotherapy Plus Androgen Deprivation, or Radiotherapy Alone REPLY SO UROLOGY LA English DT Editorial Material C1 [Parekh, Arti; Graham, Powell L.; D'Amico, Anthony V.; Nguyen, Paul L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Hoffman, Karen E.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Choueiri, Toni K.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Lank Ctr Genitourinary Oncol,Dana Farber Med Inst, Boston, MA 02115 USA. [Hu, Jim C.] Univ Calif Los Angeles, Med Ctr, Dept Urol Surg, Los Angeles, CA 90024 USA. [Bennett, Charles L.] S Carolina Coll Pharm, Charleston, SC USA. [Bennett, Charles L.] Hollings Canc Ctr, Charleston, SC USA. [Kattan, Michael W.] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA. [Sartor, Oliver] Tulane Univ, Dept Med, New Orleans, LA 70118 USA. [Sartor, Oliver] Tulane Univ, Dept Urol, New Orleans, LA 70118 USA. [Stein, Karen] Novartis, E Hanover, NJ USA. RP Parekh, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD JAN PY 2013 VL 81 IS 1 BP 134 EP 135 DI 10.1016/j.urology.2012.08.091 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 062YJ UT WOS:000312960300043 ER PT J AU Kesler, CT Liao, S Munn, LL Padera, TP AF Kesler, Cristina T. Liao, Shan Munn, Lance L. Padera, Timothy P. TI Lymphatic vessels in health and disease SO WILEY INTERDISCIPLINARY REVIEWS-SYSTEMS BIOLOGY AND MEDICINE LA English DT Review ID GROWTH-FACTOR-C; HIGH ENDOTHELIAL VENULES; GUINEA-PIG MESENTERY; SUBCAPSULAR SINUS MACROPHAGES; PROMOTES TUMOR-METASTASIS; SENTINEL-NODE BIOPSY; VEGF-D PROMOTES; NITRIC-OXIDE; IN-VIVO; ANTIANGIOGENIC THERAPY AB The lymphatic vasculature plays vital roles in tissue fluid balance, immune defense, metabolism, and cancer metastasis. In adults, lymphatic vessel formation and remodeling occur primarily during inflammation, development of the corpus luteum, wound healing, and tumor growth. Unlike the blood circulation, where unidirectional flow is sustained by the pumping actions of the heart, pumping actions intrinsic to the lymphatic vessels themselves are important drivers of lymphatic flow. This review summarizes critical components that control lymphatic physiology. WIREs Syst Biol Med 2013, 5:111124. doi: 10.1002/wsbm.1201 For further resources related to this article, please visit the WIREs website. C1 [Padera, Timothy P.] Harvard Univ, Sch Med, Dept Radiat Oncol, EL Steele Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Padera, TP (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, EL Steele Lab, Boston, MA 02115 USA. EM tpadera@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016; OI Munn, Lance/0000-0003-0698-7232; Padera, Timothy/0000-0002-3453-9384 FU NIH [R00CA137167, DP2OD008780, R21AI097745, R01HL106584, R01CA149285, T32CA073479]; NCI Federal Share/Proton Beam Income; Charles King Trust FX The authors would like to thank Drs Rakesh Jain, Dai Fukumura, and Jay Loeffler for their critical input and support. The authors are supported by NIH R00CA137167, NIH DP2OD008780, NIH R21AI097745, and NCI Federal Share/Proton Beam Income (TPP), NIH R01HL106584 and NIH R01CA149285 (LLM), NIH T32CA073479 (CTK), and Charles King Trust Fellowship (SL). NR 135 TC 21 Z9 22 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1939-5094 J9 WIRES SYST BIOL MED JI Wiley Interdiscip. Rev.-Syst. Biol PD JAN-FEB PY 2013 VL 5 IS 1 BP 111 EP 124 DI 10.1002/wsbm.1201 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 059WM UT WOS:000312736200008 PM 23209022 ER PT J AU Hagander, LE Hughes, CD Nash, K Ganjawalla, K Linden, A Martins, Y Casey, KM Meara, JG AF Hagander, Lars E. Hughes, Christopher D. Nash, Katherine Ganjawalla, Karan Linden, Allison Martins, Yolanda Casey, Kathleen M. Meara, John G. TI Surgeon Migration Between Developing Countries and the United States: Train, Retain, and Gain from Brain Drain SO WORLD JOURNAL OF SURGERY LA English DT Article ID GENERAL-SURGERY; PHYSICIAN MIGRATION; SURGICAL WORKFORCE; INTERNATIONAL RECRUITMENT; MEDICAL-STUDENTS; POOR COUNTRIES; SHORTAGE; METRICS; CANADA; GLOBALIZATION AB The critical shortage of surgeons in many low- and middle-income countries (LMICs) prevents adequate responses to surgical needs, but the factors that affect surgeon migration have remained incompletely understood. The goal of this study was to examine the importance of personal, professional, and infrastructural factors on surgeon migration from LMICs to the United States. We hypothesized that the main drivers of surgeon migration can be addressed by providing adequate domestic surgical infrastructure, surgical training programs, and viable surgical career paths. We conducted an internet-based nationwide survey of surgeons living in the US who originated from LMICs. 66 surgeons completed the survey. The most influential factors for primary migration were related to professional reasons (p a parts per thousand currency sign 0.001). Nonprofessional factors, such as concern for remuneration, family, and security were significantly less important for the initial migration decisions, but adopted a more substantial role in deciding whether or not to return after training in the United States. Migration to the United States was initially considered temporary (44 %), and a majority of the surveyed surgeons have returned to their source countries in some capacity (56 %), often on multiple occasions (80 %), to contribute to clinical work, research, and education. This study suggests that surgically oriented medical graduates from LMICs migrate primarily for professional reasons. Initiatives to improve specialist education and surgical infrastructure in LMICs have the potential to promote retention of the surgical workforce. There may be formal ways for LMICs to gain from the international pool of relocated surgeons. C1 [Hagander, Lars E.; Hughes, Christopher D.; Ganjawalla, Karan; Linden, Allison; Meara, John G.] Harvard Univ, Sch Med, Program Global Surg & Social Change, Boston, MA 02115 USA. [Hagander, Lars E.; Hughes, Christopher D.; Ganjawalla, Karan; Linden, Allison; Meara, John G.] Childrens Hosp, Dept Plast & Oral Surg, Boston, MA 02115 USA. [Hagander, Lars E.] Lund Univ, Fac Med, Dept Pediat Surg, Lund, Sweden. [Nash, Katherine] Columbia Univ, Sch Med, New York, NY USA. [Linden, Allison] Georgetown Univ Hosp, Dept Surg, Washington, DC 20007 USA. [Martins, Yolanda] Childrens Hosp Boston, Clin Res Ctr, Boston, MA USA. [Martins, Yolanda] Dana Farber Canc Inst, Ctr Populat Sci, Boston, MA 02115 USA. [Martins, Yolanda] Harvard Univ, Sch Med, Div Gen Pediat, Boston, MA USA. [Casey, Kathleen M.] Amer Coll Surg, Chicago, IL USA. RP Hagander, LE (reprint author), Harvard Univ, Sch Med, Program Global Surg & Social Change, Boston, MA 02115 USA. EM lars.hagander@childrens.harvard.edu; john.meara@childrens.harvard.edu OI Martins, Yolanda/0000-0002-3983-3531 NR 66 TC 17 Z9 18 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 EI 1432-2323 J9 WORLD J SURG JI World J.Surg. PD JAN PY 2013 VL 37 IS 1 BP 14 EP 23 DI 10.1007/s00268-012-1795-6 PG 10 WC Surgery SC Surgery GA 060WG UT WOS:000312808400003 PM 23052799 ER PT J AU Zakai, NA French, B Arnold, AM Newman, AB Fried, LF Robbins, J Chaves, P Cushman, M AF Zakai, Neil A. French, Benjamin Arnold, Alice M. Newman, Anne B. Fried, Linda F. Robbins, John Chaves, Paulo Cushman, Mary TI Hemoglobin decline, function, and mortality in the elderly: The cardiovascular health study SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; CHRONIC HEART-FAILURE; OLDER-ADULTS; FOLLOW-UP; ANEMIA; IMPACT; RISK; COHORT; WOMEN AB While anemia is associated with poor functional and mortality outcomes in the elderly, the impact of hemoglobin decline is less studied. We evaluated the determinants and consequences of hemoglobin decline in 3,758 non-anemic participants from the Cardiovascular Health Study, a prospective cohort of community-dwelling elderly =65 years old at baseline and followed for up to 16 years. Hemoglobin was measured at baseline and 3 years later and anemia defined by World Health Organization (WHO) criteria. We modeled hemoglobin decline in two ways: (1) per each 1 g/dL decrease in hemoglobin and (2) development of anemia by the WHO criteria. Among participants without baseline anemia, hemoglobin decreased by 0.4 g/dL and 9% developed anemia over 3 years. Baseline increasing age, female sex, diabetes, and kidney disease predicted hemoglobin decline over 3 years. Baseline increasing age, being African-American, and kidney disease predicted anemia development over 3 years. Hemoglobin decline was associated with subsequent worse cognitive function in men and anemia development with subsequent worse cognitive function in women. Both anemia development (HR 1.39, 95% CI 1.15, 1.69) and hemoglobin decline (HR 1.11, 95% CI 1.04, 1.18 per 1 g/dL decrease) predicted subsequent mortality in men and women. Hemoglobin decreases identified a large group of elderly individuals at risk for subsequent adverse outcomes who would not be identified using the WHO anemia criteria. These data may allow clinicians to identify at-risk elderly individuals for early intervention to improve the quality and quantity of life. Am. J. Hematol. 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Zakai, Neil A.; Cushman, Mary] Univ Vermont, Vermont Coll Med, Dept Med, Burlington, VT 05405 USA. [Zakai, Neil A.; Cushman, Mary] Univ Vermont, Vermont Coll Med, Dept Pathol, Burlington, VT 05405 USA. [French, Benjamin] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Arnold, Alice M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Newman, Anne B.; Fried, Linda F.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Fried, Linda F.] VA Pittsburgh Healthcare Syst, Dept Med, Pittsburgh, PA USA. [Robbins, John] Univ Calif Davis, Ctr Healthcare Policy & Res, Davis, CA 95616 USA. [Chaves, Paulo] Johns Hopkins Sch Publ Hlth, Div Gen Internal Med, Baltimore, MD USA. [Chaves, Paulo] Johns Hopkins Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Zakai, NA (reprint author), Univ Vermont, Coll Med, 208 S Pk Dr, Colchester, VT 05446 USA. EM neil.zakai@uvm.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU National Institute on Aging [R01 AG-023629, R01 AG-15928, R01 AG-20098, R01 AG-027058]; National Heart, Lung, and Blood Institute [N01 HC-35129, N01 HC-45133, N01 HC-75150, N01 HC-85079, N01 HC-85080, N01 HC-85081, N01 HC-85082, N01 HC-85083, N01 HC-85084, N01-HC-85085]; National Institute of Neurological Disorders and Stroke [N01 HC-85086, N01 HC-15103, N01 HC-55222, U01 HL-080295]; National Heart, Lung and Blood Institute; University of Pittsburgh Claude D. Pepper Older Americans Independence Center [R01 HL-075366]; Claude D. Pepper Older Americans Independence Center [P30 AG-024827] FX Contract grant sponsor: National Institute on Aging; Contract grant number: R01 AG-023629; Contract grant sponsor: National Heart, Lung, and Blood Institute; Contract grant numbers: N01 HC-35129, N01 HC-45133, N01 HC-75150, N01 HC-85079 through N01-HC-85085; Contract grant sponsor: National Institute of Neurological Disorders and Stroke; Contract grant numbers: N01 HC-85086, N01 HC-15103, N01 HC-55222, U01 HL-080295; Contract grant sponsor: National Institute on Aging; Contract grant numbers: R01 AG-15928, R01 AG-20098, R01 AG-027058; Contract grant sponsor: National Heart, Lung and Blood Institute and the University of Pittsburgh Claude D. Pepper Older Americans Independence Center; Contract grant number: R01 HL-075366; Contract grant sponsor: Claude D. Pepper Older Americans Independence Center; Contract grant number: P30 AG-024827. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. NR 32 TC 8 Z9 8 U1 0 U2 9 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 JAN PY 2013 VL 88 IS 1 BP 5 EP 9 DI 10.1002/ajh.23336 PG 5 WC Hematology SC Hematology GA 057BJ UT WOS:000312536500002 PM 23044913 ER PT J AU Nellore, A Kotton, CN AF Nellore, Anoma Kotton, Camille Nelson TI Screening Strategies for Tuberculosis in Children With Kidney Disease: What Is Cost-Effective? SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material ID GAMMA-RELEASE ASSAY; QUANTIFERON-TB GOLD; ORGAN TRANSPLANT RECIPIENTS; LONG-TERM HEMODIALYSIS; STAGE RENAL-DISEASE; CELL-BASED ASSAY; IN-TUBE TEST; LATENT TUBERCULOSIS; MYCOBACTERIUM-TUBERCULOSIS; SKIN-TEST C1 [Kotton, Camille Nelson] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Kotton, CN (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,Cox 5, Boston, MA 02114 USA. EM ckotton@partners.org NR 40 TC 0 Z9 0 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JAN PY 2013 VL 61 IS 1 BP 3 EP 5 DI 10.1053/j.ajkd.2012.10.003 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 054TE UT WOS:000312365500004 PM 23245736 ER PT J AU Smith, K deFilippi, C Isakova, T Gutierrez, OM Laliberte, K Seliger, S Kelley, W Duh, SH Hise, M Christenson, R Wolf, M Januzzi, J AF Smith, Kelsey deFilippi, Christopher Isakova, Tamara Gutierrez, Orlando M. Laliberte, Karen Seliger, Stephen Kelley, Walter Duh, Show-Hong Hise, Michael Christenson, Robert Wolf, Myles Januzzi, James TI Fibroblast Growth Factor 23, High-Sensitivity Cardiac Troponin, and Left Ventricular Hypertrophy in CKD SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Fibroblast growth factor 23; high-sensitivity cardiac troponin; left ventricular hypertrophy; chronic kidney disease ID CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; CHRONIC-HEMODIALYSIS PATIENTS; PERITONEAL-DIALYSIS PATIENTS; CORONARY-ARTERY-DISEASE; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; ASYMPTOMATIC PATIENTS; CLINICAL-SIGNIFICANCE; PREDICTS MORTALITY AB Background: Detectable levels of cardiac troponins are common in individuals with chronic kidney disease (CKD), even in the absence of symptomatic cardiovascular disease. Abnormal cardiac troponin values are associated with coronary artery disease and left ventricular hypertrophy (LVH) and predict poor clinical outcomes. Elevated levels of fibroblast growth factor 23 (FGF-23) contribute to LVH in CKD. We investigated the association of FGF-23 and hs-cTnI (high-sensitivity cardiac troponin I) and hs-cTnT (high-sensitivity cardiac troponin T) levels in CKD and examined the role of LVH in this association. Study Design: Cross-sectional observational study. Setting & Participants: 153 stable outpatients with non-dialysis-dependent CKD. Predictor: The primary predictor was FGF-23 level. Outcomes: hs-cTnI, hs-cTnT. Measurements: FGF-23, hs-cTnI, hs-cTnT; left ventricular mass index (LVMI) assessed by echocardiography; coronary artery calcification (CAC) measured by computed tomography. LVMI and CAC were evaluated as potential mediators of the effect of FGF-23 on hs-cTnI/T. Results: Mean age was 64 +/- 12 (SD) years, mean estimated glomerular filtration rate was 34 +/- 11 mL/min/1.73 m(2), median FGF-23 level was 120 (25th-75th percentile, 79-223) reference unit (RU)/mL, median hs-cTnI level was 6.5 (25th-75th percentile, 3.5-14.5) pg/mL, and median hs-cTnT level was 16.8 (25th-75th percentile, 11.1-33.9) pg/mL. cTnI and cTnT concentrations were higher than the 99th percentile of a healthy population in 42% and 61% of patients, respectively. In unadjusted and multivariable-adjusted analyses, hs-cTnI/T levels were associated significantly with FGF-23 levels. Adjusting for LVMI, but not CAC, weakened the association of FGF-23 and hs-cTnI/T levels. Limitations: Vitamin D levels were not measured. The prevalence of coronary artery disease may have been underestimated because it was ascertained by self-report. Conclusions: Minimally elevated cTnI and cTnT levels, detectable by high-sensitivity assays, are associated with elevated FGF-23 levels in stable outpatients with CKD. FGF-23-associated LVH may contribute to detectable hs-cTnI/T levels observed in non-dialysis-dependent patients with CKD. Am J Kidney Dis. 61(1):67-73. (C) 2012 by the National Kidney Foundation, Inc. C1 [Smith, Kelsey; Isakova, Tamara; Wolf, Myles] Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, Dept Med, Miami, FL 33136 USA. [deFilippi, Christopher; Seliger, Stephen; Hise, Michael] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Gutierrez, Orlando M.] Univ Alabama Birmingham, Dept Med, Div Nephrol, Birmingham, AL 35294 USA. [Laliberte, Karen; Januzzi, James] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Kelley, Walter; Duh, Show-Hong; Christenson, Robert] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. RP Wolf, M (reprint author), Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, Dept Med, 1120 NW 14th St,CRB 819, Miami, FL 33136 USA. EM mwolf2@med.miami.edu; jjanuzzi@partners.org FU Siemens Healthcare Diagnostics; American Society of Nephrology Student Scholars Grant; National Institutes of Health (Mallinckrodt General Clinical Research Center at Massachusetts General Hospital) [K30RR02229207, M01RR01066]; National Institutes of Health [R01DK076116] FX Funding for the main study in patients with CKD was provided by an investigator-initiated grant from Dade Behring (now Siemens Healthcare Diagnostics) to Dr deFilippi. For the present study, all hypotheses and analyses were generated and tested by the authors independently of industry support. This study was supported by the American Society of Nephrology Student Scholars Grant (to Ms Smith) and by grants from the National Institutes of Health (K30RR02229207, M01RR01066, Mallinckrodt General Clinical Research Center at Massachusetts General Hospital; and R01DK076116 to Dr Wolf). NR 49 TC 14 Z9 15 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 JAN PY 2013 VL 61 IS 1 BP 67 EP 73 DI 10.1053/j.ajkd.2012.06.022 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 054TE UT WOS:000312365500013 PM 22883134 ER PT J AU Ma, A Goetz, MB AF Ma, Andrew Goetz, Matthew Bidwell TI Capnocytophaga canimorsus Sepsis With Associated Thrombotic Thrombocytopenic Purpura SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Zoonoses; Thrombotic thrombocytopenic purpura; Capnocytophaga; Sepsis ID HEMOLYTIC-UREMIC SYNDROME; VON-WILLEBRAND-FACTOR; INFECTIONS; SEPTICEMIA; DOG AB Capnocytophaga canimorsus, a bacterium commonly transmitted via dog bites, is known to cause sepsis in immunocompromised patients. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are rare complications of infection. The authors present a case of C canimorsus sepsis and thrombotic thrombocytopenic purpura in an asplenic patient and review the relevant literature. C1 [Ma, Andrew] Cedars Sinai Med Ctr, Dept Internal Med, Los Angeles, CA 90048 USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Goetz, Matthew Bidwell] VA Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. RP Ma, A (reprint author), Cedars Sinai Med Ctr, Dept Internal Med, 8700 Beverly Blvd,Room 5512, Los Angeles, CA 90048 USA. EM Andrew.Ma@cshs.org OI Goetz, Matthew/0000-0003-4542-992X NR 16 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD JAN PY 2013 VL 345 IS 1 BP 78 EP 80 DI 10.1097/MAJ.0b013e318262db1a PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 058OS UT WOS:000312644000018 PM 22990045 ER PT J AU Grijalva, JL Huizenga, MN Sangrey, GR Das, S Kim, HB Sadri-Vakili, G Vakili, K AF Grijalva, James L. Huizenga, Megan N. Sangrey, Gavin R. Das, Sudeshna Kim, Heung Bae Sadri-Vakili, Ghazaleh Vakili, Khashayar TI Posttranslational Modifications of STAT3 during Liver Regeneration SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th Annual State of the Art Winter Symposium of the American-Society-of-Transplant-Surgeons (ASTS) Held in Conjunction with the NATCO Symposium for Advanced Transplant Professionals CY JAN 31-FEB 03, 2013 CL Miami, FL SP Amer Soc Transplant Surg (ASTS), NATCO C1 [Grijalva, James L.; Kim, Heung Bae; Vakili, Khashayar] Boston Childrens Hosp, Dept Surg, Boston, MA USA. [Das, Sudeshna] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Huizenga, Megan N.; Sangrey, Gavin R.; Sadri-Vakili, Ghazaleh] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Boston, MA 02114 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2013 VL 13 SU 2 SI SI BP 86 EP 86 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 057CT UT WOS:000312540200097 ER PT J AU Martins, PN Yeh, H Mcdaid, J Cosimi, B Hertl, M Markmann, JF AF Martins, Paulo N. Yeh, Heidi Mcdaid, James Cosimi, Ben Hertl, Martin Markmann, James F. TI Biliary Complications after Liver Transplantation from Donors after Cardiac Death (DCD) SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th Annual State of the Art Winter Symposium of the American-Society-of-Transplant-Surgeons (ASTS) Held in Conjunction with the NATCO Symposium for Advanced Transplant Professionals CY JAN 31-FEB 03, 2013 CL Miami, FL SP Amer Soc Transplant Surg (ASTS), NATCO C1 [Martins, Paulo N.; Yeh, Heidi; Mcdaid, James; Cosimi, Ben; Hertl, Martin; Markmann, James F.] Harvard Univ, Sch Med, Dept Surg, Div Transplantat,Massachusetts Gen Hosp, Boston, MA 02115 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2013 VL 13 SU 2 SI SI BP 87 EP 88 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 057CT UT WOS:000312540200103 ER PT J AU Yeh, H Markmann, JF Hunsicker, LG AF Yeh, Heidi Markmann, James F. Hunsicker, Lawrence G. TI Determinants of Liver Transplant Wait List Size SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th Annual State of the Art Winter Symposium of the American-Society-of-Transplant-Surgeons (ASTS) Held in Conjunction with the NATCO Symposium for Advanced Transplant Professionals CY JAN 31-FEB 03, 2013 CL Miami, FL SP Amer Soc Transplant Surg (ASTS), NATCO C1 [Yeh, Heidi; Markmann, James F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hunsicker, Lawrence G.] Univ Iowa, Coll Med, Iowa City, IA 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2013 VL 13 SU 2 SI SI BP 93 EP 93 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 057CT UT WOS:000312540200122 ER PT J AU Taylor, NE Chemali, JJ Brown, EN Solt, K AF Taylor, Norman E. Chemali, Jessica J. Brown, Emery N. Solt, Ken TI Activation of D1 Dopamine Receptors Induces Emergence from Isoflurane General Anesthesia SO ANESTHESIOLOGY LA English DT Article ID TEGMENTAL AREA NEURONS; FREELY MOVING CATS; SLEEP-WAKING CYCLE; BASAL GANGLIA; RATS; SKF-38393; AGONISTS; AROUSAL; INVOLVEMENT; DEPRESSION AB Background: A recent study showed that methylphenidate induces emergence from isoflurane anesthesia. Methylphenidate inhibits dopamine and norepinephrine reuptake transporters. The objective of this study was to test the hypothesis that selective dopamine receptor activation induces emergence from isoflurane anesthesia. Methods: In adult rats, we tested the effects of chloro-APB (D1 agonist) and quinpirole (D2 agonist) on time to emergence from isoflurane general anesthesia. We then performed a dose-response study to test for chloro-AP-Binduced restoration of righting during continuous isoflurane anesthesia. SCH-23390 (D1 antagonist) was used to confirm that the effects induced by chloro-APB are specifically mediated by D1 receptors. In a separate group of animals, spectral analysis was performed on surface electroencephalogram recordings to assess neurophysiologic changes induced by chloro-APB and quinpirole during isoflurane general anesthesia. Results: Chloro-APB decreased median time to emergence from 330 to 50 s. The median difference in time to emergence between the saline control group (n = 6) and the chloro-APB group (n = 6) was 222 s (95% CI: 77-534 s, Mann-Whitney test). This difference was statistically significant (P = 0.0082). During continuous isoflurane anesthesia, chloro-APB dose-dependently restored righting (n = 6) and decreased electroencephalogram delta power (n = 4). These effects were inhibited by pretreatment with SCH-23390. Quinpirole did not restore righting (n = 6) and had no significant effect on the electroencephalogram (n = 4) during continuous isoflurane anesthesia. Conclusions: Activation of D1 receptors by chloro-APB decreases time to emergence from isoflurane anesthesia and produces behavioral and neurophysiologic evidence of arousal during continuous isoflurane anesthesia. These findings suggest that selective activation of a D1 receptor-mediated arousal mechanism is sufficient to induce emergence from isoflurane general anesthesia. C1 [Taylor, Norman E.; Chemali, Jessica J.; Brown, Emery N.; Solt, Ken] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Solt, K (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,GRB 444, Boston, MA 02114 USA. EM ksolt@partners.org OI Solt, Ken/0000-0001-5328-2062 FU National Institutes of Health, Bethesda, Maryland [DP1-OD003646, K08-GM094394]; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts FX Received from the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. Submitted for publication April 10, 2012. Accepted for publication August 28, 2012. Supported by grants DP1-OD003646 and K08-GM094394 from the National Institutes of Health, Bethesda, Maryland, and the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. This work has been presented, in part, at annual meetings of the Society for Anesthesia and Sleep Medicine, Chicago, Illinois, October 14, 2011, the American Society of Anesthesiologists, Chicago, Illinois, October 15, 2011, and the Society for Neuroscience, Washington, D.C., November 13, 2011. NR 44 TC 28 Z9 29 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 2013 VL 118 IS 1 BP 30 EP 39 DI 10.1097/ALN.0b013e318278c896 PG 10 WC Anesthesiology SC Anesthesiology GA 057BM UT WOS:000312536800008 PM 23221866 ER PT J AU Parker, SJ Gallo, EJ Lindsay, M Van Eyk, JJ Dietz, HJ AF Parker, Sarah J. Gallo, Elena J. Lindsay, Mark Van Eyk, Jennifer J. Dietz, Hal J. TI Smooth muscle cell lineage heterogeneity in the aorta: Preliminary data on TGF beta signaling SO ANGIOGENESIS LA English DT Meeting Abstract C1 [Parker, Sarah J.; Gallo, Elena J.; Van Eyk, Jennifer J.; Dietz, Hal J.] Johns Hopkins Univ, Baltimore, MD USA. [Lindsay, Mark] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0969-6970 J9 ANGIOGENESIS JI Angiogenesis PD JAN PY 2013 VL 16 IS 1 BP 251 EP 251 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 058UA UT WOS:000312658800045 ER PT J AU Stylianopoulos, T Soteriou, K Fukumura, D Jain, RK AF Stylianopoulos, Triantafyllos Soteriou, Konstantinos Fukumura, Dai Jain, Rakesh K. TI Cationic Nanoparticles Have Superior Transvascular Flux into Solid Tumors: Insights from a Mathematical Model SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE Vascular permeability; Electrostatic and hydrodynamic interactions; Surface charge density; Nanomedicine; Cancer therapy ID VASCULAR-PERMEABILITY; MICROVASCULAR PERMEABILITY; INTERSTITIAL TRANSPORT; EXTRACELLULAR-MATRIX; NEOPLASTIC TISSUES; BLOOD-FLOW; DELIVERY; PENETRATION; IMPROVES; THERAPY AB Despite their great promise, only a few nanoparticle formulations have been approved for clinical use in oncology. The failure of nano-scale drugs to enhance cancer therapy is in large part due to inefficient delivery. To overcome this outstanding problem, a better understanding of how the physical properties (i.e., size, surface chemistry, and shape) of nanoparticles affect their transvascular transport in tumors is required. In this study, we developed a mathematical model for nanoparticle delivery to solid tumors taking into account electrostatic interactions between the particles and the negatively-charged pores of the vessel wall. The model predictions suggest that electrostatic repulsion has a minor effect on the transvascular transport of nanoparticles. On the contrary, electrostatic attraction, caused even by small cationic charges (surface charge density less than 3 x 10(-3) C/m(2)) can lead to a twofold or more increase in the transvascular flux of nanoparticles into the tumor interstitial space. Importantly, for every nanoparticle size, there is a value of charge density above which a steep increase in transvascular transport is predicted. Our model provides important guidelines for the optimal design of nanoparticle formulation for delivery to solid tumors. C1 [Stylianopoulos, Triantafyllos; Soteriou, Konstantinos] Univ Cyprus, Dept Mech & Mfg Engn, CY-1678 Nicosia, Cyprus. [Fukumura, Dai; Jain, Rakesh K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. RP Stylianopoulos, T (reprint author), Univ Cyprus, Dept Mech & Mfg Engn, CY-1678 Nicosia, Cyprus. EM tstylian@ucy.ac.cy; jain@steele.mgh.harvard.edu OI Stylianopoulos, Triantafyllos/0000-0002-3093-1696 FU Dyax; Med-Immune; Roche; Enlight; Noxxon; SynDevRx; Marie-Curie International Reintegration Grant [PIRG08-GA-2010-276894]; National Cancer Institute [P01-CA080124, R01-CA126642, R01-CA115767, R01-CA096915, R01-CA085140, R01-CA098706, T32-CA073479]; DoD [W81XWH-10-1-0016] FX R.K.J. received research grants from Dyax, Med-Immune and Roche; consultant fees from Dyax, Enlight, Noxxon and SynDevRx; owns equity in Enlight, SynDevRx and XTuit, serves on the Board of Directors of XTuit and Board of Trustees of H&Q Capital Management. No reagents or funding from these companies was used in these studies. Therefore, there is no significant financial or other competing interest in the work. The other authors declare no competing financial interests.; The authors thank Dr. Vikash Chauhan for his insightful comments on the manuscript. This work was supported by a Marie-Curie International Reintegration Grant (No. PIRG08-GA-2010-276894), the National Cancer Institute (P01-CA080124, R01-CA126642, R01-CA115767, R01-CA096915, R01-CA085140, R01-CA098706, T32-CA073479, Federal Share Proton Beam Program Income Grant), and a DoD Breast Cancer Research Innovator award (W81XWH-10-1-0016). NR 45 TC 26 Z9 27 U1 3 U2 68 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6964 EI 1573-9686 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD JAN PY 2013 VL 41 IS 1 BP 68 EP 77 DI 10.1007/s10439-012-0630-4 PG 10 WC Engineering, Biomedical SC Engineering GA 057QM UT WOS:000312578100008 PM 22855118 ER PT J AU Adler, N Pantell, MS O'Donovan, A Blackburn, E Cawthon, R Koster, A Opresko, P Newman, A Harris, TB Epel, E AF Adler, Nancy Pantell, Matthew S. O'Donovan, Aoife Blackburn, Elizabeth Cawthon, Richard Koster, Annemarie Opresko, Patricia Newman, Anne Harris, Tamara B. Epel, Elissa TI Educational attainment and late life telomere length in the Health, Aging and Body Composition Study SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE Socioeconomic status; Education; Telomere length; Race; Health disparities ID UNITED-STATES; SOCIOECONOMIC-STATUS; MORTALITY; DISPARITIES; STRESS; BLOOD; AGE; RACE/ETHNICITY; ASSOCIATION; EXPECTANCY AB Morbidity and mortality are greater among socially disadvantaged racial/ethnic groups and those of lower socioeconomic status (SES). Greater chronic stress exposure in disadvantaged groups may contribute to this by accelerating cellular aging, indexed by shorter age-adjusted telomere length. While studies consistently relate shorter leukocyte telomere length (LTL) to stress, the few studies, mostly from the UK, examining associations of LTL with SES have been mixed. The current study examined associations between educational attainment and LTL among 2599 high-functioning black and white adults age 70-79 from the Health, Aging and Body Composition Study. Multiple regression analyses tested associations of race/ethnicity, educational attainment and income with LTL, adjusting for potential confounders. Those with only a high school education had significantly shorter mean LTL (4806 basepairs) than those with post-high school education (4926 basepairs; B = 125, SE = 47.6, p =.009). A significant interaction of race and education (B = 207.8, SE = 98.7, p =.035) revealed more beneficial effects of post-high school education for blacks than for whites. Smokers had shorter LTL than non-smokers, but the association of education and LTL remained significant when smoking was covaried (B = 119.7, SE = 47.6, p = 012). While higher income was associated with longer LTL, the effect was not significant (p > .10). This study provides the first demonstration of an association between educational attainment and LTL in a US population where higher education appears to have a protective effect against telomere shortening, particularly in blacks. (C) 2012 Elsevier Inc. All rights reserved. C1 [Adler, Nancy; O'Donovan, Aoife; Blackburn, Elizabeth; Epel, Elissa] Univ Calif San Francisco, San Francisco, CA 94143 USA. [O'Donovan, Aoife] San Francisco VA Med Ctr, San Francisco, CA USA. [Cawthon, Richard] Univ Utah, Salt Lake City, UT 84112 USA. [Koster, Annemarie; Harris, Tamara B.] NIA, Bethesda, MD 20892 USA. [Opresko, Patricia; Newman, Anne] Univ Pittsburgh, Pittsburgh, PA 15260 USA. RP Adler, N (reprint author), 3333 Calif St,Ste 465, San Francisco, CA 94143 USA. EM nancy.adler@ucsf.edu RI Newman, Anne/C-6408-2013; Koster, Annemarie/E-7438-2010; OI Newman, Anne/0000-0002-0106-1150; Opresko, Patricia/0000-0002-6470-2189 FU NIH, National Institute on Aging; National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; NINR [R01-NR012459] FX The authors thank the Health ABC Study staff at the Pittsburgh and Memphis study sites and at the UCSF Coordinating Center, as well as the Health ABC Study participants for their time and efforts. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. The study was conducted on behalf of the Health, Aging and Body Composition (Health ABC) Study and was funded National Institute on Aging (NIA) Contracts N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA grant R01-AG028050, and NINR Grant R01-NR012459. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 26 Z9 29 U1 1 U2 27 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 JAN PY 2013 VL 27 BP 15 EP 21 DI 10.1016/j.bbi.2012.08.014 PG 7 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 058JE UT WOS:000312629100004 PM 22981835 ER PT J AU Mendez, MF Owens, EM Jimenez, EE Peppers, D Licht, EA AF Mendez, Mario F. Owens, Emily M. Jimenez, Elvira E. Peppers, Dominique Licht, Eliot A. TI Changes in personality after mild traumatic brain injury from primary blast vs. blunt forces SO BRAIN INJURY LA English DT Article DE Traumatic brain injury; concussion; blast forces; blunt forces; personality ID PERSISTENT POSTCONCUSSIVE SYMPTOMS; POSTTRAUMATIC-STRESS-DISORDER; SYSTEMS BEHAVIOR SCALE; IRAQ WAR VETERANS; INTERPERSONAL-BEHAVIOR; ASSESSMENT INVENTORY; EXPLOSIVE BLAST; SERVICE MEMBERS; MECHANISMS; TBI AB Introduction: Injuries from explosive devices can cause blast-force injuries, including mild traumatic brain injury (mTBI). Objective: This study investigated changes in personality from blast-force mTBI in comparison to blunt-force mTBI. Methods: Clinicians and significant others assessed US veterans who sustained pure blast-force mTBI (n = 12), as compared to those who sustained pure blunt-force mTBI (n = 12). Inclusion criteria included absence of any mixed blast-blunt trauma and absence of post-traumatic stress disorder. Measures included the Interpersonal Measure of Psychopathy (IMP), the Big Five Inventory (BFI), the Interpersonal Adjectives Scale (IAS) and the Frontal Systems Behaviour Scale (FrSBe). Results: There were no group differences on demographic or TBI-related variables. Compared to the Blunt Group, the Blast Group had more psychopathy on the IM-P, with anger, frustration, toughness and boundary violations and tended to more neuroticism on the BFI. When pre-TBI and post-TBI assessments were compared on the IAS and FrSBe, only the patients with blast force mTBI had become more cold-hearted, aloof-introverted and apathetic. Conclusion: These results suggest that blast forces alone can cause negativistic behavioural changes when evaluated with selected measures of personality. Further research on isolated blast-force mTBI should focus on these personality changes and their relationship to blast over-pressure. C1 [Mendez, Mario F.; Owens, Emily M.; Jimenez, Elvira E.] 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.; Licht, Eliot A.] VA Greater Los Angeles Healthcare Ctr, Neurol Sect, Los Angeles, CA 90073 USA. [Peppers, Dominique] VA Greater Los Angeles Healthcare Ctr, Sect Phys Med & Rehabil, Los Angeles, CA 90073 USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit 691 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@UCLA.edu FU Veterans Affairs Administration FX This research was made possible by a grant from the Veterans Affairs Administration. NR 68 TC 6 Z9 7 U1 6 U2 41 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 EI 1362-301X J9 BRAIN INJURY JI Brain Inj. PD JAN PY 2013 VL 27 IS 1 BP 10 EP 18 DI 10.3109/02699052.2012.722252 PG 9 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 059IY UT WOS:000312699300002 PM 23252434 ER PT J AU Moghanaki, D Koontz, BF Karlin, JD Wan, W Mukhopadhay, N Hagan, MP Anscher, MS AF Moghanaki, Drew Koontz, Bridget F. Karlin, Jeremy D. Wan, Wen Mukhopadhay, Nitai Hagan, Michael P. Anscher, Mitchell S. TI Elective irradiation of pelvic lymph nodes during postprostatectomy salvage radiotherapy SO CANCER LA English DT Article DE prostate cancer; radiotherapy; lymph nodes; salvage radiotherapy; elective lymph node; whole pelvis; pelvic lymph nodes; prostatectomy; postprostatectomy; biochemical relapse ID PROSTATE-SPECIFIC ANTIGEN; CONFORMAL RADIATION-THERAPY; RELAPSE-FREE SURVIVAL; BIOCHEMICAL RECURRENCE; RADICAL PROSTATECTOMY; PATHOLOGICAL STAGE; CANCER; RISK; ADENOCARCINOMA; FAILURE AB BACKGROUND: Success rates with salvage radiotherapy (SRT) in men who have a postprostatectomy biochemical relapse are suboptimal. One treatment-intensification strategy includes elective irradiation of the pelvic lymph nodes with whole pelvis radiotherapy (WPRT). METHODS: An inter-institutional retrospective cohort study compared outcomes for patients who received SRT at 2 separate academic institutions with disparate treatment paradigms: almost exclusively favoring WPRT (n = 112) versus limiting treatment to the prostate bed (PBRT) (n = 135). Patients were excluded if they had lymph node involvement or if they received androgen-deprivation therapy. The Cox proportional hazards model was used to adjust for potential confounders. RESULTS: In total, 247 patients were analyzed with a median follow-up of 4 years. The pre-SRT prostate-specific antigen (PSA) level (adjusted hazard ratio [HR], 1.58; P < .0001) and a Gleason score of 8 to 10 (adjusted HR, 3.21; P < .0001) were identified as independent predictors of increased risk of biochemical PSA progression after SRT. However, WPRT was not independently associated with biochemical progression-free survival in the multivariate model (adjusted HR, 0.79; P = .20). Neither low-risk patients nor high-risk patients (defined a priori by a preoperative PSA level =20 ng/mL, a pathologic Gleason score between 8 and 10, or pathologic T3 tumor classification) benefited from WPRT. Overall survival was similar between treatment groups. When restricting the analysis to patients with pre-SRT PSA levels =0.4 ng/mL (n = 139), WPRT was independently associated with a 53% reduction in the risk of biochemical progression (adjusted HR, 0.47; P = .031). CONCLUSIONS: WPRT did not improve outcomes among the entire group but was independently associated with improved biochemical control among patients with pre-SRT PSA levels =0.4 ng/mL. Cancer 2013. (c) 2012 American Cancer Society. C1 [Moghanaki, Drew; Karlin, Jeremy D.; Hagan, Michael P.; Anscher, Mitchell S.] Virginia Commonwealth Univ, Dept Radiat Oncol, Richmond, VA 23291 USA. [Moghanaki, Drew; Hagan, Michael P.] Hunter Holmes McGuire Vet Affairs Med Ctr, Radiat Oncol Serv, Richmond, VA USA. [Koontz, Bridget F.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA. [Wan, Wen; Mukhopadhay, Nitai] Virginia Commonwealth Univ, Dept Biostat, Richmond, VA 23291 USA. [Hagan, Michael P.] US Dept Vet Affairs, Natl Radiat Oncol Program, Richmond, VA USA. RP Moghanaki, D (reprint author), Virginia Commonwealth Univ, Dept Radiat Oncol, POB 91734, Richmond, VA 23291 USA. EM dmoghanaki@vcu.edu OI Anscher, Mitchell/0000-0003-4480-111X NR 19 TC 16 Z9 16 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JAN 1 PY 2013 VL 119 IS 1 BP 52 EP 60 DI 10.1002/cncr.27712 PG 9 WC Oncology SC Oncology GA 057DT UT WOS:000312543000010 PM 22736478 ER PT J AU Stock, W Johnson, JL Stone, RM Kolitz, JE Powell, BL Wetzler, M Westervelt, P Marcucci, G DeAngelo, DJ Vardiman, JW McDonnell, D Mrozek, K Bloomfield, CD Larson, RA AF Stock, Wendy Johnson, Jeffrey L. Stone, Richard M. Kolitz, Jonathan E. Powell, Bayard L. Wetzler, Meir Westervelt, Peter Marcucci, Guido DeAngelo, Daniel J. Vardiman, James W. McDonnell, Diane Mrozek, Krzysztof Bloomfield, Clara D. Larson, Richard A. TI Dose intensification of daunorubicin and cytarabine during treatment of adult acute lymphoblastic leukemia Results of cancer and leukemia group B study 19802 SO CANCER LA English DT Article DE adults with acute lymphoblastic leukemia; phase 2 study; dose intensification; daunorubicin; cytarabine; central nervous system prophylaxis ID ACUTE LYMPHOCYTIC-LEUKEMIA; PROSPECTIVE RANDOMIZED TRIAL; CRANIAL IRRADIATION; YOUNG-ADULTS; FRACTIONATED CYCLOPHOSPHAMIDE; HYPER-CVAD; RISK; ADOLESCENTS; CHILDREN; REGIMEN AB BACKGROUND: Cancer and Leukemia Group B (CALGB) Study 19802, a phase 2 study, evaluated whether dose intensification of daunorubicin and cytarabine could improve disease-free survival (DFS) in adults with acute lymphoblastic leukemia (ALL) and whether high-dose systemic and intrathecal methotrexate could replace cranial radiotherapy for central nervous system (CNS) prophylaxis. METHODS: One hundred sixty-one eligible, previously untreated patients ages 16 to 82 years (median age, 40 years) were enrolled, and 33 (20%) were aged =60 years. RESULTS: One hundred twenty-eight patients (80%) achieved complete remission (CR). Dose intensification of daunorubicin and cytarabine was feasible. At a median follow-up of 10.4 years for surviving patients, the 5-year DFS rate was 25% (95% confidence interval, 18%-33%), and the overall survival (OS) rate was 30% (95% confidence interval, 23%-37%). Patients aged <60 years who received the 80 mg/m2 dose of daunorubicin had a DFS of 33% (95% confidence interval, 22%-44%) and an OS of 39% (95% confidence interval, 29%-49%) at 5 years. Eighty-four patients (52%) relapsed, including 9 patients (6%) who had isolated CNS relapses. The omission of cranial irradiation did not result in higher than historic CNS relapse rates. CONCLUSIONS: Intensive systemic, oral, and intrathecal methotrexate dosing permitted the omission of CNS irradiation in adult patients with ALL. This intensive approach using higher doses of daunorubicin and cytarabine failed to result in an overall improvement in DFS or OS compared with historic CALGB studies. Future therapeutic strategies for adults with ALL should be tailored to specific age and molecular genetic subsets. Cancer 2013. (c) 2012 American Cancer Society. C1 [Stock, Wendy; Vardiman, James W.; McDonnell, Diane; Larson, Richard A.] Univ Chicago, Chicago, IL 60637 USA. [Stock, Wendy; Vardiman, James W.; McDonnell, Diane; Larson, Richard A.] Ctr Comprehens Canc, Chicago, IL USA. [Johnson, Jeffrey L.] Duke Univ, Canc & Leukemia Grp B, Stat Off, Durham, NC USA. [Stone, Richard M.; DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kolitz, Jonathan E.] N Shore Univ, Dept Med, Manhasset, NY USA. [Powell, Bayard L.] Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. [Marcucci, Guido; Mrozek, Krzysztof; Bloomfield, Clara D.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Wetzler, Meir] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Westervelt, Peter] Washington Univ, Siteman Comprehens Canc Ctr, St Louis, MO USA. RP Stock, W (reprint author), Univ Chicago Hosp, 5841 S Maryland,M-C 2115, Chicago, IL 60637 USA. EM wstock@medicine.bsd.uchicago.edu RI Mrozek, Krzysztof/A-3142-2008; OI Larson, Richard/0000-0001-9168-3203 FU National Cancer Institute [CA31946, CA33601, CA41287, CA32291, CA35279, CA03927, CA02599, CA101140, CA77658]; Coleman Leukemia Research Foundation; University of Chicago Comprehensive Cancer Center FX This work was supported in part by National Cancer Institute grants CA31946, CA33601, CA41287, CA32291, CA35279, CA03927, CA02599, CA101140, and CA77658; by the Coleman Leukemia Research Foundation; and by the University of Chicago Comprehensive Cancer Center. NR 37 TC 29 Z9 30 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JAN 1 PY 2013 VL 119 IS 1 BP 90 EP 98 DI 10.1002/cncr.27617 PG 9 WC Oncology SC Oncology GA 057DT UT WOS:000312543000014 PM 22744771 ER PT J AU Vickers, AJ Bennette, C Kibel, AS Black, A Izmirlian, G Stephenson, AJ Bochner, B AF Vickers, Andrew J. Bennette, Caroline Kibel, Adam S. Black, Amanda Izmirlian, Grant Stephenson, Andrew J. Bochner, Bernard TI Who should be included in a clinical trial of screening for bladder cancer? A decision analysis of data from the prostate, lung, colorectal, and ovarian cancer screening trial SO CANCER LA English DT Article DE bladder cancer; screening; tobacco; clinical trials; research design ID HEMATURIA; MEN; RISK; PRESENTATIONS AB BACKGROUND: Because of its relatively low incidence, bladder cancer screening might have a better ratio of benefits to harms if it is restricted to a high-risk population. Data from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial were used and simple decision analytic techniques were applied to compare different eligibility criteria for a screening trial. METHODS: For a variety of possible eligibility criteria, the percentage of the population aged 55 years to 74 years and classified as being at high risk for developing invasive or high-grade carcinoma, and therefore likely to benefit from screening, was calculated. Regression models were used to calculate a risk score based on age, sex, smoking history, and family history of bladder cancer. The reduction in cases was calculated given hypothetical risk reductions associated with screening. The trade-off between patients screened and tumors avoided was calculated as a net benefit. RESULTS: The 5-year probability of being diagnosed with invasive bladder cancer was 0.24%. Using a risk score > 6 or > 8 as the eligibility criterion for a trial was generally superior to including all older adults. In a typical scenario, a risk score > 6 would result in approximately 25% of the population being screened to prevent 57 invasive or high-grade bladder cancers per 100,000 population; screening the entire population would prevent only an additional 38 cases. CONCLUSIONS: Screening for bladder cancer can be optimized by restricting it to a subgroup of patients considered to be at elevated risk. Different eligibility criteria for a screening trial can be compared rationally using decision-analytic techniques. Cancer 2013. (c) 2012 American Cancer Society. C1 [Vickers, Andrew J.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Bennette, Caroline] Univ Washington, Pharmaceut Outcomes Res & Policy Program, Seattle, WA 98195 USA. [Kibel, Adam S.] Brigham & Womens Hosp, Dept Urol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Black, Amanda] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Izmirlian, Grant] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Stephenson, Andrew J.] Cleveland Clin, Dept Urol, Cleveland, OH 44106 USA. [Bochner, Bernard] Mem Sloan Kettering Canc Ctr, Dept Urol, New York, NY 10021 USA. RP Vickers, AJ (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 1275 York Ave, New York, NY 10021 USA. EM vickersa@mskcc.org OI Vickers, Andrew/0000-0003-1525-6503 FU Prostate Cancer Foundation; Sidney Kimmel Center for Prostate and Urologic Cancers; SPORE grant from the National Cancer Institute [P50-CA92629] FX Supported in part by funds from David H. Koch provided through the Prostate Cancer Foundation, the Sidney Kimmel Center for Prostate and Urologic Cancers, and a P50-CA92629 SPORE grant from the National Cancer Institute to Dr. P. T. Scardino. NR 16 TC 9 Z9 9 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JAN 1 PY 2013 VL 119 IS 1 BP 143 EP 149 DI 10.1002/cncr.27692 PG 7 WC Oncology SC Oncology GA 057DT UT WOS:000312543000020 PM 22736219 ER PT J AU Partridge, AH Norris, VW Blinder, VS Cutter, BA Halpern, MT Malin, J Neuss, MN Wolff, AC AF Partridge, Ann H. Norris, Virginia W. Blinder, Victoria S. Cutter, Bruce A. Halpern, Michael T. Malin, Jennifer Neuss, Michael N. Wolff, Antonio C. CA ASCO Breast Canc Registry Pilot St TI Implementing a breast cancer registry and treatment plan/summary program in clinical practice: A pilot program SO CANCER LA English DT Article DE treatment plan; treatment summary; quality of care; quality assessment; breast cancer ID PRIMARY-CARE PHYSICIANS; ONCOLOGY PRACTICE; SURVIVORSHIP CARE; PRACTICE GUIDELINES; FOLLOW-UP; QUALITY; PERSPECTIVES; PROVIDERS; PLANS AB BACKGROUND: There is a need to better measure and improve the quality of oncology care and improve communication with patients and other providers. The American Society of Clinical Oncology Breast Cancer Registry (BCR) pilot evaluated the feasibility and acceptability of prospective data collection for quality assessment in daily clinical practice. Data were used to create and share treatment plans/summaries (TPSs) at the point of care. METHODS: Using a web-based tool, 20 diverse practices entered clinical data on each new early-stage breast cancer patient into the BCR for 14 months (September 2009 through November 2010). The tool created individual TPSs that were shared with patients. Practices received practice-specific and aggregate BCR quality measures data, participated in a survey, and received a participation stipend. RESULTS: Twenty practices entered 2014 patients into the BCR, collecting demographic, clinical, and treatment information. Fifty-two percent of practice participants replied to an end-of-pilot survey: 73% were satisfied with the BCR and web-based tool, 31% expressed concern regarding time and effort, and 52% reported additional practice costs during the pilot. Among those who created or shared the TPSs, 90% thought the documents improved oncologist-patient communication, and 95% favored using BCR data for practice quality improvement. CONCLUSIONS: Prospective data collection for quality assessment is feasible and allows sharing of TPSs with patients at the point of care. Future efforts should focus on decreasing implementation burden to practices, broadening participation, examining costs, and, most importantly, assessing its effects on patient outcomes. Cancer 2013. (c) 2012 American Cancer Society. C1 [Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Norris, Virginia W.] Amer Soc Clin Oncol, Alexandria, VA USA. [Blinder, Victoria S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Partridge, Ann H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Cutter, Bruce A.] Grp Hlth Cooperat, Spokane, WA USA. [Halpern, Michael T.] RTI Int, Washington, DC USA. [Malin, Jennifer] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Malin, Jennifer] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Neuss, Michael N.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Wolff, Antonio C.] Johns Hopkins Kimmel Canc Ctr, Baltimore, MD USA. RP Partridge, AH (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM ahpartridge@partners.org OI Wolff, Antonio/0000-0003-3734-1063 FU Susan G. Komen for the Cure FX This research was funded by Susan G. Komen for the Cure (to the American Society of Clinical Oncology). NR 27 TC 4 Z9 4 U1 3 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JAN 1 PY 2013 VL 119 IS 1 BP 158 EP 163 DI 10.1002/cncr.27625 PG 6 WC Oncology SC Oncology GA 057DT UT WOS:000312543000022 PM 23197186 ER PT J AU Blinder, VS Norris, VW Peacock, NW Griggs, JJ Harrington, DP Moore, A Theriault, RL Partridge, AH AF Blinder, Victoria S. Norris, Virginia W. Peacock, Nancy W. Griggs, Jennifer J. Harrington, David P. Moore, Anne Theriault, Richard L. Partridge, Ann H. CA Amer Soc Clinical Oncology TI Patient perspectives on breast cancer treatment plan and summary documents in community oncology care A pilot program SO CANCER LA English DT Article DE survivorship; breast cancer; treatment plan; treatment summary; survivorship care plan ID SURVIVORSHIP CARE; FOLLOW-UP; PHYSICIANS; PROVIDERS; QUALITY AB BACKGROUND: Although the routine use of treatment plans and summaries (TPSs) has been recommended to improve the quality of cancer care, limited data exist about their impact on quality, including patient satisfaction and coordination of care. METHODS: Patients received TPSs as part of the American Society of Clinical Oncology Breast Cancer Registry (BCR) pilot program of 20 community oncology practices. Participants were surveyed 2 to 4 weeks after receiving a TPS to evaluate their perceptions of the document. Patients who were receiving chemotherapy received the TPS as separate plan and summary documents (at the start and the end of treatment) and could complete 2 surveys. Others received a single integrated TPS. Eligible survey participants had stage 0 through III breast cancer and were enrolled in the BCR. RESULTS: Of 292 consented patients, 174 (60%) completed at least 1 survey. Of 157 patients who recalled receiving a TPS, 148 (94%) believed that the documents improved patient-physician communication, and 128 (82%) believed that they improved communication between physicians; 113 (72%) said the documents increased their peace of mind, whereas 2 (1%) had less peace of mind. Of 152 patients (97%) who still had their documents, 147 (97%) said they were useful, and 94 (62%) had given or planned to give the documents to another physician. All 63 patients who were surveyed after receiving a summary recommended that practices continue to provide TPSs to patients. CONCLUSIONS: Participants in this study expressed high satisfaction with TPSs. Additional research is needed to study the broad-scale implementation of the BCR and to evaluate the impact of routine use of TPSs on the quality of care delivered. Cancer 2013. (c) 2012 American Cancer Society. C1 [Blinder, Victoria S.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, Ctr Hlth Policy & Outcomes, New York, NY 10065 USA. [Norris, Virginia W.] Amer Soc Clin Oncol, Alexandria, VA USA. [Peacock, Nancy W.] Tennessee Oncol PLLC, Nashville, TN USA. [Griggs, Jennifer J.] Univ Michigan, Sch Med, Dept Internal Med, Div Hematol Oncol, Ann Arbor, MI USA. [Harrington, David P.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Moore, Anne] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Theriault, Richard L.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. [Partridge, Ann H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Partridge, Ann H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Blinder, VS (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, Ctr Hlth Policy & Outcomes, 300 E 66th St,14th Floor, New York, NY 10065 USA. EM blinderv@mskcc.org FU Susan G. Komen for the Cure FX This research was funded by Susan G. Komen for the Cure. NR 24 TC 10 Z9 10 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JAN 1 PY 2013 VL 119 IS 1 BP 164 EP 172 DI 10.1002/cncr.27856 PG 9 WC Oncology SC Oncology GA 057DT UT WOS:000312543000023 PM 23197335 ER PT J AU Haas, L Maryniuk, M Beck, J Cox, CE Duker, P Edwards, L Fisher, EB Hanson, L Kent, D Kolb, L McLaughlin, S Orzeck, E Piette, JD Rhinehart, AS Rothman, R Sklaroff, S Tomky, D Tomky, D Youssef, G AF Haas, Linda Maryniuk, Melinda Beck, Joni Cox, Carla E. Duker, Paulina Edwards, Laura Fisher, Edwin B. Hanson, Lenita Kent, Daniel Kolb, Leslie McLaughlin, Sue Orzeck, Eric Piette, John D. Rhinehart, Andrew S. Rothman, Russell Sklaroff, Sara Tomky, Donna Tomky, Donna Youssef, Gretchen CA 2012 Standards Revision Task Force TI National Standards for Diabetes Self-Management Education and Support SO DIABETES CARE LA English DT Article ID RANDOMIZED-CONTROLLED-TRIAL; CHRONIC CARE MODEL; CHRONIC DISEASE MANAGEMENT; QUALITY-OF-LIFE; AFRICAN-AMERICAN; GLYCEMIC CONTROL; CLINICAL CHARACTERISTICS; MEDICARE BENEFICIARIES; REGISTERED DIETITIANS; COMPLICATIONS TRIAL C1 [Haas, Linda] VA Puget Sound Hlth Care Syst Hosp & Specialty Me, Seattle, WA USA. [Maryniuk, Melinda] Joslin Diabet Ctr, Boston, MA 02215 USA. [Beck, Joni] Univ Oklahoma, Hlth Sci Ctr, Coll Med, Edmond, OK USA. [Cox, Carla E.] Western Montana Clin, Missoula, MT USA. [Duker, Paulina] Amer Diabet Assoc, Diabet Educ Clin Programs, Alexandria, VA USA. [Edwards, Laura] Ctr Healthy N Carolina, Apex, NC USA. [Fisher, Edwin B.] Univ N Carolina, Amer Acad Family Phys Fdn, Peers Progress, Chapel Hill, NC USA. [Fisher, Edwin B.] Univ N Carolina, Dept Hlth Behav, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Hanson, Lenita] Ultracare Endocrine & Diabet Consultants, Venice, FL USA. [Kent, Daniel] Grp Hlth Cent Specialty Clin, Seattle, WA USA. [Kolb, Leslie] Amer Assoc Diabet Educators, Diabet Educ Accreditat Program, Chicago, IL USA. [McLaughlin, Sue] On Site Hlth & Wellness LLC, Omaha, NE USA. [Orzeck, Eric] Endocrinol Associates, Houston, TX USA. [Piette, John D.] VA Ctr Clin Management Res, Ann Arbor, MI USA. [Piette, John D.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Rhinehart, Andrew S.] Johnston Mem Diabet Care Ctr, Abingdon, VA USA. [Rothman, Russell] Vanderbilt Univ, Med Ctr, Ctr Hlth Serv Res, Nashville, TN USA. [Tomky, Donna] ABQ Hlth Partners, Dept Endocrinol & Diabet, Albuquerque, NM USA. [Youssef, Gretchen] MedStar Hlth, MedStar Diabet Inst, Washington, DC USA. RP Haas, L (reprint author), VA Puget Sound Hlth Care Syst Hosp & Specialty Me, Seattle, WA USA. EM linda.haas@va.gov; melinda.maryniuk@joslin.harvard.edu NR 161 TC 68 Z9 70 U1 4 U2 30 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2013 VL 36 SU 1 BP S100 EP S108 DI 10.2337/dc13-S100 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 062HB UT WOS:000312909000009 PM 23264420 ER PT J AU Nauck, M Horton, E Andjelkovic, M Ampudia-Blasco, FJ Parusel, CT Boldrin, M Balena, R AF Nauck, M. Horton, E. Andjelkovic, M. Ampudia-Blasco, F. J. Parusel, C. T. Boldrin, M. Balena, R. CA T-Emerge Study Grp TI Taspoglutide, a once-weekly glucagon-like peptide 1 analogue, vs. insulin glargine titrated to target in patients with Type 2 diabetes: an open-label randomized trial SO DIABETIC MEDICINE LA English DT Article ID HUMAN GLP-1 ANALOG; GLYCEMIC CONTROL; ASSOCIATION; EXENATIDE; METFORMIN; PLACEBO; SULFONYLUREA; STATEMENT; ALGORITHM; WEIGHT AB Aims To compare the efficacy and safety of once-weekly taspoglutide with insulin glargine in patients with advanced Type 2 diabetes failing metformin and sulphonylurea combination therapy. Methods This open-label, parallel-group, multi-centre trial randomized 1049 patients continuing metformin 1:1:1 to taspoglutide 10 mg once weekly, taspoglutide 20 mg once weekly or insulin glargine once daily with forced titration to fasting plasma glucose = 6.1 mmol/l. Sulphonylureas were discontinued before randomization. The primary endpoint was change in HbA1c after 24 weeks. Results After 24 weeks, least-square mean changes from baseline in HbA1c in patients receiving taspoglutide 10 mg [-8 mmol/mol (se 1)] [-0.77% (se 0.05)] or taspoglutide 20 mg [-11 mmol/mol (se 1)] [-0.98% (se 0.05)] were non-inferior to insulin glargine [-9 mmol/mol (se 1)] [-0.84% (se 0.05)]; treatment difference of 0.07% (95% CI -0.06 to 0.21) and -0.14% (95% CI -0.28 to -0.01), for taspoglutide 10 and 20 mg, respectively, vs. insulin glargine. Taspoglutide was associated with more adverse events (mainly gastrointestinal) and significantly less hypoglycaemia than insulin glargine. Conclusions Compared with insulin glargine, taspoglutide provided non-inferior HbA1c reductions associated with less hypoglycaemia, but more gastrointestinal adverse events. Diabet. Med. 30, 109-113 (2013) C1 [Nauck, M.] Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany. [Horton, E.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Andjelkovic, M.; Parusel, C. T.; Balena, R.] F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. [Ampudia-Blasco, F. J.] Clin Univ Hosp, Valencia, Spain. [Boldrin, M.] Roche Pharmaceut, Nutley, NJ USA. RP Nauck, M (reprint author), Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany. EM nauck@diabeteszentrum.de FU DIABATE/Boehringer-Ingelheim; MSD; Incretin Expert Program/Lilly Deutschland GmbH; Medscape LLC; Berlin Chemie AG; Eli Lilly; Novartis Pharma; AstraZeneca; Boehringer-Ingelheim; GlaxoSmithKline; Lilly Deutschland; MetaCure Inc; Roche Pharma AG; Novo Nordisk; Tolerx Inc; Amylin; F. Hoffmann-La Roche AG, Basel, Switzerland FX MN has received consulting and/or advisory board honoraria from F. Hoffmann-La Roche, Boehringer-Ingelheim, Eli Lilly, GlaxoSmithKline, Janssen Global Services, MSD, Novartis Pharma, Novo Nordisk, Sanofi-Aventis, Takeda, Versartis, AstraZeneca and Berlin Chemie AG; honoraria for lectures from Novo Nordisk, Berlin Chemie AG, Lilly Deutschland GmbH, MSD, Boehringer-Ingelheim, AstraZeneca, Roche Pharma AG and Novartis Pharma; payment for development of educational presentations from DIABATE/Boehringer-Ingelheim, MSD, Incretin Expert Program/Lilly Deutschland GmbH and Medscape LLC; and institutional grants from Berlin Chemie AG, Eli Lilly, MSD, Novartis Pharma, AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Lilly Deutschland, MetaCure Inc, Roche Pharma AG, Novo Nordisk and Tolerx Inc. EH has received research grants from Amylin and Eli Lilly and honoraria for lectures from Merck, and serves on advisory boards or is a consultant for Amylin, Boehringer-Ingelheim, ChemoCentryx, GI Dynamics, Gilead Sciences, MacroGenics, Medtronic, Merck & Co., Roche, Takeda NA and Theracos. FJA-B has received honoraria for board membership from the Clinic University Hospital, Valencia, Spain. RB is an employee of Eli Lilly and Company Ltd. and is a shareholder and previous employee of F. Hoffman-La Roche. CTP, MA and MB are employees and shareholders of F. Hoffmann-La Roche.; Funding for this study was provided by F. Hoffmann-La Roche AG, Basel, Switzerland. The sponsor was involved in study design, data collection, data review and data analysis. The authors thank the study investigators, their staff, clinical trial personnel and the study participants. Study investigators are listed in the Supporting Information (Appendix S1). The authors also thank Neena Sarkar PhD from F. Hoffmann-La Roche for assistance with statistical analyses. All authors had full access to the data. MN had the final decision to submit the manuscript for publication and is the guarantor for its content. Support for third-party writing assistance for this manuscript, furnished by Giles Brooke PhD and Susan Sutch PharmD, Evidence Scientific Solutions Ltd, was provided by F. Hoffmann-La Roche. NR 13 TC 20 Z9 22 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD JAN PY 2013 VL 30 IS 1 BP 109 EP 113 DI 10.1111/dme.12003 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 057GD UT WOS:000312550100020 PM 22937895 ER PT J AU Lichtenhan, JT Cooper, NP Guinan, JJ AF Lichtenhan, Jeffery T. Cooper, Nigel P. Guinan, John J., Jr. TI A New Auditory Threshold Estimation Technique for Low Frequencies: Proof of Concept SO EAR AND HEARING LA English DT Article ID BRAIN-STEM RESPONSE; OTOACOUSTIC EMISSION MEASUREMENTS; TUNING CURVES; NERVE FIBERS; ROUND WINDOW; HAIR-CELLS; GUINEA-PIG; COCHLEAR NERVE; PHASE-LOCKING; HEARING AB Objectives: Presently available nonbehavioral methods to estimate auditory thresholds perform less well at frequencies below 1 kHz than at 1 kHz and above. For many uses, such as providing accurate infant hearing aid amplification for low-frequency vowels, an accurate nonbehavioral method to estimate low-frequency thresholds is needed. A novel technique was developed to estimate low-frequency cochlear thresholds based on the use of a previously reported waveform. It was determined how well the method worked by comparing the resulting thresholds to thresholds from onset-response compound action potentials (CAPs) and single-auditory-nerve (AN)- fibers in cats. A long-term goal is to translate this technique for use in humans. Design: An electrode near the cochlea records a combination of cochlear microphonic (CM) and neural responses. In response to low-frequency, near threshold-level tones, the CM is almost sinusoidal whereas the neural responses occur preferentially at one phase of the tone. If the tone is presented again but with its polarity reversed, the neural response keeps the same shape, but shifts 1/2 cycle in time. Averaging responses to tones presented separately at opposite polarities overlaps and interleaves the neural responses and yields a waveform in which the CM is canceled and the neural response appears twice each tone cycle, that is, the resulting neural response is mostly at twice the tone frequency. The resultant waveform is referred to as "the auditory nerve overlapped waveform" (ANOW). In this study, ANOW level functions were measured in anesthetized cats from 10 to 80 dB SPL in 10 dB steps using tones between 0.3 and 1 kHz. As a response metric, the magnitude of the ANOW component was calculated at twice the tone frequency (ANOW2f). The ANOW threshold was the sound level where the interpolated ANOW2f crossed a statistical criterion that was higher than 95% of the noise floor distribution. ANOW thresholds were compared with onset-CAP thresholds from the same recordings and single-AN-fiber thresholds from the same animals. Results: ANOW and onset-CAP level functions were obtained for 0.3 to 1 kHz tones, and single-AN-fiber responses from cats. Except at 1 kHz, typical ANOW thresholds were mostly 10 to 20 dB more sensitive than onset-CAP thresholds and 10 to 20 dB less sensitive than the most sensitive single-AN-fiber thresholds. Conclusions: ANOW provides frequency-specific estimates of cochlear neural thresholds over a frequency range that is important for hearing but is not well accessed by nonbehavioral, objective methods. Results suggest that with further targeted development, the ANOW low-frequency threshold estimation technique can be useful both clinically in humans and in basic-science animal experiments. (Ear & Hearing 2013;34:42-51) C1 [Lichtenhan, Jeffery T.; Guinan, John J., Jr.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. [Lichtenhan, Jeffery T.; Guinan, John J., Jr.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Cooper, Nigel P.] Keele Univ, Sch Life Sci, ISTM Neurosci, Keele, Staffs, England. [Guinan, John J., Jr.] MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. RP Lichtenhan, JT (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM jlichtenhan@gmail.com FU National Institutes of Health, National Institute on Deafness and Other Communication Disorders [F32 DC010112, RO1 DC00235, R01 DC03687, P30 DC005209]; National Institutes of Health FX This work was supported by grants F32 DC010112, RO1 DC00235, R01 DC03687, and P30 DC005209 from the National Institutes of Health, National Institute on Deafness and Other Communication Disorders.; J.T.L. and J.J.G. currently receive grants from the National Institutes of Health. The other author have no funding or conflicts of interest to disclose. NR 50 TC 15 Z9 15 U1 2 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0196-0202 EI 1538-4667 J9 EAR HEARING JI Ear Hear. PD JAN-FEB PY 2013 VL 34 IS 1 BP 42 EP 51 DI 10.1097/AUD.0b013e31825f9bd3 PG 10 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 058NE UT WOS:000312639800006 PM 22874644 ER PT J AU Moreyra, AE Deng, YZ Wilson, AC Cosgrove, NM Kostis, WJ Kostis, JB AF Moreyra, Abel E. Deng, Yingzi Wilson, Alan C. Cosgrove, Nora M. Kostis, William J. Kostis, John B. CA MIDAS 18 Study Grp TI Incidence and trends of heart failure admissions after coronary artery bypass grafting surgery SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE CABG; Heart Failure; Trends ID LEFT-VENTRICULAR DYSFUNCTION; CONVERTING-ENZYME-INHIBITION; MYOCARDIAL-INFARCTION; MORTALITY; DATABASE; OUTCOMES; THERAPY; DISEASE AB Factors related to hospitalization for heart failure (HF) following coronary artery bypass grafting (CABG) surgery were studied. Patients (n 65 377) undergoing CABG surgery in New Jersey from 1998 to 2007 were identified from the state cardiac surgery database; subsequent hospitalizations for HF were assessed using the Myocardial Infarction Data Acquisition System database. Patients were classified based on pre-operative ejection fraction (EF). Multivariate models were used to identify factors related to HF admission and mortality. Post-CABG HF admission rates among patients with pre-operative EF 35 increased over the 10-year period (P 0.02), but no significant trend was seen among patients with EF epsilon 35. Independent factors associated with post-CABG HF admission within 2 years were: EF, age, female gender, Black race, smoking, diabetes, renal disease, hypertension, and cerebrovascular disease. Pre-operative use of beta-blockers increased over the years (P 0.0001) and reduced the risk of admission for HF by 13, with greater benefit in patients with lower EF. Mortality remained unchanged from 1998 to 2007, averaging 1.8 in-hospital and 5.1 and 7.2 at 1-year and 2-year follow-up, respectively. Pre-operative EF is a strong predictor of HF admission within 2 years after CABG surgery. The use of beta-blockers decreased HF admission after CABG, especially in patients with EF 35. Despite the more pronounced benefit and increasing use of beta-blockers in patients with a low EF, HF admission rates in this group of patients are rising. This suggests that more comprehensive management of factors associated with HF is necessary. C1 [Moreyra, Abel E.; Deng, Yingzi; Wilson, Alan C.; Cosgrove, Nora M.; Kostis, John B.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Cardiovasc Inst New Jersey, New Brunswick, NJ 08901 USA. [Moreyra, Abel E.; Deng, Yingzi; Wilson, Alan C.; Cosgrove, Nora M.; Kostis, John B.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med, New Brunswick, NJ 08901 USA. [Kostis, John B.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Moreyra, AE (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Cardiovasc Inst New Jersey, 125 Paterson St, New Brunswick, NJ 08901 USA. EM moreyrae@umdnj.edu FU Robert Wood Johnson Foundation; Schering-Plough Foundation FX The Robert Wood Johnson Foundation; the Schering-Plough Foundation. NR 23 TC 1 Z9 1 U1 0 U2 0 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 JAN PY 2013 VL 15 IS 1 BP 46 EP 53 DI 10.1093/eurjhf/hfs154 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 058NX UT WOS:000312641900007 PM 23097068 ER PT J AU Mentz, RJ Allen, BD Kwasny, MJ Konstam, MA Udelson, JE Ambrosy, AP Fought, AJ Vaduganathan, M O'Connor, CM Zannad, F Maggioni, AP Swedberg, K Bonow, RO Gheorghiade, M AF Mentz, Robert J. Allen, Bradley D. Kwasny, Mary J. Konstam, Marvin A. Udelson, James E. Ambrosy, Andrew P. Fought, Angela J. Vaduganathan, Muthiah O'Connor, Christopher M. Zannad, Faiez Maggioni, Aldo P. Swedberg, Karl Bonow, Robert O. Gheorghiade, Mihai TI Influence of documented history of coronary artery disease on outcomes in patients admitted for worsening heart failure with reduced ejection fraction in the EVEREST trial SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Heart failure; Coronary artery disease; Outcomes; Hospitalization ID CARDIAC TROPONIN-T; ISCHEMIC CARDIOMYOPATHY; VASOPRESSIN ANTAGONISM; CLINICAL DETERMINANTS; SUBSEQUENT MORTALITY; TOLVAPTAN EVEREST; OLDER PATIENTS; DOUBLE-BLIND; REVASCULARIZATION; HOSPITALIZATION AB Data on the prognosis of heart failure (HF) patients with coronary artery disease (CAD) have been conflicting. We describe the clinical characteristics and mode-specific outcomes of HF patients with reduced ejection fraction (EF) and documented CAD in a large randomized trial. EVEREST was a prospective, randomized trial of vasopressin-2 receptor blockade, in addition to standard therapy, in 4133 patients hospitalized with worsening HF and reduced EF. Patients were classified as having CAD based on patient-reported myocardial infarction (MI) or coronary revascularization. We analysed the characteristics and outcomes [all-cause mortality and cardiovascular (CV) mortality/HF hospitalization] of patients with and without documented CAD. All events were centrally adjudicated. Documented CAD was present in 2353 patients (57). Patients with CAD were older and had more co-morbidities compared with those without CAD. Patients with CAD were more likely to receive a beta-blocker, but less likely to receive an angiotensin-converting enzyme (ACE) inhibitor or aldosterone antagonist (P 0.01). After risk adjustment, patients with documented CAD had similar mortality [hazard ratio (HR) 1.12, 95 confidence interval (CI) 0.971.30], but were at an increased risk for CV mortality/HF hospitalization (HR 1.25, 95 CI 1.121.41) due to an increased risk for HF hospitalization (HR 1.26, 95 CI 1.101.44). Patients with CAD had increased HF- and MI-related events, but similar rates of sudden cardiac death. Documented CAD in patients hospitalized for worsening HF with reduced EF was associated with a higher burden of co-morbidities, lower use of HF therapies (except beta-blockers), and increased HF hospitalization, while all-cause mortality was similar. C1 [Bonow, Robert O.; Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. [Mentz, Robert J.; O'Connor, Christopher M.] Duke Univ, Med Ctr, Durham, NC USA. [Konstam, Marvin A.; Udelson, James E.] Tufts Med Ctr, Cardiovasc Ctr, Boston, MA USA. [Ambrosy, Andrew P.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Vaduganathan, Muthiah] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zannad, Faiez] Nancy Univ, Nancy, France. [Maggioni, Aldo P.] Associaz Nazl Medici Cardiol Osped Res Ctr, Florence, Italy. [Swedberg, Karl] Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden. RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu OI Maggioni, Aldo Pietro/0000-0003-2764-6779 FU Otsuka, Inc., Rockville, Maryland; Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Otsuka; JNJ; Amgen; Trevena; AstraZeneca; Servier FX Financial and material support for the EVEREST trial was provided by Otsuka, Inc., Rockville, Maryland. Mary Kwasny conducted all final analyses for this report with funding from the Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois.; M. A. K. receives research grants from and is a consultant for Otsuka, JNJ, Amgen, and Trevena. C. M. O is a consultant for Merck, Trevena, Novella, Pfizer, GE Healthcare, Roche, Amgen, Martek, Actelion, and JNJ. F. Z. has received honoraria from and served on advisory boards for Pfizer. A. P. M. receives honoraria from Otsuka. K. S. receives research grants from AstraZeneca, Servier, and Amgen; honoraria from AstraZeneca, Otsuka, Servier, and Amgen; and is a consultant for Cytokinetics, Servier, and Novartis. M. G. is a consultant for Abbott Labs, Astellas, AstraZeneca, Bayer Schering PharmaAG, CorThera Inc., Cytokinetics Inc., DebioPharm S. A., Errekappa Terapeutici (Milan, Italy), Glaxo Smith Kline, JNJ, Medtronic, Novartis Pharma AG, Otsuka, Sigma Tau, Solvay Pharmaceuticals, and Pericor Therapeutics. The other authors declare no conflict of interest. NR 36 TC 8 Z9 8 U1 0 U2 4 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 JAN PY 2013 VL 15 IS 1 BP 61 EP 68 DI 10.1093/eurjhf/hfs139 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 058NX UT WOS:000312641900009 PM 22968743 ER PT J AU Dean, JC AF Dean, Jesse C. TI Proprioceptive Feedback and Preferred Patterns of Human Movement SO EXERCISE AND SPORT SCIENCES REVIEWS LA English DT Review DE metabolic energy; motor adaptation; motor control; optimization; resonant frequency; sensory feedback ID HUMAN WALKING; GASTROCNEMIUS-MUSCLE; METABOLIC COST; BOUNCING TASK; ADAPTATION; FREQUENCY; OPTIMIZATION; INTEGRATION; NEUROPATHY; STABILITY AB DEAN, J.C. Proprioceptive feedback and preferred patterns of human movement. Exerc. Sport Sci. Rev., Vol. 41, No. 1, pp. 36-43, 2013. During cyclical tasks, humans often prefer stereotyped movement patterns. Although minimization of metabolic energy expenditure commonly is proposed as an underlying motor control goal, the mechanism by which humans choose their preferred movement pattern is not clear. We hypothesize that humans use proprioceptive feedback, which provides information about body mechanics in the identification of the preferred pattern of movement. C1 [Dean, Jesse C.] Med Univ S Carolina, Coll Hlth Profess, Div Phys Therapy, Charleston, SC 29425 USA. [Dean, Jesse C.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Dean, JC (reprint author), Med Univ S Carolina, Coll Hlth Profess, Div Phys Therapy, 77 President St,MSC 700, Charleston, SC 29425 USA. EM deaje@musc.edu OI Dean, Jesse/0000-0003-2034-4217 FU National Institutes of Health [1 R21 HD064964-01A1]; U.S. Department of Veterans Affairs [1 IK2 RX000750-01A1] FX Jesse C. Dean is currently receiving a grant (1 R21 HD064964-01A1) from the National Institutes of Health and a grant (1 IK2 RX000750-01A1) from the U.S. Department of Veterans Affairs. NR 35 TC 6 Z9 6 U1 2 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0091-6331 J9 EXERC SPORT SCI REV JI Exerc. Sport Sci. Rev. PD JAN PY 2013 VL 41 IS 1 BP 36 EP 43 DI 10.1097/JES.0b013e3182724bb0 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 058WN UT WOS:000312665700007 PM 23038242 ER PT J AU Bosak, T Liang, B Wu, TD Templer, SP Evans, A Vali, H Guerquin-Kern, JL Klepac-Ceraj, V Friedman, J Sim, MS Mui, J AF Bosak, T. Liang, B. Wu, T. -D. Templer, S. P. Evans, A. Vali, H. Guerquin-Kern, J. -L. Klepac-Ceraj, V. Friedman, Jonathan Sim, M. S. Mui, J. TI Cyanobacterial diversity and activity in modern conical microbialites (vol 10, pg 384, 2012) SO GEOBIOLOGY LA English DT Correction C1 [Bosak, T.; Liang, B.; Templer, S. P.; Evans, A.; Sim, M. S.] MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA. [Liang, B.] Acad Sinica, Inst Earth Sci, Taipei 115, Taiwan. [Wu, T. -D.; Guerquin-Kern, J. -L.] Univ Paris 11, INSERM, F-91405 Orsay, France. [Wu, T. -D.; Guerquin-Kern, J. -L.] Inst Curie, Lab Microscopie Ion, F-91405 Orsay, France. [Templer, S. P.] Roche Mol Diagnost, Basel, Switzerland. [Vali, H.; Mui, J.] McGill Univ, Facil Electron Microscopy Res, Montreal, PQ, Canada. [Vali, H.] McGill Univ, Dept Anat & Cell Biol, Montreal, PQ, Canada. [Klepac-Ceraj, V.] Forsyth Inst, Cambridge, MA USA. [Klepac-Ceraj, V.] Wellesley Coll, Dept Biol Sci, Wellesley, MA 02181 USA. [Friedman, Jonathan] MIT, Computat & Syst Biol Initiat, Cambridge, MA 02139 USA. RP Bosak, T (reprint author), MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA. RI Vali, Hojatollah/F-3511-2012 OI Vali, Hojatollah/0000-0003-3464-9943 NR 1 TC 2 Z9 2 U1 1 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1472-4677 J9 GEOBIOLOGY JI Geobiology PD JAN PY 2013 VL 11 IS 1 BP 100 EP 100 DI 10.1111/gbi.12016 PG 1 WC Biology; Environmental Sciences; Geosciences, Multidisciplinary SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences & Ecology; Geology GA 057CM UT WOS:000312539500008 ER PT J AU Tian, JW Hu, SN Sun, YL Yu, H Han, X Cheng, W Ban, X Zhang, SS Yu, B Jang, IK AF Tian, Jinwei Hu, Sining Sun, Yanli Yu, Huai Han, Xue Cheng, Wen Ban, Xiang Zhang, Shaosong Yu, Bo Jang, Ik-Kyung TI Vasa vasorum and plaque progression, and responses to atorvastatin in a rabbit model of atherosclerosis: contrast-enhanced ultrasound imaging and intravascular ultrasound study SO HEART LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; INTRAPLAQUE NEOVASCULARIZATION; ANGIOGENESIS; INHIBITION; QUANTIFICATION; INFLAMMATION; SIMVASTATIN; EXPRESSION; STATINS; GROWTH AB Objectives To serially investigate the relationship between vasa vasorum (VV) proliferation and plaque progression in vivo, and the effects of atorvastatin on VV and atherosclerosis as assessed by contrast-enhanced ultrasound (CEUS) and intravascular ultrasound (IVUS) imaging. Methods Carotid atherosclerosis was induced in rabbits with a high-cholesterol diet for 20 weeks and balloon injury. At week 16, following the imaging of the right common carotid arteries by CEUS and IVUS, 20 rabbits were randomised into a control or atorvastatin group (2 mg/kg/day). At week 20, CEUS and IVUS were repeated. Normalised maximal video-intensity enhancement (MVE) was calculated to quantify the density of VV. Plaque volume was determined by IVUS. Results When compared with the control group, lipid levels were not significantly lower following 4 weeks of atorvastatin administration. The increases in the normalised MVE over time were greater in the control group than in the atorvastatin group (p=0.001). The increase in plaque volume from 16 to 20 weeks was significantly greater in the control group than in the atorvastatin group (p=0.001). There was a positive relationship between changes in normalised MVE and plaque volume (r=0.72, p=0.002). Conclusions There was a positive correlation between VV density and plaque progression. Atorvastatin significantly inhibits the development of adventitial VV and progression of atherosclerosis independent of lowering the cholesterol level. C1 [Tian, Jinwei; Yu, Huai; Yu, Bo] Harbin Med Univ, Affiliated Hosp 2, Key Labs Myocardial Ischaemia, Chinese Minist Educ,Cardiol Div, Harbin 150086, Heilongjiang, Peoples R China. [Han, Xue; Cheng, Wen] Harbin Med Univ, Affiliated Hosp 3, Ultrasound Dept, Harbin 150086, Heilongjiang, Peoples R China. [Ban, Xiang] Harbin Med Univ, Pathol Dept, Harbin 150086, Heilongjiang, Peoples R China. [Zhang, Shaosong] St Jude Med Westford, LightLab Imaging, Boston, MA USA. [Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div, Boston, MA USA. RP Yu, B (reprint author), Harbin Med Univ, Affiliated Hosp 2, Key Labs Myocardial Ischaemia, Chinese Minist Educ,Cardiol Div, Harbin 150086, Heilongjiang, Peoples R China. EM yubodr@163.com FU National Natural Science Foundation of China [81171430/H1816] FX Bo Yu was supported by grant 81171430/H1816 from the National Natural Science Foundation of China. NR 29 TC 10 Z9 11 U1 1 U2 14 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 JAN PY 2013 VL 99 IS 1 BP 48 EP 54 DI 10.1136/heartjnl-2012-302775 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 057EF UT WOS:000312544600012 PM 23100286 ER PT J AU Das, SR Pluta, J Mancuso, L Kliot, D Orozco, S Dickerson, BC Yushkevich, PA Wolk, DA AF Das, Sandhitsu R. Pluta, John Mancuso, Lauren Kliot, Dasha Orozco, Sylvia Dickerson, Bradford C. Yushkevich, Paul A. Wolk, David A. TI Increased functional connectivity within medial temporal lobe in mild cognitive impairment SO HIPPOCAMPUS LA English DT Article DE hippocampus; functional connectivity; medial temporal lobe; fMRI; MCI; entorhinal cortex; correlation ID ALZHEIMERS-DISEASE; HIPPOCAMPAL SUBFIELDS; BLOOD-FLOW; BRAIN; MRI; ACTIVATION; BIOMARKERS; RESOLUTION; NETWORK; FMRI AB Pathology at preclinical and prodromal stages of Alzheimer's disease (AD) may manifest itself as measurable functional change in neuronal networks earlier than detectable structural change. Functional connectivity as measured using resting-state functional magnetic resonance imaging has emerged as a useful tool for studying disease effects on baseline states of neuronal networks. In this study, we use high resolution MRI to label subregions within the medial temporal lobe (MTL), a site of early pathology in AD, and report an increase in functional connectivity in amnestic mild cognitive impairment between entorhinal cortex and subregions of the MTL, with the strongest effect in the anterior hippocampus. However, our data also replicated the effects of decreased connectivity of the MTL to other nodes of the default mode network reported by other researchers. This dissociation of changes in functional connectivity within the MTL versus the MTL's connection with other neocortical structures can help enrich the characterization of early stages of disease progression in AD. (c) 2012 Wiley Periodicals, Inc. C1 [Das, Sandhitsu R.; Pluta, John; Orozco, Sylvia; Yushkevich, Paul A.] Univ Penn, Dept Radiol, PICSL, Philadelphia, PA 19104 USA. [Pluta, John] Univ Penn, Ctr Funct Neuroimaging, Dept Neurol, Philadelphia, PA 19104 USA. [Mancuso, Lauren; Kliot, Dasha; Wolk, David A.] Univ Penn, Alzheimer Dis Ctr, Philadelphia, PA 19104 USA. [Mancuso, Lauren; Kliot, Dasha; Wolk, David A.] Univ Penn, Penn Memory Ctr, Philadelphia, PA 19104 USA. [Mancuso, Lauren; Kliot, Dasha; Wolk, David A.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Frontotemporal Dementia Unit, Boston, MA 02114 USA. [Dickerson, Bradford C.] Harvard Univ, Sch Med, Boston, MA USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Massachusetts Alzheimers Dis Res Ctr, Boston, MA 02114 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Das, SR (reprint author), Univ Penn, Dept Radiol, PICSL, Philadelphia, PA 19104 USA. EM sudas@seas.upenn.edu OI Yushkevich, Paul/0000-0001-8543-4016 FU Penn-Pfizer Alliance Grant [10295]; [NIH K25 AG027785]; [NIH K23 AG028018]; [NIH R01 AG037376]; [NIH R01 AG029411]; [NIH P50 AG005134]; [NIH P30 AG010124] FX Grant sponsor: Penn-Pfizer Alliance Grant numbers: 10295; Grant numbers: NIH K25 AG027785, NIH K23 AG028018, NIH R01 AG037376, NIH R01 AG029411, NIH P50 AG005134, NIH P30 AG010124 NR 30 TC 17 Z9 18 U1 1 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PD JAN PY 2013 VL 23 IS 1 BP 1 EP 6 DI 10.1002/hipo.22051 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 057BW UT WOS:000312537800001 PM 22815064 ER PT J AU Chiang, S Oliva, E AF Chiang, Sarah Oliva, Esther TI Recent developments in uterine mesenchymal neoplasms SO HISTOPATHOLOGY LA English DT Review DE endometrial stromal tumours; immunohistochemistry; leiomyosarcoma; mesenchymal tumours; molecular profiles ID ENDOMETRIAL STROMAL SARCOMA; SMOOTH-MUSCLE TUMORS; CORD-LIKE DIFFERENTIATION; JAZF1-JJAZ1 GENE FUSION; PROGESTERONE-RECEPTOR EXPRESSION; BILATERAL SALPINGO-OOPHORECTOMY; BENIGN METASTASIZING LEIOMYOMA; IN-SITU HYBRIDIZATION; NUCLEAR BETA-CATENIN; HIGH-GRADE SARCOMAS AB Chiang S & Oliva E (2013) Histopathology 62, 124-137 Recent developments in uterine mesenchymal neoplasms Smooth muscle and endometrial stromal tumours represent the two most common uterine mesenchymal neoplasms that may present diagnostic dilemmas for the practising surgical pathologist. Recent changes in morphological and staging criteria, as well as the discovery of new immunohistochemical markers, have improved the diagnosis and classification of these tumours. We highlight the difficulty in distinguishing tumour cell necrosis from infarct-type necrosis and the limited utility of p16 immunohistochemical expression in the diagnosis of leiomyosarcoma. We also discuss the controversial use of mitotic activity and necrosis as prognostic factors in endometrial stromal sarcomas. Emerging genetic information has also greatly expanded our understanding of 'sarcomagenesis' in both tumour types and may provide insight into potential therapeutic targets for the treatment of leiomyosarcoma and endometrial stromal sarcomas, harboring MED12 (mediator complex subunit 12) mutations and recurrent gene rearrangements, respectively. In this review, we discuss the core updates in the diagnosis and classification of uterine leiomyosarcomas and endometrial stromal sarcomas, highlighting new and important molecular genetic findings that may drive pathogenesis. C1 [Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Oliva, E (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,WRN 2, Boston, MA 02114 USA. EM eoliva@partners.org NR 158 TC 26 Z9 27 U1 3 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD JAN PY 2013 VL 62 IS 1 BP 124 EP 137 DI 10.1111/his.12048 PG 14 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 057AJ UT WOS:000312533600009 PM 23240674 ER EF