FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Hartwell, KJ LeMatty, T McRae-Clark, AL Gray, KM George, MS Brady, KT AF Hartwell, Karen J. LeMatty, Todd McRae-Clark, Aimee L. Gray, Kevin M. George, Mark S. Brady, Kathleen T. TI Resisting the Urge to Smoke and Craving during a Smoking Quit Attempt on Varenicline: Results from a Pilot fMRI Study SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article ID NICOTINE DEPENDENCE; LABORATORY MODEL; CUE-REACTIVITY; ABSTINENCE; CESSATION; ACTIVATION; BUPROPION; RESPONSES; COGNITION; MOOD AB Background: Varenicline has been shown to reduce cigarette craving during a quit attempt. Objectives: Use BOLD fMRI to explore differences in smoking cue reactivity at baseline and after five weeks of varenicline smoking cessation treatment. Methods: Treatment-seeking nicotine-dependent adult smokers underwent BOLD fMRI scans with block presentation of visual smoking, neutral, and rest cues under two conditions: craving or resisting the urge to smoke at baseline and following 5 weeks of standard varenicline therapy. Data were analyzed using FMRI Expert Analysis Tool, version 5.98 of Functional Magnetic Imaging of the Brain Software Library focused on the smoking vs. neutral cue contrast at the individual and group level, Z>2.3 with cluster threshold p=0.05. Results: Twenty-one participants were scanned at baseline and 16 completed the study; 10 were abstinent at the 2nd session, confirmed with urinary cotinine. In the Crave Condition no significant differences were found between the abstinent and non-abstinent groups at either time point. During the baseline Resist Condition, the abstinent group compared to the non-abstinent group demonstrated activation in a distributed network involved in alertness, learning and memory. Additionally, within the abstinent group, increased activation of the superior frontal gyrus was found at baseline compared to week 5. Conclusion: Successful smoking cessation with varenicline is associated with increased activation, prior to a quit attempt, in brain areas related to attentiveness and memory while resisting the urge to smoke Scientific Significance: Varenicline may exert effects by both reducing craving and enhancing resistance to smoking urges during cue-elicited craving. C1 [Hartwell, Karen J.; LeMatty, Todd; McRae-Clark, Aimee L.; Gray, Kevin M.; George, Mark S.; Brady, Kathleen T.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Hartwell, Karen J.; George, Mark S.; Brady, Kathleen T.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Hartwell, KJ (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 67 President St,MSC 861, Charleston, SC 29425 USA. EM hartwelk@musc.edu RI McRae-Clark, Aimee/I-3341-2013 OI McRae-Clark, Aimee/0000-0002-9774-318X FU NCRR NIH HHS [UL1 RR029882]; NICHD NIH HHS [K12 HD055885, K12HD055885]; NIDA NIH HHS [5R21DA026085-02, R21 DA026085] NR 33 TC 5 Z9 5 U1 2 U2 22 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PD MAR PY 2013 VL 39 IS 2 BP 92 EP 98 DI 10.3109/00952990.2012.750665 PG 7 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 093IH UT WOS:000315184600005 PM 23421569 ER PT J AU Oliva, EM Trafton, JA Harris, AHS Gordon, AJ AF Oliva, Elizabeth M. Trafton, Jodie A. Harris, Alex H. S. Gordon, Adam J. TI Trends in Opioid Agonist Therapy in the Veterans Health Administration: Is Supply Keeping up with Demand? SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE opioid agonist therapy; buprenorphine; veterans; office-based treatment; VA; VHA; methadone ID SUBSTANCE-ABUSE TREATMENT; BUPRENORPHINE; METHADONE; DEPENDENCE; ADDICTION; ADOPTION; COSTS AB Background: Opioid agonist therapy (OAT) through addiction specialty clinic settings (clinic-based OAT) using methadone or buprenorphine or office-based settings using buprenorphine (office-based OAT) is an evidence-based treatment for opioid dependence. The low number of clinic-based OATs available to veterans (N = 53) presents a barrier to OAT access; thus, the expansion in office-based OAT has been encouraged. Objectives: To examine trends in office-based OAT utilization over time and whether availability of office-based OAT improved the proportion of veterans with opioid use disorders treated with OAT. Methods: We examined Veterans Health Administration (VHA) administrative data for evidence of buprenorphine prescribing and clinic-based OAT clinic stops from October 2003 through September 2010 [fiscal years (FY) 2004-2010]. Results: The number of patients receiving buprenorphine increased from 300 at 27 facilities in FY2004 to 6147 at 118 facilities in FY2010. During this time, the number of patients diagnosed with an opioid use disorder increased by 45%; however, the proportion of opioid use disorder patients receiving OAT remained relatively stable, ranging from 25% to 27%, Conclusions: Office-based OAT utilization and the number of opioid use disorder veterans treated with OAT are increasing at the same rate over time, suggesting that office-based OAT is being used to meet the growing need for OAT care. Although office-based OAT is increasingly being used within the VHA and may be one way the VHA is keeping up with the demand for OAT, more research is needed to understand how to engage a greater proportion of opioid use disorder patients in treatment. C1 [Oliva, Elizabeth M.; Trafton, Jodie A.; Harris, Alex H. S.] VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA 94025 USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Mental Hlth Res Educ & Clin Ctr, Pittsburgh, PA USA. [Gordon, Adam J.] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. RP Oliva, EM (reprint author), VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, 795 Willow Rd,MPD 152, Menlo Pk, CA 94025 USA. EM elizabeth.oliva@va.gov NR 21 TC 8 Z9 8 U1 3 U2 9 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PD MAR PY 2013 VL 39 IS 2 BP 103 EP 107 DI 10.3109/00952990.2012.741167 PG 5 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 093IH UT WOS:000315184600007 PM 23421571 ER PT J AU Tanner, RM Gutierrez, OM Judd, S McClellan, W Bowling, CB Bradbury, BD Safford, MM Cushman, M Warnock, D Muntner, P AF Tanner, Rikki M. Gutierrez, Orlando M. Judd, Suzanne McClellan, William Bowling, C. Barrett Bradbury, Brian D. Safford, Monika M. Cushman, Mary Warnock, David Muntner, Paul TI Geographic Variation in CKD Prevalence and ESRD Incidence in the United States: Results From the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Chronic kidney disease; geography; end-stage renal disease ID CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; GLOMERULAR-FILTRATION-RATE; RISK; POPULATION; JAPAN; DEATH; CARE AB Background: It is not known whether geographic differences in the prevalence of chronic kidney disease exist and are associated with end-stage renal disease (ESRD) incidence rates across the United States. Study Design: Cross-sectional and ecologic. Setting & Participants: White (n = 16,410) and black (n = 11,109) participants from across the continental United States in the population-based Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. Predictor: Geographic region, defined by the 18 networks of the US ESRD Network Program. Outcomes & Measurements: Albuminuria, defined as albumin-creatinine ratio >= 30 mg/g, and decreased estimated glomerular filtration rate (eGFR), defined as <60 mL/min/1.73 m(2), were measured in the REGARDS Study. ESRD incidence rates were obtained from the US Renal Data System. Results: For whites, the network-specific prevalence of albuminuria ranged from 8.4% (95% CI, 3.3%-13.5%) in Network 15 to 14.8% (95% CI, 8.0%-21.6%) in Network 3, and decreased eGFR ranged from 4.3% (95% CI, 2.0%-6.6%) in Network 4 to 16.7% (95% CI, 12.7%-20.7%) in Network 7. For blacks, the prevalence of albuminuria ranged from 12.1% (95% CI, 8.7%-15.5%) in Network 5 to 26.5% (95% CI, 16.7%-36.3%) in Network 4, and decreased eGFR ranged from 6.7% (95% CI, 5.0%-8.4%) in Network 17/18 to 13.4% (95% CI, 7.8%-19.1%) in Network 12. Spearman correlation coefficients for the prevalence of albuminuria and decreased eGFR with network-specific ESRD incidence rates were 0.49 and 0.24, respectively, for whites and 0.29 and 0.25, respectively, for blacks. Limitations: There were few cases of albuminuria and decreased eGFR in some geographic regions. Conclusions: In the United States, substantial geographic variations in the prevalence of albuminuria and decreased eGFR exist, but were correlated only modestly with ESRD incidence, suggesting the chronic kidney disease burden may not explain the geographic variation in ESRD incidence. Am J Kidney Dis. 61(3):395-403. (C) 2013 by the National Kidney Foundation, Inc. C1 [Tanner, Rikki M.; Gutierrez, Orlando M.; Judd, Suzanne; Bowling, C. Barrett; Safford, Monika M.; Warnock, David; Muntner, Paul] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [McClellan, William] Emory Univ, Atlanta, GA 30322 USA. [Bowling, C. Barrett] Birmingham VA Med Ctr, Birmingham, AL USA. [Bradbury, Brian D.] Amgen Inc, Ctr Observat Res, Thousand Oaks, CA 91320 USA. [Bradbury, Brian D.] Univ Calif Los Angeles, Dept Epidemiol, Los Angeles, CA USA. [Cushman, Mary] Univ Vermont, Burlington, VT USA. RP Muntner, P (reprint author), Univ Alabama Birmingham, Dept Epidemiol, 1665 Univ Blvd,Ste 230J, Birmingham, AL 35294 USA. EM pmuntner@uab.edu FU National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Department of Health and Human Services [U01 NS041588]; Amgen Corp FX Support: This research project is supported by cooperative agreement U01 NS041588 from the National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Department of Health and Human Services. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NINDS or NIH. Representatives of the funding agency were involved in the review of the manuscript but not directly involved in the collection, management, analysis, or interpretation of the data. Additional funding was provided by an investigator-initiated grant-in-aid from Amgen Corp to Dr Warnock. NR 31 TC 10 Z9 11 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAR PY 2013 VL 61 IS 3 BP 395 EP 403 DI 10.1053/j.ajkd.2012.10.018 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 090GF UT WOS:000314966600009 PM 23228944 ER PT J AU Zhao, W Marchani, EE Cheung, CYK Steinbart, EJ Schellenberg, GD Bird, TD Wijsman, EM AF Zhao, Wei Marchani, Elizabeth E. Cheung, Charles Y. K. Steinbart, Ellen J. Schellenberg, Gerard D. Bird, Thomas D. Wijsman, Ellen M. TI Genome scan in familial late-onset Alzheimer's disease: A locus on chromosome 6 contributes to age-at-onset SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE linkage analysis; MCMC; oligogenic; dementia; age-censored ID NEUROTROPHIC FACTOR BDNF; MONTE-CARLO SEGREGATION; LINKAGE ANALYSIS; APOLIPOPROTEIN-E; GENETIC ASSOCIATION; MULTIPLE IMPUTATION; QUANTITATIVE TRAIT; OF-ONSET; SYSTEMATIC METAANALYSES; OLIGOGENIC SEGREGATION AB Alzheimer's disease (AD) is a common, genetically complex, fatal neurodegenerative disorder of late life. Although several genes are known to play a role in early-onset AD, identification of the genetic basis of late onset AD (LOAD) has been challenging, with only the APOE gene known to have a high contribution to both AD risk and age-at-onset. Here, we present the first genome-scan analysis of the complete, well-characterized University of Washington LOAD sample of 119 pedigrees, using age-at-onset as the trait of interest. The analysis approach used allows for a multilocus trait model while at the same time accommodating age censoring, effects of APOE as a known genetic covariate, and full pedigree and marker information. The results provide strong evidence for linkage of loci contributing to age-at-onset to genomic regions on chromosome 6q16.3, and to 19q13.42 in the region of the APOE locus. There was evidence for interaction between APOE and the locus on chromosome 6q and suggestive evidence for linkage to chromosomes 11p13, 15q12-14, and 19p13.12. These results provide the first independent confirmation of an AD age-at-onset locus on chromosome 6 and suggest that further efforts towards identifying the underlying causal locus or loci are warranted. (c) 2013 Wiley Periodicals, Inc. C1 [Zhao, Wei; Cheung, Charles Y. K.; Wijsman, Ellen M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Marchani, Elizabeth E.; Bird, Thomas D.; Wijsman, Ellen M.] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [Steinbart, Ellen J.; Bird, Thomas D.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Steinbart, Ellen J.; Bird, Thomas D.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Schellenberg, Gerard D.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA. [Wijsman, Ellen M.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. RP Wijsman, EM (reprint author), Univ Washington, Dept Med, Div Med Genet, Box 357720, Seattle, WA 98195 USA. EM wijsman@u.washington.edu OI Wijsman, Ellen/0000-0002-2725-6669 FU National Institutes of Health (NIH) [P50 AG005136, T32 AG000258, K99 AG040184]; Veterans Affairs Research Funds; Metropolitan Life Foundation; [NIH U24 AG021886] FX We thank the patients and their families, whose help and participation made this work possible. We thank Leslie Leong and Hiep Nguyen for technical assistance; Adele Sadovnick, Leonard Heston, and Haydeh Payami for family material; and David Cook for discussions. Supported by National Institutes of Health (NIH) grants P50 AG005136, T32 AG000258, and K99 AG040184; Veterans Affairs Research Funds; and The Metropolitan Life Foundation. Some samples used in this study were obtained from the National Cell Repository for Alzheimer's Disease (NCRAD), supported by NIH U24 AG021886. NR 92 TC 1 Z9 1 U1 2 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD MAR PY 2013 VL 162B IS 2 BP 201 EP 212 DI 10.1002/ajmg.b.32133 PG 12 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 095JP UT WOS:000315330800012 PM 23355194 ER PT J AU Fallows, RR Hilsabeck, RC AF Fallows, Robert R. Hilsabeck, Robin C. TI Comparing Two Methods of Delivering Neuropsychological Feedback SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Feedback; Written information; Neuropsychology ID WRITTEN INFORMATION; CONTROLLED-TRIAL; NATIONAL-SURVEY; MIXED METHODS; PERCEPTIONS; INTERVENTION; ADOLESCENT; SERVICE AB Feedback methods have been studied in medical and psychotherapy settings, but limited research is available in neuropsychology. The purpose of this study was to examine whether supplementing oral feedback with written information would lead to greater retention of information and improved adherence to recommendations. Seventy-two veterans were enrolled in the study and randomized to receive oral feedback only or oral feedback with written information. The participants were then interviewed immediately after feedback and 1 month later by phone. Univariate analyses revealed that the written group freely recalled more recommendations at the phone interview; however, there were no differences in recall of diagnostic information or the number of recommendations attempted. Findings indicate that receiving supplemental written information improves recall of recommendations and that patients prefer to receive written information in addition to oral feedback. Recommendations to improve the retention of feedback information are discussed. C1 [Fallows, Robert R.; Hilsabeck, Robin C.] S Texas Vet Hlth Care Syst, Psychol Serv, San Antonio, TX USA. [Hilsabeck, Robin C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. RP Hilsabeck, RC (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, MS 7792, San Antonio, TX 78229 USA. EM hilsabeck@uthscsa.edu NR 38 TC 4 Z9 4 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD MAR PY 2013 VL 28 IS 2 BP 180 EP 188 DI 10.1093/arclin/acs142 PG 9 WC Psychology, Clinical; Psychology SC Psychology GA 092YS UT WOS:000315159500010 PM 23315402 ER PT J AU Cea, M Cagnetta, A Patrone, F Nencioni, A Gobbi, M Anderson, KC AF Cea, Michele Cagnetta, Antonia Patrone, Franco Nencioni, Alessio Gobbi, Marco Anderson, Kenneth C. TI Intracellular NAD(+) depletion induces autophagic death in multiple myeloma cells SO AUTOPHAGY LA English DT Editorial Material DE multiple myeloma; nicotinamide phosphoribosyltransferase; PI3K/MTORC1; TFEB; cancer treatment AB Multiple myeloma (MM) is a clonal B-cell malignancy characterized by the proliferation of plasma cells in the bone marrow. Despite recent therapeutic advances, MM remains an incurable disease. Therefore, research has focused on defining new aspects in MM biology that can be therapeutically targeted. Compelling evidence suggests that malignant cells have a higher nicotinamide adenine dinucleotide (NAD+) turnover rate than normal cells, suggesting that this biosynthetic pathway represents an attractive target for cancer treatment. We recently reported that an intracellular NAD+-depleting agent, FK866, exerts its anti-MM effect by triggering autophagic cell death via transcriptional-dependent (transcription factor EB, TFEB) and -independent (PI3K-MTORC1) mechanisms. Our findings link intracellular NAD+ levels to autophagy in MM cells, providing the rationale for novel targeted therapies in MM. C1 [Cea, Michele; Cagnetta, Antonia; Anderson, Kenneth C.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA 02215 USA. [Cea, Michele; Cagnetta, Antonia; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Res, Boston, MA 02115 USA. [Cea, Michele; Cagnetta, Antonia; Patrone, Franco; Nencioni, Alessio; Gobbi, Marco] IRCCS Univ Hosp San Martino IST, Dept Hematol & Oncol, Genoa, Italy. RP Cea, M (reprint author), Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA 02215 USA. EM michele_cea@dfci.harvard.edu; kenneth_anderson@dfci.harvard.edu FU NCI NIH HHS [P01 CA078378, P50 CA100707, P01 CA155258]; PHS HHS [R0-1 50947, R0-1 73878] NR 0 TC 13 Z9 13 U1 0 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD MAR PY 2013 VL 9 IS 3 BP 410 EP 412 DI 10.4161/auto.22866 PG 3 WC Cell Biology SC Cell Biology GA 094XY UT WOS:000315300000013 PM 23221771 ER PT J AU Wahler, A Beyer, AS Keller, IE Schnack, C von Einem, B Propper, C Boeckers, TM Peltan, ID Strickland, DK Hyman, BT von Arnim, CAF AF Wahler, Anke Beyer, Anja-Silke Keller, Ilona E. Schnack, Cathrin von Einem, Bjoern Proepper, Christian Boeckers, Tobias M. Peltan, Ithan D. Strickland, Dudley K. Hyman, Bradley T. von Arnim, Christine A. F. TI Engulfment adaptor phosphotyrosine-binding-domain-containing 1 (GULP1) is a nucleocytoplasmic shuttling protein and is transactivationally active together with low-density lipoprotein receptor-related protein 1 (LRP1) SO BIOCHEMICAL JOURNAL LA English DT Article DE adaptor protein; Alzheimer's disease; amyloid precursor protein; engulfment adaptor phosphotyrosine-binding-domain-containing 1 (GULP1); transactivation ID AMYLOID PRECURSOR PROTEIN; INTRACELLULAR DOMAIN; APOPTOTIC CELLS; TRANSCRIPTIONAL ACTIVATOR; ALZHEIMERS-DISEASE; FE65; LOCALIZATION; PROTEOLYSIS; EXPRESSION; CLEARANCE AB APP (amyloid precursor protein) and LRP1 (low-density lipoprotein receptor-related protein 1) have been implicated in the pathogenesis of AD (Alzheimer's disease). They are functionally linked by Fe65, a PTB (phosphotyrosine-binding)domain-containing adaptor protein that binds to intracellular NPxY-motifs of APP and LRP1, thereby influencing expression levels, cellular trafficking and processing. Additionally, Fe65 has been reported to mediate nuclear signalling in combination with intracellular domains of APP and LRP1. We have previously identified another adaptor protein, GULP1 (engulfment adaptor PTB-domain-containing 1). In the present study we characterize and compare nuclear trafficking and transactivation of GULP1 and Fe65 together with APP and LRP1 and report differential nuclear trafficking of adaptors when APP or LRP1 are co-expressed. The observed effects were additionally supported by a reporter-plasmid-based transactivation assay. The results from the present study indicate that Fe65 might have signalling properties together with APP and LRP1, whereas GULP1 only mediates LRP1 transactivation. C1 [Wahler, Anke; Beyer, Anja-Silke; Keller, Ilona E.; Schnack, Cathrin; von Einem, Bjoern; von Arnim, Christine A. F.] Univ Ulm, Dept Neurol, D-89081 Ulm, Germany. [Proepper, Christian; Boeckers, Tobias M.] Univ Ulm, Inst Anat & Cell Biol, D-89081 Ulm, Germany. [Peltan, Ithan D.; Hyman, Bradley T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. [Strickland, Dudley K.] Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA. RP von Arnim, CAF (reprint author), Univ Ulm, Dept Neurol, D-89081 Ulm, Germany. EM christine.arnim@uni-ulm.de OI Peltan, Ithan/0000-0003-1730-234X FU Ernst Schering Foundation; Land Baden-Wurttemberg [1423/74]; National Institutes for Health [HL050784, L054710] FX A.W. is a recipient of a doctoral fellowship from the Ernst Schering Foundation. This work was supported by Land Baden-Wurttemberg [grant number 1423/74 (to C.A.F.v.A.)] and the National Institutes for Health [grant numbers HL050784 and L054710 (to D K S.)] NR 39 TC 1 Z9 1 U1 0 U2 6 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAR 1 PY 2013 VL 450 BP 333 EP 343 DI 10.1042/BJ20121100 PN 2 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 094HJ UT WOS:000315253300009 PM 23167255 ER PT J AU Nanji, KC Ferris, TG Torchiana, DF Meyer, GS AF Nanji, Karen C. Ferris, Timothy G. Torchiana, David F. Meyer, Gregg S. TI Overarching goals: a strategy for improving healthcare quality and safety? SO BMJ QUALITY & SAFETY LA English DT Review ID ADVERSE EVENTS; COMPETITION AB The management literature reveals that many successful organisations have strategic plans that include a bold 'stretch-goal' to stimulate progress over a ten-to-thirty-year period. A stretch goal is clear, compelling and easily understood. It serves as a unifying focal point for organisational efforts. The ambitiousness of such goals has been emphasised with the phrase Big Hairy Audacious Goal ('BHAG'). President Kennedy's proclamation in 1961 that 'this Nation should commit itself to achieving the goal, before this decade is out, of landing a man on the moon and returning him safely to earth' provides a famous example. This goal energised the US National Aeronautics and Space Administration, and it captured the attention of the American public and resulted in one of the largest accomplishments of any organisation. The goal set by Sony, a small, cash-strapped electronics company in the 1950s, to change the poor image of Japanese products around the world represents a classic BHAG. Few examples of quality goals that conform to the BHAG definition exist in the healthcare literature. However, the concept may provide a useful framework for organisations seeking to transform the quality of care they deliver. This review examines the merits and cautions of setting overarching quality goals to catalyse quality improvement efforts, and assists healthcare organisations with determining whether to adopt these goals. C1 [Nanji, Karen C.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Nanji, Karen C.; Ferris, Timothy G.; Torchiana, David F.; Meyer, Gregg S.] Harvard Univ, Sch Med, Boston, MA USA. [Nanji, Karen C.; Ferris, Timothy G.; Torchiana, David F.; Meyer, Gregg S.] Massachusetts Gen Phys Org, Boston, MA USA. RP Nanji, KC (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM knanji@partners.org NR 35 TC 2 Z9 2 U1 1 U2 13 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 MAR PY 2013 VL 22 IS 3 BP 187 EP 193 DI 10.1136/bmjqs-2012-001082 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 093JX UT WOS:000315189200002 PM 23204514 ER PT J AU Armand, P Welch, S Kim, HT LaCasce, AS Jacobsen, ED Davids, MS Jacobson, C Fisher, DC Brown, JR Coughlin, E Freedman, AS Chen, YB AF Armand, Philippe Welch, Sarah Kim, Haesook T. LaCasce, Ann S. Jacobsen, Eric D. Davids, Matthew S. Jacobson, Caron Fisher, David C. Brown, Jennifer R. Coughlin, Erin Freedman, Arnold S. Chen, Yi-Bin TI Prognostic factors for patients with diffuse large B cell lymphoma and transformed indolent lymphoma undergoing autologous stem cell transplantation in the positron emission tomography era SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE prognostic factors; autologous stem cell transplant; diffuse large B-cell lymphoma; transformed indolent lymphoma; PET ID NON-HODGKINS-LYMPHOMA; HIGH-DOSE THERAPY; BONE-MARROW TRANSPLANTATION; FOLLICULAR LYMPHOMA; SALVAGE CHEMOTHERAPY; RITUXIMAB; SURVIVAL; SUPPORT; TRIAL; SCAN AB In the positron emission tomography (PET) era, traditional prognostic factors may not apply for patients with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) undergoing autologous stem cell transplantation (ASCT). Moreover, little is known about prognostic factors in patients transplanted for transformed indolent lymphoma (TIL). We conducted a retrospective study of 143 patients with R/R DLBCL and TIL who were transplanted in the last decade and had a post-salvage PET scan. We examined prognostic factors in both groups, and constructed a prognostic score for DLBCL patients. For patients with DLBCL, post-salvage PET response was an important prognostic factor. Advanced age and symptomatic relapse were also significantly associated with outcome. A simple score could stratify patients into three risk groups with 4-year post-ASCT overall survival of 84%, 59%, and 10%, and 4-year progression-free survival of 67%, 41% and 0% (P<0 center dot 0001 for both). However, none of those factors (including PET response to salvage) appeared relevant for patients with TIL, despite their comparable overall outcome. Our prognostic score for DLBCL patients undergoing ASCT may be useful for prognostication, for stratification in clinical trials, and to motivate the design of new strategies for patients in the high-risk group, who may not derive benefit from standard ASCT. C1 [Armand, Philippe; LaCasce, Ann S.; Jacobsen, Eric D.; Davids, Matthew S.; Jacobson, Caron; Fisher, David C.; Brown, Jennifer R.; Freedman, Arnold S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Welch, Sarah] Boston Univ, Sch Med, Div Grad Med Sci, Boston, MA 02118 USA. [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Coughlin, Erin; Chen, Yi-Bin] Massachusetts Gen Hosp, Div Hematol Oncol, Bone Marrow Transplant Unit, Boston, MA 02114 USA. RP Armand, P (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM parmand@partners.org FU American Society of Hematology Scholar Award; ASCO/Conquer Cancer Foundation Career Development Award FX P.A. is supported by an American Society of Hematology Scholar Award and by an ASCO/Conquer Cancer Foundation Career Development Award. NR 30 TC 20 Z9 20 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAR PY 2013 VL 160 IS 5 BP 608 EP 617 DI 10.1111/bjh.12176 PG 10 WC Hematology SC Hematology GA 092AW UT WOS:000315092200006 PM 23278720 ER PT J AU Hwang, JC Sharma, AG Eliott, D AF Hwang, John Chopin Sharma, Ashish G. Eliott, Dean TI Fellow eye vitrectomy for proliferative diabetic retinopathy in an inner city population SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID OUTCOMES AB Aim To describe the rate of fellow eye vitrectomy for proliferative diabetic retinopathy in an inner city population. Methods Retrospective interventional case series. Medical and surgical records of 434 consecutive eyes of 358 patients undergoing primary diabetic vitrectomy in an inner city institutional practice were reviewed. Kaplan-Meier statistical analysis was employed to evaluate the rate of fellow eye vitrectomy and visual outcomes were determined for patients with >= 3 months follow-up. Results Fellow eyes underwent diabetic vitrectomy at a rate of 24% within 1 year, 34% within 3 years and 36% within 5 years of primary vitrectomy. A surgical indication of non-clearing vitreous haemorrhage (VH) in the primary eye was associated with a lower rate of fellow eye surgery compared with non-clearing VH with extrafoveal traction retinal detachment (TRD) at years 1, 3 and 5 (p <= 0.02), and TRD at years 3 and 5 (p <= 0.03). Younger patients underwent fellow eye vitrectomy at a higher rate than older patients (p <= 0.01). Surgical intervention was associated with improvement in mean visual acuity (p<0.01). Conclusions Approximately a third of fellow eyes required diabetic vitrectomy within 3 years of primary eye vitrectomy. Primary eye surgical indication and younger age were significant predictors of need for fellow eye surgery. C1 [Hwang, John Chopin] Retina Associates Orange Cty, Laguna Hills, CA USA. [Sharma, Ashish G.] Retina Consultants SW Florida, Ft Myers, FL USA. [Eliott, Dean] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Eliott, D (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Dean_Eliott@meei.harvard.edu NR 7 TC 1 Z9 1 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD MAR PY 2013 VL 97 IS 3 BP 297 EP 301 DI 10.1136/bjophthalmol-2012-302233 PG 5 WC Ophthalmology SC Ophthalmology GA 092ZW UT WOS:000315162500012 PM 23314578 ER PT J AU Cooley, ME Finn, KT Wang, Q Roper, K Morones, S Shi, L Litrownik, D Marcoux, JP Zaner, K Hayman, LL AF Cooley, Mary E. Finn, Kathleen T. Wang, Qian Roper, Kristin Morones, Sandra Shi, Ling Litrownik, Dan Marcoux, J. Paul Zaner, Ken Hayman, Laura L. TI Health Behaviors, Readiness to Change, and Interest in Health Promotion Programs Among Smokers With Lung Cancer and Their Family Members A Pilot Study SO CANCER NURSING LA English DT Article DE Health promotion; Lung cancer; Multiple risk reduction interventions; Patient-family member dyads ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; POPULATION-BASED SURVEY; PHYSICAL-ACTIVITY; SMOKING-CESSATION; RISK BEHAVIORS; SURVIVORS ADHERENCE; STRESS-MANAGEMENT; BREAST-CANCER; HEART-DISEASE AB Background: The diagnosis of lung cancer presents an opportunity to motivate individuals to adopt health-promoting behavior. Little attention has been given to using this opportunity to also motivate relatives to change their health behaviors. Objectives: The objectives of this study were to describe health behaviors and readiness to change lifestyle, identify interest in health promotion programs, and examine concordance of health behaviors among smokers with lung cancer and their family members. Methods: Cross-sectional data were collected once from 37 lung cancer patient-family member dyads. Standardized questionnaires were used to collect data. Descriptive statistics and percent agreement were used for analyses. Results: Lung cancer patients and their family members had high rates of continued smoking (43% vs 30%), low intake of fruits and vegetables (92% vs 95%), and high rates of physical inactivity (84% vs 84%). Patients and family members indicated readiness to change behaviors within the next 6 months ranging from 63% for physical activity, 73% for diet, and 88% to quit smoking for patients and 81% for physical activity, 58% for diet, and 91% to quit smoking for family members. Interest in participating in a multiple behavioral risk reduction program was high for patients and family members. Conclusions: The majority of patients and their family members have multiple behavioral risk factors placing them at risk for poor health outcomes. Implications for Practice: Oncology nurses are in a unique position to provide leadership in assessing health behaviors and implementing evidence-based interventions to enhance outcomes for patient-family member dyads with lung cancer. C1 [Cooley, Mary E.; Wang, Qian; Roper, Kristin; Marcoux, J. Paul] Dana Farber Canc Inst, Boston, MA 02115 USA. [Morones, Sandra; Shi, Ling; Hayman, Laura L.] Univ Massachusetts, Boston, MA 02125 USA. [Finn, Kathleen T.; Zaner, Ken] Boston Med Ctr, Boston, MA USA. [Litrownik, Dan] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Cooley, ME (reprint author), Dana Farber Canc Inst, Cantor Ctr, Res Nursing Serv, 450 Brookline Ave,LW 521, Boston, MA 02115 USA. EM mary_cooley@dfci.harvard.edu FU National Cancer Institute [U56 CA 118635, K07 CA92696] FX Source of support: National Cancer Institute U56 CA 118635 prepilot funding awarded to Drs Cooley and Hayman (principal investigators Karen M. Emmons and Adam Colon-Carmona) and K07 CA92696 (principal investigator Dr Cooley). NR 77 TC 11 Z9 11 U1 2 U2 27 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0162-220X EI 1538-9804 J9 CANCER NURS JI Cancer Nurs. PD MAR-APR PY 2013 VL 36 IS 2 BP 145 EP 154 DI 10.1097/NCC.0b013e31825e4359 PG 10 WC Oncology; Nursing SC Oncology; Nursing GA 093JT UT WOS:000315188800013 PM 22791213 ER PT J AU Durand, ML AF Durand, M. L. TI Endophthalmitis SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Review DE Bacterial endophthalmitis; Candida endophthalmitis; endogenous endophthalmitis; endophthalmitis; fungal endophthalmitis; keratitis-related endophthalmitis; mould endophthalmitis; post-injection endophthalmitis; postoperative endophthalmitis; post-traumatic endophthalmitis ID ENDOGENOUS BACTERIAL ENDOPHTHALMITIS; POSTCATARACT SURGERY ENDOPHTHALMITIS; ANTERIOR SEGMENT SYNDROME; ENDOTHELIAL GROWTH-FACTOR; CATARACT-SURGERY; INTRAVITREAL INJECTION; POSTOPERATIVE ENDOPHTHALMITIS; RISK-FACTORS; POSTTRAUMATIC ENDOPHTHALMITIS; FUNGAL ENDOPHTHALMITIS AB Endophthalmitis means bacterial or fungal infection inside the eye involving the vitreous and/or aqueous humors. Most cases are exogenous and occur after eye surgery, after penetrating ocular trauma, or as an extension of corneal infection. An increasing number of cases are occurring after intravitreal injections of anti-vascular endothelial growth factor (VEGF) medications. Endophthalmitis may also be endogenous, arising from bacteraemic or fungaemic seeding of the eye. The infected eye never serves as a source of bacteraemia or fungaemia, however. The most common pathogens in endophthalmitis vary by category. Coagulase-negative staphylococci are the most common causes of post-cataract endophthalmitis, and these bacteria and viridans streptococci cause most cases of post-intravitreal anti-VEGF injection endophthalmitis, Bacillus cereus is a major cause of post-traumatic endophthalmitis, and Staphylococcus aureus and streptococci are important causes of endogenous endophthalmitis associated with endocarditis. In Taiwan and other East Asian nations, Klebsiella pneumoniae causes most cases of endogenous endophthalmitis, in association with liver abscess. Endogenous fungal endophthalmitis in hospitalized patients is usually caused by Candida species, particularly Candida albicans. Acute endophthalmitis is a medical emergency. The most important component of treatment is the intravitreal injection of antibiotics, along with vitrectomy in severe cases. Systemic antibiotics should be used in cases of endogenous endophthalmitis and exogenous fungal endophthalmitis, but their role in exogenous bacterial endophthalmitis is uncertain. Repeated intravitreal injections of antibiotics may be necessary if there is no response to the initial therapy. Many eyes that receive prompt and appropriate treatment will recover useful vision. C1 [Durand, M. L.] Massachusetts Eye & Ear Infirm, Infect Dis Serv, Boston, MA 02114 USA. [Durand, M. L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Durand, M. L.] Harvard Univ, Sch Med, Boston, MA USA. RP Durand, ML (reprint author), Massachusetts Gen Hosp, Cox 5,55 Fruit St, Boston, MA 02114 USA. EM mdurand@partners.org NR 58 TC 50 Z9 51 U1 0 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1198-743X J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PD MAR PY 2013 VL 19 IS 3 BP 227 EP 234 DI 10.1111/1469-0691.12118 PG 8 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 096OY UT WOS:000315415300012 PM 23438028 ER PT J AU Brown, JR AF Brown, Jennifer R. TI Ibrutinib (PCI-32765), the First BTK (Bruton's Tyrosine Kinase) Inhibitor in Clinical Trials SO CURRENT HEMATOLOGIC MALIGNANCY REPORTS LA English DT Article DE PCI32765; BTK; Kinase; Lymphocytosis; CLL; Ibrutinib ID CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELL RECEPTOR; FLUDARABINE; RITUXIMAB; SURVIVAL; CYCLOPHOSPHAMIDE; OFATUMUMAB AB Ibrutinib is a potent covalent kinase inhibitor that targets BTK. BTK, or Bruton's tyrosine kinase, is an obvious target for therapy of B cell diseases because inactivating mutations lead to B cell aplasia in humans and the disease X-linked agammaglobulinemia. Ibrutinib has modest cytotoxicity against CLL cells in vitro but also blocks trophic stimuli from the microenvironment. As with other inhibitors of the BCR pathway, ibrutinib causes rapid nodal reduction and response associated with rapid increase in lymphocytosis, which then returns to baseline over time. The ORR of ibrutinib in relapsed refractory CLL is 67 % with PFS 88 % at 15 months. In a cohort of untreated patients 65 years and over, the estimated 15 month PFS is 96 %. Registration trials have been initiated, and the difficult task that remains is to determine where in the course of CLL therapy this drug will have the greatest impact and benefit for patients. C1 [Brown, Jennifer R.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Brown, JR (reprint author), Harvard Univ, Sch Med, 450 Brookline Ave, Boston, MA 02215 USA. EM Jbrown2@partners.org FU Sanofi; Pharmacyclics FX J. Brown: consultant for Avila, Novartis, Emergent, Celgene, Genentech, Pharmacyclics, Sanofi; received funding for investigator initiated clinical trial from Genzyme (now Sanofi); travel/accommodation expenses covered or reimbursed by Pharmacyclics. NR 24 TC 30 Z9 34 U1 0 U2 29 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1558-8211 J9 CURR HEMATOL MALIG R JI Curr. Hematol. Malig. Rep. PD MAR PY 2013 VL 8 IS 1 BP 1 EP 6 DI 10.1007/s11899-012-0147-9 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 095OO UT WOS:000315344100001 PM 23296407 ER PT J AU Boot, M Volkening, LK Butler, DA Laffel, LMB AF Boot, M. Volkening, L. K. Butler, D. A. Laffel, L. M. B. TI The impact of blood glucose and HbA1c goals on glycaemic control in children and adolescents with Type 1 diabetes SO DIABETIC MEDICINE LA English DT Article ID METABOLIC-CONTROL; MANAGEMENT; OUTCOMES; YOUTH; INVOLVEMENT; PREDICTORS; ADHERENCE; MELLITUS; CARE AB Aims To evaluate parents' goals and parents' perceptions of physicians' goals for blood glucose and HbA1c in children and adolescents with Type 1 diabetes. Methods In a cross-sectional observational assessment, parents (80% mothers) of 153 children/adolescents (56% female), aged 12.9 +/- 2.3years (range 816years) with Type 1 diabetes for 6.3 +/- 3.5years, completed surveys regarding their goals and their perceptions of physicians' goals for their child's blood glucose and HbA1c levels. Results Children/adolescents had a mean HbA1c of 69 +/- 16mmol/mol (8.4 +/- 1.4%) and checked blood glucose levels 3.8 +/- 1.2times/day; 23% received pump therapy. Almost half of parents reported a blood glucose goal of 130 (80180)mg/dl [7.2 (4.410)mmol/l]; 75% of parents reported a HbA1c goal of 4264mmol/mol (68%). HbA1c was significantly lower when parents reported HbA1c goals 64mmol/mol (8%) vs. >64mmol/mol (>8%) [67 +/- 14mmol/mol (8.3 +/- 1.2%) vs. 76 +/- 20mmol/mol (9.1 +/- 1.8%), respectively, P=0.02]. Parents' blood glucose and HbA1c goals were tightly linked with parents' perceptions of physicians' blood glucose and HbA1c goals (69% concordant, P<0.0001; 88% concordant, P<0.0001, respectively). Conclusions There was a significant association between lower parent HbA1c goals and lower child/adolescent HbA1c. Further, parents appear to set glycaemic goals based upon their perceptions of physician goals. Future studies should assess the relationship between parents' perceptions of health-care providers' goals and health-care providers' actual goals and the impact of unified family/provider goal-setting on glycaemic control. C1 [Boot, M.; Volkening, L. K.; Butler, D. A.; Laffel, L. M. B.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Genet & Epidemiol Sect, Boston, MA 02215 USA. RP Laffel, LMB (reprint author), Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Genet & Epidemiol Sect, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu FU Charles H. Hood Foundation; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK046887]; Diabetes and Endocrinology Research Center [P30DK036836]; Katherine Adler Astrove Youth Education Fund; Maria Griffin Drury Pediatric Fund FX This study was supported in part by the Charles H. Hood Foundation, grant R01DK046887 from the National Institute of Diabetes and Digestive and Kidney Diseases, the Diabetes and Endocrinology Research Center (P30DK036836), the Katherine Adler Astrove Youth Education Fund and the Maria Griffin Drury Pediatric Fund. NR 19 TC 3 Z9 3 U1 3 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD MAR PY 2013 VL 30 IS 3 BP 333 EP 337 DI 10.1111/dme.12083 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 095MT UT WOS:000315339300019 PM 23190135 ER PT J AU Sohn, K Wende, AR Abel, ED Moreno, AP Sachse, FB Punske, BB AF Sohn, Kwanghyun Wende, Adam R. Abel, E. Dale Moreno, Alonso P. Sachse, Frank B. Punske, Bonnie B. TI Absence of glucose transporter 4 diminishes electrical activity of mouse hearts during hypoxia SO EXPERIMENTAL PHYSIOLOGY LA English DT Article ID GLUCOSE-TRANSPORTER GLUT4; VOLTAGE-SENSITIVE DYE; GUINEA-PIG HEARTS; ACTION-POTENTIAL DURATION; RAT CARDIAC MYOCYTES; RATE-LIMITING STEPS; PAPILLARY MUSCLE; CYTOCHALASIN-D; IN-VIVO; GLUT4-DEFICIENT HEARTS AB New Findings center dot What is the central question of this study? The aim of this study was to examine quantitatively whether glucose transporter 4 deficiency leads to more severe alterations in cardiac electrical activity during cardiac stress. center dot What is the main finding and what is its importance? When compared with hearts from corresponding control littermates, the measured epicardial potentials from the surface of cardiac-selective glucose transporter 4-ablated mouse hearts during hypoxia showed the following differences: (i) significant decreases in the maximal downstroke of the potentials; (ii) increased activation time; and (iii) greater alterations in the activation sequence. Insulin resistance, which characterizes type 2 diabetes, is associated with reduced translocation of glucose transporter 4 (GLUT4) to the plasma membrane following insulin stimulation, and diabetic patients with insulin resistance show a higher incidence of ischaemia, arrhythmias and sudden cardiac death. The aim of this study was to examine whether GLUT4 deficiency leads to more severe alterations in cardiac electrical activity during cardiac stress due to hypoxia. To fulfil this aim, we compared cardiac electrical activity from cardiac-selective GLUT4-ablated (G4H/) mouse hearts and corresponding control (CTL) littermates. A custom-made cylindrical cage' electrode array measured potentials (Ves) from the epicardium of isolated, perfused mouse hearts. The normalized average of the maximal downstroke of Ves (|dVes/dtmin|na), which we previously introduced as an index of electrical activity in normal, ischaemic and hypoxic hearts, was used to assess the effects of GLUT4 deficiency on electrical activity. The |dVes/dtmin|na of G4H/ and CTL hearts decreased by 75 and 47%, respectively (P < 0.05), 30 min after the onset of hypoxia. Administration of insulin attenuated decreases in values of |dVes/dtmin|na in G4H/ hearts as well as in CTL hearts, during hypoxia. In general, however, G4H/ hearts showed a severe alteration of the propagation sequence and a prolonged total activation time. Results of this study demonstrate that reduced glucose availability associated with insulin resistance and a reduction in GLUT4-mediated glucose transport impairs electrical activity during hypoxia, and may contribute to cardiac vulnerability to arrhythmias in diabetic patients. C1 [Sohn, Kwanghyun; Moreno, Alonso P.; Sachse, Frank B.; Punske, Bonnie B.] Univ Utah, Nora Eccles Harrison Cardiovasc Res & Training In, Salt Lake City, UT 84112 USA. [Sohn, Kwanghyun; Moreno, Alonso P.; Sachse, Frank B.; Punske, Bonnie B.] Univ Utah, Dept Bioengn, Salt Lake City, UT 84112 USA. [Sohn, Kwanghyun] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Wende, Adam R.; Abel, E. Dale] Univ Utah, Sch Med, Div Endocrinol Metab & Diabet, Program Mol Med, Salt Lake City, UT 84112 USA. [Moreno, Alonso P.; Punske, Bonnie B.] Univ Utah, Sch Med, Div Cardiol, Salt Lake City, UT 84112 USA. RP Punske, BB (reprint author), Univ Utah, Nora Eccles Harrison Cardiovasc Res & Training In, 95 South 2000 East, Salt Lake City, UT 84112 USA. EM punske@cvrti.utah.edu OI Sachse, Frank/0000-0003-4987-705X; Wende, Adam/0000-0002-5536-4675 FU Richard A. and Nora Eccles Fund for Cardiovascular Research; Nora Eccles Treadwell Foundation; American Heart Association Western States Affiliate Postdoctoral Fellowship; Juvenile Diabetes Research Foundation; [UO1 HL087947] FX This work was supported by the Richard A. and Nora Eccles Fund for Cardiovascular Research and awards from the Nora Eccles Treadwell Foundation. A. R. W. was supported by an American Heart Association Western States Affiliate Postdoctoral Fellowship and an Advanced Postdoctoral Fellowship from the Juvenile Diabetes Research Foundation. E. D. A. was supported by UO1 HL087947. The authors wish to acknowledge Dr Philip Ershler and Mr Bruce Steadman for the design and development of the data acquisition hardware and Mr Ted Dustman for his efforts in designing our data processing software. In addition, we would like to acknowledge the technical expertise and support of Alicja Booth, Jayne Davis and Nancy Allen. NR 73 TC 3 Z9 4 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0958-0670 J9 EXP PHYSIOL JI Exp. Physiol. PD MAR PY 2013 VL 98 IS 3 BP 746 EP 757 DI 10.1113/expphysiol.2012.070235 PG 12 WC Physiology SC Physiology GA 094XJ UT WOS:000315298200020 PM 23180812 ER PT J AU Avci, P Sadasivam, M Gupta, A De Melo, WCMA Huang, YY Yin, R Chandran, R Kumar, R Otufowora, A Nyame, T Hamblin, MR AF Avci, Pinar Sadasivam, Magesh Gupta, Asheesh De Melo, Wanessa C. M. A. Huang, Ying-Ying Yin, Rui Chandran, Rakkiyappan Kumar, Raj Otufowora, Ayodeji Nyame, Theodore Hamblin, Michael R. TI Animal models of skin disease for drug discovery SO EXPERT OPINION ON DRUG DISCOVERY LA English DT Review DE alopecia; animal models; dermatitis; dermatology; dermatomyositis; psoriasis; scleroderma; skin cancer; transgenic mouse models; wound healing ID CHEMOTHERAPY-INDUCED ALOPECIA; DYSTROPHIC EPIDERMOLYSIS-BULLOSA; CUTANEOUS LUPUS-ERYTHEMATOSUS; ENGINEERED MOUSE MODELS; ATOPIC-DERMATITIS; TRANSGENIC MICE; IN-VIVO; HAIR LOSS; MURINE MODEL; THERAPEUTIC INTERVENTION AB Introduction: Discovery of novel drugs, treatments, and testing of consumer products in the field of dermatology is a multi-billion dollar business. Due to the distressing nature of many dermatological diseases, and the enormous consumer demand for products to reverse the effects of skin photodamage, aging, and hair loss, this is a very active field. Areas covered: In this paper, we will cover the use of animal models that have been reported to recapitulate to a greater or lesser extent the features of human dermatological disease. There has been a remarkable increase in the number and variety of transgenic mouse models in recent years, and the basic strategy for constructing them is outlined. Expert opinion: Inflammatory and autoimmune skin diseases are all represented by a range of mouse models both transgenic and normal. Skin cancer is mainly studied in mice and fish. Wound healing is studied in a wider range of animal species, and skin infections such as acne and leprosy also have been studied in animal models. Moving to the more consumer-oriented area of dermatology, there are models for studying the harmful effect of sunlight on the skin, and testing of sunscreens, and several different animal models of hair loss or alopecia. C1 [Avci, Pinar; Sadasivam, Magesh; Gupta, Asheesh; De Melo, Wanessa C. M. A.; Huang, Ying-Ying; Yin, Rui; Chandran, Rakkiyappan; Kumar, Raj; Otufowora, Ayodeji; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Avci, Pinar; Gupta, Asheesh; Huang, Ying-Ying; Yin, Rui; Kumar, Raj; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Nyame, Theodore] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg, Boston, MA 02115 USA. [Gupta, Asheesh] Def Inst Physiol & Allied, Delhi 110054, India. [De Melo, Wanessa C. M. A.] Univ Fed Sao Paulo, Sao Carlos, SP, Brazil. [Yin, Rui] Third Mil Med Univ, Southwest Hosp, Dept Dermatol, Chongqing 400038, Peoples R China. [Sadasivam, Magesh; Chandran, Rakkiyappan] Amity Univ Uttar Pradesh, Amity Inst Nanotechnol, Noida 201303, India. [Huang, Ying-Ying] Guangxi Med Univ, Aesthet & Plast Ctr, Nanning, Peoples R China. [Hamblin, Michael R.] Harvard Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomedicine, Boston, MA 02115 USA. EM hamblin@helix.mgh.harvard.edu RI Huang, Ying-ying/G-3153-2011; Kumar, Raj/M-3662-2014; OI Huang, Ying-ying/0000-0003-3066-6981; Hamblin, Michael/0000-0001-6431-4605 FU US NIH [R01AI050875]; Department of Science and Technology, Government of India (BOYCAST Fellowship); National Natural Science Foundation of China [81172495] FX We are grateful to VJB de Arce for editorial assistance. Research in the Hamblin laboratory is supported by the US NIH (R01AI050875). A Gupta was supported by Department of Science and Technology, Government of India (BOYCAST Fellowship 2010-11). Rui Yin was supported by the National Natural Science Foundation of China (Grant No. 81172495). NR 187 TC 10 Z9 10 U1 1 U2 36 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1746-0441 J9 EXPERT OPIN DRUG DIS JI Expert. Opin. Drug Discov. PD MAR PY 2013 VL 8 IS 3 BP 331 EP 355 DI 10.1517/17460441.2013.761202 PG 25 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 093BF UT WOS:000315166000007 PM 23293893 ER PT J AU Souter, I Batsis, M Karmon, AE Petrozza, JC AF Souter, Irene Batsis, Maria Karmon, Anatte E. Petrozza, John C. TI Should Infertile Women with Normal TSH Levels (> 5.0mIU/L) Strive for a Stricter Preconception TSH cut-off? The Effects of a Lower TSH Threshold on the Outcome of Ovulation Induction/Intrauterine Insemination (OI/IUI) Cycles SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 61st Annual Meeting of the Pacific-Coast-Reproductive-Society (PCRS) CY APR 17-21, 2013 CL Indian Wells, CA SP Pacific Coast Reproduct Soc (PCRS) C1 [Souter, Irene; Batsis, Maria; Karmon, Anatte E.; Petrozza, John C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrinol & Infertil Div,Fertil Ctr,Dept, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 MAR PY 2013 VL 99 IS 3 SU S BP S18 EP S19 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 094RP UT WOS:000315281800033 ER PT J AU Dowty, JG Win, AK Buchanan, DD Lindor, NM Macrae, FA Clendenning, M Antill, YC Thibodeau, SN Casey, G Gallinger, S Le Marchand, L Newcomb, PA Haile, RW Young, GP James, PA Giles, GG Gunawardena, SR Leggett, BA Gattas, M Boussioutas, A Ahnen, DJ Baron, JA Parry, S Goldblatt, J Young, JP Hopper, JL Jenkins, MA AF Dowty, James G. Win, Aung K. Buchanan, Daniel D. Lindor, Noralane M. Macrae, Finlay A. Clendenning, Mark Antill, Yoland C. Thibodeau, Stephen N. Casey, Graham Gallinger, Steve Le Marchand, Loic Newcomb, Polly A. Haile, Robert W. Young, Graeme P. James, Paul A. Giles, Graham G. Gunawardena, Shanaka R. Leggett, Barbara A. Gattas, Michael Boussioutas, Alex Ahnen, Dennis J. Baron, John A. Parry, Susan Goldblatt, Jack Young, Joanne P. Hopper, John L. Jenkins, Mark A. TI Cancer Risks for MLH1 and MSH2 Mutation Carriers SO HUMAN MUTATION LA English DT Article DE Lynch syndrome; MLH1; MSH2; risk; penetrance; cancer; colorectal cancer; endometrial cancer; segregation analysis; Colon CFR ID NONPOLYPOSIS COLORECTAL-CANCER; MISMATCH-REPAIR GENES; BODY-MASS INDEX; LYNCH-SYNDROME; COLON-CANCER; FAMILY REGISTRY; BREAST-CANCER; ENDOMETRIAL CANCER; GERMLINE MUTATIONS; PROSTATE-CANCER AB We studied 17,576 members of 166 MLH1 and 224 MSH2 mutation-carrying families from the Colon Cancer Family Registry. Average cumulative risks of colorectal cancer (CRC), endometrial cancer (EC), and other cancers for carriers were estimated using modified segregation analysis conditioned on ascertainment criteria. Heterogeneity in risks was investigated using a polygenic risk modifier. Average CRC cumulative risks at the age of 70 years (95% confidence intervals) for MLH1 and MSH2 mutation carriers, respectively, were estimated to be 34% (25%50%) and 47% (36%60%) for male carriers and 36% (25%51%) and 37% (27%50%) for female carriers. Corresponding EC risks were 18% (9.1%34%) and 30% (18%45%). A high level of CRC risk heterogeneity was observed (P<0.001), with cumulative risks at the age of 70 years estimated to follow U-shaped distributions. For example, 17% of male MSH2 mutation carriers have estimated lifetime risks of 0%10% and 18% have risks of 90%100%. Therefore, average risks are similar for the two genes but there is so much individual variation about the average that large proportions of carriers have either very low or very high lifetime cancer risks. Our estimates of CRC and EC cumulative risks for MLH1 and MSH2 mutation carriers are the most precise currently available. C1 [Dowty, James G.; Win, Aung K.; Hopper, John L.; Jenkins, Mark A.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Parkville, Vic 3010, Australia. [Buchanan, Daniel D.; Clendenning, Mark; Young, Joanne P.] Queensland Inst Med Res, Familial Canc Lab, Brisbane, Qld 4006, Australia. [Lindor, Noralane M.] Mayo Clin, Dept Med Genet, Rochester, MN USA. [Macrae, Finlay A.] Royal Melbourne Hosp, Dept Colorectal Med & Genet, Parkville, Vic 3050, Australia. [Antill, Yoland C.] Cabrini Hlth, Familial Canc Ctr, Melbourne, Vic, Australia. [Antill, Yoland C.] So Hlth, Familial Canc Ctr, Clayton, Vic, Australia. [Thibodeau, Stephen N.; Gunawardena, Shanaka R.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Casey, Graham; Haile, Robert W.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Gallinger, Steve] Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. [Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. [Young, Graeme P.] Flinders Univ S Australia, Ctr Canc Prevent & Control, Bedford Pk, SA, Australia. [James, Paul A.; Boussioutas, Alex] Peter MacCallum Canc Ctr, Familial Canc Ctr, Melbourne, Vic, Australia. [Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Leggett, Barbara A.] Royal Brisbane & Womens Hosp Res Fdn, Conjoint Gastroenterol Lab, Clin Res Ctr, Brisbane, Qld, Australia. [Leggett, Barbara A.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Gattas, Michael] Royal Childrens Hosp, Queensland Clin Genet Serv, Herston, Qld, Australia. [Boussioutas, Alex] Univ Melbourne, Royal Melbourne Hosp, Dept Med, Parkville, Vic 3010, Australia. [Ahnen, Dennis J.] Univ Colorado, Sch Med, Dept Med, Denver, CO USA. [Ahnen, Dennis J.] Denver VA Med Ctr, Denver, CO USA. [Baron, John A.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Parry, Susan] Auckland City Hosp, New Zealand Familial Gastrointestinal Canc Regist, Auckland, New Zealand. [Goldblatt, Jack] Univ Western Australia, Genet Serv & Familial Canc Program Western Austra, Sch Paediat & Child Hlth, Perth, WA 6009, Australia. RP Dowty, JG (reprint author), Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Parkville, Vic 3010, Australia. EM jdowty@unimelb.edu.au RI Gallinger, Steven/E-4575-2013; James, Paul/G-2943-2014; Jenkins, Mark/P-7803-2015; Leggett, Barbara/D-3579-2011; OI Jenkins, Mark/0000-0002-8964-6160; Dowty, James/0000-0003-2383-0886; Giles, Graham/0000-0003-4946-9099; Boussioutas, Alex/0000-0002-8109-6897; Win, Aung Ko/0000-0002-2794-5261; Buchanan, Daniel/0000-0003-2225-6675 FU NCI NIH HHS [R01 CA122340, CA-95-011, K05 CA152715, K22 CA095011, P50 CA116201, R01 CA128978, U01 CA069398, U01 CA069631, U01 CA074783, U01 CA074794, U01 CA074799, U01 CA074800, U01 CA074806, U01 CA097735, U24 CA074783, U24 CA074794, U24 CA074799, U24 CA074800, U24 CA074806, U24 CA097735] NR 43 TC 44 Z9 44 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD MAR PY 2013 VL 34 IS 3 BP 490 EP 497 DI 10.1002/humu.22262 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 093IX UT WOS:000315186400011 PM 23255516 ER PT J AU Mahalingam, M Hoang, MP AF Mahalingam, Meera Hoang, Mai P. TI Porocarcinoma: an exceedingly rare tumor or a tumor eclipse phenomenon?-Reply SO HUMAN PATHOLOGY LA English DT Letter C1 [Mahalingam, Meera] Boston Univ, Sch Med, Dermatopathol Sect, Dept Dermatol, Boston, MA 01228 USA. [Hoang, Mai P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Mahalingam, M (reprint author), Boston Univ, Sch Med, Dermatopathol Sect, Dept Dermatol, Boston, MA 01228 USA. EM mmahalin@bu.edu; mhoang@partners.org OI Mahalingam, Meera/0000-0002-2800-9985 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAR PY 2013 VL 44 IS 3 BP 449 EP 449 DI 10.1016/j.humpath.2012.11.010 PG 1 WC Pathology SC Pathology GA 092MI UT WOS:000315126300020 PM 23290010 ER PT J AU Hong, O Chin, DL Ronis, DL AF Hong, OiSaeng Chin, Dal Lae Ronis, David L. TI Predictors of Hearing Protection Behavior Among Firefighters in the United States SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE Hearing protection; Firefighter; Predictors; Noise-induced hearing loss ID HEALTH-PROMOTION MODEL; CONSTRUCTION WORKERS USE; NOISE EXPOSURE; INTERVENTION; EFFICACY AB Noise-induced hearing loss (NIHL) is a major occupational health problem that can be prevented through the use of hearing protection devices (HPDs). The purpose of this study is to identify significant factors related to firefighters' use of HPDs. A total of 404 firefighters from 35 fire departments in multiple states in the United States participated in an Internet-based survey from March 2010 to May 2011. Pearson correlations and multiple regression analysis suggested that several modifying and cognitive-perceptual factors were significantly related to HPD use, including noise exposure, interpersonal influences, organizational support, perceived barriers to HPD use, and perceived susceptibility to hearing loss. The multiple regression model explained 56% (R (2) = .56, adjusted R (2) = .54) of the variance in firefighters' use of HPDs (F (13, 372) = 35.65, p < .001). Future research should focus on incorporating these significant predictors into effective behavioral interventions designed to promote the use of HPDs in this population. C1 [Hong, OiSaeng; Chin, Dal Lae] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. [Ronis, David L.] Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. [Ronis, David L.] US Dept Vet Affairs, Ctr Clin Management Res, Ann Arbor, MI USA. [Hong, OiSaeng] Univ Calif San Francisco, Sch Nursing, Occupat & Environm Hlth Nursing Program, San Francisco, CA 94143 USA. RP Hong, O (reprint author), Univ Calif San Francisco, Sch Nursing, Occupat & Environm Hlth Nursing Program, 2 Koret Way,Room N 531D, San Francisco, CA 94143 USA. EM oisaeng.hong@nursing.ucsf.edu NR 37 TC 4 Z9 4 U1 1 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PD MAR PY 2013 VL 20 IS 1 BP 121 EP 130 DI 10.1007/s12529-011-9207-0 PG 10 WC Psychology, Clinical SC Psychology GA 094NQ UT WOS:000315271400017 PM 22161219 ER PT J AU Wang, SK Hu, Y Simmer, JP Seymen, F Estrella, NMRP Pal, S Reid, BM Yildirim, M Bayram, M Bartlett, JD Hu, JCC AF Wang, S. -K. Hu, Y. Simmer, J. P. Seymen, F. Estrella, N. M. R. P. Pal, S. Reid, B. M. Yildirim, M. Bayram, M. Bartlett, J. D. Hu, J. C. -C. TI Novel KLK4 and MMP20 Mutations Discovered by Whole-exome Sequencing SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE dental enamel; amelogenesis imperfecta; tooth; metalloproteases; serine proteases; human FAM83H protein ID HYPOMATURATION AMELOGENESIS-IMPERFECTA; JUNCTIONAL EPIDERMOLYSIS-BULLOSA; PEPTIDASE 4; ENAMEL; GENE; MMP-20; EXPRESSION; DYSTROPHY; CLEAVAGE; FAM83H AB Non-syndromic amelogenesis imperfecta (AI) is a collection of isolated inherited enamel malformations that follow X-linked, autosomal-dominant, or autosomal-recessive patterns of inheritance. The AI phenotype is also found in syndromes. We hypothesized that whole-exome sequencing of AI probands showing simplex or recessive patterns of inheritance would identify causative mutations among the known candidate genes for AI. DNA samples obtained from 12 unrelated probands with AI were analyzed. Disease-causing mutations were identified in three of the probands: a novel single-nucleotide deletion in both KLK4 alleles (g.6930delG; c.245delG; p.Gly82Alafs*87) that shifted the reading frame, a novel missense transition mutation in both MMP20 alleles (g.15390A>G; c.611A>G; p.His204Arg) that substituted arginine for an invariant histidine known to coordinate a structural zinc ion, and a previously described nonsense transition mutation in a single allele of FAM83H (c.1379G>A; g.5663G>A; p.W460*). Erupted molars and cross-sections from unerupted parts of the mandibular incisors of Mmp20 null mice were characterized by scanning electron microscopy. Their enamel malformations closely correlated with the enamel defects displayed by the proband with the MMP20 mutation. We conclude that whole-exome sequencing is an effective means of identifying disease-causing mutations in kindreds with AI, and this technique should prove clinically useful for this purpose. C1 [Wang, S. -K.; Hu, Y.; Simmer, J. P.; Pal, S.; Reid, B. M.; Hu, J. C. -C.] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48108 USA. [Seymen, F.; Yildirim, M.; Bayram, M.] Istanbul Univ, Fac Dent, Dept Pedodont, Istanbul, Turkey. [Estrella, N. M. R. P.] Univ Michigan, Sch Dent, Dept Orthodont & Pediat Dent, Ann Arbor, MI 48108 USA. [Bartlett, J. D.] Forsyth Inst, Dept Cytokine Biol, Cambridge, MA USA. RP Simmer, JP (reprint author), Univ Michigan, Sch Dent, Dept Biol & Mat Sci, 1210 Eisenhower Pl, Ann Arbor, MI 48108 USA. EM jsim-mer@umich.edu FU NIDCR/NIH [DE019775, DE019622, DE015846] FX We thank the families in this study for their participation. This work was supported by the NIDCR/NIH (Grants DE019775, DE019622, and DE015846). The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 30 TC 23 Z9 24 U1 2 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAR PY 2013 VL 92 IS 3 BP 266 EP 271 DI 10.1177/0022034513475626 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 089MG UT WOS:000314914100011 PM 23355523 ER PT J AU Jenkins, MK Moon, JJ AF Jenkins, Marc K. Moon, James J. TI Response to Comment on "The Role of Naive T Cell Precursor Frequency and Recruitment in Dictating Immune Response Magnitude" SO JOURNAL OF IMMUNOLOGY LA English DT Letter C1 [Jenkins, Marc K.] Univ Minnesota, Sch Med, Dept Microbiol, Ctr Immunol, Minneapolis, MN 55455 USA. [Moon, James J.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Moon, James J.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Moon, James J.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Charlestown, MA 02129 USA. RP Jenkins, MK (reprint author), Univ Minnesota, Sch Med, Dept Microbiol, Ctr Immunol, 2101 6th St SE,Campus Code 2641, Minneapolis, MN 55455 USA. EM jenki002@umn.edu RI Jenkins, Marc/G-1063-2012 OI Jenkins, Marc/0000-0001-8009-7655 NR 0 TC 1 Z9 1 U1 0 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 MAR 1 PY 2013 VL 190 IS 5 BP 1896 EP 1896 DI 10.4049/jimmunol.1290080 PG 1 WC Immunology SC Immunology GA 091ZT UT WOS:000315089100002 PM 23544199 ER PT J AU Sheth, SA Eskandar, EN AF Sheth, Sameer A. Eskandar, Emad N. TI Obsessive-compulsive disorder Response SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material C1 [Sheth, Sameer A.; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Sheth, SA (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 MAR PY 2013 VL 118 IS 3 BP 490 EP 490 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 094DW UT WOS:000315244200002 ER PT J AU Sheth, SA Neal, J Tangherlini, F Mian, MK Gentil, A Cosgrove, GR Eskandar, EN Dougherty, DD AF Sheth, Sameer A. Neal, Jonathan Tangherlini, Frances Mian, Matthew K. Gentil, Andre Cosgrove, G. Rees Eskandar, Emad N. Dougherty, Darin D. TI Limbic system surgery for treatment-refractory obsessive-compulsive disorder: a prospective long-term follow-up of 64 patients Clinical article SO JOURNAL OF NEUROSURGERY LA English DT Article DE cingulotomy; obsessive-compulsive disorder; psychiatric neurosurgery; depression; functional neurosurgery ID DEEP BRAIN-STIMULATION; BASAL GANGLIA; CINGULOTOMY; DEPRESSION; LEUCOTOMY; CIRCUITS; ILLNESS AB Object. Obsessive-compulsive disorder (OCD) is a common and disabling psychiatric illness, and in a significant proportion of patients with OCD the disease is refractory to conventional pharmacotherapy and psychotherapy. For more than half a century, patients with severe, treatment-resistant OCD have been treated with stereotactic limbic system lesions, including dorsal anterior cingulotomy. The authors present their results describing the efficacy and durability of limbic system surgery for OCD, characterizing a large cohort of patients treated at a single institution with a mean follow-up of more than 5 years. Methods. The authors identified 64 consecutive patients undergoing cingulotomy for refractory OCD at the Massachusetts General Hospital between 1989 and 2009. Changes in OCD and major depressive disorder symptom severity were assessed at both the initial and most recent postoperative follow-up by using the Yale-Brown Obsessive Compulsive Scale and the Beck Depression Inventory, respectively. Full and partial OCD symptom responses were defined as Yale-Brown Obsessive Compulsive Scale score reductions of a >= 35% and 25%-34%, respectively. Results. Regarding OCD symptom improvement, at the first postoperative follow-up (mean 10.7 months), 35% of patients demonstrated a full response and 7% were partial responders. Thirty patients had a subsequent procedure (repeat cingulotomy or subcaudate tractotomy). By the most recent follow-up (mean 63.8 months), rates climbed to 47% and 22% for full and partial responses, respectively. Of the 24 patients with at least a partial response at initial follow-up, 20 (83%) retained at least a partial response at final follow-up. Comorbid major depressive disorder severity decreased by 17% at the most recent follow-up. Conclusions. Limbic system surgery based on initial cingulotomy offers a durable and effective treatment option for appropriately selected patients with severe OCD who have not responded to conventional pharmacotherapy or psychotherapy. (http://thejns.org/doi/abs/10.3171/2012.11.JNS12389) C1 [Sheth, Sameer A.; Neal, Jonathan; Tangherlini, Frances; Mian, Matthew K.; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Dougherty, Darin D.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Mian, Matthew K.; Eskandar, Emad N.; Dougherty, Darin D.] Harvard Univ, Sch Med, Boston, MA USA. [Gentil, Andre] Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. [Cosgrove, G. Rees] Brown Univ, Warren Alpert Med Sch, Dept Neurosurg, Providence, RI 02912 USA. RP Sheth, SA (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White 502, Boston, MA 02114 USA. EM sasheth@partners.org NR 25 TC 25 Z9 25 U1 0 U2 5 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 MAR PY 2013 VL 118 IS 3 BP 491 EP 497 DI 10.3171/2012.11.JNS12389 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 094DW UT WOS:000315244200003 PM 23240700 ER PT J AU Hauptman, JS Dadour, A Oh, T Baca, CB Vickrey, BG Vassar, SD Sankar, R Salamon, N Vinters, HV Mathern, GW AF Hauptman, Jason S. Dadour, Andrew Oh, Taemin Baca, Christine B. Vickrey, Barbara G. Vassar, Stefanie D. Sankar, Raman Salamon, Noriko Vinters, Harry V. Mathern, Gary W. TI Sociodemographic changes over 25 years of pediatric epilepsy surgery at UCLA SO JOURNAL OF NEUROSURGERY-PEDIATRICS LA English DT Article DE socioeconomic disparity; seizure; craniotomy; health inequity; epilepsy ID TEMPORAL-LOBE EPILEPSY; UNITED-STATES; DISPARITIES; OUTCOMES; RACE/ETHNICITY; CHILDREN; SEIZURE; ACCESS; CARE AB Object. Low income, government insurance, and minority status are associated with delayed treatment for neurosurgery patients. Less is known about the influence of referral location and how socioeconomic factors and referral patterns evolve over time. For pediatric epilepsy surgery patients at the University of California, Los Angeles (UCLA), this study determined how referral location and sociodemographic features have evolved over 25 years. Methods. Children undergoing epilepsy neurosurgery at UCLA (453 patients) were classified by location of residence and compared with clinical epilepsy and sociodemographic factors. Results. From 1986 to 2010, referrals from Southern California increased (+33%) and referrals from outside of California decreased (-19%). Over the same period, the number of patients with preferred provider organization (PPO) and health maintenance organization (HMO) insurance increased (+148% and +69%, respectively) and indemnity insurance decreased (-96%). Likewise, the number of Hispanics (+117%) and Asians (100%) increased and Caucasians/whites decreased (-24%). The number of insurance companies decreased from 52 carriers per 100 surgical patients in 1986-1990 to 19 per 100 in 2006-2010. Patients living in the Eastern US had a younger age at surgery (-46%), shorter intervals from seizure onset to referral for evaluation (-28%) and from presurgical evaluation to surgery (-61%) compared with patients from Southern California. The interval from seizure onset to evaluation was shorter (-33%) for patients from Los Angeles County compared with those living in non-California Western US states. Conclusions. Referral locations evolved over 25 years at UCLA, with more cases coming from local regions; the percentage of minority patients also increased. The interval from seizures onset to surgery was shortest for patients living farthest from UCLA but still within the US. Geographic location and race/ethnicity was not associated with differences in becoming seizure free after epilepsy surgery in children. (http://thejns.org/doi/abs/10.3171/2012.11.PEDS12359) C1 [Hauptman, Jason S.; Dadour, Andrew; Oh, Taemin; Mathern, Gary W.] Univ Calif Los Angeles, David Geffen Sch Med, Mattel Childrens Hosp, Dept Neurosurg, Los Angeles, CA 90095 USA. [Baca, Christine B.; Vickrey, Barbara G.; Vassar, Stefanie D.; Sankar, Raman; Vinters, Harry V.] Univ Calif Los Angeles, David Geffen Sch Med, Mattel Childrens Hosp, Dept Neurol, Los Angeles, CA 90095 USA. [Sankar, Raman] Univ Calif Los Angeles, David Geffen Sch Med, Mattel Childrens Hosp, Dept Pediat, Los Angeles, CA 90095 USA. [Mathern, Gary W.] Univ Calif Los Angeles, David Geffen Sch Med, Mattel Childrens Hosp, Dept Psychiat & BioBehav Med, Los Angeles, CA 90095 USA. [Sankar, Raman] Univ Calif Los Angeles, David Geffen Sch Med, Mattel Childrens Hosp, Div Pediat Neurol, Los Angeles, CA 90095 USA. [Salamon, Noriko] Univ Calif Los Angeles, David Geffen Sch Med, Mattel Childrens Hosp, Div Neuroradiol, Los Angeles, CA 90095 USA. [Vinters, Harry V.] Univ Calif Los Angeles, David Geffen Sch Med, Mattel Childrens Hosp, Sect Neuropathol, Los Angeles, CA 90095 USA. [Baca, Christine B.; Vickrey, Barbara G.] VA Greater Los Angeles Hlth Care Syst, Dept Neurol, Los Angeles, CA USA. RP Mathern, GW (reprint author), 710 Westwood Plaza,Room 2123, Los Angeles, CA 90095 USA. EM gmathern@ucla.edu FU Epilepsy Foundation [213971]; NIH (National Institute on Aging, National Institute of Neurological Disorders and Stroke); US Veterans Administration Health Services Research and Development Service; American Heart Association; SCAN Foundation; Kansas City Area Life Sciences Institute; UCB Pharma; Sunovion; Upsher-Smith; Supernus; Lundbeck Pharma; Pfizer; University of California Pediatric Neuropathology Consortium; NeuroPace, Inc.; NIH [R01 NS38992]; [NIH-M11079933] FX Dr. Baca receives salary support from the Epilepsy Foundation Grant 213971. Dr. Vickrey serves on scientific advisory boards for the Sports Concussion Institute, National Multiple Sclerosis Society, and the NIH; serves on the editorial boards of Neurorehabilitation and Neural Repair and Circulation, Cardiovascular Quality and Outcomes, and is a section editor for Stroke; receives research support from the NIH (National Institute on Aging, National Institute of Neurological Disorders and Stroke), the US Veterans Administration Health Services Research and Development Service, the American Heart Association, and SCAN Foundation; and received funding for travel and a speaker honorarium from the Kansas City Area Life Sciences Institute. Dr. Sankar serves on scientific advisory boards for and has received honoraria and funding for travel from UCB Pharma, Sunovion, Upsher-Smith, Supernus, and Lundbeck Pharma; receives royalties from the publication of Pediatric Neurology, 3rd ed. (Demos Publishing, 2008) and Epilepsy: Mechanisms, Models, and Translational Perspectives (CRC Press, 2011); serves on speakers' bureaus for and has received speaker honoraria from UCB, GlaxoSmithKline, and Lundbeck. He receives funding from NIH-M11079933 (co-primary investigator) and from Pfizer (Lyrica pediatric partial seizures trial). He serves on the editorial board for Epilepsy & Behavior. Dr. Vinters is on the editorial boards of Neuropathology and Applied Neurobiology, Neuropathology, Journal of Neuroscience Research, and the Korean Journal of Pathology. The Harry V. Vinters laboratory was supported in part by the University of California Pediatric Neuropathology Consortium, and Harry V. Vinters trust owns shares in and receives dividends from the following makers of drugs and medical equipment: GE, 3M, Pfizer, Teva Pharma, and GlaxoSmithKline. The Vinters laboratory has received research funding in the past from NeuroPace, Inc. Dr. Mathern received research funding from NIH grant R01 NS38992, which partially supported this paper. He is also on the editorial boards for Neurology, Epilepsy Research, Epileptic Disorders, and Epilepsy & Seizures. He serves on the Data Management Committee for NeuroPace, Inc. NR 16 TC 4 Z9 5 U1 0 U2 3 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 MAR PY 2013 VL 11 IS 3 BP 250 EP 255 DI 10.3171/2012.11.PEDS12359 PG 6 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 094DV UT WOS:000315244100004 PM 23331214 ER PT J AU Hruby, A Ngwa, JS Renstrom, F Wojczynski, MK Ganna, A Hallmans, G Houston, DK Jacques, PF Kanoni, S Lehtimaki, T Lemaitre, RN Manichaikul, A North, KE Ntalla, I Sonestedt, E Tanaka, T van Rooij, FJA Bandinelli, S Djousse, L Grigoriou, E Johansson, I Lohman, KK Pankow, JS Raitakari, OT Riserus, U Yannakoulia, M Zillikens, MC Hassanali, N Liu, YM Mozaffarian, D Papoutsakis, C Syvanen, AC Uitterlinden, AG Viikari, J Groves, CJ Hofman, A Lind, L McCarthy, MI Mikkila, V Mukamal, K Franco, OH Borecki, IB Cupples, LA Dedoussis, GV Ferrucci, L Hu, FB Ingelsson, E Kahonen, M Kao, WHL Kritchevsky, SB Orho-Melander, M Prokopenko, I Rotter, JI Siscovick, DS Witteman, JCM Franks, PW Meigs, JB McKeown, NM Nettleton, JA AF Hruby, Adela Ngwa, Julius S. Renstrom, Frida Wojczynski, Mary K. Ganna, Andrea Hallmans, Goran Houston, Denise K. Jacques, Paul F. Kanoni, Stavroula Lehtimaki, Terho Lemaitre, Rozenn N. Manichaikul, Ani North, Kari E. Ntalla, Ioanna Sonestedt, Emily Tanaka, Toshiko van Rooij, Frank J. A. Bandinelli, Stefania Djousse, Luc Grigoriou, Efi. Johansson, Ingegerd Lohman, Kurt K. Pankow, James S. Raitakari, Olli T. Riserus, Ulf Yannakoulia, Mary Zillikens, M. Carola Hassanali, Neelam Liu, Yongmei Mozaffarian, Dariush Papoutsakis, Constantina Syvanen, Ann-Christine Uitterlinden, Andre G. Viikari, Jorma Groves, Christopher J. Hofman, Albert Lind, Lars McCarthy, Mark I. Mikkila, Vera Mukamal, Kenneth Franco, Oscar H. Borecki, Ingrid B. Cupples, L. Adrienne Dedoussis, George V. Ferrucci, Luigi Hu, Frank B. Ingelsson, Erik Kahonen, Mika Kao, W. H. Linda Kritchevsky, Stephen B. Orho-Melander, Marju Prokopenko, Inga Rotter, Jerome I. Siscovick, David S. Witteman, Jacqueline C. M. Franks, Paul W. Meigs, James B. McKeown, Nicola M. Nettleton, Jennifer A. TI Higher Magnesium Intake Is Associated with Lower Fasting Glucose and Insulin, with No Evidence of Interaction with Select Genetic Loci, in a Meta-Analysis of 15 CHARGE Consortium Studies SO JOURNAL OF NUTRITION LA English DT Article ID TYPE-2 DIABETES-MELLITUS; WHOLE-GRAIN INTAKE; DOUBLE-BLIND; COFFEE CONSUMPTION; DIETARY MAGNESIUM; ENVIRONMENT INTERACTIONS; CARDIOVASCULAR-DISEASE; NONDIABETIC SUBJECTS; METABOLIC SYNDROME; PROSPECTIVE COHORT AB Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesium intake and fasting glucose and insulin. Fifteen studies from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided data from up to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (In-pmol/L) and 2) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose [beta = -0.009 mmol/L (95% CI: -0.013, -0.005), P< 0.0001] and insulin (-0.020 In-pmo/L (95% CI: -0.024, -0.017), P< 0.0001]. No magnesium-related SNP or interaction between any SNP and magnesium reached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed a nominal association (uncorrected P= 0.03) with glucose, and rs11558471 in SLC30A8and rs3740393 near CNNM2showed a nominal interaction (uncorrected, both P = 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence and magnesium interaction with select loci suggests that further investigation is warranted. J. Nutr. 143: 345-353, 2013. C1 [Hruby, Adela; Jacques, Paul F.; McKeown, Nicola M.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Ngwa, Julius S.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Renstrom, Frida; Hu, Frank B.; Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Renstrom, Frida; Sonestedt, Emily; Orho-Melander, Marju; Franks, Paul W.] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Renstrom, Frida; Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Wojczynski, Mary K.; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Ganna, Andrea; Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Houston, Denise K.; Kritchevsky, Stephen B.] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA. [Kanoni, Stavroula] Wellcome Trust Sanger Inst, Hinxton, England. [Kanoni, Stavroula; Grigoriou, Efi.; Yannakoulia, Mary; Papoutsakis, Constantina; Dedoussis, George V.] Harokopio Univ Athens, Dept Nutr & Dietet, Athens, Greece. [Lehtimaki, Terho] Fimlab Labs, Tampere, Finland. [Lehtimaki, Terho] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Lehtimaki, Terho] Tampere Univ Hosp, Tampere, Finland. [Lemaitre, Rozenn N.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Manichaikul, Ani] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Manichaikul, Ani] Univ Virginia, Dept Publ Hlth Sci, Div Biostat & Epidemiol, Charlottesville, VA USA. [North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Ntalla, Ioanna; Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [van Rooij, Frank J. A.; Zillikens, M. Carola; Uitterlinden, Andre G.; Hofman, Albert; Franco, Oscar H.; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [van Rooij, Frank J. A.; Zillikens, M. Carola; Uitterlinden, Andre G.; Hofman, Albert; Franco, Oscar H.; Witteman, Jacqueline C. M.] Netherlands Consortium Hlth Aging, Netherlands Genom Initiat, Leiden, Netherlands. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy. [Djousse, Luc] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Djousse, Luc; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Djousse, Luc] Boston Vet Affairs Healthcare Syst, Massachusetts Vet Epidemiol & Res Informat Ctr, Boston, MA USA. [Djousse, Luc] Boston Vet Affairs Healthcare Syst, Ctr Geriatr Res Educ & Clin, Boston, MA USA. [Johansson, Ingegerd] Umea Univ, Dept Odontol, Umea, Sweden. [Lohman, Kurt K.] Wake Forest Sch Med, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC USA. [Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Raitakari, Olli T.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland. [Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Riserus, Ulf] Uppsala Univ, Dept Publ Hlth & Caring Sci Clin Nutr & Metab, Uppsala, Sweden. [Zillikens, M. Carola; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Hassanali, Neelam; Groves, Christopher J.; McCarthy, Mark I.; Prokopenko, Inga] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Liu, Yongmei] Wake Forest Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC USA. [Mozaffarian, Dariush] Harvard Univ, Sch Publ Hlth, Dept Epidemiol & Nutr, Boston, MA 02115 USA. [Mozaffarian, Dariush] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Syvanen, Ann-Christine] Uppsala Univ, Mol Med & Sci Life Lab, Dept Med Sci, Uppsala, Sweden. [Viikari, Jorma] Univ Turku, Dept Med, Turku, Finland. [Viikari, Jorma] Turku Univ Hosp, FIN-20520 Turku, Finland. [Lind, Lars] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [McCarthy, Mark I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England. [Mikkila, Vera] Univ Helsinki, Dept Food & Environm Sci, Helsinki, Finland. [Mukamal, Kenneth] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Cupples, L. Adrienne] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Kahonen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland. [Kahonen, Mika] Univ Tampere, FIN-33101 Tampere, Finland. [Kao, W. H. Linda] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Prokopenko, Inga] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Clin Epidemiol Unit, Boston, MA 02114 USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Diabet Res Unit, Boston, MA 02114 USA. [Nettleton, Jennifer A.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA. RP McKeown, NM (reprint author), Tufts Univ, Friedman Sch Nutr Sci & Policy, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. EM nicola.mckeown@tufts.edu RI Prokopenko, Inga/H-3241-2014; Sonestedt, Emily/I-3814-2016; Djousse, Luc/F-5033-2017; OI Prokopenko, Inga/0000-0003-1624-7457; Sonestedt, Emily/0000-0002-0747-4562; Djousse, Luc/0000-0002-9902-3047; Cupples, L. Adrienne/0000-0003-0273-7965; Kritchevsky, Stephen/0000-0003-3336-6781; Franks, Paul/0000-0002-0520-7604; Ganna, Andrea/0000-0002-8147-240X FU Pfizer Nutrition FX The full author list and affiliations are included in Supplemental Table 4 in the "Online Supporting Material" link in the online posting of the article and from the same link in the online table of contents at http://jn.nutrition.org. O.H.F. is the recipient of a grant from Pfizer Nutrition to establish a center for research on aging (ErasmusAGE). All other authors declared no conflicts of interest NR 40 TC 23 Z9 23 U1 1 U2 10 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAR PY 2013 VL 143 IS 3 BP 345 EP 353 DI 10.3945/jn.112.172049 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 093EC UT WOS:000315173500014 PM 23343670 ER PT J AU Shah, GN Price, TO Banks, WA Morofuji, Y Kovac, A Ercal, N Sorenson, CM Shin, ES Sheibani, N AF Shah, Gul N. Price, Tulin O. Banks, William A. Morofuji, Yoichi Kovac, Andrej Ercal, Nuran Sorenson, Christine M. Shin, Eui S. Sheibani, Nader TI Pharmacological Inhibition of Mitochondrial Carbonic Anhydrases Protects Mouse Cerebral Pericytes from High Glucose-Induced Oxidative Stress and Apoptosis SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID BLOOD-BRAIN-BARRIER; MICROVASCULAR PERICYTES; ENDOTHELIAL-CELLS; NITRIC-OXIDE; HYPERGLYCEMIA; EXPRESSION; COMPLICATIONS; PLURIPOTENT; DAMAGE; MODEL AB Diabetes-associated complications in the microvasculature of the brain are caused by oxidative stress, generated by overproduction of reactive oxygen species from hyperglycemia-induced accelerated oxidative metabolism of glucose. Pericytes, essential for the viability of the microvasculature, are especially susceptible to oxidative stress. Mitochondrial carbonic anhydrases, regulators of the oxidative metabolism of glucose, determine the rate of reactive oxygen species production and inhibition of mitochondrial carbonic anhydrases rescues glucose-induced pericyte loss in the diabetic mouse brain. We hypothesized that high glucose induces intracellular oxidative stress and pericyte apoptosis and that inhibition of mitochondrial carbonic anhydrases protects pericytes from oxidative stress-induced apoptosis. To validate our hypothesis, conditionally immortalized cerebral pericyte (IPC) cultures were established from Immortomice to investigate the effect of high glucose on oxidative stress and pericyte apoptosis. The IPCs expressed pericyte markers and induced high transendothelial electrical resistance and low permeability in brain endothelial cell monolayers comparable with pericytes in primary cultures. The IPCs also secreted cytokines constitutively and in response to lipopolysaccharide similar to pericytes. High glucose caused oxidative stress and apoptosis of these cells, with both oxidative stress and apoptosis significantly reduced after mitochondrial carbonic anhydrase inhibition. These results provide the first evidence that pharmacological inhibition of mitochondrial carbonic anhydrases attenuates pericyte apoptosis caused by high glucose-induced oxidative stress. Carbonic anhydrase inhibitors have a long history of safe clinical use and can be immediately evaluated for this new indication in translational research. Thus, mitochondrial carbonic anhydrases may provide a new therapeutic target for oxidative stress-related illnesses of the brain. C1 [Shah, Gul N.; Price, Tulin O.] St Louis Univ, Dept Internal Med, Edward A Doisy Res Ctr, Div Endocrinol, St Louis, MO 63104 USA. [Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Banks, William A.; Morofuji, Yoichi; Kovac, Andrej] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. [Ercal, Nuran] Missouri Univ Sci & Technol, Dept Chem, Rolla, MO USA. [Sorenson, Christine M.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pediat, Madison, WI USA. [Shin, Eui S.; Sheibani, Nader] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI USA. RP Shah, GN (reprint author), St Louis Univ, Dept Internal Med, Edward A Doisy Res Ctr, Div Endocrinol, 1100 S Grand Blvd,DRC 315, St Louis, MO 63104 USA. EM shahgn@slu.edu FU National Institutes of Health [R01-DK083485, RC4-EY021357, EY016695, P30-EY016665, P30-CA014520] FX This study was supported by the National Institutes of Health [Grants R01-DK083485, RC4-EY021357, EY016695, P30-EY016665, and P30-CA014520]. NR 40 TC 13 Z9 14 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 MAR PY 2013 VL 344 IS 3 BP 637 EP 645 DI 10.1124/jpet.112.201400 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 093LD UT WOS:000315192500010 PM 23249625 ER PT J AU Robinson-Cohen, C Littman, AJ Duncan, GE Roshanravan, B Ikizler, TA Himmelfarb, J Kestenbaum, BR AF Robinson-Cohen, Cassianne Littman, Alyson J. Duncan, Glen E. Roshanravan, Baback Ikizler, T. Alp Himmelfarb, Jonathan Kestenbaum, Bryan R. TI Assessment of Physical Activity in Chronic Kidney Disease SO JOURNAL OF RENAL NUTRITION LA English DT Article ID OLDER-ADULTS; ACTIVITY QUESTIONNAIRE; ACTIVITY SCALE; UNITED-STATES; ELDERLY PASE; EXERCISE; ACCELEROMETER; HEALTH; HEMODIALYSIS; INFLAMMATION AB Background: Physical inactivity plays an important role in the development of kidney disease and its complications; however, the validity of standard tools for measuring physical activity (PA) is not well understood. Study Design: We investigated the performance of several readily available and widely used PA and physical function questionnaires, individually and in combination, against accelerometry among a cohort of chronic kidney disease (CKD) participants. Setting and Participants: Forty-six participants from the Seattle Kidney Study, an observational cohort study of persons with CKD, completed the Physical Activity Scale for the Elderly, Human Activity Profile (HAP), Medical Outcomes Study SF-36 questionnaire, and the Four-week Physical Activity History questionnaires. We simultaneously measured PA using an Actigraph GT3X accelerometer during a 14-day period. We estimated the validity of each instrument by testing its associations with log-transformed accelerometry counts. We used the Akaike information criterion to investigate the performance of combinations of questionnaires. Results: All questionnaire scores were significantly associated with log-transformed accelerometry counts. The HAP correlated best with accelerometry counts (r(2) = 0.32) followed by SF-36 (r(2) = 0.23). Forty-three percent of the variability in accelerometry counts data was explained by a model that combined the HAP, SF-36, and Four-week Physical Activity History questionnaires. Conclusion: A combination of measurement tools can account for a modest component of PA in patients with CKD; however, a substantial proportion of PA is not captured by standard assessments. (c) 2013 by the National Kidney Foundation, Inc. All rights reserved. C1 [Robinson-Cohen, Cassianne; Littman, Alyson J.; Duncan, Glen E.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Robinson-Cohen, Cassianne; Roshanravan, Baback; Himmelfarb, Jonathan; Kestenbaum, Bryan R.] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA. [Littman, Alyson J.] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Duncan, Glen E.] Univ Washington, Nutr Sci Program, Seattle, WA 98195 USA. [Roshanravan, Baback; Himmelfarb, Jonathan; Kestenbaum, Bryan R.] Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA. [Ikizler, T. Alp] Vet Adm Tennessee Valley Healthcare Syst, Nashville, TN USA. [Ikizler, T. Alp] Vanderbilt Univ, Div Nephrol, Nashville, TN USA. RP Robinson-Cohen, C (reprint author), Univ Washington, Harborview Med Ctr, Kidney Res Inst, Box 359606,325 9th Ave, Seattle, WA 98104 USA. EM cassyrc@u.washington.edu RI Duncan, Glen/A-3771-2008; OI Duncan, Glen/0000-0001-6909-1869; Robinson-Cohen, Cassianne/0000-0003-4783-7046 FU Office of Research and Development Cooperative Studies Program, Department of Veterans Affairs; Seattle Epidemiologic Research and Information Center of the Department of Veterans Affairs; VA Rehabilitation Career Development Award [6982] FX This material is based on work supported in part by the Office of Research and Development Cooperative Studies Program, Department of Veterans Affairs. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. The Seattle Epidemiologic Research and Information Center of the Department of Veterans Affairs supported the involvement of all of the authors in this research. A.J.L. was supported by VA Rehabilitation Career Development Award (#6982). NR 40 TC 12 Z9 12 U1 2 U2 17 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1051-2276 J9 J RENAL NUTR JI J. Renal Nutr. PD MAR PY 2013 VL 23 IS 2 BP 123 EP 131 DI 10.1053/j.jrn.2012.04.008 PG 9 WC Nutrition & Dietetics; Urology & Nephrology SC Nutrition & Dietetics; Urology & Nephrology GA 093NN UT WOS:000315198700014 PM 22739659 ER PT J AU Weiner, RB Picard, MH AF Weiner, Rory B. Picard, Michael H. TI Quality in Echocardiography: Does It Make a Difference? SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Editorial Material ID CENTER THINK-TANK; PROGNOSTIC IMPLICATIONS; ACHIEVING QUALITY; OUTCOMES RESEARCH; AMERICAN-SOCIETY; OF-CARDIOLOGY; RECOMMENDATIONS; REGURGITATION; COLLEGE; HEART C1 Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Picard, MH (reprint author), Cardiac Ultrasound Lab, Yawkey 5E,55 Fruit St, Boston, MA 02114 USA. EM mhpicard@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 17 TC 2 Z9 2 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD MAR PY 2013 VL 26 IS 3 BP 243 EP 245 DI 10.1016/j.echo.2013.01.009 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 094US UT WOS:000315290200005 PM 23439073 ER PT J AU Rojas, CA Jaimes, C Abbara, S AF Rojas, Carlos Andres Jaimes, Camilo Abbara, Suhny TI Ventricular Septal Defects Embryology and Imaging Findings SO JOURNAL OF THORACIC IMAGING LA English DT Article DE ventricular septal defects; interventricular septum; congenital heart disease ID CONGENITAL HEART-DISEASE; INVASIVE OXIMETRY; QUANTIFICATION; CLOSURE; ADULTS; CT AB Ventricular septal defects are the most common congenital abnormality diagnosed in children and the second most common congenital heart condition diagnosed in adults. Depending on their location in the interventricular septum, ventricular septal defects are described as perimembranous, muscular, subarterial, and inflow. Awareness of the embryologic basis of these defects helps understand the anatomy and recognize their typical appearance on imaging. Diagnostic imaging plays a role in the characterization of the defect, identification of associated anomalies, and evaluation of hemodynamic repercussion, all of which contribute to guide treatment. C1 [Rojas, Carlos Andres] Univ S Florida, Dept Radiol, Tampa, FL 33612 USA. [Jaimes, Camilo] Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA 19104 USA. [Abbara, Suhny] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Cardiovasc Imaging, Boston, MA USA. RP Rojas, CA (reprint author), Univ S Florida, Dept Radiol, 12901 Bruce B Downs Blvd POB 17, Tampa, FL 33612 USA. EM caranrojas@gmail.com NR 30 TC 1 Z9 1 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0883-5993 J9 J THORAC IMAG JI J. Thorac. Imaging PD MAR PY 2013 VL 28 IS 2 BP W28 EP W34 DI 10.1097/RTI.0b013e31824b5b95 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 095QX UT WOS:000315350700002 PM 22516928 ER PT J AU Kibel, AS AF Kibel, Adam S. TI To Biopsy or Not to Biopsy: Minimizing the Risk of Prostate Needle Biopsy SO JOURNAL OF UROLOGY LA English DT Editorial Material ID PROPHYLAXIS; CANCER C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Urol,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kibel, AS (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Urol,Dana Farber Canc Inst, Boston, MA 02115 USA. NR 10 TC 2 Z9 2 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAR PY 2013 VL 189 IS 3 BP 796 EP 797 DI 10.1016/j.juro.2012.12.015 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 092HB UT WOS:000315109600002 PM 23246850 ER PT J AU Barry, MJ Cantor, A Roehrborn, CG AF Barry, Michael J. Cantor, Alan Roehrborn, Claus G. CA CAMUS Study Grp TI Relationships Among Participant International Prostate Symptom Score, Benign Prostatic Hyperplasia Impact Index Changes and Global Ratings of Change in a Trial of Phytotherapy in Men with Lower Urinary Tract Symptoms SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic hyperplasia; lower urinary tract symptoms; health status index; psychometrics ID HEALTH-STATUS; COMBAT TRIAL; SATISFACTION; MODERATE; OVERLAP; WOMEN AB Purpose: We related changes in American Urological Association symptom index scores with bother measures and global ratings of change in men with lower urinary tract symptoms who were enrolled in a saw palmetto trial. Materials and Methods: To be eligible for study men were 45 years old or older, and had a peak uroflow of 4 ml per second or greater and an American Urological Association symptom index score of 8 to 24. Participants self-administered the American Urological Association symptom index, International Prostate Symptom Score quality of life item, Benign Prostatic Hyperplasia Impact Index and 2 global change questions at baseline, and at 24, 48 and 72 weeks. Results: In 357 participants global ratings of a little better were associated with a mean decrease in American Urological Association symptom index scores from 2.8 to 4.1 points across 3 time points. The analogous range for mean decreases in Benign Prostatic Hyperplasia Impact Index scores was 1.0 to 1.7 points and for the International Prostate Symptom Score quality of life item it was 0.5 to 0.8 points. At 72 weeks for the first global change question each change measure discriminated between participants who rated themselves at least a little better vs unchanged or worse 70% to 72% of the time. A multivariate model increased discrimination to 77%. For the second global change question each change measure correctly discriminated ratings of at least a little better vs unchanged or worse 69% to 74% of the time and a multivariate model increased discrimination to 79%. Conclusions: Changes in American Urological Association symptom index scores could discriminate between participants rating themselves at least a little better vs unchanged or worse. Our findings support the practice of powering studies to detect group mean differences in American Urological Association symptom index scores of at least 3 points. C1 [Barry, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cantor, Alan] Univ Alabama Birmingham, Birmingham, AL USA. [Roehrborn, Claus G.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM mbarry@partners.org FU National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases [U01 DK63795, U01 DK63797, U01 DK63825, U01 DK63835, U01 DK63866, U01 DK63833, U01 DK63862, U01 DK63840, U01 DK63883, U01 DK63831, U01 DK63778, U01 DK63788]; National Center for Complementary and Alternative Medicine; Office of Dietary Supplements, National Institutes of Health FX Supported by National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases Cooperative Agreements U01 DK63795, U01 DK63797, U01 DK63825, U01 DK63835, U01 DK63866, U01 DK63833, U01 DK63862, U01 DK63840, U01 DK63883, U01 DK63831, U01 DK63778 and U01 DK63788, the National Center for Complementary and Alternative Medicine, and the Office of Dietary Supplements, National Institutes of Health. NR 12 TC 10 Z9 10 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAR PY 2013 VL 189 IS 3 BP 987 EP 992 DI 10.1016/j.juro.2012.08.257 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 092HB UT WOS:000315109600062 PM 23017510 ER PT J AU Gaughan, EM Cryer, SK Yeap, BY Jackman, DM Costa, DB AF Gaughan, Elizabeth M. Cryer, Sarah K. Yeap, Beow Y. Jackman, David M. Costa, Daniel B. TI Family history of lung cancer in never smokers with non-small-cell lung cancer and its association with tumors harboring EGFR mutations SO LUNG CANCER LA English DT Article DE Lung cancer; Non-small-cell lung cancer; Family history; Never smokers; Epidermal growth factor receptor; EGFR; Anaplastic lymphoma kinase; ALK; KRAS ID GENETIC-VARIANTS; RISK-FACTORS; SUSCEPTIBILITY; RESISTANCE; ERLOTINIB; DISEASE AB Introduction: Inherited susceptibility to lung cancer is understudied. Never smokers are an important subgroup of patients enriched for tumors harboring oncogene aberrations in the EGFR and ALK genes. We aimed to better characterize the incidence of family history of lung cancer among never smokers with NSCLC. Methods: Clinicopathologic data, tumor genotype, family history of cancer, and specifically family history of lung cancer from 230 consecutive never smokers was retrospectively compiled and analyzed. Results: In our cohort, the median age was 56 years, 67% were women, 75% were white, 59% had advanced NSCLC and 87% had adenocarcinoma histology. In these tumors, 98/230 (42%) had an EGFR mutation, 17/155 (11%) had KRAS mutations and 27/127 (21%) had an ALK translocation. Family history of any cancer was common (57%) and specific family history of lung cancer was present in 42/230 cases (18%). The percentage of cases with family history of lung cancer was higher in the EGFR mutated versus EGFR wild-type NSCLCs. Out of the cases with a family history of any cancer, 22/53 (41.5%) EGFR mutated, 1/5 (20%) KRAS mutated and 3/19 (15.5%) ALK translocated cohorts had a family history of lung cancer. The ratio of family history of lung cancer to family history of cancer was significantly higher in the EGFR mutated cohort when compared to the ALK translocated plus KRAS mutated cohorts (p = 0.039). Conclusions: Family history of lung cancer is common in never smokers with NSCLC, and there seems to be a particular link in families in which the proband has an EGFR mutated tumor when compared to ALK translocated or KRAS mutated tumors. Further study of families with EGFR-mutated NSCLC may yield insights into the pathogenesis of this tumor type. (c) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Gaughan, Elizabeth M.; Costa, Daniel B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol,Dept Med, Boston, MA 02215 USA. [Cryer, Sarah K.; Jackman, David M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol,Dept Med Oncol, Boston, MA 02115 USA. [Yeap, Beow Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Costa, DB (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol Oncol, 330 Brookline Ave, Boston, MA 02215 USA. EM dbcosta@bidmc.harvard.edu OI Costa, Daniel/0000-0002-0689-395X FU American Society of Clinical Oncology Conquer Cancer Foundation; American Cancer Society grant [RSG 11-186]; National Institutes of Health [CA090578]; Pfizer; Roche; AstraZeneca; Genentech; Foundation Medicine FX This work was funded in part through fellowships from the American Society of Clinical Oncology Conquer Cancer Foundation (DBC), an American Cancer Society grant RSG 11-186 (DBC), and National Institutes of Health grants CA090578 (BYY, DMJ, DBC).; DBC has received consulting fees from Pfizer, Roche and AstraZeneca. DMJ has received consulting fees from Genentech and Foundation Medicine. EMG, BYY and SKC have no conflicts to disclose. No other conflict of interest is stated. NR 23 TC 12 Z9 12 U1 1 U2 13 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD MAR PY 2013 VL 79 IS 3 BP 193 EP 197 DI 10.1016/j.lungcan.2012.12.002 PG 5 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 094BV UT WOS:000315238900001 PM 23273562 ER PT J AU Nishino, M Cardarella, S Dahlberg, SE Jackman, DM Ramaiya, NH Hatabu, H Rabin, MS Janne, PA Johnson, BE AF Nishino, Mizuki Cardarella, Stephanie Dahlberg, Suzanne E. Jackman, David M. Ramaiya, Nikhil H. Hatabu, Hiroto Rabin, Michael S. Jaenne, Pasi A. Johnson, Bruce E. TI Radiographic assessment and therapeutic decisions at RECIST progression in EGFR-mutant NSCLC treated with EGFR tyrosine kinase inhibitors SO LUNG CANCER LA English DT Article DE Lung cancer; Computed tomography; Drug resistance; Epidermal growth factor receptor mutations; EGFR tyrosine kinase inhibitors; RECIST ID CELL LUNG-CANCER; GROWTH-FACTOR RECEPTOR; RESPONSE EVALUATION CRITERIA; GUIDELINE VERSION 1.1; ACQUIRED-RESISTANCE; SOLID TUMORS; 1ST-LINE TREATMENT; IMATINIB MESYLATE; CLINICAL-TRIAL; OPEN-LABEL AB Purpose: Advanced NSCLC harboring epidermal growth factor receptor (EGFR) mutations treated with EGFR tyrosine kinase inhibitors (TKIs) typically progresses after initial response due to acquired resistance. TKIs are often continued beyond progressive disease by RECIST. We investigated the practice of continuing EGFR-TKIs after RECIST-PD via CT findings. Methods: Among 101 advanced NSCLC patients with sensitizing EGFR mutations treated with first-line EGFR-TKIs, 70 patients had baseline and at least one follow-up CT for retrospective radiographic assessments using RECIST1.1; 56 patients had experienced PD by the data closure date of June 2011. Results:Among 56 patients experiencing PD, 82% were female, median age was 63 years, 50% were never-smokers, 57% had distant metastasis, 57% had exon 19 deletion, and 89% were treated with erlotinib. 49 patients (88%) continued TKI therapy beyond retrospectively assessed PD. 31/32 (97%) patients who progressed by an increase in their target lesions continued TKI. 13/16 (81%) patients who progressed by appearance of a new lesion remained on TKI. 5/6 (83%) patients with both increase of target lesions and new lesion at PD continued TKI. Two patients with PD in non-target lesions discontinued therapy at PD. In 49 continuing patients, the median time from retrospectively assessed RECIST-PD to termination of TKI was 10.1 months. Conclusions: 88% of EFGR-mutant NSCLC patients who progressed on first-line TKI continued therapy beyond RECIST-PD, which is not the single determining factor for terminating TKI in EGFR-mutant NSCLC patients. Additional radiographically defined progression criteria are needed for this population. (c) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Nishino, Mizuki; Ramaiya, Nikhil H.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Cardarella, Stephanie; Jackman, David M.; Rabin, Michael S.; Jaenne, Pasi A.; Johnson, Bruce E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Cardarella, Stephanie; Jackman, David M.; Rabin, Michael S.; Jaenne, Pasi A.; Johnson, Bruce E.] Brigham & Womens Hosp, Boston, MA 02215 USA. [Dahlberg, Suzanne E.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Nishino, Mizuki; Ramaiya, Nikhil H.; Hatabu, Hiroto] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02215 USA. RP Nishino, M (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM Mizuki_Nishino@DFCI.HARVARD.EDU FU NCI [1K23CA157631]; National Institutes of Health [1RO1CA114465-01, 5R21 CA11627-02]; National Cancer Institute Specialized Program of Research Excellence in Lung Cancer [2P50CA090578-06]; Genentech Inc; Doris and William Krupp Research Fund in Thoracic Oncology; American Society of Clinical Oncology Translational Research Professorship FX The investigators were supported by 1K23CA157631 (NCI) (M.N.), Grants 1RO1CA114465-01 (B.E.J. and P.A.J.) and 5R21 CA11627-02 (H.H.) from the National Institutes of Health, Grant No. 2P50CA090578-06 (B.E.J. and P.A.J.) from the National Cancer Institute Specialized Program of Research Excellence in Lung Cancer, and a grant from Genentech Inc, as well as by the Doris and William Krupp Research Fund in Thoracic Oncology and American Society of Clinical Oncology Translational Research Professorship. NR 41 TC 28 Z9 30 U1 0 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD MAR PY 2013 VL 79 IS 3 BP 283 EP 288 DI 10.1016/j.lungcan.2012.11.007 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 094BV UT WOS:000315238900014 PM 23254265 ER PT J AU Qin, L Schmidt, EJ Tse, ZTH Santos, J Hoge, WS Tempany-Afdhal, C Butts-Pauly, K Dumoulin, CL AF Qin, Lei Schmidt, Ehud J. Tse, Zion Tsz Ho Santos, Juan Hoge, William S. Tempany-Afdhal, Clare Butts-Pauly, Kim Dumoulin, Charles L. TI Prospective motion correction using tracking coils SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE intracavity coil imaging; prospective motion correction; cardiac MRI; tracking coils ID SPHERICAL NAVIGATOR ECHOES; MAGNETIC-RESONANCE; PROSTATE-CANCER; INTRAVASCULAR MRI; SURFACE COIL; LOOP COIL; CATHETER; INTERVENTIONS; SWINE; ARRAY AB Intracavity imaging coils provide higher signal-to-noise than surface coils and have the potential to provide higher spatial resolution in shorter acquisition times. However, images from these coils suffer from physiologically induced motion artifacts, as both the anatomy and the coils move during image acquisition. We developed prospective motion-correction techniques for intracavity imaging using an array of tracking coils. The system had <50 ms latency between tracking and imaging, so that the images from the intracavity coil were acquired in a frame of reference defined by the tracking array rather than by the system's gradient coils. Two-dimensional gradient-recalled and three-dimensional electrocardiogram-gated inversion-recovery-fast-gradient-echo sequences were tested with prospective motion correction using ex vivo hearts placed on a moving platform simulating both respiratory and cardiac motion. Human abdominal tests were subsequently conducted. The tracking array provided a positional accuracy of 0.7 +/- 0.5 mm, 0.6 +/- 0.4 mm, and 0.1 +/- 0.1 mm along the X, Y, and Z directions at a rate of 20 frames-per-second. The ex vivo and human experiments showed significant image quality improvements for both in-plane and through-plane motion correction, which although not performed in intracavity imaging, demonstrates the feasibility of implementing such a motion-correction system in a future design of combined tracking and intracavity coil. Magn Reson Med, 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Qin, Lei] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02215 USA. [Schmidt, Ehud J.; Tse, Zion Tsz Ho; Hoge, William S.; Tempany-Afdhal, Clare] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Santos, Juan] Heart Vista Inc, Palo Alto, CA USA. [Butts-Pauly, Kim] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA. [Dumoulin, Charles L.] Cincinnati Childrens Hosp Med Ctr, Dept Radiol, Cincinnati, OH USA. RP Qin, L (reprint author), Dana Farber Canc Inst, Boston, MA 02215 USA. EM lei_qin@dfci.harvard.edu FU NIH [P41 RR019703, R01 CA11288, R01 CA111981-01, AHA 10SDG261039] FX Grant sponsor: NIH; Grant numbers: P41 RR019703, R01 CA11288, R01 CA111981-01, and AHA 10SDG261039. NR 35 TC 17 Z9 17 U1 0 U2 12 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 MAR PY 2013 VL 69 IS 3 BP 749 EP 759 DI 10.1002/mrm.24310 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 095JU UT WOS:000315331300016 PM 22565377 ER PT J AU Kong, J Jensen, K Loiotile, R Cheetham, A Wey, HY Tan, Y Rosen, B Smoller, JW Kaptchuk, TJ Gollub, RL AF Kong, Jian Jensen, Karin Loiotile, Rita Cheetham, Alexandra Wey, Hsiao-Ying Tan, Ying Rosen, Bruce Smoller, Jordan W. Kaptchuk, Ted J. Gollub, Randy L. TI Functional connectivity of the frontoparietal network predicts cognitive modulation of pain SO PAIN LA English DT Article DE Cue effect; Expectancy; fMRI; Functional connectivity; Independent component analysis; Placebo analgesia; Resting state ID ANTERIOR CINGULATE CORTEX; RESTING HUMAN BRAIN; PLACEBO ANALGESIA; INDIVIDUAL-DIFFERENCES; MEMORY PERFORMANCE; STATE; ANTICIPATION; EXPERIENCE; SYSTEM; FMRI AB The experience of pain can be significantly influenced by expectancy (predictive cues). This ability to modulate pain has the potential to affect therapeutic analgesia substantially and constitutes a foundation for nonpharmacological pain relief. In this study, we investigated (1) brain regions involved in visual cue modulation of pain during anticipation of pain, pain administration, and pain rating; and (2) the association between pretest resting state functional connectivity and the magnitude of cue effects on pain ratings. We found that after cue conditioning, visual cues can significantly modulate subjective pain ratings. Functional magnetic resonance imaging results suggested that brain regions pertaining to the frontoparietal network (prefrontal and parietal cortex) and a pain/emotion modulatory region (rostral anterior cingulate cortex) are involved in cue modulation during both pain anticipation and administration stage. Most interestingly, we found that pretest resting state functional connectivity between the frontoparietal network (as identified by independent component analysis) and the rostral anterior cingulate cortex/medial prefrontal cortex was positively associated with cue effects on pain rating changes. We believe that these findings will shed new light on our understanding of variable cue/expectancy effects across individuals and how the intrinsic connectivity of the brain may influence expectancy-induced modulation of pain. (C) 2012 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved. C1 [Kong, Jian; Jensen, Karin; Loiotile, Rita; Cheetham, Alexandra; Wey, Hsiao-Ying; Tan, Ying; Smoller, Jordan W.; Gollub, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Kong, Jian; Wey, Hsiao-Ying; Rosen, Bruce; Gollub, Randy L.] MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. [Kaptchuk, Ted J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Program Placebo Studies, Boston, MA 02215 USA. RP Kong, J (reprint author), 120 2nd Ave,Room 101C, Charlestown, MA 02129 USA. EM kongj@nmr.mgh.harvard.edu OI Gollub, Randy L./0000-0002-9434-4044; Jensen, Karin/0000-0003-2521-3160 FU National Center for Complementary and Alternative Medicine (NCCAM) [KO1AT003883]; NCCAM [R21AT004497, R01AT005280, R01AT006364, K24AT004095, PO1-AT002048]; National Institute on Drug Abuse (NIDA) [R03AT218317]; National Center for Research Resources [M01-RR-01066, UL1 RR025758-01, P41RR14075]; Swedish Society for Medical Research; Swedish Council for Working Life and Social Research FX This work was supported by KO1AT003883 National Center for Complementary and Alternative Medicine (NCCAM), R21AT004497 (NCCAM), R03AT218317 National Institute on Drug Abuse (NIDA), R01AT006364 (NCCAM) to Jian Kong, R01AT005280 (NCCAM) to Randy Gollub, K24AT004095 (NCCAM) to Ted Kaptchuk, PO1-AT002048 (NCCAM) to Bruce Rosen, M01-RR-01066 and UL1 RR025758-01 for Clinical Research Center Biomedical Imaging Core from National Center for Research Resources, and P41RR14075 for Center for Functional Neuroimaging Technologies from National Center for Research Resources. Karin Jensen receives support from the Swedish Society for Medical Research and the Swedish Council for Working Life and Social Research. The authors thank Dr. Tom Zeffiro for his valuable suggestions and consultation on data analysis methods and Mr. Magnus Gyllensward for his help in figure preparation. NR 62 TC 37 Z9 38 U1 6 U2 36 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD MAR PY 2013 VL 154 IS 3 BP 459 EP 467 DI 10.1016/j.pain.2012.12.004 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 094XW UT WOS:000315299800020 PM 23352757 ER PT J AU Wang, P Schuetz, C Ross, A Dai, GP Markmann, JF Moore, A AF Wang, Ping Schuetz, Christian Ross, Alana Dai, Guangping Markmann, James F. Moore, Anna TI Immune Rejection after Pancreatic Islet Cell Transplantation: In Vivo Dual Contrast-enhanced MR Imaging in a Mouse Model SO RADIOLOGY LA English DT Article ID ENDOTHELIAL-CELLS; T-CELLS; GRAFT COPOLYMER; XENOGRAFTS; REVASCULARIZATION; SURVIVAL; MICE AB Purpose: To detect adoptively transferred immune attack in a mouse model of islet cell transplantation by using a long-circulating paramagnetic T1 contrast agent, a protected graft copolymer (PGC) that is covalently linked to gadolinium- diethylenetriaminepentaacetic acid with fluorescein isothiocyanate (Gd-DTPA-F), which accumulates in the sites of inflammation that are characterized by vascular disruption. Materials and Methods: All animal experiments were performed in compliance with institutional guidelines and approved by the subcommittee on research animal care. Six nonobese diabetic severe combined immunodeficiency mice received transplanted human islet cells under the kidney capsule and adoptively transferred 5 X 10(6) splenocytes from 6-weekold nonobese diabetic mice. These mice also served as control subjects for comparison of pre-and postadoptive transfer MR imaging results. Mice that received phosphate-buffered saline solution only were included as nonadoptive-transfer control subjects (n = 2). In vivo magnetic resonance (MR) imaging was performed before and 17 hours after intravenous injections of PGC-Gd-DTPA-F, followed by histologic examination. Statistical differences were analyzed by means of a paired Student t test and repeated two-way analysis of variance. Results: MR imaging results showed significantly greater accumulation of PGC-Gd-DTPA-F in the graft area after immune attack initiated by adoptive transfer of splenocytes compared with that of the same area before the transfer (T1, 137.2 msec +/- 39.3 and 239.5 msec +/- 17.6, respectively; P < .001). These results were confirmed at histologic examination, which showed considerable leakage of the contrast agent into the islet cell interstitium. Conclusion: PGC-Gd-DTPA-F-enhanced MR imaging allows for the in vivo assessment of vascular damage of the graft T cell challenge. (C) RSNA, 2012 C1 [Wang, Ping; Ross, Alana; Dai, Guangping; Moore, Anna] Harvard Univ, Massachusetts Gen Hosp, MGH MIT HMS Athinoula Martinos Ctr Biomed Imaging, Mol Imaging Lab,Dept Radiol,Med Sch, Boston, MA 02129 USA. [Schuetz, Christian; Markmann, James F.] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Div Transplantat,Med Sch, Boston, MA 02129 USA. RP Moore, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, MGH MIT HMS Athinoula Martinos Ctr Biomed Imaging, Mol Imaging Lab,Dept Radiol,Med Sch, Bldg 75,149 13th St, Boston, MA 02129 USA. EM amoore@helix.mgh.harvard.edu OI Schuetz, Christian/0000-0002-6828-4543; Wang, Ping/0000-0001-6712-8939 FU NIAID NIH HHS [R01 AI057851]; NIDDK NIH HHS [R01 DK072137, R01DK072137] NR 35 TC 5 Z9 5 U1 0 U2 41 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 MAR PY 2013 VL 266 IS 3 BP 822 EP 830 DI 10.1148/radiol.12121129 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 094YC UT WOS:000315300400014 PM 23264346 ER PT J AU Pandharipande, PV Eisenberg, JD Lee, RJ Gilmore, ME Turan, EA Singh, S Kalra, MK Liu, B Kong, CY Gazelle, GS AF Pandharipande, Pari V. Eisenberg, Jonathan D. Lee, Richard J. Gilmore, Michael E. Turan, Ekin A. Singh, Sarabjeet Kalra, Mannudeep K. Liu, Bob Kong, Chung Yin Gazelle, G. Scott TI Patients with Testicular Cancer Undergoing CT Surveillance Demonstrate a Pitfall of Radiation-induced Cancer Risk Estimates: The Timing Paradox SO RADIOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY SCANS; STAGE HODGKINS LYMPHOMA; INFORMED-CONSENT; LIFE EXPECTANCY; CONVENIENT APPROXIMATION; IONIZING-RADIATION; DECISION-MAKING; DOSE-RESPONSE; I SEMINOMA; EXPOSURE AB Purpose: To demonstrate a limitation of lifetime radiation-induced cancer risk metrics in the setting of testicular cancer surveillance-in particular, their failure to capture the delayed timing of radiation-induced cancers over the course of a patient's lifetime. Materials and Methods: Institutional review board approval was obtained for the use of computed tomographic (CT) dosimetry data in this study. Informed consent was waived. This study was HIPAA compliant. A Markov model was developed to project outcomes in patients with testicular cancer who were undergoing CT surveillance in the decade after orchiectomy. To quantify effects of early versus delayed risks, life expectancy losses and lifetime mortality risks due to testicular cancer were compared with life expectancy losses and lifetime mortality risks due to radiation-induced cancers from CT. Projections of life expectancy loss, unlike lifetime risk estimates, account for the timing of risks over the course of a lifetime, which enabled evaluation of the described limitation of lifetime risk estimates. Markov chain Monte Carlo methods were used to estimate the uncertainty of the results. Results: As an example of evidence yielded, 33-year-old men with stage I seminoma who were undergoing CT surveillance were projected to incur a slightly higher lifetime mortality risk from testicular cancer (598 per 100 000; 95% uncertainty interval [UI]: 302, 894) than from radiation-induced cancers (505 per 100 000; 95% UI: 280, 730). However, life expectancy loss attributable to testicular cancer (83 days; 95% UI: 42, 124) was more than three times greater than life expectancy loss attributable to radiation-induced cancers (24 days; 95% UI: 13, 35). Trends were consistent across modeled scenarios. Conclusion: Lifetime radiation risk estimates, when used for decision making, may overemphasize radiation-induced cancer risks relative to short-term health risks. (C) RSNA, 2012 C1 [Pandharipande, Pari V.; Eisenberg, Jonathan D.; Gilmore, Michael E.; Turan, Ekin A.; Kong, Chung Yin; Gazelle, G. Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Pandharipande, Pari V.; Eisenberg, Jonathan D.; Gilmore, Michael E.; Turan, Ekin A.; Singh, Sarabjeet; Kalra, Mannudeep K.; Liu, Bob; Kong, Chung Yin; Gazelle, G. Scott] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Lee, Richard J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Pandharipande, Pari V.; Lee, Richard J.; Singh, Sarabjeet; Kalra, Mannudeep K.; Liu, Bob; Kong, Chung Yin; Gazelle, G. Scott] Harvard Univ, Sch Med, Boston, MA 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 Medical Imaging and Technology Alliance FX Financial activities related to the present article: none to disclose. Financial activities not related to the present article: institution receives grant from Medical Imaging and Technology Alliance, a Division of the National Electrical Manufacturers Association ( research grant for unrelated research, but pertinent to CT, author is principle investigator). Other relationships: none to disclose. J.D.E. No relevant conflicts of interest to disclose. R.J.L. No relevant conflicts of interest to disclose. M.E.G. No relevant conflicts of interest to disclose. E.A.T. No relevant conflicts of interest to disclose. S.S. No relevant conflicts of interest to disclose. M.K.K. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: author receives payment for lecture from GE Healthcare for continuing education-accredited course lecture; author receives money for travel from GE Healthcare for continuing education-accredited course. Other relationships: none to disclose. B.L. No relevant conflicts of interest to disclose. C.Y.K. No relevant conflicts of interest to disclose. G.S.G. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: author is consultant for GE Healthcare. Other relationships: none to disclose. NR 50 TC 21 Z9 21 U1 0 U2 3 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 MAR PY 2013 VL 266 IS 3 BP 896 EP 904 DI 10.1148/radiol.12121015 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 094YC UT WOS:000315300400022 PM 23249573 ER PT J AU Muir, ER Zhang, Y Nateras, OSE Peng, Q Duong, TQ AF Muir, Eric R. Zhang, Yi Nateras, Oscar San Emeterio Peng, Qi Duong, Timothy Q. TI Human Vitreous: MR Imaging of Oxygen Partial Pressure SO RADIOLOGY LA English DT Article ID PROLIFERATIVE DIABETIC-RETINOPATHY; NUCLEAR CATARACT; RETINAL OXYGENATION; TEMPERATURE; VITRECTOMY; EYE; BODY; TENSION; LENS; AGE AB Purpose: To develop a magnetic resonance (MR) imaging approach to noninvasively image quantitative Po-2 in the human vitreous. Materials and Methods: Human studies were approved by the institutional review board with informed consent obtained from all subjects and were HIPAA compliant. Animal studies were performed with animal care committee approval. An MR imaging method to measure the longitudinal relaxation rate, or R1, of water was implemented with a 3.0-T MR imager. R1 was calibrated in water phantoms at multiple Po-2 and temperature conditions (n = 10) and in ex vivo animal vitreous (n = 2). Vitreous Po-2 was imaged in three human volunteers (age range, 26-28 years) in multiple sessions on separate days to evaluate reproducibility. The effects of temperature and ambient air were evaluated by acquiring data with the eye open and closed. Statistical analysis consisted of t tests, with P less than .05 indicating significant difference. Results: Calibrations of phantoms and ex vivo vitreous yielded an R1 association with oxygen of 0.209 sec(-1) + Po-2 . 2.07 X 10(-4) sec(-1)/mm Hg at 37 degrees C, and an association with temperature (Delta[1/R1]/Delta Temperature) of 0.106 sec/degrees C +/- 0.009 (standard deviation). A difference in R1 was found between the phantoms and vitreous. If uncorrected, vitreal Po2 would be significantly overestimated (P,.001). In vivo human vitreous Po-2 maps were spatially heterogeneous, with a whole vitreous Po 2 of 16.7 mm Hg 6 6.5 (eye closed). Measurements between open and closed eyes showed spatially dependent R1 differences, which translated to temperature differences of 0.34-0.83 C across the eye. Conclusion: This study established an MR imaging protocol to image quantitative vitreous Po-2 noninvasively and evaluated effects from vitreal macromolecules, temperature gradients, and ambient air on vitreal Po-2 values. Measurement of vitreous Po-2 with MR imaging has the potential to be used to study eye diseases noninvasively. (C) RSNA, 2012 C1 [Muir, Eric R.; Zhang, Yi; Nateras, Oscar San Emeterio; 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. [Zhang, Yi; Nateras, Oscar San Emeterio; 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. [Peng, Qi] Albert Einstein Coll Med, Dept Radiol, New York, NY USA. [Peng, Qi] Montefiore Med Ctr, New York, NY USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008; Muir, Eric/H-8830-2013 FU NEI NIH HHS [EY018855, R01 EY018855, R01 EY014211]; NHLBI NIH HHS [T32 HL007446, T32HL007446]; NIH HHS [P51 OD011133] NR 29 TC 5 Z9 5 U1 0 U2 8 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 MAR PY 2013 VL 266 IS 3 BP 905 EP 911 DI 10.1148/radiol.12120777 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 094YC UT WOS:000315300400023 PM 23220896 ER PT J AU Loustau, M Wiendl, H Ferrone, S Carosella, ED AF Loustau, M. Wiendl, H. Ferrone, S. Carosella, E. D. TI HLA-G 2012 conference: the 15-year milestone update SO TISSUE ANTIGENS LA English DT Review DE human leukocyte antigen-G ID NATURAL-KILLER-CELLS; REGULATORY T-CELLS; MULTIPLE-SCLEROSIS; UP-REGULATION; G MOLECULE; INHIBITORY RECEPTOR; DENDRITIC CELLS; G EXPRESSION; G ANTIGEN; PATHWAY AB The non-classical human leukocyte antigen (HLA) Class I molecule HLA-G is best known for its tolerogenic function at the maternal-fetal interface, where it protects the fetus from destruction by the immune system of its mother. Yet, HLA-G has been the topic of intense investigations and its functions reach much further than originally believed. International conferences on HLA-G have taken place every 3 years since 1998, and the Sixth International Conference on HLA-G, that took place in Paris in July 2012. It counted 180 attendees from 28 countries, 35 speakers in plenary sessions, and 63 presentations of research in symposia and poster sessions, bringing new insight in HLA-G research. Here we summarize the major advances on the function and nature of HLA-G molecule that were reported, with particular interest on the findings in new mechanisms of action through regulatory cells, its relevance in cancer as well as in the molecular structure and functions of HLA-G, which are key for its clinical application. C1 [Loustau, M.; Carosella, E. D.] Hop St Louis, CEA, Inst Emerging Dis & Innovat Therapies iMETI, Res Div Hematol & Immunol SRHI, Paris, France. [Loustau, M.; Carosella, E. D.] Univ Paris Diderot, UMR E Inst Univ Hematol 5, St Louis Hosp, F-75475 Paris, France. [Wiendl, H.] Univ Munster, Dept Neurol Inflammatory Disorders Nervous Syst &, D-48149 Munster, Germany. [Ferrone, S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Carosella, ED (reprint author), Hop St Louis, CEA, Inst Emerging Dis & Innovat Therapies iMETI, Res Div Hematol & Immunol SRHI, Paris, France. EM Edgardo.Carosella@cea.fr NR 31 TC 12 Z9 14 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD MAR PY 2013 VL 81 IS 3 BP 127 EP 136 DI 10.1111/tan.12053 PG 10 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 089PF UT WOS:000314921800001 PM 23347068 ER PT J AU Zhang, G Wang, P Qiu, Z Qin, X Lin, X Li, N Huang, H Liu, H Hua, W Chen, Z Zhao, H Li, W Shen, H AF Zhang, G. Wang, P. Qiu, Z. Qin, X. Lin, X. Li, N. Huang, H. Liu, H. Hua, W. Chen, Z. Zhao, H. Li, W. Shen, H. TI Distant lymph nodes serve as pools of Th1 cells induced by neonatal BCG vaccination for the prevention of asthma in mice SO ALLERGY LA English DT Article DE asthma; Bacillus CalmetteGuerin; migration; neonatal vaccination; Th1 cells ID INDUCED AIRWAY HYPERRESPONSIVENESS; MEMORY T-CELLS; MYCOBACTERIUM-TUBERCULOSIS; CYTOKINE PRODUCTION; IMMUNE-RESPONSES; DENDRITIC CELLS; IFN-GAMMA; INFECTION; INTERLEUKIN-12; INFLAMMATION AB Background Neonatal Bacillus CalmetteGuerin (BCG) vaccination induces vigorous T-helper type 1 (Th1) responses and inhibits allergy-related airway dysfunction, but the exact mechanisms remain unclear. The objective of this study was to address where the Th1 cells induced by neonatal BCG vaccination are generated and stored, and how they are recruited into the inflamed airway for the prevention of allergen-induced airway inflammation. Methods We vaccinated neonatal C57BL/6 mice with BCG in a mouse model of asthma and analyzed the expression and function of Th1 cells in vivo and in vitro. Results BCG vaccinationinduced Th1 cells in the local inguinal lymph nodes (ILN) migrated into the lungs upon inhaled ovalbumin (OVA) challenge in OVA-sensitized mice. These CD4+ T cells in the ILN exhibited potentials of activation, proliferation and cytokine secretion and expressed high levels of CXCR3. Adoptive transfer of CD4+ T cells from BCG-treated ILN significantly decreased allergic airway responses. In addition, the protective effect of BCG vaccination against allergic airway inflammation was lost upon the excision of the ILN. Conclusions These data demonstrate that ILN serves as a weapon' pool of Th1 cells following BCG vaccination, and these cells are ready for the migration into the inflamed lungs upon the allergen challenge, thereby inhibiting allergen-induced airway disorder. C1 [Zhang, G.; Wang, P.; Qiu, Z.; Lin, X.; Li, N.; Huang, H.; Liu, H.; Hua, W.; Chen, Z.; Li, W.; Shen, H.] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Resp & Crit Care Med, Hangzhou 310009, Zhejiang, Peoples R China. [Qin, X.] Peoples Hosp Guangxi Zhuang Autonomous Reg, Dept Resp Dis, Nanning, Peoples R China. [Zhao, H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Boston, MA USA. [Shen, H.] State Key Lab Resp Dis, Guangzhou, Guangdong, Peoples R China. RP Shen, H (reprint author), Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Resp & Crit Care Med, Hangzhou 310009, Zhejiang, Peoples R China. EM hh_shen@yahoo.com.cn FU National Natural Science Foundation of China for Distinguished Young Scholars [30825019]; National Natural Science Foundation of China [81070013]; Major and Key Program of Zhejiang Province [2008C03002-2] FX We would like to thank Drs. Ming Yan (College of Biomedical Engineering & Instrument Science, Zhejiang University), Zhijian Cai (Institute of Immunology, Zhejiang University), Yungui Wang (Institute of Hematology, Zhejiang University), and Youfa Zhu (Department of Pathology, Zhejiang University) for their technical assistance. This study was supported in part by the grants from National Natural Science Foundation of China for Distinguished Young Scholars (No. 30825019, Shen HH) and National Natural Science Foundation of China (No. 81070013, Shen HH), and Major and Key Program of Zhejiang Province (2008C03002-2, Li W). NR 32 TC 5 Z9 6 U1 3 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 J9 ALLERGY JI Allergy PD MAR PY 2013 VL 68 IS 3 BP 330 EP 338 DI 10.1111/all.12099 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 089NG UT WOS:000314916700008 PM 23346957 ER PT J AU Nargiso, JE Friend, KB Egan, C Florin, P Stevenson, J Amodei, B Barovier, L AF Nargiso, Jessica E. Friend, Karen B. Egan, Crystelle Florin, Paul Stevenson, John Amodei, Brenda Barovier, Linda TI Coalitional Capacities and Environmental Strategies to Prevent Underage Drinking SO AMERICAN JOURNAL OF COMMUNITY PSYCHOLOGY LA English DT Article DE Coalitions; Prevention; Capacity; Measurement; Training and technical assistance ID COMMUNITY-BASED PREVENTION; HEALTH PROMOTION; DRUG-ABUSE; ALCOHOL; SYSTEMS; TRIAL; INTERVENTIONS; PENNSYLVANIA; PARTNERSHIPS; PREVALENCE AB Coalitions are the most common platform for implementing community-level environmental strategies (ES), such as media, policy, or enforcement for substance use prevention. The current study examines the associations between two types of coalition capacity (general and innovation-specific) and ES implementation efforts and outputs within 14 intervention communities over a three-year period. Efforts refer to the amount of energy exerted to implement an ES while outputs refer to the materials produced through these efforts. Quantitative measures of capacity were provided by coalition key informants and expert-raters. Additionally, Training and Technical Assistance (TTA) provided proactively to improve the implementation of ES was also examined. Greater general capacity, as rated by a coalition informant, was associated with more ES policy effort. Both expert-rated general and innovation-specific capacity, however, were associated with greater ES outputs. Study results also found that community coalitions that endorsed weaker mobilization, structure and task leadership, (measures of general capacity), utilized more TTA compared to those who perceived their coalition as having greater capacity. Moreover, communities that utilized more TTA resources reported a greater number of successful policy changes. The study supports the need to consider both general and innovation-specific capacity for ES implementation and offers promising preliminary findings regarding the role of TTA for improving coalitions' capacity to facilitate policy change. C1 [Nargiso, Jessica E.; Friend, Karen B.] Brown Univ, Ctr Alcohol & Addict Studies, Warren Alpert Med Sch, Providence, RI 02912 USA. [Friend, Karen B.] Pacific Inst Res & Evaluat, Decis Sci Inst, Pawtucket, RI 02860 USA. [Egan, Crystelle] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Florin, Paul; Stevenson, John] Univ Rhode Isl, Dept Psychol, Kingston, RI 02881 USA. [Amodei, Brenda] Dev Disabil & Hosp, Dept Behav Healthcare, Cranston, RI 02920 USA. [Barovier, Linda] Educ Dev Ctr Inc, Waltham, MA 02453 USA. RP Nargiso, JE (reprint author), Brown Univ, Ctr Alcohol & Addict Studies, Warren Alpert Med Sch, Box G-S121-4, Providence, RI 02912 USA. EM Jessica_Nargiso@brown.edu NR 33 TC 8 Z9 8 U1 2 U2 15 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0562 J9 AM J COMMUN PSYCHOL JI Am. J. Community Psychol. PD MAR PY 2013 VL 51 IS 1-2 BP 222 EP 231 DI 10.1007/s10464-012-9536-4 PG 10 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Social Work SC Public, Environmental & Occupational Health; Psychology; Social Work GA 088KV UT WOS:000314834100019 PM 22752558 ER PT J AU Levy, BP AF Levy, Bruce P. TI Implementation and User Satisfaction With Forensic Laboratory Information Systems in Death Investigation Offices SO AMERICAN JOURNAL OF FORENSIC MEDICINE AND PATHOLOGY LA English DT Article DE coroner; laboratory information management system; medical examiner ID MEDICAL-EXAMINERS; SURVEILLANCE; LIMS; PREVENTION; MANAGEMENT; COMPUTER; DATABASE; STATES AB The use of laboratory information management systems (LIMSs) in forensic pathology and death investigation systems has lagged behind the greater pathology community. Yet the logistical needs of a modern medical examiner or coroner office could be well served by a robust forensic LIMS, and the data stored in a forensic LIMS could be effectively mined for the protection of the public's health and safety. In spring 2007, the National Association of Medical Examiners conducted a survey of its members to determine the use of and satisfaction with forensic LIMS. This survey was repeated in the fall of 2011. The responses to the 2 surveys were compared to note any trends or changes to LIMS use by medical examiners and coroners. Although the use of LIMS has increased in the 4 1/2 years between surveys, 18% of death investigation systems still do not have a forensic LIMS. The percentage of offices with home-developed systems has increased, whereas the user's satisfaction with these systems has decreased. This may be due to limited budgets to either purchase or develop systems. The integration of images into these systems has increased, but not nearly to the level that should be present in an image-dependent field. Users of these systems are cognizant of the features that a forensic LIMS should have to ensure the smooth operation of a death investigation office. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Levy, BP (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM forensicdoc@me.com NR 22 TC 0 Z9 0 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-7910 EI 1533-404X J9 AM J FOREN MED PATH JI Am. J. Forensic Med. Pathol. PD MAR PY 2013 VL 34 IS 1 BP 63 EP 67 DI 10.1097/PAF.0b013e31827ab5c6 PG 5 WC Medicine, Legal; Pathology SC Legal Medicine; Pathology GA 089NI UT WOS:000314916900018 PM 23361076 ER PT J AU Ahn, R Alpert, EJ Purcell, G Konstantopoulos, WM McGahan, A Cafferty, E Eckardt, M Conn, KL Cappetta, K Burke, TF AF Ahn, Roy Alpert, Elaine J. Purcell, Genevieve Konstantopoulos, Wendy Macias McGahan, Anita Cafferty, Elizabeth Eckardt, Melody Conn, Kathryn L. Cappetta, Kate Burke, Thomas F. TI Human Trafficking Review of Educational Resources for Health Professionals SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Review ID SEX TRAFFICKING; VIOLENCE; WOMEN; EXPLOITATION; GIRLS AB Context: Human trafficking is an increasingly well-recognized human rights violation that is estimated to involve more than 2 million victims worldwide each year. The health consequences of this issue bring victims into contact with health systems and healthcare providers, thus providing the potential for identification and intervention. A robust healthcare response, however, requires a healthcare workforce that is aware of the health impact of this issue; educated about how to identify and treat affected individuals in a compassionate, culturally aware, and trauma-informed manner; and trained about how to collaborate efficiently with law enforcement, case management, and advocacy partners. This article describes existing educational offerings about human trafficking designed for a healthcare audience and makes recommendations for further curriculum development. Evidence acquisition: A keyword search and structured analysis of peer-reviewed and gray literature, conducted in 2011 and 2012, yielded 27 items that provide basic guidance to health professionals on human trafficking. Evidence synthesis: The 27 resources differed substantially in format, length, scope, and intended audience. Topic areas covered by these resources included trafficking definitions and scope, health consequences, victim identification, appropriate treatment, referral to services, legal issues, and security. None of the educational resources has been rigorously evaluated. Conclusions: There is a clear need to develop, implement, and evaluate high-quality education and training programs that focus on human trafficking for healthcare providers. (Am J Prev Med 2013;44(3):283-289) (C) 2013 American Journal of Preventive Medicine C1 [Ahn, Roy; Alpert, Elaine J.; Purcell, Genevieve; Konstantopoulos, Wendy Macias; McGahan, Anita; Cafferty, Elizabeth; Eckardt, Melody; Conn, Kathryn L.; Cappetta, Kate; Burke, Thomas F.] Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, Boston, MA 02114 USA. [Burke, Thomas F.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Burke, Thomas F.] Childrens Hosp, Div Gen Pediat, Boston, MA 02115 USA. [Ahn, Roy; Konstantopoulos, Wendy Macias; Burke, Thomas F.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [McGahan, Anita] Univ Toronto, Rotman Sch Management, Toronto, ON, Canada. [McGahan, Anita] Univ Toronto, Munk Sch Global Affairs, Toronto, ON, Canada. [Alpert, Elaine J.] Univ British Columbia, Coll Hlth Disciplines, Vancouver, BC V5Z 1M9, Canada. RP Ahn, R (reprint author), Massachusetts Gen Hosp, 0 Emerson Pl,Suite 104, Boston, MA 02114 USA. EM RAHN@partners.org OI Eckardt, Melody/0000-0001-9066-9856 FU Give Way to Freedom FX The authors acknowledge Give Way to Freedom, a private foundation, for providing financial support to complete this review. NR 48 TC 16 Z9 16 U1 5 U2 67 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 MAR PY 2013 VL 44 IS 3 BP 283 EP 289 DI 10.1016/j.amepre.2012.10.025 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 090FZ UT WOS:000314965900013 PM 23415126 ER PT J AU Boudreau, ADA Kurowski, DS Gonzalez, WI Dimond, MA Oreskovic, NM AF Boudreau, Alexy D. Arauz Kurowski, Daniel S. Gonzalez, Wanda I. Dimond, Melissa A. Oreskovic, Nicolas M. TI Latino Families, Primary Care, and Childhood Obesity A Randomized Controlled Trial SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID QUALITY-OF-LIFE; GENERIC CORE SCALES; PHYSICAL-ACTIVITY; EARLY INTERVENTION; CLINICAL-TRIALS; UNITED-STATES; US CHILDREN; OVERWEIGHT; HEALTH; PREVALENCE AB Background: Few successful treatment modalities exist to address childhood obesity. Given Latinos' strong identity with family, a family-focused intervention may be able to control Latino childhood obesity. Purpose: To assess the feasibility and effectiveness of a family-centered, primary care-based approach to control childhood obesity through lifestyle choices. Design: Randomized waitlist controlled trial in which control participants received the intervention 6 months after the intervention group. Setting/participants: Forty-one Latino children with BMI >85%, aged 9-12 years, and their caregivers were recruited from an urban community health center located in a predominantly low-income community. Intervention: Children and their caregivers received 6 weeks of interactive group classes followed by 6 months of culturally sensitive monthly in-person or phone coaching to empower families to incorporate learned lifestyles and to address both family and social barriers to making changes. Main outcomes measures: Caregiver report on child and child self-reported health-related quality of life (HRQoL); metabolic markers of obesity; BMI; and accelerometer-based physical activity were measured July 2010-November 2011 and compared with post-intervention assessments conducted at 6 months and as a function of condition assignment. Data were analyzed in 2012. Results: Average attendance rate to each group class was 79%. Socio-environmental and family factors, along with knowledge, were cited as barriers to changing lifestyles to control obesity. Caregiver proxy and child self-reported HRQoL improved for both groups with a larger but not nonsignificant difference among intervention vs control group children (p=0.33). No differences were found between intervention and control children for metabolic markers of obesity, BMI, or physical activity. Conclusions: Latino families are willing to participate in group classes and health coaching to control childhood obesity. It may be necessary for primary care to partner with community initiatives to address childhood obesity in a more intense manner. C1 [Boudreau, Alexy D. Arauz; Oreskovic, Nicolas M.] Harvard Univ, Sch Med, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA USA. [Gonzalez, Wanda I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mass Gen Hosp Children, Boston, MA USA. [Dimond, Melissa A.] MGH Ctr Community Hlth Improvement, Boston, MA USA. [Kurowski, Daniel S.] Ctr Home Care Policy & Res, New York, NY USA. RP Boudreau, ADA (reprint author), Massachusetts Gen Hosp, Mass Gen Hosp Children, Ctr Child & Adolescent Hlth Res & Policy, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM aarauz@partners.org OI Oreskovic, Nicolas/0000-0001-8702-8636 FU Robert Wood Johnson Foundation; Robert Wood Johnson Foundation through its national program, SaludAmerica! The RWJF Research Network to Prevent Obesity Among Latino Children; Massachusetts General Hospital Multicultural Affairs Career Development Award; Harvard Catalyst Clinical Research Center, NIH, National Center for Research Resources, General Clinical Research Centers Program [1 UL1 RR025758-01] FX Publication of this article was supported by the Robert Wood Johnson Foundation.; This study was funded by the Robert Wood Johnson Foundation through its national program, SaludAmerica! The RWJF Research Network to Prevent Obesity Among Latino Children (www.salud-america.org). Salud America!, led by the Institute for Health Promotion Research at The University of Texas Health Science Center at San Antonio, Texas, unites Latino researchers and advocates seeking environmental and policy solutions to the epidemic.; The study was also supported by the Massachusetts General Hospital Multicultural Affairs Career Development Award. The authors acknowledge the partnership of the Massachusetts General Hospital Disparities Solution Center. In addition, the authors acknowledge the generous support from the Harvard Catalyst Clinical Research Center, Grant No. 1 UL1 RR025758-01, NIH, National Center for Research Resources, General Clinical Research Centers Program. Finally, we would like to acknowledge Dhruv Khullar for his excellent work as a research assistant in helping to set up the initial phase of this project. NR 56 TC 17 Z9 17 U1 4 U2 27 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 MAR PY 2013 VL 44 IS 3 SU 3 BP S247 EP S257 DI 10.1016/j.amepre.2012.11.026 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 090FD UT WOS:000314963700012 ER PT J AU Cortes, DE Millan-Ferro, A Schneider, K Vega, RR Caballero, AE AF Cortes, Dharma E. Millan-Ferro, Andreina Schneider, Karen Vega, Rodolfo R. Caballero, A. Enrique TI Food Purchasing Selection Among Low-Income, Spanish-Speaking Latinos SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID UNITED-STATES; DIABETES-MELLITUS; OBESITY; CONSUMPTION; ADOLESCENTS; CHILDREN; PRICES; RISK AB Background: In the U.S., poverty has been linked to both obesity and disease burden. Latinos in the U.S. are disproportionately affected by poverty, and over the past 10 years, the percentage of overweight U.S. Latino youth has approximately doubled. Buying low-cost food that is calorie-dense and filling has been linked to obesity. Low-income individuals tend to favor energy-dense foods because of their low cost, and economic decisions made during food purchasing have physiologic repercussions. Diets based on energy-dense foods tend to be high in processed staples, such as refined grains, added sugars, and added fats. These diets have been linked to a higher risk of obesity, type 2 diabetes, and cardiovascular disease. Purpose: This pilot study conducted ethnographic qualitative analyses combined with quantitative analyses to understand grocery shopping practices among 20 Spanish-speaking, low-income Latino families. The purpose was to analyze food selection practices in order to determine the effect of nutrition education on changes in shopping practices to later develop educational tools to promote selection of healthier food options. Methods: Participants received tailored, interactive, nutrition education during three to five home visits and a supermarket tour. Grocery store receipts for grocery purchases collected at baseline and at the end of the project were analyzed for each family to extract nutritional content of purchased foods. Nutritional content was measured with these factors in mind: quantity, calories, fats, carbohydrates, fiber, protein, and percentage of sugary beverages and processed food. Data were collected in 2010-2011 and analyzed in 2011-2012. Results: After receiving between three and five home-based nutrition education sessions and a supermarket tour over a 6-month period, many families adopted instructions on buying budget-friendly, healthier alternative foods. Findings indicate that participating families decreased the total number of calories and calories per dollar purchased from baseline to post-education (median total calories: baseline, 20,191; post-education, 15,991, p=0.008); median calories per dollar: baseline, 404; post-education, 320, p=0.008). The median grams of carbohydrates per dollar (baseline, 66, post-education, 45) and median calories from processed food (baseline, 11,000, post-education, 7845) were not reduced (p=0.06). Conclusions: This pilot study demonstrated that grocery shopping practices are an important factor to address in nutrition education among Spanish-speaking, low-income individuals, and that there maybe ways to encourage low-income, Latino families to purchase healthier foods. Findings challenged arguments suggesting that such an approach is not possible because of the high cost of healthier foods. (Am J Prev Med 2013;44(3S3):S267-S273) (c) 2013 American Journal of Preventive Medicine C1 [Cortes, Dharma E.] Univ Massachusetts Boston, Mauricio Gaston Inst Latino Community Dev & Publ, Boston, MA 02125 USA. [Millan-Ferro, Andreina; Caballero, A. Enrique] Joslin Diabet Ctr, Boston, MA 02215 USA. [Schneider, Karen; Vega, Rodolfo R.] JSI Res & Training Inst Inc, Boston, MA USA. RP Cortes, DE (reprint author), Univ Massachusetts Boston, Mauricio Gaston Inst Latino Community Dev & Publ, 100 Morrissey Blvd, Boston, MA 02125 USA. EM decortes@aol.com FU Robert Wood Johnson Foundation; Robert Wood Johnson Foundation through its national program, Salud America! The RWJF Research Network to Prevent Obesity among Latino Children FX Publication of this article was supported by the Robert Wood Johnson Foundation.; This study was funded by the Robert Wood Johnson Foundation through its national program, Salud America! The RWJF Research Network to Prevent Obesity among Latino Children (www.salud-america.org). Salud America!, led by the Institute for Health Promotion Research at The University of Texas Health Science Center at San Antonio, Texas, unites Latino researchers and advocates seeking environmental and policy solutions to the epidemic. NR 27 TC 16 Z9 16 U1 1 U2 58 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 MAR PY 2013 VL 44 IS 3 SU 3 BP S267 EP S273 DI 10.1016/j.amepre.2012.11.012 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 090FD UT WOS:000314963700014 PM 23415192 ER PT J AU Antonescu, CR Romeo, S Zhang, L Nafa, K Hornick, JL Nielsen, GP Mino-Kenudson, M Huang, HY Mosquera, JM Dei Tos, PA Fletcher, CDM AF Antonescu, Cristina R. Romeo, Salvatore Zhang, Lei Nafa, Khedoudja Hornick, Jason L. Nielsen, Gunnlaugur Petur Mino-Kenudson, Mari Huang, Hsuan-Ying Mosquera, Juan-Miguel Dei Tos, Paolo A. Fletcher, Christopher D. M. TI Dedifferentiation in Gastrointestinal Stromal Tumor to an Anaplastic KIT-negative Phenotype: A Diagnostic Pitfall Morphologic and Molecular Characterization of 8 Cases Occurring Either De Novo or After Imatinib Therapy SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE gastrointestinal stromal tumor; dedifferentiation; KIT; imatinib ID IMATINIB MESYLATE; BRAF MUTATIONS; RESISTANCE; INHIBITOR; LEIOMYOSARCOMA; HETEROGENEITY; MECHANISMS; GIST AB Most gastrointestinal stromal tumors (GISTs) can be recognized by their monotonous cytologic features and overexpression of KIT oncoprotein. Altered morphology and loss of CD117 reactivity has been described previously after chronic imatinib treatment; however, this phenomenon has not been reported in imatinib-naive tumors. Eight patients with abrupt transition from a classic CD117-positive spindle cell GIST to an anaplastic CD117-negative tumor were investigated for underlying molecular mechanisms of tumor progression. Pathologic and molecular analysis was performed on each of the 2 components. Genomic DNA polymerase chain reaction for KIT, PDGFRA, BRAF, and KRAS hot spot mutations and fluorescence in situ hybridization for detecting KIT gene copy number alterations were performed. TP53 mutational analysis was performed in 5 cases. There were 7 men and 1 woman, with an age range of 23 to 65 years. Five of the primary tumors were located in the stomach, and 1 case each originated in the small bowel, colon, and rectum. In 3 patients, the dedifferentiated component occurred in the setting of imatinib resistance, whereas the remaining 5 occurred de novo. The dedifferentiated component had an anaplastic appearance, including 1 angio-sarcomatous phenotype, with high mitotic activity and necrosis, and showed complete loss of CD117 (8/8) and CD34 (5/8) expression and de novo expression of either cytokeratin (4/8) or desmin (1/8). There was no difference in the KIT genotype between the 2 components. However, 2 imatinib-resistant tumors showed coexistence of KIT exon 11 and exon 13 mutations. Fluorescence in situ hybridization showed loss of 1 KIT gene in 3 cases and low-level amplification of KIT in 2 other cases in the CD117-negative component, compared with the CD117-positive area. TP53 mutation was identified in 1/5 cases tested, being present in both components. In summary, dedifferentiation in GIST may occur either de novo or after chronic imatinib exposure and can represent a diagnostic pitfall. This phenomenon is not related to additional KIT mutations, but might be secondary to genetic instability, either represented by loss of heterozygosity or low level of KIT amplification. C1 [Antonescu, Cristina R.; Zhang, Lei; Nafa, Khedoudja] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Mosquera, Juan-Miguel] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Hornick, Jason L.; Fletcher, Christopher D. M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Nielsen, Gunnlaugur Petur; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Romeo, Salvatore; Dei Tos, Paolo A.] Treviso Gen Hosp, Treviso, Italy. [Huang, Hsuan-Ying] Kaohsiung Chang Gung Mem Hosp, Kaohsiung, Taiwan. [Huang, Hsuan-Ying] Chang Gung Univ, Coll Med, Kaohsiung, Taiwan. RP Antonescu, CR (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. EM antonesc@mskcc.org FU ACS MRSG [CCE-106841, P01CA47179, P50 CA 140146-01]; Life Raft Group; GIST Cancer Research Fund; Shuman Family Fund for GIST Research FX Supported in part by ACS MRSG CCE-106841 (CRA), P01CA47179 (CRA), P50 CA 140146-01 (CRA), Life Raft Group (CRA), GIST Cancer Research Fund (CRA), and Shuman Family Fund for GIST Research (CRA). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. NR 24 TC 20 Z9 24 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 2013 VL 37 IS 3 BP 385 EP 392 DI 10.1097/PAS.0b013e31826c1761 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 092BY UT WOS:000315095000008 PM 23348204 ER PT J AU Young, RH Ulbright, TM Policarpio-Nicolas, MLC AF Young, Robert H. Ulbright, Thomas M. Policarpio-Nicolas, Maria Luisa C. TI Yolk Sac Tumor With a Prominent Polyvesicular Vitelline Pattern A Report of Three Cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ovary; yolk sac tumor; polyvesicular vitelline ID ENDODERMAL SINUS TUMOR; OVARY; CARCINOMA; PURE AB We report 3 cases of the rare polyvesicular vitelline variant of ovarian yolk sac tumor (YST). The patients were 23, 29, and 43 years old, and all presented with large unilateral adnexal masses confined to the ovary. One tumor was predominantly cystic, and the other 2 had prominent cystic components; all 3 also had solid components. Microscopic examination of the cystic regions showed dilated cysts that largely effaced the stroma resulting in a honeycomb-like appearance. The solid foci were characterized predominantly by small tubules in a fibrous stroma; the tubules exhibited variably conspicuous cystic dilatation to merge with the microcystic appearance. The tumor cells varied from large and primitive-appearing to flattened and deceptively innocuous when lining large cysts. They were immunoreactive for a-fetoprotein and glypican-3. Non-polyvesicular vitelline components of YST were present focally in 2 cases (hepatoid in one, reticular and endometrioid like in the second). Two patients are disease free after 20 and 26 years, respectively; disease-free follow-up is of short duration in the third case (2 years). The good long-term outcome in 2 cases supports prior evidence that suggests that the natural history of this form of YST may be more indolent than conventional forms of the tumor. C1 [Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Ulbright, Thomas M.] Indiana Univ, Indiana Univ Sch Med, Hlth Pathol Lab, Indianapolis, IN 46204 USA. [Policarpio-Nicolas, Maria Luisa C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. RP Young, RH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, 55 Fruit St, Boston, MA 02114 USA. EM rhyoung@partners.org NR 18 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 2013 VL 37 IS 3 BP 393 EP 398 DI 10.1097/PAS.0b013e31827dcc2b PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 092BY UT WOS:000315095000009 PM 23348213 ER PT J AU Levine, DJ Riley, DJ Jorgensen, JH McClain, WD Tio, F Visvesvara, GS Abboud-Werner, SL AF Levine, Deborah J. Riley, Daniel J. Jorgensen, James H. McClain, William D. Tio, Fermin Visvesvara, Govinda S. Abboud-Werner, Sherry L. TI Key Diagnostic Features of Granulomatous Interstitial Nephritis Due to Encephalitozoon cuniculi in a Lung Transplant Recipient SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE microsporidia; lung; kidney; transplant; albendazole ID BONE-MARROW-TRANSPLANTATION; ENTEROCYTOZOON-BIENEUSI; MICROSPORIDIOSIS; AIDS; INFECTION; MYOSITIS; PATIENT; GENOTYPES AB Microsporidia are increasingly recognized as opportunistic pathogens in immunocompromised organ transplant recipients (OTR). Disseminated infection due to Encephalitozoon sp. is reported mainly in human immunodeficiency virus (HIV)-positive patients and rarely in HIV-negative OTR. The clinical spectrum ranges from keratoconjunctivitis, to pneumonitis, to acute kidney injury. The kidney is a common site for disseminated infection; however, specialized techniques are required for definitive diagnosis. We report the first case of disseminated Encephalitozoon cuniculi infection in an HIV-negative lung transplant recipient diagnosed on renal biopsy. Five months after transplant, he presented with fever and a lung infiltrate and developed acute kidney injury. Renal biopsy showed granulomatous interstitial nephritis with gram-positive rod-shaped organisms with a "belt-like stripe" in tubular epithelial cells. Electron microscopy, polymerase chain reaction, and mammalian cell cultures of the urine sediment confirmed E. cuniculi infection. Retrospective review of a previous lung biopsy showed similar organisms. On the basis of electron microscopy findings, the patient was treated with albendazole, and immunosuppressive therapy was reduced. However, the patient expired due to Aspergillus pneumonia and disseminated E. cuniculi infection. Microsporidia should be considered in cases of fever of unknown origin and/or multiorgan infection in HIV-negative OTR when other causes have been excluded, as successful treatment requires early detection. C1 [Levine, Deborah J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Pulm Dis, San Antonio, TX 78229 USA. [Riley, Daniel J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Jorgensen, James H.; McClain, William D.; Tio, Fermin; Abboud-Werner, Sherry L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Jorgensen, James H.; McClain, William D.; Tio, Fermin; Abboud-Werner, Sherry L.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Visvesvara, Govinda S.] Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, Atlanta, GA USA. RP Abboud-Werner, SL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM abboudwerner@uthscsa.edu NR 33 TC 4 Z9 4 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 2013 VL 37 IS 3 BP 447 EP 452 DI 10.1097/PAS.0b013e31827e1968 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 092BY UT WOS:000315095000017 PM 23388129 ER PT J AU Young, RH AF Young, Robert H. TI Robert E. Scully, MD OBITUARY SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Biographical-Item C1 [Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA USA. RP Young, RH (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, 55 Fruit St, Boston, MA 02114 USA. EM rhyoung@partners.org NR 1 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 2013 VL 37 IS 3 BP 464 EP 466 DI 10.1097/PAS.0b013e318280c2ce PG 3 WC Pathology; Surgery SC Pathology; Surgery GA 092BY UT WOS:000315095000023 PM 23520610 ER PT J AU Lawson, KM Back, SE Hartwell, KJ Maria, MMS Brady, KT AF Lawson, Katie M. Back, Sudie E. Hartwell, Karen J. Maria, Megan Moran-Santa Brady, Kathleen T. TI A Comparison of Trauma Profiles among Individuals with Prescription Opioid, Nicotine, or Cocaine Dependence SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; SEXUAL ABUSE; DSM-IV; ASSOCIATION; POPULATION; PREVALENCE; SMOKING; PTSD AB Background and Objectives Exposure to traumatic events is common among individuals with substance use disorders. Little is known, however, about the trauma histories among individuals with various types of addiction. Methods The present study compared the trauma histories (general, sexual, physical and emotional) of non-treatment seeking outpatients dependent on prescription opioids (n=41), nicotine (n=87) or cocaine (n=73). The Life Stressor ChecklistRevised (LSC-R) was completed by participants to assess childhood and adult trauma. Results The findings revealed that all three groups endorsed high levels of trauma exposure, with 96.5% of the entire sample experiencing at least one traumatic event in their lifetime. The prescription opiate group experienced a greater number of general and total traumas than the nicotine group. However, no group differences in the number of emotional, physical, or sexual traumas were revealed. The prescription opiate group reported a younger age of first traumatic event than the cocaine group, and was significantly more likely to report childhood traumatic events than both the cocaine and nicotine groups. Conclusions and Scientific Significance The findings provide clinically relevant information that may help improve screening, interventions, and preventative efforts. (Am J Addict 2013;22:127-131) C1 [Back, Sudie E.; Hartwell, Karen J.; Maria, Megan Moran-Santa; Brady, Kathleen T.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Hartwell, Karen J.; Brady, Kathleen T.] Ralph H Johnson VAMC, Charleston, SC USA. RP Lawson, KM (reprint author), 430 Biobehav Hlth Bldg, University Pk, PA 16802 USA. EM kml5509@psu.edu FU NCRR NIH HHS [UL1 RR029882]; NICHD NIH HHS [K12 HD055885, 5 K12 HD055885‐02]; NIDA NIH HHS [K23 DA021228, K24 DA000435, K24 DA00435, R33 DA036085‐03] NR 22 TC 7 Z9 7 U1 2 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD MAR-APR PY 2013 VL 22 IS 2 BP 127 EP 131 DI 10.1111/j.1521-0391.2013.00319.x PG 5 WC Substance Abuse SC Substance Abuse GA 092AK UT WOS:000315091000007 PM 23414497 ER PT J AU Lozano, BE LaRowe, SD Smith, JP Tuerk, P Roitzsch, J AF Lozano, Brian E. LaRowe, Steven D. Smith, Joshua P. Tuerk, Peter Roitzsch, John TI Brief Motivational Feedback May Enhance Treatment Entry in Veterans with Comorbid Substance Use and Psychiatric Disorders SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID INTERVENTION; DRINKING AB Background and Objectives There are limited investigations of brief interventions to facilitate treatment entry among individuals with substance use disorders. This study investigated the effectiveness of brief motivational feedback (BMF) for increasing entry into intensive substance abuse treatment in veteran patients. Methods Veteran patients (N=84) with substance use disorders referred for an intake assessment in a substance abuse specialty clinic received either (i) intake assessment plus BMF or (ii) intake assessment as usual (AAU). BMF consisted of brief motivational enhancement feedback pertaining to estimates of alcohol and drug consumption, money spent on drugs and alcohol, and self-reported problems due to substance abuse. Primary outcome was entry in treatment groups in an intensive outpatient program for substance abuse. Results Patients in BMF and AAU conditions did not significantly differ on indices of treatment entry. However, among patients with comorbid substance dependence and psychiatric disorders, those who received BMF were significantly more likely to enter outpatient treatment groups. Conclusions and Scientific Significance The addition of motivational feedback to a standard intake assessment enhanced substance abuse treatment entry among veteran patients with comorbid substance use disorders and psychiatric disorders. These preliminary findings extend the use of motivational feedback to facilitate entry into substance abuse treatment among veteran patients with comorbid substance use and psychiatric disorders. Furthermore, they suggest opportunity for more effective patient-treatment matching based on initial motivation and other individual factors such as psychiatric comorbidity. (Am J Addict 2013;22:132-135) C1 [Lozano, Brian E.; LaRowe, Steven D.; Tuerk, Peter] Ralph H Johnson VAMC, Charleston, SC 29401 USA. [Lozano, Brian E.; LaRowe, Steven D.; Smith, Joshua P.; Tuerk, Peter; Roitzsch, John] Med Univ S Carolina, Charleston, SC 29425 USA. RP Lozano, BE (reprint author), Ralph H Johnson VAMC, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM brian.lozano@va.gov NR 11 TC 1 Z9 1 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD MAR-APR PY 2013 VL 22 IS 2 BP 132 EP 135 DI 10.1111/j.1521-0391.2013.00315.x PG 4 WC Substance Abuse SC Substance Abuse GA 092AK UT WOS:000315091000008 PM 23414498 ER PT J AU Lee, LN Susarla, SM Hohman, MH Henstrom, DK Cheney, ML Hadlock, TA AF Lee, Linda N. Susarla, Srinivas M. Hohman, Marc H. Henstrom, Douglas K. Cheney, Mack L. Hadlock, Tessa A. TI A Comparison of Facial Nerve Grading Systems SO ANNALS OF PLASTIC SURGERY LA English DT Article DE facial paralysis; facial analysis; House-Brackmann; Facogram; facial nerve; facial nerve grading system ID HOUSE-BRACKMANN; PARALYSIS; FACE AB Purpose: This study aimed to compare a computerized tool to standard objective clinical scales for global and zone-specific assessment of facial nerve function. Methods: This was a retrospective review of 77 patients with facial paralysis who underwent facial videography. Videos were independently scored by 3 facial nerve specialists using the House-Brackmann Scales (HBI and HBII). Digital scoring was performed with Facogram software. Scores were recorded and compared using intraclass and Pearson (r) correlations. Results: Interobserver correlation was high with HBII, with overall scores in excellent agreement (intraclass correlation range, 0.78-0.95; P <= 0.0001). There were strong correlations between Facogram and HBII (r >= 0.67, P <= 0.0001) and strong intraobserver correlations between HBI and HBII (r >= 0.71, P <= 0.0001). The HBII required more clinician time [mean (SD), 72 (21) seconds per case], compared with Facogram, which did not require any clinician time. Conclusions: An automated, zone-specific facial analysis tool can eliminate clinician subjectivity and allow standardized assessment of facial paralysis. C1 [Lee, Linda N.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Lee, Linda N.; Hohman, Marc H.; Cheney, Mack L.; Hadlock, Tessa A.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Susarla, Srinivas M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Susarla, Srinivas M.] Massachusetts Gen Hosp, Dept Oral Maxillofacial Surg, Boston, MA 02114 USA. [Hohman, Marc H.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Head & Neck Surg, Boston, MA 02114 USA. [Henstrom, Douglas K.] Univ Iowa, Dept Otolaryngol, Div Facial Plast & Reconstruct Surg, Iowa, IA USA. [Cheney, Mack L.; Hadlock, Tessa A.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Facial Nerve Ctr, Div Head & Neck Surg, Boston, MA 02114 USA. RP Lee, LN (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Linda_lee@meei.harvard.edu OI Susarla, Srinivas/0000-0003-0155-8260 NR 15 TC 10 Z9 12 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD MAR PY 2013 VL 70 IS 3 BP 313 EP 316 DI 10.1097/SAP.0b013e31826acb2c PG 4 WC Surgery SC Surgery GA 092BI UT WOS:000315093400014 PM 23241802 ER PT J AU Ashitate, Y Lee, BT Laurence, RG Lunsford, E Hutteman, M Oketokoun, R Choi, HS Frangioni, JV AF Ashitate, Yoshitomo Lee, Bernard T. Laurence, Rita G. Lunsford, Elaine Hutteman, Merlijn Oketokoun, Rafiou Choi, Hak Soo Frangioni, John V. TI Intraoperative Prediction of Postoperative Flap Outcome Using the Near-Infrared Fluorophore Methylene Blue SO ANNALS OF PLASTIC SURGERY LA English DT Article DE flap perfusion; predictive capability; methylene blue; near-infrared fluorescence imaging ID FLUORESCENCE IMAGING-SYSTEM; FREE-TISSUE TRANSFER; REAL-TIME; VASCULAR COMPROMISE; INDOCYANINE GREEN; BLOOD-FLOW; ANGIOGRAPHY; PERFUSION; RECONSTRUCTION; IDENTIFICATION AB Methylene blue (MB) is a near-infrared fluorophore that provides a stable visual map of skin perfusion after intravenous injection. We explored the capability of MB to predict submental flap postoperative outcome using a single intraoperative measurement. Submental flaps were created in N = 15 pigs and imaged using the FLARE imaging system immediately after surgery and at 72 hours. Using the first 3 pigs, optimal MB dosing was found to be 2.0 mg/kg. Training and validation sets of 6 pigs each were then used for receiver operating characteristic analysis. In the training set, a contrast-to-background ratio (CBR) threshold of 1.24 provided the highest sensitivity and specificity to predict tissue necrosis at 72 hours. In the validation set, this threshold provided a prediction sensitivity of 95.3% and a specificity of 98.0%. We demonstrate that a single intraoperative near-infrared measurement can predict submental flap outcome at 72 hours. C1 [Ashitate, Yoshitomo; Laurence, Rita G.; Lunsford, Elaine; Hutteman, Merlijn; Oketokoun, Rafiou; Choi, Hak Soo; Frangioni, John V.] Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA 02215 USA. [Ashitate, Yoshitomo] Hokkaido Univ, Grad Sch Med, Div Canc Diagnost & Therapeut, Sapporo, Hokkaido, Japan. [Lee, Bernard T.] Beth Israel Deaconess Med Ctr, Dept Surg, Div Plast & Reconstruct Surg, Boston, MA 02215 USA. [Hutteman, Merlijn] Leiden Univ, Med Ctr, Dept Surg, NL-2300 RA Leiden, Netherlands. [Frangioni, John V.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. RP Frangioni, JV (reprint author), BIDMC, Room SL B05,330 Brookline Ave, Boston, MA 02215 USA. EM jfrangio@bidmc.harvard.edu RI Choi, Hak Soo/C-9954-2011; Lee, Bernard/K-1106-2016 OI Lee, Bernard/0000-0002-5533-3166 FU National Institutes of Health [R01-CA-115296, R01-EB-005805] FX Author J.V.F. supported by funds from National Institutes of Health grants R01-CA-115296 (National Cancer Institute) and R01-EB-005805 (National Institute of Biomedical Imaging and Bioengineering). The other authors have nothing to declare. NR 31 TC 7 Z9 7 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD MAR PY 2013 VL 70 IS 3 BP 360 EP 365 DI 10.1097/SAP.0b013e318236babe PG 6 WC Surgery SC Surgery GA 092BI UT WOS:000315093400023 PM 22395044 ER PT J AU Margalit, DN Sreedhara, M Chen, YH Catalano, PJ Nguyen, PL Golshan, M Overmoyer, BA Harris, JR Brock, JE AF Margalit, Danielle N. Sreedhara, Meera Chen, Yu-Hui Catalano, Paul J. Nguyen, Paul L. Golshan, Mehra Overmoyer, Beth A. Harris, Jay R. Brock, Jane E. TI Microinvasive Breast Cancer: ER, PR, and HER-2/neu Status and Clinical Outcomes after Breast-Conserving Therapy or Mastectomy SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID CARCINOMA-IN-SITU; INVASIVE DUCTAL CARCINOMA; LYMPH-NODE METASTASIS; LONG-TERM; PROGESTERONE-RECEPTOR; PATHOLOGICAL FINDINGS; ESTROGEN-RECEPTOR; NEGATIVITY; RECURRENCE; EXPRESSION AB Contemporary clinical outcomes of microinvasive breast cancer (MIBC), defined as no focus > 1 mm, are not well characterized. We document the immunophenotype, incidence of axillary metastases, and rate of recurrence in a well-defined case series. We reviewed 83 consecutive patients with MIBC from 1997 to 2005. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2/neu) receptor status were assessed. The cumulative incidence of local recurrence (LR) and nodal/distant recurrence was calculated. Predictors of recurrence were identified and effect estimates determined. Fifty-two patients (63 %) underwent breast-conserving therapy (BCT) and 31 (37 %) underwent mastectomy. Sixty-one percent had ER-positive disease and 49 % had HER-2/neu-positive disease. Three (4 %) of 68 patients with sentinel node mapping or axillary dissection had single node micrometastases, and none had macrometastases or multiple nodes involved. Median follow-up was 6.4 years, with 6 LRs, 2 regional nodal recurrences, and 2 concurrent local/distant recurrences. The 5-year cumulative incidence of recurrence (local, nodal, or distant) was 5.3 % (95 % confidence interval [CI] 2.0-13.4) for all patients, and among BCT patients, the 5-year cumulative incidence of LR was 4.2 % (95 % CI 0.7-12.7). HER-2/neu overexpression was not associated with recurrence (P = 0.46). Close/positive margins (a parts per thousand currency sign2 mm) were significantly associated with an increased risk of LR after BCT or mastectomy (hazard ratio 8.8; 95 % CI 1.6-48.8; P = 0.003). MIBC has a favorable prognosis, and HER-2/neu overexpression, although highly prevalent, is not significantly associated with recurrence. Axillary metastases at diagnosis are small and infrequent. The cumulative incidence of LR after BCT is acceptable; however, our data confirm that negative margins (> 2 mm) are required for optimal BCT outcomes. C1 [Margalit, Danielle N.; Sreedhara, Meera; Nguyen, Paul L.; Harris, Jay R.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Chen, Yu-Hui; Catalano, Paul J.] Brigham & Womens Hosp, Dana Farber Canc Inst, Harvard Canc Consortium, Boston, MA 02115 USA. [Golshan, Mehra] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg, Boston, MA 02115 USA. [Overmoyer, Beth A.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Brock, Jane E.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. RP Margalit, DN (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM jebrock@partners.org NR 27 TC 9 Z9 10 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 MAR PY 2013 VL 20 IS 3 BP 811 EP 818 DI 10.1245/s10434-012-2640-8 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 090RW UT WOS:000314998000017 PM 22956068 ER PT J AU Camp, MS Greenup, RA Taghian, A Coopey, SB Specht, M Gadd, M Hughes, K Smith, BL AF Camp, Melissa S. Greenup, Rachel A. Taghian, Alphonse Coopey, Suzanne B. Specht, Michelle Gadd, Michele Hughes, Kevin Smith, Barbara L. TI Application of ACOSOG Z0011 Criteria Reduces Perioperative Costs SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID LYMPH-NODE DISSECTION; BREAST-CANCER; AXILLARY DISSECTION; NEOADJUVANT CHEMOTHERAPY; BIOPSY; COMPLICATIONS; TRIAL; WOMEN; MODEL; CARE AB The ACOSOG Z0011 (Z0011) trial concluded that sentinel lymph node biopsy (SLNB) without completion axillary lymph node dissection (ALND) provides excellent regional control in women with T1-T2 sentinel lymph node (SLN) positive breast cancers receiving breast conservation therapy. We determined whether application of Z0011 guidelines would reduce costs. A retrospective chart review of patients with invasive breast cancer treated with lumpectomy and SLNB at our institution during 2009 was performed. We determined the number of overnight hospital admissions following ALND and estimated costs pertaining to the perioperative surgical management of the axilla patients actually received, and compared those to the estimated number of inpatient days and perioperative costs if Z0011 guidelines had been followed for eligible patients. The 2011 Medicare Fee Schedule was used to estimate costs for procedures, and costs for OR time were estimated using procedure length and cost of OR time per minute. A total of 71 patients underwent lumpectomy with SLNB and had at least 1 positive SLN. Estimated costs related to perioperative surgical management of the axilla were $322,775, and there were 36 overnight admissions. Applying Z0011 criteria, 51 patients (72 %) would have been eligible to forego completion ALND. Estimated costs would have been $264,513 with 13 overnight admissions, translating into a cost savings of $58,262 and 23 fewer overnight admissions. Application of Z0011 guidelines resulted in cost savings, with a 64 % reduction in inpatient hospital days and an 18 % reduction in early perioperative costs. C1 [Camp, Melissa S.; Greenup, Rachel A.; Coopey, Suzanne B.; Specht, Michelle; Gadd, Michele; Hughes, Kevin; Smith, Barbara L.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Taghian, Alphonse] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Camp, MS (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. EM Blsmith1@partners.org OI Hughes, Kevin/0000-0003-4084-6484 NR 16 TC 12 Z9 13 U1 0 U2 4 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 MAR PY 2013 VL 20 IS 3 BP 836 EP 841 DI 10.1245/s10434-012-2664-0 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA 090RW UT WOS:000314998000020 PM 23010735 ER PT J AU Kaufman, KM Zhao, J Kelly, JA Hughes, T Adler, A Sanchez, E Ojwang, JO Langefeld, CD Ziegler, JT Williams, AH Comeau, ME Marion, MC Glenn, SB Cantor, RM Grossman, JM Hahn, BH Song, YW Yu, CY James, JA Guthridge, JM Brown, EE Alarcon, GS Kimberly, RP Edberg, JC Ramsey-Goldman, R Petri, MA Reveille, JD Vila, LM Anaya, JM Boackle, SA Stevens, AM Freedman, BI Criswell, LA Pons-Estel, BA Lee, JH Lee, JS Chang, DM Scofield, RHA Gilkeson, GS Merrill, JT Niewold, TB Vyse, TJ Bae, SC Alarcon-Riquelme, ME Jacob, CO Sivils, KM Gaffney, PM Harley, JB Sawalha, AH Tsao, BP AF Kaufman, Kenneth M. Zhao, Jian Kelly, Jennifer A. Hughes, Travis Adler, Adam Sanchez, Elena Ojwang, Joshua O. Langefeld, Carl D. Ziegler, Julie T. Williams, Adrienne H. Comeau, Mary E. Marion, Miranda C. Glenn, Stuart B. Cantor, Rita M. Grossman, Jennifer M. Hahn, Bevra H. Song, Yeong Wook Yu, Chack-Yung James, Judith A. Guthridge, Joel M. Brown, Elizabeth E. Alarcon, Graciela S. Kimberly, Robert P. Edberg, Jeffrey C. Ramsey-Goldman, Rosalind Petri, Michelle A. Reveille, John D. Vila, Luis M. Anaya, Juan-Manuel Boackle, Susan A. Stevens, Anne M. Freedman, Barry I. Criswell, Lindsey A. Pons-Estel, Bernardo A. Lee, Joo-Hyun Lee, Ji-Seon Chang, Deh-Ming Scofield, R. Hal A. Gilkeson, Gary S. Merrill, Joan T. Niewold, Timothy B. Vyse, Timothy James Bae, Sang-Cheol Alarcon-Riquelme, Marta E. Jacob, Chaim O. Sivils, Kathy Moser Gaffney, Patrick M. Harley, John B. Sawalha, Amr H. Tsao, Betty P. CA Argentine Collaborat Grp Biolupus Network TI Fine mapping of Xq28: both MECP2 and IRAK1 contribute to risk for systemic lupus erythematosus in multiple ancestral groups SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID GENOME-WIDE ASSOCIATION; KAPPA-B ACTIVATION; ACETYLTRANSFERASE ARD1; GENETIC SUSCEPTIBILITY; BINDING-PROTEIN; IDENTIFICATION; HAPLOTYPE; REPLICATION; VARIANTS; INSIGHTS AB Objectives The Xq28 region containing IRAK1 and MECP2 has been identified as a risk locus for systemic lupus erythematosus (SLE) in previous genetic association studies. However, due to the strong linkage disequilibrium between IRAK1 and MECP2, it remains unclear which gene is affected by the underlying causal variant(s) conferring risk of SLE. Methods We fine-mapped >= 136 SNPs in a similar to 227 kb region on Xq28, containing IRAK1, MECP2 and seven adjacent genes (L1CAM, AVPR2, ARHGAP4, NAA10, RENBP, HCFC1 and TMEM187), for association with SLE in 15 783 case-control subjects derived from four different ancestral groups. Results Multiple SNPs showed strong association with SLE in European Americans, Asians and Hispanics at p < 5 x 10(-8) with consistent association in subjects with African ancestry. Of these, six SNPs located in the TMEM187-IRAK1-MECP2 region captured the underlying causal variant(s) residing in a common risk haplotype shared by all four ancestral groups. Among them, rs1059702 best explained the Xq28 association signals in conditional testings and exhibited the strongest p value in transancestral meta-analysis (p(meta) = 1.3 x 10(-27), OR = 1.43), and thus was considered to be the most likely causal variant. The risk allele of rs1059702 results in the amino acid substitution S196F in IRAK1 and had previously been shown to increase NF-kappa B activity in vitro. We also found that the homozygous risk genotype of rs1059702 was associated with lower mRNA levels of MECP2, but not IRAK1, in SLE patients (p = 0.0012) and healthy controls (p = 0.0064). Conclusions These data suggest contributions of both IRAK1 and MECP2 to SLE susceptibility. C1 [Kaufman, Kenneth M.; Harley, John B.] Cincinnati Childrens Hosp, Med Ctr, Div Rheumatol, Cincinnati, OH USA. [Kaufman, Kenneth M.; Harley, John B.] Cincinnati Childrens Hosp, Med Ctr, Ctr Autoimmune Genom & Etiol, Cincinnati, OH USA. [Kaufman, Kenneth M.; Merrill, Joan T.; Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Zhao, Jian; Grossman, Jennifer M.; Hahn, Bevra H.; Tsao, Betty P.] Univ Calif Los Angeles, Div Rheumatol, Los Angeles, CA USA. [Kelly, Jennifer A.; Hughes, Travis; Adler, Adam; Sanchez, Elena; Glenn, Stuart B.; James, Judith A.; Guthridge, Joel M.; Scofield, R. Hal A.; Alarcon-Riquelme, Marta E.; Sivils, Kathy Moser; Gaffney, Patrick M.; Sawalha, Amr H.] Oklahoma Med Res Fdn, Arthritis & Clin Immunol Program, Oklahoma City, OK 73104 USA. [Ojwang, Joshua O.] Brevard Coll, Dept Chem, Palm Bay, FL USA. [Langefeld, Carl D.; Ziegler, Julie T.; Williams, Adrienne H.; Comeau, Mary E.; Marion, Miranda C.] Wake Forest Sch Med, Dept Biostat, Winston Salem, NC USA. [Cantor, Rita M.] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA. [Song, Yeong Wook] Seoul Natl Univ, Div Rheumatol, Seoul, South Korea. [Yu, Chack-Yung] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA. [James, Judith A.; Scofield, R. Hal A.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Brown, Elizabeth E.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA. [Brown, Elizabeth E.; Alarcon, Graciela S.; Kimberly, Robert P.; Edberg, Jeffrey C.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Ramsey-Goldman, Rosalind] Northwestern Univ, Feinberg Sch Med, Div Rheumatol, Chicago, IL 60611 USA. [Petri, Michelle A.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Reveille, John D.] Univ Texas Houston, Hlth Sci Ctr, Dept Internal Med, Houston, TX 77225 USA. [Vila, Luis M.] Univ Puerto Rico, Dept Med, San Juan, PR 00936 USA. [Anaya, Juan-Manuel] Univ Rosario, Ctr Autoimmune Dis Res, Bogota, Colombia. [Boackle, Susan A.] Univ Colorado Denver, Div Rheumatol, Aurora, CO USA. [Stevens, Anne M.] Univ Washington, Dept Pediat, Div Rheumatol, Seattle, WA 98195 USA. [Stevens, Anne M.] Seattle Childrens Res Inst, Ctr Immun & Immunotherapies, Seattle, WA USA. [Freedman, Barry I.] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA. [Criswell, Lindsey A.] Univ Calif San Francisco, Dept Med, Rosalind Russell Med Res Ctr Arthrit, San Francisco, CA USA. [Pons-Estel, Bernardo A.; Argentine Collaborat Grp] Dept Med, Rosario, Santa Fe, Argentina. [Lee, Joo-Hyun] Inje Univ, Coll Med, Ilsan Paik Hosp, Dept Rheumatol, Gimhae, South Korea. [Lee, Ji-Seon; Bae, Sang-Cheol] Hanyang Univ, Hosp Rheumat Dis, Dept Rheumatol, Seoul 133791, South Korea. [Chang, Deh-Ming] Natl Def Med Ctr, Taipei, Taiwan. [Scofield, R. Hal A.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Gilkeson, Gary S.] Med Univ S Carolina, Dept Med, Div Rheumatol, Charleston, SC 29425 USA. [Merrill, Joan T.] Oklahoma Med Res Fdn, Clin Pharmacol Program, Oklahoma City, OK 73104 USA. [Niewold, Timothy B.] Univ Chicago, Rheumatol Sect, Chicago, IL 60637 USA. [Niewold, Timothy B.] Univ Chicago, Gwen Knapp Ctr Lupus & Immunol Res, Chicago, IL 60637 USA. [Vyse, Timothy James] Kings Coll London, Div Genet & Mol Med, London WC2R 2LS, England. [Vyse, Timothy James] Kings Coll London, Div Immunol, London WC2R 2LS, England. [Alarcon-Riquelme, Marta E.; Biolupus Network] Pfizer Univ Granada Junta Andalucia, Ctr Genom Invest Oncol GENYO, Granada, Spain. [Jacob, Chaim O.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. RP Kaufman, KM (reprint author), MLC 15012,3333 Burnet Ave, Cincinnati, OH 45229 USA. EM kaufman.kenneth@cchmc.org RI Zhao, Jian/E-6292-2012; Yu, Chack-Yung/E-4360-2011; Anaya, Juan-Manuel/J-1960-2016; Sanchez, Elena/B-4140-2017; OI Anaya, Juan-Manuel/0000-0002-6444-1249; Sanchez, Elena/0000-0002-7041-5485; Universidad del Rosario, Biblioteca/0000-0003-3491-9392; Kimberly, Robert/0000-0002-5330-3086; Alarcon Riquelme, Marta Eugenia/0000-0002-7632-4154; Niewold, Timothy/0000-0003-3532-6660 FU US National Institutes of Health [R01AR43814, R01AR043274, R01AI063274, N01AR62277, R3724717, AR042460, P01AI083194, P20RR020143, R01AR33062, P30AR055385, 5UL1RR025777, P30048311, K08AI083790, LRPAI071651, R01CA141700]; Lupus Research Institute; Merit Award from the US Department of Veterans Affairs; Alliance for Lupus Research; Arthritis National Research Foundation Eng Tan Scholar Award; Arthritis Foundation; Korea Healthcare Technology R&D Project, Ministry for Health and Welfare, Republic of Korea [A111218-11-GM01]; Korean R&D Programme of MKE/KEIT [10035615]; Swedish Research Council; Swedish Association Against Rheumatism; King Gustaf Vth 80th Jubilee Foundation; Fundacion Instituto de Salud Carlos III [PS0900129]; European FEDER funds; Consejeria de Salud de Andalucia [PI-0012]; Wenner Gren Foundation; Wellcome Trust; Arthritis Research UK; CTSA Grant from the National Center for Research Resources, Kirkland Scholar Award [I ULI RR025014-02]; Wake Forest University Health Sciences Center for Public Health Genomics; Federico Wilhelm Agricola Foundation Research; US National Institutes of Health. [RC1AR058621, UL1RR024999, K24AR002138, P602AR30692, P01AR49084, UL1RR025741, R01AR051545-01A2, P30AR053483, P30GM103510, U19AI082714, R21AI070304, 1U54RR23417-01, P60AR053308, M01RR-00079, P60AR049459, UL1RR029882] FX Support for this work was obtained from the US National Institutes of Health grants: R01AR43814 (BPT), R01AR043274 (KLM), R01AI063274 (PMG), N01AR62277 (JBH), R3724717 (JBH), AR042460 (JBH), P01AI083194 (JBH), P20RR020143 (JBH), P01AR49084 (RPK and EEB), R01AR33062 (RPK), P30AR055385 (EEB), 5UL1RR025777 (RPK and JCE), R01AR33062 (RPK), P01AR49084 (RPK, JCE, EEB, GSA, JDR, RRG, LMB and MAP), P30048311 (EEB), K08AI083790 (TBN), LRPAI071651 (TBN), R01CA141700 (MEAR), RC1AR058621 (MEAR) and UL1RR024999 (TBN), K24AR002138 (RRG), P602AR30692 (RRG), P01AR49084 (RRG), UL1RR025741 (RRG), R01AR051545-01A2 (AMS), P30AR053483 (JAJ and JMG), P30GM103510 (JAJ), U19AI082714 (JAJ and JMG), R21AI070304 (SAB), 1U54RR23417-01 (JDR), P60AR053308 (LAC), M01RR-00079 (LAC), P60AR049459 (DLK) and UL1RR029882 (DLK). This study was also supported by a grant from Lupus Research Institute (BPT, TBN), the Merit Award from the US Department of Veterans Affairs (JBH and GSG), The Alliance for Lupus Research (KLM, TBN, LAC and COJ), the Arthritis National Research Foundation Eng Tan Scholar Award (TBN), the Arthritis Foundation (AMS and PMG), the Korea Healthcare Technology R&D Project, Ministry for Health and Welfare, Republic of Korea (A111218-11-GM01; SCB) and Korean R&D Programme of MKE/KEIT (10035615; YWS). Additional funding awarded from the Swedish Research Council, Swedish Association Against Rheumatism and the King Gustaf Vth 80th Jubilee Foundation and the Fundacion Instituto de Salud Carlos III PS0900129 partially funded through European FEDER funds and the Consejeria de Salud de Andalucia PI-0012, the Wenner Gren Foundation for support (CG), the Wellcome Trust (TJV), Arthritis Research UK (TJV), CTSA Grant Number I ULI RR025014-02 (AMS) from the National Center for Research Resources, Kirkland Scholar Award (LAC), Wake Forest University Health Sciences Center for Public Health Genomics (CDL, MCC, MCM, and PSR) and the Federico Wilhelm Agricola Foundation Research grant (BAPE). NR 40 TC 29 Z9 30 U1 3 U2 14 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD MAR PY 2013 VL 72 IS 3 BP 437 EP 444 DI 10.1136/annrheumdis-2012-201851 PG 8 WC Rheumatology SC Rheumatology GA 088BQ UT WOS:000314809200021 PM 22904263 ER PT J AU Dai, TH Gupta, A Huang, YY Yin, R Murray, CK Vrahas, MS Sherwood, ME Tegos, GP Hamblin, MR AF Dai, Tianhong Gupta, Asheesh Huang, Ying-Ying Yin, Rui Murray, Clinton K. Vrahas, Mark S. Sherwood, Margaret E. Tegos, George P. Hamblin, Michael R. TI Blue Light Rescues Mice from Potentially Fatal Pseudomonas aeruginosa Burn Infection: Efficacy, Safety, and Mechanism of Action SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANTIMICROBIAL PHOTODYNAMIC THERAPY; MRSA IN-VITRO; WOUND INFECTIONS; HELICOBACTER-PYLORI; ULTRAVIOLET-LIGHT; VISIBLE-LIGHT; INACTIVATION; BACTERIA; MODEL; RESISTANCE AB Blue light has attracted increasing attention due to its intrinsic antimicrobial effect without the addition of exogenous photosensitizers. However, the use of blue light for wound infections has not been established yet. In this study, we demonstrated the efficacy of blue light at 415 nm for the treatment of acute, potentially lethal Pseudomonas aeruginosa burn infections in mice. Our in vitro studies demonstrated that the inactivation rate of P. aeruginosa cells by blue light was approximately 35-fold higher than that of keratinocytes (P = 0.0014). Transmission electron microscopy revealed blue light-mediated intracellular damage to P. aeruginosa cells. Fluorescence spectroscopy suggested that coproporphyrin III and/or uroporphyrin III are possibly the intracellular photosensitive chromophores associated with the blue light inactivation of P. aeruginosa. In vivo studies using an in vivo bioluminescence imaging technique and an area-under-the-bioluminescence-time-curve (AUBC) analysis showed that a single exposure of blue light at 55.8 J/cm(2), applied 30 min after bacterial inoculation to the infected mouse burns, reduced the AUBC by approximately 100-fold in comparison with untreated and infected mouse burns (P < 0.0001). Histological analyses and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assays indicated no significant damage in the mouse skin exposed to blue light at the effective antimicrobial dose. Survival analyses revealed that blue light increased the survival rate of the infected mice from 18.2% to 100% (P < 0.0001). In conclusion, blue light therapy might offer an effective and safe alternative to conventional antimicrobial therapy for P. aeruginosa burn infections. C1 [Dai, Tianhong; Gupta, Asheesh; Huang, Ying-Ying; Yin, Rui; Sherwood, Margaret E.; Tegos, George P.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Dai, Tianhong; Gupta, Asheesh; Huang, Ying-Ying; Yin, Rui; Tegos, George P.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Gupta, Asheesh] Def Inst Physiol & Allied Sci, Delhi, India. [Huang, Ying-Ying] Guangxi Med Univ, Dept Pathol, Nanning, Guangxi, Peoples R China. [Gupta, Asheesh] Third Mil Med Univ, Southwest Hosp, Dept Dermatol, Chongqing, Peoples R China. [Murray, Clinton K.] Brooke Army Med Ctr, Infect Dis Serv, Ft Sam Houston, TX 78234 USA. [Vrahas, Mark S.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Tegos, George P.] Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Huang, Ying-ying/G-3153-2011; OI Huang, Ying-ying/0000-0003-3066-6981; Hamblin, Michael/0000-0001-6431-4605 FU Airlift Research Foundation [109421]; COTA/Smith Nephew grant [2012-16]; CIMIT Innovation grant [13-1033]; NIH [RO1AI050875] FX This study was supported in part by Airlift Research Foundation Extremity Trauma Research grant 109421 (to T. D.), COTA/Smith & Nephew grant 2012-16 (to T. D.), CIMIT Innovation grant 13-1033 (to T. D.), and NIH grant RO1AI050875 (to M. R. H.). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 28 Z9 33 U1 2 U2 29 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 MAR PY 2013 VL 57 IS 3 BP 1238 EP 1245 DI 10.1128/AAC.01652-12 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 090GU UT WOS:000314968100018 PM 23262998 ER PT J AU Naar, AM AF Naeaer, Anders M. TI Anti-atherosclerosis or No Anti-atherosclerosis That is the miR-33 question SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Editorial Material DE mir-33; atherosclerosis; LDLr; HDL-C; antisense ID CHOLESTEROL HOMEOSTASIS; METABOLIC-DISORDERS; HDL C1 Harvard Univ, Dept Cell Biol, Sch Med, Massachusetts Gen Hosp,Canc Ctr, Charlestown, MA 02129 USA. RP Naar, AM (reprint author), Harvard Univ, Dept Cell Biol, Sch Med, Massachusetts Gen Hosp,Canc Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM naar@helix.mgh.harvard.edu FU NIDDK NIH HHS [R01 DK094184] NR 16 TC 9 Z9 9 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAR PY 2013 VL 33 IS 3 BP 447 EP 448 DI 10.1161/ATVBAHA.112.301021 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 089DS UT WOS:000314890200006 PM 23407174 ER PT J AU Koseoglu, S Dilks, JR Peters, CG Fitch-Tewfik, JL Fadel, NA Jasuja, R Italiano, JE Haynes, CL Flaumenhaft, R AF Koseoglu, Secil Dilks, James R. Peters, Christian G. Fitch-Tewfik, Jennifer L. Fadel, Nathalie A. Jasuja, Reema Italiano, Joseph E., Jr. Haynes, Christy L. Flaumenhaft, Robert TI Dynamin-Related Protein-1 Controls Fusion Pore Dynamics During Platelet Granule Exocytosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE dynamin-related protein-1; exocytosis; fusion pore; platelets; thrombosis ID ISCHEMIA-REPERFUSION INJURY; SINGLE VESICLE RELEASE; MITOCHONDRIAL DIVISION; CHROMAFFIN CELLS; QUANTAL SIZE; MOUSE MODEL; MEMBRANE; FISSION; DRP1; INHIBITORS AB Objective-Platelet granule exocytosis serves a central role in hemostasis and thrombosis. Recently, single-cell amperometry has shown that platelet membrane fusion during granule exocytosis results in the formation of a fusion pore that subsequently expands to enable the extrusion of granule contents. However, the molecular mechanisms that control platelet fusion pore expansion and collapse are not known. Methods and Results-We identified dynamin-related protein-1 (Drp1) in platelets and found that an inhibitor of Drp1, mdivi-1, blocked exocytosis of both platelet dense and a-granules. We used single-cell amperometry to monitor serotonin release from individual dense granules and, thereby, measured the effect of Drp1 inhibition on fusion pore dynamics. Inhibition of Drp1 increased spike width and decreased prespike foot events, indicating that Drp1 influences fusion pore formation and expansion. Platelet-mediated thrombus formation in vivo after laser-induced injury of mouse cremaster arterioles was impaired after infusion of mdivi-1. Conclusion-These results demonstrate that inhibition of Drp1 disrupts platelet fusion pore dynamics and indicate that Drp1 can be targeted to control thrombus formation in vivo. (Arterioscler Thromb Vasc Biol. 2013;33:481-488.) C1 [Dilks, James R.; Peters, Christian G.; Fitch-Tewfik, Jennifer L.; Fadel, Nathalie A.; Jasuja, Reema; Flaumenhaft, Robert] Harvard Univ, Sch Med, Dept Med, Div Hemostasis & Thrombosis,BIDMC, Boston, MA USA. [Koseoglu, Secil; Haynes, Christy L.] Univ Minnesota, Dept Chem, Minneapolis, MN 55455 USA. [Italiano, Joseph E., Jr.] Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. [Italiano, Joseph E., Jr.] Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA. RP Flaumenhaft, R (reprint author), Beth Israel Deaconess Med Ctr, Ctr Life Sci, Room 939,3 Blackfan Circle, Boston, MA 02215 USA. EM rflaumen@bidmc.harvard.edu OI Haynes, Christy/0000-0002-5420-5867 FU National Institutes of Health (NIH) [HL87203]; NIH New Innovator Award [OD004258-01]; American Heart Association [0840043 N] FX This work was supported by National Institutes of Health (NIH) grant HL87203 (R. Flaumenhaft) and NIH New Innovator Award to C. L. Haynes (OD004258-01). R. Flaumenhaft is a recipient of an Established Investigator Award from the American Heart Association (0840043 N). NR 44 TC 9 Z9 9 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAR PY 2013 VL 33 IS 3 BP 481 EP + DI 10.1161/ATVBAHA.112.255737 PG 18 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 089DS UT WOS:000314890200012 PM 23288151 ER PT J AU Liu, J Feener, EP AF Liu, Jia Feener, Edward P. TI Plasma kallikrein-kinin system and diabetic retinopathy SO BIOLOGICAL CHEMISTRY LA English DT Review DE bradykinin receptor; diabetic retinopathy; plasma kallikrein-kinin system; retina; vascular permeability ID RETINAL VASCULAR-PERMEABILITY; B-1 RECEPTOR ANTAGONIST; NITRIC-OXIDE SYNTHASE; FACTOR-XII; IN-VIVO; HEREDITARY ANGIOEDEMA; THROMBUS FORMATION; UP-REGULATION; RISK-FACTORS; BRADYKININ AB Diabetic retinopathy (DR) occurs, to some extent, in most people with at least 20 years' duration of diabetes mellitus. The progression of DR to its sight-threatening stages is usually associated with the worsening of underlying retinal vascular dysfunction and disease. The plasma kallikrein-kinin system (KKS) is activated during vascular injury, where it mediates important functions in innate inflammation, blood flow, and coagulation. Recent findings from human vitreous proteomics and experimental studies on diabetic animal models have implicated the KKS in contributing to DR. Vitreous fluid from people with advanced stages of DR contains increased levels of plasma KKS components, including plasma kallikrein (PK), coagulation factor XII, and high-molecular-weight kininogen. Both bradykinin B1 and B2 receptor isoforms (B1R and B2R, respectively) are expressed in human retina, and retinal B1R levels are increased in diabetic rodents. The activation of the intraocular KKS induces retinal vascular permeability, vasodilation, and retinal thickening, and these responses are exacerbated in diabetic rats. Preclinical studies have shown that the administration of PK inhibitors and B1R antagonists to diabetic rats ameliorates retinal vascular hyperpermeability and inflammation. These findings suggest that components of plasma KKS are potential therapeutic targets for diabetic macular edema. C1 [Liu, Jia; Feener, Edward P.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med,Res Div, Boston, MA 02215 USA. RP Feener, EP (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med,Res Div, 1 Joslin Pl, Boston, MA 02215 USA. EM edward.feener@joslin.harvard.edu FU US National Institutes of Health [EY019029, DK36836]; JDRF [17-2011-251] FX This work was supported in part by the US National Institutes of Health (grants EY019029 and DK36836) and the JDRF grant 17-2011-251. NR 77 TC 13 Z9 13 U1 0 U2 20 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1431-6730 J9 BIOL CHEM JI Biol. Chem. PD MAR PY 2013 VL 394 IS 3 BP 319 EP 328 DI 10.1515/hsz-2012-0316 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 087JN UT WOS:000314757700002 PM 23362193 ER PT J AU Zhan, HC Cardozo, C Yu, WN Wang, AT Moliterno, AR Dang, CV Spivak, JL AF Zhan, Huichun Cardozo, Christopher Yu, Wayne Wang, Antai Moliterno, Alison R. Dang, Chi V. Spivak, Jerry L. TI MicroRNA deregulation in polycythemia vera and essential thrombocythemia patients SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE MicroRNA; Myeloproliferative neoplasm; Polycythemia vera; Essential thrombocythemia; Hematopoiesis ID HEMATOPOIETIC STEM-CELLS; TYROSINE KINASE JAK2; MYELOPROLIFERATIVE DISORDERS; ERYTHROID-DIFFERENTIATION; SECONDARY MYELOFIBROSIS; MYELOID METAPLASIA; EXPRESSION; MUTATION; ERYTHROPOIESIS; JAK2V617F AB Polycythemia vera (PV) and essential thrombocythemia (ET) are the two most common myeloproliferative neoplasms. The same JAK2(V617F) mutation can be found in both disorders and is able to recapitulate many of the phenotypic abnormalities of these diseases in the murine models. The disease phenotype is also influenced by other unknown genetic or epigenetic factors. MicroRNAs (miRNA) are 18-24 nucleotides single-stranded non-protein-coding RNAs that function primarily as gene repressors by binding to their target messenger RNAs. We performed miRNA expression profiling by oligonucleotide microarray analysis in purified peripheral blood CD34+ cells from eight JAK2(V617F)-positive PV patients and six healthy donors. A quantitative reverse-transcription polymerase chain reaction assay was used to verify differential miRNA expression. Since erythrocytosis is the only feature that distinguishes PV from ET, we also compared specific miRNA expression in the nucleated erythroid cells directly descended from the early erythroid progenitor cells of PV and ET patients. Our data indicate that significant miRNA deregulation occurs in PV CD34+ cells and confirm a genetic basis for the gender-specific differences that characterize PV with respect to miRNA. The results of our study also suggest that deregulated miRNAs may represent an important mechanism by which the PV erythrocytosis and ET thrombocytosis phenotypes are determined. Published by Elsevier Inc. C1 [Zhan, Huichun; Cardozo, Christopher] James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Zhan, Huichun; Wang, Antai] Columbia Univ, Med Ctr, New York, NY USA. [Cardozo, Christopher] Mt Sinai Sch Med, New York, NY USA. [Yu, Wayne; Moliterno, Alison R.; Spivak, Jerry L.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Dang, Chi V.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Zhan, HC (reprint author), James J Peters VA Med Ctr, Room 3F-12,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Huichun.Zhan@va.gov FU Veterans Affairs Career Development Award [10959632]; Veterans Affairs Rehabilitation Research and Development Service grant [B9212-C] FX Huichun Zhan is currently supported by the Veterans Affairs Career Development Award (grant 10959632) and Veterans Affairs Rehabilitation Research and Development Service grant B9212-C. We would like to thank Drs. Katia Basso, David Dominguez, and Riccardo Dalla-Favera from Columbia University for their assistance in microRNA analysis. We thank Drs. Min Lu and Ronald Hoffman from Mount Sinai School of Medicine for their assistance in the colony formation assay. We thank Drs. Yan Makeyev and Imitiaz Patel for providing precious patient samples. We thank Hai Xu from Johns Hopkins University for his assistance in microRNA microarray experiments. We thank Drs. Azra Raza and Naomi Galili from Columbia University Medical Center, Drs. Erik Langhoff, Mary Sano, and Elisa Sanchez-Valencia from James J. Peters VA Medical Center, and Dr. Robert Brodsky from Johns Hopkins University for their continuing support throughout this work. NR 50 TC 9 Z9 9 U1 0 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAR PY 2013 VL 50 IS 3 BP 190 EP 195 DI 10.1016/j.bcmd.2012.11.009 PG 6 WC Hematology SC Hematology GA 091UE UT WOS:000315074500010 PM 23265742 ER PT J AU Smucny, J Rojas, DC Eichman, LC Tregellas, JR AF Smucny, Jason Rojas, Donald C. Eichman, Lindsay C. Tregellas, Jason R. TI Neuronal effects of auditory distraction on visual attention SO BRAIN AND COGNITION LA English DT Article DE Attention; Dorsolateral prefrontal cortex; Fusiform gyrus; Pre-supplementary motor area; Posterior cingulate; Distraction ID ANTERIOR CINGULATE CORTEX; PREFRONTAL CORTEX; SUSTAINED ATTENTION; HEMODYNAMIC-RESPONSE; SELECTIVE ATTENTION; FUNCTIONAL-ANATOMY; PERFORMANCE; BRAIN; TASK; FMRI AB Selective attention in the presence of distraction is a key aspect of healthy cognition. The underlying neurobiological processes, have not, however, been functionally well characterized. In the present study, we used functional magnetic resonance imaging to determine how ecologically relevant distracting noise affects cortical activity in 27 healthy adults during two versions of the visual Sustained Attention To Response Task (SARI) that differ in difficulty (and thus attentional load). A significant condition (noise or silence) by task (easy or difficult) interaction was observed in several areas, including dorsolateral prefrontal cortex (DLPFC), fusiform gyrus (FG), posterior cingulate (PCC), and pre-supplementary motor area (PreSMA). Post hoc analyses of interaction effects revealed deactivation of DLPFC, PCC, and PreSMA during distracting noise under conditions of low attentional load, and activation of FG and PCC during distracting noise under conditions of high attentional load. These results suggest that distracting noise may help alert subjects to task goals and reduce demands on cortical resources during tasks of low difficulty and attentional load. Under conditions of higher load, however, additional cognitive resources may be required in the presence of noise. (C) 2012 Elsevier Inc. All rights reserved. C1 [Smucny, Jason; Rojas, Donald C.; Tregellas, Jason R.] Univ Colorado, Neurosci Program, Aurora, CO 80045 USA. [Smucny, Jason; Rojas, Donald C.; Eichman, Lindsay C.; Tregellas, Jason R.] Denver VA Med Ctr, Res Serv, Denver, CO USA. [Rojas, Donald C.; Eichman, Lindsay C.; Tregellas, Jason R.] Univ Colorado, Dept Psychiat, Aurora, CO 80045 USA. RP Tregellas, JR (reprint author), Univ Colorado, Dept Psychiat, Anschutz Med Campus,Bldg 500,4th Floor, Aurora, CO 80045 USA. EM Jason.Smucny@ucdenver.edu; Don.Rojas@ucden-ver.edu; Lindsay.Eichman@ucdenver.edu; Jason.Tregel-las@ucdenver.edu RI Tregellas, Jason/J-3637-2015; OI Rojas, Don/0000-0001-6560-9616; Smucny, Jason/0000-0001-5656-7987 FU VA Biomedical Laboratory and Clinical Science Research and Development Service; National Association for Research in Schizophrenia and Affective Disorders (NARSAD); Blowitz-Ridgeway Foundation FX The authors thank Debra Singel for help with fMRI data acquisition. The research was supported by the VA Biomedical Laboratory and Clinical Science Research and Development Service, the National Association for Research in Schizophrenia and Affective Disorders (NARSAD) and the Blowitz-Ridgeway Foundation. NR 49 TC 8 Z9 8 U1 2 U2 38 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD MAR PY 2013 VL 81 IS 2 BP 263 EP 270 DI 10.1016/j.bandc.2012.11.008 PG 8 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 091RN UT WOS:000315067600012 PM 23291265 ER PT J AU Liu, YH Wang, AL Marchese, AD Kacmarek, RM Jiang, Y AF Liu, Y. H. Wang, A. L. Marchese, A. D. Kacmarek, R. M. Jiang, Y. TI Jet or intensive care unit ventilator during simulated percutaneous transtracheal ventilation: a lung model study SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE airway obstruction; equipment; ventilators; ventilation; transtracheal ID DIFFICULT-AIRWAY; MAJOR COMPLICATIONS; NATIONAL-SURVEY; MANAGEMENT; ANESTHESIA; AVAILABILITY; UK; ANESTHETISTS; INTUBATION; GUIDELINES AB Percutaneous transtracheal ventilation (PTV) via a jet ventilator (PTJV) is considered a rescue technique in difficult airway management. However, whether a conventional ventilator can generate adequate ventilation via PTV is not known. Our goal was to evaluate the tidal volume (V-T) generated by a conventional ventilator during simulated PTV compared with PTJV in a lung model. A lung model simulating an adult lung was used. A catheter was inserted throughthe artificial trachea and connected to either a jet ventilator or a conventional ventilator. The direction of catheter insertion was perpendicular to the trachea, pointing towards the lung and away from the lung. The jet ventilator was operated at 344.7 kPa. The conventional ventilator was operated in the pressure mode at peak inspiratory pressures of 4090 cm H2O. The jet ventilator generated larger V-T [817 (336) ml] when the catheter was pointing towards the lung than when pointing away from the lung or perpendicular to the trachea [121 (41) and 69 (24) ml, respectively, P0.01]. With the conventional ventilator, changes in V-T at different direction of catheter insertion were much less [222 (81) ml catheter pointing towards the lung, 229 (121) ml perpendicular to the trachea, and 187 (97) ml away from the lung]. Our result demonstrated that PTJV was effective only when the catheter was pointing towards the lung and requires high operating pressure. A conventional ventilator can generate reasonable minute ventilation through the transtracheal catheter less dependent on directions of catheter insertion and should be considered during emergent PTV. C1 [Liu, Y. H.] Chinese Peoples Liberat Army Gen Hosp, Anaesthesia & Operat Ctr, Beijing, Peoples R China. [Liu, Y. H.; Kacmarek, R. M.; Jiang, Y.] Massachusetts Gen Hosp, Dept Anaesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Marchese, A. D.; Kacmarek, R. M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Wang, A. L.] Jining Med Coll, Dept Surg, Jining, Peoples R China. RP Jiang, Y (reprint author), Massachusetts Gen Hosp, Dept Anaesthesia Crit Care & Pain Med, 55 Fruit St,Jackson 422, Boston, MA 02114 USA. EM yjiang@partners.org FU Department of Anaesthesia, Critical Care, and Pain Medicine; Department of Respiratory Care, Massachusetts General Hospital, Boston, MA, USA FX This project was funded by the Department of Anaesthesia, Critical Care, and Pain Medicine and the Department of Respiratory Care, Massachusetts General Hospital, Boston, MA, USA. NR 19 TC 2 Z9 2 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD MAR PY 2013 VL 110 IS 3 BP 456 EP 462 DI 10.1093/bja/aes417 PG 7 WC Anesthesiology SC Anesthesiology GA 092LR UT WOS:000315123800019 PM 23171722 ER PT J AU Leenders, M Bhattacharjee, S Vineis, P Stevens, V Bueno-de-Mesquita, H Shu, XO Amundadottir, L Gross, M Tobias, GS Wactawski-Wende, J Arslan, AA Duell, EJ Fuchs, CS Gallinger, S Hartge, P Hoover, RN Holly, EA Jacobs, EJ Klein, AP Kooperberg, C LaCroix, A Li, DH Mandelson, MT Olson, SH Petersen, G Risch, HA Yu, K Wolpin, BM Zheng, W Agalliu, I Albanes, D Boutron-Ruault, MC Bracci, PM Buring, JE Canzian, F Chang, K Chanock, SJ Cotterchio, M Gaziano, JM Giovanucci, EL Goggins, M Hallmans, G Hankinson, SE Hoffman-Bolton, JA Hunter, DJ Hutchinson, A Jacobs, KB Jenab, M Khaw, KT Kraft, P Krogh, V Kurtz, RC McWilliams, RR Mendelsohn, JB Patel, AV Rabe, KG Riboli, E Tjonneland, A Trichopoulos, D Virtamo, J Visvanathan, K Elena, JW Yu, H Zeleniuch-Jacquotte, A Stolzenberg-Solomon, RZ AF Leenders, Max Bhattacharjee, Samsiddhi Vineis, Paolo Stevens, Victoria Bueno-de-Mesquita, H. Bas Shu, Xiao-Ou Amundadottir, Laufey Gross, Myron Tobias, Geoffrey S. Wactawski-Wende, Jean Arslan, Alan A. Duell, Eric J. Fuchs, Charles S. Gallinger, Steven Hartge, Patricia Hoover, Robert N. Holly, Elizabeth A. Jacobs, Eric J. Klein, Alison P. Kooperberg, Charles LaCroix, Andrea Li, Donghui Mandelson, Margaret T. Olson, Sara H. Petersen, Gloria Risch, Harvey A. Yu, Kai Wolpin, Brian M. Zheng, Wei Agalliu, Ilir Albanes, Demetrius Boutron-Ruault, Marie-Christine Bracci, Paige M. Buring, Julie E. Canzian, Federico Chang, Kenneth Chanock, Stephen J. Cotterchio, Michelle Gaziano, J. Michael Giovanucci, Edward L. Goggins, Michael Hallmans, Goeran Hankinson, Susan E. Hoffman-Bolton, Judith A. Hunter, David J. Hutchinson, Amy Jacobs, Kevin B. Jenab, Mazda Khaw, Kay-Tee Kraft, Peter Krogh, Vittorio Kurtz, Robert C. McWilliams, Robert R. Mendelsohn, Julie B. Patel, Alpa V. Rabe, Kari G. Riboli, Elio Tjonneland, Anne Trichopoulos, Dimitrios Virtamo, Jarmo Visvanathan, Kala Elena, Joanne W. Yu, Herbert Zeleniuch-Jacquotte, Anne Stolzenberg-Solomon, Rachael Z. TI Polymorphisms in genes related to one-carbon metabolism are not related to pancreatic cancer in PanScan and PanC4 SO CANCER CAUSES & CONTROL LA English DT Article DE Pancreatic cancer; One-carbon metabolism; Polymorphisms; Biomarkers; Epidemiology ID GENOME-WIDE ASSOCIATION; FOLATE INTAKE; DNA METHYLATION; RISK; METAANALYSIS; DIETARY; HOMOCYSTEINE; CARCINOGENESIS; SUSCEPTIBILITY; PROSTATE AB The evidence of a relation between folate intake and one-carbon metabolism (OCM) with pancreatic cancer (PanCa) is inconsistent. In this study, the association between genes and single-nucleotide polymorphisms (SNPs) related to OCM and PanCa was assessed. Using biochemical knowledge of the OCM pathway, we identified thirty-seven genes and 834 SNPs to examine in association with PanCa. Our study included 1,408 cases and 1,463 controls nested within twelve cohorts (PanScan). The ten SNPs and five genes with lowest p values (< 0.02) were followed up in 2,323 cases and 2,340 controls from eight case-control studies (PanC4) that participated in PanScan2. The correlation of SNPs with metabolite levels was assessed for 649 controls from the European Prospective Investigation into Cancer and Nutrition. When both stages were combined, we observed suggestive associations with PanCa for rs10887710 (MAT1A) (OR 1.13, 95 %CI 1.04-1.23), rs1552462 (SYT9) (OR 1.27, 95 %CI 1.02-1.59), and rs7074891 (CUBN) (OR 1.91, 95 %CI 1.12-3.26). After correcting for multiple comparisons, no significant associations were observed in either the first or second stage. The three suggested SNPs showed no correlations with one-carbon biomarkers. This is the largest genetic study to date to examine the relation between germline variations in OCM-related genes polymorphisms and the risk of PanCa. Suggestive evidence for an association between polymorphisms and PanCa was observed among the cohort-nested studies, but this did not replicate in the case-control studies. Our results do not strongly support the hypothesis that genes related to OCM play a role in pancreatic carcinogenesis. C1 [Leenders, Max; Vineis, Paolo; Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Leenders, Max; Bueno-de-Mesquita, H. Bas] Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, NL-3508 GA Utrecht, Netherlands. [Bhattacharjee, Samsiddhi; Amundadottir, Laufey; Tobias, Geoffrey S.; Hartge, Patricia; Hoover, Robert N.; Yu, Kai; Albanes, Demetrius; Chanock, Stephen J.; Hutchinson, Amy; Jacobs, Kevin B.; Mendelsohn, Julie B.; Stolzenberg-Solomon, Rachael Z.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Vineis, Paolo] HuGeF Fdn, Turin, Italy. [Stevens, Victoria; LaCroix, Andrea; Patel, Alpa V.] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. [Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Dept Med, Vanderbilt Epidemiol Ctr, Div Epidemiol,Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Amundadottir, Laufey; Chanock, Stephen J.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Gross, Myron] Univ Minnesota, Sch Med, Dept Lab Med Pathol, Minneapolis, MN 55455 USA. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Arslan, Alan A.] NYU, Dept Obstet & Gynecol, Sch Med, New York, NY 10016 USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Dept Environm Med, Sch Med, New York, NY 10016 USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Inst Canc, New York, NY USA. [Duell, Eric J.] Catalan Inst Oncol ICO IDIBELL, Barcelona, Spain. [Fuchs, Charles S.; Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fuchs, Charles S.; Wolpin, Brian M.; Giovanucci, Edward L.; Hankinson, Susan E.; Hunter, David J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Fuchs, Charles S.; Wolpin, Brian M.; Buring, Julie E.; Gaziano, J. Michael; Giovanucci, Edward L.; Hankinson, Susan E.; Hunter, David J.] Harvard Univ, Sch Med, Boston, MA USA. [Gallinger, Steven] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Holly, Elizabeth A.; Bracci, Paige M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Jacobs, Eric J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Klein, Alison P.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Klein, Alison P.] Johns Hopkins Med Inst, Dept Epidemiol, Bloomberg Sch Publ Heath, Sol Goldman Pancreat Res Ctr, Baltimore, MD 21205 USA. [Kooperberg, Charles; Mandelson, Margaret T.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Li, Donghui] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. [Mandelson, Margaret T.] Grp Hlth Ctr Hlth Studies, Seattle, WA USA. [Olson, Sara H.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Petersen, Gloria; Rabe, Kari G.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Risch, Harvey A.; Yu, Kai] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Agalliu, Ilir] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Boutron-Ruault, Marie-Christine] Univ Paris 11, Inst Gustave Roussy, INSERM, Villejuif, France. [Buring, Julie E.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Buring, Julie E.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Canzian, Federico] German Canc Res Ctr DFKZ, Div Canc Epidemiol, Heidelberg, Germany. [Chang, Kenneth] Univ Calif Irvine, Irvine Med Ctr, Comprehens Digest Dis Ctr, Orange, CA 92668 USA. [Cotterchio, Michelle] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Cotterchio, Michelle] Canc Care Ontario, Prevent & Canc Control, Toronto, ON, Canada. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Phys Hlth Study, Div Aging, Boston, MA 02115 USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Phys Hlth Study, Div Cardiovasc Med, Boston, MA 02115 USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Phys Hlth Study, Div Prevent Med, Boston, MA 02115 USA. [Gaziano, J. Michael] Vet Affairs Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Giovanucci, Edward L.; Hankinson, Susan E.; Hunter, David J.; Kraft, Peter; Trichopoulos, Dimitrios] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovanucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Goggins, Michael] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Goggins, Michael] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Goggins, Michael] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Hallmans, Goeran] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Hoffman-Bolton, Judith A.; Visvanathan, Kala] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Hutchinson, Amy; Jacobs, Kevin B.] NCI, Core Genotyping Facil, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Jacobs, Kevin B.] Bioinformed Consulting Serv, Gaithersburg, MD USA. [Jenab, Mazda] WHO, IARC, Lyon, France. [Khaw, Kay-Tee] Univ Cambridge, Addenbrookes Hosp, Dept Publ Hlth & Primary Care, Cambridge CB2 2QQ, England. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Krogh, Vittorio] Ist Nazl Tumori, Fdn Ist Recovero & Cura Carattere Sci IRCCS, Nutr Epidemiol Unit, I-20133 Milan, Italy. [Kurtz, Robert C.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [McWilliams, Robert R.] Mayo Clin, Div Med Oncol, Rochester, MN USA. [Tjonneland, Anne] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. [Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Elena, Joanne W.] NCI, Div Canc Prevent & Populat Control, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Leenders, M (reprint author), Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, F02-618,Postal Box 85500, NL-3508 GA Utrecht, Netherlands. EM M.Leenders-6@umcutrecht.nl RI Boutron Ruault, Marie-Christine/G-3705-2013; Gallinger, Steven/E-4575-2013; Boutron, Marie-Christine/K-8168-2013; Albanes, Demetrius/B-9749-2015; Boutron-Ruault, Marie-Christine/H-3936-2014; Krogh, Vittorio/K-2628-2016; Amundadottir, Laufey/L-7656-2016; Tobias, Geoffrey/M-4135-2016; OI Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303; Krogh, Vittorio/0000-0003-0122-8624; Amundadottir, Laufey/0000-0003-1859-8971; Tobias, Geoffrey/0000-0002-2878-8253; Duell, Eric J/0000-0001-5256-0163 FU Intramural Research Program of the National Institutes of Health, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services; World Cancer Research Fund [2008/51] FX This research was supported by the Intramural Research Program of the National Institutes of Health, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services. This study has been funded by the World Cancer Research Fund (Grant No. 2008/51 to PV). For full acknowledgments, please see electronic supplementary material. NR 32 TC 2 Z9 2 U1 0 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 MAR PY 2013 VL 24 IS 3 BP 595 EP 602 DI 10.1007/s10552-012-0138-0 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 090KC UT WOS:000314976900019 PM 23334854 ER PT J AU Hoang, MT Mock, JR Hoang, MP Cohen, JB Le, LQ AF Hoang, M. T. Mock, J. R. Hoang, M. P. Cohen, J. B. Le, L. Q. TI An exophytic, bleeding nodule on the left malar region Sebaceous carcinoma (SC) SO CLINICAL AND EXPERIMENTAL DERMATOLOGY LA English DT Editorial Material ID MUIR-TORRE-SYNDROME; TUMORS C1 [Hoang, M. T.; Mock, J. R.; Cohen, J. B.; Le, L. Q.] Univ Texas SW Med Ctr Dallas, Dept Dermatol, Dallas, TX 75390 USA. [Hoang, M. P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hoang, M. P.] Harvard Univ, Sch Med, Boston, MA USA. RP Le, LQ (reprint author), Univ Texas SW Med Ctr Dallas, Dept Dermatol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM lu.le@utsouthwestern.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0307-6938 J9 CLIN EXP DERMATOL JI Clin. Exp. Dermatol. PD MAR PY 2013 VL 38 IS 2 BP 217 EP 218 DI 10.1111/j.1365-2230.2012.04400.x PG 2 WC Dermatology SC Dermatology GA 090JR UT WOS:000314975800029 PM 22681240 ER PT J AU Atherton, S Holmquist, J AF Atherton, S. Holmquist, J. TI Transitions in Care: Clinical Nurse Specialist Developed Patient Safety Measures for Prevention of Healthcare-Associated Infections SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract C1 [Atherton, S.; Holmquist, J.] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAR-APR PY 2013 VL 27 IS 2 BP E60 EP E60 PG 1 WC Nursing SC Nursing GA 088YK UT WOS:000314873600154 ER PT J AU David, CM Shaffer, B Zellars, R AF David, C. M. Shaffer, B. Zellars, R. TI Clinical Nurse Specialist Led Fall Program: Improving Performance Through Environment Sweeps SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract C1 [David, C. M.; Shaffer, B.; Zellars, R.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAR-APR PY 2013 VL 27 IS 2 BP E12 EP E13 PG 2 WC Nursing SC Nursing GA 088YK UT WOS:000314873600031 ER PT J AU Loudon, T AF Loudon, T. TI Identification of Clinical Deterioration: Clinical Nurse Specialist Implementation of Modified Early Warning System (MEWS) to Support Transition to Higher Level of Care in the Acute Care Setting SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract C1 [Loudon, T.] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAR-APR PY 2013 VL 27 IS 2 BP E61 EP E61 PG 1 WC Nursing SC Nursing GA 088YK UT WOS:000314873600156 ER PT J AU Richardson, J AF Richardson, J. TI The Inpatient to Outpatient Transition: Clinical Nurse Specialist Facilitating Evidence-Based Practice in Primary Care SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract C1 [Richardson, J.] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAR-APR PY 2013 VL 27 IS 2 BP E60 EP E61 PG 2 WC Nursing SC Nursing GA 088YK UT WOS:000314873600155 ER PT J AU Richardson, J Atherton, S Holmquist, J Loudon, T AF Richardson, J. Atherton, S. Holmquist, J. Loudon, T. TI The Value of the Clinical Nurse Specialist: Improving Patient Outcomes Across Transitions in Care SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract C1 [Richardson, J.; Atherton, S.; Holmquist, J.; Loudon, T.] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAR-APR PY 2013 VL 27 IS 2 BP E60 EP E60 PG 1 WC Nursing SC Nursing GA 088YK UT WOS:000314873600153 ER PT J AU Ballen, KK Barker, JN AF Ballen, Karen K. Barker, Juliet N. TI Has umbilical cord blood transplantation for AML become mainstream? SO CURRENT OPINION IN HEMATOLOGY LA English DT Review DE acute myeloid leukemia; allogeneic transplantation; umbilical cord blood ID STEM-CELL TRANSPLANTATION; ANTI-HLA ANTIBODIES; MYELOABLATIVE CONDITIONING REGIMEN; UNRELATED DONORS; ACUTE-LEUKEMIA; BONE-MARROW; HEMATOLOGICAL MALIGNANCIES; HEMATOPOIETIC ENGRAFTMENT; RETROSPECTIVE ANALYSIS; ADULT RECIPIENTS AB Purpose of review We discuss outcomes after umbilical cord blood (UCB) transplantation (UCBT) for patients with acute myeloid leukemia (AML) and compare these outcomes to results after transplantation of other allogeneic graft sources. Recent findings Survival after UCBT has improved considerably over the past 10 years. Multiple retrospective studies using either myeloablative or reduced intensity conditioning have shown disease-free survival after UCBT that is comparable to that of matched related or unrelated donors. Improved unit selection, conditioning, graft manipulation, and supportive care are all emerging strategies to further improve outcomes, although disease status and center expertise remain key components of successful UCBT outcome. Summary UCBT should be considered in all high-risk AML patients in whom allogeneic stem cell transplantation is indicated but who lack a matched related or unrelated donor. UCBT can thereby now be thought of as a 'mainstream' treatment of high-risk AML. C1 [Ballen, Karen K.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Barker, Juliet N.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Ballen, KK (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, 0 Emerson,Suite 118, Boston, MA 02114 USA. EM kballen@partners.org FU NCI NIH HHS [P30 CA008748] NR 39 TC 6 Z9 6 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD MAR PY 2013 VL 20 IS 2 BP 144 EP 149 DI 10.1097/MOH.0b013e32835dd936 PG 6 WC Hematology SC Hematology GA 088OI UT WOS:000314844100010 PM 23314845 ER PT J AU Abel, GA Koreth, J AF Abel, Gregory A. Koreth, John TI Optimal positioning of hematopoietic stem cell transplantation for older patients with myelodysplastic syndromes SO CURRENT OPINION IN HEMATOLOGY LA English DT Review DE allogeneic transplantation; hypomethylating agent; myelodysplasia; quality of life; reduced-intensity conditioning ID ACUTE MYELOID-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; QUALITY-OF-LIFE; PROGNOSTIC SCORING SYSTEM; BONE-MARROW-TRANSPLANTATION; 1ST COMPLETE REMISSION; COMORBIDITY INDEX; UNRELATED DONORS; PHASE-III; MYELOPROLIFERATIVE DISORDERS AB Purpose of review This review examines reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (HSCT) for older patients (age >60 years) with myelodysplastic syndromes (MDS), focusing on how to choose candidates for HSCT as well as data on the comparative effectiveness of RIC HSCT versus other treatment approaches. Recent findings For some older patients with MDS, there may be a survival advantage for RIC HSCT compared with nontransplantation approaches. Health service approaches suggest that optimal treatment choice varies with MDS risk. For those with low/intermediate-1 International Prognostic Scoring System (IPSS) risk, non-HSCT treatments may be preferred, but for intermediate-2/high IPSS patients, RIC HSCT may be better, even after adjusting for quality of life (QoL). Summary The optimal positioning of HSCT for older patients with MDS is evolving. Available data suggest that for older patients with higher risk MDS, if their QoL is affected and they are medically fit, RIC HSCT may lead to more favourable outcomes. Prospective trials in older patients with MDS are necessary to confirm the putative benefit of RIC HSCT. C1 [Abel, Gregory A.; Koreth, John] Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02215 USA. [Abel, Gregory A.] Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, Boston, MA 02215 USA. RP Koreth, J (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Oncol, D1B05,450 Brookline Ave, Boston, MA 02215 USA. EM john_koreth@dfci.harvard.edu FU Leukemia and Lymphoma Society FX We thank Drs. Joseph Antin, Corey Cutler and David Steensma for their helpful comments and suggestions on this manuscript. This work was partially supported by a scholar in clinical research award from the Leukemia and Lymphoma Society. NR 52 TC 7 Z9 8 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1065-6251 EI 1531-7048 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD MAR PY 2013 VL 20 IS 2 BP 150 EP 156 DI 10.1097/MOH.0b013e32835d8e8e PG 7 WC Hematology SC Hematology GA 088OI UT WOS:000314844100011 PM 23298879 ER PT J AU Moatamed, NA Apple, SK Bennett, CJ Aronson, WJ Klisak, I Shirley, BJ Moatamed, F AF Moatamed, Neda A. Apple, Sophia K. Bennett, Carol J. Aronson, William J. Klisak, Ivana Shirley, Bobbi-Jo Moatamed, Farhad TI Exclusion of the uniform tetraploid cells significantly improves specificity of the urine fish assay SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE voided urine; bladder wash; FISH; sensitivity; specificity ID IN-SITU HYBRIDIZATION; SUPERFICIAL BLADDER-CANCER; BTA TRAK ASSAY; VOIDED URINE; UROTHELIAL CARCINOMA; FLOW-CYTOMETRY; FOLLOW-UP; PAPANICOLAOU EXAMINATION; INTERPHASE CYTOGENETICS; DNA-PLOIDY AB The urine fluorescence in situ hybridization (FISH) assay (UroVysion), with the current scoring criteria, has a higher sensitivity than routine cytopathology but a lower specificity. Among 215 urine FISH tests we performed, 45 had associated histopathology and clinical follow up. In this study, a cell with four signals for each probe was classified as a uniform tetraploid cell (UTC); a presumed reparative cell which is currently classified as an abnormal cell in the FDA approved assay. By using the existing criteria, the tests were scored as positive or negative before and after exclusion of the UTCs. Before the exclusion, 24 positive, 13 negative, seven false positive, and one false negative result were obtained with 96% sensitivity and 65% specificity. After the exclusion, the results changed to 22 positive, 19 negative, one false positive, and three false negatives resulting in a 88% sensitivity of 88% and a 95% specificity; a significant improvement in the specificity. We conclude that exclusion of the UTCs as abnormal cells would result in a more solid performance of the FISH assay. Diagn. Cytopathol. 2013. (c) 2011 Wiley Periodicals, Inc. C1 [Moatamed, Neda A.; Apple, Sophia K.; Moatamed, Farhad] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Klisak, Ivana; Shirley, Bobbi-Jo; Moatamed, Farhad] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Bennett, Carol J.] VA Greater Los Angeles Healthcare Syst, Dept Surg, Urol Sect, Los Angeles, CA USA. RP Moatamed, NA (reprint author), Dept Pathol & Lab Med, 10833 Le Conte Ave,BOX 951732,1P-241 CHS, Los Angeles, CA 90095 USA. EM nmoatamed@mednet.ucla.edu FU Department of Veterans Affairs, as part of the Laboratory Quality Assurance program FX Contract grant sponsor: Department of Veterans Affairs, as part of the Laboratory Quality Assurance program. NR 49 TC 4 Z9 4 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD MAR PY 2013 VL 41 IS 3 BP 218 EP 225 DI 10.1002/dc.21831 PG 8 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 092EH UT WOS:000315101500006 PM 21987521 ER PT J AU Moussa, I Hermann, A Messenger, JC Dehmer, GJ Weaver, WD Rumsfeld, JS Masoudi, FA AF Moussa, Issam Hermann, Anthony Messenger, John C. Dehmer, Gregory J. Weaver, W. Douglas Rumsfeld, John S. Masoudi, Frederick A. TI The NCDR CathPCI Registry: a US national perspective on care and outcomes for percutaneous coronary intervention SO HEART LA English DT Article ID CARDIOVASCULAR DATA REGISTRY; MORTALITY RISK PREDICTION; STRATEGIES AB Aims: The NCDR CathPCI Registry collects detailed clinical, process-of-care and outcomes data for patients undergoing coronary angiography and percutaneous coronary intervention (PCI) in the USA. The registry contributes to quality of care by providing data feedback on a wide range of performance metrics to participating centres and by facilitating local and national quality improvement efforts. Interventions: No treatments are mandated, participating centres receive routine quality-of-care and outcomes performance feedback reports and access to a quality dashboard for personalized performance reports. Population: Patients undergoing cardiac catheterization and PCI are retrospectively identified. No informed consent is required, as data are anonymised. From inception in 1998, more than 12 million records have been submitted from 1577 participating US centres. Baseline data: Approximately 250 fields encompassing patient demographics, medical history and risk factors, hospital presentation, initial cardiac status, procedural details, medications, laboratory values, and in-hospital outcomes. Linkages with outside sources of data have permitted longitudinal outcomes assessment in some cases. Centre personnel enter the data into the registry, in some cases facilitated by software vendors. There are non-financial incentives for centre participation. Data completeness is noteworthy with most fields missing at rates less than 5%. A comprehensive data quality program is employed to enhance data validity. Endpoints: Main outcome measures include quality process metrics and in-hospital patient outcomes. Data are available for research by application to: http://www.ncdr.com C1 [Moussa, Issam] Mayo Clin, Div Cardiol, Jacksonville, FL 32224 USA. [Hermann, Anthony] Amer Coll Cardiol Fdn, Washington, DC USA. [Messenger, John C.; Masoudi, Frederick A.] Univ Colorado, Div Cardiol, Cardiac & Vasc Ctr, Aurora, CO 80045 USA. [Dehmer, Gregory J.] Scott & White Healthcare, Div Cardiol, Coll Med, Texas A&M Hlth Sci Ctr, Temple, TX USA. [Weaver, W. Douglas] Henry Ford Hosp, Div Cardiol, Detroit, MI 48202 USA. [Rumsfeld, John S.] Denver VA Med Ctr, Cardiol Sect, Denver, CO USA. RP Masoudi, FA (reprint author), Univ Colorado, Div Cardiol, Anschutz Med Campus,Box B132,12401 17th Ave, Aurora, CO 80045 USA. EM fred.masoudi@ucdenver.edu NR 12 TC 25 Z9 25 U1 0 U2 3 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 MAR PY 2013 VL 99 IS 5 BP 297 EP 303 DI 10.1136/heartjnl-2012-303379 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 091EX UT WOS:000315033300004 PM 23322530 ER PT J AU Schwacke, JH Spainhour, JCG Ierardi, JL Chaves, JM Arthur, JM Janech, MG Velez, JCQ AF Schwacke, John H. Spainhour, John Christian G. Ierardi, Jessalyn L. Chaves, Jose M. Arthur, John M. Janech, Michael G. Velez, Juan Carlos Q. TI Network Modeling Reveals Steps in Angiotensin Peptide Processing SO HYPERTENSION LA English DT Article DE mass spectrometry; proteomics; renin-angiotensin system; systems biology ID CONVERTING ENZYME-INHIBITION; AMINOPEPTIDASE-A; DIABETIC-NEPHROPATHY; BAYESIAN NETWORKS; PARTIAL ESCAPE; RAT; RECEPTOR; SYSTEM; KIDNEY; ACE AB New insights into the intrarenal renin-angiotensin (Ang) system have modified our traditional view of the system. However, many finer details of this network of peptides and associated peptidases remain unclear. We hypothesized that a computational systems biology approach, applied to peptidomic data, could help to unravel the network of enzymatic conversions. We built and refined a Bayesian network model and a dynamic systems model starting from a skeleton created with established elements of the renin-Ang system and further developed it with archived matrix-assisted laser desorption ionization-time of flight mass spectra from experiments conducted in mouse podocytes exposed to exogenous Ang substrates. The model-building process suggested previously unrecognized steps, 3 of which were confirmed in vitro, including the conversion of Ang(2-10) to Ang(2-7) by neprilysin, Ang(1-9) to Ang(2-9), and Ang(1-7) to Ang(2-7) by aminopeptidase A. These data suggest a wider role of neprilysin and aminopeptidase A in glomerular formation of bioactive Ang peptides and shunting their formation. Other steps were also suggested by the model, and supporting evidence for those steps was evaluated using model-comparison methods. Our results demonstrate that systems biology methods applied to peptidomic data are effective in identifying novel steps in the Ang peptide processing network, and these findings improve our understanding of the glomerular renin-Ang system. (Hypertension. 2013;61:690-700.). circle Online Data Supplement C1 [Schwacke, John H.; Spainhour, John Christian G.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Ierardi, Jessalyn L.; Chaves, Jose M.; Arthur, John M.; Janech, Michael G.; Velez, Juan Carlos Q.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Arthur, John M.; Janech, Michael G.; Velez, Juan Carlos Q.] Ralph H Johnson Vet Affairs Med Ctr, Med Serv, Charleston, SC USA. [Arthur, John M.; Janech, Michael G.; Velez, Juan Carlos Q.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC USA. RP Velez, JCQ (reprint author), Med Univ S Carolina, Div Nephrol, Clin Sci Bldg,829 96 Jonathan Lucas St, Charleston, SC 29425 USA. EM velezj@musc.edu RI Velez, Juan Carlos/N-3782-2016; OI Janech, Michael/0000-0002-3202-4811 FU National Institute of General Medicine [5T32GM74934-8]; Department of Veterans' Affairs [CDA-2]; Nephcure Foundation; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) [DK080944-04]; Dialysis Clinics Incorporated; NIDDK of the NIH [1R01DK080234] FX J.C.G. Spainhour was supported under a training grant from the National Institute of General Medicine (5T32GM74934-8). M. G. Janech was supported by Career Development Awards (CDA) through the Department of Veterans' Affairs (CDA-2) and the Nephcure Foundation. J.C.Q. Velez is supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) (DK080944-04) and Dialysis Clinics Incorporated. J.H. Schwacke was supported, in part, by a grant from NIDDK of the NIH (1R01DK080234). NR 69 TC 12 Z9 12 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAR PY 2013 VL 61 IS 3 BP 690 EP + DI 10.1161/HYPERTENSIONAHA.111.00318 PG 18 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 089DC UT WOS:000314888600023 PM 23283355 ER PT J AU Gaur, AH Bundy, DG Gao, C Werner, EJ Billett, AL Hord, JD Siegel, JD Dickens, D Winkle, C Miller, MR AF Gaur, Aditya H. Bundy, David G. Gao, Cuilan Werner, Eric J. Billett, Amy L. Hord, Jeff D. Siegel, Jane D. Dickens, David Winkle, Cindi Miller, Marlene R. CA Children's Hosp Assoc Hematology O TI Surveillance of Hospital-Acquired Central Line-Associated Bloodstream Infections in Pediatric Hematology-Oncology Patients: Lessons Learned, Challenges Ahead SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID INTENSIVE-CARE-UNIT; CHILDREN; CANCER AB Across 36 US pediatric oncology centers, 576 central line-associated bloodstream infections (CLABSIs) were reported over a 21-month period. Most infections occurred in those with leukemia and/or profound neutropenia. The contribution of viridans streptococci infections was striking. Study findings depict the contemporary epidemiology of CLABSIs in hospitalized pediatric cancer patients. Infect Control Hosp Epidemiol 2013;34(3):316-320 C1 [Gaur, Aditya H.; Gao, Cuilan] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Bundy, David G.] Med Univ S Carolina, Charleston, SC 29425 USA. [Werner, Eric J.] Hosp Kings Daughters, Norfolk, VA USA. [Billett, Amy L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Billett, Amy L.] Boston Childrens Hosp, Boston, MA USA. [Hord, Jeff D.] Akron Childrens Hosp, Akron, OH USA. [Siegel, Jane D.] Childrens Med Ctr, Dallas, TX 75235 USA. [Dickens, David] Helen DeVos Childrens Hosp, Grand Rapids, MI USA. [Winkle, Cindi] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Miller, Marlene R.] Childrens Hosp Assoc, Alexandria, VA USA. RP Gaur, AH (reprint author), St Jude Childrens Res Hosp, Dept Infect Dis, MS 600,262 Danny Thomas Pl, Memphis, TN 38105 USA. EM aditya.gaur@stjude.org OI Dickens, David/0000-0001-8821-6022 FU Agency for Healthcare Research and Quality [R18HS019590]; American Lebanese Syrian Associated Charities FX This work was supported by the Agency for Healthcare Research and Quality (R18HS019590) and the American Lebanese Syrian Associated Charities. The funding sources had no role or input into the design or conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript. NR 20 TC 10 Z9 10 U1 0 U2 9 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD MAR PY 2013 VL 34 IS 3 BP 316 EP 320 DI 10.1086/669513 PG 5 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 088CG UT WOS:000314810800016 PM 23388370 ER PT J AU Semaan, A Mert, I Munkarah, AR Bandyopadhyay, S Mahdi, HS Winer, IS Nucci, MR Hussein, Y Quershi, F Hayek, K Tabassum, F Alosh, B Schultz, DS Cote, ML Van de Vijver, KK Morris, RT Oliva, E Ali-Fehmi, R AF Semaan, Assaad Mert, Ismail Munkarah, Adnan R. Bandyopadhyay, Sudeshna Mahdi, Haider S. Winer, Ira S. Nucci, Marisa R. Hussein, Yaser Quershi, Faisal Hayek, Kinda Tabassum, Farah Alosh, Baraa Schultz, Daniel S. Cote, Michele L. Van de Vijver, Koen K. Morris, Robert T. Oliva, Esther Ali-Fehmi, Rouba TI Clinical and Pathologic Characteristics of Serous Carcinoma Confined to the Endometrium: A Multi-institutional Study SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE Serous endometrial cancer; Endometrial polyp; No myometrial invasion ID PAPILLARY; CANCERS; SPREAD; POLYPS AB The objective of this study was to analyze the clinical and pathologic factors in patients with uterine serous carcinoma confined to the endometrium. A total of 236 uterine serous carcinoma patients from the pathology databases of 4 large academic institutions were included in the study. Clinical and pathologic variables were analyzed, including patient demographics, tumor size (<= 2 vs. >2cm), myometrial invasion, lymphovascular invasion, lymph node status, tumor location (endometrium vs. polyp), cervical involvement, lower uterine segment involvement, FIGO stage, pelvic washings, recurrence, overall survival, and progression-free survival. Of 236 patients, 55 (23%) had tumors limited to the endometrium. Forty-four patients (80%) had Stage IA tumors. The tumor was confined to a polyp in 17 (30.9%) patients. Twenty patients (36.4%) had tumor sizes >2cm and 12 (21.8%) exhibited lymphovascular invasion. Only 3 patients (5.4 %) had cervical stromal involvement. Thirty-three (66%) patients underwent pelvic and para-aortic lymphadenectomy with 2 positive para-aortic lymph nodes identified. Seven (12.7%) patients had positive washings, whereas 8 patients (14.5 %) had disease recurrence. At a median follow-up of 46 months, there was no difference in overall survival (P = 0.216) or progression-free survival (P = 0.063) between patients with tumors confined to a polyp, patients with tumors confined to the endometrium, and patients with tumors present in both polyp and the endometrium. Uterine serous carcinoma with only endometrial involvement, even when confined to a polyp, can be associated with poor prognosis, further stressing the importance of complete surgical staging and adjuvant treatment in this setting. C1 [Semaan, Assaad; Mert, Ismail; Winer, Ira S.; Morris, Robert T.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Munkarah, Adnan R.] Henry Ford Hlth Syst, Dept Obstet & Gynecol, Detroit, MI USA. [Bandyopadhyay, Sudeshna; Hussein, Yaser; Quershi, Faisal; Hayek, Kinda; Tabassum, Farah; Alosh, Baraa; Ali-Fehmi, Rouba] Wayne State Univ, Dept Pathol, Detroit, MI 48201 USA. [Mahdi, Haider S.] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Nucci, Marisa R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Schultz, Daniel S.] Henry Ford Hlth Syst, Dept Pathol, Detroit, MI USA. [Cote, Michele L.] Wayne State Univ, Dept Oncol, Detroit, MI 48201 USA. [Van de Vijver, Koen K.; Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Ali-Fehmi, R (reprint author), Wayne State Univ, Dept Pathol, 3990 John R, Detroit, MI 48201 USA. EM rali@med.wayne.edu NR 18 TC 9 Z9 10 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD MAR PY 2013 VL 32 IS 2 BP 181 EP 187 DI 10.1097/PGP.0b013e318273fc55 PG 7 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 089LZ UT WOS:000314913400009 PM 23370657 ER PT J AU Young, RH AF Young, Robert H. TI Robert E. Scully, MD Obituary SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Biographical-Item C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Young, RH (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM rhyoung@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD MAR PY 2013 VL 32 IS 2 BP 242 EP 245 DI 10.1097/PGP.0b013e3182830a1c PG 4 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 089LZ UT WOS:000314913400019 PM 23534067 ER PT J AU Roth, LM Young, RH AF Roth, Lawrence M. Young, Robert H. TI Aleksander Talerman, MD, Ph.D., FRC Path. Obituary SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Biographical-Item C1 [Roth, Lawrence M.; Young, Robert H.] Indiana Univ Sch Med, Dept Pathol, Indianapolis, IN 46202 USA. [Roth, Lawrence M.; Young, Robert H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA USA. RP Roth, LM (reprint author), Indiana Univ Sch Med, Dept Pathol, Van Nuys Med Sci Bldg 128,635 Barnhill Dr, Indianapolis, IN 46202 USA. EM lroth@iupui.edu NR 1 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD MAR PY 2013 VL 32 IS 2 BP 246 EP 247 DI 10.1097/PGP.0b013e3182830a30 PG 2 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 089LZ UT WOS:000314913400020 PM 23534068 ER PT J AU Lu, XM Tompkins, RG Fischman, AJ AF Lu, X. -M. Tompkins, R. G. Fischman, A. J. TI Nitric oxide activates intradomain disulfide bond formation in the kinase loop of Akt1/PKB alpha after burn injury SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE Akt1/protein kinase B alpha; S-nitrosylation; disulfide bond; MS/MS ID INDUCED INSULIN-RESISTANCE; S-NITROSYLATED PROTEINS; CAPLC-Q-TOFMICRO; SKELETAL-MUSCLE; CRYSTAL-STRUCTURE; TARGETED DISRUPTION; MASS-SPECTROMETRY; CRITICALLY-ILL; THERMAL-INJURY; AKT AB Severe burn injury is an acute inflammatory state with massive alterations in gene expression and levels of growth factors, cytokines and free radicals. During the catabolic processes, changes in insulin sensitivity and skeletal muscle wasting (unintended loss of 5-15% of lean body mass) are observed clinically. Here, we reveal a novel molecular mechanism of Akt1/protein kinase B alpha (Akt1/PKB alpha) regulated via cross-talking between dephosphorylation of Thr(308) and S-nitrosylation of CyS296 post severe burn injury, which were characterized using nano-LC interfaced with tandem quadrupole time-of-fight mass spectrometry (Q-TOF)(micro) tandem mass spectrometry in both in vitro and in vivo studies. For the in vitro studies, Akt1/PKB alpha was S-nitrosylated with S-nitrosoglutathione and derivatized by three methods. The derivatives were isolated by SDS-PAGE, trypsinized and analyzed by the tandem MS. For the in vivo studies, Akt1/PKB alpha in muscle lysates from burned rats was immuno-precipitated, derivatized with HPDP-Biotin and analyzed as above. The studies demonstrated that the NO free radical reacts with the free thiol of Cys(296) to produce a Cys(296)-SNO intermediate which accelerates interaction with Cys(310) to form Cys(296)-Cys(310) in the kinase loop. MS/MS sequence analysis indicated that the dipeptide, linked via Cys(296)-Cys(310), underwent dephosphorylation at Thr(308). These effects were not observed in lysates from sham animals. As a result of this dual effect of burn injury, the loose conformation that is slightly stabilized by the Lys(297)-Thr(308) salt bridge may be replaced by a more rigid structure which may block substrate access. Together with the findings of our previous report concerning mild IRS-1 integrity changes post burn, it is reasonable to conclude that the impaired Akt1/PKB alpha has a major impact on FOXO3 subcellular distribution and activities. C1 [Lu, X. -M.; Tompkins, R. G.] Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. [Lu, X. -M.; Tompkins, R. G.; Fischman, A. J.] Harvard Univ, Sch Med, Boston, MA USA. [Lu, X. -M.; Tompkins, R. G.; Fischman, A. J.] Shriners Hosp Children, Boston, MA 02114 USA. RP Fischman, AJ (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM aajjff@gmail.com FU National Institutes of Health [NIGMS P50 GM21000]; Shriners Hospital for Children FX This study was supported in part by grants from the National Institutes of Health (NIGMS P50 GM21000) and Shriners Hospital for Children. NR 48 TC 5 Z9 5 U1 0 U2 4 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD MAR PY 2013 VL 31 IS 3 BP 740 EP 750 DI 10.3892/ijmm.2013.1241 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 089IZ UT WOS:000314905500031 PM 23314241 ER PT J AU Likhacheva, A Pinnix, CC Parikh, NR Allen, PK McAleer, MF Chiu, MS Sulman, EP Mahajan, A Guha-Thakurta, N Prabhu, SS Cahill, DP Luo, D Shiu, AS Brown, PD Chang, EL AF Likhacheva, Anna Pinnix, Chelsea C. Parikh, Neil R. Allen, Pamela K. McAleer, Mary F. Chiu, Max S. Sulman, Erik P. Mahajan, Anita Guha-Thakurta, Nandita Prabhu, Sujit S. Cahill, Daniel P. Luo, Dershan Shiu, Almon S. Brown, Paul D. Chang, Eric L. TI Predictors of Survival in Contemporary Practice After Initial Radiosurgery for Brain Metastases SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID GAMMA-KNIFE SURGERY; STEREOTACTIC RADIOSURGERY; RADIATION-THERAPY; RANDOMIZED-TRIAL; SINGLE METASTASES; CLINICAL ARTICLE; RADIOTHERAPY; NUMBER; TUMORS AB Purpose: The number of brain metastases (BM) is a major consideration in determining patient eligibility for stereotactic radiosurgery (SRS), but the evidence for this popular practice is equivocal. The purpose of this study was to determine whether, following multivariate adjustment, the number and volume of BM held prognostic significance in a cohort of patients initially treated with SRS alone. Methods and Materials: A total of 251 patients with primary malignancies, including non-small cell lung cancer (34%), melanoma (30%), and breast carcinoma (16%), underwent SRS for initial treatment of BM. SRS was used as the sole management (62% of patients) or was combined with salvage treatment with SRS (22%), whole-brain radiation therapy (WBRT; 13%), or resection (3%). Median follow-up time was 9.4 months. Survival was determined using the Kaplan-Meier method. Cox regression was used to assess the effects of patient factors on distant brain failure (DBF), local control (LC), and overall survival (OS). Results: LC at 1 year was 94.6%, and median time to DBF was 10 months. Median OS was 11.1 months. On multivariate analysis, statistically significant predictors of OS were presence of extracranial disease (hazard ratio [HR], 4.2, P<.001), total tumor volume greater than 2 cm(3) (HR, 1.98; P<.001), age >= 60 years (HR, 1.67; P=.002), and diagnosis-specific graded prognostic assessment (HR, 0.71; P<.001). The presence of extracranial disease was a statistically significant predictor of DBF (HR, 2.15), and tumor volume was predictive of LC (HR, 4.56 for total volume >2 cm(3)). The number of BM was not predictive of DBF, LC, or OS. Conclusions: The number of BM is not a strong predictor for clinical outcomes following initial SRS for newly diagnosed BM. Other factors including total treatment volume and systemic disease status are better determinants of outcome and may facilitate appropriate use of SRS or WBRT. (C) 2013 Elsevier Inc. C1 [Likhacheva, Anna; Pinnix, Chelsea C.; Allen, Pamela K.; McAleer, Mary F.; Sulman, Erik P.; Mahajan, Anita; Brown, Paul D.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Parikh, Neil R.] Baylor Coll Med, Houston, TX 77030 USA. [Chiu, Max S.] Univ Nebraska, Lincoln, NE USA. [Guha-Thakurta, Nandita] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX 77030 USA. [Prabhu, Sujit S.] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA. [Cahill, Daniel P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Luo, Dershan; Shiu, Almon S.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. [Chang, Eric L.] Univ So Calif, Dept Radiat Oncol, Los Angeles, CA USA. RP Chang, EL (reprint author), USC Norris Canc Hosp, Dept Radiat Oncol, USC Keck Sch Med, 1441 Eastlake Ave,NOR G-356, Los Angeles, CA 90033 USA. EM eric.chang@med.usc.edu OI Cahill, Daniel/0000-0003-2552-6546 FU NCI NIH HHS [P30 CA016672] NR 27 TC 29 Z9 30 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 1 PY 2013 VL 85 IS 3 BP 656 EP 661 DI 10.1016/j.ijrobp.2012.05.047 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 086MA UT WOS:000314687000026 PM 22898384 ER PT J AU Adakun, SA Siedner, MJ Muzoora, C Haberer, JE Tsai, AC Hunt, PW Martin, JN Bangsberg, DR AF Adakun, Susan A. Siedner, Mark J. Muzoora, Conrad Haberer, Jessica E. Tsai, Alexander C. Hunt, Peter W. Martin, Jeff N. Bangsberg, David R. TI Higher Baseline CD4 Cell Count Predicts Treatment Interruptions and Persistent Viremia in Patients Initiating ARVs in Rural Uganda SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 7th Conference of the International-Association-of-Physicians-in-AIDS-Care CY JUN, 2012 CL Miami, FL SP Int Assoc Phys AIDS Care DE adherence; test and treat; Uganda; HIV/AIDS; adherence monitoring; MEMS ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-INFECTED ADULTS; NORTH-AMERICA; ADHERENCE; IMPACT; AIDS; PROPHYLAXIS; PREVENTION; HOUSEHOLDS; AFRICA AB We examined the association between CD4 cell count and adherence in a cohort of Ugandans initiating antiretrovirals (ARVs). Outcomes were (a) adherence <90%; (b) any treatment interruptions. >72 hours; (c) number of treatment interruptions; and (d) HIV-RNA >400 copies/mL. We fit regression models to estimate associations with our exposure of interest, baseline CD4 cell count >= 250 cells/mu L (n = 60) vs <250 cells/mu L (n = 413). CD4 cell count >250 cells/mu L was independently associated with increased odds and number of treatment interruptions and increased odds of persistent viremia. Interventions to support adherence in patients with higher CD4 cell counts should be considered as drug availability to this population increases. C1 [Adakun, Susan A.; Muzoora, Conrad; Bangsberg, David R.] Mbarara Univ Sci & Technol, Dept Med, Mbarara, Uganda. [Siedner, Mark J.; Bangsberg, David R.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Ctr Global Hlth, Boston, MA 02114 USA. [Haberer, Jessica E.] Massachusetts Gen Hosp, Dept Med, Ctr Global Hlth, Div Internal Med, Boston, MA 02114 USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, Dept Psychiat, Div Global Psychiat, Ctr Global Hlth, Boston, MA 02114 USA. [Hunt, Peter W.] Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA USA. [Martin, Jeff N.] Univ Calif San Francisco, Div Clin Epidemiol, Dept Epidemiol & Biostat, San Francisco, CA USA. [Bangsberg, David R.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA USA. RP Adakun, SA (reprint author), Mbarara Univ Sci & Technol, POB 1410, Mbarara, Uganda. EM adakunsusan@yahoo.com OI Tsai, Alexander/0000-0001-6397-7917 FU FIC NIH HHS [R24 TW007988]; NIAID NIH HHS [P30 AI27763, T32 AI007433, P30 AI027763]; NIMH NIH HHS [K23 MH087228, K23 MH096620, K24 MH087227, K24 MH87227, R01 MH054907, R01MH54907] NR 31 TC 19 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAR 1 PY 2013 VL 62 IS 3 BP 317 EP 321 DI 10.1097/QAI.0b013e3182800daf PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 088WT UT WOS:000314869300020 PM 23242160 ER PT J AU Hernandez, R Prohaska, TR Wang, PC Sarkisian, CA AF Hernandez, Rosalba Prohaska, Thomas R. Wang, Pin-Chieh Sarkisian, Catherine A. TI The Longitudinal Relationship Between Depression and Walking Behavior in Older Latinos: The "(sic)Caminemos!" Study SO JOURNAL OF AGING AND HEALTH LA English DT Article DE older adults; Hispanics; Latinos; depressive symptomatology; physical activity; longitudinal analyses ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; PHYSICAL-ACTIVITY; MEXICAN-AMERICANS; SOCIAL SUPPORT; DOSE-RESPONSE; SELF-EFFICACY; ADULTS; EXERCISE; PARTICIPATION AB Objectives: This study sought to evaluate the relationship between baseline depression and prospective engagement in walking and exercise behavior after enrollment in an exercise intervention. Methods: The study used baseline, 1-month, 12-month, and 24-month in-person interview and pedometer data collected from Latinos aged > 60 years participating in an exercise intervention (AiCaminemos!) at 27 senior centers (n = 572). Results: After joining an exercise intervention, and when using continuous pedometer data and scores from the Yale Physical Activity Survey (YPAS) as the outcomes of interest, older adults with baseline depression exhibited comparable levels of physical activity across time when compared to their nondepressed counterparts. Significant difference in physical activity levels between the depressed and nondepressed subgroups no longer existed within one month of initiating the exercise intervention. Discussion: Among sedentary older Latino adults, having depression may not delay exercise initiation nor does it appear to prevent achievement or maintenance of an exercise program. C1 [Hernandez, Rosalba] NW Feinberg Sch Med, Dept Prevent Med, Chicago, IL USA. [Hernandez, Rosalba; Prohaska, Thomas R.] Univ Illinois, Sch Publ Hlth, Chicago, IL USA. [Prohaska, Thomas R.] George Mason Univ, Coll Hlth & Human Serv, Fairfax, VA 22030 USA. [Wang, Pin-Chieh; Sarkisian, Catherine A.] Vet Adm Greater Los Angeles Healthcare Syst, Geriatr Res Educ Clin Ctr, Los Angeles, CA USA. [Wang, Pin-Chieh; Sarkisian, Catherine A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Geriatr, Los Angeles, CA 90095 USA. RP Hernandez, R (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, 680 N Lake Shore Dr,Suite 1400, Chicago, IL 60611 USA. EM rosalba.hernandez@northwestern.edu FU NHLBI NIH HHS [5T32 HL069771-10, T32 HL069771]; NIA NIH HHS [R01 AG024460, R01 AG024460-05, P30 AG028748, P30AG028748] NR 57 TC 4 Z9 4 U1 3 U2 17 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0898-2643 J9 J AGING HEALTH JI J. Aging Health PD MAR PY 2013 VL 25 IS 2 BP 319 EP 341 DI 10.1177/0898264312468488 PG 23 WC Gerontology; Health Policy & Services SC Geriatrics & Gerontology; Health Care Sciences & Services GA 087NV UT WOS:000314769500006 PM 23264440 ER PT J AU Rosenfeld, A Christensen, V Daya, M AF Rosenfeld, Anne Christensen, Vivian Daya, Mohamud TI Long Enough to Act? Symptom and Behavior Patterns Prior to Out-of-Hospital Sudden Cardiac Death SO JOURNAL OF CARDIOVASCULAR NURSING LA English DT Article DE myocardial infarction; narrative analysis; out-of-hospital death; sudden cardiac death; symptoms ID ACUTE MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROMES; TREATMENT-SEEKING DELAY; HEART-DISEASE; UNITED-STATES; FAMILY REPORTS; REDUCE DELAY; WOMEN; ARREST; CARE AB Background: Sudden cardiac death is a major cause of death in the United States. Most cases occur outside the hospital, yet little is known about the symptoms and actions of individuals who die before reaching the hospital. Objective: The purpose of this study was to describe the symptoms, symptom management, and care-seeking patterns in sudden cardiac death victims. Methods: This cross-sectional study used qualitative and quantitative data collection methods to obtain descriptions of symptoms and treatment-seeking delay from family members and bystanders (respondents) in 140 cases of sudden cardiac death due to presumed myocardial infarction. Decedents were identified from death certificate data from the state of Oregon in the United States. Respondents completed a survey of demographics and myocardial infarction symptoms and an in-depth interview. Narrative analysis was used to analyze qualitative data. Results: Three behavior patterns or trajectory types were developed focusing on key characteristics of the symptom patterns, the meanings attributed to those symptoms, the actions taken by the decedents and their family members or bystanders, and the time course of events. Each case was categorized as 1 trajectory type. The trajectory types are Normal Day (n = 49), Something Not Right (n = 62), and Thought It Was Something Else (n = 29). The key distinction across the trajectory types is the perception and interpretation of symptoms and the resulting actions between symptom perception and death. Conclusions: This study is 1 of the first to describe what victims of sudden cardiac death are doing and thinking during the period between symptom onset and collapse. The trajectory types identified in this study suggest that misinterpretation of symptoms (the Something Not Right and Thought It Was Something Else groups) is common among victims and bystanders. C1 [Rosenfeld, Anne] Oregon Hlth & Sci Univ, Sch Nursing, Portland, OR 97201 USA. [Christensen, Vivian] Portland VA Med Ctr, Evidence Based Synth Program, Coordinating Ctr, Portland, OR USA. [Daya, Mohamud] Oregon Hlth & Sci Univ, Dept Emergency Med, Portland, OR 97201 USA. RP Rosenfeld, A (reprint author), Univ Arizona, Coll Nursing, POB 210203, Tucson, AZ 85721 USA. EM arosenfeld@nursing.arizona.edu FU American Heart Association Pacific Mountain Affiliate [0450040Z] FX This study was funded by American Heart Association Pacific Mountain Affiliate Grant in Aid 0450040Z. NR 45 TC 0 Z9 0 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0889-4655 J9 J CARDIOVASC NURS JI J. Cardiovasc. Nurs. PD MAR-APR PY 2013 VL 28 IS 2 BP 166 EP 175 DI 10.1097/JCN.0b013e3182452410 PG 10 WC Cardiac & Cardiovascular Systems; Nursing SC Cardiovascular System & Cardiology; Nursing GA 091AR UT WOS:000315021600015 PM 22343214 ER PT J AU Ananthakrishnan, AN McGinley, EL AF Ananthakrishnan, Ashwin N. McGinley, Emily L. TI Infection-related hospitalizations are associated with increased mortality in patients with inflammatory bowel diseases SO JOURNAL OF CROHNS & COLITIS LA English DT Article DE Infections; Immunosuppression; Crohn's disease; Ulcerative colitis ID CLOSTRIDIUM-DIFFICILE INFECTION; SAFETY PROFILE; INFLIXIMAB; DIARRHEA; OUTCOMES; IMPACT; RISKS AB Introduction: Serious infections are an important side effect of immunosuppressive therapy used to treat Crohn's disease (CD) and ulcerative colitis (UC). There have been no nationally representative studies examining the spectrum of infection related hospitalizations in patients with IBD. Methods: Our study consisted of all adult CD and UC related hospitalizations from the Nationwide Inpatient Sample 2007, a national hospitalization database in the United States. We then identified all infection-related hospitalizations through codes for either the specific infections or disease processes (sepsis, pneumonia, etc.). Predictors of infections as well as the excess morbidity associated with infections were determined using multivariate regression models. Results: There were an estimated 67,221 hospitalizations related to infections in IBD patients, comprising 27.5% of all IBD hospitalizations. On multivariate analysis, infections were independently associated with age, co-morbidity, malnutrition, TPN, and bowel surgery. Infection-related hospitalizations had a four-fold greater mortality (OR 4.4, 95% CI 3.7-5.2). However, this varied by type of infection with the strongest effect seen for sepsis (OR 15.3, 95% CI 12.4-18.6), pneumonia (OR 3.6, 95% CI 2.9-4.5) and C. difficile (OR 3.2, 95% CI 2.6-4.0), and weaker effects for urinary infections (OR 1.4, 95%Cl 1.1-1.7). Infections were also associated with an estimated 2.3 days excess hospital stay (95% CI 2.2-2.5) and $12,482 in hospitalization charges. Conclusion: Infections account for significant morbidity and mortality in patients with IBD and disproportionately impact older IBD patients with greater co-morbidity. Pneumonia, sepsis and C difficile infection are associated with the greatest excess mortality risk. (C) 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved. C1 [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.] Harvard Univ, Sch Med, Boston, MA USA. [McGinley, Emily L.] Med Coll Wisconsin, Ctr Patient Care & Outcomes & Res, Milwaukee, WI 53226 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@partners.org FU American Gastroenterological Association FX Ananthakrishnan is supported in part by a grant from the American Gastroenterological Association. NR 23 TC 30 Z9 31 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1873-9946 J9 J CROHNS COLITIS JI J. Crohns Colitis PD MAR 1 PY 2013 VL 7 IS 2 BP 107 EP 112 DI 10.1016/j.crohns.2012.02.015 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 089HK UT WOS:000314901400002 PM 22440891 ER PT J AU Schuster, MG Meibohm, A Lloyd, L Strom, B AF Schuster, Mindy G. Meibohm, Anne Lloyd, Lisa Strom, Brian TI Risk factors and outcomes of Candida krusei bloodstream infection: A matched, case-control study SO JOURNAL OF INFECTION LA English DT Article DE Candida krusei; Candidemia; Risk factors; Case-control ID INTENSIVE-CARE-UNIT; ANTIMICROBIAL SURVEILLANCE PROGRAM; BONE-MARROW-TRANSPLANTATION; IN-VITRO SUSCEPTIBILITIES; IMMUNOCOMPROMISED PATIENTS; ANTIFUNGAL SUSCEPTIBILITY; ATTRIBUTABLE MORTALITY; NOSOCOMIAL CANDIDEMIA; CHANGING EPIDEMIOLOGY; SPECIES DISTRIBUTION AB Objectives: To investigate the risk factors and outcomes associated with Candida krusei bloodstream. Methods: We performed a case control study of patients with C. krusei bloodstream infection at the University of Pennsylvania from 1982 to 2010. Controls were without candidemia, and matched to cases on duration of hospitalization and underlying disease. Results: We enrolled 34 cases and 114 matched controls. Most subjects (62%) had hematologic malignancies. In the multivariate model, including a priori the duration of fluconazole use (OR 1.06; 95% CI 1.00, 1.11) and days of neutropenia (OR 1.01; 95% CI 0.98, 1.13), risk factors associated with C. krusei bloodstream infection were splenectomy (OR 11.66; 95% CI 1.04, 130.64), and exposure to antimicrobials with anaerobic activity (OR 5.74; 95% CI 1.76, 18.67). Outcomes of infected patients were poor. Only 32% of case patients survived to hospital discharge, compared to 89% of controls. For 48% death was attributed to C. krusei infection. Conclusions: C. krusei bloodstream infection occurs most commonly in neutropenic patients with hematologic malignancy. The association with prior fluconazole exposure is less marked than previously described. Splenectomy and the receipt of antimicrobials with anaerobic activity are significant risk factors. The outcome of infected patients remains poor, despite appropriate antifungal therapy. (C) 2012 Published by Elsevier Ltd on behalf of The British Infection Association. C1 [Schuster, Mindy G.; Strom, Brian] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Lloyd, Lisa] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Schuster, MG (reprint author), Univ Penn, 3 Silverstein,Suite E,3400 Spruce St, Philadelphia, PA 19104 USA. EM Mindy.Schuster2@uphs.upenn.edu NR 37 TC 6 Z9 6 U1 0 U2 9 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0163-4453 J9 J INFECTION JI J. Infect. PD MAR PY 2013 VL 66 IS 3 BP 278 EP 284 DI 10.1016/j.jinf.2012.11.002 PG 7 WC Infectious Diseases SC Infectious Diseases GA 087ZP UT WOS:000314803900008 PM 23174708 ER PT J AU Hansson, EM Lendahl, U AF Hansson, E. M. Lendahl, U. TI Regenerative medicine for the treatment of heart disease SO JOURNAL OF INTERNAL MEDICINE LA English DT Review DE biomaterials; cell therapy; ES cell; iPS cell; myocardial infarction; stem cell ID PLURIPOTENT STEM-CELLS; ACUTE MYOCARDIAL-INFARCTION; BONE-MARROW-CELLS; RANDOMIZED CONTROLLED-TRIAL; MYOBLAST TRANSPLANTATION; PROGENITOR CELLS; ISCHEMIC CARDIOMYOPATHY; FUNCTIONAL-PROPERTIES; PARACRINE MECHANISMS; DEFINED FACTORS AB Hansson EM, Lendahl U (Harvard University, Cambridge, USA; Massachusetts General Hospital, Boston, USA; Karolinska Institute, Stockholm, Sweden). Regenerative medicine for the treatment of heart disease (Review). J Intern Med 2013; 273: 235-245. Heart failure is a major cause of mortality worldwide with a steady increase in prevalence. There is currently no available cure beyond orthotopic heart transplantation, which for a number of reasons is an option only for a small fraction of all patients. Considerable hope has therefore been placed on the possibility of treating a failing heart by replacing lost cardiomyocytes, either through transplantation of various types of stem cells or by boosting endogenous regenerative mechanisms in the heart. Here, we review the current status of stem and progenitor cell-based therapies for heart disease. We discuss the pros and cons of different stem and progenitor cell types that can be considered for transplantation and describe recent advances in the understanding of how cardiomyocytes normally differentiate and how these cells can be generated from more immature cells ex vivo. Finally, we consider the possibility of activation of endogenous stem and progenitor cells to treat heart failure. C1 [Hansson, E. M.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Hansson, E. M.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Richard B Simches Res Ctr CPZN 3200, Boston, MA 02114 USA. [Lendahl, U.] Karolinska Inst, Dept Cell & Mol Biol, Stockholm, SE, Sweden. RP Hansson, EM (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Richard B Simches Res Ctr CPZN 3200, 185 Cambridge St, Boston, MA 02114 USA. EM ehansson@partners.org OI Lendahl, Urban/0000-0001-9543-8141 FU Hjart-lungfonden; Swedish Research Council; Theme Center for Regenerative Medicine; Swedish Cancer Society; Knut och Alice Wallenbergs Stiftelse FX We apologize to our colleagues whose work could not be cited due to limitations to the length of this review. EMH is a Wenner-Gren Foundation fellow and is supported by Hjart-lungfonden. UL is supported by the Swedish Research Council (DBRM; Linneus Center in Developmental Biology and Regenerative Medicine), the Theme Center for Regenerative Medicine, the Swedish Cancer Society, and Knut och Alice Wallenbergs Stiftelse (WIRM; the Wallenberg Institute for Regenerative Medicine). NR 83 TC 12 Z9 13 U1 2 U2 34 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD MAR PY 2013 VL 273 IS 3 BP 235 EP 245 DI 10.1111/joim.12033 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 092DC UT WOS:000315098100002 PM 23331408 ER PT J AU Bhatia, N Xiao, TZ Rosenthal, KA Siddiqui, IA Thiyagarajan, S Smart, B Meng, Q Zuleger, CL Mukhtar, H Kenney, SC Albertini, MR Longley, BJ AF Bhatia, Neehar Xiao, Tony Z. Rosenthal, Kimberly A. Siddiqui, Imtiaz A. Thiyagarajan, Saravanan Smart, Brendan Meng, Qiao Zuleger, Cindy L. Mukhtar, Hasan Kenney, Shannon C. Albertini, Mark R. Longley, B. Jack TI MAGE-C2 Promotes Growth and Tumorigenicity of Melanoma Cells, Phosphorylation of KAP1, and DNA Damage Repair SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID DOUBLE-STRAND BREAKS; METASTATIC MELANOMA; ANTIGEN-EXPRESSION; MULTIPLE-MYELOMA; GENE-EXPRESSION; GERM-CELLS; CANCER; TESTIS; APOPTOSIS; PROGRESSION AB Melanoma-associated antigen-encoding (MAGE) genes are expressed in melanoma and other cancers but not in normal somatic cells. MAGE expression is associated with aggressive tumor growth, poor clinical outcome, and resistance to chemotherapy, but the mechanisms have not been completely elucidated. In this study, we show that downregulation of MAGE-C2 in A375 melanoma cells and low-passage cultures from human metastatic melanomas (MRA cells) results in increased apoptosis and decreased growth of tumor xenografts in athymic nude mice. Previously, we showed that MAGE-C2 binds KAP1, a scaffolding protein that regulates DNA repair. Phosphorylation of KAP1-Serine 824 (Ser824) by ataxia-telangiectasia mutated (ATM) kinase is necessary for repair of DNA double-strand breaks (DSBs); now we show that MAGE-C2 knockdown reduces, whereas MAGE-C2 overexpression increases, ATM kinase dependent phosphorylation of KAP1-Ser824. We demonstrate that MAGE-C2 increases co-precipitation of KAP1 with ATM and that binding of MAGE-C2 to KAP1 is necessary for increased KAP1-Ser824 phosphorylation. Furthermore, ectopic expression of MAGE-C2 enhances repair of I-Scel endonuclease induced DSBs in U-2OS cells. As phosphorylation of KAP1-Ser824 facilitates relaxation of heterochromatin, which is necessary for DNA repair and cellular proliferation, our results suggest that MAGE-C2 can promote tumor growth by phosphorylation of KAP1-Ser824 and by enhancement of DNA damage repair. Journal of Investigative Dermatology (2013) 133, 759-767; doi:10.1038/jid.2012.355; published online 25 October 2012 C1 [Bhatia, Neehar; Zuleger, Cindy L.; Albertini, Mark R.] Univ Wisconsin, Carbone Canc Ctr, Dept Med, Madison, WI 53705 USA. [Xiao, Tony Z.; Rosenthal, Kimberly A.; Siddiqui, Imtiaz A.; Smart, Brendan; Mukhtar, Hasan; Longley, B. Jack] Univ Wisconsin, Dept Dermatol, Madison, WI 53705 USA. [Thiyagarajan, Saravanan] Mazumdar Shaw Canc Ctr, Bangalore, Karnataka, India. [Meng, Qiao; Kenney, Shannon C.] Univ Wisconsin, McArdle Lab Canc Res, Madison, WI 53706 USA. [Albertini, Mark R.] William S Middleton Mem Vet Adm Med Ctr, Med Serv, Madison, WI USA. RP Bhatia, N (reprint author), Univ Wisconsin, Carbone Canc Ctr, Dept Med, WI Inst Med Res 4040, 1111 Highland Ave, Madison, WI 53705 USA. EM bneehar@medicine.wisc.edu; bjlongley@dermatology.wisc.edu FU University of Wisconsin Carbone Cancer Center, the Office of Research and Development, Biomedical Laboratory Research and Development Service, Department of Veterans Affairs; National Cancer Institute [P30 CA014520]; Gretchen and Andrew Dawes Melanoma Research Fund; Ann's Hope Foundation; Jay Van Sloan Memorial from the Steve Leuthold Family; Tim Eagle Memorial FX We acknowledge Dr Maria Jasin for providing us modified U2-OS cells for DNA repair assay, and Dr Andrew Simpson and Dr Otavia Caballero for reagents. We also thank Dr V.S. Setaluri for critical suggestions and support. We are grateful to Tisha Kawahara for support with the IRB protocol. This work was supported by the University of Wisconsin Carbone Cancer Center, the Office of Research and Development, Biomedical Laboratory Research and Development Service, Department of Veterans Affairs; by Grant P30 CA014520 from the National Cancer Institute; the Gretchen and Andrew Dawes Melanoma Research Fund; Ann's Hope Foundation; the Jay Van Sloan Memorial from the Steve Leuthold Family; and the Tim Eagle Memorial. The contents do not represent the views of the Department of Veterans Affairs or of the United States Government. Melanoma patient samples were used under UW-Madison Health Sciences IRB protocol number M-2009-1157. NR 38 TC 16 Z9 17 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2013 VL 133 IS 3 BP 759 EP 767 DI 10.1038/jid.2012.355 PG 9 WC Dermatology SC Dermatology GA 090VQ UT WOS:000315008500024 PM 23096706 ER PT J AU Gordon, CT Vuillot, A Marlin, S Gerkes, E Henderson, A AlKindy, A Holder-Espinasse, M Park, SS Omarjee, A Sanchis-Borja, M Ben Bdira, E Oufadem, M Sikkema-Raddatz, B Stewart, A Palmer, R McGowan, R Petit, F Delobel, B Speicher, MR Aurora, P Kilner, D Pellerin, P Simon, M Bonnefont, JP Tobias, ES Garcia-Minaur, S Bitner-Glindzicz, M Lindholm, P Meijer, BA Abadie, V Denoyelle, F Vazquez, MP Rotky-Fast, C Couloigner, V Pierrot, S Manach, Y Breton, S Hendriks, YMC Munnich, A Jakobsen, L Kroisel, P Lin, A Kaban, LB Basel-Vanagaite, L Wilson, L Cunningham, ML Lyonnet, S Amiel, J AF Gordon, Christopher T. Vuillot, Alice Marlin, Sandrine Gerkes, Erica Henderson, Alex AlKindy, Adila Holder-Espinasse, Muriel Park, Sarah S. Omarjee, Asma Sanchis-Borja, Mateo Ben Bdira, Eya Oufadem, Myriam Sikkema-Raddatz, Birgit Stewart, Alison Palmer, Rodger McGowan, Ruth Petit, Florence Delobel, Bruno Speicher, Michael R. Aurora, Paul Kilner, David Pellerin, Philippe Simon, Marie Bonnefont, Jean-Paul Tobias, Edward S. Garcia-Minaur, Sixto Bitner-Glindzicz, Maria Lindholm, Pernille Meijer, Brigitte A. Abadie, Veronique Denoyelle, Francoise Vazquez, Marie-Paule Rotky-Fast, Christa Couloigner, Vincent Pierrot, Sebastien Manach, Yves Breton, Sylvain Hendriks, Yvonne M. C. Munnich, Arnold Jakobsen, Linda Kroisel, Peter Lin, Angela Kaban, Leonard B. Basel-Vanagaite, Lina Wilson, Louise Cunningham, Michael L. Lyonnet, Stanislas Amiel, Jeanne TI Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID QUESTION MARK EAR; CONGENITAL AURICULAR CLEFT; PARKINSON-WHITE-SYNDROME; PROTEIN ALPHA-SUBUNITS; PHOSPHOLIPASE-C-BETA; CONDYLAR SYNDROME; ALAGILLE SYNDROME; DYSGNATHIA COMPLEX; DELETION; MICE AB Background Auriculocondylar syndrome (ACS) is a rare craniofacial disorder consisting of micrognathia, mandibular condyle hypoplasia and a specific malformation of the ear at the junction between the lobe and helix. Missense heterozygous mutations in the phospholipase C, beta 4 (PLCB4) and guanine nucleotide binding protein (G protein), a inhibiting activity polypeptide 3 (GNAI3) genes have recently been identified in ACS patients by exome sequencing. These genes are predicted to function within the G protein-coupled endothelin receptor pathway during craniofacial development. Results We report eight additional cases ascribed to PLCB4 or GNAI3 gene lesions, comprising six heterozygous PLCB4 missense mutations, one heterozygous GNAI3 missense mutation and one homozygous PLCB4 intragenic deletion. Certain residues represent mutational hotspots; of the total of 11 ACS PLCB4 missense mutations now described, five disrupt Arg621 and two disrupt Asp360. The narrow distribution of mutations within protein space suggests that the mutations may result in dominantly interfering proteins, rather than haploinsufficiency. The consanguineous parents of the patient with a homozygous PLCB4 deletion each harboured the heterozygous deletion, but did not present the ACS phenotype, further suggesting that ACS is not caused by PLCB4 haploinsufficiency. In addition to ACS, the patient harbouring a homozygous deletion presented with central apnoea, a phenotype that has not been previously reported in ACS patients. Conclusions These findings indicate that ACS is not only genetically heterogeneous but also an autosomal dominant or recessive condition according to the nature of the PLCB4 gene lesion. C1 [Gordon, Christopher T.; Vuillot, Alice; Omarjee, Asma; Sanchis-Borja, Mateo; Ben Bdira, Eya; Oufadem, Myriam; Munnich, Arnold; Lyonnet, Stanislas; Amiel, Jeanne] Hop Necker Enfants Malad, INSERM, U781, F-75015 Paris, France. [Gordon, Christopher T.; Vuillot, Alice; Omarjee, Asma; Sanchis-Borja, Mateo; Ben Bdira, Eya; Oufadem, Myriam; Munnich, Arnold; Lyonnet, Stanislas; Amiel, Jeanne] Univ Paris 05, Sorbonne Paris Cite, Inst Imagine, Paris, France. [Marlin, Sandrine] Hop Enfants Armand Trousseau, AP HP, Serv Genet Med, Ctr Reference Surdites Genet, Paris, France. [Gerkes, Erica; Sikkema-Raddatz, Birgit] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [Henderson, Alex] Newcastle Upon Tyne Hosp NHS Fdn Trust, No Genet Serv, Newcastle Upon Tyne, Tyne & Wear, England. [AlKindy, Adila] Sultan Qaboos Univ Hosp, Dept Genet, Muscat, Oman. [Holder-Espinasse, Muriel; Petit, Florence] CHRU Lille, Hop Jeanne de Flandre, Serv Genet Clin, Lille, France. [Park, Sarah S.; Cunningham, Michael L.] Seattle Childrens Res Inst, Ctr Tissue & Cell Sci, Seattle, WA USA. [Stewart, Alison] W Midlands Reg Genet Serv, Birmingham, W Midlands, England. [Palmer, Rodger; Wilson, Louise] Great Ormond St Hosp Sick Children, NE Thames Reg Genet Serv, London, England. [McGowan, Ruth] N Scotland Reg Genet Serv, Aberdeen, Scotland. [Delobel, Bruno] Hop St Vincent de Paul, Lab Genet Chromosom, Lille, France. [Speicher, Michael R.; Kroisel, Peter] Med Univ Graz, Inst Human Genet, Graz, Austria. [Aurora, Paul; Kilner, David] Great Ormond St Hosp Sick Children, London, England. [Pellerin, Philippe] CHRU Lille, Ctr Reference Malformat Craniomaxillofaciales Rar, Lille, France. [Simon, Marie; Bonnefont, Jean-Paul; Munnich, Arnold; Lyonnet, Stanislas; Amiel, Jeanne] Hop Necker Enfants Malad, AP HP, Dept Genet, F-75015 Paris, France. [Tobias, Edward S.] Univ Glasgow, Yorkhill Hosp, Sch Med, Glasgow, Lanark, Scotland. [Garcia-Minaur, Sixto] La Paz Univ Hosp, Inst Med & Mol Genet, Madrid, Spain. [Bitner-Glindzicz, Maria] UCL, Inst Child Hlth, London, England. [Lindholm, Pernille; Jakobsen, Linda] Rigshosp, Copenhagen Univ Hosp, Dept Plast & Reconstruct Surg, Copenhagen, Denmark. [Meijer, Brigitte A.] Kennemer Gasthuis, Dept Oral & Maxillofacial Surg, Haarlem, Netherlands. [Abadie, Veronique] Univ Paris 05, Hop Necker Enfants Malad, Serv Pediat Gen, Paris, France. [Denoyelle, Francoise] Univ Paris 06, Armand Trousseau Childrens Hosp, AP HP, INSERM,UMR S587, Paris, France. [Denoyelle, Francoise] Univ Paris 06, Armand Trousseau Childrens Hosp, AP HP, Dept Pediat Otolaryngol, Paris, France. [Vazquez, Marie-Paule] Hop Necker Enfants Malad, AP HP, CRMR Malformat Face & Cavite Buccale, Serv Chirurg Maxillofaciale & Plast, F-75015 Paris, France. [Vazquez, Marie-Paule] Univ Paris 05, UFR Med Paris Descartes, Paris, France. [Vazquez, Marie-Paule] Ctr Rech Cordeliers, UMR S 872, Paris, France. [Rotky-Fast, Christa] Med Univ Graz, Dept Pediat & Adolescence Med, Graz, Austria. [Couloigner, Vincent; Pierrot, Sebastien; Manach, Yves] Univ Paris 05, Hop Necker Enfants Malad, AP HP, Serv ORL Pediat, Paris, France. [Breton, Sylvain] Hop Necker Enfants Malad, AP HP, Serv Imagerie Pediat, F-75015 Paris, France. [Breton, Sylvain] Univ Paris 05, Anat Lab, Paris, France. [Hendriks, Yvonne M. C.] Free Univ Amsterdam, Med Ctr, Dept Clin Genet, Amsterdam, Netherlands. [Lin, Angela] MassGen Hosp Children, Genet Unit, Boston, MA USA. [Kaban, Leonard B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Basel-Vanagaite, Lina] Schneider Childrens Med Ctr Israel, Petah Tiqwa, Israel. [Basel-Vanagaite, Lina] Rabin Med Ctr, Raphael Recanati Genet Inst, Petah Tiqwa, Israel. [Basel-Vanagaite, Lina] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Basel-Vanagaite, Lina] Rabin Med Ctr, Felsenstein Med Res Ctr, Petah Tiqwa, Israel. [Cunningham, Michael L.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Cunningham, Michael L.] Seattle Childrens Hosp, Craniofacial Ctr, Seattle, WA USA. RP Gordon, CT (reprint author), Hop Necker Enfants Malad, INSERM, U781, Tour Lavoisier 2Eme Etage,149 Rue Sevres, F-75015 Paris, France. EM chris.gordon@inserm.fr; jeanne.amiel@inserm.fr RI Speicher, Michael/B-5362-2013; Bitner-Glindzicz, Maria/A-4231-2009; Gordon, Christopher/F-1267-2017; OI Speicher, Michael/0000-0003-0105-955X; Gordon, Christopher/0000-0002-9300-8399; petit, florence/0000-0002-1368-1023 FU Ecole de l'Inserm Liliane Bettencourt; Jean Renny Endowment for Craniofacial Research; E-Rare CRANIRARE; Fondation pour la Recherche Medicale FX This work was supported by funding from the Ecole de l'Inserm Liliane Bettencourt (AV), the Jean Renny Endowment for Craniofacial Research (MLC), E-Rare CRANIRARE (SL) and the Fondation pour la Recherche Medicale (JA). NR 65 TC 16 Z9 16 U1 0 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 EI 1468-6244 J9 J MED GENET JI J. Med. Genet. PD MAR PY 2013 VL 50 IS 3 BP 174 EP 186 DI 10.1136/jmedgenet-2012-101331 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 088ZR UT WOS:000314877600007 PM 23315542 ER PT J AU Cougle, JR Bernstein, A Zvolensky, MJ Vujanovic, AA Macatee, RJ AF Cougle, Jesse R. Bernstein, Amit Zvolensky, Michael J. Vujanovic, Anka A. Macatee, Richard J. TI Validation of Self-Report Measures of Emotional and Physical Distress Tolerance SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE Distress tolerance; Discomfort tolerance; Construct validity; Assessment; Anxiety sensitivity ID ANXIETY SENSITIVITY; INTOLERANCE; DISORDERS AB The Distress Tolerance Scale (DTS) and Discomfort Intolerance Scale (DIS) are self-report measures developed for the assessment of emotional and physical distress tolerance, respectively. However, little evidence exists for their construct and specifically criterion-related validity. The current study examined the associations of these self-report measures with lab-based assessments of perceived emotional tolerance and physical discomfort tolerance. Undergraduate participants (N = 166) were administered four film clips intended to induce sadness, disgust, fear, and anger, and a handgrip persistence task intended to elicit physical discomfort. The DTS, but not the DIS, was significantly associated with self-reported emotional tolerance and perceived threat associated with each film after controlling for emotional intensity. Among DTS subscales, the absorption subscale was the only subscale incrementally predictive of negative perceptions of the sad film, the appraisal subscale was incrementally predictive of negative perceptions of the other three films, and little support for the incremental validity of the tolerance and regulation subscales was found. The DTS also incrementally predicted tolerance and perceived threat of film-elicited emotions across films after controlling for anxiety sensitivity. The DIS was only marginally predictive of handgrip task persistence and was unrelated to emotional film perceptions. Overall, these findings uniquely add to the empirical literature on the construct and criterion-related validity of the DTS and DIS. C1 [Cougle, Jesse R.; Macatee, Richard J.] Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. [Bernstein, Amit] Univ Haifa, Dept Psychol, IL-31999 Haifa, Israel. [Zvolensky, Michael J.] Univ Houston, Dept Psychol, Houston, TX USA. [Vujanovic, Anka A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. [Vujanovic, Anka A.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Cougle, JR (reprint author), Florida State Univ, Dept Psychol, 1107 W Call St, Tallahassee, FL 32306 USA. EM cougle@psy.fsu.edu NR 26 TC 3 Z9 3 U1 4 U2 9 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD MAR PY 2013 VL 35 IS 1 BP 76 EP 84 DI 10.1007/s10862-012-9317-2 PG 9 WC Psychology, Clinical SC Psychology GA 087QD UT WOS:000314776100008 ER PT J AU Schmidt, B Yoon, SS AF Schmidt, Benjamin Yoon, Sam S. TI D1 versus D2 lymphadenectomy for gastric cancer SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Review DE gastric adenocarcinoma; lymphadenectomy; surgery; stage; survival ID LYMPH-NODE DISSECTION; PRESERVING TOTAL GASTRECTOMY; RANDOMIZED CONTROLLED-TRIAL; DISEASE-SPECIFIC SURVIVAL; UNITED-STATES; SURGICAL TRIAL; HELICOBACTER-PYLORI; D-2 RESECTIONS; STAGING SYSTEM; CLINICAL-TRIAL AB Significant variability exists throughout the world in the extent of lymphadenectomy that is performed for gastric adenocarcinoma. D2 lymphadenectomy is the standard lymphadenectomy performed in high incidence countries such as Japan and South Korea, and less extensive lymphadenectomies are often performed in lower incidence countries such as the Unites States. This article reviews the evidence on the extent of lymphadenectomy that should be performed for gastric adenocarcinoma. J. Surg. Oncol. 2013;107:259264. (c) 2012 Wiley Periodicals, Inc. C1 [Yoon, Sam S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Yoon, SS (reprint author), Massachusetts Gen Hosp, Dept Surg, Yawkey 7B,55 Fruit St, Boston, MA 02114 USA. EM syoon@partners.org FU NCI NIH HHS [T32 CA071345] NR 60 TC 24 Z9 26 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4790 EI 1096-9098 J9 J SURG ONCOL JI J. Surg. Oncol. PD MAR PY 2013 VL 107 IS 3 BP 259 EP 264 DI 10.1002/jso.23127 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA 088WZ UT WOS:000314869900006 PM 22513454 ER PT J AU Kougias, P Tiwari, V Barshes, NR Bechara, CF Lowery, B Pisimisis, G Berger, DH AF Kougias, Panagiotis Tiwari, Vikram Barshes, Neal R. Bechara, Carlos F. Lowery, Briauna Pisimisis, George Berger, David H. TI Modeling anesthetic times. Predictors and implications for short-term outcomes SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Modeling; Regression; Anesthetic length; Precision ID SURGERY; EXPENDITURES; VARIABILITY; DURATION; THEATER AB Background: Little is known about the predictors of anesthetic times and impact of anesthetic and operative times on patient outcomes. Methods: We documented operative case length, anesthetic induction time length, and anesthetic recovery time length in 1713 consecutive patients who underwent elective vascular surgical interventions. We recorded patient and procedure-related characteristics that might influence the anesthetic time length, including a variable for possible July effect. Multivariate linear regression was used to model the length of anesthetic times. Multivariate logistic regression was used to model the impact of anesthetic and operative time lengths on a composite outcome of perioperative (30-d postoperative) death, myocardial infarction, cardiac arrhythmias, stroke, and congestive heart failure. Results: Statistically significant predictors of anesthetic induction time included body mass index, anesthesia type, and procedure type. Statistically significant predictors of anesthetic recovery time included operative case length, procedure type, and anesthesia type. After adjusting for the statistically significant covariates of total blood transfusion, history of coronary artery disease, and procedure type, there was a trend for increased likelihood of the composite end point as a function of operative time (odds ratio, 1.14; 95% confidence interval, 0.97-1.33; P = 0.09), which did not reach statistical significance. Multivariate analysis showed no association between the anesthetic time and composite end point. Conclusions: Modeling individually anesthetic induction and recovery time on the basis of operative and anesthetic procedure characteristics is feasible. Anesthetic and operative times do not impact perioperative morbidity and mortality. Published by Elsevier Inc. C1 [Kougias, Panagiotis; Barshes, Neal R.; Bechara, Carlos F.; Lowery, Briauna; Pisimisis, George; Berger, David H.] Baylor Coll Med, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. [Tiwari, Vikram] Vanderbilt Univ, Med Ctr, Director Perioperat Serv, Nashville, TN USA. RP Kougias, P (reprint author), Houston VAMC, Michael E DeBakey Dept Surg, 2002 Holcombe Blvd,OCL 112, Houston, TX 77030 USA. EM pkougias@bcm.edu NR 14 TC 5 Z9 5 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 0022-4804 J9 J SURG RES JI J. Surg. Res. PD MAR PY 2013 VL 180 IS 1 BP 1 EP 7 DI 10.1016/j.jss.2012.10.007 PG 7 WC Surgery SC Surgery GA 089LQ UT WOS:000314912400008 PM 23158406 ER PT J AU Di Eusanio, M Patel, HJ Nienaber, CA Montgomery, DM Korach, A Sundt, TM DeVincentiis, C Voehringer, M Peterson, MD Myrmel, T Folesani, G Larsen, M Desai, ND Bavaria, JE Appoo, JJ Kieser, TM Fattori, R Eagle, K Di Bartolomeo, R Trimarchi, S AF Di Eusanio, Marco Patel, Himanshu J. Nienaber, Christoph A. Montgomery, Daniel M. Korach, Amit Sundt, Thoralf M. DeVincentiis, Carlo Voehringer, Matthias Peterson, Mark D. Myrmel, Truls Folesani, Gianluca Larsen, Magnus Desai, Nimesh D. Bavaria, Joseph E. Appoo, Jehangir J. Kieser, Teresa M. Fattori, Rossella Eagle, Kim Di Bartolomeo, Roberto Trimarchi, Santi TI Patients with type A acute aortic dissection presenting with major brain injury: Should we operate on them? SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT Aortic Surgery Symposium of the American-Association-for-Thoracic-Surgery CY APR 26-27, 2012 CL New York, NY SP Amer Assoc Thorac Surg ID INTERNATIONAL REGISTRY; NEUROLOGICAL DYSFUNCTION; DISEASE; REPAIR; INSIGHTS; SURGERY; STROKE; IRAD; COMA AB Objectives: The management strategy remains controversial for patients presenting with type A acute aortic dissection with cerebrovascular accident or coma. The present study aimed to help guide surgeons treating these high-risk patients. Methods: Of 1873 patients with type A acute aortic dissection enrolled in the International Registry for Acute Dissection, 87 (4.7%) presented with cerebrovascular accident and 54 (2.9%) with coma. The hospital and 5-year results were stratified by the presence and type of brain injury (no injury vs stroke vs coma) and management type (medical vs surgical). Independent predictors of short-and mid-term survival were identified. Results: Presentation with shock, hypotension, or tamponade (46.8% vs 25.2%; P < .001) and arch vessel involvement (55.0% vs 36.1%; P < .001) was more likely in patients with brain injury. Surgical management was avoided more often in patients with coma (33.3%) or cerebrovascular accident (24.1%) than in those without brain injury (11.1%; P < .001). The overall hospital mortality was 22.7% without brain injury, 40.2% with cerebrovascular accident, and 63.0% with coma (P < .001). Mortality varied among the management types for both cerebrovascular accident (76.2% medical vs 27.0% surgical; P < .001) and coma (100% medical vs 44.4% surgical; P < .001). Postoperatively, cerebrovascular accident and coma resolved in 84.3% and 78.8% of cases, respectively. On logistic regression analysis, surgery was protective against mortality in patients presenting with brain injury (odds ratio 0.058; P < .001). The 5-year survival of patients presenting with cerebrovascular accident and comawas 23.8% and 0% after medical management versus 67.1% and 57.1% after surgery (log rank, P < .001), respectively. Conclusions: Brain injury at presentation adversely affects hospital survival of patients with type A acute aortic dissection. In the present observational study, the patients selected to undergo surgery demonstrated improved late survival and frequent reversal of neurologic deficits. (J Thorac Cardiovasc Surg 2013;145:S213-21) C1 [Di Eusanio, Marco; Folesani, Gianluca; Fattori, Rossella; Di Bartolomeo, Roberto] St Orsola Marcello Malpighi Hosp, Dept Cardiac Surg, Bologna, Italy. [Patel, Himanshu J.; Montgomery, Daniel M.; Eagle, Kim] Univ Michigan, Dept Cardiac Surg, Ann Arbor, MI 48109 USA. [Nienaber, Christoph A.] Univ Hosp Eppendorf Rostock, Dept Internal Med, Rostock, Germany. [Korach, Amit] Hadassah Hebrew Univ Med Ctr, Dept Cardiothorac Surg, Jerusalem, Israel. [Sundt, Thoralf M.] Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA. [DeVincentiis, Carlo; Trimarchi, Santi] IRCCS Policlin San Donato, Thorac Aort Res Ctr, San Donato Milanese, Italy. [Voehringer, Matthias] Robert Bosch Krankenhaus, Dept Cardiol, Stuttgart, Germany. [Peterson, Mark D.] St Michaels Hosp, Div Cardiac Surg, Toronto, ON M5B 1W8, Canada. [Myrmel, Truls; Larsen, Magnus] Univ Tromso Hosp, Dept Cardiothorac & Vasc Surg, N-9012 Tromso, Norway. [Desai, Nimesh D.; Bavaria, Joseph E.] Univ Penn, Sch Med, Dept Cardiovasc Surg, Philadelphia, PA 19104 USA. [Appoo, Jehangir J.; Kieser, Teresa M.] Univ Calgary, Med Ctr, Dept Cardiac Surg, Calgary, AB, Canada. RP Di Eusanio, M (reprint author), Univ Bologna, Dept Cardiac Surg, Policlin St Orsola Malpighi, Pad 25,Via Massarenti 9, I-40128 Bologna, Italy. EM marco.dieusanio2@unibo.it RI Trimarchi, Santi/J-7361-2016; OI Trimarchi, Santi/0000-0001-5996-3264; di bartolomeo, roberto/0000-0003-3965-5779 NR 16 TC 15 Z9 15 U1 1 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 MAR PY 2013 VL 145 IS 3 SU S BP S213 EP + DI 10.1016/j.jtcvs.2012.11.054 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 089BQ UT WOS:000314884000040 PM 23410778 ER PT J AU Sundt, TM AF Sundt, Thoralf M. TI Indications for aortic aneurysmectomy: Too many variables and not enough equations? SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID HUMAN ASCENDING AORTA; THORACIC AORTA; DISSECTION; GUIDELINES; BEHAVIOR; RUPTURE; EVENTS; RATES; SIZE AB Endografting for treatment of thoracic aortic pathology continues to gain popularity; in some countries, endovascular aortic repair numbers now exceed open surgery cases. The skills and understanding of open surgical teams are not always translated into endovascular interventions, which may be led by a cardiologist or vascular surgeon with little knowledge of thoracic pathology. The indications for intervention on the dilated aorta continue to be debated despite volumes of literature and multisocietal guidelines. The challenge of making a binary decision in the face of competing continuous risks depends on a best guess as to when the risk of the natural history of the disease exceeds that of the operation. Unfortunately, we have more information about average risk than actual (patient-specific) risk, and only for some of the variables determining those risks. Individual patient-specific operative risk can be calculated for some procedures by means of the Society of Thoracic Surgeons database, although surgeon-specific risk models are really required. On the other side of the balance, aortic dissection and rupture represent material failure of the aortic wall when tensile stress exceeds tensile strength. When framed in this way, it is not surprising that diameter is imprecise, as this is only one of the variables in the law of Laplace. The circumferential (hoop) stress is the product of radius and intraluminal pressure, divided by wall thickness. We also have no good measures of the material properties of the wall that determine strength, although a great deal of attention has been paid to the genetic markers for aortic wall abnormalities. Other factors, such as smoking or poorly controlled hypertension, likely should enter into our clinical assessment because they impact wall strength as well. For now, discussions with patients should be framed with all these elements in mind. (J Thorac Cardiovasc Surg 2013;145:S126-9) C1 [Sundt, Thoralf M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Sundt, Thoralf M.] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP Sundt, TM (reprint author), Harvard Univ, Sch Med, Cox 652,55 Fruit St, Boston, MA 02114 USA. EM tsundt@partners.org NR 27 TC 3 Z9 3 U1 0 U2 5 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 MAR PY 2013 VL 145 IS 3 SU S BP S126 EP S129 DI 10.1016/j.jtcvs.2012.11.067 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 089BQ UT WOS:000314884000024 PM 23410769 ER PT J AU Trimarchi, S Tolenaar, JL Jonker, FHW Murray, B Tsai, TT Eagle, KA Rampoldi, V Verhagen, HJM van Herwaarden, JA Moll, FL Muhs, BE Elefteriades, JA AF Trimarchi, Santi Tolenaar, Jip L. Jonker, Frederik H. W. Murray, Brian Tsai, Thomas T. Eagle, Kim A. Rampoldi, Vincenzo Verhagen, Hence J. M. van Herwaarden, Joost A. Moll, Frans L. Muhs, Bart E. Elefteriades, John A. TI Importance of false lumen thrombosis in type B aortic dissection prognosis SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID INTERNATIONAL REGISTRY; ECHOCARDIOGRAPHY; PATENCY; REPAIR AB Background: Partial thrombosis of the false lumen has been reported as a significant predictor of mortality during follow-up in patients with acute type B aortic dissection. The purpose of this study was to investigate the correlation of false lumen thrombosis and aortic expansion during follow-up in patients with acute type B aortic dissection. Methods: All medically treated patients with acute type B aortic dissection observed in 4 cardiovascular referral centers between 1998 and 2011, with admission and follow-up computed tomography or magnetic resonance imaging scans, were included. Aortic diameters of the dissected aortas were measured at 4 levels on the baseline and follow-up scans, and annual growth rates were calculated. Univariate and multivariate regression analyses were used to investigate the effect of false lumen thrombosis on aortic growth rate. Results: A total of 84 patients were included, of whom 40 (47.6%) had a partially thrombosed false lumen, 7 (8.3%) had a completely thrombosed false lumen, and 37 (44.0%) had a patent false lumen. A total of 273 of the 336 (81.3%) evaluated aortic levels were dissected segments. Overall, the mean aortic diameter increased significantly at all evaluated levels (P <. 001). Univariate analysis showed that annual aortic growth rates were significantly higher in those segments having a false lumen with partial thrombosis (mean, 4.25 +/- 10.2) when compared with the patent group (mean, 2.10 +/- 5.56; P = .035). In multivariate analysis, partial lumen thrombosis was an independent predictor of higher aortic growth (adjusted mean difference, 2.05 mm/year; 95% confidence interval, 0.10-4.01; P = .040). Conclusions: In patients with acute type B aortic dissection, aortic segments with a partially thrombosed false lumen have a significantly higher annual aortic growth rate when compared with those presenting with patent or complete thrombosis of the false lumen. Therefore, patients with partial thrombosis require more intensive follow-up and may benefit from prophylactic intervention. (J Thorac Cardiovasc Surg 2013;145:S208-12) C1 [Trimarchi, Santi; Tolenaar, Jip L.; Rampoldi, Vincenzo] Policlin San Donato IRCCS, Thorac Aort Res Ctr, Milan, Italy. [Jonker, Frederik H. W.] Maasstad Hosp, Dept Surg, Rotterdam, Netherlands. [Murray, Brian; Elefteriades, John A.] Yale Univ, Sch Med, Sect Cardiac Surg, New Haven, CT USA. [Tsai, Thomas T.] Denver VA Med Ctr, Div Cardiol & Intervent Cardiol, Denver, CO USA. [Eagle, Kim A.] Univ Michigan Hlth Syst, Ctr Cardiovasc, Ann Arbor, MI USA. [Verhagen, Hence J. M.] Erasmus MC, Dept Vasc Surg, Rotterdam, Netherlands. [van Herwaarden, Joost A.; Moll, Frans L.] Univ Med Ctr Utrecht, Dept Vasc Surg, Utrecht, Netherlands. [Muhs, Bart E.] Yale Univ, Sch Med, Vasc Surg Sect, New Haven, CT USA. RP Trimarchi, S (reprint author), Univ Milan, Thorac Aort Res Ctr, Policlin San Donato IRCCS, Piazza Malan 2, I-20097 San Donato Milanese, MI, Italy. EM santi.trimarchi@unimi.it RI Trimarchi, Santi/J-7361-2016 OI Trimarchi, Santi/0000-0001-5996-3264 NR 15 TC 34 Z9 34 U1 0 U2 9 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 MAR PY 2013 VL 145 IS 3 SU S BP S208 EP S212 DI 10.1016/j.jtcvs.2012.11.048 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 089BQ UT WOS:000314884000039 PM 23260434 ER PT J AU Desormeaux, A Coutu, M Medjahed, H Pacheco, B Herschhorn, A Gu, C Xiang, SH Mao, YD Sodroski, J Finzi, A AF Desormeaux, Anik Coutu, Mathieu Medjahed, Halima Pacheco, Beatriz Herschhorn, Alon Gu, Christopher Xiang, Shi-Hua Mao, Youdong Sodroski, Joseph Finzi, Andres TI The Highly Conserved Layer-3 Component of the HIV-1 gp120 Inner Domain Is Critical for CD4-Required Conformational Transitions SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ENVELOPE GLYCOPROTEIN TRIMER; CD4 RECEPTOR; SOLUBLE CD4; HTLV-III; TRANSMEMBRANE GLYCOPROTEIN; NEUTRALIZING ANTIBODIES; CD4-BOUND CONFORMATION; MOLECULAR CLONE; AIDS PATIENTS AB The trimeric envelope glycoprotein (Env) of human immunodeficiency virus type 1 (HIV-1) mediates virus entry into host cells. CD4 engagement with the gp120 exterior envelope glycoprotein subunit represents the first step during HIV-1 entry. CD4-induced conformational changes in the gp120 inner domain involve three potentially flexible topological layers (layers 1, 2, and 3). Structural rearrangements between layer 1 and layer 2 have been shown to facilitate the transition of the envelope glycoprotein trimer from the unliganded to the CD4-bound state and to stabilize gp120-CD4 interaction. However, our understanding of CD4-induced conformational changes in the gp120 inner domain remains incomplete. Here, we report that a highly conserved element of the gp120 inner domain, layer 3, plays a pivot-like role in these allosteric changes. In the unliganded state, layer 3 modulates the association of gp120 with the Env trimer, probably by influencing the relationship of the gp120 inner and outer domains. Importantly, layer 3 governs the efficiency of the initial gp120 interaction with CD4, a function that can also be fulfilled by filling the Phe43 cavity. This work defines the functional importance of layer 3 and completes a picture detailing the role of the gp120 inner domain in CD4-induced conformational transitions in the HIV-1 Env trimer. C1 [Desormeaux, Anik; Coutu, Mathieu; Medjahed, Halima; Finzi, Andres] Univ Montreal, CHUM, Ctr Rech, Montreal, PQ, Canada. [Desormeaux, Anik; Coutu, Mathieu; Medjahed, Halima; Finzi, Andres] Univ Montreal, Dept Microbiol & Immunol, Montreal, PQ H3C 3J7, Canada. [Finzi, Andres] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada. [Xiang, Shi-Hua] Univ Nebraska, Sch Vet Med & Biomed Sci, Nebraska Ctr Virol, Lincoln, NE USA. [Pacheco, Beatriz; Herschhorn, Alon; Gu, Christopher; Mao, Youdong; Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Pacheco, Beatriz; Herschhorn, Alon; Gu, Christopher; Mao, Youdong; Sodroski, Joseph] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Aids, Boston, MA 02115 USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Sodroski, Joseph] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA USA. RP Finzi, A (reprint author), Univ Montreal, CHUM, Ctr Rech, Montreal, PQ, Canada. EM andres.finzi@umontreal.ca FU amfAR Mathilde Krim Fellowship in Basic Biomedical Research [108092-50-RKVA]; Canada Foundation for Innovation [29866]; CIHR [257792]; FRQS [24639]; National Institutes of Health [AI24755, AI67854]; International AIDS Vaccine Initiative FX This work was supported by an amfAR Mathilde Krim Fellowship in Basic Biomedical Research (Phase II, no. 108092-50-RKVA), by a Canada Foundation for Innovation Program Leader grant (no. 29866), by a CIHR operating grant (no. 257792), and by an FRQS Establishment of Young Scientist grant (no. 24639) to A.F. A.F. is the recipient of an FRSQ Chercheur Boursier Junior 1 Fellowship (no. 24639). This work was also supported by grants from the National Institutes of Health (AI24755 and AI67854), by the International AIDS Vaccine Initiative, and by the late William F. McCarty-Cooper. NR 72 TC 25 Z9 25 U1 0 U2 20 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2013 VL 87 IS 5 BP 2549 EP 2562 DI 10.1128/JVI.03104-12 PG 14 WC Virology SC Virology GA 088ZL UT WOS:000314876900017 PM 23255784 ER PT J AU Csiszar, A Sosnowska, D Tucsek, Z Gautam, T Toth, P Losonczy, G Colman, RJ Weindruch, R Anderson, RM Sonntag, WE Ungvari, Z AF Csiszar, Anna Sosnowska, Danuta Tucsek, Zsuzsanna Gautam, Tripti Toth, Peter Losonczy, Gyorgy Colman, Ricki J. Weindruch, Richard Anderson, Rozalyn M. Sonntag, William E. Ungvari, Zoltan TI Circulating Factors Induced by Caloric Restriction in the Nonhuman Primate Macaca Mulatta Activate Angiogenic Processes in Endothelial Cells SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Dietary restriction; Vascular aging; Angiogenesis; Microcirculation; Cardiovascular system ID VASCULAR OXIDATIVE STRESS; LEWIS DWARF RATS; MEMBRANE REDOX SYSTEM; SMOOTH-MUSCLE-CELLS; KAPPA-B ACTIVATION; RHESUS-MONKEYS; DIETARY RESTRICTION; LIFE-SPAN; MITOCHONDRIAL BIOGENESIS; BODY-COMPOSITION AB Moderate caloric restriction (CR) without malnutrition increases healthspan in virtually every species studied, including nonhuman primates. In mice, CR exerts significant microvascular protective effects resulting in increased microvascular density in the heart and the brain, which likely contribute to enhanced tolerance to ischemia and improved cardiac performance and cognitive function. Yet, the underlying mechanisms by which CR confer microvascular protection remain elusive. To test the hypothesis that circulating factors triggered by CR regulate endothelial angiogenic capacity, we treated cultured human endothelial cells with sera derived from Macaca mulatta on long-term (over 10 years) CR. Cells treated with sera derived from ad-libitum-fed control monkeys served as controls. We found that factors present in CR sera upregulate vascular endothelial growth factor (VEGF) signaling and stimulate angiogenic processes, including endothelial cell proliferation and formation of capillary-like structures. Treatment with CR sera also tended to increase cellular migration (measured by a wound-healing assay using electric cellsubstrate impedance sensing [ECIS] technology) and adhesion to collagen. Collectively, we find that circulating factors induced by CR promote endothelial angiogenic processes, suggesting that increased angiogenesis may be a potential mechanism by which CR improves cardiac function and prevents vascular cognitive impairment. C1 [Csiszar, Anna; Sosnowska, Danuta; Tucsek, Zsuzsanna; Gautam, Tripti; Toth, Peter; Sonntag, William E.; Ungvari, Zoltan] Univ Oklahoma, Hlth Sci Ctr, Dept Geriatr Med, Reynolds Oklahoma Ctr Aging, Norman, OK 73019 USA. [Csiszar, Anna; Sonntag, William E.; Ungvari, Zoltan] Univ Oklahoma, Hlth Sci Ctr, Peggy & Charles Stephenson Canc Ctr, Norman, OK 73019 USA. [Losonczy, Gyorgy] Semmelweis Univ, Dept Pulmonol, H-1085 Budapest, Hungary. [Colman, Ricki J.] Univ Wisconsin, William S Middleton Mem Vet Hosp, Wisconsin Natl Primate Res Center, Madison, WI 53706 USA. [Weindruch, Richard; Anderson, Rozalyn M.] Univ Wisconsin, William S Middleton Mem Vet Hosp, Sch Med & Publ Hlth, Dept Med, Madison, WI 53706 USA. [Weindruch, Richard; Anderson, Rozalyn M.] Univ Wisconsin, William S Middleton Mem Vet Hosp, Geriatr Res Educ & Clin Ctr, Madison, WI 53706 USA. RP Csiszar, A (reprint author), Univ Oklahoma HSC, Reynolds Oklahoma Ctr Aging, Dept Geriatr Med, 975 NE 10th St,BRC 1303, Oklahoma City, OK 73104 USA. EM anna-csiszar@ouhsc.edu; zoltan-ungvari@ouhsc.edu FU American Federation for Aging Research; Oklahoma Center for the Advancement of Science and Technology; University of Oklahoma College of Medicine Alumni Association; American Heart Association; National Institutes of Health (NIH) [AG031085, AT006526, P01 AG011915, P51 RR000167, AG038747, NS056218, P01 AG11370]; Ellison Medical Foundation; Arkansas Claude Pepper Older Americans Independence Center at University of Arkansas Medical Center; NCRR [RR15459-01, RR020141-01]; Donald W. Reynolds Foundation FX This work was supported by grants from the American Federation for Aging Research (to A. C.), the Oklahoma Center for the Advancement of Science and Technology (to A. C., Z.U., and W. E. S.), the University of Oklahoma College of Medicine Alumni Association (to A. C.), the American Heart Association (to A. C., P. T., and Z.U.), the National Institutes of Health (NIH) (AG031085 to A. C., AT006526 to Z.U., P01 AG011915 to R. W., P51 RR000167 to W.N.P.R.C., and AG038747, NS056218, and P01 AG11370 to W. E. S.), the Ellison Medical Foundation (to W. E. S.), and the Arkansas Claude Pepper Older Americans Independence Center at University of Arkansas Medical Center (to A. C.). This research was conducted in part at a facility constructed with support from Research Facilities Improvement Program grant numbers RR15459-01 and RR020141-01 from NCRR.; The authors would like to express their gratitude for the support of the Donald W. Reynolds Foundation, which funds aging research at the University of Oklahoma Health Sciences Center under its Aging and Quality of Life Program. NR 124 TC 19 Z9 20 U1 3 U2 15 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 MAR PY 2013 VL 68 IS 3 BP 235 EP 249 DI 10.1093/gerona/gls158 PG 15 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 088PM UT WOS:000314847600003 PM 22904098 ER PT J AU Duong, VH Jaglal, MV Zhang, L Kale, V Lancet, JE Komrokji, RS List, AF AF Duong, Vu H. Jaglal, Michael V. Zhang, Ling Kale, Vishakha Lancet, Jeffrey E. Komrokji, Rami S. List, Alan F. TI Phase II pilot study of oral dasatinib in patients with higher-risk myelodysplastic syndrome (MDS) who failed conventional therapy SO LEUKEMIA RESEARCH LA English DT Article DE Myelodysplastic syndromes; Myelodysplastic-myeloproliferative diseases; Dasatinib; Azacitidine; Decitabine ID ACUTE MYELOID-LEUKEMIA; SRC FAMILY KINASES; SCORING SYSTEM; ONCOLOGY-GROUP; TRISOMY-8; EXPRESSION; INHIBITOR; SURVIVAL; IMPACT; LYN AB Given evidence for the role of Src family kinases, especially Lyn kinase, in myeloblast proliferation and the in vitro inhibitory activity of dasatinib on Src and Lyn, we conducted a phase II study to assess overall response to 100 mg/day dasatinib in patients with higher-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia, or acute myeloid leukemia arising from MDS and who had failed prior treatment with azanucleoside analogs. Among 18 patients treated, 3 responded, 4 had stable disease, and 10 experienced disease progression. Toxicities were limited and consistent with previous reports. Dasatinib appears to be safe but with limited efficacy. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Duong, Vu H.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Jaglal, Michael V.; Zhang, Ling; Lancet, Jeffrey E.; Komrokji, Rami S.; List, Alan F.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Kale, Vishakha] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Komrokji, RS (reprint author), H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr,FOB 3,Room 3117, Tampa, FL 33612 USA. EM rami.komrokji@moffitt.org OI Jaglal, Michael/0000-0002-4305-2535 FU Bristol-Myers Squibb FX We thank Rasa Hamilton (Moffitt Cancer Center) for editorial assistance. This study was funded by Bristol-Myers Squibb. NR 26 TC 8 Z9 8 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD MAR PY 2013 VL 37 IS 3 BP 300 EP 304 DI 10.1016/j.leukres.2012.11.001 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 088XP UT WOS:000314871500014 PM 23273539 ER PT J AU Goulet, JL Brandt, C Crystal, S Fiellin, DA Gibert, C Gordon, AJ Kerns, RD Maisto, S Justice, AC AF Goulet, Joseph L. Brandt, Cynthia Crystal, Stephen Fiellin, David A. Gibert, Cynthia Gordon, Adam J. Kerns, Robert D. Maisto, Stephen Justice, Amy C. TI Agreement Between Electronic Medical Record-based and Self-administered Pain Numeric Rating Scale Clinical and Research Implications SO MEDICAL CARE LA English DT Article DE veterans; pain screening; electronic medical records ID 5TH VITAL SIGN; COGNITIVE IMPAIRMENT; DIABETES PATIENTS; VETERANS; MANAGEMENT; DEPRESSION; PREVALENCE; QUALITY; SYSTEM; CARE AB Background: Pain screening may improve the quality of care by identifying patients in need of further assessment and management. Many health care systems use the numeric rating scale (NRS) for pain screening, and record the score in the patients' electronic medical record (EMR). Objective: Determine the level of agreement between EMR and patient survey NRS, and whether discrepancies vary by demographic and clinical characteristics. Methods: We linked survey data from a sample of veterans receiving care in 8 Veterans Affairs medical facilities, to EMR data including an NRS collected on the day of the survey to compare responses to the NRS question from these 2 sources. We assessed correlation, agreement on clinical cut-points (eg, severe), and, using the survey as the gold standard, whether patient characteristics were associated with a discrepancy on moderate-severe pain. Results: A total of 1643 participants had a survey and EMR NRS score on the same day. The correlation was 0.56 (95% confidence interval, 0.52-0.59), but the mean EMR score was significantly lower than the survey score (1.72 vs. 2.79; P < 0.0001). Agreement was moderate (kappa = 0.35). Characteristics associated with an increased odds of a discrepancy included: diabetes [adjusted odds ratio (AOR) = 1.48], posttraumatic stress disorder (AOR = 1.59), major depressive disorder (AOR = 1.81), other race versus white (AOR = 2.29), and facility in which care was received. Conclusions: The underestimation of pain using EMR data, especially clinically actionable levels of pain, has important clinical and research implications. Improving the quality of pain care may require better screening. C1 [Goulet, Joseph L.; Brandt, Cynthia; Kerns, Robert D.; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. [Goulet, Joseph L.; Kerns, Robert D.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Brandt, Cynthia] Yale Univ, Sch Med, Dept Anesthesiol, New Haven, CT 06510 USA. [Crystal, Stephen] Rutgers State Univ, Inst Hlth, Ctr Hlth Serv Res Pharmacotherapy Chron Dis Manag, New Brunswick, NJ 08903 USA. [Fiellin, David A.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Gibert, Cynthia] VA Med Ctr, Washington, DC USA. [Gibert, Cynthia] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Gordon, Adam J.] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. [Kerns, Robert D.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. [Kerns, Robert D.] Yale Univ, Sch Med, Dept Psychol, New Haven, CT 06510 USA. [Maisto, Stephen] VA Syracuse, Syracuse, NY USA. [Maisto, Stephen] Syracuse Univ, Dept Psychol, Syracuse, NY USA. [Justice, Amy C.] Yale Univ, Sch Med, Sch Med & Publ Hlth, New Haven, CT USA. RP Goulet, JL (reprint author), VA Connecticut Healthcare Syst, 950 Campbell Ave,Bldg 35A,Room 2-207, West Haven, CT 06516 USA. EM joseph.goulet@va.gov OI Fiellin, David/0000-0002-4006-010X; Goulet, Joseph/0000-0002-0842-804X FU National Institute on Alcohol and Alcohol Abuse [U01 AA 13566, U10 AA 13566]; VA HSR&D Research Enhancement Award Program [REAP 08-266]; AHRQ [U18-HS016097] FX Supported by National Institute on Alcohol and Alcohol Abuse (U01 AA 13566 and U10 AA 13566), and VA HSR&D Research Enhancement Award Program (REAP 08-266). S. C.'s work is supported in part by AHRQ U18-HS016097. NR 41 TC 18 Z9 19 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAR PY 2013 VL 51 IS 3 BP 245 EP 250 DI 10.1097/MLR.0b013e318277f1ad PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 090NE UT WOS:000314985100007 PM 23222528 ER PT J AU Walensky, LD AF Walensky, Loren D. TI PROTEIN-PROTEIN INTERACTIONS A PUMA mechanism unfolds SO NATURE CHEMICAL BIOLOGY LA English DT News Item ID P53; ACTIVATION; APOPTOSIS; BAX C1 [Walensky, Loren D.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Walensky, Loren D.] Dana Farber Canc Inst, Linde Program Canc Chem Biol, Boston, MA 02115 USA. RP Walensky, LD (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM loren_walensky@dfci.harvard.edu FU NCI NIH HHS [R01 CA050239]; NIGMS NIH HHS [R01 GM090299] NR 10 TC 0 Z9 0 U1 0 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD MAR PY 2013 VL 9 IS 3 BP 141 EP 143 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 092OW UT WOS:000315132900005 PM 23416398 ER PT J AU Mroz, EA Rocco, JW AF Mroz, Edmund A. Rocco, James W. TI MATH, a novel measure of intratumor genetic heterogeneity, is high in poor-outcome classes of head and neck squamous cell carcinoma SO ORAL ONCOLOGY LA English DT Article DE Head and neck cancer; Intratumor heterogeneity; Tumor biomarkers; Next-generation DNA sequencing; Somatic mutations; TP53; Human papillomavirus; Cigarette smoking ID HUMAN-PAPILLOMAVIRUS; OROPHARYNGEAL CANCER; EVOLUTION; PROGRESSION; DIVERSITY; SURVIVAL; MUTATIONS AB Objectives: Differences among cancer cells within a tumor are important in tumorigenesis and treatment resistance, yet no measure of intratumor heterogeneity is suitable for routine application. We developed a quantitative measure of intratumor genetic heterogeneity, based on differences among mutated loci in the mutant-allele fractions determined by next-generation sequencing (NGS) of tumor DNA. We then evaluated the application of this measure to head and neck squamous cell carcinoma (HNSCC). Materials and methods: We analyzed published electronically available NGS results for 74 HNSCC. For each tumor we calculated mutant-allele tumor heterogeneity (MATH) as the ratio of the width to the center of its distribution of mutant-allele fractions among tumor-specific mutated loci. Results: Intratumor heterogeneity assessed by MATH was higher in three poor-outcome classes of HNSCC: tumors with disruptive mutations in the TP53 gene (versus wild-type TP53 or non-disruptive mutations), tumors negative versus positive for human papillomavirus (even when restricted to tumors having wild-type TP53), and HPV-negative tumors from smokers with more pack-years of cigarette exposure (with TP53 status taken into account). Conclusion: The relation of this type of intratumor heterogeneity to HNSCC outcome classes supports its further evaluation as a prognostic biomarker. As NGS of tumor DNA becomes widespread in clinical research and practice, MATH should provide a simple, quantitative, and clinically practical biomarker to help evaluate relations of intratumor genetic heterogeneity to outcome in any type of cancer. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Mroz, Edmund A.; Rocco, James W.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Mroz, Edmund A.; Rocco, James W.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Rocco, James W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Rocco, James W.] Harvard Univ, Sch Med, Boston, MA USA. RP Rocco, JW (reprint author), Massachusetts Gen Hosp, Jackson 904G,55 Fruit St, Boston, MA 02114 USA. EM jrocco@partners.org FU Norman Knight Fund; Flight Attendant Medical Research Institute; National Institute of Dental and Craniofacial Research [R01 DE022087]; National Cancer Institute [R21 CA119591] FX The Norman Knight Fund, the Flight Attendant Medical Research Institute, the National Institute of Dental and Craniofacial Research (R01 DE022087), and the National Cancer Institute (R21 CA119591). NR 22 TC 28 Z9 28 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 J9 ORAL ONCOL JI Oral Oncol. PD MAR PY 2013 VL 49 IS 3 BP 211 EP 215 DI 10.1016/j.oraloncology.2012.09.007 PG 5 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 088XT UT WOS:000314871900010 PM 23079694 ER PT J AU Morse, LR Sudhakar, S Lazzari, AA Tun, C Garshick, E Zafonte, R Battaglino, RA AF Morse, L. R. Sudhakar, S. Lazzari, A. A. Tun, C. Garshick, E. Zafonte, R. Battaglino, R. A. TI Sclerostin: a candidate biomarker of SCI-induced osteoporosis SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE Bone biomarker; Osteoporosis; Rehabilitation medicine; Sclerostin; Spinal cord injury ID SPINAL-CORD-INJURY; X-RAY ABSORPTIOMETRY; REDUCES OSTEOCYTE EXPRESSION; BONE-MINERAL DENSITY; MECHANICAL STIMULATION; ASSOCIATION; PROTEINS; MARKERS; MICE AB We assessed several circulating proteins as candidate biomarkers of bone status in men with chronic spinal cord injury. We report that sclerostin is significantly associated with bone mineral content and bone density at all skeletal sites tested. We found no association between bone and any other tested biomarker. Spinal cord injury results in severe osteoporosis. To date, no circulating biomarker of spinal cord injury (SCI)-induced osteoporosis has been identified. We recently reported that circulating sclerostin is associated with bone density in chronic SCI. In this study, we assessed several circulating proteins as candidate biomarkers of bone in men with chronic SCI. We assessed the relationship between bone mineral content or bone density and the following circulating bone-related proteins: sclerostin, DKK-1, soluble receptor activator of nuclear factor kappa B ligand, osteoprotegerin, osteocalcin, and c-telopeptide in 39 men with chronic SCI and 10 men with no SCI. After adjusting for age, lower sclerostin levels were significantly associated with lower bone mineral content and bone density at all skeletal sites tested (p = 0.0002-0.03). No other circulating protein was associated with bone mineral content or bone mineral density (p = 0.18-0.99). These findings suggest that circulating sclerostin reflects the severity of bone loss and is a candidate biomarker of osteoporosis severity in chronic SCI. C1 [Morse, L. R.; Zafonte, R.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Morse, L. R.; Sudhakar, S.; Zafonte, R.] Spaulding Rehabil Hosp, Spaulding Harvard SCI Model Syst, Boston, MA USA. [Morse, L. R.; Battaglino, R. A.] Forsyth Inst, Cambridge, MA 02142 USA. [Morse, L. R.] VA Boston Healthcare Syst, Spinal Cord Injury Serv, Boston, MA USA. [Lazzari, A. A.] VA Boston Healthcare Syst, Primary Care & Rehabil Sect, Boston, MA USA. [Lazzari, A. A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Tun, C.] VA Boston Healthcare Syst, Rehabil Med Serv, Boston, MA USA. [Garshick, E.] VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, Med Serv, Boston, MA USA. [Garshick, E.] Harvard Univ, Brigham & Womens Hosp, Channing Lab, Dept Med,Med Sch, Boston, MA 02115 USA. [Battaglino, R. A.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Battaglino, R. A.] Forsyth Inst, Skeletal Biol Dept, Cambridge, MA 02142 USA. RP Battaglino, RA (reprint author), Forsyth Inst, Skeletal Biol Dept, 245 1st St, Cambridge, MA 02142 USA. EM rbattaglino@forsyth.org RI battaglino, ricardo/D-2892-2015; Morse, Leslie/C-9442-2015 OI Morse, Leslie/0000-0002-7426-6341 FU National Institute of Child Health and Human Development [R21HD057030, R21HD057030-02S1]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [1R01AR059270]; Office of Research and Development, Rehabilitation Research and Development [B6618R] FX This study received support from: the National Institute of Child Health and Human Development [R21HD057030 and R21HD057030-02S1], the National Institute of Arthritis and Musculoskeletal and Skin Diseases [1R01AR059270], and the Office of Research and Development, Rehabilitation Research and Development [Merit Review Grant B6618R]. NR 27 TC 13 Z9 14 U1 0 U2 16 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD MAR PY 2013 VL 24 IS 3 BP 961 EP 968 DI 10.1007/s00198-012-2072-0 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089DH UT WOS:000314889100022 PM 22801952 ER PT J AU Parikh, H Jia, JP Zhang, XJ Chung, CC Jacobs, KB Yeager, M Boland, J Hutchinson, A Burdett, L Hoskins, J Risch, HA Stolzenberg-Solomon, RZ Chanock, SJ Wolpin, BM Petersen, GM Fuchs, CS Hartge, P Amundadottir, L AF Parikh, Hemang Jia, Jinping Zhang, Xijun Chung, Charles C. Jacobs, Kevin B. Yeager, Meredith Boland, Joseph Hutchinson, Amy Burdett, Laura Hoskins, Jason Risch, Harvey A. Stolzenberg-Solomon, Rachael Z. Chanock, Stephen J. Wolpin, Brian M. Petersen, Gloria M. Fuchs, Charles S. Hartge, Patricia Amundadottir, Laufey TI A Resequence Analysis of Genomic Loci on Chromosomes 1q32.1, 5p15.33, and 13q22.1 Associated With Pancreatic Cancer Risk SO PANCREAS LA English DT Article DE pancreatic cancer; targeted resequencing; GWAS; susceptibility loci; SNP; 1000G ID COHORT-CONSORTIUM PANSCAN; SUSCEPTIBILITY LOCI; WIDE ASSOCIATION; POOLED-ANALYSIS; TERT-CLPTM1L LOCUS; VARIANTS; LUNG; PROSTATE; HISTORY AB Objective: The objective of this study was to fine-map common pancreatic cancer susceptibility regions. Methods: We conducted targeted Roche-454 resequencing across 428 kb in 3 genomic regions identified in genome-wide association studies (GWAS) of pancreatic cancer, on chromosomes 1q32.1, 5p15.33, and 13q22.1. Results: An analytical pipeline for calling genotypes was developed using HapMap samples sequenced on chr5p15.33. Concordance to 1000 Genomes data for chr5p15.33 was greater than 96%. The concordance for chr1q32.1 and chr13q22.1 with pancreatic cancer GWAS data was greater than 99%. Between 9.2% and 19.0% of variants detected were not present in 1000 Genomes for the respective continental population. The majority of completely novel single-nucleotide polymorphisms (SNPs) were less common (minor allele frequency [MAF], <= 5%) or rare (MAF, <= 2%), illustrating the value of enlarging test sets for discovery of less common variants. Using the data set, we examined haplotype blocks across each region using a tag SNP analysis (r(2) > 0.8 for MAF of >= 5%) and determined that at least 196, 243, and 63 SNPs are required for fine-mapping chr1q32.1, chr5p15.33, and chr13q22.1, respectively, in European populations. Conclusions: We have characterized germline variation in 3 regions associated with pancreatic cancer risk and show that targeted resequencing leads to the discovery of novel variants and improves the completeness of germline sequence variants for fine-mapping GWAS susceptibility loci. C1 [Parikh, Hemang; Jia, Jinping; Chung, Charles C.; Hoskins, Jason; Chanock, Stephen J.; Amundadottir, Laufey] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Parikh, Hemang; Jia, Jinping; Zhang, Xijun; Chung, Charles C.; Jacobs, Kevin B.; Yeager, Meredith; Boland, Joseph; Hutchinson, Amy; Burdett, Laura; Hoskins, Jason; Stolzenberg-Solomon, Rachael Z.; Chanock, Stephen J.; Hartge, Patricia; Amundadottir, Laufey] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Zhang, Xijun; Jacobs, Kevin B.; Yeager, Meredith; Boland, Joseph; Hutchinson, Amy; Burdett, Laura] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA. [Risch, Harvey A.] Yale Univ, Sch Med, Sch Publ Hlth, New Haven, CT USA. [Wolpin, Brian M.; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wolpin, Brian M.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Wolpin, Brian M.; Fuchs, Charles S.] Harvard Univ, Sch Med, Boston, MA USA. [Petersen, Gloria M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. RP Amundadottir, L (reprint author), NIH, Lab Translat Genom, Div Canc Epidemiol & Genet, 8717 Grovemont Circle, Gaithersburg, MD 20877 USA. EM amundadottirl@mail.nih.gov RI Hoskins, Jason/F-5672-2012; Amundadottir, Laufey/L-7656-2016 OI Hoskins, Jason/0000-0001-6944-1996; Amundadottir, Laufey/0000-0003-1859-8971 FU Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH) [HHSN261200800001E] FX This work was supported in part by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH) under contract no. HHSN261200800001E. NR 37 TC 4 Z9 4 U1 1 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD MAR PY 2013 VL 42 IS 2 BP 209 EP 215 DI 10.1097/MPA.0b013e318264cea5 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 090JL UT WOS:000314975200005 PM 23295781 ER PT J AU Chen, MC Go, VLW Wu, SV AF Chen, Monica C. Go, Vay Liang W. Wu, S. Vincent TI Identification and Characterization of Corticotropin Releasing Hormone (CRH) Type 1 System in Human Pancreatic Neuroendocrine Tumors SO PANCREAS LA English DT Meeting Abstract C1 [Chen, Monica C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Go, Vay Liang W.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Wu, S. Vincent] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 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 0885-3177 J9 PANCREAS JI Pancreas PD MAR PY 2013 VL 42 IS 2 BP 371 EP 371 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 090JL UT WOS:000314975200045 ER PT J AU Chen, MC Go, VLW Pham, H Mulugeta, M Solorzano, S Martin, MG Tache, Y Wu, SV AF Chen, Monica C. Go, Vay Liang W. Hung Pham Mulugeta, Million Solorzano, Sergio Martin, Martin G. Tache, Yvette Wu, S. Vincent TI Regulation of Corticotropin Releasing Hormone (CRH) and Urocortin Family Peptide Expression in Human Carcinoid BON Cells SO PANCREAS LA English DT Meeting Abstract C1 [Chen, Monica C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Go, Vay Liang W.; Hung Pham; Mulugeta, Million; Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Solorzano, Sergio; Martin, Martin G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. [Tache, Yvette; Wu, S. Vincent] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 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 0885-3177 J9 PANCREAS JI Pancreas PD MAR PY 2013 VL 42 IS 2 BP 371 EP 372 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 090JL UT WOS:000314975200046 ER PT J AU Choti, MA Bobiak, S Strosberg, JR Benson, AB Bloomston, PM Yao, JC Zornosa, CC Bergsland, EK Kulke, MH Nakakura, EK Shah, MH AF Choti, Michael A. Bobiak, Sarah Strosberg, Jonathan R. Benson, Al B., III Bloomston, P. Mark Yao, James C. Zornosa, Carrie C. Bergsland, Emily K. Kulke, Matthew H. Nakakura, Eric K. Shah, Manisha H. TI Prevalence of Functional Tumors in Neuroendocrine Carcinoma: An Analysis from the NCCN NET Database SO PANCREAS LA English DT Meeting Abstract C1 [Choti, Michael A.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA. [Bobiak, Sarah; Zornosa, Carrie C.] Natl Comprehens Canc Network, Ft Washington, PA 19034 USA. [Strosberg, Jonathan R.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Benson, Al B., III] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Bloomston, P. Mark; Shah, Manisha H.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Bloomston, P. Mark; Shah, Manisha H.] Solove Res Inst, Columbus, OH 43210 USA. [Yao, James C.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Bergsland, Emily K.; Nakakura, Eric K.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Kulke, Matthew H.] Dana Farber Canc Inst, Boston, MA 02215 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 0885-3177 J9 PANCREAS JI Pancreas PD MAR PY 2013 VL 42 IS 2 BP 372 EP 372 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 090JL UT WOS:000314975200047 ER PT J AU Kulke, MH Chan, JA Ryan, DP Meyerhardt, JA Fuchs, CS Abrams, T Regan, E Brady, R Weber, J Campos, T Kvols, LK Strosberg, JR AF Kulke, Matthew H. Chan, Jennifer A. Ryan, David P. Meyerhardt, Jeffrey A. Fuchs, Charles S. Abrams, Thomas Regan, Eileen Brady, Rachel Weber, Jill Campos, Tiffany Kvols, Larry K. Strosberg, Jonathan R. TI A Multi-Institutional Phase II Open-Label Study of AMG 479 in Advanced Carcinoid and Pancreatic Neuroendocrine Tumors SO PANCREAS LA English DT Meeting Abstract C1 [Kulke, Matthew H.; Chan, Jennifer A.; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Abrams, Thomas; Regan, Eileen; Brady, Rachel] Dana Farber Canc Inst, Boston, MA 02215 USA. [Ryan, David P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Weber, Jill; Campos, Tiffany; Kvols, Larry K.; Strosberg, Jonathan R.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 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 0885-3177 J9 PANCREAS JI Pancreas PD MAR PY 2013 VL 42 IS 2 BP 377 EP 377 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 090JL UT WOS:000314975200064 ER PT J AU Qian, ZR Ter-Minassian, M Chan, JA Imamura, Y Hooshmand, SM Kuchiba, A Morikawa, T Brais, LK Daskalova, A Heafield, R Lin, XH Christiani, DC Fuchs, CS Ogino, S Kulke, MH AF Qian, Zhi Rong Ter-Minassian, Monica Chan, Jennifer A. Imamura, Yu Hooshmand, Susanne M. Kuchiba, Aya Morikawa, Teppei Brais, Lauren K. Daskalova, Anastassia Heafield, Rachel Lin, Xihong Christiani, David C. Fuchs, Charles S. Ogino, Shuji Kulke, Matthew H. TI Expression of MTOR Pathway Components and Association With Clinical Outcomes in Neuroendocrine Tumors SO PANCREAS LA English DT Meeting Abstract C1 [Qian, Zhi Rong; Ter-Minassian, Monica; Chan, Jennifer A.; Imamura, Yu; Hooshmand, Susanne M.; Kuchiba, Aya; Morikawa, Teppei; Brais, Lauren K.; Daskalova, Anastassia; Heafield, Rachel; Fuchs, Charles S.; Ogino, Shuji; Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Qian, Zhi Rong; Ter-Minassian, Monica; Chan, Jennifer A.; Imamura, Yu; Hooshmand, Susanne M.; Kuchiba, Aya; Morikawa, Teppei; Brais, Lauren K.; Daskalova, Anastassia; Heafield, Rachel; Fuchs, Charles S.; Ogino, Shuji; Kulke, Matthew H.] Harvard Univ, Sch Med, Boston, MA USA. [Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Ter-Minassian, Monica; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Christiani, David C.; Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD MAR PY 2013 VL 42 IS 2 BP 379 EP 379 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 090JL UT WOS:000314975200073 ER PT J AU Schnabel, CA Kerr, SE Sullivan, P Zhang, Y Singh, V Carey, B Erlander, MG Highsmith, WE Brachtel, EF Dry, SM AF Schnabel, Catherine A. Kerr, Sarah E. Sullivan, Peggy Zhang, Yi Singh, Veena Carey, Brittany Erlander, Mark G. Highsmith, W. Edward Brachtel, Elena F. Dry, Sarah M. TI Use of a 92-gene Molecular Classifier to Predict the Site of Origin for Primary and Metastatic Tumors with Neuroendocrine Differentiation SO PANCREAS LA English DT Meeting Abstract C1 [Schnabel, Catherine A.; Zhang, Yi; Singh, Veena; Erlander, Mark G.] BioTheranostics Inc, San Diego, CA USA. [Kerr, Sarah E.; Highsmith, W. Edward] Mayo Clin, Rochester, MN USA. [Sullivan, Peggy; Dry, Sarah M.] Univ Calif Los Angeles, Los Angeles, CA USA. [Carey, Brittany; Brachtel, Elena F.] Massachussetts Gen Hosp, Boston, MA 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 0885-3177 J9 PANCREAS JI Pancreas PD MAR PY 2013 VL 42 IS 2 BP 380 EP 380 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 090JL UT WOS:000314975200074 ER PT J AU Ter-Minassian, M Chan, JA Hooshmand, SM Brais, LK Daskalova, A Heafield, R Buchanan, L Qian, ZR Lin, XH Christiani, DC Kulke, MH AF Ter-Minassian, Monica Chan, Jennifer A. Hooshmand, Susanne M. Brais, Lauren K. Daskalova, Anastassia Heafield, Rachel Buchanan, Laurie Qian, Zhi Rong Lin, Xihong Christiani, David C. Kulke, Matthew H. TI Duration and Type of Presenting Symptoms in Patients with Neuroendocrine Tumor (NET) SO PANCREAS LA English DT Meeting Abstract C1 [Ter-Minassian, Monica; Chan, Jennifer A.; Hooshmand, Susanne M.; Brais, Lauren K.; Daskalova, Anastassia; Heafield, Rachel; Buchanan, Laurie; Qian, Zhi Rong; Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ter-Minassian, Monica; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 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 0885-3177 J9 PANCREAS JI Pancreas PD MAR PY 2013 VL 42 IS 2 BP 384 EP 384 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 090JL UT WOS:000314975200088 ER PT J AU Yao, JC Pavel, ME Fazio, N Kulke, M Singh, S Shah, G Klimovsky, J Strosberg, J AF Yao, James C. Pavel, Marianne E. Fazio, Nicola Kulke, Matthew Singh, Simron Shah, Gaurav Klimovsky, Judith Strosberg, Jonathan TI RADIANT-4: A Randomized, Double-blind, Multicenter, Phase III Study of Everolimus Versus Placebo in the Treatment of Patients With Advanced Non-functional NET of GI or Lung Origin SO PANCREAS LA English DT Meeting Abstract C1 [Yao, James C.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Pavel, Marianne E.] Charite, Campus Virchow Klinikum, D-10117 Berlin, Germany. [Fazio, Nicola] European Inst Oncol, I-20141 Milan, Italy. [Kulke, Matthew] Dana Farber Canc Inst, Boston, MA 02215 USA. Sunnybrook Odette Canc Ctr, Toronto, ON M4N 3M5, Canada. [Singh, Simron; Shah, Gaurav; Klimovsky, Judith] Novartis, Florham Pk, NJ 07932 USA. [Strosberg, Jonathan] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 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 0885-3177 J9 PANCREAS JI Pancreas PD MAR PY 2013 VL 42 IS 2 BP 386 EP 386 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 090JL UT WOS:000314975200096 ER PT J AU Zornosa, CC Choti, MA Bobiak, S Kulke, MH Yao, JC Bergsland, EK Nakakura, EK Bloomston, PM Benson, AB Shah, MH Strosberg, JR AF Zornosa, Carrie C. Choti, Michael A. Bobiak, Sarah Kulke, Matthew H. Yao, James C. Bergsland, Emily K. Nakakura, Eric K. Bloomston, P. Mark Benson, Al B., III Shah, Manisha H. Strosberg, Jonathan R. TI Baseline Demographics of Neuroendocrine Tumor Patients Presenting to Seven National Comprehensive Cancer Network (NCCN) Institutions: Development of a Multi-Institutional Outcomes Database SO PANCREAS LA English DT Meeting Abstract C1 [Zornosa, Carrie C.; Bobiak, Sarah] Natl Comprehens Canc Network, Ft Washington, PA 19034 USA. [Choti, Michael A.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA. [Kulke, Matthew H.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Yao, James C.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Bergsland, Emily K.; Nakakura, Eric K.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Bloomston, P. Mark; Shah, Manisha H.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Bloomston, P. Mark; Shah, Manisha H.] Solove Res Inst, Columbus, OH 43210 USA. [Benson, Al B., III] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Strosberg, Jonathan R.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 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 0885-3177 J9 PANCREAS JI Pancreas PD MAR PY 2013 VL 42 IS 2 BP 387 EP 387 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 090JL UT WOS:000314975200099 ER PT J AU Schendan, HE Ganis, G AF Schendan, Haline E. Ganis, Giorgio TI Face-specificity is robust across diverse stimuli and individual people, even when interstimulus variance is zero SO PSYCHOPHYSIOLOGY LA English DT Article DE Sensation; Perception; EEG; ERP; Cognition; Individual differences; Learning; Memory; Normal volunteers ID PERCEPTUAL VARIANCE; HUMAN BRAIN; N170; ACCOUNT; CORTEX AB The N170 is a brain electrical potential proposed to index the earliest time of categorical perception of faces in occipitotemporal visual areas implicated in face cognition, being more negative for faces than nonface objects between 120 and 200ms. The interstimulus variance (ISV) account instead explained N170 face-specificity as an artifact due to objects varying more visually than faces. Ganis, Smith, and Schendan (2012) tested this account directly, finding that N170 face-specificity remains even when ISV is eliminated. Here, N170 peak amplitude and face-specificity is quantified for individual stimuli and participants, revealing that the right hemisphere N170 is especially sensitive to stimulus variability. Further, ISV contributes 0 to 37% to N170 face-specificity. These findings provide evidence for optimizing face processing science. The paradigm can apply to any research in which ISV may be uncontrolled (e.g., category comparisons). C1 [Schendan, Haline E.; Ganis, Giorgio] Univ Plymouth, Sch Psychol, Cognit Inst, Plymouth PL4 8AA, Devon, England. [Schendan, Haline E.; Ganis, Giorgio] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Ganis, Giorgio] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Schendan, HE (reprint author), Univ Plymouth, Sch Psychol, Plymouth PL4 8AA, Devon, England. EM haline.schendan@plymouth.ac.uk RI sebastianovitsch, stepan/G-8507-2013; OI Ganis, Giorgio/0000-0001-6175-2618; Schendan, Haline/0000-0001-8925-5605 FU Plymouth University FX Research was supported by Plymouth University. NR 15 TC 2 Z9 4 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD MAR PY 2013 VL 50 IS 3 BP 287 EP 291 DI 10.1111/psyp.12013 PG 5 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 087JL UT WOS:000314757500007 PM 23350993 ER PT J AU Fan, X Borba, CPC Copeland, P Hayden, D Freudenreich, O Goff, DC Henderson, DC AF Fan, X. Borba, C. P. C. Copeland, P. Hayden, D. Freudenreich, O. Goff, D. C. Henderson, D. C. TI Metabolic effects of adjunctive aripiprazole in clozapine-treated patients with schizophrenia SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE antipsychotics; schizophrenia; metabolic syndrome ID ATYPICAL ANTIPSYCHOTIC-DRUGS; PLACEBO-CONTROLLED TRIAL; GLUCOSE-TOLERANCE TEST; INSULIN-RESISTANCE; DOUBLE-BLIND; WEIGHT-GAIN; POSTMENOPAUSAL WOMEN; DIABETES-MELLITUS; SKELETAL-MUSCLE; PARTICLE-SIZE AB Fan X, Borba CPC, Copeland P, Hayden D, Freudenreich O, Goff DC, Henderson DC. Metabolic effects of adjunctive aripiprazole in clozapine-treated patients with schizophrenia. Objective: This study examined the effects of adjunctive aripiprazole therapy on metabolism in clozapine-treated patients with schizophrenia. Method: In an 8-week randomized, double-blind, placebo-controlled study, subjects received either aripiprazole (15mg/day) or placebo. At baseline and week 8, metabolic parameters were assessed by the frequently sampled intravenous glucose tolerance test, nuclear magnetic resonance spectroscopy and whole-body dual-energy X-ray absorptiometry (DXA). Results: Thirty subjects completed the study (16 in the aripiprazole group and 14 in the placebo group). Glucose effectiveness measured by the frequently sampled intravenous glucose tolerance test improved significantly in the aripiprazole group (0.003 +/- 0.006 vs. 0.005 +/- 0.007/min, P=0.010). The aripiprazole group showed significant reductions in both plasma low-density lipoprotein (LDL) levels (15.1 +/- 19.8 vs. 4.4 +/- 22.5mg/dl, P=0.019) and LDL particle numbers (376 +/- 632 vs. 36 +/- 301nm, P=0.035). Further, there was a significant reduction in the lean mass (1125 +/- 1620 vs. 607 +/- 1578g, P=0.011) measured by whole-body DXA scan in the aripiprazole group. All values were expressed as mean +/- standard deviation, aripiprazole vs. placebo. Conclusion: Adjunctive therapy with aripiprazole may have some metabolic benefits in clozapine-treated patients with schizophrenia. C1 [Fan, X.; Borba, C. P. C.; Freudenreich, O.; Goff, D. C.; Henderson, D. C.] Massachusetts Gen Hosp, Dept Psychiat, Schizophrenia Program, Boston, MA 02114 USA. [Fan, X.; Borba, C. P. C.; Copeland, P.; Freudenreich, O.; Goff, D. C.; Henderson, D. C.] Harvard Univ, Sch Med, Boston, MA USA. [Copeland, P.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Hayden, D.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Fan, X (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM xiaoduo.fan@umassmed.edu FU National Institutes of Health [5R01MH072635]; National Institutes of Health, National Center for Research Resources General Clinical Research Centers Program (MGH Clinical research Center) [M01-RR-01066, UL1 RR025758-01]; Eli Lilly; AstraZeneca; Bristol-Myer-Squibb; Janssen; Pfizer; Cephalon; Bristol-Myers Squibb; Indevus Pharmaceuticals; H. Lundbeck; Schering-Plough; Takeda; Biovail; Sovay; Hoffman-La Roche; Cypress; Dainippon Sumitomo; Abbott Laboratories; Genentech; Novartis; PamLab; GlaxoSmithKline; Endo Pharmaceuticals; Solvay; Covance; Alkermis FX This study was supported by Grant 5R01MH072635 from the National Institutes of Health (Dr. Henderson), Grant M01-RR-01066 and Grant UL1 RR025758-01 from the National Institutes of Health, National Center for Research Resources General Clinical Research Centers Program (MGH Clinical research Center).; Dr. Fan has received research support or honoraria from Eli Lilly, AstraZeneca, Bristol-Myer-Squibb, Janssen and Pfizer. Dr. Freudenreich has received research support or honoraria from AstraZeneca, Bristol-Myer-Squibb, Janssen, Eli Lilly, Cephalon and Pfizer. Dr. Goff has received research support or honoraria from Bristol-Myers Squibb, Indevus Pharmaceuticals, H. Lundbeck, Schering-Plough, Eli Lilly, Takeda, Biovail, Sovay, Hoffman-La Roche, Cypress, Dainippon Sumitomo, Abbott Laboratories, Genentech, Pfizer, Janssen, Novartis, PamLab and GlaxoSmithKline and Endo Pharmaceuticals. He served on a DSMB for Otsuka. Dr. Henderson has received research support or honoraria from Takeda, Janssen, Solvay, Novartis, Covance, Alkermis and Pfizer. Dr. Borba, Dr. Copeland and Mr. Hayden report no competing interests. NR 55 TC 26 Z9 27 U1 2 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD MAR PY 2013 VL 127 IS 3 BP 217 EP 226 DI 10.1111/acps.12009 PG 10 WC Psychiatry SC Psychiatry GA 088RH UT WOS:000314853200007 PM 22943577 ER PT J AU Gandy, S Haroutunian, V DeKosky, ST Sano, M Schadt, EE AF Gandy, Sam Haroutunian, Vahram DeKosky, Steven T. Sano, Mary Schadt, Eric E. TI CR1 and the "Vanishing Amyloid" Hypothesis of Alzheimer's Disease SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID OLDEST-OLD; DEMENTIA; GENE C1 [Gandy, Sam; Haroutunian, Vahram; Sano, Mary] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Gandy, Sam; Haroutunian, Vahram; Sano, Mary] Icahn Sch Med Mt Sinai, Alzheimers Dis Res Ctr, New York, NY 10029 USA. [Gandy, Sam] Icahn Sch Med Mt Sinai, Ctr Cognit Hlth, New York, NY 10029 USA. [Gandy, Sam] Icahn Sch Med Mt Sinai, NFL Neurol Ctr, New York, NY 10029 USA. [Schadt, Eric E.] Icahn Sch Med Mt Sinai, Inst Genom & Multiscale Biol, New York, NY 10029 USA. [Schadt, Eric E.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Gandy, Sam; Haroutunian, Vahram; Sano, Mary] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [DeKosky, Steven T.] Univ Virginia, Charlottesville, VA USA. RP Gandy, S (reprint author), Icahn Sch Med Mt Sinai, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. EM samuel.gandy@mssm.edu FU BLRD VA [I01 BX000348]; NIA NIH HHS [AG02219, AG025204, AG042965, AG05133, AG05138, AG14449, P01 AG002219, P01 AG014449, P01 AG025204, P50 AG005133, P50 AG005138, RF1 AG042965]; NINDS NIH HHS [NS075685, R01 NS075685] NR 15 TC 8 Z9 9 U1 2 U2 25 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 2013 VL 73 IS 5 BP 393 EP 395 DI 10.1016/j.biopsych.2013.01.013 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 085SP UT WOS:000314634900002 PM 23399469 ER PT J AU McCormick, AV Wheeler, JM Guthrie, CR Liachko, NF Kraemer, BC AF McCormick, Allyson V. Wheeler, Jeanna M. Guthrie, Chris R. Liachko, Nicole F. Kraemer, Brian C. TI Dopamine D2 Receptor Antagonism Suppresses Tau Aggregation and Neurotoxicity SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Alzheimer's disease; antipsychotics; dopamine; drug screen; protein aggregation; tau ID PLACEBO-CONTROLLED TRIALS; CAENORHABDITIS-ELEGANS; ALZHEIMERS-DISEASE; C-ELEGANS; TAUOPATHY; DEMENTIA; METAANALYSIS; PLAQUES; TANGLES; PROTEIN AB Background: Tauopathies, including Alzheimer's disease and frontotemporal dementia, are diseases characterized by the formation of pathological tau protein aggregates in the brain and progressive neurodegeneration. Presently no effective disease-modifying treatments exist for tauopathies. Methods: To identify drugs targeting tau neurotoxicity, we have used a Caenorhabditis elegans model of tauopathy to screen a drug library containing 1120 compounds approved for human use for the ability to suppress tau-induced behavioral effects. Results: One compound, the typical antipsychotic azaperone, improved the motility of tau transgenic worms, reduced levels of insoluble tau, and was protective against neurodegeneration. We found that azaperone reduces insoluble tau in a human cell culture model of tau aggregation and that other antipsychotic drugs (flupenthixol, perphenazine, and zotepine) also ameliorate the effects of tau expression in both models. Conclusions: Reduction of dopamine signaling through the dopamine D2 receptor with the use of gene knockouts in Caenorhabditis elegans or RNA interference knockdown in human cell culture has similar protective effects against tau toxicity. These results suggest dopamine D2 receptor antagonism holds promise as a potential neuroprotective strategy for targeting tau aggregation and neurotoxicity. C1 [McCormick, Allyson V.; Wheeler, Jeanna M.; Guthrie, Chris R.; Liachko, Nicole F.; Kraemer, Brian C.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Kraemer, Brian C.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. RP Kraemer, BC (reprint author), Univ Washington Med, Seattle Vet Affairs Puget Sound Hlth Care Syst, Div Gerontol, 1660 S Columbian Way, Seattle, WA 98108 USA. EM kraemerb@u.washington.edu FU Alzheimer's Association [IIRG-08-90627]; Department of Veterans Affairs; National Institutes of Health [R01NS064131] FX This work was supported by a grant from the Alzheimer's Association (IIRG-08-90627, made possible in part by a generous gift from Sherrill Miller). Support was also provided by the Department of Veterans Affairs and a National Institutes of Health grant [R01NS064131] to BK. NR 24 TC 14 Z9 17 U1 0 U2 21 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 2013 VL 73 IS 5 BP 464 EP 471 DI 10.1016/j.biopsych.2012.08.027 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 085SP UT WOS:000314634900012 PM 23140663 ER PT J AU Kobayashi, E Iyer, AK Hornicek, FJ Amiji, MM Duan, ZF AF Kobayashi, Eisuke Iyer, Arun K. Hornicek, Francis J. Amiji, Mansoor M. Duan, Zhenfeng TI Lipid-functionalized Dextran Nanosystems to Overcome Multidrug Resistance in Cancer: A Pilot Study SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID MESOPOROUS SILICA NANOPARTICLES; P-GLYCOPROTEIN EXPRESSION; CARCINOMA CELL-LINE; DRUG-RESISTANCE; OVARIAN-CANCER; POLYMERIC NANOPARTICLES; ENHANCED PERMEABILITY; PACLITAXEL RESISTANCE; PROGNOSTIC-FACTORS; RNA INTERFERENCE AB The toxicity of anticancer agents and the difficulty in delivering drugs selectively to tumor cells pose a challenge in overcoming multidrug resistance (MDR). Recently, nanotechnology has emerged as a powerful tool in addressing some of the barriers to drug delivery, including MDR in cancer, by utilizing alternate routes of cellular entry and targeted delivery of drugs and genes. However, it is unclear whether doxorubicin (Dox) can be delivered by nanotechnologic approaches. We asked whether (1) Dox-loaded lipid-functionalized dextran-based biocompatible nanoparticles (Dox/NP) can reverse MDR, (2) Dox/NP has more potent cytotoxic effect on MDR tumors than poly(ethylene glycol)-modified liposomal Dox (PLD), and (3) multidrug resistance protein 1 (MDR1) small interfering RNA loaded in these nanoparticles (siMDR1/NP) can modulate MDR. To create stable Dox/NP and siMDR1/NP, we used two different lipid-modified dextran derivatives. The effect of Dox or Dox/NP was tested on drug-sensitive osteosarcoma (KHOS) and ovarian cancer (SKOV-3) cell cultures in triplicate and their respective MDR counterparts KHOSR2 and SKOV-3(TR) in triplicate. We determined the effects on drug retention, transfection efficacy of siMDR1/NP, and P-glycoprotein expression and the antiproliferative effect between Dox/NP and PLD in MDR tumor cells. Fluorescence microscopy revealed efficient uptake of the Dox/NP and fluorescently tagged siMDR1/NP. Dox/NP showed five- to 10-fold higher antiproliferative activity at the 50% inhibitory concentration than free Dox in tumor cells. Dox/NP showed twofold higher activity than PLD in MDR tumor cells. siMDR1/NP (100 nM) suppressed P-glycoprotein expression in KHOSR2. Dextran-lipid nanoparticles are a promising platform for delivering Dox and siRNAs. Biocompatible dextran-based nanoparticles that are directly translatable to clinical medicine may lead to new potential therapeutics for reversing MDR in patients with cancer. C1 [Kobayashi, Eisuke; Hornicek, Francis J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. [Kobayashi, Eisuke; Hornicek, Francis J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Kobayashi, Eisuke; Hornicek, Francis J.; Duan, Zhenfeng] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Iyer, Arun K.; Amiji, Mansoor M.] Northeastern Univ, Dept Pharmaceut Sci, Sch Pharm, Boston, MA 02115 USA. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, 100 Blossom St,Jackson 1115, Boston, MA 02114 USA. EM zduan@partners.org RI Amiji, Mansoor/A-4365-2014; OI Amiji, Mansoor/0000-0001-6170-881X; Iyer, Arun/0000-0002-4428-0222 FU National Cancer Institute/NIH [UO1-CA 151452]; Gattegno Fund; Wechsler Fund; Kenneth Stanton Fund for Sarcoma (Nashua, NH, USA); Sarcoma Foundation of America (Damascus, MD, USA); Chordoma Foundation (Durham, NC, USA) FX The institution of one or more of the authors certifies that they have received during the study period funding from grants from the National Cancer Institute/NIH (UO1-CA 151452) (MMA, ZD), Gattegno and Wechsler Funds (FJH, ZD), Kenneth Stanton Fund for Sarcoma (Nashua, NH, USA) (FJH, ZD), Sarcoma Foundation of America (Damascus, MD, USA) (ZD), and The Chordoma Foundation (Durham, NC, USA) (ZD). Each author certifies that he or she, or a member of his or her immediate family, has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. NR 59 TC 23 Z9 23 U1 0 U2 44 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 MAR PY 2013 VL 471 IS 3 BP 915 EP 925 DI 10.1007/s11999-012-2610-2 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 084EC UT WOS:000314518500030 PM 23011844 ER PT J AU Palioura, S Chodosh, J Pineda, R AF Palioura, Sotiria Chodosh, James Pineda, Roberto TI A Novel Approach to the Management of a Progressive Descemet Membrane Tear in a Patient With Keratoglobus and Acute Hydrops SO CORNEA LA English DT Article DE keratoglobus; corneal hydrops; DSAEK; corneal ectasia; keratoconus ID ACUTE CORNEAL HYDROPS; INTRACAMERAL INJECTION; KERATOCONUS; DEGENERATION; SECONDARY; C3F8 AB Purpose: To report a case of corneal hydrops in a patient with keratoglobus that was managed with endothelial keratoplasty to achieve corneal stability and prevent a limbus-to-limbus tear in Descemet membrane. Methods: A 30-year-old man with keratoglobus presented with corneal hydrops in his left eye resulting from a central vertical tear in Descemet membrane. His other eye had been previously treated with penetrating keratoplasty using a large graft (an 11-mm donor graft to a 10-mm recipient bed) because of a limbus-to-limbus tear in Descemet membrane without resolution of his edema. An attempt to approximate the edges of the Descemet tear in the left eye by an intracameral air injection failed, and the tear continued to progress peripherally. An endothelial keratoplasty button with anchoring sutures was placed over the Descemet tear because of excessive localized edema. Results: One month after insertion of the sutured endothelial keratoplasty button, the edema had resolved, and 1 year later, the tear remains sealed. The patient's visual acuity improved from counting fingers at 1 foot to 20/100. Conclusions: Reconstitution of the posterior corneal surface in keratoglobus-induced hydrops can be achieved with endothelial keratoplasty over the Descemet tear. Preventing progression of a central Descemet tear is essential to bypass the need for a large-diameter penetrating keratoplasty graft and its complications in a young patient with a history of bilateral corneal hydrops. C1 [Palioura, Sotiria; Chodosh, James; Pineda, Roberto] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea Serv,Dept Ophthalmol, Boston, MA 02114 USA. RP Pineda, R (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM roberto_pineda@meei.har-vard.edu FU Research to Prevent Blindness Inc, New York FX Supported in part by an unrestricted grant to the Department of Ophthalmology, Harvard Medical School, from Research to Prevent Blindness Inc, New York. NR 9 TC 0 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD MAR PY 2013 VL 32 IS 3 BP 355 EP 358 DI 10.1097/ICO.0b013e31825cea80 PG 4 WC Ophthalmology SC Ophthalmology GA 088FH UT WOS:000314818700022 PM 22893098 ER PT J AU Tamez, H Kalim, S Thadhani, RI AF Tamez, Hector Kalim, Sahir Thadhani, Ravi I. TI Does vitamin D modulate blood pressure? SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE active vitamin D analogs; blood pressure and hypertension; renin-angiotensin-aldosterone axis; vitamin D ID RENIN-ANGIOTENSIN SYSTEM; 25-HYDROXYVITAMIN D LEVELS; NUTRITION EXAMINATION SURVEY; RANDOMIZED CONTROLLED-TRIAL; 3RD NATIONAL-HEALTH; INCIDENT HYPERTENSION; 1,25-DIHYDROXYVITAMIN D-3; CARDIOVASCULAR-DISEASE; PARATHYROID-HORMONE; D SUPPLEMENTATION AB Purpose of review Both vitamin D deficiency and hypertension are highly prevalent. It is unclear whether vitamin D modulates blood pressure and therefore whether vitamin D testing and therapy should become part of routine hypertension prevention and management. This article provides an overview of the data, with special emphasis on the work published in the last 2 years. Recent findings Several animal studies corroborate the strong effect of vitamin D on the renin-angiotensin-aldosterone axis. Small and large observational studies have found associations between vitamin D, increased blood pressure, and the risk of developing hypertension. In contrast, recent data from randomized trials are mixed. Two randomized trials with approximately 1 year of follow-up detected no association between vitamin D treatment and blood pressure, whereas another study of active vitamin D reported a 9-mmHg decrease in systolic blood pressure. Meta-analyses have linked vitamin D levels with blood pressure, but the effect of vitamin D administration on blood pressure remains controversial. Summary Vitamin D deficiency is asociated with high blood pressure in observational studies. This effect is thought to be partly mediated through regulation of the renin-angiotensin-aldosterone axis. However, randomized clinical trials and their meta-analyses have yielded inconclusive results. Large randomized trials focusing on patients with severe vitamin D deficiency and hypertension are needed before vitamin D can be recommended for the prevention or treatment of hypertension. C1 [Tamez, Hector; Kalim, Sahir; Thadhani, Ravi I.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. RP Tamez, H (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Bulfinch 127, Boston, MA 02114 USA. EM htamez@partners.org FU Abbott Laboratories; National Institutes of Health [K24 DK094872, R01 DK094486] FX R.I.T. has a research grant from Abbott Laboratories and is supported by grants K24 DK094872 and R01 DK094486 from the National Institutes of Health. H.T. and S.K. have no conflicts of interest. NR 44 TC 22 Z9 27 U1 1 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD MAR PY 2013 VL 22 IS 2 BP 204 EP 209 DI 10.1097/MNH.0b013e32835d919b PG 6 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 086PC UT WOS:000314696900011 PM 23299053 ER PT J AU Christov, M Pereira, R Wesseling-Perry, K AF Christov, Marta Pereira, Renata Wesseling-Perry, Kate TI Bone biopsy in renal osteodystrophy: continued insights into a complex disease SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE African-American; chronic kidney disease mineral and bone disorder; fibroblast growth factor 23; osteocyte; pediatric ID CHRONIC KIDNEY-DISEASE; GROWTH-FACTOR 23; ADYNAMIC BONE; HEMODIALYSIS-PATIENTS; SECONDARY HYPERPARATHYROIDISM; CORONARY CALCIFICATION; PARATHYROID-HORMONE; MINERAL METABOLISM; TURNOVER; CALCIUM AB Purpose of review The pathogenesis and optimal therapy of renal bone disease remains poorly understood in chronic kidney disease (CKD) and dialysis patients. Bone biopsy is thus far the only window into cellular and molecular events in bone. This review will focus on recent insights into the pathophysiology of renal bone disease, as highlighted by bone biopsy, and discuss implications for treatment. Recent findings Abnormalities in bone physiology start very early in children and adults with CKD, when most clinically measurable mineral metabolism parameters are normal. In addition, racial differences, known to exist in serum markers such as parathyroid hormone, also appear prominent in the bone, suggesting that clinical treatment guidelines may not address the needs of all patient populations. The effects of treatments for secondary hyperparathyroidism on bone may be unexpected. Summary With the help of bone biopsy studies, molecular insights into the pathogenesis of renal osteodystrophy are beginning to emerge. Current therapies may have unexpected effects on bone physiology. C1 [Christov, Marta] Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02214 USA. [Christov, Marta] Massachusetts Gen Hosp, Div Endocrinol, Boston, MA 02114 USA. [Pereira, Renata; Wesseling-Perry, Kate] UCLA Sch Med, Los Angeles, CA USA. RP Christov, M (reprint author), Beth Israel Deaconess Med Ctr, 185 Pilgrim Rd,Farr8 Renal Unit, Boston, MA 02214 USA. EM mchrist3@bidmc.harvard.edu FU NIDDK NIH HHS [K08 DK093608] NR 33 TC 3 Z9 6 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD MAR PY 2013 VL 22 IS 2 BP 210 EP 215 DI 10.1097/MNH.0b013e32835dda01 PG 6 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 086PC UT WOS:000314696900012 PM 23318700 ER PT J AU Mount, DB AF Mount, David B. TI The kidney in hyperuricemia and gout SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE allopurinol; colchicine; febuxostat; gout; transporter; uric acid ID SERUM URIC-ACID; NUTRITION EXAMINATION SURVEY; OF-RHEUMATOLOGY GUIDELINES; US GENERAL-POPULATION; URATE TRANSPORTER; ESSENTIAL-HYPERTENSION; METABOLIC SYNDROME; RENAL EXCRETION; NATIONAL-HEALTH; ADVERSE EVENTS AB Purpose of review Gout is a painful inflammatory arthritis associated with hyperuricemia, with a prevalence of almost 10 million in the USA. Reduced renal excretion of urate is the underlying hyperuricemic mechanism in the vast majority of gout patients; most of the genes that affect serum urate level (SUA) encode urate transporters or associated regulatory proteins. Acquired influences can also modulate SUA and renal urate excretion, sometimes precipitating acute gout. Coincidentally, the prevalence of renal comorbidities in gout - hypertension, chronic kidney disease (CKD), and nephrolithiasis - is very high. Recent findings Recent advances in genetics and molecular physiology have greatly enhanced the understanding of renal reabsorption and secretion of filtered urate. Moreover, baseline SUA appears to be set by the net balance of absorption and secretion across epithelial cells in the kidney and intestine. There have also been substantial advances in the management of gout in patients with CKD. Summary The stage is set for an increasingly molecular understanding of baseline and regulated urate transport by the kidney and intestine. The increasing prevalence of gout with CKD will be balanced by an expanding spectrum of therapeutic options for this important disease. C1 [Mount, David B.] VA Boston Healthcare Syst, Brigham & Womens Hosp, Div Renal, Boston, MA USA. RP Mount, DB (reprint author), R Oom 540,4 Blackfan Circle, Boston, MA 02115 USA. EM david.mount2@va.gov FU NIH [DK070756]; Veterans Administration; Takeda FX The author's research in this area has been supported by the NIH (DK070756) and the Veterans Administration. He is the recipient of an investigator-initiated research grant from Takeda. NR 74 TC 15 Z9 16 U1 2 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD MAR PY 2013 VL 22 IS 2 BP 216 EP 223 DI 10.1097/MNH.0b013e32835ddad2 PG 8 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 086PC UT WOS:000314696900013 PM 23318701 ER PT J AU Lai, PS Christiani, DC AF Lai, Peggy S. Christiani, David C. TI Long-term respiratory health effects in textile workers SO CURRENT OPINION IN PULMONARY MEDICINE LA English DT Review DE byssinosis; chronic obstructive pulmonary disease; endotoxin; lung; textile; vegetable dust ID OBSTRUCTIVE PULMONARY-DISEASE; CHRONIC LUNG-DISEASE; AIR-FLOW OBSTRUCTION; COTTON DUST; VENTILATORY CAPACITY; ENDOTOXIN EXPOSURE; BYSSINOSIS; EPIDEMIOLOGY; PREDICTORS; REACTIVITY AB Purpose of review Over 60 million people worldwide work in the textile or clothing industry. Recent studies have recognized the contribution of workplace exposures to chronic lung diseases, in particular chronic obstructive pulmonary disease (COPD). Early studies in textile workers have focused on the relationship between hemp or cotton dust exposure and the development of a syndrome termed byssinosis. The purpose of this review is to evaluate the effect of long-term exposure to organic dust in textile workers on chronic respiratory disease in the broader context of disease classifications, such as reversible or irreversible obstructive lung disease (i.e. asthma or COPD), and restrictive lung disease. Recent findings Cessation of exposure to cotton dust leads to improvement in lung function. Recent animal models have suggested a shift in the lung macrophage: dendritic cell population ratio as a potential mechanistic explanation for persistent inflammation in the lung due to repeated cotton dust-related endotoxin exposure. Other types of textile dust, such as silk, may contribute to COPD in textile workers. Summary Textile dust-related obstructive lung disease has characteristics of both asthma and COPD. Significant progress has been made in the understanding of chronic lung disease due to organic dust exposure in textile workers. C1 [Lai, Peggy S.; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth Environm & Occupat Med & Epide, Boston, MA 02115 USA. [Lai, Peggy S.; Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA USA. RP Lai, PS (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Bulfinch 148,55 Fruit St, Boston, MA 02114 USA. EM pslai@hsph.harvard.edu OI Lai, Peggy/0000-0001-9501-8606 FU NIOSH [RO1OH02421]; NIH [ES000002, F32 ES020082] FX Funded by grants RO1OH02421 from NIOSH, ES000002 and F32 ES020082 from NIH. NR 47 TC 19 Z9 19 U1 0 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-5287 EI 1531-6971 J9 CURR OPIN PULM MED JI Curr. Opin. Pulm. Med. PD MAR PY 2013 VL 19 IS 2 BP 152 EP 157 DI 10.1097/MCP.0b013e32835cee9a PG 6 WC Respiratory System SC Respiratory System GA 081UX UT WOS:000314349000010 PM 23361196 ER PT J AU Moon, HS Dincer, F Mantzoros, CS AF Moon, H. -S. Dincer, F. Mantzoros, C. S. TI Amylin-induced downregulation of hippocampal neurogenesis is attenuated by leptin in a STAT3/AMPK/ERK-dependent manner in mice SO DIABETOLOGIA LA English DT Article DE Adiponectin; Amylin; Hippocampal neurogenesis; Leptin; STAT3 signalling ID LONG-TERM POTENTIATION; IN-VITRO; ADIPONECTIN RECEPTORS; ADULT NEUROGENESIS; ALZHEIMERS-DISEASE; INSULIN-RESISTANCE; EX-VIVO; OBESITY; MEMORY; NEUROENDOCRINE AB Both leptin and insulin sensitivity have been linked with pathophysiological processes involving the central nervous system in general, and the hippocampus in particular, but the role of leptin in hippocampal neurogenesis has not yet been elucidated. Also, no previous studies have evaluated whether amylin or the endogenous insulin sensitiser adiponectin interact with leptin to alter hippocampal neurogenesis in mouse hippocampal neuronal (HN) cells or investigated the role of leptin, amylin or adiponectin signalling in mouse HN cells. Hippocampal neurogenesis and leptin, amylin and adiponectin signalling were studied in vitro using mouse H19-7 HN cell lines. Amylin decreased cell proliferation in a dose-dependent manner. This effect was diminished by leptin administration and was dependent on signal transducer and activator of transcription 3 (STAT3)/AMP-activated protein kinase (AMPK)/extracellular signal-regulated kinase (ERK). Adiponectin effects were null. We also observed, using immunocytochemical analysis, that amylin decreased activation of microtubule-associated protein 2, a specific neurite outgrowth marker, and synapsin, a specific synaptogenesis marker. By contrast, both effects were attenuated by co-administration of leptin. Finally, we observed that these effects were blocked by pre-treatment with AG490, a STAT3 inhibitor, and STAT3 small interfering RNA administration. Our data suggest that amylin in pharmacological concentrations may have a neurotoxic effect whereas leptin in physiological and pharmacological concentrations has a protective effect counteracting amylin-decreased hippocampal neurogenesis via STAT3/AMPK/ERK signalling in mouse H19-7 HN cell lines. Overall, our data support a novel role for leptin and amylin in the processes of mouse hippocampal neurogenesis and provide new insights into the mechanisms of neurogenic regulation. C1 [Moon, H. -S.; Dincer, F.; Mantzoros, C. S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02130 USA. [Mantzoros, C. S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA 02130 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Sch Med, Boston VA Healthcare Syst, Endocrinol Sect, JP9B52A,150S Huntington Ave, Boston, MA 02130 USA. EM cmantzor@bidmc.harvard.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [58785, 79929, 81913]; Clinical Science Research and Development Service of the Veterans Affairs (VA) Office of Research and Development [1I01CX000422-01A1] FX The Mantzoros Laboratory was supported by the National Institute of Diabetes and Digestive and Kidney Diseases grants 58785, 79929 and 81913, and by Award No. 1I01CX000422-01A1 from the Clinical Science Research and Development Service of the Veterans Affairs (VA) Office of Research and Development. NR 43 TC 10 Z9 10 U1 0 U2 19 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD MAR PY 2013 VL 56 IS 3 BP 627 EP 634 DI 10.1007/s00125-012-2799-3 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 084IH UT WOS:000314531700022 PM 23224631 ER PT J AU Hong, NJL Hornicek, FJ Harmon, DC Choy, E Chen, YL Yoon, SS Nielsen, GP Szymonifka, J Yeap, BY DeLaney, TF Mullen, JT AF Hong, Nicole J. Look Hornicek, Francis J. Harmon, David C. Choy, Edwin Chen, Yen-Lin Yoon, Sam S. Nielsen, G. Petur Szymonifka, Jackie Yeap, Beow Y. DeLaney, Thomas F. Mullen, John T. TI Neoadjuvant chemoradiotherapy for patients with high-risk extremity and truncal sarcomas: A 10-year single institution retrospective study SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Sarcoma; Neoadjuvant; Chemoradiotherapy; Chemotherapy; Survival; Toxicity; Recurrence; Radiation ID SOFT-TISSUE SARCOMAS; RADIATION-THERAPY; POSTOPERATIVE RADIOTHERAPY; PREOPERATIVE RADIATION; ADJUVANT CHEMOTHERAPY; SURGICAL MARGINS; HIGH-GRADE; POSITIVE MARGINS; RANDOMIZED-TRIAL; LOCAL-CONTROL AB Background: Patients with large, high-grade extremity and truncal soft tissue sarcomas (STS) are at considerable risk for recurrence. A regimen of pre-operative chemotherapy consisting of mesna, adriamycin, ifosfamide and dacarbazine (MAID), interdigitated with radiotherapy (RT), followed by resection and post-operative chemotherapy with or without RT, has demonstrated high rates of local and distant control. The goal of this study is to assess outcomes in a recent cohort of patients treated on this regimen. Methods: We retrospectively reviewed records of 66 consecutive patients with STS of the extremity or trunk who were treated with the aforementioned regimen from May 2000 to April 2011. Clinicopathologic characteristics and patient outcomes were analysed. Results: Sixty-six patients were analysed and were equally divided between grade 2 and 3 tumours. Margins were negative in 57 (89%) patients and positive in seven (11%) patients. At a median follow-up of 46 months, there were six (9%) locoregional and 20 (30%) distant recurrences. The locoregional and distant 5-year recurrence-free survival (RFS) rates were 91% and 64%, respectively. The 5-year overall (OS) and disease-specific survival rates were 86% and 89%, respectively. There were no treatment-related deaths or secondary myelodysplasias. Thirty-four (52%) patients had grade 3 or 4 acute haematologic chemotherapy-related toxicity. There were no statistically significant predictors of OS or RFS. Conclusions: For a contemporary cohort of patients with high-risk extremity and truncal STS, a regimen of neoadjuvant chemoradiotherapy and surgery continues to result in high rates of survival with tolerable short- and long-term toxicity. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Hong, Nicole J. Look; Yoon, Sam S.; Mullen, John T.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hornicek, Francis J.] Harvard Univ, Sch Med, Dept Orthoped Oncol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Harmon, David C.; Choy, Edwin] Harvard Univ, Sch Med, Dept Med Oncol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chen, Yen-Lin; DeLaney, Thomas F.] Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nielsen, G. Petur] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Szymonifka, Jackie; Yeap, Beow Y.] Harvard Univ, Sch Med, Dept Biostat, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mullen, JT (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM jmullen@partners.org OI Choy, Edwin/0000-0001-9896-8084 FU NCI Cancer Center [NIH 5 P30 CA06516] FX Biostatistics Core of Dana-Farber/Harvard Cancer Center supported by NCI Cancer Center Support Grant # NIH 5 P30 CA06516. NR 29 TC 19 Z9 19 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 MAR PY 2013 VL 49 IS 4 BP 875 EP 883 DI 10.1016/j.ejca.2012.10.002 PG 9 WC Oncology SC Oncology GA 088QB UT WOS:000314849300014 ER PT J AU Chaudhuri, SE Merfeld, DM AF Chaudhuri, Shomesh E. Merfeld, Daniel M. TI Signal detection theory and vestibular perception: III. Estimating unbiased fit parameters for psychometric functions SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE Maximum likelihood estimation; Generalized linear models; GLM; Psychophysics; Threshold; Vestibular ID BIAS; THRESHOLDS; BOOTSTRAP AB Psychophysics generally relies on estimating a subject's ability to perform a specific task as a function of an observed stimulus. For threshold studies, the fitted functions are called psychometric functions. While fitting psychometric functions to data acquired using adaptive sampling procedures (e.g., "staircase" procedures), investigators have encountered a bias in the spread ("slope" or "threshold") parameter that has been attributed to the serial dependency of the adaptive data. Using simulations, we confirm this bias for cumulative Gaussian parametric maximum likelihood fits on data collected via adaptive sampling procedures, and then present a bias-reduced maximum likelihood fit that substantially reduces the bias without reducing the precision of the spread parameter estimate and without reducing the accuracy or precision of the other fit parameters. As a separate topic, we explain how to implement this bias reduction technique using generalized linear model fits as well as other numeric maximum likelihood techniques such as the Nelder-Mead simplex. We then provide a comparison of the iterative bootstrap and observed information matrix techniques for estimating parameter fit variance from adaptive sampling procedure data sets. The iterative bootstrap technique is shown to be slightly more accurate; however, the observed information technique executes in a small fraction (0.005 %) of the time required by the iterative bootstrap technique, which is an advantage when a real-time estimate of parameter fit variance is required. C1 [Chaudhuri, Shomesh E.; Merfeld, Daniel M.] Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. [Merfeld, Daniel M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Merfeld, DM (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM shomesh_chaudhuri@meei.harvard.edu; dan_merfeld@meei.harvard.edu FU National Institutes of Health/National Institute of Deafness and Other Communication Disorders [DC04158]; National Institutes of Health [1S10RR028832] FX We thank Faisal Karmali, Wei Wang, Torin Clark, and Luzia Grabherr for reviewing a draft of this manuscript. This research was supported by the National Institutes of Health/National Institute of Deafness and Other Communication Disorders grant DC04158. The Orchestra computational cluster is supported by the National Institutes of Health shared equipment grant 1S10RR028832. NR 30 TC 6 Z9 6 U1 2 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD MAR PY 2013 VL 225 IS 1 BP 133 EP 146 DI 10.1007/s00221-012-3354-7 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 087OW UT WOS:000314772600011 PM 23250442 ER PT J AU Pichler, I Schwienbacher, C Zanon, A Fuchsberger, C Serafin, A Facheris, MF Marroni, F Pattaro, C Shen, YP Tellgren-Roth, C Gyllensten, U Gusella, JF Hicks, AA Pramstaller, PP AF Pichler, Irene Schwienbacher, Christine Zanon, Alessandra Fuchsberger, Christian Serafin, Alice Facheris, Maurizio F. Marroni, Fabio Pattaro, Cristian Shen, Yiping Tellgren-Roth, Christian Gyllensten, Ulf Gusella, James F. Hicks, Andrew A. Pramstaller, Peter P. TI Fine-Mapping of Restless Legs Locus 4 (RLS4) Identifies a Haplotype over the SPATS2L and KCTD18 Genes SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE Restless legs syndrome; Familial form; Genetics; Isolated population; RLS4 ID TYROLEAN POPULATION ISOLATE; SUSCEPTIBILITY LOCUS; LINKAGE ANALYSIS; MAPS; EPIDEMIOLOGY AB Restless legs syndrome (RLS) is a sleep-related movement disorder that affects up to 15 % of the population. Linkage studies have identified several genomic loci in single families (12q, 14q, 9p, 2q, 20p and 16p, respectively). However, confirmation of these loci has not always been achieved, and causative mutations have not yet been identified. The locus on chromosome 2q33 (RLS4) was identified in two South Tyrolean families who shared a haplotype of microsatellite marker alleles across an 8.2-cM region. To pinpoint the gene localisation within RLS4, additional families from the same geographic region were evaluated, and linkage was replicated in one family. Within the candidate region, we initially found a haplotype of 23 single nucleotide polymorphism markers spanning 131.6 Kb shared by all affected members of the three linked families. Using a next generation sequencing approach, we further restricted the shared candidate region to 46.9 Kb over the potassium channel-related gene KCTD18 and exons 10-13 of SPATS2L. C1 [Pichler, Irene; Schwienbacher, Christine; Zanon, Alessandra; Serafin, Alice; Facheris, Maurizio F.; Pattaro, Cristian; Hicks, Andrew A.; Pramstaller, Peter P.] Univ Lubeck, Ctr Biomed, European Acad Bozen Bolzano EURAC, Affiliated Inst, I-39100 Bozen Bolzano, Italy. [Schwienbacher, Christine] Univ Ferrara, Dept Expt & Diagnost Med, I-44100 Ferrara, Italy. [Fuchsberger, Christian] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Marroni, Fabio] Inst Appl Genom, Udine, Italy. [Shen, Yiping; Gusella, James F.] Massachusetts Gen Hosp, Mol Neurogenet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Shen, Yiping] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Shen, Yiping] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Shen, Yiping] Shanghai Jiao Tong Univ, Shanghai Childrens Med Ctr, Sch Med, Shanghai 200030, Peoples R China. [Tellgren-Roth, Christian; Gyllensten, Ulf] Uppsala Univ, Dept Immunol Genet & Pathol, Rudbeck Lab, SciLifeLab Uppsala, Uppsala, Sweden. [Gusella, James F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, Bolzano, Italy. [Pramstaller, Peter P.] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. RP Pramstaller, PP (reprint author), Univ Lubeck, Ctr Biomed, European Acad Bozen Bolzano EURAC, Affiliated Inst, Drususallee 1, I-39100 Bozen Bolzano, Italy. EM peter.pramstaller@eurac.edu RI Pramstaller, Peter/C-2357-2008; Hicks, Andrew/E-9518-2017; OI Hicks, Andrew/0000-0001-6320-0411; Tellgren-Roth, Christian/0000-0003-0502-3693; Marroni, Fabio/0000-0002-1556-5907; Pichler, Irene/0000-0001-8251-0757; Fuchsberger, Christian/0000-0002-5918-8947 FU Ministry of Health and Department of Educational Assistance; University and Research of the Autonomous Province of Bolzano; South Tyrolean Sparkasse Foundation FX The authors are grateful to the study participants and the primary care physicians of the villages for their participation and collaboration in this research project. We thank Martin Gogele and Daniel Taliun for their technical support. The study was supported by the Ministry of Health and Department of Educational Assistance, University and Research of the Autonomous Province of Bolzano and the South Tyrolean Sparkasse Foundation. NR 16 TC 3 Z9 3 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD MAR PY 2013 VL 49 IS 3 BP 600 EP 605 DI 10.1007/s12031-012-9891-5 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 086QN UT WOS:000314701300022 PM 23054586 ER PT J AU Lim, SN Gladman, SJ Dyall, SC Patel, U Virani, N Kang, JX Priestley, JV Michael-Titus, AT AF Lim, Siew-Na Gladman, Stacy J. Dyall, Simon C. Patel, Urva Virani, Nabeel Kang, Jing X. Priestley, John V. Michael-Titus, Adina T. TI Transgenic mice with high endogenous omega-3 fatty acids are protected from spinal cord injury SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Transgenic fat-1 mice; Spinal cord injury; Omega-3 fatty acids; Neuroprotection ID TRAUMATIC BRAIN-INJURY; CENTRAL-NERVOUS-SYSTEM; FATTY-ACIDS; DOCOSAHEXAENOIC ACID; LEUKOCYTE MOBILIZATION; FUNCTIONAL RECOVERY; FAT-1 MICE; RAT; NEUROTOXICITY; METABOLISM AB Omega-3 polyunsaturated fatty acids have been shown to have therapeutic potential in a variety of neurological disorders, including acute traumatic injury of the spinal cord. We addressed the question whether the neuroprotective effect of these compounds after spinal cord injury could also be seen when their level is raised in tissues prophylactically, prior to injury. In this study we used transgenic fat-1 mice to examine whether enriching spinal cord tissue in endogenous omega-3 polyunsaturated fatty acids has an effect on the outcome after compression spinal cord injury. The results demonstrate that after thoracic compression spinal cord injury, fat-1 mice display better locomotor recovery compared with the wild-type mice on a high omega-6 diet (high omega-6 polyunsaturated fatty acids in tissues), and wild-type mice on a normal diet (controls). This is associated with a significant increase in neuronal and oligodendrocyte survival and a decrease in non-phosphorylated neurofilament loss. The protection from spinal cord injury in fat-1 mice was also correlated with a reduction in microglia/macrophage activation and in pro-inflammatory mediators. In vitro experiments in dorsal root ganglia primary sensory neurons further demonstrated that a fat-1 tissue background confers robust neuroprotection against a combined mechanical stretch and hypoxic injury. In conclusion, our studies support the hypothesis that a raised omega-3 polyunsaturated fatty acid level and an altered tissue omega-6/omega-3 ratio prior to injury leads to a much improved outcome after spinal cord injury. (C) 2012 Elsevier Inc. All rights reserved. C1 [Lim, Siew-Na; Gladman, Stacy J.; Dyall, Simon C.; Patel, Urva; Virani, Nabeel; Priestley, John V.; Michael-Titus, Adina T.] Barts & London Queen Marys Sch Med & Dent, Blizard Inst, Ctr Neurosci & Trauma, London, England. [Lim, Siew-Na] Chang Gung Mem Hosp, Dept Neurol, Taipei 10591, Taiwan. [Lim, Siew-Na] Chang Gung Univ, Coll Med, Taipei, Taiwan. [Dyall, Simon C.] Roehampton Univ, Whitelands Coll, Dept Life Sci, London, England. [Kang, Jing X.] Massachusetts Gen Hosp, Dept Med, Lab Lipid Med & Technol, Boston, MA 02114 USA. [Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Michael-Titus, AT (reprint author), Barts & London Queen Marys Sch Med & Dent, Blizard Inst Cell & Mol Sci, Ctr Neurosci & Trauma, 4 Newark St, London, England. EM a.t.michael-titus@qmul.ac.uk OI Gladman, Stacy/0000-0002-7112-4516; Dyall, Simon/0000-0001-7591-4219 FU Chang Gung Memorial Hospital, Taiwan [CMRPG360622] FX This work was supported by Chang Gung Memorial Hospital, Taiwan (CMRPG360622). We gratefully acknowledge the assistance of Patrick Pallier, Laura Poddighe and Rasall Choudhury with preparatory staining for the Abercrombie correction. NR 46 TC 17 Z9 17 U1 2 U2 20 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD MAR PY 2013 VL 51 SI SI BP 104 EP 112 DI 10.1016/j.nbd.2012.10.021 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 085PQ UT WOS:000314627100012 PM 23123586 ER PT J AU Holt, CL Wang, MQ Clark, EM Williams, BR Schulz, E AF Holt, Cheryl L. Wang, Min Qi Clark, Eddie M. Williams, Beverly Rosa Schulz, Emily TI Religious involvement and physical and emotional functioning among African Americans: The mediating role of religious support SO PSYCHOLOGY & HEALTH LA English DT Article DE religion; religious support; African Americans; functioning; depression ID SOCIAL SUPPORT; HEALTH CONNECTION; DEPRESSION; MODEL; SPIRITUALITY; PERCEPTIONS; MORTALITY; SAMPLE; ADULTS; SCALES AB Objectives: Religious social support may in part account for the relationship between religious involvement and health-related outcomes. African Americans, on average, tend to have relatively high levels of religious involvement, and suffer a higher burden of health conditions than other groups. This study aimed to examine whether religious social support played a mediating role between religious involvement and physical and emotional functioning, and depressive symptoms. Design: The study used a cross sectional telephone survey among a national probability sample of African Americans (n=803). Study participants completed telephone interviews and data were analysed using structural equation modelling. Main outcome measures: Physical and emotional functioning and depressive symptoms served as study outcomes. Results: In both the emotional functioning and depressive symptoms models, the indirect effect test from religious behaviours to emotional religious support indicated evidence for mediation. There was no mediation for the physical functioning model. Conclusion: Implications for faith-based health promotion interventions are discussed. C1 [Holt, Cheryl L.; Wang, Min Qi] Univ Maryland, Sch Publ Hlth, Dept Behav & Community Hlth, College Pk, MD 20742 USA. [Clark, Eddie M.] St Louis Univ, Dept Psychol, St Louis, MO 63103 USA. [Williams, Beverly Rosa] Birmingham VA Med Ctr, Div Gerontol Geriatr Palliat Care, Dept Med, Birmingham, AL USA. [Williams, Beverly Rosa] Univ Alabama Birmingham, Birmingham, AL USA. [Schulz, Emily] Arizona Sch Hlth Sci, Dept Occupat Therapy, Mesa, AZ USA. RP Holt, CL (reprint author), Univ Maryland, Sch Publ Hlth, Dept Behav & Community Hlth, College Pk, MD 20742 USA. EM cholt14@umd.edu NR 45 TC 12 Z9 12 U1 2 U2 18 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0887-0446 J9 PSYCHOL HEALTH JI Psychol. Health PD MAR 1 PY 2013 VL 28 IS 3 BP 267 EP 283 DI 10.1080/08870446.2012.717624 PG 17 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary SC Public, Environmental & Occupational Health; Psychology GA 089LH UT WOS:000314911500003 PM 22928653 ER PT J AU Scala, S Pousada, A Stone, WS Thermenos, HW Manschreck, TC Tsuang, MT Faraone, SV Seidman, LJ AF Scala, Silvia Pousada, Andrea Stone, William S. Thermenos, Heidi W. Manschreck, Theo C. Tsuang, Ming T. Faraone, Stephen V. Seidman, Larry J. TI Verbal and visual-spatial memory impairment in youth at familial risk for schizophrenia or affective psychosis: A pilot study SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Family high-risk; Psychosis; Memory; Psychopathology; Vulnerability ID UNAFFECTED 1ST-DEGREE RELATIVES; BIPOLAR DISORDER; NEUROCOGNITIVE ENDOPHENOTYPES; MULTIGENERATIONAL FAMILIES; COGNITIVE DEFICITS; EUTHYMIC PATIENTS; GENETIC RISK; YOUNG-ADULTS; METAANALYSIS; DYSFUNCTION AB Background: Schizophrenia and affective psychoses share several common biological origins, particularly genetic susceptibility. Kraepelin posited that differing clinical expressions in these disorders reflect different etiopathologies. We tested a neuropsychological component of this hypothesis by evaluating verbal memory and visual memory performance in nonpsychotic youth at familial risk for psychosis, taking into account contributions to memory dysfunction including executive processing and psychopathology. Methods: Teenage and young adults (ages 13-25) at familial high-risk (FHR) for schizophrenia (HR-SCZ, n=41) or affective psychosis (HR-AFF, n=24) were compared to community controls (CC, n=54) on verbal (Miller-Selfridge Context Memory) and visual (Rey-Osterrieth Complex Figure) memory tests in which the roles of strategy and contextual processing on distinct recall domains could be assessed. Effects of psychopathology, vigilance and working memory were investigated to determine their influence on memory performance. Results: HR-AFF and HR-SCZ exhibited similarly impaired memory profiles and elevated levels of psychopathology compared to CC. HR-SCZ were significantly impaired on both verbal memory and visual-spatial memory, while HR-AFF in verbal memory only. However, effect sizes, in the medium range, were largely comparable between the two HR groups. Deficits in verbal recall and in visual memory organization remained significant after adjustment for confounders. Conclusions: Youth at FHR for psychosis present relatively common memory deficits across both visual-spatial and verbal modalities that are not explained by current psychopathology, vigilance or working memory deficits. Deficits in organizing information to be recalled represent a promising trait of psychosis vulnerability. (C) 2012 Elsevier B.V. All rights reserved. C1 [Scala, Silvia] Univ Verona, Dept Publ Hlth & Community Med, Sect Psychiat & Clin Psychol, I-37134 Verona, Italy. [Scala, Silvia; Pousada, Andrea; Stone, William S.; Thermenos, Heidi W.; Tsuang, Ming T.; Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat,Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr,Div Publ Psychiat, Boston, MA 02115 USA. [Thermenos, Heidi W.; Seidman, Larry J.] Harvard Univ, Sch Med, MIT, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Thermenos, Heidi W.; Seidman, Larry J.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Manschreck, Theo C.] Harvard Univ, Commonwealth Massachusetts Res Ctr, Sch Med, Dept Psychiat,John C Corrigan Mental Hlth Ctr, Fall River, MA 02720 USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, La Jolla, CA 92093 USA. [Tsuang, Ming T.] Inst Genom Med, La Jolla, CA 92093 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Physiol, Syracuse, NY 13210 USA. RP Seidman, LJ (reprint author), Massachusetts Mental Hlth Ctr, Commonwealth Res Ctr, 5th Floor,75 Fenwood Rd, Boston, MA 02115 USA. EM lseidman@bidmc.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU Stanley Medical Research Institute; National Association for Research on Schizophrenia and Depression (NARSAD); Commonwealth Research Center of the Massachusetts Department of Mental Health [SCDMH82101008006]; [MH43518]; [MH65562]; [MH63951]; [MH46318] FX Stanley Medical Research Institute (LJS); National Association for Research on Schizophrenia and Depression (NARSAD; MTT, LJS); MH43518 and MH65562 (MTT, LJS); MH63951 (LJS); MH46318 (MTT); The Commonwealth Research Center of the Massachusetts Department of Mental Health (SCDMH82101008006; LJS). NR 71 TC 7 Z9 7 U1 2 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 2013 VL 144 IS 1-3 BP 122 EP 128 DI 10.1016/j.schres.2012.11.027 PG 7 WC Psychiatry SC Psychiatry GA 088GI UT WOS:000314821400018 PM 23312552 ER PT J AU McClure, MM Harvey, PD Bowie, CR Iacoviello, B Siever, LJ AF McClure, Margaret M. Harvey, Philip D. Bowie, Christopher R. Iacoviello, Brian Siever, Larry J. TI Functional outcomes, functional capacity, and cognitive impairment in schizotypal personality disorder SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia spectrum; Cognition; Functional outcome; Performance-based assessments; Schizotypal personality disorder ID WORKING-MEMORY; NEUROPSYCHOLOGICAL DYSFUNCTION; SKILLS ASSESSMENT; SCHIZOPHRENIA; PERFORMANCE; SPECIFICITY; SENSITIVITY; DISABILITY; DETERMINANTS; RELIABILITY AB Background: Individuals with schizotypal personality disorder (SPD) exhibit impaired cognitive functioning in a pattern similar to that found in schizophrenia; less clear is the extent to which these individuals also share schizophrenia patients' impairments in functional capacity and real-world functioning. Method: We evaluated 46 SPD patients, as well as 38 individuals with avoidant personality disorder (AvPD) and 55 healthy controls (HC) on: cognitive functioning, real-world functioning (employment and residential status), and functional capacity (indexed by the UPSA, a performance-based skills assessment). Results: We found that individuals with SPD exhibited worse performance on both the cognitive battery and the UPSA than the other groups; they were also less likely to be employed and to be living independently. Additionally, cognitive and UPSA performance in the SPD group was intercorrelated to a degree comparable to what has been found in schizophrenia, and this relationship was not present in the AvPD group. Finally, real-world functioning was related to UPSA performance for both patient groups. Conclusions: SPD patients exhibit impaired real-world functioning suggesting that these deficits extend across the schizophrenia spectrum. In addition, there is supportive evidence for the validity and importance of performance-based measures such as the UPSA to predict everyday outcomes across the schizophrenia spectrum. Published by Elsevier B.V. C1 [McClure, Margaret M.; Iacoviello, Brian; Siever, Larry J.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [McClure, Margaret M.; Siever, Larry J.] VA VISN3 Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. [McClure, Margaret M.] Fairfield Univ, Dept Psychol, Fairfield, CT 06430 USA. [Harvey, Philip D.] Univ Miami, Miller Sch Med, Dept Psychiat, Miami, FL 33136 USA. [Harvey, Philip D.] Miami VA Med Ctr, Res Serv, Miami, FL USA. [Bowie, Christopher R.] Queens Univ, Kingston, ON, Canada. RP McClure, MM (reprint author), James J Peters VAMC, VA VISN MIRECC 3, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Margaret.McNamara@mssm.edu FU NIMH [MH 56140, MH 78775]; VA VISN-3 MIRECC; National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [MO1-RR-00071] FX This research was supported by NIMH Grant Number MH 56140 to Dr. Siever, NIMH Grant Number MH 78775 to Dr. Harvey, and by the VA VISN-3 MIRECC. This research was also supported by Grant Number MO1-RR-00071 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH. NR 38 TC 13 Z9 13 U1 2 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 2013 VL 144 IS 1-3 BP 146 EP 150 DI 10.1016/j.schres.2012.12.012 PG 5 WC Psychiatry SC Psychiatry GA 088GI UT WOS:000314821400022 PM 23375943 ER PT J AU Schorge, JO AF Schorge, John O. TI Cervical Cancer Screening SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. RP Schorge, JO (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. EM jschorge@partners.org NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD MAR PY 2013 VL 56 IS 1 BP 1 EP 2 DI 10.1097/GRF.0b013e31828365f4 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 082ML UT WOS:000314396000001 PM 23318572 ER PT J AU Tambouret, RH AF Tambouret, Rosemary H. TI The Evolution of the Papanicolaou Smear SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article DE Papanicolaou smear; cervicovaginal cytology; cancer screening ID LABORATORY IMPROVEMENT AMENDMENTS; CERVICAL-CANCER; CLINICAL LABORATORIES; FEDERAL-REGULATION; BETHESDA SYSTEM; CYTOLOGY; MORTALITY; CARCINOMA; PATHOLOGY; ICELAND AB The Papanicolaou smear or cervicovaginal cytology has been the mainstay of screening for cervical cancer in women of over 60 years. In this article, the origins of the Pap smear as a screening method and the many changes associated with the use of the Pap smear are detailed. C1 Massachusetts Gen Hosp, Cytopathol Fellowship Program, Boston, MA 02114 USA. RP Tambouret, RH (reprint author), Massachusetts Gen Hosp, Cytopathol Fellowship Program, Boston, MA 02114 USA. EM rtambouret@partners.org NR 40 TC 2 Z9 2 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD MAR PY 2013 VL 56 IS 1 BP 3 EP 9 DI 10.1097/GRF.0b013e318282b982 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 082ML UT WOS:000314396000002 PM 23314726 ER PT J AU Lui, R AF Lui, Raymond TI Clinical Utility of HPV Testing SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article DE cervical cancer screening; HPV testing; human papilloma virus; Pap smear ID INVASIVE CERVICAL-CANCER; ATYPICAL SQUAMOUS-CELLS; HUMAN-PAPILLOMAVIRUS INFECTION; INTERNATIONAL INCIDENCE RATES; UNDETERMINED SIGNIFICANCE; UNITED-STATES; RANDOMIZED-TRIAL; ABSOLUTE RISK; CYTOLOGY; WOMEN AB Testing for human papilloma virus (HPV) has been shown to be more sensitive than cervical cytology in detecting both high-grade and low-grade dysplasia. When screening for cervical cancer, unfortunately, the HPV test lacks specificity and has limited its usefulness as a primary screening modality for cervical cancer. In this chapter, we will review HPV and its role in cervical cancer, the utilization of HPV testing in current practice, and the possible future utilization of HPV and its role in screening C1 Massachusetts Gen Hosp, Colposcopy Clin, Vincent Obstet & Gynecol, Boston, MA 02114 USA. RP Lui, R (reprint author), Massachusetts Gen Hosp, Colposcopy Clin, Vincent Obstet & Gynecol, Boston, MA 02114 USA. EM rlui@partners.org NR 48 TC 4 Z9 4 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD MAR PY 2013 VL 56 IS 1 BP 17 EP 24 DI 10.1097/GRF.0b013e31827af708 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 082ML UT WOS:000314396000004 PM 23314715 ER PT J AU Schorge, JO Rauh-Hain, JA AF Schorge, John O. Rauh-Hain, Jose Alejandro TI Atypical Glandular Cells SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article DE atypical glandular cells; adenocarcinoma in situ; cervical adenocarcinoma ID UNDETERMINED SIGNIFICANCE AGUS; CERVICAL CYTOLOGY; INCIDENCE TRENDS; BETHESDA SYSTEM; UNITED-STATES; PAP TESTS; ADENOCARCINOMA; WOMEN; TERMINOLOGY; GUIDELINES AB Less than 1% of Pap smears are interpreted as having atypical glandular cells. Because of the rarity of diagnosis, providers are frequently unfamiliar with both the workup and the potential ramifications. Comprehensive evaluation is required in all cases to exclude a spectrum of possible diagnoses. Although colposcopy, human papillomavirus DNA testing, endocervical curettage, and endometrial sampling should be the initial part of the evaluation, these procedures may not identify any specific etiology. The aim of this review is to provide the most current strategy for management of this rare, but suspicious Pap test result. C1 [Schorge, John O.; Rauh-Hain, Jose Alejandro] Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. RP Schorge, JO (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, Yawkey 9E, Boston, MA 02114 USA. EM jschorge@partners.org NR 30 TC 3 Z9 3 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD MAR PY 2013 VL 56 IS 1 BP 35 EP 43 DI 10.1097/GRF.0b013e3182823849 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 082ML UT WOS:000314396000006 PM 23314725 ER PT J AU Coleman, CA AF Coleman, Carrie A. TI Evaluation and Management of Abnormal Cervical Cytology During Pregnancy SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article DE abnormal pap smear; pregnancy; colposcopy ID 2006 CONSENSUS GUIDELINES; WOMEN AB Pregnancy is a particularly motivating time for a woman to access the health care system and seek out preventative services. Papanicolaou screening is a routine part of the initial examination. Although the vast majority of smears will have a normal result, it is important for providers to be aware of the appropriate evaluation of abnormal cervical cytology in this unique population because the standard management algorithms do not always apply. For example, colposcopy during pregnancy is a safe and effective tool, but endocervical curettage is contraindicated. In addition, for most diagnoses, more aggressive intervention is often best delayed. C1 Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Coleman, CA (reprint author), Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. EM cacoleman@partners.org NR 14 TC 4 Z9 5 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-9201 EI 1532-5520 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD MAR PY 2013 VL 56 IS 1 BP 51 EP 54 DI 10.1097/GRF.0b013e31828365b8 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 082ML UT WOS:000314396000008 PM 23318571 ER PT J AU del Carmen, MG Avila-Wallace, M AF del Carmen, Marcela G. Avila-Wallace, Maria TI Effect of Health Care Disparities on Screening SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article DE cervical cancer; disparities; prevention; screening ID SPECIAL POPULATIONS NETWORKS; AFRICAN-AMERICAN WOMEN; CERVICAL-CANCER; UNITED-STATES; HISPANIC WOMEN; BREAST; PROGRAM; US; STAGE; INTERVENTION AB Significant declines in the incidence and mortality rates of cervical cancer have occurred in the United States since the introduction of the Papanicolaou (Pap) test. Unfortunately, a reduction in the burden of cervical cancer is not equal across all ethnic and racial groups; significant disparities exist. Disparities are reflected not only in mortality and incidence rates, but also in screening rates. We review barriers to screening and effective approaches towards overcoming them. As minority populations increase over the next few decades, it becomes ever more urgent to employ interventions that will reduce the burden of cervical cancer among diverse groups. C1 [del Carmen, Marcela G.; Avila-Wallace, Maria] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol, Boston, MA USA. RP del Carmen, MG (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, Yawkey 9E, Boston, MA 02114 USA. EM mdelcarmen@partners.org NR 46 TC 7 Z9 7 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 EI 1532-5520 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD MAR PY 2013 VL 56 IS 1 BP 65 EP 75 DI 10.1097/GRF.0b013e31827af75a PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 082ML UT WOS:000314396000010 PM 23314716 ER PT J AU Bradford, L Goodman, A AF Bradford, Leslie Goodman, Annekathryn TI Cervical Cancer Screening and Prevention in Low-resource Settings SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article DE cervical cancer; low-resource setting; developing countries; screening; VIA; HPV-DNA testing ID RANDOMIZED CONTROLLED-TRIAL; VISUAL INSPECTION METHODS; HUMAN-PAPILLOMAVIRUS; ACETIC-ACID; DEVELOPING-COUNTRIES; COST-EFFECTIVENESS; INTRAEPITHELIAL NEOPLASIA; POOLED ANALYSIS; POOR SETTINGS; SINGLE-VISIT AB Cervical cancer is both preventable and curable, yet it remains one of the leading causes of mortality in women worldwide. Approximately 88% of cervical cancer cases are diagnosed in low-resource countries, yet very few resources are allocated to prevention and treatment programs. In fact, it is estimated that only 5% of women in low-resources countries are screened appropriately for cervical cancer. Cytology-based programs are not feasible because of lack of healthcare infrastructure and cost, thus alternative methods of cancer screening, such as visual inspection with acetic acid and HPV-DNA testing, have been intensively studied and are reviewed in this article. C1 [Bradford, Leslie; Goodman, Annekathryn] Massachusetts Gen Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Goodman, A (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. EM jschorge@partners.org NR 73 TC 16 Z9 16 U1 3 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD MAR PY 2013 VL 56 IS 1 BP 76 EP 87 DI 10.1097/GRF.0b013e31828237ac PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 082ML UT WOS:000314396000011 PM 23337844 ER PT J AU Fitzsimmons, J Kubicki, M Shenton, ME AF Fitzsimmons, Jennifer Kubicki, Marek Shenton, Martha E. TI Review of functional and anatomical brain connectivity findings in schizophrenia SO CURRENT OPINION IN PSYCHIATRY LA English DT Review DE diffusion tensor imaging; fractional anisotropy; functional magnetic resonance; schizophrenia; white matter ID WHITE-MATTER ABNORMALITIES; FRACTIONAL ANISOTROPY; 1ST-EPISODE PSYCHOSIS; RADIAL DIFFUSIVITY; GENETIC LIABILITY; INTERNAL CAPSULE; CORPUS-CALLOSUM; ANTERIOR LIMB; DEFAULT MODE; INTEGRITY AB Purpose of review We review diffusion tensor imaging (DTI) studies that investigate white matter abnormalities in patients with chronic schizophrenia, first episode schizophrenia, and those who are at genetic risk for developing schizophrenia. Additionally, we include studies that combine DTI and functional MRI (fMRI) to investigate brain connectivity abnormalities. Recent findings Schizophrenia is a complex mental disorder with a peak age of onset in early adulthood. Abnormalities in white matter tracts, which connect brain regions into functional networks, are most likely relevant for understanding structural and functional brain abnormalities in schizophrenia. Dysconnectivity between brain regions, in fact, is thought to underlie cognitive abnormalities in schizophrenia but little is known about how alterations at the functional level relate to abnormalities in anatomical connectivity. DTI has become one of the most popular tools in brain research to address such questions. Here we review white matter abnormalities using DTI with the aim of understanding dysconnectivity of brain regions and their implications in schizophrenia. Summary Advances in DTI and in combining DTI with fMRI provide new insight into anatomical and functional connections in the brain, and for studying dysconnectivity in schizophrenia. C1 [Fitzsimmons, Jennifer; Kubicki, Marek; Shenton, Martha E.] Harvard Univ, Sch Med, Dept Psychiat, Psychiat Neuroimaging Lab,Brigham & Womens Hosp, Boston, MA 02115 USA. [Kubicki, Marek; Shenton, Martha E.] Harvard Univ, Sch Med, Dept Radiol, Surg Planning Lab,MRI Div,Brigham & Womens Hosp, Boston, MA 02115 USA. [Shenton, Martha E.] VA Boston Healthcare Syst, Boston, MA USA. RP Fitzsimmons, J (reprint author), Psychiat Neuroimaging Lab, 1249 Boylston St,2nd Floor, Boston, MA 02215 USA. EM jfitzsimmons@bwh.harvard.edu FU Department of Veterans Affairs Merit Awards; National Institute of Mental Health [R01 MH 50740] FX The present research was supported by the Department of Veterans Affairs Merit Awards (MES) and by the grant from the National Institute of Mental Health (R01 MH 50740 to MES). NR 67 TC 97 Z9 102 U1 6 U2 86 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD MAR PY 2013 VL 26 IS 2 BP 172 EP 187 DI 10.1097/YCO.0b013e32835d9e6a PG 16 WC Psychiatry SC Psychiatry GA 082MZ UT WOS:000314397400007 PM 23324948 ER PT J AU Mohammad, OM DeLisi, LE AF Mohammad, Othman M. DeLisi, Lynn E. TI N400 in schizophrenia patients SO CURRENT OPINION IN PSYCHIATRY LA English DT Review DE event related potentials; language; N400; priming; schizophrenia ID EVENT-RELATED POTENTIALS; FORMAL THOUGHT-DISORDER; BRAIN POTENTIALS; SEMANTIC MEMORY; ELECTROPHYSIOLOGICAL EVIDENCE; LEXICAL DECISION; WORD REPETITION; LANGUAGE; ERP; ABNORMALITIES AB Purpose of review The purpose of this article is to review major findings in event related potential (ERP) research in schizophrenia patients, specifically focusing on the N400 component. Recent findings Patients with chronic schizophrenia have difficulty using 'context' (understanding the meaning of the word relative to the sentence) in sentence processing studies and often show differences from control populations in language experiments using word priming. Both of these observations are associated with an abnormal N400 ERP component when compared with nonpsychotic individuals. Many studies of language function rely on priming paradigms that use pairs of words such that the first word in a pair is a 'prime' and a second word in a pair is a 'target', separated from the prime by a period of time known as the Stimulus Onset Asynchrony (SOA). If the SOA is short (i.e., below 400 ms) then it is believed that a priming study examines primarily processes of initial activation within semantic networks; if it is long (i.e., more than 400 ms) then it is believed that a priming study examines primarily processes of context use, generating predictions and matching these predictions against upcoming semantic information. Priming paradigms that use long SOAs are consistently associated with a more negative N400 (hence lack of priming) in schizophrenia, whereas priming paradigms using a short SOA produce either a normal N400 priming response or hyperpriming as shown by a reduced N400 and related to a hypothesized too rapid automatic spread of activation within the semantic memory pathway. Apparent differences among reported study results are likely due to paradigm differences that tap into different aspects of language processing. Although the presence of both hyperactivation within semantic networks and difficulties with the use of context is well known in schizophrenia, it is unclear whether these abnormalities are also present prior to illness onset in people who are at risk for development of schizophrenia or even present at the onset of illness. Summary In order to clarify the findings reviewed here, future studies will be needed that focus on examining the N400 response in young people at high risk for developing the illness using multiple paradigms that probe different aspects of language function. C1 [Mohammad, Othman M.] Boston Childrens Hosp, Boston, MA USA. [Mohammad, Othman M.; DeLisi, Lynn E.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [DeLisi, Lynn E.] VA Boston Healthcare Syst, Boston, MA USA. RP DeLisi, LE (reprint author), 940 Belmont Ave, Brockton, MA 02301 USA. EM DeLisi76@AOL.com NR 56 TC 12 Z9 13 U1 4 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD MAR PY 2013 VL 26 IS 2 BP 196 EP 207 DI 10.1097/YCO.0b013e32835d9e56 PG 12 WC Psychiatry SC Psychiatry GA 082MZ UT WOS:000314397400009 PM 23340116 ER PT J AU Bogoch, II Andrews, JR Nagami, EH Rivera, AM Gandhi, RT Stone, D AF Bogoch, I. I. Andrews, J. R. Nagami, E. H. Rivera, A. M. Gandhi, R. T. Stone, D. TI Clinical predictors for the aetiology of peripheral lymphadenopathy in HIV-infected adults SO HIV MEDICINE LA English DT Article DE biopsy; HIV; lymphadenopathy; opportunistic infection; tuberculosis ID NEEDLE-ASPIRATION-CYTOLOGY; HUMAN-IMMUNODEFICIENCY-VIRUS; BIOPSY; INDIA AB Objectives The aim of the study was to determine the aetiology and clinical predictors of peripheral lymphadenopathy in HIV-infected individuals during the antiretroviral (ARV) era in a nontuberculosis endemic setting. Methods A multicentred, retrospective cohort study of peripheral lymph node biopsies in HIV-positive adults was carried out. A total of 107 charts were identified and reviewed for clinical features, lymphadenopathy size, and ARV use and duration. Biopsy results were categorized, and multivariate logistic regression determined independent predictors of lymphadenopathy aetiology. Results Evaluation of 107 peripheral lymph node biopsies revealed that 42.9% of peripheral lymphadenopathy was attributable to malignancy, 49.5% to reactive changes, and 7.5% to infections, with only 2.8% of all cases secondary to tuberculosis. Fevers, weight loss, ARV use, and lower viral loads are significantly associated with nonreactive lymphadenopathy. Conclusions Lymphadenopathy is likely to be reactive or malignant in nontuberculosis endemic regions. Readily available clinical features can aid clinicians in predicting the underlying aetiology, those at risk for malignancy, and who to biopsy. C1 [Bogoch, I. I.; Andrews, J. R.; Gandhi, R. T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Bogoch, I. I.; Andrews, J. R.; Gandhi, R. T.] Harvard Univ, Sch Med, Boston, MA USA. [Nagami, E. H.; Gandhi, R. T.] Ragon Inst MGH MIT & Harvard, Boston, MA USA. [Rivera, A. M.; Stone, D.] Tufts Med Ctr, Div Infect Dis, Boston, MA USA. [Nagami, E. H.; Stone, D.] Lemuel Shattuck Hosp, Boston, MA USA. RP Bogoch, II (reprint author), Massachusetts Gen Hosp, COX 5,55 Fruit St, Boston, MA 02114 USA. EM ibogoch@partners.org OI Andrews, Jason/0000-0002-5967-251X FU National Institute of Allergy and Infectious Diseases [T32 AI007433-20]; NIH [R01 AI066992-04A1, G08LM008830-01, U01 AI 694722, 2P30 AI060354-06] FX This study was unfunded. JRA is supported by the National Institute of Allergy and Infectious Diseases (T32 AI007433-20). RTG is supported by NIH R01 AI066992-04A1 and NIH G08LM008830-01 and by a grant to the AIDS Clinical Trials Group (NIH U01 AI 694722). RTG and EHN are supported by a grant to the Harvard University Center for AIDS Research (NIH 2P30 AI060354-06). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, which played no role in the study design, methods, interpretation of results, the content of this manuscript, or the decision to submit it for publication. NR 13 TC 3 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-2662 J9 HIV MED JI HIV Med. PD MAR PY 2013 VL 14 IS 3 BP 182 EP 186 DI 10.1111/j.1468-1293.2012.01035.x PG 5 WC Infectious Diseases SC Infectious Diseases GA 083MW UT WOS:000314469500008 PM 22805116 ER PT J AU Merritt, MA Cramer, DW Vitonis, AF Titus, LJ Terry, KL AF Merritt, Melissa A. Cramer, Daniel W. Vitonis, Allison F. Titus, Linda J. Terry, Kathryn L. TI Dairy foods and nutrients in relation to risk of ovarian cancer and major histological subtypes SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE dairy foods; calcium; vitamin D; lactose; ovarian cancer ID DIETARY-FAT INTAKE; GALACTOSE CONSUMPTION; POOLED ANALYSIS; VITAMIN-D; FREQUENCY QUESTIONNAIRE; MILK CONSUMPTION; LACTOSE INTAKE; UNITED-STATES; 12 COHORT; METABOLISM AB Inconsistent results for the role of dairy food intake in relation to ovarian cancer risk may reflect the potential adverse effects of lactose, which has been hypothesized to increase gonadotropin levels, and the beneficial antiproliferative effects of calcium and vitamin D. Using data from the New England case-control study (1,909 cases and 1,989 controls), we examined dairy foods and nutrients in relation to risk of ovarian cancer overall, histological subtypes and rapidly fatal versus less aggressive disease. We used logistic regression and polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). In models that were simultaneously adjusted for total (dietary plus supplements) calcium, total vitamin D and lactose, we observed a decreased overall risk of ovarian cancer with high intake of total calcium [Quartile 4 (Q4, >1,319 mg/day) vs. Quartile 1 (Q1, <655 mg/day), OR = 0.62, 95% CI = 0.49-0.79]; the inverse association was strongest for serous borderline and mucinous tumors. High intake of total vitamin D was not associated overall with ovarian cancer risk, but was inversely associated with risk of serous borderline (Q4, >559 IU/day vs. Q1, <164 IU/day, OR = 0.51, 95% CI = 0.34-0.76) and endometrioid tumors (Q4 vs. Q1, OR = 0.55, 95% CI = 0.39-0.80). We found no evidence that lactose intake influenced ovarian cancer risk or that risk varied by tumor aggressiveness in the analyses of intake of dairy foods and nutrients. The overall inverse association with high intake of calcium and the inverse associations of calcium and vitamin D with specific histological subtypes warrant further investigation. C1 [Merritt, Melissa A.; Cramer, Daniel W.; Terry, Kathryn L.] Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02115 USA. [Merritt, Melissa A.; Cramer, Daniel W.; Vitonis, Allison F.; Terry, Kathryn L.] Harvard Univ, OB GYN Epidemiol Ctr, Brigham & Womens Hosp, Dept Obstet & Gynecol,Med Sch, Boston, MA 02115 USA. [Merritt, Melissa A.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Titus, Linda J.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH 03756 USA. RP Merritt, MA (reprint author), Harvard Univ, OB GYN Epidemiol Ctr, Brigham & Womens Hosp, Dept Obstet & Gynecol,Med Sch, 221 Longwood Ave, Boston, MA 02115 USA. EM merritt@jimmy.harvard.edu FU National Cancer Institute, NIH [R01CA54419, P50CA105009, R25CA098566]; Department of Defense [W81XWH-10-1-0280]; Ovarian Cancer Research Fund Liz Tilberis Scholar Award FX Grant sponsor: National Cancer Institute, NIH; Grant numbers: R01CA54419, P50CA105009, R25CA098566; Grant sponsor: Department of Defense; Grant number: W81XWH-10-1-0280; Grant sponsor: Ovarian Cancer Research Fund Liz Tilberis Scholar Award NR 49 TC 12 Z9 14 U1 1 U2 30 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 1 PY 2013 VL 132 IS 5 BP 1114 EP 1124 DI 10.1002/ijc.27701 PG 11 WC Oncology SC Oncology GA 078AU UT WOS:000314071300014 PM 22740148 ER PT J AU Lau, EF Holcomb, PJ Kuperberg, GR AF Lau, Ellen F. Holcomb, Phillip J. Kuperberg, Gina R. TI Dissociating N400 Effects of Prediction from Association in Single-word Contexts SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID LEXICAL-DECISION TASK; EVENT-RELATED POTENTIALS; SENTENCE-LEVEL CONTEXT; LANGUAGE COMPREHENSION; SPREADING ACTIVATION; WORKING-MEMORY; BRAIN POTENTIALS; SEMANTIC INTEGRATION; RIGHT-HEMISPHERE; UPCOMING WORDS AB When a word is preceded by a supportive context such as a semantically associated word or a strongly constraining sentence frame, the N400 component of the ERP is reduced in amplitude. An ongoing debate is the degree to which this reduction reflects a passive spread of activation across long-term semantic memory representations as opposed to specific predictions about upcoming input. We addressed this question by embedding semantically associated prime-target pairs within an experimental context that encouraged prediction to a greater or lesser degree. The proportion of related items was used to manipulate the predictive validity of the prime for the target while holding semantic association constant. A semantic category probe detection task was used to encourage semantic processing and to preclude the need for a motor response on the trials of interest. A larger N400 reduction to associated targets was observed in the high than the low relatedness proportion condition, consistent with the hypothesis that predictions about upcoming stimuli make a substantial contribution to the N400 effect. We also observed an earlier priming effect (205-240 msec) in the high-proportion condition, which may reflect facilitation because of form-based prediction. In summary, the results suggest that predictability modulates N400 amplitude to a greater degree than the semantic content of the context. C1 [Lau, Ellen F.; Kuperberg, Gina R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lau, Ellen F.; Holcomb, Phillip J.; Kuperberg, Gina R.] Tufts Univ, Medford, MA USA. [Lau, Ellen F.] Univ Maryland, College Pk, MD 20742 USA. RP Lau, EF (reprint author), Univ Maryland, Dept Linguist, 1401 Marie Mount Hall, College Pk, MD 20742 USA. EM ellenlau@umd.edu FU National Institute of Mental Health [R01MH071635]; National Institute of Child Health and Human Development [F32HD063221] FX The authors thank Eric Fields and Sorabh Kothari for their assistance with this project. This work was funded by the National Institute of Mental Health (R01MH071635 to G. R. K.) and the National Institute of Child Health and Human Development (F32HD063221 to E. F. L.). NR 94 TC 44 Z9 45 U1 3 U2 38 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD MAR PY 2013 VL 25 IS 3 BP 484 EP 502 PG 19 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 082AD UT WOS:000314363200012 PM 23163410 ER PT J AU Samagh, SP Kramer, EJ Melkus, G Laron, D Bodendorfer, BM Natsuhara, K Kim, HT Liu, XH Feeley, BT AF Samagh, Sanjum P. Kramer, Erik J. Melkus, Gerd Laron, Dominique Bodendorfer, Blake M. Natsuhara, Kyle Kim, Hubert T. Liu, Xuhui Feeley, Brian T. TI MRI quantification of fatty infiltration and muscle atrophy in a mouse model of rotator cuff tears SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE rotator cuff; muscle atrophy; fatty infiltration; MRI; mouse ID SUPRASCAPULAR NEUROPATHY; REPAIR; SHEEP; SUPRASPINATUS; DEGENERATION; VOLUME; WATER AB Rotator cuff pathology is the most common shoulder problem seen by orthopedic surgeons. Rotator cuff muscle fatty infiltration and muscle atrophy are common in larger tears and are considered predicting factors for the prognosis of cuff repair. Clinically, MRI is the gold standard in determining fatty infiltration and muscle atrophy; however, analysis for MRI imaging is primarily qualitative in nature with the results lacking further validation. We have recently developed a mouse model of rotator cuff tears. The goal of this study is to quantify and verify rotator cuff muscle atrophy and fatty infiltration using high-resolution MRI in our mouse model. The rotator cuff muscles were analyzed for fat using a triglyceride quantification assay (TQA), muscle volume was measured through water displacement (WD), and histology. The study revealed that MRI had a high correlation with fat as measured with histology and TQA (R2?=?098). MRI also correlated well with atrophy measured with WD and wet weight. This suggests that MRI is a reliable modality in evaluating the progression of fatty infiltration and muscle atrophy following rotator cuff tears in a small animal model. (C) 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 421426, 2013 C1 [Samagh, Sanjum P.; Kramer, Erik J.; Natsuhara, Kyle; Kim, Hubert T.; Liu, Xuhui] San Francisco VA Med Ctr, Dept Vet Affairs, San Francisco, CA USA. [Samagh, Sanjum P.; Laron, Dominique; Bodendorfer, Blake M.; Kim, Hubert T.; Liu, Xuhui; Feeley, Brian T.] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA USA. [Melkus, Gerd] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. RP Feeley, BT (reprint author), Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA USA. EM feeleyb@orthosurg.ucsf.edu OI Melkus, Gerd/0000-0001-5387-8958 FU Orthopaedic Research Education Foundation (OREF) FX Grant sponsor: Orthopaedic Research Education Foundation (OREF). NR 33 TC 15 Z9 15 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD MAR PY 2013 VL 31 IS 3 BP 421 EP 426 DI 10.1002/jor.22233 PG 6 WC Orthopedics SC Orthopedics GA 076TJ UT WOS:000313980600012 PM 22991068 ER PT J AU Yang, W Liu, XZ Choy, E Mankin, H Hornicek, FJ Duan, ZF AF Yang, Wen Liu, Xianzhe Choy, Edwin Mankin, Henry Hornicek, Francis J. Duan, Zhenfeng TI Targeting hedgehog-GLI-2 pathway in osteosarcoma SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE osteosarcoma; hedgehog; GLI-2 ID SIGNAL TRANSDUCER; CELL-GROWTH; CANCER; INHIBITION; APOPTOSIS; STAT3; GLI2 AB Osteosarcoma is the most common primary malignant tumor of bone. Patients with localized osteosarcoma are routinely treated with chemotherapy and surgery. However, many of these patients eventually relapse after these treatments. In such cases, there are limited treatment options for these patients and most will eventually die with metastatic disease. Therefore, it is imperative to identify better therapeutic strategies. Hedgehog-GLI is responsible for the development of vertebrate embryonic and tumorigenesis. Specifically, the transcription factor, GLI-2, plays a key role in development of normal prostate. Aberrant activation of GLI-2 is correlated with various malignancies. We observe that GLI-2 is highly expressed in osteosarcoma cell lines, and this correlates with poor clinical outcomes in patients. Knockdown of GLI-2 by siRNA decreases osteosarcoma cell proliferation and viability, which eventually induces cell death as revealed in both in 2D and 3D cultures. In addition, we notice that administration of GLI-2 siRNA can increase the sensitivity of osteosarcoma cells to chemotherapeutic drugs. These findings suggest GLI-2 is required for osteosarcoma cell proliferation and survival. GLI-2 may be exploited as a therapeutic target for the treatment of osteosarcoma patients. (C) 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 502509, 2013 C1 [Yang, Wen; Liu, Xianzhe; Choy, Edwin; Mankin, Henry; Hornicek, Francis J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. [Yang, Wen; Liu, Xianzhe; Choy, Edwin; Mankin, Henry; Hornicek, Francis J.; Duan, Zhenfeng] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Yang, Wen] Huazhong Univ Sci & Technol, Union Hosp, Dept Anesthesiol, Tongji Med Coll, Wuhan 430022, Peoples R China. [Liu, Xianzhe] Huazhong Univ Sci & Technol, Union Hosp, Dept Orthopaed Surg, Tongji Med Coll, Wuhan 430022, Peoples R China. [Mankin, Henry; Hornicek, Francis J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. EM zduan@partners.org OI Choy, Edwin/0000-0001-9896-8084 FU Sarcoma Foundation of America; Gattegno and Wechsler Funds; Kenneth Stanton Fund; Jennifer Hunter Yates Foundation FX Dr. Duan is supported, in part, through a grant from Sarcoma Foundation of America.; Grant sponsor: Gattegno and Wechsler Funds (partial support); Grant sponsor: Kenneth Stanton Fund; Grant sponsor: Jennifer Hunter Yates Foundation; Grant sponsor: Sarcoma Foundation of America (partial support). NR 22 TC 14 Z9 17 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD MAR PY 2013 VL 31 IS 3 BP 502 EP 509 DI 10.1002/jor.22230 PG 8 WC Orthopedics SC Orthopedics GA 076TJ UT WOS:000313980600023 PM 22968906 ER PT J AU Suganuma, R Wang, LL Sano, H Naranjo, A London, WB Seeger, RC Hogarty, MD Gastier-Foster, JM Look, AT Park, JR Maris, JM Cohn, SL Amann, G Beiske, K Cullinane, CJ d'Amore, ESG Gambini, C Jarzembowski, JA Joshi, VV Navarro, S Peuchmaur, M Shimada, H AF Suganuma, Rie Wang, Larry L. Sano, Hideki Naranjo, Arlene London, Wendy B. Seeger, Robert C. Hogarty, Michael D. Gastier-Foster, Julie M. Look, A. Thomas Park, Julie R. Maris, John M. Cohn, Susan L. Amann, Gabriele Beiske, Klaus Cullinane, Catherine J. d'Amore, Emanuele S. G. Gambini, Claudio Jarzembowski, Jason A. Joshi, Vijay V. Navarro, Samuel Peuchmaur, Michel Shimada, Hiroyuki TI Peripheral neuroblastic tumors with genotype-phenotype discordance: A report from the Children's Oncology Group and the International Neuroblastoma Pathology Committee SO PEDIATRIC BLOOD & CANCER LA English DT Article DE genotype-phenotype correlation; immunohistochemistry; International Neuroblastoma Pathology Classification; MYCN; neuroblastoma; prognosis ID MYC GENE AMPLIFICATION; SCHWANNIAN STROMA-POOR; N-MYC; CANCER; BIOLOGY; STAGE; GANGLIONEUROBLASTOMA; CLASSIFICATION; PROGNOSIS; DIAGNOSIS AB Background Of 4,706 peripheral neuroblastic tumors (pNTs) registered on the Children's Cancer Group and Children's Oncology Group Neuroblastoma Study between 1989 and 2010, 51 cases (1.1%) had genotypephenotype discordance characterized by MYCN amplification (indicating poor prognosis) and Favorable Histology (indicating better prognosis). Procedure To distinguish prognostic subgroups in the genotypephenotype discordant pNTs, two subgroups, conventional and bull's eye, were identified based on the nuclear morphology. The conventional tumors (35 cases) included: Neuroblastoma, poorly differentiated subtype (NB-PD, 26 cases) with salt-and-pepper nuclei; neuroblastoma, differentiating subtype (4 cases); ganglioneuroblastoma, intermixed (3 cases); and ganglioneuroma, maturing subtype (2 cases). The bull's eye tumors included NB-PD with prominent nucleoli (16 cases). Clinicopathologic characteristics of these two subgroups were analyzed. N-myc protein expression was tested immunohistochemically on available tumors. Results No significant difference was found between these two subgroups in the distribution of prognostic factors such as age at diagnosis, clinical stage, histopathology category/subtype, mitosis-karyorrhexis index, ploidy, 1p LOH, and unbalanced 11q LOH. However, prognosis of the patients with conventional tumors (5-year EFS 85.7 +/- 12.2%;OS 89.3 +/- 10.3%) was significantly better than those with bull's eye tumors (EFS 31.3 +/- 13.0%; OS 42.9 +/- 16.2%; P = 0.0010 and 0.0008, respectively). Immunohistochemically all (11/11) tested conventional tumors were negative, and 10/11 tested bull's eye tumors were positive for N-myc protein expression. Conclusions Based on the presence or absence of prominent nucleoli (the putative site of RNA synthesis/accumulation leading to N-myc protein expression), two prognostic subgroups, conventional with a better prognosis and bull's eye with a poor prognosis, were distinguished among the genotypephenotype discordant pNTs. Pediatr Blood Cancer 2013; 60: 363370. (C) 2012 Wiley Periodicals, Inc. C1 [Suganuma, Rie; Wang, Larry L.; Shimada, Hiroyuki] Childrens Hosp Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90027 USA. [Suganuma, Rie; Wang, Larry L.; Seeger, Robert C.; Shimada, Hiroyuki] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Sano, Hideki] Fukushima Med Univ, Sch Med, Dept Pediat, Fukushima, Japan. [Naranjo, Arlene] Univ Florida, Coll Med, Dept Biostat, Gainesville, FL USA. [Naranjo, Arlene] Univ Florida, Coll Publ Hlth & Hlth Profess, Dept Biostat, Gainesville, FL USA. [London, Wendy B.] Childrens Hosp Boston, Boston, MA USA. [London, Wendy B.] Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr, Boston, MA USA. [Seeger, Robert C.] Childrens Hosp Los Angeles, Div Hematol Oncol, Los Angeles, CA 90027 USA. [Hogarty, Michael D.; Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Oncol, Philadelphia, PA 19104 USA. [Gastier-Foster, Julie M.] Ohio Univ, Coll Med, Nationwide Childrens Hosp, Dept Pathol & Lab Med, Columbus, OH USA. [Look, A. Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Park, Julie R.] Seattle Childrens Hosp, Dept Pediat, Seattle, WA USA. [Park, Julie R.] Univ Washington, Sch Med, Seattle, WA USA. [Cohn, Susan L.] Univ Chicago, Dept Pediat, Div Hematol Oncol, Chicago, IL 60637 USA. [Amann, Gabriele] Med Univ Vienna, AKH, Clin Inst Pathol, Vienna, Austria. [Beiske, Klaus] Univ Oslo, Rikshosp, Oslo Univ Hosp, Dept Pathol, N-0027 Oslo, Norway. [Cullinane, Catherine J.] Leeds Teaching Hosp Trust, St Jamess Univ Hosp, Dept Histopathol, Leeds, W Yorkshire, England. [d'Amore, Emanuele S. G.] Osped S Bortolo, Dept Anat Pathol, Vicenza, Italy. [Gambini, Claudio] IRCCS Ist G Gaslini, Dept Res & Diagnost, Genoa, Italy. [Jarzembowski, Jason A.] Childrens Hosp Wisconsin, Dept Pathol, Milwaukee, WI 53201 USA. [Joshi, Vijay V.] Virginia Commonwealth Univ, Med Coll Virginia, Dept Pathol, Richmond, VA 23298 USA. [Navarro, Samuel] Univ Valencia, Sch Med, Dept Pathol, Valencia, Spain. [Peuchmaur, Michel] Univ Paris Diderot, Hop R Debre, APHP, Serv Pathol, Paris, France. RP Shimada, H (reprint author), Childrens Hosp Los Angeles, Dept Pathol & Lab Med, 4650 Sunset Blvd,MS 43, Los Angeles, CA 90027 USA. EM hshimada@chla.usc.edu OI Jarzembowski, Jason/0000-0002-9027-5686; Cohn, Susan/0000-0001-5749-7650 FU National Institutes of Health [U10 CA98413, U10 CA98543]; CHLA Research Institute; Showa University FX Grant sponsor: National Institutes of Health; Grant numbers: U10 CA98413, U10 CA98543.; We thank Xingchao Wang, BS, HT (ASCP) at Children's Hospital Los Angeles for his technical support in immunohistochemistry. We also thank Akira Toki, MD, PhD (Division of Pediatric Surgery, Department of Surgery, Showa University School of Medicine, Tokyo, Japan) for his encouragement and discussion during the project. Many thanks also goes to Dr. Nilsa Ramirez and Ms. Wanda Smith at Nationwide Children's Hospital for their continuous support in this project. This study was supported by the NIH grants U10 CA98413 (COG SDC grant) and U10 CA98543 (COG Chair's grant), the Merit Award to Hiroyuki Shimada from the CHLA Research Institute and the Showa University Research Grant for Young Researchers. NR 36 TC 3 Z9 4 U1 2 U2 9 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAR PY 2013 VL 60 IS 3 BP 363 EP 370 DI 10.1002/pbc.24238 PG 8 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 073ET UT WOS:000313727000004 PM 22744966 ER PT J AU Raney, B Huh, W Hawkins, D Hayes-Jordan, A Million, L Rodeberg, D Teot, L Anderson, J AF Raney, Beverly Huh, Winston Hawkins, Douglas Hayes-Jordan, Andrea Million, Lynn Rodeberg, David Teot, Lisa Anderson, James CA Children's Oncology Grp TI Outcome of patients with localized orbital sarcoma who relapsed following treatment on Intergroup Rhabdomyosarcoma Study Group (IRSG) Protocols-III and -IV, 1984-1997: A report from the Children's Oncology Group SO PEDIATRIC BLOOD & CANCER LA English DT Article DE outcome after recurrence; pediatric; adolescent orbital sarcoma ID OF-PEDIATRIC-ONCOLOGY; NONMETASTATIC RHABDOMYOSARCOMA; 3RD; ADOLESCENTS; RECURRENCE; CHILDHOOD; SURVIVAL; THERAPY; PATTERN; TUMORS AB Background We wanted to ascertain patterns of recurrence, re-treatment, and outcome among 188 eligible patients treated for localized orbital sarcoma on IRSG Protocols III/IV, 1984-1997. Procedure Retrospective chart review. Results Twenty-four of 188 patients (12.8%) developed local (n = 22) or distant relapse (n = 2) at 0.057-7.05 years (median, 1.58) after enrollment. Ages at study entry were 0.14-17 years (median, 5 years). Initial tumor operations included biopsy (n = 20) or gross resection with microscopic residual (n = 4). Initial tumor diameters were 0.57 cm (median, 3). Pathologic subtypes were embryonal rhabdomyosarcoma (ERMS, n = 19), sarcoma not otherwise specified (n = 2), and alveolar RMS, botryoid ERMS, or undifferentiated sarcoma (n = 1 each). Initial treatment included vincristine/dactinomycin (n = 24) including an alkylator (n = 4) and radiotherapy (RT, n = 21). Twenty patients responded, 14 completely, 6 partially. After recurrence, patients underwent orbital exenteration (n = 10), enucleation (2), tumor excision (3), or biopsy (1); 7 had no operation, and 1 had no data. Post-relapse chemotherapy included combinations of etoposide (n = 14 patients), doxorubicin (14), ifosfamide (12), cyclophosphamide (7), and dacarbazine (n = 1). Six patients received RT, including four previously treated and two not irradiated initially. Two patients died; one at 1.79 years after contralateral brain metastasis followed by local recurrence, and another at 2.49 years after multiple local recurrences. Twenty-two patients (91.7%) survived sarcoma-free for 0.04-17 years (median, 6.9) after relapse, and 18 of 22 (82%) were alive >= 5 years after relapse. Conclusion Survival following recurrent localized orbital sarcoma appears likely after vigorous re-treatment given with curative intent. Pediatr Blood Cancer 2013; 60: 371-376. (C) 2012 Wiley Periodicals, Inc. C1 [Raney, Beverly; Huh, Winston; Hayes-Jordan, Andrea] UT MD Anderson Canc Ctr, Div Pediat, Houston, TX USA. [Raney, Beverly; Huh, Winston; Hayes-Jordan, Andrea] UT MD Anderson Canc Ctr, Childrens Canc Hosp, Houston, TX USA. [Hawkins, Douglas] Univ Washington, Sch Med, Seattle Childrens Hosp, Seattle, WA USA. [Hawkins, Douglas] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Million, Lynn] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Rodeberg, David] Univ Pittsburgh, Pittsburgh, PA USA. [Teot, Lisa] Dana Farber Canc Inst, Boston, MA 02115 USA. [Anderson, James] Univ Nebraska Med Ctr, Omaha, NE USA. RP Raney, B (reprint author), 2903 White Rock Dr, Austin, TX 78757 USA. EM rbraney@austin.rr.com FU National Cancer Institute [CA-24507, CA-29511, CA-72989, CA-98543]; National Cancer Institute, Bethesda, MD [CA-24507, CA-29511, CA-72989, CA-98543] FX Grant sponsor: National Cancer Institute; Grant numbers: CA-24507, CA-29511, CA-72989, CA-98543.; This work was supported in part by Grants CA-24507, CA-29511, CA-72989, and CA-98543 from the National Cancer Institute, Bethesda, MD. A complete listing of grant support for research conducted by CCG and POG before initiation of the COG grant in 2003 is available online at http://www.childrensoncologygroup.org/admin/grantinfo.htm NR 22 TC 6 Z9 7 U1 0 U2 9 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAR PY 2013 VL 60 IS 3 BP 371 EP 376 DI 10.1002/pbc.24289 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 073ET UT WOS:000313727000005 PM 22961750 ER PT J AU Han, CNN Xie, WL Yang, M Hsieh, CL Drouin, S Lee, GSM Kantoff, PW AF Han Christine Ngoc Nguyen Xie, Wanling Yang, Ming Hsieh, Chen-Lin Drouin, Sarah Lee, Gwo-Shu Mary Kantoff, Philip W. TI Expression differences of circulating microRNAs in metastatic castration resistant prostate cancer and low-risk, localized prostate cancer SO PROSTATE LA English DT Article DE circulating microRNAs; prostate cancer; castration resistant prostate cancer ID BIOMARKERS; CARCINOMA; THERAPY; CELLS AB BACKGROUND Recent studies show that microRNAs (miRNAs), small non-coding RNAs that negatively regulate gene expression, may have potential for monitoring cancer status. We investigated circulating miRNAs in prostate cancer that may be associated with the progression of hormone-sensitive primary tumors to metastatic castration resistant prostate cancer (CRPC) after androgen deprivation therapy. METHODS Using genome-wide expression profiling by TaqMan Human MicroRNA Arrays (Applied Biosystems) and/or quantitative real-time polymerase chain reaction, we compared the expression levels of miRNAs in serum samples from 28 patients of low-risk localized disease, 30 of high-risk localized disease and 26 of metastatic CRPC. RESULTS We demonstrated that serum samples from patients of low risk, localized prostate cancer and metastatic CRPC patients exhibit distinct circulating miRNA signatures. MiR-375, miR-378*, and miR-141 were significantly over-expressed in serum from CRPC patients compared with serum from low-risk localized patients, while miR-409-3p was significantly under-expressed. In prostate primary tumor samples, miR-375 and miR-141 also had significantly higher expression levels compared with those in normal prostate tissue. CONCLUSIONS Circulating miRNAs, particularly miR-375, miR-141, miR-378*, and miR-409-3p, are differentially expressed in serum samples from prostate cancer patients. In the search for improved minimally invasive methods to follow cancer pathogenesis, the correlation of disease status with the expression patterns of circulating miRNAs may indicate the potential importance of circulating miRNAs as prognostic markers for prostate cancer progression. Prostate 73: 346354, 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Han Christine Ngoc Nguyen; Yang, Ming; Hsieh, Chen-Lin; Drouin, Sarah; Lee, Gwo-Shu Mary; Kantoff, Philip W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Han Christine Ngoc Nguyen; Xie, Wanling; Yang, Ming; Hsieh, Chen-Lin; Drouin, Sarah; Lee, Gwo-Shu Mary; Kantoff, Philip W.] Harvard Univ, Sch Med, Boston, MA USA. [Xie, Wanling] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. RP Lee, GSM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM gwo-shu_lee@dfci.harvard.edu; philip_kantoff@dfci.harvard.edu RI Yang, Ming/G-4705-2012 OI Yang, Ming/0000-0002-7722-7487 FU SPORE in Prostate Cancer (PWK) [2 P50 CA090381-06] FX Grant sponsor: SPORE in Prostate Cancer (PWK); Grant number: 2 P50 CA090381-06. NR 24 TC 1 Z9 1 U1 3 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-4137 J9 PROSTATE JI Prostate PD MAR PY 2013 VL 73 IS 4 BP 346 EP 354 DI 10.1002/pros.22572 PG 9 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 076WZ UT WOS:000313991200002 ER PT J AU Abern, MR Aronson, WJ Terris, MK Kane, CJ Presti, JC Amling, CL Freedland, SJ AF Abern, Michael R. Aronson, William J. Terris, Martha K. Kane, Christopher J. Presti, Joseph C., Jr. Amling, Christopher L. Freedland, Stephen J. TI Delayed radical prostatectomy for intermediate-risk prostate cancer is associated with biochemical recurrence: Possible implications for active surveillance from the SEARCH database SO PROSTATE LA English DT Article DE prostatic neoplasms; prostatectomy; retropubic; treatment outcome; active surveillance ID DISEASE RECURRENCE; MEN; BIOPSY; DEATH; DIAGNOSIS; MORTALITY; OUTCOMES; THERAPY; IMPACT; TIME AB INTRODUCTION Active surveillance (AS) is increasingly accepted as appropriate management for low-risk prostate cancer (PC) patients. It is unknown whether delaying radical prostatectomy (RP) is associated with increased risk of biochemical recurrence (BCR) for men with intermediate-risk PC. METHODS We performed a retrospective analysis of 1,561 low and intermediate-risk men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database treated with RP between 1988 and 2011. Patients were stratified by interval between diagnosis and RP (=3, 36, 69, or >9 months) and by risk using the D'Amico classification. Cox proportional hazard models were used to analyze BCR. Logistic regression was used to analyze positive surgical margins (PSM), extracapsular extension (ECE), and pathologic upgrading. RESULTS Overall, 813 (52%) men were low-risk, and 748 (48%) intermediate-risk. Median follow-up among men without recurrence was 52.9 months, during which 437 men (38.9%) recurred. For low-risk men, RP delays were unrelated to BCR, ECE, PSM, or upgrading (all P?>?0.05). For intermediate-risk men, however, delays >9 months were significantly related to BCR (HR: 2.10, P?=?0.01) and PSM (OR: 4.08, P?9 months were associated with BCR in subsets of intermediate-risk men with biopsy Gleason score =3?+?4 (HR: 2.51, P?9 months predicted greater BCR and PSM risk. If confirmed in future studies, this suggests delayed RP for intermediate-risk PC may compromise outcomes. Prostate 73: 409417, 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Abern, Michael R.; Freedland, Stephen J.] Duke Univ, Sch Med, Dept Surg, Div Urol Surg, Durham, NC 27705 USA. [Aronson, William J.] VA Greater Los Angeles Healthcare Syst, Dept Surg, Urol Sect, Los Angeles, CA USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. [Terris, Martha K.] VAMC, Urol Sect, Augusta, GA USA. [Terris, Martha K.] Med Coll Georgia, Urol Sect, Augusta, GA 30912 USA. [Kane, Christopher J.] Univ Calif San Diego, Div Urol, San Diego, CA USA. [Presti, Joseph C., Jr.] Stanford Univ, Sch Med, Dept Urol, Palo Alto, CA 94304 USA. [Presti, Joseph C., Jr.] VAMC, Urol Sect, Palo Alto, CA USA. [Amling, Christopher L.] Oregon Hlth & Sci Univ, Dept Urol, Portland, OR USA. [Freedland, Stephen J.] VAMC, Urol Sect, Durham, NC USA. RP Abern, MR (reprint author), Duke Univ, Sch Med, Dept Surg, Div Urol Surg, 200 Trent Dr,DUMC Box 2804, Durham, NC 27705 USA. EM michael.abern@duke.edu OI Terris, Martha/0000-0002-3843-7270 NR 33 TC 26 Z9 26 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-4137 J9 PROSTATE JI Prostate PD MAR PY 2013 VL 73 IS 4 BP 409 EP 417 DI 10.1002/pros.22582 PG 9 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 076WZ UT WOS:000313991200009 PM 22996686 ER PT J AU Terrin, N Rodday, AM Tighiouart, H Chang, G Parsons, SK AF Terrin, Norma Rodday, Angie Mae Tighiouart, Hocine Chang, Grace Parsons, Susan K. CA Journeys Recovery Study TI Parental emotional functioning declines with occurrence of clinical complications in pediatric hematopoietic stem cell transplant SO SUPPORTIVE CARE IN CANCER LA English DT Article DE Pediatric hematopoietic stem cell transplant; Parental emotional functioning; Parental distress; Transplant-related toxicity ID BONE-MARROW-TRANSPLANTATION; CHILDREN; DISTRESS; MOTHERS; DEPRESSION; DISEASE; ANXIETY; STRESS; GRAFT AB Parents' stress levels are high prior to their child's hematopoietic stem cell transplant (HSCT) and during transplant hospitalization, usually abating after discharge. Nevertheless, a subgroup of parents continues to experience frequent anxiety and mood disruption, the causes of which are not well understood. The purpose of this study was to assess whether clinical complications of HSCT could explain variation in parents' recovery of emotional functioning. Pediatric HSCT recipients (n = 165) aged 5-18 and their parents were followed over the first year post-transplant. Health-related quality of life assessments and medical chart reviews were performed at each time period (baseline, 45 days, 3, 6, and 12 months). We tested the association between clinical complications [acute and chronic graft versus host disease (aGVHD and cGVHD), organ toxicity, and infection] and longitudinally measured parental emotional functioning, as assessed by the Child Health-Ratings Inventories. The models used maximum likelihood estimation with repeated measures. In adjusted analyses covering the early time period (45 days and 3 months), aGVHD grade a parts per thousand yen2, intermediate or poor organ toxicity, and systemic infection were associated with decreases in mean parental emotional functioning of 5.2 (p = 0.086), 5.8 (p = 0.052), and 5.1 (p = 0.023) points, respectively. In the later time period (6 and 12 months), systemic infection was associated with a decrease of 20 points (p < 0.0001). cGVHD was not significantly associated. When children experience clinical complications after HSCT, parental emotional functioning can be impacted. Intervening at critical junctures could mitigate potential negative consequences for parents and their children. C1 [Terrin, Norma; Rodday, Angie Mae; Tighiouart, Hocine; Parsons, Susan K.] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA 02111 USA. [Terrin, Norma; Parsons, Susan K.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Chang, Grace] VA Boston Healthcare Syst, Brockton, MA 02301 USA. RP Terrin, N (reprint author), Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, 800 Washington St,Box 063, Boston, MA 02111 USA. EM nterrin@tuftsmedicalcenter.org FU American Cancer Society [RSGPB-02-186-01-PBP]; NIH [R01 CA119196] FX This study was supported by American Cancer Society grant RSGPB-02-186-01-PBP (Parsons, PI) and NIH grant R01 CA119196 (Parsons, PI). NR 24 TC 10 Z9 10 U1 1 U2 17 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD MAR PY 2013 VL 21 IS 3 BP 687 EP 695 DI 10.1007/s00520-012-1566-9 PG 9 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 081FD UT WOS:000314301900004 PM 22936494 ER PT J AU Mosher, CE Champion, VL Azzoli, CG Hanna, N Jalal, SI Fakiris, AJ Birdas, TJ Okereke, IC Kesler, KA Einhorn, LH Monahan, PO Ostroff, JS AF Mosher, Catherine E. Champion, Victoria L. Azzoli, Christopher G. Hanna, Nasser Jalal, Shadia I. Fakiris, Achilles J. Birdas, Thomas J. Okereke, Ikenna C. Kesler, Kenneth A. Einhorn, Lawrence H. Monahan, Patrick O. Ostroff, Jamie S. TI Economic and social changes among distressed family caregivers of lung cancer patients SO SUPPORTIVE CARE IN CANCER LA English DT Article DE Lung cancer; Family caregiving; Economic; Financial; Employment; Psychological distress ID QUALITY-OF-LIFE; INFORMAL CAREGIVERS; HOSPITAL ANXIETY; DEPRESSION SCALE; MENTAL-HEALTH; BURDEN; CARE; SUPPORT; STRESS; IMPACT AB Although costs of lung cancer care have been documented, economic and social changes among lung cancer patients' family caregivers have yet to be fully examined. In addition, research has not focused on caregivers with greater need for support services. This study examined various economic and social changes among distressed family caregivers of lung cancer patients during the initial months of cancer care in the USA. Lung cancer patients' primary family caregivers with significant anxiety or depressive symptoms were recruited from three medical centers within 12 weeks of the patient's new oncology visit. Caregivers (N = 83) reported demographic and medical information and caregiving burden at baseline. Seventy-four caregivers reported anxiety and depressive symptoms and economic and social changes 3 months later. Seventy-four percent of distressed caregivers experienced one or more adverse economic or social changes since the patient's illness. Common changes included caregivers' disengagement from most social and leisure activities (56 %) and, among employed caregivers (n = 49), reduced hours of work (45 %). In 18 % of cases, a family member quit work or made another major lifestyle change due to caregiving. Additionally, 28 % of caregivers reported losing the main source of family income, and 18 % reported losing most or all of the family savings. Loss of the main source of family income and disengagement from most social and leisure activities predicted greater caregiver distress. Findings suggest that distressed caregivers of lung cancer patients experience high rates of adverse economic and social changes that warrant clinical and research attention. C1 [Mosher, Catherine E.] Indiana Univ Purdue Univ Indianapolis, Dept Psychol, Indianapolis, IN 46202 USA. [Champion, Victoria L.] Indiana Univ, Sch Nursing, Indianapolis, IN 46202 USA. [Azzoli, Christopher G.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Hanna, Nasser; Jalal, Shadia I.; Einhorn, Lawrence H.] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA. [Fakiris, Achilles J.] Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC 27514 USA. [Birdas, Thomas J.; Okereke, Ikenna C.; Kesler, Kenneth A.] Indiana Univ Sch Med, Dept Surg, Indianapolis, IN 46202 USA. [Monahan, Patrick O.] Indiana Univ Sch Med, Dept Biostat, Indianapolis, IN 46202 USA. [Ostroff, Jamie S.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10022 USA. RP Mosher, CE (reprint author), Indiana Univ Purdue Univ Indianapolis, Dept Psychol, 402 N Blackford St,LD 124, Indianapolis, IN 46202 USA. EM cemosher@iupui.edu OI Ostroff, Jamie/0000-0003-2671-5680 FU National Cancer Institute [R03CA139862, F32CA130600]; National Center for Research Resources [KL2 RR025760] FX This study was supported by Grant No. R03CA139862 from the National Cancer Institute. CM was supported by F32CA130600 from the National Cancer Institute and KL2 RR025760 (A. Shekhar, PI) from the National Center for Research Resources. The authors would like to thank the study participants, the thoracic oncology teams at Memorial Sloan-Kettering Cancer Center, Indiana University Simon Cancer Center, and the Roudebush VA Medical Center, Scarlett Ho, Aigul Amankeldi, Shannon M. Christy, and undergraduate students for their assistance. NR 33 TC 10 Z9 10 U1 2 U2 25 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD MAR PY 2013 VL 21 IS 3 BP 819 EP 826 DI 10.1007/s00520-012-1585-6 PG 8 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 081FD UT WOS:000314301900018 PM 22945881 ER PT J AU Wang, ZH Sagotsky, J Taylor, T Shironoshita, P Deisboeck, TS AF Wang, Zhihui Sagotsky, Jonathan Taylor, Thomas Shironoshita, Patrick Deisboeck, Thomas S. TI Accelerating cancer systems biology research through Semantic Web technology SO WILEY INTERDISCIPLINARY REVIEWS-SYSTEMS BIOLOGY AND MEDICINE LA English DT Review ID CELL LUNG-CANCER; MATHEMATICAL-MODEL; LIFE SCIENCES; TUMOR-GROWTH; ONTOLOGIES; FUTURE; IMPLEMENTATION; REPRESENTATION; EVOLUTION; DISCOVERY AB Cancer systems biology is an interdisciplinary, rapidly expanding research field in which collaborations are a critical means to advance the field. Yet the prevalent database technologies often isolate data rather than making it easily accessible. The Semantic Web has the potential to help facilitate web-based collaborative cancer research by presenting data in a manner that is self-descriptive, human and machine readable, and easily sharable. We have created a semantically linked online Digital Model Repository (DMR) for storing, managing, executing, annotating, and sharing computational cancer models. Within the DMR, distributed, multidisciplinary, and inter-organizational teams can collaborate on projects, without forfeiting intellectual property. This is achieved by the introduction of a new stakeholder to the collaboration workflow, the institutional licensing officer, part of the Technology Transfer Office. Furthermore, the DMR has achieved silver level compatibility with the National Cancer Institute's caBIG, so users can interact with the DMR not only through a web browser but also through a semantically annotated and secure web service. We also discuss the technology behind the DMR leveraging the Semantic Web, ontologies, and grid computing to provide secure inter-institutional collaboration on cancer modeling projects, online grid-based execution of shared models, and the collaboration workflow protecting researchers' intellectual property. WIREs Syst Biol Med 2013, 5:135151. doi: 10.1002/wsbm.1200 For further resources related to this article, please visit the WIREs website. C1 [Wang, Zhihui] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA. [Sagotsky, Jonathan; Deisboeck, Thomas S.] Massachusetts Gen Hosp, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Charlestown, MA USA. [Taylor, Thomas; Shironoshita, Patrick] INFOTECH Soft Inc, Miami, FL USA. RP Deisboeck, TS (reprint author), Massachusetts Gen Hosp, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Charlestown, MA USA. EM deisboec@helix.mgh.harvard.edu FU NIH [CA 113004]; Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging; Department of Radiology at Massachusetts General Hospital FX This work has been supported in part by NIH grant CA 113004 and by the Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging and the Department of Radiology at Massachusetts General Hospital. Both CViT.org and DMR/CMEF are currently hosted at INFOTECH SOFT Inc. NR 69 TC 7 Z9 7 U1 0 U2 30 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 MAR-APR PY 2013 VL 5 IS 2 BP 135 EP 151 DI 10.1002/wsbm.1200 PG 17 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 079MZ UT WOS:000314176000002 PM 23188758 ER PT J AU Bedoya, CA Traeger, L Trinh, NH Chang, T Brill, C Hails, K Hagan, P Flaherty, K Yeung, A AF Bedoya, C. Andres Traeger, Lara Nhi-Ha Trinh Chang, Trina Brill, Charlotte Hails, Katherine Hagan, Patrick Flaherty, Katherine Yeung, Albert TI IMPACT OF A CULTURALLY-FOCUSED PSYCHIATRIC CONSULTATION INTERVENTION ON DEPRESSIVE SYMPTOMS AMONG LATINO PRIMARY CARE PATIENTS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Bedoya, C. Andres; Traeger, Lara; Nhi-Ha Trinh; Chang, Trina; Yeung, Albert] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bedoya, C. Andres; Traeger, Lara; Nhi-Ha Trinh; Chang, Trina; Yeung, Albert] Harvard Med Sch, Boston, MA USA. [Flaherty, Katherine] ABT Associates Inc, Cambridge, MA USA. [Brill, Charlotte] Univ Washington, Seattle, WA 98195 USA. [Hails, Katherine] Childrens Hosp, Boston, MA 02115 USA. [Hagan, Patrick] Smith Coll, Northampton, MA 01063 USA. EM abedoya@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA 3113 BP S179 EP S179 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928001274 ER PT J AU Benedict, C Traeger, L Rasheed, M Zhou, E Bustillo, NE Kava, B Soloway, M Antoni, M Penedo, FJ AF Benedict, Catherine Traeger, Lara Rasheed, Mikal Zhou, Eric Bustillo, Natalie E. Kava, Bruce Soloway, Mark Antoni, Michael Penedo, Frank J. TI QUALITY OF LIFE IN MEN WITH PROSTATE CANCER: LONG-TERM EFFECTS OF A PSYCHOSOCIAL INTERVENTION SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Benedict, Catherine; Rasheed, Mikal; Zhou, Eric; Bustillo, Natalie E.; Antoni, Michael] Univ Miami, Psychol, Coral Gables, FL 33124 USA. [Antoni, Michael] Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL USA. [Kava, Bruce; Soloway, Mark] Miller Sch Med, Urol, Miami, FL USA. [Traeger, Lara] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. [Penedo, Frank J.] Northwestern Univ, Feinberg Sch Med, Med Social Sci, Boston, MA USA. EM cbenedict@psy.miami.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA D-003 BP S258 EP S258 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928001588 ER PT J AU Chandwani, K Zhao, FM Morrow, GR Deshields, T Manola, J Fisch, MJ AF Chandwani, Kavita Zhao, Fengmin Morrow, Gary R. Deshields, Teresa Manola, Judith Fisch, Michael J. TI PATIENT-CLINICIAN DISCORDANCE (PCD), DISTRESS, AND QUALITY OF LIFE (QOL) IN CANCER SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Chandwani, Kavita; Morrow, Gary R.] Univ Rochester, Med Ctr, Wilmot Canc Ctr, Rochester, NY 14623 USA. [Fisch, Michael J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Zhao, Fengmin; Manola, Judith] Dana Farber Canc Ctr, Boston, MA USA. [Deshields, Teresa] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO 63110 USA. EM kavita_chandwani@urmc.rochester.edu FU PHS [CA37604, CA17145]; NCI, NIH; DHHS FX PHS Grants CA37604, CA17145, and NCI, NIH, and DHHS grants NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA B-013 BP S100 EP S100 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928000392 ER PT J AU Chiu, CJ Lu, FH Hsu, YC Lee, SL Wray, LA Beverly, EA AF Chiu, Ching-Ju Lu, Feng-Hwa Hsu, Yu-Ching Lee, Siao-Ling Wray, Linda A. Beverly, Elizabeth A. TI IDENTIFICATION OF RISK GROUPS DEVELOPING DEPRESSION AFTER DIABETES DIAGNOSIS: GROUP-BASED TRAJECTORY MODELING APPROACH SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Chiu, Ching-Ju; Lu, Feng-Hwa; Hsu, Yu-Ching; Lee, Siao-Ling] Natl Cheng Kung Univ, Inst Gerontol, Tainan, Taiwan. [Lu, Feng-Hwa] Natl Cheng Kung Univ Hosp, Family Med, Tainan, Taiwan. [Wray, Linda A.] Penn State Univ, Biobehav Hlth, State Coll, PA USA. [Hsu, Yu-Ching] Tainan Hosp, Chinese Med, Tainan, Taiwan. [Beverly, Elizabeth A.] Joslin Diabet Med Ctr, Boston, MA USA. EM cjchiu@mail.ncku.edu.tw NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA C-057 BP S205 EP S205 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928001375 ER PT J AU Cohen, L Wolpert, H Ritholz, M Kaufman, F AF Cohen, Larry Wolpert, Howard Ritholz, Marilyn Kaufman, Francine TI FACING DIABETES AS A NATION: MAXIMIZING HEALTH THROUGH TECHNOLOGY AND COMMUNITY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Cohen, Larry] Prevent Inst, Oakland, CA 94607 USA. [Wolpert, Howard] Joslin Diabet Ctr, Sect Adult Diabet, Boston, MA 02215 USA. [Ritholz, Marilyn] Harvard Med Sch, Joslin Diabet Ctr, Mental Hlth Psychiat, Boston, MA USA. [Kaufman, Francine] Univ Southern Calif, Keck Sch Med, Los Angeles, CA USA. [Kaufman, Francine] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA 2103 BP S81 EP S81 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928000316 ER PT J AU Cooley, ME Lobach, DF Abrahm, JL Braun, I Rabin, MS Berry, DL AF Cooley, Mary E. Lobach, David F. Abrahm, Janet L. Braun, Illana Rabin, Michael S. Berry, Donna L. TI DECISION SUPPORT FOR SYMPTOM AND QUALITY OF LIFE MANAGEMENT SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Cooley, Mary E.; Abrahm, Janet L.; Braun, Illana; Rabin, Michael S.; Berry, Donna L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lobach, David F.] Religent Hlth Inc, Raleigh, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA 2003 BP S55 EP S55 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928000216 ER PT J AU Deguchi, M Oropeza, ME Nigg, C Niederman, R Efird, J Valente, T AF Deguchi, Mikako Oropeza, Martha E. Nigg, Claudio Niederman, Richard Efird, Jimmy Valente, Tom TI THE MINO'AKA (SMILE) PROJECT: LESSONS LEARNED FROM PILOTING AN EVIDENCE BASED ORAL HEALTH PROGRAM FOR CHILDREN SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Deguchi, Mikako; Oropeza, Martha E.; Nigg, Claudio] Univ Hawaii Manoa, Dept Publ Hlth Sci, Honolulu, HI 96826 USA. [Niederman, Richard] Forsyth Inst, Dept Appl Oral Hlth Sci, Cambridge, MA USA. [Efird, Jimmy] East Carolina Univ, Publ Hlth, Greenville, NC USA. [Valente, Tom] Univ Southern Calif, Prevent Med, Los Angeles, CA USA. EM meo3@hawaii.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA 3093 BP S174 EP S174 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928001254 ER PT J AU Gonzalez, JS Cagliero, E Psaros, C Wexler, D Delahanty, L Perry, N Blashill, A Safren, S AF Gonzalez, Jeffrey S. Cagliero, Enrico Psaros, Christina Wexler, Deborah Delahanty, Linda Perry, Nicholas Blashill, Aaron Safren, Steven TI COGNITIVE BEHAVIORAL THERAPY FOR ADHERENCE AND DEPRESSION IN ADULTS WITH TYPE 2 DIABETES: ACUTE AND MAINTENANCE OUTCOMES FROM A RANDOMIZED CONTROLLED TRIAL SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Gonzalez, Jeffrey S.] Yeshiva Univ, Albert Einstein Coll Med, Bronx, NY 10461 USA. [Cagliero, Enrico; Psaros, Christina; Wexler, Deborah; Delahanty, Linda; Perry, Nicholas; Blashill, Aaron; Safren, Steven] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. EM jeffrey.gonzalez@einstein.yu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA 3114 BP S179 EP S179 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928001275 ER PT J AU Goodrich, DE Kilbourne, AM Chermack, S Bauer, MS AF Goodrich, David E. Kilbourne, Amy M. Chermack, Steve Bauer, Mark S. TI TWO-YEAR OUTCOMES FROM THE SMAHRT TRIAL TO REDUCE CVD RISK IN VETERANS WITH BIPOLAR DISORDER SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Goodrich, David E.; Kilbourne, Amy M.; Chermack, Steve] VA Ann Arbor Healthcare Syst, Ctr Clin Management Res, Ann Arbor, MI 48105 USA. [Goodrich, David E.; Kilbourne, Amy M.; Chermack, Steve] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. [Bauer, Mark S.] VA Boston Healthcare Syst, Boston, MA USA. EM david.goodrich2@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA B-078 BP S115 EP S115 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928001023 ER PT J AU Hartigan, DB Viswanath, K AF Hartigan, Danielle Blanch Viswanath, Kasisomayajula TI CANCER SURVIVORS' USE OF MULTIPLE INFORMATION SOURCES FOR CANCER-RELATED INFORMATION: THE MORE THE MERRIER? SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hartigan, Danielle Blanch] NCI, Off Canc Survivorship, Rockville, MD 20892 USA. [Viswanath, Kasisomayajula] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Viswanath, Kasisomayajula] Harvard Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA USA. EM danielleblanch@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA B-017 BP S101 EP S101 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928000396 ER PT J AU Hartigan, DB Viswanath, K AF Hartigan, Danielle Blanch Viswanath, Kasisomayajula TI SOCIOECONOMIC AND SOCIODEMOGRAPHIC PREDICTORS OF SOURCES OF CANCER-RELATED INFORMATION USED BY CANCER SURVIVORS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hartigan, Danielle Blanch] NCI, Off Canc Survivorship, Rockville, MD 20892 USA. [Viswanath, Kasisomayajula] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Viswanath, Kasisomayajula] Harvard Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA USA. EM danielleblanch@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA B-016 BP S101 EP S101 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928000395 ER PT J AU Hooker, SA Ross, K Masters, KS Park, C Allen, LA Bekelman, DB Grigsby, M AF Hooker, Stephanie A. Ross, Kaile Masters, Kevin S. Park, Crystal Allen, Larry A. Bekelman, David B. Grigsby, Megan TI EFFECTS OF A SPIRITUAL INTERVENTION FOR HEART FAILURE PATIENTS: THE DENVER SPIRITED HEART PILOT STUDY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hooker, Stephanie A.; Ross, Kaile; Masters, Kevin S.; Grigsby, Megan] Univ Colorado, Denver, CO 80220 USA. [Park, Crystal] Univ Connecticut, Storrs, CT USA. [Allen, Larry A.; Bekelman, David B.] Univ Colorado, Sch Med, Aurora, CO USA. [Hooker, Stephanie A.; Bekelman, David B.] Denver Vet Affairs Med Ctr, Denver, CO USA. EM stephanie.hooker@ucdenver.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA C-039 BP S201 EP S201 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928001358 ER PT J AU Hooker, SA Ross, K Masters, KS Park, C Allen, LA Bekelman, DB Grigsby, M AF Hooker, Stephanie A. Ross, Kaile Masters, Kevin S. Park, Crystal Allen, Larry A. Bekelman, David B. Grigsby, Megan TI QUALITATIVE EVALUATION OF A PSYCHOSPIRITUAL INTERVENTION FOR CHRONIC HEART FAILURE (HF) PATIENTS: THE DENVER SPIRITED HEART PILOT STUDY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hooker, Stephanie A.; Ross, Kaile; Masters, Kevin S.; Grigsby, Megan] Univ Colorado, Denver, CO 80220 USA. [Allen, Larry A.; Bekelman, David B.] Univ Colorado, Sch Med, Aurora, CO USA. [Hooker, Stephanie A.; Bekelman, David B.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Park, Crystal] Univ Connecticut, Storrs, CT USA. EM stephanie.hooker@ucdenver.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA 2037 BP S64 EP S64 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928000250 ER PT J AU Koblitz, AR Kaufman, A Park, E Klein, W Ferrer, R AF Koblitz, Amber R. Kaufman, Annette Park, Elyse Klein, William Ferrer, Rebecca TI LUNG CANCER-RELATED RISK PERCEPTIONS IN THE NATIONAL LUNG SCREENING TRIAL: RELIABILITY AND PREDICTION ACROSS TIME SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Koblitz, Amber R.; Kaufman, Annette; Klein, William; Ferrer, Rebecca] NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Park, Elyse] Massachusetts Gen Hosp, Dept Psychiat, Ctr Canc, Boston, MA 02114 USA. EM amber.koblitz@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA 3084 BP S171 EP S171 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928001245 ER PT J AU Kobrin, S Tanaka, M Han, P Sepucha, K Naveed, S Moser, R AF Kobrin, Sarah Tanaka, Miho Han, Paul Sepucha, Karen Naveed, Sana Moser, Richard TI SHARED DECISION MAKING MEASURES: PROMOTING HARMONIZED DATA USING THE NATIONAL CANCER INSTITUTE'S GRID-ENABLED MEASURES (GEM) PORTAL SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Kobrin, Sarah; Tanaka, Miho; Naveed, Sana; Moser, Richard] NCI, Rockville, MD 20852 USA. [Han, Paul] Maine Med Ctr, Scarborough, ME USA. [Sepucha, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM miho.tanaka@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA 3047 BP S161 EP S161 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928001203 ER PT J AU Lewis, M Bann, C Sterba, K Thorpe, CT Carpenter, D DeVellis, R AF Lewis, Megan Bann, Carla Sterba, Katherine Thorpe, Carolyn T. Carpenter, Delesha DeVellis, Robert TI ADHERENCE MEDIATES THE LINK BETWEEN DYADIC EFFICACY AND WELL-BEING AMONG COUPLES MANAGING CHRONIC ILLNESS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Lewis, Megan; Bann, Carla] Res Triangle Inst, Res Triangle Pk, NC 27709 USA. [Sterba, Katherine] Med Univ South Carolina, Charleston, SC USA. [Thorpe, Carolyn T.] Univ Pittsburgh, Pittsburgh, PA USA. [Thorpe, Carolyn T.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Carpenter, Delesha; DeVellis, Robert] Univ North Carolina Chapel Hill, Chapel Hill, NC USA. EM melewis@rti.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA C-125 BP S220 EP S220 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928001435 ER PT J AU Littman, AJ Boyko, EJ Arterburn, DE Haselkorn, JK Sangeorzan, BJ AF Littman, Alyson J. Boyko, Edward J. Arterburn, David E. Haselkorn, Jodie K. Sangeorzan, Bruce J. TI PHYSICAL ACTIVITIES, BARRIERS, AND FACILITATORS IN VETERANS WITH AMPUTATIONS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Littman, Alyson J.; Boyko, Edward J.] VA Puget Sound, Epidemiol, Seattle, WA USA. [Littman, Alyson J.] UW, Epidemiol, Seattle, WA USA. [Arterburn, David E.] Grp Hlth Res Inst, Seattle, WA USA. [Arterburn, David E.; Haselkorn, Jodie K.] VA Puget Sound, Multiple Sclerosis Ctr Excellence West, Seattle, WA USA. [Haselkorn, Jodie K.] UW, Rehabil Med, Seattle, WA USA. [Sangeorzan, Bruce J.] VA Puget Sound, Rehabil R&D Ctr Excellence Limb Loss Prevent & Pr, Seattle, WA USA. EM alyson@u.washington.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA B-166 BP S136 EP S136 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928001106 ER PT J AU Lovejoy, TI AF Lovejoy, Travis I. TI GENDER AND SEXUAL ORIENTATION MODERATE THE EFFECTS OF MOTIVATIONAL INTERVIEWING IN REDUCING SEXUAL RISK BEHAVIOR IN HIV plus OLDER ADULTS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Lovejoy, Travis I.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR 97239 USA. EM travis.lovejoy@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA D-066 BP S273 EP S273 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928002047 ER PT J AU Michalek, AK Prochaska, J Kan, D Banys, P Batki, S Clift, W Lane, P Young, R AF Michalek, Anne K. Prochaska, Judith Kan, David Banys, Peter Batki, Steven Clift, William Lane, Patricia Young, Rebecca TI EFFECTIVE INTERVENTION RECRUITMENT & RETENTION STRATEGIES: WE BUILT IT AND THEY CAME ... AND RETURNED! SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Michalek, Anne K.; Prochaska, Judith; Kan, David; Banys, Peter; Batki, Steven] Univ Calif San Francisco, San Francisco, CA 94109 USA. [Kan, David; Banys, Peter; Batki, Steven; Clift, William; Lane, Patricia; Young, Rebecca] San Francisco VA Med Ctr, San Francisco, CA USA. [Prochaska, Judith] Stanford Univ, Stanford, CA 94305 USA. EM anne.michalek@ucsf.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA A-220 BP S54 EP S54 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928000212 ER PT J AU O'Cleirigh, C Lerner, J Gordan, J Safren, S AF O'Cleirigh, Conall Lerner, Jonathan Gordan, Janna Safren, Steven TI THE IMPACT ON ANXIETY SYMPTOMS OF A CBT INTERVENTION TO TREAT MOOD DISORDERS AMONG PATIENTS WITH HIV IN TREATMENT FOR SUBSTANCE DEPENDENCE: A SECONDARY ANALYSIS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [O'Cleirigh, Conall; Lerner, Jonathan; Gordan, Janna; Safren, Steven] Massachusetts Gen Hosp, Boston, MA 02114 USA. [O'Cleirigh, Conall; Lerner, Jonathan; Gordan, Janna; Safren, Steven] Harvard Med Sch, Boston, MA USA. EM COCLEIRIGH@PARTNERS.ORG NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA 2041 BP S65 EP S65 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928000254 ER PT J AU O'Cleirigh, C Carrico, AW Taylor, W Pantalone, D AF O'Cleirigh, Conall Carrico, Adam W. Taylor, Wade Pantalone, David TI ADAPTING CBT INTERVENTIONS FOR USE WITH MARGINALIZED PATIENT GROUPS MANAGING THE CHALLENGES OF HIV, MENTAL HEALTH, AND SUBSTANCE USE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [O'Cleirigh, Conall] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Carrico, Adam W.] Univ San Francisco, Sch Nursing, San Francisco, CA 94117 USA. [Taylor, Wade] Fenway Hlth, Fenway Inst, Boston, MA USA. [Pantalone, David] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. EM COCLEIRIGH@PARTNERS.ORG NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA 2038 BP S64 EP S64 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928000251 ER PT J AU O'Neill, S Selby, JV Houston, TK Cooley, ME Knight, SJ AF O'Neill, Suzanne Selby, Joe V. Houston, Thomas K. Cooley, Mary E. Knight, Sara J. TI PATIENT-CENTERED OUTCOMES RESEARCH INSTITUTE AND PARTNERS: IMPROVING PATIENT OUTCOMES THROUGH BEHAVIORAL MEDICINE RESEARCH SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [O'Neill, Suzanne] Georgetown Univ, Washington, DC USA. [Cooley, Mary E.] Patient Ctr Outcomes Res Inst, Washington, DC USA. [Houston, Thomas K.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Selby, Joe V.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Knight, Sara J.] VA Off Res & Dev UCSF, San Francisco, CA USA. EM sco4@georgetown.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA 2001 BP S55 EP S55 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928000214 ER PT J AU Oropeza, ME Valente, T Nigg, C Efird, J Deguchi, M Niederman, R AF Oropeza, Martha E. Valente, Tom Nigg, Claudio Efird, Jimmy Deguchi, Mikako Niederman, Richard TI EXPLORING THE RELATIONSHIP BETWEEN ORAL HEALTH SOCIAL NETWORKS, ATTITUDE AND STAGE OF CHANGE IN AFTERSCHOOL STAFF SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Oropeza, Martha E.; Nigg, Claudio; Deguchi, Mikako] Univ Hawaii Manoa, Publ Hlth Sci, Honolulu, HI 96826 USA. [Valente, Tom] Univ Southern Calif, Prevent Med, Los Angeles, CA USA. [Efird, Jimmy] East Carolina Univ, Publ Hlth, Greenville, NC USA. [Niederman, Richard] Forsyth Inst, Dept Appl Oral Hlth Sci, Cambridge, MA USA. EM meo3@hawaii.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA 3094 BP S174 EP S174 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928001255 ER PT J AU Ramanadhan, S Rao, M Mendez, S Viswanath, K AF Ramanadhan, Shoba Rao, Meg Mendez, Samuel Viswanath, Kasisomayajula TI SOCIAL MEDIA USE BY COMMUNITY-BASED ORGANIZATIONS IN THREE MASSACHUSETTS COMMUNITIES: A CONTENT ANALYSIS HIGHLIGHTING PATTERNS AND OPPORTUNITIES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Ramanadhan, Shoba; Mendez, Samuel; Viswanath, Kasisomayajula] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA. [Rao, Meg] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Viswanath, Kasisomayajula] Harvard Sch Publ Hlth, Boston, MA USA. EM shoba_ramanadhan@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA A-132 BP S34 EP S34 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928000131 ER PT J AU Richard, N Tavares, M Goodson, M AF Richard, Niederman Tavares, Mary Goodson, Max TI FORSYTHKIDS SCHOOL-BASED COMPREHENSIVE CARIES PREVENTION PROGRAM SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Richard, Niederman; Tavares, Mary; Goodson, Max] Forsyth Inst, Boston, MA USA. FU NIH-NIMHD [U24 MD006964]; NIH-NIDCR [R34 DE022272] FX Supported by NIH-NIMHD / U24 MD006964 and NIH-NIDCR / R34 DE022272 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA 3092 BP S173 EP S173 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928001253 ER PT J AU Ritholz, M AF Ritholz, Marilyn TI LIVING WITH DIABETES IN RELATIONSHIPS: HOW PARENTS AND PARTNERS CAN SUPPORT CHRONIC DISEASE MANAGEMENT SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Ritholz, Marilyn] Joslin Diabet Ctr, Behav & Mental Hlth Res, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA 2033 BP S63 EP S63 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928000246 ER PT J AU Ritholz, MD AF Ritholz, Marilyn D. TI CONSIDERING THE HUMAN SIDE OF DIABETES TECHNOLOGY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Ritholz, Marilyn D.] Harvard Med Sch, Joslin Diabet Ctr, Mental Hlth Psychiat, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA 2105 BP S81 EP S81 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928000318 ER PT J AU Ruddy, K Greaney, M Sprunck, K Meyer, M Emmons, K Partridge, A AF Ruddy, Kathryn Greaney, Mary Sprunck, Kim Meyer, Meghan Emmons, Karen Partridge, Ann TI YOUNG WOMEN WITH BREAST CANCER: NEEDS AND POTENTIAL INTERVENTIONS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Ruddy, Kathryn; Meyer, Meghan; Partridge, Ann] Dana Farber Canc Inst, Med Breast Oncol, Boston, MA 02215 USA. [Greaney, Mary; Sprunck, Kim; Emmons, Karen] DFCI, Populat Sci, Boston, MA 02215 USA. EM kim_sprunckharrild@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA D-029 BP S265 EP S265 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928002014 ER PT J AU Sanford, S Zhao, F Salsman, M Chang, V Wagner, I Fisch, M AF Sanford, Stacy Zhao, F. Salsman, M. Chang, V. Wagner, I. Fisch, M. TI SYMPTOM BURDEN AMONG YOUNG ADULTS WITH BREAST OR COLORECTAL CANCER (ECOG E2Z02) SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Sanford, Stacy; Salsman, M.; Wagner, I.] Northwestern Univ, Chicago, IL 60611 USA. [Zhao, F.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chang, V.] UMDNJ, VA New Jersey Hlth Care Syst, East Orange, NJ USA. [Fisch, M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. EM ssanford@nmff.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA 2015 BP S58 EP S58 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928000228 ER PT J AU Schneider, K Magidson, J Whited, MC Pagoto, SL AF Schneider, Kristin Magidson, Jessica Whited, Matthew C. Pagoto, Sherry L. TI CLINICAL SEMINAR IN BEHAVIORAL ACTIVATION TREATMENT FOR DEPRESSION WITH COMORBID HEALTH CONDITIONS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Schneider, Kristin] Rosalind Franklin Univ, Psychol, N Chicago, IL USA. [Magidson, Jessica] Univ Maryland, College Pk, MD 20742 USA. [Magidson, Jessica] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Whited, Matthew C.] East Carolina Univ, Greenville, NC USA. [Pagoto, Sherry L.] Univ Massachusetts, Sch Med, Worcester, MA USA. EM kristin.schneider@rosalindfranklin.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA 1007 BP S3 EP S3 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928000008 ER PT J AU Taylor, W Safren, S Mayer, K O'Cleirigh, C AF Taylor, Wade Safren, Steven Mayer, Kenneth O'Cleirigh, Conall TI PILOT OUTCOMES FOR A CBT INTERVENTION TO ADDRESS SEXUAL RISK AND ENGAGEMENT IN CARE AMONG HIV-INFECTED AFRICAN-AMERICAN MEN WHO HAVE SEX WITH MEN SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Taylor, Wade; Mayer, Kenneth] Fenway Hlth, Fenway Inst, Boston, MA 02118 USA. [Safren, Steven; O'Cleirigh, Conall] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM wtaylor@fenwayhealth.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA 2039 BP S64 EP S64 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928000252 ER PT J AU Trivedi, R Beaver, K Zeliadt, SB Nelson, K Eugenio, E Rosland, AM Grimesey, J Bouldin, E Piette, JD AF Trivedi, Ranak Beaver, Kristine Zeliadt, Steven B. Nelson, Karin Eugenio, Evercita Rosland, Ann-Marie Grimesey, Jackie Bouldin, Erin Piette, John D. TI WHO ARE INFORMAL CAREGIVERS? RESULTS FROM A NATIONALLY-REPRESENTATIVE US SURVEY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Trivedi, Ranak; Zeliadt, Steven B.; Nelson, Karin] Univ Washington, VA Puget Sound, Seattle, WA 98101 USA. [Beaver, Kristine; Eugenio, Evercita; Grimesey, Jackie; Bouldin, Erin] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Rosland, Ann-Marie; Piette, John D.] Univ Michigan, VA Ann Arbor Hlth Care Syst, Ann Arbor, MI 48109 USA. EM ranak.trivedi@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA B-124 BP S126 EP S126 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928001066 ER PT J AU Tucker-Seeley, RD Allen, J Yang, M Anne, S Sorensen, G AF Tucker-Seeley, Reginald D. Allen, Jennifer Yang, May Anne, Stoddard Sorensen, Glorian TI AMONG LOW-INCOME HOUSING RESIDENTS WHO SMOKE IS MATERIAL HARDSHIP ASSOCIATED WITH THE DECISION TO QUIT? SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Tucker-Seeley, Reginald D.; Allen, Jennifer; Sorensen, Glorian] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA. [Yang, May; Anne, Stoddard] NERI, Watertown, MA USA. EM reginald_tucker-seeley@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA D-196 BP S303 EP S303 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928002168 ER PT J AU Valentine, SE Pantalone, DW Woodward, EN O'Cleirigh, C AF Valentine, Sarah E. Pantalone, David W. Woodward, Eva N. O'Cleirigh, Conall TI SYNDEMIC INDICATORS PREDICT POOR MEDICATION ADHERENCE AND INCREASED HEALTH CARE UTILIZATION FOR URBAN HIV-POSITIVE SEXUAL MINORITY MEN SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Valentine, Sarah E.; Woodward, Eva N.] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. [Pantalone, David W.] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. [O'Cleirigh, Conall] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. EM sevalentine@suffolk.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA C-064 BP S206 EP S206 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928001380 ER PT J AU Wolpert, H AF Wolpert, Howard TI CLINICAL BENEFITS AND PRACTICAL BARRIERS TO ADOPTION OF DIABETES TECHNOLOGIES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Wolpert, Howard] Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA 2104 BP S81 EP S81 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928000317 ER PT J AU Light-McGroary, K Goodlin, SJ AF Light-McGroary, KellyAnn Goodlin, Sarah J. TI The challenges of understanding and managing pain in the heart failure patient SO CURRENT OPINION IN SUPPORTIVE AND PALLIATIVE CARE LA English DT Review DE heart failure; opioids; pain AB Purpose of review Heart failure is a leading cause of significant disability and death throughout the world. The assessment and management of pain syndromes in heart failure require specialized knowledge of the pathophysiology of pain and of heart failure. Effective treatment entails an understanding of the physical, psychological, spiritual and social aspects of the pain experience and how pharmacological interventions need to be carefully tailored in this patient population. As we intensify technology to manage the challenges of heart failure it is critical that we review as a profession this critical issue. Recent findings We will review the various aspects of the pain experience for the heart failure patient, disease-specific treatment modalities and ways to incorporate existing expertise in pain management in to the care of these complex patients. Most recently the Pain Assessment, Incidence & Nature in Heart Failure trial has been completed and is currently in publication. This study was the first attempt at trying to understand the complexity of pain in the heart failure patients and will be the foundation for future work. Summary In closing, as palliative care and hospice move further in to the care of patients with complex, chronic illnesses, it is essential that we take this foundational work and expand upon it. Recognizing that pain and suffering in the heart failure patient is multidimensional and that the physical experience of pain is multifactorial is the beginning of developing expertise and improving the quality of care delivered to these patients. C1 [Light-McGroary, KellyAnn] Univ Iowa Hosp & Clin, Dept Med, Iowa City, IA 52242 USA. [Goodlin, Sarah J.] Portland VA Med Ctr, Portland, OR USA. RP Light-McGroary, K (reprint author), Univ Iowa Hosp & Clin, 200 Hawkins Dr,T402-GH, Iowa City, IA 52242 USA. EM Kellyann-light-mcgroary@uiowa.edu NR 12 TC 5 Z9 5 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1751-4258 EI 1751-4266 J9 CURR OPIN SUPPORT PA JI Curr. Opin Support Palliat. Car. PD MAR PY 2013 VL 7 IS 1 BP 14 EP 20 DI 10.1097/SPC.0b013e32835c1f2f PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AJ2IC UT WOS:000337478100004 PM 23254859 ER PT J AU Hartmann, AS Rief, W Hilbert, A AF Hartmann, Andrea Sabrina Rief, Winfried Hilbert, Anja TI Impulsivity and negative mood in adolescents with loss of control eating and ADHD symptoms: an experimental study SO EATING AND WEIGHT DISORDERS-STUDIES ON ANOREXIA BULIMIA AND OBESITY LA English DT Article DE Impulsivity; Negative mood; Stop signal task; Loss of control eating; Attention deficit hyperactivity disorder; Adolescents ID DEFICIT HYPERACTIVITY DISORDER; TEST MEAL INTAKE; BEHAVIORAL-INHIBITION; SOCIAL EXCLUSION; BULIMIA-NERVOSA; CHILDREN; OBESE; ATTENTION; SAMPLE; WOMEN AB The aim of the study was to experimentally examine the reactivity of mood and impulsivity to negative mood induction in adolescents with loss of control (LOC) eating and adolescents with attention deficit hyperactivity disorder (ADHD) symptoms. The study included eighty-eight adolescents with LOC eating, ADHD symptoms, and control. Participants self-reported on mood and participated in a stop signal task before and after negative mood induction with Cyberball. Groups did not differ in impulsivity at baseline (p > .05). The LOC group presented with greater increase of negative mood than the ADHD group, and with greater increase of impulsivity than both other groups from pre- to post-Cyberball (p < .05). Stronger reactivity of negative mood and impulsivity in LOC eating corroborates findings in adults that the concepts' association might be specific to binge eating disorder. Additionally, findings add to previous results showing emotion regulation deficits in LOC eating. Future research should examine the concepts' impact on actual eating behavior including binge eating. C1 [Hartmann, Andrea Sabrina] Massachusetts Gen Hosp, Boston, MA 02214 USA. [Hartmann, Andrea Sabrina] Harvard Univ, Sch Med, Boston, MA 02214 USA. [Rief, Winfried] Univ Marburg, Dept Psychol, D-35032 Marburg, Germany. [Hilbert, Anja] Univ Hosp Leipzig, Leipzig, Germany. RP Hartmann, AS (reprint author), Massachusetts Gen Hosp, Simches Res Bldg,2nd Floor,185 Cambridge St, Boston, MA 02214 USA. EM ahartmann1@partners.org; rief@staff.uni-marburg.de; Anja.Hilbert@medizin.uni-leipzig.de FU German Research Foundation [HI 1111/1-2, HI 1111/1-3] FX This research was supported by Grant HI 1111/1-2, 3 from the German Research Foundation awarded to Anja Hilbert. NR 51 TC 6 Z9 6 U1 3 U2 32 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1124-4909 EI 1590-1262 J9 EAT WEIGHT DISORD-ST JI Eat. Weight Disord.-Stud. Anorex. PD MAR PY 2013 VL 18 IS 1 BP 53 EP 60 DI 10.1007/s40519-013-0004-4 PG 8 WC Psychiatry SC Psychiatry GA AA0PL UT WOS:000330797600008 PM 23757251 ER PT J AU O'Day, DH Huber, RJ AF O'Day, Danton H. Huber, Robert J. TI Matricellular Signal Transduction Involving Calmodulin in the Social Amoebozoan Dictyostelium SO GENES LA English DT Review DE matricellular; signal transduction; EGF-like repeats; extracellular matrix; calmodulin; morphogenesis; cell differentiation; development AB The social amoebozoan Dictyostelium discoideum undergoes a developmental sequence wherein an extracellular matrix (ECM) sheath surrounds a group of differentiating cells. This sheath is comprised of proteins and carbohydrates, like the ECM of mammalian tissues. One of the characterized ECM proteins is the cysteine-rich, EGF-like (EGFL) repeat-containing, calmodulin (CaM)-binding protein (CaMBP) CyrA. The first EGFL repeat of CyrA increases the rate of random cell motility and cyclic AMP-mediated chemotaxis. Processing of full-length CyrA (similar to 63 kDa) releases two major EGFL repeat-containing fragments (similar to 45 kDa and similar to 40 kDa) in an event that is developmentally regulated. Evidence for an EGFL repeat receptor also exists and downstream intracellular signaling pathways involving CaM, Ras, protein kinase A and vinculin B phosphorylation have been characterized. In total, these results identify CyrA as a true matricellular protein comparable in function to tenascin C and other matricellular proteins from mammalian cells. Insight into the regulation and processing of CyrA has also been revealed. CyrA is the first identified extracellular CaMBP in this eukaryotic microbe. In keeping with this, extracellular CaM (extCaM) has been shown to be present in the ECM sheath where it binds to CyrA and inhibits its cleavage to release the 45 kDa and 40 kDa EGFL repeat-containing fragments. The presence of extCaM and its role in regulating a matricellular protein during morphogenesis extends our understanding of CaM-mediated signal transduction in eukaryotes. C1 [O'Day, Danton H.] Univ Toronto, Dept Biol, Mississauga, ON L5L 1C6, Canada. [O'Day, Danton H.] Univ Toronto, Dept Cell & Syst Biol, Toronto, ON M5S 3G5, Canada. [Huber, Robert J.] Harvard Univ, Massachusetts Gen Hosp, Ctr Human Genet Res, Med Sch,Richard B Simches Res Ctr, Boston, MA 02114 USA. RP O'Day, DH (reprint author), Univ Toronto, Dept Biol, 3359 Mississauga Rd North, Mississauga, ON L5L 1C6, Canada. EM rhuber@chgr.mgh.harvard.edu; rhuber@chgr.mgh.harvard.edu FU Canada Graduate Scholarship from the Natural Sciences and Engineering Research Council of Canada; [A6807] FX This review 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 48 TC 0 Z9 0 U1 0 U2 0 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2073-4425 J9 GENES-BASEL JI Genes PD MAR PY 2013 VL 4 IS 1 BP 33 EP 45 DI 10.3390/genes4010033 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA V36YE UT WOS:000209242700002 PM 24705101 ER PT J AU Lesselroth, BJ Adams, K Tallett, S Wood, SD Keeling, A Cheng, K Church, VL Felder, R Tran, H AF Lesselroth, Blake J. Adams, Kathleen Tallett, Stephanie Wood, Scott D. Keeling, Amy Cheng, Karen Church, Victoria L. Felder, Robert Hanna Tran TI Design of Admission Medication Reconciliation Technology: A Human Factors Approach to Requirements and Prototyping SO HERD-HEALTH ENVIRONMENTS RESEARCH & DESIGN JOURNAL LA English DT Article DE Evidence-based design; human factors; patient-centered care; safety; technology ID CARE INFORMATION-SYSTEMS; ADVERSE DRUG EVENTS; HEALTH-CARE; HOSPITAL ADMISSION; PATIENT SAFETY; TIME; PHARMACISTS; PHYSICIANS; EFFICIENCY; IMPLEMENTATION AB OBJECTIVE: Our objectives were to (1) develop an in-depth understanding of the workflow and information flow in medication reconciliation, and (2) design medication reconciliation support technology using a combination of rapid-cycle prototyping and human-centered design. BACKGROUND: Although medication reconciliation is a national patient safety goal, limitations both of physical environment and in workflow can make it challenging to implement durable systems. We used several human factors techniques to gather requirements and develop a new process to collect a medication history at hospital admission. METHODS: We completed an ethnography and time and motion analysis of pharmacists in order to illustrate the processes used to reconcile medications. We then used the requirements to design prototype multimedia software for collecting a bedside medication history. We observed how pharmacists incorporated the technology into their physical environment and documented usability issues. RESULTS: Admissions occurred in three phases: (1) list compilation, (2) order processing, and (3) team coordination. Current medication reconciliation processes at the hospital average 19 minutes to complete and do not include a bedside interview. Use of our technology during a bedside interview required an average of 29 minutes. The software represents a viable proof-of-concept to automate parts of history collection and enhance patient communication. However, we discovered several usability issues that require attention. CONCLUSIONS: We designed a patient-centered technology to enhance how clinicians collect a patient's medication history. By using multiple human factors methods, our research team identified system themes and design constraints that influence the quality of the medication reconciliation process and implementation effectiveness of new technology. C1 [Lesselroth, Blake J.; Church, Victoria L.] Portland VA Med Ctr, Portland Patient Safety Ctr Inquiry, Portland, OR USA. [Lesselroth, Blake J.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. [Adams, Kathleen; Tallett, Stephanie; Felder, Robert; Hanna Tran] Portland VA Med Ctr, Portland, OR USA. [Wood, Scott D.] VHA Off Informat & Analyt Informat Patient Safety, Ann Arbor, MI USA. [Keeling, Amy] Univ Washington, Sch Art, Div Design, Seattle, WA 98195 USA. [Cheng, Karen] Univ Washington, Sch Art, Div Design, Visual Commun Design Program, Seattle, WA 98195 USA. RP Lesselroth, BJ (reprint author), Portland VA Med Ctr, Portland Patient Safety Ctr Inquiry, Dept Med, Mail Code P3 MED,3720 SW US Vet Hosp Dr, Portland, OR 97239 USA. EM blake.lesselroth@va.gov NR 62 TC 0 Z9 0 U1 2 U2 4 PU VENDOME GROUP LLC PI NEW YORK PA 6 EAST 32 ST, 8 FLOOR, NEW YORK, NY 10016 USA SN 1937-5867 EI 2167-5112 J9 HERD-HEALTH ENV RES JI Herd-Health Env. Res. Des. J. PD SPR PY 2013 VL 6 IS 3 BP 30 EP 48 PG 19 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AN9LY UT WOS:000340929500004 PM 23817905 ER PT J AU Tyc, VL Puleo, E Emmons, K de Moor, JS Ford, JS AF Tyc, Vida L. Puleo, Elaine Emmons, Karen de Moor, Janet S. Ford, Jennifer S. TI Smoking Restrictions Among Households of Childhood and Young Adult Cancer Survivors: Implications for Tobacco Control Efforts SO JOURNAL OF ADOLESCENT AND YOUNG ADULT ONCOLOGY LA English DT Article DE survivors; smoking; restrictions; tobacco AB Purpose: This study assessed the prevalence of smoking restrictions among households of survivors of childhood and young adult cancer who smoke. It also examined the relationship between home smoking restrictions and motivation to quit smoking, as well as other smoking, psychosocial, and environmental factors. Methods: Participants included 374 smokers who were childhood or young adult cancer survivors (between the ages of 18 and 55 years) recruited from five cancer centers to participate in a randomized smoking cessation trial. Survivors completed baseline measures about the smoking restrictions in their households, their smoking behavior, and related psychological and environmental factors, which are the focus of the current manuscript. Results: Almost 54% of survivors reported that smoking was prohibited in their households. Living with a nonsmoking partner, having a strict smoking policy at work, and not being nicotine dependent all increased the likelihood of having a total home smoking ban. Participants who were older, smoked more cigarettes per day over the prior week, and received prior chemotherapy were less likely to reside in households that adopted total bans. Conclusion: Findings suggest that socio-environmental factors and current smoking behaviors are associated with complete smoking restrictions in the homes of survivors. These factors should be considered when communicating with survivors about the importance of establishing strict smoking policies in their private residences. C1 [Tyc, Vida L.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Puleo, Elaine] Univ Massachusetts, Amherst, MA 01003 USA. [Emmons, Karen] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [de Moor, Janet S.] Ohio State Univ, Coll Publ Hlth, Columbus, OH 43210 USA. [Ford, Jennifer S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Tyc, VL (reprint author), St Jude Childrens Res Hosp, Dept Psychol, 262 Danny Thomas Pl,Mail Stop 740, Memphis, TN 38105 USA. EM vida.tyc@stjude.org FU National Cancer Institute [5R01CA106914-05, 1K05CA124415] FX This study was funded by the National Cancer Institute grants 5R01CA106914-05 and 1K05CA124415. NR 48 TC 1 Z9 1 U1 2 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2156-5333 EI 2156-535X J9 J ADOLESC YOUNG ADUL JI J. Adolesc. Young Adult Oncol. PD MAR PY 2013 VL 2 IS 1 BP 17 EP 24 DI 10.1089/jayao.2012.0019 PG 8 WC Oncology SC Oncology GA V39II UT WOS:000209404300004 ER PT J AU Antshel, KM Kaul, P Biederman, J Spencer, TJ Hier, BO Hendricks, K Faraone, SV AF Antshel, Kevin M. Kaul, Prashant Biederman, Joseph Spencer, Thomas J. Hier, Bridget O. Hendricks, Kaitlin Faraone, Stephen V. TI Posttraumatic Stress Disorder in Adult Attention-Deficit/Hyperactivity Disorder: Clinical Features and Familial Transmission SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; EMOTIONAL SELF-REGULATION; QUALITY-OF-LIFE; SUBTHRESHOLD DIAGNOSES; LATE-ONSET; NICOTINE EXPOSURE; RISK ANALYSIS; CHILDREN; ADHD; COMORBIDITY AB Objective: Attention-deficit/hyperactivity disorder (ADHD) is characterized by clinically significant functional impairment due to symptoms of inattention and/or hyperactivity and impulsivity. Previous research suggests a link, in child samples, between ADHD and posttraumatic stress disorder (PTSD), which is characterized by (1) chronically reexperiencing a traumatic event, (2) hyperarousal, and (3) avoiding stimuli associated with the trauma while exhibiting numbed responsiveness. This study sought to address the link between ADHD and PTSD in adults by providing a comprehensive comparison of ADHD patients with and without PTSD across multiple variables including demographics, patterns of psychiatric comorbidities, functional impairments, quality of life, social adjustment, and familial transmission. Method: Participants in our controlled family study conducted between 1998 and 2003 were 190 adults with DSM-IV ADHD who were attending an outpatient mental health clinic in Boston, Massachusetts; 16 adults with DSM-IV ADHD who were recruited by advertisement from the greater Boston area; and 123 adult controls without ADHD who were recruited by advertisement from the greater Boston area. All available first-degree relatives also participated. Subjects completed a large battery of self-report measures (the Quality of Life Enjoyment and Satisfaction Questionnaire, items from the Current Behavior Scale, the Social Adjustment Scale Self-Report, and the Four Factor Index of Social Status) designed to assess various psychiatric and functional parameters. Diagnoses were made using data obtained from structured psychiatric interviews (Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version, and the Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Epidemiologic Version). Results: The lifetime prevalence of PTSD was significantly higher among adults with ADHD compared with controls (10.0% vs 1.6%; P = .004). Participants with ADHD and those with ADHD + PTSD did not differ in core symptoms of ADHD nor in age at onset, but those with ADHD + PTSD had higher rates of psychiatric comorbidity than those with ADHD only (including higher lifetime rates of major depressive disorder, oppositional defiant disorder, social phobia, agoraphobia, and generalized anxiety disorder) and worse quality of life ratings for all domains. Familial risk analysis revealed that relatives of ADHD probands without PTSD had elevated rates of both ADHD (51%) and PTSD (12%) that significantly differed from rates among relatives of controls (7% [P <= .001] and 0% [P <= .05], respectively). A similar pattern of elevated risk for ADHD and PTSD (80% and 40%) was observed in relatives of probands with ADHD + PTSD (P <= .001 for both conditions). Conclusions: The comorbidity of PTSD and ADHD in adults leads to greater clinical severity in terms of psychiatric comorbidity and psychosocial functioning. The familial coaggregation of the 2 disorders suggests that these disorders share familial risk factors and that their co-occurrence is not due to diagnostic errors. (C) Copyright 2013 Physicians Postgraduate Press, Inc. C1 [Antshel, Kevin M.; Kaul, Prashant; Hier, Bridget O.; Hendricks, Kaitlin; Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. [Antshel, Kevin M.] Syracuse Univ, Dept Psychol, Syracuse, NY USA. [Kaul, Prashant] Vet Affairs Med Ctr, Dept Mental Hlth, Syracuse, NY USA. [Biederman, Joseph; Spencer, Thomas J.] Massachusetts Gen Hosp, Dept Psychiat, Clin & Res Programs Pediat Psychopharmacol & Adul, Boston, MA 02114 USA. [Biederman, Joseph; Spencer, Thomas J.] Harvard Univ, Sch Med, Boston, MA USA. RP Faraone, SV (reprint author), SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, 750 E Adams St, Syracuse, NY 13210 USA. EM sfaraone@childpsychresearch.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIH [R01MH57934] FX This work was supported by NIH grant R01MH57934 to Dr Faraone. NR 40 TC 13 Z9 13 U1 3 U2 15 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAR PY 2013 VL 74 IS 3 BP E197 EP E204 DI 10.4088/JCP.12m07698 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AA4VH UT WOS:000331094000002 PM 23561240 ER PT J AU Chuang, SK AF Chuang, Sung-Kiang TI There Is Modest Evidence That Systemic Acyclovir or Valacyclovir Prevents Recurrent Herpes Labialis SO JOURNAL OF EVIDENCE-BASED DENTAL PRACTICE LA English DT Editorial Material C1 [Chuang, Sung-Kiang] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Chuang, Sung-Kiang] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Chuang, SK (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. EM sungkiangchuang@gmail.com NR 3 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1532-3382 J9 J EVID-BASED DENT PR JI J. Evid.-Based Dent. Pract. PD MAR PY 2013 VL 13 IS 1 BP 16 EP 17 DI 10.1016/j.jebdp.2013.01.004 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA V37RW UT WOS:000209293900005 PM 23481008 ER PT J AU Friedlander, AH AF Friedlander, Arthur H. TI Carotid Artery Calcifications are a Risk Indicator for Both Stroke and Myocardial Infarction SO JOURNAL OF EVIDENCE-BASED DENTAL PRACTICE LA English DT Letter C1 [Friedlander, Arthur H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Friedlander, Arthur H.] Ronald Reagan UCLA Med Ctr, Hosp Dent Serv, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. RP Friedlander, AH (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arthur.friedlander@va.gov NR 5 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1532-3382 J9 J EVID-BASED DENT PR JI J. Evid.-Based Dent. Pract. PD MAR PY 2013 VL 13 IS 1 BP 37 EP 37 DI 10.1016/j.jebdp.2012.12.002 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA V37RW UT WOS:000209293900015 PM 23481018 ER PT J AU Wolfe, BE Kelly-Weeder, S Malcom, AW McKenery, M AF Wolfe, Barbara E. Kelly-Weeder, Susan Malcom, Alexis W. McKenery, Michael TI Accuracy of Self-Reported Body Weight and Height in Remitted Anorexia Nervosa SO JOURNAL OF THE AMERICAN PSYCHIATRIC NURSES ASSOCIATION LA English DT Article DE anorexia nervosa; eating disorders; body weight; body mass index; remission ID EATING-DISORDERS; YOUNG-WOMEN; REPLICATION AB BACKGROUND: The literature reflects contradictory evidence on the ability of persons with anorexia nervosa (AN) to accurately report body weight and height. Furthermore, it is currently unknown if individuals are able to correctly report their weight and height following weight recovery from AN. OBJECTIVE: This study examined the accuracy of self-reported body weight and height following remission from anorexia nervosa (RAN). DESIGN: Individuals included women with RAN (n = 45), anorexia nervosa (AN; n = 23), and controls (CON; n = 71). Subjective body mass index (BMI; kg/m(2)) was calculated from self-reported weight and height; objective BMI was calculated using values obtained with standard measures. RESULTS: Subjective weights were significantly less than objective weights for the RAN and CON groups (p < .005). These groups reported being taller resulting in lower subjective BMIs (p < .001). The AN group did not significantly differ on subjective and objective weight, height, or BMI. CONCLUSIONS: Results highlight the importance of objective measures for early identification/relapse prevention. C1 [Wolfe, Barbara E.; Kelly-Weeder, Susan] Boston Coll, Connell Sch Nursing, Chestnut Hill, MA 02467 USA. [Malcom, Alexis W.] Mill City Med Grp, Lowell, MA USA. [McKenery, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wolfe, BE (reprint author), Boston Coll, Connell Sch Nursing, Cushing Hall,Rm 433A,140 Commonwealth Ave, Chestnut Hill, MA 02467 USA. EM barbara.wolfe.1@bc.edu FU U.S. Public Health Service, National Institutes of Health [R01 MH057395, K23 NR011175, M01 RR0132] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Supported in part by Grants R01 MH057395, K23 NR011175, and M01 RR0132 from the U.S. Public Health Service, National Institutes of Health. NR 14 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 1078-3903 EI 1532-5725 J9 J AM PSYCHIAT NURSES JI J. Am. Psych. Nurses Assoc. PD MAR-APR PY 2013 VL 19 IS 2 BP 66 EP 70 DI 10.1177/1078390313481062 PG 5 WC Nursing; Psychiatry SC Nursing; Psychiatry GA AJ2RB UT WOS:000337506100004 PM 23514932 ER PT J AU Mifflin, J Pomeroy, E AF Mifflin, Jeffrey Stepenoff, Bonnie TI FROM MISSOURI: An American Farmer Looks Back SO JOURNAL OF THE WEST LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ABC-CLIO PI SANTA BARBARA PA 130 CREMONA DR, SANTA BARBARA, CA 93117 USA SN 0022-5169 EI 1930-0115 J9 J WEST JI J. West PD SPR PY 2013 VL 52 IS 2 BP 90 EP 90 PG 1 WC History SC History GA V39AM UT WOS:000209383900021 ER PT J AU Atmanli, A Domian, IJ AF Atmanli, Ayhan Domian, Ibrahim J. TI Generation of Aligned Functional Myocardial Tissue Through Microcontact Printing SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Stem Cell Biology; Issue 73; Bioengineering; Biomedical Engineering; Medicine; Molecular Biology; Cellular Biology; Anatomy; Physiology; Tissue Engineering; Cardiology; Cell Biology; Embryonic Stem Cells; ESCs; Micropatterning; Microcontact Printing; Cell Alignment; Heart Progenitors; in vitro Differentiation; Transgenic Mice; Mouse Embryonic Stem Cells; stem cells; myocardial tissue; PDMS; FACS; flow cytometry; animal model AB Advanced heart failure represents a major unmet clinical challenge, arising from the loss of viable and/or fully functional cardiac muscle cells. Despite optimum drug therapy, heart failure represents a leading cause of mortality and morbidity in the developed world. A major challenge in drug development is the identification of cellular assays that accurately recapitulate normal and diseased human myocardial physiology in vitro. Likewise, the major challenges in regenerative cardiac biology revolve around the identification and isolation of patient-specific cardiac progenitors in clinically relevant quantities. These cells have to then be assembled into functional tissue that resembles the native heart tissue architecture. Microcontact printing allows for the creation of precise micropatterned protein shapes that resemble structural organization of the heart, thus providing geometric cues to control cell adhesion spatially. Herein we describe our approach for the isolation of highly purified myocardial cells from pluripotent stem cells differentiating in vitro, the generation of cell growth surfaces micropatterned with extracellular matrix proteins, and the assembly of the stem cell-derived cardiac muscle cells into anisotropic myocardial tissue. C1 [Atmanli, Ayhan; Domian, Ibrahim J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Atmanli, Ayhan; Domian, Ibrahim J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Domian, Ibrahim J.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Domian, IJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM idomian@partners.org FU National Science Foundation [ECS-0335765] FX This work was performed in part at the Center for Nanoscale Systems (CNS), a member of the National Nanotechnology Infrastructure Network (NNIN), which is supported by the National Science Foundation under NSF award no. ECS-0335765. CNS is part of Harvard University. NR 21 TC 2 Z9 2 U1 1 U2 6 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD MAR PY 2013 IS 73 AR UNSP e50288 DI 10.3791/50288 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V36QW UT WOS:000209226900041 PM 23542789 ER PT J AU Connors, EC Yazzolino, LA Sanchez, J Merabet, LB AF Connors, Erin C. Yazzolino, Lindsay A. Sanchez, Jaime Merabet, Lotfi B. TI Development of an Audio-based Virtual Gaming Environment to Assist with Navigation Skills in the Blind SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Medicine; Issue 73; Behavior; Neuroscience; Anatomy; Physiology; Neurobiology; Ophthalmology; Psychology; Behavior and Behavior Mechanisms; Technology; Industry; virtual environments; action video games; blind; audio; rehabilitation; indoor navigation; spatial cognitive map; Audio-based Environment Simulator; virtual reality; cognitive psychology; clinical techniques AB Audio-based Environment Simulator (AbES) is virtual environment software designed to improve real world navigation skills in the blind. Using only audio based cues and set within the context of a video game metaphor, users gather relevant spatial information regarding a building's layout. This allows the user to develop an accurate spatial cognitive map of a large-scale three-dimensional space that can be manipulated for the purposes of a real indoor navigation task. After game play, participants are then assessed on their ability to navigate within the target physical building represented in the game. Preliminary results suggest that early blind users were able to acquire relevant information regarding the spatial layout of a previously unfamiliar building as indexed by their performance on a series of navigation tasks. These tasks included path finding through the virtual and physical building, as well as a series of drop off tasks. We find that the immersive and highly interactive nature of the AbES software appears to greatly engage the blind user to actively explore the virtual environment. Applications of this approach may extend to larger populations of visually impaired individuals. C1 [Connors, Erin C.; Yazzolino, Lindsay A.; Merabet, Lotfi B.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Lab Visual Neuroplast,Dept Ophthalmol, Cambridge, MA 02138 USA. [Sanchez, Jaime] Univ Chile, Dept Comp Sci, Santiago, Chile. [Sanchez, Jaime] Univ Chile, CARE, Santiago, Chile. RP Merabet, LB (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Lab Visual Neuroplast,Dept Ophthalmol, Cambridge, MA 02138 USA. EM lotfi_merabet@meei.harvard.edu FU NIH/NEI [RO1 EY019924] FX The authors would like to thank Rabih Dow, Padma Rajagopal, Molly Connors and the staff of the Carroll Center for the Blind (Newton MA, USA) for their support in carrying out this research. This work was supported by the NIH/NEI grant: RO1 EY019924. NR 13 TC 5 Z9 5 U1 4 U2 8 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD MAR PY 2013 IS 73 AR UNSP e50272 DI 10.3791/50272 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V36QW UT WOS:000209226900039 ER PT J AU Lin, PY Roche-Labarbe, N Dehaes, M Carp, S Fenoglio, A Barbieri, B Hagan, K Grant, PE Franceschini, MA AF Lin, Pei-Yi Roche-Labarbe, Nadege Dehaes, Mathieu Carp, Stefan Fenoglio, Angela Barbieri, Beniamino Hagan, Katherine Grant, P. Ellen Franceschini, Maria Angela TI Non-invasive Optical Measurement of Cerebral Metabolism and Hemodynamics in Infants SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Medicine; Issue 73; Developmental Biology; Neurobiology; Neuroscience; Biomedical Engineering; Anatomy; Physiology; Near infrared spectroscopy; diffuse correlation spectroscopy; cerebral hemodynamic; cerebral metabolism; brain injury screening; brain health; brain development; newborns; neonates; imaging; clinical techniques AB Perinatal brain injury remains a significant cause of infant mortality and morbidity, but there is not yet an effective bedside tool that can accurately screen for brain injury, monitor injury evolution, or assess response to therapy. The energy used by neurons is derived largely from tissue oxidative metabolism, and neural hyperactivity and cell death are reflected by corresponding changes in cerebral oxygen metabolism (CMRO2). Thus, measures of CMRO2 are reflective of neuronal viability and provide critical diagnostic information, making CMRO2 an ideal target for bedside measurement of brain health. Brain-imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) yield measures of cerebral glucose and oxygen metabolism, but these techniques require the administration of radionucleotides, so they are used in only the most acute cases. Continuous-wave near-infrared spectroscopy (CWNIRS) provides non-invasive and non-ionizing radiation measures of hemoglobin oxygen saturation (SO2) as a surrogate for cerebral oxygen consumption. However, SO2 is less than ideal as a surrogate for cerebral oxygen metabolism as it is influenced by both oxygen delivery and consumption. Furthermore, measurements of SO2 are not sensitive enough to detect brain injury hours after the insult (1,2), because oxygen consumption and delivery reach equilibrium after acute transients (3). We investigated the possibility of using more sophisticated NIRS optical methods to quantify cerebral oxygen metabolism at the bedside in healthy and brain-injured newborns. More specifically, we combined the frequency-domain NIRS (FDNIRS) measure of SO2 with the diffuse correlation spectroscopy (DCS) measure of blood flow index (CBFi) to yield an index of CMRO2 (CMRO2i) (4,5). With the combined FDNIRS/DCS system we are able to quantify cerebral metabolism and hemodynamics. This represents an improvement over CWNIRS for detecting brain health, brain development, and response to therapy in neonates. Moreover, this method adheres to all neonatal intensive care unit (NICU) policies on infection control and institutional policies on laser safety. Future work will seek to integrate the two instruments to reduce acquisition time at the bedside and to implement real-time feedback on data quality to reduce the rate of data rejection. C1 [Lin, Pei-Yi; Roche-Labarbe, Nadege; Carp, Stefan; Hagan, Katherine; Franceschini, Maria Angela] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. [Roche-Labarbe, Nadege] Univ Caen Basse Normandie, Lab PALM, Caen, France. [Dehaes, Mathieu; Fenoglio, Angela; Grant, P. Ellen] Harvard Univ, Sch Med, Boston Childrens Hosp, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Cambridge, MA 02138 USA. [Barbieri, Beniamino] ISS INC, Colorado Springs, CO USA. RP Lin, PY (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. EM ivylin@nmr.mgh.harvard.edu RI Roche-Labarbe, Nadege/N-9101-2015 OI Roche-Labarbe, Nadege/0000-0002-5010-0400 FU NIH [R01-HD042908, R21- HD058725, P41- RR14075, R43-HD071761]; Clinical Translational Science Award [UL1RR025758]; Brigham and Women's Hospital from the National Center for Research Resources FX The authors thank all the families for their participation in this study and the nurses, physicians, and staff in the Neonatal ICU, the Special Care Nursery, Pediatric Neurology, and the maternity units at Massachusetts General Hospital, Brigham and Women's Hospital and Boston Children's Hospital for their help and support. In particular we thank Linda J. Van Marter, Robert M. Insoft, Jonathan H. Cronin, Julianne Mazzawi, and Steven A. Ringer. The authors also thank Marcia Kocienski-Filip, Yvonne Sheldon, Alpna Aggarwall, Maddy Artunguada and Genevieve Nave for their assistance during measurements. This project is supported by NIH R01-HD042908, R21- HD058725, P41- RR14075 and R43-HD071761. Marcia Kocienski-Filip and Yvonne Sheldon are supported by the Clinical Translational Science Award UL1RR025758 to Harvard University and Brigham and Women's Hospital from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NR 24 TC 5 Z9 5 U1 2 U2 8 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD MAR PY 2013 IS 73 AR UNSP e4379 DI 10.3791/4379 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V36QW UT WOS:000209226900009 PM 23524854 ER PT J AU Pino, EC Webster, CM Carr, CE Soukas, AA AF Pino, Elizabeth C. Webster, Christopher M. Carr, Christopher E. Soukas, Alexander A. TI Biochemical and High Throughput Microscopic Assessment of Fat Mass in Caenorhabditis Elegans SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Genetics; Issue 73; Biochemistry; Cellular Biology; Molecular Biology; Developmental Biology; Physiology; Anatomy; Caenorhabditis elegans; Obesity; Energy Metabolism; Lipid Metabolism; C. elegans; fluorescent lipid staining; lipids; Nile red; fat; high throughput screening; obesity; gas chromatography; mass spectrometry; GC/MS; animal model AB The nematode C. elegans has emerged as an important model for the study of conserved genetic pathways regulating fat metabolism as it relates to human obesity and its associated pathologies. Several previous methodologies developed for the visualization of C. elegans triglyceride-rich fat stores have proven to be erroneous, highlighting cellular compartments other than lipid droplets. Other methods require specialized equipment, are time-consuming, or yield inconsistent results. We introduce a rapid, reproducible, fixative-based Nile red staining method for the accurate and rapid detection of neutral lipid droplets in C. elegans. A short fixation step in 40% isopropanol makes animals completely permeable to Nile red, which is then used to stain animals. Spectral properties of this lipophilic dye allow it to strongly and selectively fluoresce in the yellow-green spectrum only when in a lipid-rich environment, but not in more polar environments. Thus, lipid droplets can be visualized on a fluorescent microscope equipped with simple GFP imaging capability after only a brief Nile red staining step in isopropanol. The speed, affordability, and reproducibility of this protocol make it ideally suited for high throughput screens. We also demonstrate a paired method for the biochemical determination of triglycerides and phospholipids using gas chromatography mass-spectrometry. This more rigorous protocol should be used as confirmation of results obtained from the Nile red microscopic lipid determination. We anticipate that these techniques will become new standards in the field of C. elegans metabolic research. C1 [Pino, Elizabeth C.; Webster, Christopher M.; Soukas, Alexander A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Pino, Elizabeth C.; Webster, Christopher M.; Soukas, Alexander A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Pino, Elizabeth C.; Webster, Christopher M.; Soukas, Alexander A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Carr, Christopher E.] MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA. RP Soukas, AA (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM asoukas@chgr.mgh.harvard.edu OI Carr, Christopher/0000-0002-7946-5622 FU NIH/NIDDK [K08DK087941, 5T32DK007028]; Ellison Medical Foundation; Charles H. Hood Foundation FX We would like to thank Michael Kacergis for technical assistance and Lianfeng Wu for discussions and reading the manuscript. This work was supported by a career development award from the NIH/NIDDK (K08DK087941 to A.A.S.), a NIH/NIDDK training grant (5T32DK007028 to E.C.P.), the Ellison Medical Foundation New Scholar in Aging Award (to A.A.S), and the Charles H. Hood Foundation Child Health Research Award (to A.A.S.). NR 39 TC 1 Z9 1 U1 2 U2 8 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD MAR PY 2013 IS 73 AR UNSP e50180 DI 10.3791/50180 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V36QW UT WOS:000209226900026 ER PT J AU Zappaterra, MW LaMantia, AS Walsh, CA Lehtinen, MK AF Zappaterra, Mauro W. LaMantia, Anthony S. Walsh, Christopher A. Lehtinen, Maria K. TI Isolation of Cerebrospinal Fluid from Rodent Embryos for use with Dissected Cerebral Cortical Explants SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Neuroscience; Issue 73; Neurobiology; Developmental Biology; Anatomy; Physiology; Stem Cell Biology; Cellular Biology; Biomedical Engineering; Medicine; Surgery; Neural Stem Cells (NSCs); stem cells; Cerebral Cortex; Cerebrospinal Fluid; CSF; ventricular embryonic CSF; Isolation; Brain; Cerebral Cortical Explant; tissue; culture; mouse; animal model AB The CSF is a complex fluid with a dynamically varying proteome throughout development and in adulthood. During embryonic development, the nascent CSF differentiates from the amniotic fluid upon closure of the anterior neural tube. CSF volume then increases over subsequent days as the neuroepithelial progenitor cells lining the ventricles and the choroid plexus generate CSF. The embryonic CSF contacts the apical, ventricular surface of the neural stem cells of the developing brain and spinal cord. CSF provides crucial fluid pressure for the expansion of the developing brain and distributes important growth promoting factors to neural progenitor cells in a temporally-specific manner. To investigate the function of the CSF, it is important to isolate pure samples of embryonic CSF without contamination from blood or the developing telencephalic tissue. Here, we describe a technique to isolate relatively pure samples of ventricular embryonic CSF that can be used for a wide range of experimental assays including mass spectrometry, protein electrophoresis, and cell and primary explant culture. We demonstrate how to dissect and culture cortical explants on porous polycarbonate membranes in order to grow developing cortical tissue with reduced volumes of media or CSF. With this method, experiments can be performed using CSF from varying ages or conditions to investigate the biological activity of the CSF proteome on target cells. C1 [Zappaterra, Mauro W.] VA Greater Los Angeles Healthcare Syst, Dept Phys Med & Rehabil, Los Angeles, CA USA. [LaMantia, Anthony S.] George Washington Univ, Sch Med & Hlth Sci, Inst Neurosci, Dept Pharmacol & Physiol, Washington, DC 20052 USA. [Walsh, Christopher A.] Boston Childrens Hosp, Div Genet, Dept Med, Boston, MA USA. [Walsh, Christopher A.] Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA USA. [Lehtinen, Maria K.] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Pathol, Cambridge, MA 02138 USA. RP Lehtinen, MK (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Pathol, Cambridge, MA 02138 USA. EM Maria.Lehtinen@childrens.harvard.edu FU NIH [R00 NS072192, HD029178, 2 RO1NS032457]; Children's Hospital Boston Career Development Fellowship/Harvard Medical School Shore Fellowship; Alfred P. Sloan Foundation FX We are grateful for support from the NIH (Award numbers R00 NS072192 to M.K.L., HD029178 to A-S.L., and 2 RO1NS032457 to C.A.W.). M.K.L. is the recipient of the Children's Hospital Boston Career Development Fellowship/Harvard Medical School Shore Fellowship and a Fellow of the Alfred P. Sloan Foundation. C.A.W. is an Investigator of the Howard Hughes Medical Institute. NR 12 TC 0 Z9 0 U1 0 U2 1 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD MAR PY 2013 IS 73 AR UNSP e50333 DI 10.3791/50333 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V36QW UT WOS:000209226900050 PM 23524481 ER PT J AU Osser, DN Patterson, RD AF Osser, David N. Patterson, Robert D. TI On the Value of Evidence-Based Psychopharmacology Algorithms SO KLINIK PSIKOFARMAKOLOJI BULTENI-BULLETIN OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Editorial Material ID SOUTH SHORE PROGRAM; PRACTICE GUIDELINE; PROJECT; UPDATE; SCHIZOPHRENIA; DEPRESSION; DISORDER; MEDICINE; BIASES; CARE C1 [Osser, David N.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton Div, Brockton, MA 02301 USA. [Patterson, Robert D.] Harvard Univ, Sch Med, McLean Hosp, Belmont, MA 02478 USA. RP Osser, DN (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton Div, 940 Belmont St, Brockton, MA 02301 USA. EM david.osser@va.gov; bpatterson5961@gmail.com NR 33 TC 2 Z9 2 U1 0 U2 1 PU KURE ILETISIM GRUBU A S PI ISTANBUL PA SIRACEVIZLER CAD 43/3 SISLI, ISTANBUL, 34381, TURKEY SN 1017-7833 J9 KLIN PSIKOFARMAKOL B JI Klin. Psikofarmakol. Bul. PD MAR PY 2013 VL 23 IS 1 BP 1 EP 5 DI 10.5455/bcp.19691231040000 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA AM6NT UT WOS:000339982600001 ER PT J AU Erlendsson, AM Taudorf, EH Eriksson, AH Zibert, JR Paasch, U Anderson, RR Haedersdal, M AF Erlendsson, Andres M. Taudorf, Elisabeth H. Eriksson, Andre H. Zibert, John R. Paasch, Uwe Anderson, R. Rox Haedersdal, Merete TI FRACTIONAL LASER-MEDIATED DELIVERY OF INGENOL MEBUTATE - PRELIMINARY RESULTS FROM AN IN VITRO FRANZ CELL STUDY SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Univ Copenhagen, Bispebjerg Hosp, Copenhagen, Denmark. LEO Pharma AS, Ballerup, Denmark. Univ Leipzig, D-04109 Leipzig, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2013 VL 45 SU 25 MA 1 BP 1 EP 1 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA V38YX UT WOS:000209379800002 ER PT J AU Chuang, G Farinelli, W Avram, M Anderson, RR AF Chuang, Gary Farinelli, William Avram, Mathew Anderson, R. Rox TI SMOKE PLUME FROM LASER HAIR REMOVAL: GAS-CHROMATOGRAPHY ANALYSIS SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 [Chuang, Gary; Farinelli, William; Avram, Mathew; Anderson, R. Rox] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2013 VL 45 SU 25 MA 35 BP 13 EP 13 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA V38YX UT WOS:000209379800036 ER PT J AU Jalian, HR Avram, M Stankiewicz, K Shofner, J Tannous, Z AF Jalian, H. Ray Avram, Mathew Stankiewicz, Kelly Shofner, Joshua Tannous, Zeina TI COMBINED PULSED DYE LASER AND Nd:YAG LASER FOR THE TREATMENT OF BASAL CELL CARCINOMA SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Lebanese Amer Univ, Beirut, Lebanon. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2013 VL 45 SU 25 MA 47 BP 17 EP 17 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA V38YX UT WOS:000209379800048 ER PT J AU Yin, R Lin, L Xiao, Y Hao, F Hamblin, M AF Yin, Rui Lin, Lin Xiao, Yan Hao, Fei Hamblin, Michael TI COMBINATION ALA-PDT AND ABLATIVE FRACTIONAL ERBIUM LASER (2940 nm) ON THE TREATMENT OF SEVERE ACNE SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Third Mil Med Univ, Southwest Hosp, Chongqing, Peoples R China. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2013 VL 45 SU 25 MA 49 BP 18 EP 18 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA V38YX UT WOS:000209379800050 ER PT J AU Jalian, HR Avram, M Anderson, RR AF Jalian, H. Ray Avram, Mathew Anderson, R. Rox TI RARE SIDE EFFECTS ASSOCIATED WITH CRYOLIPOLYSIS SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 [Jalian, H. Ray; Avram, Mathew; Anderson, R. Rox] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2013 VL 45 SU 25 MA 53 BP 19 EP 19 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA V38YX UT WOS:000209379800054 ER PT J AU Ortiz, A Truong, S Serowka, K Kelly, K AF Ortiz, Arisa Truong, Samuel Serowka, Kathryn Kelly, Kristen TI 1320 nm Nd:YAG LASER FOR IMPROVING THE APPEARANCE OF ONYCHOMYCOSIS SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Calif Irvine, Irvine, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2013 VL 45 SU 25 MA 54 BP 19 EP 20 PG 2 WC Dermatology; Surgery SC Dermatology; Surgery GA V38YX UT WOS:000209379800055 ER PT J AU Shek, SY Yeung, CK Chan, JCY Chan, HHL AF Shek, Samantha Y. Yeung, C. K. Chan, Johnny C. Y. Chan, Henry H. L. TI EFFICACY OF A HIGH-INTENSITY FOCUSED ULTRASOUND DEVICE FOR NON-INVASIVE BODY CONTOURING SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2013 VL 45 SU 25 MA 60 BP 22 EP 22 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA V38YX UT WOS:000209379800061 ER PT J AU Salinas, H Lin, A Cooper, R Cooper, J AF Salinas, Harry Lin, Alex Cooper, Robert Cooper, Jason TI NOVEL TREATMENT OF PERIORAL RHYTIDES BY SUBCISION COMBINED WITH Er:YAG LASER RESURFACING SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Waters Edge Surg Ctr, Stuart, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2013 VL 45 SU 25 MA 64 BP 23 EP 23 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA V38YX UT WOS:000209379800065 ER PT J AU Gutierrez-Herrera, E Vacas-Jacques, P Zapol, W Anderson, RR Franco, W AF Gutierrez-Herrera, Enoch Vacas-Jacques, Paulino Zapol, Warren Anderson, R. Rox Franco, Walfre TI MINIMALLY INVASIVE OXYGEN SENSOR TO MONITOR MYO AND HEMOGLOBIN SATURATION IN MUSCLE OF MARINE MAMMALS SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 [Gutierrez-Herrera, Enoch; Vacas-Jacques, Paulino; Zapol, Warren; Anderson, R. Rox; Franco, Walfre] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2013 VL 45 SU 25 MA 75 BP 26 EP 27 PG 2 WC Dermatology; Surgery SC Dermatology; Surgery GA V38YX UT WOS:000209379800074 ER PT J AU Haak, CS Farinelli, WA Tam, J Doukas, AG Anderson, RR Haedersdal, M AF Haak, Christina S. Farinelli, William A. Tam, Joshua Doukas, Apostolos G. Anderson, R. Rox Haedersdal, Merete TI FRACTIONAL LASER-ASSISTED DELIVERY OF METHYL AMINOLEVULINATE: IMPACT OF LASER CHANNEL DEPTH AND INCUBATION TIME SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Univ Copenhagen, Bispebjerg Hosp, Copenhagen, Denmark. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2013 VL 45 SU 25 MA 78 BP 27 EP 28 PG 2 WC Dermatology; Surgery SC Dermatology; Surgery GA V38YX UT WOS:000209379800077 ER PT J AU Lewis, WF Farinelli, WA Doukas, AG Franco, W Anderson, RR Sakamoto, FH AF Lewis, William F. Farinelli, William A. Doukas, Apostolos G. Franco, Walfre Anderson, R. Rox Sakamoto, Fernanda H. TI FLUORESCENCE IMAGING OF SEBACEOUS GLAND PORPHYRINS IN VIVO INDUCED BY ALA, USING LONG WAVELENGTH EXCITATION SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 [Lewis, William F.; Farinelli, William A.; Doukas, Apostolos G.; Franco, Walfre; Anderson, R. Rox; Sakamoto, Fernanda H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2013 VL 45 SU 25 MA 77 BP 27 EP 27 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA V38YX UT WOS:000209379800076 ER PT J AU Purschke, M Wang, Y Taghados, SJ Farinelli, WA Franco, W Anderson, RR Doukas, A AF Purschke, Martin Wang, Ying Taghados, Seyed Javid Farinelli, William A. Franco, Walfre Anderson, R. Rox Doukas, Apostolos TI A NOVEL ULTRAVIOLET FLUORESCENCE IMAGING TECHNIQUE AS A NON-INVASIVE AND RAPID METHOD TO MONITOR EPIDERMAL GROWTH SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 [Purschke, Martin; Wang, Ying; Taghados, Seyed Javid; Farinelli, William A.; Franco, Walfre; Anderson, R. Rox; Doukas, Apostolos] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2013 VL 45 SU 25 MA 76 BP 27 EP 27 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA V38YX UT WOS:000209379800075 ER PT J AU Haedersdal, M Sakamoto, FH Farinelli, WA Doukas, AG Tam, J Anderson, RR AF Haedersdal, Merete Sakamoto, Fernanda H. Farinelli, William A. Doukas, Apostolos G. Tam, Joshua Anderson, R. Rox TI PRETREATMENT WITH ABLATIVE FRACTIONAL LASER CHANGES KINETICS AND BIODISTRIBUTION OF TOPICAL 5-AMINOLEVULINIC ACID AND METHYL AMINOLEVULINATE SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Univ Copenhagen, Bispebjerg Hosp, Copenhagen, Denmark. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2013 VL 45 SU 25 MA 79 BP 28 EP 28 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA V38YX UT WOS:000209379800078 ER PT J AU Tan, WB Jia, WC Sun, V Mihm, M Nelson, JS AF Tan, Wenbin Jia, Wangcun Sun, Victor Mihm, Martin Nelson, J. Stuart TI TOPICAL RAPAMYCIN SUPPRESSES THE ANGIOGENESIS PATHWAYS INDUCED BY PULSED DYE LASER SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Univ Calif Irvine, Beckman Laser Inst & Med Clin, Irvine, CA 92715 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2013 VL 45 SU 25 MA 85 BP 30 EP 30 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA V38YX UT WOS:000209379800084 ER PT J AU Franco, W Taghados, SJ Ortiz, A Farinelli, WA Anderson, RR Doukas, AG AF Franco, Walfre Taghados, Seyed Javid Ortiz, Arisa Farinelli, William A. Anderson, R. Rox Doukas, Apostolos G. TI ULTRAVIOLET FLUORESCENCE IMAGING OF THE SKIN RESPONSE TO IRRITANT CONTACT DERMATITIS AND TAPE STRIPPING SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 [Franco, Walfre; Taghados, Seyed Javid; Ortiz, Arisa; Farinelli, William A.; Anderson, R. Rox; Doukas, Apostolos G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2013 VL 45 SU 25 MA 109 BP 37 EP 38 PG 2 WC Dermatology; Surgery SC Dermatology; Surgery GA V38YX UT WOS:000209379800106 ER PT J AU Dai, TH Gupta, A Huang, YY Yin, R Murray, C Vrahas, M Kielian, T Hamblin, M AF Dai, Tianhong Gupta, Asheesh Huang, Yingying Yin, Rui Murray, Clinton Vrahas, Mark Kielian, Tammy Hamblin, Michael TI BLUE LIGHT ELIMINATES COMMUNITY-ACQUIRED METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS IN INFECTED MOUSE SKIN ABRASIONS SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. Brooke Army Med Ctr, Infect Dis Serv, Houston, TX USA. Univ Nebraska Med Ctr, Omaha, NE USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2013 VL 45 SU 25 MA 121 BP 41 EP 41 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA V38YX UT WOS:000209379800116 ER PT J AU Echague, AV Casas, G Rivera, FP Nieto, S Schomacker, K Anderson, RR AF Vila Echague, Agustina Casas, Gabriel Perez Rivera, Fabian Nieto, Silvana Schomacker, Kevin Anderson, R. Rox TI OVER TIME HISTOLOGICAL TISSUE CHANGES AFTER NON-INVASIVE TREATMENT WITH A 1210 nm LASER SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Hosp Alemaan Deutsch, Inst Pathol, Buenos Aires, DF, Argentina. Consejo Nacl Invest Cient & Tecn, CEMIC, Buenos Aires, DF, Argentina. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2013 VL 45 SU 25 MA 129 BP 44 EP 44 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA V38YX UT WOS:000209379800123 ER PT J AU Taudorf, EH Haak, CS Erlendsson, AM Philipsen, PA Paasch, U Anderson, RR Haedersdal, M AF Taudorf, Elisabeth Hjardem Haak, Christina Skovboelling Erlendsson, Andres Maar Philipsen, Peter Alshede Paasch, Uwe Anderson, R. Rox Haedersdal, Merete TI SPECIFIC MICROPORE DIMENSIONS FROM VARYING SETTINGS WITH A PORTABLE FRACTIONAL ERBIUM LASER-HISTOLOGICAL DATA FROM EX VIVO PORCINE SKIN SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Univ Copenhagen, Bispebjerg Hosp, Copenhagen, Denmark. Univ Leipzig, D-04109 Leipzig, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2013 VL 45 SU 25 MA 140 BP 47 EP 48 PG 2 WC Dermatology; Surgery SC Dermatology; Surgery GA V38YX UT WOS:000209379800134 ER PT J AU Hamblin, M Xuan, WJ Huang, LY Huang, SF AF Hamblin, Michael Xuan, Weijun Huang, Liyi Huang, Shih-Fong TI TRANSCRANIAL LOW-LEVEL LASER (LIGHT) THERAPY IN MICE: TRAMAUTIC BRAIN INJURY AND BEYOND SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 [Hamblin, Michael; Xuan, Weijun; Huang, Liyi; Huang, Shih-Fong] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2013 VL 45 SU 25 MA 154 BP 50 EP 51 PG 2 WC Dermatology; Surgery SC Dermatology; Surgery GA V38YX UT WOS:000209379800143 ER PT J AU Haak, CS Togsverd-Bo, K Thaysen-Petersen, D Wulf, HC Paasch, U Anderson, RR Haedersdal, M AF Haak, Christina S. Togsverd-Bo, Katrine Thaysen-Petersen, Daniel Wulf, Hans Christian Paasch, Uwe Anderson, R. Rox Haedersdal, Merete TI CONVENTIONAL vs FRACTIONAL LASER-MEDIATED PHOTODYNAMIC THERAPY OF DIFFICULT TO TREAT BASAL CELL CARCINOMAS - A RANDOMIZED CLINICAL TRIAL SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Univ Copenhagen, Bispebjerg Hosp, Copenhagen, Denmark. Univ Leipzig, D-04109 Leipzig, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2013 VL 45 SU 25 MA 178 BP 58 EP 58 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA V38YX UT WOS:000209379800166 ER PT J AU Ribeiro, M Kato, I Sabino, C Yoshimura, T Hamblin, M Prates, R AF Ribeiro, Martha Kato, Ilka Sabino, Caetano Yoshimura, Tania Hamblin, Michael Prates, Renato TI EVALUATION OF VARIABLES INVOLVED IN ANTIFUNGAL PHOTODYNAMIC THERAPY SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 IPEN CNEN SP, Ctr Lasers & Applicat, Sao Paulo, Brazil. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RI Sabino, Caetano/K-8356-2013; Sabino, Caetano/D-4196-2016 OI Sabino, Caetano/0000-0002-2048-2823 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2013 VL 45 SU 25 MA 217 BP 62 EP 62 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA V38YX UT WOS:000209379800179 ER PT J AU Cohen, AN Chinman, MJ Hamilton, AB Whelan, F Young, AS AF Cohen, Amy N. Chinman, Matthew J. Hamilton, Alison B. Whelan, Fiona Young, Alexander S. TI Using Patient-facing Kiosks to Support Quality Improvement at Mental Health Clinics SO MEDICAL CARE LA English DT Article DE health information technology; quality improvement; mental health ID RANDOMIZED CONTROLLED-TRIAL; PRIMARY-CARE; SELF-ASSESSMENT; SCHIZOPHRENIA; ILLNESS; IMPLEMENTATION; DEPRESSION; OUTCOMES; PROGRAM; INTERVENTION AB Objectives: Evidence-based services improve outcomes in schizophrenia, but most patients at mental health clinics do not receive such services. This gap in care has been perpetuated by a lack of routinely collected data on patients' clinical status and the treatments they receive. However, routine data collection can be completed by patients themselves, especially when aided by health information technology. It is not known whether these data can be used to improve care quality. Methods: In a controlled trial, 8 medical centers of the Veterans Health Administration were assigned to implementation or usual care. A total of 571 patients with schizophrenia were overweight and had not used evidence-based weight services. The implementation strategy included data from patient-facing kiosks, continuous data feedback, clinical champions, education, social marketing, and evidence-based quality improvement teams. Mixed methods evaluated the impact of the kiosks on utilization of and retention in weight services. Results: Compared with usual care, implementation resulted in individuals being more likely to use weight services, availing services >5 weeks sooner, and continuing to use the services 3 times more. When compared with the year before implementation, patients at implementation sites saw a 3-fold increase in treatment visits. Usual care resulted in no change. Conclusions: Mental health clinics have been slow to adopt health information technology. This study is among the first to implement and evaluate automated collection of data from patients at these clinics. Patient-facing kiosks are feasible in routine care and provide data that can be used to substantially improve the quality of care. C1 [Cohen, Amy N.; Hamilton, Alison B.; Young, Alexander S.] VA Desert Pacific Mental Illness Res Educ & Clin, Los Angeles, CA USA. [Cohen, Amy N.; Hamilton, Alison B.; Young, Alexander S.] VA Hlth Serv Res & Dev Ctr Excellence Study Healt, Palo Alto, CA USA. [Cohen, Amy N.; Hamilton, Alison B.; Whelan, Fiona; Young, Alexander S.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Chinman, Matthew J.] VA VISN 4 Mental Illness Res Educ & Clin Ctr MIRE, Philadelphia, PA USA. [Chinman, Matthew J.] RAND, Pittsburgh, PA USA. RP Cohen, AN (reprint author), Greater Los Angeles VA Healthcare Ctr, 11301 Wilshire Blvd 210A, Los Angeles, CA 90073 USA. EM amy.cohen@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service Quality Enhancement Research Initiative (QUERI) [MNT 03-213]; VA Desert Pacific Mental Illness Research, Education and Clinical Center (MIRECC); UCLA-RAND NIMH Partnered Research Center for Quality Care [P30 MH082760] FX Supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service Quality Enhancement Research Initiative (QUERI; MNT 03-213), and VA Desert Pacific Mental Illness Research, Education and Clinical Center (MIRECC) and by the UCLA-RAND NIMH Partnered Research Center for Quality Care (P30 MH082760). The views expressed in this article are those of the authors and do not necessarily represent the views of the affiliated institutions. NR 40 TC 7 Z9 7 U1 2 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 MAR PY 2013 VL 51 IS 3 SU 1 BP S13 EP S20 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AJ7YH UT WOS:000337917300004 PM 23407006 ER PT J AU Gabrielian, S Yuan, A Andersen, RM McGuire, J Rubenstein, L Sapir, N Gelberg, L AF Gabrielian, Sonya Yuan, Anita Andersen, Ronald M. McGuire, James Rubenstein, Lisa Sapir, Negar Gelberg, Lillian TI Chronic Disease Management for Recently Homeless Veterans A Clinical Practice Improvement Program to Apply Home Telehealth Technology to a Vulnerable Population SO MEDICAL CARE LA English DT Article DE homeless; disease management; peer support ID MENTALLY-ILL; PEER SUPPORT; HEALTH-CARE; SYSTEMS; ACCESS AB Background: Although vulnerable populations may benefit from in-home health information technologies (HIT) that promote disease self-management, there is a "digital divide" in which these groups are often unlikely to use such programs. We describe the early phases of applying and testing an existing Veterans Affairs (VA) HIT-care management program, Care Coordination Home Telehealth (CCHT), to recently homeless Veterans in the US Department of Housing and Urban Development-VA Supportive Housing (HUD-VASH) program. Peers were used to support patient participation. Methods: CCHT uses in-home messaging devices to provide health education and daily questions about clinical indicators from chronic illness care guidelines, with patient responses reviewed by VHA nurses. Patients could also receive adjunctive peer support. We used medical record review, Veteran interviews, and staff surveys to "diagnose" barriers to CCHT use, assess program acceptability, explore the role of peer support, and inform future quality improvement. Subjects: Fourteen eligible Veterans in HUD-VASH agreed to CCHT participation. Ten of these Veterans opted to have adjunctive peer support and the other 4 enrolled in CCHT usual care. Results: Although barriers to enrollment/engagement must be addressed, this subset of Veterans in HUD-VASH was satisfied with CCHT. Most Veterans did not require support from peers to engage in CCHT but valued peer social assistance amidst the isolation felt in their scattered-site homes. Conclusions: HIT tools hold promise for in-home care management for recently housed Veterans. Patient-level barriers to enrollment must be addressed in the next steps of quality improvement, testing and evaluating peer-driven CCHT recruitment. C1 [Gabrielian, Sonya] Vet Adm Greater Los Angeles, Mental Illness Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. [Yuan, Anita; Gelberg, Lillian] Vet Adm Greater Los Angeles, Dept Primary Care, Los Angeles, CA 90073 USA. [Andersen, Ronald M.; Gelberg, Lillian] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [McGuire, James] Vet Hlth Adm Justice Programs, Washington, DC USA. [Rubenstein, Lisa; Sapir, Negar] Vet Adm Greater Los Angeles, Hlth Serv Res & Dev Ctr Excellence Study Healthca, Los Angeles, CA USA. [Rubenstein, Lisa] RAND Corp, Santa Monica, CA USA. [Gelberg, Lillian] Univ Calif Los Angeles, Dept Family Med, Los Angeles, CA USA. RP Gabrielian, S (reprint author), Vet Adm Greater Los Angeles, Mental Illness Res Educ & Clin Ctr, VA Healthcare Ctr, 11301 Wilshire Blvd,210A Los Angeles, Los Angeles, CA 90073 USA. EM sonya.gabrielian@va.gov FU PACT Demonstration Laboratory initiative is provided by the VA Office of Patient Care Services; VISN 22 VA Assessment and Improvement Lab for Patient Centered Care (VAIL-PCC) [XVA 65-018]; Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs; Office of Academic Affiliations, Advanced Fellowship Program in Health Services Research, Department of Veterans Affairs [TPP 65-013]; NIDA [DA 022445]; UCLA/DREW Project EXPORT, National Center on Minority Health and Health Disparities [P20MD000148/P20MD000182]; VAIL-PCC [XVA 650-18] FX This work was undertaken as part of the Veterans Administration's PACT Demonstration Laboratory initiative, supporting and evaluating VA's transition to a patient-centered medical home. Funding for the PACT Demonstration Laboratory initiative is provided by the VA Office of Patient Care Services. In particular, this project was supported by the VISN 22 VA Assessment and Improvement Lab for Patient Centered Care (VAIL-PCC) (XVA 65-018; PI: Rubenstein). S. G. was supported by the Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs. A.Y. was supported by the Office of Academic Affiliations, Advanced Fellowship Program in Health Services Research, Department of Veterans Affairs (TPP 65-013). L. G. and R. M. A. were supported in part by NIDA DA 022445. R. M. A. received additional support from the UCLA/DREW Project EXPORT, National Center on Minority Health and Health Disparities, P20MD000148/P20MD000182. L. R. and N.S. were supported in part by VAIL-PCC (XVA 650-18). NR 21 TC 6 Z9 6 U1 2 U2 17 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 MAR PY 2013 VL 51 IS 3 SU 1 BP S44 EP S51 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AJ7YH UT WOS:000337917300008 PM 23407011 ER PT J AU Hynes, DM Whittier, ER Owens, A AF Hynes, Denise M. Whittier, Erika R. Owens, Arika TI Health Information Technology and Implementation Science Partners in Progress in the VHA INTRODUCTION SO MEDICAL CARE LA English DT Editorial Material DE Veterans; health information technology; electronic health record; quality improvement; implementation research; qualitative analysis ID SELF-ASSESSMENT; QUERI; CARE; SCHIZOPHRENIA; QUALITY; ILLNESS AB Background: The Veterans Health Administration (VHA) Quality Enhancement Research Initiative (QUERI) has demonstrated how implementation science can enhance the quality of health care. During this time an increasing number of implementation research projects have developed or utilized health information technology (HIT) innovations to leverage the VHA's electronic health record and information systems. Objective: To describe the HIT approaches used and to characterize the facilitators and barriers to progress within implementation research projects in the VHA QUERI program. Participants: Nine case studies were selected from among 88 projects and represented 8 of 14 HIT categories identified. Each case study included key informants whose roles on the project were principal investigator, implementation science and informatics development. Approach: We conducted documentation analysis and semi-structured in-person interviews with key informants for each of the 9 case studies. We used qualitative analysis software to identify and thematically code information and interview responses. Results: Thematic analyses revealed 3 domains or pathways critical to progression through the QUERI steps. These pathways addressed: (1) compliance and collaboration with information technology policies and procedures; (2) operating within organizational policies and building collaborations with end users, clinicians, and administrators; and (3) obtaining and maintaining research resources and approvals. Conclusion: Sustained efforts in HIT innovation and in implementation science in the Veterans Health Administration demonstrates the interdependencies of these initiatives and the critical pathways that can contribute to progress. Other health care quality improvement efforts that rely on HIT can learn from the Veterans Health Administration experience. C1 [Hynes, Denise M.; Whittier, Erika R.; Owens, Arika] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, VA Informat Resource Ctr, Hines, IL 60141 USA. [Hynes, Denise M.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, CMC3, Hines, IL 60141 USA. [Hynes, Denise M.] Univ Illinois, Dept Med, Chicago, IL USA. [Hynes, Denise M.] Univ Illinois, Ctr Clin & Translat Sci, Chicago, IL USA. RP Hynes, DM (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, VA Informat Resource Ctr, 5th & Roosevelt Rd,Bldg 18,Room 206 151-V, Hines, IL 60141 USA. EM denise.hynes@va.gov NR 23 TC 3 Z9 3 U1 3 U2 5 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 MAR PY 2013 VL 51 IS 3 SU 1 BP S6 EP S12 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AJ7YH UT WOS:000337917300003 PM 23407014 ER PT J AU Hynes, DM AF Hynes, Denise M. TI Health Information Technology in VHA Quality Improvement Research Overview INTRODUCTION SO MEDICAL CARE LA English DT Editorial Material DE administrative data; database; health information technology; personal health record; electronic health record; health services research; quality improvement; telehealth; Veterans; secure messaging C1 [Hynes, Denise M.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, VA Informat Resource Ctr VIReC, Hines, IL 60141 USA. [Hynes, Denise M.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, CMC3, Hines, IL 60141 USA. [Hynes, Denise M.] Univ Illinois, Dept Med, Chicago, IL USA. [Hynes, Denise M.] Univ Illinois, Ctr Clin & Translat Sci, Chicago, IL USA. RP Hynes, DM (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Informat Resource Ctr, 5th & Roosevelt Rd,Bldg 18,Room 206 151-V, Hines, IL 60141 USA. EM denise.hynes@va.gov NR 10 TC 0 Z9 0 U1 1 U2 2 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 MAR PY 2013 VL 51 IS 3 SU 1 BP S4 EP S5 PG 2 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AJ7YH UT WOS:000337917300002 PM 23407010 ER PT J AU McInnes, DK Solomon, JL Shimada, SL Petrakis, BA Bokhour, BG Asch, SM Nazi, KM Houston, TK Gifford, AL AF McInnes, D. Keith Solomon, Jeffrey L. Shimada, Stephanie L. Petrakis, Beth A. Bokhour, Barbara G. Asch, Steven M. Nazi, Kim M. Houston, Thomas K. Gifford, Allen L. TI Development and Evaluation of an Internet and Personal Health Record Training Program for Low-income Patients With HIV or Hepatitis C SO MEDICAL CARE LA English DT Article DE vulnerable populations; health informatics; HIV; hepatitis C; veterans ID BEHAVIORAL SKILLS MODEL; ANTIRETROVIRAL THERAPY; CARE UTILIZATION; DIGITAL DIVIDE; DEEP SOUTH; INFORMATION; ACTIVATION; ADHERENCE; INTERVENTION; MOTIVATION AB Background: Vulnerable populations face difficulties accessing and using the internet and personal health record (PHR) systems for health-related purposes. Populations disconnected from the internet also tend to be disconnected from health care services. Objectives: To develop and evaluate an intervention to increase skills in health-related internet and PHR use for vulnerable populations with limited computer and internet experience. Research Design: Preevaluation and postevaluation using quantitative surveys, semistructured interviews, focus groups, and ethnographic observation. Subjects: Fourteen low-income Veterans receiving care at Veterans Affairs medical centers for human immunodeficiency virus or hepatitis C. Measures: Internet and PHR use, self-efficacy, patient activation, disease knowledge, predictors of medication adherence. Results: At follow-up one (FU1), mean number of internet for health features used increased from 1.57 to 4.07 (P < 0.001) as did number of PHR features, from 0.36 to 2.00 (P < 0.001). Mean self-efficacy increased at FU1, from 7.12 to 8.60, (P = 0.009) and was maintained at follow-up two (FU2). Patient activation increased only at FU2, from 3.42 to 3.61 (P = 0.03). Disease specific knowledge showed borderline increase at FU1, from 67.9% to 72.2% (P = 0.05), whereas there were no changes in predictors of medication adherence. Qualitative findings underscored the interest in using internet and PHRs and their contribution to increased engagement in care. Training cost per participant was $287. Conclusions: Group training of vulnerable patients represents a cost-effective method to increase internet and PHR skills, and improve patient confidence in finding health-related information, making online health-related transactions, and interacting with health care providers. C1 [McInnes, D. Keith; Solomon, Jeffrey L.; Shimada, Stephanie L.; Petrakis, Beth A.; Bokhour, Barbara G.; Houston, Thomas K.; Gifford, Allen L.] ENRM VA Med Ctr, VA QUERI Program, Bedford, MA 01730 USA. [McInnes, D. Keith; Solomon, Jeffrey L.; Shimada, Stephanie L.; Petrakis, Beth A.; Bokhour, Barbara G.; Houston, Thomas K.; Gifford, Allen L.] ENRM VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. [McInnes, D. Keith; Shimada, Stephanie L.; Bokhour, Barbara G.; Gifford, Allen L.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Asch, Steven M.] VA Palo Alto Healthcare Syst, VA QUERI Program, Palo Alto, CA USA. [Asch, Steven M.] VA Palo Alto Healthcare Syst, Ctr Hlth Care Evaluat, Palo Alto, CA USA. [Asch, Steven M.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [Nazi, Kim M.] US Dept Vet Affairs, Vet & Consumers Hlth Informat Off, Off Informat & Analyt, Vet Hlth Adm, Washington, DC USA. [Houston, Thomas K.] Univ Massachusetts, Dept Quantitat Hlth Sci, Sch Med, Worcester, MA 01605 USA. [Gifford, Allen L.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP McInnes, DK (reprint author), ENRM VA Med Ctr, VA QUERI Program, Bldg 70,200 Springs Rd, Bedford, MA 01730 USA. EM keith.mcinnes@va.gov FU Department of Veterans Affairs (VA) Quality Enhancement Research Initiatives (QUERI) HIV/Hepatitis and eHealth (RRP) [09-192]; VA Health Services Research and Development Career Development Award (CDA) [09-016] FX Supported by the Department of Veterans Affairs (VA) Quality Enhancement Research Initiatives (QUERI) HIV/Hepatitis and eHealth (RRP#09-192). In addition, D. K. M. was supported by a VA Health Services Research and Development Career Development Award (CDA#09-016). NR 41 TC 12 Z9 12 U1 3 U2 12 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 MAR PY 2013 VL 51 IS 3 SU 1 BP S62 EP S66 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AJ7YH UT WOS:000337917300011 PM 23407015 ER PT J AU Nazi, KM Hogan, TP McInnes, DK Woods, SS Graham, G AF Nazi, Kim M. Hogan, Timothy P. McInnes, D. Keith Woods, Susan S. Graham, Gail TI Evaluating Patient Access to Electronic Health Records Results From a Survey of Veterans SO MEDICAL CARE LA English DT Article DE PHR; personal health record; EHR; eHealth; access; portal ID MEDICAL-RECORDS; MEANINGFUL USE; TECHNOLOGIES; CARE AB Objective: Personal Health Records (PHRs) tethered to an Electronic Health Record (EHR) offer patients unprecedented access to their personal health information. At the Department of Veteran Affairs (VA), the My HealtheVet Pilot Program was an early PHR prototype enabling patients to import 18 types of information, including clinical notes and laboratory test results, from the VA EHR into a secure PHR portal. The goal of this study was to explore Veteran perceptions about this access to their medical records, including perceived value and effect on satisfaction, self-care, and communication. Methods: Patients enrolled in the pilot program were invited to participate in a web-based survey. Results: Among 688 Veteran respondents, there was a high degree of satisfaction with the pilot program, with 84% agreeing that the information and services were helpful. The most highly ranked feature was access to personal health information from the VA EHR. The majority of respondents (72%) indicated that the pilot Web site made it easy for them to locate relevant information. Most participants (66%) agreed that the pilot program helped improve their care, with 90% indicating that they would recommend it to another Veteran. Conclusions: Veterans' primary motivation for use of the pilot Web site was the ability to access their own personal health information from the EHR. With patients viewing such access as beneficial to their health and care, PHRs with access to EHR data are positioned to improve health care quality. Making additional information accessible to patients is crucial to meet their needs and preferences. C1 [Nazi, Kim M.] US Dept Vet Affairs, Vet & Consumers Hlth Informat Off, Off Informat & Analyt, Vet Hlth Adm, Washington, DC USA. [Hogan, Timothy P.; McInnes, D. Keith] Edith Nourse Rogers Mem Vet Hosp, Ctr Hlth Qual Outcomes & Econ Res, Natl eHlth QUERI Coordinating Ctr, Bedford, MA USA. [Hogan, Timothy P.] Edith Nourse Rogers Mem Vet Hosp, eHlth Qual Enhancement Res Initiat QUERI, Natl eHlth QUERI Coordinating Ctr, Bedford, MA USA. [Hogan, Timothy P.] Univ Massachusetts, Sch Med, Div Hlth Informat & Implementat Sci, Worcester, MA USA. [McInnes, D. Keith] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Woods, Susan S.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. [Woods, Susan S.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Woods, Susan S.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. [Graham, Gail] US Dept Vet Affairs, Off Informat & Analyt, Vet Hlth Adm, Washington, DC USA. RP Nazi, KM (reprint author), Stratton VA Med Ctr, 113 Holland Ave, Albany, NY 12208 USA. EM kim.nazi@va.gov NR 28 TC 21 Z9 21 U1 1 U2 11 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 MAR PY 2013 VL 51 IS 3 SU 1 BP S52 EP S56 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AJ7YH UT WOS:000337917300009 PM 23407012 ER PT J AU Shimada, SL Hogan, TP Rao, SR Allison, JJ Quill, AL Feng, H Phillips, BD Nazi, KM Haidary, ST Houston, TK AF Shimada, Stephanie L. Hogan, Timothy P. Rao, Sowmya R. Allison, Jeroan J. Quill, Ann L. Feng, Hua Phillips, Barrett D. Nazi, Kim M. Haidary, Susan T. Houston, Thomas K. TI Patient-Provider Secure Messaging in VA Variations in Adoption and Association With Urgent Care Utilization SO MEDICAL CARE LA English DT Article DE veterans; urgent care; ambulatory care; continuity; implementation; secure messaging; Internet ID KAISER PERMANENTE; MEDICAL HOME; IMPLEMENTATION; FRAMEWORK; QUALITY; ACCESS; IMPACT AB Background: The Veterans Health Administration has implemented patient to clinical team electronic asynchronous secure messaging (SM). This disruptive technology has the potential to support continuous, coordinated quality care, but limited evidence supports this connection. Objectives: The objective of this paper is to (1) measure SM implementation and identify facility characteristics associated with higher rates of adoption and (2) understand the association of SM use and noncontinuity care [ie, urgent care (UC)] utilization rates. Measures: We conducted a retrospective cohort study of 132 VA facilities implementing SM in primary care. We used a combination of cross-sectional survey data on predictors of SM implementation and longitudinal data (July 2010-June 2012) on use of SM and UC. Results: Human resources (coordinator and staff/volunteer availability to directly assist Veterans), computer resources (computers and computer rooms for Veterans), and leadership support for coordinators were associated with increased SM adoption rates. Higher SM use was associated with lower UC rates; early adopters of SM achieved a greater decrease in UC utilization over time than later adopters. Conclusions: In this exploratory analysis of early SM implementation in VA, we found a path of associations linking SM and reductions in UC utilization. These results suggest a need for further examination of the relationship between SM and its effects on health care utilization patterns. C1 [Shimada, Stephanie L.; Hogan, Timothy P.; Rao, Sowmya R.; Allison, Jeroan J.; Quill, Ann L.; Feng, Hua; Phillips, Barrett D.; Houston, Thomas K.] Edith Nourse Rogers Mem Vet Hosp, CHQOER, Bedford, MA 01730 USA. [Shimada, Stephanie L.; Hogan, Timothy P.; Rao, Sowmya R.; Allison, Jeroan J.; Quill, Ann L.; Feng, Hua; Phillips, Barrett D.; Houston, Thomas K.] eHlth Qual Enhancement Res Initiat QUERI, Amherst, MA USA. [Shimada, Stephanie L.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Hogan, Timothy P.; Rao, Sowmya R.; Allison, Jeroan J.; Feng, Hua; Phillips, Barrett D.; Houston, Thomas K.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Nazi, Kim M.; Haidary, Susan T.] US Dept Vet Affairs, Vet & Consumers Hlth Informat Off, Off Informat & Analyt, Vet Hlth Adm, Washington, DC USA. RP Shimada, SL (reprint author), Edith Nourse Rogers Mem Vet Hosp, 200 Springs Rd 152, Bedford, MA 01730 USA. EM stephanie.shimada@va.gov FU eHealth Quality Enhancement Research Initiative [EHQ 10-190]; VA Career Development Award [CDA 10-210]; University of Massachusetts Center for Clinical and Translational Research; NIH Clinical and Translational Sciences Award [1UL1RR031982-01] FX The authors acknowledge the eHealth Quality Enhancement Research Initiative (EHQ 10-190) for funding to support this paper. Dr Shimada's efforts were covered by a VA Career Development Award (CDA 10-210). Drs Allison and Houston were supported by the University of Massachusetts Center for Clinical and Translational Research, funding by NIH Clinical and Translational Sciences Award (1UL1RR031982-01). Theresa Hancock and Alex Hersh of the Veterans/Consumers Health Informatics Office, D. Keith McInnes and Beth Ann Petrakis of the eHealth QUERI, Tracey Martin and other My HealtheVet coordinators were also instrumental to data collection. NR 20 TC 12 Z9 12 U1 2 U2 3 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 MAR PY 2013 VL 51 IS 3 SU 1 BP S21 EP S28 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AJ7YH UT WOS:000337917300005 PM 23407007 ER PT J AU Spears, GV Roth, CP Miake-Lye, IM Saliba, D Shekelle, PG Ganz, DA AF Spears, Gwendolyn V. Roth, Carol P. Miake-Lye, Isomi M. Saliba, Debra Shekelle, Paul G. Ganz, David A. TI Redesign of an Electronic Clinical Reminder to Prevent Falls in Older Adults SO MEDICAL CARE LA English DT Article DE quality improvement; fall prevention; primary care; clinical reminder ID PRIMARY-CARE PRACTICES; URINARY-INCONTINENCE; GERIATRIC SYNDROMES; QUALITY INDICATORS; MOBILITY PROBLEMS; INTERVENTION; FACILITATORS; PERCEPTIONS; MANAGEMENT; PHYSICIANS AB Background: Falls are the leading cause of unintentional injury among US older adults. Guidelines recommend screening patients for fall risk, and providing exercise for patients with gait and balance problems. We redesigned an electronic clinical reminder to improve identification and management of Veterans at high risk for falls, and piloted the reminder in 3 Veterans Health Administration community-based outpatient clinics. Methods: This project had 5 key elements: (1) case finding, (2) efficient collection of condition-specific clinical data, (3) clinical reminders to prompt appropriate care, (4) patient and family education materials, and (5) primary care provider (PCP) decision support/PCP and staff education. We reviewed clinical reminder reports, interviewed nurses and PCPs, directly observed clinic operations, and watched nurses and PCPs use the clinical reminder with a dummy patient record to determine areas in need of improvement. Results: Over a 1-year period, 2943 Veterans aged 75 years and older visited the 3 clinics, with 2264 screened for fall risk by the intake nurse, yielding 472 positive screens. PCPs completed gait, balance, and strength evaluations on 231 screen-positive Veterans. Among the 162 Veterans who had a gait, balance, or strength problem on evaluation and were free of advanced dementia or poor prognosis, 39 were offered physical therapy or exercise. PCPs and nurses held divergent opinions about the clinical reminder and the project, with PCPs more negative and nurses more positive. Conclusions: A fall prevention clinical reminder can be incorporated into routine care, but low referral rates to exercise programs suggest that further quality improvement cycles are needed. C1 [Spears, Gwendolyn V.; Miake-Lye, Isomi M.; Saliba, Debra; Shekelle, Paul G.; Ganz, David A.] VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA USA. [Roth, Carol P.] RAND Corp, Santa Monica, CA USA. [Saliba, Debra; Ganz, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Saliba, Debra; Shekelle, Paul G.; Ganz, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Saliba, Debra] Univ Calif Los Angeles, Borun Ctr Gerontol Res, Los Angeles, CA USA. [Saliba, Debra] Los Angeles Jewish Home, Los Angeles, CA USA. RP Ganz, DA (reprint author), VA Greater Los Angeles Healthcare Syst 11G, 11301 Wilshire Blvd,Bldg 220,Room 313, Los Angeles, CA 90073 USA. EM dganz@mednet.ucla.edu FU US Department of Veterans Affairs, Veterans Health Administration Quality Enhancement Research Initiative [RRP 09-202]; VA Career Development Award from the VA Health Services Research & Development (HSR&D) Service through the VA Greater Los Angeles HSR&D Center of Excellence [VA CD2 08-012-1]; John A. Hartford Foundation; American Federation for Aging Research through the UCLA Geriatrics Center of Excellence; VA Greater Los Angeles HSR&D Center of Excellence [LIP 65-127]; Robert Wood Johnson Foundation Physician Faculty Scholars Program FX Supported by the US Department of Veterans Affairs, Veterans Health Administration Quality Enhancement Research Initiative (Project # RRP 09-202). David Ganz was supported by a VA Career Development Award from the VA Health Services Research & Development (HSR&D) Service (Project # VA CD2 08-012-1) through the VA Greater Los Angeles HSR&D Center of Excellence. Additional support was provided by the John A. Hartford Foundation and the American Federation for Aging Research through the UCLA Geriatrics Center of Excellence, a locally initiated project through the VA Greater Los Angeles HSR&D Center of Excellence (LIP 65-127), and the Robert Wood Johnson Foundation Physician Faculty Scholars Program. NR 19 TC 3 Z9 3 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 MAR PY 2013 VL 51 IS 3 SU 1 BP S37 EP S43 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AJ7YH UT WOS:000337917300007 PM 23407009 ER PT J AU Tsai, TT Box, TL Gethoffer, H Noonan, G Varosy, PD Maddox, TM Fihn, SD Gross, TP Jesse, RL Rumsfeld, JS AF Tsai, Thomas T. Box, Tamara L. Gethoffer, Hans Noonan, Gregory Varosy, Paul D. Maddox, Thomas M. Fihn, Stephan D. Gross, Thomas P. Jesse, Robert L. Rumsfeld, John S. TI Feasibility of Proactive Medical Device Surveillance The VA Clinical Assessment Reporting and Tracking (CART) Program SO MEDICAL CARE LA English DT Article DE patient safety; device safety; cardiovascular ID COMPREHENSIVE APPROACH; SAFETY NET; STENTS; HOLES AB Background: Timely identification and reporting of medical device problems is critical to postmarket device surveillance programs to maximize patient safety. Cardiac catheterization laboratories are high-device utilization areas well suited for device surveillance. Objective: To demonstrate the feasibility of the national VA Clinical Assessment, Reporting, and Tracking (CART) system, embedded in the electronic health record of all 76 VA cardiac catheterization laboratories, to document unexpected problems with medical devices at the point of care. Methods: We evaluated 260,258 consecutive cardiac catheterization and/or percutaneous coronary intervention procedures on 175,098 Veterans between August 2006 and February 2012. Unexpected device problems (UDPs) encountered for any equipment used during a procedure were entered by clinicians at the point of care as part of regular care documentation. All UDPs were reviewed in collaboration with the FDA to ascertain the likelihood of a device defect (eg, in manufacture or design) and/or contributing to a procedural complication (level I, unlikely; level II, possibly; level III, likely). Results: Of the 260,258 procedure reports, 974 (0.37%) UDP's were reported by 71 (92.2%) of the 76 VA hospitals. After triage, 739 (75.9%) were deemed level I, 196 (20.1%) level II, and 39 (4.0%) level III. Of the 39 level III reports, 12 (30.7%) are in the submission phase as a FDA MedWatch report. The number of monthly UDP reports increased significantly from 2006 to 2012 (P < 0.001). Conclusions: Leveraging a clinical application embedded in the electronic health record and in collaboration with FDA, a proactive national cardiac device surveillance program has been successfully implemented in the VA. C1 [Tsai, Thomas T.; Box, Tamara L.; Gethoffer, Hans; Noonan, Gregory; Varosy, Paul D.; Maddox, Thomas M.; Rumsfeld, John S.] Univ Colorado, VA Eastern Colorado Hlth Care Syst, Dept Med, CART Coordinating Ctr, Denver, CO 80220 USA. [Fihn, Stephan D.] VA Hlth Serv R&D, Off Analyt & Business Intelligence, Seattle, WA USA. [Fihn, Stephan D.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Gross, Thomas P.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Jesse, Robert L.; Rumsfeld, John S.] VA Cent Off, Washington, DC USA. [Jesse, Robert L.] Richmond VA Med Ctr, Richmond, VA USA. RP Tsai, TT (reprint author), Univ Colorado, VA Eastern Colorado Hlth Care Syst, Dept Med, CART Coordinating Ctr,Cardiol Sect 111B, 1055 Clermont St, Denver, CO 80220 USA. EM thomas.tsai@va.gov NR 18 TC 11 Z9 11 U1 0 U2 3 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 MAR PY 2013 VL 51 IS 3 SU 1 BP S57 EP S61 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AJ7YH UT WOS:000337917300010 PM 23407013 ER PT J AU Guinan, E Boudreau, KJ Lakhani, KR AF Guinan, Eva Boudreau, Kevin J. Lakhani, Karim R. TI Experiments in Open Innovation at Harvard Medical School SO MIT SLOAN MANAGEMENT REVIEW LA English DT Article AB This article examines an experiment in open innovation applied to scientific research on Type 1 diabetes at Harvard Medical School. In the traditional research process, a single research team typically carries through each stage of the process-from generating the idea to raising money to carrying out the research and publishing the results. Harvard Catalyst, a pan-Harvard agency with a mission to speed biomedical research from the lab to patients' bedsides, modified the traditional grant proposal process as an experiment in bringing greater openness into every stage of research. Participation was successfully extended to nontraditional actors. In the end, 150 new hypotheses and research pathways were proposed. Teams were invited to propose projects on the 12 most promising of these; today, seven teams are carrying out the research. The Harvard Catalyst experience suggests that open-innovation principles can be adopted even within a well-established and experienced innovation-driven organization. C1 [Guinan, Eva] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Guinan, Eva] Dana Farber Canc Inst, Boston, MA USA. [Guinan, Eva] Harvard Catalyst, Innovat & Implementat Program, Boston, MA USA. [Boudreau, Kevin J.] London Business Sch, London, England. [Boudreau, Kevin J.] Harvard Univ, Inst Quantitat Social Sci, Harvard NASA Tournament Lab, Cambridge, MA 02138 USA. [Lakhani, Karim R.] Harvard Univ, Sch Business, Cambridge, MA 02138 USA. RP Guinan, E (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 20 TC 5 Z9 5 U1 3 U2 8 PU SLOAN MANAGEMENT REVIEW ASSOC, MIT SLOAN SCHOOL MANAGEMENT PI CAMBRIDGE PA 77 MASSACHUSETTS AVE, E60-100, CAMBRIDGE, MA 02139-4307 USA SN 1532-9194 J9 MIT SLOAN MANAGE REV JI MIT Sloan Manage. Rev. PD SPR PY 2013 VL 54 IS 3 BP 45 EP + PG 10 WC Business; Management SC Business & Economics GA V37MN UT WOS:000209280000010 ER PT J AU Gaudet, MM Kuchenbaecker, KB Vijai, J Klein, RJ Kirchhoff, T McGuffog, L Barrowdale, D Dunning, AM Lee, A Dennis, J Healey, S Dicks, E Soucy, P Sinilnikova, O Pankratz, VS Wang, XS Eldridge, RC Tessier, DC Vincent, D Bacot, F Hogervorst, FBL Peock, S Stoppa-Lyonnet, D Peterlongo, P Schmutzler, RK Nathanson, KL Piedmonte, M Singer, CF Thomassen, M Hansen, TVO Neuhausen, SL Blanco, I Greene, MH Garber, J Weitzel, JN Andrulis, IL Goldgar, DE D'Andrea, E Caldes, T Nevanlinna, H Osorio, A van Rensburg, EJ Arason, A Rennert, G van den Ouweland, AMW van der Hout, AH Kets, CM Aalfs, CM Wijnen, JT Ausems, MGEM Frost, D Ellis, S Fineberg, E Platte, R Evans, DG Jacobs, C Adlard, J Tischkowitz, M Porteous, ME Damiola, F Golmard, L Barjhoux, L Longy, M Belotti, M Ferrer, SF Mazoyer, S Spurdle, AB Manoukian, S Barile, M Genuardi, M Arnold, N Meindl, A Sutter, C Wappenschmidt, B Domchek, SM Pfeiler, G Friedman, E Jensen, UB Robson, M Shah, S Lazaro, C Mai, PL Benitez, J Southey, MC Schmidt, MK Fasching, PA Peto, J Humphreys, MK Wang, Q Michailidou, K Sawyer, EJ Burwinkel, B Guenel, P Bojesen, SE Milne, RL Brenner, H Lochmann, M Aittomaki, K Dork, T Margolin, S Mannermaa, A Lambrechts, D Chang-Claude, J Radice, P Giles, GG Haiman, CA Winqvist, R Devillee, P Garcia-Closas, M Schoof, N Hooning, MJ Cox, A Pharoah, PDP Jakubowska, A Orr, N Gonzalez-Neira, A Pita, G Alonso, MR Hall, P Couch, FJ Simard, J Altshuler, D Easton, DF Chenevix-Trench, G Antoniou, AC Offit, K AF Gaudet, Mia M. Kuchenbaecker, Karoline B. Vijai, Joseph Klein, Robert J. Kirchhoff, Tomas McGuffog, Lesley Barrowdale, Daniel Dunning, Alison M. Lee, Andrew Dennis, Joe Healey, Sue Dicks, Ed Soucy, Penny Sinilnikova, Olgam. Pankratz, Vernon S. Wang, Xianshu Eldridge, Ronald C. Tessier, Daniel C. Vincent, Daniel Bacot, Francois Hogervorst, Frans B. L. Peock, Susan Stoppa-Lyonnet, Dominique Peterlongo, Paolo Schmutzler, Rita K. Nathanson, Katherine L. Piedmonte, Marion Singer, Christian F. Thomassen, Mads Hansen, Thomas V. O. Neuhausen, Susan L. Blanco, Ignacio Greene, Mark H. Garber, Judith Weitzel, Jeffrey N. Andrulis, Irene L. Goldgar, David E. D'Andrea, Emma Caldes, Trinidad Nevanlinna, Heli Osorio, Ana van Rensburg, Elizabeth J. Arason, Adalgeir Rennert, Gad van den Ouweland, Ans M. W. van der Hout, Annemarie H. Kets, Carolien M. Aalfs, Cora M. Wijnen, Juul T. Ausems, Margreet G. E. M. Frost, Debra Ellis, Steve Fineberg, Elena Platte, Radka Evans, D. Gareth Jacobs, Chris Adlard, Julian Tischkowitz, Marc Porteous, Mary E. Damiola, Francesca Golmard, Lisa Barjhoux, Laure Longy, Michel Belotti, Muriel Ferrer, Sandra Fert Mazoyer, Sylvie Spurdle, Amanda B. Manoukian, Siranoush Barile, Monica Genuardi, Maurizio Arnold, Norbert Meindl, Alfons Sutter, Christian Wappenschmidt, Barbara Domchek, Susan M. Pfeiler, Georg Friedman, Eitan Jensen, Uffe Birk Robson, Mark Shah, Sohela Lazaro, Conxi Mai, Phuong L. Benitez, Javier Southey, Melissa C. Schmidt, Marjanka K. Fasching, Peter A. Peto, Julian Humphreys, Manjeet K. Wang, Qin Michailidou, Kyriaki Sawyer, Elinor J. Burwinkel, Barbara Guenel, Pascal Bojesen, Stig E. Milne, Roger L. Brenner, Hermann Lochmann, Magdalena Aittomaki, Kristiina Doerk, Thilo Margolin, Sara Mannermaa, Arto Lambrechts, Diether Chang-Claude, Jenny Radice, Paolo Giles, Graham G. Haiman, Christopher A. Winqvist, Robert Devillee, Peter Garcia-Closas, Montserrat Schoof, Nils Hooning, Maartje J. Cox, Angela Pharoah, Paul D. P. Jakubowska, Anna Orr, Nick Gonzalez-Neira, Anna Pita, Guillermo Rosario Alonso, M. Hall, Per Couch, Fergus J. Simard, Jacques Altshuler, David Easton, Douglas F. Chenevix-Trench, Georgia Antoniou, Antonis C. Offit, Kenneth CA KConFab Investigators Ontario Canc Genetics Network HEBON EMBRACE GEMO Study Collaborators GENICA Network TI Identification of a BRCA2-Specific Modifier Locus at 6p24 Related to Breast Cancer Risk SO PLOS GENETICS LA English DT Article ID BRCA2 MUTATION CARRIERS; TRANSCRIPTION FACTOR AP-2; GENOME-WIDE ASSOCIATION; COMMON VARIANTS; SUSCEPTIBILITY ALLELES; OVARIAN-CANCER; ZNF365; POPULATION; CONSORTIUM; SUBTYPES AB Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9 x 10(-8)). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer. C1 [Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Kuchenbaecker, Karoline B.; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Dennis, Joe; Dicks, Ed; Peock, Susan; Frost, Debra; Ellis, Steve; Fineberg, Elena; Platte, Radka; Evans, D. Gareth; Humphreys, Manjeet K.; Wang, Qin; Michailidou, Kyriaki; Pharoah, Paul D. P.; Easton, Douglas F.; Antoniou, Antonis C.; EMBRACE] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England. [Vijai, Joseph; Robson, Mark; Shah, Sohela; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Clin Genet Serv, New York, NY 10021 USA. [Klein, Robert J.] Mem Sloan Kettering Canc Ctr, Program Canc Biol & Genet, New York, NY 10021 USA. [Kirchhoff, Tomas] NYU, Dept Environm Med, Div Epidemiol, Sch Med, New York, NY 10016 USA. [Dunning, Alison M.; Pharoah, Paul D. P.; Easton, Douglas F.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England. [Healey, Sue; Spurdle, Amanda B.; Chenevix-Trench, Georgia] Queensland Inst Med Res, Genet & Populat Hlth Div, Brisbane, Qld 4006, Australia. [Soucy, Penny; Simard, Jacques] Ctr Hosp Univ Quebec, Canc Genom Lab, Quebec City, PQ, Canada. [Soucy, Penny; Simard, Jacques] Univ Laval, Quebec City, PQ, Canada. [Sinilnikova, Olgam.] Hosp Civils Lyon, Unite Mixte Genet Constitut Canc Frequents, Ctr Leon Berard, Lyon, France. [Pankratz, Vernon S.; Damiola, Francesca; Barjhoux, Laure; Mazoyer, Sylvie] Univ Lyon 1, INSERM U1052, CNRS UMR5286, Ctr Rech Cancerol Lyon, F-69365 Lyon, France. [Wang, Xianshu; Couch, Fergus J.] Mayo Clin, Dept Hlth Sci, Rochester, MN USA. [Eldridge, Ronald C.; Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Tessier, Daniel C.] Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Vincent, Daniel; Bacot, Francois] Ctr Innovat Genome Quebec, Montreal, PQ, Canada. [Vincent, Daniel; Bacot, Francois] McGill Univ, Montreal, PQ, Canada. [Hogervorst, Frans B. L.] Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands. [Stoppa-Lyonnet, Dominique; Golmard, Lisa; Belotti, Muriel] Inst Curie, Dept Tumour Biol, Paris, France. [Stoppa-Lyonnet, Dominique] Inst Curie, INSERM U830, Paris, France. [Stoppa-Lyonnet, Dominique] Univ Paris 05, Sorbonne Paris Cite, Paris, France. [KConFab Investigators] Peter MacCallum Canc Ctr, Kathleen Cuningham Consortium Res Familial Breast, Melbourne, Vic, Australia. [Peterlongo, Paolo; Radice, Paolo] Fdn IRCCS Ist Nazl Tumori, Unit Mol Bases Genet Risk & Genet Testing, Dept Prevent & Predict Med, Milan, Italy. [Radice, Paolo] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy. [Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Hosp Cologne, Cologne, Germany. [Nathanson, Katherine L.; Domchek, Susan M.] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Nathanson, Katherine L.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Piedmonte, Marion] Roswell Pk Canc Inst, Gynecol Oncol Grp, Stat & Data Ctr, Buffalo, NY 14263 USA. [Singer, Christian F.; Pfeiler, Georg] Med Univ Vienna, Dept Obstet & Gyncol, Vienna, Austria. [Singer, Christian F.; Pfeiler, Georg] Med Univ Vienna, Ctr Comprehens Canc, Vienna, Austria. [Thomassen, Mads] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark. [Andrulis, Irene L.; Ontario Canc Genetics Network] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Hansen, Thomas V. O.] Copenhagen Univ Hosp, Ctr Genom Med, Rigshosp, Copenhagen, Denmark. [Neuhausen, Susan L.] City Hope Natl Med Ctr, Dept Populat Sci, Beckman Res Inst, Duarte, CA USA. [Blanco, Ignacio] IDIBELL Catalan Inst Oncol, Genet Counseling Unit, Hereditary Canc Program, Barcelona, Spain. [Greene, Mark H.; Mai, Phuong L.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Garber, Judith] Dana Farber Partners CancerCare, Dept Med Oncol, Boston, MA USA. [Weitzel, Jeffrey N.] City Hope Natl Med Ctr, Clin Canc Genet, City Hope Clin Canc Genet Community Res Network, Duarte, CA USA. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A1, Canada. [Goldgar, David E.] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA. [D'Andrea, Emma] Univ Padua, Dept Surg Oncol & Gastroenterol, Padua, Italy. [D'Andrea, Emma] Ist Oncolog Veneto IOV IRCCS, Immunol & Mol Oncol Unit, Padua, Italy. [Caldes, Trinidad] Hosp Clin San Carlos, Mol Oncol Lab, IdISSC, Madrid, Spain. [Nevanlinna, Heli] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland. [Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Osorio, Ana; Benitez, Javier; Milne, Roger L.] Spanish Natl Canc Ctr CNIO, Human Genet Grp, Madrid, Spain. [Osorio, Ana; Benitez, Javier] Biomed Network Rare Dis CIBERER, Madrid, Spain. [van Rensburg, Elizabeth J.] Univ Pretoria, Dept Genet, ZA-0002 Pretoria, South Africa. [Arason, Adalgeir] Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland. [Arason, Adalgeir] Univ Iceland, BMC, Fac Med, Reykjavik, Iceland. [Rennert, Gad] Clalit Natl Israeli Canc Control Ctr, Haifa, Israel. [Rennert, Gad] Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel. [Rennert, Gad] B Rappaport Fac Med, Haifa, Israel. [van den Ouweland, Ans M. W.] Erasmus Univ, Dept Clin Genet, Family Canc Clin, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [van der Hout, Annemarie H.] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [Kets, Carolien M.] Radboud Univ Nijmegen, Dept Human Genet, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Aalfs, Cora M.] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands. [Wijnen, Juul T.; Devillee, Peter] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands. [Wijnen, Juul T.] Leiden Univ, Dept Clin Genet, Med Ctr, NL-2300 RA Leiden, Netherlands. [Ausems, Margreet G. E. M.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [HEBON] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. [Jacobs, Chris] Guys & St Thomas NHS Fdn Trust, London, England. [Adlard, Julian] Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England. [Tischkowitz, Marc] Univ Cambridge, Dept Med Genet, Cambridge, England. [Porteous, Mary E.] Western Gen Hosp, South East Scotland Reg Genet Serv, Edinburgh EH4 2XU, Midlothian, Scotland. [Longy, Michel] Univ Bordeaux, Canc Genet Unit, INSERM U916, Inst Bergonie, Bordeaux, France. [Ferrer, Sandra Fert] Hotel Dieu Ctr Hosp, Lab Genet Chromosom, Chambery, France. [Manoukian, Siranoush] Fdn IRCCS Ist Nazl Tumori INT, Unit Med Genet, Dept Prevent & Predict Med, Milan, Italy. [Barile, Monica] Ist Europeo Oncol, Div Canc Prevent & Genet, Milan, Italy. [Genuardi, Maurizio] Univ Florence, Fiorgen Fdn Pharmacogenom, Florence, Italy. [Genuardi, Maurizio] Univ Florence, Unit Med Genet, Dept Clin Physiopathol, Florence, Italy. [Arnold, Norbert] Univ Kiel, Univ Hosp Schleswig Holstein, Kiel, Germany. [Meindl, Alfons; Lochmann, Magdalena] Tech Univ Munich, Klinikum Rechts Isar, Dept Obstet & Gynaecol, Div Tumor Genet, D-80290 Munich, Germany. [Sutter, Christian] Heidelberg Univ, Heidelberg, Germany. [Friedman, Eitan] Chaim Sheba Med Ctr, Tel Aviv, Israel. [Jensen, Uffe Birk] Aarhus Univ Hosp, Dept Clin Genet, DK-8000 Aarhus, Denmark. [Lazaro, Conxi] IDIBELL Catalan Inst Oncol, Hereditary Canc Program, Mol Diagnost Unit, Barcelona, Spain. [Southey, Melissa C.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Schmidt, Marjanka K.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands. [Fasching, Peter A.] Univ Hosp Erlangen, Univ Breast Ctr Franconia, Dept Gynecol & Obstet, Erlangen, Germany. [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Peto, Julian] London Sch Hyg & Trop Med, London WC1, England. [Sawyer, Elinor J.] Guys St Thomas NHS Fdn Trust Partnership Kings Co, Div Canc Studies, NIHR Comprehens Biomed Res Ctr, London, England. [Burwinkel, Barbara] Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany. [Burwinkel, Barbara] German Canc Res Ctr, Mol Epidemiol Grp, Heidelberg, Germany. [Guenel, Pascal] INSERM, CESP Ctr Res Epidemiol & Populat Health, Environm Epidemiol Canc U1018, Villejuif, France. [Guenel, Pascal] Univ Paris 11, UMR S 1018, Villejuif, France. [Bojesen, Stig E.] Copenhagen Gen Populat Study, Copenhagen, Denmark. [Bojesen, Stig E.] Univ Copenhagen, Dept Clin Biochem, Herlev Hosp, Copenhagen Univ Hosp, Copenhagen, Denmark. [Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany. Univ Tubingen, Tubingen, Germany. Deutsch Krebsforschungszentrum DKFZ, Heidelberg, Germany. German Social Accid Insurance IPA, Inst Prevent & Occupat Med, Bochum, Germany. Univ Saarland, Inst & Outpatient Clin Occupat Med, Med Ctr, Homburg, Germany. Univ Saarland, Fac Med, Homburg, Germany. Univ Bonn, Inst Pathol, Fac Med, Bonn, Germany. [GENICA Network] Johanniter Krankenhaus, Dept Internal Med, Evangel Kliniken Bonn gGmbH, Bonn, Germany. [Aittomaki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland. [Doerk, Thilo] Hannover Med Sch, Dept Obstet & Gynecol, Hannover, Germany. [Margolin, Sara] Karolinska Inst, Dept Pathol & Oncol, Stockholm, Sweden. [Mannermaa, Arto] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Bioctr Kuopio, Sch Med,Canc Ctr Eastern Finland, Kuopio, Finland. [Mannermaa, Arto] Kuopio Univ Hosp, Imaging Ctr, Dept Clin Pathol, SF-70210 Kuopio, Finland. [Lambrechts, Diether] Katholieke Univ Leuven VIB, Vesalius Res Ctr, Louvain, Belgium. [Lambrechts, Diether] Katholieke Univ Leuven, Lab Translat Genet, Dept Oncol, Louvain, Belgium. [Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Giles, Graham G.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Winqvist, Robert] Univ Oulu, Oulu Univ Hosp, Lab Canc Genet & Tumor Biol, Dept Clin Genet, Oulu, Finland. [Winqvist, Robert] Univ Oulu, Oulu Univ Hosp, Bioctr Oulu, Oulu, Finland. [Devillee, Peter] Leiden Univ, Dept Pathol, Med Ctr, Leiden, Netherlands. [Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England. [Garcia-Closas, Montserrat] Inst Canc Res, Div Breast Canc Res, Sutton, Surrey, England. [Garcia-Closas, Montserrat; Orr, Nick; Hall, Per] Inst Canc Res, Div Breast Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. [Schoof, Nils] Karolinska Inst, Stockholm, Sweden. [Hooning, Maartje J.] Erasmus Univ, Dept Med Oncol, Med Ctr, Rotterdam, Netherlands. [Cox, Angela] Univ Sheffield, CRUK YCR Sheffield Canc Res Ctr, Dept Oncol, Sheffield, S Yorkshire, England. [Jakubowska, Anna] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland. [Gonzalez-Neira, Anna; Pita, Guillermo; Rosario Alonso, M.] Spanish Natl Canc Res Ctr CNIO, Human Genotyping CEGEN Unit, Human Canc Genet Program, Madrid, Spain. [Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol & Med, Boston, MA 02114 USA. [Altshuler, David] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Gaudet, MM (reprint author), Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. EM offitk@mskcc.org RI Klein, Robert/K-1888-2013; Dork, Thilo/J-8620-2012; Brenner, Hermann/B-4627-2017; manoukian, siranoush/E-7132-2017; Spurdle, Amanda/A-4978-2011; Jakubowska, Anna/O-8050-2014; Altshuler, David/A-4476-2009; Verdrengh, Evelien/H-4571-2012; Blanco, Ignacio/D-2565-2013; Gonzalez-Neira, Anna/C-5791-2015; Garcia-Closas, Montserrat /F-3871-2015; Osorio, Ana/I-4324-2014; Joseph, Vijai/J-9158-2013; Radice, Paolo/O-3119-2013; Jansen van Rensburg, Elizabeth (Lizette)/B-9104-2011; Arnold, Norbert/E-3012-2010; Andrulis, Irene/E-7267-2013 OI Dennis, Joe/0000-0003-4591-1214; Dunning, Alison Margaret/0000-0001-6651-7166; Nevanlinna, Heli/0000-0002-0916-2976; Cox, Angela/0000-0002-5138-1099; Kirchhoff, Tomas/0000-0002-9055-2364; Jacobs, Chris/0000-0002-9557-9080; Giles, Graham/0000-0003-4946-9099; VENAT-BOUVET, Laurence/0000-0002-0716-2550; Evans, Gareth/0000-0002-8482-5784; Klein, Robert/0000-0003-3539-5391; Brenner, Hermann/0000-0002-6129-1572; manoukian, siranoush/0000-0002-6034-7562; Barton, David E/0000-0002-2031-9719; Robson, Mark/0000-0002-3109-1692; Nathanson, Katherine/0000-0002-6740-0901; Spurdle, Amanda/0000-0003-1337-7897; Barrowdale, Daniel/0000-0003-1661-3939; Altshuler, David/0000-0002-7250-4107; Blanco, Ignacio/0000-0002-7414-7481; Garcia-Closas, Montserrat /0000-0003-1033-2650; Osorio, Ana/0000-0001-8124-3984; Joseph, Vijai/0000-0002-7933-151X; Arnold, Norbert/0000-0003-4523-8808; FU University of Eastern Finland; Cancer Fund of North Savo; National Breast Cancer Foundation; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria; Cancer Councils of New South Wales, Tasmania; Cancer Councils of New South Wales, South Australia; Cancer Foundation of Western Australia; United States Army Medical Research and Materiel Command [DAMD17-01-1-0729]; Cancer Council of Tasmania; NHMRC [199600]; NHMRC; Cancer Australia [628333]; National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea [1020350]; Stichting tegen Kanker [232-2008, 196-2010]; FWO; KULPFV/10/016-SymBioSysII; Deutsche Krebshilfe e.V. [70-2892-BR I]; Hamburg Cancer Society; German Cancer Research Center; Federal Ministry of Education and Research (BMBF) [01KH0402]; NIH [CA128978, CA63464, CA54281, CA098758, CA132839]; NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; U.S. Department of Defence Ovarian Cancer Idea award [W81XWH-10-1-0341]; Breast Cancer Research Foundation; Komen Foundation for the Cure; Fondazione Italiana per la Ricerca sul Cancro; Italian Association for Cancer Research (AIRC) [IG 8713]; Italian Ministry of Health ("Progetto Tumori Femminili"); Italian citizens; Fondazione IRCCS Istituto Nazionale Tumori; VicHealth and Cancer Council Victoria; Australian NHMRC [209057, 251553, 504711]; Jewish General Hospital; Niehaus Clinical Cancer Genetics Initiative; Andrew Sabin Family Foundation; Lymphoma Foundation; Quebec Breast Cancer Foundation; Canadian Institutes of Health Research [CRN-87521]; Ministry of Economic Development, Innovation and Export Trade [PSR-SIIRI-701]; Intramural Research Program of the US National Cancer Institute, NIH; Westat, Rockville, MD [NO2-CP-11019-50, N02-CP-65504]; Clalit Health Services in Israel; Israel Cancer Association; Breast Cancer Research Foundation (BCRF); Russian Federation for Basic Research [11-04-00227, 12-04-00928, 12-04-01490]; Federal Agency for Science and Innovations, Russia [02.740.11.0780]; Finnish Cancer Foundation; Academy of Finland; University of Oulu; Oulu University Hospital; Dutch Cancer Society [RUL 1997-1505, DDHK 2004-3124, DDHK 2009-4318]; Biobanking and Biomolecular Resources Research Infrastructure [BBMRI-NL CP16]; Ohio State University Comprehensive Cancer Center; Ministry of Science, Technology and Innovation, Ministry of Higher Education [UM.C/HlR/MOHE/06]; Cancer Research Initiatives Foundation; National Cancer Institute, Department of Health and Human Services, USA; Marit and Hans Rausings Initiative Against Breast Cancer; Agency for Science, Technology and Research of Singapore (A*STAR); U.S. National Institute of Health (NIH); Susan G. Komen Breast Cancer Foundation; Yorkshire Cancer Research [S295, S299, S305PA]; Malaysian Ministry of Science, Technology and Innovation; Ministry of Higher Education [UM.C/HIR/MOHE/06]; Cancer Research UK [[C490/A10124][C8197/A10123]; Swedish Cancer Society; U.S. National Cancer Institute (NIH/NCI); Ralph and Marion Falk Medical Research Trust; Entertainment Industry Fund National Women's Cancer Research Alliance,; Jonsson Comprehensive Cancer Center Foundation; UCSF Cancer Risk Program; Helen Diller Family Comprehensive Cancer Center; Breakthrough Breast Cancer; Institute of Cancer Research (ICR); NHS; CRUK; National Institutes of Health (NIH) [R01-CA102776, R01-CA083855]; Rooney Family Foundation; Susan G. Komen Foundation for the Cure; Facdonald Family Foundation; Victorian Cancer Agency; Cancer Australia; American Cancer Society [SIOP-06-258-01-COUN]; Ligue National Contre le Cancer; Association "Le cancer du sein, parlons-en!" Award; Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program; [C8197/A10865]; [PBZ_KBN_122/P05/2004] FX Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, the Academy of Finland, and by the strategic funding of the University of Eastern Finland. Kathleen Cuningham Consortium for Research into Familial Breast Cancer: kConFab is supported by grants from the National Breast Cancer Foundation and the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund; the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia; and the Cancer Foundation of Western Australia. G Chenevix-Trench and AB Spurdle are NHMRC Senior Research Fellows. Financial support for the AOCS was provided by the United States Army Medical Research and Materiel Command [DAMD17-01-1-0729], the Cancer Council of Tasmania and Cancer Foundation of Western Australia, and the NHMRC [199600]. G Chenevix-Trench is supported by the NHMRC. The Clinical Follow Up Study (funded 2001-2009 by NHMRC and currently by the National Breast Cancer Foundation and Cancer Australia #628333) Korean Hereditary Breast Cancer Study: KOHBRA is supported by a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea (1020350). Leuven Multidisciplinary Breast Centre: LMBC is supported by the 'Stichting tegen Kanker' (232-2008 and 196-2010). D Lambrechts is supported by the FWO and the KULPFV/10/016-SymBioSysII. Mammary Carcinoma Risk Factor Investigation: The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I], the Hamburg Cancer Society, the German Cancer Research Center, and the genotype work in part by the Federal Ministry of Education and Research (BMBF) Germany [01KH0402]. Mayo Clinic: MAYO is supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341), and grants from the Breast Cancer Research Foundation and the Komen Foundation for the Cure. Milan Breast Cancer Study Group: MBCSG was funded by grants from Fondazione Italiana per la Ricerca sul Cancro (Special Project "Hereditary tumors"), Italian Association for Cancer Research (AIRC, IG 8713), Italian Ministry of Health ("Progetto Tumori Femminili"), and by Italian citizens who allocated the 561000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects "5 x 1000"). Melbourne Collaborative Cohort Study: MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057, 251553 and 504711 and by infrastructure provided by Cancer Council Victoria. McGill University: The McGill Study was supported by Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade. Multi-Ethnic Cohort: The MEC was supported by NIH grants CA63464, CA54281, CA098758, and CA132839. Memorial Sloan-Kettering Cancer Center: The MSKCC was supported by Breast Cancer Research Foundation, Niehaus Clinical Cancer Genetics Initiative, Andrew Sabin Family Foundation, and Lymphoma Foundation. Montreal Gene-Environment Breast Cancer Study: The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program grant CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade grant PSR-SIIRI-701.; J Simard is Chairholder of the Canada Research Chair in Oncogenetics. National Cancer Institute: The research of MH Greene and PL Mai was supported by the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Rockville, MD. National Israeli Cancer Control Center: NICCC is supported by Clalit Health Services in Israel. Some of its activities are supported by the Israel Cancer Association and the Breast Cancer Research Foundation (BCRF), New York. N. N. Petrov Institute of Oncology: The NNPIO study has been supported by the Russian Federation for Basic Research (grants 11-04-00227, 12-04-00928, and 12-04-01490) and the Federal Agency for Science and Innovations, Russia (contract 02.740.11.0780). Oulu Breast Cancer Study: The OBCS was supported by research grants from the Finnish Cancer Foundation, the Academy of Finland, the University of Oulu, and the Oulu University Hospital. Leiden University Medical Centre Breast Cancer Study: The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL CP16). The Ohio State University Comprehensive Cancer Center: OSUCCG is supported by the Ohio State University Comprehensive Cancer Center. SEABASS is supported by the Ministry of Science, Technology and Innovation, Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation. The U. S. National Cancer Institute Polish Breast Cancer Study: The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. Karolinska Mammography Project for Risk Prediction of Breast Cancer - prevalent cases: The pKARMA study was supported by Marit and Hans Rausings Initiative Against Breast Cancer. Rotterdam Breast Cancer Study: The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). Singapore and Sweden Breast Cancer Study: The SASBAC study was supported by funding from the Agency for Science, Technology and Research of Singapore (A*STAR), the U.S. National Institute of Health (NIH), and the Susan G. Komen Breast Cancer Foundation. Sheffield Breast Cancer Study: The SBCS was supported by Yorkshire Cancer Research S295, S299, and S305PA. South East Asian Breast Cancer Association Study: SEABASS is supported by the Ministry of Science, Technology and Innovation, Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation. The Malaysian Breast Cancer Genetic Study is funded by research grants from the Malaysian Ministry of Science, Technology and Innovation; Ministry of Higher Education (UM.C/HIR/MOHE/06);and charitable funding from Cancer Research Initiatives Foundation. Study of Epidemiology and Risk Factors in Cancer Heredity: SEARCH is funded by programmegrants from Cancer Research UK [C490/A10124][C8197/A10123]. AM Dunning was funded by [C8197/A10865]. Sheba Medical Centre: The SMC study was partially funded through a grant by the Israel Cancer Association and the funding for the Israeli Inherited Breast Cancer Consortium. Swedish Breast Cancer Study: SWE-BRCA collaborators are supported by the Swedish Cancer Society. IHCC-Szczecin Breast Cancer Study: The SZBCS was supported by Grant PBZ_KBN_122/P05/2004. The University of Chicago Center for Clinical Cancer Genetics and Global Health: UCHICAGO is supported by grants from the U.S.; National Cancer Institute (NIH/NCI) and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women's Cancer Research Alliance, and the Breast Cancer Research Foundation. University of California Los Angeles: The UCLA study was supported by the Jonsson Comprehensive Cancer Center Foundation and the Breast Cancer Research Foundation. University of California San Francisco: The UCSF study was supported by the UCSF Cancer Risk Program and the Helen Diller Family Comprehensive Cancer Center. United Kingdom Breakthrough Generations Study: The UKBGS is funded by Breakthrough Breast Cancer and the Institute of Cancer Research (ICR). ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. United Kingdom Familial Ovarian Cancer Registries: UKFOCR was supported by a project grant from CRUK to PDP Pharoah. University of Pennsylvania: The UPENN study was supported by the National Institutes of Health (NIH) (R01-CA102776 and R01-CA083855), Breast Cancer Research Foundation, Rooney Family Foundation, Susan G. Komen Foundation for the Cure, and the Facdonald Family Foundation. Victorian Familial Cancer Trials Group: The VFCTG study was supported by the Victorian Cancer Agency, Cancer Australia, and National Breast Cancer Foundation. Women's Cancer Program: The WCP at the Samuel Oschin Comprehensive Cancer Institute is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN). Genetic Modifiers of Cancer Risk in BRCA1/2 Mutation Carriers (GEMO) study: The study was supported by the Ligue National Contre le Cancer, the Association "Le cancer du sein, parlons-en!" Award, and the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 51 Z9 51 U1 3 U2 14 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD MAR PY 2013 VL 9 IS 3 AR e1003173 DI 10.1371/journal.pgen.1003173 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 116EY UT WOS:000316866700001 PM 23544012 ER PT J AU Baruch, L AF Baruch, Lawrence TI Laboratory Monitoring of Anticoagulant Medications: Focus on Novel Oral Anticoagulants SO POSTGRADUATE MEDICINE LA English DT Article DE apixaban; coagulation assays; dabigatran; edoxaban; rivaroxaban ID INDUCED CLOTTING TIME; FACTOR-XA INHIBITOR; DIRECT THROMBIN INHIBITORS; PATHOLOGISTS CONFERENCE XXXI; ECARIN CHROMOGENIC ASSAY; NONVALVULAR ATRIAL-FIBRILLATION; PARTIAL THROMBOPLASTIN TIME; DIRECT FXA-INHIBITORS; HEALTHY MALE-SUBJECTS; DABIGATRAN ETEXILATE AB Novel oral anticoagulants, direct thrombin inhibitors, and factor Xa inhibitors are being introduced into clinical practice. In contrast to vitamin K antagonists, such as warfarin, these novel agents, because of their relatively wide therapeutic range and predictable pharmacokinetics, have been evaluated in clinical trials and approved for clinical use without the need for routine coagulation monitoring. On occasion, it will be important to assess the anticoagulant status of patients treated with these agents. As a result of their targeted mechanisms of action, they affect standard coagulation assays differently than vitamin K antagonists and heparins, and such assay results may not provide clinically useful information. Thus, less commonly used coagulation assays (eg, chromogenic anti-factor Xa activity assays, diluted thrombin time, and ecarin-based clotting tests) may be introduced into clinical practice. These assays are currently limited by the absence of validated therapeutic targets and lack of standardization across laboratories, vendors, and medication classes. This article provides an overview of the coagulation assays and their potential role in determining the anticoagulant status of patients treated with the emerging anticoagulants. C1 James J Peters VA Med Ctr, Program Med, Bronx, NY 10468 USA. RP Baruch, L (reprint author), James J Peters VA Med Ctr, Program Med, Bronx, NY 10468 USA. FU Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI) FX This work was supported by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI). Editorial assistance was provided by Annie Rowe, PhD, CMPP, of UBC-Envision Group, which was contracted by BIPI for these services. The author meets criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE), was fully responsible for all content and editorial decisions, and was involved at all stages of manuscript development. The author received no compensation related to the development of the manuscript. NR 70 TC 2 Z9 2 U1 0 U2 4 PU JTE MULTIMEDIA PI WEST CONSHOHOCKEN PA 18 ELIZABETH ST, STE 110, WEST CONSHOHOCKEN, PA 19428 USA SN 0032-5481 EI 1941-9260 J9 POSTGRAD MED JI Postgrad. Med. PD MAR PY 2013 VL 125 IS 2 DI 10.3810/pgm.2013.03.2647 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AX2SJ UT WOS:000346794200013 PM 23816779 ER PT J AU Schunemann, HJ Tugwell, P Reeves, BC Akl, EA Santesso, N Spencer, FA Shea, B Wells, G Helfand, M AF Schuenemann, Holger J. Tugwell, Peter Reeves, Barnaby C. Akl, Elie A. Santesso, Nancy Spencer, Frederick A. Shea, Beverley Wells, George Helfand, Mark TI Non-randomized studies as a source of complementary, sequential or replacement evidence for randomized controlled trials in systematic reviews on the effects of interventions SO RESEARCH SYNTHESIS METHODS LA English DT Review DE GRADE; observational studies; non randomized studies; decision making; systematic reviews AB The terms applicability, generalizability, external validity and transferability are related, sometimes used interchangeably and have in common that they lack a clear and consistent definition in the classic epidemiological literature. However, all of these terms generally describe one overarching theme: whether or not available research evidence can be directly utilized to answer the healthcare questions at hand, ideally supported by a judgment about the degree of confidence for this utilization. This concept has been called directness. The objectives of this paper were to delineate how non-randomized studies (NRS) inform judgments in relation to directness and the concepts that it encompasses in the context of systematic reviews. We will briefly review what is known and describe the theoretical and practical issues as well as offer guidance to those tackling the challenges of judging directness and using research evidence to answer healthcare questions with evidence from NRS. In particular, we suggest a framework in which authors can use NRS as a complement, sequence or replacement for randomized controlled trials (RCTs) by focusing on judgments about the population, intervention, comparison and outcomes. Authors of systematic reviews will use NRS to complement judgments about the inconsistencies, the rationale and credibility of subgroup analysis, the baseline risk estimates for the determination of absolute benefits and downsides, and the directness of surrogate outcomes. This evidence includes contextual or supplementary evidence. Authors of systematic review and other summaries of the evidence use NRS as sequential evidence to provide evidence when insufficient evidence is available for an outcome from RCTs, but NRS evidence is available (e.g., long-term harms). Use of evidence from NRS may also serve to replace RCT evidence when NRS provide equivalent (or potentially higher) confidence in the evidence (i.e. quality) compared to indirect evidence from RCTs. These judgments will be made in the context of other domains that influence the overall quality of the body of evidence, including the risk of bias, publication bias (i.e. limitations in the detailed study design and execution), inconsistency, imprecision and factors that increase our confidence in effects. This article will support systematic reviewers in their interaction with decision makers, that is, those who use the systematic review to develop guidelines, address health policy makers, and make clinical decisions, by making these judgments transparent. Copyright (C) 2013 John Wiley & Sons, Ltd. C1 [Schuenemann, Holger J.; Akl, Elie A.; Santesso, Nancy] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON L8S 4K1, Canada. [Schuenemann, Holger J.; Spencer, Frederick A.] McMaster Univ, Dept Med, Hamilton, ON L8S 4K1, Canada. [Tugwell, Peter; Shea, Beverley; Wells, George] Ottawa Hosp, Res Inst, Clin Epidemiol Unit, Ottawa, ON, Canada. [Reeves, Barnaby C.] Univ Bristol, Bristol Royal Infirm, Bristol Heart Inst, Bristol, Avon, England. [Akl, Elie A.] Amer Univ Beirut, Dept Internal Med, Beirut, Lebanon. [Helfand, Mark] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. [Helfand, Mark] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. RP Schunemann, HJ (reprint author), McMaster Univ, Hlth Sci Ctr, Dept Clin Epidemiol & Biostat, Room 2C10B,1280 Main St W, Hamilton, ON L8S 4K1, Canada. EM schuneh@mcmaster.ca FU Agency for Healthcare Quality and Research (through the Ottawa Collaborating Centre of the Agency for Healthcare Quality and Research); Cochrane Collaboration Discretionary Fund; UK National Institute for Health Research Bristol Cardiovascular Biomedical Research Unit FX The Workshop was supported financially by the Agency for Healthcare Quality and Research (through the Ottawa Collaborating Centre of the Agency for Healthcare Quality and Research) and by a grant from the Cochrane Collaboration Discretionary Fund. BCR is supported in part by the UK National Institute for Health Research Bristol Cardiovascular Biomedical Research Unit. The views expressed in this article are those of the authors and not necessarily those of the funding bodies, The Cochrane Collaboration or its registered entities, committees or working groups, The Campbell Collaboration or the Patient Centered Outcomes Research Institute. NR 20 TC 22 Z9 22 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1759-2879 EI 1759-2887 J9 RES SYNTH METHODS JI Res. Synth. Methods PD MAR PY 2013 VL 4 IS 1 SI SI BP 49 EP 62 DI 10.1002/jrsm.1078 PG 14 WC Mathematical & Computational Biology; Multidisciplinary Sciences SC Mathematical & Computational Biology; Science & Technology - Other Topics GA V38ZN UT WOS:000209381400006 PM 26053539 ER PT J AU McDermott, S Gervais, DA AF McDermott, Shaunagh Gervais, Debra A. TI Radiofrequency Ablation of Liver Tumors SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Article DE radiofrequency ablation; liver; hepatocellular carcinoma; metastases; technique AB Radiofrequency ablation (RFA) is an alternative therapy for hepatocellular carcinoma and liver metastases when resection cannot be performed or, in the case of hepatocellular carcinoma, when transplant cannot be performed in a timely enough manner to avoid the risk of dropping off the transplant list. RFA has the advantage of being a relatively low-risk minimally invasive procedure used in the treatment of focal liver tumors. This review article discusses the current evidence supporting RFA of liver tumors, as well as the indications, complications, and follow-up algorithms used after RFA. C1 [McDermott, Shaunagh; Gervais, Debra A.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Dept Radiol, Boston, MA 02114 USA. [Gervais, Debra A.] Massachusetts Gen Hosp, Dept Radiol, Div Pediat Imaging, Boston, MA 02114 USA. RP McDermott, S (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Dept Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM smcdermott1@partners.org NR 51 TC 10 Z9 11 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD MAR PY 2013 VL 30 IS 1 BP 49 EP 55 DI 10.1055/s-0033-1333653 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V40YD UT WOS:000209513000007 PM 24436517 ER PT J AU Liu, SY Buka, SL Kubzansky, LD Kawachi, I Gilman, SE Loucks, EB AF Liu, Sze Yan Buka, Stephen L. Kubzansky, Laura D. Kawachi, Ichiro Gilman, Stephen E. Loucks, Eric B. TI Sheepskin effects of education in the 10-year Framingham risk of coronary heart disease SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE CHD risk; Education; Sheepskin effect AB While the association between education and adult health is well documented, it is unclear whether quantity (i.e. years of schooling) or credentials (i.e. degrees) drive this association. Individuals with degrees may have better health than their non-credentialed counterparts given similar years of schooling, the so-called "sheepskin" effect. This paper contributes to this line of inquiry by examining associations of educational degree and years of schooling with the Framingham Risk Score, a measure of 10-year risk of coronary heart disease (CHD), using data from a unique birth cohort (the New England Family Study; participants mean age 42 years) with prospective information on childhood health and intelligence quotient (IQ). According to our results, years of schooling were inversely associated with 10-year CHD risk in the unadjusted model but not in the fully adjusted models that included degree attainment. By contrast, associations between degree attainment and 10-year CHD risk remained significant in the fully adjusted models that included years of schooling. College degree holders had 10-year CHD risk 19% (95% CI: -33%, -2%) lower than individuals with HS degrees or less in the fully adjusted models. Subanalyses evaluating sheepskin effects on the individual components of the 10-year CHD risk algorithm showed the expected education gradient was generally noted for each of the individual components, with decreasing prevalence of "high risk" values associated with higher degree credentials. Our results suggest educational credentials provide an additional benefit to risk of coronary heart disease beyond schooling. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Liu, Sze Yan; Buka, Stephen L.; Kubzansky, Laura D.; Kawachi, Ichiro; Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Buka, Stephen L.; Loucks, Eric B.] Brown Univ, Dept Epidemiol, Providence, RI 02912 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. RP Liu, SY (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 677 Huntington Ave, Boston, MA 02115 USA. EM szeliu@harvard.hsph.edu RI Buka, Stephen/H-7335-2014; Gilman, Stephen/E-7632-2010; Loucks, Eric/I-1272-2014 OI Buka, Stephen/0000-0002-8578-9308; Gilman, Stephen/0000-0002-8331-6419; Loucks, Eric/0000-0002-9962-0386 FU NIA NIH HHS [R01 AG023397]; NICHD NIH HHS [R24 HD041020] NR 36 TC 3 Z9 3 U1 0 U2 9 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 MAR PY 2013 VL 80 BP 31 EP 36 DI 10.1016/j.socscimed.2012.12.026 PG 6 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA V39YW UT WOS:000209447300005 PM 23415589 ER PT J AU Caspi, CE Kawachi, I Subramanian, SV Tucker-Seeley, R Sorensen, G AF Caspi, Caitlin E. Kawachi, Ichiro Subramanian, S. V. Tucker-Seeley, Reginald Sorensen, Glorian TI The social environment and walking behavior among low-income housing residents SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE USA; Environment; Social capital; Safety; Social disorder; Physical activity; Low-income housing AB Walking, both for leisure and for travel/errands, counts toward meeting physical activity recommendations. Both social and physical neighborhood environmental features may encourage or inhibit walking. This study examined social capital, perceived safety, and disorder in relation to walking behavior among a population of low-income housing residents. Social and physical disorder were assessed by systematic social observation in the area surrounding 20 low-income housing sites in greater Boston. A cross-sectional survey of 828 residents of these housing sites provided data on walking behavior, socio-demographics, and individual-level social capital and perceived safety of the areas in and around the housing site. Community social capital and safety were calculated by aggregating individual scores to the level of the housing site. Generalized estimating equations were used to estimate prevalence rate ratios for walking less than 10 min per day for a) travel/errands, b) leisure and c) both travel/errands and leisure. 21.8% of participants walked for travel/errands less than 10 min per day, 34.8% for leisure, and 16.8% for both kinds of walking. In fully adjusted models, those who reported low individual-level social capital and safety also reported less overall walking and less walking for travel/errands. Unexpectedly, those who reported low social disorder also reported less walking for leisure, and those who reported high community social capital also walked less for all outcomes. Physical disorder and community safety were not associated with walking behavior. For low-income housing residents, neighborhood social environmental variables are unlikely the most important factors in determining walking behavior. Researchers should carefully weigh the respective limitations of subjective and objective measures of the social environment when linking them to health outcomes. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Caspi, Caitlin E.; Kawachi, Ichiro; Subramanian, S. V.; Tucker-Seeley, Reginald; Sorensen, Glorian] Harvard Univ, Sch Publ Hlth, Boston, MA 02114 USA. [Tucker-Seeley, Reginald; Sorensen, Glorian] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Caspi, CE (reprint author), Harvard Univ, Sch Publ Hlth, 677 Huntingon Ave, Boston, MA 02114 USA. EM caitlincaspi@gmail.com FU National Cancer Institute [5R01CA111310-04]; National Cancer Institute by the Harvard Education Program in Cancer Prevention and Control [5R25CA057711-17, 2R25CA057711-16] FX We gratefully acknowledge the efforts of the Health in Common Research Team: Anne Stoddard, Jennifer Allen, Amy Harley, Marty Alvarez-Reeves, Brianna Wadler, Brittany Bricen, Suze Jean-Felix, May Yang, David Wilson, and Ruth Lederman. The authors also thank the Cambridge Housing Authority, the Somerville Housing Authority, and the Chelsea Housing Authority, the resident participants and resident service coordinators at collaborating housing site. This research was supported by Grant 5R01CA111310-04 from the National Cancer Institute. Funding support for the lead author (CC) was also provided through the National Cancer Institute by the Harvard Education Program in Cancer Prevention and Control 5R25CA057711-17 and 2R25CA057711-16. Funding agencies played no role in this study and the contents of this manuscript are solely the responsibility of the authors. NR 62 TC 7 Z9 7 U1 2 U2 11 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 MAR PY 2013 VL 80 BP 76 EP 84 DI 10.1016/j.socscimed.2012.11.030 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA V39YW UT WOS:000209447300010 PM 23312303 ER PT J AU Guanci, MM AF Guanci, Mary McKenna TI Olympic Cooling Cap for Neonatal Hypoxic Arrest SO THERAPEUTIC HYPOTHERMIA AND TEMPERATURE MANAGEMENT LA English DT Letter C1 Massachusetts Gen Hosp, Neurosci ICU, Boston, MA 02114 USA. RP Guanci, MM (reprint author), Massachusetts Gen Hosp, Neurosci ICU, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2153-7658 EI 2153-7933 J9 THER HYPOTHERMIA TEM JI Ther. Hypothermia Temp. Manag. PD MAR 1 PY 2013 VL 3 IS 1 BP 34 EP 35 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA V38PZ UT WOS:000209356600014 ER PT J AU Sweeney, AC Weitlauf, JC Manning, EA Sze, JA Waldrop, AE Hasser, C AF Sweeney, Alison C. Weitlauf, Julie C. Manning, Elizabeth A. Sze, Jocelyn A. Waldrop, Angela E. Hasser, Caitlin TI Intimate Partner Violence: Perspectives on Universal Screening for Women in VHA Primary Care SO WOMENS HEALTH ISSUES LA English DT Editorial Material ID POSTTRAUMATIC-STRESS-DISORDER; MILITARY SEXUAL TRAUMA; MENTAL-HEALTH; UNINTENDED PREGNANCY; DOMESTIC VIOLENCE; FEMALE-PATIENTS; VETERANS; PREVALENCE; DEPRESSION; SYMPTOMS C1 [Sweeney, Alison C.] Michael E DeBakey VA Med Ctr, Dept Vet Affairs, Houston, TX 77030 USA. [Weitlauf, Julie C.; Manning, Elizabeth A.] VA Palo Alto Hlth Care Syst, Dept Vet Affairs, Palo Alto, CA USA. [Weitlauf, Julie C.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Sze, Jocelyn A.] San Francisco VA Med Ctr, Dept Vet Affairs, San Francisco, CA USA. [Waldrop, Angela E.; Hasser, Caitlin] Univ Calif San Francisco, Dept Psychiat, San Francisco VA Med Ctr, Dept Vet Affairs, San Francisco, CA USA. RP Sweeney, AC (reprint author), Michael E DeBakey VA Med Ctr, Dept Vet Affairs, 2002 Holcombe Blvd 116B, Houston, TX 77030 USA. EM alison.sweeney@va.gov NR 61 TC 5 Z9 5 U1 3 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD MAR-APR PY 2013 VL 23 IS 2 BP E73 EP E76 DI 10.1016/j.whi.2012.12.004 PG 4 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA AO1WD UT WOS:000341105300002 PM 23415320 ER PT J AU Yuen, EK Herbert, JD Forman, EM Goetter, EM Comer, R Bradley, JC AF Yuen, Erica K. Herbert, James D. Forman, Evan M. Goetter, Elizabeth M. Comer, Ronald Bradley, Jean-Claude TI Treatment of Social Anxiety Disorder Using Online Virtual Environments in Second Life SO BEHAVIOR THERAPY LA English DT Article DE social anxiety; virtual reality; Second Life; telehealth; telepsychology ID COGNITIVE-BEHAVIORAL THERAPY; CONTROLLED EFFECTIVENESS TRIAL; NEGATIVE EVALUATION SCALE; SHEEHAN DISABILITY SCALE; REALITY EXPOSURE THERAPY; DEPRESSION INVENTORY-II; COMMITMENT THERAPY; UNITED-STATES; CONCURRENT VALIDITY; PANIC DISORDER AB Over 80% of people with social anxiety disorder (SAD) do not receive any type of treatment, despite the existence of effective evidence-based treatments. Barriers to treatment include lack of trained therapists (particularly in non-metropolitan areas), logistical difficulties (e.g., cost, time, transportation), concerns regarding social stigma, and fear of negative evaluation from health care providers. Interventions conducted through electronic communication media, such as the Internet, have the potential to reach individuals who otherwise would not have access to evidence-based treatments. Second Life is an online virtual world that holds great promise in the widespread delivery of evidence-based treatments. We assessed the feasibility, acceptability, and initial efficacy of an acceptance-based behavior therapy in Second Life to treat adults with generalized SAD. Participants (n=14) received 12 sessions of weekly therapy and were assessed at pretreatment, midtreatment, post-treatment, and follow-up. Participants and therapists rated the treatment program as acceptable and feasible, despite frequently encountered technical difficulties. Analyses showed significant pretreatment to follow-up improvements in social anxiety symptoms, depression, disability, and quality of life, with effect sizes comparable to previously published results of studies delivering in-person cognitive behavior therapy for SAD. Implications and future directions are discussed. C1 [Yuen, Erica K.] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. [Herbert, James D.] Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. RP Herbert, JD (reprint author), Univ Penn, Dept Psychol, 119 Stratton,1341 Chestnut St, Philadelphia, PA 19104 USA. EM james.herbert@drexel.edu RI Forman, Evan/I-1042-2012; OI Bradley, Jean-Claude/0000-0001-7144-4846 NR 68 TC 19 Z9 19 U1 10 U2 85 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 J9 BEHAV THER JI Behav. Therapy PD MAR PY 2013 VL 44 IS 1 BP 51 EP 61 PG 11 WC Psychology, Clinical SC Psychology GA 074XW UT WOS:000313849400005 PM 23312426 ER PT J AU Shenhav, A Barrett, LF Bar, M AF Shenhav, Amitai Barrett, Lisa Feldman Bar, Moshe TI Affective value and associative processing share a cortical substrate SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE LA English DT Article DE Valence; Context; Prefrontal cortex; Object recognition ID VENTROMEDIAL PREFRONTAL CORTEX; MEDIAL ORBITOFRONTAL CORTEX; BRAINS DEFAULT NETWORK; HUMAN CEREBRAL-CORTEX; DECISION-MAKING; SELECTIVE ATTENTION; MACAQUE MONKEYS; MEMORY; EMOTION; CONTEXT AB The brain stores information in an associative manner so that contextually related entities are connected in memory. Such associative representations mediate the brain's ability to generate predictions about which other objects and events to expect in a given context. Likewise, the brain encodes and is able to rapidly retrieve the affective value of stimuli in our environment. That both contextual associations and affect serve as building blocks of numerous mental functions often makes interpretation of brain activation ambiguous. A critical brain region where such activation has often resulted in equivocal interpretation is the medial orbitofrontal cortex (mOFC), which has been implicated separately in both affective and associative processing. To characterize its role more unequivocally, we tested whether activity in the mOFC was most directly attributable to affective processing, associative processing, or a combination of both. Subjects performed an object recognition task while undergoing fMRI scans. Objects varied independently in their affective valence and in their degree of association with other objects (associativity). Analyses revealed an overlapping sensitivity whereby the left mOFC responded both to increasingly positive affective value and to stronger associativity. These two properties individually accounted for mOFC response, even after controlling for their interrelationship. The role of the mOFC is either general enough to encompass associations that link stimuli both with reinforcing outcomes and with other stimuli or abstract enough to use both valence and associativity in conjunction to inform downstream processes related to perception and action. These results may further point to a fundamental relationship between associativity and positive affect. C1 [Shenhav, Amitai] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Shenhav, Amitai; Barrett, Lisa Feldman; Bar, Moshe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Barrett, Lisa Feldman; Bar, Moshe] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02129 USA. [Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Bar, Moshe] Bar Ilan Univ, Gonda Ctr Multidisciplinary Brain Res, IL-52900 Ramat Gan, Israel. [Shenhav, Amitai] Princeton Univ, Princeton Neurosci Inst, Princeton, NJ 08540 USA. RP Shenhav, A (reprint author), Princeton Univ, Princeton Neurosci Inst, Green Hall 3-N-12, Princeton, NJ 08540 USA. EM ashenhav@princeton.edu FU NSF [0842947]; National Institutes of Health [DP1OD003312]; NIH [R01EY019477] FX Note We are grateful to J. Boshyan, M. Rosen, and K. Shepherd for assistance in data collection, T. Benner for technical guidance, E. Aminoff for assistance in stimulus collection, and S. Gagnon for assistance with analysis and helpful comments on the manuscript. This work was supported by an NSF Graduate Research Fellowship awarded to A.S., National Institutes of Health Director's Pioneer Award (DP1OD003312) to L.F.B., and NIH R01EY019477 and NSF 0842947 to M.B. NR 98 TC 15 Z9 15 U1 5 U2 35 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-7026 J9 COGN AFFECT BEHAV NE JI Cogn. Affect. Behav. Neurosci. PD MAR PY 2013 VL 13 IS 1 BP 46 EP 59 DI 10.3758/s13415-012-0128-4 PG 14 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 077VW UT WOS:000314058400004 PM 23090717 ER PT J AU Psutka, SP Feldman, AS McDougal, WS McGovern, FJ Mueller, P Gervais, DA AF Psutka, Sarah P. Feldman, Adam S. McDougal, W. Scott McGovern, Francis J. Mueller, Peter Gervais, Debra A. TI Long-Term Oncologic Outcomes After Radiofrequency Ablation for T1 Renal Cell Carcinoma SO EUROPEAN UROLOGY LA English DT Article DE Radiofrequency ablation; Renal cell carcinoma; Small renal masses; Renal mass biopsy; Disease-specific survival ID RADIO-FREQUENCY ABLATION; PARTIAL NEPHRECTOMY; THERMAL ABLATION; FOLLOW-UP; MASSES; METAANALYSIS; EXPERIENCE; TUMORS; CRYOABLATION; SURVEILLANCE AB Background: Radiofrequency ablation(RFA) of renal cell carcinoma(RCC) is used to obtain local control of small renal masses. However, available long-term oncologic outcomes for RFA of RCC are limited by small numbers, short follow-up, and lack of pathologic diagnoses. Objective: To assess the oncologic effectiveness of RFA for the treatment of biopsy-proven RCC. Design, setting, and participants: Exclusion criteria included prior RCC or metastatic RCC, familial syndromes, or T2 RCC. We retrospectively reviewed long-term oncologic outcomes for 185 patients with sporadic T1 RCC. Median follow-up was 6.43 yr (interquartile range [IQR]: 5.3-7.7). Outcome measurements and statistical analysis: The chi-square test and Wilcoxon rank-sum tests were used to compare proportions and medians, respectively. Disease-specific survival and overall survival (OS) were calculated using Kaplan-Meier analysis, then stratified by tumor stage, and comparisons were made using log-rank analysis. The 5-yr disease-free survival (DFS) and OS rates are reported. A p value <0.05 was considered statistically significant. Results and limitations: Median tumor size was 3 cm (IQR: 2.1-3.9 cm). Tumor stage was T1a: 143 (77.3%) or T1b: 42 (22.7%). Twenty-four patients (13%) were retreated for residual disease. There were 12 local recurrences (6.5%), 6 recurrences in T1a disease (4.2%) and 6 in T1b disease (14.3%) (p = 0.0196). Median time to recurrence was 2.5 yr. Local salvage RFA was performed in six patients, of whom five remain disease free at 3.8-yr median follow-up. Tumor stage was the only significant predictor of DFS on multivariate analysis. At last follow-up, 164 patients (88.6%) were disease free (T1a: n = 132 [92.3%]; T1b: n = 32 [76.2%]; p = 0.0038). OS was similar regardless of stage (p = 0.06). Five patients developed metachronous renal tumors (2.7%). Four patients developed extrarenal metastases (2.2%), three of whom died of metastatic RCC (1.6%). Conclusions: In poor surgical candidates, RFA results in durable local control and low risk of recurrence in T1a RCC. Higher stage correlates with a decreased disease-free survival. Long-term surveillance is necessary following RFA. Patient selection based on tumor characteristics, comorbid disease, and life expectancy is of paramount importance. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved. C1 [Psutka, Sarah P.; Feldman, Adam S.; McDougal, W. Scott; McGovern, Francis J.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Mueller, Peter; Gervais, Debra A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP McDougal, WS (reprint author), Massachusetts Gen Hosp, Dept Urol, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM wmcdougal@partners.org NR 37 TC 101 Z9 106 U1 3 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD MAR PY 2013 VL 63 IS 3 BP 486 EP 492 DI 10.1016/j.eururo.2012.08.062 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 078NZ UT WOS:000314107100019 PM 22959191 ER PT J AU Halfond, R Corona, R Moon, A AF Halfond, Raquel Corona, Rosalie Moon, Anya TI Latino Parent and Adolescent Perceptions of Hoped-for and Feared Possible Selves for Adolescents SO JOURNAL OF ADOLESCENT RESEARCH LA English DT Article DE possible selves; Latino; adolescents; parents; school achievement; teen pregnancy ID SEXUAL RISK; INTERVENTION; COMMUNICATION; MOTHERS; AMERICAN; ACHIEVEMENT; PSYCHOLOGY; ETHNICITY; IDENTITY; BEHAVIOR AB The authors examined Latino parent and adolescent reports of hoped-for and feared possible selves for adolescents. Twenty-nine Latino parents (18 mothers, 11 fathers) and their 18 adolescents participated in semistructured individual interviews. Interviews were digitally recorded, transcribed, and coded for themes via content analysis. Themes that emerged included achievement, interpersonal, personal characteristics, financial-material, cultural roots, and risk behaviors. More parents than adolescents mentioned feared interpersonal selves such as being a teenage parent. Findings suggest that Latino parents and adolescents express hopes and fears for future outcomes that are not consistent with the high rates of school dropout and teen pregnancy among Latino adolescents. Results shed light on strategies for program and policy prevention efforts. C1 [Halfond, Raquel] Harbor UCLA Med Ctr, Child & Adolescent Psychiat Div, Torrance, CA 90509 USA. [Halfond, Raquel; Corona, Rosalie; Moon, Anya] Virginia Commonwealth Univ, Richmond, VA USA. [Moon, Anya] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Halfond, R (reprint author), Harbor UCLA Med Ctr, Child & Adolescent Psychiat Div, 1000 W Carson St,Box 498, Torrance, CA 90509 USA. EM halfondrw@vcu.edu NR 66 TC 1 Z9 1 U1 4 U2 24 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0743-5584 J9 J ADOLESCENT RES JI J. Adolesc. Res. PD MAR PY 2013 VL 28 IS 2 BP 209 EP 240 DI 10.1177/0743558412457818 PG 32 WC Psychology, Developmental SC Psychology GA 077YM UT WOS:000314065300004 ER PT J AU Vanderburg, CR Clarke, MSF AF Vanderburg, Charles R. Clarke, Mark S. F. TI Laser capture microdissection of metachromatically stained skeletal muscle allows quantification of fiber type specific gene expression SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE Skeletal muscle; Fiber type; Laser capture microdissection (LCM); Atrophy; Expression profiling ID CALCIUM-PUMP GENE; SIGNALING PATHWAYS; SOLEUS MUSCLE; ATROPHY; MASS; IDENTIFICATION; HYPERTROPHY; MODEL; RATS AB Skeletal muscle contains various myofiber types closely associated with satellite stem cells, vasculature, and neurons, thus making it difficult to perform genetic or proteomic expression analysis with sufficient cellular specificity to resolve differences at the individual cell or myofiber type level. Here, we describe the combination of a simple histochemical method capable of simultaneously identifying Type I, IIA, IIB, and IIC myofibers followed by laser capture micro-dissection (LCM) to compare the expression profiles of individual fiber types, myonuclear domains, and satellite cells in frozen muscle sections of control and atrophied muscle. Quantitative RT-PCR (qPCR) was used to verify the integrity of the cell-specific RNAs harvested after histologic staining, while qPCR for specific genes of interest was used to quantify atrophy-associated changes in mRNA. Our data demonstrate that the differential myofiber atrophy previously described by histologic means is related to differential expression of atrophy-related genes, such as MuRF1 and MAFbx (a.k.a. Atrogin-1), within different myofiber type populations. This spatially resolved molecular pathology (SRMP) technique allowed quantitation of atrophy-related gene products within individual fiber types that could not be resolved by expression analysis of the whole muscle. The present study demonstrates the importance of fiber type specific expression profiling in understanding skeletal muscle biology especially during muscle atrophy and provides a practical method of performing such research. C1 [Vanderburg, Charles R.] Massachusetts Gen Hosp, Harvard NeuroDiscovery Ctr, Boston, MA 02114 USA. [Clarke, Mark S. F.] Univ Houston, Dept Hlth & Human Performance, Houston, TX 77204 USA. [Clarke, Mark S. F.] Dept Hlth & Human Performance, Lab Integrated Physiol, Houston, TX 77204 USA. RP Clarke, MSF (reprint author), Dept Hlth & Human Performance, Lab Integrated Physiol, 3855 Holman St,Room 104D, Houston, TX 77204 USA. EM mclarke@central.uh.edu NR 29 TC 7 Z9 7 U1 2 U2 15 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD MAR PY 2013 VL 375 IS 1-2 BP 159 EP 170 DI 10.1007/s11010-012-1538-x PG 12 WC Cell Biology SC Cell Biology GA 077MR UT WOS:000314032300017 PM 23196635 ER PT J AU Yun, SM Cho, SJ Song, JC Song, SY Jo, SA Jo, C Yoon, K Tanzi, RE Choi, EJ Koh, YH AF Yun, Sang-Moon Cho, Sun-Jung Song, Jae Chun Song, Sung Yeon Jo, Sangmee Ahn Jo, Chulman Yoon, Keejung Tanzi, Rudolph E. Choi, Eui-Ju Koh, Young Ho TI SUMO1 modulates A beta generation via BACE1 accumulation SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; BACE1; SUMO1; Amyloid peptide ID AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; TRANSGENIC MICE; ENZYMATIC-ACTIVITY; SECRETASE ACTIVITY; TARGET PROTEINS; MODIFIER SUMO; UBIQUITIN; SUMOYLATION; EXPRESSION AB Accumulation of disease-related proteins is a characteristic event observed in the pathogenesis of neurodegenerative diseases. beta-secretase (BACE)-1, which initiates generation of beta-amyloid (A beta), is increased in the Alzheimer's diseased brain. However, the mechanisms of BACE1 accumulation in Alzheimer's disease are largely unknown. In this report, we found that small ubiquitin-like modifier (SUMO)-1 interacts with the dileucine motif of BACE1 and regulates the level of BACE1 protein. This was proved by the coimmunoprecipitation, and gain or loss of function experiments. Altering 3 SUMO isoforms affects BACE1 protein levels, and consequently results in altered amyloid precursor protein processing and A beta generation. BACE1 levels were increased in response to A beta or apoptosis, but not in cells lacking SUMO1. A beta increased SUMO1 protein levels in rat cortical neurons. Moreover, SUMO1 immunoreactivity was increased in the amyloid precursor protein transgenic mice. Furthermore, the C-terminus fragments of BACE1 containing dileucine motif reduced A beta generation by SUMO1 overexpression. Our study indicates SUMO1 is not only a novel and potent regulator of BACE1 accumulation and A beta generation but also a potential therapeutic target for Alzheimer's disease. (c) 2013 Elsevier Inc. All rights reserved. C1 [Yun, Sang-Moon; Cho, Sun-Jung; Song, Jae Chun; Song, Sung Yeon; Jo, Chulman; Koh, Young Ho] Korea Natl Inst Hlth, Ctr Biomed Sci, Div Brain Dis, Chungcheongbuk Do, South Korea. [Yun, Sang-Moon; Choi, Eui-Ju] Korea Univ, Sch Life Sci & Biotechnol, Seoul, South Korea. [Jo, Sangmee Ahn] Dankook Univ, Coll Pharm, Dept Pharm, Chungnam, South Korea. [Yoon, Keejung] Sungkyunkwan Univ, Sch Life ScienceandBiotechnol, Suwon, South Korea. [Tanzi, Rudolph E.] Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA USA. RP Koh, YH (reprint author), Korea Natl Inst Hlth, Ctr Biomed Sci, Div Brain Dis, Chungcheongbuk Do, South Korea. EM kohyoungho122@gmail.com FU Ministry of Health and Welfare; Korea National Institute of Health Intramural Research Grant [091-4845-300-210-13] FX We are deeply indebted to Drs. Olli A. Janne for providing SUMO1-knockout and wild type primary MEFs. We also thank Dr. Seongman Kang for providing the GFP-A beta1-42 plasmid cDNA. This study was supported by a grant of the Ministry of Health and Welfare and Korea National Institute of Health Intramural Research Grant (091-4845-300-210-13). NR 42 TC 18 Z9 18 U1 1 U2 41 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAR PY 2013 VL 34 IS 3 BP 650 EP 662 DI 10.1016/j.neurobiolaging.2012.08.005 PG 13 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 065AF UT WOS:000313117900002 PM 22975420 ER PT J AU Sperling, RA Johnson, KA Doraiswamy, PM Reiman, EM Fleisher, AS Sabbagh, MN Sadowsky, CH Carpenter, A Davis, MD Lu, M Flitter, M Joshi, AD Clark, CM Grundman, M Mintun, MA Skovronsky, DM Pontecorvo, MJ AF Sperling, Reisa A. Johnson, Keith A. Doraiswamy, P. Murali Reiman, Eric M. Fleisher, Adam S. Sabbagh, Marwan N. Sadowsky, Carl H. Carpenter, Alan Davis, Mat D. Lu, Ming Flitter, Matthew Joshi, Abhinay D. Clark, Christopher M. Grundman, Michael Mintun, Mark A. Skovronsky, Daniel M. Pontecorvo, Michael J. CA AV45-A05 Study Grp TI Amyloid deposition detected with florbetapir F 18 (F-18-AV-45) is related to lower episodic memory performance in clinically normal older individuals SO NEUROBIOLOGY OF AGING LA English DT Article DE Memory; Amyloid; Aging ID PRECLINICAL ALZHEIMERS-DISEASE; MILD COGNITIVE IMPAIRMENT; A-BETA; FUNCTIONAL CONNECTIVITY; NONDEMENTED INDIVIDUALS; IN-VIVO; DEMENTIA; DECLINE; ADULTS; PREDICTION AB The objective of this study was to evaluate the relationship of amyloid burden, as assessed by florbetapir F 18 (F-18-AV-45) amyloid positron emission tomography, and cognition in healthy older control (HC) subjects. Seventy-eight HC subjects were assessed with a brief cognitive test battery and positron emission tomography (PET) imaging with 18F-AV-45. A standard uptake value ratio was computed for mean data from 6 cortical regions using a whole cerebellum reference region. Scans were also visually rated as amyloid positive or amyloid negative by 3 readers. Higher standard uptake value ratio correlated with lower immediate memory (r = -0.33; p = 0.003) and delayed recall scores (r = -0.25; p = 0.027). Performance on immediate recall was also lower in the visually rated amyloid positive compared with amyloid negative HC (p = 0.04), with a similar trend observed in delayed recall (p = 0.06). These findings support the hypothesis that higher amyloid burden is associated with lower memory performance among clinically normal older subjects. Longitudinal follow-up is ongoing to determine whether 18F-AV-45 may also predict subsequent cognitive decline. (C) 2013 Elsevier Inc. All rights reserved. C1 [Sperling, Reisa A.; Johnson, Keith A.] Harvard Univ, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Dept Neurol, Boston, MA 02115 USA. [Sperling, Reisa A.; Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Johnson, Keith A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Doraiswamy, P. Murali] Duke Univ, Med Ctr, Durham, NC USA. [Reiman, Eric M.; Fleisher, Adam S.] Banner Alzheimers Inst, San Diego, CA USA. [Fleisher, Adam S.] Univ Calif San Diego, San Diego, CA 92103 USA. [Sabbagh, Marwan N.] Banner Sun Hlth Res Inst, Phoenix, AZ USA. [Sadowsky, Carl H.] Nova SE Univ, Ft Lauderdale, FL 33314 USA. [Lu, Ming; Flitter, Matthew; Joshi, Abhinay D.; Clark, Christopher M.; Mintun, Mark A.; Skovronsky, Daniel M.; Pontecorvo, Michael J.] Avid Radiopharmaceut, Philadelphia, PA USA. [Davis, Mat D.] Univ Penn, Philadelphia, PA 19104 USA. [Grundman, Michael] Global R&D Partners LLC, San Diego, CA USA. RP Sperling, RA (reprint author), 221 Longwood Ave, Boston, MA 02115 USA. EM reisa@rics.bwh.harvard.edu FU Harvard Aging Brain Study [P01AG036694]; Avid Pharmaceuticals; Avid/Lilly FX Drs. Sperling and Johnson's efforts were supported by; P01AG036694-the Harvard Aging Brain Study. The authors wish to acknowledge the clinical research staff at all of the A05 study centers, and the dedication of research participants in this study. This report is dedicated to Dr. Chris Clark, who sadly passed away during the preparation of this manuscript, but contributed greatly to this work and the field of Alzheimer's disease.; The phase II study was funded by Avid Pharmaceuticals.; Dr. Sperling has served as a site investigator for Avid, Bristol-Myers-Squibb, Elan, Janssen, Pfizer, and Wyeth, a consultant to Bayer, Bristol-Myers-Squibb, Elan, Eisai, Janssen, Pfizer, and Wyeth, and an unpaid consultant to Avid. She has received speaking honoraria from Pfizer, Janssen, Eli Lilly, and Bayer. Dr. Johnson has served as a site investigator for Avid, Pfizer, Janssen, Bristol-Myers-Squibb, and as a consultant to Bristol-Myers-Squibb and Bayer. Dr. Doraiswamy has served as a paid advisor/speaker and/or received research grants from Avid/Lilly and several pharmaceutical companies. He owns stock in Sonexa and Clarimedix. Dr. Reiman has served as a paid consultant to Eli Lilly for its amyloid-modifying drug development programs, but has not served as a paid consultant to Eli Lilly or Avid for the development of florbetapir F18, and has served as a site investigator for Eli Lilly and Avid. Dr. Fleisher is a consultant for Lilly SAB and has received grant funding from Avid. Dr. Sabbagh has served as a site investigator for Avid, BMS, Elan, Janssen, Pfizer, Wyeth, Baxter, Bayer, GE, Lilly, Genentech, Eisai, Ceregene, and Celgene, and a consultant to BMS, Bayer, Lilly, Avid, Amerisciences, Eisai, and Takeda. Dr. Sadowsky is on the speaker's bureau for Novartis, Forest and Axona, and is a site investigator for Avid. Dr. Davis performed statistical analysis under a consulting contract from Avid. Dr. Grundman is a paid consultant to Avid, Eli Lilly, and other pharmaceutical companies. Drs. Carpenter, Davis, Flitter, Joshi, Mintun, Skovronsky, and Pontecorvo are all employees of Avid Radiopharmaceuticals. NR 47 TC 49 Z9 49 U1 2 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAR PY 2013 VL 34 IS 3 BP 822 EP 831 DI 10.1016/j.neurobiolaging.2012.06.014 PG 10 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 065AF UT WOS:000313117900015 PM 22878163 ER PT J AU McGill, LA Ismail, T Nielles-Vallespin, S Ferreira, P Scott, AD Roughton, M Kilner, PJ Ho, SY McCarthy, KP Gatehouse, PD de Silva, R Speier, P Feiweier, T Mekkaoui, C Sosnovik, DE Prasad, SK Firmin, DN Pennell, DJ AF McGill, Laura-Ann Ismail, Tevfik Nielles-Vallespin, Sonia Ferreira, Pedro Scott, Andrew D. Roughton, Michael Kilner, Philip J. Ho, S. Yen McCarthy, Karen P. Gatehouse, Peter D. de Silva, Ranil Speier, Peter Feiweier, Thorsten Mekkaoui, Choukkri Sosnovik, David E. Prasad, Sanjay K. Firmin, David N. Pennell, Dudley J. TI reproducibility of in-vivo diffusion tensor cardiovascular magnetic resonance in hypertrophic cardiomyopathy (vol 14, pg 86, 2012) SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Correction C1 [McGill, Laura-Ann; Ismail, Tevfik; Nielles-Vallespin, Sonia; Ferreira, Pedro; Scott, Andrew D.; Roughton, Michael; Kilner, Philip J.; Ho, S. Yen; McCarthy, Karen P.; Gatehouse, Peter D.; de Silva, Ranil; Prasad, Sanjay K.; Firmin, David N.; Pennell, Dudley J.] Royal Brompton Hosp, Cardiovasc Magnet Resonance Unit, London SW3 6LY, England. [McGill, Laura-Ann; Nielles-Vallespin, Sonia; Ferreira, Pedro; Scott, Andrew D.; Kilner, Philip J.; Ho, S. Yen; McCarthy, Karen P.; de Silva, Ranil; Prasad, Sanjay K.; Firmin, David N.; Pennell, Dudley J.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Nielles-Vallespin, Sonia] NHLBI, NIH, DHHS, Bethesda, MD 20892 USA. [Speier, Peter; Feiweier, Thorsten] Siemens AG Med Solut, MR R&D, Erlangen, Germany. [Mekkaoui, Choukkri; Sosnovik, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA USA. RP Firmin, DN (reprint author), Royal Brompton Hosp, Cardiovasc Magnet Resonance Unit, London SW3 6LY, England. EM d.firmin@imperial.ac.uk NR 1 TC 2 Z9 2 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1097-6647 J9 J CARDIOVASC MAGN R JI J. Cardiov. Magn. Reson. PD FEB 28 PY 2013 VL 15 AR 22 DI 10.1186/1532-429X-15-22 PG 1 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 128AI UT WOS:000317739900001 ER PT J AU Kufe, DW AF Kufe, D. W. TI MUC1-C oncoprotein as a target in breast cancer: activation of signaling pathways and therapeutic approaches SO ONCOGENE LA English DT Review DE MUC1; breast cancer; oncoprotein; signaling pathways; targeted agents ID GROWTH-FACTOR RECEPTOR; CARCINOMA-ASSOCIATED ANTIGEN; MUCIN 1 ONCOPROTEIN; BETA-CATENIN; CYCLIN D1; GENE-EXPRESSION; LUNG-CANCER; C-SRC; PHOSPHOINOSITIDE 3-KINASE; PROGNOSTIC-SIGNIFICANCE AB Mucin 1 (MUC1) is a heterodimeric protein formed by two subunits that is aberrantly overexpressed in human breast cancer and other cancers. Historically, much of the early work on MUC1 focused on the shed mucin subunit. However, more recent studies have been directed at the transmembrane MUC1-C-terminal subunit (MUC1-C) that functions as an oncoprotein. MUC1-C interacts with EGFR (epidermal growth factor receptor), ErbB2 and other receptor tyrosine kinases at the cell membrane and contributes to activation of the PI3K -> AKT and mitogen-activated protein kinase kinase (MEK)-> extracellular signal-regulated kinase (ERK) pathways. MUC1-C also localizes to the nucleus where it activates the Wnt/beta-catenin, signal transducer and activator of transcription (STAT) and NF (nuclear factor)-kappa B RelA pathways. These findings and the demonstration that MUC1-C is a druggable target have provided the experimental basis for designing agents that block MUC1-C function. Notably, inhibitors of the MUC1-C subunit have been developed that directly block its oncogenic function and induce death of breast cancer cells in vitro and in xenograft models. On the basis of these findings, a first-in-class MUC1-C inhibitor has entered phase I evaluation as a potential agent for the treatment of patients with breast cancers who express this oncoprotein. Oncogene (2013) 32, 1073-1081; doi:10.1038/onc.2012.158; published online 14 May 2012 C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Kufe, DW (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave,Dana 830, Boston, MA 02215 USA. EM donald_kufe@dfci.harvard.edu FU National Cancer Institute [CA97098] FX This work has been supported by Grant CA97098 awarded by the National Cancer Institute. NR 103 TC 90 Z9 94 U1 5 U2 28 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 28 PY 2013 VL 32 IS 9 BP 1073 EP 1081 DI 10.1038/onc.2012.158 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 110FU UT WOS:000316428800001 PM 22580612 ER PT J AU Zheng, HX Cai, YD Wang, YD Cui, XB Xie, TT Li, WJ Peng, L Zhang, Y Wang, ZQ Wang, J Jiang, B AF Zheng, H. X. Cai, Y. D. Wang, Y. D. Cui, X. B. Xie, T. T. Li, W. J. Peng, L. Zhang, Y. Wang, Z. Q. Wang, J. Jiang, B. TI Fas signaling promotes motility and metastasis through epithelial-mesenchymal transition in gastrointestinal cancer SO ONCOGENE LA English DT Article DE Fas signaling; metastasis; motility; epithelial-mesenchymal transition ID TUMOR PROGRESSION; COLORECTAL CANCER.; GLIOMA-CELLS; CD95; EXPRESSION; COLON; GROWTH; LIVER; ACTIVATION; MECHANISMS AB Fas signaling was reported to participate in cell apoptosis. However, this pathway has also been shown to promote tumor cell motility, leading to the hypothesis that Fas signaling may induce epithelial mesenchymal transition (EMT) to promote metastasis. The effects of Fas-ligand (FasL) treatment and inhibition of Fas signaling on colorectal and gastric cancer cells were tested using motility assay, immunofluorescence, RT-PCR and immunoblot analyses. Fas signaling downregulated epithelial markers, upregulated mesenchymal markers and promoted motility in gastrointestinal (GI) cancer cells. FasL treatment also increased the expression of EMT transcriptional factors in the nucleus and induced a spindle shape cell morphology in these cells. Knockdown of Snail or Twist expression significantly decreased FasL-induced motility. The ERK1/2 pathway was activated by Fas signaling and is required for FasL-induced EMT and motility. Moreover, oxaliplatin, a chemotherapeutic agent, induced EMT partly through Fas signaling. Evaluation of human GI clinical specimens showed that FasL expression increased whereas E-cadherin expression decreased during GI cancer progression. Both markers were significantly inversely correlated. Tissue samples with a non-EMT phenotype were mainly distributed in patients with early cancer stages, whereas samples with an EMT phenotype were mostly distributed in patients with advanced cancer stages. A non-EMT phenotype significantly correlated with better prognosis. Altogether, these data indicate that Fas signaling may induce EMT to promote tumor motility and metastasis in GI cancer in vivo and in vitro. Oncogene (2013) 32, 1183-1192; doi:0.1038/onc.2012.126; published online 16 April 2012 C1 [Zheng, H. X.; Cai, Y. D.; Wang, Y. D.; Cui, X. B.; Xie, T. T.; Li, W. J.; Peng, L.; Zhang, Y.; Wang, Z. Q.; Wang, J.; Jiang, B.] Southern Med Univ, Nanfang Hosp, Dept Gastroenterol, Guangdong Prov Key Lab Gastroenterol, Guangzhou 510515, Guangdong, Peoples R China. [Cai, Y. D.] China Acad Chinese Med Sci, Xiyuan Hosp, Dept Gastroenterol, Beijing, Peoples R China. [Peng, L.] Mt Sinai Sch Med, Dept Med, Inst Immunol, New York, NY USA. [Zhang, Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wang, Z. Q.] Mt Sinai Sch Med, Dept Pathol, New York, NY USA. RP Jiang, B (reprint author), Southern Med Univ, Nanfang Hosp, Dept Gastroenterol, Guanzhoudabaobei 1838, Guangzhou 510515, Guangdong, Peoples R China. EM prof.jiang@yahoo.com.cn RI Cui, XiaoBing/K-8159-2012 OI Cui, XiaoBing/0000-0002-5460-0357 FU Science and Technology Project of Guangzhou [2009Z1-E051]; Nanfang Hospital President Foundation [2011C015] FX This study was supported by Science and Technology Project of Guangzhou (2009Z1-E051) and Nanfang Hospital President Foundation(2011C015). NR 33 TC 26 Z9 26 U1 2 U2 22 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD FEB 28 PY 2013 VL 32 IS 9 BP 1183 EP 1192 DI 10.1038/onc.2012.126 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 110FU UT WOS:000316428800012 PM 22508480 ER PT J AU Hollon, JR Cureton, PA Martin, ML Puppa, ELL Fasano, A AF Hollon, Justin R. Cureton, Pamela A. Martin, Margaret L. Puppa, Elaine L. Leonard Fasano, Alessio TI Trace gluten contamination may play a role in mucosal and clinical recovery in a subgroup of diet-adherent non-responsive celiac disease patients SO BMC GASTROENTEROLOGY LA English DT Article DE Celiac disease; Refractory celiac disease; Refractory sprue; Non-responsive celiac disease; Gluten-free diet ID ADULT PATIENTS; UNITED-STATES; DIAGNOSIS; MANAGEMENT; CHILDREN; PREVALENCE; SYMPTOMS; SPECTRUM; SPRUE AB Background: Patients with persistent symptoms and/or villous atrophy despite strict adherence to a gluten-free diet (GFD) have non-responsive celiac disease (NRCD). A subset of these patients has refractory celiac disease (RCD), yet some NRCD patients may simply be reacting to gluten cross-contamination. Here we describe the effects of a 3-6 month diet of whole, unprocessed foods, termed the Gluten Contamination Elimination Diet (GCED), on NRCD. We aim to demonstrate that this diet reclassifies the majority of patients thought to have RCD type 1 (RCD1). Methods: We reviewed the records of all GFD-adherent NRCD patients cared for in our celiac center from 2005-2011 who were documented to have started the GCED. Response to the GCED was defined as being asymptomatic after the diet, with normal villous architecture on repeat biopsy, if performed. Results: Prior to the GCED, all patients were interviewed by an experienced dietitian and no sources of hidden gluten ingestion were identified. 17 patients completed the GCED; 15 were female (88%). Median age at start of the GCED was 42 years (range 6-73). Fourteen patients (82%) responded to the GCED. Six patients met criteria for RCD prior to the GCED; 5 (83%) were asymptomatic after the GCED and no longer meet RCD criteria. Of the 14 patients who responded to the GCED, 11 (79%) successfully returned to a traditional GFD without resurgence of symptoms. Conclusions: The GCED may be an effective therapeutic option for GFD-adherent NRCD patients. Response to this diet identifies a subgroup of patients, previously classified as RCD1, that is not truly refractory to dietary treatment. Preventing an inaccurate diagnosis of RCD1 avoids immunotherapy. Most patients are able to return to a traditional GFD without return of symptoms. C1 [Hollon, Justin R.] Johns Hopkins Univ, Sch Med, Div Pediat Gastroenterol, Baltimore, MD 21218 USA. [Cureton, Pamela A.; Martin, Margaret L.; Puppa, Elaine L. Leonard] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Cureton, Pamela A.; Fasano, Alessio] Massachusetts Gen Hosp, Ctr Celiac Res, Boston, MA 02114 USA. [Cureton, Pamela A.; Fasano, Alessio] Massachusetts Gen Hosp Children, Div Pediat Gastroenterol & Nutr, Boston, MA USA. RP Hollon, JR (reprint author), Johns Hopkins Univ, Sch Med, Div Pediat Gastroenterol, 600 North Wolfe St,Brady 320, Baltimore, MD 21218 USA. EM jhollon1@jhmi.edu NR 35 TC 19 Z9 21 U1 2 U2 20 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-230X J9 BMC GASTROENTEROL JI BMC Gastroenterol. PD FEB 28 PY 2013 VL 13 AR 40 DI 10.1186/1471-230X-13-40 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 103WS UT WOS:000315950800001 PM 23448408 ER PT J AU Snuderl, M Batista, A Kirkpatrick, ND de Almodovar, CR Riedemann, L Walsh, EC Anolik, R Huang, YH Martin, JD Kamoun, W Knevels, E Schmidt, T Farrar, CT Vakoc, BJ Mohan, N Chung, EH Roberge, S Peterson, T Bais, C Zhelyazkova, BH Yip, S Hasselblatt, M Rossig, C Niemeyer, E Ferrara, N Klagsbrun, M Duda, DG Fukumura, D Xu, L Carmeliet, P Jain, RK AF Snuderl, Matija Batista, Ana Kirkpatrick, Nathaniel D. de Almodovar, Carmen Ruiz Riedemann, Lars Walsh, Elisa C. Anolik, Rachel Huang, Yuhui Martin, John D. Kamoun, Walid Knevels, Ellen Schmidt, Thomas Farrar, Christian T. Vakoc, Benjamin J. Mohan, Nishant Chung, Euiheon Roberge, Sylvie Peterson, Teresa Bais, Carlos Zhelyazkova, Boryana H. Yip, Stephen Hasselblatt, Martin Rossig, Claudia Niemeyer, Elisabeth Ferrara, Napoleone Klagsbrun, Michael Duda, Dan G. Fukumura, Dai Xu, Lei Carmeliet, Peter Jain, Rakesh K. TI Targeting Placental Growth Factor/Neuropilin 1 Pathway Inhibits Growth and Spread of Medulloblastoma SO CELL LA English DT Article ID TUMOR-GROWTH; DOSE-ESCALATION; CELL-LINE; PHASE-I; ANGIOGENESIS; CANCER; PLGF; METASTASIS; RESISTANCE; TB-403 AB Medulloblastoma is the most common pediatric malignant brain tumor. Although current therapies improve survival, these regimens are highly toxic and are associated with significant morbidity. Here, we report that placental growth factor (PlGF) is expressed in the majority of medulloblastomas, independent of their subtype. Moreover, high expression of PlGF receptor neuropilin 1 (Nrp1) correlates with poor overall survival in patients. We demonstrate that PlGF and Nrp1 are required for the growth and spread of medulloblastoma: PlGF/Nrp1 blockade results in direct antitumor effects in vivo, resulting in medulloblastoma regression, decreased metastasis, and increased mouse survival. We reveal that PlGF is produced in the cerebellar stroma via tumor-derived Sonic hedgehog (Shh) and show that PlGF acts through Nrp1-and not vascular endothelial growth factor receptor 1-to promote tumor cell survival. This critical tumor-stroma interaction-mediated by Shh, PlGF, and Nrp1 across medulloblastoma subtypes-supports the development of therapies targeting PlGF/Nrp1 pathway. C1 [Snuderl, Matija; Zhelyazkova, Boryana H.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Batista, Ana; Kirkpatrick, Nathaniel D.; Riedemann, Lars; Walsh, Elisa C.; Anolik, Rachel; Huang, Yuhui; Martin, John D.; Kamoun, Walid; Chung, Euiheon; Roberge, Sylvie; Peterson, Teresa; Niemeyer, Elisabeth; Duda, Dan G.; Fukumura, Dai; Xu, Lei; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. [Vakoc, Benjamin J.; Mohan, Nishant] Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. [Snuderl, Matija; Batista, Ana; Kirkpatrick, Nathaniel D.; Riedemann, Lars; Walsh, Elisa C.; Anolik, Rachel; Huang, Yuhui; Martin, John D.; Kamoun, Walid; Farrar, Christian T.; Vakoc, Benjamin J.; Mohan, Nishant; Chung, Euiheon; Roberge, Sylvie; Peterson, Teresa; Niemeyer, Elisabeth; Klagsbrun, Michael; Duda, Dan G.; Fukumura, Dai; Xu, Lei; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [de Almodovar, Carmen Ruiz] Katholieke Univ Leuven, Vesalius Res Ctr, Lab Angiogenesis & Neurovasc Link, B-3000 Louvain, Belgium. [de Almodovar, Carmen Ruiz; Knevels, Ellen; Schmidt, Thomas; Carmeliet, Peter] VIB, Vesalius Res Ctr, Lab Angiogenesis & Neurovasc Link, B-3000 Louvain, Belgium. [Farrar, Christian T.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Vakoc, Benjamin J.; Mohan, Nishant] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Bais, Carlos; Ferrara, Napoleone] Genentech Inc, San Francisco, CA 94080 USA. [Yip, Stephen] Univ British Columbia, Vancouver Gen Hosp, Dept Pathol & Lab Med, Vancouver, BC V5Z 4E6, Canada. [Hasselblatt, Martin] Univ Hosp Munster, Inst Neuropathol, D-48149 Munster, Germany. [Rossig, Claudia] Univ Hosp Munster, Dept Pediat Hematol & Oncol, D-48149 Munster, Germany. [Klagsbrun, Michael] Childrens Hosp Boston, Vasc Biol Program, Dept Surg, Boston, MA 02115 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu RI Riedemann, Lars/J-5725-2014; Martin, John/L-6892-2016; OI Riedemann, Lars/0000-0002-9510-1845; Martin, John/0000-0002-9828-8203; Huang, Yuhui/0000-0003-1985-3575; Hasselblatt, Martin/0000-0003-2707-8484; Snuderl, Matija/0000-0003-0752-0917; Schmidt, Thomas/0000-0002-7166-3675 FU Hoffmann-La Roche; NIH [R01CA163815, P01CA080124, R01CA096915, S10RR027070, R01CA126642, R01CA159258, K25AG029415, R21CA155862, CA37392, CA45548, R01CA163528, P41-EB015903]; Department of Defense (DoD) [W81XWH-10-1-0016]; Belgian Government [IUAP06/30]; Flemish Government; Concerted Research Activities, Stichting Emmanuel van der Schueren (Belgium) [GOA2006/11]; American Cancer Society [120733-RSG-11-073-01-TBG, RSG-12-199-01-TBG]; BrainCare BC; DoD [W81XWH-11-1-0619]; Calabresi Career Development Award [2K12CA090354]; Mildred-Scheel-Fellowship (Deutsche Krebshilfe); Rolf Dierichs Stiftung; [T32-CA073479] FX We would like to thank Drs. J. M. Olson, M. Dewerchin, A. J. Iafrate, E. di Tomaso, M. Ancukiewicz, S. Goel, D. Kodack, K. Munro, B. Seed, R. Wechsler-Reya, and M. Weidner for invaluable suggestions and experimental assistance and Ms. C. J. Smith, A. Khachatryan, K. Kinzel, and B. Riesmeier for technical assistance. This study was supported by a grant from Hoffmann-La Roche and NIH grant R01CA163815 (to R. K. J.). The study was partially supported by NIH grants P01CA080124 (to R. K. J., D. G. D., D. F., and L. X.), R01CA096915 and S10RR027070 (to D. F.), R01CA126642 (to R. K. J.), and R01CA159258 (to D. G. D.); Department of Defense (DoD) Breast Cancer Research Innovator Award W81XWH-10-1-0016 (to R. K. J.); Belgian Government grant IUAP06/30 (to P. C.); Flemish Government long-term structural funding Methusalem (to P. C.); the Concerted Research Activities, Stichting Emmanuel van der Schueren (Belgium), GOA2006/11 (to P. C.); and American Cancer Society grants 120733-RSG-11-073-01-TBG (to D. G. D.) and RSG-12-199-01-TBG (to L. X.). C. T. F. is supported by NIH grants K25AG029415 and R21CA155862. M. K.'s work is supported by NIH grants CA37392 and CA45548. B. J. V.'s work is supported by NIH grants R01CA163528 and P41-EB015903. S. Y.'s work is supported by BrainCare BC. Y. H. is supported by DoD Research Fellowship W81XWH-11-1-0619. N. D. K. was supported by T32-CA073479. M. S. was supported by the Calabresi Career Development Award 2K12CA090354. L. R. received funding from Mildred-Scheel-Fellowship (Deutsche Krebshilfe) and from Rolf Dierichs Stiftung. P. C. has patent applications claiming subject matter related to this report, which may result in royalty payments. R. K. J. is a member of Board of Trustees of H& Q Healthcare Investors and H&Q Life Sciences Investors. NR 39 TC 70 Z9 72 U1 2 U2 57 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD FEB 28 PY 2013 VL 152 IS 5 BP 1065 EP 1076 DI 10.1016/j.cell.2013.01.036 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 100OK UT WOS:000315710300014 PM 23452854 ER PT J AU Boros, E Caravan, P AF Boros, Eszter Caravan, Peter TI Structure-Relaxivity Relationships of Serum Albumin Targeted MRI Probes Based on a Single Amino Acid Gd Complex SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CONTRAST AGENTS; PHYSICOCHEMICAL CHARACTERIZATION; GADOLINIUM; BINDING; ENHANCEMENT; MS-325; MEDIA AB The Gd(III) complex of DO3A-N-alpha-aminopropionate, Gd(DOTAla), was used to generate a small library of putative MRI probes targeted to human serum albumin (HSA). Ten compounds were synthesized via multistep organic synthesis, and the corresponding Gd complexes were investigated for their affinity to HSA, lipophilicity, and relaxivity in the absence and presence of HSA. Negative charge and moderate lipophilicity correlate with increased HSA affinity and relaxivity C1 [Boros, Eszter; Caravan, Peter] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Med Sch, Charlestown, MA 02129 USA. RP Caravan, P (reprint author), Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Med Sch, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM caravan@nmr.mgh.harvard.edu FU Swiss National Science Foundation; National Institute of Biomedical Imaging and Bioengineering (NIBIB) [R01EB009062]; National Center for Research Resources (NCRR) [P41RR14075] FX E.B. acknowledges the Swiss National Science Foundation for a fellowship for prospective researchers. Nathaniel Kenton is acknowledged for synthesis of DOTAla and Fmoc-DOTAla according to ref 19. This work was supported in part by Award R01EB009062 from the National Institute of Biomedical Imaging and Bioengineering (NIBIB) and Award P41RR14075 from the National Center for Research Resources (NCRR). NR 23 TC 12 Z9 12 U1 0 U2 33 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD FEB 28 PY 2013 VL 56 IS 4 BP 1782 EP 1786 DI 10.1021/jm4000177 PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 100NG UT WOS:000315707300036 PM 23391162 ER PT J AU Adair, BD Xiong, JP Alonso, JL Hyman, BT Arnaout, MA AF Adair, Brian D. Xiong, Jian-Ping Alonso, Jose Luis Hyman, Bradley T. Arnaout, M. Amin TI EM Structure of the Ectodomain of Integrin CD11b/CD18 and Localization of Its Ligand-Binding Site Relative to the Plasma Membrane SO PLOS ONE LA English DT Article ID DEPENDENT ADHESION SITE; CRYSTAL-STRUCTURE; A-DOMAIN; CONFORMATIONAL-CHANGES; EXTRACELLULAR SEGMENT; I-DOMAIN; ACTIVATION; ALPHA(IIB)BETA(3); ALPHA-V-BETA-3; RECEPTOR AB One-half of the integrin alpha-subunit Propeller domains contain and extra vWFA domain (alpha A domain), which mediates integrin binding to extracellular physiologic ligands via its metal-ion-dependent adhesion site (MIDAS). We used electron microscopy to determine the 3D structure of the alpha A-containing ectodomain of the leukocyte integrin CD11b/CD18 (alpha M beta 2) in its inactive state. A well defined density for alpha A was observed within a bent ectodomain conformation, while the structure of the ectodomain in complex with the Fab fragment of mAb107, which binds at the MIDAS face of CD11b and stabilizes the inactive state, further revealed that alpha A is restricted to a relatively small range of orientations relative to the Propeller domain. Using Fab 107 as probe in fluorescent lifetime imaging microscopy (FLIM) revealed that alpha A is positioned relatively far from the membrane surface in the inactive state, and a systematic orientation search revealed that the MIDAS face would be accessible to extracellular ligand in the inactive state of the full-length cellular integrin. These studies are the first to define the 3D EM structure of an alpha A-containing integrin ectodomain and to position the ligand-binding face of alpha A domain in relation to the plasma membrane, providing new insights into current models of integrin activation. C1 [Adair, Brian D.; Xiong, Jian-Ping; Arnaout, M. Amin] Massachusetts Gen Hosp, Struct Biol Program, Charlestown, MA USA. [Adair, Brian D.; Xiong, Jian-Ping; Alonso, Jose Luis; Hyman, Bradley T.; Arnaout, M. Amin] Harvard Univ, Sch Med, Charlestown, MA USA. [Alonso, Jose Luis; Arnaout, M. Amin] Massachusetts Gen Hosp, Leukocyte Biol & Inflammat Program, Charlestown, MA USA. [Hyman, Bradley T.] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA USA. [Hyman, Bradley T.] Massachusetts Gen Hosp, Inst Neurodegenerat Dis, Charlestown, MA USA. RP Arnaout, MA (reprint author), Massachusetts Gen Hosp, Struct Biol Program, Charlestown, MA USA. EM aarnaout1@partners.org FU National Institutes of Health [DK48549, DK50305, DK068253] FX This research was supported by grants DK48549, DK50305 and DK068253 from the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 1 Z9 1 U1 1 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 28 PY 2013 VL 8 IS 2 AR e57951 DI 10.1371/journal.pone.0057951 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 098DA UT WOS:000315524900209 PM 23469114 ER PT J AU Seed, KD Lazinski, DW Calderwood, SB Camilli, A AF Seed, Kimberley D. Lazinski, David W. Calderwood, Stephen B. Camilli, Andrew TI A bacteriophage encodes its own CRISPR/Cas adaptive response to evade host innate immunity SO NATURE LA English DT Article ID CAS SYSTEMS; PHAGE; INTERFERENCE; ARCHAEA; DEFENSE; RNA; DNA; RESISTANCE; EVOLUTION; PATHOGEN AB Bacteriophages (or phages) are the most abundant biological entities on earth, and are estimated to outnumber their bacterial prey by tenfold(1). The constant threat of phage predation has led to the evolution of a broad range of bacterial immunity mechanisms that in turn result in the evolution of diverse phage immune evasion strategies, leading to a dynamic co-evolutionary arms race(2,3). Although bacterial innate immune mechanisms against phage abound, the only documented bacterial adaptive immune system is the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins) system, which provides sequence-specific protection from invading nudeic acids, including phage(4-11). Here we show a remarkable turn of events, in which a phage-encoded CRISPR/Cas system is used to counteract a phage inhibitory chromosomal island of the bacterial host. A successful lytic infection by the phage is dependent on sequence identity between CRISPR spacers and the target chromosomal island. In the absence of such targeting, the phage-encoded CRISPR/Cas system can acquire new spacers to evolve rapidly and ensure effective targeting of the chromosomal island to restore phage replication. C1 [Seed, Kimberley D.; Lazinski, David W.; Camilli, Andrew] Tufts Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02111 USA. [Seed, Kimberley D.; Lazinski, David W.; Camilli, Andrew] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Calderwood, Stephen B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Camilli, A (reprint author), Tufts Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02111 USA. EM andrew.camilli@tufts.edu FU US National Institutes of Health [AI055058, AI045746, AI058935] FX The authors thank the Tufts University Core Facility for sequencing and computational support. This work was supported by US National Institutes of Health grants AI055058 (A.C.), AI045746 (A.C.) and AI058935 (S.B.C.). A.C. is a Howard Hughes Medical Institute Investigator. NR 30 TC 85 Z9 91 U1 18 U2 152 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 28 PY 2013 VL 494 IS 7438 BP 489 EP 491 DI 10.1038/nature11927 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 099YI UT WOS:000315661500041 PM 23446421 ER PT J AU Uihlein, A Greenwald, J Russell, SJ AF Uihlein, Alexander Greenwald, Jeffrey Russell, Steven J. TI Case 35-2012: A Man with Weakness, Anorexia, and Diffuse Pain Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID HYPOGONADISM; DISEASE C1 [Uihlein, Alexander; Greenwald, Jeffrey; Russell, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Uihlein, A (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 28 PY 2013 VL 368 IS 9 BP 874 EP 875 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 096ET UT WOS:000315387700028 PM 23445105 ER PT J AU Cote, GM Sawyer, DB Chabner, BA AF Cote, Gregory M. Sawyer, Douglas B. Chabner, Bruce A. TI ERBB2 Inhibition and Heart Failure Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID CARDIOMYOCYTE PROLIFERATION C1 [Cote, Gregory M.; Chabner, Bruce A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Sawyer, Douglas B.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. RP Cote, GM (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM gcote@partners.org NR 2 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 28 PY 2013 VL 368 IS 9 BP 876 EP 876 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 096ET UT WOS:000315387700030 PM 23445109 ER PT J AU Oaklander, AL Long, DM Larvie, M Davidson, CJ AF Oaklander, Anne Louise Long, Donlin M. Larvie, Mykol Davidson, Christian J. TI Case 7-2013: A 77-Year-Old Woman with Long-Standing Unilateral Thoracic Pain and Incontinence SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SACRAL PERINEURIAL CYSTS; TARLOV CYSTS; MENINGEAL CYSTS; MICROSURGICAL TREATMENT; PREVALENCE C1 [Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Larvie, Mykol] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Oaklander, Anne Louise; Davidson, Christian J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Oaklander, Anne Louise] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Larvie, Mykol] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Davidson, Christian J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Long, Donlin M.] Johns Hopkins Univ, Dept Neurosurg, Baltimore, MD USA. RP Oaklander, AL (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. FU Aptiv Solutions; Seikagaku FX Dr. Long reports receiving consulting fees from Aptiv Solutions and Seikagaku. No other potential conflict of interest relevant to this article was reported. NR 26 TC 5 Z9 5 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 28 PY 2013 VL 368 IS 9 BP 853 EP 861 DI 10.1056/NEJMcpc1114034 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 096ET UT WOS:000315387700013 PM 23445097 ER PT J AU Chen, L Stuart, L Ohsumi, TK Burgess, S Varshney, GK Dastur, A Borowsky, M Benes, C Lacy-Hulbert, A Schmidt, EV AF Chen, Li Stuart, Lynda Ohsumi, Toshiro K. Burgess, Shawn Varshney, Gaurav K. Dastur, Anahita Borowsky, Mark Benes, Cyril Lacy-Hulbert, Adam Schmidt, Emmett V. TI Transposon activation mutagenesis as a screening tool for identifying resistance to cancer therapeutics SO BMC CANCER LA English DT Article DE Transposon mutagenesis; Chemotherapy; Resistance; Gene activation ID PDZ DOMAIN PROTEINS; INSERTIONAL MUTAGENESIS; STEM-CELLS; SIGNALING COMPLEXES; DRUG-SENSITIVITY; SLEEPING-BEAUTY; ION CHANNELS; GENOME; PIGGYBAC; EXPRESSION AB Background: The development of resistance to chemotherapies represents a significant barrier to successful cancer treatment. Resistance mechanisms are complex, can involve diverse and often unexpected cellular processes, and can vary with both the underlying genetic lesion and the origin or type of tumor. For these reasons developing experimental strategies that could be used to understand, identify and predict mechanisms of resistance in different malignant cells would be a major advance. Methods: Here we describe a gain-of-function forward genetic approach for identifying mechanisms of resistance. This approach uses a modified piggyBac transposon to generate libraries of mutagenized cells, each containing transposon insertions that randomly activate nearby gene expression. Genes of interest are identified using next-gen high-throughput sequencing and barcode multiplexing is used to reduce experimental cost. Results: Using this approach we successfully identify genes involved in paclitaxel resistance in a variety of cancer cell lines, including the multidrug transporter ABCB1, a previously identified major paclitaxel resistance gene. Analysis of co-occurring transposons integration sites in single cell clone allows for the identification of genes that might act cooperatively to produce drug resistance a level of information not accessible using RNAi or ORF expression screening approaches. Conclusion: We have developed a powerful pipeline to systematically discover drug resistance in mammalian cells in vitro. This cost-effective approach can be readily applied to different cell lines, to identify canonical or context specific resistance mechanisms. Its ability to probe complex genetic context and non-coding genomic elements as well as cooperative resistance events makes it a good complement to RNAi or ORF expression based screens. C1 [Chen, Li; Dastur, Anahita; Benes, Cyril] Massachusetts Gen Hosp, Ctr Canc Res, Ctr Mol Therapeut, Charlestown, MA 02129 USA. [Chen, Li; Dastur, Anahita; Benes, Cyril] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Chen, Li; Stuart, Lynda; Lacy-Hulbert, Adam; Schmidt, Emmett V.] Massachusetts Gen Hosp, Program Dev Immunol, Boston, MA 02115 USA. [Chen, Li; Stuart, Lynda; Lacy-Hulbert, Adam; Schmidt, Emmett V.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Ohsumi, Toshiro K.; Borowsky, Mark] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02115 USA. [Ohsumi, Toshiro K.; Borowsky, Mark] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Burgess, Shawn; Varshney, Gaurav K.] NHGRI, Dev Genom Sect, Genome Technol Branch, Bethesda, MD 20892 USA. RP Chen, L (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Ctr Mol Therapeut, CNY 149 Rm7308,13th St, Charlestown, MA 02129 USA. EM lchen13@partners.org RI Varshney, Gaurav/L-5261-2014; OI Burgess, Shawn/0000-0003-1147-0596; Lacy-Hulbert, Adam/0000-0003-2162-0156; Varshney, Gaurav K./0000-0002-0429-1904 FU National Institutes of Health [U01-AI070330]; Wellcome Trust [086357] FX This work was supported by National Institutes of Health grant (U01-AI070330). LC, AD, and CB received additional funding from the Wellcome Trust (086357). NR 50 TC 10 Z9 10 U1 0 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD FEB 27 PY 2013 VL 13 AR 93 DI 10.1186/1471-2407-13-93 PG 15 WC Oncology SC Oncology GA 103NA UT WOS:000315922700001 PM 23442791 ER PT J AU Loftis, JM Wilhelm, CJ Vandenbark, AA Huckans, M AF Loftis, Jennifer M. Wilhelm, Clare J. Vandenbark, Arthur A. Huckans, Marilyn TI Partial MHC/Neuroantigen Peptide Constructs: A Potential Neuroimmune-Based Treatment for Methamphetamine Addiction SO PLOS ONE LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; BLOOD-BRAIN-BARRIER; MIGRATION INHIBITORY FACTOR; CELL-RECEPTOR LIGAND; WHITE-MATTER; DEPENDENT INDIVIDUALS; MICROGLIAL ACTIVATION; COGNITIVE ENHANCEMENT; PSYCHIATRIC-SYMPTOMS; STIMULANT ADDICTION AB Relapse rates following current methamphetamine abuse treatments are very high (similar to 40-60%), and the neuropsychiatric impairments (e. g., cognitive deficits, mood disorders) that arise and persist during remission from methamphetamine addiction likely contribute to these high relapse rates. Pharmacotherapeutic development of medications to treat addiction has focused on neurotransmitter systems with only limited success, and there are no Food and Drug Administration approved pharmacotherapies for methamphetamine addiction. A growing literature shows that methamphetamine alters peripheral and central immune functions and that immune factors such as cytokines, chemokines, and adhesion molecules play a role in the development and persistence of methamphetamine induced neuronal injury and neuropsychiatric impairments. The objective of this study was to evaluate the efficacy of a new immunotherapy, partial MHC/neuroantigen peptide construct (RTL551; pI-A(b)/mMOG-35-55), in treating learning and memory impairments induced by repeated methamphetamine exposure. C57BL/6J mice were exposed to two different methamphetamine treatment regimens (using repeated doses of 4 mg/kg or 10 mg/kg, s.c.). Cognitive performance was assessed using the Morris water maze and CNS cytokine levels were measured by multiplex assay. Immunotherapy with RTL551 improved the memory impairments induced by repeated methamphetamine exposure in both mouse models of chronic methamphetamine addiction. Treatment with RTL551 also attenuated the methamphetamine induced increases in hypothalamic interleukin-2 (IL-2) levels. Collectively, these initial results indicate that neuroimmune targeted therapies, and specifically RTL551, may have potential as treatments for methamphetamine-induced neuropsychiatric impairments. C1 [Loftis, Jennifer M.; Wilhelm, Clare J.; Vandenbark, Arthur A.; Huckans, Marilyn] Portland VA Med Ctr, Portland, OR USA. [Huckans, Marilyn] Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR USA. [Loftis, Jennifer M.; Wilhelm, Clare J.; Huckans, Marilyn] Oregon Hlth & Sci Univ, Dept Psychiat, Sch Med, Portland, OR 97201 USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Sch Med, Dept Neurol, Portland, OR 97201 USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Sch Med, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. RP Loftis, JM (reprint author), Portland VA Med Ctr, Portland, OR USA. EM loftisj@ohsu.edu FU National Institutes of Health [RC1DA028537, R41DA029345]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research and Development; Methamphetamine Abuse Research Center, Portland, OR [NIDA P50DA018165] FX This work was supported by National Institutes of Health grants RC1DA028537 and R41DA029345 to JML and MH. JML (Research Scientist) and MH (Staff Psychologist and Neuropsychologist) are supported by career development awards from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research and Development. This research was supported, in part, by the Methamphetamine Abuse Research Center, Portland, OR (NIDA P50DA018165). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 61 TC 5 Z9 5 U1 2 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 27 PY 2013 VL 8 IS 2 AR e56306 DI 10.1371/journal.pone.0056306 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 098BN UT WOS:000315519000021 PM 23460798 ER PT J AU Srinivasan, L Asaad, WF Ginat, DT Gale, JT Dougherty, DD Williams, ZM Sejnowski, TJ Eskandar, EN AF Srinivasan, Lakshminarayan Asaad, Wael F. Ginat, Daniel T. Gale, John T. Dougherty, Darin D. Williams, Ziv M. Sejnowski, Terrence J. Eskandar, Emad N. TI Action Initiation in the Human Dorsal Anterior Cingulate Cortex SO PLOS ONE LA English DT Article ID MEDIAL FRONTAL-CORTEX; SUPPLEMENTARY MOTOR AREA; PREFRONTAL CORTEX; NEURAL ACTIVITY; SELECTIVE ATTENTION; RESPONSE-INHIBITION; NEURONAL-ACTIVITY; ARM MOVEMENTS; MONKEY; CINGULOTOMY AB The dorsal anterior cingulate cortex (dACC) has previously been implicated in processes that influence action initiation. In humans however, there has been little direct evidence connecting dACC to the temporal onset of actions. We studied reactive behavior in patients undergoing therapeutic bilateral cingulotomy to determine the immediate effects of dACC ablation on action initiation. In a simple reaction task, three patients were instructed to respond to a specific visual cue with the movement of a joystick. Within minutes of dACC ablation, the frequency of false starts increased, where movements occurred prior to presentation of the visual cue. In a decision making task with three separate patients, the ablation effect on action initiation persisted even when action selection was intact. These findings suggest that human dACC influences action initiation, apart from its role in action selection. C1 [Srinivasan, Lakshminarayan] Univ Calif Los Angeles, Neural Signal Proc Lab, Dept Radiol, Los Angeles, CA 90024 USA. [Asaad, Wael F.] Brown Univ, Dept Neurosurg, Alpert Med Sch, Providence, RI 02912 USA. [Asaad, Wael F.] Rhode Isl Hosp, Brown Inst Brain Sci, Providence, RI 02912 USA. [Asaad, Wael F.] Norman Prince Neurosci Inst, Providence, RI 02912 USA. [Ginat, Daniel T.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Gale, John T.; Dougherty, Darin D.; Williams, Ziv M.; Eskandar, Emad N.] Harvard Univ, Sch Med, Boston, MA USA. [Gale, John T.] Cleveland Clin, Dept Neurosci, Cleveland, OH 44106 USA. [Gale, John T.] Cleveland Clin, Ctr Neurol Restorat, Cleveland, OH 44106 USA. [Dougherty, Darin D.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Williams, Ziv M.; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Sejnowski, Terrence J.] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA. [Sejnowski, Terrence J.] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA. RP Srinivasan, L (reprint author), Univ Calif Los Angeles, Neural Signal Proc Lab, Dept Radiol, Los Angeles, CA 90024 USA. EM ls2@nsplab.org RI Asaad, Wael/I-8485-2012 OI Asaad, Wael/0000-0003-4406-9096 FU American Heart Association Scientist Development Grant [11SDG7550015]; DARPA Reliable Neural-Interface Technology (RE-NET) Program; UCLA Radiology Exploratory Development Grant; Massachusetts Biomedical Research Corporation; Howard Hughes Medical Institute; National Science Foundation [IOB 0645886]; National Institutes of Health [NEI R01EY017658, NIDA R01DA026297, NIMH MH086400]; Klingenstein Foundation FX LS is supported by the American Heart Association Scientist Development Grant (11SDG7550015), the DARPA Reliable Neural-Interface Technology (RE-NET) Program, and the UCLA Radiology Exploratory Development Grant. WFA is supported by a Tosteson award from the Massachusetts Biomedical Research Corporation. TJS is supported by the Howard Hughes Medical Institute. EE is supported by grants from the National Science Foundation (IOB 0645886), the National Institutes of Health (NEI R01EY017658, NIDA R01DA026297, NIMH MH086400), the Howard Hughes Medical Institute, and the Klingenstein Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 61 TC 9 Z9 9 U1 1 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 27 PY 2013 VL 8 IS 2 AR e55247 DI 10.1371/journal.pone.0055247 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 098BN UT WOS:000315519000006 PM 23460783 ER PT J AU Tao, WC Higgs, MH Spain, WJ Ransom, CB AF Tao, Wucheng Higgs, Matthew H. Spain, William J. Ransom, Christopher B. TI Postsynaptic GABA(B) Receptors Enhance Extrasynaptic GABA(A) Receptor Function in Dentate Gyrus Granule Cells SO JOURNAL OF NEUROSCIENCE LA English DT Article ID LONG-TERM POTENTIATION; TONIC INHIBITION; RAT HIPPOCAMPUS; MOLECULAR-BASIS; B RECEPTORS; ACTIVATION; NEURONS; MODULATION; LOCALIZATION; EXCITABILITY AB Ambient GABA in the brain tonically activates extrasynaptic GABA(A) receptors, and activity-dependent changes in ambient GABA concentration can also activate GABA(B) receptors. To investigate an interaction between postsynaptic GABA(B) and GABA(A) receptors, we recorded GABA(A) currents elicited by exogenous GABA (10 mu M) from dentate gyrus granule cells (DGGCs) in adult rat hippocampal slices. The GABA(B) receptor agonist baclofen (20 mu M) enhanced GABA(A) currents. This enhancement was blocked by the GABA(B) receptor antagonist CGP 55845 and intracellular solutions containing the GTP analog GDP-beta-s, indicating that baclofen was acting on postsynaptic GABA(B) receptors. Modulation of GABA(A) currents by postsynaptic GABA(B) receptors was not observed in CA1 pyramidal cells or layer 2/3 cortical pyramidal neurons. Baclofen reduced the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) but did not alter sIPSC amplitude or kinetics. Thus, GABA(A) receptors activated at synapses were not modulated by postsynaptic GABA(B) receptors. In contrast, tonic GAB(A) currents and currents activated by the GABA(A) receptor delta subunit-selective agonist THIP (10 mu M) were potentiated by baclofen. Our data indicate that postsynaptic GABA(B) receptors enhance the function of extrasynaptic GABA(A) receptors, including delta subunit-containing receptors that mediate tonic inhibition in DGGCs. The modulation of GABA(A) receptor function by postsynaptic GABA(B) receptors is a newly identified mechanism that will influence the inhibitory tone of DGGCs when GABA(B) and GABA(A) receptors are both activated. C1 [Higgs, Matthew H.; Spain, William J.; Ransom, Christopher B.] Vet Affairs Puget Sound Hlth Care Syst, Epilepsy Ctr Excellence, Seattle, WA 98108 USA. [Tao, Wucheng; Higgs, Matthew H.; Spain, William J.] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA. [Spain, William J.; Ransom, Christopher B.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. RP Ransom, CB (reprint author), Univ Washington, Dept Neurol, Epilepsy Ctr Excellence, VA Puget Sound, 1600 South Columbian Way, Seattle, WA 98108 USA. EM cbr5@uw.edu FU Veterans Affairs (VA) Merit Review Award; VA Career Development Award; VA Epilepsy Centers of Excellence FX This work was supported by a Veterans Affairs (VA) Merit Review Award (W.J.S.), a VA Career Development Award (C.B.R.), and the VA Epilepsy Centers of Excellence (C.B.R., W.J.S., M.H.H.). The authors appreciate the expert technical assistance of Sue Usher and discussions with Professor Bertil Hille during the course of experiments. NR 36 TC 28 Z9 31 U1 0 U2 9 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD FEB 27 PY 2013 VL 33 IS 9 BP 3738 EP 3743 DI 10.1523/JNEUROSCI.4829-12.2013 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 098ZO UT WOS:000315588000002 PM 23447585 ER PT J AU Kokel, D Dunn, TW Ahrens, MB Alshut, R Cheung, CYJ Saint-Amant, L Bruni, G Mateus, R van Ham, TJ Shiraki, T Fukada, Y Kojima, D Yeh, JRJ Mikut, R von Lintig, J Engert, F Peterson, RT AF Kokel, David Dunn, Timothy W. Ahrens, Misha B. Alshut, Ruediger Cheung, Chung Yan J. Saint-Amant, Louis Bruni, Giancarlo Mateus, Rita van Ham, Tjakko J. Shiraki, Tomoya Fukada, Yoshitaka Kojima, Daisuke Yeh, Jing-Ruey J. Mikut, Ralf von Lintig, Johannes Engert, Florian Peterson, Randall T. TI Identification of Nonvisual Photomotor Response Cells in the Vertebrate Hindbrain SO JOURNAL OF NEUROSCIENCE LA English DT Article ID ZEBRAFISH DANIO-RERIO; DEEP BRAIN; IN-VIVO; PHOTORECEPTIVE MOLECULE; LARVAL ZEBRAFISH; LOCOMOTOR NETWORK; GANGLION-CELLS; LIGHT; PINEAL; OPSIN AB Nonvisual photosensation enables animals to sense light without sight. However, the cellular and molecular mechanisms of nonvisual photobehaviors are poorly understood, especially in vertebrate animals. Here, we describe the photomotor response (PMR), a robust and reproducible series of motor behaviors in zebrafish that is elicited by visual wavelengths of light but does not require the eyes, pineal gland, or other canonical deep-brain photoreceptive organs. Unlike the relatively slow effects of canonical nonvisual pathways, motor circuits are strongly and quickly (seconds) recruited during the PMR behavior. We find that the hindbrain is both necessary and sufficient to drive these behaviors. Using in vivo calcium imaging, we identify a discrete set of neurons within the hindbrain whose responses to light mirror the PMR behavior. Pharmacological inhibition of the visual cycle blocks PMR behaviors, suggesting that opsin-based photoreceptors control this behavior. These data represent the first known light-sensing circuit in the vertebrate hindbrain. C1 [Kokel, David; Cheung, Chung Yan J.; Bruni, Giancarlo; Mateus, Rita; van Ham, Tjakko J.; Yeh, Jing-Ruey J.; Peterson, Randall T.] Harvard Univ, Cardiovasc Res Ctr, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. [Kokel, David; Cheung, Chung Yan J.; Bruni, Giancarlo; Mateus, Rita; van Ham, Tjakko J.; Yeh, Jing-Ruey J.; Peterson, Randall T.] Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med,Dept Med, Charlestown, MA 02129 USA. [Kokel, David; Cheung, Chung Yan J.; Bruni, Giancarlo; Mateus, Rita; van Ham, Tjakko J.; Peterson, Randall T.] Broad Inst, Cambridge, MA 02142 USA. [Dunn, Timothy W.; Ahrens, Misha B.; Engert, Florian] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Shiraki, Tomoya; Fukada, Yoshitaka; Kojima, Daisuke] Univ Tokyo, Dept Biophys & Biochem, Grad Sch Sci, Tokyo 1130033, Japan. [Alshut, Ruediger; Mikut, Ralf] Karlsruhe Inst Technol, Inst Appl Comp Sci, D-76128 Karlsruhe, Germany. [Saint-Amant, Louis] Univ Montreal, Montreal, PQ H3C 3J7, Canada. [von Lintig, Johannes] Case Western Reserve Univ, Sch Med, Dept Pharmacol, Cleveland, OH 44106 USA. RP Kokel, D (reprint author), Harvard Univ, Cardiovasc Res Ctr, Massachusetts Gen Hosp, Sch Med, 149 13th St, Charlestown, MA 02129 USA. EM dkokel@cvrc.mgh.harvard.edu; peterson@cvrc.mgh.harvard.edu RI van Ham, Tjakko/I-2382-2013; Kojima, Daisuke/G-4958-2014; Mikut, Ralf /A-5949-2013; van Ham, Tjakko/A-1989-2015; OI Kojima, Daisuke/0000-0003-2658-780X; Mikut, Ralf /0000-0001-9100-5496; van Ham, Tjakko/0000-0002-2175-8713; Shiraki, Tomoya/0000-0003-0447-007X; Bruni, Giancarlo/0000-0003-2850-4633 FU National Institutes of Health [K01MH091449, R01MH086867, R21MH085205, DP1 NS082121, R01DA030304]; Japan Society for the Promotion of Science; National Science Foundation Graduate Research Fellowship; Sir Henry Wellcome Postdoctoral Fellowship from the Wellcome Trust; Charles and Ann Sanders MGH Research Scholar award FX This work was supported by National Institutes of Health Grants K01MH091449 to D. Kokel, R01MH086867 and R21MH085205 to R.T.P., and DP1 NS082121 and R01DA030304 to T.W.D. and F.E. This work was supported in part by Grants-in-Aid for Scientific Research from Japan Society for the Promotion of Science to Y.F. and D. Kojima, T.W.D. was supported by the National Science Foundation Graduate Research Fellowship. M.B.A. was supported by a Sir Henry Wellcome Postdoctoral Fellowship from the Wellcome Trust. R.T.P. was supported by the Charles and Ann Sanders MGH Research Scholar award. We thank John Dowling and members of our research groups for encouragement and advice. NR 62 TC 27 Z9 27 U1 3 U2 21 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD FEB 27 PY 2013 VL 33 IS 9 BP 3834 EP 3843 DI 10.1523/JNEUROSCI.3689-12.2013 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 098ZO UT WOS:000315588000012 PM 23447595 ER PT J AU Cruz, RJ Dew, MA Myaskovsky, L Goodpaster, B Fox, K Fontes, P DiMartini, A AF Cruz, Ruy J., Jr. Dew, Mary Amanda Myaskovsky, Larissa Goodpaster, Bret Fox, Kristen Fontes, Paulo DiMartini, Andrea TI Objective Radiologic Assessment of Body Composition in Patients with End-Stage Liver Disease: Going Beyond the BMI SO TRANSPLANTATION LA English DT Article DE Radiologic assessment; Assessment liver transplant candidates; Body composition; Cachexia ID COMPUTED-TOMOGRAPHY; MASS INDEX; INSULIN SENSITIVITY; SARCOPENIC OBESITY; ADIPOSE-TISSUE; MUSCLE MASS; MORTALITY; CIRRHOSIS; HEMODIALYSIS; SURVIVAL AB Background. Body mass index (BMI) is a commonly used but likely inexact measure of body composition for patients with end-stage liver disease. For this reason, we examined whether body composition measurements from direct visualization on computed tomography (CT) scans provide new insights in both the degree of malnutrition and the discordant combinations such as obesity with muscle mass loss. This technology is widely used in other medically ill populations but not yet in liver transplantation. Methods. We examined actual body composition using abdominal CT scan data and software designed to measure fat and muscle compartments. Results. In 234 liver transplant candidates, we found that BMI was highly and significantly correlated to subcutaneous and visceral fat. However, we additionally found that, even among obese patients, cachexia, as defined by muscle mass, was common, with 56% of those with BMI above 30 being cachexic. We also found that patients with nonalcoholic steatohepatitis, compared with other types of liver diseases, were significantly more likely to have larger amounts of visceral fat while also having less muscle. In an exploratory analysis, muscle mass corrected for height was a significant predictor of posttransplantation survival. Conclusions. Body composition by CT scan data provides a specific method to identify obesity and muscle wasting for end-stage liver disease patients. Whether these data can aid in the prognostication of outcomes and survival requires further investigation. C1 [Cruz, Ruy J., Jr.; Fontes, Paulo; DiMartini, Andrea] Univ Pittsburgh, Dept Transplantat Surg, Med Ctr, Pittsburgh, PA USA. [Dew, Mary Amanda; Myaskovsky, Larissa; Fox, Kristen; DiMartini, Andrea] Univ Pittsburgh, Dept Psychiat, Med Ctr, Pittsburgh, PA USA. [Dew, Mary Amanda] Univ Pittsburgh, Dept Psychol, Med Ctr, Pittsburgh, PA 15260 USA. [Dew, Mary Amanda] Univ Pittsburgh, Dept Epidemiol, Med Ctr, Pittsburgh, PA 15261 USA. [Myaskovsky, Larissa; Goodpaster, Bret] Univ Pittsburgh, Dept Med, Med Ctr, Pittsburgh, PA USA. [Goodpaster, Bret] Univ Pittsburgh, Med Ctr, Dept Hlth & Phys Educ, Pittsburgh, PA USA. [Dew, Mary Amanda] Univ Pittsburgh, Dept Biostat, Med Ctr, Pittsburgh, PA 15261 USA. [Fontes, Paulo; DiMartini, Andrea] Univ Pittsburgh, Starzl Transplant Inst, Med Ctr, Pittsburgh, PA USA. [Myaskovsky, Larissa] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [DiMartini, Andrea] Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. RP DiMartini, A (reprint author), Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA. EM dimartiniaf@upmc.edu FU National Institute of Digestive Disorders and Kidney Diseases (Rockville, MD) [R01 DK066266]; National Center for Research Resources, a component of the National Institutes of Health [5UL1 RR024153-04]; National Institutes of Health Roadmap for Medical Research; Starzl Transplant Institute Junior Investigator Award FX R.J.C.J. received the Starzl Transplant Institute Junior Investigator Award to conduct this research. This research is also funded by grant R01 DK066266 from the National Institute of Digestive Disorders and Kidney Diseases (Rockville, MD) and grant 5UL1 RR024153-04 from the National Center for Research Resources, a component of the National Institutes of Health, and National Institutes of Health Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the National Institute of Digestive Disorders and Kidney Diseases, National Center for Research Resources or National Institutes of Health. Information on National Center for Research Resources is available at http://www.ncrr.nih.gov/. NR 24 TC 20 Z9 20 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD FEB 27 PY 2013 VL 95 IS 4 BP 617 EP 622 DI 10.1097/TP.0b013e31827a0f27 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 093NS UT WOS:000315199200017 PM 23348896 ER PT J AU Walling, AM Asch, SM Lorenz, KA Wenger, NS AF Walling, Anne M. Asch, Steven M. Lorenz, Karl A. Wenger, Neil S. TI Impact of Consideration of Transplantation on End-of-Life Care for Patients During a Terminal Hospitalization SO TRANSPLANTATION LA English DT Article DE Transplant; End-of-life care; Palliative care; Quality of care ID LIVER-TRANSPLANTATION; SUSTAINING TREATMENTS; PALLIATIVE CARE; ADVANCED CANCER; PREFERENCES; OUTCOMES AB Background. Many patients considered for transplantation die before receiving the organ, underlining the importance of providing high-quality symptomatic relief and communication for all transplant patients. Methods. To study how consideration of transplantation affects the end-of-life care received by patients, care was evaluated by abstracting medical records for 496 adults who died in one high-volume transplant medical center between April 2005 and April 2006. Sixteen quality indicators from the Assessing Care of Vulnerable Elders set that focused on communication and symptom management were measured to calculate an overall patient-level quality score. We evaluated the predictors of quality of end-of-life care, with the main independent variable being whether the patient was being considered for transplantation. Restricting to patients who died an "expected death," we also evaluated the end-of-life treatments received. Results. Twenty-five percent of decedent patients were considered for transplantation. In adjusted models, patients considered for transplantation received lower-quality end-of-life care, had longer hospital stays before death, and were more likely to receive aggressive life-sustaining treatments. Conclusions. Care models should incorporate an emphasis on symptom relief and communication along with transplant preparation. C1 [Walling, Anne M.; Wenger, Neil S.] Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Wenger, Neil S.] Univ Calif Los Angeles, Hlth Syst Eth Ctr, Los Angeles, CA 90024 USA. [Lorenz, Karl A.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. [Walling, Anne M.; Wenger, Neil S.] RAND Hlth, Santa Monica, CA USA. [Asch, Steven M.] VA Palo Alto Healthcare Syst, Menlo Pk, CA USA. [Asch, Steven M.] Stanford Sch Med, Palo Alto, CA USA. [Walling, Anne M.] Univ Calif Los Angeles, Div Gen Internal Med, Los Angeles, CA 90024 USA. RP Walling, AM (reprint author), Univ Calif Los Angeles, Div Gen Internal Med, 911 Broxton Plaza, Los Angeles, CA 90024 USA. EM awalling@mednet.ucla.edu FU National Palliative Care Research Center Career Development Award FX This project was supported by a donation from Mary Kay Farley to RAND Health. A.M.W. was supported by a National Palliative Care Research Center Career Development Award. NR 20 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD FEB 27 PY 2013 VL 95 IS 4 BP 641 EP 646 DI 10.1097/TP.0b013e318277f238 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 093NS UT WOS:000315199200021 PM 23197177 ER PT J AU Matarese, G La Rocca, C Moon, HS Huh, JY Brinkoetter, MT Chou, SR Perna, F Greco, D Kilim, HP Gao, CY Arampatzi, K Wang, ZX Mantzoros, CS AF Matarese, Giuseppe La Rocca, Claudia Moon, Hyun-Seuk Huh, Joo Young Brinkoetter, Mary T. Chou, Sharon Perna, Francesco Greco, Dario Kilim, Holly P. Gao, Chuanyun Arampatzi, Kalliope Wang, Zhaoxi Mantzoros, Christos S. TI Selective capacity of metreleptin administration to reconstitute CD4(+) T-cell number in females with acquired hypoleptinemia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID HUMAN PHYSIOLOGY; LEPTIN C1 [Matarese, Giuseppe; La Rocca, Claudia] Univ Salerno, Dipartimento Med & Chirurg, I-84081 Baronissi, Italy. [Matarese, Giuseppe; La Rocca, Claudia] Univ Naples Federico II, Dipartimento Biol & Patol Cellulare & Mol, Consiglio Nazl Ric, Lab Immunol,Ist Endocrinol & Oncol Sperimentale, I-80131 Naples, Italy. [Perna, Francesco] Univ Naples Federico II, Dipartimento Med Clin & Sperimentale, I-80131 Naples, Italy. [Moon, Hyun-Seuk; Huh, Joo Young; Brinkoetter, Mary T.; Chou, Sharon; Kilim, Holly P.; Gao, Chuanyun; Arampatzi, Kalliope; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Greco, Dario] Karolinska Inst, Dept Biosci & Nutr, S-14183 Stockholm, Sweden. [Wang, Zhaoxi] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Sect Endocrinol, Boston, MA 02130 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu NR 4 TC 0 Z9 0 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 26 PY 2013 VL 110 IS 9 BP 3225 EP 3226 DI 10.1073/pnas.1214554110 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 102JW UT WOS:000315841900014 ER PT J AU Matarese, G La Rocca, C Moon, HS Huh, JY Brinkoetter, MT Chou, S Perna, F Greco, D Kilim, HP Gao, CY Arampatzi, K Wang, ZX Mantzoros, CS AF Matarese, Giuseppe La Rocca, Claudia Moon, Hyun-Seuk Huh, Joo Young Brinkoetter, Mary T. Chou, Sharon Perna, Francesco Greco, Dario Kilim, Holly P. Gao, Chuanyun Arampatzi, Kalliope Wang, Zhaoxi Mantzoros, Christos S. TI Selective capacity of metreleptin administration to reconstitute CD4(+) T-cell number in females with acquired hypoleptinemia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CD4 cells; metabolism; nutritional status ID ACTIVE ANTIRETROVIRAL THERAPY; INSULIN-RESISTANCE; IMMUNE-RESPONSE; METABOLIC SYNDROME; HUMAN LEPTIN; PROBE LEVEL; RECEPTOR; IMMUNODEFICIENCY; SURVIVAL; LYMPHOCYTES AB Edited by Philippa Marrack, Howard Hughes Medical Institute, National Jewish Health, Denver, CO, and approved December 19, 2012 (received for review August 24, 2012) Leptin is an adipocyte-derived hormone that controls food intake and reproductive and immune functions in rodents. In uncontrolled human studies, low leptin levels are associated with impaired immune responses and reduced T-cell counts; however, the effects of leptin replacement on the adaptive immune system have not yet been reported in the context of randomized, controlled studies and/or in conditions of chronic acquired leptin deficiency. To address these questions, we performed a randomized, double-blinded, placebo-controlled trial of recombinant methionyl-human leptin (metreleptin) administration in replacement doses in women experiencing the female triad (hypothalamic amenorrhea) with acquired chronic hypoleptinemia induced by negative energy balance. Metreleptin restored both CD4(+) T-cell counts and their in vitro proliferative responses in these women. These changes were accompanied by a transcriptional signature in which genes relevant to cell survival and hormonal response were up-regulated, and apoptosis genes were down-regulated in circulating immune cells. We also observed that signaling pathways involved in cell growth/survival/proliferation, such as the STAT3, AMPK, mTOR, ERK1/2, and Akt pathways, were activated directly by acute in vivo metreleptin administration in peripheral blood mononuclear cells and CD4(+) T-cells both from subjects with chronic hypoleptinemia and from normoleptinemic, lean female subjects. Our data show that metreleptin administration, in doses that normalize circulating leptin levels, induces transcriptional changes, activates intracellular signaling pathways, and restores CD4(+) T-cell counts. Thus, metreleptin may prove to be a safe and effective therapy for selective CD4(+) T-cell immune reconstitution in hypoleptinemic states such as tuberculosis and HIV infection in which CD4(+) T cells are reduced. C1 [Matarese, Giuseppe; La Rocca, Claudia] Univ Salerno, Dipartimento Med & Chirurg, I-84081 Baronissi, Italy. [Matarese, Giuseppe; La Rocca, Claudia] Univ Naples Federico II, Dipartimento Biol & Patol Cellulare & Mol, Consiglio Nazl Ric, Ist Endocrinol & Oncol Sperimentale,Lab Immunol, I-80131 Naples, Italy. [Perna, Francesco] Univ Naples Federico II, Dipartimento Med Clin & Sperimentale, I-80131 Naples, Italy. [Moon, Hyun-Seuk; Huh, Joo Young; Brinkoetter, Mary T.; Chou, Sharon; Kilim, Holly P.; Gao, Chuanyun; Arampatzi, Kalliope; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Greco, Dario] Karolinska Inst, Dept Biosci & Nutr, S-14183 Stockholm, Sweden. [Wang, Zhaoxi] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA 02130 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu RI Moon, Hyun-Seuk/G-8576-2015 OI Moon, Hyun-Seuk/0000-0002-5216-2090 FU National Institute of Diabetes and Digestive and Kidney Diseases [DK58785, DK79929, DK81913, AG032030]; National Institutes of Health-National Center for Research [UL1 RR025758, M01-RR-01032]; Harvard Clinical and Translational Science Center; National Center for Research Resources; European Union Ideas Programme; European Research Council Starting Grant "menTORingTregs" [310496]; Telethon-Juvenal Diabetes Research Foundation [GJT08004]; Fondi per la Ricerca di Base Medical Research in Italy [RBNE08HWLZ] FX We thank Claudio Procaccini, Fortunate Carbone, and Mario Galgani for critical reading of the manuscript; Jean Chan, MD, for contributions during initial phases of the study; and the nurses, technicians, and nutritionists at the Beth Israel Deaconess Medical Center General Clinical Research Center and Core Laboratory for their assistance in the conduct of the study. Amylin Pharmaceuticals supplied recombinant human leptin for this study and approved the design of the study but had no role in study design; conduct of the study; collection, management, analysis, or interpretation of the data; or the preparation, review, or approval of the manuscript. The C.S.M. laboratory is supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants DK58785, DK79929, DK81913, and AG032030. Funding also was received from the National Institutes of Health-National Center for Research Grants UL1 RR025758 and M01-RR-01032; the Harvard Clinical and Translational Science Center; and the National Center for Research Resources. G.M. is supported by grants from the European Union Ideas Programme, European Research Council Starting Grant "menTORingTregs" 310496, Telethon-Juvenal Diabetes Research Foundation Grant GJT08004, and Fondi per la Ricerca di Base Medical Research in Italy Grant RBNE08HWLZ. NR 47 TC 22 Z9 23 U1 0 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 26 PY 2013 VL 110 IS 9 BP E818 EP E827 DI 10.1073/pnas.1214554110 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 130VH UT WOS:000317947700006 PM 23382191 ER PT J AU Emerling, BM Benes, CH Poulogiannis, G Bell, EL Courtney, K Liu, H Choo-Wing, R Bellinger, G Tsukazawa, KS Brown, V Signoretti, S Soltoff, SP Cantley, LC AF Emerling, Brooke M. Benes, Cyril H. Poulogiannis, George Bell, Eric L. Courtney, Kevin Liu, Hui Choo-Wing, Rayman Bellinger, Gary Tsukazawa, Kazumi S. Brown, Victoria Signoretti, Sabina Soltoff, Stephen P. Cantley, Lewis C. TI Identification of CDCP1 as a hypoxia-inducible factor 2 alpha (HIF-2 alpha) target gene that is associated with survival in clear cell renal cell carcinoma patients SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE kidney cancer; oxygen deprivation ID DOMAIN-CONTAINING PROTEIN-1; CUB-DOMAIN; PKC-DELTA; PROLYL HYDROXYLATION; TUMOR-CELLS; HIF-ALPHA; VHL LOSS; CANCER; SRC; INHIBITION AB CUB domain-containing protein 1 (CDCP1) is a transmembrane protein that is highly expressed in stem cells and frequently overexpressed,and tyrosine-phosphorylated in cancer. CDCP1 promotes cancer cell metastasis. However, the mechanisms that regulate CDCP1 are not well-defined. Here we show that hypoxia induces CDCP1 expression and tyrosine phosphorylation in hypoxia-inducible factor (HIF)-2 alpha-, but not HIF-l alpha-, dependent fashion. shRNA knockdown of CDCP1 impairs cancer cell migration under hypoxic conditions, whereas overexpression of HIF-2 alpha promotes the growth of tumor xenografts in association with enhanced CDCP1 expression and tyrosine phosphorylation. Immunohistochemistry analysis of tissue microarray samples from tumors of patients with clear cell renal cell carcinoma shows that increased CDCP1 expression correlates with decreased overall survival. Together, these data support a critical role for CDCP1 as a unique HIF-2 alpha target gene involved in the regulation of cancer metastasis, and suggest that CDCP1 is a biomarker and potential therapeutic target for metastatic cancers. C1 [Emerling, Brooke M.; Poulogiannis, George; Liu, Hui; Choo-Wing, Rayman; Bellinger, Gary; Tsukazawa, Kazumi S.; Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Emerling, Brooke M.; Poulogiannis, George; Liu, Hui; Choo-Wing, Rayman; Bellinger, Gary; Tsukazawa, Kazumi S.; Soltoff, Stephen P.; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. [Benes, Cyril H.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Benes, Cyril H.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Bell, Eric L.] MIT, Dept Biol, Paul F Glenn Lab, Cambridge, MA 02139 USA. [Courtney, Kevin; Brown, Victoria; Signoretti, Sabina] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Courtney, Kevin] Univ Texas SW Med Ctr Dallas, Div Hematol Oncol, Dallas, TX 75390 USA. [Brown, Victoria; Signoretti, Sabina] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Cantley, LC (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. EM lewis_cantley@hms.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU National Institutes of Health [5R01GM056203-15]; American Cancer Society (ACS) [PF-08215-01-TBE]; DF/HCC Career Development Award FX We thank William G. Kaelin for the HIF-2 alpha antibody and for the RCC cell lines, Victoria Petkova for the qRT-PCR analysis (Real Time PCR Core, BIDMC), and the entire DF/HCC Kidney Cancer Specialized Programs of Research Excellence (SPORE) team. This work was supported by National Institutes of Health Grant 5R01GM056203-15 (to L.C.C.), American Cancer Society (ACS) Grant PF-08215-01-TBE, and a DF/HCC Career Development Award (to B.M.E.). G.P. is a Pfizer Fellow of the Life Sciences Research Foundation. NR 34 TC 16 Z9 17 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 26 PY 2013 VL 110 IS 9 BP 3483 EP 3488 DI 10.1073/pnas.1222435110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 102JW UT WOS:000315841900059 PM 23378636 ER PT J AU Seok, J Warren, HS Cuenca, AG Mindrinos, MN Baker, HV Xu, WH Richards, DR McDonald-Smith, GP Gao, H Hennessy, L Finnerty, CC Lopez, CM Honari, S Moore, EE Minei, JP Cuschieri, J Bankey, PE Johnson, JL Sperry, J Nathens, AB Billiar, TR West, MA Jeschke, MG Klein, MB Gamelli, RL Gibran, NS Brownstein, BH Miller-Graziano, C Calvano, SE Mason, PH Cobb, JP Rahme, LG Lowry, SF Maier, RV Moldawer, LL Herndon, DN Davis, RW Xiao, WZ Tompkins, RG AF Seok, Junhee Warren, H. Shaw Cuenca, Alex G. Mindrinos, Michael N. Baker, Henry V. Xu, Weihong Richards, Daniel R. McDonald-Smith, Grace P. Gao, Hong Hennessy, Laura Finnerty, Celeste C. Lopez, Cecilia M. Honari, Shari Moore, Ernest E. Minei, Joseph P. Cuschieri, Joseph Bankey, Paul E. Johnson, Jeffrey L. Sperry, Jason Nathens, Avery B. Billiar, Timothy R. West, Michael A. Jeschke, Marc G. Klein, Matthew B. Gamelli, Richard L. Gibran, Nicole S. Brownstein, Bernard H. Miller-Graziano, Carol Calvano, Steve E. Mason, Philip H. Cobb, J. Perren Rahme, Laurence G. Lowry, Stephen F. Maier, Ronald V. Moldawer, Lyle L. Herndon, David N. Davis, Ronald W. Xiao, Wenzhong Tompkins, Ronald G. CA Inflammation Host Response Injury TI Genomic responses in mouse models poorly mimic human inflammatory diseases SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE human disease; translational medicine; inflammation; immune response; injury ID LEUKOCYTE GENE-EXPRESSION; HUMAN IMMUNOLOGY; INFECTIOUS-DISEASES; SEPSIS; MICE; RESISTANCE; TOLERANCE; ENDOTOXIN; ANIMALS; INJURY AB A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R-2 between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases. C1 [Seok, Junhee; Mindrinos, Michael N.; Xu, Weihong; Gao, Hong; Davis, Ronald W.; Xiao, Wenzhong] Stanford Univ, Stanford Genome Technol Ctr, Stanford, CA 94305 USA. [Warren, H. Shaw] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat & Med, Boston, MA 02114 USA. [Cobb, J. Perren] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol & Crit Care Med, Boston, MA 02114 USA. [Rahme, Laurence G.; Xiao, Wenzhong; Tompkins, Ronald G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Cuenca, Alex G.; Baker, Henry V.; Lopez, Cecilia M.; Moldawer, Lyle L.] Univ Florida, Coll Med, Dept Surg, Gainesville, FL 32610 USA. [Richards, Daniel R.] Ingenuity Inc, Redwood City, CA 94063 USA. [McDonald-Smith, Grace P.; Mason, Philip H.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Hennessy, Laura; Honari, Shari] Harborview Med Ctr, Dept Surg, Seattle, WA 98195 USA. [Finnerty, Celeste C.; Herndon, David N.] Univ Texas Med Branch, Shriners Hosp Children, Galveston, TX 77550 USA. [Finnerty, Celeste C.; Herndon, David N.] Univ Texas Med Branch, Dept Surg, Galveston, TX 77550 USA. [Moore, Ernest E.; Johnson, Jeffrey L.] Univ Colorado, Dept Surg, Denver, CO 80045 USA. [Minei, Joseph P.] Univ Texas SW Med Ctr Dallas, Dept Surg, Parkland Mem Hosp, Dallas, TX 75390 USA. [Cuschieri, Joseph; Klein, Matthew B.; Gibran, Nicole S.; Maier, Ronald V.] Univ Washington, Sch Med, Dept Surg, Harborview Med Ctr, Seattle, WA 98195 USA. [Bankey, Paul E.; Miller-Graziano, Carol] Univ Rochester, Sch Med, Dept Surg, Rochester, NY 14642 USA. [Sperry, Jason; Billiar, Timothy R.] Univ Pittsburgh, Dept Surg, Med Ctr, Presbyterian Univ Hosp, Pittsburgh, PA 15213 USA. [Nathens, Avery B.] Univ Toronto, St Michaels Hosp, Dept Surg, Toronto, ON M5B 1W8, Canada. [West, Michael A.] Univ Calif San Francisco, Dept Surg, San Francisco Gen Hosp, San Francisco, CA 94143 USA. [Jeschke, Marc G.] Univ Toronto, Div Plast & Reconstruct Surg, Dept Surg, Toronto, ON M4N 3M5, Canada. [Gamelli, Richard L.] Loyola Univ, Stritch Sch Med, Dept Surg, Chicago, IL 60153 USA. [Brownstein, Bernard H.] Washington Univ, Sch Med, Dept Anesthesiol, St Louis, MO 63110 USA. [Calvano, Steve E.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Surg, New Brunswick, NJ 08903 USA. RP Davis, RW (reprint author), Stanford Univ, Stanford Genome Technol Ctr, Stanford, CA 94305 USA. EM dbowe@stanford.edu; wxiao1@partners.org; rtompkins@partners.org OI xiao, wenzhong/0000-0003-4944-6380 FU Defense Advanced Research Projects Agency [W9111NF-10-1-0271]; National Institute on Disability and Rehabilitation Research [H133A070026]; National Institute of General Medical Sciences [5P50GM060338, 5R01GM056687, R24GM102656, 5U54GM062119]; National Human Genome Research Institute [P01HG000205] FX The datasets reported in the paper are available on GEO with accession numbers listed in SI Appendix. This work was supported by Defense Advanced Research Projects Agency Grant W9111NF-10-1-0271 (to H.S.W.), National Institute on Disability and Rehabilitation Research Grant H133A070026 (to D.N.H.), National Institute of General Medical Sciences Grants 5P50GM060338 (to D.N.H.), 5R01GM056687 (to D.N.H.), R24GM102656 (to W. Xiao), and 5U54GM062119 (to R.G.T.), and National Human Genome Research Institute Grant P01HG000205 (to R.W.D.). NR 34 TC 1009 Z9 1014 U1 15 U2 177 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 26 PY 2013 VL 110 IS 9 BP 3507 EP 3512 DI 10.1073/pnas.1222878110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 102JW UT WOS:000315841900063 PM 23401516 ER PT J AU Bohr, S Patel, SJ Shen, KY Vitalo, AG Brines, M Cerami, A Berthiaume, F Yarmush, ML AF Bohr, Stefan Patel, Suraj J. Shen, Keyue Vitalo, Antonia G. Brines, Michael Cerami, Anthony Berthiaume, Francois Yarmush, Martin L. TI Alternative erythropoietin-mediated signaling prevents secondary microvascular thrombosis and inflammation within cutaneous burns SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE thermal injury; hypoxia; oxidative stress; leukocyte infiltration; cell adhesion molecules ID KERATINOCYTE GROWTH-FACTOR; BETA-COMMON-RECEPTOR; TNF-ALPHA; BARRIER FUNCTION; TERTIARY STRUCTURE; CELLS; INJURY; ANGIOGENESIS; REGENERATION; EXPRESSION AB Alternate erythropoietin (EPO)-mediated signaling via the heteromeric receptor composed of the EPO receptor and the beta-common receptor (CD131) exerts the tissue-protective actions of EPO in various types of injuries. Herein we investigated the effects of the EPO derivative helix beta surface peptide (synonym: ARA290), which specifically triggers alternate EPO-mediated signaling, but does not bind the erythropoietic EPO receptor homodimer, on the progression of secondary tissue damage following cutaneous burns. For this purpose, a deep partial thickness cutaneous burn injury was applied on the back of mice, followed by systemic administration of vehicle or ARA290 at 1, 12, and 24 h postburn. With vehicle-only treatment, wounds exhibited secondary microvascular thrombosis within 24 h postburn, and subsequent necrosis of the surrounding tissue, thus converting to a full-thickness injury within 48 h. On the other hand, when ARA290 was systemically administered, patency of the microvasculature was maintained. Furthermore, ARA290 mitigated the innate inflammatory response, most notably tumor necrosis factor-alpha mediated signaling. These findings correlated with long-term recovery of initially injured yet viable tissue cornponents. In conclusion, ARA290 may be a promising therapeutic approach to prevent the conversion of partial- to full-thickness burn injuries. In a clinical setting, the decrease in burn depth and area would likely reduce the necessity for extensive surgical debridement as well as secondary wound closure by means of skin grafting. This use of ARA290 is consistent with its tissue-protective properties previously reported in other models of injury, such as myocardial infarction and hemorrhagic shock. C1 [Bohr, Stefan; Patel, Suraj J.; Shen, Keyue; Vitalo, Antonia G.; Yarmush, Martin L.] Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. [Bohr, Stefan; Patel, Suraj J.; Shen, Keyue; Vitalo, Antonia G.; Yarmush, Martin L.] Shriners Hosp Children, Boston, MA 02114 USA. [Brines, Michael; Cerami, Anthony] Araim Pharmaceut, Ossining, NY 10562 USA. [Berthiaume, Francois; Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. RP Yarmush, ML (reprint author), Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. EM ireis@sbi.org OI Brines, Michael/0000-0003-4151-4449 FU Shriners Hospital for Children; Deutsche Forschungsgemeinschaft (Germany) [GZ: BO3468/2-1] FX The peptides ARA290 and ARA297 were kindly provided by Araim Pharmaceuticals, Inc. (Ossining, NY). This work was funded by the Shriners Hospital for Children. S.B. is a recipient of Deutsche Forschungsgemeinschaft (Germany) postdoctoral fellowship Award GZ: BO3468/2-1. S.J.P. was supported by a Shriners Hospital for Children postdoctoral fellowship award. NR 39 TC 21 Z9 22 U1 0 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 26 PY 2013 VL 110 IS 9 BP 3513 EP 3518 DI 10.1073/pnas.1214099110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 102JW UT WOS:000315841900064 PM 23401545 ER PT J AU Mebazaa, A Gayat, E Lassus, J Meas, T Mueller, C Maggioni, A Peacock, F Spinar, J Harjola, VP van Kimmenade, R Pathak, A Mueller, T Tavazzi, L Disomma, S Metra, M Pascual-Figal, D Laribi, S Logeart, D Nouira, S Sato, N Parenica, J Deye, N Boukef, R Collet, C Van den Berghe, G Cohen-Solal, A Januzzi, JL AF Mebazaa, Alexandre Gayat, Etienne Lassus, Johan Meas, Taly Mueller, Christian Maggioni, Aldo Peacock, Frank Spinar, Jindrich Harjola, Veli-Pekka van Kimmenade, Roland Pathak, Atul Mueller, Thomas Tavazzi, Luigi diSomma, Salvatore Metra, Marco Pascual-Figal, Domingo Laribi, Said Logeart, Damien Nouira, Semir Sato, Naoki Parenica, Jiri Deye, Nicolas Boukef, Riadh Collet, Corinne Van den Berghe, Greet Cohen-Solal, Alain Januzzi, James L., Jr. CA GREAT Network TI Association Between Elevated Blood Glucose and Outcome in Acute Heart Failure Results From an International Observational Cohort SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE acute heart failure; blood glucose; 30-day mortality; hyperglycemia ID ACUTE MYOCARDIAL-INFARCTION; STRESS HYPERGLYCEMIA; NATRIURETIC PEPTIDE; DIABETES-MELLITUS; ADMISSION GLUCOSE; ROC CURVE; MORTALITY; DISEASE; RECLASSIFICATION; NORMALIZATION AB Objective The aim of this analysis was to assess the association between elevated blood glucose level and mortality in acute heart failure (AHF). Background Elevated blood glucose has been reported to be prognostically meaningful in patients with cardiac diagnoses, such as coronary artery disease. The short-term prognostic impact of hyperglycemia in AHF is unknown, however. Methods In a multinational cohort of AHF, we examined the ability of blood glucose concentrations at presentation to predict all-cause mortality by 30 days. Fully adjusted models for prognosis included a previous diagnosis of diabetes mellitus as a covariate. Results A total of 6,212 subjects with AHF (mean age, 72 years; 52.5% male) were studied; the median blood glucose concentration on arrival at the hospital was 7.5 mmol/l (135 mg/dl), and 41% had a previous diagnosis of diabetes mellitus (DM). After 30 days, 618 patients (10%) had died. Compared with survivors, decedents had significantly higher median blood glucose concentrations (8.9 mmol/l vs. 7.4 mmol/l; p < 0.0001). In the fully adjusted model, an elevated blood glucose level was an independent predictor of 30-day mortality in AHF (odds ratio: 2.19; 95% confidence interval: 1.69 to 2.83; p < 0.001). The risk associated with an elevated blood glucose level appeared consistent across all subgroups of patients, including patients with preserved (hazard ratio: 5.41; 95% confidence interval: 2.44 to 12.0; p < 0.0001) and impaired systolic function (hazard ratio: 2.37; 95% confidence interval: 1.57 to 3.59; p < 0.0001). Furthermore, in reclassification analyses, elevated blood glucose added significant prognostic information to clinical parameters alone (4.4% net reclassification improvement; p = 0.01). Conclusions Among patients with AHF, blood glucose concentrations at presentation are powerfully prognostic for 30-day mortality, independent of a diagnosis of diabetes mellitus or other clinical variables. Because blood glucose is easily modifiable, it may represent a valid target for therapeutic intervention. (J Am Coll Cardiol 2013;61:820-9) (C) 2013 by the American College of Cardiology Foundation C1 [Mebazaa, Alexandre; Gayat, Etienne] Univ Paris Diderot, AP HP, Lariboisiere Univ Hosp, Dept Anesthesiol & Intens Care, Paris, France. [Mebazaa, Alexandre; Gayat, Etienne; Meas, Taly; Logeart, Damien; Deye, Nicolas; Collet, Corinne; Cohen-Solal, Alain] INSERM, UMR 942, Paris, France. [Lassus, Johan] Univ Helsinki, Cent Hosp, Dept Med, Helsinki, Finland. [Meas, Taly] Univ Paris Diderot, AP HP, Lariboisiere Univ Hosp, Dept Endocrinol, Paris, France. [Mueller, Christian] Univ Basel Hosp, Dept Internal Med, CH-4031 Basel, Switzerland. [Maggioni, Aldo] ANMCO Res Ctr, Florence, Italy. [Peacock, Frank] Cleveland Clin, Emergency Med Inst, Cleveland, OH 44106 USA. [Spinar, Jindrich; Parenica, Jiri] Masaryk Univ, Fac Med, Univ Hosp Brno, Dept Internal Med & Cardiol, Brno, Czech Republic. [Harjola, Veli-Pekka] Univ Helsinki, Cent Hosp, Div Emergency Care, Helsinki, Finland. [van Kimmenade, Roland] Univ Med Ctr, Utrecht, Netherlands. [Pathak, Atul] Toulouse Univ Hosp, Dept Cardiol, Toulouse, France. [Mueller, Thomas] Konventhosp Barmherzige Brueder, Dept Lab Med, Linz, Austria. [Tavazzi, Luigi] Maria Cecilia Hosp, Ettore Sansavini Hlth Sci Fdn, GVM Care & Res, Cotignola, Italy. [diSomma, Salvatore] Univ Roma La Sapienza, SantAndrea Hosp, Emergency Dept, Rome, Italy. [Metra, Marco] Univ Brescia, Dept Expt & Appl Med, Brescia, Italy. [Pascual-Figal, Domingo] Univ Murcia, Fac Med, Dept Med, Virgen de la Arrixaca Hosp,Cardiol Serv, Murcia, Spain. [Laribi, Said; Cohen-Solal, Alain] Univ Paris Diderot, AP HP, Lariboisiere Univ Hosp, Dept Emergency Med, Paris, France. [Logeart, Damien; Boukef, Riadh] Univ Paris Diderot, AP HP, Lariboisiere Univ Hosp, Dept Cardiol, Paris, France. [Nouira, Semir] Fattouma Bourguiba Univ Hosp, Emergency Dept, Monastir, Tunisia. [Nouira, Semir] Fattouma Bourguiba Univ Hosp, Res Unit UR06SP21, Monastir, Tunisia. [Sato, Naoki] Musashi Kosugi Hosp, Nippon Med Sch, Tokyo, Japan. [Deye, Nicolas] Univ Paris Diderot, AP HP, Lariboisiere Univ Hosp, Paris, France. [Van den Berghe, Greet] Univ Leuven, Univ Hosp Leuven, Dept Intens Care Med, Louvain, Belgium. [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Mebazaa, A (reprint author), Lariboisiere Univ Hosp, Dept Anesthesiol & Intens Care, 2 Rue Ambroise Pare, F-75010 Paris, France. EM alexandre.mebazaa@lrb.aphp.fr RI Pascual Figal, Domingo /B-3794-2008; Laribi, Said/D-5229-2014; Harjola, Veli-Pekka/G-9229-2015; Kimmenade, R.R.J./L-4432-2015; Laribi, said/S-3693-2016; OI Maggioni, Aldo Pietro/0000-0003-2764-6779; Pascual Figal, Domingo /0000-0002-4993-9540; boukef, riadh/0000-0001-7469-930X; Metra, Marco/0000-0001-6691-8568; Nouira, Semir/0000-0002-0137-5491 FU INSERM [AAP2009/AM]; Roche Diagnostics; Siemens; Critical Diagnostics; Brahms; Sphingotec; Bayer HealthCare AG; Pronota; Otsuka; Daiichi-Sankyo; Astellas; Mochida; Chugai; Servier; Medtronic; St. Jude Medical; Vifor Pharma; Boston Scientific; Lone Star Heart Inc.; Bristol-Myers Squibb; Cardiorentis; Quintiles FX This work was supported by a grant from INSERM (AAP2009/AM). Dr. Januzzi has received support from Roche Diagnostics, Siemens, Critical Diagnostics, Brahms, and Sphingotec. Dr. Mebazaa has received consultant fees from Bayer HealthCare AG; honoraria from Alere, Cardiorentis, Edwards, Thermofisher, and Orion; and a research grant from Pronota. Dr. Metra receives honoraria for speeches and is a member of the advisory board and/or steering committee of Corthera, Bayer, Novartis, Servier, and Abbott Vascular. Dr. Sato receives research support and honoraria from Otsuka, Daiichi-Sankyo, Astellas, and Mochida; honoraria from Eisai and Boston Scientific; and consulting fees from Chugai. Dr. Tavazzi receives consulting fees from Servier and research grants from Medtronic, St. Jude Medical, Vifor Pharma, Boston Scientific, Lone Star Heart Inc., Bristol-Myers Squibb, Cardiorentis, and Quintiles. The first 2 authors contributed equally to this work. NR 47 TC 41 Z9 43 U1 1 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 26 PY 2013 VL 61 IS 8 BP 820 EP 829 DI 10.1016/j.jacc.2012.11.054 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 093NU UT WOS:000315199400005 PM 23333145 ER PT J AU Frelinger, AL Bhatt, DL Lee, RD Mulford, DJ Wu, JT Nudurupati, S Nigam, A Lampa, M Brooks, JK Barnard, MR Michelson, AD AF Frelinger, Andrew L., III Bhatt, Deepak L. Lee, Ronald D. Mulford, Darcy J. Wu, Jingtao Nudurupati, Sai Nigam, Anu Lampa, Michael Brooks, Julie K. Barnard, Marc R. Michelson, Alan D. TI Clopidogrel Pharmacokinetics and Pharmacodynamics Vary Widely Despite Exclusion or Control of Polymorphisms (CYP2C19, ABCB1, PON1), Noncompliance, Diet, Smoking, Co-Medications (Including Proton Pump Inhibitors), and Pre-Existent Variability in Platelet Function SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE drugs; pharmacokinetics; platelets; receptors; risk factors ID CIGARETTE-SMOKING; ASSOCIATION; REACTIVITY; EFFICACY; TRIAL; PARAOXONASE-1; ABSORPTION; RESISTANCE; PRASUGREL; GENOTYPE AB Objectives This study sought to determine whether known genetic, drug, dietary, compliance, and lifestyle factors affecting clopidogrel absorption and metabolism fully account for the variability in clopidogrel pharmacokinetics and pharmacodynamics. Background Platelet inhibition by clopidogrel is highly variable. Patients with reduced inhibition have increased risk for major adverse cardiovascular events. Identification of factors contributing to clopidogrel's variable response is needed to improve platelet inhibition and reduce risk for cardiovascular events. Methods Healthy subjects (n = 160; ages 20 to 53 years; homozygous CYP2C19 extensive metabolizer genotype; no nicotine for 6 weeks, prescription drugs for 4 weeks, over-the-counter drugs for 2 weeks, and no caffeine or alcohol for 72 h; confined; restricted diet) received clopidogrel 75 mg/day for 9 days, at which time clopidogrel pharmacokinetic and pharmacodynamic endpoints were measured. Results At steady-state, clopidogrel active metabolite (clopidogrel(AM)) pharmacokinetics varied widely between subjects (coefficients of variation [CVs] 33.8% and 40.2% for clopidogrel(AM) area under the time-concentration curve and peak plasma concentration, respectively). On-treatment vasodilator stimulated phosphoprotein P2Y(12) platelet reactivity index (PRI), maximal platelet aggregation (MPA) to adenosine phosphate, and VerifyNow P2Y12 platelet response units (PRU) also varied widely (CVs 32% to 53%). All identified factors together accounted for only 18% of intersubject variation in pharmacokinetic parameters and 32% to 64% of intersubject variation in PRI, MPA, and PRU. High on-treatment platelet reactivity was present in 45% of subjects. Conclusions: Clopidogrel pharmacokinetics and pharmacodynamics vary widely despite rigorous exclusion or control of known disease, polymorphisms (CYP2C19, CYP3A5, ABCB1, PON1), noncompliance, co-medications, diet, smoking, alcohol, demographics, and pre-treatment platelet hyperreactivity. Thus, as yet unidentified factors contribute to high on-treatment platelet reactivity with its known increased risk of major adverse cardiovascular events. (A Study of the Effects of Multiple Doses of Dexiansoprazole, Lansoprazole, Omeprazole or Esomeprazole on the Pharmacokinetics and Pharmacodynamics of Clopidogrel in Healthy Participants: NCT00942175) (J Am Coll Cardiol 2013;61:872-9) (c) 2013 by the American College of Cardiology Foundation C1 [Frelinger, Andrew L., III; Nigam, Anu; Lampa, Michael; Brooks, Julie K.; Barnard, Marc R.; Michelson, Alan D.] Boston Childrens Hosp, Div Hematol Oncol, Ctr Platelet Res Studies, Dana Farber Canc Inst, Boston, MA 02115 USA. [Frelinger, Andrew L., III; Bhatt, Deepak L.; Michelson, Alan D.] Harvard Univ, Sch Med, Boston, MA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Lee, Ronald D.; Mulford, Darcy J.; Wu, Jingtao; Nudurupati, Sai] Takeda Global Res & Dev Ctr Inc, Deerfield, IL USA. RP Frelinger, AL (reprint author), Boston Childrens Hosp, Div Hematol Oncol, Ctr Platelet Res Studies, Karp 07212,300 Longwood Ave, Boston, MA 02115 USA. EM Andrew.Frelinger@childrens.harvard.edu FU Takeda Global Research & Development Center, Inc., Deerfield, Illinois; GLSynthesis; Lilly; Amarin; AstraZeneca; Bristol-Myers Squibb; Eisai; Ethicon; Medtronic; Sanofi Aventis; The Medicines Company FX From the *Center for Platelet Research Studies, Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts; dagger Harvard Medical School, Boston, Massachusetts; double dagger VA Boston Healthcare System, Brigham and Women's Hospital, Boston, Massachusetts; and the Takeda Global Research & Development Center, Inc., Deerfield, Illinois. This study was supported in part by a research grant from Takeda Global Research & Development Center, Inc., Deerfield, Illinois to Children's Hospital Boston (Alan D. Michelson, principal investigator). Drs. Frelinger and Michelson have received research grants from GLSynthesis and Lilly. Dr. Michelson has been a member of the Data Monitoring Committee of a clinical trial sponsored by Lilly. Dr. Bhatt is a member of the Advisory Board for Medscape Cardiology; a member of the Board of Directors for the Boston VA Research Institute and the Society of Chest Pain Centers; and is the Chair of the American Heart Association Get With The Guidelines Science Subcommittee; he has received honoraria from the American College of Cardiology (Editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), WebMD (CME steering committees); and is Senior Associate Editor, Journal of Invasive Cardiology. Dr. Bhatt has also received research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, and The Medicines Company; and he has performed unfunded research with FlowCo, PLx Pharma, and Takeda. Drs Lee, Mulford, Wu, and Nudurupati are employees of Takeda Global Research & Development Center, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 28 TC 84 Z9 87 U1 3 U2 42 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 26 PY 2013 VL 61 IS 8 BP 872 EP 879 DI 10.1016/j.jacc.2012.11.040 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 093NU UT WOS:000315199400013 PM 23333143 ER PT J AU Fukuzawa, T Fukazawa, M Ueda, O Shimada, H Kito, A Kakefuda, M Kawase, Y Wada, NA Goto, C Fukushima, N Jishage, K Honda, K King, GL Kawabe, Y AF Fukuzawa, Taku Fukazawa, Masanori Ueda, Otoya Shimada, Hideaki Kito, Aki Kakefuda, Mami Kawase, Yosuke Wada, Naoko A. Goto, Chisato Fukushima, Naoshi Jishage, Kou-ichi Honda, Kiyofumi King, George L. Kawabe, Yoshiki TI SGLT5 Reabsorbs Fructose in the Kidney but Its Deficiency Paradoxically Exacerbates Hepatic Steatosis Induced by Fructose SO PLOS ONE LA English DT Article ID INSULIN-RESISTANCE; GLUCOSE-TRANSPORTER; METABOLIC SYNDROME; RAT-KIDNEY; GLUT2; EXPRESSION; DISEASE; CONSUMPTION; INTESTINE; MANNOSE AB Although excessive fructose intake is epidemiologically linked with dyslipidemia, obesity, and diabetes, the mechanisms regulating plasma fructose are not well known. Cells transfected with sodium/glucose cotransporter 5 (SGLT5), which is expressed exclusively in the kidney, transport fructose in vitro; however, the physiological role of this transporter in fructose metabolism remains unclear. To determine whether SGLT5 functions as a fructose transporter in vivo, we established a line of mice lacking the gene encoding SGLT5. Sodium-dependent fructose uptake disappeared in renal brush border membrane vesicles from SGLT5-deficient mice, and the increased urinary fructose in SGLT5-deficient mice indicated that SGLT5 was the major fructose reabsorption transporter in the kidney. From this, we hypothesized that urinary fructose excretion induced by SGLT5 deficiency would ameliorate fructose-induced hepatic steatosis. To test this hypothesis we compared SGLT5-deficient mice with wild-type mice under conditions of long-term fructose consumption. Paradoxically, however, fructose-induced hepatic steatosis was exacerbated in the SGLT5-deficient mice, and the massive urinary fructose excretion was accompanied by reduced levels of plasma triglycerides and epididymal fat but fasting hyperinsulinemia compared with fructose-fed wild-type mice. There was no difference in food consumption, water intake, or plasma fructose between the two types of mice. No compensatory effect by other transporters reportedly involved in fructose uptake in the liver and kidney were indicated at the mRNA level. These surprising findings indicated a previously unrecognized link through SGLT5 between renal fructose reabsorption and hepatic lipid metabolism. C1 [Fukuzawa, Taku; Fukazawa, Masanori; Ueda, Otoya; Shimada, Hideaki; Kito, Aki; Wada, Naoko A.; Fukushima, Naoshi; Jishage, Kou-ichi; Honda, Kiyofumi; Kawabe, Yoshiki] Chugai Pharmaceut Co Ltd, Div Res, Shizuoka, Japan. [Kakefuda, Mami; Kawase, Yosuke; Goto, Chisato] Chugai Res Inst Med Sci Inc, Shizuoka, Japan. [King, George L.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. RP Fukazawa, M (reprint author), Chugai Pharmaceut Co Ltd, Div Res, Shizuoka, Japan. EM fukazawamsn@chugai-pharm.co.jp FU Chugai Pharmaceutical Co., Ltd.; Sanofi Aventis FX No sources of funding outside Chugai Pharmaceutical Co., Ltd. supported this work, and there are no current external funding sources for this study.; T. Fukuzawa, M. Fukazawa, O. Ueda, H. Shimada, A. Kito, N.A. Wada, N. Fukushima, K. Jishage, K. Honda, and Y. Kawabe are employees of Chugai Pharmaceutical Co., Ltd. M. Kakefuda, Y. Kawase, and C. Goto are employees of Chugai Research Institute for Medical Science, Inc. These employments do not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. George L. King has received a grant from Sanofi Aventis for research unrelated to the current study. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. NR 40 TC 4 Z9 5 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 25 PY 2013 VL 8 IS 2 AR e56681 DI 10.1371/journal.pone.0056681 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 115ZB UT WOS:000316849500022 PM 23451068 ER PT J AU Yoong, J Park, ER Greer, JA Jackson, VA Gallagher, ER Pirl, WF Back, AL Temel, JS AF Yoong, Jaclyn Park, Elyse R. Greer, Joseph A. Jackson, Vicki A. Gallagher, Emily R. Pirl, William F. Back, Anthony L. Temel, Jennifer S. TI Early Palliative Care in Advanced Lung Cancer A Qualitative Study SO JAMA INTERNAL MEDICINE LA English DT Article ID OF-LIFE CARE; TEAMS IMPROVE OUTCOMES; MEDICINE CONSULTATION; CLINICAL ONCOLOGY; AMERICAN SOCIETY; CONTROLLED-TRIAL; OUTPATIENT; END; RECOMMENDATIONS; COMMUNICATION AB Background: Early ambulatory palliative care (PC) is an emerging practice, and its key elements have not been defined. We conducted a qualitative analysis of data from a randomized controlled trial that demonstrated improved quality of life, mood, and survival in patients with newly diagnosed metastatic non-small cell lung cancer who received early PC integrated with standard oncologic care vs standard oncologic care alone. Our objectives were to (1) identify key elements of early PC clinic visits, (2) explore the timing of key elements, and (3) compare the content of PC and oncologic visit notes at the critical time points of clinical deterioration and radiographic disease progression. Methods: We randomly selected 20 patients who received early PC and survived within 4 periods: less than 3 months (n=5), 3 to 6 months (n=5), 6 to 12 months (n=5), and 12 to 24 months (n=5). We performed content analysis on PC and oncologic visit notes from the electronic health records of these patients. Results: Addressing symptoms and coping were the most prevalent components of the PC clinic visits. Initial vis-its focused on building relationships and rapport with patients and their families and on illness understanding, including prognostic awareness. Discussions about resuscitation preferences and hospice predominantly occurred during later visits. Comparing PC and oncologic care visits around critical time points, both included discussions about symptoms and illness status; however, PC visits emphasized psychosocial elements, such as coping, whereas oncologic care visits focused on cancer treatment and management of medical complications. Conclusions: Early PC clinic visits emphasize managing symptoms, strengthening coping, and cultivating illness understanding and prognostic awareness in a responsive and time-sensitive model. During critical clinical time points, PC and oncologic care visits have distinct features that suggest a key role for PC involvement and enable oncologists to focus on cancer treatment and managing medical complications. C1 [Yoong, Jaclyn; Park, Elyse R.; Greer, Joseph A.; Jackson, Vicki A.; Gallagher, Emily R.; Pirl, William F.; Temel, Jennifer S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Back, Anthony L.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. RP Temel, JS (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 7E, Boston, MA 02114 USA. EM jtemel@partners.org FU American Society of Clinical Oncology Conquer Cancer Foundation Career Development Award FX This study was funded by an American Society of Clinical Oncology Conquer Cancer Foundation Career Development Award. NR 44 TC 62 Z9 62 U1 3 U2 28 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD FEB 25 PY 2013 VL 173 IS 4 BP 283 EP 290 DI 10.1001/jamainternmed.2013.1874 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 153NZ UT WOS:000319610400007 PM 23358690 ER PT J AU Smith, AK AF Smith, Alexander K. TI Palliative Care An Approach for All Internists SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID CONTROLLED-TRIAL; CANCER; OUTCOMES C1 [Smith, Alexander K.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94941 USA. [Smith, Alexander K.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Smith, AK (reprint author), Univ Calif San Francisco, Dept Med, 4150 Clement St,181G, San Francisco, CA 94941 USA. EM aksmith@ucsf.edu FU NIA NIH HHS [K23 AG040772] NR 7 TC 1 Z9 1 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD FEB 25 PY 2013 VL 173 IS 4 BP 291 EP 292 DI 10.1001/jamainternmed.2013.1888 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 153NZ UT WOS:000319610400008 PM 23358724 ER PT J AU Gross, R Bellamy, SL Chapman, J Han, XY O'Duor, J Palmer, SC Houts, PS Coyne, JC Strom, BL AF Gross, Robert Bellamy, Scarlett L. Chapman, Jennifer Han, Xiaoyan O'Duor, Jacqueline Palmer, Steven C. Houts, Peter S. Coyne, James C. Strom, Brian L. TI Managed Problem Solving for Antiretroviral Therapy Adherence A Randomized Trial SO JAMA INTERNAL MEDICINE LA English DT Article ID SELF-ADMINISTERED THERAPY; HIV-INFECTED PATIENTS; MEDICATION ADHERENCE; HEALTH LITERACY; VIRAL LOAD; PROTEASE; FAILURE; INTERVENTIONS; SUPPRESSION; RESISTANCE AB Background: Adherence to antiretroviral therapy is critical to successful treatment of human immunodeficiency virus (HIV). Few interventions have been demonstrated to improve both adherence and virologic outcomes. We sought to determine whether an intervention derived from problem solving theory, Managed Problem Solving (MAPS), would improve antiretroviral outcomes. Methods: We conducted a randomized investigator blind trial of MAPS compared with usual care in HIV-1 infected individuals at 3 HIV clinics in Philadelphia, Pennsylvania. Eligible patients had plasma HIV-1 viral loads greater than 1000 copies/mL and were initiating or changing therapy. Managed Problem Solving consists of 4 in-person and 12 telephone-based meetings with a trained interventionist, then monthly follow-up calls for a year. Primary outcome was medication adherence measured using electronic monitors, summarized as fraction of doses taken quarterly over 1 year. Secondary outcome was undetectable HIV viral load over 1 year. We assessed 218 for eligibility, with 190 eligible and 180 enrolled, 91 randomized to MAPS and 89 to usual care. Fifty-six participants were lost to follow-up: 33 in the MAPS group and 23 in usual care group. Results: In primary intention-to-treat analyses, the odds of being in a higher adherence category was 1.78 (95% CI, 1.07-2.96) times greater for MAPS than usual care. In secondary analyses, the odds of an undetectable viral load was 1.48 (95% CI, 0.94-2.31) times greater for MAPS than usual care. In as-treated analyses, the effect of MAPS was stronger for both outcomes. There was neither a difference by prior treatment status nor change in effect over time. Conclusions: Managed Problem Solving is an effective antiretroviral adherence intervention over the first year with a new regimen. It was equally effective at improving adherence in treatment experienced and naive patients and did not lose effect over time. Implementation of MAPS should be strongly considered where resources are available. Trial Registration: clinicaltrials.gov Identifier: NCT00130273 C1 [Gross, Robert; Bellamy, Scarlett L.; Chapman, Jennifer; Han, Xiaoyan; Strom, Brian L.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Palmer, Steven C.; Coyne, James C.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Gross, Robert; O'Duor, Jacqueline] Univ Penn, Perelman Sch Med, Div Infect Dis, Philadelphia, PA 19104 USA. [Gross, Robert; Bellamy, Scarlett L.; Chapman, Jennifer; Han, Xiaoyan; Strom, Brian L.] Univ Penn, Perelman Sch Med, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Gross, Robert; O'Duor, Jacqueline] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Gross, Robert] Vet Affairs Med Ctr, Philadelphia, PA USA. [Houts, Peter S.] Penn State Univ, Coll Med, Hershey, PA USA. [Coyne, James C.] Univ Groningen, Univ Med Ctr Groningen, Dept Hlth Sci, Hlth Psychol Sect, Groningen, Netherlands. RP Gross, R (reprint author), Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Div Infect Dis,Dept Med, 804 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM grossr@mail.med.upenn.edu FU National Institute of Mental Health [R01 MH067498]; National Center for Research Resources [UL1 RR024134]; Penn Center for AIDS Research [P30 AI 045008] FX The study was supported by R01 MH067498 from the National Institute of Mental Health, UL1 RR024134 from the National Center for Research Resources, core services and support from the Penn Center for AIDS Research (P30 AI 045008), and career support from the Philadelphia Veterans Affairs Medical Center (Dr Gross). NR 40 TC 23 Z9 23 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD FEB 25 PY 2013 VL 173 IS 4 BP 300 EP 306 DI 10.1001/jamainternmed.2013.2152 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 153NZ UT WOS:000319610400011 PM 23358784 ER PT J AU Bangsberg, DR Haberer, JE AF Bangsberg, David R. Haberer, Jessica E. TI Lifetime HIV Antiretroviral Therapy Adherence Intervention Timing Is Everything SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID EXPECTANCY; RESISTANCE; TRIALS; UGANDA; TIME C1 [Bangsberg, David R.; Haberer, Jessica E.] Massachusetts Gen Hosp MGH Ctr Global Hlth, Dept Med, Boston, MA USA. [Bangsberg, David R.; Haberer, Jessica E.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Bangsberg, David R.] Ragon Inst MGH Massachusetts Inst Technol & Harva, Charlestown, MA USA. [Bangsberg, David R.] Mbarara Univ Sci & Technol, Fac Med, Mbarara, Uganda. RP Bangsberg, DR (reprint author), MGH Ctr Global Hlth, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM dbangsberg@partners.org FU NIMH NIH HHS [K24 MH087227, K23 MH087228, K-24 MH 087227, K-23 MH 087228, MH 54807] NR 11 TC 1 Z9 1 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD FEB 25 PY 2013 VL 173 IS 4 BP 306 EP 307 DI 10.1001/jamainternmed.2013.2858 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 153NZ UT WOS:000319610400012 PM 23358810 ER PT J AU Udell, JA Steg, PG Bhatt, DL AF Udell, Jacob A. Steg, Philippe Gabriel Bhatt, Deepak L. TI Impact of Loneliness and Living Alone Reply SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Udell, Jacob A.] Univ Toronto, Womens Coll Hosp, Dept Med, Div Cardiovasc, Toronto, ON, Canada. [Steg, Philippe Gabriel] Univ Paris Diderot, Sorbonne Paris Cite, INSERM U698, Paris, France. [Steg, Philippe Gabriel] Hop Bichat Claude Bernard, AP HP, Dept Cardiol, F-75877 Paris, France. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. RP Bhatt, DL (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy, Boston, MA 02132 USA. EM dlbhattmd@post.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD FEB 25 PY 2013 VL 173 IS 4 BP 322 EP 323 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 153NZ UT WOS:000319610400023 PM 23440235 ER PT J AU Odden, MC Peralta, CA Covinsky, KE AF Odden, Michelle C. Peralta, Carmen A. Covinsky, Kenneth E. TI Walking Speed Is a Useful Marker of Frailty in Older Persons Reply SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Odden, Michelle C.] Oregon State Univ, Sch Biol & Populat Hlth Sci, Corvallis, OR 97330 USA. [Peralta, Carmen A.; Covinsky, Kenneth E.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Peralta, Carmen A.; Covinsky, Kenneth E.] San Francisco VA Med Ctr, Med Serv, San Francisco, CA USA. RP Odden, MC (reprint author), Oregon State Univ, Sch Biol & Populat Hlth Sci, 321 Milam Hall, Corvallis, OR 97330 USA. EM Michelle.Odden@oregonstate.edu NR 2 TC 1 Z9 1 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD FEB 25 PY 2013 VL 173 IS 4 BP 326 EP 326 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 153NZ UT WOS:000319610400029 ER PT J AU Yang, YF Cao, ZH Tian, L Garvey, WT Cheng, GJ AF Yang, Youfeng Cao, Zehong Tian, Ling Garvey, W. Timothy Cheng, Guangjie TI VPO1 Mediates ApoE Oxidation and Impairs the Clearance of Plasma Lipids SO PLOS ONE LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; VASCULAR PEROXIDASE 1; HEME-CONTAINING PEROXIDASE; APOLIPOPROTEIN-E; DEFICIENT MICE; CHOLESTEROL TRANSPORT; TNF-ALPHA; OX-LDL; ATHEROSCLEROSIS; MYELOPEROXIDASE AB Objective: ApoE is an abundant component of chylomicron, VLDL, IDL, and HDL. It binds to multiple types of lipids and is implicated in cholesterol and triglyceride homeostasis. Oxidation of ApoE plays a crucial role in the genesis of atherosclerosis. It is proposed that heme-containing peroxidases (hPx) are major mediators of lipoprotein oxidization. Vascular peroxidase 1 (VPO1) is a recently-discovered hPx, which is expressed in cardiovascular system, lung, liver etc. and secreted into plasma. Its plasma concentration is three orders of magnitude of that of myeloperoxidase. If VPO1 mediates ApoE oxidation and affects the lipid metabolism remains to be elucidated. Methods: Recombinant ApoE and VPO1 were expressed and purified from stably-expressing cell lines deriving from HEK293 cells. ApoE oxidation was carried out by VPO1 in the presence of H2O2 and chloride. ApoE oxidation was verified by a variety of approaches including immunoblot and amino acid analyses. To evaluate the functional changes in VPO1-oxidized ApoE, lipid emulsion particle binding assays were employed. Results: Oxidized ApoE binds weaker to lipid emulsion particles, which mimic the large lipid complexes in vivo. In lipid efflux assay, oxidized ApoE showed reduced capability in efflux of lipids from foam cells. Mice administrated with oxidized ApoE via blood exhibited weaker clearance ability of plasma lipids. Conclusions: Our data suggest that VPO1 is a new mediator regulating lipid homeostasis, implying a role in genesis and development of atherosclerosis. C1 [Yang, Youfeng; Cao, Zehong; Cheng, Guangjie] Univ Alabama Birmingham, Dept Med, Div Pulm Allergy & Crit Care Med, Birmingham, AL USA. [Tian, Ling; Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL USA. [Garvey, W. Timothy] Birmingham VA Med Ctr, Birmingham, AL USA. RP Cheng, GJ (reprint author), Univ Alabama Birmingham, Dept Med, Div Pulm Allergy & Crit Care Med, Birmingham, AL USA. EM gjcheng@uab.edu OI Cheng, Guangjie/0000-0002-9368-379X FU National Heart, Blood, and Lung Institute; National Institute of Allergy and Infectious Diseases, National Institutes of Health [R01 HL086836, R21AI101642]; National Institutes of Health [DK-083562, DK-038764]; Merit Review program of the Department of Veterans Affairs; UAB Diabetes Research and Training Center [P60-DK079626] FX This work was supported by the National Heart, Blood, and Lung Institute, and National Institute of Allergy and Infectious Diseases, National Institutes of Health under Award Number R01 HL086836 and R21AI101642 (to GC). WTG was supported by the National Institutes of Health (Award Number DK-083562 and DK-038764), the Merit Review program of the Department of Veterans Affairs, and the UAB Diabetes Research and Training Center (P60-DK079626). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 6 Z9 6 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 25 PY 2013 VL 8 IS 2 AR e57571 DI 10.1371/journal.pone.0057571 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 115ZB UT WOS:000316849500115 PM 23451244 ER PT J AU Jordaan, G Liao, W Sharma, S AF Jordaan, Gwen Liao, Wei Sharma, Sanjai TI E-cadherin gene re-expression in chronic lymphocytic leukemia cells by HDAC inhibitors SO BMC CANCER LA English DT Article DE CLL; E-cadherin; Aberrant splicing; Nonsense mediated decay; Chromatin modeling; HDAC inhibitors; Wnt pathway ID WNT SIGNALING PATHWAY; BETA-CATENIN; HISTONE DEACETYLASE; CANCER; EXPRESSION; EPIGENETICS; ACTIVATION; CHROMATIN; TRANSACTIVATION; IDENTIFICATION AB Background: The tumor suppressor gene E-cadherin gene is frequently silenced in chronic lymphocytic leukemia (CLL) cells and results in wnt-pathway activation. We analyzed the role of histone epigenetic modifications in E-cadherin gene silencing. Methods: CLL specimens were treated with histone deacetylase inhibitor (HDACi) MS-275 and analyzed for E-cadherin expression with western blot and RT-PCR analysis. The downstream effects of HDACi treated leukemic cells were studied by analyzing the effect on wnt-pathway signaling. HDACi induced alterations in E-cadherin splicing were investigated by transcript specific real time PCR analysis. Results: Treatment of CLL specimens with histone deacetylase inhibitors (HDACi) treatment resulted in an increase of the E-cadherin RNA transcript (5 to 119 fold increase, n=10) in eight out of ten CLL specimens indicating that this gene is down regulated by histone hypoacetylation in a majority of CLL specimens. The E-cadherin re-expression in CLL specimens was noted by western blot analysis as well. Besides epigenetic silencing another mechanism of E-cadherin inactivation is aberrant exon 11 splicing resulting in an alternatively spliced transcript that lacks exon 11 and is degraded by the non-sense mediated decay (NMD) pathway. Our chromatin immunoprecipitation experiments show that HDACi increased the acetylation of histones H3 and H4 in the E-cadherin promoter region. This also affected the E-cadherin exon 11 splicing pattern as HDACi treated CLL specimens preferentially expressed the correctly spliced transcript and not the exon 11 skipped aberrant transcript. The re-expressed E-cadherin binds to beta-catenin with inhibition of the active wnt-beta-catenin pathway in these cells. This resulted in a down regulation of two wnt target genes, LEF and cyclinD1 and the wnt pathway reporter. Conclusion: The E-cadherin gene is epigenetically modified and hypoacetylated in CLL leukemic cells. Treatment of CLL specimens with HDACi MS-275 activates transcription from this silent gene with expression of more correctly spliced E-cadherin transcripts as compared to the aberrant exon11 skipped transcripts that in turn inhibits the wnt signaling pathway. The data highlights the role of epigenetic modifications in altering gene splicing patterns. C1 [Jordaan, Gwen; Liao, Wei; Sharma, Sanjai] Univ Calif Los Angeles, Sch Med, Div Hematol Oncol, Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA 90073 USA. RP Sharma, S (reprint author), Univ Calif Los Angeles, Sch Med, Div Hematol Oncol, Greater Los Angeles VA Healthcare Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM sasharma@mednet.ucla.edu FU Flight Attendant Medical Research Institute Fund (FAMRI); Veterans Administration Merit Review Grant FX The authors thank Dr. Alan Lichtenstein for clinical samples and useful discussions. This work was supported by a grant from Flight Attendant Medical Research Institute Fund (FAMRI) and Veterans Administration Merit Review Grant to SS. NR 55 TC 9 Z9 11 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD FEB 25 PY 2013 VL 13 AR 88 DI 10.1186/1471-2407-13-88 PG 11 WC Oncology SC Oncology GA 099RD UT WOS:000315638000001 PM 23432814 ER PT J AU Pereira, MJN Ouyang, B Sundback, CA Lang, N Friehs, I Mureli, S Pomerantseva, I McFadden, J Mochel, MC Mwizerwa, O del Nido, P Sarkar, D Masiakos, PT Langer, R Ferreira, LS Karp, JM AF Pereira, Maria Jose Nunes Ouyang, Ben Sundback, Cathryn A. Lang, Nora Friehs, Ingeborg Mureli, Shwetha Pomerantseva, Irina McFadden, Jacob Mochel, Mark C. Mwizerwa, Olive del Nido, Pedro Sarkar, Debanjan Masiakos, Peter T. Langer, Robert Ferreira, Lino S. Karp, Jeffrey M. TI A Highly Tunable Biocompatible and Multifunctional Biodegradable Elastomer SO ADVANCED MATERIALS LA English DT Article DE elastomers; biodegradable polymers; biocompatible materials; drug delivery; biomacromolecules ID POLY(GLYCEROL SEBACATE); MYOCARDIAL-INFARCTION; TISSUE; DEGRADATION; POLYURETHANE; DELIVERY; BEHAVIOR; PATCH C1 [Pereira, Maria Jose Nunes; Ouyang, Ben; Mureli, Shwetha; Sarkar, Debanjan; Karp, Jeffrey M.] Harvard Univ, Harvard MIT Div Hlth Sci & Technol, Brigham & Womens Hosp,Sch Med, Div Biomed Engn,Ctr Regenerat Therapeut,Dept Med, Cambridge, MA 02139 USA. [Pereira, Maria Jose Nunes; Ferreira, Lino S.] Univ Coimbra, CNC Ctr Neurosci & Cell Biol, Biocant Biotechnol Innovat Ctr, P-3004517 Coimbra, Portugal. [Sundback, Cathryn A.; Pomerantseva, Irina; McFadden, Jacob; Mwizerwa, Olive; Masiakos, Peter T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA. [Lang, Nora; Friehs, Ingeborg; del Nido, Pedro] Harvard Univ, Childrens Hosp Boston, Sch Med, Dept Cardiac Surg, Boston, MA 02115 USA. [Mochel, Mark C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sarkar, Debanjan] SUNY Buffalo, Dept Biomed Engn, Buffalo, NY 14260 USA. [Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Langer, Robert] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. RP Ferreira, LS (reprint author), Univ Coimbra, CNC Ctr Neurosci & Cell Biol, Biocant Biotechnol Innovat Ctr, P-3004517 Coimbra, Portugal. EM lino@biocant.pt; jkarp@rics.bwh.harvard.edu RI Sarkar, Debanjan/C-6093-2017; OI Sarkar, Debanjan/0000-0002-6666-3152; ferreira, lino/0000-0001-8985-9302 FU National Institutes of Health [GM086433, DE013023]; Portuguese Foundation for Science and Technology [SFR/BD/43013/2008]; MIT-Portugal program (bioengineering focus area) FX We would like to thank Admet Inc. for generously providing an eXpert 7601 mechanical tester that was instrumental for this work. This work was supported by National Institutes of Health grant GM086433 to J.M.K. and National Institutes of Health grant DE013023 to R. L. M.J.P. acknowledges the Portuguese Foundation for Science and Technology (fellowship SFR/BD/43013/2008) and the MIT-Portugal program (bioengineering focus area). NR 27 TC 29 Z9 29 U1 13 U2 147 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 0935-9648 J9 ADV MATER JI Adv. Mater. PD FEB 25 PY 2013 VL 25 IS 8 BP 1209 EP 1215 DI 10.1002/adma.201203824 PG 7 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 092ES UT WOS:000315102600020 PM 23239051 ER PT J AU Friebely, J Rigotti, NA Chang, YC Hall, N Weiley, V Dempsey, J Hipple, B Nabi-Burza, E Murphy, S Woo, H Winickoff, JP AF Friebely, Joan Rigotti, Nancy A. Chang, Yuchiao Hall, Nicole Weiley, Victoria Dempsey, Janelle Hipple, Bethany Nabi-Burza, Emara Murphy, Sybil Woo, Heide Winickoff, Jonathan P. TI Parent smoker role conflict and planning to quit smoking: a cross-sectional study SO BMC PUBLIC HEALTH LA English DT Article DE Parent smoker identity; Parent smoker role conflict; Tobacco smoke exposure; Readiness to quit; Stages of change; Tobacco control; Pediatrics; Smoking cessation; Parent child dyad ID ENVIRONMENTAL TOBACCO-SMOKE; CHILDREN; IDENTITY; INTERVENTION; ASSOCIATION; CESSATION; EXPOSURE; STAGE AB Background: Role conflict can motivate behavior change. No prior studies have explored the association between parent/smoker role conflict and readiness to quit. The objective of the study is to assess the association of a measure of parent/smoker role conflict with other parent and child characteristics and to test the hypothesis that parent/smoker role conflict is associated with a parent's intention to quit smoking in the next 30 days. As part of a cluster randomized controlled trial to address parental smoking (Clinical Effort Against Secondhand Smoke Exposure-CEASE), research assistants completed exit interviews with 1980 parents whose children had been seen in 20 Pediatric Research in Office Settings (PROS) practices and asked a novel identity-conflict question about "how strongly you agree or disagree" with the statement, "My being a smoker gets in the way of my being a parent." Response choices were dichotomized as "Strongly Agree" or "Agree" versus "Disagree" or "Strongly Disagree" for the analysis. Parents were also asked whether they were "seriously planning to quit smoking in 30 days." Chi-square and logistic regression were performed to assess the association between role conflict and other parent/children characteristics. A similar strategy was used to determine whether role conflict was independently associated with intention to quit in the next 30 days. Methods: As part of a RTC in 20 pediatric practices, exit interviews were held with smoking parents after their child's exam. Parents who smoked were asked questions about smoking behavior, smoke-free home and car rules, and role conflict. Role conflict was assessed with the question, "Please tell me how strongly you agree or disagree with the statement: 'My being a smoker gets in the way of my being a parent.' (Answer choices were: "Strongly agree, Agree, Disagree, Strongly Disagree.") Results: Of 1980 eligible smokers identified, 1935 (97%) responded to the role-conflict question, and of those, 563 (29%) reported experiencing conflict. Factors that were significantly associated with parent/smoker role conflict in the multivariable model included: being non-Hispanic white, allowing home smoking, the child being seen that day for a sick visit, parents receiving any assistance for their smoking, and planning to quit in the next 30 days. In a separate multivariable logistic regression model, parent/smoker role conflict was independently associated with intention to quit in the next 30 days [AOR 2.25 (95% CI 1.80-2.18)]. Conclusion: This study demonstrated an association between parent/smoker role conflict and readiness to quit. Interventions that increase parent/smoker role conflict might act to increase readiness to quit among parents who smoke. C1 [Friebely, Joan; Hall, Nicole; Dempsey, Janelle; Hipple, Bethany; Nabi-Burza, Emara; Murphy, Sybil; Winickoff, Jonathan P.] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA 02114 USA. [Weiley, Victoria; Woo, Heide] Amer Acad Pediat, Pediat Res Off Settings, Elk Grove Village, IL USA. [Rigotti, Nancy A.; Chang, Yuchiao] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Winickoff, Jonathan P.] Amer Acad Pediat, AAP Richmond Ctr Excellence, Elk Grove Village, IL USA. [Friebely, Joan; Rigotti, Nancy A.; Hall, Nicole; Hipple, Bethany; Nabi-Burza, Emara; Murphy, Sybil; Winickoff, Jonathan P.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. RP Winickoff, JP (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA 02114 USA. EM jwinickoff@partners.org FU National Institutes of Health NCI [R01CA127127]; National Institute on Drug Abuse; Agency for Healthcare Research and Quality; American Academy of Pediatrics (AAP); Flight Attendant Medical Research Institute; Pediatric Research in Office Settings (PROS) Network from the HRSA MCHB [HRSA 5-UA6-10-001] FX This study was supported by the National Institutes of Health NCI grant R01CA127127 (to Dr. Winickoff), the National Institute on Drug Abuse, the Agency for Healthcare Research and Quality, and the American Academy of Pediatrics (AAP). This study was also partially supported by a grant from the Flight Attendant Medical Research Institute to the AAP Julius B. Richmond Center. In addition, the Pediatric Research in Office Settings (PROS) Network receives core funding from the HRSA MCHB (HRSA 5-UA6-10-001) and the AAP. The funders had no role in the design or conduct of the study; collection, management, analysis and interpretation of the data; or preparation, review and approval of the manuscript. We especially appreciate the efforts of the PROS practices and practitioners. The pediatric practices or individual practitioners who enrolled participants in the larger study are listed here by AAP Chapter: Alaska: Anchorage Pediatric Group, LLC (Anchorage); Connecticut: Hospital of Saint Raphaels (New Haven); Illinois: Community Health Improvement Center (Decatur); Maryland: Cambridge Pediatrics LLC (Waldorf); Massachusetts: Quabbins Pediatrics (Ware), RiverBend Medical Group - Springfield Office (Springfield); Missouri: Priority Care Pediatrics LLC (Kansas City); New Mexico: Las Vegas Clinic for Children and Youth; PA (Las Vegas); Ohio: Bryan Medical Group (Bryan), The Cleveland Clinic Wooster (Wooster); Oklahoma: Shawnee Medical Center Clinic (Shawnee); Oregon: Siskiyou Pediatric Clinic LLP (Grants Pass); Pennsylvania: Pennridge Pediatric Associates (Sellersville); South Carolina: Inlet Pediatrics (Murrells Inlet); South Dakota: Avera McGreevy Clinic (Sioux Falls); Tennessee: Raleigh Group PC (Memphis); Virginia: Pediatrics of Kempsville PC (Virginia Beach), Riverside Pediatric Center (Newport News), The Clinic (Richlands); West Virginia: Shenandoah Community Health Center (Martinsburg). NR 23 TC 7 Z9 7 U1 0 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD FEB 22 PY 2013 VL 13 AR 164 DI 10.1186/1471-2458-13-164 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 119TQ UT WOS:000317121000001 PM 23433098 ER PT J AU Teo, AKK Windmueller, R Johansson, BB Dirice, E Njolstad, PR Tjora, E Raeder, H Kulkarni, RN AF Teo, Adrian K. K. Windmueller, Rebecca Johansson, Bente B. Dirice, Ercument Njolstad, Pal R. Tjora, Erling Raeder, Helge Kulkarni, Rohit N. TI Derivation of Human Induced Pluripotent Stem Cells from Patients with Maturity Onset Diabetes of the Young SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEFINED FACTORS AB Maturity onset diabetes of the young (MODY) is an autosomal dominant disease. Despite extensive research, the mechanism by which a mutant MODY gene results in monogenic diabetes is not yet clear due to the inaccessibility of patient samples. Induced pluripotency and directed differentiation toward the pancreatic lineage are now viable and attractive methods to uncover the molecular mechanisms underlying MODY. Here we report, for the first time, the derivation of human induced pluripotent stem cells (hiPSCs) from patients with five types of MODY: MODY1 (HNF4A), MODY2 (GCK), MODY3 (HNF1A), MODY5 (HNF1B), and MODY8 (CEL) with a polycistronic lentiviral vector expressing a Cre-excisable human "stem cell cassette" containing the four reprogramming factors OCT4, KLF4, SOX2, and CMYC. These MODY-hiPSCs morphologically resemble human pluripotent stem cells (hPSCs), express pluripotency markers OCT4, SOX2, NANOG, SSEA-4, and TRA-1-60, give rise to derivatives of the three germ layers in a teratoma assay, and are karyotypically normal. Overall, our MODYhiPSCs serve as invaluable tools to dissect the role of MODY genes in the development of pancreas and islet cells and to evaluate their significance in regulating beta cell function. This knowledge will aid future attempts aimed at deriving functional mature beta cells from hPSCs. C1 [Teo, Adrian K. K.; Windmueller, Rebecca; Dirice, Ercument; Kulkarni, Rohit N.] Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA. [Teo, Adrian K. K.; Windmueller, Rebecca; Dirice, Ercument; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Njolstad, Pal R.; Tjora, Erling; Raeder, Helge] Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway. [Johansson, Bente B.] Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway. [Johansson, Bente B.; Njolstad, Pal R.; Raeder, Helge] Univ Bergen, Dept Med 2, KG Jebsen Ctr Diabet Res, N-5021 Bergen, Norway. RP Kulkarni, RN (reprint author), Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM rohit.kulkarni@joslin.harvard.edu RI Teo, Adrian/A-4009-2013; Dirice, Ercument/B-2825-2017; OI Teo, Adrian/0000-0001-5901-7075; Johansson, Bente Berg/0000-0001-8893-1915 FU Harvard Stem Cell Institute [SG-0078-12-00]; National Institutes of Health [RO1 DK 67536] FX This work was supported in part by a grant from the Harvard Stem Cell Institute Agreement SG-0078-12-00 (to R.N.K.) and in part by National Institutes of Health Grant RO1 DK 67536 (to R.N.K.). NR 11 TC 31 Z9 33 U1 5 U2 11 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 22 PY 2013 VL 288 IS 8 BP 5353 EP 5356 DI 10.1074/jbc.C112.428979 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 095NY UT WOS:000315342500009 PM 23306198 ER PT J AU Hosokawa, H Dip, PV Merkulova, M Bakulina, A Zhuang, ZJ Khatri, A Jian, XY Keating, SM Bueler, SA Rubinstein, JL Randazzo, PA Ausiello, DA Gruber, G Marshansky, V AF Hosokawa, Hiroyuki Dip, Phat Vinh Merkulova, Maria Bakulina, Anastasia Zhuang, Zhenjie Khatri, Ashok Jian, Xiaoying Keating, Shawn M. Bueler, Stephanie A. Rubinstein, John L. Randazzo, Paul A. Ausiello, Dennis A. Grueber, Gerhard Marshansky, Vladimir TI The N Termini of a-Subunit Isoforms Are Involved in Signaling between Vacuolar H+-ATPase (V-ATPase) and Cytohesin-2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOTIDE EXCHANGE FACTOR; CIRCULAR-DICHROISM SPECTRA; PROTEIN SECONDARY STRUCTURE; VESICULAR TRAFFICKING; ARF ACTIVATION; PROTON PUMPS; FACTOR ARNO; PH-SENSOR; RECEPTOR; A2-SUBUNIT AB Previously, we reported an acidification-dependent interaction of the endosomal vacuolar H+-ATPase (V-ATPase) with cytohesin-2, a GDP/GTP exchange factor (GEF), suggesting that it functions as a pH-sensing receptor. Here, we have studied the molecular mechanism of signaling between the V-ATPase, cytohesin-2, and Arf GTP-binding proteins. We found that part of the N-terminal cytosolic tail of the V-ATPase a2-subunit (a2N), corresponding to its first 17 amino acids (a2N(1-17)), potently modulates the enzymatic GDP/GTP exchange activity of cytohesin-2. Moreover, this peptide strongly inhibits GEF activity via direct interaction with the Sec7 domain of cytohesin-2. The structure of a2N(1-17) and its amino acids Phe(5), Met(10), and Gln(14) involved in interaction with Sec7 domain were determined by NMR spectroscopy analysis. In silico docking experiments revealed that part of the V-ATPase formed by its a2N(1-17) epitope competes with the switch 2 region of Arf1 and Arf6 for binding to the Sec7 domain of cytohesin-2. The amino acid sequence alignment and GEF activity studies also uncovered the conserved character of signaling between all four (a1-a4) a-subunit isoforms of mammalian V-ATPase and cytohesin-2. Moreover, the conserved character of this phenomenon was also confirmed in experiments showing binding of mammalian cytohesin-2 to the intact yeast V-ATPase holo-complex. Thus, here we have uncovered an evolutionarily conserved function of the V-ATPase as a novel cytohesin-signaling receptor. C1 [Hosokawa, Hiroyuki; Merkulova, Maria; Zhuang, Zhenjie; Ausiello, Dennis A.; Marshansky, Vladimir] Massachusetts Gen Hosp, Simches Res Ctr, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. [Hosokawa, Hiroyuki; Merkulova, Maria; Zhuang, Zhenjie; Ausiello, Dennis A.; Marshansky, Vladimir] Massachusetts Gen Hosp, Simches Res Ctr, Div Nephrol, Boston, MA 02114 USA. [Ausiello, Dennis A.; Marshansky, Vladimir] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Dip, Phat Vinh; Grueber, Gerhard] Nanyang Technol Univ, Sch Biol Sci, Div Struct Biol & Biochem, Singapore 637551, Singapore. [Bakulina, Anastasia] State Res Ctr Virol & Biotechnol VECTOR, Koltsov 630559, Novosibirsk Reg, Russia. [Khatri, Ashok] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Khatri, Ashok] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Jian, Xiaoying; Randazzo, Paul A.] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Keating, Shawn M.; Bueler, Stephanie A.; Rubinstein, John L.] Hosp Sick Children, Res Inst, Mol Struct & Funct Program, Toronto, ON M5G 1X8, Canada. [Keating, Shawn M.; Rubinstein, John L.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1X8, Canada. RP Marshansky, V (reprint author), Massachusetts Gen Hosp, Simches Res Ctr, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. EM Marshansky.Vladimir@mgh.harvard.edu RI Bakulina, Anastasia/A-6215-2014; OI Dip, Phat Vinh/0000-0002-1535-9644; Rubinstein, John/0000-0003-0566-2209 FU National Institutes of Health Grant [DK038452, DK57521]; Boston Area Diabetes Endocrinology Research Center Grant [DK057521-08]; National Institutes of Health Intramural Program of NCI; Canadian Institutes of Health Research Grant [MOP 81294]; A*STAR Biomedical Research Council Grant [09/1/22/19/609]; Center for the Study of Inflammatory Bowel Disease [DK43351]; Singapore International Graduate Award (SINGA) [20092010S10303] FX This work was supported, in whole or in part, by National Institutes of Health Grant DK038452. This work was also supported by Boston Area Diabetes Endocrinology Research Center Grant DK057521-08 (to V. M.).; Recipient of a Singapore International Graduate Award (SINGA, 20092010S10303).; Supported by the National Institutes of Health Intramural Program of NCI.; Supported by Canadian Institutes of Health Research Grant MOP 81294.; Supported by A*STAR Biomedical Research Council Grant 09/1/22/19/609.; We thank Dr. Dennis Brown for critical reading and constructive suggestions during the preparation of this manuscript. We are grateful to Dr. Masamitsu Futai and Dr. James Casanova for providing cDNA encoding V-ATPase a2-isoform and cytohesin-2, respectively. We are also grateful to Dr. Sylvain Bourgoin for the generous gift of SecinH3 inhibitor. The Microscopy Core Facility of the Program in Membrane Biology received additional support from National Institutes of Health Grant DK57521 to BADERC and Grant DK43351 to Center for the Study of Inflammatory Bowel Disease. NR 68 TC 21 Z9 21 U1 1 U2 15 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 22 PY 2013 VL 288 IS 8 BP 5896 EP 5913 DI 10.1074/jbc.M112.409169 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 095NY UT WOS:000315342500059 PM 23288846 ER PT J AU Aukrust, I Bjorkhaug, L Negahdar, M Molnes, J Johansson, BB Muller, Y Haas, W Gygi, SP Sovik, O Flatmark, T Kulkarni, RN Njolstad, PR AF Aukrust, Ingvild Bjorkhaug, Lise Negahdar, Maria Molnes, Janne Johansson, Bente B. Muller, Yvonne Haas, Wilhelm Gygi, Steven P. Sovik, Oddmund Flatmark, Torgeir Kulkarni, Rohit N. Njolstad, Pal R. TI SUMOylation of Pancreatic Glucokinase Regulates Its Cellular Stability and Activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DIABETES-MELLITUS; ISLET GLUCOKINASE; PROTEIN STABILITY; ENZYME UBC9; BETA-CELLS; GLUCOSE; GENE; SUMO; IDENTIFICATION; ACTIVATION AB Glucokinase is the predominant hexokinase expressed in hepatocytes and pancreatic beta-cells, with a pivotal role in regulating glucose-stimulated insulin secretion, illustrated by glucokinase gene mutations causing monogenic diabetes and congenital hyperinsulinemic hypoglycemia. A complex tissue-specific network of mechanisms regulates this enzyme, and a major unanswered question in glucokinase biology is how post-translational modifications control the function of the enzyme. Here, we show that the pancreatic isoform of human glucokinase is SUMOylated in vitro, using recombinant enzymes, and in insulin-secreting model cells. Three N-terminal lysines unique for the pancreatic isoform (Lys-12/Lys-13 and/or Lys-15) may represent one SUMOylation site, with an additional site (Lys-346) common for the pancreatic and the liver isoform. SUMO-1 and E2 overexpression stabilized preferentially the wild-type human pancreatic enzyme in MIN6 beta-cells, and SUMOylation increased the catalytic activity of recombinant human glucokinase in vitro and also of glucokinase in target cells. Small ubiquitin-like modifier conjugation represents a novel form of post-translational modification of the enzyme, and it may have an important regulatory function in pancreatic beta-cells. C1 [Aukrust, Ingvild; Bjorkhaug, Lise; Negahdar, Maria; Molnes, Janne; Johansson, Bente B.; Muller, Yvonne; Sovik, Oddmund; Njolstad, Pal R.] KG Jebsen Ctr Diabet Res, Dept Clin Med, N-5020 Bergen, Norway. [Aukrust, Ingvild; Bjorkhaug, Lise; Molnes, Janne; Muller, Yvonne; Flatmark, Torgeir] Univ Bergen, Dept Biomed, N-5020 Bergen, Norway. [Aukrust, Ingvild; Bjorkhaug, Lise; Negahdar, Maria; Johansson, Bente B.; Muller, Yvonne] Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway. [Aukrust, Ingvild; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Joslin Diabet Ctr, Boston, MA 02215 USA. [Molnes, Janne; Johansson, Bente B.; Njolstad, Pal R.] Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway. [Haas, Wilhelm; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Bjorkhaug, L (reprint author), Univ Bergen, Dept Clin Med, N-5020 Bergen, Norway. EM lise.gundersen@pedi.uib.no; pal.njolstad@uib.no OI Johansson, Bente Berg/0000-0001-8893-1915; Gundersen, Lise Bjorkhaug/0000-0002-9695-4559 FU National Institutes of Health [RO1 DK067536]; Helse Vest, Innovest; Novo Nordisk Foundation; Bergen Medical Research Foundation; University of Bergen; Nils Norman Foundation; Norwegian Diabetes Association; Meltzer Foundation; KG Jebsen Foundation; European Research Council FX This work was supported, in whole or in part, by National Institutes of Health Grant RO1 DK067536 (to R.N.K.). This work was also supported by Helse Vest, Innovest, the Novo Nordisk Foundation, the Bergen Medical Research Foundation, the University of Bergen, the Nils Norman Foundation, the Norwegian Diabetes Association, the Meltzer Foundation, the KG Jebsen Foundation, and the European Research Council (to P.R.N.). NR 57 TC 14 Z9 14 U1 0 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 22 PY 2013 VL 288 IS 8 BP 5951 EP 5962 DI 10.1074/jbc.M112.393769 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 095NY UT WOS:000315342500063 PM 23297408 ER PT J AU Biju, KC Santacruz, RA Chen, C Zhou, Q Yao, JM Rohrabaugh, SL Clark, RA Roberts, JL Phillips, KA Imam, SZ Li, SL AF Biju, K. C. Santacruz, Rene A. Chen, Cang Zhou, Qing Yao, Jiemin Rohrabaugh, Sara L. Clark, Robert A. Roberts, James L. Phillips, Kimberley A. Imam, Syed Z. Li, Senlin TI Bone marrow-derived microglia-based neurturin delivery protects against dopaminergic neurodegeneration in a mouse model of Parkinson's disease SO NEUROSCIENCE LETTERS LA English DT Article DE Parkinson's disease; Gene therapy; Neurodegenerative disease; Neurotrophic factors; Dopamine ID GENE-THERAPY; NEUROTROPHIC FACTOR; TRANSPLANTATION; GDNF; CNS AB Although neurotrophic factors have long been recognized as potent agents for protecting against neuronal degeneration, clinical success in treating Parkinson's disease and other neurodegenerative disorders has been hindered by difficulties in delivery of trophic factors across the blood brain barrier (BBB). Bone marrow hematopoietic stem cell-based gene therapy is emerging as a promising tool for overcoming drug delivery problems, as myeloid cells can cross the BBB and are recruited in large numbers to sites of neurodegeneration, where they become activated microglia that can secrete trophic factors. We tested the efficacy of bone marrow-derived microglial delivery of neurturin (NTN) in protecting dopaminergic neurons against neurotoxin-induced death in mice. Bone marrow cells were transduced ex vivo with lentivirus expressing the NTN gene driven by a synthetic macrophage-specific promoter. Infected bone marrow cells were then collected and transplanted into recipient animals. Eight weeks after transplantation, the mice were injected with the neurotoxin1-methyl-4-phenyl-1,2,3,6-tetrahydropuridine (MPTP) for seven days to induce dopaminergic neurodegeneration. Microglia-mediated NTN delivery dramatically ameliorated MPTP-induced degeneration of tyrosine hydroxylase (TH)-positive neurons of the substantia nigra and their terminals in the striatum. Microglia-mediated NTN delivery also induced significant recovery of synaptic marker staining in the striatum of MPTP-treated animals. Functionally, NTN treatment restored MPTP-induced decline in general activity, rearing behavior, and food intake. Thus, bone marrow-derived microglia can serve as cellular vehicles for sustained delivery of neurotrophic factors capable of mitigating dopaminergic injury. Published by Elsevier Ireland Ltd. C1 [Biju, K. C.; Santacruz, Rene A.; Chen, Cang; Zhou, Qing; Yao, Jiemin; Rohrabaugh, Sara L.; Clark, Robert A.; Li, Senlin] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Santacruz, Rene A.; Li, Senlin] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Roberts, James L.; Li, Senlin] Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Clark, Robert A.; Roberts, James L.; Li, Senlin] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Roberts, James L.] Trinity Univ, Dept Biol, San Antonio, TX 78212 USA. [Phillips, Kimberley A.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA. [Imam, Syed Z.] US FDA, Div Neurotoxicol, NCTR, Jefferson, AR USA. RP Li, SL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM lis1@uthscsa.edu OI Phillips, Kimberley/0000-0002-5517-3596 FU NIH [NS046004, AG024579]; Veterans Health Administration; NIH Clinical and Translational Science Award [UL1 TR0000149] FX This work was supported by NIH grants (NS046004 and AG024579), a Merit Review Grant from the Veterans Health Administration, and a NIH Clinical and Translational Science Award (UL1 TR0000149) Pilot Project grant awarded to S.L. NR 23 TC 11 Z9 11 U1 0 U2 13 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD FEB 22 PY 2013 VL 535 BP 24 EP 29 DI 10.1016/j.neulet.2012.12.034 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 095XK UT WOS:000315368100005 PM 23295906 ER PT J AU Huang, FW Hodis, E Xu, MJ Kryukov, GV Chin, L Garraway, LA AF Huang, Franklin W. Hodis, Eran Xu, Mary Jue Kryukov, Gregory V. Chin, Lynda Garraway, Levi A. TI Highly Recurrent TERT Promoter Mutations in Human Melanoma SO SCIENCE LA English DT Article AB Systematic sequencing of human cancer genomes has identified many recurrent mutations in the protein-coding regions of genes but rarely in gene regulatory regions. Here, we describe two independent mutations within the core promoter of telomerase reverse transcriptase (TERT), the gene coding for the catalytic subunit of telomerase, which collectively occur in 50 of 70 (71%) melanomas examined. These mutations generate de novo consensus binding motifs for E-twenty-six (ETS) transcription factors, and in reporter assays, the mutations increased transcriptional activity from the TERT promoter by two-to fourfold. Examination of 150 cancer cell lines derived from diverse tumor types revealed the same mutations in 24 cases (16%), with preliminary evidence of elevated frequency in bladder and hepatocellular cancer cells. Thus, somatic mutations in regulatory regions of the genome may represent an important tumorigenic mechanism. C1 [Huang, Franklin W.; Hodis, Eran; Xu, Mary Jue; Kryukov, Gregory V.; Garraway, Levi A.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Huang, Franklin W.; Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Huang, Franklin W.; Hodis, Eran; Xu, Mary Jue; Garraway, Levi A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hodis, Eran; Xu, Mary Jue] MIT, Harvard Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA. [Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Houston, TX 77030 USA. RP Garraway, LA (reprint author), Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. EM levi_garraway@dfci.harvard.edu RI Kryukov, Gregory/A-9592-2008; Waha, Andreas/J-2950-2014 FU NIH [T32 CA009172]; Mittelman Family Fellowship; National Institute of General Medical Sciences [T32GM07753]; American Cancer Society; NIH New Innovator Award [DP2OD002750]; National Cancer Institute [R33CA126674]; Novartis Institutes for Biomedical Research; Melanoma Research Alliance; Starr Cancer Consortium FX We thank S. N. Wagner, D. Schadendorf, J. A. Wargo, and D. S. B. Hoon for contribution of samples; K. Cibulskis for assistance with whole-genome sequence data analysis; and E. Nickerson for coordination of validation/extension studies. This work was supported by NIH grant T32 CA009172 (F. W. H.), the Mittelman Family Fellowship (F. W. H.), National Institute of General Medical Sciences grant T32GM07753 (E. H.), the American Cancer Society (M. J. X.), NIH New Innovator Award DP2OD002750 (L. A. G.), National Cancer Institute grant R33CA126674 (L. A. G.), the Novartis Institutes for Biomedical Research (G. V. K. and L. A. G.), the Melanoma Research Alliance (L. A. G.), and the Starr Cancer Consortium (L. C. and L. A. G.). L. A. G. is on the Scientific Advisory Board of Millennium Pharmaceuticals, is a paid consultant for and holds equity in Foundation Medicine, and is a paid consultant for and sponsored research recipient from Novartis. The BAM files for the CCLE Whole Genome Sequencing data corresponding to the TERT locus can be accessed at ftp://tertguest:broad@ftp.broadinstitute.org. NR 10 TC 523 Z9 533 U1 6 U2 81 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD FEB 22 PY 2013 VL 339 IS 6122 BP 957 EP 959 DI 10.1126/science.1229259 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 092UX UT WOS:000315149600049 PM 23348506 ER PT J AU Amabile, G Welner, RS Nombela-Arrieta, C D'Alise, AM Di Ruscio, A Ebralidze, AK Kraytsberg, Y Ye, M Kocher, O Neuberg, DS Khrapko, K Silberstein, LE Tenen, DG AF Amabile, Giovanni Welner, Robert S. Nombela-Arrieta, Cesar D'Alise, Anna Morena Di Ruscio, Annalisa Ebralidze, Alexander K. Kraytsberg, Yevgenya Ye, Min Kocher, Olivier Neuberg, Donna S. Khrapko, Konstantin Silberstein, Leslie E. Tenen, Daniel G. TI In vivo generation of transplantable human hematopoietic cells from induced pluripotent stem cells SO BLOOD LA English DT Article ID HUMAN FIBROBLASTS; DIFFERENTIATION; PROGENITORS; BLOOD; VITRO; INDUCTION; EFFICIENT; MOUSE; MYC AB Lineage-restricted cells can be reprogrammed to a pluripotent state known as induced pluripotent stem (iPS) cells through overexpression of 4 transcription factors. iPS cells are similar to human embryonic stem (hES) cells and have the same ability to generate all the cells of the human body, including blood cells. However, this process is extremely inefficient and to date has been unsuccessful at differentiating iPS into hematopoietic stem cells (HSCs). We hypothesized that iPS cells, injected into NOD. Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ immunocompromised (NSG) mice could give rise to hematopoietic stem/progenitor cells (HSPCs) during teratoma formation. Here, we report a novel in vivo system in which human iPS cells differentiate within teratomas to derive functional myeloid and lymphoid cells. Similarly, HSPCs can be isolated from teratoma parenchyma and reconstitute a human immune system when transplanted into immunodeficient mice. Our data provide evidence that in vivo generation of patient customized cells is feasible, providing materials that could be useful for transplantation, human antibody generation, and drug screening applications. C1 [Amabile, Giovanni; Welner, Robert S.; D'Alise, Anna Morena; Di Ruscio, Annalisa; Ebralidze, Alexander K.; Kraytsberg, Yevgenya; Ye, Min; Kocher, Olivier; Khrapko, Konstantin; Tenen, Daniel G.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Amabile, Giovanni; Welner, Robert S.; Nombela-Arrieta, Cesar; D'Alise, Anna Morena; Di Ruscio, Annalisa; Ebralidze, Alexander K.; Kraytsberg, Yevgenya; Ye, Min; Silberstein, Leslie E.; Tenen, Daniel G.] Harvard Stem Cell Inst, Boston, MA USA. [Amabile, Giovanni; Welner, Robert S.; Di Ruscio, Annalisa; Ebralidze, Alexander K.; Kraytsberg, Yevgenya; Ye, Min; Khrapko, Konstantin] Beth Israel Deaconess Med Ctr, Dept Hematol Oncol, Boston, MA 02215 USA. [Nombela-Arrieta, Cesar; Silberstein, Leslie E.] Childrens Hosp, Dept Lab Med, Joint Program Transfus Med, Boston, MA 02115 USA. [Neuberg, Donna S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Tenen, Daniel G.] Natl Univ Singapore, Canc Sci Inst, Singapore 117548, Singapore. RP Tenen, DG (reprint author), Harvard Univ, Sch Med, Harvard Stem Cell Inst, Ctr Life Sci, 3 Blackfan Circle, Boston, MA 02115 USA. EM dtenen@bidmc.harvard.edu OI Nombela-Arrieta, Cesar/0000-0003-0415-259X; Tenen, Daniel/0000-0002-6423-3888 FU Collegio Ghislieri fellowship program; Jose Carreras fellowship program; long-term Human Frontier fellowship; Harvard Stem Cell Institute; Amelia Peabody Foundation FX The authors are grateful to Paul Kincade (OMRF) for providing the OP9, OP9-GFP, OP9W3a, and OP9D cell lines and for critical reading of the paper. The authors thank Riccardo Cortese and Alfredo Nicosia (CEINGE) for sharing protocols and suggestions during immunizations experiments. The authors are grateful to Linda Clayton (Dana-Farber Cancer Institute) for suggestions regarding the T-cell experiments. G. A. was supported by the Collegio Ghislieri fellowship program. R. S. W. was supported by the Jose Carreras fellowship program. C.N.A. was supported by the long-term Human Frontier fellowship.; This work was supported by the Harvard Stem Cell Institute and a grant from the Amelia Peabody Foundation. NR 38 TC 71 Z9 73 U1 6 U2 38 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 21 PY 2013 VL 121 IS 8 BP 1255 EP 1264 DI 10.1182/blood-2012-06-434407 PG 10 WC Hematology SC Hematology GA 182NK UT WOS:000321750000010 PM 23212524 ER PT J AU Ghobrial, IM Campigotto, F Murphy, TJ Boswell, EN Banwait, R Azab, F Chuma, S Kunsman, J Donovan, A Masood, F Warren, D Rodig, S Anderson, KC Richardson, PG Weller, E Matous, J AF Ghobrial, Irene M. Campigotto, Federico Murphy, Timothy J. Boswell, Erica N. Banwait, Ranjit Azab, Feda Chuma, Stacey Kunsman, Janet Donovan, Amanda Masood, Farzana Warren, Diane Rodig, Scott Anderson, Kenneth C. Richardson, Paul G. Weller, Edie Matous, Jeffrey TI Results of a phase 2 trial of the single-agent histone deacetylase inhibitor panobinostat in patients with relapsed/refractory Waldenstrom macroglobulinemia SO BLOOD LA English DT Review ID CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; MULTIPLE-MYELOMA; HUMAN CANCER; II TRIAL; LBH589; MANAGEMENT; LYMPHOMA; UPDATE AB The present study aimed to determine the safety and activity of the histone deacetylase inhibitor panobinostat in patients with relapsed/refractory Waldenstrom macroglobulinemia (WM). Eligibility criteria included patients with relapsed/refractory WM with any number of prior therapies. Patients received panobinostat at 30 mg 3 times a week; 12 of 36 (33%) patients were enrolled at 25 mg dose. A total of 36 patients received therapy. The median age was 62 years (range, 47-80) and the median number of prior therapies was 3 (range, 1-8). All of the patients had received prior rituximab. Minimal response (MR) or better was achieved in 47% of patients (90% confidence interval [CI], 33-62), with 22% partial remissions and 25% MR. In addition, 18 (50%) patients achieved stable disease and none showed progression while on therapy. The median time to first response was 1.8 months (range, 1.7-3.2). The median progression-free survival was 6.6 months(90% CI, 5.5-14.8). Grade 3 and 4 toxicities included thrombocytopenia (67%), neutropenia (36%), anemia (28%), leukopenia (22%), and fatigue (11%). We conclude that panobinostat is an active therapeutic agent in patients with relapsed/refractory WM. This study (www.clinicaltrials.gov identifier: NCT00936611) establishes a role for histone deacetylase inhibitors as an active class of therapeutic agents in WM. C1 [Ghobrial, Irene M.; Boswell, Erica N.; Banwait, Ranjit; Azab, Feda; Chuma, Stacey; Kunsman, Janet; Donovan, Amanda; Masood, Farzana; Warren, Diane; Anderson, Kenneth C.; Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Campigotto, Federico; Weller, Edie] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Murphy, Timothy J.; Matous, Jeffrey] Rocky Mt Canc Ctr, Colorado Springs, CO USA. [Rodig, Scott] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM irene_ghobrial@dfci.harvard.edu FU Novartis [1R01F0003743]; International Waldenstrom Macroglobulinemia Foundation; Michelle and Steven Kirsch Laboratory for Waldenstrom Macroglobulinemia; Heje Fellowship for Waldenstrom FX This study was supported in part by a research grant from Novartis (1R01F0003743), the International Waldenstrom Macroglobulinemia Foundation, the Michelle and Steven Kirsch Laboratory for Waldenstrom Macroglobulinemia, and the Heje Fellowship for Waldenstrom. NR 26 TC 33 Z9 33 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD FEB 21 PY 2013 VL 121 IS 8 BP 1296 EP 1303 DI 10.1182/blood-2012-06-439307 PG 8 WC Hematology SC Hematology GA 182NK UT WOS:000321750000014 PM 23287861 ER PT J AU Salaverria, I Royo, C Carvajal-Cuenca, A Clot, G Navarro, A Valera, A Song, JY Woroniecka, R Rymkiewicz, G Klapper, W Hartmann, EM Sujobert, P Wlodarska, I Ferry, JA Gaulard, P Ott, G Rosenwald, A Lopez-Guillermo, A Quintanilla-Martinez, L Harris, NL Jaffe, ES Siebert, R Campo, E Bea, S AF Salaverria, Itziar Royo, Cristina Carvajal-Cuenca, Alejandra Clot, Guillem Navarro, Alba Valera, Alejandra Song, Joo Y. Woroniecka, Renata Rymkiewicz, Grzegorz Klapper, Wolfram Hartmann, Elena M. Sujobert, Pierre Wlodarska, Iwona Ferry, Judith A. Gaulard, Philippe Ott, German Rosenwald, Andreas Lopez-Guillermo, Armando Quintanilla-Martinez, Leticia Harris, Nancy L. Jaffe, Elaine S. Siebert, Reiner Campo, Elias Bea, Silvia TI CCND2 rearrangements are the most frequent genetic events in cyclin D1(-) mantle cell lymphoma SO BLOOD LA English DT Article ID NUCLEAR EXPRESSION; SOX11 EXPRESSION; GENOME; TARGET; OVEREXPRESSION; AMPLIFICATIONS; TRANSLOCATION; PATHOGENESIS; NEOPLASMS; DIAGNOSIS AB Cyclin D1(-) mantle cell lymphomas (MCLs) are not well characterized, in part because of the difficulties in their recognition. SOX11 has been identified recently as a reliable biomarker of MCL that is also expressed in the cyclin D1(-) variant. We investigated 40 lymphomas with MCL morphology and immunophenotype that were negative for cyclin D1 expression/t(11;14)(q13;q32) but positive for SOX11. These tumors presented clinically with generalized lymphadenopathy, advanced stage, and poor outcome (5-year overall survival, 48%). Chromosomal rearrangements of the CCND2 locus were detected in 55% of the cases, with an IG gene as partner in 18 of 22, in particular with light chains (10 IGK@ and 5 IGL@). No mutations in the phosphorylation motifs of CCND1, CCND2, or CCND3 were detected. The global genomic profile and the high complexity of the 32 cyclin D1(-)SOX11(+) MCL patients analyzed by copy number arrays were similar to the conventional cyclin D1(+)/SOX11(+) MCL. 17p deletions and high Ki67 expression conferred a significantly worse outcome for the patients. This comprehensive characterization of a large series of cyclin D1(-) MCL patients indicates that these tumors are clinically and biologically similar to the conventional cyclin D1(+) MCL and provides a basis for the proper identification and clinical management of these patients. C1 [Salaverria, Itziar; Royo, Cristina; Carvajal-Cuenca, Alejandra; Clot, Guillem; Navarro, Alba; Valera, Alejandra; Campo, Elias; Bea, Silvia] Univ Barcelona, Inst Invest Biomed August Pi & Sunyer, Dept Pathol, Hematopathol Unit,Hosp Clin, Barcelona, Spain. [Salaverria, Itziar; Siebert, Reiner] Univ Kiel, Univ Hosp Schleswig Holstein Campus Kiel, Inst Human Genet, Kiel, Germany. [Song, Joo Y.; Jaffe, Elaine S.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Woroniecka, Renata] Maria Sklodowska Curie Mem Inst & Oncol Ctr, Cytogenet Lab, Warsaw, Poland. [Rymkiewicz, Grzegorz] Maria Sklodowska Curie Mem Inst & Oncol Ctr, Dept Pathol, Warsaw, Poland. [Klapper, Wolfram] Univ Kiel, Hematopathol Sect, Dept Pathol, Kiel, Germany. [Klapper, Wolfram] Univ Kiel, Lymph Node Registry, Kiel, Germany. [Hartmann, Elena M.; Rosenwald, Andreas] Univ Wurzburg, Inst Pathol, Wurzburg, Germany. [Sujobert, Pierre; Gaulard, Philippe] Hop Henri Mondor, F-94010 Creteil, France. [Wlodarska, Iwona] Katholieke Univ Leuven, Ctr Human Genet, Louvain, Belgium. [Ferry, Judith A.; Harris, Nancy L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ott, German] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany. [Ott, German] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany. [Lopez-Guillermo, Armando] Hosp Clin Barcelona, Hematopathol Unit, Dept Hematol, Barcelona, Spain. [Quintanilla-Martinez, Leticia] Univ Tubingen, Inst Pathol, Tubingen, Germany. RP Bea, S (reprint author), Ctr Esther Koplowitz, 2nd Floor,Rossello 153, Barcelona 08036, Spain. EM sbea@clinic.cat RI Siebert, Reiner/A-8049-2010; Navarro, Alba/H-2611-2015; Royo, Cristina/H-3193-2015; SALAVERRIA, ITZIAR/L-2246-2015; Song, Joo/E-5356-2016; Jaffe, Elaine/G-8984-2014; Klapper, Wolfram/S-6314-2016; Bea, Silvia/K-7699-2014; OI Navarro, Alba/0000-0002-4041-0974; Royo, Cristina/0000-0002-1214-4656; SALAVERRIA, ITZIAR/0000-0002-2427-9822; Song, Joo/0000-0003-3497-2513; Jaffe, Elaine/0000-0003-4632-0301; Bea, Silvia/0000-0001-7192-2385; Campo, elias/0000-0001-9850-9793 FU Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias [PI08/0077, PI11/01177]; Alexander von Humboldt Foundation; Subprograma Juan de la Cierva Ministerio de Ciencia e Innovacion [JCI-2011-10232]; Instituto de Salud Carlos III, Beca Predoctoral de Formacion en Investigacion en Salud Comision Interministerial de Ciencia y Tecnologia Espanola [FI08/00347, SAF08/3630]; Red Tematica de Investigacion Cooperativa del Cancer [RD06/0020/0039 ISCIII]; Spanish Ministry of Science and Innovation; European Regional Development Fund (Unio Europea "Una manera de fer Europa") FX This study was supported by the Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias (PI08/0077; PI11/01177 to S. B.), Alexander von Humboldt Foundation (to I. S.) and Subprograma Juan de la Cierva Ministerio de Ciencia e Innovacion (JCI-2011-10232 to I. S.), Instituto de Salud Carlos III, Beca Predoctoral de Formacion en Investigacion en Salud (FI08/00347 to C. R.) Comision Interministerial de Ciencia y Tecnologia Espanola (SAF08/3630 to E. C.), Red Tematica de Investigacion Cooperativa del Cancer (RD06/0020/0039 ISCIII to E. C.), and the Spanish Ministry of Science and Innovation and European Regional Development Fund (Unio Europea "Una manera de fer Europa"). NR 33 TC 36 Z9 39 U1 1 U2 10 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 21 PY 2013 VL 121 IS 8 BP 1394 EP 1402 DI 10.1182/blood-2012-08-452284 PG 9 WC Hematology SC Hematology GA 182NK UT WOS:000321750000024 PM 23255553 ER PT J AU Gao, C Dimitrov, T Yong, KJ Tatetsu, H Jeong, HW Luo, HR Bradner, JE Tenen, DG Chai, L AF Gao, Chong Dimitrov, Todor Yong, Kol Jia Tatetsu, Hiro Jeong, Ha-won Luo, Hongbo R. Bradner, James E. Tenen, Daniel G. Chai, Li TI Targeting transcription factor SALL4 in acute myeloid leukemia by interrupting its interaction with an epigenetic complex SO BLOOD LA English DT Article ID GERM-CELL TUMORS; CHRONIC MYELOGENOUS LEUKEMIA; EARLY EMBRYONIC-DEVELOPMENT; HOMEOTIC GENE SPALT; YOLK-SAC TUMORS; ENDOMETRIAL CARCINOMA; DEACETYLASE COMPLEX; DIAGNOSTIC UTILITY; REPRESSOR COMPLEX; NERVOUS-SYSTEM AB An exciting recent approach to targeting transcription factors in cancer is to block formation of oncogenic complexes. We investigated whether interfering with the interaction of the transcription factor SALL4, which is critical for leukemic cell survival, and its epigenetic partner complex represents a novel therapeutic approach. The mechanism of SALL4 in promoting leukemogenesis is at least in part mediated by its repression of the tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) through its interaction with a histone deacetylase (HDAC) complex. In this study, we demonstrate that a peptide can compete with SALL4 in interacting with the HDAC complex and reverse its effect on PTEN repression. Treating SALL4-expressing malignant cells with this peptide leads to cell death that can be rescued by a PTEN inhibitor. The antileukemic effect of this peptide can be confirmed on primary human leukemia cells in culture and in vivo, and is identical to that of down-regulation of SALL4 in these cells using an RNAi approach. In summary, our results demonstrate a novel peptide that can block the specific interaction between SALL4 and its epigenetic HDAC complex in regulating its target gene, PTEN. Furthermore, targeting SALL4 with this approach could be an innovative approach in treating leukemia. (Blood. 2013;121(8):1413-1421) C1 [Gao, Chong; Dimitrov, Todor; Tatetsu, Hiro; Jeong, Ha-won; Chai, Li] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol,Joint Program Transfus Med, Boston, MA 02115 USA. [Yong, Kol Jia; Tenen, Daniel G.] Natl Univ Singapore, Canc Sci Inst Singapore, Ctr Translat Med, Singapore 117548, Singapore. [Luo, Hongbo R.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Lab Med, Boston, MA 02115 USA. [Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Tenen, Daniel G.] Harvard Stem Cell Inst, Boston, MA USA. RP Chai, L (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol,Joint Program Transfus Med, 75 Francis St, Boston, MA 02115 USA. EM lchai@partners.org OI Tenen, Daniel/0000-0002-6423-3888 FU National Institutes of Health [PO1 DK080665, RO1HL092437, PO1HL095489] FX This work was supported in part by the National Institutes of Health (grant PO1 DK080665 to D. G. T. and grants RO1HL092437 and PO1HL095489 to L.C.). NR 48 TC 20 Z9 24 U1 1 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 21 PY 2013 VL 121 IS 8 BP 1413 EP 1421 DI 10.1182/blood-2012-04-424275 PG 9 WC Hematology SC Hematology GA 182NK UT WOS:000321750000026 PM 23287862 ER PT J AU Switzer, GE Bruce, JG Myaskovsky, L DiMartini, A Shellmer, D Confer, DL Abress, LK King, RJ Harnaha, AG Ohngemach, S Dew, MA AF Switzer, Galen E. Bruce, Jessica G. Myaskovsky, Larissa DiMartini, Andrea Shellmer, Diana Confer, Dennis L. Abress, Linda K. King, Roberta J. Harnaha, Allyson G. Ohngemach, Sibylle Dew, Mary Amanda TI Race and ethnicity in decisions about unrelated hematopoietic stem cell donation SO BLOOD LA English DT Article ID BONE-MARROW DONATION; AFRICAN-AMERICANS; ORGAN DONATION; UNITED-STATES; DONORS; REGISTRY; TRANSPLANTATION; WILLINGNESS; KNOWLEDGE; ATTITUDES AB Large international registries of potential unrelated hematopoietic stem cell (HSC) donors, including the National Marrow Donor program (NMDP), continue to face difficulties finding matched donors for racial/ethnic minorities. One reason, in addition to the generally less common HLA types among minority patients, is the much higher registry attrition rate of racial/ethnic minorities compared with whites. Reasons for the higher attrition among minority potential donors remain unexplained. The goal of our cross-sectional telephone interview study was to generate a diverse sample of potential HSC donors who have preliminarily matched a patient and to identify factors associated with race/ethnicity and with the decision to continue toward potential donation or to opt out of the registry. Multiple culturally related, psychosocial, and donation-related factors were associated both with race/ethnic group membership and attrition from the registry. The most consistent factor associated with opting out of the registry across all race/ethnic groups was ambivalence about donation: doubts and worries, feeling unsure about donation, wishing someone else would donate in one's place. Our findings suggest that universal donor recruitment and management approaches based on reducing donation-related ambivalence and tailored messages and strategies for each of the individual race/ethnic groups are important. (Blood. 2013;121(8):1469-1476) C1 [Switzer, Galen E.; Myaskovsky, Larissa] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Switzer, Galen E.; Myaskovsky, Larissa] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Switzer, Galen E.; Bruce, Jessica G.; Myaskovsky, Larissa; DiMartini, Andrea; Harnaha, Allyson G.; Ohngemach, Sibylle; Dew, Mary Amanda] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Switzer, Galen E.] Univ Pittsburgh, Dept Clin & Translat Sci, Pittsburgh, PA USA. [DiMartini, Andrea; Shellmer, Diana] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Confer, Dennis L.; Abress, Linda K.; King, Roberta J.] Natl Marrow Donor Program, Minneapolis, MN USA. [Dew, Mary Amanda] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. [Dew, Mary Amanda] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Dew, Mary Amanda] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. RP Switzer, GE (reprint author), Div Gen Internal Med, Iroquois Bldg,Ste 502,3600 Forbes Ave, Pittsburgh, PA 15213 USA. EM switzerge@upmc.edu FU National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD [R01 HL081405] FX This project was supported by a grant from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (R01 HL081405). NR 37 TC 22 Z9 23 U1 6 U2 9 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 21 PY 2013 VL 121 IS 8 BP 1469 EP 1476 DI 10.1182/blood-2012-06-437343 PG 8 WC Hematology SC Hematology GA 182NK UT WOS:000321750000033 PM 23258921 ER PT J AU Cohen, KS Cheng, S Larson, MG Cupples, LA McCabe, EL Wang, YA Ngwa, JS Martin, RP Klein, RJ Hashmi, B Ge, Y O'Donnell, CJ Vasan, RS Shaw, SY Wang, TJ AF Cohen, Kenneth S. Cheng, Susan Larson, Martin G. Cupples, L. Adrienne McCabe, Elizabeth L. Wang, Ying A. Ngwa, Julius S. Martin, Roderick P. Klein, Rachael J. Hashmi, Basma Ge, Yin O'Donnell, Christopher J. Vasan, Ramachandran S. Shaw, Stanley Y. Wang, Thomas J. TI Circulating CD34(+) progenitor cell frequency is associated with clinical and genetic factors SO BLOOD LA English DT Article ID CORONARY-ARTERY-DISEASE; ACUTE MYOCARDIAL-INFARCTION; GENOME-WIDE ASSOCIATION; CARDIOVASCULAR RISK; ENDOTHELIAL-CELLS; STATIN THERAPY; HEART-DISEASE; DYSFUNCTION; MOBILIZATION; POPULATION AB Circulating blood CD34(+) cells consist of hematopoietic stem/progenitor cells, angiogenic cells, and endothelial cells. In addition to their clinical use in hematopoietic stem cell transplantation, CD34(+) cells may also promote therapeutic neovascularization. Therefore, understanding the factors that influence circulating CD34(+) cell frequency has wide implications for vascular biology in addition to stem cell transplantation. In the present study, we examined the clinical and genetic characteristics associated with circulating CD34(+) cell frequency in a large, community-based sample of 1786 Framingham Heart Study participants. Among subjects without cardiovascular disease (n = 1595), CD34(+) frequency was inversely related to older age, female sex, and smoking. CD34(+) frequency was positively related to weight, serum total cholesterol, and statin therapy. Clinical covariates accounted for 6.3% of CD34(+) variability. CD34(+) frequency was highly heritable (h(2) = 54%; P < .0001). Genome-wide association analysis of CD34(+) frequency identified suggestive associations at several loci, including OR4C12 (chromosome 11; P = 6.7 x 10(-7)) and ENO1 and RERE (chromosome 1; P = 8.8 x 10(-7)). CD34(+) cell frequency is reduced in older subjects and is influenced by environmental factors including smoking and statin use. CD34(+) frequency is highly heritable. The results of the present study have implications for therapies that use CD34+ cell populations and support efforts to better understand the genetic mechanisms that underlie CD34(+) frequency. C1 [Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Cohen, Kenneth S.; Martin, Roderick P.; Klein, Rachael J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA USA. [Cohen, Kenneth S.] Univ Chicago, Med Ctr, Hematol Oncol Sect, Chicago, IL 60637 USA. [Cheng, Susan; McCabe, Elizabeth L.; O'Donnell, Christopher J.; Shaw, Stanley Y.; Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Cheng, Susan; Larson, Martin G.; O'Donnell, Christopher J.; Vasan, Ramachandran S.; Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA 90034 USA. [Cheng, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Cupples, L. Adrienne; Wang, Ying A.; Ngwa, Julius S.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Martin, Roderick P.] Genzyme Corp, Cambridge, MA USA. [Hashmi, Basma] Harvard Univ, Dept Bioengn, Boston, MA 02115 USA. [Ge, Yin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [O'Donnell, Christopher J.] NHLBI, Ctr Populat Studies, NIH, Bethesda, MD 20892 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Div Cardiol, Boston, MA 02118 USA. [Shaw, Stanley Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. RP Wang, TJ (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB 800,55 Fruit St, Boston, MA 02114 USA. EM kcohen@medicine.bsd.uchicago.edu; shaw.stanley@mgh.harvard.edu; tjwang@partners.org OI Larson, Martin/0000-0002-9631-1254; Cupples, L. Adrienne/0000-0003-0273-7965 FU National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195, R01-HL083197, R01-HL93328]; National Institutes of Health [K99HL107642]; Ellison Foundation FX This work was supported in part by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract number N01-HC-25195, grant R01-HL083197 to T.J.W., and grant R01-HL93328 to R. S. V.). S. C. is supported in part by National Institutes of Health grant K99HL107642 and the Ellison Foundation. NR 47 TC 23 Z9 23 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD FEB 21 PY 2013 VL 121 IS 8 BP E50 EP E56 DI 10.1182/blood-2012-05-424846 PG 7 WC Hematology SC Hematology GA 182NK UT WOS:000321750000002 PM 23287867 ER PT J AU Liu, QS Sabnis, Y Zhao, Z Zhang, TH Buhrlage, SJ Jones, LH Gray, NS AF Liu, Qingsong Sabnis, Yogesh Zhao, Zheng Zhang, Tinghu Buhrlage, Sara J. Jones, Lyn H. Gray, Nathanael S. TI Developing Irreversible Inhibitors of the Protein Kinase Cysteinome SO CHEMISTRY & BIOLOGY LA English DT Review ID KAPPA-B KINASE; GROWTH-FACTOR RECEPTOR; LUNG-CANCER MODELS; COVALENT-BINDING; IN-VIVO; ACTIVE-SITE; DRUG DESIGN; TYROSINE; EGFR; SELECTIVITY AB Protein kinases are a large family of approximately 530 highly conserved enzymes that transfer a gamma-phosphate group from ATP to a variety of amino acid residues, such as tyrosine, serine, and threonine, that serves as a ubiquitous mechanism for cellular signal transduction. The clinical success of a number of kinase-directed drugs and the frequent observation of disease causing mutations in protein kinases suggest that a large number of kinases may represent therapeutically relevant targets. To date, the majority of clinical and preclinical kinase inhibitors are ATP competitive, noncovalent inhibitors that achieve selectivity through recognition of unique features of particular protein kinases. Recently, there has been renewed interest in the development of irreversible inhibitors that form covalent bonds with cysteine or other nucleophilic residues in the ATP-binding pocket. Irreversible kinase inhibitors have a number of potential advantages including prolonged pharmacodynamics, suitability for rational design, high potency, and ability to validate pharmacological specificity through mutation of the reactive cysteine residue. Here, we review recent efforts to develop cysteine-targeted irreversible protein kinase inhibitors and discuss their modes of recognizing the ATP-binding pocket and their biological activity profiles. In addition, we provided an informatics assessment of the potential "kinase cysteinome" and discuss strategies for the efficient development of new covalent inhibitors. C1 [Liu, Qingsong; Zhang, Tinghu; Buhrlage, Sara J.; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Liu, Qingsong; Zhang, Tinghu; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Sabnis, Yogesh] Pfizer Ltd, World Wide Med Chem, Computat Chem, Sandwich CT13 9NJ, Kent, England. [Sabnis, Yogesh] UCB NewMed, UCB Pharma, BE-1420 Braine Lalleud, Belgium. [Zhao, Zheng] Chinese Acad Sci, High Field Magnet Lab, Hefei 230031, Anhui, Peoples R China. [Jones, Lyn H.] Pfizer, World Wide Med Chem, BioTherapeut Chem, Chem Biol Grp, Cambridge, MA 02140 USA. RP Jones, LH (reprint author), Pfizer, World Wide Med Chem, BioTherapeut Chem, Chem Biol Grp, Cambridge, MA 02140 USA. EM lyn.jones@pfizer.com; nathanael_gray@dfci.harvard.edu OI liu, qing song/0000-0002-7829-2547; Jones, Lyn/0000-0002-8388-5865 FU NCI NIH HHS [R01 CA130876]; NIGMS NIH HHS [P41 GM079575] NR 74 TC 151 Z9 151 U1 14 U2 129 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD FEB 21 PY 2013 VL 20 IS 2 BP 146 EP 159 DI 10.1016/j.chembiol.2012.12.006 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 104FZ UT WOS:000315978600007 PM 23438744 ER PT J AU Modjarrad, K Mohraz, M Madani, N AF Modjarrad, Kayvon Mohraz, Minoo Madani, Navid TI Iran needs global support to fight HIV SO NATURE LA English DT Letter C1 [Modjarrad, Kayvon] NIAID, Bethesda, MD 20892 USA. [Mohraz, Minoo] Univ Tehran Med Sci, Tehran, Iran. [Madani, Navid] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Modjarrad, K (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM kayvon.modjarrad@nih.gov NR 1 TC 1 Z9 1 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD FEB 21 PY 2013 VL 494 IS 7437 BP 314 EP 314 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 095CS UT WOS:000315312900022 PM 23426315 ER PT J AU Chen, JJ Rosas, HD Salat, DH AF Chen, J. Jean Rosas, H. Diana Salat, David H. TI The Relationship between Cortical Blood Flow and Sub-Cortical White-Matter Health across the Adult Age Span SO PLOS ONE LA English DT Article ID MILD COGNITIVE IMPAIRMENT; VASCULAR RISK-FACTORS; DIFFUSION TENSOR; ALZHEIMERS-DISEASE; CORPUS-CALLOSUM; OLDER-ADULTS; NEUROVASCULAR MECHANISMS; CEREBRAL HYPOPERFUSION; HYPERTENSIVE PATIENTS; SPATIAL STATISTICS AB Degeneration of cerebral white matter is commonly observed in aging, and the associated degradation in neural connectivity contributes to cognitive decline in older adults. Vascular dysfunction has been implicated as a potential mechanism for general age-related neural tissue deterioration; however, no prior study has examined the direct relationship between cortical vascular health and subcortical white-matter integrity. In this work, we aimed to determine whether blood supply to the brain is associated with microstructural integrity of connective tissue, and whether such associations are regionally specific and mainly accounted for by aging. We examined the association between cerebral blood flow (CBF) in the cortical mantle, measured using arterial spin labeling (ASL), and subcortical white-matter integrity, measured using diffusion tensor imaging (DTI), in a group of healthy adults spanning early to late adulthood. We found cortical CBF to be significantly associated with white-matter integrity throughout the brain. In addition, these associations were only partially tied to aging, as they remained even when statistically controlling for age, and when restricting the analyses to a young subset of the sample. Furthermore, vascular risk was not a prominent determinant of these effects. These findings suggest that the overall blood supply to the brain is an important indicator of white-matter health in the normal range of variations amongst adults, and that the decline in CBF with advancing age may potentially exacerbate deterioration of the connective anatomy of the brain. C1 [Chen, J. Jean] Univ Toronto, Rotman Res Inst, Baycrest Ctr Geriatr Care, Toronto, ON, Canada. [Chen, J. Jean; Rosas, H. Diana; Salat, David H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. [Chen, J. Jean; Salat, David H.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Rosas, H. Diana] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Salat, David H.] VA Boston Healthcare Syst, Neuroimaging Res Vet Ctr, Boston, MA USA. RP Chen, JJ (reprint author), Univ Toronto, Rotman Res Inst, Baycrest Ctr Geriatr Care, Toronto, ON, Canada. EM jchen@rotman-baycrest.on.ca FU National Institutes of Health [R01NR010827, NS042861, P41RR14075]; Canadian Institutes of Health Research; Athinoula A. Martinos Center for Biomedical Imaging FX This research was supported by National Institutes of Health grants R01NR010827, NS042861, and P41RR14075, as well as by fellowship funding from the Canadian Institutes of Health Research (to JJC) and the Athinoula A. Martinos Center for Biomedical Imaging. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 85 TC 17 Z9 17 U1 3 U2 18 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 21 PY 2013 VL 8 IS 2 AR e56733 DI 10.1371/journal.pone.0056733 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 093IT UT WOS:000315186000042 PM 23437228 ER PT J AU Weisberg, E Liu, QS Zhang, X Nelson, E Sattler, M Liu, FY Nicolais, M Zhang, JM Mitsiades, C Smith, RW Stone, R Galinsky, I Nonami, A Griffin, JD Gray, N AF Weisberg, Ellen Liu, Qingsong Zhang, Xin Nelson, Erik Sattler, Martin Liu, Feiyang Nicolais, Maria Zhang, Jianming Mitsiades, Constantine Smith, Robert W. Stone, Richard Galinsky, Ilene Nonami, Atsushi Griffin, James D. Gray, Nathanael TI Selective Akt Inhibitors Synergize with Tyrosine Kinase Inhibitors and Effectively Override Stroma-Associated Cytoprotection of Mutant FLT3-Positive AML Cells SO PLOS ONE LA English DT Article ID LYMPHOBLASTIC-LEUKEMIA CELLS; CONSTITUTIVE ACTIVATION; FLT3 INHIBITORS; APOPTOSIS; MUTATIONS; SURVIVAL; RESISTANCE; THERAPIES; PATHWAYS; CONTACT AB Objectives: Tyrosine kinase inhibitor (TKI)-treated acute myeloid leukemia (AML) patients commonly show rapid and significant peripheral blood blast cell reduction, however a marginal decrease in bone marrow blasts. This suggests a protective environment and highlights the demand for a better understanding of stromal: leukemia cell communication. As a strategy to improve clinical efficacy, we searched for novel agents capable of potentiating the stroma-diminished effects of TKI treatment of mutant FLT3-expressing cells. Methods: We designed a combinatorial high throughput drug screen using well-characterized kinase inhibitor-focused libraries to identify novel kinase inhibitors capable of overriding stromal-mediated resistance to TKIs, such as PKC412 and AC220. Standard liquid culture proliferation assays, cell cycle and apoptosis analysis, and immunoblotting were carried out with cell lines or primary AML to validate putative candidates from the screen and characterize the mechanism(s) underlying observed synergy. Results and Conclusions: Our study led to the observation of synergy between selective Akt inhibitors and FLT3 inhibitors against mutant FLT3-positive AML in either the absence or presence of stroma. Our findings are consistent with evidence that Akt activation is characteristic of mutant FLT3-transformed cells, as well as observed residual Akt activity following FLT3 inhibitor treatment. In conclusion, our study highlights the potential importance of Akt as a signaling factor in leukemia survival, and supports the use of the co-culture chemical screen to identify agents able to potentiate TKI anti-leukemia activity in a cytoprotective microenvironment. C1 [Weisberg, Ellen; Nelson, Erik; Sattler, Martin; Nicolais, Maria; Mitsiades, Constantine; Smith, Robert W.; Stone, Richard; Galinsky, Ilene; Nonami, Atsushi; Griffin, James D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Liu, Qingsong; Zhang, Xin; Zhang, Jianming; Gray, Nathanael] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Liu, Feiyang] Chinese Acad Sci, High Field Magnet Lab, Hefei, Anhui, Peoples R China. RP Weisberg, E (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM ellen_weisberg@dfci.harvard.edu; james_griffin@dfci.harvard.edu OI liu, qing song/0000-0002-7829-2547 FU National Institutes of Health (NIH) Library of Integrated Network-Based Cellular Signatures (LINCS) grant [HG006097]; Chinese Academy of Science High Magnetic Field Laboratory training grant; NIH grant [CA66996]; CAS FX Grant Support: QL and NG are supported by National Institutes of Health (NIH) Library of Integrated Network-Based Cellular Signatures (LINCS) grant HG006097. FL is supported by a Chinese Academy of Science High Magnetic Field Laboratory training grant. JDG is supported by NIH grant CA66996. FL is supported by CAS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 14 Z9 15 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 21 PY 2013 VL 8 IS 2 AR e56473 DI 10.1371/journal.pone.0056473 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 093IT UT WOS:000315186000029 PM 23437141 ER PT J AU Jang, H Shin, H AF Jang, Hyeran Shin, Hyunjin TI Current trends in the development and application of molecular technologies for cancer epigenetics SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Cancer; Epigenetic; Technology; Butyrate; Histone modifications; Diet; Methyl sources ID GENOMIC DNA METHYLATION; COVALENT HISTONE MODIFICATIONS; MODEL-BASED ANALYSIS; LARGE-BOWEL CANCER; CHAIN FATTY-ACIDS; SODIUM-BUTYRATE; GENE-EXPRESSION; DEFICIENT DIET; COLON-CANCER; GLOBAL DNA AB Current progress in epigenetic research supports the view that diet and dietary components are important in cancer etiology by enhancing or inhibiting carcinogenesis. Since diet and dietary factors may significantly contribute to the causation and progression of many cancers, it is important to find the molecular mechanisms of action of such dietary factors for cancer prevention and treatment. Recently, the role of epigenetic mechanisms in the cancer development and progression has attracted more attention as additional evidence along with traditional DNA sequence based mechanisms such as mutations and structural re-arrangements. Such an increasing interest in cancer epigenetics has also accelerated the development and application of molecular assays and tools for DNA methylation detection and histone modification enrichment analysis. In this paper, key assays and methods for epigenetic research are reviewed and discussed in terms of their utility and usability. In addition, more advanced methods for genome-wide analysis are introduced as part of upcoming research trends and directions. (C) 2013 Baishideng. All rights reserved. C1 [Jang, Hyeran] Boston Univ, Sch Med, Endocrinol Sect, Boston, MA 02118 USA. [Shin, Hyunjin] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. RP Shin, H (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, 665 Huntington Ave, Boston, MA 02215 USA. EM ulexis.dfci@gmail.com NR 100 TC 3 Z9 4 U1 0 U2 16 PU BAISHIDENG PUBL GRP CO LTD PI WANCHAI PA ROOM 1701, 17-F, HENAN BUILDING, NO. 90, JAFFE RD, WANCHAI, HONG KONG 100025, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD FEB 21 PY 2013 VL 19 IS 7 BP 1030 EP 1039 DI 10.3748/wjg.v19.i7.1030 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 093PI UT WOS:000315203400008 PM 23467485 ER PT J AU Simmons, LH Guimaraes, AR Zukerberg, LR AF Simmons, Leigh H. Guimaraes, Alexander R. Zukerberg, Lawrence R. TI Case 6-2013: A 54-Year-Old Man with Recurrent Diarrhea SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ZOLLINGER-ELLISON-SYNDROME; CELIAC-DISEASE; DIAGNOSIS C1 [Simmons, Leigh H.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Guimaraes, Alexander R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Zukerberg, Lawrence R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Simmons, Leigh H.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Guimaraes, Alexander R.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Zukerberg, Lawrence R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Simmons, LH (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. FU New England Research Institute; Immunogen FX Dr. Simmons reports receiving consulting fees from New England Research Institute; and Dr. Zukerberg, receiving consulting fees from Immunogen and providing expert testimony for law firms and insurance groups on cases related to leukemia, lymphoma, and gastrointestinal cancers. No other potential conflict of interest relevant to this article was reported. NR 16 TC 2 Z9 2 U1 1 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 21 PY 2013 VL 368 IS 8 BP 757 EP 765 DI 10.1056/NEJMcpc1208149 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 092CG UT WOS:000315095800012 PM 23425169 ER PT J AU Mishra, P Li, RJ St James, S Mak, RH Williams, CL Yue, Y Berbeco, RI Lewis, JH AF Mishra, Pankaj Li, Ruijiang St James, Sara Mak, Raymond H. Williams, Christopher L. Yue, Yong Berbeco, Ross I. Lewis, John H. TI Evaluation of 3D fluoroscopic image generation from a single planar treatment image on patient data with a modified XCAT phantom SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID INDEPENDENT COMPONENT ANALYSIS; RESPIRATORY MOTION MODEL; LUNG-TUMOR TRACKING; COMPUTED-TOMOGRAPHY; RADIOTHERAPY; DEFORMATION; ALGORITHMS; ARTIFACTS; MARKERS AB Accurate understanding and modeling of respiration-induced uncertainties is essential in image-guided radiotherapy. Explicit modeling of the overall lung motion and interaction among different organs promises to be a useful approach. Recently, preliminary studies on 3D fluoroscopic treatment imaging and tumor localization based on principal component analysis motion models and cost function optimization have shown encouraging results. However, the performance of this technique for varying breathing parameters and under realistic conditions remains unclear and thus warrants further investigation. In this work, we present a systematic evaluation of a 3D fluoroscopic image generation algorithm via two different approaches. In the first approach, the model's accuracy is tested for changing parameters for sinusoidal breathing. These parameters include changing respiratory motion amplitude, period and baseline shift. The effects of setup error, imaging noise and different tumor sizes are also examined. In the second approach, we test the model for anthropomorphic images obtained from a modified XCAT phantom. This set of experiments is important as all the underlying breathing parameters are simultaneously tested, as in realistic clinical conditions. Based on our simulation results for more than 250 s of breathing data for eight different lung patients, the overall tumor localization accuracies of the model in left-right, anterior-posterior and superior-inferior directions are 0.1 +/- 0.1, 0.5 +/- 0.5 and 0.8 +/- 0.8 mm, respectively. 3D tumor centroid localization accuracy is 1.0 +/- 0.9 mm. C1 [Mishra, Pankaj; St James, Sara; Mak, Raymond H.; Williams, Christopher L.; Yue, Yong; Berbeco, Ross I.; Lewis, John H.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Mishra, Pankaj; St James, Sara; Mak, Raymond H.; Williams, Christopher L.; Yue, Yong; Berbeco, Ross I.; Lewis, John H.] Harvard Univ, Sch Med, Boston, MA USA. [Li, Ruijiang] Stanford Univ, Sch Med, Dept Radiat Oncol, Stanford, CA 94305 USA. RP Mishra, P (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM pmishra@lroc.harvard.edu; jhlewis@lroc.harvard.edu FU Radiological Society of North America [RSCH1206]; NIH/NCI [1K99CA166186] FX The authors would like to express their gratitude to Drs Seiko Nishioka of the Department of Radiology, NTT Hospital, Sapporo, Japan and Hiroki Shirato of the Department of Radiation Medicine, Hokkaido University School of Medicine, Sapporo, Japan for sharing the Hokkaido dataset. The project described was supported by Award Numbers RSCH1206 (JHL) from the Radiological Society of North America and NIH/NCI 1K99CA166186 (RL). NR 26 TC 10 Z9 10 U1 0 U2 4 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD FEB 21 PY 2013 VL 58 IS 4 BP 841 EP 858 DI 10.1088/0031-9155/58/4/841 PG 18 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 082MT UT WOS:000314396800008 PM 23337614 ER PT J AU Besemer, A Paganetti, H Bednarz, B AF Besemer, Abigail Paganetti, Harald Bednarz, Bryan TI The clinical impact of uncertainties in the mean excitation energy of human tissues during proton therapy SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID MONTE-CARLO SIMULATIONS; SCATTERING CROSS-SECTIONS; ELECTRONIC STOPPING POWER; LIQUID WATER; RANGE UNCERTAINTIES; DOSE DISTRIBUTIONS; ORGANIC-COMPOUNDS; ALPHA-PARTICLES; BEAM RANGES; IONS AB Uncertainties in the estimated mean excitation energies (I-values) needed for calculating proton stopping powers can be in the order of 10-15%, which introduces a fundamental limitation in the accuracy of proton range determination. Previous efforts have quantified shifts in proton depth dose distributions due to I-value uncertainties in water and homogenous tissue phantoms. This study is the first to quantify the clinical impact of I-value uncertainties on proton dose distributions within patient geometries. A previously developed Geant4 based Monte Carlo code was used to simulate a proton treatment plan for three patients (prostate, pancreases, and liver) with varying tissue I-values. A uniform variation study was conducted in which the tissue I-values were varied by +/- 5% and +/- 10% of the nominal values as well as a probabilistic variation study in which the I-values were randomly sampled according to a normal distribution with the mean equal to the nominal I-value and a standard deviation of 5 and 10% of the nominal values. Modification of tissue I-values impacted both the proton range and SOBP width. R-90 range shifts up to 7.7 mm (4.4.%) and R-80 range shifts up to 4.8 mm (1.9%) from the nominal range were recorded. Modulating the tissue I-values by 10% the nominal value resulted in up to a 3.5% difference mean dose in the target volumes and organs at risk compared to the nominal case. The range and dose differences were the largest for the deeper-seated prostate and pancreas cases. The treatments that were simulated with randomly sampled I-values resulted in range and dose differences that were generally within the upper and lower bounds set by the 10% uniform variations. This study demonstrated the impact of I-value uncertainties on patient dose distributions. Clearly, sub-millimeter precision in proton therapy would necessitate a reduction in I-value uncertainties to ensure an efficacious clinical outcome. C1 [Besemer, Abigail; Bednarz, Bryan] Univ Wisconsin, Wisconsin Inst Med Res, Dept Med Phys, Madison, WI 53715 USA. [Paganetti, Harald] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Besemer, A (reprint author), Univ Wisconsin, Wisconsin Inst Med Res, Dept Med Phys, Madison, WI 53715 USA. EM bbednarz2@wisc.edu FU Morgridge Institute for Research; NIH/NCI grant 'Proton Therapy Research' [P01 CA-21239] FX Funding for this research was partially supported by the Morgridge Institute for Research. HP was supported by NIH/NCI grant P01 CA-21239 'Proton Therapy Research'. The authors would like to thank the UW-Madison Center for High Throughput Computing (CHTC) for providing computational support and Jan Schuemann for providing relevant data. NR 41 TC 13 Z9 13 U1 0 U2 13 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD FEB 21 PY 2013 VL 58 IS 4 BP 887 EP 902 DI 10.1088/0031-9155/58/4/887 PG 16 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 082MT UT WOS:000314396800010 PM 23337713 ER PT J AU Ayan, AS Lin, HB Yeager, C Deville, C McDonough, J Zhu, TC Anderson, N Bar Ad, V Lu, HM Both, S AF Ayan, Ahmet S. Lin, Haibo Yeager, Caitlyn Deville, Curtiland McDonough, James Zhu, Timothy C. Anderson, Nathan Bar Ad, Voichita Lu, Hsiao-Ming Both, Stefan TI Should image rotation be addressed during routine cone-beam CT quality assurance? SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY; GEOMETRIC CALIBRATION; RADIATION-THERAPY; SYSTEMS AB The purpose of this study is to investigate whether quality assurance (QA) for cone-beam computed tomography (CBCT) image rotation is necessary in order to ensure the accuracy of CBCT based image-guided radiation therapy (IGRT) and adaptive radiotherapy (ART). Misregistration of angular coordinates during CBCT acquisition may lead to a rotated reconstructed image. If target localization is performed based on this image, an under-or over-dosage of the target volume (TV) and organs at risk (OARs) may occur. Therefore, patient CT image sets were rotated by 1 degrees up to 3 degrees and the treatment plans were recalculated to quantify changes in dose-volume histograms. A computer code in C++ was written to model the TV displacement and overlap area of an ellipse shape at the target and dose prescription levels corresponding to the image rotation. We investigated clinical scenarios in IGRT and ART in order to study the implications of image rotation on dose distributions for: (1) lateral TV and isocenter (SBRT), (2) central TV and isocenter (IMRT), (3) lateral TV and isocenter (IMRT). Mathematical analysis showed the dose coverage of TV depends on its shape, size, location, and orientation relative to the isocenter. Evaluation of three first scenario for theta = 1 degrees showed variations in TV D95 in the context of IGRT and ART when compared to the original plan were within 2.7 +/- 2.6% and 7.7 +/- 6.9% respectively while variations in the second and third scenarios were less significant (<0.5%) for the angular range evaluated. However a larger degree of variation was found in terms of minimum and maximum doses for target and OARs. The rotation of CBCT image data sets may have significant dosimetric consequences in IGRT and ART. The TV's location relative to isocenter and shape determine the extent of alterations in dose indicators. Our findings suggest that a CBCT QA criterion of 1 degrees would be a reasonable action level to ensure accurate dose delivery. C1 [Ayan, Ahmet S.; Lin, Haibo; Yeager, Caitlyn; Deville, Curtiland; McDonough, James; Zhu, Timothy C.; Anderson, Nathan; Bar Ad, Voichita; Both, Stefan] Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Lu, Hsiao-Ming] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Ayan, AS (reprint author), Ohio State Univ, Wexner Med Ctr, Dept Radiat Oncol, Columbus, OH 43210 USA. EM ahmetsedat.ayan@gmail.com RI Lin, Haibo/D-9589-2011; Deville, Curtiland/B-2819-2013; OI Lin, Haibo/0000-0001-7476-0967; Deville, Curtiland/0000-0003-4846-6486; Zhu, Timothy/0000-0003-2842-8984 NR 16 TC 2 Z9 2 U1 0 U2 13 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD FEB 21 PY 2013 VL 58 IS 4 BP 1059 EP 1073 DI 10.1088/0031-9155/58/4/1059 PG 15 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 082MT UT WOS:000314396800021 PM 23363650 ER PT J AU Marangoni, F Murooka, TT Manzo, T Kim, EY Carrizosa, E Elpek, NM Mempel, TR AF Marangoni, Francesco Murooka, Thomas T. Manzo, Teresa Kim, Edward Y. Carrizosa, Esteban Elpek, Natalie M. Mempel, Thorsten R. TI The Transcription Factor NFAT Exhibits Signal Memory during Serial T Cell Interactions with Antigen-Presenting Cells SO IMMUNITY LA English DT Article ID DENDRITIC CELLS; IN-VIVO; LYMPH-NODES; IMMUNOLOGICAL SYNAPSE; STROMAL CELLS; CUTTING EDGE; CA2+ SIGNALS; STOP SIGNAL; ACTIVATION; TUMOR AB Interactions with antigen-presenting cells (APCs) interrupt T cell migration through tissues and trigger signaling pathways that converge on the activation of transcriptional regulators, including nuclear factor of activated T cells (NFAT), which control T cell function and differentiation. Both stable and unstable modes of cognate T cell-APC interactions have been observed in vivo, but the functional significance of unstable, serial contacts has remained unclear. Here we used multiphoton intravital microscopy in lymph nodes and tumors to show that while NFAT nuclear import was fast (t(1/2) (max)similar to 1 min), nuclear export was slow (t(1/2)similar to 20 min) in T cells. During delayed export, nuclear NFAT constituted a short-term imprint of transient TCR signals and remained transcriptionally active for the T cell tolerance gene Egr2, but not for the effector gene Ifng, which required continuous TCR triggering for expression. This provides a potential mechanistic basis for the observation that a predominance of unstable APC interactions correlates with the induction of T cell tolerance. C1 [Marangoni, Francesco; Murooka, Thomas T.; Manzo, Teresa; Kim, Edward Y.; Carrizosa, Esteban; Elpek, Natalie M.; Mempel, Thorsten R.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Marangoni, Francesco; Murooka, Thomas T.; Kim, Edward Y.; Carrizosa, Esteban; Mempel, Thorsten R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Mempel, TR (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. EM tmempel@mgh.harvard.edu RI Marangoni, Francesco/I-9087-2012 OI Marangoni, Francesco/0000-0002-2490-849X FU NIH [AI073457, CA150975, AI0178897, AI097052]; Dana Foundation; MGH Fund for Medical Discovery Fellowship; MGH ECOR Tosteson Postdoctoral Fellowship Award FX We thank Jose Aramburu, Ulrich von Andrian, Shiv Pillai, James Moon, and Anjana Rao for helpful suggestions and critical reading of the manuscript, as well as Harald von Boehmer, Jose Aramburu, Vigo Heissmeyer, Roberto Bonasio, Sean Megason, Paul Allen, and Jason McCarthy for providing key reagents. We are indebted to Julia Kahn from the laboratory of Dai Fukumura for technical advice. T. R. M. was supported by NIH grants AI073457, CA150975, AI0178897, and AI097052 as well as a grant by the Dana Foundation. F. M. was supported by an MGH Fund for Medical Discovery Fellowship. T. T. M. was supported by the MGH ECOR Tosteson Postdoctoral Fellowship Award. NR 48 TC 48 Z9 48 U1 2 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD FEB 21 PY 2013 VL 38 IS 2 BP 237 EP 249 DI 10.1016/j.immuni.2012.09.012 PG 13 WC Immunology SC Immunology GA AA2RC UT WOS:000330940800007 PM 23313588 ER PT J AU Cortez-Retamozo, V Etzrodt, M Newton, A Ryan, R Pucci, F Sio, SW Kuswanto, W Rauch, PJ Chudnovskiy, A Iwamoto, Y Kohler, R Marinelli, B Gorbatov, R Wojtkiewicz, G Panizzi, P Mino-Kenudson, M Forghani, R Figueiredo, JL Chen, JW Xavier, R Swirski, FK Nahrendorf, M Weissleder, R Pittet, MJ AF Cortez-Retamozo, Virna Etzrodt, Martin Newton, Andita Ryan, Russell Pucci, Ferdinando Sio, Selena W. Kuswanto, Wilson Rauch, Philipp J. Chudnovskiy, Aleksey Iwamoto, Yoshiko Kohler, Rainer Marinelli, Brett Gorbatov, Rostic Wojtkiewicz, Gregory Panizzi, Peter Mino-Kenudson, Mari Forghani, Reza Figueiredo, Jose-Luiz Chen, John W. Xavier, Ramnik Swirski, Filip K. Nahrendorf, Matthias Weissleder, Ralph Pittet, Mikael J. TI Angiotensin II Drives the Production of Tumor-Promoting Macrophages SO IMMUNITY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; MYOCARDIAL-INFARCTION; DENDRITIC CELLS; LUNG ADENOCARCINOMA; SPLENIC RESERVOIR; LYMPHOID ORGANS; MYELOID CELLS; CANCER; MONOCYTES; INFLAMMATION AB Macrophages frequently infiltrate tumors and can enhance cancer growth, yet the origins of the macrophage response are not well understood. Here we address molecular mechanisms of macrophage production in a conditional mouse model of lung adenocarcinoma. We report that overproduction of the peptide hormone Angiotensin II (AngII) in tumor-bearing mice amplifies self-renewing hematopoietic stem cells (HSCs) and macrophage progenitors. The process occurred in the spleen but not the bone marrow, and was independent of hemodynamic changes. The effects of AngII required direct hormone ligation on HSCs, depended on S1P(1) signaling, and allowed the extramedullary tissue to supply new tumor-associated macrophages throughout cancer progression. Conversely, blocking AngII production prevented cancer-induced HSC and macrophage progenitor amplification and thus restrained the macrophage response at its source. These findings indicate that AngII acts upstream of a potent macrophage amplification program and that tumors can remotely exploit the hormone's pathway to stimulate cancer-promoting immunity. C1 [Cortez-Retamozo, Virna; Etzrodt, Martin; Newton, Andita; Pucci, Ferdinando; Sio, Selena W.; Kuswanto, Wilson; Rauch, Philipp J.; Chudnovskiy, Aleksey; Iwamoto, Yoshiko; Kohler, Rainer; Marinelli, Brett; Gorbatov, Rostic; Wojtkiewicz, Gregory; Panizzi, Peter; Forghani, Reza; Figueiredo, Jose-Luiz; Chen, John W.; Swirski, Filip K.; Nahrendorf, Matthias; Weissleder, Ralph; Pittet, Mikael J.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Xavier, Ramnik] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Xavier, Ramnik] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Xavier, Ramnik] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ryan, Russell; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Pittet, MJ (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM mpittet@mgh.harvard.edu RI Etzrodt, Martin/P-3325-2015; OI Etzrodt, Martin/0000-0003-1928-3904; Forghani, Reza/0000-0002-8572-1864; Panizzi, Peter/0000-0003-0141-8807 FU NIH [P50-CA86355, R01-AI084880, R56-AI084880]; MGH-Center for Systems Biology [U54-CA126515]; AACR Centennial Predoctoral Fellowship; Boehringer Ingelheim Fonds FX The authors thank Jessica Truelove (MGH) for imaging and Michael Waring and Adam Chicoine (Ragon Institute, MGH) for sorting cells. This work was supported in part by NIH grants P50-CA86355, R01-AI084880, R56-AI084880, and MGH-Center for Systems Biology (to M.J.P.) and U54-CA126515 (to R. W.). M. E. is part of the International PhD program "Cancer and Immunology" at the University of Lausanne, Switzerland, and was supported by the AACR Centennial Predoctoral Fellowship and the Boehringer Ingelheim Fonds. NR 51 TC 48 Z9 50 U1 2 U2 19 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD FEB 21 PY 2013 VL 38 IS 2 BP 296 EP 308 DI 10.1016/j.immuni.2012.10.015 PG 13 WC Immunology SC Immunology GA AA2RC UT WOS:000330940800012 PM 23333075 ER PT J AU Spector, JM Reisman, J Lipsitz, S Desai, P Gawande, AA AF Spector, Jonathan M. Reisman, Jonathan Lipsitz, Stuart Desai, Priya Gawande, Atul A. TI Access to essential technologies for safe childbirth: a survey of health workers in Africa and Asia SO BMC PREGNANCY AND CHILDBIRTH LA English DT Article DE Neonatal mortality; Maternal mortality; Childbirth; Developing world; Health technology ID MATERNAL MORTALITY; NEONATAL DEATHS; SURVIVAL 1; NEWBORN; INTERVENTIONS AB Background: The reliable availability of health technologies, defined as equipment, medicines, and consumable supplies, is essential to ensure successful childbirth practices proven to prevent avoidable maternal and newborn mortality. The majority of global maternal and newborn deaths take place in Africa and Asia, yet few data exist that describe the availability of childbirth-related health technologies in these regions. We conducted a cross-sectional survey of health workers in Africa and Asia in order to profile the availability of health technologies considered to be essential to providing safe childbirth care. Methods: Health workers in Africa and Asia were surveyed using a web-based questionnaire. A list of essential childbirth-related health technologies was drawn from World Health Organization guidelines for preventing and managing complications associated with the major causes of maternal and newborn mortality globally. Demographic data describing each birth center were obtained and health workers reported on the availability of essential childbirth-related health technologies at their centers. Comparison analyses were conducted using Rao-Scott chi-square test statistics. Results: Health workers from 124 birth centers in 26 African and 15 Asian countries participated. All facilities exhibited gaps in the availability of essential childbirth-related health technologies. Availability was significantly reduced in birth centers that had lower birth volumes and those from lower income countries. On average across all centers, health workers reported the availability of 18 of 23 essential childbirth-related health technologies (79%; 95% CI, 74%, 84%). Low-volume facilities suffered severe shortages; on average, these centers reported reliable availability of 13 of 23 technologies (55%; 95% CI, 39%, 71%). Conclusions: Substantial gaps exist in the availability of essential childbirth-related health technologies across health sector levels in Africa and Asia. Strategies that facilitate reliable access to vital health technologies in these regions are an urgent priority. C1 [Spector, Jonathan M.; Desai, Priya; Gawande, Atul A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Reisman, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Dept Internal Med Pediat, Boston, MA 02114 USA. [Lipsitz, Stuart] Brigham & Womens Hosp, Dept Gen Med, Boston, MA 02115 USA. RP Reisman, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Internal Med Pediat, Boston, MA 02114 USA. EM Reisman.jonathan@gmail.com OI Gawande, Atul/0000-0002-1824-9176 NR 29 TC 4 Z9 4 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2393 J9 BMC PREGNANCY CHILDB JI BMC Pregnancy Childbirth PD FEB 20 PY 2013 VL 13 AR 43 DI 10.1186/1471-2393-13-43 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 140KK UT WOS:000318652800001 PM 23421767 ER PT J AU Malinowska, IA Lee, N Kumar, V Thiele, EA Franz, DN Ashwal, S Sagalowsky, A DiMario, FJ Cutler, D Krueger, D Camposano, S Paolini, J Dabora, SL AF Malinowska, Izabela A. Lee, Nancy Kumar, Vidhya Thiele, Elizabeth A. Franz, David Neal Ashwal, Stephen Sagalowsky, Arthur DiMario, Francis J., Jr. Cutler, Drew Krueger, Darcy Camposano, Susana Paolini, Jan Dabora, Sandra L. TI Similar Trends in Serum VEGF-D Levels and Kidney Angiomyolipoma Responses with Longer Duration Sirolimus Treatment in Adults with Tuberous Sclerosis SO PLOS ONE LA English DT Article ID GROWTH FACTOR-D; PULMONARY LYMPHANGIOLEIOMYOMATOSIS; SOLID TUMORS; COMPLEX; TSC2; WOMEN; HETEROZYGOSITY; MUTATIONS; GENE AB Context: We have previously shown that serum VEGF-D is elevated at baseline, correlates with kidney angiomyolipoma size at baseline and 12 months, and decreases with sirolimus treatment in adults with tuberous sclerosis complex (TSC). To further investigate the utility of serum VEGF-D for longer term monitoring of TSC kidney disease, we present VEGF-D level results with 24 month follow-up. Objective: To compare 24 month VEGF-D levels in two subgroups of sirolimus treated patients (OFF SIROLIMUS AFTER 12 MONTHS or ON SIROLIMUS AFTER 12 MONTHS). Design and Intervention(s): Serum VEGF-D was measured in samples collected from subjects enrolled in a phase 2 multicenter trial evaluating sirolimus for the treatment of kidney angiomyolipomas associated with TSC or TSC/LAM. All participants were treated with sirolimus from 0-12 months. During months 12-24, sirolimus was discontinued in one subgroup. The other subgroup was treated with additional sirolimus. Setting: Adult TSC participants were recruited from six clinical sites in the United States (comprehensive TSC clinics, 5; urology clinic, 1). Patients: There were 28 TSC patients who completed all 24 months of the study and serum samples were available at 24 months from 18/28 patients. Main Outcome Measure(s): We compared the percent change in VEGF-D levels (baseline to 24 months) in patients from the two treatment subgroups. Results: At 24 months, VEGF-D levels decreased by 67% compared with baseline (to 787+/-426 pg/ml) in the ON SIROLIMUS AFTER 12 MONTHS group versus a 13% decrease (to 2971+/-4014 pg/ml) in the OFF SIROLIMUS AFTER 12 MONTHS group (p = 0.013, Mann-Whitney test). A similar trend was observed in kidney angiomyolipoma size but not in pulmonary function tests. Conclusions Serum VEGF-D may be useful for monitoring response to treatment with sirolimus and kidney angiomyolipoma size in patients with TSC, but confirmation is needed. C1 [Malinowska, Izabela A.; Lee, Nancy; Kumar, Vidhya; Dabora, Sandra L.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Thiele, Elizabeth A.; Camposano, Susana; Paolini, Jan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Franz, David Neal; Krueger, Darcy] Childrens Med Ctr, Dept Pediat, Cincinnati, OH USA. [Ashwal, Stephen] Loma Linda Univ, Dept Neurol, Loma Linda, CA 92350 USA. [Sagalowsky, Arthur] Univ Texas SW Med Ctr Dallas, Dept Urol, Dallas, TX 75390 USA. [DiMario, Francis J., Jr.] Connecticut Childrens Med Ctr, Dept Pediat Neurol, Hartford, CT USA. [Cutler, Drew] Loma Linda Univ, Loma Linda, CA 92350 USA. RP Dabora, SL (reprint author), East Boston Neighborhood Hlth Ctr, Boston, MA USA. EM sandy.dabora@gmail.com RI Malinowska, Izabela/A-4816-2013 FU NIH/National Cancer Institute [R01CA107164]; Tuberous Sclerosis Alliance planning and supplement grants; Brigham and Women's Hospital Research Institute Bridge Funding award FX This project was funded by the following grants to S. Dabora: NIH/National Cancer Institute (R01CA107164), Tuberous Sclerosis Alliance planning and supplement grants, and the Brigham and Women's Hospital Research Institute Bridge Funding award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 4 Z9 5 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 20 PY 2013 VL 8 IS 2 AR e56199 DI 10.1371/journal.pone.0056199 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 093IE UT WOS:000315184200045 PM 23437092 ER PT J AU Wang, XD Liu, AP Wu, YY Wang, P AF Wang, Xiao-Dong Liu, A-Ping Wu, Yin-Yuan Wang, Peng TI Rapid Extraction of Lexical Tone Phonology in Chinese Characters: A Visual Mismatch Negativity Study SO PLOS ONE LA English DT Article ID RIGHT CEREBRAL HEMISPHERE; WORD RECOGNITION; CATEGORICAL PERCEPTION; HUMAN BRAIN; ELECTROPHYSIOLOGICAL EVIDENCE; AUTOMATIC ACTIVATION; CROSSMODAL BINDING; LINGUISTIC PITCH; MEMORY TRACES; CORTEX AB Background: In alphabetic languages, emerging evidence from behavioral and neuroimaging studies shows the rapid and automatic activation of phonological information in visual word recognition. In the mapping from orthography to phonology, unlike most alphabetic languages in which there is a natural correspondence between the visual and phonological forms, in logographic Chinese, the mapping between visual and phonological forms is rather arbitrary and depends on learning and experience. The issue of whether the phonological information is rapidly and automatically extracted in Chinese characters by the brain has not yet been thoroughly addressed. Methodology/Principal Findings: We continuously presented Chinese characters differing in orthography and meaning to adult native Mandarin Chinese speakers to construct a constant varying visual stream. In the stream, most stimuli were homophones of Chinese characters: The phonological features embedded in these visual characters were the same, including consonants, vowels and the lexical tone. Occasionally, the rule of phonology was randomly violated by characters whose phonological features differed in the lexical tone. Conclusions/Significance: We showed that the violation of the lexical tone phonology evoked an early, robust visual response, as revealed by whole-head electrical recordings of the visual mismatch negativity (vMMN), indicating the rapid extraction of phonological information embedded in Chinese characters. Source analysis revealed that the vMMN was involved in neural activations of the visual cortex, suggesting that the visual sensory memory is sensitive to phonological information embedded in visual words at an early processing stage. C1 [Wang, Xiao-Dong] Nanyang Technol Univ, Div Psychol, Sch Humanities & Social Sci, Singapore 639798, Singapore. [Liu, A-Ping] Anhui Univ, Dept Econ, Hefei 230039, Peoples R China. [Wu, Yin-Yuan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Wu, Yin-Yuan] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA. [Liu, A-Ping; Wang, Peng] Chinese Acad Sci, Inst Tech Biol & Agr Engn, CAS Key Lab Ion Beam Bioengn, Hefei, Peoples R China. RP Wang, XD (reprint author), Nanyang Technol Univ, Div Psychol, Sch Humanities & Social Sci, Singapore 639798, Singapore. EM XD-Wang@ntu.edu.sg NR 77 TC 5 Z9 5 U1 2 U2 28 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 20 PY 2013 VL 8 IS 2 AR e56778 DI 10.1371/journal.pone.0056778 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 093IE UT WOS:000315184200159 ER PT J AU Koh, Y Ballana, E Este, J Engelman, A AF Koh, Yasuhiro Ballana, Ester Este, Jose Engelman, Alan TI Polymorphic LEDGF/p75 variants support efficient HIV-1 infection ex vivo SO AIDS LA English DT Letter ID DISEASE PROGRESSION; CHROMATIN-BINDING; INTEGRATION; IDENTIFICATION; PROTEINS; DOMAINS C1 [Koh, Yasuhiro; Engelman, Alan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Koh, Yasuhiro; Engelman, Alan] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Ballana, Ester; Este, Jose] Univ Autonoma Barcelona, Hosp Germans Trias & Pujol, IrsiCaixa, Badalona, Spain. RP Engelman, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 450 Brookline Ave,CLS 1010, Boston, MA 02215 USA. EM alan_engelman@dfci.harvard.edu RI Este, Jose/B-5509-2008; OI Este, Jose/0000-0002-1436-5823; Ballana, Ester/0000-0002-5215-7363 FU NIAID NIH HHS [R01 AI039394, R37 AI039394, AI039394] NR 18 TC 3 Z9 3 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD FEB 20 PY 2013 VL 27 IS 4 BP 665 EP 667 DI 10.1097/QAD.0b013e32835af34c PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 094SM UT WOS:000315284100022 PM 23364444 ER PT J AU Gordon, LI Hong, FX Fisher, RI Bartlett, NL Connors, JM Gascoyne, RD Wagner, H Stiff, PJ Cheson, BD Gospodarowicz, M Advani, R Kahl, BS Friedberg, JW Blum, KA Habermann, TM Tuscano, JM Hoppe, RT Horning, SJ AF Gordon, Leo I. Hong, Fangxin Fisher, Richard I. Bartlett, Nancy L. Connors, Joseph M. Gascoyne, Randy D. Wagner, Henry Stiff, Patrick J. Cheson, Bruce D. Gospodarowicz, Mary Advani, Ranjana Kahl, Brad S. Friedberg, Jonathan W. Blum, Kristie A. Habermann, Thomas M. Tuscano, Joseph M. Hoppe, Richard T. Horning, Sandra J. TI Randomized Phase III Trial of ABVD Versus Stanford V With or Without Radiation Therapy in Locally Extensive and Advanced-Stage Hodgkin Lymphoma: An Intergroup Study Coordinated by the Eastern Cooperative Oncology Group (E2496) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INVOLVED-FIELD RADIOTHERAPY; ITALIANO LINFOMI; DISEASE; CHEMOTHERAPY; CONSOLIDATION; RISK; MOPP AB Purpose Although ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) has been established as the standard of care in patients with advanced Hodgkin lymphoma, newer regimens have been investigated, which have appeared superior in early phase II studies. Our aim was to determine if failure-free survival was superior in patients treated with the Stanford V regimen compared with ABVD. Patients and Methods The Eastern Cooperative Oncology Group, along with the Cancer and Leukemia Group B, the Southwest Oncology Group, and the Canadian NCIC Clinical Trials Group, conducted this randomized phase III trial in patients with advanced Hodgkin lymphoma. Stratification factors included extent of disease (localized v extensive) and International Prognostic Factors Project Score (0 to 2 v 3 to 7). The primary end point was failure-free survival (FFS), defined as the time from random assignment to progression, relapse, or death, whichever occurred first. Overall survival, a secondary end point, was measured from random assignment to death as a result of any cause. This design provided 87% power to detect a 33% reduction in FFS hazard rate, or a difference in 5-year FFS of 64% versus 74% at two-sided .05 significance level. Results There was no significant difference in the overall response rate between the two arms, with complete remission and clinical complete remission rates of 73% for ABVD and 69% for Stanford V. At a median follow-up of 6.4 years, there was no difference in FFS: 74% for ABVD and 71% for Stanford V at 5 years (P = .32). Conclusion ABVD remains the standard of care for patients with advanced Hodgkin lymphoma. J Clin Oncol 31:684-691. (c) 2012 by American Society of Clinical Oncology C1 [Gordon, Leo I.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Gordon, Leo I.] Robert H Lurie Comprehens Canc Ctr, Chicago, IL USA. [Stiff, Patrick J.] Loyola Univ, Ctr Canc, Maywood, IL 60153 USA. [Hong, Fangxin] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Fisher, Richard I.; Friedberg, Jonathan W.] Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA. [Bartlett, Nancy L.] Washington Univ, Siteman Canc Ctr, St Louis, MO USA. [Connors, Joseph M.; Gascoyne, Randy D.] British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 4E6, Canada. [Gospodarowicz, Mary] Univ Toronto, Toronto, ON, Canada. [Wagner, Henry] Penn State Hershey Canc Inst, Hershey, PA USA. [Cheson, Bruce D.] Georgetown Univ, Ctr Hosp, Washington, DC USA. [Advani, Ranjana; Hoppe, Richard T.; Horning, Sandra J.] Stanford Univ, Stanford, CA 94305 USA. [Tuscano, Joseph M.] Univ Calif Davis, Sacramento, CA USA. [Kahl, Brad S.] Univ Wisconsin, Ctr Canc, Madison, WI USA. [Blum, Kristie A.] Ohio State Univ, Columbus, OH 43210 USA. [Habermann, Thomas M.] Mayo Clin, Rochester, MN USA. RP Gordon, LI (reprint author), 676 N St Clair St, Chicago, IL 60611 USA. EM l-gordon@northwestern.edu RI Blum, Kristie/E-2768-2011; OI Gordon, Leo/0000-0003-1666-7064 FU National Cancer Institute, National Institutes of Health, Department of Health and Human Services [CA21115, CA23318, CA66636, CA17145, CA77440, CA11083, CA32102, CA46441, CA46282, CA38926, CA77202, CA21076, CA31946, CA13650] FX Supported in part by Public Health Service Grants No. CA21115, CA23318, CA66636, CA17145, CA77440, CA11083, CA32102, CA46441, CA46282, CA38926, CA77202, CA21076, CA31946, and CA13650 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. NR 28 TC 60 Z9 63 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 BP 684 EP 691 DI 10.1200/JCO.2012.43.4803 PG 8 WC Oncology SC Oncology GA 091YT UT WOS:000315086400016 PM 23182987 ER PT J AU Scott, DW Chan, FC Hong, FX Rogic, S Tan, KL Meissner, B Ben-Neriah, S Boyle, M Kridel, R Telenius, A Woolcock, BW Farinha, P Fisher, RI Rimsza, LM Bartlett, NL Cheson, BD Shepherd, LE Advani, RH Connors, JM Kahl, BS Gordon, LI Horning, SJ Steidl, C Gascoyne, RD AF Scott, David W. Chan, Fong Chun Hong, Fangxin Rogic, Sanja Tan, King L. Meissner, Barbara Ben-Neriah, Susana Boyle, Merrill Kridel, Robert Telenius, Adele Woolcock, Bruce W. Farinha, Pedro Fisher, Richard I. Rimsza, Lisa M. Bartlett, Nancy L. Cheson, Bruce D. Shepherd, Lois E. Advani, Ranjana H. Connors, Joseph M. Kahl, Brad S. Gordon, Leo I. Horning, Sandra J. Steidl, Christian Gascoyne, Randy D. TI Gene Expression-Based Model Using Formalin-Fixed Paraffin-Embedded Biopsies Predicts Overall Survival in Advanced-Stage Classical Hodgkin Lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; INTERNATIONAL PROGNOSTIC SCORE; TUMOR MICROENVIRONMENT; T-CELLS; DISEASE; MACROPHAGES; MARKER; INFECTION; BEACOPP; SAMPLES AB Purpose Our aim was to reliably identify patients with advanced-stage classical Hodgkin lymphoma (cHL) at increased risk of death by developing a robust predictor of overall survival (OS) using gene expression measured in routinely available formalin-fixed paraffin-embedded tissue (FFPET). Methods Expression levels of 259 genes, including those previously reported to be associated with outcome in cHL, were determined by digital expression profiling of pretreatment FFPET biopsies from 290 patients enrolled onto the E2496 Intergroup trial comparing doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and Stanford V regimens in locally extensive and advanced-stage cHL. A model for OS separating patients into low- and high-risk groups was produced using penalized Cox regression. The model was tested in an independent cohort of 78 patients enriched for treatment failure but otherwise similar to patients in a population-based registry of patients treated with ABVD. Weighted analysis methods generated unbiased estimates of predictor performance in the population-based registry. Results A 23-gene outcome predictor was generated. The model identified a population at increased risk of death in the validation cohort. There was a 29% absolute difference in 5-year OS between the high- and low-risk groups (63% v 92%, respectively; log-rank P < .001; hazard ratio, 6.7; 95% CI, 2.6 to 17.4). The predictor was superior to the International Prognostic Score and CD68 immunohistochemistry in multivariate analyses. Conclusion A gene expression-based predictor, developed in and applicable to routinely available FFPET biopsies, identifies patients with advanced-stage cHL at increased risk of death when treated with standard-intensity up-front regimens. J Clin Oncol 31:692-700. (c) 2012 by American Society of Clinical Oncology C1 [Scott, David W.; Chan, Fong Chun; Tan, King L.; Meissner, Barbara; Ben-Neriah, Susana; Boyle, Merrill; Kridel, Robert; Telenius, Adele; Woolcock, Bruce W.; Connors, Joseph M.; Steidl, Christian; Gascoyne, Randy D.] BC Canc Agency, Ctr Lymphoid Canc, Vancouver, BC V5Z 1L3, Canada. [Rogic, Sanja] Univ British Columbia, Ctr High Throughput Biol, Vancouver, BC V5Z 1M9, Canada. [Shepherd, Lois E.] Queens Univ, Natl Canc Inst, Canada Clin Trials Grp, Kingston, ON, Canada. [Hong, Fangxin] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Fisher, Richard I.] Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA. [Rimsza, Lisa M.] Univ Arizona, Tucson, AZ USA. [Bartlett, Nancy L.] Washington Univ, Sch Med, St Louis, MO USA. [Woolcock, Bruce W.] Georgetown Univ Hosp, Washington, DC 20007 USA. [Advani, Ranjana H.] Stanford Univ, Stanford, CA 94305 USA. [Horning, Sandra J.] Genentech Inc, San Francisco, CA USA. [Kahl, Brad S.] Univ Wisconsin, Madison, WI USA. [Gordon, Leo I.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Farinha, Pedro] Ctr Hosp Lisboa Cent, Lisbon, Portugal. RP Gascoyne, RD (reprint author), BC Canc Agcy, Dept Pathol & Expt Therapeut, 675 W 10th Ave,Room 5-113, Vancouver, BC V5Z 1L3, Canada. EM rgascoyn@bccancer.bc.ca OI Gordon, Leo/0000-0003-1666-7064; Farinha, Pedro/0000-0001-9364-9391 FU Roche Canada; Seattle Genetics; Public Health Service from the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services [CA21115, CA23318, CA66636, CA17145, CA11083, CA32102, CA38926, CA77202, CA21076, CA77470]; Terry Fox Foundation Strategic Health Research Training Program in Cancer Research at Canadian Institutes of Health Research [TGT-53912]; Cancer Research Society; Michael Smith Foundation; Canadian Institutes of Health Research [178536] FX Although all authors completed the disclosure declaration, the following author(s) and/or an author's immediate family member(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Employment or Leadership Position: None Consultant or Advisory Role: Randy D. Gascoyne, Celgene (C), Roche Canada (C) Stock Ownership: None Honoraria: Randy D. Gascoyne, Roche Canada Research Funding: Randy D. Gascoyne, Roche Canada, Seattle Genetics Expert Testimony: None Other Remuneration: None; Supported in part by Public Health Service Grants No. CA21115, CA23318, CA66636, CA17145, CA11083, CA32102, CA38926, CA77202, CA21076, and CA77470 from the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. Biospecimens were provided by the Eastern Cooperative Oncology Group Pathology Coordinating Office and Reference Laboratory. D.W.S. and K.L.T. were supported by postdoctoral fellowships of the Terry Fox Foundation Strategic Health Research Training Program in Cancer Research at Canadian Institutes of Health Research (Grant No. TGT-53912). C.S. was supported by postdoctoral fellowships of the Cancer Research Society (Steven E. Drabin Fellowship) and the Michael Smith Foundation for Health Research. R.D.G. receives funding support from the Canadian Institutes of Health Research (Grant No. 178536). NR 30 TC 53 Z9 53 U1 0 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 BP 692 EP 700 DI 10.1200/JCO.2012.43.4589 PG 9 WC Oncology SC Oncology GA 091YT UT WOS:000315086400017 PM 23182984 ER PT J AU Temel, JS Greer, JA Gallagher, ER Jackson, VA Lennes, IT Muzikansky, A Park, ER Pirl, WF AF Temel, Jennifer S. Greer, Joseph A. Gallagher, Emily R. Jackson, Vicki A. Lennes, Inga T. Muzikansky, Alona Park, Elyse R. Pirl, William F. TI Electronic Prompt to Improve Outpatient Code Status Documentation for Patients With Advanced Lung Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ILL HOSPITALIZED-PATIENTS; OF-LIFE COMMUNICATION; CARDIOPULMONARY-RESUSCITATION; PALLIATIVE CARE; DECISION-MAKING; CARDIAC-ARREST; LAST PHASE; END; PREFERENCES; DEATH AB Purpose Rates of documentation of end-of-life care preferences in the medical record remain low, even among patients with incurable malignancies. We therefore conducted a two-phase study to develop and assess the effect of electronic prompts to encourage oncology clinicians to document code status in the outpatient electronic health record (EHR) of patients with advanced lung cancers. Patients and Methods To determine the optimal delivery, content, and timing of the electronic prompt, we first facilitated focus groups with oncology clinicians at an affiliated medical center. Given this feedback, we developed e-mail reminders timed to the start of each new chemotherapy regimen. Between July 2009 and January 2011, 102 eligible patients with incurable lung cancer were approached, and 100 agreed to participate. We compared e-mail prompt participants (EPPs) with a cohort of 100 consecutive historical controls who began therapy for incurable lung cancer at least 1 year before the start of this study. The primary outcome measure was clinician documentation of code status in the EHR. Results EPPs were similar to historical controls, with no significant differences in demographic or clinical characteristics. At 1-year follow-up, 33.7% (n = 33/98) of EPPs had a code status documented in the outpatient EHR compared with 14.5% (n = 12/83) of historical controls (P = .003). Mean time to code status documentation was significantly shorter in EPPs (8.6 months [95% CI, 7.6 to 9.5]) compared with controls (10.5 months [95% CI, 9.8 to 11.3]; P = .004). Conclusion e-mail prompts may improve the rate and timing of code status documentation in the EHR and warrant further investigation. J Clin Oncol 31:710-715. (c) 2013 by American Society of Clinical Oncology C1 [Temel, Jennifer S.; Greer, Joseph A.; Gallagher, Emily R.; Jackson, Vicki A.; Lennes, Inga T.; Muzikansky, Alona; Park, Elyse R.; Pirl, William F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Temel, JS (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 7E, Boston, MA 02114 USA. EM jtemel@partners.org FU American Cancer Society FX Supported by the American Cancer Society (principal investigator Temel) and gifts from the Thoracic Oncology Quality of Life Fund. NR 44 TC 20 Z9 20 U1 0 U2 8 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 BP 710 EP 715 DI 10.1200/JCO.2012.43.2203 PG 6 WC Oncology SC Oncology GA 091YT UT WOS:000315086400019 PM 23284038 ER PT J AU Songer, JE Eatock, RA AF Songer, Jocelyn E. Eatock, Ruth Anne TI Tuning and Timing in Mammalian Type I Hair Cells and Calyceal Synapses SO JOURNAL OF NEUROSCIENCE LA English DT Article ID VESTIBULAR-NERVE AFFERENTS; PERIPHERAL INNERVATION PATTERNS; ACTIVATED POTASSIUM CHANNELS; SEMICIRCULAR CANAL AMPULLAE; MOUSE INNER-EAR; SQUIRREL-MONKEY; DEVELOPMENTAL ACQUISITION; MECHANICAL STIMULATION; DISCHARGE PROPERTIES; TRANSMITTER RELEASE AB Afferent nerve fibers in the central zones of vestibular epithelia form calyceal endings around type I hair cells and have phasic response properties that emphasize fast head motions. We investigated how stages from hair-cell transduction to calyceal spiking contribute tuning and timing to central (striolar)-zone afferents of the rat saccular epithelium. In an excised preparation, we deflected individual hair bundles with rigid probes driven with steps and sinusoids (0.5-500 Hz) and recorded whole-cell responses from hair cells and calyces at room temperature and body temperature. In immature hair cells and calyces (postnatal days (P) 1-P4), tuning sharpened at each stage. Transducer adaptation and membrane-charging time produced bandpass filtering of the receptor potential with best frequencies of 10-30 Hz and phase leads below 10 Hz. For small stimuli, electrical resonances sharply tuned the hair-cell membrane in the frequency range of 5-40 Hz. The synaptic delay of quantal transmission added a phase lag at frequencies above 10 Hz. The influence of spike thresholds at the calyceal spike initiation stage sharpened tuning and advanced response phase. Two additional mechanisms strongly advanced response phase above 10 Hz when present: (1) maturing (P7-P9) type I hair cells acquired low-voltage-activated channels that shortened the rise time of the receptor potential and (2) some calyces had nonquantal transmission with little synaptic delay. By reducing response time, the identified inner-ear mechanisms (transducer adaptation, low-voltage-activated channels, nonquantal transmission, and spike triggering) may compensate for transmission delays in vestibular reflex pathways and help stabilize posture and gaze during rapid head motions. C1 [Songer, Jocelyn E.; Eatock, Ruth Anne] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Eatock, Ruth Anne] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Songer, Jocelyn E.; Eatock, Ruth Anne] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. RP Eatock, RA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA. EM eatock@meei.harvard.edu RI Eatock, Ruth/F-6404-2013; OI Eatock, Ruth Anne/0000-0001-7547-2051 FU National Institutes of Health [R01 DC002290]; National Space Biomedical Research Institute through National Aeronautics and Space Administration [NCC 9-58] FX This study was supported by National Institutes of Health (R01 DC002290 and American Recovery & Reinvestment Act supplement) and National Space Biomedical Research Institute through National Aeronautics and Space Administration NCC 9-58 (J.E.S.). We thank Ben Winterroth, Tilly Kimm, Alison Casserly, and the Engineering Group at Eaton-Peabody Laboratories for technical assistance, and Dianna Sands and Jess Cunha for administrative assistance. We thank Drs. John Guinan, Radha Kalluri, and Dan Merfeld for helpful comments on an earlier version of this manuscript. NR 72 TC 24 Z9 24 U1 0 U2 13 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD FEB 20 PY 2013 VL 33 IS 8 BP 3706 EP 3724 DI 10.1523/JNEUROSCI.4067-12.2013 PG 19 WC Neurosciences SC Neurosciences & Neurology GA 093MJ UT WOS:000315195700045 PM 23426697 ER PT J AU Olson, APJ Tierney, LM AF Olson, Andrew P. J. Tierney, Lawrence M., Jr. TI Remarkably Wise SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Olson, Andrew P. J.] Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA. [Tierney, Lawrence M., Jr.] San Francisco VA Med Ctr, Med Serv, San Francisco, CA USA. [Tierney, Lawrence M., Jr.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Olson, APJ (reprint author), Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA. EM olso5714@umn.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 20 PY 2013 VL 309 IS 7 BP 669 EP 670 DI 10.1001/jama.2013.196 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 091EK UT WOS:000315032000021 PM 23423412 ER PT J AU Bajor, LA Lai, ZS Goodrich, DE Miller, CJ Penfold, RB Kim, HM Bauer, MS Kilbourne, AM AF Bajor, Laura A. Lai, Zongshan Goodrich, David E. Miller, Christopher J. Penfold, Robert B. Kim, Hyungjin Myra Bauer, Mark S. Kilbourne, Amy M. TI Posttraumatic stress disorder, depression, and health-related quality of life in patients with bipolar disorder: Review and new data from a multi-site community clinic sample SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Quality of life; Bipolar disorder; Posttraumatic stress disorders; Comorbidity ID TREATMENT ENHANCEMENT PROGRAM; SELF-REPORTED DIAGNOSIS; COGNITIVE-BEHAVIORAL THERAPY; COMORBID ANXIETY DISORDERS; ALCOHOL-USE DISORDERS; PUBLIC-SECTOR SAMPLE; I DISORDER; STEP-BD; 2ND-GENERATION ANTIDEPRESSANTS; PSYCHOSOCIAL INTERVENTIONS AB Background: Evidence suggests that patients with bipolar disorder have an elevated risk for comorbid posttraumatic stress disorder (PTSD) compared to those without a bipolar diagnosis. Although bipolar disorder is associated with decreased health-related quality of life (HRQOL), it is unclear whether comorbid PTSD interacts to affect HRQOL. Method: Baseline data from a multi-site study of patients with bipolar disorder were analyzed. Patient surveys ascertained clinical and demographic information, including physical and mental HRQOL based on the SF-12, mood symptoms (PHQ-9, Internal State Scale), and self-reported co-occurring conditions including PTSD. Results: Overall (N=384), 44.9% of patients self-reported co-occurring PTSD. Patients with PTSD had lower physical and mental HRQOL scores compared to those without PTSD (mean (SD) for those with and without PTSD, respectively): Mental Component Scale score 30.51 (8.22) and 32.86 (8.35); Physical Component Scale score 35.56 (7.77) and 37.21 (7.20). After adjusting for demographic and clinical factors including mood symptoms, multiple linear regression analyses revealed that PTSD was no longer significantly associated with physical or mental HRQOL; however, depressive symptoms were independently associated with mental HRQOL (Beta -0.63, p < 0.01). Conclusion: Depressive symptoms may explain the association between PTSD and mental HRQOL. Clinicians working with these patients will want to emphasize treatment of depression as important towards improving HRQOL for this group. Published by Elsevier B.V. C1 [Bajor, Laura A.; Miller, Christopher J.; Bauer, Mark S.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. [Lai, Zongshan; Goodrich, David E.; Kim, Hyungjin Myra; Kilbourne, Amy M.] VA Ann Arbor Ctr Clin Management Res, Ann Arbor, MI USA. [Bajor, Laura A.; Bauer, Mark S.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Kilbourne, Amy M.] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. [Penfold, Robert B.] Grp Hlth Res Inst, Seattle, WA USA. [Penfold, Robert B.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Kim, Hyungjin Myra] Univ Michigan, Ctr Stat Consultat & Res, Ann Arbor, MI 48109 USA. RP Bajor, LA (reprint author), VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, 150S Huntington Ave 152M, Boston, MA USA. EM laura_bajor@hms.harvard.edu OI Goodrich, David/0000-0003-3232-2189 FU NIMH [R01 MH79994]; Department of Veterans Affairs Research Grant [IIR 10-314] FX This work was supported by NIMH (R01 MH79994 to AMK) and the Department of Veterans Affairs Research Grant (IIR 10-314 to MSB). The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 82 TC 8 Z9 8 U1 3 U2 28 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD FEB 20 PY 2013 VL 145 IS 2 BP 232 EP 239 DI 10.1016/j.jad.2012.08.005 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 078IN UT WOS:000314092100013 PM 23021820 ER PT J AU Ansari, IUH Allen, T Berical, A Stock, PG Barin, B Striker, R AF Ansari, Israr-ul H. Allen, Todd Berical, Andrew Stock, Peter G. Barin, Burc Striker, Rob TI Phenotypic analysis of NS5A variant from liver transplant patient with increased cyclosporine susceptibility SO VIROLOGY LA English DT Article DE Hepatitis C virus; Transplantation; Cyclophilin inhibitor; Cyclosporine; Antiviral ID HEPATITIS-C-VIRUS; CYCLOPHILIN INHIBITORS; DOMAIN-II; PROTEIN; RESISTANCE; INFECTION; NS5A-CYCLOPHILIN; IDENTIFICATION; ALISPORIVIR; SUBSTRATE AB Hepatitis C virus (HCV) replication is limited by cyclophilin inhibitors but it remains unclear how viral genetic variations influence susceptibility to cyclosporine (cyclosporine A, CsA), a cyclophilin inhibitor. In this study HCV from liver transplant patients was sequenced before and after CsA exposure. Phenotypic analysis of NS5A sequence was performed by using HCV sub genomic replicon to determine CsA susceptibility. The data indicates an atypical proline at position 328 in NS5A causes increases CsA sensitivity both in the context of genotype 1a and 1b residues. Point mutants mimicking other naturally occurring residues at this position also increased (Ala) or decreased (Arg) replicon sensitivity to CsA relative to the typical threonine (genotype la) or serine (genotype lb) at this position. This work has implications for treatment of HCV by cyclophilin inhibitors. Published by Elsevier Inc. C1 [Striker, Rob] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53726 USA. [Ansari, Israr-ul H.; Striker, Rob] Univ Wisconsin, Madison, WI USA. [Allen, Todd; Berical, Andrew] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stock, Peter G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Barin, Burc] EMMES Corp, Rockville, MD USA. RP Striker, R (reprint author), William S Middleton Mem Vet Adm Med Ctr, 3207 Microbial Sci,1550 Linden Dr, Madison, WI 53726 USA. EM rtstriker@wisc.edu RI Allen, Todd/F-5473-2011 FU American Cancer Society [07-077-01]; Office of Research and Development, Biomedical Laboratory R&D Service, Department of Veterans Affairs; National Institute of Allergy and Infectious Diseases [AI052748] FX We gratefully acknowledge the patients and other investigators involved in the solid organ transplantation in HIV (HIV-TR Study AI052748) and the Project Manager, Rodney Rogers. This work was supported by the American Cancer Society Research Scholar Grant (07-077-01) to R.S., by the Office of Research and Development, Biomedical Laboratory R&D Service, Department of Veterans Affairs. Patient samples were obtained via the solid organ transplantation in HIV: Multi-site study (HIV-TR study AI052748) funded by the National Institute of Allergy and Infectious Diseases. NR 28 TC 5 Z9 5 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD FEB 20 PY 2013 VL 436 IS 2 BP 268 EP 273 DI 10.1016/j.virol.2012.11.018 PG 6 WC Virology SC Virology GA 083EX UT WOS:000314446600003 PM 23290631 ER PT J AU Aizer, AA Gu, XM Choueiri, TK Martin, NE Hu, JC Nguyen, PL AF Aizer, Ayal A. Gu, Xiangmei Choueiri, Toni K. Martin, Neil E. Hu, Jim C. Paul Linh Nguyen TI Overtreatment of low-risk prostate cancer in the United States: Incidence, cost, complications, and implications for the screening debate SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Harvard Radiat Oncol Program, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Med Sch, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 161 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600162 ER PT J AU Aizer, AA Paly, JJ Zietman, AL Nguyen, PL Beard, C Rao, SK Kaplan, ID Niemierko, A Hirsch, MS Wu, CL Olumi, AF Michaelson, MD D'Amico, AV Efstathiou, JA AF Aizer, Ayal A. Paly, Jonathan J. Zietman, Anthony L. Paul Linh Nguyen Beard, Clair Rao, Sandhya K. Kaplan, Irving D. Niemierko, Andrzej Hirsch, Michelle S. Wu, Chin-Lee Olumi, Aria F. Michaelson, M. Dror D'Amico, Anthony Victor Efstathiou, Jason Alexander TI Multidisciplinary care and management of very low-risk prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Harvard Radiat Oncol Program, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 55 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600056 ER PT J AU Bambury, RM Iyer, G Riester, M Werner, L Schultz, N Stack, EC Park, R Loda, M Ostrovnaya, I Kantoff, PW Bajorin, DF Solit, DB Michor, F Bellmunt, J Rosenberg, JE AF Bambury, Richard M. Iyer, Gopa Riester, Markus Werner, Lillian Schultz, Nikolaus Stack, Edward C. Park, Rachel Loda, Massimo Ostrovnaya, Irina Kantoff, Philip W. Bajorin, Dean F. Solit, David B. Michor, Franziska Bellmunt, Joaquim Rosenberg, Jonathan E. TI Peroxisome proliferator-activated receptor gamma (PPARG) gene amplifications in urothelial carcinoma (UC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Weill Cornell Med Coll, New York, NY USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Hosp Mar IMIM, Barcelona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 279 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600279 ER PT J AU Bambury, RM Riester, M Bellmunt, J Stack, EC Werner, L Park, R Iyer, G Loda, M Kantoff, PW Michor, F Rosenberg, JE AF Bambury, Richard M. Riester, Markus Bellmunt, Joaquim Stack, Edward C. Werner, Lillian Park, Rachel Iyer, Gopa Loda, Massimo Kantoff, Philip W. Michor, Franziska Rosenberg, Jonathan E. TI Genomic characterization of metastatic urothelial carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Weill Cornell Med Coll, New York, NY USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Univ Hosp Mar IMIM, Barcelona, Spain. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 247 PG 2 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600247 ER PT J AU Barnett, CM Heinrich, MC Nelson, DA Lim, JY Beadling, C Warrick, A Neff, T Thomas, G Garzotto, M Higano, CS Beer, TM Qian, DZ AF Barnett, Christine M. Heinrich, Michael C. Nelson, Dylan A. Lim, Jeong Youn Beadling, Carol Warrick, Andrea Neff, Tanaya Thomas, George Garzotto, Mark Higano, Celestia S. Beer, Tomasz M. Qian, David Z. TI Genomic analysis of prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Knight Diagnost Labs, Portland, OR 97201 USA. Univ Washington, Seattle Canc Care Alliance, Puget Sound Oncol Consortium, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 80 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600081 ER PT J AU Choueiri, TK Je, YJ Sonpavde, G Galsky, MD Kaymakcalan, M Nguyen, PL Schutz, F Heng, DYC Richards, CJ AF Choueiri, Toni K. Je, Youjin Sonpavde, Guru Galsky, Matt D. Kaymakcalan, Marina Nguyen, Paul Linh Schutz, Fabio Heng, Daniel Yick Chin Richards, Christopher J. TI Incidence and risk of treatment-related mortality in patients with renal cell cancer (RCC) and non-RCC treated with mammalian target of rapamycin (mTOR) inhibitors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Kyung Hee Univ, Seoul, South Korea. Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. Hosp St Jose, Sao Paulo, Brazil. Tom Baker Canc Clin, Calgary, AB, Canada. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 347 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600347 ER PT J AU Choueiri, TK Jacobus, SJ Qu, AQ Sweeney, C Appleman, LJ Tretter, CPG Bubley, GJ Elfiky, A Park, R Stack, EC Signoretti, S Walsh, MK Steele, G Hirsch, MS Krajewski, KM Taplin, ME Rosenberg, JE Ross, RW AF Choueiri, Toni K. Jacobus, Susanna J. Qu, Angela Q. Sweeney, Christopher Appleman, Leonard Joseph Tretter, Christopher P. G. Bubley, Glenn J. Elfiky, Aymen Park, Rachel Stack, Edward C. Signoretti, Sabina Walsh, Meghara K. Steele, Graeme Hirsch, Michelle S. Krajewski, Katherine Maragaret Taplin, Mary-Ellen Rosenberg, Jonathan E. Ross, Robert W. TI A phase II multicenter study of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) chemotherapy with pegfilgrastim support in patients (pts) muscle-invasive urothelial cancer (MIUC): Safety, pathologic, radiologic, and molecular correlates SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Pittsburgh, Pittsburgh, PA USA. Lahey Clin Fdn, Burlington, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Urol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 278 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600278 ER PT J AU Devlin, PM AF Devlin, Phillip M. TI Surface applicator high-dose-rate fractionated brachytherapy for conservative definitive management of extramammilary Paget's disease of the penis, scrotum, and mons pubis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 [Devlin, Phillip M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 333 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600333 ER PT J AU Fan, AC Leppert, J Liliental, JE Xu, LW Thong, AE Yost, C Yaghi, A Brooks, JD Harshman, LC Sabatti, C Srinivas, S Felsher, DW AF Fan, Alice C. Leppert, John Liliental, Joanna E. Xu, Liwen Thong, Alan E. Yost, Christine Yaghi, Alia Brooks, James D. Harshman, Lauren Christine Sabatti, Chiara Srinivas, Sandy Felsher, Dean W. TI Nanoscale proteomic profiling to define diagnostic signatures and biomarkers of therapeutic activity in patients with RCC SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Stanford Univ, Sch Med, Stanford, CA 94305 USA. Stanford Univ, Stanford, CA 94305 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Stanford Med Ctr, Stanford, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 432 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600429 ER PT J AU Fleming, MT Scher, HI Fizazi, K Taplin, ME Forer, D Hirmand, M De Bono, JS AF Fleming, Mark T. Scher, Howard I. Fizazi, Karim Taplin, Mary-Ellen Forer, David Hirmand, Mohammad De Bono, Johann Sebastian TI Long-term responders to enzalutamide (ENZA) during the phase III AFFIRM trial: Baseline characteristics and efficacy outcomes SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Virginia Oncol Associates, Norfolk, VA USA. Mem Sloan Kettering Canc Ctr, Sidney Kimmel Ctr Prostate & Urol Canc, New York, NY 10021 USA. Univ Paris 11, Orsay, France. Dana Farber Canc Inst, Boston, MA 02115 USA. Medivation Inc, San Francisco, CA USA. Inst Canc Res, Sutton, Surrey, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 20 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600023 ER PT J AU Galsky, MD Xie, WL Nakabayashi, M Ross, RW Fennessy, FM Tempany, CM Choueiri, TK Khine, K Kantoff, PW Taplin, ME Oh, WK AF Galsky, Matt D. Xie, Wanling Nakabayashi, Mari Ross, Robert W. Fennessy, Fiona M. Tempany, Clare M. Choueiri, Toni K. Khine, Krystal Kantoff, Philip W. Taplin, Mary-Ellen Oh, William K. TI Paradoxical significance of endorectal MRI (erMRI) response to neoadjuvant chemotherapy in patients with high-risk localized prostate cancer (HRLPC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Med Oncol, New York, NY USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Infin Pharmaceut Inc, Cambridge, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 23 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600026 ER PT J AU Gartrell, BA Ying, J Sivendran, S Agarwal, N Boucher, KM Choueiri, TK Sonpavde, G Oh, WK Galsky, MD AF Gartrell, Benjamin Adam Ying, Jian Sivendran, Shanthi Agarwal, Neeraj Boucher, Kenneth M. Choueiri, Toni K. Sonpavde, Guru Oh, William K. Galsky, Matt D. TI Pulmonary complications with the use of mTOR inhibitors in targeted cancer therapy: A systematic review and meta-analysis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Montefiore Med Ctr, Div Oncol, Bronx, NY 10467 USA. Univ Utah, Dept Internal Med, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. Lancaster Gen Hlth, Hematol Oncol Med Specialists, Lancaster, PA USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Sch Med, Boston, MA 02115 USA. Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Med Oncol, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 362 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600360 ER PT J AU Gray, PJ Fedewa, SA Shipley, WU Lin, CC Virgo, KS Kibel, AS Kamat, AM Rosenberg, JE Jemal, A Zietman, AL Efstathiou, JA AF Gray, Phillip J. Fedewa, Stacey A. Shipley, William U. Lin, Chun Chieh Virgo, Katherine S. Kibel, Adam Stuart Kamat, Ashish M. Rosenberg, Jonathan E. Jemal, Ahmedin Zietman, Anthony L. Efstathiou, Jason Alexander TI Clinical-pathologic stage discrepancy in patients with bladder cancer treated with radical cystectomy: Associations with clinical variables and survival SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Harvard Radiat Oncol Program, Boston, MA USA. Amer Canc Soc, Atlanta, GA 30329 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 248 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600248 ER PT J AU Guancial, EA Werner, L Bellmunt, J Nikitas, N Stack, EC Lis, R Signoretti, S Loda, M Regan, MM Park, RS O'Brien, R Berman, DM Bamias, A Rosenberg, JE AF Guancial, Elizabeth A. Werner, Lillian Bellmunt, Joaquim Nikitas, Nikitas Stack, Edward C. Lis, Rosina Signoretti, Sabina Loda, Massimo Regan, Meredith M. Park, Rachel S. O'Brien, Robert Berman, David M. Bamias, Aristotelis Rosenberg, Jonathan E. TI Relationship of ERCC1 genotype variant with mRNA expression and ERCC1 protein levels in advanced urothelial carcinoma (UC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Univ Hosp del Mar IMIM, Barcelona, Spain. Univ Athens, Athens, Greece. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. HECOG, Athens, Greece. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 260 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600260 ER PT J AU Harshman, LC Wood, L Srinivas, S Heng, DYC Choueiri, TK AF Harshman, Lauren Christine Wood, Lori Srinivas, Sandy Heng, Daniel Yick Chin Choueiri, Toni K. TI First-line mTOR inhibition in metastatic renal cell carcinoma (mRCC): An analysis from the International mRCC Database Consortium SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. Stanford Med Ctr, Stanford, CA USA. Tom Baker Canc Clin, Calgary, AB, Canada. Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Brigham & Womens Hos, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 430 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600427 ER PT J AU Hutson, TE Dang, LH Lauer, RC Starodub, A Hauke, RJ Galsky, MD Bylow, KA Cowey, CL Bibby, DC Kremmidiotis, G Doolin, EE Lavranos, TC Sonpavde, G Logan, T Hahn, NM Sweeney, C Sarantopoulos, J AF Hutson, Thomas E. Dang, Long H. Lauer, Richard C. Starodub, Alexander Hauke, Ralph J. Galsky, Matt D. Bylow, Kathryn A. Cowey, Charles Lance Bibby, David C. Kremmidiotis, Gabriel Doolin, Elizabeth E. Lavranos, Tina C. Sonpavde, Guru Logan, Theodore Hahn, Noah M. Sweeney, Christopher Sarantopoulos, John CA Hoosier Oncology Grp TI Updated phase I results of a phase I/II trial of BNC105P with everolimus in patients with metastatic renal cell carcinoma (mRCC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 McKesson Specialty Hlth, US Oncol Res, The Woodlands, TX USA. Baylor Charles A Sammons Canc Ctr Texas Oncol PA, Dallas, TX USA. Univ Florida, Gainesville, FL USA. Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA. Indiana Univ, Hlth Goshen Ctr Canc Care, Goshen, IN USA. Nebraska Canc Specialists, Omaha, NE USA. Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. Bionomics Ltd, Thebarton, Australia. Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas Hlth Sci Ctr San Antonio, Inst Drug Dev, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 397 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600394 ER PT J AU Kaymakcalan, M Je, YJ Sonpavde, G Galsky, MD Nguyen, PL Schutz, F Heng, DYC Richards, CJ Choueiri, TK AF Kaymakcalan, Marina Je, Youjin Sonpavde, Guru Galsky, Matt D. Paul Linh Nguyen Schutz, Fabio Heng, Daniel Yick Chin Richards, Christopher J. Choueiri, Toni K. TI Incidence and risk of infections in renal cell cancer (RCC) and non-RCC patients treated with everolimus and temsirolimus: A meta-analysis of randomized control trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Kyung Hee Univ, Seoul, South Korea. Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Med Oncol, New York, NY USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Hosp St Jose, Sao Paulo, Brazil. Tom Baker Canc Clin, Calgary, AB, Canada. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Lank Ctr Genitourinary Onco, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 353 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600351 ER PT J AU Kovtun, K Wolfsberger, LD Niedermayr, T Neubauer, E Murciano-Goroff, YR Beard, C D'Amico, AV Martin, NE Orio, PF Nguyen, PL AF Kovtun, Konstantin Wolfsberger, Luciant D. Niedermayr, Thomas Neubauer, Emily Murciano-Goroff, Yonina R. Beard, Clair D'Amico, Anthony Victor Martin, Neil E. Orio, Peter F. Nguyen, Paul Linh TI Dosimetic quality and evolution of edema after prostate brachytherapy for small prostates: Implications for the use of newer isotopes SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 [Kovtun, Konstantin; Wolfsberger, Luciant D.; Niedermayr, Thomas; Neubauer, Emily; Murciano-Goroff, Yonina R.; Beard, Clair; D'Amico, Anthony Victor; Martin, Neil E.; Orio, Peter F.; Nguyen, Paul Linh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 232 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600232 ER PT J AU Kovtun, K Penzkofer, T Agrawal, N Kapur, T Fedorov, A Cormack, RA D'Amico, AV Tempany, CM Nguyen, PL AF Kovtun, Konstantin Penzkofer, Tobias Agrawal, Neha Kapur, Tina Fedorov, Andriy Cormack, Robert A. D'Amico, Anthony Victor Tempany, Clare M. Nguyen, Paul Linh TI Location of local recurrence after MRI-guided partial prostate brachytherapy targeting only the peripheral zone: Implications for focal therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 149 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600150 ER PT J AU Kroeger, N Xie, WL Lee, JL Bjarnason, GA Knox, JJ MacKenzie, MJ Wood, L Srinivas, S Vaishamayan, UN Rha, SY Pal, SK Donskov, F Agarwal, N Kollmannsberger, CK Tan, MH North, SA Rini, BI Choueiri, TK Heng, DYC AF Kroeger, Nils Xie, Wanling Lee, Jae-Lyun Bjarnason, Georg A. Knox, Jennifer J. MacKenzie, Mary J. Wood, Lori Srinivas, Sandy Vaishamayan, Ulka N. Rha, Sun Young Pal, Sumanta Kumar Donskov, Frede Agarwal, Neeraj Kollmannsberger, Christian K. Tan, Min-Han North, Scott A. Rini, Brian I. Choueiri, Toni K. Heng, Daniel Yick Chin TI Metastatic non-clear cell renal cell carcinoma (nccRCC) treated with targeted therapy agents: Applying the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model to predict outcomes SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Tom Baker Canc Clin, Calgary, AB, Canada. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea. Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. London Reg Canc Program, London, ON, Canada. Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. Stanford Med Ctr, Stanford, CA USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Yonsei Univ, Coll Med, Yonsei Canc Ctr, Seoul, South Korea. City Hope Natl Med Ctr, Duarte, CA USA. Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Natl Canc Ctr, Singapore, Singapore. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 396 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600393 ER PT J AU Martin, NE Chen, MH Beard, C Nguyen, PL Loffredo, M Renshaw, AA Kantoff, PW D'Amico, AV AF Martin, Neil E. Chen, Ming-Hui Beard, Clair Nguyen, Paul Linh Loffredo, Marian Renshaw, Andrew A. Kantoff, Philip W. D'Amico, Anthony Victor TI Age, comorbidity, and the risk of death in men with PSA failure following radiation therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Connecticut, Storrs, CT USA. Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. Baptist Hosp Miami, Miami, FL USA. RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 82 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600083 ER PT J AU Master, VA Wang, DSP Tai, CGL Sesay, M Kilbridge, KL Goodman, M Jani, AB AF Master, Viraj A. Wang, Daniel Shin-Ping Tai, Caroline Gar-Ling Sesay, Musu Kilbridge, Kerry L. Goodman, Michael Jani, Ashesh B. TI Severe lack of comprehension of common prostate health terminology in underserved populations: External validation SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Emory Univ, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 71 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600072 ER PT J AU McDermott, DF Manola, J Pins, M Flaherty, KT Atkins, MB Dutcher, JP George, DJ Margolin, KA DiPaola, RS AF McDermott, David F. Manola, Judith Pins, Michael Flaherty, Keith T. Atkins, Michael B. Dutcher, Janice P. George, Daniel J. Margolin, Kim Allyson DiPaola, Robert S. TI The BEST trial (E2804): A randomized phase II study of VEGF, RAF kinase, and mTOR combination targeted therapy (CTT) with bevacizumab (bev), sorafenib (sor), and temsirolimus (tem) in advanced renal cell carcinoma (RCC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Illinois, Coll Med, Chicago, IL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. Continuum Canc Ctr New York, St Lukes Roosevelt Hosp Ctr, New York, NY USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Washington, Seattle, WA 98195 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ USA. NR 0 TC 5 Z9 5 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 345 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600345 ER PT J AU McDermott, DF Drake, CG Sznol, M Choueiri, TK Powderly, JD Smith, DC Wigginton, JM Kollia, G Gupta, AK Atkins, MB AF McDermott, David F. Drake, Charles G. Sznol, Mario Choueiri, Toni K. Powderly, John D. Smith, David C. Wigginton, Jon M. Kollia, Georgia Gupta, Ashok Kumar Atkins, Michael B. TI Clinical activity and safety of antiprogrammed death-1 (PD-1) (BMS-936558/MDX-1106/ONO-4538) in patients (pts) with previously treated, metastatic renal cell carcinoma (mRCC): An updated analysis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Yale Canc Ctr, New Haven, CT USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Lank Ctr Genitourinary Onco, Boston, MA 02115 USA. Carolina BioOncol Inst, Huntersville, NC USA. Univ Michigan, Ann Arbor, MI 48109 USA. Bristol Myers Squibb Co, Princeton, NJ USA. Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 351 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600349 ER PT J AU McKay, RR Kroeger, N Xie, WL Lee, JL Knox, JJ Bjarnason, GA MacKenzie, MJ Wood, L Srinivas, S Vaishampayan, UN Rha, SY Pal, SK Donskov, F Tantravahi, S Rini, BI Heng, DYC Choueiri, TK AF McKay, Rana R. Kroeger, Nils Xie, Wanling Lee, Jae-Lyun Knox, Jennifer J. Bjarnason, Georg A. MacKenzie, Mary J. Wood, Lori Srinivas, Sandy Vaishampayan, Ulka N. Rha, Sun Young Pal, Sumanta Kumar Donskov, Frede Tantravahi, Srinivas Rini, Brian I. Heng, Daniel Yick Chin Choueiri, Toni K. TI Impact of bone and liver metastases (BM, LM) in patients with metastatic renal cell carcinoma (mRCC) treated with molecularly targeted agents (MTAs): Results from the International mRCC Database Consortium (IMDC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Tom Baker Canc Clin, Calgary, AB, Canada. Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. London Reg Canc Program, London, ON, Canada. Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. Stanford Med Ctr, Stanford, CA USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Yonsei Univ, Coll Med, Yonsei Canc Ctr, Seoul, South Korea. City Hope Natl Med Ctr, Duarte, CA USA. Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 394 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600391 ER PT J AU Milowsky, MI Dittrich, C Martinez, ID Jagdev, S Millard, FE Sweeney, C Bajorin, DF Cerbone, L Dunn, RM Sen, P Shi, M Kay, ACM Squires, M Sternberg, CN AF Milowsky, Matthew I. Dittrich, Christian Martinez, Ignacio Duran Jagdev, Satinder Millard, Frederick E. Sweeney, Christopher Bajorin, Dean F. Cerbone, Linda Dunn, Robert M. Sen, Paramita Shi, Michael Kay, Andrea C. M. Squires, Matthew Sternberg, Cora N. TI Final results of a multicenter, open-label phase II trial of dovitinib (TKI258) in patients with advanced urothelial carcinoma with either mutated or nonmutated FGFR3 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. Kaiser Franz Josef Spital, LBI ACR VIEnna, Vienna, Austria. Kaiser Franz Josef Spital, ACR ITR VIEnna, Vienna, Austria. CIOCC Grp Hosp Madrid, Madrid, Spain. St Jamess Inst Oncol, Leeds, W Yorkshire, England. Univ Calif San Diego, La Jolla, CA 92093 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. San Camillo & Forlanini Hosp, Rome, Italy. Novartis Pharmaceut, E Hanover, NJ USA. NR 0 TC 4 Z9 4 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 255 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600255 ER PT J AU Mirabeau-Beale, K Chen, MH D'Amico, AV AF Mirabeau-Beale, Kristina Chen, Ming-Hui D'Amico, Anthony Victor TI Prior cancer diagnosis in men with nonmetastatic prostate cancer and the risk of prostate cancer specific and all-cause mortality SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Harvard Radiat Oncol Program, Boston, MA USA. Univ Connecticut, Storrs, CT USA. Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol,Med Sch, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 70 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600071 ER PT J AU Molina, AM Hutson, TE Larkin, JMG Gold, A Andresen, C Wood, K Motzer, RJ Michaelson, MD AF Molina, Ana M. Hutson, Thomas E. Larkin, James M. G. Gold, Anne Andresen, Corina Wood, Karen Motzer, Robert John Michaelson, M. Dror TI A phase Ib clinical trial of the multitargeted kinase inhibitor lenvatinib (E7080) in combination with everolimus for treatment of metastatic renal cell carcinoma (RCC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. Royal Marsden NHS Fdn Trust, London, England. Eisai Inc, Woodcliff Lake, NJ USA. Eisai Ltd, Hatfield, Herts, England. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 358 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600356 ER PT J AU Nanda, A Chen, MH Moran, BJ Braccioforte, MH D'Amico, AV AF Nanda, Akash Chen, Ming-Hui Moran, Brian Joseph Braccioforte, Michelle H. D'Amico, Anthony Victor TI Intermediate versus short-course hormone therapy and mortality in men with high-risk prostate cancer treated with radiation therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 MD Anderson Canc Ctr Orlando, Orlando, FL USA. Univ Connecticut, Storrs, CT USA. Prostate Canc Fdn Chicago, Westmont, IL USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 83 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600084 ER PT J AU O'Donnell, E Gray, KP Ravi, P Sweeney, C AF O'Donnell, Elizabeth Gray, Kathryn P. Ravi, Praful Sweeney, Christopher TI A meta-analysis of patient outcomes with subcentimeter disease after chemotherapy for metastatic nonseminomatous germ cell tumor (NSGCT) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 [O'Donnell, Elizabeth; Gray, Kathryn P.; Ravi, Praful; Sweeney, Christopher] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 324 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600324 ER PT J AU O'Donnell, E Gray, KP Hirsch, MS Ravi, P Beard, C Sweeney, C AF O'Donnell, Elizabeth Gray, Kathryn P. Hirsch, Michelle S. Ravi, Praful Beard, Clair Sweeney, Christopher TI A 10-year retrospective review of germ cell tumors not cured with cisplatin-based chemotherapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 325 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600325 ER PT J AU Paly, JJ Hallemeier, CL Biggs, PJ Niemierko, A Roeder, F Martinez-Monge, R Whitson, JM Calvo, FA Fastner, G Wong, W Ellis, RJ Efstathiou, JA AF Paly, Jonathan J. Hallemeier, Christopher Leigh Biggs, Peter J. Niemierko, Andrzej Roeder, Falk Martinez-Monge, Rafael Whitson, Jared Myers Calvo, Felipe A. Fastner, Gerd Wong, William Ellis, Rodney J. Efstathiou, Jason Alexander TI Outcomes for a multi-institutional cohort of patients treated with intra-operative radiation therapy for advanced or recurrent renal cell carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin, Rochester, MN USA. Univ Clin Heidelberg, Heidelberg, Germany. Univ Navarra, Navarra, Spain. Univ Calif San Francisco, San Francisco, CA 94143 USA. Hosp Gen Univ Gregorio Maranon, Madrid, Spain. Paracelsus Med Univ, Salzburg, Austria. Mayo Clin, Scottsdale, AZ USA. Case Western Reserve Univ, Univ Hosp Case Med Ctr, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 442 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600439 ER PT J AU Petrylak, DP Kantoff, PW Mega, AE Vogelzang, NJ Stephenson, J Fleming, MT Stambler, N Petrini, M Huang, K Israel, RJ AF Petrylak, Daniel Peter Kantoff, Philip W. Mega, Anthony E. Vogelzang, Nicholas J. Stephenson, Joe Fleming, Mark T. Stambler, Nancy Petrini, Michaela Huang, Kathleen Israel, Robert Joseph TI Prostate-specific membrane antigen antibody drug conjugate (PSMA ADC): A phase I trial in metastatic castration-resistant prostate cancer (mCRPC) previously treated with a taxane SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Columbia Univ, Med Ctr, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brown Univ, Oncol Grp, Providence, RI 02912 USA. Comprehens Canc Ctr Nevada, Las Vegas, NV USA. US Oncol Res, Las Vegas, NV USA. Canc Ctr Carolinas, Greenville, SC USA. Virginia Oncol Associates, Norfolk, VA USA. Progen Pharmaceut Inc, Tarrytown, NY USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 119 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600120 ER PT J AU Pond, GR Agarwal, N Bellmunt, J Choueiri, TK Qu, AQ Fougeray, R Niegisch, G Galsky, MD Wong, YN Stadler, WM Sridhar, SS Sternberg, CN Sonpavde, G AF Pond, Gregory Russell Agarwal, Neeraj Bellmunt, Joaquim Choueiri, Toni K. Qu, Angela Q. Fougeray, Ronan Niegisch, Guenter Galsky, Matt D. Wong, Yu-Ning Stadler, Walter Michael Sridhar, Srikala S. Sternberg, Cora N. Sonpavde, Guru TI Impact of baseline prognostic factors on progression-free survival at 6 months (PFS6) and response in patients receiving second-line therapy for advanced urothelial carcinoma (UC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 McMaster Univ, Hamilton, ON, Canada. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. Univ Hosp Mar, Barcelona, Spain. Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Med Sch, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Rech Pierre Fabre, Boulogne, France. Univ Dusseldorf, Dept Urol, Dusseldorf, Germany. Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Chicago, Chicago, IL 60637 USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. San Camillo & Forlanini Hosp, Rome, Italy. Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 301 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600301 ER PT J AU Qu, AQ Choueiri, TK Jacobus, SJ Rosenberg, JE Ramaiya, NH Krajewski, KM AF Qu, Angela Q. Choueiri, Toni K. Jacobus, Susanna J. Rosenberg, Jonathan E. Ramaiya, Nikhil H. Krajewski, Katherine Maragaret TI Radiologic response (RR) by MRI in patients (pts) with muscle-invasive urothelial cancer (MIUC) undergoing neoadjuvant chemotherapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 283 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600283 ER PT J AU Rathkopf, DE Smith, MR De Bono, JS Logothetis, C Shore, ND De Souza, PL Fizazi, K Mulders, P Mainwaring, PN Hainsworth, JD Beer, TM North, SA Fradet, Y Griffin, TW Park, YC Kheoh, TS Small, EJ Scher, HI Molina, A Ryan, CJ AF Rathkopf, Dana E. Smith, Matthew Raymond De Bono, Johann Sebastian Logothetis, Christopher Shore, Neal D. De Souza, Paul L. Fizazi, Karim Mulders, Peter Mainwaring, Paul N. Hainsworth, John D. Beer, Tomasz M. North, Scott A. Fradet, Yves Griffin, Thomas W. Park, Youn Choi Kheoh, Thian San Small, Eric Jay Scher, Howard I. Molina, Arturo Ryan, Charles J. TI Updated interim analysis (IA) of COU-AA-302, a randomized phase III study of abiraterone acetate (AA) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) without prior chemotherapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Royal Marsden Hosp, Inst Canc Res, Sutton, Surrey, England. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Carolina Urol Res Ctr, Myrtle Beach, SC USA. Univ Western Sydney, Sch Med, Ingham Inst, Liverpool, Australia. Inst Gustave Roussy, Villejuif, France. Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. Haematol Clin Australasia, Brisbane, Qld, Australia. Oncol Clin Australasia, Brisbane, Qld, Australia. Sarah Cannon Res Inst, Nashville, TN USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Univ Laval, Quebec City, PQ, Canada. Janssen Res & Dev, Los Angeles, CA USA. Janssen Res & Dev, Raritan, NJ USA. Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RI Mulders, Peter/H-8076-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 5 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600009 ER PT J AU Scher, HI Fizazi, K Saad, F Chi, KN Taplin, ME Sternberg, CN Armstrong, AJ Hirmand, M Forer, D De Bono, JS AF Scher, Howard I. Fizazi, Karim Saad, Fred Chi, Kim N. Taplin, Mary-Ellen Sternberg, Cora N. Armstrong, Andrew J. Hirmand, Mohammad Forer, David De Bono, Johann Sebastian TI Impact of on-study corticosteroid use on efficacy and safety in the phase III AFFIRM study of enzalutamide (ENZA), an androgen receptor inhibitor SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Mem Sloan Kettering Canc Ctr, Sidney Kimmel Ctr Prostate & Urol Canc, New York, NY 10021 USA. Univ Paris 11, Orsay, France. Univ Montreal, Ctr Hosp, Montreal, PQ, Canada. British Columbia Canc Agcy, Vancouver Canc Ctr, Vancouver, BC V5Z 4E6, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. San Camillo & Forlanini Hosp, Rome, Italy. Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC USA. Medivation Inc, San Francisco, CA USA. Inst Canc Res, Sutton, Surrey, England. NR 0 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 6 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600010 ER PT J AU Schoenfeld, JD Margalit, DN Shui, IM Kasperzyk, JL Sesso, HD Martin, NE Nguyen, PL Kantoff, PW Rider, JR Mucci, LA AF Schoenfeld, Jonathan D. Margalit, Danielle Nina Shui, Irene M. Kasperzyk, Julie L. Sesso, Howard D. Martin, Neil E. Paul Linh Nguyen Kantoff, Philip W. Rider, Jennifer R. Mucci, Lorelei A. TI Associations between single nucleotide polymorphisms (SNPs) in inflammation-related genes and quality of life after radiation therapy (RT) for prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Harvard Radiat Oncol Program, Boston, MA USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 2 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600006 ER PT J AU Schweizer, MT Bardia, A Blackford, AL Lin, JQ Armstrong, AJ King, S Rudek, MA Yegnasubramanian, ST Carducci, MA AF Schweizer, Michael Thomas Bardia, Aditya Blackford, Amanda L. Lin, Jianqing Armstrong, Andrew J. King, Serina Rudek, Michelle A. Yegnasubramanian, Srinivasan Thomas Carducci, Michael Anthony TI A prostate cancer clinical trials consortium trial of disulfiram (D) in men with nonmetastatic recurrent prostate cancer (PCa) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp Canc Ctr, Boston, MA USA. Thomas Jefferson Univ, Jefferson Kimmel Canc Ctr, Philadelphia, PA 19107 USA. Duke Univ Med Ctr, Duke Canc Inst, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 219 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600219 ER PT J AU Shah, A Motiwala, S O'Dwyer, PJ Flaherty, KT Keefe, SM AF Shah, Amishi Motiwala, Shweta O'Dwyer, Peter J. Flaherty, Keith T. Keefe, Stephen Michael TI Increase in blood pressure with sorafenib exposure in renal cell carcinoma versus other solid tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Univ Penn, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 384 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600381 ER PT J AU Shelton, JB Skolarus, TA Ryoo, JJ Malin, J Antonio, ALM He, R Saigal, C AF Shelton, Jeremy B. Skolarus, Ted A. Ryoo, Joan Joonsun Malin, Jennifer Antonio, Anna Liza M. He, Ren Saigal, Christopher TI Specification and validation of prostate cancer quality-of-care e-measures in the Veterans Health Administration (VHA) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA. Univ Michigan, Ann Arbor, MI 48109 USA. Kaiser Permanente, Los Angeles Med Ctr, Los Angeles, CA USA. WellPoint Inc, Indianapolis, IN USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 178 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600179 ER PT J AU Sivendran, S Ying, J Gartrell, BA Agarwal, N Boucher, KM Choueiri, TK Sonpavde, G Oh, WK Galsky, MD AF Sivendran, Shanthi Ying, Jian Gartrell, Benjamin Adam Agarwal, Neeraj Boucher, Kenneth M. Choueiri, Toni K. Sonpavde, Guru Oh, William K. Galsky, Matt D. TI Metabolic complications with the use of mTOR inhibitors for cancer therapy: A systematic review and meta-analysis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Lancaster Gen Hlth, Lancaster, PA USA. Univ Utah, Dept Internal Med, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. Montefiore Med Ctr, Div Oncol, Bronx, NY 10467 USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA. Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Med Oncol, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 398 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600395 ER PT J AU Small, EJ Higano, CS Kantoff, PW Whitmore, JB Frohlich, MW Petrylak, DP AF Small, Eric Jay Higano, Celestia S. Kantoff, Philip W. Whitmore, James Boyd Frohlich, Mark Walter Petrylak, Daniel Peter TI Relationship of sipuleucel-T with time to first use of opioid analgesics (TFOA) in patients (pts) with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC) on the IMPACT trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. Univ Washington, Sch Med, Seattle, WA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Dendreon Corp, Seattle, WA USA. Yale Univ, Smilow Canc Hosp, New Haven, CT USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 74 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600075 ER PT J AU Smith, MR Halabi, S Ryan, CJ Stadler, WM Hussain, A Vogelzang, NJ Hauke, RJ Sanford, BL Small, EJ AF Smith, Matthew Raymond Halabi, Susan Ryan, Charles J. Stadler, Walter Michael Hussain, Arif Vogelzang, Nicholas J. Hauke, Ralph J. Sanford, Ben L. Small, Eric Jay TI Efficacy and safety of zoledronic acid in men with castration-sensitive prostate cancer and bone metastases: Results of CALGB 90202 (Alliance) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Duke Univ, Med Ctr, Alliance Stat & Data Ctr, Durham, NC USA. USCF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. Univ Chicago, Chicago, IL 60637 USA. Univ Maryland, Baltimore, MD 21201 USA. Comprehens Canc Ctr Nevada, Las Vegas, NV USA. Univ Nebraska Med Ctr, Omaha, NE USA. Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 27 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600030 ER PT J AU Smith, MR Antonarakis, ES Ryan, CJ Berry, WR Shore, N Liu, G Alumkal, JJ Higano, CS Maneval, EC Rathkopf, DE AF Smith, Matthew Raymond Antonarakis, Emmanuel S. Ryan, Charles J. Berry, William R. Shore, Neal Liu, Glenn Alumkal, Joshi J. Higano, Celestia S. Maneval, Edna Chow Rathkopf, Dana E. TI ARN-509 in men with high-risk nonmetastatic castration-resistant prostate cancer (CRPC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. USCF, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. US Oncol, Canc Ctr North Carolina, Raleigh, NC USA. Grand Strand Urol, Myrtle Beach, SC USA. Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. Univ Washington, Sch Med, Seattle, WA USA. Aragon Pharmaceut, San Diego, CA USA. Mem Sloan Kettering Canc Ctr, Sidney Kimmel Ctr Prostate & Urol Canc, New York, NY 10021 USA. RI Antonarakis, Emmanuel/E-4550-2011 NR 0 TC 6 Z9 6 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 7 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600011 ER PT J AU Strock, J Gray, KP Nakabayashi, M Evan, C O'Donnell, E Pomerantz, M Kantoff, PW Sweeney, C AF Strock, Jessica Gray, Kathryn P. Nakabayashi, Mari Evan, Carolyn O'Donnell, Elizabeth Pomerantz, Mark Kantoff, Philip W. Sweeney, Christopher TI Characterization of patients who present with de novo metastatic prostate cancer: Single-institution database analysis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 [Strock, Jessica; Gray, Kathryn P.; Nakabayashi, Mari; Evan, Carolyn; O'Donnell, Elizabeth; Pomerantz, Mark; Kantoff, Philip W.; Sweeney, Christopher] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 33 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600035 ER PT J AU Tombal, B Borre, M Rathenborg, P Werbrouck, P Heidenreich, A Iversen, P Baskin-Bey, ES Perabo, F Phung, D Smith, MR AF Tombal, Bertrand Borre, Michael Rathenborg, Per Werbrouck, Patrick Heidenreich, Axel Iversen, Peter Baskin-Bey, Edwina S. Perabo, Frank Phung, De Smith, Matthew Raymond TI Enzalutamide monotherapy: Phase II study results in patients with hormone-naive prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Catholic Univ Louvain, Clin Univ St Luc, B-1200 Brussels, Belgium. Arhus Univ Hosp, Dept Urol, Skejby, Denmark. Herlev Hosp, DK-2730 Herlev, Denmark. AZ Groeninge Kortrijk, Kortrijk, Belgium. Klin & Poliklin Urol, North Rhine Westphalia, Germany. Univ Copenhagen, Rigshosp, DK-2100 Copenhagen, Denmark. Astellas Pharma Europe Ltd, Staines, England. Astellas Pharma Inc, Leiderdorp, Netherlands. Astellas Pharma Europe BV, Leiderdorp, Netherlands. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 18 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600021 ER PT J AU Tsao, CK Gray, KP Nakabayashi, M Evan, C Galsky, MD Kantoff, PW Oh, WK Pomerantz, M AF Tsao, Che-Kai Gray, Kathryn P. Nakabayashi, Mari Evan, Caroline Galsky, Matt D. Kantoff, Philip W. Oh, William K. Pomerantz, Mark TI Association of Gleason 9-10 prostate cancer with worse outcomes compared to Gleason 8 disease SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Mt Sinai Sch Med, Div Hematol & Med Oncol, Tisch Canc Inst, New York, NY USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 157 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600158 ER PT J AU Xu, RN Horick, N McGovern, FJ Dahl, DM Feldman, AS Blute, ML Olumi, AF Michaelson, MD AF Xu, Rena Horick, Nora McGovern, Francis J. Dahl, Douglas M. Feldman, Adam S. Blute, Michael L. Olumi, Aria F. Michaelson, M. Dror TI Prognostic significance of indeterminate lung nodules in renal cell carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 377 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600374 ER PT J AU Sigova, AA Mullen, AC Molinie, B Gupta, S Orlando, DA Guenther, MG Almada, AE Lin, C Sharp, PA Giallourakis, CC Young, RA AF Sigova, Alla A. Mullen, Alan C. Molinie, Benoit Gupta, Sumeet Orlando, David A. Guenther, Matthew G. Almada, Albert E. Lin, Charles Sharp, Phillip A. Giallourakis, Cosmas C. Young, Richard A. TI Divergent transcription of long noncoding RNA/mRNA gene pairs in embryonic stem cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE development; expression ID ACTIVE GENES; REGULATORY CIRCUITRY; HUMAN PROMOTERS; ANTISENSE RNA; HISTONE H3; REVEALS; MOUSE; DIFFERENTIATION; EXPRESSION; GENOME AB Many long noncoding RNA (lncRNA) species have been identified in mammalian cells, but the genomic origin and regulation of these molecules in individual cell types is poorly understood. We have generated catalogs of lncRNA species expressed in human and murine embryonic stem cells and mapped their genomic origin. A surprisingly large fraction of these transcripts (>60%) originate from divergent transcription at promoters of active protein-coding genes. The divergently transcribed lncRNA/mRNA gene pairs exhibit coordinated changes in transcription when embryonic stem cells are differentiated into endoderm. Our results reveal that transcription of most lncRNA genes is coordinated with transcription of protein-coding genes. C1 [Sigova, Alla A.; Mullen, Alan C.; Gupta, Sumeet; Orlando, David A.; Guenther, Matthew G.; Lin, Charles; Young, Richard A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Mullen, Alan C.; Molinie, Benoit; Giallourakis, Cosmas C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Almada, Albert E.; Lin, Charles; Sharp, Phillip A.; Young, Richard A.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Almada, Albert E.; Sharp, Phillip A.] David H Koch Inst Integrat Canc Res, Cambridge, MA 02140 USA. [Giallourakis, Cosmas C.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Giallourakis, CC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. EM CGIALLOURAKIS@partners.org; young@wi.mit.edu RI Young, Richard/F-6495-2012 OI Young, Richard/0000-0001-8855-8647 FU National Institutes of Health [HG002668, GM34277, DK090122]; American Gastroenterological Association; Damon Runyon Cancer Research Foundation; National Cancer Institute Cancer Center Support (Core) Grant [P30-CA14051] FX We thank members of the R.A.Y. laboratory and George Bell (BaRC) for helpful discussions; Lee Lawton for providing murine H3K4me3 ChIP-seq data; and the Whitehead Institute Genome Technology Core for help with high-throughput sequencing. This work was supported by National Institutes of Health Grants HG002668 (to R.A.Y.), GM34277 (to P. A. S.), and DK090122 (to A. C. M.); the American Gastroenterological Association (A. C. M.); the Damon Runyon Cancer Research Foundation (A. A. S.); and in part by National Cancer Institute Cancer Center Support (Core) Grant P30-CA14051. NR 49 TC 149 Z9 152 U1 0 U2 41 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 19 PY 2013 VL 110 IS 8 BP 2876 EP 2881 DI 10.1073/pnas.1221904110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103YC UT WOS:000315954400059 PM 23382218 ER PT J AU Gostissa, M Bianco, JM Malkin, DJ Kutok, JL Rodig, SJ Morse, HC Bassing, CH Alt, FW AF Gostissa, Monica Bianco, Julia M. Malkin, Daniel J. Kutok, Jeffery L. Rodig, Scott J. Morse, Herbert C., III Bassing, Craig H. Alt, Frederick W. TI Conditional inactivation of p53 in mature B cells promotes generation of nongerminal center-derived B-cell lymphomas SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MARGINAL ZONE LYMPHOMA; CHROMOSOMAL TRANSLOCATIONS; SOMATIC HYPERMUTATION; ONCOGENIC TRANSLOCATIONS; GENOMIC INSTABILITY; P53-DEFICIENT MICE; BREAST-CANCER; HISTONE H2AX; MOUSE MODEL; DNA BREAKS AB The p53 tumor suppressor exerts a central role in protecting cells from oncogenic transformation. Accordingly, the p53 gene is mutated in a large number of human cancers. In mice, germ-line inactivation of p53 confers strong predisposition to development of different types of malignancies, but the early onset of thymic lymphomas in the majority of the animals prevents detailed studies of tumorigenesis in other tissues. Here, we use the Cre/Lox approach to inactivate p53 in mature B cells in mice (referred to as "CP" B cells) and find that such p53 inactivation results in the routine development of IgM-positive CP peripheral B-cell lymphomas. The CP lymphomas generally appear to arise, even in mice subjected to immunization protocols to activate germinal center reaction, from naive B cells that had not undergone immunoglobulin (Ig) heavy chain gene class switching or somatic hypermutation. In contrast to thymic lymphomas that arise in p53-deficient mice, which generally lack clonal translocations, nearly all analyzed CP B-cell tumors carried clonal translocations. However, in contrast to spontaneous translocations in other mouse B-cell tumor models, CP B-cell tumor translocations were not recurrent and did not involve Ig loci. Therefore, CP tumors might provide models for human lymphomas lacking Ig translocations, such as splenic marginal zone B-cell lymphoma or Waldenstrom macroglobulinemia. Our studies indicate that deletion of p53 is sufficient to trigger transformation of mature B cells and support the notion that p53 deficiency may allow accumulation of oncogenic translocations in B cells. C1 [Gostissa, Monica; Bianco, Julia M.; Malkin, Daniel J.; Alt, Frederick W.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston Childrens Hosp, Boston, MA 02115 USA. [Gostissa, Monica; Bianco, Julia M.; Malkin, Daniel J.; Alt, Frederick W.] Harvard Univ, Sch Med, Program Cellular & Mol Med, Boston Childrens Hosp, Boston, MA 02115 USA. [Gostissa, Monica; Bianco, Julia M.; Malkin, Daniel J.; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Kutok, Jeffery L.; Rodig, Scott J.] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Morse, Herbert C., III] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Bassing, Craig H.] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston Childrens Hosp, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu OI Morse, Herbert/0000-0002-9331-3705 FU National Institutes of Health [5P01CA92625, CA098285]; Leukemia and Lymphoma Society of America (LLS) Specialized Center of Research grant; Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases FX We thank Roberto Chiarle for helpful suggestions. This work was supported by National Institutes of Health Grants 5P01CA92625 and CA098285 and a Leukemia and Lymphoma Society of America (LLS) Specialized Center of Research grant (to F. W. A.). This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases (to H. C. M.). M. G. was an LLS senior fellow. C. H. B. is an LLS Scholar. F. W. A. is an investigator of the Howard Hughes Medical Institute. NR 48 TC 11 Z9 11 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 19 PY 2013 VL 110 IS 8 BP 2934 EP 2939 DI 10.1073/pnas.1222570110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103YC UT WOS:000315954400069 PM 23382223 ER PT J AU Khan, S Gramfort, A Shetty, NR Kitzbichler, MG Ganesan, S Moran, JM Lee, SM Gabrieli, JDE Tager-Flusberg, HB Joseph, RM Herbert, MR Hamalainen, MS Kenet, T AF Khan, Sheraz Gramfort, Alexandre Shetty, Nandita R. Kitzbichler, Manfred G. Ganesan, Santosh Moran, Joseph M. Lee, Su Mei Gabrieli, John D. E. Tager-Flusberg, Helen B. Joseph, Robert M. Herbert, Martha R. Haemaelaeinen, Matti S. Kenet, Tal TI Local and long-range functional connectivity is reduced in concert in autism spectrum disorders SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE coherence; parvalbumin ID HIPPOCAMPAL THETA RHYTHM; SPACE SEPARATION METHOD; GAMMA-OSCILLATIONS; BRAIN CONNECTIVITY; NEURAL SYNCHRONIZATION; MEG; FREQUENCY; CHILDREN; EEG; INDIVIDUALS AB Long-range cortical functional connectivity is often reduced in autism spectrum disorders (ASD), but the nature of local cortical functional connectivity in ASD has remained elusive. We used magnetoencephalography to measure task-related local functional connectivity, as manifested by coupling between the phase of alpha oscillations and the amplitude of gamma oscillations, in the fusiform face area (FFA) of individuals diagnosed with ASD and typically developing individuals while they viewed neutral faces, emotional faces, and houses. We also measured task-related long-range functional connectivity between the FFA and the rest of the cortex during the same paradigm. In agreement with earlier studies, long-range functional connectivity between the FFA and three distant cortical regions was reduced in the ASD group. However, contrary to the prevailing hypothesis in the field, we found that local functional connectivity within the FFA was also reduced in individuals with ASD when viewing faces. Furthermore, the strength of long-range functional connectivity was directly correlated to the strength of local functional connectivity in both groups; thus, long-range and local connectivity were reduced proportionally in the ASD group. Finally, the magnitude of local functional connectivity correlated with ASD severity, and statistical classification using local and long-range functional connectivity data identified ASD diagnosis with 90% accuracy. These results suggest that failure to entrain neuronal assemblies fully both within and across cortical regions may be characteristic of ASD. C1 [Khan, Sheraz; Shetty, Nandita R.; Kitzbichler, Manfred G.; Ganesan, Santosh; Herbert, Martha R.; Kenet, Tal] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02129 USA. [Gramfort, Alexandre; Haemaelaeinen, Matti S.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02129 USA. [Khan, Sheraz; Shetty, Nandita R.; Kitzbichler, Manfred G.; Ganesan, Santosh; Herbert, Martha R.; Haemaelaeinen, Matti S.; Kenet, Tal] Harvard Univ, MIT, AA Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Boston, MA 02129 USA. [Moran, Joseph M.; Lee, Su Mei; Gabrieli, John D. E.] MIT, McGovern Inst, Cambridge, MA 02139 USA. [Moran, Joseph M.; Lee, Su Mei; Gabrieli, John D. E.; Haemaelaeinen, Matti S.] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Tager-Flusberg, Helen B.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Joseph, Robert M.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Kenet, T (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02129 USA. EM tal@nmr.mgh.harvard.edu RI Hamalainen, Matti/C-8507-2013; OI Khan, Sheraz/0000-0002-6792-3577 FU Autism Consortium; Nancy Lurie Marks Family Foundation; Autism Speaks; National Center for Research Resources [P41RR14075]; National Institute for Biomedical Imaging and Bioengineering [5R01EB009048]; National Science Foundation from the Cognitive Rhythms Collaborative: A Discovery Network [1042134]; John D. and Catherine T. MacArthur Foundation Research Network on Early Experience and Brain Development FX We thank Charles A. Nelson for his help and contributions to the initiation of the project; Elizabeth Redcay, Jasmin Cloutier, and Dan O'Young for their help in collecting structural MRI scans; and Lee Mavros for her help with recruitment and assessment of participants. This work was supported by the Autism Consortium (J.D.E.G., R.M.J., H.B.T.-F., and T. K.), the Nancy Lurie Marks Family Foundation (T. K.), Autism Speaks (T. K.), Grant P41RR14075 from the National Center for Research Resources (to M. S. H.), Grant 5R01EB009048 from the National Institute for Biomedical Imaging and Bioengineering (to M. S. H.), and National Science Foundation Grant 1042134 from the Cognitive Rhythms Collaborative: A Discovery Network (to M. S. H.). Development of the MacBrain Face Stimulus Set was overseen by Nim Tottenham and supported by the John D. and Catherine T. MacArthur Foundation Research Network on Early Experience and Brain Development. Please contact Nim Tottenham at tott0006@tc.umn.edu for more information concerning the stimulus set. NR 62 TC 75 Z9 76 U1 2 U2 53 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 19 PY 2013 VL 110 IS 8 BP 3107 EP 3112 DI 10.1073/pnas.1214533110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103YC UT WOS:000315954400098 PM 23319621 ER PT J AU Peng, J Li, QL Wigglesworth, K Rangarajan, A Kattamuri, C Peterson, RT Eppig, JJ Thompson, TB Matzuk, MM AF Peng, Jia Li, Qinglei Wigglesworth, Karen Rangarajan, Adithya Kattamuri, Chandramohan Peterson, Randall T. Eppig, John J. Thompson, Thomas B. Matzuk, Martin M. TI Growth differentiation factor 9:bone morphogenetic protein 15 heterodimers are potent regulators of ovarian functions SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE female reproduction; in vitro maturation; TGF-beta signaling ID OOCYTE DEVELOPMENTAL COMPETENCE; INCREASED OVULATION RATE; GRANULOSA-CELLS; GENE-EXPRESSION; IN-VITRO; SYNERGISTIC ROLES; CUMULUS EXPANSION; ACTIVIN RECEPTOR; MAMMALIAN OVARY; BMP15 AB The TGF-beta superfamily is the largest family of secreted proteins in mammals, and members of the TGF-beta family are involved in most developmental and physiological processes. Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15), oocyte-secreted paralogs of the TGF-beta superfamily, have been shown genetically to control ovarian physiology. Although previous studies found that GDF9 and BMP15 homodimers can modulate ovarian pathways in vitro, the functional species-specific significance of GDF9:BMP15 heterodimers remained unresolved. Therefore, we engineered and produced purified recombinant mouse and human GDF9 and BMP15 homodimers and GDF9:BMP15 heterodimers to compare their molecular characteristics and physiological functions. In mouse granulosa cell and cumulus cell expansion assays, mouse GDF9 and human BMP15 homodimers can up-regulate cumulus expansion-related genes (Ptx3, Has2, and Ptgs2) and promote cumulus expansion in vitro, whereas mouse BMP15 and human GDF9 homodimers are essentially inactive. However, we discovered that mouse GDF9:BMP15 heterodimer is similar to 10- to 30-fold more biopotent than mouse GDF9 homodimer, and human GDF9:BMP15 heterodimer is similar to 1,000- to 3,000-fold more bioactive than human BMP15 homodimer. We also demonstrate that the heterodimers require the kinase activities of ALK4/5/7 and BMPR2 to activate SMAD2/3 but unexpectedly need ALK6 as a coreceptor in the signaling complex in granulosa cells. Our findings that GDF9:BMP15 heterodimers are the most bioactive ligands in mice and humans compared with homodimers explain many puzzling genetic and physiological data generated during the last two decades and have important implications for improving female fertility in mammals. C1 [Peng, Jia; Matzuk, Martin M.] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Peng, Jia; Matzuk, Martin M.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Rangarajan, Adithya; Matzuk, Martin M.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Matzuk, Martin M.] Baylor Coll Med, Dept Pharmacol, Houston, TX 77030 USA. [Matzuk, Martin M.] Baylor Coll Med, Ctr Drug Discovery, Houston, TX 77030 USA. [Matzuk, Martin M.] Baylor Coll Med, Ctr Reprod Med, Houston, TX 77030 USA. [Li, Qinglei] Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX 77843 USA. [Wigglesworth, Karen; Eppig, John J.] Jackson Lab, Bar Harbor, ME 04609 USA. [Kattamuri, Chandramohan; Thompson, Thomas B.] Univ Cincinnati, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45221 USA. [Peterson, Randall T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Peterson, Randall T.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Matzuk, MM (reprint author), Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. EM mmatzuk@bcm.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [R01-HD33438, R01-HD23839] FX We thank Julio Agno and Lang Ma for technical support, Dr. Stephanie Pangas for the COV434 cells and excellent discussions, Dr. Karen Lyons for the gift of the Alk6-null mice, Shirley Baker for help with manuscript formatting, and members of the M. M. M. and Pangas laboratories for critical comments. These studies were supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development through Grants R01-HD33438 (to M. M. M. and T. B. T.) and R01-HD23839 (to J.J.E.). NR 50 TC 69 Z9 75 U1 4 U2 17 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 19 PY 2013 VL 110 IS 8 BP E776 EP E785 DI 10.1073/pnas.1218020110 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103YC UT WOS:000315954400020 PM 23382188 ER PT J AU Brinkhaus, B Ortiz, M Witt, CM Roll, S Linde, K Pfab, F Niggemann, B Hummelsberger, J Treszl, A Ring, J Zuberbier, T Wegscheider, K Willich, SN AF Brinkhaus, Benno Ortiz, Miriam Witt, Claudia M. Roll, Stephanie Linde, Klaus Pfab, Florian Niggemann, Bodo Hummelsberger, Josef Treszl, Andras Ring, Johannes Zuberbier, Torsten Wegscheider, Karl Willich, Stefan N. TI Acupuncture in Patients With Seasonal Allergic Rhinitis A Randomized Trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CONTROLLED CLINICAL-TRIAL; EXPERIMENTALLY INDUCED ITCH; I HYPERSENSITIVITY ITCH; QUALITY-OF-LIFE; CROSSOVER TRIAL; ATOPIC ECZEMA; ALTERNATIVE MEDICINE; RHINOCONJUNCTIVITIS; COMPLEMENTARY; QUESTIONNAIRE AB Background: Acupuncture is frequently used to treat seasonal allergic rhinitis (SAR) despite limited scientific evidence. Objective: To evaluate the effects of acupuncture in patients with SAR. Design: Randomized, controlled multicenter trial. (ClinicalTrials.gov:NCT00610584) Setting: 46 specialized physicians in 6 hospital clinics and 32 private outpatient clinics. Patients: 422 persons with SAR and IgE sensitization to birch and grass pollen. Intervention: Acupuncture plus rescue medication (RM) (cetirizine) (n = 212), sham acupuncture plus RM (n = 102), or RM alone (n = 108). Twelve treatments were provided over 8 weeks in the first year. Measurements: Changes in the Rhinitis Quality of Life Questionnaire (RQLQ) overall score and the RM score (RMS) from baseline to weeks 7 and 8 and week 16 in the first year and week 8 in the second year after randomization, with predefined noninferiority margins of -0.5 point (RQLQ) and -1.5 points (RMS). Results: Compared with sham acupuncture and with RM, acupuncture was associated with improvement in RQLQ score (sham vs. acupuncture mean difference, 0.5 point [97.5% CI, 0.2 to 0.8 point; P < 0.001]; RM vs. acupuncture mean difference, 0.7 point [97.5% CI, 0.4 to 1.0 point; P < 0.001]) and RMS (sham vs. acupuncture mean difference, 1.1 points [97.5% CI, 0.4 to 1.9 points; P < 0.001]; RM vs. acupuncture mean difference, 1.5 points [97.5% CI, 0.8 to 2.2 points; P < 0.001]). There were no differences after 16 weeks in the first year. After the 8-week follow-up phase in the second year, small improvements favoring real acupuncture over the sham procedure were noted (RQLQ mean difference, 0.3 point [95% CI, 0.03 to 0.6 point; P = 0.032]; RMS mean difference, 1.0 point [95% CI, 0.2 to 1.9 points; P = 0.018]). Limitation: The study was not powered to detect rare adverse events, and the RQLQ and RMS values were low at baseline. Conclusion: Acupuncture led to statistically significant improvements in disease-specific quality of life and antihistamine use measures after 8 weeks of treatment compared with sham acupuncture and with RM alone, but the improvements may not be clinically significant. C1 [Brinkhaus, Benno; Ortiz, Miriam; Witt, Claudia M.; Roll, Stephanie; Zuberbier, Torsten; Willich, Stefan N.] Charite Univ Med Ctr, D-10098 Berlin, Germany. [Niggemann, Bodo] German Red Cross Hosp Westend, D-14050 Berlin, Germany. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Tech Univ Munich, Helmholtz Ctr Munich, D-80290 Munich, Germany. Int Soc Chinese Med, Munich, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Med Ctr Eppendorf, Hamburg, Germany. [Linde, Klaus] Tech Univ Munich, Klinikum Rechts Isar, Inst Gen Practice, D-81667 Munich, Germany. [Pfab, Florian; Ring, Johannes] Christine Kuhne Ctr Allergy Res & Educ, D-80797 Munich, Germany. [Treszl, Andras; Wegscheider, Karl] Univ Med Ctr Eppendorf, Dept Med Biometry & Epidemiol, D-20246 Hamburg, Germany. RP Brinkhaus, B (reprint author), Charite Univ Med Ctr, Inst Social Med Epidemiol & Hlth Econ, D-10098 Berlin, Germany. EM stephanie.roll@charite.de FU German Research Foundation [WI 957/16-1] FX By grant WI 957/16-1 from the German Research Foundation. NR 46 TC 36 Z9 40 U1 2 U2 28 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 19 PY 2013 VL 158 IS 4 BP 225 EP 234 DI 10.7326/0003-4819-158-4-201302190-00002 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 098WR UT WOS:000315580300013 PM 23420231 ER PT J AU Duggal, P Thio, CL Wojcik, GL Goedert, JJ Mangia, A Latanich, R Kim, AY Lauer, GM Chung, RT Peters, MG Kirk, GD Mehta, SH Cox, AL Khakoo, SI Alric, L Cramp, ME Donfield, SM Edlin, BR Tobler, LH Busch, MP Alexander, G Rosen, HR Gao, XJ Abdel-Hamid, M Apps, R Carrington, M Thomas, DL AF Duggal, Priya Thio, Chloe L. Wojcik, Genevieve L. Goedert, James J. Mangia, Alessandra Latanich, Rachel Kim, Arthur Y. Lauer, Georg M. Chung, Raymond T. Peters, Marion G. Kirk, Gregory D. Mehta, Shruti H. Cox, Andrea L. Khakoo, Salim I. Alric, Laurent Cramp, Matthew E. Donfield, Sharyne M. Edlin, Brian R. Tobler, Leslie H. Busch, Michael P. Alexander, Graeme Rosen, Hugo R. Gao, Xiaojiang Abdel-Hamid, Mohamed Apps, Richard Carrington, Mary Thomas, David L. TI Genome-Wide Association Study of Spontaneous Resolution of Hepatitis C Virus Infection: Data From Multiple Cohorts SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID SPONTANEOUS CLEARANCE; GENETIC-VARIATION; HCV INFECTION; VIRAL LOAD; HLA; VIREMIA; GENOTYPE; PERSISTENCE; POPULATION; VARIANTS AB Background: Hepatitis C virus (HCV) infections occur worldwide and either spontaneously resolve or persist and markedly increase the person's lifetime risk for cirrhosis and hepatocellular carcinoma. Although HCV persistence occurs more often in persons of African ancestry and persons with genetic variants near interleukin-28B (IL-28B), the genetic basis is not well-understood. Objective: To evaluate the host genetic basis for spontaneous resolution of HCV infection. Design: 2-stage, genome-wide association study. Setting: 13 international multicenter study sites. Patients: 919 persons with serum HCV antibodies but no HCV RNA (spontaneous resolution) and 1482 persons with serum HCV antibodies and HCV RNA (persistence). Measurements: Frequencies of 792 721 single nucleotide polymorphisms (SNPs). Results: Differences in allele frequencies between persons with spontaneous resolution and persistence were identified on chromosomes 19q13.13 and 6p21.32. On chromosome 19, allele frequency differences localized near IL-28B and included rs12979860 (overall per-allele OR, 0.45; P = 2.17 x 10(-30)) and 10 additional SNPs spanning 55 000 base pairs. On chromosome 6, allele frequency differences localized near genes for HLA class II and included rs4273729 (overall per-allele OR, 0.59; P = 1.71 x 10(-16)) near DQB1*03:01 and an additional 116 SNPs spanning 1 090 000 base pairs. The associations in chromosomes 19 and 6 were independent and additive and explain an estimated 14.9% (95% CI, 8.5% to 22.6%) and 15.8% (CI, 4.4% to 31.0%) of the variation in HCV resolution in persons of European and African ancestry, respectively. Replication of the chromosome 6 SNP, rs4272729, in an additional 745 persons confirmed the findings (P = 0.015). Limitation: Epigenetic effects were not studied. Conclusion: IL-28B and HLA class II are independently associated with spontaneous resolution of HCV infection, and SNPs marking IL-28B and DQB1*03:01 may explain approximately 15% of spontaneous resolution of HCV infection. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. NCI, Rockville, MD 20852 USA. IRCCS Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Ragon Inst Harvard, Boston, MA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Blood Syst Res Inst, Viral Reference Lab, San Francisco, CA 94118 USA. Blood Syst Res Inst, Repository Core, San Francisco, CA 94118 USA. Univ Southampton, Southampton, Hants, England. Southampton Gen Hosp, Southampton SO9 4XY, Hants, England. Univ Toulouse 3, F-31062 Toulouse, France. Plymouth Hosp NHS Trust, SW Liver Unit, Plymouth, Devon, England. Rho, Chapel Hill, NC USA. State Univ New York Downstate Coll Med, Brooklyn, NY USA. Cambridge Univ Hosp NHS Fdn Trust, Cambridge, England. Addenbrookes Hosp, Cambridge, England. Univ Colorado, Denver, CO 80045 USA. Menia Univ, Al Minya, Egypt. Natl Hepatol & Trop Dis Res Inst, Viral Hepatitis Res Lab, Cairo, Egypt. Frederick Natl Lab Canc Res, Canc & Inflammat Program, Expt Immunol Lab, Sci Applicat Int Corp Frederick, Frederick, MD USA. RP Thomas, DL (reprint author), Johns Hopkins Sch Med, 1830 E Monument St,Suite 437, Baltimore, MD 21287 USA. EM pduggal@jhsph.edu; dthomas@jhmi.edu OI Edlin, Brian/0000-0001-8172-8797; Khakoo, Salim/0000-0002-4057-9091 FU Office of AIDS Research, National Institutes of Health; Frederick National Laboratory for Cancer Research; Office of AIDS Research through the Center for Inherited Diseases at Johns Hopkins University; National Institute on Drug Abuse [R01013324, DA033541, DA12568, DA04334]; National Institute of Allergy and Infectious Diseases [U19AI088791, AI082630]; Frederick National Laboratory for Cancer Research [HHSN261200800001E]; National Institutes of Health; National Institute of Allergy and Infectious Diseases; National Cancer Institute [UO1-AI-35042, UL1-RR025005, UO1-AI-35043, UO1-AI-35039, UO1-AI-35040, UO1-AI-35041]; National Institute of Allery and Infectious Diseases [UO1-AI35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI34993, UO1-AI-42590]; National Institute of Child Health and Human Development [UO1-HD-32632]; [R01HL076902]; [R01-DA16159]; [R01-DA21550]; [UL1-RR024996] FX Office of AIDS Research, National Institutes of Health, and Frederick National Laboratory for Cancer Research.; This project was funded in whole or in part by the Office of AIDS Research through the Center for Inherited Diseases at Johns Hopkins University, the National Institute on Drug Abuse (R01013324, DA033541, DA12568, and DA04334), the National Institute of Allergy and Infectious Diseases (U19AI088791 and AI082630), and the Frederick National Laboratory for Cancer Research (contract HHSN261200800001E). This research was supported in part by the Intramural Research Programs of the National Institutes of Health and the Frederick National Laboratory for Cancer Research. The MACS is funded by the National Institute of Allergy and Infectious Diseases, with additional supplemental funding from the National Cancer Institute (UO1-AI-35042, UL1-RR025005, UO1-AI-35043, UO1-AI-35039, UO1-AI-35040, and UO1-AI-35041). The WIHS is funded by the National Institute of Allery and Infectious Diseases (UO1-AI35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI34993, and UO1-AI-42590) and by the National Institute of Child Health and Human Development (UO1-HD-32632). The REVELL cohort was funded by R01HL076902. Swann cohort was funded by R01-DA16159, R01-DA21550, and UL1-RR024996. NR 38 TC 82 Z9 82 U1 0 U2 8 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 19 PY 2013 VL 158 IS 4 BP 235 EP 245 DI 10.7326/0003-4819-158-4-201302190-00003 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 098WR UT WOS:000315580300014 PM 23420232 ER PT J AU Jensen, MO Hagege, AA Otsuji, Y Levine, RA AF Jensen, Morten O. Hagege, Albert A. Otsuji, Yutaka Levine, Robert A. CA Leducq Transatlantic MITRAL TI The Unsaddled Annulus Biomechanical Culprit in Mitral Valve Prolapse? SO CIRCULATION LA English DT Editorial Material DE Editorials; biomechanics; mitral valve; mitral valve prolapse; mitral valve insufficiency; mitral valve annulus ID 3-DIMENSIONAL ECHOCARDIOGRAPHIC-ASSESSMENT; ANNULOPLASTY RINGS; SADDLE SHAPE; IN-VITRO; REGURGITATION; LEAFLET; REPAIR; RECONSTRUCTION; EXPERIENCE; DYNAMICS C1 [Jensen, Morten O.] Aarhus Univ Hosp, Dept Cardiothorac & Vasc Surg, DK-8000 Aarhus, Denmark. [Hagege, Albert A.] Univ Paris 05, Fac Med, Paris, France. [Hagege, Albert A.] Paris Cardiovasc Res Ctr, INSERM, U633, Paris, France. [Hagege, Albert A.] Hop Europeen Georges Pompidou, AP HP, Dept Cardiol, Paris, France. [Otsuji, Yutaka] Univ Occupat & Environm Hlth, Dept Internal Med 2, Kitakyushu, Fukuoka 807, Japan. [Levine, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA USA. RP Levine, RA (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St,Yawkey 5068, Boston, MA 02114 USA. EM rlevine@partners.org FU NHLBI NIH HHS [HL109506, K24 HL067434, K24 HL67434, R01 HL072265, R01 HL109506, R01 HL72265] NR 35 TC 13 Z9 13 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 19 PY 2013 VL 127 IS 7 BP 766 EP 768 DI 10.1161/CIRCULATIONAHA.112.000628 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 094YS UT WOS:000315302200013 PM 23429895 ER PT J AU Johnson, AD Hwang, SJ Voorman, A Morrison, A Peloso, GM Hsu, YH Thanassoulis, G Newton-Cheh, C Rogers, IS Hoffmann, U Freedman, JE Fox, CS Psaty, BM Boerwinkle, E Cupples, LA O'Donnell, CJ AF Johnson, Andrew D. Hwang, Shih-Jen Voorman, Arend Morrison, Alanna Peloso, Gina M. Hsu, Yi-Hsiang Thanassoulis, George Newton-Cheh, Christopher Rogers, Ian S. Hoffmann, Udo Freedman, Jane E. Fox, Caroline S. Psaty, Bruce M. Boerwinkle, Eric Cupples, L. Adrienne O'Donnell, Christopher J. TI Resequencing and Clinical Associations of the 9p21.3 Region A Comprehensive Investigation in the Framingham Heart Study SO CIRCULATION LA English DT Article DE atherosclerosis; calcium; genetics; myocardial infarction; risk factors ID GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; SINGLE NUCLEOTIDE POLYMORPHISMS; ABDOMINAL AORTIC-ANEURYSM; CHROMOSOME 9P21; MYOCARDIAL-INFARCTION; COMMON SNPS; VARIANTS; LOCUS; ANRIL AB Background-9p21.3 is among the most strongly replicated regions for cardiovascular disease. There are few reports of sequencing the associated 9p21.3 interval. We set out to sequence the 9p21.3 region followed by a comprehensive study of genetic associations with clinical and subclinical cardiovascular disease and its risk factors, as well as with copy number variation and gene expression, in the Framingham Heart Study (FHS). Methods and Results-We sequenced 281 individuals (94 with myocardial infarction, 94 with high coronary artery calcium levels, and 93 control subjects free of elevated coronary artery calcium or myocardial infarction), followed by genotyping and association in >7000 additional FHS individuals. We assessed genetic associations with clinical and subclinical cardiovascular disease, risk factor phenotypes, and gene expression levels of the protein-coding genes CDKN2A and CDKN2B and the noncoding gene ANRIL in freshly harvested leukocytes and platelets. Within this large sample, we found strong associations of 9p21.3 variants with increased risk for myocardial infarction, higher coronary artery calcium levels, and larger abdominal aorta diameters and no evidence for association with traditional cardiovascular disease risk factors. No common protein-coding variation, variants in splice donor or acceptor sites, or copy number variation events were observed. By contrast, strong associations were observed between genetic variants and gene expression, particularly for a short isoform of ANRIL and for CDKN2B. Conclusions-Our thorough genomic characterization of 9p21.3 suggests common variants likely account for observed disease associations and provides further support for the hypothesis that complex regulatory variation affecting ANRIL and CDKN2B gene expression may contribute to increased risk for clinically apparent and subclinical coronary artery disease and aortic disease. (Circulation. 2013;127:799-810.) C1 [Johnson, Andrew D.; Hwang, Shih-Jen; Peloso, Gina M.; Thanassoulis, George; Fox, Caroline S.; Cupples, L. Adrienne; O'Donnell, Christopher J.] NHLBI, NIH, Framingham Heart Study, Framingham, MA USA. [Johnson, Andrew D.; Hwang, Shih-Jen; Fox, Caroline S.; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [Voorman, Arend] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Morrison, Alanna; Boerwinkle, Eric] Baylor Coll Med, Texas Med Ctr, Program Human Genet, Houston, TX 77030 USA. [Peloso, Gina M.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Hsu, Yi-Hsiang] Harvard Univ, Sch Med, Hebrew SeniorLife Inst Aging Res, Boston, MA USA. [Thanassoulis, George] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Rogers, Ian S.; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Broad Inst Harvard & MIT, Program Med & Populat Genet, Boston, MA USA. [Rogers, Ian S.] Stanford Univ, Div Cardiovasc Med, Stanford, CA 94305 USA. [Freedman, Jane E.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Hlth Res Inst, Seattle, WA USA. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP O'Donnell, CJ (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM odonnellc@nhlbi.nih.gov RI Johnson, Andrew/G-6520-2013; OI Cupples, L. Adrienne/0000-0003-0273-7965 FU National Heart, Lung, and Blood Institute (NHLBI) DNA Resequencing and Genotyping Program [N01-HV-48194]; NHLBI's FHS [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R21-AR056405]; NHLBI [RC2-HL02419, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01-HL-087641, R01-HL-59367, R01-HL-086694, N01-HC-85239, N01-HC-85079, N01-HC-85080]; National Human Genome Research Institute [U01-HG-004402]; National Institutes of Health [HHSN268200625226C, UL1-RR-025005]; NIH Roadmap for Medical Research; National Institute on Aging [AG-023629, AG-15928, AG-20098, AG-027058]; National Center of Advancing Translational Technologies Clinical & Translational Science Institute [UL1TR000124]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; NHLBI. [N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HHSN268201200036C, HL080295, HL087652, HL105756, 1T32 HL076136] FX Resequencing provided via the National Heart, Lung, and Blood Institute (NHLBI) DNA Resequencing and Genotyping Program by N01-HV-48194. Work on CNV calling and the FHS LD map was supported by the NHLBI's FHS (contract No. N01-HC-25195) and its contract with Affymetrix, Inc for genotyping services (contract No. N02-HL-6-4278). A portion of this research used the Linux Cluster for Genetic Analysis (LinGA-II), funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. CNV calling was supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases grant R21-AR056405. Whole genome sequencing in CHS and ARIC was conducted as part of the CHARGE-S (Cohorts for Heart and Aging Research in Genome Epidemiology Consortium) sequencing programming supported by NHLBI Grand Opportunity grant RC2-HL02419. The ARIC Study is supported by NHLBI contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022 and grants R01-HL-087641, R01-HL-59367, and R01-HL-086694; National Human Genome Research Institute contract U01-HG-004402; and National Institutes of Health contract HHSN268200625226C. The infrastructure was supported in part by grant No. UL1-RR-025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. The CHS research was supported by NHLBI contracts N01-HC-85239, N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, and HHSN268201200036C and NHLBI grants HL080295, HL087652, and HL105756, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the National Institute on Aging. See also the CHS Web site (http://www.chsnhlbi.org/pi.htm). DNA handling and genotyping was supported in part by National Center of Advancing Translational Technologies Clinical & Translational Science Institute grant UL1TR000124 and National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center. We thank Daniel Levy and Dr O'Donnell for genotyping funding. Dr Rogers was supported by NHLBI 1T32 HL076136. Dr Johnson was supported by an NHLBI Intramural Research Training Award fellowship. NR 41 TC 31 Z9 33 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 19 PY 2013 VL 127 IS 7 BP 799 EP 810 DI 10.1161/CIRCULATIONAHA.112.111559 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 094YS UT WOS:000315302200017 PM 23315372 ER PT J AU Schiros, CG Gladden, JD Clark, D Gupta, H Lloyd, SG McGiffin, DC Ahmed, MI Aban, I Dell'Italia, LJ Perry, G Denney, TS AF Schiros, Chun G. Gladden, James D. Clark, Donald, III Gupta, Himanshu Lloyd, Steven G. McGiffin, David C. Ahmed, Mustafa I. Aban, Inmaculada Dell'Italia, Louis J. Perry, Gilbert Denney, Thomas S., Jr. TI Response to Letter Regarding Article, "Magnetic Resonance Imaging With 3-Dimensional Analysis of Left Ventricular Remodeling in Isolated Mitral Regurgitation: Implications Beyond Dimensions" SO CIRCULATION LA English DT Letter C1 [Schiros, Chun G.; Gladden, James D.; Clark, Donald, III; Gupta, Himanshu; Lloyd, Steven G.; McGiffin, David C.; Ahmed, Mustafa I.] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Aban, Inmaculada] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA. [Dell'Italia, Louis J.; Perry, Gilbert] Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Denney, Thomas S., Jr.] Auburn Univ, Dept Elect & Comp Engn, Samuel Ginn Coll Engn, Auburn, AL 36849 USA. RP Schiros, CG (reprint author), Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 19 PY 2013 VL 127 IS 7 BP E462 EP E462 DI 10.1161/CIRCULATIONAHA.112.134858 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 094YS UT WOS:000315302200011 PM 23550297 ER PT J AU Cesano, A Putta, S Rosen, DB Cohen, AC Gayko, U Mathi, K Woronicz, J Hawtin, RE Cripe, L Sun, ZX Tallman, MS Paietta, E AF Cesano, Alessandra Putta, Santosh Rosen, David B. Cohen, Aileen C. Gayko, Urte Mathi, Kavita Woronicz, John Hawtin, Rachael E. Cripe, Larry Sun, Zhuoxin Tallman, Martin S. Paietta, Elisabeth TI Functional Pathway Analysis Using SCNP of FLT3 Receptor Pathway Deregulation in AML Provides Prognostic Information Independent from Mutational Status SO PLOS ONE LA English DT Article ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; ACUTE MYELOGENOUS LEUKEMIA; SIGNAL TRANSDUCER; NPM1 MUTATIONS; POOR-PROGNOSIS; HEMATOPOIETIC-CELLS; NORMAL CYTOGENETICS; NORMAL KARYOTYPE; TYROSINE KINASE AB FMS-like tyrosine kinase 3 receptor (FLT3) internal tandem duplication (ITD) mutations result in constitutive activation of this receptor and have been shown to increase the risk of relapse in patients with acute myeloid leukemia (AML); however, substantial heterogeneity in clinical outcomes still exists within both the ITD mutated and unmutated AML subgroups, suggesting alternative mechanisms of disease relapse not accounted by FLT3 mutational status. Single cell network profiling (SCNP) is a multiparametric flow cytometry based assay that simultaneously measures, in a quantitative fashion and at the single cell level, both extracellular surface marker levels and changes in intracellular signaling proteins in response to extracellular modulators. We previously reported an initial characterization of FLT3 ITD-mediated signaling using SCNP. Herein SCNP was applied sequentially to two separate cohorts of samples collected from elderly AML patients at diagnosis. In the first (training) study, AML samples carrying unmutated, wild-type FLT3 (FLT3 WT) displayed a wide range of induced signaling, with a fraction having signaling profiles comparable to FLT3 ITD AML samples. Conversely, the FLT3 ITD AML samples displayed more homogeneous induced signaling, with the exception of patients with low (, 40%) mutational load, which had profiles comparable to FLT3 WT AML samples. This observation was then confirmed in an independent (verification) cohort. Data from the second cohort were also used to assess the association between SCNP data and disease-free survival (DFS) in the context of FLT3 and nucleophosmin (NPM1) mutational status among patients who achieved complete remission (CR) to induction chemotherapy. The combination of SCNP read outs together with FLT3 and NPM1 molecular status improved the DFS prediction accuracy of the latter. Taken together, these results emphasize the value of comprehensive functional assessment of biologically relevant signaling pathways in AML as a basis for the development of highly predictive tests for guidance of post-remission therapy. C1 [Cesano, Alessandra; Putta, Santosh; Rosen, David B.; Cohen, Aileen C.; Gayko, Urte; Mathi, Kavita; Woronicz, John; Hawtin, Rachael E.] Nodality Inc, San Francisco, CA USA. [Cripe, Larry; Sun, Zhuoxin; Tallman, Martin S.; Paietta, Elisabeth] Eastern Cooperat Oncol Grp ECOG, Boston, MA USA. [Cripe, Larry] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. [Sun, Zhuoxin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Paietta, Elisabeth] Montefiore Med Ctr, North Div, Bronx, NY 10467 USA. RP Cesano, A (reprint author), Nodality Inc, San Francisco, CA USA. EM Alessandra.Cesano@Nodality.com FU Nodality, Inc. FX This study was funded by Nodality, Inc. The funder contributed to study design, data collection and analysis, decision to publish, and preparation of the manuscript. NR 55 TC 3 Z9 3 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 19 PY 2013 VL 8 IS 2 AR e56714 DI 10.1371/journal.pone.0056714 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 093HR UT WOS:000315182800032 PM 23431389 ER PT J AU Gui, DY Lewis, CA Vander Heiden, MG AF Gui, Dan Y. Lewis, Caroline A. Vander Heiden, Matthew G. TI Allosteric Regulation of PKM2 Allows Cellular Adaptation to Different Physiological States SO SCIENCE SIGNALING LA English DT Article ID PYRUVATE-KINASE M2; TUMOR-GROWTH; CANCER METABOLISM; ISOFORM; FRUCTOSE-1,6-BISPHOSPHATE; INHIBITION; ACTIVATORS; BINDING; SERINE; CONVERSION AB Pyruvate kinase isoform M2 (PKM2) activity is subject to complex allosteric regulation. Recently, serine and SAICAR (succinylaminoimidazolecarboxamide ribose-5'-phosphate) were identified as previously unrecognized activators of PKM2. These findings add additional complexity to how PKM2 is regulated in cells and support the notion that modulating PKM2 activity enables cells to adapt their metabolic state to specific physiological contexts. C1 [Gui, Dan Y.; Lewis, Caroline A.; Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Vander Heiden, Matthew G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Vander Heiden, MG (reprint author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM mvh@mit.edu NR 27 TC 22 Z9 22 U1 1 U2 29 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD FEB 19 PY 2013 VL 6 IS 263 AR pe7 DI 10.1126/scisignal.2003925 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 094ZA UT WOS:000315303000001 PM 23423437 ER PT J AU Bodur, C Kutuk, O Karsli-Uzunbas, G Isimjan, TT Harrison, P Basaga, H AF Bodur, Cagri Kutuk, Ozgur Karsli-Uzunbas, Gizem Isimjan, Tayirjan T. Harrison, Paul Basaga, Huveyda TI Pramanicin Analog Induces Apoptosis in Human Colon Cancer Cells: Critical Roles for Bcl-2, Bim, and p38 MAPK Signaling SO PLOS ONE LA English DT Article ID NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; TRANSCRIPTION FACTOR; DEPENDENT APOPTOSIS; ENDOTHELIAL-CELLS; MOLECULAR-CLONING; ANTIFUNGAL AGENT; GENE-EXPRESSION; FAMILY PROTEINS; BREAST-CANCER AB Pramanicin (PMC) is an antifungal agent that was previously demonstrated to exhibit antiangiogenic and anticancer properties in a few in vitro studies. We initially screened a number of PMC analogs for their cytotoxic effects on HCT116 human colon cancer cells. PMC-A, the analog with the most potent antiproliferative effect was chosen to further interrogate the underlying mechanism of action. PMC-A led to apoptosis through activation of caspase-9 and -3. The apoptotic nature of cell death was confirmed by abrogation of cell death with pretreatment with specific caspase inhibitors. Stress-related MAPKs JNK and p38 were both activated concomittantly with the intrinsic apoptotic pathway. Moreover, pharmacological inhibition of p38 proved to attenuate the cell death induction while pretreatment with JNK inhibitor did not exhibit a protective effect. Resistance of Bax -/- cells and the protective nature of caspase-9 inhibition indicate that mitochondria play a central role in PMC-A induced apoptosis. Early post-exposure elevation of cellular Bim and Bax was followed by a marginal Bcl-2 depletion and Bid cleavage. Further analysis revealed that Bcl-2 downregulation occurs at the mRNA level and is critical to mediate PMC-A induced apoptosis, as ectopic Bcl-2 expression substantially spared the cells from death. Conversely, forced expression of Bim proved to significantly increase cell death. In addition, analyses of p53-/- cells demonstrated that Bcl-2/Bim/Bax modulation and MAPK activations take place independently of p53 expression. Taken together, p53-independent transcriptional Bcl-2 downregulation and p38 signaling appear to be the key modulatory events in PMC-A induced apoptosis. C1 [Bodur, Cagri; Karsli-Uzunbas, Gizem; Basaga, Huveyda] Sabanci Univ, Biol Sci & Bioengn Program, Istanbul, Turkey. [Kutuk, Ozgur] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Isimjan, Tayirjan T.; Harrison, Paul] McMaster Univ, Dept Chem & Chem Biol, Hamilton, ON, Canada. RP Basaga, H (reprint author), Sabanci Univ, Biol Sci & Bioengn Program, Istanbul, Turkey. EM huveyda@sabanciuniv.edu FU Sabanci University faculty research funds FX The funding for the work was provided by Sabanci University faculty research funds. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 69 TC 6 Z9 10 U1 0 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 18 PY 2013 VL 8 IS 2 AR e56369 DI 10.1371/journal.pone.0056369 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 092YP UT WOS:000315159200040 PM 23441183 ER PT J AU Crawford, F Anandan, C Chappell, FM Murray, GD Price, JF Sheikh, A Simpson, CR Maxwell, M Stansby, GP Young, MJ Abbott, CA Boulton, AJ Boyko, EJ Kastenbauer, T Leese, GP Monami, M Monteiro-Soares, M Rith-Najarian, SJ Veves, A Coates, N Jeffcoate, WJ Leech, N Fahey, T Tierney, J AF Crawford, Fay Anandan, Chantelle Chappell, Francesca M. Murray, Gordon D. Price, Jacqueline F. Sheikh, Aziz Simpson, Colin R. Maxwell, Martin Stansby, Gerard P. Young, Matthew J. Abbott, Caroline A. Boulton, Andrew J. M. Boyko, Edward J. Kastenbauer, Thomas Leese, Graham P. Monami, Matteo Monteiro-Soares, Matilde Rith-Najarian, Stephen J. Veves, Aristidis Coates, Nikki Jeffcoate, William J. Leech, Nicola Fahey, Tom Tierney, Jayne TI Protocol for a systematic review and individual patient data meta-analysis of prognostic factors of foot ulceration in people with diabetes: the international research collaboration for the prediction of diabetic foot ulcerations (PODUS) SO BMC MEDICAL RESEARCH METHODOLOGY LA English DT Review ID METHODOLOGICAL STANDARDS; MULTIPLE IMPUTATION; EPIDEMIOLOGY STROBE; GUIDELINES; STATEMENT; RULES AB Background: Diabetes-related lower limb amputations are associated with considerable morbidity and mortality and are usually preceded by foot ulceration. The available systematic reviews of aggregate data are compromised because the primary studies report both adjusted and unadjusted estimates. As adjusted meta-analyses of aggregate data can be challenging, the best way to standardise the analytical approach is to conduct a meta-analysis based on individual patient data (IPD). There are however many challenges and fundamental methodological omissions are common; protocols are rare and the assessment of the risk of bias arising from the conduct of individual studies is frequently not performed, largely because of the absence of widely agreed criteria for assessing the risk of bias in this type of review. In this protocol we propose key methodological approaches to underpin our IPD systematic review of prognostic factors of foot ulceration in diabetes. Review questions; 1. What are the most highly prognostic factors for foot ulceration (i.e. symptoms, signs, diagnostic tests) in people with diabetes? 2. Can the data from each study be adjusted for a consistent set of adjustment factors? 3. Does the model accuracy change when patient populations are stratified according to demographic and/or clinical characteristics? Methods: MEDLINE and EMBASE databases from their inception until early 2012 were searched and the corresponding authors of all eligible primary studies invited to contribute their raw data. We developed relevant quality assurance items likely to identify occasions when study validity may have been compromised from several sources. A confidentiality agreement, arrangements for communication and reporting as well as ethical and governance considerations are explained. We have agreement from the corresponding authors of all studies which meet the eligibility criteria and they collectively possess data from more than 17000 patients. We propose, as a provisional analysis plan, to use a multi-level mixed model, using "study" as one of the levels. Such a model can also allow for the within-patient clustering that occurs if a patient contributes data from both feet, although to aid interpretation, we prefer to use patients rather than feet as the unit of analysis. We intend to only attempt this analysis if the results of the investigation of heterogeneity do not rule it out and the model diagnostics are acceptable. Discussion: This review is central to the development of a global evidence-based strategy for the risk assessment of the foot in patients with diabetes, ensuring future recommendations are valid and can reliably inform international clinical guidelines. C1 [Crawford, Fay] Newcastle Upon Tyne Hosp NHS Fdn Trust, Freeman Rd Hosp, Dept Vasc Surg, Newcastle Upon Tyne NE7 7DN, Tyne & Wear, England. [Anandan, Chantelle; Chappell, Francesca M.; Murray, Gordon D.; Price, Jacqueline F.; Sheikh, Aziz; Simpson, Colin R.; Maxwell, Martin] Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, Edinburgh EH8 9AG, Midlothian, Scotland. [Stansby, Gerard P.] Fac Med Sci, Sch Surg & Reprod Sci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Young, Matthew J.] Royal Infirm Edinburgh NHS Trust, Dept Diabet, Edinburgh EH16 4SA, Midlothian, Scotland. [Abbott, Caroline A.] Univ Manchester, Ctr Endocrinol & Diabet, Inst Human Dev, Core Technol Facil, Manchester M13 9NT, Lancs, England. [Boulton, Andrew J. M.] Manchester Royal Infirm, Div Med, Manchester M13 9WL, Lancs, England. [Boyko, Edward J.] Univ Washington, Epidemiol Res & Informat Ctr, VA Puget Sound Hlth Care Syst, Seattle, WA 98101 USA. [Kastenbauer, Thomas] Sci Consulting & Clin Monitoring SCCM, A-1220 Vienna, Austria. [Leese, Graham P.] Univ Dundee, Ninewells Hosp & Med Sch, Dept Diabet & Endocrinol, Dundee DD1 9SY, Scotland. [Monami, Matteo] AOU Careggi, Sez Diabetol, Florence, Italy. [Monteiro-Soares, Matilde] Ctr Hosp Vila Nova de Gaia Espinho EPE, Unidade 1, Serv Endocrinol Pe Diabet, P-4434502 Vila Nova De Gaia, Portugal. [Rith-Najarian, Stephen J.] Cass Lake Indian Hlth Serv Hosp, Cass Lake, MN 56633 USA. [Veves, Aristidis] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Coates, Nikki] Newcastle Hosp Community Hlth, Podiatry Dept, Geoffrey Rhodes Clin, Newcastle Upon Tyne NE6 2UZ, Tyne & Wear, England. [Jeffcoate, William J.] City Hosp Nottingham, Dept Diabet & Endocrinol, Nottingham NG5 1PB, England. [Leech, Nicola] Royal Victoria Infirm, Ward 31, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. [Fahey, Tom] Royal Coll Surgeons Ireland, Dublin 2, Ireland. [Tierney, Jayne] MRC, Clin Trials Unit, London WC2B 6NH, England. RP Crawford, F (reprint author), Newcastle Upon Tyne Hosp NHS Fdn Trust, Freeman Rd Hosp, Dept Vasc Surg, Newcastle Upon Tyne NE7 7DN, Tyne & Wear, England. EM Fay.crawford@ed.ac.uk RI Sheikh, Aziz /D-2818-2009; Simpson, Colin/L-7180-2014; Monteiro-Soares, Matilde/F-7192-2013; Fahey, Tom/C-9367-2012; FMUP, CINTESIS/C-6631-2014 OI Sheikh, Aziz /0000-0001-7022-3056; Simpson, Colin/0000-0002-5194-8083; Monteiro-Soares, Matilde/0000-0002-4586-2910; Murray, Gordon/0000-0001-9866-4734; Fahey, Tom/0000-0002-5896-5783; FMUP, CINTESIS/0000-0001-7248-2086 FU National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme [10/57/08] FX This project was funded by the National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme (project number 10/57/08) and will be published in full in Health Technology Assessment. NR 33 TC 8 Z9 9 U1 1 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2288 J9 BMC MED RES METHODOL JI BMC Med. Res. Methodol. PD FEB 15 PY 2013 VL 13 AR 22 DI 10.1186/1471-2288-13-22 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 107OW UT WOS:000316228700001 PM 23414550 ER PT J AU Reichmann, WM LaValley, MP Gagnon, DR Losina, E AF Reichmann, William M. LaValley, Michael P. Gagnon, David R. Losina, Elena TI Impact of misspecifying the distribution of a prognostic factor on power and sample size for testing treatment interactions in clinical trials SO BMC MEDICAL RESEARCH METHODOLOGY LA English DT Article DE Simulation design; Interaction; Conditional power; Adaptive design; Sample size re-estimation ID SUBGROUP ANALYSES; RANDOMIZED-TRIALS AB Background: Interaction in clinical trials presents challenges for design and appropriate sample size estimation. Here we considered interaction between treatment assignment and a dichotomous prognostic factor with a continuous outcome. Our objectives were to describe differences in power and sample size requirements across alternative distributions of a prognostic factor and magnitudes of the interaction effect, describe the effect of misspecification of the distribution of the prognostic factor on the power to detect an interaction effect, and discuss and compare three methods of handling the misspecification of the prognostic factor distribution. Methods: We examined the impact of the distribution of the dichotomous prognostic factor on power and sample size for the interaction effect using traditional one-stage sample size calculation. We varied the magnitude of the interaction effect, the distribution of the prognostic factor, and the magnitude and direction of the misspecification of the distribution of the prognostic factor. We compared quota sampling, modified quota sampling, and sample size re-estimation using conditional power as three strategies for ensuring adequate power and type I error in the presence of a misspecification of the prognostic factor distribution. Results: The sample size required to detect an interaction effect with 80% power increases as the distribution of the prognostic factor becomes less balanced. Misspecification such that the actual distribution of the prognostic factor was more skewed than planned led to a decrease in power with the greatest loss in power seen as the distribution of the prognostic factor became less balanced. Quota sampling was able to maintain the empirical power at 80% and the empirical type I error at 5%. The performance of the modified quota sampling procedure was related to the percentage of trials switching the quota sampling scheme. Sample size re-estimation using conditional power was able to improve the empirical power under negative misspecifications (i.e. skewed distributions) but it was not able to reach the target of 80% in all situations. Conclusions: Misspecifying the distribution of a dichotomous prognostic factor can greatly impact power to detect an interaction effect. Modified quota sampling and sample size re-estimation using conditional power improve the power when the distribution of the prognostic factor is misspecified. Quota sampling is simple and can prevent misspecification of the prognostic factor, while maintaining power and type I error. C1 [Reichmann, William M.; Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Reichmann, William M.; LaValley, Michael P.; Gagnon, David R.; Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Gagnon, David R.] Massachusetts Vet Epidemiol Res & Informat Ctr, VA Cooperat Studies Program, Boston, MA USA. [Reichmann, William M.] Brigham & Womens Hosp, Orthoped & Arthrit Ctr Outcomes Res, Boston, MA 02115 USA. RP Reichmann, WM (reprint author), Brigham & Womens Hosp, Dept Orthoped Surg, 75 Francis St, Boston, MA 02115 USA. EM breich315@gmail.com OI Gagnon, David/0000-0002-6367-3179; LaValley, Michael/0000-0002-8488-5170 FU National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases [T32 AR055885, K24 AR057827] FX This research was supported in part by the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases grants T32 AR055885 and K24 AR057827. NR 13 TC 0 Z9 0 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2288 J9 BMC MED RES METHODOL JI BMC Med. Res. Methodol. PD FEB 15 PY 2013 VL 13 AR 21 DI 10.1186/1471-2288-13-21 PG 18 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 111WN UT WOS:000316552200001 PM 23414513 ER PT J AU Niehorster, DC Peli, E Haun, A Li, L AF Niehorster, Diederick C. Peli, Eli Haun, Andrew Li, Li TI Influence of Hemianopic Visual Field Loss on Visual Motor Control SO PLOS ONE LA English DT Article ID LINE BISECTION; HOMONYMOUS HEMIANOPIA; DRIVING PERFORMANCE; STEERING CONTROL; HUMAN-OPERATOR; ACTIVE CONTROL; NEGLECT; REHABILITATION; DEFECTS; APHASIA AB Background: Homonymous hemianopia (HH) is an anisotropic visual impairment characterized by the binocular inability to see one side of the visual field. Patients with HH often misperceive visual space. Here we investigated how HH affects visual motor control. Methods and Findings: Seven patients with complete HH and no neglect or cognitive decline and seven gender-and age-matched controls viewed displays in which a target moved randomly along the horizontal or the vertical axis. They used a joystick to control the target movement to keep it at the center of the screen. We found that the mean deviation of the target position from the center of the screen along the horizontal axis was biased toward the blind side for five out of seven HH patients. More importantly, while the normal vision controls showed more precise control and larger response amplitudes when the target moved along the horizontal rather than the vertical axis, the control performance of the HH patients was not different between these two target motion experimental conditions. Conclusions: Compared with normal vision controls, HH affected patients' control performance when the target moved horizontally (i.e., along the axis of their visual impairment) rather than vertically. We conclude that hemianopia affects the use of visual information for online control of a moving target specific to the axis of visual impairment. The implications of the findings for driving in hemianopic patients are discussed. C1 [Niehorster, Diederick C.; Li, Li] Univ Hong Kong, Dept Psychol, Hong Kong, Hong Kong, Peoples R China. [Peli, Eli; Haun, Andrew] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA USA. RP Niehorster, DC (reprint author), Univ Hong Kong, Dept Psychol, Hong Kong, Hong Kong, Peoples R China. EM dcniehorster@hku.hk; lili@hku.hk RI Niehorster, Diederick/E-9325-2010; Haun, Andrew/I-4956-2012 OI Niehorster, Diederick/0000-0002-4672-8756; Haun, Andrew/0000-0001-9458-8957 FU Research Grants Council of Hong Kong [HKU 7478/08H]; NIH [EY12890] FX This study was supported by a grant from the Research Grants Council of Hong Kong (HKU 7478/08H) to L. Li, http://www.ugc.edu.hk, and a grant from the NIH (EY12890) to E. Peli, http://www.nih.gov/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 64 TC 6 Z9 6 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 15 PY 2013 VL 8 IS 2 AR e56615 DI 10.1371/journal.pone.0056615 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 099EQ UT WOS:000315603700066 PM 23457594 ER PT J AU Lam, D Fard, AM Buckley, B Jalali, B AF Lam, Daniel Fard, Ali M. Buckley, Brandon Jalali, Bahram TI Digital broadband linearization of optical links SO OPTICS LETTERS LA English DT Article ID MICROWAVE PHOTONICS; TRANSMISSION; PERFORMANCE; MODULATOR; RECEIVER AB We present a digital postprocessing linearization technique to efficiently suppress dynamic distortions added to a wideband signal in an analog optical link. Our technique achieves up to 35 dB suppression of intermodulation distortions over multiple octaves of signal bandwidth. In contrast to conventional linearization methods, it does not require excessive analog bandwidth for performing digital correction. This is made possible by regenerating undesired distortions from the captured output, and subtracting it from the distorted digitized signal. Moreover, we experimentally demonstrate a record spurious-free dynamic range of 120 dB . Hz(2/3) over a 6 GHz electrical signal bandwidth. While our digital broadband linearization technique advances state-of-the-art optical links, it can also be applied to other nonlinear dynamic systems. (c) 2013 Optical Society of America C1 [Lam, Daniel; Buckley, Brandon; Jalali, Bahram] Univ Calif Los Angeles, Dept Elect Engn, Los Angeles, CA 90095 USA. [Fard, Ali M.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Fard, Ali M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Buckley, Brandon] Univ Calif Los Angeles, Dept Phys, Los Angeles, CA 90095 USA. [Buckley, Brandon; Jalali, Bahram] Calif NanoSyst Inst, Los Angeles, CA 90095 USA. RP Lam, D (reprint author), Univ Calif Los Angeles, Dept Elect Engn, Los Angeles, CA 90095 USA. EM dwlam@ucla.edu FU U.S. Defense Advanced Research Projects Agency (DARPA); National Science Foundation (NSF) through CIAN ERC [EEC-0812072] FX This work was partially supported by the U.S. Defense Advanced Research Projects Agency (DARPA) and the National Science Foundation (NSF) through CIAN ERC under Grant No. EEC-0812072. NR 17 TC 22 Z9 22 U1 0 U2 8 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD FEB 15 PY 2013 VL 38 IS 4 BP 446 EP 448 PG 3 WC Optics SC Optics GA 099EB UT WOS:000315601700020 PM 23455097 ER PT J AU Mathewkutty, S Sethi, SS Aneja, A Shah, K Iyengar, RL Hermann, L Khakimov, S Razzouk, L Esquitin, R Vedanthan, R Benjamin, TA Grace, M Nisenbaum, R Ramanathan, K Ramanathan, L Chesebro, J Farkouh, ME AF Mathewkutty, Shiny Sethi, Sanjum S. Aneja, Ashish Shah, Kshitij Iyengar, Rupa L. Hermann, Luke Khakimov, Sayyar Razzouk, Louai Esquitin, Ricardo Vedanthan, Rajesh Benjamin, Terrie-Ann Grace, Marie Nisenbaum, Rosane Ramanathan, Krishnan Ramanathan, Lakshmi Chesebro, James Farkouh, Michael E. TI Biomarkers After Risk Stratification in Acute Chest Pain (from the BRIC Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE CORONARY SYNDROMES; NATRIURETIC PEPTIDE; EMERGENCY-DEPARTMENT; ST-ELEVATION; MYOCARDIAL-INFARCTION; CT ANGIOGRAPHY; CYSTATIN-C; OUTCOMES; DIAGNOSIS; ISCHEMIA AB Current models incompletely risk-stratify patients with acute chest pain. In this study, N-terminal pro-B-type natriuretic peptide and cystatin C were incorporated into a contemporary chest pain triage algorithm in a clinically stratified population to improve acute coronary syndrome discrimination. Adult patients with chest pain presenting without myocardial infarction (n = 382) were prospectively enrolled from 2008 to 2009. After clinical risk stratification, N-terminal pro-B-type natriuretic peptide and cystatin C were measured and standard care was performed. The primary end point was the result of a clinical stress test. The secondary end point was any major adverse cardiac event at 6 months. Associations were determined through multivariate stratified analyses. In the low-risk group, 76 of 78 patients with normal levels of the 2 biomarkers had normal stress test results (negative predictive value 97%). Normal biomarkers predicted normal stress test results with an odds ratio of 10.56 (p = 0.006). In contrast, 26 of 33 intermediate-risk patients with normal levels of the 2 biomarkers had normal stress test results (negative predictive value 79%). Biomarkers and stress test results were not associated in the intermediate-risk group (odds ratio 2.48, p = 0.09). There were 42 major adverse cardiac events in the overall cohort. No major adverse cardiac events occurred at 6 months in the low-risk subgroup that underwent stress testing. In conclusion, N-terminal pro-B-type natriuretic peptide and cystatin C levels predict the results of stress tests in low-risk patients with chest pain but should not be substituted for stress testing in intermediate-risk patients. There is potential for their use in the early discharge of low-risk patients after clinical risk stratification. (C) 2013 Elsevier Inc. All rights reserved. (Am J Cardiol 2013;111:493-498) C1 [Mathewkutty, Shiny; Sethi, Sanjum S.; Iyengar, Rupa L.; Khakimov, Sayyar; Vedanthan, Rajesh; Farkouh, Michael E.] Mt Sinai Sch Med, Zena & Michael Wiener Cardiovasc Inst, New York, NY 10029 USA. [Hermann, Luke] Mt Sinai Sch Med, Dept Emergency Med, New York, NY USA. [Grace, Marie; Ramanathan, Lakshmi] Mt Sinai Sch Med, Dept Pathol, New York, NY USA. [Aneja, Ashish] Case Western Reserve Univ, Metrohlth Campus, Heart & Vasc Ctr, Cleveland, OH 44106 USA. [Shah, Kshitij] James J Peters VA Med Ctr, Dept Med, Bronx, NY USA. [Razzouk, Louai] NYU, Div Cardiol, New York, NY USA. [Esquitin, Ricardo] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiol, Boston, MA 02215 USA. [Benjamin, Terrie-Ann] Cleveland Clin, Dept Med, Cleveland, OH 44106 USA. [Nisenbaum, Rosane] Univ Toronto, Ctr Res Inner City Hlth, Toronto, ON, Canada. [Nisenbaum, Rosane] Univ Toronto, Appl Hlth Res Ctr, Toronto, ON, Canada. [Nisenbaum, Rosane] Univ Toronto, Keenan Res Ctr, Li Ka Shing Knowledge Inst, St Michaels Hosp, Toronto, ON, Canada. [Nisenbaum, Rosane] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Ramanathan, Krishnan] Univ British Columbia, St Pauls Hosp, Div Cardiol, Vancouver, BC V5Z 1M9, Canada. [Chesebro, James] Univ Massachusetts, Sch Med, Div Cardiovasc Med, Worcester, MA USA. [Farkouh, Michael E.] Univ Toronto, Peter Munk Cardiac Ctr, Toronto, ON, Canada. [Farkouh, Michael E.] Univ Toronto, Li Ka Shing Knowledge Inst, Toronto, ON, Canada. RP Farkouh, ME (reprint author), Mt Sinai Sch Med, Zena & Michael Wiener Cardiovasc Inst, New York, NY 10029 USA. EM michael.farkouh@mssm.edu OI Razzouk, Louai/0000-0002-0306-6182; Esquitin, Ricardo/0000-0002-3475-3671 FU Radiometer (Bronshoj, Denmark); Ontario Ministry of Health and Long-Term Care, Toronto, Ontario, Canada FX This study was sponsored partly by Radiometer (Bronshoj, Denmark).; Dr. Nisenbaum gratefully acknowledges the support of the Ontario Ministry of Health and Long-Term Care, Toronto, Ontario, Canada. The views expressed in this publication are the views of the investigators and do not necessarily reflect the views of the Ontario Ministry of Health and Long-Term Care. NR 30 TC 4 Z9 6 U1 0 U2 5 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 15 PY 2013 VL 111 IS 4 BP 493 EP 498 DI 10.1016/j.amjcard.2012.10.032 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 095GN UT WOS:000315322800006 PM 23218997 ER PT J AU Greene, SJ Vaduganathan, M Lupi, L Ambrosy, AP Mentz, RJ Konstam, MA Nodari, S Subacius, HP Fonarow, GC Bonow, RO Gheorghiade, M AF Greene, Stephen J. Vaduganathan, Muthiah Lupi, Laura Ambrosy, Andrew P. Mentz, Robert J. Konstam, Marvin A. Nodari, Savina Subacius, Hans P. Fonarow, Gregg C. Bonow, Robert O. Gheorghiade, Mihai CA EVEREST Trial Invest TI Prognostic Significance of Serum Total Cholesterol and Triglyceride Levels in Patients Hospitalized for Heart Failure With Reduced Ejection Fraction (from the EVEREST Trial) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID REVERSE EPIDEMIOLOGY; MORTALITY; RISK; TOLVAPTAN; SURVIVAL; REGISTRY; PROGRAM; OBESITY; MARKER AB Lower cholesterol levels are associated with worse outcomes in patients with chronic heart failure (HF) and have been shown to predict in-hospital mortality. The relation between lipid profile and postdischarge outcomes in patients hospitalized for worsening HF is less clear. In this post hoc analysis of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST), 3,957 patients hospitalized for worsening HF with ejection fractions <= 40% were examined. Baseline total cholesterol and triglyceride levels were measured <48 hours after admission and evaluated as continuous variables. The primary end points of all-cause mortality and cardiovascular mortality or hospitalization for HF were compared using Cox regression models. Patient characteristics at randomization were also compared among quartiles of total cholesterol. Patients with lower total cholesterol tended to have lower blood pressure, ejection fractions, serum sodium, and albumin, and were more likely to have worse HF functional class, to have higher natriuretic peptide levels, and to have histories of diabetes mellitus, renal insufficiency, and coronary revascularization (all p values <0.001). After adjustment for baseline clinical risk factors, total cholesterol was predictive of all-cause mortality (hazard ratio 0.73, 95% confidence interval 0.63 to 0.85, p <0.001) and cardiovascular mortality or hospitalization for HF (hazard ratio 0.73, 95% confidence interval 0.66 to 0.82, p <0.001) at median follow-up of 9.9 months. Lower baseline triglyceride level was also associated with worse outcomes. In conclusion, lower baseline total cholesterol is correlated with a high-risk patient profile and is a marker of disease severity in patients hospitalized for worsening HF with reduced ejection fraction. Baseline total cholesterol and triglyceride levels are predictive of mortality and HF rehospitalization beyond traditional risk factors. (C) 2013 Elsevier Inc. All rights reserved. (Am J Cardiol 2013;111:574-581) C1 [Greene, Stephen J.; Bonow, Robert O.; Gheorghiade, Mihai] Northwestern Univ Feinberg, Sch Med, Ctr Cardiovasc Innovat, Chicago, IL USA. [Subacius, Hans P.] Northwestern Univ Feinberg, Sch Med, Div Cardiol, Dept Med, Chicago, IL USA. [Vaduganathan, Muthiah] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. [Lupi, Laura; Nodari, Savina] Univ Brescia, Dept Cardiol, Brescia, Italy. [Ambrosy, Andrew P.] Stanford Univ, Sch Med, Dept Med, Stanford, CA USA. [Mentz, Robert J.] Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA. [Konstam, Marvin A.] Tufts Med Ctr, Dept Med, Div Cardiol, Boston, MA USA. [Fonarow, Gregg C.] Ahmanson UCLA Cardiomyopathy Ctr, Div Cardiol, Los Angeles, CA USA. RP Gheorghiade, M (reprint author), Northwestern Univ Feinberg, Sch Med, Ctr Cardiovasc Innovat, Chicago, IL USA. EM m-gheorghiade@northwestern.edu OI Subacius, Haris/0000-0003-4061-1220 FU Otsuka, Inc., Rockville, Maryland; Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois FX Financial and material support for the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) was provided by Otsuka, Inc., Rockville, Maryland. Database management was performed by the sponsor. Mr. Subacius conducted all final analyses for this report with funding from the Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois. NR 23 TC 13 Z9 15 U1 0 U2 7 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 15 PY 2013 VL 111 IS 4 BP 574 EP 581 DI 10.1016/j.amjcard.2012.10.042 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 095GN UT WOS:000315322800020 PM 23206923 ER PT J AU O'Rourke, EJ Kuballa, P Xavier, R Ruvkun, G AF O'Rourke, Eyleen J. Kuballa, Petric Xavier, Ramnik Ruvkun, Gary TI omega-6 Polyunsaturated fatty acids extend life span through the activation of autophagy SO GENES & DEVELOPMENT LA English DT Article DE C. elegans; fasting; lipid; autophagy; polyunsaturated fatty acids (PUFA); longevity ID CAENORHABDITIS-ELEGANS; C. ELEGANS; LINOLEIC-ACID; ARACHIDONIC-ACID; RECEPTOR NHR-49; GENE-EXPRESSION; PPAR-ALPHA; METABOLISM; RESTRICTION; INHIBITION AB Adaptation to nutrient scarcity depends on the activation of metabolic programs to efficiently use internal reserves of energy. Activation of these programs in abundant food regimens can extend life span. However, the common molecular and metabolic changes that promote adaptation to nutritional stress and extend life span are mostly unknown. Here we present a response to fasting, enrichment of omega-6 polyunsaturated fatty acids (PUFAs), which promotes starvation resistance and extends Caenorhabditis elegans life span. Upon fasting, C. elegans induces the expression of a lipase, which in turn leads to an enrichment of omega-6 PUFAs. Supplementing C. elegans culture media with these omega-6 PUFAs increases their resistance to starvation and extends their life span in conditions of food abundance. Supplementation of C. elegans or human epithelial cells with these omega-6 PUFAs activates autophagy, a cell recycling mechanism that promotes starvation survival and slows aging. Inactivation of C. elegans autophagy components reverses the increase in life span conferred by supplementing the C. elegans diet with these fasting-enriched omega-6 PUFAs. We propose that the salubrious effects of dietary supplementation with omega-3/6 PUFAs (fish oils) that have emerged from epidemiological studies in humans may be due to a similar activation of autophagic programs. C1 [O'Rourke, Eyleen J.; Ruvkun, Gary] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. [O'Rourke, Eyleen J.; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Kuballa, Petric; Xavier, Ramnik] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Kuballa, Petric; Xavier, Ramnik] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Ruvkun, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu FU [R01DK070147]; [K99DK087928] FX We thank members of the Ruvkun, Ausubel, and Kaplan laboratories for helpful comments, especially A. Lee-Conery for help with longevity experiments; J. Larkins-Ford for performing Biosort analyses; J. Rapley, J. Avruch, R. Niedra, and B. Seed for sharing expertise and reagents for mammalian experiments; and H.Y. Mak, A. Soukas, M. Van Gilst, M. Freeman, A. Saghatelian, and A. Tyler for protocols, access to equipment, and discussions on lipid measurements. We thank Dr. Mitani and the National Bioresource Project for strains. We also thank C. Danna for helpful suggestions and comments on the manuscript. This work was supported by grants R01DK070147 (to G. R.) and K99DK087928 (to E.J.O'R.). E.J.O'R. designed the overall studies, performed the experiments, and wrote the manuscript. G. R. revised the manuscript. P. K. and R. X. provided GFP-hLC3B and GFP-hLC3B-G120A HeLa cells and ATG16L1-proficient and ATG16L1-deficient mouse embryonic fibroblasts and revised the manuscript. NR 63 TC 35 Z9 36 U1 0 U2 24 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD FEB 15 PY 2013 VL 27 IS 4 BP 429 EP 440 DI 10.1101/gad.205294.112 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 094TI UT WOS:000315286300008 PM 23392608 ER PT J AU Wang, DH Hoing, S Patterson, HC Ahmad, UM Rathinam, VAK Rajewsky, K Fitzgerald, KA Golenbock, DT AF Wang, Donghai Hoeing, Susanne Patterson, Heide Christine Ahmad, Umtul M. Rathinam, Vijay A. K. Rajewsky, Klaus Fitzgerald, Katherine A. Golenbock, Douglas T. TI Inflammation in Mice Ectopically Expressing Human Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne (PAPA) Syndrome-associated PSTPIP1 A230T Mutant Proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; AUTOINFLAMMATORY DISEASES; PYRIN; ASC; ACTIVATION; MUTATIONS; CRE; IL-1-BETA; ANAKINRA; FEVER AB Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Syndrome (PAPA syndrome) is an autoinflammatory disease caused by aberrant production of the proinflammatory cytokine interleukin-1. Mutations in the gene encoding proline serine threonine phosphatase-interacting protein-1 (PSTPIP1) have been linked to PAPA syndrome. PSTPIP1 is an adaptor protein that interacts with PYRIN, the protein encoded by the Mediterranean Fever (MEFV) gene whose mutations cause Familial Mediterranean Fever (FMF). However, the pathophysiological function of PSTPIP1 remains to be elucidated. We have generated mouse strains that either are PSTPIP1 deficient or ectopically express mutant PSTPIP1. Results from analyzing these mice suggested that PSTPIP1 is not an essential regulator of the Nlrp3, Aim2, or Nlrc4 inflammasomes. Although common features of human PAPA syndrome such as pyogenic arthritis and skin inflammation were not recapitulated in the mouse model, ectopic expression of the mutant but not the wild type PSTPIP1 in mice lead to partial embryonic lethality, growth retardation, and elevated level of circulating proinflammatory cytokines. C1 [Wang, Donghai; Ahmad, Umtul M.; Rathinam, Vijay A. K.; Fitzgerald, Katherine A.; Golenbock, Douglas T.] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA. [Hoeing, Susanne; Rajewsky, Klaus] Harvard Univ, Sch Med, Immune Dis Inst, Boston Childrens Hosp, Boston, MA 02115 USA. [Hoeing, Susanne; Rajewsky, Klaus] Harvard Univ, Sch Med, Program Cellular & Mol Immunol, Boston Childrens Hosp, Boston, MA 02115 USA. [Patterson, Heide Christine] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Patterson, Heide Christine] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Patterson, Heide Christine] Tech Univ Muenchen, Klinikum Rechts Isar, Inst Klin Chem & Pathobiochem, D-81675 Munich, Germany. RP Wang, DH (reprint author), Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, 364 Plantat St, Worcester, MA 01605 USA. EM donghai.wang@umassmed.edu; douglas.golenbock@umassmed.edu FU National Institutes of Health [1 R21 AI095871-01]; New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases postdoctoral fellowship (National Institutes of Health) [U54 AI057159] FX This work was supported, in whole or in part, by National Institutes of Health Grant 1 R21 AI095871-01 (to D. G. and D. W.).; Supported by the New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases postdoctoral fellowship (National Institutes of Health U54 AI057159). NR 23 TC 16 Z9 16 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 15 PY 2013 VL 288 IS 7 BP 4594 EP 4601 DI 10.1074/jbc.M112.443077 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 095ND UT WOS:000315340400009 PM 23293022 ER PT J AU Alessi, C Vitiello, MV AF Alessi, Cathy Vitiello, Michael V. TI Primary Insomnia in Older Persons SO AMERICAN FAMILY PHYSICIAN LA English DT Editorial Material C1 [Alessi, Cathy] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Vitiello, Michael V.] Univ Washington, Seattle, WA 98195 USA. RP Alessi, C (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD FEB 15 PY 2013 VL 87 IS 4 BP 280 EP 281 PG 2 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 090UX UT WOS:000315006600008 ER PT J AU An, JB Liu, HR Magyar, CE Guo, YC Veena, MS Srivatsan, ES Huang, JT Rettig, MB AF An, Jiabin Liu, Huiren Magyar, Clara E. Guo, Yanchuan Veena, Mysore S. Srivatsan, Eri S. Huang, Jiaoti Rettig, Matthew B. TI Hyperactivated JNK Is a Therapeutic Target in pVHL-Deficient Renal Cell Carcinoma SO CANCER RESEARCH LA English DT Article ID HIPPEL-LINDAU PROTEIN; HYPOXIA-INDUCIBLE FACTOR; EMBRYONIC STEM-CELLS; C-JUN; E-CADHERIN; TUMOR SUPPRESSION; KINASE SAPK/JNK; VHL; PHOSPHORYLATION; GENE AB Clear cell renal cell carcinomas (RCC), the major histologic subtype of RCC accounting for more than 80% of cases, are typified by biallelic inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene. Although accumulation of hypoxia-inducible factor alpha (HIF-alpha) is the most well-studied effect of VHL inactivation, direct inhibition of HIF alpha or restoration of wild-type pVHL protein expression has not proved readily feasible, given the limitations associated with pharmacologic targeting of transcription factors (i.e., HIF-a) and gene replacement therapy of tumor suppressor genes (i.e., VHL). Here, we have established that phosphorylated c-Jun, a substrate of the c-Jun-NH2-kinase (JNK), is selectively activated in clear cell RCC patient specimens. Using multiple isogenic cell lines, we show that HIF-alpha-independent JNK hyperactivation is unique to the pVHL-deficient state. Importantly, pVHL-deficient RCCs are dependent upon JNK activity for in vitro and in vivo growth. A multistep signaling pathway that links pVHL loss to JNK activation involves the formation of a CARD9/BCL10/TRAF6 complex as a proximal signal to sequentially stimulate TAK1 (MAPKKK), MKK4 (MAPKK), and JNK (MAPK). JNK stimulates c-Jun phosphorylation, activation, and dimerization with c-Fos to form a transcriptionally competent AP1 complex that drives transcription of the Twist gene and induces epithelial-mesenchymal transition. Thus, JNK represents a novel molecular target that is selectively activated in and drives the growth of pVHL-deficient clear cell RCCs. These findings can serve as the preclinical foundation for directed efforts to characterize potent pharmacologic inhibitors of the JNK pathway for clinical translation. Cancer Res; 73(4); 1374-85. (C) 2012 AACR. C1 [An, Jiabin; Liu, Huiren; Rettig, Matthew B.] VA Greater Los Angeles Healthcare Syst, Dept Med, Div Hematol Oncol, Los Angeles, CA USA. [Veena, Mysore S.; Srivatsan, Eri S.] VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. [An, Jiabin; Liu, Huiren; Rettig, Matthew B.] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol Oncol, Dept Urol, Los Angeles, CA 90095 USA. [Magyar, Clara E.; Huang, Jiaoti] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol Oncol, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Veena, Mysore S.; Srivatsan, Eri S.] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol Oncol, Dept Surg, Los Angeles, CA 90095 USA. [Rettig, Matthew B.] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol Oncol, Dept Med, Los Angeles, CA 90095 USA. [Guo, Yanchuan] Chinese Acad Sci, Tech Inst Phys & Chem, Beijing, Peoples R China. RP Rettig, MB (reprint author), UCLA VAGLAHS, 11301 Wilshire Blvd,Bldg 500,Room 4237, Los Angeles, CA 90073 USA. EM mrettig@mednet.ucla.edu FU Department of Veterans Affairs; NIH [2P30DK041301] FX The authors thank G. Thomas (Institute of Cancer Research, United Kingdom) for the isogenic pairs of ACHN and SN12C cell lines, W. Kaelin (Dana Farber Cancer Institute) for the 786-0 lines and the CARD9 plasmids, and B. Zbar (National Cancer Institute) for the UMRC6 and UOK121 pairs. The Vector Core (NIH grant 2P30DK041301) at the David Geffen School of Medicine prepared and titered lentiviral particles.; This work was supported by a Merit Review grant (M.B. Rettig) from the Department of Veterans Affairs. NR 36 TC 15 Z9 20 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 15 PY 2013 VL 73 IS 4 BP 1374 EP 1385 DI 10.1158/0008-5472.CAN-12-2362 PG 12 WC Oncology SC Oncology GA 091DR UT WOS:000315029800012 PM 23393199 ER PT J AU Mallampalli, RK Glasser, JR Coon, TA Chen, BB AF Mallampalli, Rama K. Glasser, Jennifer R. Coon, Tiffany A. Chen, Bill B. TI Calmodulin protects Aurora B on the midbody to regulate the fidelity of cytokinesis SO CELL CYCLE LA English DT Article DE Aurora B; FBXL2; calmodulin; mitosis; midbody ID SPINDLE POLE BODY; CTP-PHOSPHOCHOLINE CYTIDYLYLTRANSFERASE; SCF UBIQUITIN LIGASE; KINASE INHIBITOR; F-BOX; CHROMOSOME SEGREGATION; MITOTIC PROGRESSION; CELLS; DEGRADATION; COMPLETION AB Aurora B kinase is an integral regulator of cytokinesis as it stabilizes the intercellular canal within the midbody to ensure proper chromosomal segregation during cell division. Here we identified an E3 ligase subunit, F-box protein FBXL2, that by recognizing a calmodulin binding signature within Aurora B, ubiquitinates and removes the kinase from the midbody. Calmodulin, by competing with the F-box protein for access to the calmodulin binding signature, protected Aurora B from FBXL2. Calmodulin co-localized with Aurora B on the midbody, preserved Aurora B levels in cells, and stabilized intercellular canals during delayed abscission. Genetic or pharmaceutical depletion of endogenous calmodulin significantly reduced Aurora B protein levels at the midbody resulting in tetraploidy and multi-spindle formation. The calmodulin inhibitor, calmidazolium, reduced Aurora B protein levels resulting in tetraploidy, mitotic arrest, and apoptosis of tumorigenic cells and profoundly inhibited tumor formation in athymic nude mice. These observations indicate molecular interplay between Aurora B and calmodulin in telophase and suggest that calmodulin acts as a checkpoint sensor for chromosomal segregation errors during mitosis. C1 [Mallampalli, Rama K.; Glasser, Jennifer R.; Coon, Tiffany A.; Chen, Bill B.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Chen, Bill B.] Univ Pittsburgh, Acute Lung Injury Ctr Excellence, Pittsburgh, PA USA. [Mallampalli, Rama K.] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA USA. RP Chen, BB (reprint author), Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. EM chenb@upmc.edu FU US Department of Veterans Affairs; National Institutes of Health [HL116472, HL096376, HL097376, HL098174] FX We thank D. W. Gerlich for providing pH2B-mCherry-IRES-puro2 and pMyrPalm-mEGFP plasmids. This material is based upon work supported, in part, by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. This work was supported by a Merit Review Award from the US Department of Veterans Affairs and National Institutes of Health R01 grants HL116472 (to B. B. C.), HL096376, HL097376 and HL098174 (to R.K.M.). NR 65 TC 5 Z9 5 U1 0 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD FEB 15 PY 2013 VL 12 IS 4 BP 663 EP 673 DI 10.4161/cc.23586 PG 11 WC Cell Biology SC Cell Biology GA 089PR UT WOS:000314923000022 PM 23370391 ER PT J AU Zaid, TM Yeung, TL Thompson, MS Leung, CS Harding, T Co, NN Schmandt, RS Kwan, SY Rodriguez-Aguay, C Lopez-Berestein, G Sood, AK Wong, KK Birrer, MJ Mok, SC AF Zaid, Tarrik M. Yeung, Tsz-Lun Thompson, Melissa S. Leung, Cecilia S. Harding, Tom Co, Ngai-Na Schmandt, Rosie S. Kwan, Suet-Ying Rodriguez-Aguay, Cristian Lopez-Berestein, Gabriel Sood, Anil K. Wong, Kwong-Kwok Birrer, Michael J. Mok, Samuel C. TI Identification of FGFR4 as a Potential Therapeutic Target for Advanced-Stage, High-Grade Serous Ovarian Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; FACTOR RECEPTORS; BLADDER-CANCER; BREAST-CANCER; MUTATIONS; CARCINOMA; EXPRESSION; CISPLATIN; PACLITAXEL; BINDING AB Purpose: To evaluate the prognostic value of fibroblast growth factor receptor 4 (FGFR4) protein expression in patients with advanced-stage, high-grade serous ovarian cancer, delineate the functional role of FGFR4 in ovarian cancer progression, and evaluate the feasibility of targeting FGFR4 in serous ovarian cancer treatment. Experimental Design: Immunolocalization of FGFR4 was conducted on 183 ovarian tumor samples. The collected FGFR4 expression data were correlated with overall survival using Kaplan-Meier and Cox regression analyses. The effects of FGFR4 silencing on ovarian cancer cell growth, survival, invasiveness, apoptosis, and FGF1-mediated signaling pathway activation were evaluated by transfecting cells with FGFR4-specific siRNAs. An orthotopic mouse model was used to evaluate the effect of injection of FGFR4-specific siRNAs and FGFR4 trap protein encapsulated in nanoliposomes on ovarian tumor growth in vivo. Results: Overexpression of FGFR4 protein was significantly associated with decreased overall survival durations. FGFR4 silencing significantly decreased the proliferation, survival, and invasiveness and increased apoptosis of ovarian cancer cells. Also, downregulation of FGFR4 significantly abrogated the mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-kappa B), and WNT signaling pathways, which are activated by FGF1. Targeting FGFR4 with the FGFR4-specific siRNAs and FGFR4 trap protein significantly decreased ovarian tumor growth in vivo. Conclusions: FGFR4 is a prognostic marker for advanced-stage, high-grade serous ovarian carcinoma. Silencing FGFR4 and inhibiting ligand-receptor binding significantly decrease ovarian tumor growth both in vitro and in vivo, suggesting that targeting ovarian cancer cells with high levels of FGFR4 protein expression is a new therapeutic modality for this disease and will improve survival of it. Clin Cancer Res; 19(4); 809-20. (c) 2012 AACR. C1 [Zaid, Tarrik M.; Yeung, Tsz-Lun; Thompson, Melissa S.; Leung, Cecilia S.; Co, Ngai-Na; Schmandt, Rosie S.; Kwan, Suet-Ying; Sood, Anil K.; Wong, Kwong-Kwok; Mok, Samuel C.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA. [Rodriguez-Aguay, Cristian; Lopez-Berestein, Gabriel] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. [Lopez-Berestein, Gabriel; Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. [Lopez-Berestein, Gabriel; Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Ctr RNA Interference & Noncoding RNA, Houston, TX 77030 USA. [Harding, Tom] Five Prime Therapeut Inc, San Francisco, CA USA. [Birrer, Michael J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Mok, SC (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Unit 1362, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM scmok@mdanderson.org OI Wong, Kwong-Kwok/0000-0002-0375-6669; Kwan, Suet Ying/0000-0002-8222-3827 FU Gilder Foundation; MD Anderson Ovarian Cancer SPORE grant from the National Institutes of Health [P50 CA083639]; MD Anderson Cancer Center [CA016672]; [R01 CA133057]; [RC4 CA156551]; [U54 CA151668] FX This study was supported in part by grants R01 CA133057 (S.C. Mok), RC4 CA156551 (M.J. Birrer), and U54 CA151668 (A.K. Sood); the Gilder Foundation (A.K. Sood); and MD Anderson Ovarian Cancer SPORE grant P50 CA083639 (S.C. Mok) from the National Institutes of Health. This research is supported in part by the MD Anderson Cancer Center Support Grant CA016672. NR 42 TC 26 Z9 26 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 15 PY 2013 VL 19 IS 4 BP 809 EP 820 DI 10.1158/1078-0432.CCR-12-2736 PG 12 WC Oncology SC Oncology GA 091CJ UT WOS:000315026200007 PM 23344261 ER PT J AU Reardon, DA Groves, MD Wen, PY Nabors, L Mikkelsen, T Rosenfeld, S Raizer, J Barriuso, J McLendon, RE Suttle, AB Ma, B Curtis, CM Dar, MM de Bono, J AF Reardon, David A. Groves, Morris D. Wen, Patrick Y. Nabors, Louis Mikkelsen, Tom Rosenfeld, Steve Raizer, Jeffrey Barriuso, Jorge McLendon, Roger E. Suttle, A. Benjamin Ma, Bo Curtis, C. Martin Dar, Mohammed M. de Bono, Johann TI A Phase I/II Trial of Pazopanib in Combination with Lapatinib in Adult Patients with Relapsed Malignant Glioma SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; RECURRENT GLIOBLASTOMA-MULTIFORME; INTEGRATED GENOMIC ANALYSIS; PROGRESSION-FREE SURVIVAL; HIGH-GRADE GLIOMAS; II TRIAL; TUMOR ANGIOGENESIS; KINASE INHIBITORS; ANTI-VEGF; IN-VIVO AB Purpose: Increased mitogenic signaling and angiogenesis, frequently facilitated by somatic activation of EGF receptor (EGFR; ErbB1) and/or loss of PTEN, and VEGF overexpression, respectively, drive malignant glioma growth. We hypothesized that patients with recurrent glioblastoma would exhibit differential antitumor benefit based on tumor PTEN/EGFRvIII status when treated with the antiangiogenic agent pazopanib and the ErbB inhibitor lapatinib. Experimental Design: A phase II study evaluated the antitumor activity of pazopanib 400 mg/d plus lapatinib 1,000 mg/d in patients with grade 4 malignant glioma and known PTEN/EGFRvIII status not receiving enzyme-inducing anticonvulsants (EIAC). The phase II study used a two-stage Green-Dahlberg design for futility. An independent, parallel phase I component determined the maximum-tolerated regimen (MTR) of pazopanib and lapatinib in patients with grade 3/4 glioma receiving EIACs. Results: The six-month progression-free survival (PFS) rates in phase II (n = 41) were 0% and 15% in the PTEN/EGFRvIII-positive and PTEN/EGFRvIII-negative cohorts, respectively, leading to early termination. Two patients (5%) had a partial response and 14 patients (34%) had stable disease lasting 8 or more weeks. In phase I (n = 34), the MTR was not reached. On the basis of pharmacokinetic and safety review, a regimen of pazopanib 600 mg plus lapatinib 1,000 mg, each twice daily, was considered safe. Concomitant EIACs reduced exposure to pazopanib and lapatinib. Conclusions: The antitumor activity of this combination at the phase II dose tested was limited. Pharmacokinetic data indicated that exposure to lapatinib was subtherapeutic in the phase II evaluation. Evaluation of intratumoral drug delivery and activity may be essential for hypothesis-testing trials with targeted agents in malignant glioma. Clin Cancer Res; 19(4); 900-8. (C) 2012 AACR. C1 [Reardon, David A.; Wen, Patrick Y.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Groves, Morris D.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Nabors, Louis] Univ Alabama Birmingham, Birmingham, AL USA. [Mikkelsen, Tom] Henry Ford Hlth Syst, Detroit, MI USA. [Rosenfeld, Steve] Columbia Univ, New York, NY USA. [Raizer, Jeffrey] Northwestern Univ, Chicago, IL 60611 USA. [Barriuso, Jorge; de Bono, Johann] Inst Canc Res, Chester Beatty Labs, London SW3 6JB, England. [Barriuso, Jorge; de Bono, Johann] Royal Marsden Hosp NHS Fdn Trust, London, England. [McLendon, Roger E.] Duke Univ, Med Ctr, Durham, NC USA. [Suttle, A. Benjamin; Ma, Bo; Curtis, C. Martin; Dar, Mohammed M.] GlaxoSmithKline, Res Triangle Pk, NC USA. RP Reardon, DA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM David_Reardon@DFCI.harvard.edu FU GlaxoSmithKline, Philadelphia FX This study was sponsored by GlaxoSmithKline, Philadelphia, PA. Medical editorial assistance was also funded by GlaxoSmithKline. NR 47 TC 30 Z9 30 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 15 PY 2013 VL 19 IS 4 BP 900 EP 908 DI 10.1158/1078-0432.CCR-12-1707 PG 9 WC Oncology SC Oncology GA 091CJ UT WOS:000315026200015 PM 23363814 ER PT J AU Yap, TA Arkenau, HT Camidge, DR George, S Serkova, NJ Gwyther, SJ Spratlin, JL Lal, R Spicer, J Desouza, NM Leach, MO Chick, J Poondru, S Boinpally, R Gedrich, R Brock, K Stephens, A Eckhardt, SG Kaye, SB Demetri, G Scurr, M AF Yap, Timothy A. Arkenau, Hendrik-Tobias Camidge, D. Ross George, Suzanne Serkova, Natalie J. Gwyther, Stephen J. Spratlin, Jennifer L. Lal, Rohit Spicer, James Desouza, Nandita M. Leach, Martin O. Chick, Jon Poondru, Srinivasu Boinpally, Ramesh Gedrich, Richard Brock, Katie Stephens, Andrew Eckhardt, S. Gail Kaye, Stan B. Demetri, George Scurr, Michelle TI First-in-Human Phase I Trial of Two Schedules of OSI-930, a Novel Multikinase Inhibitor, Incorporating Translational Proof-of-Mechanism Studies SO CLINICAL CANCER RESEARCH LA English DT Article ID GASTROINTESTINAL STROMAL TUMORS; RECEPTOR TYROSINE KINASES; CLINICAL-TRIALS; SOLID TUMORS; ANTITUMOR-ACTIVITY; SOFT-TISSUE; C-KIT; CANCER; ANGIOGENESIS; SUNITINIB AB Purpose: OSI-930 is a novel, potent, oral small-molecule receptor tyrosine kinase inhibitor, predominantly against VEGF receptors (VEGFR), c-Kit, and platelet-derived growth factor receptors. A phase I trial was undertaken to determine safety, maximum-tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and antitumor activity of OSI-930 in patients with advanced solid tumors. Experimental Design: OSI-930 was administered once or twice a day using a modified accelerated titration design. Pharmacokinetics and plasma soluble VEGFR2 (sVEGFR2) studies were undertaken. Dynamic contrast-enhanced MRI (DCE-MRI) and 2[18F]fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) MTD expansion cohorts were conducted. Results: Fifty-eight patients received OSI-930 in 2 schedules; once a day schedule: 12 patients at doses up to 1,600 mg without reaching MTD; twice a day schedule: 46 patients at 400 mg (n = 7), 500 mg (n = 31), and 600 mg(n = 8). Dose-limiting toxicities were observed at 600 mg twice a day (n = 3): G3 rash (n = 2) and G4 gamma-glutamyltransferase, establishing the MTD at 500 mg twice a day. Common G1-2 toxicities included fatigue, diarrhea, nausea, and rash. Antitumor responses were seen in 2 patients with advanced ovarian cancer [Response Evaluation Criteria in Solid Tumors (RECIST) partial response (PR) (n = 1); GCIG CA125 response (n = 1)]. Eleven of 19 heavily pretreated imatinib-resistant patients with gastrointestinal stromal tumors achieved RECIST stable disease (median duration: 126 days), with FDG-PET scans showing PRs in 4 of 9 patients. OSI-930 exposure increased with dose; substantial decreases in sVEGFR levels were observed with OSI-930 twice a day doses >= 400 mg, while DCE-MRI responses were shown in 4 of 6 patients. Conclusions: OSI-930 is safe and well tolerated, with pharmacokinetic-pharmacodynamic data supporting proof-of-mechanism with clinically relevant antitumor activity. Clin Cancer Res; 19(4); 909-19. (c) 2012 AACR. C1 [Yap, Timothy A.; Arkenau, Hendrik-Tobias; Lal, Rohit; Spicer, James; Kaye, Stan B.; Scurr, Michelle] Royal Marsden NHS Fdn Trust, Drug Dev Unit, Sutton SM2 5PT, Surrey, England. [Yap, Timothy A.; Kaye, Stan B.; Scurr, Michelle] Inst Canc Res, Div Clin Studies, Sutton, Surrey, England. [Desouza, Nandita M.; Leach, Martin O.] Inst Canc Res, Canc Res UK, Sutton, Surrey, England. [Desouza, Nandita M.; Leach, Martin O.] Inst Canc Res, Engn & Phys Sci Res Council, Canc Imaging Ctr, Sutton, Surrey, England. [Gwyther, Stephen J.] E Surrey Hosp, Redhill, Surrey, England. [Camidge, D. Ross; Serkova, Natalie J.; Spratlin, Jennifer L.; Eckhardt, S. Gail] Univ Colorado, Denver, CO 80202 USA. [George, Suzanne; Demetri, George] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chick, Jon; Poondru, Srinivasu; Boinpally, Ramesh; Gedrich, Richard; Brock, Katie; Stephens, Andrew] OSI Pharmaceut LLC, Northbrook, IL USA. RP Kaye, SB (reprint author), Royal Marsden NHS Fdn Trust, Drug Dev Unit, Downs Rd, Sutton SM2 5PT, Surrey, England. EM stan.kaye@rmh.nhs.uk RI leach, martin/C-2248-2008 OI leach, martin/0000-0002-0756-5368 FU Bayer; Novartis; OSI Pharmaceuticals LLC; Cancer Research UK; Engineering and Physical Sciences Research Council; Experimental Cancer Medicine Centre; NIH Research Biomedical Research Centre FX D.R. Camidge is a consultant/advisory board member of OSI Pharmaceuticals. S. George has commercial research grants from Bayer and Novartis and is a consultant/advisory board member of Bayer, GSK, and Pfizer. A. Stephens has ownership interest (including patents) in OSI Pharmaceuticals. S.B. Kaye is a consultant/advisory board member of Astellas Advisory Board. No potential conflicts of interest were disclosed by the other authors.; This study was supported by OSI Pharmaceuticals LLC, a wholly owned subsidiary of Astellas US LLC. The Drug Development Unit of the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research is supported in part by a program grant from Cancer Research UK. The Cancer Imaging Centre at the Institute of Cancer Research is supported by Cancer Research UK and Engineering and Physical Sciences Research Council. Support was also provided by the Experimental Cancer Medicine Centre (to The Institute of Cancer Research) and the NIH Research Biomedical Research Centre (jointly to the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research). NR 36 TC 7 Z9 7 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 15 PY 2013 VL 19 IS 4 BP 909 EP 919 DI 10.1158/1078-0432.CCR-12-2258 PG 11 WC Oncology SC Oncology GA 091CJ UT WOS:000315026200016 PM 23403628 ER PT J AU Zhu, AX Gold, PJ El-Khoueiry, AB Abrams, TA Morikawa, H Ohishi, N Ohtomo, T Philip, PA AF Zhu, Andrew X. Gold, Philip J. El-Khoueiry, Anthony B. Abrams, Thomas A. Morikawa, Hideo Ohishi, Norihisa Ohtomo, Toshihiko Philip, Philip A. TI First-in-Man Phase I Study of GC33, a Novel Recombinant Humanized Antibody Against Glypican-3, in Patients with Advanced Hepatocellular Carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID EXPRESSION; GROWTH; MARKER; PROMOTES; TUMORS AB Purpose: GC33 is a novel recombinant fully humanized monoclonal antibody that binds to human glypican-3 (GPC3). The antitumor activity of GC33 was shown in preclinical models of hepatocellular carcinoma (HCC). This first-in-man clinical trial was conducted to evaluate the safety, pharmacokinetic characteristics, and preliminary efficacy of GC33 in patients with advanced HCC. Experimental Design: Patients with measurable, histologically proven, advanced HCC were enrolled to a dose-escalation study of GC33 (2.5-20 mg/kg) given intravenously weekly. The primary endpoint was to determine the maximum tolerated dose of GC33 for further development. Pharmacokinetic characteristics were measured in serum samples. Immunohistochemistry was conducted on tumor biopsies to evaluate GPC3 expression. Tumor response was assessed every 8 weeks using Response Evaluation Criteria in Solid Tumors criteria. Results: Twenty patients were enrolled and treated with GC33. A maximum tolerated dose was not reached as there were no dose-limiting toxicities (DLT) up to the highest planned dose level. Common adverse events with all grades included fatigue (50%), constipation (35%), headache (35%), and hyponatremia (35%). The incidence of adverse events seemed not to be dose dependent. Trough serum concentrations at steady state were in excess of target concentration at doses of 5 mg/kg or greater. Median time to progression (TTP) was 26.0 weeks in the GPC3 high expression group and 7.1 weeks in the low expression group (P = 0.033). Conclusion: This study shows that GC33 was well tolerated in advanced HCC and provides preliminary evidence that GPC3 expression in HCC may be associated with the clinical benefit to GC33 that warrants prospective evaluation. Clin Cancer Res; 19(4); 920-8. (c) 2012 AACR. C1 [Zhu, Andrew X.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Abrams, Thomas A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gold, Philip J.] Swedish Canc Inst, Seattle, WA USA. [El-Khoueiry, Anthony B.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Morikawa, Hideo; Ohishi, Norihisa; Ohtomo, Toshihiko] Chugai Pharmaceut Co Ltd, Tokyo, Japan. [Philip, Philip A.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI 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 FU Genentech Roche; Chugai Pharmaceutical Co. Ltd. FX A. El-khoueiry has a commercial research grant, honoraria from speakers' bureau from, and is a consultant/advisory board member for Genentech Roche. No potential conflicts of interest were disclosed by the other authors.; This study was funded by Chugai Pharmaceutical Co. Ltd. NR 26 TC 43 Z9 45 U1 1 U2 14 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 15 PY 2013 VL 19 IS 4 BP 920 EP 928 DI 10.1158/1078-0432.CCR-12-2616 PG 9 WC Oncology SC Oncology GA 091CJ UT WOS:000315026200017 PM 23362325 ER PT J AU Katholnig, K Kaltenecker, CC Hayakawa, H Rosner, M Lassnig, C Zlabinger, GJ Gaestel, M Muller, M Hengstschlager, M Horl, WH Park, JM Saemann, MD Weichhart, T AF Katholnig, Karl Kaltenecker, Christopher C. Hayakawa, Hiroko Rosner, Margit Lassnig, Caroline Zlabinger, Gerhard J. Gaestel, Matthias Mueller, Mathias Hengstschlaeger, Markus Hoerl, Walter H. Park, Jin Mo Saeemann, Marcus D. Weichhart, Thomas TI p38 alpha Senses Environmental Stress To Control Innate Immune Responses via Mechanistic Target of Rapamycin SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; P38 MAPK; MAMMALIAN TARGET; DENDRITIC CELLS; COMPLEX 1; MTOR; PHOSPHORYLATION; PATHWAY; TISSUE; AKT AB The MAPK p38 alpha senses environmental stressors and orchestrates inflammatory and immunomodulatory reactions. However, the molecular mechanism how p38 alpha controls immunomodulatory responses in myeloid cells remains elusive. We found that in monocytes and macrophages, p38 alpha activated the mechanistic target of rapamycin (mTOR) pathway in vitro and in vivo. p38 alpha signaling in myeloid immune cells promoted IL-10 but inhibited IL-12 expression via mTOR and blocked the differentiation of proinflammatory CD4(+) Th1 cells. Cellular stress induced p38 alpha-mediated mTOR activation that was independent of PI3K but dependent on the MAPK-activated protein kinase 2 and on the inhibition of tuberous sclerosis 1 and 2, a negative regulatory complex of mTOR signaling. Remarkably, p38 alpha and PI3K concurrently modulated mTOR to balance IL-12 and IL-10 expression. Our data link p38 alpha to mTOR signaling in myeloid immune cells that is decisive for tuning the immune response in dependence on the environmental milieu. The Journal of Immunology, 2013, 190: 1519-1527. C1 [Katholnig, Karl; Kaltenecker, Christopher C.; Hoerl, Walter H.; Saeemann, Marcus D.; Weichhart, Thomas] Med Univ Vienna, Dept Internal Med 3, Clin Div Nephrol & Dialysis, A-1090 Vienna, Austria. [Hayakawa, Hiroko; Park, Jin Mo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Hayakawa, Hiroko; Park, Jin Mo] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Rosner, Margit; Hengstschlaeger, Markus; Weichhart, Thomas] Med Univ Vienna, Inst Med Genet, A-1090 Vienna, Austria. [Lassnig, Caroline; Mueller, Mathias] Univ Vet Med Vienna, Inst Anim Breeding & Genet & Biomodels Austria, A-1210 Vienna, Austria. [Zlabinger, Gerhard J.] Med Univ Vienna, Inst Immunol, A-1090 Vienna, Austria. [Gaestel, Matthias] Hannover Med Sch, Dept Physiol Chem, D-30625 Hannover, Germany. RP Weichhart, T (reprint author), Med Univ Vienna, Inst Med Genet, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. EM thomas.weichhart@meduniwien.ac.at RI Weichhart, Thomas/J-3531-2014 OI Weichhart, Thomas/0000-0002-4349-0797 FU Else-Kroner Fresensius Stiftung; Austrian Science Foundation Fonds zur Forderung der Wissenschaftlichen Forschung [SFB F28]; Austrian Federal Ministry for Science and Research (GEN-AU III Austromouse); National Institutes of Health [AI074957]; Deutsche Forschungsgemeinschaft FX This work was supported by the Else-Kroner Fresensius Stiftung (to T. W. and M. D. S.), the Austrian Science Foundation Fonds zur Forderung der Wissenschaftlichen Forschung (SFB F28 to C. L. and M. M.), the Austrian Federal Ministry for Science and Research (GEN-AU III Austromouse to C. L. and M. M.), the National Institutes of Health (Grant AI074957 to J.M.P.), and the Deutsche Forschungsgemeinschaft (to M.G.). NR 50 TC 16 Z9 16 U1 1 U2 15 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 15 PY 2013 VL 190 IS 4 BP 1519 EP 1527 DI 10.4049/jimmunol.1202683 PG 9 WC Immunology SC Immunology GA 088HS UT WOS:000314825400016 PM 23315073 ER PT J AU Leonard, DA Cetrulo, CL McGrouther, DA Sachs, DH AF Leonard, David A. Cetrulo, Curtis L., Jr. McGrouther, Duncan A. Sachs, David H. TI Induction of Tolerance of Vascularized Composite Allografts SO TRANSPLANTATION LA English DT Review DE Tolerance; Vascularized composite allotransplantation ID MAJOR HISTOCOMPATIBILITY COMPLEX; LARGE-ANIMAL-MODEL; DONOR BONE-MARROW; MIXED LYMPHOHEMATOPOIETIC CHIMERISM; HEMATOPOIETIC-CELL TRANSPLANTATION; MINIATURE SWINE; NONHUMAN-PRIMATES; TISSUE ALLOTRANSPLANTATION; FACIAL TRANSPLANTATION; MULTILINEAGE CHIMERISM AB Vascularized composite allotransplantation has become established as a clinical specialty since the first successful hand transplant was performed in 1998. Data now available indicate that hand and face transplants offer patients good functional outcomes and significant improvements in quality of life. Despite the debilitating nature of the injuries treated by such transplants, the defects are generally not life threatening, making it difficult for physicians to recommend life-long immunosuppression that can itself have grave consequences. One potential solution to this dilemma is the induction of immunologic tolerance of the tissue transplants because tolerance would eliminate the need for such immunosuppression. Transplant tolerance may also prevent chronic rejection, a significant source of late graft loss after organ transplantation. Induction of mixed hematopoietic chimerism is a robust approach to establishing such transplant tolerance, which recently led to the first clinical application of a tolerance induction protocol for kidney transplantation. In this manuscript, we review the current status of VCA and of research directed toward bringing a tolerance approach to the VCA field. We also discuss the potential clinical significance of these studies and outline the remaining obstacles to introduction of a tolerance induction protocol to clinical practice in hand or face transplantation. C1 [Leonard, David A.; Cetrulo, Curtis L., Jr.; Sachs, David H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. [Leonard, David A.; McGrouther, Duncan A.] Univ Manchester, Sch Med, Dept Plast & Reconstruct Surg Res, Manchester, Lancs, England. RP Sachs, DH (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E Bldg 149,13th St, Boston, MA 02129 USA. EM david.sachs@tbrc.mgh.harvard.edu NR 54 TC 16 Z9 16 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD FEB 15 PY 2013 VL 95 IS 3 BP 403 EP 409 DI 10.1097/TP.0b013e31826d886d PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 088DI UT WOS:000314813600006 PM 23114532 ER PT J AU Stein, DJ Koenen, KC Friedman, MJ Hill, E McLaughlin, KA Petukhova, M Ruscio, AM Shahly, V Spiegel, D Borges, G Bunting, B Caldas-de-Almeida, JM de Girolamo, G Demyttenaere, K Florescu, S Haro, JM Karam, EG Kovess-Masfety, V Lee, S Matschinger, H Mladenova, M Posada-Villa, J Tachimori, H Viana, MC Kessler, RC AF Stein, Dan J. Koenen, Karestan C. Friedman, Matthew J. Hill, Eric McLaughlin, Katie A. Petukhova, Maria Ruscio, Ayelet Meron Shahly, Victoria Spiegel, David Borges, Guilherme Bunting, Brendan Caldas-de-Almeida, Jose Miguel de Girolamo, Giovanni Demyttenaere, Koen Florescu, Silvia Maria Haro, Josep Karam, Elie G. Kovess-Masfety, Viviane Lee, Sing Matschinger, Herbert Mladenova, Maya Posada-Villa, Jose Tachimori, Hisateru Viana, Maria Carmen Kessler, Ronald C. TI Dissociation in Posttraumatic Stress Disorder: Evidence from the World Mental Health Surveys SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Dissociation; dissociative subtype; DSM-5; epidemiology; nosology; posttraumatic stress disorder; World Mental Health Surveys ID NATIONAL COMORBIDITY SURVEY; ADULT PSYCHIATRIC-DISORDERS; CHILDHOOD ADVERSITIES; LATENT STRUCTURE; COMBAT VETERANS; PTSD; TRAUMA; EXPERIENCES; DSM-5; ABUSE AB Background: Although the proposal for a dissociative subtype of posttraumatic stress disorder (PTSD) in DSM-5 is supported by considerable clinical and neurobiological evidence, this evidence comes mostly from referred samples in Western countries. Cross-national population epidemiologic surveys were analyzed to evaluate generalizability of the subtype in more diverse samples. Methods: Interviews were administered to 25,018 respondents in 16 countries in the World Health Organization World Mental Health Surveys. The Composite International Diagnostic Interview was used to assess 12-month DSM-IV PTSD and other common DSM-IV disorders. Items from a checklist of past-month nonspecific psychological distress were used to assess dissociative symptoms of depersonalization and derealization. Differences between PTSD with and without these dissociative symptoms were examined across a variety of domains, including index trauma characteristics, prior trauma history, childhood adversity, sociodemographic characteristics, psychiatric comorbidity, functional impairment, and treatment seeking. Results: Dissociative symptoms were present in 14.4% of respondents with 12-month DSM-IV/Composite International Diagnostic Interview PTSD and did not differ between high and low/middle income countries. Symptoms of dissociation in PTSD were associated with high counts of re-experiencing symptoms and net of these symptom counts with male sex, childhood onset of PTSD, high exposure to prior (to the onset of PTSD) traumatic events and childhood adversities, prior histories of separation anxiety disorder and specific phobia, severe role impairment, and suicidality. Conclusion: These results provide community epidemiologic data documenting the value of the dissociative subtype in distinguishing a meaningful proportion of severe and impairing cases of PTSD that have distinct correlates across a diverse set of countries. C1 [Stein, Dan J.] Univ Cape Town, Dept Psychiat & Mental Hlth, ZA-7925 Cape Town, South Africa. [Koenen, Karestan C.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. [Friedman, Matthew J.] US Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder, Hanover, NH USA. Geisel Sch Med Dartmouth, Hanover, NH USA. [Hill, Eric; Petukhova, Maria; Shahly, Victoria; Kessler, Ronald C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [McLaughlin, Katie A.] Harvard Univ, Sch Med, Div Gen Pediat, Childrens Hosp Boston, Boston, MA 02115 USA. [Ruscio, Ayelet Meron] Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. [Spiegel, David] Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, Stanford, CA 94305 USA. [Borges, Guilherme] Natl Inst Psychiat Mexico, Div Epidemiol & Psychosocial Res, Dept Epidemiol Res, Mexico City, DF, Mexico. Metropolitan Autonomous Univ, Mexico City, DF, Mexico. [Bunting, Brendan] Univ Ulster, Psychol Res Inst, Coleraine BT52 1SA, Londonderry, North Ireland. [Caldas-de-Almeida, Jose Miguel] Univ Nova Lisboa, Fac Ciencias Med, Chron Dis Res Ctr, P-1200 Lisbon, Portugal. [Caldas-de-Almeida, Jose Miguel] Univ Nova Lisboa, Fac Ciencias Med, Dept Mental Hlth, P-1200 Lisbon, Portugal. [de Girolamo, Giovanni] Ctr S Giovanni Dio Fatebenefratelli, Ist Ricovero & Cura Carattere Sci, Brescia, Italy. [Demyttenaere, Koen] Univ Hosp Gasthuisberg, Dept Psychiat, B-3000 Louvain, Belgium. [Florescu, Silvia] Natl Sch Publ Hlth Management & Profess Dev, Hlth Serv Res & Evaluat Ctr, Bucharest, Romania. [Maria Haro, Josep] Ctr Invest Biomed Red Salud Mental, Barcelona, Spain. [Karam, Elie G.] Balamand Univ, Fac Med, Inst Dev Res Advocacy & Appl Care, Med Inst Neuropsychol Disorders,St George Hosp Un, Beirut, Lebanon. [Kovess-Masfety, Viviane] Univ Paris 05, Equipes Accueil 4069, Paris, France. [Kovess-Masfety, Viviane] Ecole Hautes Etud Sante Publ, Sch Publ Hlth, Dept Epidemiol, Paris, France. [Lee, Sing] Chinese Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China. [Matschinger, Herbert] Univ Leipzig, Inst Social Med Occupat Hlth & Publ Hlth, Publ Hlth Res Unit, D-04109 Leipzig, Germany. [Mladenova, Maya] New Bulgarian Univ, Sofia, Bulgaria. [Posada-Villa, Jose] Pontificia Univ Javeriana, Inst Colombiano Sistema Nervioso, Bogota, Colombia. [Tachimori, Hisateru] Natl Ctr Neurol & Psychiat, Natl Inst Mental Hlth, Tokyo, Japan. [Viana, Maria Carmen] Univ Fed Espirito Santo, Dept Social Med, Vitoria, Brazil. RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM Kessler@hcp.med.harvard.edu RI Lee, Sing/O-2136-2015; Haro, Josep Maria/D-1423-2011; Stein, Dan/A-1752-2008; Faculdade de Ciencias Medicas, Nova Medical School/K-6209-2013; OI Haro, Josep Maria/0000-0002-3984-277X; Stein, Dan/0000-0001-7218-7810; Viana, Maria Carmen/0000-0002-0464-4845; caldas de almeida, jose miguel/0000-0003-1902-6772; Borges, Guilherme/0000-0002-3269-0507; McLaughlin, Katie/0000-0002-1362-2410 FU United States National Institute of Mental Health [R01MH070884]; John D. and Catherine T. MacArthur Foundation; Pfizer Foundation; US Public Health Service [R13-MH066849, R01-MH069864, R01-MH092526, R01-DA016558]; Fogarty International Center [FIRCA R03-TW006481]; Pan American Health Organization; Eli Lilly & Company Foundation; Ortho-McNeil Pharmaceutical, Inc.; GlaxoSmithKline; Bristol-Myers Squibb; Shire Pharmaceuticals; State of Sao Paulo Research Foundation [03/00204-3]; Ministry of Health; National Center for Public Health Protection; Ministry of Social Protection; European Commission [QLG5-1999-01042, SANCO 2004123]; Piedmont Region (Italy); Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III, Spain [FIS 00/0028]; Ministerio de Ciencia y Tecnologia, Spain [SAF 2000-158-CE]; Departament de Salut, Generalitat de Catalunya, Spain, Instituto de Salud Carlos III [CIBER CB06/02/0046, RETICS RD06/0011 REM-TAP]; Japan Ministry of Health, Labour and Welfare [H13-SHOGAI-023, H14-TOKUBETSU-026, H16-KOKORO-013]; Lebanese Ministry of Public Health; World Health Organization (Lebanon), National Institute of Health/Fogarty International Center [R03 TW006481-01]; Astra Zeneca; Eli Lilly; Hikma Pharm; Janssen Cilag; MSD; Novartis; Pfizer; Sanofi Aventis; Servier; National Institute of Psychiatry Ramon de la Fuente [INPRFMDIES 4280]; National Council on Science and Technology [CONACyT-G30544-H]; PanAmerican Health Organization; Health & Social Care Research & Development Division of the Public Health Agency; Champalimaud Foundation; Gulbenkian Foundation; Foundation for Science and Technology; National Institute of Statistics-National Centre for Training in Statistics, Statistics [70]; Ministry of Public Health; Eli Lilly Romania Societate cu Responsabilitate Limitata; National Institute of Mental Health [U01-MH60220]; National Institute of Drug Abuse; Substance Abuse and Mental Health Services Administration; Robert Wood Johnson Foundation [044708]; John W. Alden Trust; Abbott; Eli-Lilly; Jazz Pharmaceuticals; Johnson Johnson; Lundbeck; Orion; Pharmacia; Roche; Solvay; Sumitomo; Takeda; Tikvah; Wyeth; AstraZeneca; EliLilly; Analysis Group Inc.; Eli Lilly Company; EPI-Q; Johnson & Johnson Pharmaceuticals; Ortho-McNeil Janssen Scientific Affairs.; Pfizer Inc.; Sanofi-Aventis Groupe; Shire US, Inc. FX The research reported here was carried out in conjunction with the World Health Organization World Mental Health (WMH) Survey Initiative. These activities were supported by the United States National Institute of Mental Health (R01MH070884), the John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, the US Public Health Service (R13-MH066849, R01-MH069864, R01-MH092526, and R01-DA016558), the Fogarty International Center (FIRCA R03-TW006481), the Pan American Health Organization, the Eli Lilly & Company Foundation, Ortho-McNeil Pharmaceutical, Inc., GlaxoSmithKline, Bristol-Myers Squibb, and Shire Pharmaceuticals. The Sao Paulo Megacity Mental Health Survey is supported by the State of Sao Paulo Research Foundation Thematic Project Grant 03/00204-3. The Bulgarian Epidemiological Study of common mental disorders is supported by the Ministry of Health and the National Center for Public Health Protection. The Beijing, Peoples Republic of China World Mental Health Survey Initiative is supported by the Pfizer Foundation. The Colombian National Study of Mental Health is supported by the Ministry of Social Protection. The European Study of the Epidemiology of Mental Disorders project is funded by the European Commission (Contracts QLG5-1999-01042; SANCO 2004123), the Piedmont Region (Italy), Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III, Spain (FIS 00/0028), Ministerio de Ciencia y Tecnologia, Spain (SAF 2000-158-CE), Departament de Salut, Generalitat de Catalunya, Spain, Instituto de Salud Carlos III (CIBER CB06/02/0046, RETICS RD06/0011 REM-TAP), and other local agencies and by an unrestricted educational grant from GlaxoSmithKline. The World Mental Health Japan Survey is supported by the Grant for Research on Psychiatric and Neurological Diseases and Mental Health (H13-SHOGAI-023, H14-TOKUBETSU-026, H16-KOKORO-013) from the Japan Ministry of Health, Labour and Welfare. The Lebanese National Mental Health Survey (Lebanese Evaluation of the Burden of Ailments and Needs Of the Nation) is supported by the Lebanese Ministry of Public Health, the World Health Organization (Lebanon), National Institute of Health/Fogarty International Center (R03 TW006481-01), anonymous private donations to the Institute for Development, Research, Advocacy & Applied Care, Lebanon, and unrestricted Grants from Astra Zeneca, Eli Lilly, GlaxoSmithKline, Hikma Pharm, Janssen Cilag, MSD, Novartis, Pfizer, Sanofi Aventis, and Servier. The Mexican National Comorbidity Survey is supported by The National Institute of Psychiatry Ramon de la Fuente (INPRFMDIES 4280) and by the National Council on Science and Technology (CONACyT-G30544-H), with supplemental support from the PanAmerican Health Organization. The Northern Ireland Study of Mental Health was funded by the Health & Social Care Research & Development Division of the Public Health Agency. The Portuguese Mental Health Study was carried out by the Department of Mental Health, Faculty of Medical Sciences, NOVA University of Lisbon, with collaboration of the Portuguese Catholic University, and was funded by Champalimaud Foundation, Gulbenkian Foundation, Foundation for Science and Technology and Ministry of Health.; The Romania WMH study projects ''Policies in Mental Health Area'' and ''National Study regarding Mental Health and Services Use'' were carried out by National School of Public Health & Health Services Management (former National Institute for Research & Development in Health), with technical support of Metro Media Transilvania, the National Institute of Statistics-National Centre for Training in Statistics, Statistics Contract 70, Cheyenne Services Societate cu Responsabilitate Limitata, Statistics Netherlands and were funded by Ministry of Public Health (former Ministry of Health) with supplemental support of Eli Lilly Romania Societate cu Responsabilitate Limitata. The US National Comorbidity Survey Replication is supported by the National Institute of Mental Health (U01-MH60220) with supplemental support from the National Institute of Drug Abuse, the Substance Abuse and Mental Health Services Administration, the Robert Wood Johnson Foundation (Grant 044708), and the John W. Alden Trust.; Dr. Stein has received research grants and/or consultancy honoraria from Abbott, Astra Zeneca, Eli-Lilly, GlaxoSmithKline, Jazz Pharmaceuticals, Johnson & Johnson, Lundbeck, Orion, Pfizer, Pharmacia, Roche, Servier, Solvay, Sumitomo, Takeda, Tikvah, and Wyeth. Dr. Demyttenaere has served on advisory boards and speaker bureaus for and has research grants from AstraZeneca, EliLilly, GlaxoSmithKline, Lundbeck, Takeda, and Servier. Dr. Haro has been a consultant for AstraZeneca, Eli Lilly and Co., and Lundbeck. Dr. Kessler has been a consultant for AstraZeneca, Analysis Group, Bristol-Myers Squibb, Cerner-Galt Associates, Eli Lilly & Company, GlaxoSmithKline Inc., HealthCore Inc., Health Dialog, Integrated Benefits Institute, John Snow Inc., Kaiser Permanente, Matria Inc., Mensante, Merck & Co Inc., Ortho-McNeil Janssen Scientific Affairs, Pfizer Inc., Primary Care Network, Research Triangle Institute, Sanofi-Aventis Groupe, Shire US Inc., SRA International Inc., Takeda Global Research & Development, Transcept Pharmaceuticals Inc., and Wyeth-Ayerst; has served on advisory boards for Appliance Computing II, Eli Lilly & Company, Mindsite, Ortho-McNeil Janssen Scientific Affairs, Plus One Health Management, and Wyeth-Ayerst; and has had research support for his epidemiological studies from Analysis Group Inc., Bristol-Myers Squibb, Eli Lilly & Company, EPI-Q, GlaxoSmithKline, Johnson & Johnson Pharmaceuticals, Ortho-McNeil Janssen Scientific Affairs., Pfizer Inc., Sanofi-Aventis Groupe, and Shire US, Inc. Drs. Koenen and Friedman, Mr. Hill, and Drs. McLaughlin, Petukhova, Ruscio, Shahly, Spiegel, Borges, Bunting, Caldas-de-Almeida, de Girolamo, Florescu, Karam, Kovess-Masfety, Lee, Matschinger, Mladenova, Posada-Villa, Tachimori, and Viana report no biomedical financial interests or potential conflicts of interest. NR 60 TC 67 Z9 67 U1 5 U2 60 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD FEB 15 PY 2013 VL 73 IS 4 BP 302 EP 312 DI 10.1016/j.biopsych.2012.08.022 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 085SG UT WOS:000314634000004 PM 23059051 ER PT J AU Graham, BM Milad, MR AF Graham, Bronwyn M. Milad, Mohammed R. TI Blockade of Estrogen by Hormonal Contraceptives Impairs Fear Extinction in Female Rats and Women SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Anxiety; estradiol; estrous cycle; fear conditioning; gonadal hormones; menstrual cycle ID PREFRONTAL CORTEX; RHESUS-MONKEYS; RECEPTOR-BETA; DISORDERS; ESTRADIOL; PROGESTERONE; MECHANISMS; MODULATE; AMYGDALA; STRESS AB Background: Fear extinction is a laboratory model of fear inhibition and is the basis of exposure therapy for anxiety disorders. Emerging evidence from naturally cycling female rodents and women indicates that estrogens are necessary to the consolidation of fear extinction. Hormonal contraceptives (HCs) inhibit estrogen production; yet, their effects on fear extinction are unknown. Methods: We used a cross-species translational approach to investigate the impact of HCs and estradiol supplementation on fear extinction in healthy women (n = 76) and female rats (n = 140). Results: Women using HCs exhibited significantly poorer extinction recall compared with naturally cycling women. The extinction impairment was also apparent in HC-treated female rats and was associated with reduced serum estradiol levels. The impairment could be rescued in HC-treated rats either by terminating HC treatment after fear learning or by systemic injection of estrogen-receptor agonists before fear extinction, all of which restored serum estradiol levels. Finally, a single administration of estradiol to naturally cycling women significantly enhanced their ability to recall extinction memories. Conclusions: Together, these findings suggest that HCs may impact women's ability to inhibit fear but that this impairment is not permanent and could potentially be alleviated with estrogen treatment. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Milad, MR (reprint author), Massachusetts Gen Hosp, CNY 2614,Bldg 149,13th St, Charlestown, MA 02129 USA. EM milad@nmr.mgh.harvard.edu FU National Institute of Mental Health [K01MH080346, 1R01MH097880-01]; Department of Psychiatry at Massachusetts General Hospital; American Australian Association; Harvard Clinical and Translational Science Center Grant from the National Center for Research Resources [1UL1 RR025758-01] FX This work was supported by National Institute of Mental Health Grants K01MH080346 and 1R01MH097880-01 and institutional funds from the Department of Psychiatry at Massachusetts General Hospital to MRM and a Neurological Fellowship from the American Australian Association to BMG. The project was also supported by Harvard Clinical and Translational Science Center Grant (1UL1 RR025758-01) from the National Center for Research Resources. NR 33 TC 65 Z9 65 U1 0 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD FEB 15 PY 2013 VL 73 IS 4 BP 371 EP 378 DI 10.1016/j.biopsych.2012.09.018 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 085SG UT WOS:000314634000012 PM 23158459 ER PT J AU Freedman, RA Hughes, ME Ottesen, RA Weeks, JC He, YL Wong, YN Theriault, R Keating, NL AF Freedman, Rachel A. Hughes, Melissa E. Ottesen, Rebecca A. Weeks, Jane C. He, Yulei Wong, Yu-Ning Theriault, Richard Keating, Nancy L. TI Use of adjuvant trastuzumab in women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer by race/ethnicity and education within the National Comprehensive Cancer Network SO CANCER LA English DT Article DE breast cancer; disparities; trastuzumab; race; socioeconomic status ID III COLON-CANCER; OLDER WOMEN; SOCIOECONOMIC-STATUS; MEDICARE PATIENTS; CHEMOTHERAPY; THERAPY; SURVIVAL; DISPARITIES; OUTCOMES; CARDIOTOXICITY AB BACKGROUND. Trastuzumab for human epidermal growth factor receptor 2 (HER2)-positive breast cancer is highly efficacious yet costly and time-intensive, and few data are available about its use. The authors of this report examined receipt and completion of adjuvant trastuzumab by race/ethnicity and education for women with HER2-positive disease. METHODS. The National Comprehensive Cancer Network Breast Cancer Outcomes Database was used to identify 1109 women who were diagnosed with stage I through III, HER2-positive breast cancer during September 2005 through December 2008 and were followed for 1 year. The authors used multivariable logistic regression to assess the association of race/ethnicity and education with the receipt of trastuzumab and, among those women who initiated trastuzumab, with the completion of > 270 days of therapy. RESULTS. The cohort was 75% white, 8% black, and 9% Hispanic; and 20% of women had attained a high school degree or less. Most women (83%) received trastuzumab, and no significant differences were observed according to race/ethnicity or socioeconomic status. Among the women who initiated trastuzumab, 73% of black women versus 87% of white women (P = .007) and 70% of women with less than a high school education versus 90% of women with a college degree completed > 270 days of therapy (P = .006). In adjusted analyses, black women (vs white women) and women without a high school degree (vs those with a college degree) had lower odds of completing therapy (black women: odds ratio, 0.45; 95% confidence interval, 0.27-074; white women: odds ratio, 0.27, 95% confidence interval, 0.14-0.51). CONCLUSIONS. Differences in completing trastuzumab therapy were observed according to race and educational attainment among women who received treatment at National Comprehensive Cancer Network centers. Efforts to assure the appropriate use of trastuzumab and to understand treatment barriers are needed and may lead to improved outcomes. The authors report differences in the rate at which patients complete treatment with trastuzumab according to race and education among women who receive treatment at National Comprehensive Cancer Network centers. Efforts to assure the appropriate use of trastuzumab and to understand treatment barriers are needed and may lead to improved outcomes. Cancer 2013. (c) 2012 American Cancer Society. C1 [Freedman, Rachel A.; Hughes, Melissa E.; Weeks, Jane C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Hughes, Melissa E.; Weeks, Jane C.] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02215 USA. [Ottesen, Rebecca A.] City Hope Natl Med Ctr, Div Biostat, Duarte, CA 91010 USA. [He, Yulei; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Wong, Yu-Ning] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Theriault, Richard] Univ Texas MD Anderson Canc Ctr, Dept Med Oncol, Houston, TX 77030 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. RP Freedman, RA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM rafreedman@partners.org FU Susan G. Komen for the Cure Foundation; National Cancer Institute [P50 CA89393] FX This work was funded in part by the Susan G. Komen for the Cure Foundation and by grant P50 CA89393 from the National Cancer Institute to Dana-Farber Cancer Institute. NR 39 TC 22 Z9 22 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD FEB 15 PY 2013 VL 119 IS 4 BP 839 EP 846 DI 10.1002/cncr.27831 PG 8 WC Oncology SC Oncology GA 086BC UT WOS:000314657000020 PM 23011924 ER PT J AU Zafar, SY Malin, JL Grambow, SC Abbott, DH Kolimaga, JT Zullig, LL Weeks, JC Ayanian, JZ Kahn, KL Ganz, PA Catalano, PJ West, DW Provenzale, D AF Zafar, S. Yousuf Malin, Jennifer L. Grambow, Steven C. Abbott, David H. Kolimaga, Jane T. Zullig, Leah L. Weeks, Jane C. Ayanian, John Z. Kahn, Katherine L. Ganz, Patricia A. Catalano, Paul J. West, Dee W. Provenzale, Dawn CA Canc Care Outcomes Res & Surveilla TI Chemotherapy Use and Patient Treatment Preferences in Advanced Colorectal Cancer A Prospective Cohort Study SO CANCER LA English DT Article DE colorectal cancer; decision making; patient preference; cohort studies; quality of health care ID III COLON-CANCER; CARE OUTCOMES RESEARCH; ADJUVANT CHEMOTHERAPY; DECISION-MAKING; BREAST-CANCER; RANDOMIZED-TRIAL; THERAPY; AGE; COMORBIDITY; SURGERY AB BACKGROUND: The objective of this study was to determine how patient preferences guide the course of palliative chemotherapy for advanced colorectal cancer. METHODS: Eligible patients with metastatic colorectal cancer (mCRC) were enrolled nationwide in a prospective, population-based cohort study. Data were obtained through medical record abstraction and patient surveys. Logistic regression analysis was used to evaluate patient characteristics associated with visiting medical oncology and receiving chemotherapy and patient characteristics, beliefs, and preferences associated with receiving >1 line of chemotherapy and receiving combination chemotherapy. RESULTS: Among 702 patients with mCRC, 91% consulted a medical oncologist; and among those, 82% received chemotherapy. Patients ages 65 to 75 years and aged 75 years were less likely to visit an oncologist, as were patients who were too sick to complete their own survey. In adjusted analyses, patients aged 75 years who had moderate or severe comorbidity were less likely to receive chemotherapy, as were patients who were too sick to complete their own survey. Patients received chemotherapy even if they believed that chemotherapy would not extend their life (90%) or that chemotherapy would not likely help with cancer-related problems (89%), or patients preferred treatment focusing on comfort even if it meant not living as long (90%). Older patients were less likely to receive combination first-line therapy. Patient preferences and beliefs were not associated with receipt of >1 line of chemotherapy or combination chemotherapy. CONCLUSIONS: The majority of patients received chemotherapy even if they expressed negative or marginal preferences or beliefs regarding chemotherapy. Patient preferences and beliefs were not associated with the intensity or number of chemotherapy regimens. Cancer 2013. (c) 2012 American Cancer Society. C1 [Zafar, S. Yousuf] Duke Canc Inst, Durham, NC 27710 USA. [Zafar, S. Yousuf; Grambow, Steven C.; Abbott, David H.; Kolimaga, Jane T.; Zullig, Leah L.; Provenzale, Dawn] Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Malin, Jennifer L.] Greater Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. [Malin, Jennifer L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Med Oncol, Los Angeles, CA 90095 USA. [Grambow, Steven C.] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. [Kolimaga, Jane T.] Duke Univ, Med Ctr, Dept Med, Div Gastroenterol, Durham, NC 27710 USA. [Zullig, Leah L.] Univ N Carolina, Dept Hlth Policy & Management, Chapel Hill, NC USA. [Weeks, Jane C.] Dana Farber Canc Inst, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Ayanian, John Z.] Harvard Univ, Dept Hlth Care Policy, Sch Med, Cambridge, MA 02138 USA. [Ayanian, John Z.] Brigham & Womens Hosp Boston, Div Gen Med, Boston, MA USA. [Kahn, Katherine L.] RAND Corp, Santa Monica, CA USA. [Kahn, Katherine L.] Univ Calif Los Angeles, Dept Med, Div Gen Internal Med, Los Angeles, CA 90024 USA. [Kahn, Katherine L.] Univ Calif Los Angeles, Dept Med, Div Hlth Serv Res, Los Angeles, CA 90024 USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Catalano, Paul J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Catalano, Paul J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [West, Dee W.] Canc Prevent Inst Calif, Fremont, CA USA. [West, Dee W.] Stanford Sch Med, Stanford, CA USA. RP Zafar, SY (reprint author), Duke Canc Inst, DUMC 3505, Durham, NC 27710 USA. EM yousuf.zafar@duke.edu RI Grambow, Steven/E-1422-2015; OI Grambow, Steven/0000-0001-6037-3253; Zafar, S. Yousuf/0000-0002-9039-5258 FU American Cancer Society; Duke Cancer Institute; National Cancer Institute [5R25CA116339, U01 CA093344, U01 CA093332]; Harvard Medical School/Northern California Cancer Center [U01 CA093324]; RAND/UCLA [U01 CA093348]; University of Alabama at Birmingham [U01 CA093329]; University of Iowa [U01 CA093339]; Agency for Healthcare Research Quality [03-438MO-03]; Department of Veterans Affairs [HSRDCRS 02-164] FX Dr. Zafar is supported by an American Cancer Society Mentored Research Scholar Grant and the Duke Cancer Institute Cancer Control Pilot Award. Dr. Zullig is supported by the National Cancer Institute (5R25CA116339). This work and the CanCORS Consortium are supported by grants from the National Cancer Institute to the Statistical Coordinating Center (U01 CA093344) and the National Cancer Institute-supported Primary Data Collection and Research Centers (Dana-Farber Cancer Institute/Cancer Research Network [U01 CA093332]; Harvard Medical School/Northern California Cancer Center [U01 CA093324]; RAND/UCLA [U01 CA093348]; University of Alabama at Birmingham [U01 CA093329]; the University of Iowa [U01 CA093339]; and the University ofNorth Carolina [U01 CA093326]); the Agency for Healthcare Research Quality (03-438MO-03); and by a Department of Veterans Affairs grant to the Durham Veterans Affairs Medical Center (HSRDCRS 02-164). NR 33 TC 20 Z9 20 U1 1 U2 20 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 FEB 15 PY 2013 VL 119 IS 4 BP 854 EP 862 DI 10.1002/cncr.27815 PG 9 WC Oncology SC Oncology GA 086BC UT WOS:000314657000022 PM 22972673 ER PT J AU Morgans, AK Smith, MR O'Malley, AJ Keating, NL AF Morgans, Alicia K. Smith, Matthew R. O'Malley, A. James Keating, Nancy L. TI Bone density testing among prostate cancer survivors treated with androgen-deprivation therapy SO CANCER LA English DT Article DE prostate cancer; cancer survivorship; male osteoporosis; androgen deprivation therapy; side effects of treatment ID MINERAL DENSITY; RACIAL-DIFFERENCES; HORMONE AGONISTS; OLDER MEN; OSTEOPOROSIS; FRACTURE; CARCINOMA; RISK; MASS; MORTALITY AB BACKGROUND. Androgen-deprivation therapy (ADT) causes bone loss and fractures. Guidelines recommend bone density testing before and during ADT to characterize fracture risk. The authors of the current report assessed bone density testing among men who received ADT for 1 year. METHODS. Surveillance, Epidemiology, and End Results/Medicare data were used to identify 28,960 men aged > 65 years with local/regional prostate cancer diagnosed from 2001 to 2007 who were followed through 2009 and who received 1 year of continuous ADT. Bone density testing was documented in the 18-month period beginning 6 months before ADT initiation. Logistic regression was used to identify the factors associated with bone density testing. RESULTS. Among men who received 1 year of ADT, 10.2% had a bone density assessment from 6 months before starting ADT through 1 year after. Bone density testing increased over time (14.5% of men who initiated ADT in 2007-2008 vs 6% of men who initiated ADT in 2001-2002; odds ratio for 2007-2008 vs 2001-2002, 2.29; 95% confidence interval, 1.83-2.85). Less bone density testing was observed among men aged 85 years versus men ages 66 to 69 years (odds ratio, 0.76; 95% confidence interval, 0.65-0.89), among black men versus white men (odds ratio, 0.72; 95% confidence interval, 0.61-0.86), and among men in areas with lower educational attainment (P < .001). Men who visited a medical oncologist and/or a primary care provider in addition to a urologist had higher odds of testing than men who only consulted a urologist (P < .001). CONCLUSIONS. Few men who received ADT for prostate cancer underwent bone density testing, particularly older men, black men, and those living in areas with low educational attainment. Visiting a medical oncologist was associated with increased odds of testing. Interventions are needed to increase bone density testing among men who receive long-term ADT. Data on bone density testing for nonmilitary populations of prostate cancer survivors in the United States who have received long-term androgen-deprivation therapy (ADT) have not been published. The current analysis of Surveillance, Epidemiology, and End Results/Medicare data suggests that few prostate cancer survivors who receive long-term ADT undergo bone density testing; and several key populations, including African Americans and older men, have considerably lower rates of bone density screening. Cancer 2013. (c) 2012 American Cancer Society. C1 [Morgans, Alicia K.; Smith, Matthew R.] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. [O'Malley, A. James; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02115 USA. RP 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 Prostate Cancer Foundation; California Department of Public Health [103885]; National Cancer Institute [N01-PC-35136, N01-PC-35139, N02-PC-15105]; Centers for Disease Control and Prevention's National Program of Cancer Registries [U55/CCR921930-02] FX This study was funded by the Prostate Cancer Foundation.; The collection of the California cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute's Surveillance, Epidemiology and End Results Program under contract N01-PC-35136 awarded to the Northern California Cancer Center, contract N01-PC-35139 awarded to the University of Southern California, and contract N02-PC-15105 awarded to the Public Health Institute; and the Centers for Disease Control and Prevention's National Program of Cancer Registries, under agreement #U55/CCR921930-02 awarded to the Public Health Institute. The ideas and opinions expressed herein are those of the author(s) and endorsement by the State of California, Department of Public Health the National Cancer Institute, and the Centers for Disease Control and Prevention or their Contractors and Subcontractors is not intended nor should be inferred. NR 35 TC 12 Z9 12 U1 1 U2 8 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 FEB 15 PY 2013 VL 119 IS 4 BP 863 EP 870 DI 10.1002/cncr.27830 PG 8 WC Oncology SC Oncology GA 086BC UT WOS:000314657000023 PM 23065626 ER PT J AU Friedrich, P Ortiz, R Strait, K Fuentes, S Gamboa, Y Arambu, I Ah-Chu-Sanchez, M London, W Rodriguez-Galindo, C Antillon-Klussmann, F Baez, F AF Friedrich, Paola Ortiz, Roberta Strait, Kelly Fuentes, Soad Gamboa, Yessica Arambu, Ingrid Ah-Chu-Sanchez, Maria London, Wendy Rodriguez-Galindo, Carlos Antillon-Klussmann, Federico Baez, Fulgencio CA Cent Amer Assoc Pediat Hemtologist TI Pediatric Sarcoma in Central America Outcomes, Challenges, and Plans for Improvement SO CANCER LA English DT Article DE pediatric sarcoma; developing countries; treatment abandonment; outcomes research; international outreach ID ACUTE LYMPHOBLASTIC-LEUKEMIA; SOFT-TISSUE SARCOMAS; DEVELOPING-COUNTRY; INCOME COUNTRIES; EL SALVADOR; CANCER; CHILDREN; ABANDONMENT; THERAPY; EPIDEMIOLOGY AB BACKGROUND: Children with cancer in middle-income countries have inferior outcomes compared with similar children in high-income countries. The magnitude and drivers of this survival gap are not well understood. In the current report, the authors sought to describe patterns of clinical presentation, magnitude of treatment abandonment, and survival in children with sarcoma in Central America. METHODS: A retrospective review was conducted of hospital-based registries from national pediatric oncology referral centers. Patients with newly diagnosed osteosarcoma, Ewing sarcoma, rhabdomyosarcoma (RMS), and soft tissue sarcoma (STS) between January 1, 2000 and December 31, 2009 were included. Survival analyses were performed first using standard definitions of overall survival (OS) and event-free survival (EFS) and then with abandonment included as an event (abandonment-sensitive OS and abandonment-sensitive EFS). RESULTS: In total, 785 new cases of pediatric sarcoma were reported (264 diagnoses of osteosarcoma, 175 diagnoses of Ewing sarcoma, 240 diagnoses of RMS, and 106 diagnoses of STS). The rate of metastatic disease at presentation was high (osteosarcoma, 38%; Ewing sarcoma, 39%; RMS, 29%; and STS, 21%). The treatment abandonment rate also was high, particularly among patients with extremity bone sarcomas (osteosarcoma, 30%; Ewing sarcoma, 15%; RMS, 25%; and STS, 15%). Of 559 patients who experienced a first event, 59% had either recurrent or progressive disease. The 4-year OS rate (+/- standard error) was 40% +/- 3%, and the EFS rate was 30% +/- 2%; however, these rates decreased further to 31% +/- 2% and 24% +/- 2%, respectively, when abandonment was taken into account. CONCLUSIONS: The current results indicated that high rates of metastases and treatment abandonment and difficulty with upfront treatment effectiveness are important contributors to the poor survival of children with pediatric sarcomas in Central America. Initiatives for early diagnosis, psychosocial support, quality improvement, and multidisciplinary care are warranted to improve outcomes. Cancer 2013. (c) 2012 American Cancer Society. C1 [Friedrich, Paola; Strait, Kelly; London, Wendy; Rodriguez-Galindo, Carlos] Dana Farber Childrens Hosp Canc Ctr, Dept Pediat Hematol Oncol, Boston, MA USA. [Ortiz, Roberta; Baez, Fulgencio] La Mascota Childrens Hosp, Dept Pediat Oncol, Managua, Nicaragua. [Fuentes, Soad; Antillon-Klussmann, Federico] Benjamin Bloom Natl Childrens Hosp, Dept Pediat Oncol, San Salvador, El Salvador. [Gamboa, Yessica] Natl Childrens Hosp, Dept Pediat Oncol, San Jose, Costa Rica. [Arambu, Ingrid] Maternal & Child Hosp, Dept Pediat Oncol, Tegucigalpa, Honduras. [Ah-Chu-Sanchez, Maria] Childrens Hosp, Dept Pediat Oncol, Panama City, Panama. Dept Pediat Oncol, Natl Pediat Oncol Unit, Guatemala City, Guatemala. RP Friedrich, P (reprint author), Dana Farber Canc Inst, 450 Brookline Ave D322A, Boston, MA 02115 USA. EM paola_friedrich-medina@dfci.harvard.edu OI Friedrich, Paola/0000-0002-5265-3113 FU Dana-Farber/Children's Hospital Cancer Center Global Health Initiative; St. Jude Children's Research Hospital International Outreach Program; National Institutes of Health [T32 HL 7574, R25 CA092203] FX We gratefully acknowledge support from the Dana-Farber/Children's Hospital Cancer Center Global Health Initiative and the St. Jude Children's Research Hospital International Outreach Program, and we thank the Central American Association of Pediatric Hematologists and Oncologists data managers and clinical staff for their inspiring work.; Dr. Friedrich was supported by Pathophysiology of Human Blood Cells (T32 HL 7574) and Program in Cancer Outcomes Research Training (R25 CA092203), both National Institutes of Health training grants. NR 36 TC 11 Z9 11 U1 0 U2 13 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 FEB 15 PY 2013 VL 119 IS 4 BP 871 EP 879 DI 10.1002/cncr.27816 PG 9 WC Oncology SC Oncology GA 086BC UT WOS:000314657000024 PM 22972687 ER PT J AU Ahearn, EP Chen, P Hertzberg, M Cornette, M Suvalsky, L Cooley-Olson, D Swanlund, J Eickhoff, J Becker, T Krahn, D AF Ahearn, Eileen P. Chen, Peijun Hertzberg, Michael Cornette, Michelle Suvalsky, Lori Cooley-Olson, Deanna Swanlund, Jamie Eickhoff, Jens Becker, Tara Krahn, Dean TI Suicide attempts in veterans with bipolar disorder during treatment with lithium, divalproex, and atypical antipsychotics SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Bipolar; Suicide; Atypical antipsychotics ID SCHIZOPHRENIA-PATIENTS; CLOZAPINE TREATMENT; BEHAVIOR; TRIAL; RISK; PHARMACOTHERAPY; HALOPERIDOL; RISPERIDONE; AGGRESSION; PREVENTION AB Suicide attempt rates were assessed in 1306 subjects in this 6 year retrospective study of Bipolar disorder. Participants were Veterans from 5 different Veterans Administration Hospitals who met criteria for bipolar type 1 or 2 and who had at least one prescription for lithium or divalproex or both during the study period. This study focused on the impact of atypical antipsychotics on the suicide attempt rate when used in addition to or in place of lithium or divalproex. Medication exposure was calculated using computerized pharmacy records. Suicide attempts were established through chart review including emergency room records, inpatient records, and outpatient records. There were a total of 117 suicide attempts and 2 suicide completions during the study period. Most attempts (59%) occurred when patients were on no medications. Nearly 90% of subjects spent an average of 45 months during the 6 year period on none of the aforementioned medications. The lowest percentage of suicide attempts (15%) occurred while on lithium, 21% while on divalproex and 24% while on atypical antipsychotics. When total months of exposure were taken into account, the lowest attempt rate occurred on lithium plus divalproex (6.3 attempts per 10,000 months of exposure), followed by divalproex alone (7.0 attempts/10,000 months of exposure), and lithium alone (7.7 attempts per 10,000 months of exposure). Patients on atypical antipsychotics alone had an attempt rate of 26.1 attempts per 10,000 months of exposure. In this study, lithium and divalproex provided protection against suicide attempts. Results need to be replicated in future prospective studies and clearly strategies for improving medication compliance among veterans are warranted. Published by Elsevier B.V. C1 [Ahearn, Eileen P.; Cooley-Olson, Deanna; Swanlund, Jamie; Krahn, Dean] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. [Ahearn, Eileen P.; Eickhoff, Jens; Becker, Tara; Krahn, Dean] Univ Wisconsin, Madison, WI USA. [Chen, Peijun] Louis Stokes Cleveland VA Med Ctr, Cleveland, OH USA. [Chen, Peijun] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Hertzberg, Michael] Durham VA Med Ctr, Durham, NC USA. [Hertzberg, Michael] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Cornette, Michelle] Med Coll Wisconsin, Milwaukee, WI USA. [Suvalsky, Lori] Minneapolis VA Med Ctr, Minneapolis, MN USA. RP Ahearn, EP (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace, Madison, WI 53705 USA. EM Eileen.Ahearn@va.gov FU American Foundation for Suicide Prevention FX This work was supported by a grant from the American Foundation for Suicide Prevention. The Foundation had no direct involvement in the study other than to provide funding. NR 30 TC 9 Z9 11 U1 1 U2 21 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD FEB 15 PY 2013 VL 145 IS 1 BP 77 EP 82 DI 10.1016/j.jad.2012.07.015 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 078IK UT WOS:000314091800011 PM 22871534 ER PT J AU Harkness, JH Hitzemann, RJ Edmunds, S Phillips, TJ AF Harkness, John H. Hitzemann, Robert J. Edmunds, Stephanie Phillips, Tamara J. TI Effects of sodium butyrate on methamphetamine-sensitized locomotor activity SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Sensitization; Psychostimulant; Histone acetylation; Epigenetics; Addiction ID INDUCED BEHAVIORAL SENSITIZATION; HISTONE DEACETYLASE INHIBITORS; INCENTIVE-SENSITIZATION; GENE-EXPRESSION; INBRED MICE; DELTA-FOSB; ADDICTION; COCAINE; MECHANISMS; STIMULATION AB Neuroadaptations associated with behavioral sensitization induced by repeated exposure to methamphetamine (MA) appear to be involved in compulsive drug pursuit and use. Increased histone acetylation, an epigenetic effect resulting in altered gene expression, may promote sensitized responses to psychostimulants. The role of histone acetylation in the expression and acquisition of MA-induced locomotor sensitization was examined by measuring the effect of histone deacetylase inhibition by sodium butyrate (NaB). For the effect on expression, mice were treated repeatedly with MA (10 days of 2 mg/kg MA) or saline (10 days), and then vehicle or NaB (630 mg/kg, intraperitoneally) was administered 30 min prior to MA challenge and locomotor response was measured. NaB treatment increased the locomotor response to MA in both acutely MA treated and sensitized animals. For acquisition, NaB was administered 30 min prior to each MA exposure (10 days of 1 or 2 mg/kg), but not prior to the MA challenge test. Treatment with NaB during the sensitization acquisition period significantly increased locomotor activation by MA in sensitized mice only. NaB alone did not significantly alter locomotor activity. Acute NaB or MA, but not the combination, increased striatal acetylation at histone H4. Repeated treatment with MA, but not NaB or MA plus NaB, increased striatal acetylation at histone H3. Although increased histone acetylation may alter the expression of genes involved in acute locomotor response to MA and in the acquisition of MA-induced sensitization, results for acetylation at H3 and H4 showed little correspondence with behavior. Published by Elsevier B.V. C1 [Harkness, John H.; Hitzemann, Robert J.; Edmunds, Stephanie; Phillips, Tamara J.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. [Harkness, John H.; Hitzemann, Robert J.; Phillips, Tamara J.] Oregon Hlth & Sci Univ, Methamphetamine Abuse Res Ctr, Portland, OR 97239 USA. [Hitzemann, Robert J.; Edmunds, Stephanie; Phillips, Tamara J.] Portland VA Med Ctr, Portland, OR 97239 USA. RP Phillips, TJ (reprint author), VA Med Ctr, R&D32,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM harknesj@ohsu.edu; hitzeman@ohsu.edu; edmundss@ohsu.edu; phillipt@ohsu.edu FU Department of Veterans Affairs, and NIDA/NIH [T32DA07262, P50DA018165] FX This work was supported by the Department of Veterans Affairs, and NIDA/NIH grants T32DA07262 and P50DA018165. Thank you to James Stafford for helpful discussions regarding the IHC procedure and interpretation. NR 43 TC 6 Z9 6 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 EI 1872-7549 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD FEB 15 PY 2013 VL 239 BP 139 EP 147 DI 10.1016/j.bbr.2012.10.046 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 079CA UT WOS:000314146600017 PM 23137698 ER PT J AU Jacobson, KR Theron, D Kendall, EA Franke, MF Barnard, M van Helden, PD Victor, TC Streicher, EM Murray, MB Warren, RM AF Jacobson, Karen R. Theron, Danie Kendall, Emily A. Franke, Molly F. Barnard, Marinus van Helden, Paul D. Victor, Tommie C. Streicher, Elizabeth M. Murray, Megan B. Warren, Robin M. TI Implementation of GenoType MTBDRplus Reduces Time to Multidrug-Resistant Tuberculosis Therapy Initiation in South Africa SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE multidrug-resistant tuberculosis; MTBDRplus; rapid molecular diagnostic ID TREATMENT OUTCOMES; DIAGNOSIS; METAANALYSIS; TB AB Background. Diagnosis of drug resistance and timely initiation of multidrug-resistant (MDR) tuberculosis therapy are essential to reduce transmission and improve patient outcomes. We sought to determine whether implementation of the rapid MTBDRplus diagnostic shortened the time from specimen collection to patient MDR tuberculosis therapy initiation. Methods. We conducted a retrospective cohort analysis of 197 MDR tuberculosis patients treated at Brewels-kloof, a rural tuberculosis hospital in Western Cape Province, South Africa, between 2007 and 2011. Results. Eighty-nine patients (45%) were tested using conventional liquid culture and drug susceptibility testing (DST) on solid medium and 108 (55%) were tested using the MTBDRplus assay after positive acid-fast bacilli or culture. Median time from sample taken to therapy initiation was reduced from 80 days (interquartile range [IQR] 62-100) for conventional DST to 55 days (IQR 37.5-78) with the MTBDRplus. Although the laboratory processing time declined significantly, operational delays persisted both in the laboratory and the clinical infrastructure for getting patients started on treatment. In multivariate analysis, patients tested using the MTBDRplus test had a reduced risk of starting treatment 60 days or more after sputum collection of 0.52 (P < .0001) compared with patients tested with culture-based DST, after adjustment for smear status and site of disease. Conclusions. Use of MTBDRplus significantly reduced time to MDR tuberculosis treatment initiation. However, DST reporting to clinics was delayed by more than 1 week due, in part, to laboratory operational delays, including dependence on smear and culture positivity prior to MTBDRplus performance. In addition, once MDR tuberculosis was reported, delays in contacting patients and initiating therapy require improvements in clinical infrastructure. C1 [Jacobson, Karen R.] Harvard Univ, Massachusetts Gen Hosp, Div Infect Dis, Sch Publ Hlth, Boston, MA 02114 USA. [Kendall, Emily A.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Sch Publ Hlth, Boston, MA 02114 USA. [Franke, Molly F.; Murray, Megan B.] Harvard Univ, Sch Publ Hlth, Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02114 USA. [Murray, Megan B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02114 USA. [Jacobson, Karen R.; Barnard, Marinus; van Helden, Paul D.; Victor, Tommie C.; Streicher, Elizabeth M.; Warren, Robin M.] Univ Stellenbosch, Ctr Excellence Biomed TB Res,Dept Sci & Technol, Div Mol Biol & Human Genet,Fac Med & Hlth Sci, Natl Res Fdn,Med Res Council,Ctr Mol & Cellular B, Cape Town, South Africa. [Barnard, Marinus] Natl Hlth Lab Serv, Cape Town, South Africa. [Theron, Danie] Brewelskloof Hosp, Worcester, South Africa. RP Jacobson, KR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Infect Dis, Sch Publ Hlth, 55 Fruit St,GRJ5-5, Boston, MA 02114 USA. EM krjacobson@partners.org OI Kendall, Emily/0000-0002-0083-422X; Streicher, Elizabeth/0000-0003-3901-1981; Jacobson, Karen/0000-0003-4239-3685 FU Burroughs Wellcome Fund/American Society of Tropical Medicine and Hygiene Postdoctoral Fellowship in Tropical Infectious Diseases; National Institutes of Health/Fogarty International Center [1K01 TW009213]; Partner Center of Excellence Travel Grant FX This work was supported by a Burroughs Wellcome Fund/American Society of Tropical Medicine and Hygiene Postdoctoral Fellowship in Tropical Infectious Diseases (K. R. J.), the National Institutes of Health/Fogarty International Center (1K01 TW009213; K. R. J.), and a Partner Center of Excellence Travel Grant (E. A. K.). NR 19 TC 34 Z9 34 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 15 PY 2013 VL 56 IS 4 BP 503 EP 508 DI 10.1093/cid/cis920 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 077UR UT WOS:000314054400006 PM 23090928 ER PT J AU Riley, LE Beigi, RH AF Riley, Laura E. Beigi, Richard H. TI Maternal Pertussis Vaccination: Protecting Neonates From Infection SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material C1 [Riley, Laura E.] Harvard Univ, Massachusetts Gen Hosp, Dept Obstet Gynecol & Reprod Biol, Sch Med, Boston, MA 02214 USA. [Beigi, Richard H.] Univ Pittsburgh, Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci, Div Reprod Infect Dis,Med Ctr, Pittsburgh, PA 15213 USA. [Beigi, Richard H.] Univ Pittsburgh, Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci, Div Obstet Specialties,Med Ctr, Pittsburgh, PA 15213 USA. RP Riley, LE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Obstet Gynecol & Reprod Biol, Sch Med, 32 Fruit St, Boston, MA 02214 USA. EM lriley@partners.org NR 9 TC 0 Z9 0 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 15 PY 2013 VL 56 IS 4 BP 545 EP 547 DI 10.1093/cid/cis924 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 077UR UT WOS:000314054400013 PM 23097590 ER PT J AU Levison, JH Wood, R Scott, CA Ciaranello, AL Martinson, NA Rusu, C Losina, E Freedberg, KA Walensky, RP AF Levison, Julie H. Wood, Robin Scott, Callie A. Ciaranello, Andrea L. Martinson, Neil A. Rusu, Corina Losina, Elena Freedberg, Kenneth A. Walensky, Rochelle P. TI The Clinical and Economic Impact of Genotype Testing at First-line Antiretroviral Therapy Failure for HIV-Infected Patients in South Africa SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE HIV; resistance testing; antiretroviral treatment failure; resource-limited settings ID COST-EFFECTIVENESS ANALYSIS; RESOURCE-LIMITED SETTINGS; DRUG-RESISTANCE; VIROLOGICAL FAILURE; RECOMMENDATIONS; EMTRICITABINE; EFAVIRENZ; MORTALITY; HIV/AIDS; REGIMENS AB Background. In resource-limited settings, genotype testing at virologic failure on first-line antiretroviral therapy (ART) may identify patients with wild-type (WT) virus. After adherence counseling, these patients may safely and effectively continue first-line ART, thereby delaying more expensive second-line ART. Methods. We used the Cost-Effectiveness of Preventing AIDS Complications International model of human immunodeficiency virus (HIV) disease to simulate a South African cohort of HIV-infected adults at first-line ART failure. Two strategies were examined: no genotype vs genotype, assuming availability of protease inhibitor-based second-line ART. Model inputs at first-line ART failure were mean age 38 years, mean CD4 173/mu L, and WT virus prevalence 20%; genotype cost was $300 per test and delay to results, 3 months. Outcomes included life expectancy, per-person costs (2010 US dollars), and incremental cost-effectiveness ratios (dollars per years of life saved [YLS]). Results. No genotype had a projected life expectancy of 106.1 months, which with genotype increased to 108.3 months. Per-person discounted lifetime costs were $16 360 and $16 540, respectively. Compared to no genotype, genotype was very cost-effective, by international guidance, at $900/YLS. The cost-effectiveness of genotype was sensitive to prevalence of WT virus (very cost-effective when prevalence >= 12%), CD4 at first-line ART failure, and ART efficacy. Genotype-associated delays in care >= 5 months decreased survival and made no genotype the preferred strategy. When the test cost was <$100, genotype became cost-saving. Conclusions. Genotype resistance testing at first-line ART failure is very cost-effective in South Africa. The cost-effectiveness of this strategy will depend on prevalence of WT virus and timely response to genotype results. C1 [Levison, Julie H.; Ciaranello, Andrea L.; Freedberg, Kenneth A.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Scott, Callie A.; Rusu, Corina; Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Levison, Julie H.; Ciaranello, Andrea L.; Rusu, Corina; Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Wood, Robin] Univ Cape Town, Desmond Tutu HIV Ctr, Inst Infect Dis & Mol Med, Dept Med, Johannesburg, South Africa. [Martinson, Neil A.] Univ Witwatersrand, Perinatal HIV Res Unit, Johannesburg, South Africa. [Martinson, Neil A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Levison, Julie H.; Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.] Harvard Univ, Harvard Ctr AIDS Res, Boston, MA 02115 USA. [Levison, Julie H.; Ciaranello, Andrea L.; Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.] Harvard Univ, Sch Med, Boston, MA USA. RP Levison, JH (reprint author), Massachusetts Gen Hosp, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jlevison@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU National Institute of Allergy and Infectious Diseases [T32 AI007433, R01 AI058736, K01AI078754, K24 AI062476, AI48526]; National Heart, Lung, and Blood Institute [HL090312]; Fogarty International Center [RTW007370]; Harvard Center for AIDS Research [P30 AI060354] FX This work was supported by the National Institute of Allergy and Infectious Diseases (T32 AI007433, R01 AI058736, K01AI078754, K24 AI062476, AI48526); National Heart, Lung, and Blood Institute (HL090312); Fogarty International Center (RTW007370); and Harvard Center for AIDS Research (P30 AI060354). NR 40 TC 14 Z9 14 U1 0 U2 13 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 15 PY 2013 VL 56 IS 4 BP 587 EP 597 DI 10.1093/cid/cis887 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 077UR UT WOS:000314054400022 PM 23087386 ER PT J AU Premereur, E Janssen, P Vanduffel, W AF Premereur, Elsie Janssen, Peter Vanduffel, Wim TI FEF-microstimulation causes task-dependent modulation of occipital fMRI activity SO NEUROIMAGE LA English DT Article DE Saccades; Attention; Macaque; fMRI; FEF ID FRONTAL EYE FIELD; LATERAL INTRAPARIETAL AREA; VISUAL-CORTEX; ELECTRICAL MICROSTIMULATION; SPATIAL ATTENTION; CONTRAST AGENT; MACAQUE; SIGNALS; MOVEMENTS; MONKEYS AB Electrical microstimulation of FEF (FEF-EM) modulates neuronal activity in area V4 (Moore and Armstrong, 2003) and elicits functional magnetic resonance imaging (fMRI) activations in visual cortex in a bottom-up dependent manner (Ekstrom et al., 2008). Here we test the hypothesis that FEF-EM-induced modulations of fMRI activity are also function of task demands, which would suggest top-down dependent gating of FEF signals in early visual cortex. We scanned two monkeys performing a visually guided saccade task; a passive fixation task with a very similar visual display; and a passive fixation task without peripheral dots. We found increased effects of FEF-EM on fMRI-activity in visual cortex during saccades compared to fixation, indicating that the FEF-EM induced modulation is task-dependent. Finally, the effect of FEF-EM is mainly present in voxels which were less activated by visual stimuli in the absence of electrical stimulation. Our results show that the FEF-EM-induced pattern of activation in early visual cortex is topographically specific and more pronounced during increased task demands. These results fit with models suggesting that FEF is an important source modulating activity in early sensory cortex and that these influences can be enhanced by coincident bottom-up or top-down signals. (C) 2012 Elsevier Inc. All rights reserved. C1 [Premereur, Elsie; Janssen, Peter; Vanduffel, Wim] Katholieke Univ Leuven, Lab Neuro Psychofysiol, B-3000 Louvain, Belgium. [Vanduffel, Wim] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Vanduffel, Wim] Harvard Univ, Dept Radiol, Sch Med, Cambridge, MA 02138 USA. RP Vanduffel, W (reprint author), Katholieke Univ Leuven, Lab Neuro Psychofysiol, O&N 2 Herestr 49 Bus 1021, B-3000 Louvain, Belgium. EM wim@nmr.mgh.harvard.edu FU Fonds voor Wetenschappelijk Onderzoek [G.0713.09, G.0622.08, G.0831.11]; Interuniversity Attraction Poles [P6/29]; Excellentie Financiering [EF/05/014]; National Science Foundation [BCS-0745436]; Programma Financiering [PFV/10/008]; Geconcerteerde onderzoeksacties [GOA/10/19] FX We thank Stijn Verstraeten, Piet Kayenbergh, Gerrit Meulemans, Marc De Paep, Wouter Depuydt, Inez Puttemans and Marjan Docx for assistance, and Steve Raiguel for comments on a previous version of this manuscript. Supported by Fonds voor Wetenschappelijk Onderzoek (G.0713.09, G.0622.08, and G.0831.11), Interuniversity Attraction Poles (P6/29), Excellentie Financiering (EF/05/014), National Science Foundation (BCS-0745436), Programma Financiering (PFV/10/008), Geconcerteerde onderzoeksacties (GOA/10/19). NR 40 TC 7 Z9 7 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB 15 PY 2013 VL 67 BP 42 EP 50 DI 10.1016/j.neuroimage.2012.11.017 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 079BG UT WOS:000314144600005 PM 23186918 ER PT J AU Xu, JQ Shimony, JS Klawiter, EC Snyder, AZ Trinkaus, K Naismith, RT Benzinger, TLS Cross, AH Song, SK AF Xu, Junqian Shimony, Joshua S. Klawiter, Eric C. Snyder, Abraham Z. Trinkaus, Kathryn Naismith, Robert T. Benzinger, Tammie L. S. Cross, Anne H. Song, Sheng-Kwei TI Improved in vivo diffusion tensor imaging of human cervical spinal cord SO NEUROIMAGE LA English DT Article DE Directional diffusivity; Outlier rejection; Non-negative eigenvalue priors; Reduced FOV; Cardiac gating; Cervical spinal cord; Lateral corticospinal tract; Posterior column; Diffusion tensor imaging; Reproducibility ID WHITE-MATTER TRACTS; HIGH-RESOLUTION DTI; MULTIPLE-SCLEROSIS; OPTIC-NERVE; RADIAL DIFFUSIVITY; FIBER TRACKING; 3 TESLA; TISSUE ARCHITECTURE; PHYSIOLOGICAL NOISE; ROBUST ESTIMATION AB We describe a cardiac gated high in-plane resolution axial human cervical spinal cord diffusion tensor imaging (DTI) protocol. Multiple steps were taken to optimize both image acquisition and image processing. The former includes slice-by-slice cardiac triggering and individually tiltable slices. The latter includes (i) iterative 2D retrospective motion correction, (ii) image intensity outlier detection to minimize the influence of physiological noise, (iii) a non-linear DTI estimation procedure incorporating non-negative eigenvalue priors, and (iv) tract-specific region-of-interest (ROI) identification based on an objective geometry reference. Using these strategies in combination, radial diffusivity (lambda(perpendicular to)) was reproducibly measured in white matter (WM) tracts (adjusted mean [95% confidence interval] = 0.25 [0.22, 0.29] mu m(2)/ms), lower than previously reported lambda(perpendicular to) values in the in vivo human spinal cord DTI literature. Radial diffusivity and fractional anisotropy (FA) measured in WM varied from rostral to caudal as did mean translational motion, likely reflecting respiratory motion effect. Given the considerable sensitivity of DTI measurements to motion artifact, we believe outlier detection is indispensable in spinal cord diffusion imaging. We also recommend using a mixed-effects model to account for systematic measurement bias depending on cord segment. (C) 2012 Elsevier Inc. All rights reserved. C1 [Xu, Junqian; Klawiter, Eric C.; Snyder, Abraham Z.; Naismith, Robert T.; Cross, Anne H.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Xu, Junqian] Univ Minnesota, Ctr Magnet Resonance Res, Minneapolis, MN 55455 USA. [Shimony, Joshua S.; Snyder, Abraham Z.; Benzinger, Tammie L. S.; Song, Sheng-Kwei] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. [Klawiter, Eric C.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Trinkaus, Kathryn] Washington Univ, Sch Med, Dept Biostat, St Louis, MO USA. RP Xu, JQ (reprint author), Univ Minnesota, Ctr Magnet Resonance Res, 2021 6th St SE, Minneapolis, MN 55455 USA. EM jxu@umn.edu RI Xu, Junqian/D-2247-2009 OI Xu, Junqian/0000-0001-8438-2066 FU National Institutes of Health [P01 NS059560, R01 NS047592, K23 HD053212, UL1RR024992, K23 NS052430-01A1]; National Multiple Sclerosis Society [RG 4009]; National MS Society [FG 1782]; American Academy of Neurology Foundation Clinical Research Training Fellowship; Bracco/American Roentgen Ray Society Scholar Award; Manny and Rosalyn Rosenthal-Dr John L Trotter Chair in Neuroimmunology of Barnes-Jewish Hospital Foundation; institutional Clinical and Translational Science Award [UL1RR024992]; National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH); NIH Roadmap for Medical Research NIH; Neuroclinical Research Unit; NIH (Washington University Institute of Clinical and Translational Sciences - Brain, Behavioral and Performance Unit) [CO6 RR020092, RR024992]; [P30 NS048056] FX This work was supported by the National Institutes of Health (P01 NS059560 to AHC, R01 NS047592 to S-KS) and the National Multiple Sclerosis Society (RG 4009 to AFIC). JX was supported by a National MS Society Postdoctoral Fellowship (FG 1782). JSS was supported by National Institutes of Health (K23 HD053212). ECK was supported by an American Academy of Neurology Foundation Clinical Research Training Fellowship and the National Institutes of Health (UL1RR024992). RN was supported by the National Institutes of Health (K23 NS052430-01A1). TB was supported by a Bracco/American Roentgen Ray Society Scholar Award. AHC was supported in part by the Manny and Rosalyn Rosenthal-Dr John L Trotter Chair in Neuroimmunology of Barnes-Jewish Hospital Foundation. AZS was supported by P30 NS048056. An institutional Clinical and Translational Science Award (UL1RR024992) from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research NIH, provided funding for the Neuroclinical Research Unit where research subjects were examined. This research was also supported in part by NIH grants CO6 RR020092 and RR024992 (Washington University Institute of Clinical and Translational Sciences - Brain, Behavioral and Performance Unit). The funding source had no role in the study design or in the collection, analysis and interpretation of data. The contents of the work are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. NR 93 TC 18 Z9 18 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 FEB 15 PY 2013 VL 67 BP 64 EP 76 DI 10.1016/j.neuroimage.2012.11.014 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 079BG UT WOS:000314144600007 PM 23178538 ER PT J AU Cunha, CB Varughese, CA Mylonakis, E AF Cunha, Cheston B. Varughese, Christy A. Mylonakis, Eleftherios TI Antimicrobial stewardship programs (ASPs) The devil is in the details SO VIRULENCE LA English DT Editorial Material ID ANTIBIOTIC STEWARDSHIP; COMMUNITY HOSPITALS; STRATEGIES; RESISTANCE; IMPACT C1 [Cunha, Cheston B.; Mylonakis, Eleftherios] Brown Univ, Div Infect Dis, Alpert Sch Med, Providence, RI 02912 USA. [Varughese, Christy A.] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. RP Cunha, CB (reprint author), Brown Univ, Div Infect Dis, Alpert Sch Med, Providence, RI 02912 USA. EM ccunha@lifespan.org NR 29 TC 7 Z9 7 U1 0 U2 7 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 FEB 15 PY 2013 VL 4 IS 2 BP 147 EP 149 DI 10.4161/viru.23856 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 089FI UT WOS:000314895200005 PM 23381468 ER PT J AU Wirth, LJ Ross, DS Randolph, GW Cunnane, ME Sadow, PM AF Wirth, Lori J. Ross, Douglas S. Randolph, Gregory W. Cunnane, Mary Elizabeth Sadow, Peter M. TI Case 5-2013: A 52-Year-Old Woman with a Mass in the Thyroid SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CARCINOEMBRYONIC ANTIGEN LEVELS; FINE-NEEDLE-ASPIRATION; METASTATIC LYMPH-NODES; RET PROTOONCOGENE; FOLLOW-UP; SERUM CALCITONIN; COMPLETION THYROIDECTOMY; PROGNOSTIC-SIGNIFICANCE; PREOPERATIVE DIAGNOSIS; CONSECUTIVE PATIENTS C1 [Wirth, Lori J.; Ross, Douglas S.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Sadow, Peter M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Randolph, Gregory W.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. [Cunnane, Mary Elizabeth] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. [Wirth, Lori J.; Ross, Douglas S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Randolph, Gregory W.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Cunnane, Mary Elizabeth] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Sadow, Peter M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wirth, LJ (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. FU Bayer; Boehringer Ingelheim; Acceleron; Exelexis; Genzyme; Novo Nordisk FX Dr. Wirth reports receiving consulting fees from Bayer, Boehringer Ingelheim, Acceleron, and Exelexis; Dr. Ross, receiving consulting fees from Genzyme and Novo Nordisk; and Dr. Randolph, providing expert testimony on behalf of patients or health care providers in medicolegal cases involving surgery. No other potential conflict of interest relevant to this article was reported. NR 52 TC 6 Z9 6 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 14 PY 2013 VL 368 IS 7 BP 664 EP 673 DI 10.1056/NEJMcpc1210080 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 194VA UT WOS:000322659600012 PM 23406032 ER PT J AU Chibebe, J Fuchs, BB Sabino, CP Junqueira, JC Jorge, AC Ribeiro, MS Gilmore, MS Rice, LB Tegos, GP Hamblin, MR Mylonakis, E AF Chibebe Junior, Jose Fuchs, Beth B. Sabino, Caetano P. Junqueira, Juliana C. Jorge, AntonioO. C. Ribeiro, Martha S. Gilmore, Michael S. Rice, Louis B. Tegos, George P. Hamblin, Michael R. Mylonakis, Eleftherios TI Photodynamic and Antibiotic Therapy Impair the Pathogenesis of Enterococcus faecium in a Whole Animal Insect Model SO PLOS ONE LA English DT Article ID GALLERIA-MELLONELLA LARVAE; LOW-POWER LASER; CANDIDA-ALBICANS; CRYPTOCOCCUS-NEOFORMANS; CAENORHABDITIS-ELEGANS; EPITHELIAL-CELLS; VIRULENCE; FAECALIS; HOST; SUSCEPTIBILITY AB Enterococcus faecium has emerged as one of the most important pathogens in healthcare-associated infections worldwide due to its intrinsic and acquired resistance to many antibiotics, including vancomycin. Antimicrobial photodynamic therapy (aPDT) is an alternative therapeutic platform that is currently under investigation for the control and treatment of infections. PDT is based on the use of photoactive dye molecules, widely known as photosensitizer (PS). PS, upon irradiation with visible light, produces reactive oxygen species that can destroy lipids and proteins causing cell death. We employed Galleria mellonella (the greater wax moth) caterpillar fatally infected with E. faecium to develop an invertebrate host model system that can be used to study the antimicrobial PDT (alone or combined with antibiotics). In the establishment of infection by E. faecium in G. mellonella, we found that the G. mellonella death rate was dependent on the number of bacterial cells injected into the insect hemocoel and all E. faecium strains tested were capable of infecting and killing G. mellonella. Antibiotic treatment with ampicillin, gentamicin or the combination of ampicillin and gentamicin prolonged caterpillar survival infected by E. faecium (P = 0.0003, P = 0.0001 and P = 0.0001, respectively). In the study of antimicrobial PDT, we verified that methylene blue (MB) injected into the insect followed by whole body illumination prolonged the caterpillar survival (P = 0.0192). Interestingly, combination therapy of larvae infected with vancomycin-resistant E. faecium, with antimicrobial PDT followed by vancomycin, significantly prolonged the survival of the caterpillars when compared to either antimicrobial PDT (P = 0.0095) or vancomycin treatment alone (P = 0.0025), suggesting that the aPDT made the vancomycin resistant E. faecium strain more susceptible to vancomycin action. In summary, G. mellonella provides an invertebrate model host to study the antimicrobial PDT and to explore combinatorial aPDT-based treatments. C1 [Chibebe Junior, Jose; Junqueira, Juliana C.; Jorge, AntonioO. C.] Univ Estadual Paulista UNESP, Dept Biosci & Oral Diag, Sao Paulo, Brazil. [Chibebe Junior, Jose; Fuchs, Beth B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Chibebe Junior, Jose] Fac Pindamonhangaba, Dept Restorat Dent, Sao Paulo, Brazil. [Sabino, Caetano P.; Tegos, George P.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Sabino, Caetano P.; Ribeiro, Martha S.] Ctr Lasers & Applicat, Nucl & Energy Res Inst, Sao Paulo, Brazil. [Gilmore, Michael S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Rice, Louis B.; Mylonakis, Eleftherios] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Providence, RI 02903 USA. [Rice, Louis B.; Mylonakis, Eleftherios] Brown Univ, Miriam Hosp, Warren Alpert Med Sch, Providence, RI USA. [Tegos, George P.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Tegos, George P.] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA. [Tegos, George P.] Univ New Mexico, Ctr Mol Discovery, Albuquerque, NM 87131 USA. [Hamblin, Michael R.] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA USA. RP Chibebe, J (reprint author), Univ Estadual Paulista UNESP, Dept Biosci & Oral Diag, Sao Paulo, Brazil. EM juliana@fosjc.unesp.br; emylonakis@lifespan.org RI Junqueira, Juliana/F-7785-2012; Sabino, Caetano/K-8356-2013; 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 CAPES [PDEE 2507-11-0]; NIH [RO1 AI050875, 5U54MH084690-02]; Harvard-wide Program on Antibiotic Resistance [P01 AI083214]; US Air Force MFEL Program [FA9550-04-1-0079]; DTRA [HDTRA1-13-C-0005] FX The first author thanks CAPES (PDEE 2507-11-0) for the scholarship during the "Sandwich'' PhD Program at Harvard Medical School. Research conducted in the Mylonakis Laboratory was supported by NIH (RO1 AI050875 to EM, and the Harvard-wide Program on Antibiotic Resistance [P01 AI083214] to EM and MSG). Research conducted in the Hamblin Laboratory was supported by NIH (RO1 AI050875 to MRH) and US Air Force MFEL Program (FA9550-04-1-0079). George P. Tegos is supported by the NIH (grant 5U54MH084690-02) and DTRA (contract HDTRA1-13-C-0005). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 65 TC 7 Z9 8 U1 1 U2 14 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 14 PY 2013 VL 8 IS 2 AR e55926 DI 10.1371/journal.pone.0055926 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 099EJ UT WOS:000315602700027 PM 23457486 ER PT J AU Shoji-Kawata, S Sumpter, R Leveno, M Campbell, GR Zou, ZJ Kinch, L Wilkins, AD Sun, QH Pallauf, K MacDuff, D Huerta, C Virgin, HW Helms, JB Eerland, R Tooze, SA Xavier, R Lenschow, DJ Yamamoto, A King, D Lichtarge, O Grishin, NV Spector, SA Kaloyanova, DV Levine, B AF Shoji-Kawata, Sanae Sumpter, Rhea, Jr. Leveno, Matthew Campbell, Grant R. Zou, Zhongju Kinch, Lisa Wilkins, Angela D. Sun, Qihua Pallauf, Kathrin MacDuff, Donna Huerta, Carlos Virgin, Herbert W. Helms, J. Bernd Eerland, Ruud Tooze, Sharon A. Xavier, Ramnik Lenschow, Deborah J. Yamamoto, Ai King, David Lichtarge, Olivier Grishin, Nick V. Spector, Stephen A. Kaloyanova, Dora V. Levine, Beth TI Identification of a candidate therapeutic autophagy-inducing peptide SO NATURE LA English DT Article ID PROTEIN; DISEASE; PATHOGENESIS; MACROPHAGES; LOCALIZES; INFECTION; BECLIN-1; PATHWAY; COMPLEX; BINDING AB The lysosomal degradation pathway of autophagy has a crucial role in defence against infection, neurodegenerative disorders, cancer and ageing. Accordingly, agents that induce autophagy may have broad therapeutic applications. One approach to developing such agents is to exploit autophagy manipulation strategies used by microbial virulence factors. Here we show that a peptide, Tat-beclin 1-derived from a region of the autophagy protein, beclin 1, which binds human immunodeficiency virus (HIV)-1 Nef-is a potent inducer of autophagy, and interacts with a newly identified negative regulator of autophagy, GAPR-1 (also called GLIPR2). Tat-beclin 1 decreases the accumulation of polyglutamine expansion protein aggregates and the replication of several pathogens (including HIV-1) in vitro, and reduces mortality in mice infected with chikungunya or West Nile virus. Thus, through the characterization of a domain of beclin 1 that interacts with HIV-1 Nef, we have developed an autophagy-inducing peptide that has potential efficacy in the treatment of human diseases. C1 [Shoji-Kawata, Sanae; Sumpter, Rhea, Jr.; Leveno, Matthew; Zou, Zhongju; Sun, Qihua; Pallauf, Kathrin; Levine, Beth] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Shoji-Kawata, Sanae; Sumpter, Rhea, Jr.; Leveno, Matthew; Zou, Zhongju; Sun, Qihua; Levine, Beth] Univ Texas SW Med Ctr Dallas, Ctr Autophagy Res, Dallas, TX 75390 USA. [Campbell, Grant R.; Spector, Stephen A.] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA. [Campbell, Grant R.; Spector, Stephen A.] Rady Childrens Hosp, San Diego, CA 92123 USA. [Zou, Zhongju; Kinch, Lisa; Grishin, Nick V.; Levine, Beth] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA. [Kinch, Lisa; Huerta, Carlos; Grishin, Nick V.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA. [Wilkins, Angela D.; Lichtarge, Olivier] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [MacDuff, Donna; Virgin, Herbert W.; Lenschow, Deborah J.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Helms, J. Bernd; Eerland, Ruud; Kaloyanova, Dora V.] Univ Utrecht, Dept Biochem & Cell Biol, NL-3508 TD Utrecht, Netherlands. [Helms, J. Bernd; Eerland, Ruud; Kaloyanova, Dora V.] Univ Utrecht, Inst Biomembranes, NL-3508 TD Utrecht, Netherlands. [Tooze, Sharon A.] Canc Res UK, London Res Inst, London EC1V 4AD, England. [Xavier, Ramnik] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Xavier, Ramnik] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Xavier, Ramnik] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA. [Lenschow, Deborah J.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Yamamoto, Ai] Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. [King, David] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA. [Levine, Beth] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA. RP Levine, B (reprint author), Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. EM beth.levine@utsouthwestern.edu OI Campbell, Grant/0000-0003-3927-1994 FU NIH [U54AI057156, K08 AI099150, ROI NS077874, RO1 GM094575, ROI GM066099, ROI GM079656, ROI NS063973, ROI NS050199, U54AI057160, ROI DK083756, ROI DK086502, T32 GM008297]; NSF [CCF-0905536]; NWO-ALW Open Program [817.02.023]; Cancer Research UK; Welch Foundation [I-15-5] FX We thank M. Diamond, J. L Foster, M. Gale, N. Mizushima, D. Sabatini, M. Shiloh and T. Yoshimori for supplying critical reagent; and H. Ball, A. Bugde and E.-L Eskelinen for assistance with-peptide synthesis, infrared imaging and EM interpretation, respectively. This work was supported by NIH grants U54AI057156 (B.L), K08 AI099150 (R.S.), ROI NS077874 (S.A.S), RO1 GM094575 (N.V.G.), ROI GM066099 (O.L.), ROI GM079656 (O.L.), ROI NS063973 (A.Y.), ROI NS050199 (A.Y.), U54AI057160 (H.W.V., D.J.L.), ROI DK083756 (R.X), ROI DK086502 (R.X.), and T32 GM008297 (C.H.); NSF CCF-0905536 (O.L); an NWO-ALW Open Program Grant 817.02.023 (J.B.H.); Cancer Research UK (SAT.); and a Welch Foundation Award I-15-5 (N.V.G.). NR 27 TC 204 Z9 216 U1 7 U2 148 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 14 PY 2013 VL 494 IS 7436 BP 201 EP 206 DI 10.1038/nature11866 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 092QS UT WOS:000315137700032 PM 23364696 ER PT J AU Kamberov, YG Wang, SJ Tan, JZ Gerbault, P Wark, A Tan, LZ Yang, YJ Li, SL Tang, K Chen, H Powell, A Itan, Y Fuller, D Lohmueller, J Mao, JH Schachar, A Paymer, M Hostetter, E Byrne, E Burnett, M McMahon, AP Thomas, MG Lieberman, DE Jin, L Tabin, CJ Morgan, BA Sabeti, PC AF Kamberov, Yana G. Wang, Sijia Tan, Jingze Gerbault, Pascale Wark, Abigail Tan, Longzhi Yang, Yajun Li, Shilin Tang, Kun Chen, Hua Powell, Adam Itan, Yuval Fuller, Dorian Lohmueller, Jason Mao, Junhao Schachar, Asa Paymer, Madeline Hostetter, Elizabeth Byrne, Elizabeth Burnett, Melissa McMahon, Andrew P. Thomas, Mark G. Lieberman, Daniel E. Jin, Li Tabin, Clifford J. Morgan, Bruce A. Sabeti, Pardis C. TI Modeling Recent Human Evolution in Mice by Expression of a Selected EDAR Variant SO CELL LA English DT Article ID ECTODYSPLASIN-A RECEPTOR; TO-HIP RATIO; NF-KAPPA-B; POSITIVE SELECTION; ECTODERMAL DYSPLASIA; STATISTICAL EVALUATION; ETHNIC-DIFFERENCES; HAIR THICKNESS; HUMAN GENOME; BODY-WEIGHT AB An adaptive variant of the human Ectodysplasin receptor, EDARV370A, is one of the strongest candidates of recent positive selection from genome-wide scans. We have modeled EDAR370A in mice and characterized its phenotype and evolutionary origins in humans. Our computational analysis suggests the allele arose in central China approximately 30,000 years ago. Although EDAR370A has been associated with increased scalp hair thickness and changed tooth morphology in humans, its direct biological significance and potential adaptive role remain unclear. We generated a knockin mouse model and find that, as in humans, hair thickness is increased in EDAR370A mice. We identify new biological targets affected by the mutation, including mammary and eccrine glands. Building on these results, we find that EDAR370A is associated with an increased number of active eccrine glands in the Han Chinese. This interdisciplinary approach yields unique insight into the generation of adaptive variation among modern humans. C1 [Kamberov, Yana G.; Wark, Abigail; Tabin, Clifford J.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Kamberov, Yana G.; Burnett, Melissa; Morgan, Bruce A.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Kamberov, Yana G.; Morgan, Bruce A.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. [Burnett, Melissa] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Kamberov, Yana G.; Wang, Sijia; Tan, Longzhi; Lohmueller, Jason; Schachar, Asa; Paymer, Madeline; Hostetter, Elizabeth; Byrne, Elizabeth; Sabeti, Pardis C.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Kamberov, Yana G.; Lieberman, Daniel E.] Harvard Univ, Dept Human Evolutionary Biol, Cambridge, MA 02138 USA. [Kamberov, Yana G.; Wang, Sijia; Schachar, Asa; Paymer, Madeline; Sabeti, Pardis C.] Harvard Univ, Ctr Syst Biol, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA. [Mao, Junhao; McMahon, Andrew P.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Tan, Jingze; Yang, Yajun; Li, Shilin; Jin, Li] Fudan Univ, MOE Key Lab Contemporary Anthropol, Shanghai 200433, Peoples R China. [Gerbault, Pascale; Itan, Yuval; Thomas, Mark G.] UCL, Dept Genet Evolut & Environm, London WC1H 0PY, England. [Powell, Adam] UCL, UCL Genet Inst UGI, London WC1H 0PY, England. [Fuller, Dorian] UCL, Inst Archaeol, London WC1H 0PY, England. [Tang, Kun; Jin, Li] Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, Shanghai 200031, Peoples R China. [Chen, Hua] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Sabeti, Pardis C.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Jin, L (reprint author), Fudan Univ, MOE Key Lab Contemporary Anthropol, Shanghai 200433, Peoples R China. EM lijin.fudan@gmail.com; bruce.morgan@cbrc2.mgh.harvard.edu; pardis@broadinstitute.org RI Jin, Li/C-1468-2009; Thomas, Mark/A-2219-2012 OI Jin, Li/0000-0002-4546-2415; Thomas, Mark/0000-0002-2452-981X FU Harvard University Science and Engineering Committee Seed Fund for Interdisciplinary Science; Packard Foundation Fellowship in Science and Engineering; NIH Innovator Award [1DP2OD006514-01]; BIRT Award from NIAMS [AR055256-04S1]; NIH grant [R37 HD032443]; American School of Prehistoric Research; NSFC [30890034]; MOST [2011BAI09B00]; MOH [201002007]; AXA Research Fund; LeCHE Marie Curie FP7; NIH [R37 054364] FX This project was funded by a grant from the Harvard University Science and Engineering Committee Seed Fund for Interdisciplinary Science to CJT, PCS, BAM and DEL; a Packard Foundation Fellowship in Science and Engineering and an NIH Innovator Award 1DP2OD006514-01 to PCS; a BIRT Award AR055256-04S1 from NIAMS to BAM; an NIH grant R37 HD032443 to CJT; and funding from the American School of Prehistoric Research to DEL. Human association study work was additionally supported by NSFC 30890034; MOST 2011BAI09B00; MOH 201002007 to LJ. YI was funded by an AXA Research Fund postdoctoral fellowship and PG by the LeCHE Marie Curie FP7 framework. Work in APM's laboratory was supported by an NIH R37 054364 grant. We acknowledge the UCL Legion High Performance Computing Facility and support services and thank O. Bar Yosef, C. Zhao, E. Rohling, S. Schaffner, L. Gaffney, C. Edwards, J. Vitti, S. Tabrizi and A. Tariela for feedback on the manuscript and A. Carpenter, C. Wahlby, and M. Morgan for data analysis help. The authors declare no conflict of interest. NR 68 TC 85 Z9 91 U1 10 U2 100 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD FEB 14 PY 2013 VL 152 IS 4 BP 691 EP 702 DI 10.1016/j.cell.2013.01.016 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 089YJ UT WOS:000314945600006 PM 23415220 ER PT J AU Landau, DA Carter, SL Stojanov, P McKenna, A Stevenson, K Lawrence, MS Sougnez, C Stewart, C Sivachenko, A Wang, LL Wan, YZ Zhang, WD Shukla, SA Vartanov, A Fernandes, SM Saksena, G Cibulskis, K Tesar, B Gabriel, S Hacohen, N Meyerson, M Lander, ES Neuberg, D Brown, JR Getz, G Wu, CJ AF Landau, Dan A. Carter, Scott L. Stojanov, Petar McKenna, Aaron Stevenson, Kristen Lawrence, Michael S. Sougnez, Carrie Stewart, Chip Sivachenko, Andrey Wang, Lili Wan, Youzhong Zhang, Wandi Shukla, Sachet A. Vartanov, Alexander Fernandes, Stacey M. Saksena, Gordon Cibulskis, Kristian Tesar, Bethany Gabriel, Stacey Hacohen, Nir Meyerson, Matthew Lander, Eric S. Neuberg, Donna Brown, Jennifer R. Getz, Gad Wu, Catherine J. TI Evolution and Impact of Subclonal Mutations in Chronic Lymphocytic Leukemia SO CELL LA English DT Article ID ACUTE MYELOID-LEUKEMIA; COPY-NUMBER ALTERATION; B-CELL LYMPHOMA; CLONAL EVOLUTION; HUMAN CANCER; SOMATIC MUTATIONS; MULTIPLE-MYELOMA; GENOMIC ABERRATIONS; BREAST CANCERS; SHORT SURVIVAL AB Clonal evolution is a key feature of cancer progression and relapse. We studied intratumoral heterogeneity in 149 chronic lymphocytic leukemia (CLL) cases by integrating whole-exome sequence and copy number to measure the fraction of cancer cells harboring each somatic mutation. We identified driver mutations as predominantly clonal (e.g., MYD88, trisomy 12, and del(13q)) or subclonal (e.g., SF3B1 and TP53), corresponding to earlier and later events in CLL evolution. We sampled leukemia cells from 18 patients at two time points. Ten of twelve CLL cases treated with chemotherapy (but only one of six without treatment) underwent clonal evolution, predominantly involving subclones with driver mutations (e.g., SF3B1 and TP53) that expanded over time. Furthermore, presence of a subclonal driver mutation was an independent risk factor for rapid disease progression. Our study thus uncovers patterns of clonal evolution in CLL, providing insights into its stepwise transformation, and links the presence of subclones with adverse clinical outcomes. C1 [Landau, Dan A.; Wang, Lili; Wan, Youzhong; Zhang, Wandi; Shukla, Sachet A.; Wu, Catherine J.] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Landau, Dan A.; Stojanov, Petar; Wang, Lili; Wan, Youzhong; Zhang, Wandi; Vartanov, Alexander; Fernandes, Stacey M.; Tesar, Bethany; Brown, Jennifer R.; Wu, Catherine J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Stevenson, Kristen; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Landau, Dan A.; Carter, Scott L.; Stojanov, Petar; McKenna, Aaron; Lawrence, Michael S.; Sougnez, Carrie; Stewart, Chip; Sivachenko, Andrey; Shukla, Sachet A.; Saksena, Gordon; Cibulskis, Kristian; Gabriel, Stacey; Hacohen, Nir; Meyerson, Matthew; Lander, Eric S.; Getz, Gad] Broad Inst, Cambridge, MA 02139 USA. [Landau, Dan A.] Yale Canc Ctr, Dept Hematol, New Haven, CT 06510 USA. [Landau, Dan A.] Univ Paris Diderot, F-75013 Paris, France. [Brown, Jennifer R.; Wu, Catherine J.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA. [Hacohen, Nir] Harvard Univ, Div Allergy Immunol & Rheumatol, Dept Med, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. [Getz, Gad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Getz, Gad] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Getz, G (reprint author), Broad Inst, Cambridge, MA 02139 USA. EM gadgetz@broadinstitute.org; cwu@partners.org FU American Society of Hematology (ASH) Research Award for Fellows-in-Training; ACS Postdoctoral Fellowship; NIH [K23 CA115682]; Melton and Rosenbach Funds; Blavatnik Family Foundation; AACR (SU2C Innovative Research Grant); NHLBI [1RO1HL103532-01]; NCI [1R01CA155010-01A1]; Damon-Runyon Cancer Research Foundation [CI-38-07] FX D.A.L. dedicates this manuscript to the loving memory of his mother Nina, who passed away during the final stages of this work. We thank all members of the Broad Institute's Biological Samples, Genetic Analysis, and Genome Sequencing Platforms, who made this work possible (NHGRI-U54HG003067). D.A.L. is supported by an American Society of Hematology (ASH) Research Award for Fellows-in-Training and an ACS Postdoctoral Fellowship. J.R.B. is supported by NIH K23 CA115682, the Melton and Rosenbach Funds, and is an ASH Scholar and a LLS Clinical Research Scholar. C.J.W. acknowledges support from the Blavatnik Family Foundation, AACR (SU2C Innovative Research Grant), NHLBI (1RO1HL103532-01), NCI (1R01CA155010-01A1), and is a clinical investigator supported in part by the Damon-Runyon Cancer Research Foundation (CI-38-07). NR 59 TC 462 Z9 463 U1 12 U2 87 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD FEB 14 PY 2013 VL 152 IS 4 BP 714 EP 726 DI 10.1016/j.cell.2013.01.019 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 089YJ UT WOS:000314945600008 PM 23415222 ER PT J AU Yildirim, E Kirby, JE Brown, DE Mercier, FE Sadreyev, RI Scadden, DT Lee, JT AF Yildirim, Eda Kirby, James E. Brown, Diane E. Mercier, Francois E. Sadreyev, Ruslan I. Scadden, David T. Lee, Jeannie T. TI Xist RNA Is a Potent Suppressor of Hematologic Cancer in Mice SO CELL LA English DT Article ID X-CHROMOSOME INACTIVATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; HEMATOPOIETIC STEM-CELLS; DOSAGE COMPENSATION; MYELODYSPLASTIC SYNDROMES; MYELOID-LEUKEMIA; NONCODING RNAS; C-KIT; GENE; MOUSE AB X chromosome aneuploidies have long been associated with human cancers, but causality has not been established. In mammals, X chromosome inactivation (XCI) is triggered by Xist RNA to equalize gene expression between the sexes. Here we delete Xist in the blood compartment of mice and demonstrate that mutant females develop a highly aggressive myeloproliferative neoplasm and myelodysplastic syndrome (mixed MPN/MDS) with 100% penetrance. Significant disease components include primary myelofibrosis, leukemia, histiocytic sarcoma, and vasculitis. Xist-deficient hematopoietic stem cells (HSCs) show aberrant maturation and age-dependent loss. Reconstitution experiments indicate that MPN/MDS and myelofibrosis are of hematopoietic rather than stromal origin. We propose that Xist loss results in X reactivation and consequent genome-wide changes that lead to cancer, thereby causally linking the X chromosome to cancer in mice. Thus, Xist RNA not only is required to maintain XCI but also suppresses cancer in vivo. C1 [Yildirim, Eda; Sadreyev, Ruslan I.; Lee, Jeannie T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. [Yildirim, Eda; Sadreyev, Ruslan I.; Lee, Jeannie T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. [Brown, Diane E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Comparat Med, Boston, MA 02114 USA. [Mercier, Francois E.; Scadden, David T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA. [Brown, Diane E.; Sadreyev, Ruslan I.; Lee, Jeannie T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Yildirim, Eda; Sadreyev, Ruslan I.; Lee, Jeannie T.] Harvard Univ, Dept Genet, Sch Med, Boston, MA 02114 USA. [Kirby, James E.] Harvard Univ, Dept Pathol, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02114 USA. [Mercier, Francois E.; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Mercier, Francois E.; Scadden, David T.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Lee, JT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu OI Yildirim, Eda/0000-0002-4796-3854 FU MGH ECOR Medical Discovery Fund; Clinician-Scientist Training Award from the Canadian Institutes of Health Research FX We are grateful to members of the Lee lab for stimulating discussions. We thank R. Jaenisch for Xist2lox/Xist2lox mice, G. Pihan and A. Sohani for hematopathology advice, H. Hock for advice on Vav-Cre mice, W. Press for maintenance of Xist2lox/Xist2lox mice colony, the MGH CCM-Clinical Pathology laboratory for assistance on hematological analysis, D. Dombkowski for FACS assistance, and A.J. Zall for survival bleed collections. This work was supported by the MGH ECOR Medical Discovery Fund (E.Y.), Clinician-Scientist Training Award from the Canadian Institutes of Health Research (F.E.M.), NR 63 TC 143 Z9 150 U1 4 U2 57 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD FEB 14 PY 2013 VL 152 IS 4 BP 727 EP 742 DI 10.1016/j.cell.2013.01.034 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 089YJ UT WOS:000314945600009 PM 23415223 ER PT J AU Levine, AJ Miller, JA Shapshak, P Gelman, B Singer, EJ Hinkin, CH Commins, D Morgello, S Grant, I Horvath, S AF Levine, Andrew J. Miller, Jeremy A. Shapshak, Paul Gelman, Benjamin Singer, Elyse J. Hinkin, Charles H. Commins, Deborah Morgello, Susan Grant, Igor Horvath, Steve TI Systems analysis of human brain gene expression: mechanisms for HIV-associated neurocognitive impairment and common pathways with Alzheimer's disease SO BMC MEDICAL GENOMICS LA English DT Article DE HIV encephalitis; HIV-associated dementia; HIV-associated neurocognitive disorder; Weighted gene coexpression network analysis; WGCNA; CNS penetration effectiveness; National neuroAIDS tissue consortium; Coexpression module ID COEXPRESSION NETWORK ANALYSIS; HUMAN-IMMUNODEFICIENCY-VIRUS; NEUROAIDS TISSUE CONSORTIUM; CENTRAL-NERVOUS-SYSTEM; ANTIRETROVIRAL THERAPY; AIDS DEMENTIA; CNS PENETRATION; BASAL GANGLIA; WHITE-MATTER; TRANSCRIPTOME AB Background: Human Immunodeficiency Virus-1 (HIV) infection frequently results in neurocognitive impairment. While the cause remains unclear, recent gene expression studies have identified genes whose transcription is dysregulated in individuals with HIV-association neurocognitive disorder (HAND). However, the methods for interpretation of such data have lagged behind the technical advances allowing the decoding genetic material. Here, we employ systems biology methods novel to the field of NeuroAIDS to further interrogate extant transcriptome data derived from brains of HIV + patients in order to further elucidate the neuropathogenesis of HAND. Additionally, we compare these data to those derived from brains of individuals with Alzheimer's disease (AD) in order to identify common pathways of neuropathogenesis. Methods: In Study 1, using data from three brain regions in 6 HIV-seronegative and 15 HIV + cases, we first employed weighted gene co-expression network analysis (WGCNA) to further explore transcriptome networks specific to HAND with HIV-encephalitis (HIVE) and HAND without HIVE. We then used a symptomatic approach, employing standard expression analysis and WGCNA to identify networks associated with neurocognitive impairment (NCI), regardless of HIVE or HAND diagnosis. Finally, we examined the association between the CNS penetration effectiveness (CPE) of antiretroviral regimens and brain transcriptome. In Study 2, we identified common gene networks associated with NCI in both HIV and AD by correlating gene expression with pre-mortem neurocognitive functioning. Results: Study 1: WGCNA largely corroborated findings from standard differential gene expression analyses, but also identified possible meta-networks composed of multiple gene ontology categories and oligodendrocyte dysfunction. Differential expression analysis identified hub genes highly correlated with NCI, including genes implicated in gliosis, inflammation, and dopaminergic tone. Enrichment analysis identified gene ontology categories that varied across the three brain regions, the most notable being downregulation of genes involved in mitochondrial functioning. Finally, WGCNA identified dysregulated networks associated with NCI, including oligodendrocyte and mitochondrial functioning. Study 2: Common gene networks dysregulated in relation to NCI in AD and HIV included mitochondrial genes, whereas upregulation of various cancer-related genes was found. Conclusions: While under-powered, this study identified possible biologically-relevant networks correlated with NCI in HIV, and common networks shared with AD, opening new avenues for inquiry in the investigation of HAND neuropathogenesis. These results suggest that further interrogation of existing transcriptome data using systems biology methods can yield important information. C1 [Levine, Andrew J.; Singer, Elyse J.] Univ Calif Los Angeles, David Geffen Sch Med, Natl Neurol AIDS Bank, Dept Neurol, Los Angeles, CA 90095 USA. [Miller, Jeremy A.; Horvath, Steve] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. [Shapshak, Paul] Univ S Florida, Morsani Coll Med, Dept Med, Div Infect Dis & Int Med, Tampa, FL USA. [Shapshak, Paul] Univ S Florida, Morsani Coll Med, Dept Psychiat & Behav Med, Tampa, FL USA. [Gelman, Benjamin] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Gelman, Benjamin] Univ Texas Med Branch, Dept Neurosci & Cell Biol, Galveston, TX 77555 USA. [Hinkin, Charles H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Hinkin, Charles H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Commins, Deborah] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. [Morgello, Susan] Mt Sinai Sch Med, Manhattan HIV Brain Bank, Dept Neurol, New York, NY USA. [Morgello, Susan] Mt Sinai Sch Med, Manhattan HIV Brain Bank, Dept Neurosci, New York, NY USA. [Morgello, Susan] Mt Sinai Sch Med, Manhattan HIV Brain Bank, Dept Pathol, New York, NY USA. [Grant, Igor] Univ Calif San Diego, Dept Psychiat, Calif NeuroAIDS Tissue Network, San Diego, CA 92103 USA. [Horvath, Steve] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA USA. RP Levine, AJ (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Natl Neurol AIDS Bank, Dept Neurol, Los Angeles, CA 90095 USA. EM ajlevine@mednet.ucla.edu FU National NeuroAIDS Tissue Consortium; National Neurological AIDS Bank [U01-MH08021, R24-NS38841]; Texas NeuroAIDS Research Center [U01-MH083507, R24-NS45491]; Manhattan HIV Brain Bank [U01-MH083501, R24-MH59724]; California NeuroAIDS Tissue Network [U01-MH083506, R24-MH59745]; National Institute for Drug Abuse [R01DA030913] FX This study was funded in through the National NeuroAIDS Tissue Consortium, which consists of National Neurological AIDS Bank (U01-MH08021 and R24-NS38841 - Singer), Texas NeuroAIDS Research Center (U01-MH083507 and R24-NS45491 - Gelman), Manhattan HIV Brain Bank (U01-MH083501 and R24-MH59724 - Morgello), and California NeuroAIDS Tissue Network (U01-MH083506 and R24-MH59745 - Grant). Funding was also provided by the National Institute for Drug Abuse grant R01DA030913 (Levine & Horvath). NR 91 TC 13 Z9 14 U1 2 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1755-8794 J9 BMC MED GENOMICS JI BMC Med. Genomics PD FEB 13 PY 2013 VL 6 AR 4 DI 10.1186/1755-8794-6-4 PG 20 WC Genetics & Heredity SC Genetics & Heredity GA 124MF UT WOS:000317467800001 PM 23406646 ER PT J AU Kullgren, JT Volpp, KG Polsky, D AF Kullgren, Jeffrey T. Volpp, Kevin G. Polsky, Daniel TI Are the Healthy Behaviors of US High-Deductible Health Plan Enrollees Driven by People Who Chose These Plans? Smoking as a Case Study SO PLOS ONE LA English DT Article ID ANTE MORAL HAZARD; EMPLOYEE CHOICE; POPULATION; ENROLLMENT; INSURANCE; BENEFITS AB Purpose: To determine whether negative associations between enrollment in a high-deductible health plan (HDHP) and one exemplar unhealthy behavior - daily smoking - are found only among people who chose these plans. Design: Cross-sectional analysis of nationally-representative data. Setting: United States from 2007 to 2008. Subjects: 6,941 privately insured non-elderly adult participants in the 2007 Health Tracking Household Survey. Measures: Self-reported smoking status. Analysis: We classified subjects as HDHP or traditional health plan enrollees with employer-sponsored insurance (ESI) and no choice of plans, ESI with a choice of plans, or coverage through the non-group market. We used multivariate logistic regression to measure associations between HDHP enrollment and daily smoking within each of the 3 coverage source groups while controlling for potential confounders. Results: HDHP enrollment was associated with lower odds of smoking among individuals with ESI and a choice of plans (AOR 0.55, 95% CI 0.33-0.90) and those with non-group coverage (AOR 0.64, 95% CI 0.34-1.22), though the latter association was not statistically significant. HDHP enrollment was not associated with lower odds of smoking among individuals with ESI and no choice of plans (AOR 1.04, 95% CI 0.69-1.56). Conclusions: HDHP enrollment is associated with lower odds of smoking only among individuals who chose to enroll in an HDHP. Lower rates of unhealthy behaviors among HDHP enrollees may be a reflection of individuals who choose these plans. C1 [Kullgren, Jeffrey T.] Vet Affairs Ann Arbor Healthcare Syst, Vet Affairs Ctr Clin Management Res, Ann Arbor, MI USA. [Kullgren, Jeffrey T.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Kullgren, Jeffrey T.] Univ Michigan, Inst Healthcare Policy & Innovat, Ann Arbor, MI 48109 USA. [Volpp, Kevin G.; Polsky, Daniel] Univ Penn, Leonard Davis Inst Hlth Econ, Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Polsky, Daniel] Penn Carnegie Mellon Univ, Roybal Ctr Behav Econ & Hlth P30, Philadelphia, PA USA. [Volpp, Kevin G.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. [Volpp, Kevin G.; Polsky, Daniel] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Polsky, Daniel] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA. RP Kullgren, JT (reprint author), Vet Affairs Ann Arbor Healthcare Syst, Vet Affairs Ctr Clin Management Res, Ann Arbor, MI USA. EM jkullgre@med.umich.edu FU US Department of Veterans Affairs; Robert Wood Johnson Foundation FX The US Department of Veterans Affairs and the Robert Wood Johnson Foundation funded the study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. These contents do not represent the views of the Department of Veterans Affairs, the United States Government, or the Robert Wood Johnson Foundation. NR 32 TC 1 Z9 1 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 13 PY 2013 VL 8 IS 2 AR e56154 DI 10.1371/journal.pone.0056154 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 104DM UT WOS:000315970300120 PM 23418528 ER PT J AU Samur, MK Yan, ZY Wang, XJ Cao, QY Munshi, NC Li, C Shah, PK AF Samur, Mehmet Kemal Yan, Zhenyu Wang, Xujun Cao, Qingyi Munshi, Nikhil C. Li, Cheng Shah, Parantu K. TI canEvolve: A Web Portal for Integrative Oncogenomics SO PLOS ONE LA English DT Article ID GENE-EXPRESSION PROFILES; COPY NUMBER ALTERATIONS; CELL LUNG-CANCER; MULTIPLE-MYELOMA; ARRAY DATA; DATABASE; GENOME; MICROARRAY; SURVIVAL; QUANTIFICATION AB Background & Objective: Genome-wide profiles of tumors obtained using functional genomics platforms are being deposited to the public repositories at an astronomical scale, as a result of focused efforts by individual laboratories and large projects such as the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium. Consequently, there is an urgent need for reliable tools that integrate and interpret these data in light of current knowledge and disseminate results to biomedical researchers in a user-friendly manner. We have built the canEvolve web portal to meet this need. Results: canEvolve query functionalities are designed to fulfill most frequent analysis needs of cancer researchers with a view to generate novel hypotheses. canEvolve stores gene, microRNA (miRNA) and protein expression profiles, copy number alterations for multiple cancer types, and protein-protein interaction information. canEvolve allows querying of results of primary analysis, integrative analysis and network analysis of oncogenomics data. The querying for primary analysis includes differential gene and miRNA expression as well as changes in gene copy number measured with SNP microarrays. canEvolve provides results of integrative analysis of gene expression profiles with copy number alterations and with miRNA profiles as well as generalized integrative analysis using gene set enrichment analysis. The network analysis capability includes storage and visualization of gene co-expression, inferred gene regulatory networks and protein-protein interaction information. Finally, canEvolve provides correlations between gene expression and clinical outcomes in terms of univariate survival analysis. Conclusion: At present canEvolve provides different types of information extracted from 90 cancer genomics studies comprising of more than 10,000 patients. The presence of multiple data types, novel integrative analysis for identifying regulators of oncogenesis, network analysis and ability to query gene lists/pathways are distinctive features of canEvolve. canEvolve will facilitate integrative and meta-analysis of oncogenomics datasets. C1 [Samur, Mehmet Kemal; Yan, Zhenyu; Li, Cheng; Shah, Parantu K.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Samur, Mehmet Kemal; Yan, Zhenyu; Li, Cheng; Shah, Parantu K.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Samur, Mehmet Kemal] Akdeniz Univ, Dept Biostat & Med Informat, TR-07058 Antalya, Turkey. [Wang, Xujun] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. [Cao, Qingyi] Zhejiang Univ, Sch Med, Affiliated Hosp 1, State Key Lab Diag & Treatment Infect Dis, Hangzhou 310003, Zhejiang, Peoples R China. [Munshi, Nikhil C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Munshi, Nikhil C.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. RP Li, C (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM cli@hsph.harvard.edu; parantu.shah@gmail.com FU National Institutes of Health (NIH) [R01 GM077122]; Claudia Adams Barr Program in Innovative Basic Cancer Research; Multiple Myeloma Career Development award; National Basic Research [973] Program of China [2010CB944904]; Department of Veterans Affairs Merit Review Awards [NIH RO1-124929, PO1-155258, P50-100007, PO1-78378] FX This work was supported by National Institutes of Health (NIH) R01 GM077122 (C.L.), the Claudia Adams Barr Program in Innovative Basic Cancer Research (P.K.S.), the Multiple Myeloma Career Development award (P.K.S.) and National Basic Research [973] Program of China No. 2010CB944904 (X.W.) This work was also supported in part by NIH RO1-124929, PO1-155258, P50-100007 and PO1-78378 to N.C.M. and C.L. and from the Department of Veterans Affairs Merit Review Awards to N.C.M. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 10 Z9 12 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 13 PY 2013 VL 8 IS 2 AR e56228 DI 10.1371/journal.pone.0056228 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 104DM UT WOS:000315970300132 PM 23418540 ER PT J AU Wu, XQ Marmarelis, ME Hodi, FS AF Wu, Xinqi Marmarelis, Melina E. Hodi, F. Stephen TI Activity of the Heat Shock Protein 90 Inhibitor Ganetespib in Melanoma SO PLOS ONE LA English DT Article ID CELL-CYCLE ARREST; HSP90 INHIBITOR; METASTATIC MELANOMA; CANCER-CELLS; B-RAF; ACQUIRED-RESISTANCE; SIGNAL-TRANSDUCTION; BRAF INHIBITION; KINASE CASCADE; IN-VITRO AB Heat shock protein 90 (HSP90) is involved in the regulation of diverse biological processes such as cell signaling, proliferation and survival, and has been recently recognized as a potential target for cancer therapy. Ganetespib is a potent ATP competitive inhibitor of HSP90. Ganetespib downregulated the expression of multiple signal transducing molecules including EGFR, IGF-1R, c-Met, Akt, B-RAF and C- RAF, resulting in pronounced decrease in phosphorylation of Akt and Erk1/2 in a panel of five cutaneous melanoma cell lines including those harboring B-RAF and N-RAS mutations. Ganetespib exhibited potent antiproliferative activity on all five of these cell lines, with IC50 values between 37.5 and 84 nM. Importantly, Ganetespib is active on B-RAF mutated melanoma cells that have acquired resistance to B-RAF inhibition. Ganetespib induced apoptosis and cell cycle arrest at G1 and/or G2/M phase. Ganetespib induced cell cycle arrest was accompanied by altered expression of cyclin-dependent kinase inhibitor (CDKI) p21(Cip1) and p27(Kip1), cyclins B1, D1 and E, and/or cyclin-dependent kinases 1, 2 and 4. HSP90 is functionally important for melanoma cells and HSP90 inhibitors such as ganetespib could potentially be effective therapeutics for melanoma with various genetic mutations and acquired resistance to B-RAF inhibition. C1 [Wu, Xinqi; Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wu, Xinqi; Marmarelis, Melina E.; Hodi, F. Stephen] Harvard Univ, Sch Med, Boston, MA USA. [Wu, Xinqi; Hodi, F. Stephen] Dana Farber Brigham & Womens Canc Ctr, Melanoma Dis Ctr, Boston, MA USA. RP Hodi, FS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM stephen_hodi@dfci.harvard.edu FU Sharon Crowley Martin Memorial Fund for Melanoma Research at Dana-Farber Cancer Institute; Malcolm and Emily Mac Naught Fund for Melanoma Research at Dana-Farber Cancer Institute FX This work was supported in part by Sharon Crowley Martin Memorial Fund for Melanoma Research (F. S. Hodi), the Malcolm and Emily Mac Naught Fund for Melanoma Research (F. S. Hodi) at Dana-Farber Cancer Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 62 TC 17 Z9 17 U1 2 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 13 PY 2013 VL 8 IS 2 AR e56134 DI 10.1371/journal.pone.0056134 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 104DM UT WOS:000315970300115 PM 23418523 ER PT J AU Harrison, WJ Mattingley, JB Remington, RW AF Harrison, William J. Mattingley, Jason B. Remington, Roger W. TI Eye Movement Targets Are Released from Visual Crowding SO JOURNAL OF NEUROSCIENCE LA English DT Article ID COVERT SPATIAL ATTENTION; OBJECT RECOGNITION; PSYCHOPHYSICS TOOLBOX; ENHANCEMENT; VISION; FIELD; MICROSTIMULATION; SENSITIVITY; RESPONSES; SELECTION AB Our ability to recognize objects in peripheral vision is impaired when other objects are nearby (Bouma, 1970). This phenomenon, known as crowding, is often linked to interactions in early visual processing that depend primarily on the retinal position of visual stimuli (Pelli, 2008; Pelli and Tillman, 2008). Here we tested a new account that suggests crowding is influenced by spatial information derived from an extraretinal signal involved in eye movement preparation. We had human observers execute eye movements to crowded targets and measured their ability to identify those targets just before the eyes began to move. Beginning similar to 50 ms before a saccade toward a crowded object, we found that not only was there a dramatic reduction in the magnitude of crowding, but the spatial area with in which crowding occurred was almost halved. These changes in crowding occurred despite no change in the retinal position of target or flanking stimuli. Contrary to the notion that crowding depends on retinal signals alone, our findings reveal an important role for eye movement signals. Eye movement preparation effectively enhances object discrimination in peripheral vision at the goal of the intended saccade. These presaccadic changes may enable enhanced recognition of visual objects in the periphery during active search of visually cluttered environments. C1 [Harrison, William J.; Mattingley, Jason B.; Remington, Roger W.] Univ Queensland, Sch Psychol, St Lucia, Qld 4072, Australia. [Mattingley, Jason B.] Univ Queensland, Queensland Brain Inst, St Lucia, Qld 4072, Australia. RP Harrison, WJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA 02114 USA. EM willjharri@gmail.com RI Mattingley, Jason/J-1537-2014; OI Mattingley, Jason/0000-0003-0929-9216; Harrison, William/0000-0002-6408-0359 FU Australian Research Council (ARC) Discovery Project [DP0666772]; ARC Australian Laureate Fellowship [FL110100103] FX This research was supported by an Australian Research Council (ARC) Discovery Project awarded to R. W. R. and J.B.M. (DP0666772). J.B.M. was also supported by an ARC Australian Laureate Fellowship (FL110100103). Parts of these data were presented at the Australasian Experimental Psychology Conference in April, 2012. We thank T. S. A. Wallis for his assistance with analysis of data for Experiment 2. NR 41 TC 30 Z9 31 U1 2 U2 27 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD FEB 13 PY 2013 VL 33 IS 7 BP 2927 EP 2933 DI 10.1523/JNEUROSCI.4172-12.2013 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 089CQ UT WOS:000314887200019 PM 23407951 ER PT J AU Liu, YY Slotine, JJ Barabasi, AL AF Liu, Yang-Yu Slotine, Jean-Jacques Barabasi, Albert-Laszlo TI Observability of complex systems SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE algebraic observability; biochemical reactions; control theory ID NETWORKS; CONTROLLABILITY AB A quantitative description of a complex system is inherently limited by our ability to estimate the system's internal state from experimentally accessible outputs. Although the simultaneous measurement of all internal variables, like all metabolite concentrations in a cell, offers a complete description of a system's state, in practice experimental access is limited to only a subset of variables, or sensors. A system is called observable if we can reconstruct the system's complete internal state from its outputs. Here, we adopt a graphical approach derived from the dynamical laws that govern a system to determine the sensors that are necessary to reconstruct the full internal state of a complex system. We apply this approach to biochemical reaction systems, finding that the identified sensors are not only necessary but also sufficient for observability. The developed approach can also identify the optimal sensors for target or partial observability, helping us reconstruct selected state variables from appropriately chosen outputs, a prerequisite for optimal biomarker design. Given the fundamental role observability plays in complex systems, these results offer avenues to systematically explore the dynamics of a wide range of natural, technological and socioeconomic systems. C1 [Liu, Yang-Yu; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. [Liu, Yang-Yu; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Liu, Yang-Yu; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Comp Sci, Boston, MA 02115 USA. [Liu, Yang-Yu; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Biol, Boston, MA 02115 USA. [Liu, Yang-Yu; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Slotine, Jean-Jacques] MIT, Nonlinear Syst Lab, Cambridge, MA 02138 USA. [Slotine, Jean-Jacques] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Slotine, Jean-Jacques] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Barabasi, Albert-Laszlo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Barabasi, AL (reprint author), Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. EM alb@neu.edu RI Liu, Yang-Yu/G-8885-2011 OI Liu, Yang-Yu/0000-0003-2728-4907 FU Network Science Collaborative Technology Alliance; US Army Research Laboratory [W911NF-09-2-0053]; Defense Advanced Research Projects Agency [11645021]; Defense Threat Reduction Agency [WMD BRBAA07-J-2-0035] FX We thank J. Loscalzo, A. Sedoglavic, R. Albert, J. Faeder, J. Baranyi, A. Sharma, G. Basler, P.-J. Kim, Y.-Y. Ahn, C. Song, T. Jia, B. Barzel, and Y. Li for discussions. This work was supported by the Network Science Collaborative Technology Alliance sponsored by the US Army Research Laboratory under Agreement W911NF-09-2-0053; the Defense Advanced Research Projects Agency under Agreement 11645021; the Defense Threat Reduction Agency Award WMD BRBAA07-J-2-0035; and the generous support of Lockheed Martin. NR 32 TC 107 Z9 112 U1 5 U2 99 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 12 PY 2013 VL 110 IS 7 BP 2460 EP 2465 DI 10.1073/pnas.1215508110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 101ZL UT WOS:000315812800024 PM 23359701 ER PT J AU Kohli, P Wallentin, L Reyes, E Horrow, J Husted, S Angiolillo, DJ Ardissino, D Maurer, G Morais, J Nicolau, JC Oto, A Storey, RF James, SK Cannon, CP AF Kohli, Payal Wallentin, Lars Reyes, Eric Horrow, Jay Husted, Steen Angiolillo, Dominick J. Ardissino, Diego Maurer, Gerald Morais, Joao Nicolau, Jose C. Oto, Ali Storey, Robert F. James, Stefan K. Cannon, Christopher P. TI Reduction in First and Recurrent Cardiovascular Events With Ticagrelor Compared With Clopidogrel in the PLATO Study SO CIRCULATION LA English DT Article DE antiplatelet agents; outcomes assessment ID ACUTE CORONARY SYNDROMES; TRITON-TIMI 38; MYOCARDIAL-INFARCTION; COST-EFFECTIVENESS; STATIN THERAPY; TRIAL; THROMBOLYSIS; INSIGHTS; STRATEGY; DISEASE AB Background-We sought to evaluate the effect of potent platelet inhibition after acute coronary syndrome on total (ie, first and recurrent) occurrences of any of the primary outcome events (eg, cardiovascular death, myocardial infarction, and stroke) as well as on other ischemic events, such as urgent revascularization, (severe) recurrent ischemia, transient ischemic attacks, and arterial thrombotic events. Methods and Results-In the PLATelet inhibition and patient Outcomes (PLATO) study, 18 624 patients presenting with acute coronary syndromes randomly received ticagrelor (n=9333) or clopidogrel (n=9291). Cox proportional hazard models were used to calculate time to first event and hazard ratios. Total events were compared using a Poisson regression model, and time to second event or death was calculated with the Wei Lin Weissfeld method. Patients randomized to ticagrelor had 1057 total primary end point events versus 1225 for patients on clopidogrel (rate ratio, 0.86; 95% confidence interval, 0.79-0.93; P=0.003). The number of additional events was numerically lower for ticagrelor (189 versus 205; P=0.40), resulting in a hazard for time to second event/death of 0.80 (95% confidence interval, 0.70-0.90; P<0.001) and a number needed to treat of 54. For cardiovascular death/myocardial infarction/stroke/(severe) recurrent ischemia/transient ischemic attack/arterial thrombotic events, total events were fewer with ticagrelor (2030 versus 2290; rate ratio, 0.88; 95% confidence interval, 0.82-0.95; P<0.001), with fewer recurrent events with ticagrelor (740 versus 834; P=0.01) and a highly significant concurrent reduction in hazard for time to second event or death of 0.83 (95% confidence interval, 0.75-0.91; P<0.001). Recurrent PLATO major or Thrombolysis in Myocardial Infarction (TIMI) major non-coronary artery bypass graft bleeding events were infrequent and not different between the two therapies (P=0.96 and 0.38, respectively). Conclusions-In PLATO, treatment with ticagrelor compared with clopidogrel resulted in a reduction in total events, including first and subsequent recurrent cardiovascular events, when compared with clopidogrel. These types of analyses demonstrate an even greater absolute benefit of ticagrelor over clopidogrel than previously reported. C1 [Kohli, Payal; Cannon, Christopher P.] Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. [Kohli, Payal; Cannon, Christopher P.] Harvard Univ, Sch Med, Boston, MA USA. [Kohli, Payal] Univ Calif San Francisco, Div Cardiol, San Francisco, CA USA. [Wallentin, Lars] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Wallentin, Lars] Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden. [Reyes, Eric] Duke Clin Res Inst, Durham, NC USA. [Horrow, Jay] AstraZeneca R&D, Wilmington, DE USA. [Husted, Steen] Arhus Univ Hosp, Dept Cardiol, Aarhus, Denmark. [Angiolillo, Dominick J.] Univ Florida, Coll Med, Div Cardiovasc, Jacksonville, FL USA. [Ardissino, Diego] Azienda Osped Univ Parma, Parma, Italy. [Maurer, Gerald] Med Univ Vienna, Div Cardiol, Vienna, Austria. [Morais, Joao] Santo Andres Hosp, Leiria, Portugal. [Nicolau, Jose C.] Univ Sao Paulo, Sch Med, Inst Heart, Sao Paulo, Brazil. [Oto, Ali] Hacettepe Univ, Fac Med, TR-06100 Ankara, Turkey. [James, Stefan K.] Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England. RP Cannon, CP (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM cpcannon@partners.org RI Nicolau, Jose/E-1487-2012 FU AstraZeneca [NCT00391872]; AstraZeneca; Merck/Schering-Plow; Boehringer-Ingelheim; Bristol-Myers Squibb/Pfizer; GlaxoSmithKline; Schering-Plow; Bristol-Myers Squibb; Bayer; Bristol Myers Squibb; Sanofi-Aventis; Eli Lilly Co; Daiichi Sankyo, Inc; Medicines Company; Portola; Novartis; Medicure; Accumetrics; Arena Pharmaceuticals; Astra Zeneca; Merck; Evolva; Abbott Vascular; Otsuka; Daiichi Sankyo Inc; Eisai; CSL Parexel; Roche; MSD; Eli-Lilly/Daiichi Sankyo; Sanofi; Eli Lilly/Daiichi Sankyo; Essentialis; Regeneron; Takeda FX The PLATO trial (NCT00391872) was funded by AstraZeneca.; Dr Kohli reports honoraria from serving on an advisory board for Daiichi-Sankyo. Dr Wallentin reports research grants from AstraZeneca, Merck/Schering-Plow, Boehringer-Ingelheim, Bristol-Myers Squibb/Pfizer, and GlaxoSmithKline; being a consultant for Merck/Schering-Plow, Regado Biosciences, Evolva, Protola, C. S. L. Behring, Athera Biotechnologies, Boehringer-Ingelheim, AstraZeneca, GlaxoSmithKline, and Bristol-Myers Squibb/Pfizer; lecture fees from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb/Pfizer, GlaxoSmithKline, Schering-Plow; and honoraria from Boehringer Ingelheim, AstraZeneca, Bristol-Myers Squibb/Pfizer, GlaxoSmithKline, and Schering-Plow/Merck. Dr Horrow is an employee of AstraZeneca and has equity ownership in AstraZeneca. Dr Husted reports receiving advisory board fees from AstraZeneca, Bristol-Myers Squibb, and Bayer. Dr Angiolillo has received honoraria for lectures from Bristol Myers Squibb, Sanofi-Aventis, Eli Lilly Co, Daiichi Sankyo Inc, Astra Zeneca; and consulting fees from Bristol Myers Squibb, Sanofi-Aventis, Eli Lilly Co, Daiichi Sankyo, Inc, The Medicines Company, Portola, Novartis, Medicure, Accumetrics, Arena Pharmaceuticals, Astra Zeneca, Merck, Evolva, and Abbott Vascular; and research nd grants paid to Institution from Bristol Myers Squibb, Sanofi-Aventis, GlaxoSmithKline, Otsuka, Eli Lilly Co, Daiichi Sankyo Inc, The Medicines Company, Portola, Accumetrics, Schering-Plow, AstraZeneca, Eisai, CSL Parexel. Dr Maurer reports receiving advisory board fees from AstraZeneca, Merck, Boehringer-Ingelheim, Roche, and Bayer. Dr Morais has received payments from speakers' bureau from AstraZeneca, Bayer, and MSD; honoraria from AstraZeneca, Bayer, JABA Recordati, and MSD. Dr Nicolau reports receiving research grants and honoraria from AstraZeneca, Eli-Lilly/Daiichi Sankyo, Sanofi, MSD, and Bayer. Dr Oto reports receiving honoraria from AstraZeneca, Bristol-Myers Squibb, Servier, and serving as an advisory board member for MSD. Dr Storey reports having research grants from AstraZeneca, Eli Lilly/Daiichi Sankyo, and Merck; receiving research support from Accumetrics; and honoraria from AstraZeneca, Eli Lilly/Daiichi Sankyo, Merck, Novartis, The Medicines Company, Iroko, Sanofi-Aventis/BMS, GlaxoSmithKline, Accumetrics, Medscape, and Eisai; he also reports receiving consultancy fees from AstraZeneca, Merck, Novartis, Accumetrics, and Eisai. Dr James reports receiving institutional research grant and honoraria from AstraZeneca, Eli Lilly, Merck, and Bristol-Myers Squibb and being an advisory board member for AstraZeneca, Eli Lilly, and Merck. He also has received honoraria from The Medicines Company. Dr Cannon reports having research grants/support: Accumetrics, AstraZeneca, Essentialis, GlaxoSmithKline, Merck, Regeneron, Sanofi, Takeda. He also has served on advisory boards for Alnylam, Bristol-Myers Squibb, CSL Behring, and Pfizer, but all funds are donated to charity. He is a clinical Advisor, and holds equity in Automedics Medical Systems. NR 12 TC 33 Z9 34 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 FEB 12 PY 2013 VL 127 IS 6 BP 673 EP + DI 10.1161/CIRCULATIONAHA.112.124248 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 088XR UT WOS:000314871700011 PM 23277305 ER PT J AU Bangalore, S Fusaro, M Amoroso, N Attubato, MJ Feit, F Slater, J Kumar, S Bhatt, DL AF Bangalore, Sripal Fusaro, Mario Amoroso, Nicholas Attubato, Michael J. Feit, Frederick Slater, James Kumar, Sunil Bhatt, Deepak L. TI Response to Letter Regarding Article, "Short- and Long-Term Outcomes With Drug-Eluting and Bare-Metal Coronary Stents: A Mixed-Treatment Comparison Analysis of 117 762 Patient-years of Follow-up From Randomized Trials" SO CIRCULATION LA English DT Letter C1 [Bangalore, Sripal; Fusaro, Mario; Amoroso, Nicholas; Attubato, Michael J.; Feit, Frederick; Slater, James] NYU, Sch Med, New York, NY 10003 USA. [Kumar, Sunil] Univ Nebraska, Omaha, NE 68182 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. RP Bangalore, S (reprint author), NYU, Sch Med, New York, NY 10003 USA. OI Bangalore, Sripal/0000-0001-9485-0652 NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 12 PY 2013 VL 127 IS 6 BP E447 EP E447 DI 10.1161/CIRCULATIONAHA.112.145169 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 088XR UT WOS:000314871700003 PM 23534060 ER PT J AU Patel, MR Hellkamp, AS Lokhnygina, Y Piccini, JP Zhang, ZX Mohanty, S Singer, DE Hacke, W Breithardt, G Halperin, JL Hankey, GJ Becker, RC Nessel, CC Berkowitz, SD Califf, RM Fox, KAA Mahaffey, KW AF Patel, Manesh R. Hellkamp, Anne S. Lokhnygina, Yuliya Piccini, Jonathan P. Zhang, Zhongxin Mohanty, Surya Singer, Daniel E. Hacke, Werner Breithardt, Guenter Halperin, Jonathan L. Hankey, Graeme J. Becker, Richard C. Nessel, Christopher C. Berkowitz, Scott D. Califf, Robert M. Fox, Keith A. A. Mahaffey, Kenneth W. TI Outcomes of Discontinuing Rivaroxaban Compared With Warfarin in Patients With Nonvalvular Atrial Fibrillation Analysis From the ROCKET AF Trial (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE atrial fibrillation; factor Xa; rivaroxaban; stroke; warfarin ID THERAPY AB Objectives The purpose of this study was to understand the possible risk of discontinuation in the context of clinical care. Background Rivaroxaban is noninferior to warfarin for preventing stroke in atrial fibrillation patients. Concerns exist regarding possible increased risk of stroke and non-central nervous system (CNS) thromboembolic events early after discontinuation of rivaroxaban. Methods We undertook a post-hoc analysis of data from the ROCKET AF (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation, n = 14,624) for stroke or non-CNS embolism within 30 days after temporary interruptions of 3 days or more, early permanent study drug discontinuation, and end-of-study transition to open-label therapy. Results Stroke and non-CNS embolism occurred at similar rates after temporary interruptions (rivaroxaban: n = 9, warfarin: n = 8, 6.20 vs. 5.05/100 patient-years, hazard ratio [HR]: 1.28, 95% confidence interval [CI]: 0.49 to 3.31, p = 0.62) and after early permanent discontinuation (rivaroxaban: n = 42, warfarin: n = 36, 25.60 vs. 23.28/100 patient-years, HR: 1.10, 95% CI: 0.71 to 1.72, p = 0.66). Patients transitioning to open-label therapy at the end of the study had more strokes with rivaroxaban (n = 22) versus warfarin (n = 6, 6.42 vs. 1.73/100 patient-years, HR: 3.72, 95% CI: 1.51 to 9.16, p = 0.0044) and took longer to reach a therapeutic international normalized ratio with rivaroxaban versus warfarin. All thrombotic events within 30 days of any study drug cessation (including stroke, non-CNS embolism, myocardial infarction, and vascular death) were similar between groups (HR: 1.02, 95% CI: 0.83 to 1.26, p = 0.85). Conclusions In atrial fibrillation patients who temporarily or permanently discontinued anticoagulation, the risk of stroke or non-CNS embolism was similar with rivaroxaban or warfarin. An increased risk of stroke and non-CNS embolism was observed in rivaroxaban-treated patients compared with warfarin-treated patients after the end of the study, underscoring the importance of therapeutic anticoagulation coverage during such a transition. (J Am Coll Cardiol 2013;61:651-8) (C) 2013 by the American College of Cardiology Foundation C1 [Patel, Manesh R.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Piccini, Jonathan P.; Becker, Richard C.; Mahaffey, Kenneth W.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27705 USA. [Zhang, Zhongxin; Mohanty, Surya; Nessel, Christopher C.] Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Div Gen Med, Clin Epidemiol Unit, Boston, MA 02114 USA. [Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Hacke, Werner] Heidelberg Univ, Dept Neurol, Heidelberg, Germany. [Breithardt, Guenter] Hosp Univ Munster, Dept Cardiol & Angiol, Munster, Germany. [Halperin, Jonathan L.] Mt Sinai Med Ctr, Cardiovasc Inst, New York, NY 10029 USA. [Hankey, Graeme J.] Royal Perth Hosp, Dept Neurol, Perth, WA, Australia. [Berkowitz, Scott D.] Bayer HealthCare Pharmaceut, Montville, NJ USA. [Califf, Robert M.] Duke Univ, Med Ctr, Duke Translat Med Inst, Durham, NC USA. [Fox, Keith A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland. RP Patel, MR (reprint author), Duke Univ, Med Ctr, Dept Med, Duke Clin Res Inst, Room 0311 Terrace Level,2400 Pratt St, Durham, NC 27705 USA. EM manesh.patel@duke.edu RI Hankey, Graeme /H-4968-2014 OI Hankey, Graeme /0000-0002-6044-7328 FU Johnson & Johnson Pharmaceutical Research & Development, Raritan, New Jersey; Bayer HealthCare AG, Leverkusen, Germany; Astra Zeneca; Johnson Johnson; Janssen Pharmaceuticals; BI; Boehringer Ingelheim; Bayer Health Care; Bristol-Myers Squibb; Sanofi-Aventis; Bayer Pharmaceuticals; Bayer; Lilly; Boehringer; AstraZeneca; Bristol Myers-Squibb; Daiichi Sankyo; Eli Lilly; GlaxoSmithKline; Merck; Novartis; Sanofi; Pfizer; Polymedix; Pozen; Regado; Schering-Plough; Medicines Company FX The ROCKET AF study was sponsored by Johnson & Johnson Pharmaceutical Research & Development, Raritan, New Jersey, and Bayer HealthCare AG, Leverkusen, Germany. Dr. Patel is on the advisory board of and consulting to Baxter, Bayer Healthcare, Otsuka, CSI, Volcano, and Jansen, and receiving research grants from Astra Zeneca and Johnson & Johnson. Dr. Lokhnygina is a consultant to Johnson & Johnson and Bayer. Dr. Piccini reports that his institution receiving a research grant from Janssen Pharmaceuticals and consulting to Janssen Pharmaceuticals, Forest Research Laboratories, Medtronic, and Titan Pharmaceuticals. Dr. Mohanty is an employee of Johnson & Johnson. Dr. Singer is a consultant to Johnson & Johnson, Bayer Healthcare, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Inc., Pfizer, and CSL Behring; has received research support from Johnson & Johnson; and participating in the executive committee of a trial sponsored by Johnson & Johnson. Dr. Hacke has received honoraria, consulting to, and speaking to Boehringer Ingelheim, Bayer, and Photo-thera and receiving an unrestricted grant from BI. Dr. Breithardt is a member of scientific advisory boards of Bayer Health Care, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Otsuka Pharma, Sanofi-Aventis, and MSD and receiving fees for lectures at symposia organized by Boehringer Ingelheim, Bayer Health Care, Bristol-Myers Squibb, and Sanofi-Aventis. Dr. Halperin is a consultant to Johnson & Johnson and Bayer Healthcare. Dr. Hankey is a member of the executive committee of the ROCKET AF I study, receiving honoraria from Duke, and receiving clinical research support from the study sponsors, Bayer Pharmaceuticals and Johnson & Johnson. Dr. Becker has received research support and acting as a scientific advisor to Bayer, and Johnson & Johnson. Dr. Nessel is an employee of Johnson & Johnson. Dr. Berkowitz is an employee of Bayer HealthCare Pharmaceuticals. Dr. Califf has received research grants and consulting from Bayer and Johnson & Johnson. Dr. Fox has received research grants from Bayer, Johnson & Johnson, and Lilly; receiving hononaria and being a speaker for Bayer, Johnson & Johnson, Sanofi Aventis, and Astra Zeneca; and receiving a travel grant from Boehringer. Dr. Mahaffey has relationships with AstraZeneca, Bayer, Boehringer Ingleheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Glaxo Smith Kline, Johnson & Johnson, Merck, Novartis, Pfizer, Polymedix, Pozen, Regado Biotechnologies, Sanofi, Schering-Plough, and The Medicines Company; has received consulting fees and research grants from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers-Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, Merck, Novartis, and Sanofi; and consulting fees from: Pfizer and Polymedix; and grant support from: Pozen, Regado, Schering-Plough, and The Medicines Company. NR 10 TC 75 Z9 76 U1 0 U2 36 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 12 PY 2013 VL 61 IS 6 BP 651 EP 658 DI 10.1016/j.jacc.2012.09.057 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086CM UT WOS:000314660700010 PM 23391196 ER PT J AU Reynolds, MR AF Reynolds, Matthew R. TI Discontinuation of Rivaroxaban Filling in the Gaps SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID NONVALVULAR ATRIAL-FIBRILLATION; WARFARIN; METAANALYSIS; THERAPY C1 VA Boston Healthcare Syst, Harvard Clin Res Inst, Boston, MA 02215 USA. RP Reynolds, MR (reprint author), VA Boston Healthcare Syst, Harvard Clin Res Inst, 930-W Commonwealth Ave, Boston, MA 02215 USA. EM mreynold@bidmc.harvard.edu NR 8 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 12 PY 2013 VL 61 IS 6 BP 659 EP 660 DI 10.1016/j.jacc.2012.09.056 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086CM UT WOS:000314660700011 PM 23391197 ER PT J AU Albers, M Yan, S Kelly, K Albers, A AF Albers, Mark Yan, Sandra Kelly, Kathleen Albers, Alefiya TI Deficits in Episodic Memory of Olfactory Percepts as a Potential Biomarker for Preclinical Alzheimer's Disease SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Albers, Mark; Yan, Sandra; Kelly, Kathleen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Albers, Alefiya] Endicott Coll, Beverly, MA 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P03081 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068602050 ER PT J AU Ali, S Singhal, A Rost, N Schwamm, L AF Ali, Syed Singhal, Aneesh Rost, Natalia Schwamm, Lee TI Characteristics and Outcomes among Acute Ischemic Stroke Patients Arriving to the Hospital Via the "Front Door" vs. Transfer from Another Acute Care Hospital SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Ali, Syed] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Singhal, Aneesh; Rost, Natalia; Schwamm, Lee] 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA S49006 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068606255 ER PT J AU Ali, S Cohen, A Viswanathan, A Feske, S Rost, N Silverman, S Anderson, C Schwamm, L AF Ali, Syed Cohen, Adam Viswanathan, Anand Feske, Steven Rost, Natalia Silverman, Scott Anderson, Christopher Schwamm, Lee TI Separating Acute Stroke from Stroke Mimics in a TeleStroke Network: Differential Patient Characteristics and Exam Findings SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Ali, Syed] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Cohen, Adam; Viswanathan, Anand; Rost, Natalia; Silverman, Scott; Anderson, Christopher; Schwamm, Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Feske, Steven] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P07241 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068605223 ER PT J AU Ali, S Singhal, A Rost, N Schwamm, L AF Ali, Syed Singhal, Aneesh Rost, Natalia Schwamm, Lee TI Characteristics and Outcomes among Acute Ischemic Stroke Patients Arriving to the Hospital Via the "Front Door" vs. Transfer from Another Acute Care Hospital SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Ali, Syed] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Singhal, Aneesh; Rost, Natalia; Schwamm, Lee] 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA IN71003 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068600089 ER PT J AU Anderson, C Biffi, A Nalls, M Devan, W Schwab, K Ayres, A Valant, V Ross, O Rost, N Saxena, R Viswanathan, A Worrall, B Brott, T Goldstein, J Brown, D Broderick, J Norrving, B Greenberg, S Silliman, S Hansen, B Tirschwell, D Lindgren, A Slowik, A Schmidt, R Selim, M Gonzalez, JR Montaner, J Singleton, A Kidwell, C Woo, D Furie, K Meschia, J Rosand, J AF Anderson, Christopher Biffi, Alessandro Nalls, Michael Devan, William Schwab, Kristin Ayres, Alison Valant, Valerie Ross, Owen Rost, Natalia Saxena, Richa Viswanathan, Anand Worrall, Bradford Brott, Thomas Goldstein, Joshua Brown, Devin Broderick, Joseph Norrving, Bo Greenberg, Steven Silliman, Scott Hansen, Bjorn Tirschwell, David Lindgren, Arne Slowik, Agnieszka Schmidt, Reinhold Selim, Magdy Roquer Gonzalez, Jaume Montaner, Joan Singleton, Andrew Kidwell, Chelsea Woo, Daniel Furie, Karen Meschia, James Rosand, Jonathan TI Common Variants within Oxidative Phosphorylation Genes Influence Risk of Ischemic Stroke and Intracerebral Hemorrhage SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Anderson, Christopher; Biffi, Alessandro; Devan, William; Schwab, Kristin; Ayres, Alison; Valant, Valerie; Rost, Natalia; Saxena, Richa; Viswanathan, Anand; Goldstein, Joshua; Greenberg, Steven; Rosand, Jonathan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nalls, Michael; Singleton, Andrew] NIA, Bethesda, MD 20892 USA. [Ross, Owen; Brott, Thomas; Meschia, James] Mayo Clin, Jacksonville, FL 32224 USA. [Worrall, Bradford] Univ Virginia, Charlottesville, VA USA. [Brown, Devin] Univ Michigan, Ann Arbor, MI 48109 USA. [Broderick, Joseph; Woo, Daniel] Univ Cincinnati, Cincinnati, OH USA. [Norrving, Bo; Hansen, Bjorn; Lindgren, Arne] Lund Univ, Lund, Sweden. [Silliman, Scott] Univ Florida, Jacksonville, FL USA. [Tirschwell, David] Univ Washington, Seattle, WA 98195 USA. [Slowik, Agnieszka] Jagiellonian Univ, Krakow, Poland. [Schmidt, Reinhold] Graz Univ, St Radegund, Austria. [Selim, Magdy] BIDMC, Boston, MA USA. [Roquer Gonzalez, Jaume] Hosp del Mar, Barcelona, Spain. [Montaner, Joan] Univ Vall Dhebron, Barcelona, Spain. [Kidwell, Chelsea] Georgetown Univ, Washington, DC USA. [Furie, Karen] Brown Univ, Providence, RI 02912 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA S42002 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068606203 ER PT J AU Anderson, C Biffi, A Nalls, M Devan, W Schwab, K Ayres, A Valant, V Ross, O Rost, N Saxena, R Viswanathan, A Worrall, B Brott, T Goldstein, J Brown, D Broderick, J Norrving, B Greenberg, S Silliman, S Hansen, B Tirschwell, D Lindgren, A Slowik, A Schmidt, R Selim, M Gonzalez, JR Montaner, J Singleton, A Kidwell, C Woo, D Furie, K Meschia, J Rosand, J AF Anderson, Christopher Biffi, Alessandro Nalls, Michael Devan, William Schwab, Kristin Ayres, Alison Valant, Valerie Ross, Owen Rost, Natalia Saxena, Richa Viswanathan, Anand Worrall, Bradford Brott, Thomas Goldstein, Joshua Brown, Devin Broderick, Joseph Norrving, Bo Greenberg, Steven Silliman, Scott Hansen, Bjorn Tirschwell, David Lindgren, Arne Slowik, Agnieszka Schmidt, Reinhold Selim, Magdy Roquer Gonzalez, Jaume Montaner, Joan Singleton, Andrew Kidwell, Chelsea Woo, Daniel Furie, Karen Meschia, James Rosand, Jonathan TI Common Variants within Oxidative Phosphorylation Genes Influence Risk of Ischemic Stroke and Intracerebral Hemorrhage SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Anderson, Christopher; Biffi, Alessandro; Devan, William; Schwab, Kristin; Ayres, Alison; Valant, Valerie; Rost, Natalia; Saxena, Richa; Viswanathan, Anand; Goldstein, Joshua; Greenberg, Steven; Rosand, Jonathan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nalls, Michael] NIA, Bethesda, MD 20892 USA. [Ross, Owen; Brott, Thomas; Meschia, James] Mayo Clin, Jacksonville, FL 32224 USA. [Worrall, Bradford] Univ Virginia, Charlottesville, VA USA. [Brown, Devin] Univ Michigan, Ann Arbor, MI 48109 USA. [Broderick, Joseph; Woo, Daniel] Univ Cincinnati, Cincinnati, OH USA. [Norrving, Bo; Hansen, Bjorn; Lindgren, Arne] Lund Univ, Lund, Sweden. [Silliman, Scott] Univ Florida, Jacksonville, FL USA. [Tirschwell, David] Univ Washington, Seattle, WA 98195 USA. [Slowik, Agnieszka] Jagiellonian Univ, Krakow, Poland. [Schmidt, Reinhold] Graz Univ, St Radegund, Austria. [Selim, Magdy] BIDMC, Boston, MA USA. [Roquer Gonzalez, Jaume] Hosp del Mar, Barcelona, Spain. [Montaner, Joan] Univ Vall Dhebron, Barcelona, Spain. [Kidwell, Chelsea] Georgetown Univ, Washington, DC USA. [Furie, Karen] Brown Univ, Providence, RI 02912 USA. RI Montaner, Joan/D-3063-2015; IBIS, NEUROVASCULAR/O-1855-2015 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA IN71001 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068600087 ER PT J AU Ay, H Arsava, EM Brown, R Kittner, S McArdle, P Rosand, J Rundek, T Worrall, B Woo, D Arnett, D Rexrode, K Smoller, S Grewal, R Sacco, R Cole, J Slowik, A Lindgren, A Jimenez-Conde, J Jern, C Thijs, V Schmidt, R Sharma, P Rothwell, P Dichgans, M Lee, JM Sudlow, C Marcus, H Fornage, M Rich, S deBaker, P Mitchell, B Meschia, J AF Ay, Hakan Arsava, Ethem Murat Brown, Robert Kittner, Steven McArdle, Patrick Rosand, Jonathan Rundek, Tatjana Worrall, Bradford Woo, Daniel Arnett, Donna Rexrode, Kathryn Smoller, Sylvia Grewal, Raji Sacco, Ralph Cole, John Slowik, Agnieszka Lindgren, Arne Jimenez-Conde, Jordi Jern, Christina Thijs, Vincent Schmidt, Reinhold Sharma, Pankja Rothwell, Peter Dichgans, Martin Lee, Jin-Moo Sudlow, Cathie Marcus, Hugh Fornage, Myriam Rich, Stephen deBaker, Paul Mitchell, Braxton Meschia, James TI Etiologic Stroke Subtypes in the NINDS Stroke Genetics Network Study SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Ay, Hakan] Massachusetts Gen Hosp, Charlestown, MA USA. [Arsava, Ethem Murat] Univ Turkey, Ankara, Turkey. [Brown, Robert] Mayo Clin Rochester, Rochester, MN USA. [Kittner, Steven; McArdle, Patrick; Cole, John; Mitchell, Braxton] Univ Maryland, Baltimore, MD 21201 USA. [Rosand, Jonathan] Univ Massachusetts, Boston, MA 02125 USA. [Rundek, Tatjana; Sacco, Ralph] Univ Miami, Miami, FL USA. [Worrall, Bradford; Rich, Stephen] Univ Virginia, Charlottesville, VA USA. [Woo, Daniel] Univ Cincinnati, Cincinnati, OH USA. [Arnett, Donna] Univ Alabama Birmingham, Birmingham, AL USA. [Rexrode, Kathryn; deBaker, Paul] Brigham & Womens Hosp, Boston, MA 02115 USA. [Smoller, Sylvia] Einstein Coll Med, Bronx, NY USA. [Grewal, Raji] New Jersey Neurosci Inst, Cranbury, NJ USA. [Slowik, Agnieszka] Jagiellonian Univ, Coll Med, Krakow, Poland. [Lindgren, Arne] Skane Univ Hosp, Lund, Sweden. [Jimenez-Conde, Jordi] Hosp del Mar, IMIM, Barcelona, Spain. [Jern, Christina] Univ Gothenburg, Sahigrenska Acad, Gothenburg, Sweden. [Thijs, Vincent] Katholieke Univ Leuven Hosp, Louvain, Belgium. [Schmidt, Reinhold] Med Univ Graz, St Radegund, Austria. [Sharma, Pankja] Univ London Imperial Coll Sci Technol & Med, London, England. [Rothwell, Peter] Univ Oxford, Oxford, England. [Dichgans, Martin] Univ Munich, Munich, Germany. [Lee, Jin-Moo] Washington Univ, St Louis, MO USA. [Sudlow, Cathie] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Marcus, Hugh] St Georges Univ London, London, England. [Fornage, Myriam] Univ Texas Hlth Sci, Houston, TX USA. [Meschia, James] Mayo Clin, Florida Jacksonville, FL USA. RI Lee, Jin-Moo/K-2024-2015; JIMENEZ-CONDE, JORDI/C-1941-2012 OI Lee, Jin-Moo/0000-0002-3979-0906; 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA S32001 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068606142 ER PT J AU Boes, A Prasad, S Caviness, V Fox, M AF Boes, Aaron Prasad, Sashank Caviness, Verne Fox, Michael TI The Neuroanatomy of Peduncular Hallucinosis: A Case Series and Lesion Overlap Analysis SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Boes, Aaron; Caviness, Verne] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Prasad, Sashank] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA S18004 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068606057 ER PT J AU Bove, R Musallam, A Healy, B Raghavan, K Khoury, S Weiner, H De Jager, P Miller, K Chitnis, T AF Bove, Riley Musallam, Alexander Healy, Brian Raghavan, Kesav Khoury, Samia Weiner, Howard De Jager, Philip Miller, Karen Chitnis, Tanuja TI Hormonal Associations in the Early Disease Course in Men with Relapsing Remitting Multiple Sclerosis SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Bove, Riley] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Musallam, Alexander] Harvard Univ, Brigham & Womens Hosp, Sch Med, Brookline, MA USA. [Healy, Brian] Brigham & Womens Hosp, Brookline, MA USA. [Raghavan, Kesav; Khoury, Samia; De Jager, Philip] Harvard Univ, Sch Med, Boston, MA USA. [Weiner, Howard] Brigham & Womens Hosp, Boston, MA 02115 USA. [Miller, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chitnis, Tanuja] Harvard Univ, Sch Med, Brookline, MA 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P02128 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068601192 ER PT J AU Bove, R Musallam, A Healy, B Raghavan, K Khoury, S Weiner, H De Jager, P Miller, K Chitnis, T AF Bove, Riley Musallam, Alexander Healy, Brian Raghavan, Kesav Khoury, Samia Weiner, Howard De Jager, Philip Miller, Karen Chitnis, Tanuja TI Hormonal Associations in the Early Disease Course in Men with Relapsing Remitting Multiple Sclerosis SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Bove, Riley] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Musallam, Alexander] Harvard Univ, Sch Med, Brigham & Womens Hosp, Brookline, MA USA. [Healy, Brian] Brigham & Womens Hosp, Brookline, MA USA. [Raghavan, Kesav; Khoury, Samia; De Jager, Philip] Harvard Univ, Sch Med, Boston, MA USA. [Weiner, Howard] Brigham & Womens Hosp, Boston, MA 02115 USA. [Miller, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chitnis, Tanuja] Harvard Univ, Sch Med, Brookline, MA 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA IN82003 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068600111 ER PT J AU Chow, F Regan, S He, W Feske, S Meigs, J Grinspoon, S Triant, V AF Chow, Felicia Regan, Susan He, Wei Feske, Steven Meigs, James Grinspoon, Steven Triant, Virginia TI Incidence Rates of Intracerebral Hemorrhage Are Increased in Young and Female HIV-Infected Individuals SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Chow, Felicia] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Regan, Susan; He, Wei; Meigs, James; Grinspoon, Steven; Triant, Virginia] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Feske, Steven] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA S38004 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068606180 ER PT J AU Cudkowicz, M Shefner, J AF Cudkowicz, Merit Shefner, Jeremy CA NEALS Consortium TI STAGE 3 Clinical Trial of Ceftriaxone in Subjects with ALS SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Cudkowicz, Merit] Massachusetts Gen Hosp, Charlestown, MA USA. [Shefner, Jeremy] SUNY Upstate, Syracuse, NY USA. [NEALS Consortium] 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA S36001 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068606165 ER PT J AU Daniello, K Pathmanathan, J AF Daniello, Kate Pathmanathan, Jay TI A Case of Rapidly Progressive Dementia: Differentiating Dementia with Lewy Body from Creutzfeldt-Jacob Disease SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Daniello, Kate] Boston Univ, Brookline, MA USA. [Pathmanathan, Jay] Massachusetts Gen Hosp, Newton, MA USA. [Pathmanathan, Jay] Boston Vet Hosp, Newton, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P04214 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068603103 ER PT J AU Dickerson, B Bickart, K Brickhouse, M Sapolsky, D Barrett, L AF Dickerson, Bradford Bickart, Kevin Brickhouse, Michael Sapolsky, Daisy Barrett, Lisa TI Atrophy in Distinct Corticolimbic Networks Predicts Specific Social Symptoms in Frontotemporal Dementia SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Dickerson, Bradford; Brickhouse, Michael; Sapolsky, Daisy] Massachusetts Gen Hosp, Charlestown, MA USA. [Bickart, Kevin] Boston Univ, Boston, MA 02215 USA. [Barrett, Lisa] Northeastern Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P06055 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068604123 ER PT J AU Dickerson, B Domoto-Reilly, K Hollenbeck, M Sapolsky, D Brickhouse, M AF Dickerson, Bradford Domoto-Reilly, Kimiko Hollenbeck, Mark Sapolsky, Daisy Brickhouse, Michael TI Quantitative MRI Biomarkers of Neurodegenerative Diseases: Moving from Scientific Insights toward Clinical Practice SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Dickerson, Bradford; Hollenbeck, Mark; Sapolsky, Daisy; Brickhouse, Michael] Massachusetts Gen Hosp, Charlestown, MA USA. [Domoto-Reilly, Kimiko] 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P06030 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068604098 ER PT J AU Dickerson, B Domoto-Reilly, K Hollenbeck, M Sapolsky, D Brickhouse, M AF Dickerson, Bradford Domoto-Reilly, Kimiko Hollenbeck, Mark Sapolsky, Daisy Brickhouse, Michael TI Quantitative MRI Biomarkers of Neurodegenerative Diseases: Moving from Scientific Insights toward Clinical Practice SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Dickerson, Bradford; Hollenbeck, Mark; Sapolsky, Daisy; Brickhouse, Michael] Massachusetts Gen Hosp, Charlestown, MA USA. [Domoto-Reilly, Kimiko] 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA IN31010 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068600041 ER PT J AU Domoto-Reilly, K Sapolsky, D Negreira, A McGinnis, S Brickhouse, M Dickerson, B AF Domoto-Reilly, Kimiko Sapolsky, Daisy Negreira, Alyson McGinnis, Scott Brickhouse, Michael Dickerson, Bradford TI Regionally Specific Cortical Thinning Predicts Conversion to Dementia in Prodromal Frontotemporal Dementia (FTD) SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Domoto-Reilly, Kimiko] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sapolsky, Daisy; Negreira, Alyson; Brickhouse, Michael; Dickerson, Bradford] Massachusetts Gen Hosp, Charlestown, MA USA. [McGinnis, Scott] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P05103 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068603256 ER PT J AU Esposito, F Sorosina, M Lim, E Brambilla, P Romeo, M Rodegher, M Patsopoulos, N Osiceanu, A Keenan, B Martinelli, V Brassat, D Comi, G De Jager, P Boneschi, FM AF Esposito, Federica Sorosina, Melissa Lim, Elaine Brambilla, Paola Romeo, Marzia Rodegher, Mariaemma Patsopoulos, Nikolaos Osiceanu, Ana Keenan, Brendan Martinelli, Vittorio Brassat, David Comi, Giancarlo De Jager, Philip Boneschi, Filippo Martinelli TI An SLC9A9 Variant Influences Treatment Response in Interferon beta Treated Multiple Sclerosis Patients SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Esposito, Federica; Sorosina, Melissa; Brambilla, Paola; Romeo, Marzia; Rodegher, Mariaemma; Osiceanu, Ana; Martinelli, Vittorio; Comi, Giancarlo; Boneschi, Filippo Martinelli] Ist Sci San Raffaele, I-20132 Milan, Italy. [Lim, Elaine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lim, Elaine] Broad Inst Harvard & MIT, Boston, MA USA. [Patsopoulos, Nikolaos; Keenan, Brendan; De Jager, Philip] Brigham & Womens Hosp, Boston, MA 02115 USA. [Patsopoulos, Nikolaos; De Jager, Philip] Harvard Univ, Sch Med, Boston, MA USA. [Brassat, David] Univ Toulouse, Toulouse, France. RI brassat, david/L-2173-2014 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P05141 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068603294 ER PT J AU Foreman, P Van Cott, A Pugh, MJ AF Foreman, Perry Van Cott, Anne Pugh, Mary Jo TI Increased Mortality in Elderly Veterans Diagnosed with Epilepsy SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Foreman, Perry] Sinai Hosp, Berman Brain & Spine Inst, Baltimore, MD 21215 USA. [Van Cott, Anne] Univ Pittsburgh, Pittsburgh, PA USA. [Pugh, Mary Jo] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Pugh, Mary Jo] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P03117 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068602086 ER PT J AU Forst, D Chi, A Dietrich, J Gerstner, E Jones, S Byrne, T Hochberg, F Plotkin, S Batchelor, T AF Forst, Deborah Chi, Andrew Dietrich, Jorg Gerstner, Elizabeth Jones, SooAe Byrne, Thomas Hochberg, Fred Plotkin, Scott Batchelor, Tracy TI Methotrexate, Rituximab, Temozolomide (MRT) Induction Therapy for Elderly Patients with Primary Central Nervous System Lymphoma (PCNSL) SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Forst, Deborah; Chi, Andrew; Dietrich, Jorg; Gerstner, Elizabeth; Jones, SooAe; Byrne, Thomas; Hochberg, Fred; Plotkin, Scott; Batchelor, Tracy] Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA S56003 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068606293 ER PT J AU Forst, D Chi, A Dietrich, J Gerstner, E Jones, S Byrne, T Hochberg, F Plotkin, S Batchelor, T AF Forst, Deborah Chi, Andrew Dietrich, Jorg Gerstner, Elizabeth Jones, SooAe Byrne, Thomas Hochberg, Fred Plotkin, Scott Batchelor, Tracy TI Methotrexate, Rituximab, Temozolomide (MRT) Induction Therapy for Elderly Patients with Primary Central Nervous System Lymphoma (PCNSL) SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Forst, Deborah; Chi, Andrew; Dietrich, Jorg; Gerstner, Elizabeth; Jones, SooAe; Byrne, Thomas; Hochberg, Fred; Plotkin, Scott; Batchelor, Tracy] Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA IN101002 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068600129 ER PT J AU Fridman, V David, W Pan, J Eichler, F AF Fridman, Vera David, William Pan, Jessica Eichler, Florian TI Disease Progression in Hereditary Sensory and Autonomic Neuropathy Type I (HSAN1) SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Fridman, Vera; David, William; Pan, Jessica] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Eichler, Florian] Massachusetts Gen Hosp, Cambridge, MA 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA S26003 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068606103 ER PT J AU Goetz, C Stebbins, G Chung, K Hauser, R Miyasaki, J Nicholas, A Poewe, W Seppi, K Rascol, O Stacy, M Nutt, J Tanner, C Urkowitz, A Jaglin, J Ge, S AF Goetz, Christopher Stebbins, Glenn Chung, Kathryn Hauser, Robert Miyasaki, Janis Nicholas, Anthony Poewe, Werner Seppi, Klaus Rascol, Olivier Stacy, Mark Nutt, John Tanner, Caroline Urkowitz, Alison Jaglin, Jean Ge, Song TI No PD Dyskinesia Scale Protects Against Placebo Responses: A Comparison of Multiple Scales SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Goetz, Christopher] Rush Univ, Med Ctr, Neurol Sci Movement Disorder Sect, Chicago, IL 60612 USA. [Stebbins, Glenn; Jaglin, Jean; Ge, Song] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Chung, Kathryn] Oregon Hlth & Sci Univ, Lake Oswego, OR USA. [Chung, Kathryn] Portland VA Med Ctr, Lake Oswego, OR USA. [Hauser, Robert] Univ S Florida, Tampa, FL USA. [Miyasaki, Janis] Univ Toronto, Edmond J Safra Program Parkinsons Dis, Toronto, ON, Canada. [Nicholas, Anthony] Univ Alabama Birmingham, Birmingham, AL USA. [Nicholas, Anthony] Birmingham VA Med Ctr, Birmingham, AL USA. [Poewe, Werner; Seppi, Klaus] Med Univ Innsbruck, A-6020 Innsbruck, Austria. [Rascol, Olivier] Univ Hosp Toulouse, Clin Invest Ctr CIC9302, Toulouse, France. [Rascol, Olivier] Univ Hosp Toulouse, Dept Clin Pharmacol, INSERM, Toulouse, France. [Rascol, Olivier] Univ Hosp Toulouse, Dept Neurosci, INSERM, Toulouse, France. [Rascol, Olivier] Univ Toulouse 3, F-31062 Toulouse, France. [Stacy, Mark] Duke Univ, Durham, NC USA. [Nutt, John] Oregon Hlth & Sci Univ, Portland, OR USA. [Nutt, John] Portland VA Med Ctr, Portland, OR USA. [Tanner, Caroline] Parkinsons Inst & Clin Ctr, Sunnyvale, CA USA. [Urkowitz, Alison] Michael J Fox Fdn Parkinsons Res, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P04187 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068603076 ER PT J AU Guercio, B Donovan, N Ward, A Schultz, A Lorius, N Amariglio, R Rentz, D Johnson, K Sperling, R Marshall, G AF Guercio, Brendan Donovan, Nancy Ward, Andrew Schultz, Aaron Lorius, Natacha Amariglio, Rebecca Rentz, Dorene Johnson, Keith Sperling, Reisa Marshall, Gad TI Apathy Is Associated with Inferior Temporal Atrophy in Amnestic Mild Cognitive Impairment and Clinically Normal Elderly SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Guercio, Brendan] Harvard Univ, Sch Med, Boston, MA USA. [Donovan, Nancy] Brigham & Womens Hosp, Hingham, MA USA. [Ward, Andrew; Schultz, Aaron] Massachusetts Gen Hosp, Charlestown, MA USA. [Lorius, Natacha] Brigham & Womens Hosp, Boston, MA 02115 USA. [Amariglio, Rebecca; Rentz, Dorene; Sperling, Reisa] Brigham & Womens Hosp, Boston, MA 02115 USA. [Johnson, Keith] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Marshall, Gad] Brigham & Womens Hosp, Brookline, MA 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P07149 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068605131 ER PT J AU Hammond, E Young, C Chio, A Van den Berg, L Al-Chalabi, A Berry, J Brooks, B Shefner, J Turner, M Williams, J Li, XX Kerr, D AF Hammond, Edward Young, Carolyn Chio, Adriano Van den Berg, Leonard Al-Chalabi, Ammar Berry, James Brooks, Benjamin Shefner, Jeremy Turner, Martin Williams, James Li, Xiaoxi Kerr, Douglas TI Evaluation of a Health State Staging System Defined by Loss of Independence in Amyotrophic Lateral Sclerosis: Assessment in a Second Dataset SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Hammond, Edward] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Young, Carolyn] Walton Ctr Neurol, Liverpool, Merseyside, England. [Chio, Adriano] Univ Turin, Turin, Italy. [Van den Berg, Leonard] Univ Med Ctr Utrecht, Netherlands ALS Ctr, Utrecht, Netherlands. [Al-Chalabi, Ammar] Kings Coll London, Inst Psychiat, Dept Clin Neurosci, London WC2R 2LS, England. [Berry, James] Massachussetts Gen Hosp, Boston, MA USA. [Brooks, Benjamin] Univ N Carolina, Carolinas Med Ctr, Sch Med, Charlotte, NC 28223 USA. [Shefner, Jeremy] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [Turner, Martin] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England. [Williams, James; Li, Xiaoxi; Kerr, Douglas] Biogen Idec Inc, Cambridge, MA 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P07066 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068605048 ER PT J AU Hellman, A Duda, J Morley, J AF Hellman, Amy Duda, John Morley, James TI Continuous Non-Invasive Arterial Pressure Monitoring To Detect Autonomic Dysfunction in Parkinson's Disease SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Hellman, Amy; Duda, John; Morley, James] Univ Penn, Sch Med, Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. [Hellman, Amy; Duda, John; Morley, James] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P06101 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068604169 ER PT J AU Hsiao, J Lee, G Lu, P Teng, E AF Hsiao, Julia Lee, Grace Lu, Po Teng, Edmond TI Longitudinal Declines in Instrumental Activities of Daily Living in Stable and Progressive Mild Cognitive Impairment SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Hsiao, Julia] VA Greater Los Angeles Healthcare Syst, Neurol, Los Angeles, CA USA. [Lee, Grace; Teng, Edmond] Univ Calif Los Angeles, Los Angeles, CA USA. [Lu, Po] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Teng, Edmond] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P07154 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068605136 ER PT J AU Huang, R Chen, C Maclean, A Mukundan, S Wen, P Norden, A AF Huang, Raymond Chen, Christina Maclean, Ainsley Mukundan, Srinivasan Wen, Patrick Norden, Andrew TI Recurrent High-Grade Glioma Treated with Bevacizumab: Predictive Value of Biomarkers and Pretreatment MRI in Determining Response and Survival SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Huang, Raymond; Maclean, Ainsley; Mukundan, Srinivasan] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chen, Christina] Harvard Univ, Sch Med, Boston, MA USA. [Wen, Patrick; Norden, Andrew] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P06141 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068604209 ER PT J AU Huang, R Chen, C Maclean, A Mukundan, S Wen, P Norden, A AF Huang, Raymond Chen, Christina Maclean, Ainsley Mukundan, Srinivasan Wen, Patrick Norden, Andrew TI Recurrent High-Grade Glioma Treated with Bevacizumab: Predictive Value of Biomarkers and Pretreatment MRI in Determining Response and Survival SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Huang, Raymond; Maclean, Ainsley; Mukundan, Srinivasan] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chen, Christina] Harvard Univ, Sch Med, Boston, MA USA. [Wen, Patrick; Norden, Andrew] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA IN101008 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068600135 ER PT J AU Jette, N Pringsheim, T Day, L De Robles, P Fiest, K Hamilton, M Hogan, D Korngut, L Kwon, CS Lam, D Mah, J Marrie, RA Maxwell, C Metcalfe, A Oskoui, M Patten, S Pearson, D Reid, A Smith, E Steeves, T Svenson, L Wiebe, S Dykeman, J AF Jette, Nathalie Pringsheim, Tamara Day, Lundy De Robles, Paula Fiest, Kirsten Hamilton, Mark Hogan, David Korngut, Lawrence Kwon, Churl-Su Lam, Darren Mah, Jean Marrie, Ruth-Ann Maxwell, Colleen Metcalfe, Amy Oskoui, Maryam Patten, Scott Pearson, Dawn Reid, Aylin Smith, Eric Steeves, Thomas Svenson, Larry Wiebe, Samuel Dykeman, Jonathan TI The International Incidence and Prevalence of Neurological Diseases - Do We Really Know How Common Neurological Conditions Are? Challenges in Interpreting International Epidemiological Studies SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Jette, Nathalie; Pringsheim, Tamara; Day, Lundy; De Robles, Paula; Fiest, Kirsten; Hamilton, Mark; Hogan, David; Korngut, Lawrence; Lam, Darren; Mah, Jean; Metcalfe, Amy; Patten, Scott; Pearson, Dawn; Reid, Aylin; Smith, Eric; Wiebe, Samuel; Dykeman, Jonathan] Univ Calgary, Calgary, AB, Canada. [Kwon, Churl-Su] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Marrie, Ruth-Ann] Univ Manitoba, Winnipeg, MB, Canada. [Maxwell, Colleen] Univ Waterloo, Waterloo, ON N2L 3G1, Canada. [Oskoui, Maryam] McGill Univ, Montreal, PQ, Canada. [Steeves, Thomas] Univ Toronto, Toronto, ON, Canada. [Svenson, Larry] Alberta Hlth & Wellness, Edmonton, AB, Canada. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P04235 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068603124 ER PT J AU Jette, N Pringsheim, T Day, L De Robles, P Fiest, K Hamilton, M Hogan, D Korngut, L Kwon, CS Lam, D Mah, J Marrie, RA Maxwell, C Metcalfe, A Oskoui, M Patten, S Pearson, D Reid, A Smith, E Steeves, T Svenson, L Wiebe, S Dykeman, J AF Jette, Nathalie Pringsheim, Tamara Day, Lundy De Robles, Paula Fiest, Kirsten Hamilton, Mark Hogan, David Korngut, Lawrence Kwon, Churl-Su Lam, Darren Mah, Jean Marrie, Ruth-Ann Maxwell, Colleen Metcalfe, Amy Oskoui, Maryam Patten, Scott Pearson, Dawn Reid, Aylin Smith, Eric Steeves, Thomas Svenson, Larry Wiebe, Samuel Dykeman, Jonathan TI The International Incidence and Prevalence of Neurological Diseases - Do We Really Know How Common Neurological Conditions Are? Challenges in Interpreting International Epidemiological Studies SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Jette, Nathalie; Pringsheim, Tamara; Day, Lundy; De Robles, Paula; Fiest, Kirsten; Hamilton, Mark; Hogan, David; Korngut, Lawrence; Lam, Darren; Mah, Jean; Metcalfe, Amy; Patten, Scott; Pearson, Dawn; Reid, Aylin; Smith, Eric; Wiebe, Samuel; Dykeman, Jonathan] Univ Calgary, Calgary, AB, Canada. [Kwon, Churl-Su] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Marrie, Ruth-Ann] Univ Manitoba, Winnipeg, MB, Canada. [Maxwell, Colleen] Univ Waterloo, Waterloo, ON N2L 3G1, Canada. [Oskoui, Maryam] McGill Univ, Montreal, PQ, Canada. [Steeves, Thomas] Univ Toronto, Toronto, ON, Canada. [Svenson, Larry] Alberta Hlth & Wellness, Edmonton, AB, Canada. RI Patten, Scott/B-4434-2011 OI Patten, Scott/0000-0001-9871-4041 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA IN62002 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068600083 ER PT J AU Joshi, A Teng, E Tassniyom, K Shapira, J Mendez, M AF Joshi, Aditi Teng, Edmond Tassniyom, Kanida Shapira, Jill Mendez, Mario TI Hippocampal and Medial Temporal Sclerosis in Behavioral Variant Frontotemporal Dementia SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Joshi, Aditi; Shapira, Jill; Mendez, Mario] Univ Calif Los Angeles, Los Angeles, CA USA. [Teng, Edmond] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Tassniyom, Kanida] Khon Kaen Univ, Khon Kaen, Thailand. 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA S44007 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068606222 ER PT J AU Joshi, A Shapiro, D Jimenez, E Mather, M Shapira, J Kaiser, N Mendez, M AF Joshi, Aditi Shapiro, David Jimenez, Elvira Mather, Michelle Shapira, Jill Kaiser, Natalie Mendez, Mario TI Auditory Startle in Behavioral Variant Frontotemporal Dementia Compared to Alzheimer's Disease and Healthy Controls SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Joshi, Aditi; Mather, Michelle] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Jimenez, Elvira; Shapira, Jill; Mendez, Mario] Univ Calif Los Angeles, Los Angeles, CA USA. [Kaiser, Natalie] VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P07167 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068605149 ER PT J AU Kearney, M Ecklund, D Simpson, E Bosch, M Sweet, B Jackson, K Mahoney, K McCourt, M Thornell, B Titus, S Soodoo, N O'Brien, J Gloer, K Costigan, M Logsden-Sackett, N Huff, T Shefner, J Gutmann, L Clarke, W Torner, J Long, J Chaloner, K Bayman, E McNeil, D Koroshetz, W Kaufmann, P Cudkowicz, M Coffey, C AF Kearney, Marianne Ecklund, Dixie Simpson, Elizabeth Bosch, Michael Sweet, Bryan Jackson, Katherine Mahoney, Katy McCourt, Michelle Thornell, Brenda Titus, Sarah Soodoo, Natasha O'Brien, Janice Gloer, Katherine Costigan, Michele Logsden-Sackett, Nyla Huff, Trevis Shefner, Jeremy Gutmann, Laurie Clarke, William Torner, James Long, Jeffrey Chaloner, Kathryn Bayman, Emine McNeil, Dawn Koroshetz, Walter Kaufmann, Petra Cudkowicz, Merit Coffey, Christopher TI Network for Excellence in Neuroscience Clinical Trials, NeuroNEXT: Concept to Implementation SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Kearney, Marianne; Simpson, Elizabeth; Mahoney, Katy; McCourt, Michelle; Thornell, Brenda; Titus, Sarah; Soodoo, Natasha; O'Brien, Janice; Cudkowicz, Merit] MGH, Charlestown, MA USA. [Ecklund, Dixie; Bosch, Michael; Gloer, Katherine; Costigan, Michele; Logsden-Sackett, Nyla; Huff, Trevis; Clarke, William; Torner, James; Long, Jeffrey; Chaloner, Kathryn; Bayman, Emine; Coffey, Christopher] U Iowa, Iowa City, IA USA. [Sweet, Bryan; Jackson, Katherine] Massachusetts Gen Hosp, Charlestown, MA USA. [Shefner, Jeremy] SUNY Upstate Med Ctr, Syracuse, NY USA. [Gutmann, Laurie] W Virginia Univ, Morgantown, WV 26506 USA. [McNeil, Dawn; Koroshetz, Walter] NINDS, Bethesda, MD 20892 USA. [Kaufmann, Petra] NINDS, Rockville, MD 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P04245 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068603134 ER PT J AU Klawiter, E Alvarez, E Elsone, L Mateen, F Borisow, N Bove, R Sorum, J Mutch, K Tobyne, S Musallam, A Ruprecht, K Buckle, G Paul, F Levy, M Cross, A Jacob, A Chitnis, T Weinshenker, B AF Klawiter, Eric Alvarez, Enrique Elsone, Liene Mateen, Farrah Borisow, Nadja Bove, Riley Sorum, Jaime Mutch, Kerry Tobyne, Sean Musallam, Alexander Ruprecht, Klemens Buckle, Guy Paul, Friedemann Levy, Michael Cross, Anne Jacob, Anu Chitnis, Tanuja Weinshenker, Brian TI High Risk of Initial Symptom Onset Post-Partum in Neuromyelitis Optica SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Klawiter, Eric; Tobyne, Sean] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Alvarez, Enrique; Cross, Anne] Washington Univ, Sch Med, St Louis, MO USA. [Elsone, Liene; Mutch, Kerry; Jacob, Anu] Walton Ctr, Liverpool, Merseyside, England. [Mateen, Farrah; Levy, Michael] Johns Hopkins Univ, Baltimore, MD USA. [Borisow, Nadja; Ruprecht, Klemens; Paul, Friedemann] Charite, D-13353 Berlin, Germany. [Bove, Riley; Musallam, Alexander; Buckle, Guy; Chitnis, Tanuja] Brigham & Womens Hosp, Partners MS Ctr, Boston, MA 02115 USA. [Sorum, Jaime; Weinshenker, Brian] Mayo Clin, Rochester, MN 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA S60001 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068606313 ER PT J AU Kraakevik, J Heath, S AF Kraakevik, Jeff Heath, Susan TI My Parkinson's Story: A Novel Format For a Patient Education Video Series SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Kraakevik, Jeff] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Heath, Susan] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P04257 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068603146 ER PT J AU Kremen, S Tassniyom, K Mendez, M Teng, E AF Kremen, Sarah Tassniyom, Kanida Mendez, Mario Teng, Edmond TI Extrapyramidal Signs in Primary Progressive Aphasia: Analyses of the NACC UDS Cohort SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Kremen, Sarah] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Kremen, Sarah] Univ Calif Los Angeles, Easton Alzheimers Dis Res Ctr, Los Angeles, CA USA. [Tassniyom, Kanida] Khon Kaen Univ, Fac Med, Dept Psychiat, Khon Kaen, Thailand. [Mendez, Mario; Teng, Edmond] Greater Los Angeles VA Med Ctr, 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P06071 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068604139 ER PT J AU Krupp, L Charvet, L Serafin, D Julian, L Ackerson, J Benedict, R Braaten, E Brown, T O'Donnell, E Parrish, J Preston, T Zaccariello, M Belman, A Chitnis, T Gorman, M Kaufman, E Ness, J Patterson, M Rodriguez, M Waubant, E Weinstock-Guttman, B Yeh, A AF Krupp, Lauren Charvet, Leigh Serafin, Dana Julian, Laura Ackerson, Joseph Benedict, Ralph Braaten, Ellen Brown, Tanya O'Donnell, Ellen Parrish, Joy Preston, Thomas Zaccariello, Michael Belman, Anita Chitnis, Tanuja Gorman, Mark Kaufman, Emma Ness, Jayne Patterson, Marc Rodriguez, Moses Waubant, Emmanuelle Weinstock-Guttman, Bianca Yeh, Ann TI Impaired Cognition without Behavioral Problems in Pediatric Clinically Isolated Syndrome (CIS) SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Krupp, Lauren] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Charvet, Leigh] SUNY Stony Brook, Rockville Ctr, NY USA. [Serafin, Dana] SUNY Stony Brook, Dept Neurol, Stony Brook, NY 11794 USA. [Julian, Laura] Univ Calif San Francisco, Dept Neuropsychol, San Francisco, CA 94143 USA. [Ackerson, Joseph; Ness, Jayne] Univ Alabama Birmingham, Birmingham, AL USA. [Benedict, Ralph; Parrish, Joy] SUNY Buffalo, Jacobs Neurol Inst, Buffalo, NY 14260 USA. [Braaten, Ellen] Massachusettes Gen Hosp, Boston, MA USA. [Brown, Tanya; Zaccariello, Michael] Mayo Clin, Dept Psychiat & Psychol, Rochester, MN USA. [O'Donnell, Ellen; Gorman, Mark] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Preston, Thomas] SUNY Stony Brook, Med Ctr, Dept Neuropsychol, East Setauket, NY USA. [Belman, Anita] SUNY Stony Brook, Huntington, NY USA. [Chitnis, Tanuja] Massachusetts Gen Hosp, Brookline, MA USA. [Kaufman, Emma] SUNY Stony Brook, Dept Neurol, Med Ctr, Stony Brook, NY 11794 USA. [Patterson, Marc; Rodriguez, Moses] Mayo Clin, Rochester, MN USA. [Waubant, Emmanuelle] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Weinstock-Guttman, Bianca] Jacobs Neurol Inst, Buffalo, NY USA. [Yeh, Ann] SUNY Buffalo, Dept Neurol, Jacobs Neurol Inst, Buffalo, NY 14260 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P02113 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068601177 ER PT J AU Kursun, O Singhal, A AF Kursun, Oguzhan Singhal, Aneesh TI High Frequency of Incidental Angiographic Abnormalities in RCVS: Implications For Pathophysiology? ( P03.164) SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Kursun, Oguzhan] Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. [Singhal, Aneesh] 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P03164 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068602133 ER PT J AU Labuzetta, J Yoo, A Ali, S Fitzpatrick, K Hirsch, J Schwamm, L Rost, N AF Labuzetta, Jamie Yoo, Albert Ali, Syed Fitzpatrick, Kaitlin Hirsch, Joshua Schwamm, Lee Rost, Natalia TI Determinants of Early Outcomes in Patients with Acute Ischemic Stroke and Proximal Artery Occlusion SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Labuzetta, Jamie] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Yoo, Albert; Ali, Syed; Fitzpatrick, Kaitlin; Hirsch, Joshua; Schwamm, Lee; Rost, Natalia] 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA S02005 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068605344 ER PT J AU Lawson, R McCarthy, P Sawicki, D Berry, J Chonde, D Akeju, O Loggia, M Catana, C Hooker, J Rosen, B Cudkowicz, M Atassi, N AF Lawson, Robert McCarthy, Patricia Sawicki, Darlene Berry, James Chonde, Daniel Akeju, Oluwaseun Loggia, Marco Catana, Ciprian Hooker, Jacob Rosen, Bruce Cudkowicz, Merit Atassi, Nazem TI Microglial Activation in People with Amyotrophic Lateral Sclerosis SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Lawson, Robert; Sawicki, Darlene; Berry, James; Akeju, Oluwaseun; Rosen, Bruce; Atassi, Nazem] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McCarthy, Patricia; Loggia, Marco; Catana, Ciprian; Hooker, Jacob; Cudkowicz, Merit] Massachusetts Gen Hosp, Charlestown, MA USA. [Chonde, Daniel] Harvard Univ, Harvard MIT Dept Hlth Sci & Technol, Charlestown, MA 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P06132 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068604200 ER PT J AU Lee, E Reardon, D Schiff, D Drappatz, J Hammond, S Grimm, S Norden, A Beroukhim, R McCluskey, C Chi, A Batchelor, T Doherty, L Lafrankie, D Ruland, S Rifenburg, J Jacobs, J Smith, K Gaffey, S Gerard, M Snodgrass, S Raizer, J Wen, P AF Lee, Eudocia Reardon, David Schiff, David Drappatz, Jan Hammond, Samantha Grimm, Sean Norden, Andrew Beroukhim, Rameen McCluskey, Christine Chi, Andrew Batchelor, Tracy Doherty, Lisa Lafrankie, Debra Ruland, Sandra Rifenburg, Jennifer Jacobs, Jeanne Smith, Katrina Gaffey, Sarah Gerard, Mary Snodgrass, Susan Raizer, Jeffrey Wen, Patrick TI Interim Analysis of a Phase I/II Study of Panobinostat in Combination with Bevacizumab for Recurrent Glioblastoma SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Lee, Eudocia; Reardon, David; Hammond, Samantha; Norden, Andrew; Beroukhim, Rameen; McCluskey, Christine; Doherty, Lisa; Lafrankie, Debra; Ruland, Sandra; Rifenburg, Jennifer; Jacobs, Jeanne; Smith, Katrina; Gaffey, Sarah; Gerard, Mary; Wen, Patrick] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schiff, David] Univ Virginia, Charlottesville, VA USA. [Drappatz, Jan] Univ Pittsburgh, Pittsburgh, PA USA. [Grimm, Sean] Univ Minnesota, Minneapolis, MN USA. [Chi, Andrew; Batchelor, Tracy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Snodgrass, Susan] Novartis, E Hanover, NJ USA. [Raizer, Jeffrey] Northwestern Univ, Chicago, IL 60611 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P01094 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068600251 ER PT J AU Lee, E Reardon, D Schiff, D Drappatz, J Hammond, S Grimm, S Norden, A Beroukhim, R McCluskey, C Chi, A Batchelor, T Doherty, L Lafrankie, D Ruland, S Rifenburg, J Jacobs, J Smith, K Gaffey, S Gerard, M Snodgrass, S Raizer, J Wen, P AF Lee, Eudocia Reardon, David Schiff, David Drappatz, Jan Hammond, Samantha Grimm, Sean Norden, Andrew Beroukhim, Rameen McCluskey, Christine Chi, Andrew Batchelor, Tracy Doherty, Lisa Lafrankie, Debra Ruland, Sandra Rifenburg, Jennifer Jacobs, Jeanne Smith, Katrina Gaffey, Sarah Gerard, Mary Snodgrass, Susan Raizer, Jeffrey Wen, Patrick TI Interim Analysis of a Phase I/II Study of Panobinostat in Combination with Bevacizumab for Recurrent Glioblastoma SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Lee, Eudocia; Reardon, David; Hammond, Samantha; Norden, Andrew; Beroukhim, Rameen; McCluskey, Christine; Doherty, Lisa; Lafrankie, Debra; Ruland, Sandra; Rifenburg, Jennifer; Jacobs, Jeanne; Smith, Katrina; Gaffey, Sarah; Gerard, Mary; Wen, Patrick] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schiff, David] Univ Virginia, Charlottesville, VA USA. [Drappatz, Jan] Univ Pittsburgh, Pittsburgh, PA USA. [Grimm, Sean] Univ Minnesota, Minneapolis, MN USA. [Chi, Andrew; Batchelor, Tracy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Snodgrass, Susan] Novartis, E Hanover, NJ USA. [Raizer, Jeffrey] Northwestern Univ, Chicago, IL 60611 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA IN101005 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068600132 ER PT J AU Leitner, M Sherman, A Atassi, N Berry, J Shui, A Zach, N Walker, J Sinani, E Katsovskiy, I Schoenfeld, D Cudkowicz, M AF Leitner, Melanie Sherman, Alexander Atassi, Nazem Berry, James Shui, Amy Zach, Neta Walker, Jason Sinani, Ervin Katsovskiy, Igor Schoenfeld, David Cudkowicz, Merit TI ALS Enters the World of Big Data: Initial Description of and Results from the PRO-ACT Platform SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Leitner, Melanie; Zach, Neta] Prize4Life, Cambridge, MA USA. [Sherman, Alexander; Atassi, Nazem; Cudkowicz, Merit] Massachusetts Gen Hosp, Charlestown, MA USA. [Berry, James; Shui, Amy; Walker, Jason; Sinani, Ervin; Katsovskiy, Igor; Schoenfeld, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P07064 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068605046 ER PT J AU Lu-Emerson, C Snuderl, M Kirkpatrick, N Goveia, J Davidson, C Huang, Y Riedemann, L Ivy, P Ancukiewicz, M Stemmer-Rachamimov, A Batchelor, T Jain, R AF Lu-Emerson, Christine Snuderl, Matija Kirkpatrick, Nathaniel Goveia, Jermaine Davidson, Christian Huang, Yuhui Riedemann, Lars Ivy, Percy Ancukiewicz, Marek Stemmer-Rachamimov, Anat Batchelor, Tracy Jain, Rakesh TI Direct Evidence That Increase in Tumor-Associated Macrophages (TAMs) after Antiangiogenic Therapy Is Associated with Poor Survival in Recurrent Glioblastoma (GBM) Patients SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Lu-Emerson, Christine] Massachusetts Gen Hosp, Dept Neurooncol, Boston, MA 02114 USA. [Snuderl, Matija; Batchelor, Tracy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kirkpatrick, Nathaniel; Goveia, Jermaine; Huang, Yuhui; Riedemann, Lars; Ancukiewicz, Marek; Jain, Rakesh] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Davidson, Christian; Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ivy, Percy] NCI, Invest Drug Branch, Rockville, MD USA. RI Riedemann, Lars/J-5725-2014 OI Riedemann, Lars/0000-0002-9510-1845 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA S35001 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068606159 ER PT J AU Lu-Emerson, C Snuderl, M Kirkpatrick, N Goveia, J Davidson, C Huang, YH Riedemann, L Ivy, P Ancukiewicz, M Stemmer-Rachamimov, A Batchelor, T Jain, R AF Lu-Emerson, Christine Snuderl, Matija Kirkpatrick, Nathaniel Goveia, Jermaine Davidson, Christian Huang, Yuhui Riedemann, Lars Ivy, Percy Ancukiewicz, Marek Stemmer-Rachamimov, Anat Batchelor, Tracy Jain, Rakesh TI Direct Evidence That Increase in Tumor-Associated Macrophages (TAMs) after Antiangiogenic Therapy Is Associated with Poor Survival in Recurrent Glioblastoma (GBM) Patients SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Lu-Emerson, Christine] Massachusetts Gen Hosp, Dept Neurooncol, Boston, MA 02114 USA. [Snuderl, Matija; Batchelor, Tracy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kirkpatrick, Nathaniel; Goveia, Jermaine; Huang, Yuhui; Riedemann, Lars; Ancukiewicz, Marek; Jain, Rakesh] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Davidson, Christian; Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ivy, Percy] NCI, Invest Drug Branch, Rockville, MD 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA IN102001 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068600138 ER PT J AU Maraka, S Jiang, Q Jafari-Khouzani, K Hamidian, N Li, L Malik, S Zhang, TL Lu, M Soltanian-Zadeh, H Mitsias, P AF Maraka, Stefania Jiang, Quan Jafari-Khouzani, Kourosh Hamidian, Nasim Li, Lian Malik, Shaneela Zhang, Talan Lu, Mai Soltanian-Zadeh, Hamid Mitsias, Panayiotis TI Quantitative Assessment of Corticospinal Tract Injury on Diffusion Tensor Imaging Correlates with Motor Outcome after Ischemic Stroke SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Maraka, Stefania; Jiang, Quan; Hamidian, Nasim; Li, Lian; Malik, Shaneela; Zhang, Talan; Lu, Mai; Soltanian-Zadeh, Hamid] Henry Ford Hosp, Detroit, MI 48202 USA. [Jafari-Khouzani, Kourosh] Massachussetts Gen Hosp, Boston, MA USA. [Mitsias, Panayiotis] Stroke & Neurovasc Ctr, Detroit, MI USA. RI Soltanian-Zadeh, Hamid/K-2903-2016 OI Soltanian-Zadeh, Hamid/0000-0002-7302-6856 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P03163 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068602132 ER PT J AU Maski, K Holbrook, H Manoach, D Hanson, E Stickgold, R AF Maski, Kiran Holbrook, Hannah Manoach, Dara Hanson, Ellen Stickgold, Robert TI Sleep Architecture and Neurobehavioral and Cognitive Functioning in Children with Autistic Spectrum Disorders SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Maski, Kiran; Holbrook, Hannah; Hanson, Ellen] Boston Childrens Hosp, Boston, MA USA. [Manoach, Dara] Massachusetts Gen Hosp, Martinos Ctr, Charlestown, MA USA. [Stickgold, Robert] Beth Israel Deaconess Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P03011 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068601329 ER PT J AU McKenery, M Yu, H Li, HN Lee, A Chang, J Jankowski, S Bozik, A Orbey, A Zipf, A Cudkowicz, M Atassi, N AF McKenery, Michael Yu, Hong Li, Haining Lee, Alexandra Chang, Judith Jankowski, Stacey Bozik, Anne Orbey, Aaron Zipf, Amanda Cudkowicz, Merit Atassi, Nazem TI Regional Pattern of Symptom Spread in Amyotrophic Lateral Sclerosis (ALS) SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [McKenery, Michael; Yu, Hong; Li, Haining; Lee, Alexandra; Chang, Judith; Jankowski, Stacey; Bozik, Anne; Orbey, Aaron; Zipf, Amanda; Cudkowicz, Merit; Atassi, Nazem] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P06130 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068604198 ER PT J AU Mejia, N Cook, B AF Mejia, Nicte Cook, Benjamin TI Racial/Ethnic Disparities in Parkinson Disease Patient Care in the United States: 1996-2009 Medical Expenditure Panel Survey SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Mejia, Nicte] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cook, Benjamin] Cambridge Hlth Alliance, Ctr Multicultural Mental Hlth Res, Somerville, MA 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA S03001 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068605347 ER PT J AU Miglis, M Gibbons, C Freeman, R AF Miglis, Mitchell Gibbons, Christopher Freeman, Roy TI Sleep Disorders in Patients with Postural Tachycardia Syndrome SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Miglis, Mitchell] Stanford Univ, Redwood City, CA USA. [Gibbons, Christopher; Freeman, Roy] BIDMC, Boston, MA 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P03026 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068601344 ER PT J AU Moore, W Roubin, G Rosenfield, K Altafullah, I Ansel, G Voeks, J Meschia, J Lal, B Howard, G Brott, T AF Moore, Wesley Roubin, Gary Rosenfield, Kenneth Altafullah, Irfan Ansel, Gary Voeks, Jenifer Meschia, James Lal, Brajesh Howard, George Brott, Thomas TI Can Patient or Arterial Characteristics Guide the Choice between Carotid Angioplasty and Carotid Endarterectomy? The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Moore, Wesley] Univ Calif Los Angeles, Los Angeles Med Ctr, Los Angeles, CA USA. [Roubin, Gary] Continuum Hlth Partners, New York, NY USA. [Rosenfield, Kenneth] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Altafullah, Irfan] North Mem Med Ctr, Robbinsdale, MN USA. [Ansel, Gary] Ohio Hlth Res Inst, Columbus, OH USA. [Voeks, Jenifer] Med Univ S Carolina, Charleston, SC 29425 USA. [Meschia, James; Brott, Thomas] Mayo Clin, Jacksonville, FL 32224 USA. [Lal, Brajesh] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Howard, George] Univ Alabama Birmingham, Birmingham, AL 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P01225 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068601024 ER PT J AU Nayak, L Abrey, L DeAngelis, L Gadgeel, S Garst, J Govindan, R Kelly, K Omuro, A Peereboom, D Ramnath, N Reimers, HJ Rigas, J Robbins, HI Rosenfeld, S Wen, P AF Nayak, Lakshmi Abrey, Lauren DeAngelis, Lisa Gadgeel, Shirish Garst, Jennifer Govindan, Ramaswamy Kelly, Karen Omuro, Antonio Peereboom, David Ramnath, Nithya Reimers, Hans-Joachim Rigas, James Robbins, H. Ian Rosenfeld, Steven Wen, Patrick TI An Open-Label, Multi-Center, Phase II Study of Patupilone (EPO906), in the Treatment of Recurrent or Progressive Brain Metastases in Patients with Non-Small Cell Lung Cancer (NSCLC) SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Nayak, Lakshmi; Wen, Patrick] Dana Farber Canc Inst, Boston, MA 02115 USA. [Abrey, Lauren] Roche Pharmaceut, Wyalusing, PA USA. [DeAngelis, Lisa] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Gadgeel, Shirish] Wayne State Univ, Wertz Clin Canc Ctr, Detroit, MI USA. [Garst, Jennifer] Duke Univ, Med Ctr, Durham, NC USA. [Govindan, Ramaswamy] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63130 USA. [Kelly, Karen] Univ Calif Davis, Ctr Canc, Sacramento, CA 95817 USA. [Omuro, Antonio] MSKCC, New York, NY USA. [Peereboom, David] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Ramnath, Nithya] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Reimers, Hans-Joachim] St Louis Univ, Ctr Canc, St Louis, MO 63103 USA. [Rigas, James] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Robbins, H. Ian] Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. [Rosenfeld, Steven] Columbia Univ, Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA S56002 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068606292 ER PT J AU Nayak, L Abrey, L DeAngelis, L Gadgeel, S Garst, J Govindan, R Kelly, K Omuro, A Peereboom, D Ramnath, N Reimers, HJ Rigas, J Robbins, HI Rosenfeld, S Wen, P AF Nayak, Lakshmi Abrey, Lauren DeAngelis, Lisa Gadgeel, Shirish Garst, Jennifer Govindan, Ramaswamy Kelly, Karen Omuro, Antonio Peereboom, David Ramnath, Nithya Reimers, Hans-Joachim Rigas, James Robbins, H. Ian Rosenfeld, Steven Wen, Patrick TI An Open-Label, Multi-Center, Phase II Study of Patupilone (EPO906), in the Treatment of Recurrent or Progressive Brain Metastases in Patients with Non-Small Cell Lung Cancer (NSCLC) SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Nayak, Lakshmi; Wen, Patrick] Dana Farber Canc Inst, Boston, MA 02115 USA. [Abrey, Lauren] Roche Pharmaceut, Wyalusing, PA USA. [DeAngelis, Lisa] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Gadgeel, Shirish] Wayne State Univ, Wertz Clin Canc Ctr, Detroit, MI USA. [Garst, Jennifer] Duke Univ, Med Ctr, Durham, NC USA. [Govindan, Ramaswamy] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63130 USA. [Kelly, Karen] Univ Calif Davis, Ctr Canc, Sacramento, CA 95817 USA. [Omuro, Antonio] MSKCC, New York, NY USA. [Peereboom, David] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Ramnath, Nithya] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Reimers, Hans-Joachim] St Louis Univ, Ctr Canc, St Louis, MO 63103 USA. [Rigas, James] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Robbins, H. Ian] Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. [Rosenfeld, Steven] Columbia Univ, Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA IN102005 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068600142 ER PT J AU Neagu, M Lyons, J Norton, I Klein, J AF Neagu, Martha Lyons, Jennifer Norton, Isaiah Klein, Joshua TI Diffusion Tensor Imaging in Brainstem Tuberculoma SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Neagu, Martha] Brigham & Womens Hosp, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Lyons, Jennifer; Norton, Isaiah; Klein, Joshua] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P06184 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068604252 ER PT J AU Ng, M Kilbride, R Simon, M Eskandar, E Cole, A AF Ng, Marcus Kilbride, Ronan Simon, Mirela Eskandar, Emad Cole, Andrew TI The Role of Hippocampography and Hippocampectomy in Symptomatic Extrahippocampal Temporal Lobe Epilepsy SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Ng, Marcus; Simon, Mirela; Cole, Andrew] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kilbride, Ronan] Massachusetts Gen Hosp, Somerville, MA USA. [Eskandar, Emad] Massachusetts Gen Hosp, Neurosurg Serv, 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P04197 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068603086 ER PT J AU Pantelyat, A Freedman, R Pawlowski, S Kesari, A Duda, J Morley, J AF Pantelyat, Alexander Freedman, Rebecca Pawlowski, Stephanie Kesari, Adhithi Duda, John Morley, James TI Quantitative Assessment of Bradykinesia in Parkinson's Disease (PD) SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Pantelyat, Alexander; Duda, John; Morley, James] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Freedman, Rebecca; Kesari, Adhithi] Univ Penn, Philadelphia, PA USA. [Pawlowski, Stephanie] Philadelphia VA Med Ctr PADRECC, Philadelphia, PA USA. [Morley, James] Hosp Univ Penn, Philadelphia, PA 19104 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P04192 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068603081 ER PT J AU Park, KY Avery, R Ay, H AF Park, Kwang-Yeol Avery, Ross Ay, Hakan TI Prior beta Blocker Use Is Associated with Favorable Outcome in Patients with Acute Insular Stroke SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Park, Kwang-Yeol] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Avery, Ross] Massachusetts Gen Hosp, Charlestown, MA USA. [Ay, Hakan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P01217 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068601016 ER PT J AU Pati, S Rosenthal, E Cash, S Hochberg, L Brown, E Westover, M AF Pati, Sandipan Rosenthal, Eric Cash, Sydney Hochberg, Leigh Brown, Emery Westover, M. TI Unexpected Burst-Suppression during Sedation with Anesthetic Agents in the ICU SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Pati, Sandipan; Rosenthal, Eric; Cash, Sydney; Hochberg, Leigh; Brown, Emery; Westover, M.] 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P01027 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068600184 ER PT J AU Peterson, A Murchison, C Zabetian, C Leverenz, J Watson, G Montine, T Carney, N Bowman, G Quinn, J AF Peterson, Amie Murchison, Charles Zabetian, Cyrus Leverenz, James Watson, G. Montine, Thomas Carney, Natasha Bowman, Gene Quinn, Joseph TI The Relationship between Vitamin D and Cognitive Performance in Persons with Parkinson's SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Peterson, Amie] Portland VA OHSU, Portland, OR USA. [Murchison, Charles] OHSU, Portland, OR USA. [Zabetian, Cyrus] Univ Washington, Seattle, WA 98195 USA. [Leverenz, James] Univ Washington, Seattle, WA 98195 USA. [Watson, G.] Univ Washington, VA Puget Sound, Seattle, WA 98195 USA. [Montine, Thomas] Univ Washington, Bellevue, WA USA. [Carney, Natasha] Portland VA, Portland, OR USA. [Bowman, Gene; Quinn, Joseph] OHSU, Portland, OR 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P04170 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068603059 ER PT J AU Rascovsky, K Hodges, J Knopman, D Mendez, M Kramer, J Neuhaus, J Van Swieten, J Seelaar, H Dopper, E Onyike, C Hillis, A Josephs, K Boeve, B Kertesz, A Seeley, W Rankin, K Johnson, J Tempini, MG Rosen, H Latham, C Lee, A Kipps, C Lillo, P Piguet, O Rohrer, J Rossor, M Warren, J Fox, N Galasko, D Salmon, D Black, S Mesulam, M Weintraub, S Dickerson, B Diehl, J Pasquier, F Deramecourt, V Lebert, F Pijnenburg, Y Chow, T Manes, F Grafman, J Cappa, S Freedman, M Miller, B Grossman, M AF Rascovsky, Katya Hodges, John Knopman, David Mendez, Mario Kramer, Joel Neuhaus, John Van Swieten, John Seelaar, Harro Dopper, Elise Onyike, Chiadi Hillis, Argye Josephs, Keith Boeve, Bradley Kertesz, Andrew Seeley, William Rankin, Katherine Johnson, Julene Tempini, Maria Gorno Rosen, Howard Latham, Caroline Lee, Albert Kipps, Christopher Lillo, Patricia Piguet, Olivier Rohrer, Jonathan Rossor, Martin Warren, Jason Fox, Nic Galasko, Douglas Salmon, David Black, Sandra Mesulam, M. Weintraub, Sandra Dickerson, Bradford Diehl, Janine Pasquier, Florence Deramecourt, Vincent Lebert, Florence Pijnenburg, Yolande Chow, Tiffany Manes, Facundo Grafman, Jordan Cappa, Stefano Freedman, Morris Miller, Bruce Grossman, Murray TI Can Clinical Features Predict Tau Pathology in Patients with Behavioral Variant Frontotemporal Dementia (bvFTD)? SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Rascovsky, Katya; Grossman, Murray] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Hodges, John; Lillo, Patricia; Piguet, Olivier] Res Australia, Neurosci, Randwick, NSW, Australia. [Hodges, John; Lillo, Patricia; Piguet, Olivier] Univ New S Wales, Randwick, NSW, Australia. [Knopman, David; Josephs, Keith; Boeve, Bradley] Mayo Clin, Rochester, MN USA. [Mendez, Mario] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Kramer, Joel; Seeley, William; Rankin, Katherine; Tempini, Maria Gorno; Rosen, Howard; Latham, Caroline; Lee, Albert; Miller, Bruce] Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA. [Neuhaus, John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Van Swieten, John; Seelaar, Harro; Dopper, Elise] Erasmus MC, Rotterdam, Netherlands. [Onyike, Chiadi; Hillis, Argye] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Kertesz, Andrew] Univ Western Ontario, London, ON, Canada. [Johnson, Julene] Univ Calif San Francisco, Inst Hlth & Aging Univ, San Francisco, CA 94143 USA. [Kipps, Christopher] Univ Southampton, Wessex Neurol Ctr, Southampton, Hants, England. [Rohrer, Jonathan; Rossor, Martin; Warren, Jason; Fox, Nic] UCL Inst Neurol, Dementia Res Ctr, London, England. [Galasko, Douglas; Salmon, David] Univ Calif San Diego, San Diego, CA 92103 USA. [Galasko, Douglas] Univ Calif San Diego, VA Med Ctr, San Diego, CA 92103 USA. [Black, Sandra] Univ Toronto, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada. [Mesulam, M.; Weintraub, Sandra] Northwestern Univ, Feinberg Sch Med, Cognit Neurol & Alzheimers Dis Ctr, Chicago, IL 60611 USA. [Dickerson, Bradford] Massachusetts Gen Hosp, Charlestown, MA USA. [Dickerson, Bradford] Harvard Univ, Sch Med, Charlestown, MA USA. [Diehl, Janine] Tech Univ Munich, D-80290 Munich, Germany. [Pasquier, Florence; Deramecourt, Vincent; Lebert, Florence] Univ Lille Nord France, Lille, France. [Pijnenburg, Yolande] Vrije Univ Amsterdam, Med Ctr, Alzheimers Res Ctr, Amsterdam, Netherlands. [Pijnenburg, Yolande] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Chow, Tiffany] Univ Toronto, Rotman Res Inst, Toronto, ON, Canada. [Manes, Facundo] Univ Buenos Aires, Inst Cognit Neurol Favaloro, RA-1053 Buenos Aires, DF, Argentina. [Grafman, Jordan] Brain Injury Res Rehabil Inst Chicago, Chicago, IL USA. [Cappa, Stefano] Univ Vita Salutte San Raffaele, Milan, Italy. [Freedman, Morris] Baycrest, Neurol, Toronto, ON, Canada. [Freedman, Morris] Univ Toronto, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P05101 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068603254 ER PT J AU Ringman, J Liang, LJ Flores, M Wharton, D Goate, A Schofield, P Cairns, N Benzinger, T Fagan, A Xiong, CJ Ghetti, B McDade, E Masters, C Mayeux, R Rossor, M Sperling, R Salloway, S Marcus, D Martins, R Bateman, R Morris, J AF Ringman, John Liang, Li-Jung Flores, Martin Wharton, David Goate, Alison Schofield, Peter Cairns, Nigel Benzinger, Tammie Fagan, Anne Xiong, Chengjie Ghetti, Bernardino McDade, Eric Masters, Colin Mayeux, Richard Rossor, Martin Sperling, Reisa Salloway, Stephen Marcus, Daniel Martins, Ralph Bateman, Randall Morris, John TI Early Behavioral Changes in Familial Alzheimer's Disease: Results from the Dominantly Inherited Alzheimer Network SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Ringman, John] Easton Ctr Alzheimers Dis Res, Los Angeles, CA USA. [Liang, Li-Jung; Flores, Martin] Univ Calif Los Angeles, David Geffen Sch Med, Dept Internal Med, Los Angeles, CA 90095 USA. [Wharton, David] UCLA Dept Neurol, Easton Ctr Alzheimers Dis Res, Los Angeles, CA USA. [Goate, Alison; Cairns, Nigel; Benzinger, Tammie; Fagan, Anne; Xiong, Chengjie; Marcus, Daniel; Bateman, Randall; Morris, John] Washington Univ, Sch Med, St Louis, MO USA. [Schofield, Peter] Neurosci Res Australia, Randwick, NSW, Australia. [Ghetti, Bernardino] Indiana Univ, Indianapolis, IN 46204 USA. [McDade, Eric] Univ Pittsburgh, Pittsburgh, PA USA. [Masters, Colin] Univ Melbourne, Melbourne, Vic 3010, Australia. [Mayeux, Richard] Columbia Univ, New York, NY USA. [Rossor, Martin] UCL, London, England. [Sperling, Reisa] Brigham & Womens Univ, Massachusetts Gen Hosp, Boston, MA USA. [Salloway, Stephen] Brown Univ, Providence, RI 02912 USA. [Martins, Ralph] Edith Cowan Univ, Joondalup, Australia. 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA S24005 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068606091 ER PT J AU Rost, N Metterville, D Cloonan, L Fitzpatrick, K Kanakis, A Politei, J Sims, K AF Rost, Natalia Metterville, Danielle Cloonan, Lisa Fitzpatrick, Kaitlin Kanakis, Allison Politei, Juan Sims, Katherine TI Determinants of White Matter Hyperintensity Burden in Patients with Fabry Disease SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Rost, Natalia; Metterville, Danielle; Cloonan, Lisa; Fitzpatrick, Kaitlin; Kanakis, Allison; Sims, Katherine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Politei, Juan] Hosp Gen Agudos, Buenos Aires, DF, Argentina. 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P03171 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068602140 ER PT J AU Schultz, A Marshall, G Chhatwal, J Rentz, D Johnson, K Ward, A Wigman, S Hedden, T Van Dijk, K McLaren, D Huijbers, W Sperling, R AF Schultz, Aaron Marshall, Gad Chhatwal, Jasmeer Rentz, Dorene Johnson, Keith Ward, Andrew Wigman, Sarah Hedden, Trey Van Dijk, Koene McLaren, Donald Huijbers, Willem Sperling, Reisa TI Test-Retest Reliability of Resting State Functional Connectivity MRI in Mild Cognitive Impairment SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Schultz, Aaron] MGH, Dept Neurol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Marshall, Gad] Brigham & Womens Hosp, Brookline, MA USA. [Chhatwal, Jasmeer] Massachusetts Gen Hosp, Cambridge, MA USA. [Rentz, Dorene; Ward, Andrew; Wigman, Sarah; Huijbers, Willem; Sperling, Reisa] Brigham & Womens Hosp, Boston, MA 02115 USA. [Johnson, Keith] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hedden, Trey; Van Dijk, Koene] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [McLaren, Donald] Mass Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P06024 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068604092 ER PT J AU Schwamm, L Ali, S Davis, L Forducey, P Nystrom, K Schindler, J Schlegel, S Likosky, W Solenski, N Burt, D AF Schwamm, Lee Ali, Syed Davis, Lawrence Forducey, Pamela Nystrom, Karin Schindler, Joseph Schlegel, Sherene Likosky, William Solenski, Nina Burt, David CA Partners TeleStroke Network TI Independent Predictors of IV tPA Use in the Partners Telestroke Network: A Multistate, Multicenter Hospital Alliance in the Remote Management of Acute Ischemic Stroke SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Schwamm, Lee; Ali, Syed; Partners TeleStroke Network] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Davis, Lawrence; Forducey, Pamela] INTEGRIS Hlth, Oklahoma City, OK USA. [Nystrom, Karin; Schindler, Joseph] Yale New Haven Stroke Ctr, New Haven, CT USA. [Schlegel, Sherene; Likosky, William] Swedish Med Ctr, Seattle, WA USA. [Solenski, Nina] Univ Virginia, Charlottesville, VA USA. [Burt, David] Univ Virginia, Dept Emergency Med, Charlottesville, VA 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P05222 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068604027 ER PT J AU Schwamm, L Ali, S Davis, L Forducey, P Nystrom, K Schindler, J Schlegel, S Likosky, W Solenski, N Burt, D AF Schwamm, Lee Ali, Syed Davis, Lawrence Forducey, Pamela Nystrom, Karin Schindler, Joseph Schlegel, Sherene Likosky, William Solenski, Nina Burt, David CA Partners TeleStroke Network TI Partners Telestroke Network: Experience of a Multistate, Multicenter Hospital Alliance in the Remote Management of Acute Ischemic Stroke SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Schwamm, Lee; Partners TeleStroke Network] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ali, Syed] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Davis, Lawrence; Forducey, Pamela] INTEGRIS Hlth, Oklahoma City, OK USA. [Nystrom, Karin; Schindler, Joseph] Yale New Haven Stroke Ctr, New Haven, CT USA. [Schlegel, Sherene; Likosky, William] Swedish Med Ctr, Seattle, WA USA. [Solenski, Nina] Univ Virginia, Charlottesville, VA USA. [Burt, David] Univ Virginia, Dept Emergency Med, Charlottesville, VA 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P05213 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068604018 ER PT J AU Sherman, A Heiman-Patterson, T Katz, J Katsovskiy, I Selsov, R Sinani, E Walker, J Cudkowicz, M AF Sherman, Alexander Heiman-Patterson, Terry Katz, Jonathan Katsovskiy, Igor Selsov, Roger Sinani, Ervin Walker, Jason Cudkowicz, Merit TI NeuroBANK (TM): Integrated Clinical Data Repository Platform as a Model for Clinical Research SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Sherman, Alexander; Katsovskiy, Igor; Selsov, Roger; Sinani, Ervin; Walker, Jason] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Heiman-Patterson, Terry] Drexel Univ, Radnor, PA USA. [Katz, Jonathan] Calif Pacific Med Ctr, San Francisco, CA USA. [Cudkowicz, Merit] MGH, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P07072 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068605054 ER PT J AU Singhal, A AF Singhal, Aneesh CA Partners SPOTRIAS Investigators TI Serial MRI Findings in a Phase 2B Clinical Trial of Normobaric Oxygen Therapy (NBO) in Acute Ischemic Stroke (AIS) SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Singhal, Aneesh] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Partners SPOTRIAS Investigators] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA S42001 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068606202 ER PT J AU Singhal, A AF Singhal, Aneesh CA Partners SPOTRIAS Investigators TI A Phase IIB Clinical Trial of Normobaric Oxygen Therapy (NBO) in Acute Ischemic Stroke (AIS) SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Singhal, Aneesh; Partners SPOTRIAS Investigators] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA S02001 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068605340 ER PT J AU Singhal, A AF Singhal, Aneesh CA Partners SPOTRIAS Investigators TI Serial MRI Findings in a Phase 2B Clinical Trial of Normobaric Oxygen Therapy (NBO) in Acute Ischemic Stroke (AIS) SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Singhal, Aneesh] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Partners SPOTRIAS Investigators] Massachusetts Gen Hosp, Dept Neurol, 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA IN72002 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068600098 ER PT J AU Singhal, T Sheth, K Cho, T AF Singhal, Tarun Sheth, Kevin Cho, Tracey TI Morbidity and Mortality Conferences in ACGME Core Competencies Education for Neurology Residents SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Singhal, Tarun; Cho, Tracey] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sheth, Kevin] U Maryland, Baltimore, MD 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P04248 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068603137 ER PT J AU Tate, J Brashear, A Whitlow, C Snively, B Ozelius, L Sweadner, K Stacy, M Haq, I AF Tate, Jessica Brashear, Allison Whitlow, Christopher Snively, Beverly Ozelius, Laurie Sweadner, Kathleen Stacy, Mark Haq, Ihtsham TI Rapid-Onset Dystonia-Parkinsonism Presenting as Tremor-Dominant Parkinson's Disease SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Tate, Jessica; Brashear, Allison; Haq, Ihtsham] Wake Forest Baptist Hlth, Wake Forest Sch Med, Winston Salem, NC USA. [Whitlow, Christopher] Wake Forest Baptist Hlth, Wake Forest Sch Med, Dept Radiol, Winston Salem, NC USA. [Snively, Beverly] Wake Forest Baptist Hlth, Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Ozelius, Laurie] Mt Sinai Sch Med, New York, NY USA. [Sweadner, Kathleen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Stacy, Mark] Duke Univ, Sch Med, Duke Hlth, Durham, NC USA. RI Brashear, Allison/G-3853-2015 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P04161 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068603050 ER PT J AU Thakur, K Marmarelis, M Wahlster, S Bakhadirov, K Bhattacharyya, R Dunn, I AF Thakur, Kiran Marmarelis, Melissa Wahlster, Sarah Bakhadirov, Khamidulla Bhattacharyya, Roby Dunn, Ian TI Management of Refractory Elevated Intracranial Pressure (ICP) in an Immunocompetant Host with Cryptococcal Meningitis SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Thakur, Kiran] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. [Marmarelis, Melissa; Wahlster, Sarah] Harvard Univ, Sch Med, Boston, MA USA. [Bakhadirov, Khamidulla] Brigham & Womens Hosp, Brookline, MA USA. [Bhattacharyya, Roby] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dunn, Ian] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P03249 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068602217 ER PT J AU Topcuoglu, M Kursun, O Karatas, H Buonanno, F Singhal, A AF Topcuoglu, Mehmet Kursun, Oguzhan Karatas, Hulya Buonanno, Ferdinando Singhal, Aneesh TI Stroke in Non-Bacterial Thrombotic Endocarditis: 31-Year Experience SO NEUROLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN) CY MAR 16-23, 2013 CL San Diego, CA SP Amer Acad Neurol C1 [Topcuoglu, Mehmet] Hacettepe Univ, Dept Neurol, Ankara, Turkey. [Kursun, Oguzhan] Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. [Karatas, Hulya] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Boston, MA 02114 USA. [Buonanno, Ferdinando; Singhal, Aneesh] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Karatas, Hulya/J-1459-2013 OI Karatas, Hulya/0000-0003-4838-6320 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 12 PY 2013 VL 80 SU S MA P02023 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AB8VR UT WOS:000332068601087 ER EF